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#1

 

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Description Asymptomatic coronavirus sufferers appear to lose detectable antibodies sooner than people who have exhibited COVID-19 symptoms, according to one of the biggest studies of its kind in Britain reported on Tuesday.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#2

 

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Description We examined the association between active and passive smoking and lung cancer risk and the population attributable fraction (PAF) of lung cancer due to active smoking, in the Norwegian Women and Cancer Study, a nationally representative prospective cohort study. We followed 142,508 women, aged 31–70 years, who completed a baseline questionnaire between 1991 and 2007, through linkages to national registries through December 2015. We used Cox proportional hazards models, to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We calculated PAF to indicate what proportion of lung cancer cases could have been prevented in the absence of smoking. During the more than 2.3 million person-years of observation, we ascertained 1507 lung cancer cases. Compared with never smokers, current (HR 13.88, 95% CI 10.18–18.91) smokers had significantly increased risk of lung cancer. Female never smokers exposed to passive smoking had a 1.3-fold (HR 1.34, 95% CI 0.89–2.01) non- significantly increased risk of lung cancer, compared with never smokers. The PAF of lung cancer was 85.3% (95% CI 80.0–89.2). More than 8 in 10 lung cancer cases could have been avoided in Norway, if the women did not smoke.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#3

 

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Description Here we present a transgender male adolescent with an androgen receptor-positive serous borderline ovarian tumour in the setting of testosterone treatment for medical gender transition. To our knowledge, this is the second report of borderline tumour in a transgender individual and the first in an adolescent, an age group in which borderline tumours are extremely rare. We discuss the specific considerations of treating ovarian tumours in the transgender male population, the incompletely understood role of androgens in the genesis of ovarian epithelial neoplasia, and an emphasis on assessing cancer risk in transgender patients based on patient anatomy.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#4

 

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Description Over the past years, several studies have demonstrated that defects in DNA damage response and repair (DDR) genes are present in a significant proportion of patients with prostate cancer. These alterations, particularly mutations in BRCA2, are known to be associated with an increased risk of developing prostate cancer and more aggressive forms of the disease. There is growing evidence that certain DDR gene aberrations confer sensitivity to poly-(ADP ribose) polymerase inhibitors and/or platinum chemotherapy, while other defects might identify cases that are more likely to benefit from immune checkpoint inhibition. The potential prognostic impact and relevance for treatment selection together with the decreasing costs and broader accessibility to next-generation sequencing have already resulted in the increased frequency of genetic profiling of prostate tumours. Remarkably, almost half of all DDR genetic defects can occur in the germline, and prostate cancer patients identified as mutation carriers, as well as their families, will require appropriate genetic counselling. In this review, we summarise the current knowledge regarding the biology and clinical implications of DDR defects in prostate cancer, and outline how this evidence is prompting a change in the treatment landscape of the disease.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#5

 

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Description In tumours, hypoxia—a condition in which the demand for oxygen is higher than its availability—is well known to be associated with reduced sensitivity to radiotherapy and chemotherapy, and with immunosuppression. The consequences of hypoxia on tumour biology and patient outcomes have therefore led to the investigation of strategies that can alleviate hypoxia in cancer cells, with the aim of sensitising cells to treatments. An alternative therapeutic approach involves the design of prodrugs that are activated by hypoxic cells. Increasing evidence indicates that hypoxia is not just clinically significant in adult cancers but also in paediatric cancers. We evaluate relevant methods to assess the levels and extent of hypoxia in childhood cancers, including novel imaging strategies such as oxygen-enhanced magnetic resonance imaging (MRI). Preclinical and clinical evidence largely supports the use of hypoxia-targeting drugs in children, and we describe the critical need to identify robust predictive biomarkers for the use of such drugs in future paediatric clinical trials. Ultimately, a more personalised approach to treatment that includes targeting hypoxic tumour cells might improve outcomes in subgroups of paediatric cancer patients.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#6

 

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Description

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#7

 

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Description Stress sensing is the basis of human-machine interface, biomedical engineering, and mechanical structure detection systems. Stress sensing based on mechanoluminescence (ML) shows significant advantages of distributed detection and remote response to mechanical stimuli and is thus expected to be a key technology of next-generation tactile sensors and stress recorders. However, the instantaneous photon emission in ML materials generally requires real-time recording with a photodetector, thus limiting their application fields to real-time stress sensing. In this paper, we report a force-induced charge carrier storage (FICS) effect in deep-trap ML materials, which enables storage of the applied mechanical energy in deep traps and then release of the stored energy as photon emission under thermal stimulation. The FICS effect was confirmed in five ML materials with piezoelectric structures, efficient emission centres and deep trap distributions, and its mechanism was investigated through detailed spectroscopic characterizations. Furthermore, we demonstrated three applications of the FICS effect in electronic signature recording, falling point monitoring and vehicle collision recording, which exhibited outstanding advantages of distributed recording, long-term storage, and no need for a continuous power supply. The FICS effect reported in this paper provides not only a breakthrough for ML materials in the field of stress recording but also a new idea for developing mechanical energy storage and conversion systems. A material that records mechanical impacts and provides optical readouts at later dates shows promise for anti-counterfeiting devices and structural damage analysis. Phosphors, such as rare earth-doped silicates, can emit light in response to physical stress because they store charge carriers in easy-to-access energy states. Rong-Jun Xie from China’s Xiamen University and colleagues now report development of phosphors that release charges to less accessible ‘deep’ energy states after being stimulated mechanically. These carriers are retained in the deep states and then released on-demand as photon emissions following thermal treatments. The team demonstrated several applications for the new phosphors including sensors that can record signature traces and composite films that attach to vehicles to monitor for potential collisions.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#8

 

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Description According to the World Health Organization, Alzheimer’s disease is the most common cause of senile dementia that affects dozens of millions of people worldwide, with numbers expected to double every 20 years if more effective treatments are not forthcoming. It has long been thought that Alzheimer

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#9

 

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Description Most people infected with COVID-19 did not transmit the disease, but those that did tended to be superspreaders, according to a large study conducted in India.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#10

 

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Description Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow. The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression. Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs. Among these new drugs, we focussed on thioredoxin (Trx). Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways. The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses. In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF). Taken together, these findings suggest that Trx may be the ideal drug for treating COPD.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#11

 

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Description The liver is an important immunological organ that controls systemic tolerance. The liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and maintenance. Orchestrating the immune response in homeostasis depends on a healthy and well-toned immunological liver microenvironment, which is maintained by the crosstalk of liver-resident antigen-presenting cells and intrahepatic and liver-infiltrating leukocytes. In response to pathogens or autoantigens, tolerance is disrupted by unknown mechanisms. Intrahepatic parenchymal and nonparenchymal cells exhibit unique antigen-presenting properties. The presentation of microbial and endogenous lipid-, metabolite- and peptide-derived antigens from the gut via conventional and nonconventional mechanisms can educate intrahepatic immune cells and elicit effector responses or tolerance. Perturbation of this balance results in autoimmune liver diseases, such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Although the exact etiologies of these autoimmune liver diseases are unknown, it is thought that the disruption of tolerance towards self-antigens and microbial metabolites and lipids, as well as alterations in bile acid composition, may result in changes in effector cell activation and polarization and may reduce or impair protective anti-inflammatory regulatory T and B cell responses. Additionally, the canonical and noncanonical transmission of antigens and antigen:MHC complexes via trogocytosis or extracellular vesicles between different (non) immune cells in the liver may play a role in the induction of hepatic inflammation and tolerance. Here, we summarize emerging aspects of antigen presentation, autoantibody production, and the application of novel therapeutic approaches in the characterization and treatment of autoimmune liver diseases.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#13

 

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Description As Facebook chief Mark Zuckerberg prepares to be grilled by a Senate committee about the handling of politically-charged posts, content moderators are insisting that properly valuing their work is key.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#14

 

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Description NineSigma, representing Hisamitsu Pharmaceutical Co., Inc. (https://global.hisamitsu/), seeks potential partners to conduct R&D of novel transdermal drug delivery system using the microneedle technologies developed by the client. Having a transdermal drug delivery system [TDDS] as their s

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#15

 

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Description The immune response is a balancing act: Too much can lead to inflammatory or autoimmune disease; too little could lead to a serious infection. Regulatory T cells, or Tregs, are important players in striking this balance, acting as “brakes” on the immune response so it doesn’t go overboard. Conseq

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#16

 

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Description Cancer remodels the architecture of our chromosomes so the disease can take hold and spread, University of Virginia researchers have revealed. This remodelling is important because the arrangement of the components in our chromosomes actually affects the workings of our genes. With these renovation

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#17

 

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Description Facebook’s former and current content moderators have expressed concerns about posts intended to cause trouble or bedevil the outcome of the forthcoming election while demanding better treatment at work.

#Medicine & Human body
Field # Medicine & Human body
Updated 27 October 2020

#18

 

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Description It remains challenging to construct a complete cell lineage map of the origin of vascular endothelial cells in any vertebrate embryo. Here, we report the application of in toto light-sheet fluorescence imaging of embryos to trace the origin of vascular endothelial cells (ECs) at single-cell resolution in zebrafish. We first adapted a previously reported method to embryo mounting and light-sheet imaging, created an alignment, fusion, and extraction all-in-one software (AFEIO) for processing big data, and performed quantitative analysis of cell lineage relationships using commercially available Imaris software. Our data revealed that vascular ECs originated from broad regions of the gastrula along the dorsal–ventral and anterior–posterior axes, of which the dorsal–anterior cells contributed to cerebral ECs, the dorsal–lateral cells to anterior trunk ECs, and the ventral–lateral cells to posterior trunk and tail ECs. Therefore, this work, to our knowledge, charts the first comprehensive map of the gastrula origin of vascular ECs in zebrafish, and has potential applications for studying the origin of any embryonic organs in zebrafish and other model organisms.

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 27 October 2020

#19

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#20

 

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Description German software giant SAP on Sunday downgraded its outlook for 2020, saying a resurgence in coronavirus cases would weigh on demand from "hard hit" customers.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#21

 

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Description Doctors and biostatisticians at the University of Michigan Rogel Cancer Center have led the development and validation of a staging system to better predict outcomes and inform treatment decisions for men diagnosed with non-metastatic prostate cancer. Although it is one of the most common cancers

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#22

 

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Description German software giant SAP’s stock plummeted overnight, wiping $33.1 billion off its market capitalization in a loss eclipsing anything the enterprise software giant has seen in 20 years. 

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#23

 

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Description Although the lungs are a common target for COVID-19’s cytokine storm, so are the kidneys, making the 1 in 4 U.S. adults with diabetes resulting in diabetic kidney disease at increased risk for virus mortality. But why are the kidneys so attractive to the coronavirus? Recently published in Kidn

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#24

 

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Description SAP suffers coronavirus-induced stock plunge, but a leading partner sees strong long-term prospects

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#25

 

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Name
Description Judges will favor solo or socially distanced dancing

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#26

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#27

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#28

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#29

 

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Name
Description Trump health spokesperson planned to vaccinate Santas in $250 million campaign.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#30

 

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Description β-Globin gene mutations reduce or terminate the production of beta globin chains, of which approximately 10% are large deletions within the β-globin gene cluster. Because gene deletion leads to loss of heterozygosity at single nucleotide polymorphism (SNP), a novel method for detecting β-globin gene cluster deletions based on SNP heterozygosity analysis was established in this study. The location range of SNPs was selected according to the breakpoint of β-globin gene cluster deletions. SNPs were screened using bioinformatics analysis and population sequencing data. A novel method which enables genotyping of multiplex SNPs based on tetra-primer ARMS-PCR was designed and optimized. Forty clinical samples were tested in parallel by this method and MLPA to verify the performance of this method for detecting β-globin gene cluster deletion. Six informative SNPs were obtained, achieving heterozygote coverage of 93.3% in normal individuals. Genotyping of six SNPs were successfully integrated into two multiplex tetra-primer ARMS-PCR reactions. The sensitivity, specificity, positive predictive value and negative predictive value of the method for detecting β-globin gene cluster deletion were 100%, 96.30%, 92.86%, and 100%, respectively. This is a simple, cost-effective and novel method for detecting β-globin gene cluster deletions, which may be suitable for use in combination with MLPA for thalassemia molecular testing.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#31

 

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Description The elevation of neopterin in cerebrospinal fluid (CSF) has been reported in several neuroinflammatory disorders. However, it is not expected that neopterin alone can discriminate among different neuroinflammatory etiologies. We conducted an observational retrospective and case–control study to analyze the CSF biomarkers neopterin, total proteins, and leukocytes in a large cohort of pediatric patients with neuroinflammatory disorders. CSF samples from 277 subjects were included and classified into four groups: Viral meningoencephalitis, bacterial meningitis, acquired immune-mediated disorders, and patients with no-immune diseases (control group). CSF neopterin was analyzed with high-performance liquid chromatography. Microbiological diagnosis included bacterial CSF cultures and several specific real-time polymerase chain reactions. Molecular testing for multiple respiratory pathogens was also included. Antibodies against neuronal and glial proteins were tested. Canonical discriminant analysis of the three biomarkers was conducted to establish the best discriminant functions for the classification of the different clinical groups. Model validation was done by biomarker analyses in a new cohort of 95 pediatric patients. CSF neopterin displayed the highest values in the viral and bacterial infection groups. By applying canonical discriminant analysis, it was possible to classify the patients into the different groups. Validation analyses displayed good results for neuropediatric patients with no-immune diseases and for viral meningitis patients, followed by the other groups. This study provides initial evidence of a more efficient approach to promote the timely classification of patients with viral and bacterial infections and acquired autoimmune disorders. Through canonical equations, we have validated a new tool that aids in the early and differential diagnosis of these neuroinflammatory conditions.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#32

 

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Description Mucin 1 (MUC1) is a transmembrane glycoprotein involved in tumorigenesis of diverse cancers. However, the role of MUC1 in glioblastoma (GBM) has not yet been fully explored. In this study, the anticancer mechanism of MUC1 suppression in GBM was investigated. The expression level of MUC1 was analyzed in human glioma and paired normal brain tissues. MUC1 was overexpressed in GBM and was negatively associated with overall survival. Moreover, we silenced MUC1 to investigate its effect in GBM cell lines and found that knockdown of MUC1 inhibited cell proliferation and resulted in cell cycle arrest at G1 phase. MUC1 silencing decreased the phosphorylation of RB1 and increased the expression of CDKN1B. Gene set enrichment analysis showed that a series of genes related to cell cycle, telomere maintenance and transforming growth factor Beta (TGF-β) signaling in epithelial mesenchymal transition (EMT) were influenced by MUC1 knockdown. Notably, the reduced TERT expression levels combined with impaired telomerase activity and the switching of telomere maintenance mechanism to alternative lengthening of telomeres (ALT) were observed after MUC1 knockdown. Our results support the role of MUC1 in oncological process in GBM which can be developed as a therapeutic target for cell cycle control and telomere maintenance mechanism.

#Medicine & Human body;#Theoretical sciences
Field # Medicine & Human body
Updated 26 October 2020

#33

 

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Description Chronic fatigue syndrome (CFS) patients often suffer from severe muscle pain and an inability to exercise due to muscle fatigue. It has previously been shown that CFS skeletal muscle cells have lower levels of ATP and have AMP-activated protein kinase dysfunction. This study outlines experiments looking at the utilisation of different substrates by skeletal muscle cells from CFS patients (n = 9) and healthy controls (n = 11) using extracellular flux analysis. Results show that CFS skeletal muscle cells are unable to utilise glucose to the same extent as healthy control cells. CFS skeletal muscle cells were shown to oxidise galactose and fatty acids normally, indicating that the bioenergetic dysfunction lies upstream of the TCA cycle. The dysfunction in glucose oxidation is similar to what has previously been shown in blood cells from CFS patients. The consistency of cellular bioenergetic dysfunction in different cell types supports the hypothesis that CFS is a systemic disease. The retention of bioenergetic defects in cultured cells indicates that there is a genetic or epigenetic component to the disease. This is the first study to use cells derived from skeletal muscle biopsies in CFS patients and healthy controls to look at cellular bioenergetic function in whole cells.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#34

 

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Description Exercise has been considered as treatment and a preventive modality to alleviate depressive symptoms, but sex differences regarding specific types of exercise in association with depression have not been clearly elucidated. Here, we investigated sex differences in the association between exercise type and depression in Korean adults. Data from the Korea National Health and Nutrition Examination Survey (KNHANES) were used for this study. A total of 13,914 participants who had filled in a Patient Health Questionnaire-9 (PHQ-9) were included. The subjects’ exercise status had been evaluated with questions on strength exercise and walking, and answers were analysed in the current study using multivariate logistic regression. Male participants who reported having done strength exercise more than once in a week were less likely to be depressed after adjusting for covariates assumed to affect depression levels [adjusted odds ratio (OR) 0.60, 95% CI 0.40–0.92]. In women, walking more than once during the previous week was associated with lower depression levels after covariate adjustments (adjusted OR 0.54, CI 0.34–0.87). This study identifies the relationship between exercise and the presence of depressive symptoms and finds sex differences in the types of exercise that correlate with depression in Korean adults.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#35

 

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Description Spine degenerative conditions are becoming increasingly prevalent, affecting about 5.7% of the population in Europe, resulting in a significant reduction of life’s quality. Up to now, many materials have been used in manufacturing cage implants, used as graft substitutes, to achieve immediate and long-term spinal fixation. Particularly, titanium and its alloys are emerging as valuable candidates to develop new types of cages. The aim of this in vitro study was to evaluate the adhesion, proliferation and osteogenic differentiation of adipose derived mesenchymal stem cells (ASCs) seeded on trabecular titanium cages. ASCs adhered, proliferated and produced an abundant extracellular matrix during the 3 weeks of culture. In the presence of osteogenic medium, ASCs differentiated into osteoblast-like cells: the expression of typical bone genes, as well as the alkaline phosphatase activity, was statistically higher than in controls. Furthermore, the dispersive spectrometry microanalysis showed a marked increase of calcium level in cells grown in osteogenic medium. Plus, our preliminary data about osteoinduction suggest that this titanium implant has the potential to induce the ASCs to produce a secretome able to trigger a shift in the ASCs phenotype, possibly towards the osteogenic differentiation, as illustrated by the qRT-PCR and ALP biochemical assay results. The trabecular porous organization of these cages is rather similar to the cancellous bone structure, thus allowing the bone matrix to colonize it efficiently; for these reasons we can conclude that the architecture of this cage may play a role in modulating the osteoinductive capabilities of the implant, thus encouraging its engagement in in vivo studies for the treatment of spinal deformities and diseases.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#36

 

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Description Cerebral aneurysms should be treated on the basis of accurate rupture risk prediction. Nowadays, the rupture risk in aneurysms has been estimated using hemodynamic parameters. In this paper, we suggest a new way to predict the rupture risks in cerebral aneurysms by using fluid–structure interaction (FSI) analysis for better decision-making regarding treatment. A patient-specific model was constructed using digital subtraction angiography of 51 cerebral aneurysms. For each model, a thin-walled area (TWA) was first predicted using computational fluid dynamics (CFD), and then the highest equivalent strain in the TWA was calculated with FSI by varying wall thicknesses and mechanical properties. A critical curve was made from 16 FSI results for each patient-specific model to estimate the rupture risk. On average, the equivalent strains of the ruptured aneurysms were higher than those of the unruptured aneurysms. Furthermore, the patterns of critical curves between unruptured and ruptured aneurysms were clearly distinguishable. From the rupture risk evaluation based on the cut-off value, 24 of the 27 unruptured aneurysms and 15 of the 24 ruptured aneurysms were matched with actual-clinical setting cases. The critical curve proposed in the present study could be an effective tool for the prediction of the rupture risk of aneurysm.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#37

 

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Description Gap junctions (GJs), which are proteinaceous channels, couple adjacent cells by permitting direct exchange of intracellular molecules with low molecular weights. GJ intercellular communication (GJIC) plays a critical role in regulating behaviors of human embryonic stem cells (hESCs), affecting their proliferation and differentiation. Here we report a novel use of sonoporation that enables single cell intracellular dye loading and dynamic visualization/quantification of GJIC in hESC colonies. By applying a short ultrasound pulse to excite single microbubbles tethered to cell membranes, a transient pore on the cell membrane (sonoporation) is generated which allows intracellular loading of dye molecules and influx of Ca2+ into single hESCs. We employ live imaging for continuous visualization of intercellular dye transfer and Ca2+ diffusion in hESC colonies. We quantify cell–cell permeability based on dye diffusion using mass transport models. Our results reveal heterogeneous intercellular connectivity and a variety of spatiotemporal characteristics of intercellular Ca2+ waves in hESC colonies induced by sonoporation of single cells.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#38

 

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Description This study examines publicly available online search data in China to investigate the spread of public awareness of the 2019 novel coronavirus (SARS-CoV-2) outbreak. We found that cities that had previously suffered from SARS (in 2003–04) and have greater migration ties to Wuhan had earlier, stronger and more durable public awareness of the outbreak. Our data indicate that 48 such cities developed awareness up to 19 days earlier than 255 comparable cities, giving them an opportunity to better prepare. This study suggests that it is important to consider memory of prior catastrophic events as they will influence the public response to emerging threats.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#39

 

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Description No studies on idiopathic pulmonary fibrosis (IPF) have investigated the prognostic impact of extrapulmonary cancers in patients with IPF. We aimed to determine the prognostic impact of malignancies in patients with IPF. We retrospectively reviewed the medical records of patients diagnosed with IPF between 2001 and 2015. Patients were divided into three groups: IPF without cancer (n = 440), IPF with lung cancer (n = 69), and IPF with extrapulmonary cancer (n = 70). Of the 579 patients with IPF, 139 (24%) had cancer; the three most common types were lung (11.9%), gastric (2.4%), and colorectal (1.9%). Survival was significantly worse in patients with lung cancer than in those without cancer (hazard ratio [HR] = 1.83, 95% confidence interval [CI], 1.35–2.48) or those with extrapulmonary cancer (HR = 1.70, 95% CI, 1.14–2.54). The rate of hospitalisation for cancer-related complications was significantly higher in IPF patients with lung cancer than in those with extrapulmonary cancer. The annual rates of decline in percent predicted forced vital capacity and diffusion capacity for carbon monoxide did not differ among the groups. Physicians should pay attention to the development and progression of cancer and its prognostic impact in patients with IPF.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#40

 

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Description Inborn errors of metabolism are genetic conditions that can disrupt intermediary metabolic pathways and cause defective absorption and metabolism of dietary nutrients. In an Australian Kelpie breeding population, 17 puppies presented with intestinal lipid malabsorption. Juvenile dogs exhibited stunted postnatal growth, steatorrhea, abdominal distension and a wiry coat. Using genome-wide association analysis, an associated locus on CFA28 (Praw = 2.87E−06) was discovered and validated in a closely related population (Praw = 1.75E−45). A 103.3 kb deletion NC_006610.3CFA28:g.23380074_23483377del, containing genes Acyl-CoA Synthetase Long Chain Family Member 5 (ACSL5) and Zinc Finger DHHC-Type Containing 6 (ZDHHC6), was characterised using whole transcriptomic data. Whole transcriptomic sequencing revealed no expression of ACSL5 and disrupted splicing of ZDHHC6 in jejunal tissue of affected Kelpies. The ACSL5 gene plays a key role in long chain fatty acid absorption, a phenotype similar to that of our affected Kelpies has been observed in a knockout mouse model. A PCR-based diagnostic test was developed and confirmed fully penetrant autosomal recessive mode of inheritance. We conclude the structural variant causing a deletion of the ACSL5 gene is the most likely cause for intestinal lipid malabsorption in the Australian Kelpie.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#41

 

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Description Deep vein thrombosis (DVT) is a common but unpredictable complication of surgical interventions. To reveal an association between the blood clot contraction (retraction) and the incidence of postoperative venous thrombosis, 78 patients with brain tumors that were operated on were studied, of which 23 (29%) were diagnosed with postoperative DVT. A clot contraction assay, along with other hemostatic and hematologic tests, was performed 1–3 days before the surgery and on the 1st day and 5–7th days after the surgery. On the 1st postoperative day, clot contraction was significantly suppressed in patients who subsequently developed DVT, compared to the patients without DVT. Importantly, this difference was observed at least 5 days before DVT had developed. The weakening of contraction on the 1st postoperative day was more pronounced in the DVT patients with malignant versus benign brain tumors, atherosclerosis, hypertension, as well as in patients receiving steroids before and during the operation. These results indicate that impaired clot contraction in the postoperative period is associated with imminent DVT, suggesting that it is a prothrombotic risk factor and promotional mechanism. The clot contraction assay has a predictive value in assessing the threat of postoperative thrombosis in patients with benign and malignant brain tumors.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#42

 

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Description Huntington’s disease (HD) is a progressive, multifaceted neurodegenerative disease associated with weight loss and gut problems. Under healthy conditions, tight junction (TJ) proteins maintain the intestinal barrier integrity preventing bacterial translocation from the intestinal lumen to the systemic circulation. Reduction of TJs expression in Parkinson’s disease patients has been linked with increased intestinal permeability—leaky gut syndrome. The intestine contains microbiota, most dominant phyla being Bacteroidetes and Firmicutes; in pathogenic or disease conditions the balance between these bacteria might be disrupted. The present study investigated whether there is evidence for an increased intestinal permeability and dysbiosis in the R6/2 mouse model of HD. Our data demonstrate that decreased body weight and body length in R6/2 mice is accompanied by a significant decrease in colon length and increased gut permeability compared to wild type littermates, without any significant changes in the protein levels of the tight junction proteins (occludin, zonula occludens). Moreover, we found an altered gut microbiota in R6/2 mice with increased relative abundance of Bacteroidetes and decreased of Firmicutes. Our results indicate an increased intestinal permeability and dysbiosis in R6/2 mice and further studies investigating the clinical relevance of these findings are warranted.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#43

 

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Description Cell physiology and cellular responses to external stimuli are partly controlled through protein binding, localization, and expression level. Thus, quantification of these processes is pivotal in understanding cellular biology and disease pathophysiology. However, it can be methodologically challenging. Immunofluorescence is a powerful technique, yet quantification by this method can be hampered by auto-fluorescence. Here we describe a simple, sensitive and robust chemiluminescence-based immunoassay (chemiluminescence imaging of cells; CLIC) for relative quantification of proteins. We first employed this method to quantify complement activation in cultured mammalian cells, and to quantify membrane protein expression, shedding, binding and internalization. Moreover, through specific membrane permeabilization we were able to quantify both cytosolic and nuclear proteins, and their translocation. We validated the CLIC quantification method by performing parallel experiments with other quantification methods like ELISA, qPCR, and immunofluorescence microscopy. The workflow of the immunoassay was found to be advantageous in certain instances when compared to these quantification methods. Since the reagents used for CLIC are common to other immunoassays with no need for specialized equipment, and due to the good linearity, dynamic range and signal stability inherent to chemiluminescence, we suggest that this assay is suitable for both small scale and high throughput relative protein quantification studies in whole cells.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#44

 

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Name
Description Visualization of the surgically operated tissues is vital to improve surgical model animals including mouse. Urological surgeries for urethra include series of fine manipulations to treat the increasing number of birth defects such as hypospadias. Hence visualization of the urethral status is vital. Inappropriate urethral surgical procedure often leads to the incomplete wound healing and subsequent formation of urethro-cutaneous fistula or urethral stricture. Application of indocyanine green mediated visualization of the urethra was first performed in the current study. Indocyanine green revealed the bladder but not the urethral status in mouse. Antegrade injection of contrast agent into the bladder enabled to detect the urethral status in vivo. The visualization of the leakage of contrast agent from the operated region was shown as the state of urethral fistula in the current hypospadias mouse model and urethral stricture was also revealed. A second trial for contrast agent was performed after the initial operation and a tendency of accelerated urethral stricture was observed. Thus, assessment of post-surgical conditions of urogenital tissues can be improved by the current analyses on the urethral status.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#45

 

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Name
Description Ancient DNA (aDNA) analyses necessitate the destructive sampling of archaeological material. Currently, the cochlea, part of the osseous inner ear located inside the petrous pyramid, is the most sought after skeletal element for molecular analyses of ancient humans as it has been shown to yield high amounts of endogenous DNA. However, destructive sampling of the petrous pyramid may not always be possible, particularly in cases where preservation of skeletal morphology is of top priority. To investigate alternatives, we present a survey of human aDNA preservation for each of ten skeletal elements in a skeletal collection from Medieval Germany. Through comparison of human DNA content and quality we confirm best performance of the petrous pyramid and identify seven additional sampling locations across four skeletal elements that yield adequate aDNA for most applications in human palaeogenetics. Our study provides a better perspective on DNA preservation across the human skeleton and takes a further step toward the more responsible use of ancient materials in human aDNA studies.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#46

 

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Name
Description The burden of antibiotic resistance is currently estimated by mathematical modeling, without real count of resistance to key antibiotics. Here we report the real rate of resistance to key antibiotics in bacteria isolated from humans during a 5 years period in a large area in southeast in France. We conducted a retrospective study on antibiotic susceptibility of 539,107 clinical strains isolated from hospital and private laboratories in south of France area from January 2014 to January 2019. The resistance rate to key antibiotics as well as the proportion of bacteria classified as Difficult-to-Treat (DTR) were determined and compared with the Mann–Whitney U test, the χ2 test or the Fisher’s exact test. Among 539,037 isolates, we did not observe any significant increase or decrease in resistance to key antibiotics for 5 years, (oxacillin resistance in Staphylococcus aureus, carbapenem resistance in enterobacteria and Pseudomonas aeruginosa and 3rd generation cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae). However, we observed a significant decrease in imipenem resistance for Acinetobacter baumannii from 2014 to 2018 (24.19–12.27%; p = 0.005) and a significant increase of ceftriaxone resistance in Klebsiella pneumoniae (9.9–24.03%; p = 0.001) and Enterobacter cloacae (24.05–42.05%; p = 0.004). Of these 539,037 isolates, 1604 (0.3%) had a DTR phenotype. Over a 5-year period, we did not observe a burden of AR in our region despite a high rate of antibiotic consumption in our country. These results highlight the need for implementation of real-time AR surveillance systems which use factual data.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#47

 

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Name
Description The transcriptome of the endometrium early postpartum was profiled to determine if inflammatory gene expression was elevated in cows which subsequently developed uterine disease. Endometrial cytobrush samples were collected at 7 days postpartum (DPP) from 112 Holstein–Friesian dairy cows, from which 27 were retrospectively chosen for RNA-seq on the basis of disease classification [ten healthy and an additional 17 diagnosed with cytological endometritis (CYTO), or purulent vaginal discharge (PVD)] at 21 DPP. 297 genes were significantly differentially expressed between cows that remained healthy versus those that subsequently developed PVD, including IL1A and IL1B (adjusted p < 0.05). In contrast, only 3 genes were significantly differentially expressed in cows which subsequently developed CYTO. Accounting for the early physiological inflammatory status present in cows which do not develop disease enhanced the detection of differentially expressed genes associated with CYTO and further expression profiling in 51 additional cows showed upregulation of multiple immune genes, including IL1A, IL1B and TNFA. Despite the expected heterogeneity associated with natural infection, enhanced activation of the inflammatory response is likely a key contributory feature of both PVD and CYTO development. Prognostic biomarkers of uterine disease would be particularly valuable for seasonal-based dairy systems where any delay to conception undermines sustainability.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#48

 

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Name
Description Cancer cells accumulate somatic mutations as result of DNA damage, inaccurate repair and other mechanisms. Different genetic instability processes result in characteristic non-random patterns of DNA mutations, also known as mutational signatures. We developed mutSignatures, an integrated R-based computational framework aimed at deciphering DNA mutational signatures. Our software provides advanced functions for importing DNA variants, computing mutation types, and extracting mutational signatures via non-negative matrix factorization. Specifically, mutSignatures accepts multiple types of input data, is compatible with non-human genomes, and supports the analysis of non-standard mutation types, such as tetra-nucleotide mutation types. We applied mutSignatures to analyze somatic mutations found in smoking-related cancer datasets. We characterized mutational signatures that were consistent with those reported before in independent investigations. Our work demonstrates that selected mutational signatures correlated with specific clinical and molecular features across different cancer types, and revealed complementarity of specific mutational patterns that has not previously been identified. In conclusion, we propose mutSignatures as a powerful open-source tool for detecting the molecular determinants of cancer and gathering insights into cancer biology and treatment.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#49

 

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Name
Description Incorrect drug target identification is a major obstacle in drug discovery. Only 15% of drugs advance from Phase II to approval, with ineffective targets accounting for over 50% of these failures1–3. Advances in data fusion and computational modeling have independently progressed towards addressing this issue. Here, we capitalize on both these approaches with Rosalind, a comprehensive gene prioritization method that combines heterogeneous knowledge graph construction with relational inference via tensor factorization to accurately predict disease-gene links. Rosalind demonstrates an increase in performance of 18%-50% over five comparable state-of-the-art algorithms. On historical data, Rosalind prospectively identifies 1 in 4 therapeutic relationships eventually proven true. Beyond efficacy, Rosalind is able to accurately predict clinical trial successes (75% recall at rank 200) and distinguish likely failures (74% recall at rank 200). Lastly, Rosalind predictions were experimentally tested in a patient-derived in-vitro assay for Rheumatoid arthritis (RA), which yielded 5 promising genes, one of which is unexplored in RA.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#50

 

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Name
Description The possibility to assess pancreatic anatomy with microscopic resolution in three dimensions (3D) would significantly add to pathological analyses of disease processes. Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis with over 90% of the patients dying within 5 years after diagnosis. Cure can be achieved by surgical resection, but the efficiency remains drearily low. Here we demonstrate a method that without prior immunohistochemical labelling provides insight into the 3D microenvironment and spread of PDAC and premalignant cysts in intact surgical biopsies. The method is based solely on the autofluorescent properties of the investigated tissues using optical projection tomography and/or light-sheet fluorescence microscopy. It does not interfere with subsequent histopathological analysis and may facilitate identification of tumor-free resection margins within hours. We further demonstrate how the developed approach can be used to assess individual volumes and numbers of the islets of Langerhans in unprecedently large biopsies of human pancreatic tissue, thus providing a new means by which remaining islet mass may be assessed in settings of diabetes. Generally, the method may provide a fast approach to provide new anatomical insight into pancreatic pathophysiology.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#51

 

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Name
Description Neoadjuvant therapy is increasingly used to control local tumor spread and micrometastasis of pancreatic ductal adenocarcinoma (PDAC). Pathology assessments of treatment effects might predict patient outcomes after surgery. However, there are conflicting reports regarding the reproducibility and prognostic performance of commonly used tumor regression grading systems, namely College of American Pathologists (CAP) and Evans’ grading system. Further, the M.D. Anderson Cancer Center group (MDA) and the Japan Pancreas Society (JPS) have introduced other grading systems, while we recently proposed a new, simple grading system based on the area of residual tumor (ART). Herein, we aimed to assess and compare the reproducibility and prognostic performance of the modified ART grading system with those of the four grading systems using a multicenter cohort. The study cohort consisted of 97 patients with PDAC who had undergone post-neoadjuvant pancreatectomy at four hospitals. All patients were treated with gemcitabine and S-1 (GS)-based chemotherapies with/without radiation. Two pathologists individually evaluated tumor regression in accordance with the CAP, Evans’, JPS, MDA and ART grading systems, and interobserver concordance was compared between the five systems. The ART grading system was a 5-tiered system based on a number of 40× microscopic fields equivalent to the surface area of the largest ART. Furthermore, the final grades, which were either the concordant grades of the two observers or the majority grades, including those given by the third observer, were correlated with patient outcomes in each system. The interobserver concordance (kappa value) for Evans’, CAP, MDA, JPS and ART grading systems were 0.34, 0.50, 0.65, 0.33, and 0.60, respectively. Univariate analysis showed that higher ART grades were significantly associated with shorter overall survival (p = 0.001) and recurrence-free survival (p = 0.005), while the other grading systems did not show significant association with patient outcomes. The present study revealed that the ART grading system that was designed to be simple and more objective has achieved high concordance and showed a prognostic value; thus it may be most practical for assessing tumor regression in post-neoadjuvant resections for PDAC.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#52

 

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Name
Description The heart is an organ with high energy demands and metabolic flexibility, thus allowing for various energy substrates for ATP production under different physiological conditions. Zhang et al., Fernandez-Caggiano et al. and McCommis et al. converge on the mitochondrial pyruvate transporter as a key metabolic hub for the maintenance of cardiac metabolism and a critical determinant of cardiac metabolic plasticity during heart failure.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#53

 

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Name
Description Genome sequencing of patients with sporadic congenital hydrocephalus reveals mutations of large effect size indicative of a developmental origin for the disease.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#54

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#55

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#56

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#57

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#58

 

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Name
Description Recent advances in next-generation sequencing technologies have paved the path for a considerable amount of sequencing data at a relatively low cost. This has revolutionized the genomics and transcriptomics studies. However, different challenges are now created in handling such data with available bioinformatics platforms both in assembly and downstream analysis performed in order to infer correct biological meaning. Though there are a handful of commercial software and tools for some of the procedures, cost of such tools has made them prohibitive for most research laboratories. While individual open-source or free software tools are available for most of the bioinformatics applications, those components usually operate standalone and are not combined for a user-friendly workflow. Therefore, beginners in bioinformatics might find analysis procedures starting from raw sequence data too complicated and time-consuming with the associated learning-curve. Here, we outline a procedure for de novo transcriptome assembly and Simple Sequence Repeats (SSR) primer design solely based on tools that are available online for free use. For validation of the developed workflow, we used Illumina HiSeq reads of different tissue samples of Santalum album (sandalwood), generated from a previous transcriptomics project. A portion of the designed primers were tested in the lab with relevant samples and all of them successfully amplified the targeted regions. The presented bioinformatics workflow can accurately assemble quality transcriptomes and develop gene specific SSRs. Beginner biologists and researchers in bioinformatics can easily utilize this workflow for research purposes.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#59

 

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Name
Description Bumblebees (Hymenoptera: Apidae) are important pollinating insects that play pivotal roles in crop production and natural ecosystem services. Although protein-coding genes in bumblebees have been extensively annotated, regulatory sequences of the genome, such as promoters and enhancers, have been poorly annotated. To achieve a comprehensive profile of accessible chromatin regions and provide clues for all possible regulatory elements in the bumblebee genome, we performed ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) on Bombus terrestris samples derived from four developmental stages: egg, larva, pupa, and adult, respectively. The ATAC-seq reads were mapped to the B. terrestris reference genome, and its accessible chromatin regions were identified and characterized using bioinformatic methods. We identified 36,390 chromatin accessible regions in total, including both shared and stage-specific chromatin accessible signals. Our study will provide an important resource, not only for uncovering regulatory elements in the bumblebee genome, but also for expanding our understanding of bumblebee biology throughout development. Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13047905

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#60

 

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Name
Description COVID-19 hospitalizations may be spurring the spread of a drug-resistant fungus.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#61

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#62

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#63

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#64

 

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Name
Description Cutting transmission of the coronavirus is vital to prevent hospitals being overwhelmed and schools shutting, but also to stop it evolving

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#65

 

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Name
Description Plasmodium falciparum, a malaria-causing parasite, can live undetected in the human bloodstream for months by changing the way its genes are expressed

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#66

 

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Name
Description The latest coronavirus news updated every day including coronavirus cases, the latest news, features and interviews from New Scientist and essential information about the covid-19 pandemic

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#67

 

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Name
Description University of Oregon biologists have used a model organism to identify molecular mechanisms that produce DNA damage in sperm and contribute to male infertility following exposure to heat. In humans, the optimal temperature for sperm production is just below body temperature, in a range of about 9

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#68

 

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Name
Description A Vanderbilt cancer systems biology team has identified the enzymes that keep tumor cells growing in the presence of drug treatment, opening the door to stopping these cells dead in their tracks. An article, “An Integrative Gene Expression and Mathematical Flux-Balance Analysis Identifies Targeta

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#69

 

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Name
Description The odd-looking devices made 7-year-old Noel Ziebarth a bit nervous. They looked like something right out of a science-fiction comic book, had peculiar names like phoropter, retinoscope, and tonometer, and would be used, she learned, to examine and peer into her eyes. Sitting next to her was an e

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#70

 

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Name
Description Asked by: Anita Hashtrudi, Scotland

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#71

 

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Name
Description The predictive significance of programmed death ligand 1 (PD-L1) for programmed death 1 (PD-1) inhibitors remains unclear in gastric cancer (GC) due to the dynamic alteration by treatments. We aimed to elucidate the effects of trastuzumab (Tmab) on PD-L1 expression in GC. PD-L1 expression was evaluated by multicolour flow cytometry analysis after co-culturing GG cell lines and immune cells with Tmab. IFN-γ in the co-culture experiments was quantified. Immunohistochemistry (IHC) for PD-L1 expression using clinical samples was also performed to confirm PD-L1 alteration by Tmab. PD-L1 expression was significantly upregulated by Tmab in HER2-amplified GC cell lines co-cultured with peripheral blood mononuclear cells (PBMCs). PD-L1 upregulation by Tmab was also observed in the GC cells co-cultured with NK cells in time-dependent manner, but not with monocytes. IFN-γ concentration in conditioned media from co-cultured PBMCs and NK cells with Tmab was significantly higher and anti-IFN-γ significantly suppress the Tmab-induced PD-L1 upregulation. IHC also suggested PD-L1 upregulation after Tmab treatment. Tmab can upregulate PD-L1 expression on GC cells through interaction with NK cells. These results suggest clinical implications in the assessment of the predictive significance of PD-L1 expression for PD-1 inhibitors.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#72

 

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Name
Description Programmed death-ligand 1 (PD-L1) expression has been described in patients with malignant peritoneal mesothelioma (MPM), but treatment strategies utilising immune checkpoint inhibition are yet to be defined. Here, we examine levels of PD-L1 expression in MPM patients treated with systemic and/or intraperitoneal chemotherapy using tissue from patient tumour biopsies or resections at multiple time points. We found the mean PD-L1 expression was higher in those with a germline mutation and/or those with a higher somatic mutation burden. Moreover, PD-L1 expression was lower in patients who had received prior chemotherapy as compared to the treatment-naive cohort. Twenty patients who received chemotherapy, either systemic and/or peritoneal, between PD-L1 measurements showed marked heterogeneity. Six (30%) patients demonstrated upregulation of PD-L1, while eight (40%) demonstrated downregulation. Heterogeneity in PD-L1 expression in MPM before and after cytotoxic therapies may present an additional consideration when initiating immune checkpoint inhibition in this rare and challenging disease.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#73

 

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Name
Description The Phase 2 SCALOP trial compared gemcitabine with capecitabine-based consolidation chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC). Thirty-five systematically identified circulating biomarkers were analysed in plasma samples from 60 patients enroled in SCALOP. Each was measured in triplicate at baseline (prior to three cycles of gemcitabine-capecitabine induction chemotherapy) and, for a subset, prior to CRT. Association with overall survival (OS) was determined using univariable Cox regression and optimal thresholds delineating low to high values identified using time-dependent ROC curves. Independence from known prognostic factors was assessed using Spearman correlation and the Wilcoxon rank sum test prior to multivariable Cox regression modelling including independent biomarkers and known prognostic factors. Baseline circulating levels of C-C motif chemokine ligand 5 (CCL5) were significantly associated with OS, independent of other clinicopathological characteristics. Patients with low circulating CCL5 (CCL5low) had a median OS of 18.5 (95% CI 11.76–21.32) months compared to 11.3 (95% CI 9.86–15.51) months in CCL5high; hazard ratio 1.95 (95% CI 1.04–8.65; p = 0.037). CCL5 is an independent prognostic biomarker in LAPC. Given the known role of CCL5 in tumour invasion, metastasis and the induction of an immunosuppressive micro-environment, targeting of CCL5-mediated pathways may offer therapeutic potential in pancreatic cancer. The SCALOP trial was registered with ISRCTN, number 96169987 (registered 29 May 2008).

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#74

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#75

 

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Name
Description Post-transplant cyclophosphamide (PTCy) has become a promising option after allo-SCT, but infections may be more common than in traditional protocols. We herein report 117 consecutive adults who received PTCy-based alloSCT in our hospital: HaploSCT (34%), MRD (19%), and VUD (47%), respectively. The 18-month incidence of severe bacterial, viral, and IFI was 56%, 69%, and 8.7%, without differences between donor type, except for CMV infection and viral hemorrhagic cystitis, which had a higher incidence in the haploSCT cohort (58% vs. 43% and 30% vs. 8% on day +90, p < 0.05). Late infections by conventional respiratory viruses were common in all groups [33/87 (38%)]. The 2-year survival was 72% and did not differ by donor type. IRM at day 30, day 100, and 18 months was 1.7%, 4.4%, and 12%, without differences by donor type (p = 0.7). The primary cause of IRM was bacterial infection (42%). Grade 2–4 acute GvHD was the only independent predictor of IRM. Donor type had no impact on IRM or on survival. In our study, severe infections were common in all donor types using PTCy, with higher rates of early post-engraftment CMV-I and viral HC in haploSCT recipients, although lethal infections were uncommon and similar in all donor types.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#76

 

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Name
Description In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10−9). Investigation of nonsynonymous SNVs of the IGHV cluster in 9335 Japanese subjects identified the C allele of rs6423677, located in IGHV3-66, as the most significant reproducible association (OR = 1.25, P = 6.8 × 10−10 in 3603 cases and 5731 controls). We observed highly skewed allelic usage of IGHV3-66, wherein the rs6423677 A allele was nearly abolished in the transcripts in peripheral blood mononuclear cells of both KD patients and healthy adults. Association of the high-expression allele with KD strongly indicates some active roles of B-cells or endogenous immunoglobulins in the disease pathogenesis. Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD.

#Medicine & Human body
Field # Medicine & Human body
Updated 26 October 2020

#77

 

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Name
Description Washington imposed sanctions on a Russian research institute tied to the development of a dangerous computer program capable of causing catastrophic industrial damage, a move that Russia called illegitimate.

#Medicine & Human body;#Psychology
Field # Medicine & Human body
Updated 25 October 2020

#78

 

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Name
Description Researchers at the University of Toronto have found evidence that neutrophil immune cell activity is the missing link connecting periodontal disease with heart disease, cancer and other inflammatory conditions – possibly including COVID-19. The link between periodontal (gum) disease and other inf

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#79

 

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Name
Description In a new study published in the journal Cell, Death & Differentiation researchers at Karolinska Institutet have conducted a translational study that identified a new mechanism for controlling the breakdown of glucose in several different cancer forms. The discovery could lead to new therapeutic

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#80

 

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Name
Description As countries struggle to contain the COVID-19 pandemic, vaccination uptake is a public health priority now more than ever. Efforts to increase vaccinations vary greatly around the globe. A new McGill-led study comparing policies around the world finds broad implementation of mandatory vaccination ma

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#81

 

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Name
Description Humans are born with a part of the brain that is prewired to be receptive to seeing words and letters, setting the stage at birth for people to learn how to read, a new study suggests. Analyzing brain scans of newborns, researchers found that this part of the brain – called the “visual word form

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#82

 

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Name
Description TBD

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 25 October 2020

#83

 

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Name
Description NLRP3 (Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3) inflammasome-mediated cardiomyocytes pyroptosis plays a crucial part in progression of acute myocardial infarction (MI). GDF11 (Growth Differentiation Factor 11) has been reported to generate cytoprotective effects in phylogenesis and multiple diseases, but the mechanism that GDF11 contributes to cardioprotection of MI and cardiomyocytes pyroptosis remains poorly understood. In our study, we first determined that GDF11 was abnormally downregulated in the heart tissue of MI mice and hypoxic cardiomyocytes. Moreover, AAV9-GDF11 markedly alleviated heart function in MI mice. Meanwhile, GDF11 overexpression also decreased the pyroptosis of hypoxic cardiomyocytes. PROMO and JASPAR prediction software found that transcription factor HOXA3 was predicted as an important regulator of NLRP3, and was confirmed by ChIP assay. Further analysis identifying GDF11 promoted the Smad2/3 pathway resulted in HOXA3 overexpression. Taken together, our study implies that GDF11 prevents cardiomyocytes pyroptosis via HOXA3/NLRP3 signaling pathway in MI mice.

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#84

 

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Name
Description Letermovir is used to prevent cytomegalovirus infection in hematopoietic stem cell transplantation (HSCT) recipients. Although this agent decreases voriconazole exposure in healthy individuals, the effect of coadministration of letermovir and voriconazole in HSCT recipients is unknown. This retrospective, observational, single-center study was conducted between January 2016 and July 2019 to examine the voriconazole concentration-to-dose ratio over three periods: (A) (days −7 to −1 [day 0: day of HCST]), (B) (days 4–10), and (C) (days 11–17). Forty-two HSCT recipients administered voriconazole were divided into the following two groups based on letermovir coadministration: letermovir (n = 15) and control (n = 27). The percent change (−33.2%, p < 0.05) in the voriconazole concentration-to-dose ratio from periods A to C in the letermovir group was significantly lower than that in the control group. Therefore, frequent therapeutic drug monitoring of voriconazole concentrations and subsequent dose adjustments should be performed regularly in HSCT recipients.

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#85

 

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Name
Description Obesity is of complex origin, involving genetic and neurobehavioral factors. Genetic polymorphisms may increase the risk for developing obesity by modulating dopamine-dependent behaviors, such as reward processing. Yet, few studies have investigated the association of obesity, related genetic variants, and structural connectivity of the dopaminergic reward network. We analyzed 347 participants (age range: 20–59 years, BMI range: 17–38 kg/m2) of the LIFE-Adult Study. Genotyping for the single nucleotid polymorphisms rs1558902 (FTO) and rs1800497 (near dopamine D2 receptor) was performed on a microarray. Structural connectivity of the reward network was derived from diffusion-weighted magnetic resonance imaging at 3 T using deterministic tractography of Freesurfer-derived regions of interest. Using graph metrics, we extracted summary measures of clustering coefficient and connectivity strength between frontal and striatal brain regions. We used linear models to test the association of BMI, risk alleles of both variants, and reward network connectivity. Higher BMI was significantly associated with lower connectivity strength for number of streamlines (β = −0.0025, 95%—C.I.: [−0.004, −0.0008], p = 0.0042), and, to lesser degree, fractional anisotropy (β = −0.0009, 95%—C.I. [−0.0016, −0.00008], p = 0.031), but not clustering coefficient. Strongest associations were found for left putamen, right accumbens, and right lateral orbitofrontal cortex. As expected, the polymorphism rs1558902 in FTO was associated with higher BMI (F = 6.9, p < 0.001). None of the genetic variants was associated with reward network structural connectivity. Here, we provide evidence that higher BMI correlates with lower reward network structural connectivity. This result is in line with previous findings of obesity-related decline in white matter microstructure. We did not observe an association of variants in FTO or near DRD2 receptor with reward network structural connectivity in this population-based cohort with a wide range of BMI and age. Future research should further investigate the link between genetics, obesity and fronto-striatal structural connectivity.

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#86

 

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Name
Description Observational studies have identified gout patients are often comorbid with dyslipidemia. However, the relationship between dyslipidemia and gout is still unclear. We first performed Mendelian randomization (MR) to evaluate the causal effect of four lipid traits on gout and serum urate based on publicly available GWAS summary statistics (n ~100,000 for lipid, 69,374 for gout and 110,347 for serum urate). MR showed each standard deviation (SD) (~12.26 mg/dL) increase in HDL resulted in about 25% (95% CI 9.0%–38%, p = 3.31E−3) reduction of gout risk, with 0.09 mg/dL (95% CI: −0.12 to −0.05, p = 7.00E−04) decrease in serum urate, and each SD (~112.33 mg/dL) increase of TG was associated with 0.10 mg/dL (95% CI: 0.06–0.14, p = 9.87E−05) increase in serum urate. Those results were robust against various sensitive analyses. Additionally, independent effects of HDL and TG on gout/serum urate were confirmed with multivariable MR. Finally, mediation analysis demonstrated HDL or TG could also indirectly affect gout via the pathway of serum urate. In conclusion, our study confirmed the causal associations between HDL (and TG) and gout, and further revealed the effect of HDL or TG on gout could also be mediated via serum urate.

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#87

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#88

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#89

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 25 October 2020

#90

 

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Name
Description Developmental exposure to the environmental neurotoxin β-N-methylamino-l-alanine (BMAA), a proposed risk factor for neurodegenerative disease, can induce long-term cognitive impairments and neurodegeneration in rats. While rodent studies have demonstrated a low transfer of BMAA to the adult brain, this toxin is capable to cross the placental barrier and accumulate in the fetal brain. Here, we investigated the differential susceptibility of primary neuronal cells and neural stem cells from fetal rat hippocampus to BMAA toxicity. Exposure to 250 µM BMAA induced cell death in neural stem cells through caspase-independent apoptosis, while the proliferation of primary neurons was reduced only at 3 mM BMAA. At the lowest concentrations tested (50 and 100 µM), BMAA disrupted neural stem cell differentiation and impaired neurite development in neural stem cell-derived neurons (e.g., reduced neurite length, the number of processes and branches per cell). BMAA induced no alterations of the neurite outgrowth in primary neurons. This demonstrates that neural stem cells are more susceptible to BMAA exposure than primary neurons. Importantly, the changes induced by BMAA in neural stem cells were mitotically inherited to daughter cells. The persistent nature of the BMAA-induced effects may be related to epigenetic alterations that interfere with the neural stem cell programming, as BMAA exposure reduced the global DNA methylation in the cells. These findings provide mechanistic understanding of how early-life exposure to BMAA may lead to adverse long-term consequences, and potentially predispose for neurodevelopmental disorders or neurodegenerative disease later in life.

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#91

 

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Name
Description N6-methyladenosine (m6A) serves as the most common and conserved internal transcriptional modification. However, the roles of m6A on cervical cancer (CC) tumorigenesis are still unclear. Here, results indicated that METTL3 was significantly upregulated in CC tissue and cells, which was closely correlated with the lymph node metastasis and poor prognosis of CC patients. MeRIP-Seq analysis revealed the m6A profiles in CC cells. Functionally, METTL3 promoted the proliferation and Warburg effect (aerobic glycolysis) of CC cells. Mechanistically, METTL3 targeted the 3’-Untranslated Region (3’-UTR) of hexokinase 2 (HK2) mRNA. Moreover, METTL3 recruited YTHDF1, a m6A reader, to enhance HK2 stability. These findings demonstrated that METTL3 enhanced the HK2 stability through YTHDF1-mediated m6A modification, thereby promoting the Warburg effect of CC, which might promote a novel insight for the CC treatment.

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#92

 

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Name
Description A large study exploring possible genetic influences on cannabis use disorder has identified two regions in our DNA — one newly identified and a second that replicates a past finding — that appear to contribute to one’s risk of becoming dependent on marijuana. The findings — published in Lancet Ps

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#93

 

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Name
Description A newly developed light-sensing protein called the MCO1 opsin restores vision in blind mice when attached to retina bipolar cells using gene therapy. The National Eye Institute, part of the National Institutes of Health, provided a Small Business Innovation Research grant to Nanoscope, LLC for devel

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#94

 

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Name
Description The prescription of potentially inappropriate medications to older adults is linked to increased hospitalizations, and it costs patients, on average, more than $450 per year, according to a new University at Buffalo study. The research, which sought to determine the impact of potentially inapprop

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#95

 

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Name
Description There is an increasing body of knowledge on the influence of differential DNA methylation of specific genomic regions in psychiatric disorders. However, fewer studies have addressed global DNA methylation (GMe) levels. GMe is an estimative of biological functioning that is regulated by pervasive mechanisms able to capture the big picture of metabolic and environmental influences upon gene expression. In the present perspective article, we highlighted evidence for the relationships between cortisol and sex hormones and GMe in psychiatric disorders. We argue that the far-reaching effects of cortisol and sexual hormones on GMe may lie on the pathways linking stress and mental health. Further research on these endocrine–epigenetic links may help to explain the role of environmental stress as well as sex differences in the prevalence of psychiatric disorders.

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#96

 

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Name
Description Very preterm birth (<32 weeks of gestation) has been associated with lifelong difficulties in a variety of neurocognitive functions. Magnetic resonance imaging (MRI) combined with advanced analytical approaches have been employed in order to increase our understanding of the neurodevelopmental problems that many very preterm born individuals face as they grow up. In this review, we will focus on two novel imaging techniques that have explored relationships between specific brain mechanisms and behavioural outcomes. These are functional MRI, which maps regional, time-varying changes in brain metabolism and diffusion-weighted MRI, which measures the displacement of water molecules in tissue and provides quantitative information about tissue microstructure. Identifying the neurobiological underpinning of the long-term sequelae associated with very preterm birth could inform the development and implementation of preventative interventions (before any cognitive problem emerges) and could facilitate the identification of behavioural targets for improving the life course outcomes of very preterm individuals.

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 24 October 2020

#97

 

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Description Atg7 is an indispensable factor that plays a role in canonical nonselective autophagy. Here we show that genetic ablation of Atg7 in outer hair cells (OHCs) in mice caused stereocilium damage, somatic electromotility disturbances, and presynaptic ribbon degeneration over time, which led to the gradual wholesale loss of OHCs and subsequent early-onset profound hearing loss. Impaired autophagy disrupted OHC mitochondrial function and triggered the accumulation of dysfunctional mitochondria that would otherwise be eliminated in a timely manner. Atg7-independent autophagy/mitophagy processes could not compensate for Atg7 deficiency and failed to rescue the terminally differentiated, non-proliferating OHCs. Our results show that OHCs orchestrate intricate nonselective and selective autophagic/mitophagy pathways working in concert to maintain cellular homeostasis. Overall, our results demonstrate that Atg7-dependent autophagy plays a pivotal cytoprotective role in preserving OHCs and maintaining hearing function.

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#98

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#99

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#100

 

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Name
Description TBD

#Medicine & Human body;#Software
Field # Medicine & Human body
Updated 24 October 2020

#101

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#102

 

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Name
Description In our previous study, ETV5 mediated-angiogenesis was demonstrated to be dependent upon the PDGF-BB/PDGFR-β/Src/STAT3/VEGFA pathway in colorectal cancer (CRC). However, the ability of ETV5 to affect the efficacy of anti-angiogenic therapy in CRC requires further investigation. Gene set enrichment analysis (GSEA) and a series of experiments were performed to identify the critical candidate gene involved in Bevacizumab resistance. Furthermore, the ability of treatment targeting the candidate gene to enhance Bevacizumab sensitivity in vitro and in vivo was investigated. Our results revealed that ETV5 directly bound to the VEGFA promoter to promote translation of VEGFA. However, according to in vitro and in vivo experiments, ETV5 unexpectedly accelerated antiVEGF therapy (Bevacizumab) resistance. GSEA and additional assays confirmed that ETV5 could promote angiogenesis by inducing the secretion of another tumor angiogenesis factor (CCL2) in CRC cells to facilitate Bevacizumab resistance. Mechanistically, ETV5 upregulated CCL2 by activating STAT3 to facilitate binding with the CCL2 promoter. ETV5 induced-VEGFA translation and CCL2 secretion were mutually independent mechanisms, that induced angiogenesis by activating the PI3K/AKT and p38/MAPK signaling pathways in human umbilical vein endothelial cells (HUVECs). In CRC tissues, ETV5 protein levels were positively associated with CD31, CCL2, and VEGFA protein expression. CRC patients possessing high expression of ETV5/VEGFA or ETV5/CCL2 exhibited a poorer prognosis compared to that of other patients. Combined antiCCL2 and antiVEGFA (Bevacizumab) treatment could inhibit tumor angiogenesis and growth more effectively than single treatments in CRCs with high expression of ETV5 (ETV5+ CRCs). In conclusion, our results not only revealed ETV5 as a novel biomarker for anti-angiogenic therapy, but also indicated a potential combined therapy strategy that involved in targeting of both CCL2 and VEGFA in ETV5+ CRC.

#Medicine & Human body
Field # Medicine & Human body
Updated 24 October 2020

#103

 

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Name
Description The adaptation of a broad genomic sequencing approach in the clinical setting has been accompanied by considerations regarding the clinical utility, technical performance, and diagnostic yield compared to targeted genetic approaches. We have developed MedExome, an integrated framework for sequencing, variant calling (SNVs, Indels, and CNVs), and clinical assessment of ~4600 medically relevant genes. We compared the technical performance of MedExome with the whole-exome and targeted gene-panel sequencing, assessed the reasons for discordance, and evaluated the added clinical yield of MedExome in a cohort of unresolved subjects suspected of genetic disease. Our analysis showed that despite a higher average read depth in panels (3058 vs. 855), MedExome yielded full coverage of the enriched regions (>20X) and 99% variant concordance rate with panels. The discordance rate was associated with low-complexity regions, high-GC content, and low allele fractions, observed in both platforms. MedExome yielded full sensitivity in detecting clinically actionable variants, and the assessment of 138 patients with suspected genetic conditions resulted in 76 clinical reports (31 full [22.1%], 3 partial, and 42 uncertain/possible molecular diagnoses). MedExome sequencing has comparable performance in variant detection to gene panels. Added diagnostic yield justifies expanded implementation of broad genomic approaches in unresolved patients; however, cost-benefit and health systems impact warrants assessment.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#104

 

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Name
Description Radiotherapy (RT) is a component of therapy for head and neck cancer (HNC) with a negative nutritional impact. Our aim was to compare an early versus a conventional nutritional intervention. Retrospective study of HNC patients undergoing RT. Evolution before and after the establishment of a fast-track circuit was evaluated. A conventional group (CG) made up of patients submitted to the nutrition unit during RT after nutritional deterioration, was compared to an early group (EG) represented by patients included in a fast-track circuit, starting nutritional follow-up before the beginning of RT. Only patients with preserved oral intake were involved. Demographic, nutritional and clinical variables were analyzed. Data of hospitalizations and deaths were collected up to three months after RT. 135 subjects constituted the EG and 39 the CG. At baseline, the prevalence of malnutrition was lower in the EG (31.9% vs 69.5%, p = 0.0001), as was the need for nutritional supplements (40% vs 79.5%, p = 0.0001) or nasogastric tube (0% vs 12.8%, p = 0.0001) in comparison to the CG. Three months after RT, there were less patients with oral nutritional support in the EG (79.1% vs 96.9%, p = 0.018), and the number of emergency visits (0.75 vs 1.1 episodes per patient, p = 0.021) and hospitalizations was also lower in this group (29% vs 59%, p = 0.044). The fast-track approach made early intervention possible. Therefore, patients maintained a better nutritional status, needed less nutritional support and their evolution improved, with a significant decrease in hospitalizations.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#106

 

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Description Severe bronchopulmonary dysplasia (sBPD) can lead to long term morbidity. We created a sBPD multidisciplinary team in 2011 to optimize care and improve outcomes. Retrospective chart review of three groups between 2008 and 2016: patients with sBPD born before 2011, patients with sBPD born after 2011, and patients with moderate BPD born after 2011. Infants with sBPD after 2011 had a shorter NICU length of stay compared with children born before 2011 (mean 140 days vs 170 days p < 0.007), weighed more at discharge (z-score −0.8 vs −1.35 p = 0.01), had less failure to thrive post discharge (32% vs 51% p = 0.05) and had more well visits in the first six months of life (mean 6.7 vs 5.3 p = 0.04). No difference was observed in the rate of readmissions in the first two years of life. Our multidisciplinary team has improved the inpatient management of patients with sBPD.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#107

 

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Name
Description Joint injuries can often lead to joint disease in both humans and other animals, but a new study looking at a particular biological lubricant suggests we might have to rethink how these diseases actually develop.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#108

 

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Name
Description Leading viral immunologist Professor Lisa Ng is leveraging modern tools in the age-old battle against disease-causing pathogens.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#109

 

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Name
Description Naked mole rats are beloved for having some of the strangest mammalian superpowers. They can resist cancers, defy the usual mammalian ageing process, survive almost 20 minutes without oxygen, and tolerate surprisingly high levels of pain. 

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#110

 

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Name
Description As the pandemic marches on, many people have taken solace in the idea that as long as we keep our interactions with others brief, our coronavirus risk will remain low.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#111

 

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Name
Description Patients with non-dialysis chronic kidney disease (CKD) are at greater risk of early mortality and decreased physical function with an advance in the stage of CKD. However, the effect of exercise in these patients is unclear. This meta-analysis aimed to determine the effects of physical exercise training on the risk of mortality, kidney and physical functions, and adverse events in patients with non-dialysis CKD. The meta-analysis conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the Cochrane Handbook recommendations. On 16 August 2019, the PubMed, CINAHL, Cochrane Library databases, and Embase were electronically searched, with no restrictions for date/time, language, document type, or publication status, for eligible randomized controlled trials (RCTs) investigating the effects of exercise on mortality and kidney and physical function in patients with non-dialysis CKD. Eighteen trials (28 records), including 848 patients, were analyzed. The effects of exercise on all-cause mortality and estimated glomerular filtration rate were not significantly different from that of usual care. Exercise training improved peak/maximum oxygen consumption compared to usual care. Regular exercise improves physical and walking capacity for patients with non-dialysis CKD. Effect on leg muscle strength was unclear.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#112

 

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Name
Description Glioblastoma (GBM) is a malignant brain tumour with a dismal prognosis, despite best treatment by surgical resection, radiation therapy (RT) and chemotherapy with temozolomide (TMZ). Nanoparticle (NP) therapy is an emerging consideration due to the ability of NPs to be formulated and cross the blood brain barrier. Lanthanum oxide (La2O3) NPs are therapeutically advantageous due to the unique chemical properties of lanthanum making it cytotoxic to cancers, and able to enhance existing anti-cancer treatments. However, La2O3 NPs have yet to be thoroughly investigated in brain tumors. We show that these NPs can reach the brain after venous injection, penetrate into GBM cells via endocytosis, dissociate to be cytotoxic, and enhance the therapeutic effects of RT and TMZ. The mechanisms of cell death by La2O3 NPs were found to be multifaceted. Increasing NP concentration was correlated to increased intrinsic and extrinsic apoptosis pathway markers in a radical oxygen species (ROS)-dependent manner, as well as involving direct DNA damage and autophagic pathways within GBM patient-derived cell lines. NP interactions to sensitize GBM to RT and TMZ were shown to involve these pathways by enhancing ROS and apoptotic mechanisms. We therefore demonstrate the therapeutic potential of La2O3 NPs to treat GBM cells in vitro, and encourage translational exploration in the future.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#113

 

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Name
Description To guide the selection of osteosynthesis systems, this study compared the mechanical properties of biodegradable and titanium osteosynthesis systems. SonicPins Rx and xG were subjected to pull-out tests. Additionally, 15 biodegradable (Inion CPS 2.0 and 2.5 mm; LactoSorb 2.0 mm; Macropore 2.0 mm; Polymax 2.0 mm; BioSorb FX 2.0 mm; ResorbX 2.1 mm; Osteotrans-MX 2.0 mm with plate thicknesses 1.0 and 1.4 mm; SonicWeld Rxplate/Rxpins, xGplate/Rxpins and xGplate/xGpins 2.1 mm without and with tapping the burr hole) and six titanium (CrossDrive (2006), CrossDrive (2018), MaxDrive; all 1.5 and 2.0 mm) straight, four-hole osteosynthesis systems were evaluated. All systems were subjected to tensile, bending and torsion tests. Pull-out loads of the SonicPins were comparable (P = 0.423). Titanium systems’ tensile loads were higher than biodegradable systems (P < 0.001). CrossDrive (2018) and MaxDrive systems’ tensile and torsional stiffness were lower, accompanied with higher ductility, than corresponding CrossDrive (2006) systems (P < 0.001). Bending stiffness of 1.5 mm titanium systems was comparable to, and of the 2.0 mm systems higher than, all biodegradable systems (P < 0.001). Regarding biodegradable systems, Inion CPS 2.5 mm had highest tensile load and torsional stiffness, SonicWeld 2.1 mm highest tensile stiffness, and BioSorbFX 2.0 mm highest bending stiffness (P < 0.001). On the basis of the results of this study, the CrossDrive (2018) and MaxDrive 1.5 mm titanium systems are recommended for midface fractures (e.g., zygomatic or maxillary fractures) and osteotomies (e.g., Le Fort I osteotomy), and the CrossDrive (2018) and MaxDrive 2.0 mm titanium systems for mandibular fractures and osteotomies when a titanium osteosynthesis system is used. When there is an indication for a biodegradable osteosynthesis system, the SonicWeld 2.1 mm or BioSorbFX 2.0 mm are recommended for midface fractures and osteotomies, and the Inion CPS 2.5 mm biodegradable system for mandibular osteotomies and non-load bearing mandibular fractures, especially when high torsional forces are expected (e.g., mandibular symphysis fractures).

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#114

 

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Name
Description In flexible gastrointestinal (GI) endoscopy, endoscopic insufflation is crucial and directly affects visualization. Optimal visualization enables endoscopists to conduct better examinations and administer optimal treatments. However, endoscopic insufflation is typically performed manually and is subjective. We aimed to measure the GI endoluminal pressure during flexible GI endoscopy. Participants underwent esophagogastroduodenoscopy (EGD) at our endoscopy center. Pressure measurement was conducted after completing diagnostic or follow-up EGD. The endoluminal pressure in the esophagus and stomach was measured at 1-s intervals for 1 min while performing EGD for observational and diagnostic purposes. During the measurements, the endoscopists maintained what they subjectively considered to be adequate exposure for screening for lesions by dilating the lumen. Eighty patients were enrolled in this study. The upper GI endoluminal pressure was assessed during EGD without adverse events. The esophageal endoluminal pressure averaged 8.9 (− 3.0 to 20.7) mmHg, and the gastric endoluminal pressure averaged 10.0 (3.0–17.9) mmHg; the upper GI endoluminal pressures were not affected by patient-related factors or the number of endoscopists’ postgraduate years. We have successfully obtained the GI endoluminal pressures during EGD. Further accumulation of these data may lead to more stable and reproducible flexible endoscopic diagnosis and intervention.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#115

 

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Name
Description Motor deficits in parkinsonism are caused by degeneration of dopaminergic nigral neurons. The success of disease-modifying therapies relies on early detection of the underlying pathological process, leading to early interventions in the disease phenotype. Healthy (n = 16), REM sleep behavior disorder (RBD) (n = 14), dementia with Lewy bodies (n = 10), and Parkinson’s disease (PD) (n = 20) participants underwent 18F-AV133 vesicular monoamine transporter type-2 (VMAT2) PET to determine the integrity of the nigrostriatal pathway. Clinical, neurophysiological and neuropsychological testing was conducted to assess parkinsonian symptoms. There was reduced VMAT2 levels in RBD participants in the caudate and putamen, indicating nigrostriatal degeneration. RBD patients also presented with hyposmia and anxiety, non-motor symptoms associated with parkinsonism. 18F-AV133 VMAT2 PET allows identification of underlying nigrostriatal degeneration in RBD patients. These findings align with observations of concurrent non-motor symptoms in PD and RBD participants of the Parkinson’s Progression Markers Initiative. Together, these findings suggest that RBD subjects have prodromal parkinsonism supporting the concept of conducting neuroprotective therapeutic trials in RBD-enriched cohorts. Ongoing longitudinal follow-up of these subjects will allow us to determine the time-window of clinical progression.

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 23 October 2020

#116

 

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Name
Description We reflect on the past 10 months of clinical activity in oncology in the UK during the COVID-19 pandemic and suggest how services can be protected during subsequent waves of infection.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#117

 

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Name
Description Environmental challenges are integrated in the inmunoneuroendocrine interplay, impacting the immune system of the challenged individuals, and potentially implying transgenerational effects on their offspring. This study addressed whether dietary supplementation with thymol can modulate the immune response of adult Japanese quail when simultaneously exposed to an inoculum of inactivated Salmonella Enteritidis and a chronic heat stress (CHS). We also evaluated whether the experienced situations by adults can affect the immune response of their undisturbed offspring. In the parental generation, supplemented quail exposed to CHS had a higher inflammatory response and similar values of the heterophil/lymphocyte (H/L) ratio than those that were not supplemented. In their offspring, those chicks whose parents were exposed to CHS showed higher inflammatory response and lower antibody production. Regarding the H/L ratio, chicks whose parents were supplemented showed lower H/L ratio values. Dietary supplementation with thymol partially and positively modulated the inflammatory response and avoided H/L ratio alteration in the parental generation exposed to high environmental temperatures, suggesting these adults were better at dealing with the challenge. The lower H/L ratio values in the offspring suggests that chicks are more capable to deal with potential stressful situations associated with conventional breeding conditions.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#118

 

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Name
Description A recent study re-casts proteomic analyses as a DNA sequencing problem; by fusing in vivo-expressed proteins to their encoding mRNA, molecular interactions can be identified and quantified through high-throughput nucleic-acid sequencing.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#119

 

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Name
Description Krabbe disease (KD) is caused by a deficiency of galactosylceramidase (GALC), which induces demyelination and neurodegeneration due to accumulation of cytotoxic psychosine. Hematopoietic stem cell transplantation (HSCT) improves clinical outcomes in KD patients only if delivered pre-symptomatically. Here, we hypothesize that the restricted temporal efficacy of HSCT reflects a requirement for GALC in early brain development. Using a novel Galc floxed allele, we induce ubiquitous GALC ablation (Galc-iKO) at various postnatal timepoints and identify a critical period of vulnerability to GALC ablation between P4-6 in mice. Early Galc-iKO induction causes a worse KD phenotype, higher psychosine levels in the rodent brainstem and spinal cord, and a significantly shorter life-span of the mice. Intriguingly, GALC expression peaks during this critical developmental period in mice. Further analysis of this mouse model reveals a cell autonomous role for GALC in the development and maturation of immature T-box-brain-1 positive brainstem neurons. These data identify a perinatal developmental period, in which neuronal GALC expression influences brainstem development that is critical for KD pathogenesis. Krabbe disease is caused by GALC deficiency, leading to accumulation of cytotoxic psychosine, demyelination, and neurodegeneration. Here, the authors develop a Galc flox mouse line to model Krabbe disease and unveil that early postnatal GALC neuronal expression is critical for disease pathogenesis.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#120

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#121

 

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Name
Description Big data company Palantir is working with US health officials on a project to track the production and distribution of future COVID-19 vaccines.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#122

 

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Name
Description Toxoplasmosis and cat scratch disease, which spread parasites and bacteria, cost Australia billions each year in lost productivity and medical costs

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#123

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#124

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#125

 

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Name
Description The association between morphology of the brain and symptoms of suspected idiopathic normal pressure hydrocephalus (iNPH) is largely unknown. We investigated how ventricular expansion (width of the temporal horns [TH], callosal angle [CA], and Evans’ index [EI]) related to symptom severity in suspected iNPH. Participants (n = 168; 74.9 years ± SD 6.7; 55% females) from the general population underwent neurological examination, computed tomography, and neuropsychological testing. Multiple linear regression analysis revealed that wide TH was independently associated with all examined iNPH symptoms (p < 0.01) except for fine-motor performance, whereas a narrow CA only was associated to specific motor and cognitive functions (p < 0.05). TH and EI correlated significantly with incontinence (rs 0.17 and rs 0.16; p < 0.05). In conclusion, wide TH was significantly associated with most iNPH-symptoms. This finding potentially reflects the complex nature of the hippocampus, however further studies are needed to demonstrate functional connectivity.

#Medicine & Human body;#Software
Field # Medicine & Human body
Updated 23 October 2020

#126

 

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Name
Description In 2002, China integrated hepatitis B vaccine (HepB) into its Expanded Program on Immunization (EPI) using HepB vaccine containing 5 µg of antigen. Although not recommended nationally, there was a common clinical practice in China of screening children for anti-HBs antibody level and giving a booster dose to HBV surface antigen (HBsAg)-negative children with non-protective anti-HBs antibody levels. We report an evaluation of the protective effectiveness of the 5 µg HepB vaccine and the serological response to the booster dose. We used data from a 2014 hepatitis B serological survey to determine HBsAg positivity and anti-HBs antibody levels among children who received and did not receive a booster dose. We determined HepB coverage from the Children Immunization Information Management System (CIIMS). We obtained and analyzed reports of acute Hepatitis B (AHB) during 2008–2014 obtained from the National Notifiable Disease Reporting System (NNDRS). The HBsAg-positive rate among children who had not received a booster dose was 0.41%, and did not increase with age (i.e., time since infant immunization). The anti-HBs positivity rate among the 6% of children who received a booster dose (88.41%) was higher than among those who had not received a booster (60.85%); anti-HBs antibody levels declined with age regardless of booster dose status. There was no statistically significant difference in HBsAg positivity between children who received a booster dose and those who did not. The AHB incidence among children born between 2002 and 2007 did not increase with age. Use of routine 5 µg HepB vaccine was not associated with an increase in AHB or of HBsAg positivity by time since vaccination, providing supportive evidence that individuals vaccinated with the 5 µg HepB vaccine do not need a booster dose. Although a booster dose was associated with increases in anti-HBs antibody levels, our study provided no evidence to support the need for this clinical practice. We should continue to strengthen serological monitoring of children, especially for those born to HBsAg positive mothers.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#127

 

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Name
Description Stress hyperglycemia and insulin resistance are evolutionarily conserved metabolic adaptations to severe injury including major trauma, burns, or hemorrhagic shock (HS). In response to injury, the neuroendocrine system increases secretion of counterregulatory hormones that promote rapid mobilization of nutrient stores, impair insulin action, and ultimately cause hyperglycemia, a condition known to impair recovery from injury in the clinical setting. We investigated the contributions of adipocyte lipolysis to the metabolic response to acute stress. Both surgical injury with HS and counterregulatory hormone (epinephrine) infusion profoundly stimulated adipocyte lipolysis and simultaneously triggered insulin resistance and hyperglycemia. When lipolysis was inhibited, the stress-induced insulin resistance and hyperglycemia were largely abolished demonstrating an essential requirement for adipocyte lipolysis in promoting stress-induced insulin resistance. Interestingly, circulating non-esterified fatty acid levels did not increase with lipolysis or correlate with insulin resistance during acute stress. Instead, we show that impaired insulin sensitivity correlated with circulating levels of the adipokine resistin in a lipolysis-dependent manner. Our findings demonstrate the central importance of adipocyte lipolysis in the metabolic response to injury. This insight suggests new approaches to prevent insulin resistance and stress hyperglycemia in trauma and surgery patients and thereby improve outcomes.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#128

 

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Name
Description The diagnostic performance of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels for multiple-organ cancer screening has not been fully elucidated. However, they are widely used for real-world opportunistic screening of multiple-organ cancers. This study aimed to examine the diagnostic performance of these serum markers in multiple-organ cancer screening. Data from asymptomatic individuals subjected to opportunistic cancer screening were analyzed. The diagnostic performance of CEA and CA 19-9 was assessed for (A) upper/lower gastrointestinal cancers and (B) whole-body cancers (including both gastrointestinal and other organ cancers) using the results of upper/lower gastrointestinal endoscopy and whole-body imaging as reference. Data from 12,349 and 7616 screened individuals were used to assess the diagnostic performance of CEA and CA 19-9 for (A) and (B), respectively. For (A), the sensitivity and positive predictive value (PPV) of CEA (cut-off: 5 ng/mL) were 7.8% and 3.7%, respectively; those of CA19-9 (cut-off: 37 U/mL) were 7.4% and 2.7%, respectively. For (B), the sensitivity and PPV of CEA were 6.6% and 4.1%, respectively, and those of CA19-9 were 10.8% and 5.8%, respectively. Considering even multiple cancers, the sensitivity and PPV of CEA and CA 19-9 were low, thus confirming their limited usefulness in multiple-organ cancer screening.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#129

 

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Name
Description Neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory index (SII) are prognostic factors in epithelial ovarian cancer (EOC). Their predictive value for platinum-sensitivity and their role in recurrent EOC are unknown. A total of 375 EOC patients were retrospectively analyzed. The correlation between baseline NLR and SII, and platinum-free interval (PFI) according to first line bevacizumab treatment were analyzed using logistic regression analyses adjusted for baseline patient characteristics. Subsequently NLR and SII calculated before second line treatment initiation were evaluated to identify a potential correlation with progression-free survival (PFS) and overall survival (OS) in platinum-sensitive and in platinum-resistant population. In multivariate analysis, NLR ≥ 3 is an independent predictive factor for PFI at 6 months in the chemotherapy group (OR = 2.77, 95% CI 1.38–5.56, p = 0.004), not in bevacizumab treated patients. After having adjusted for ECOG performance status, histology, ascites, bevacizumab treatment at second line and BRCA status, NLR ≥ 3 and SII ≥ 730 are significantly associated with worse OS in platinum-sensitive (HR = 2.69, 95% CI 1.60–4.53, p = 0.002; HR = 2.11, 95% CI 1.29–3.43, p = 0.003, respectively), not in platinum-resistant EOC patients. Low NLR is an independent predictive factor for platinum-sensitivity in patients treated without bevacizumab. NLR and SII are prognostic factors in recurrent platinum-sensitive EOC patients.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#130

 

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Name
Description To determine the association between combined lifestyle factors, including healthy diet, moderate alcohol consumption, non-smoking, physical activity, and optimal weight, and cardiovascular disease (CVD) risk among younger and older adults. We conducted a literature search using PubMed, EMBASE, Cochrane Library, and EBSCO databases up to November 30, 2019 and performed dose–response analysis, subgroup analysis and meta-regression with odds ratios and 95% confidence intervals (CIs). Twenty cohort studies involving 1,090,261 participants with 46,288 cardiovascular events and mean follow-up duration of 12.33 years were included. Compared with the group with the lowest number of healthy lifestyle factors, the group with the highest number had lower CVD risk [pooled hazard ratio, 0.37 (95% CI 0.31–0.43)]. With age as an effect modifier, the lifetime risk of CVD was 0.31 (95% CI 0.24–0.41) at age 37.1–49.9 years, 0.36 (95% CI 0.30–0.45) at age 50.0–59.9 years and 0.49 (95% CI 0.38–0.63) at age 60.0–72.9 years. The hazard ratio of CVD significantly increased from 37.1 to 72.9 years of age [slope in multivariate meta-regression: 0.01 (95% CI < 0.001–0.03; p = 0.042)]. Younger adults have more cardiovascular benefits from combined healthy lifestyle factors.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#131

 

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Description Neddylation is a process by which NEDD8 is covalently conjugated to target proteins by sequential enzymatic reaction. Its role in cancer cell migration has only been recently acknowledged. Previously in cancer cell migration, the epithelial to mesenchymal transition (EMT) process has been well-known to play an important role in both invasion and metastasis by promoting mesenchymal phenotype in epithelial cells. However, the role of neddylation in the EMT process and its mechanistic details are yet to be elucidated. We recently reported that neddylation plays a crucial role in cancer cell migration through the PI3K-Akt pathway. Here, we report that inhibiting neddylation activates the hypoxia-inducible factor 1α (HIF-1α) through the PI3K-Akt pathway, which eventually regulates the EMT-activator ZEB1 (zinc finger E-box binding homeobox 1) in various cancer cell lines. As induction of HIF-1α is known to deteriorate the state of cancer and EMT process is one of the hallmarks of metastasis in cancer, our findings uncover the role of neddylation between HIF-1α and ZEB1.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#132

 

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Description Computer simulation provides an increasingly realistic picture of large-scale conformational change of proteins, but investigations remain fundamentally constrained by the femtosecond timestep of molecular dynamics simulations. For this reason, many biologically interesting questions cannot be addressed using accessible state-of-the-art computational resources. Here, we report the development of an all-atom Monte Carlo approach that permits the modelling of the large-scale conformational change of proteins using standard off-the-shelf computational hardware and standard all-atom force fields. We demonstrate extensive thermodynamic characterization of the folding process of the α-helical Trp-cage, the Villin headpiece and the β-sheet WW-domain. We fully characterize the free energy landscape, transition states, energy barriers between different states, and the per-residue stability of individual amino acids over a wide temperature range. We demonstrate that a state-of-the-art intramolecular force field can be combined with an implicit solvent model to obtain a high quality of the folded structures and also discuss limitations that still remain.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#133

 

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Description This study compared the characteristic surgical parameters and clinical effects of transoral robotic surgery (TORS) and other available methods used to alleviate obstructive sleep apnea. Articles on TORS and other surgeries for obstructive sleep apnea were identified in the PubMed and EMBASE databases. Two investigators independently reviewed the articles and classified the data for meta-analysis. The pooled effect sizes of TORS (standardized mean difference; SMD = − 2.38), coblation tongue base resection (CTBR; SMD = − 2.00) and upper airway stimulation (UAS; SMD = − 0.94) revealed significant improvement in the apnea–hypopnea index (AHI; p < 0.05). The lowest O2 saturation reported was significantly increased following TORS (SMD = 1.43), CTBR (SMD = 0.86) and UAS (SMD = 1.24, p < 0.05). Furthermore, TORS (SMD = − 2.91) and CTBR (SMD = − 1.51, p < 0.05) significantly reduced the Epworth Sleepiness Scale (ESS) score. No significant difference in operation time, success rate, or instances of complication were observed between TORS and the other compared interventions. The use of TORS in obstructive sleep apnea has the same rate of success and failure as other methods of surgical intervention for obstructive sleep apnea with no statistical difference in operation times. The reported clinical effects on the AHI, lowest O2 saturation, and ESS scores of TORS were similar to those of other surgeries.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#134

 

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Description HIV prevalence in Japan continues to increase among men who have sex with men (MSM). We built a mathematical model to describe the HIV epidemic, including acute infection and pre-exposure prophylaxis (PrEP), and projected the model to 2050. We compared current testing and treatment policies, a scenario where Japan achieves UNAIDS 90-90-90 targets, three PrEP scenarios defined by different coverage levels of 25%, 50%, and 75% among the 20% of MSM with the highest risk behavior, and combinations of these scenarios. With no change in interventions prevalence of HIV among MSM will rise to 9.0% in 2050. If Japan achieves full UNAIDS 90-90-90 targets, 84.9% of these infections would be averted. Under 50% PrEP with no expansion of testing and treatment, prevalence will reach 2.6% and 62.1% of infections would be averted by 2050. If in addition UNAIDS 90-90-90 goals are achieved, 92.7% of HIV infections would be prevented by 2050. All interventions tested in this model were cost-saving relative to the base case. Both PrEP and enhanced ART strategies can be cost-saving, and if Japan enhances its testing program for MSM and introduces PrEP, it has the potential to effectively eliminate new infections in the next 30 years.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#135

 

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Description Stroke is caused by obstructed blood flow (ischaemia) or unrestricted bleeding in the brain (haemorrhage). Global brain ischaemia occurs after restricted cerebral blood flow e.g. during cardiac arrest. Following ischaemic injury, restoration of blood flow causes ischaemia–reperfusion (I/R) injury which worsens outcome. Secondary injury mechanisms after any stroke are similar, and encompass inflammation, endothelial dysfunction, blood–brain barrier (BBB) damage and apoptosis. We developed a new model of transient global forebrain I/R injury (dual carotid artery ligation; DCAL) and compared the manifestations of this injury with those in a conventional I/R injury model (middle-cerebral artery occlusion; MCAo) and with intracerebral haemorrhage (ICH; collagenase model). MRI revealed that DCAL produced smaller bilateral lesions predominantly localised to the striatum, whereas MCAo produced larger focal corticostriatal lesions. After global forebrain ischaemia mice had worse overall neurological scores, although quantitative locomotor assessment showed MCAo and ICH had significantly worsened mobility. BBB breakdown was highest in the DCAL model while apoptotic activity was highest after ICH. VCAM-1 upregulation was specific to ischaemic models only. Differential transcriptional upregulation of pro-inflammatory chemokines and cytokines and TLRs was seen in the three models. Our findings offer a unique insight into the similarities and differences in how biological processes are regulated after different types of stroke. They also establish a platform for analysis of therapies such as endothelial protective and anti-inflammatory agents that can be applied to all types of stroke.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#136

 

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Description Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the head and neck region which mainly distributes in southern China and Southeast Asia and has a crucial association with the Epstein–Barr virus. Based on epidemiological data, both incidence and mortality of NPC have significantly declined in recent decades grounded on the improvement of living standard and medical level in an endemic region, in particular, with the clinical use of individualized chemotherapy and intensity-modulated radiotherapy (IMRT) which profoundly contributes to the cure rate of NPC patients. To tackle the challenges including local recurrence and distant metastasis in the current NPC treatment, we discussed the implication of using targeted therapy against critical molecules in various signal pathways, and how they synergize with chemoradiotherapy in the NPC treatment. Combination treatment including targeted therapy and IMRT or concurrent chemoradiotherapy is presumably to be future options, which may reduce radiation or chemotherapy toxicities and open new avenues for the improvement of the expected functional outcome for patients with advanced NPC.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#137

 

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Description Immunotherapy has limited efficacy against locally advanced pancreatic cancer (LAPC) due to the presence of an immunosuppressive microenvironment (ISM). Irreversible electroporation (IRE) can not only induce immunogenic cell death, but also alleviate immunosuppression. This study aimed to investigate the antitumor efficacy of IRE plus allogeneic γδ T cells in LAPC patients. A total of 62 patients who met the eligibility criteria were enrolled in this trial, then randomized into two groups (A: n = 30 and B: n = 32). All patients received IRE therapy and after receiving IRE, the group A patients received at least two cycles of γδ T-cell infusion as one course continuously. Group A patients had better survival than group B patients (median OS: 14.5 months vs. 11 months; median PFS: 11 months vs. 8.5 months). Moreover, the group A patients treated with multiple courses of γδ T-cell infusion had longer OS (17 months) than those who received a single course (13.5 months). IRE combined with allogeneic γδ T-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients, yielding extended survival benefits. ClinicalTrials.gov ID: NCT03180437.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#138

 

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Description One of the ways in which genes can become activated in tumors is by somatic structural genomic rearrangements leading to promoter swapping events, typically in the context of gene fusions that cause a weak promoter to be substituted for a strong promoter. While identifiable by whole genome sequencing, limited availability of this type of data has prohibited comprehensive study of the phenomenon. Here, we leveraged the fact that copy number alterations (CNAs) arise as a result of structural alterations in DNA, and that they may therefore be informative of gene rearrangements, to pinpoint recurrent promoter swapping at a previously intractable scale. CNA data from nearly 9500 human tumors was combined with transcriptomic sequencing data to identify several cases of recurrent activating intrachromosomal promoter substitution events, either involving proper gene fusions or juxtaposition of strong promoters to gene upstream regions. Our computational screen demonstrates that a combination of CNA and expression data can be useful for identifying novel fusion events with potential driver roles in large cancer cohorts.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#139

 

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Description Recent years have witnessed tremendous progress of intelligent robots brought about by mimicking human intelligence. However, current robots are still far from being able to handle multiple tasks in a dynamic environment as efficiently as humans. To cope with complexity and variability, further progress toward scalability and adaptability are essential for intelligent robots. Here, we report a brain-inspired robotic platform implemented by an unmanned bicycle that exhibits scalability of network scale, quantity and diversity to handle the changing needs of different scenarios. The platform adopts rich coding schemes and a trainable and scalable neural state machine, enabling flexible cooperation of hybrid networks. In addition, an embedded system is developed using a cross-paradigm neuromorphic chip to facilitate the implementation of diverse neural networks in spike or non-spike form. The platform achieved various real-time tasks concurrently in different real-world scenarios, providing a new pathway to enhance robots’ intelligence.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#140

 

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Name
Description Three recent studies report cryo-EM structures of amyloid fibrils of islet amyloid polypeptide (IAPP), which are linked to type 2 diabetes (T2D) pathogenesis. The results shed light on the structural basis of IAPP fibril formation, reveal remarkable similarities between IAPP and Aβ fibrils and will inform the design of anti-amyloid drugs in T2D and Alzheimer’s disease (AD).

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#141

 

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Description The eukaryotic cell cycle involves a highly orchestrated series of events in which the cellular genome is replicated during a synthesis (S) phase and each of the two resulting copies are segregated properly during mitosis (M). Host cell factor-1 (HCF-1) is a transcriptional co-regulator that is essential for and has been implicated in basic cellular processes, such as transcriptional regulation and cell cycle progression. Although a series of HCF-1 transcriptional targets have been identified, few functional clues have been provided, especially for chromosome segregation. Our results showed that HCF-1 activated CDC42 expression by binding to the −881 to −575 region upstream of the CDC42 transcription start site, and the regulation of CDC42 expression by HCF-1 was correlated with cell cycle progression. The overexpression of a spontaneously cycling and constitutively active CDC42 mutant (CDC42F28L) rescued G1 phase delay and multinucleate defects in mitosis upon the loss of HCF-1. Therefore, these results establish that HCF-1 ensures proper cell cycle progression by regulating the expression of CDC42, which indicates a possible mechanism of cell cycle coordination and the regulation mode of typical Rho GTPases.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#142

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#143

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#144

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#145

 

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Description A team of researchers affiliated with institutions in the U.K., China and Australia has developed a cleaning-healing-cleaning method that eliminates ionic defects on the surface of 3-D perovskite films. In their paper published ...

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#146

 

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Description Purdue Pharma pleaded guilty and agreed an $8.3 billion settlement to a long-running lawsuit over actions that fuelled the US opioid crisis

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#147

 

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Description The latest coronavirus news updated every day including coronavirus cases, the latest news, features and interviews from New Scientist and essential information about the covid-19 pandemic

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#148

 

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Description Apple launched its own COVID-19 app back in March, right after the coronavirus outbreak was declared a pandemic. Now, the Cupertino-based tech giant has added new improvements to the app in its latest update.

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#149

 

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Description While the world waits as patiently as it can for a COVID-19 vaccine to materialise, no shortage of questions remain. When will we have a vaccine? How will it be distributed? Will it be as effective as we hope?

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#150

 

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Description Residents who live downwind of fracking wells are likely being exposed to radioactive airborne particles, according to a new statistical analysis of public data. 

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#151

 

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Description Some committee members warn against emergency use of candidates not definitively proven safe or effective

#Medicine & Human body
Field # Medicine & Human body
Updated 23 October 2020

#152

 

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Name
Description What if measuring your wellbeing was as simple as taking your temperature?

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#153

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#154

 

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Description Social distancing measures and stiffer competition are forcing prospective pet owners to use Zoom and social media to find and meet new furry friends.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#155

 

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Description NF-κB signaling pathway has important roles in the regulation of growth and development of nervous system. This pathway has also been shown to participate in the pathogenesis of schizophrenia. Meanwhile, activity of NF-κB signaling pathway is regulated by several factors including non-coding RNAs (lncRNAs). In the current study, we evaluated expression of nine NF-κB-related lncRNAs namely DILC, ANRIL, PACER, CHAST, ADINR, DICER1-AS1, HNF1A-AS1, H19 and NKILA as well as two mRNA coding genes namely ATG5 and CEBPA in the peripheral blood of patients with schizophrenia compared with matched healthy subjects. Expressions of these genes were assessed by real time PCR technique. Expression of PACER was lower in patients with schizophrenia compared with controls (Posterior beta = − 0.684, P value = 0.049). On the other hand, expressions of CHAST, CEBPA, H19, HNF1A-AS1 and DICER1-AS1 were higher in patients compared with controls (Posterior beta = 0.39, P value = 0.005; Posterior beta = 0.844, P value < 0.0001; Posterior beta = 0.467, P value < 0.0001; Posterior beta = 1.107, P value = 0.005; Posterior beta = 0.176, P value = 0.044, respectively). We also appraised the diagnostic power of transcript quantities of CHAST, CEBPA, DICER1-AS1, H19 and HNF1A-AS1 in distinguishing between patients with schizophrenia and controls through depicting ROC curves. Based on the area under curve (AUC) values, CEBPA had the best diagnostic power (AUC = 0.948, P < 0.0001), followed by H19 (AUC = 0.815, P < 0.0001). Taken together, our study demonstrated dysregulation of NF-κB-related lncRNAs and genes in the peripheral blood of patients with schizophrenia and their potential as peripheral markers for this psychiatric condition.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#156

 

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Name
Description To evaluate the risk of iatrogenic injury when using a dual-incision minimally invasive technique to decompress the anterior and peroneal compartments of the lower leg. Forty lower extremities from 20 adult cadavers, embalmed with Thiel’s method, were subject to fasciotomy of the anterior and peroneal compartment using a dual-incision minimally invasive fasciotomy. The first incision was made 12 cm proximal to the lateral malleolus to identify and protect the superficial peroneal nerve (SPN). The second incision was made at the mid-point of the Fibula (half-way between the fibular head and the lateral malleolus). Release of the anterior and peroneal compartments was successful in all specimens. Two nerve injuries of the superficial peroneal nerve were reported. More precisely, in these cases the medial dorsal cutaneous nerve got injured during the fascial opening of the extensor compartment. Two incision minimally invasive fasciotomy to decompress the anterior and peroneal compartments of the lower leg appears to be safe with regard to the results of this study.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#157

 

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Description Matrix metalloproteinases (MMPs) are extracellular enzymes involved in the degradation of extracellular matrix (ECM) proteins. Increased expression of MMPs have been described in traumatic brain injury (TBI) and may contribute to additional tissue injury and blood–brain barrier damage. The objectives of this study were to determine longitudinal changes in cerebrospinal fluid (CSF) concentrations of MMPs after acute TBI and in relation to clinical outcomes, with patients with idiopathic normal pressure hydrocephalus (iNPH) serving as a contrast group. The study included 33 TBI patients with ventricular CSF serially sampled, and 38 iNPH patients in the contrast group. Magnetic bead-based immunoassays were utilized to measure the concentrations of eight MMPs in ventricular human CSF. CSF concentrations of MMP-1, MMP-3 and MMP-10 were increased in TBI patients (at baseline) compared with the iNPH group (p < 0.001), while MMP-2, MMP-9 and MMP-12 did not differ between the groups. MMP-1, MMP-3 and MMP-10 concentrations decreased with time after trauma (p = 0.001–0.04). Increased concentrations of MMP-2 and MMP-10 in CSF at baseline were associated with an unfavourable TBI outcome (p = 0.002–0.02). Observed variable pattern of changes in MMP concentrations indicates that specific MMPs serve different roles in the pathophysiology following TBI, and are in turn associated with clinical outcomes.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#158

 

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Description Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, disrupts the alveolar-capillary barrier, triggering pulmonary vascular leak thus inducing acute lung injury (ALI). Extracellular purines, adenosine and ATP, protected against ALI induced by purified LPS. In this study, we investigated whether these purines can impact vascular injury in more clinically-relevant E.coli (non-sterile LPS) murine ALI model. Mice were inoculated with live E. coli intratracheally (i.t.) with or without adenosine or a non-hydrolyzable ATP analog, adenosine 5′-(γ-thio)-triphosphate (ATPγS) added intravenously (i.v.). After 24 h of E. coli treatment, we found that injections of either adenosine or ATPγS 15 min prior or adenosine 3 h after E.coli insult significantly attenuated the E.coli-mediated increase in inflammatory responses. Furthermore, adenosine prevented weight loss, tachycardia, and compromised lung function in E. coli-exposed mice. Accordingly, treatment with adenosine or ATPγS increased oxygen saturation and reduced histopathological signs of lung injury in mice exposed to E. coli. Lastly, lung-targeting gene delivery of adenosine or ATPγS downstream effector, myosin phosphatase, significantly attenuated the E. coli-induced compromise of lung function. Collectively, our study has demonstrated that adenosine or ATPγS mitigates E. coli-induced ALI in mice and may be useful as an adjuvant therapy in future pre-clinical studies.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#159

 

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Description Various symptoms of the dry eye disease (DED) interfere with the quality of life and reduce work productivity. Therefore, screening, prevention, and treatment of DED are important. We aimed to investigate the potential diagnostic ability of the maximum blink interval (MBI) (the length of time participants could keep their eyes open) with disease-specific questionnaire for DED. This cross-sectional study included 365 patients (252 with DED and 113 without DED) recruited between September 2017 and December 2019. Discriminant validity was assessed by comparing the non-DED and DED groups based on the MBI with a Japanese version of the Ocular Surface Disease Index (J-OSDI) and tear film breakup time (TFBUT) with J-OSDI classifications. The MBI with J-OSDI showed good discriminant validity by known-group comparisons. The positive and predictive values of MBI with J-OSDI were 96.0% (190/198 individuals) and 37.1% (62/167 individuals), respectively. The area under the receiver operating characteristic curve (AUC) of MBI with J-OSDI was 0.938 (95% confidence interval 0.904–0.971), the sensitivity was 75.4% (190/252 individuals), and the specificity was 92.9% (105/113 individuals), which are similar to the diagnostic ability of TFBUT with J-OSDI (AUC 0.954). In conclusion, MBI with J-OSDI may be a simple, non-invasive screening test for DED.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#160

 

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Description Malaria transmission in Madagascar is highly heterogeneous, exhibiting spatial, seasonal and long-term trends. Previous efforts to map malaria risk in Madagascar used prevalence data from Malaria Indicator Surveys. These cross-sectional surveys, conducted during the high transmission season most recently in 2013 and 2016, provide nationally representative prevalence data but cover relatively short time frames. Conversely, monthly case data are collected at health facilities but suffer from biases, including incomplete reporting and low rates of treatment seeking. We combined survey and case data to make monthly maps of prevalence between 2013 and 2016. Health facility catchment populations were estimated to produce incidence rates from the case data. Smoothed incidence surfaces, environmental and socioeconomic covariates, and survey data informed a Bayesian prevalence model, in which a flexible incidence-to-prevalence relationship was learned. Modelled spatial trends were consistent over time, with highest prevalence in the coastal regions and low prevalence in the highlands and desert south. Prevalence was lowest in 2014 and peaked in 2015 and seasonality was widely observed, including in some lower transmission regions. These trends highlight the utility of monthly prevalence estimates over the four year period. By combining survey and case data using this two-step modelling approach, we were able to take advantage of the relative strengths of each metric while accounting for potential bias in the case data. Similar modelling approaches combining large datasets of different malaria metrics may be applicable across sub-Saharan Africa.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#161

 

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Description In preterm birth, the immature retina can develop a potentially blinding disorder of the eye known as retinopathy of prematurity (ROP). The vaso-proliferative phase of ROP begins at an approximate postmenstrual age (PMA) of 32 weeks. There is little or no evidence of an association between ROP development and retinal status in the early vaso-proliferative phase. We aimed to evaluate the retinal vascular findings of infants at 33–34 weeks PMA to determine their risk of ROP. We reviewed 130 serial wide-field retinal images from 65 preterm infants born before the gestational age of 31 weeks. ROP occurred more frequently in infants having a leading vascular edge within posterior Zone II. This was in contrast to normal infants, who are characterized by complete retinal vascularization up to Zone II at 34 weeks PMA. The probability of ROP development in preterm infants with retinal edge hemorrhage was 24.58 times higher than in preterm infants without retinal edge hemorrhage. Eyes with ROP that required treatment showed significantly delayed retinal vascularization accompanied by pre-plus disease. In conclusion, retinal status in the early vaso-proliferation phase might determine the risk of ROP.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#162

 

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Description Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer, but its effect on cardiovascular and metabolic function in Asian patients is still inconclusive. We prospectively assess the effects of ADT on 36 patients with advanced prostate cancer, with reference to another 24 prostate cancer patients not requiring ADT, for 2 years. Patients’ anthropometric, metabolic and vascular parameters were assessed every six-monthly. The baseline parameters of the two groups were comparable. There was a significant negative effect of the usage of ADT on the changes in BMI (p = 0.020), waist to hip ratio (p = 0.005), body fat percentage (p = 0.012), and high-density-lipoprotein (p = 0.012). ADT-patients were 4.9 times more likely to have metabolic syndrome at 24 months. (CI 0.889–27.193, p = 0.068). The Framingham risk score (p = 0.018) and pulse-wave-velocity (p = 0.024) for ADT-group were also significantly higher than controls, which signified increase in cardiovascular risk. Although there was no statistically significant difference in ischemic cardiovascular events between two groups, a trend for more events in ADT-group was observed. Therefore, Asian patients have increased cardiovascular and metabolic risks after being treated with ADT for two years. Appropriate counselling and monitoring of associated complications with ADT are essential.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#163

 

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Description The blood–brain barrier (BBB) is an efficient barrier for molecules and drugs. Multicellular 3D spheroids display reproducible BBB features and functions. The spheroids used here were composed of six brain cell types: Astrocytes, pericytes, endothelial cells, microglia cells, oligodendrocytes, and neurons. They form an in vitro BBB that regulates the transport of compounds into the spheroid. The penetration of fluorescent ultrasmall gold nanoparticles (core diameter 2 nm; hydrodynamic diameter 3–4 nm) across the BBB was studied as a function of time by confocal laser scanning microscopy, with the dissolved fluorescent dye (FAM-alkyne) as a control. The nanoparticles readily entered the interior of the spheroid, whereas the dissolved dye alone did not penetrate the BBB. We present a model that is based on a time-dependent opening of the BBB for nanoparticles, followed by a rapid diffusion into the center of the spheroid. After the spheroids underwent hypoxia (0.1% O2; 24 h), the BBB was more permeable, permitting the uptake of more nanoparticles and also of dissolved dye molecules. Together with our previous observations that such nanoparticles can easily enter cells and even the cell nucleus, these data provide evidence that ultrasmall nanoparticle can cross the blood brain barrier.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#164

 

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Description This study was to retrospectively analyze the effect of the age of embryos transfer and oocyte retrieval on the clinical pregnancy outcome in patients with simple tubal factor infertility (TFI) who received frozen-thawed embryo transfer. Patients (n = 3619) with simple TFI who underwent in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) frozen-thawed embryo transfer at our hospital were enrolled. Univariate logistic regression analysis, categorical multivariate logistic regression analysis, curve fitting and threshold effect analysis were performed. Age of embryo transfer was a significant (P < 0.05) independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rates. The Clinical pregnancy outcome declined significantly after the age of 34 years. After limiting the female oocyte retrieval age to ≤ 34 years, no significant change was detected in the clinical pregnancy, live birth, or miscarriage rate with increase of transplantation age. In conclusion, in patients with simple TFI undergoing IVF/ICSI frozen-thawed embryo transfer, age is a significant independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rate. Aging of oocytes has a greater impact on the clinical pregnancy in women with simple TFI than the aging of the body. Patients with TFI can freeze embryos in advance to preserve fertility.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#165

 

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Name
Description Stage IV breast cancer is metastatic breast cancer (MBC). Because real-world data are lacking in China, our research attempts to explore the effect of locoregional surgery on the prognosis of patients with MBC. A total of 987 patients from 10 hospitals and 2 databases in East China (2004–2018) were included in this study. Overall, 47% of patients underwent locoregional surgery, and 53% did not. Surgeons tended to perform surgery on patients with small tumours (T1/T2), positive hormone receptor (HR) markers, and metastatic sites confined to a single organ and non-visceral sites (bone only/others) (each p < 0.05). Kaplan–Meier survival curves and the log-rank test showed that median survival was longer for patients who had locoregional surgery than for those who did not (45.00 vs. 28.00 months; p < 0.001). Patients who underwent surgery after systemic treatment had better survival than those who underwent surgery immediately (p < 0.001). In most subgroups, overall survival (OS) was significantly longer in the surgery group than in the no-surgery group (each p < 0.05), except for brain metastases and triple negative breast cancer. Therefore, we concluded that locoregional surgery for the primary tumour in MBC patients was associated with a marked reduction in risk of dying except for patients with brain metastases or triple-negative subtype.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#166

 

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Name
Description Given the role of the deleted in azoospermia gene in male infertility, whether the somatic deleted in azoospermia methylation status is associated with idiopathic asthenospermia should be determined. To investigate the methylation levels of the deleted in azoospermia promoter in peripheral white blood cells from idiopathic asthenospermia patients relative to those in normozoospermia controls, 61 ethylene diamine tetraacetic acid anticoagulant blood samples were drawn from all participants for DNA isolation. The deleted in azoospermia promoter methylation ratio was detected by MassARRAY-based methylation quantification and confirmed by quantitative methylation-specific polymerase chain reaction. A MassARRAY-based methylation analysis showed that the deleted in azoospermia 3 promoter (0 to − 2 kbp) was significantly hypomethylated in peripheral white blood cells from idiopathic asthenospermia males, specifically one CpG site (− 246 to − 247). Quantitative methylation-specific polymerase chain reaction data further confirmed that the methylation level of the deleted in azoospermia 3 promoter region in idiopathic asthenospermia patients was significantly lower than that in normozoospermia males. The area under the receiver operating characteristic curve determined by quantitative methylation-specific polymerase chain reaction was 0.737 (95% confidence interval: 0.552 to 0.924), with a sensitivity of 53.9% and a specificity of 88.2% at a cut-off level of 74.7%. Therefore, our results suggested that methylation ratio detection of the deleted in azoospermia 3 promoter region by real-time polymerase chain reaction assay is a promising and feasible tool for liquid biopsy in the clinical laboratories. The methylation status of other reported infertility-related genes should also be investigated in peripheral white blood cells.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#167

 

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Name
Description Malignant gliomas are primary brain tumours with an infiltrative growth pattern, often with contrast enhancement on magnetic resonance imaging (MRI). However, it is well known that tumour infiltration extends beyond the visible contrast enhancement. The aim of this study was to investigate if there is contrast enhancement not detected visually in the peritumoral oedema of malignant gliomas by using relaxometry with synthetic MRI. 25 patients who had brain tumours with a radiological appearance of malignant glioma were prospectively included. A quantitative MR-sequence measuring longitudinal relaxation (R1), transverse relaxation (R2) and proton density (PD), was added to the standard MRI protocol before surgery. Five patients were excluded, and in 20 patients, synthetic MR images were created from the quantitative scans. Manual regions of interest (ROIs) outlined the visibly contrast-enhancing border of the tumours and the peritumoral area. Contrast enhancement was quantified by subtraction of native images from post GD-images, creating an R1-difference-map. The quantitative R1-difference-maps showed significant contrast enhancement in the peritumoral area (0.047) compared to normal appearing white matter (0.032), p = 0.048. Relaxometry detects contrast enhancement in the peritumoral area of malignant gliomas. This could represent infiltrative tumour growth.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#168

 

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Name
Description This systematic review and meta-analysis aimed to evaluate the impact of COVID-19 on pregnant women. We searched for qualified studies in PubMed, Embase, and Web of Science. The clinical characteristics of pregnant women with COVID-19 and their infants were reported as means and proportions with 95% confidence interval. Eleven studies involving with 9032 pregnant women with COVID-19 and 338 infants were included in the meta-analysis. Pregnant women with COVID-19 have relatively mild symptoms. However, abnormal proportions of laboratory parameters were similar or even increased, compared to general population. Around 30% of pregnant women with COVID-19 experienced preterm delivery, whereas the mean birth weight was 2855.9 g. Fetal death and detection of SARS-CoV-2 were observed in about 2%, whereas neonatal death was found to be 0.4%. In conclusion, the current review will serve as an ideal basis for future considerations in the treatment and management of COVID-19 in pregnant women.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#169

 

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Name
Description In countries with low endemic Methicillin-resistant Staphylococcus aureus (MRSA) prevalence, identification of risk groups at hospital admission is considered more cost-effective than universal MRSA screening. Predictive statistical models support the selection of suitable stratification factors for effective screening programs. Currently, there are no universal guidelines in Germany for MRSA screening. Instead, a list of criteria is available from the Commission for Hospital Hygiene and Infection Prevention (KRINKO) based on which local strategies should be adopted. We developed and externally validated a model for individual prediction of MRSA carriage at hospital admission in the region of Southeast Lower Saxony based on two prospective studies with universal screening in Braunschweig (n = 2065) and Wolfsburg (n = 461). Logistic regression was used for model development. The final model (simplified to an unweighted score) included history of MRSA carriage, care dependency and cancer treatment. In the external validation dataset, the score showed a sensitivity of 78.4% (95% CI: 64.7–88.7%), and a specificity of 70.3% (95% CI: 65.0–75.2%). Of all admitted patients, 25.4% had to be screened if the score was applied. A model based on KRINKO criteria showed similar sensitivity but lower specificity, leading to a considerably higher proportion of patients to be screened (49.5%).

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#170

 

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Name
Description Levodopa-entacapone-carbidopa intestinal gel (LECIG) provides continuous drug delivery through intrajejunal infusion. The aim of this study was to characterize the population pharmacokinetics of levodopa following LECIG and levodopa-carbidopa intestinal gel (LCIG) infusion to investigate suitable translation of dose from LCIG to LECIG treatment, and the impact of common variations in the dopa-decarboxylase (DDC) and catechol-O-methyltransferase (COMT) genes on levodopa pharmacokinetics. A non-linear mixed-effects model of levodopa pharmacokinetics was developed using plasma concentration data from a double-blind, cross-over study of LCIG compared with LECIG in patients with advanced Parkinson’s disease (n = 11). All patients were genotyped for rs4680 (polymorphism of the COMT gene), rs921451 and rs3837091 (polymorphisms of the DDC gene). The final model was a one compartment model with a high fixed absorption rate constant, and a first order elimination, with estimated apparent clearances (CL/F), of 27.9 L/h/70 kg for LCIG versus 17.5 L/h/70 kg for LECIG, and apparent volume of distribution of 74.4 L/70 kg. Our results thus suggest that the continuous maintenance dose of LECIG, on a population level, should be decreased by approximately 35%, to achieve similar drug exposure as with LCIG. An effect from entacapone was identified on all individuals, regardless of COMT rs4680 genotype. The individuals with higher DDC and COMT enzyme activity showed tendencies towards higher levodopa CL/F. The simultaneous administration of entacapone to LCIG administration results in a 36.5% lower apparent levodopa clearance, and there is a need for lower continuous maintenance doses, regardless of patients’ COMT genotype.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#171

 

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Name
Description Adipose tissue secretes molecules that can promote activity in Crohn’s disease. We aimed to evaluate the role of serum adipokines as possible biomarkers in Crohn’s disease. Serum samples were obtained from 40 patients with endoscopically active or quiescent Crohn’s disease and 36 healthy controls. Serum leptin, ghrelin, resistin and adiponectin levels were analysed by Multiplex in a Luminex 200 system technology. Receiver Operating Characteristic curves were performed to evaluate the adipokines discriminatory capacity. A logistic regression adjusted by possible confounders (i.e. gender, age, BMI) was performed for those adipokines that showed an area under the curve > 0.7. No differences were found in age, gender or BMI among groups. Distribution for serum resistin was different among the three groups of study, and only this adipokine showed an area under the curve of 0.75 comparing actives patients and healthy control groups. Resistin median concentration was selected as a cut-off for a logistic regression analysis; odds ratio along its 95% confidence interval adjusted by gender, age, and BMI yielded a value of 5.46 (1.34–22.14) comparing actives patients and healthy controls. High concentration of serum resistin is probably associated to activity, being this association independent of gender, age or BMI.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#172

 

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Name
Description Single-cell RNA sequencing (scRNA-seq) resolves heterogenous cell populations in tissues and helps to reveal single-cell level function and dynamics. In neuroscience, the rarity of brain tissue is the bottleneck for such study. Evidence shows that, mouse and human share similar cell type gene markers. We hypothesized that the scRNA-seq data of mouse brain tissue can be used to complete human data to infer cell type composition in human samples. Here, we supplement cell type information of human scRNA-seq data, with mouse. The resulted data were used to infer the spatial cellular composition of 3702 human brain samples from Allen Human Brain Atlas. We then mapped the cell types back to corresponding brain regions. Most cell types were localized to the correct regions. We also compare the mapping results to those derived from neuronal nuclei locations. They were consistent after accounting for changes in neural connectivity between regions. Furthermore, we applied this approach on Alzheimer’s brain data and successfully captured cell pattern changes in AD brains. We believe this integrative approach can solve the sample rarity issue in the neuroscience.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#173

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#174

 

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Name
Description A newly identified mechanism of piRNA-mediated post-transcriptional regulation of gene expression is associated with pathological hypertrophy, cardiac remodelling and heart failure.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#176

 

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Name
Description Pancreatic adenocarcinoma (PDAC) is an extremely malignant tumor that is associated with low survival rates. Fisetin is a natural flavonoid that shows diverse antitumor effects, including DNA damage, in various cancers. Increasing studies have demonstrated that epigenetic modifications play critical roles in DNA-damage response. However, the epigenetic regulation mechanism of fisetin in cancers is hardly studied. RFXAP is a critical transcription factor for MHC II molecules, however, its transcriptional role in PDAC is poorly understood. The anti-PDAC effect of fisetin was measured by CCK-8, flow cytometry, xenograft tumor nude mice model. DNA-damage levels were examined by immunofluorescence. Bioinformatics analysis was used to examine the expression of RFXAP and other genes involved in DNA-damage response. ChIP sequencing was used to explore the transcriptional role of RFXAP. The expression of target gene KDM4A was measured by qRT-PCR and western blots. KDM4A promoter activity was analyzed using dual-luciferase reporter assay. RFXAP overexpressing or silencing of PDAC cells was used to explore the effect of RFXAP in DNA damage induced by fisetin. We found that fisetin inhibited cell proliferation and induced DNA damage and S-phase arrest in PDAC. Expression of RFXAP and other DNA-damage response genes were upregulated by fisetin. We revealed that RFXAP expression was relatively low in PDAC and correlated with tumor stage and poor prognosis. Then we explored the transcriptional role of RFXAP and found that RFXAP targeted KDM4A, a special demethylase specific for tri- and dimethylated histone H3K36. We found that overexpression of RFXAP upregulated KDM4A and attenuated methylation of H3K36, thereby impairing DNA repair and enhancing the DNA damage induced by fisetin, while RFXAP silencing showed the opposite effect. We also found the function of fisetin in enhancing the effect of chemotherapy on pancreatic cancer cells. Our findings revealed that fisetin induced DNA damage via RFXAP/KDM4A-dependent histone H3K36 demethylation, thus causing inhibition of proliferation in PDAC.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#177

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#178

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#179

 

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Name
Description The coronavirus and others are no lone wolves, they cooperate and compete with one another. Understanding these social interactions could help us fight them

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#180

 

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Name
Description Self-driving Lyft taxis return to Las Vegas with autonomous partner Motional after coronavirus shutdowns.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#181

 

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Name
Description A rise of frail patients in hospitals and high patient-to-nurse ratios can be a significant problem in healthcare. Robots capable of assisting patients in moving and preventing falls can help to ensure the safety of patients. A recent study proposes a risk-aware planning framework. It combines learn

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#182

 

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Name
Description For people with multiple sclerosis, a disease of the central nervous system, exercise is a proven way to hold off symptoms of fatigue and loss of mobility. But those same symptoms of the disease can cause such mobility issues in some people with MS that even getting started with exercising is too di

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#183

 

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Name
Description "No one should keep money they got by breaking the law," advocates say.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#184

 

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Name
Description Gene therapy-based treatment such as optogenetics offers a potentially powerful way to bypass damaged photoreceptors in retinal degenerative diseases and use the remaining retinal cells for functionalization to achieve photosensitivity. However, current approaches of optogenetic treatment rely on opsins that require high intensity light for activation thus adding to the challenge for use as part of a wearable device. Here, we report AAV2 assisted delivery of highly photosensitive multi-characteristic opsin (MCO1) into ON-bipolar cells of mice with retinal degeneration to allow activation by ambient light. Rigorous characterization of delivery efficacy by different doses of AAV2 carrying MCO1 (vMCO1) into targeted cells showed durable expression over 6 months after delivery as measured by reporter expression. The enduring MCO1 expression was correlated with the significantly improved behavioral outcome, that was longitudinally measured by visual water-maze and optomotor assays. The pro/anti-inflammatory cytokine levels in plasma and vitreous humor of the vMCO1-injected group did not change significantly from baseline or control group. Furthermore, biodistribution studies at various time points after injection in animal groups injected with different doses of vMCO1 showed non-detectable vector copies in non-targeted tissues. Immunohistochemistry of vMCO1 transfected retinal tissues showed bipolar specific expression of MCO1 and the absence of immune/inflammatory response. Furthermore, ocular imaging using SD-OCT showed no change in the structural architecture of vMCO1-injected eyes. Induction of ambient light responsiveness to remaining healthy bipolar cells in subjects with retinal degeneration will allow the retinal circuitry to gain visual acuity without requiring an active stimulation device.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#185

 

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Name
Description Tobacco smoking is still a widespread habit in pregnant and breastfeeding women. While the role of these risk factors on neonatal outcomes has been deeply studied, their effect on human milk composition is still not completely clear. This study aimed to report the most up to date evidence about the alteration of breast milk composition of smoking breastfeeding mothers compared to non-smoking ones. We performed a systematic review by searching PubMed, Embase, and Cochrane Library databases. Evaluated data were extracted and critically analyzed by two independent authors. PRISMA guidelines were applied, and the risk of bias was assessed (ROBINS), as was the methodological quality of the included studies (GRADE). After applying the inclusion criteria, we included 20 studies assessed as medium or high quality. In all the studies, we analyzed data regarding 1769 mothers (398 smokers and 971 nonsmokers). Smoking was associated with a lower content of lipids, calories, and proteins. Moreover, it was characterized by decreased antioxidant properties and an altered immune status. Smoking during pregnancy and breastfeeding is significantly associated with an alteration of milk metabolic properties. Further studies are needed to investigate how these changes can alter newborns’ development and outcomes and which molecular patterns are involved.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#186

 

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Name
Description The limitations of using race in biomedicine are important to recognize because race is often afforded more biological value than can be scientifically justified — and less social value than it commands.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#187

 

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Name
Description In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the ‘gut–brain axis’. These processes may affect human health, as certain animal behaviours appear to correlate with the composition of gut bacteria, and disruptions in microbial communities have been implicated in several neurological disorders. Most insights about host–microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to neurological disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health. In this Review, Morais, Schreiber and Mazmanian discuss emerging and exciting evidence of intricate and potentially important connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to complex behaviours.

#Medicine & Human body;#Theoretical sciences
Field # Medicine & Human body
Updated 22 October 2020

#188

 

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Name
Description Accumulating evidence indicates that the dysregulation of the miRNAs/mRNA-mediated carcinogenic signaling pathway network is intimately involved in glioma initiation and progression. In the present study, by performing experiments and bioinformatics analysis, we found that RPN2 was markedly elevated in glioma specimens compared with normal controls, and its upregulation was significantly linked to WHO grade and poor prognosis. Knockdown of RPN2 inhibited tumor proliferation and invasion, promoted apoptosis, and enhanced temozolomide (TMZ) sensitivity in vitro and in vivo. Mechanistic investigation revealed that RPN2 deletion repressed β-catenin/Tcf-4 transcription activity partly through functional activation of glycogen synthase kinase-3β (GSK-3β). Furthermore, we showed that RPN2 is a direct functional target of miR-181c. Ectopic miR-181c expression suppressed β-catenin/Tcf-4 activity, while restoration of RPN2 partly reversed this inhibitory effect mediated by miR-181c, implying a molecular mechanism in which TMZ sensitivity is mediated by miR-181c. Taken together, our data revealed a new miR-181c/RPN2/wnt/β-catenin signaling axis that plays significant roles in glioma tumorigenesis and TMZ resistance, and it represents a potential therapeutic target, especially in GBM.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#189

 

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Name
Description Adjuvant targeted therapy (TT) improves relapse free survival in patients with resected BRAF mutant stage III melanoma. The outcomes and optimal management of patients who relapse after adjuvant TT is unknown. Patients from twenty-one centres with recurrent melanoma after adjuvant TT were included. Disease characteristics, adjuvant therapy, recurrence, treatment at relapse and outcomes were examined. Eighty-five patients developed recurrent melanoma; nineteen (22%) during adjuvant TT. Median time to first recurrence was 18 months and median follow-up from first recurrence was 31 months. Fifty-eight (68%) patients received immunotherapy (IT) or TT as 1st line systemic therapy at either first or subsequent recurrence and had disease that was assessable for response. Response to anti-PD-1 (±trial agent), combination ipilimumab-nivolumab, TT rechallenge and ipilimumab monotherapy was 63%, 62% 25% and 10% respectively. Twenty-eight (33%) patients had died at census, all from melanoma. Two-year OS was 84% for anti-PD-1 therapy (±trial agent), 92% for combination ipilimumab and nivolumab, 49% for TT and 45% for ipilimumab monotherapy (p = 0.028). Patients who relapse after adjuvant TT respond well to subsequent anti-PD-1 based therapy and have outcomes similar to those seen when first line anti-PD-1 therapy is used in stage IV melanoma.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#190

 

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Name
Description Understanding the risk of reinfection with SARS-CoV-2 in exposed cohorts provides an avenue to understanding the path to protection against SARS-CoV-2 for vaccine development.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#191

 

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Name
Description Narrow-bandwidth signals and relaxed neural-recording parameters can substantially reduce the power requirements of brain–machine interfaces without degrading their performance.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#192

 

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Name
Description Wearable piezoelectric thin films integrated with multiphysics modelling and three-dimensional digital image correlation can decode facial expressions in real time.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#193

 

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Name
Description Facebook moderators in Hyderabad, responsible for deleting offensive content, were forced to return to work as early in July despite COVID-19 pandemic.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#194

 

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Name
Description As the coronavirus pandemic drags on, subsequent waves of infections are reaching staggering new heights, and more people are losing loved ones. Regardless of how each country has chosen to meet this challenge, economies are struggling, causing bus

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#195

 

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Name
Description Neuromyelitis optica (NMO; also known as Devic syndrome) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. In most patients, NMO is caused by pathogenetic serum IgG autoantibodies to aquaporin 4 (AQP4), the most abundant water-channel protein in the central nervous system. In a subset of patients negative for AQP4-IgG, pathogenetic serum IgG antibodies to myelin oligodendrocyte glycoprotein, an antigen in the outer myelin sheath of central nervous system neurons, are present. Other causes of NMO (such as paraneoplastic disorders and neurosarcoidosis) are rare. NMO was previously associated with a poor prognosis; however, treatment with steroids and plasma exchange for acute attacks and with immunosuppressants (in particular, B cell-depleting agents) for attack prevention has greatly improved the long-term outcomes. Recently, a number of randomized controlled trials have been completed and the first drugs, all therapeutic monoclonal antibodies, have been approved for the treatment of AQP4-IgG-positive NMO and its formes frustes. Neuromyelitis optica is an autoimmune disorder of the central nervous system characterized by episodes of optic neuritis and transverse myelitis. This Primer provides an overview of the epidemiology, pathophysiology, diagnosis and treatment of this disorder.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#196

 

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Name
Description The latest coronavirus news updated every day including coronavirus cases, the latest news, features and interviews from New Scientist and essential information about the covid-19 pandemic

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#197

 

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Name
Description Ulcers are open wounds that fail to heal. They are caused or exacerbated by poor blood and nerve supply and in the case of foot ulcers, bad feet architecture. In severe cases, they can lead to amputation and there are an estimated 8,000 preventable foot amputations in Australia every year. Tho

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#198

 

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Name
Description According to the Mayo Clinic, about 15% of couples are infertile, and male infertility plays a role in over one-third of these cases. Often, problems with sperm development are to blame. Now, researchers reporting in ACS Nano have found a way to deliver a protein important for sperm cell production

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#199

 

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Name
Description Martin Enge’s research group at the Department of Oncology-Pathology has developed a new method for joint analysis of a cell’s state and accumulated genetic variation in single cells, applied to childhood leukaemias and other cancers. The article is published in the journal Molecular Cell.

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#200

 

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Name
Description A multidisciplinary team of researchers at McMaster University have discovered a structural feature of human bone that has never been studied before under a microscope, bringing scientists closer to advancing bone implants and treatments for bone diseases. Using a plasma focused ion beam micr

#Medicine & Human body
Field # Medicine & Human body
Updated 22 October 2020

#201

 

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Name
Description Exposure to urology is essential for medical undergraduates to prepare them with the competencies required to manage basic urological conditions and to generate interest in the specialty. However, despite the existence of national curricula, the lack of urological exposure and falling competition ratios indicate a need for an evaluation of urological teaching in medical schools.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#202

 

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Name
Description A population-level disease monitoring system that employs at-home self-swab kits is being expanded today, at no cost to participants, as part of an infection prevalence study in the San Francisco Bay Area. The system could ...

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#203

 

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Name
Description When it comes to covid-19, we all have different levels of risk we're comfortable with. Setting a weekly "contact budget" can make it easier to decide which risks are worth taking

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#204

 

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Name
Description A new superwhite paint is so reflective that it can cool a surface to below the surrounding air temperature, even under sunlight. It could help reduce the use of energy-intensive air conditioning in hot countries

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#205

 

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Name
Description The latest coronavirus news updated every day including coronavirus cases, the latest news, features and interviews from New Scientist and essential information about the covid-19 pandemic

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#206

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#207

 

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Name
Description So far, we haven't seen much change in the coronavirus, but as we develop more therapies and potentially a vaccine it could mutate

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#208

 

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Name
Description To boost their chances of fertilising a nest-load of eggs, male dusky frillgoby fish use their tailfin to fan away the sperm deposited by rivals

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#209

 

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Description British researchers on Tuesday said they hope to expose healthy volunteers to the virus that causes COVID-19 in a groundbreaking study to discover the amount needed for people to become infected.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#210

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#211

 

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Name
Description Dr. Eric Topol says that, based on existing numbers, the odds of catching COVID-19 a second time after recovering are about one in a million.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#212

 

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Name
Description Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy. Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 163 patients. Their functional role in drug sensitivity was assessed in vitro. We identified 490 DMRs following exposure to therapy, of which 31 were CLL-specific and independent of changes occurring in normal B-cell development. Seventeen DMR-associated genes were identified as differentially expressed following treatment in an independent cohort. Methylation of the HOXA4, MAFB and SLCO3A1 DMRs was associated with post-treatment patient survival, with HOXA4 displaying the strongest association. Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib. Our study demonstrates enrichment for multiple CLL-specific epigenetic traits in response to chemotherapy that predict patient outcomes, and particularly implicate epigenetic silencing of HOXA4 in reducing the sensitivity of CLL cells to therapy.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#213

 

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Name
Description A teen from Texas has won a national science competition for identifying a molecule that can bind and potentially disable SARS-CoV-2.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#214

 

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Name
Description It could help understand infection, but experts are skeptical it will speed vaccines.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#215

 

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Name
Description Standardized approaches to measuring clinical utility will enable more robust evaluations of genetic tests. To characterize how clinical utility has been measured, this scoping review examined outcomes used to operationalize this concept in the context of genetic testing, spanning relevant literature (2015–2017). The search strategy and analysis were guided by the Fryback and Thornbury hierarchical model of efficacy (FT Model). Through searches in Ovid MEDLINE, EMBASE and Web of Science, 194 publications were identified for inclusion. Two coders reviewed titles, abstracts, and full texts to determine eligibility. Results were analyzed using thematic and frequency analyses. This review generated a catalog of outcomes mapped to the efficacy domains of the FT Model. The degree of representation observed in each domain varied by the clinical purpose and clinical indication of genetic testing. Diagnostic accuracy (68%), technical (28.4%), and patient outcome (28.4%) efficacy studies were represented at the highest rate. Findings suggest that the FT Model is suitable for the genetics context however domain refinements may be warranted. More diverse clinical settings, robust study designs, and novel strategies for measuring clinical utility are needed.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#216

 

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Name
Description Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by progressive loss of motor neurons (MNs) and subsequent muscle weakness. These pathological features are associated with numerous cellular changes, including alteration in mitochondrial morphology and function. However, the molecular mechanisms associating mitochondrial structure with ALS pathology are poorly understood. In this study, we found that Dynamin-related protein 1 (Drp1) was dephosphorylated in several ALS models, including those with SOD1 and TDP-43 mutations, and the dephosphorylation was mediated by the pathological induction of protein phosphatase 1 (PP1) activity in these models. Suppression of the PP1-Drp1 cascade effectively prevented ALS-related symptoms, including mitochondrial fragmentation, mitochondrial complex I impairment, axonal degeneration, and cell death, in primary neuronal culture models, iPSC-derived human MNs, and zebrafish models in vivo. These results suggest that modulation of PP1-Drp1 activity may be a therapeutic target for multiple pathological features of ALS.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#217

 

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Name
Description The function of Keap1 (Kelch-like ECH-associated protein 1), a sensor of oxidative and electrophilic stress, in the radiosensitivity of cancer cells remains elusive. Here, we investigated the effects of pharmacological inhibition of Keap1 with ML344 on radiosensitivity, DNA double-strand break (DSB) repair and autophagy in head and neck squamous cell carcinoma (HNSCC) cell lines. Our data demonstrate that Keap1 inhibition enhances HNSCC cell radiosensitivity. Despite elevated, Nrf2-dependent activity of non-homologous end joining (NHEJ)-related DNA repair, Keap1 inhibition seems to impair DSB repair through delayed phosphorylation of DNA-PKcs. Moreover, Keap1 inhibition elicited autophagy and increased p62 levels when combined with X-ray irradiation. Our findings suggest HNSCC cell radiosensitivity, NHEJ-mediated DSB repair, and autophagy to be co-regulated by Keap1.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#218

 

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Name
Description Iron overload is a relatively common clinical condition resulting from disorders such as hereditary hemochromatosis, thalassemia, sickle cell disease, and myelodysplasia that can lead to progressive fibrosis and eventually cirrhosis of the liver. Therefore, it is essential to recognize the disease process at the earliest stage. Liver biopsy is the reference test for the assessment of liver fibrosis. It also allows for quantifying liver iron concentration (LIC) in patients. However, this is an invasive method with significant limitations and possible risks. Magnetic resonance imaging (MRI) and evaluation of the R2* relaxation rate can be an alternative to biopsy for assessing LIC. However, it causes a need for accurate R2* data corresponding to standard value for further comparison with examined patients. This study aimed to assess the normative values of liver R2* in healthy individuals. A total of 100 volunteers that met established criteria were enrolled in the study: 36 (36%) men and 64 (64%) women. The mean age was 22.9 years (range 20 to 32 years). R2* was estimated by an MRI exam with a 1.5 T clinical magnetic resonance scanner. Images for measuring the LIC and liver fat concentration were obtained using the IDEAL-IQ technique for liver imaging. The Mean (SD) liver R2* was 28.34 (2.25) s−1 (95% CI, 27.78–28.90, range 23.67–33.00 s−1) in females, 29.57 (3.20) s−1 (95% CI, 28.49–30.66, range 23.93–37.77 s−1) in males, and 28.72 (2.69) s−1 (range 23.67–37.77 s−1) in the whole group. R2* value in this particular population with a high proportion of young women did not exceed 38 s−1. In the absence of fibrosis or steatosis, liver stiffness and fat fraction did not show any relationship with R2*.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#219

 

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Name
Description Large repository of blood samples from military personnel provides invaluable resource for PNNL biomedical scientists Routine serial blood draws during military personnel’s service are proving to be an invaluable bank of specimens for health researchers. Using samples collected at enlistme

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#220

 

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Name
Description Obstructive sleep apnea (OSA) has a bidirectional relationship with insulin resistance conditions; however, the mechanism remains unclear. This study aimed to compare dynamic nocturnal glucose changes among patients with OSA of varying levels of severity and evaluate temporal changes associated with the cardinal features of OSA (sympathetic hyperactivation, intermittent hypoxemia, and sleep fragmentation) in nondiabetic subjects. Nocturnal glucose was measured with a continuous glucose monitoring device every 5 min during polysomnography (PSG). The OSA features were evaluated using heart rate variability (HRV), minimum saturation, and electroencephalography. Eleven subjects with moderate to severe OSA and 12 subjects with no or mild OSA were evaluated. Those with moderate to severe OSA showed an increasing trend in blood glucose levels after sleep onset, whereas those without or with mild OSA showed a decreasing trend (F = 8.933, p < 0.001). Delta band power also showed different trends during sleep between the two groups (F = 2.991, p = 0.009), and minimum saturation remained lower in the moderate to severe OSA group than in the no or mild OSA group. High degrees of coupling between nocturnal glucose levels and each OSA feature were observed. Altered trends in nocturnal glucose in moderate to severe OSA may reflect glucose intolerance and result in metabolic consequences. Managing the features of sleep-related OSA may have implications for metabolic management in the future.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#221

 

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Name
Description The endangered California Condor (Gymnogyps californianus) is the largest New World Vulture in North America. Despite recovery program success in saving the species from extinction, condors remain compromised by lead poisoning and limited genetic diversity. The latter makes this species especially vulnerable to infectious diseases. Thus, taking advantage of the program of blood lead testing in Arizona, condor blood samples from 2008 to 2018 were screened for haemosporidian parasites using a nested polymerase chain reaction (PCR) protocol that targets the parasite mitochondrial cytochrome b gene. Plasmodium homopolare (Family Plasmodiidae, Order Haemosporida, Phylum Apicomplexa), was detected in condors captured in 2014 and 2017. This is the first report of a haemosporidian species infecting California Condors, and the first evidence of P. homopolare circulating in the Condor population from Arizona. Although no evidence of pathogenicity of P. homopolare in Condors was found, this study showed that the California Condors from Arizona are exposed to haemosporidian parasites that likely are spilling over from other local bird species. Thus, active surveillance should be an essential part of conservation efforts to mitigate the impact of infectious diseases, an increasingly recognized cause of global wildlife extinctions worldwide, particularly in avian populations considered vulnerable or endangered.

#Medicine & Human body;#Psychology
Field # Medicine & Human body
Updated 21 October 2020

#222

 

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Name
Description Triple-negative breast cancer (TNBC) accounts for 15–20% of breast cancer cases in the United States, lacks targeted therapeutic options, and is associated with a 40–80% risk of recurrence. Thus, identifying actionable targets in treatment-naïve and chemoresistant TNBC is a critical unmet medical need. To address this need, we performed high-throughput drug viability screens on human tumor cells isolated from 16 patient-derived xenograft models of treatment-naïve primary TNBC. The models span a range of TNBC subtypes and exhibit a diverse set of putative driver mutations, thus providing a unique patient-derived, molecularly annotated pharmacologic resource that is reflective of TNBC. We identified therapeutically actionable targets including kinesin spindle protein (KSP). The KSP inhibitor targets the mitotic spindle through mechanisms independent of microtubule stability and showed efficacy in models that were resistant to microtubule inhibitors used as part of the current standard of care for TNBC. We also observed subtype selectivity of Prima-1Met, which showed higher levels of efficacy in the mesenchymal subtype. Coupling pharmacologic data with genomic and transcriptomic information, we showed that Prima-1Met activity was independent of its canonical target, mutant p53, and was better associated with glutathione metabolism, providing an alternate molecularly defined biomarker for this drug.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#223

 

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Name
Description With the COVID-19 pandemic still raging, a 14-year-old from Texas has won a national science competition for identifying a molecule that can bind to the virus and potentially disable it.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#224

 

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Name
Description A range of common household items – including mouthwash, nasal rinses, and even diluted baby shampoo – have been found to inactivate a form of human coronavirus in new research, highlighting another potential avenue to reduce transmission rates

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#225

 

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Name
Description Exhausting exercise can disturb immune and gastrointestinal functions. Nevertheless, the impact of it on mucosal-associated lymphoid tissue has not been studied in depth. Here, we aim to establish the effects of an intensive training and exhausting exercise on the mucosal immunity of rats and to approach the mechanisms involved. Rats were submitted to a high-intensity training consisting of running in a treadmill 5 days per week for 5 weeks, involving 2 weekly exhaustion tests. At the end, samples were obtained before (T), immediately after (TE) and 24 h after (TE24) an additional final exhaustion test. The training programme reduced the salivary production of immunoglobulin A, impaired the tight junction proteins’ gene expression and modified the mesenteric lymph node lymphocyte composition and function, increasing the ratio between Tαβ+ and B lymphocytes, reducing their proliferation capacity and enhancing their interferon-γ secretion. As a consequence of the final exhaustion test, the caecal IgA content increased, while it impaired the gut zonula occludens expression and enhanced the interleukin-2 and interferon-γ secretion. Our results indicate that intensive training for 5 weeks followed or not by an additional exhaustion disrupts the mucosal-associated lymphoid tissue and the intestinal epithelial barrier integrity in rats.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#226

 

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Name
Description Human cancer cell lines are frequently used as model systems to study molecular mechanisms and genetic changes in cancer. However, the model is repeatedly criticized for its lack of proximity to original patient tumors. Therefore, understanding to what extent cell lines cultured under artificial conditions reflect the phenotypic and genomic profiles of their corresponding parental tumors is crucial when analyzing their biological properties. To directly compare molecular alterations between patient tumors and derived cell lines, we have established new cancer cell lines from four patients with gastrointestinal tumors. Tumor entities comprised esophageal cancer, colon cancer, rectal cancer and pancreatic cancer. Phenotype and genotype of both patient tumors and derived low-passage cell lines were characterized by immunohistochemistry (22 different antibodies), array-based comparative genomic hybridization and targeted next generation sequencing (48-gene panel). The immunophenotype was highly consistent between patient tumors and derived cell lines; the expression of most markers in cell lines was concordant with the respective parental tumor and characteristic for the respective tumor entities in general. The chromosomal aberration patterns of the parental tumors were largely maintained in the cell lines and the distribution of gains and losses was typical for the respective cancer entity, despite a few distinct differences. Cancer gene mutations (e.g., KRAS, TP53) and microsatellite status were also preserved in the respective cell line derivates. In conclusion, the four examined newly established cell lines exhibited a phenotype and genotype closely recapitulating their parental tumor. Hence, newly established cancer cell lines may be useful models for further pharmacogenomic studies.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#227

 

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Name
Description Gene expression analysis is emerging as a new diagnostic tool in transplant pathology, in particular for the diagnosis of antibody-mediated rejection. Diagnostic gene expression panels are defined on the basis of their pathophysiological relevance, but also need to be tested for their robustness across different preservatives and analysis platforms. The aim of this study is the investigate the effect of tissue sampling and preservation on candidate genes included in a renal transplant diagnostic panel. Using the NanoString platform, we compared the expression of 219 genes in 51 samples, split for formalin-fixation and paraffin-embedding (FFPE) and RNAlater preservation (RNAlater). We found that overall, gene expression significantly correlated between FFPE and RNAlater samples. However, at the individual gene level, 46 of the 219 genes did not correlate across the 51 matched FFPE and RNAlater samples. Comparing gene expression results using NanoString and qRT-PCR for 18 genes in the same pool of RNA (RNAlater), we found a significant correlation in 17/18 genes. Our study indicates that, in samples from the same routine diagnostic renal transplant biopsy procedure split for FFPE and RNAlater, 21% of 219 genes of potential biological significance do not correlate in expression. Whether this is due to fixatives or tissue sampling, selection of gene panels for routine diagnosis should take this information into consideration.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#228

 

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Name
Description The brain-derived neurotrophic factor (BDNF) protein is essential for neuronal development. Val66Met (rs6265) is a functional polymorphism at codon 66 of the BDNF gene that affects neuroplasticity and has been associated with cognition, brain structure and function. The aim of this study was to clarify the relationship between BDNF Val66Met polymorphism and neuronal oscillatory activity, using the electroencephalogram (EEG), in a normative cohort. Neurotypical (N = 92) young adults were genotyped for the BDNF Val66Met polymorphism and had eyes open resting-state EEG recorded for four minutes. Focal increases in right fronto-parietal delta, and decreases in alpha-1 and right hemispheric alpha-2 amplitudes were observed for the Met/Met genotype group compared to Val/Val and Val/Met groups. Stronger frontal topographies were demonstrated for beta-1 and beta-2 in the Val/Met group versus the Val/Val group. Findings highlight BDNF Val66Met genotypic differences in EEG spectral amplitudes, with increased cortical excitability implications for Met allele carriers.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#229

 

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Name
Description The prognostic role of marital status on colorectal signet ring cell carcinoma (SRCC) has not been studied. In this study, the correlation of marital status with prognosis of colorectal SRCC was analyzed. Eligible subjects were extracted from the Surveillance, Epidemiology, and End Results (SEER) dataset from 2004 to 2015, followed by comparison of cancer-specific survival (CSS) and overall survival (OS) between married and unmarried group. 3152 patients were identified including 1777 married patients (56.38%). Married populations tended to be more patients aged < 65, male, receiving chemotherapy, and less black race and large tumor size compared to unmarried group (all P < 0.05).Moreover, 5-year CSS (30.04% vs. 28.19%, P = 0.0013) and OS rates (26.68% vs. 22.94%, P < 0.0001) were superior in married population. Multivariate analysis revealed that marital status was an independent favorable prognostic indicator, and married population had better CSS (HR: 0.898; 95% CI: 0.822–0.980; P = 0.016) and OS (HR: 0.898; 95%CI: 0.827–0.975; P = 0.011).In addition, CSS as well as OS were superior in married populations than unmarried ones in most subgroups. Marital status was an independent prognostic factor for survival in patients with colorectal SRCC. Additionally, married patients obtained better survival advantages.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#230

 

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Name
Description PRDX4, a member of peroxiredoxin family, is largely concentrated in the endoplasmic reticulum (ER) and plays a pivotal role in the redox relay during oxidative protein folding as well as in peroxidase reactions. A testis-specific PRDX4 variant transcript (PRDX4t) lacks the conventional exon 1, which encodes the signal peptide that is required for entry into the ER lumen, but instead carries alternative exon 1, which is transcribed from the upstream promoter in a testis-specific manner and results in the PRDX4t protein being localized in the cytosol. However, the potential roles of PRDX4t in male genital action remain unknown. Using a CRISPR/Cas9 system, we first disrupted the testis-specific promoter/exon 1 and generated mice that were specifically deficient in PRDX4t. The resulting PRDX4t knockout (KO) mice underwent normal spermatogenesis and showed no overt abnormalities in the testis. Mating PRDX4t KO male mice with wild-type (WT) female mice produced normal numbers of offspring, indicating that a PRDX4t deficiency alone had no effect on fertility in the male mice. We then generated mice lacking both PRDX4 and PRDX4t by disrupting exon 2, which is communal to these variants. The resulting double knockout (DKO) mice were again fertile, and mature sperm isolated from the epididymis of DKO mice exhibited a normal fertilizing ability in vitro. In the meantime, the protein levels of glutathione peroxidase 4 (GPX4), which plays an essential role in the disulfide bond formation during spermatogenesis, were significantly increased in the testis and caput epididymis of the DKO mice compared with the WT mice. Based on these results, we conclude that the disruption of the function of PRDX4t in the spermatogenic process appears to be compensated by other factors including GPX4.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#231

 

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Name
Description The Covid-19 pandemic has contributed to a delay in cancer research.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#232

 

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Name
Description Stress in adolescence can regulate vulnerability to traumatic stress in adulthood through region-specific epigenetic activity and catecholamine levels. We hypothesized that stress in adolescence would increase adult trauma vulnerability by impairing extinction-retention, a deficit in PTSD, by (1) altering class IIa histone deacetylases (HDACs), which integrate effects of stress on gene expression, and (2) enhancing norepinephrine in brain regions regulating cognitive effects of trauma. We investigated the effects of adolescent-stress on adult vulnerability to severe stress using the single-prolonged stress (SPS) model in male rats. Rats were exposed to either (1) adolescent-stress (33–35 postnatal days) then SPS (58–60 postnatal days; n = 14), or (2) no adolescent-stress and SPS (58–60 postnatal days; n = 14), or (3) unstressed conditions (n = 8). We then measured extinction-retention, norepinephrine, HDAC4, and HDAC5. As expected, SPS exposure induced an extinction–retention deficit. Adolescent-stress prior to SPS eliminated this deficit, suggesting adolescent-stress conferred resiliency to adult severe stress. Adolescent-stress also conferred region-specific resilience to norepinephrine changes. HDAC4 and HDAC5 were down-regulated following SPS, and these changes were also modulated by adolescent-stress. Regulation of HDAC levels was consistent with the pattern of cognitive effects of SPS; only animals exposed to SPS without adolescent-stress exhibited reduced HDAC4 and HDAC5 in the prelimbic cortex, hippocampus, and striatum. Thus, HDAC regulation caused by severe stress in adulthood interacts with stress history such that seemingly conflicting reports describing effects of adolescent stress on adult PTSD vulnerability may stem in part from dynamic HDAC changes following trauma that are shaped by adolescent stress history.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#233

 

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Name
Description Vasovagal syncope (VVS) is well-known to occur in patients undergoing phlebotomy, however, there have been no large-scale studies of the incidence of VVS in the blood collection room. The aim of our present retrospective study was to investigate the conditions of phlebotomy and determine the incidence/factors predisposing to the development of VVS. We investigated 677,956 phlebotomies performed in outpatients in the blood collection room, to explore factors predisposing to the development of VVS. Our analysis revealed an overall incidence of VVS of 0.004% and suggested that use of more than 5 blood collection tubes and a waiting time of more than 15 min were associated with a higher risk of VVS. The odds ratios of these factors were 8.10 (95% CI 3.76–17.50) and 3.69 (95% CI 0.87–15.60), respectively. This is the large-scale study to analyze factors of the development of VVS in the blood collection room, and according to our results, use of a large number of blood collection tubes and a prolonged waiting time for phlebotomy may be risk factors for the development of VVS.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#234

 

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Name
Description Concrete can be harmful to the environment due to its high energy consumption and CO2 emission and also has a potential crack formation, which can promote a drop in its strength. Therefore, concrete is considered as a non-sustainable material. The mechanisms by which bacterial oxidation of organic carbon can precipitate calcite that may fill the voids and cracks on cement-based materials have been extensively investigated to prevent and heal the micro-cracks formation. Hence, this study focused on utilizing a new alkaliphilic bacterial strain indigenous to an Indonesian site, Lysinibacillus sphaericus strain SKC/VA-1, incorporated with calcium lactate pentahydrate, as a low-cost calcium source, with various bacterial inoculum concentrations. The bacterium was employed in this study due to its ability to adapt to basic pH, thus improving the physical properties and rejuvenating the micro-cracks. Experimentally, the addition of calcium lactate pentahydrate slightly affected the mortar properties. Likewise, bacteria-incorporated mortar exhibited an enhancement in the physical properties of mortar. The highest improvement of mechanical properties (an increase of 45% and 36% for compressive and indirect tensile strength, respectively) was achieved by the addition of calcium lactate pentahydrate incorporated with 10% v/v bacterial inoculum [about 7 × 107 CFU/ml (colony-forming unit/ml)]. The self-healing took place more rapidly on bacterial mortar supplemented with calcium lactate pentahydrate than on the control specimen. XRD analysis demonstrated that the mineralogical composition of self-healing precipitates was primarily dominated by calcite (CaCO3), indicating the capacity of L. sphaericus strain SKC/VA-1 to precipitate calcite through organic carbon oxidation for self-healing the artificial crack on the mortar. To our knowledge, this is the first report on the potential utilization of the bacterium L. sphaericus incorporated with calcium lactate pentahydrate to increase the mortar properties, including its self-healing ability. However, further study with the water-cement ratio variation is required to investigate the possibility of using L. sphaericus and calcium lactate pentahydrate as an alternative method rather than reducing the water-cement ratio to enhance the mortar properties.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#235

 

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Name
Description Incidental meningiomas (IMs) are the most common intracranial neoplasms, especially in perimenopausal women. There is ongoing debate on whether their incidence is increased by hormone replacement therapy. Meningiomas often express estrogen receptors, which were linked to higher proliferative activity according to some reports. Consequently, there is a theoretical risk of estrogen-based HRT (e-HRT) leading to an increase in tumor growth and thus altering the natural history of IMs. However, clinical data is lacking to support this notion. To identify differences in the natural history of IM after e-HRT exposure. We queried the NorthShore Meningioma Database for patients with ≥ 6 months of e-HRT. They were compared with age-matched IM controls. Forty patients were included in the e-HRT group (mean age 62.1 ± 12.0 years; mean duration of HRT 5.3 ± 4.5 years) and 80 in the no-HRT group (mean age 62.2 ± 12 years). Radiographic appearance was similar between groups. The average 2D tumor diameter was 35% lower in the e-HRT group (p = 0.02), with an absolute growth-rate of half of the no-HRT group (p = 0.02). Radiographic and clinical progression-free survival were 1.2 years and 3.3 years longer in the e-HRT group, respectively. These preliminary results suggest that e-HRT may be safe in incidental meningiomas.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#236

 

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Name
Description We hypothesize that first trimester circulating micro particle (CMP) proteins will define preeclampsia risk while identifying clusters of disease subtypes among cases. We performed a nested case–control analysis among women with and without preeclampsia. Cases diagnosed < 34 weeks’ gestation were matched to controls. Plasma CMPs were isolated via size exclusion chromatography and analyzed using global proteome profiling based on HRAM mass spectrometry. Logistic models then determined feature selection with best performing models determined by cross-validation. K-means clustering examined cases for phenotypic subtypes and biological pathway enrichment was examined. Our results indicated that the proteins distinguishing cases from controls were enriched in biological pathways involved in blood coagulation, hemostasis and tissue repair. A panel consisting of C1RL, GP1BA, VTNC, and ZA2G demonstrated the best distinguishing performance (AUC of 0.79). Among the cases of preeclampsia, two phenotypic sub clusters distinguished cases; one enriched for platelet degranulation and blood coagulation pathways and the other for complement and immune response-associated pathways (corrected p < 0.001). Significantly, the second of the two clusters demonstrated lower gestational age at delivery (p = 0.049), increased protein excretion (p = 0.01), more extreme laboratory derangement (p < 0.0001) and marginally increased diastolic pressure (p = 0.09). We conclude that CMP-associated proteins at 12 weeks’ gestation predict the overall risk of developing early preeclampsia and indicate distinct subtypes of pathophysiology and clinical morbidity.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#237

 

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Name
Description We argue that the evidence remains insufficient for use of intraoperative radiotherapy (IORT) in women with early stage breast cancer outside of a clinical trial, as the recently reported TARGIT-A trial does not provide sufficient evidence to conclude that IORT is superior to no radiotherapy.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#238

 

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Name
Description A large fraction of patients with diabetes mellitus require insulin treatment to control glucose metabolism; however, this treatment brings risks of hypoglycaemia and provides suboptimal metabolic control. Transplantation of stem cell-derived pancreatic islet cells could be an ideal solution, which is approaching clinical translation.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#239

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#240

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#241

 

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Name
Description The aim of this study was to use texture analysis to establish quantitative CT-based imaging features to predict clinical severity in patients with acute alcohol-associated hepatitis (AAH). A secondary aim was to compare the performance of texture analysis to deep learning. In this study, mathematical texture features were extracted from CT slices of the liver for 34 patients with a diagnosis of AAH and 35 control patients. Recursive feature elimination using random forest (RFE-RF) was used to identify the best combination of features to distinguish AAH from controls. These features were subsequently used as predictors to determine associated clinical values. To compare machine learning with deep learning approaches, a 2D dense convolutional neural network (CNN) was implemented and trained for the classification task of AAH. RFE-RF identified 23 top features used to classify AAH images, and the subsequent model demonstrated an accuracy of 82.4% in the test set. The deep learning CNN demonstrated an accuracy of 70% in the test set. We show that texture features of the liver are unique in AAH and are candidate quantitative biomarkers that can be used in prospective studies to predict the severity and outcomes of patients with AAH.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#242

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#243

 

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Name
Description Baffling statistics and their impact on our emotions can make it hard to evaluate risk in this pandemic. But there are simple steps you can take to put risk in context and feel more confident in your decisions

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#244

 

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Name
Description New generation CRISPR technology lays foundation for therapeutics to treat a wide range of inherited ocular diseases. A breakthrough study, led by researchers from the University of California, Irvine, results in the restoration of retinal and visual functions of mice models suffering from inherite

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#245

 

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Description Study shows using intranasal delivery method may reduce inflammation in the brain. Intranasal administration of an anti-inflammatory drug helped reduce disease progression in a preclinical model of multiple sclerosis, according to recent research out of the University of Alberta. Christopher

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#246

 

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Description Extracellular vesicles (EVs), nanometer-sized messengers that travel between cells to deliver cues and cargo, are promising tools for the next generation of therapies for everything from autoimmune and neurodegenerative diseases to cancer and tissue injuries. EVs have already been shown to help h

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#247

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#248

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#249

 

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Name
Description Facebook moderators were reportedly pressured by their employer Genpact to return to office despite safety concerns over the ongoing coronavirus-induced pandemic. Genpact, a third-party contracting firm that handles Facebook&rsquo;s moderation operations, has reportedly been asking its employees to return to offices in Hyderabad since as early as July.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#250

 

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Description Targeting a cytokine called IL-34 could help patients with a drug-resistant form of breast cancer known as triple negative breast cancer.

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#251

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#252

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#253

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 21 October 2020

#254

 

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Name
Description A UK trial that involves intentionally infecting healthy volunteers with the coronavirus will start in January if approved by health authorities. The aim is to establish the minimum infectious dose before testing potential vaccines

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#255

 

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Description The UK’s flagship covid-19 infection tracking survey has been deluged by complaints, with volunteers calling it an “absolute shambles” and “disappointing and frustrating”

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#256

 

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Description The latest coronavirus news updated every day including coronavirus cases, the latest news, features and interviews from New Scientist and essential information about the covid-19 pandemic

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#257

 

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Description One of the leading laboratories accredited with U.S. Government agencies has released test results which confirm that Path-Away® - a plant-based active ingredient that contains no chemicals or alcohol - can kill the actual virus that causes COVID-19 within two minutes, the global distributor of Path

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#258

 

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Description After being released from Walter Reed National Military Medical Center on October 5, US President Donald Trump praised the doctors who treated him for covid-19 and promised that the public would soon have a vaccine against the deadly coronavirus. “We have the best medicines in the world, and very shortly they are all getting approved,…

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#259

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#260

 

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Name
Description Forget the recent debacle in the stock exchanges globally. Experts are of the opinion that while the rest of the…...

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#261

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#262

 

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Name
Description In prior work, we identified a novel gene-by-stress association of EBF1’s common variation (SNP rs4704963) with obesity (i.e., hip, waist) in Whites, which was further strengthened through multiple replications using our synthetic stress measure. We now extend this prior work in a precision medicine framework to find the risk group using harmonized data from 28,026 participants by evaluating the following: (a) EBF1 SNPxSTRESS interaction in Blacks; (b) 3-way interaction of EBF1 SNPxSTRESS with sex, race, and age; and (c) a race and sex-specific path linking EBF1 and stress to obesity to fasting glucose to the development of cardiometabolic disease risk. Our findings provided additional confirmation that genetic variation in EBF1 may contribute to stress-induced human obesity, including in Blacks (P = 0.022) that mainly resulted from race-specific stress due to “racism/discrimination” (P = 0.036) and “not meeting basic needs” (P = 0.053). The EBF1 gene-by-stress interaction differed significantly (P = 1.01e−03) depending on the sex of participants in Whites. Race and age also showed tentative associations (Ps = 0.103, 0.093, respectively) with this interaction. There was a significant and substantially larger path linking EBF1 and stress to obesity to fasting glucose to type 2 diabetes for the EBF1 minor allele group (coefficient = 0.28, P = 0.009, 95% CI = 0.07-0.49) compared with the same path for the EBF1 major allele homozygotes in White females and also a similar pattern of the path in Black females. Underscoring the race-specific key life-stress indicators (e.g., racism/discrimination) and also the utility of our synthetic stress, we identified the potential risk group of EBF1 and stress-induced human obesity and cardiometabolic disease.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#263

 

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Description Robots that currently exist on the market typically use sensors for navigating their environment and performing different tasks. The sensors, however, do not process the data themselves, but sent it to a single processing unit. This results in the need for heavy wiring, delayed response times, and c

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#264

 

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Name
Description The company had 249 million daily active users in the third quarter.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#265

 

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Name
Description Photoreceptors, the primary site of phototransduction in the retina, require energy and metabolites to constantly renew their outer segments. They preferentially consume most glucose through aerobic glycolysis despite possessing abundant mitochondria and enzymes for oxidative phosphorylation (OXPHOS). Exactly how photoreceptors balance aerobic glycolysis and mitochondrial OXPHOS to regulate their survival is still unclear. We crossed rhodopsin-Cre mice with hexokinase 2 (HK2)-floxed mice to study the effect of knocking down HK2, the first rate-limiting enzyme in glycolysis, on retinal health and metabolic remodeling. Immunohistochemistry and Western blots were performed to study changes in photoreceptor-specific proteins and key enzymes in glycolysis and the tricarboxylic acid (TCA) cycle. Changes in retinal structure and function were studied by optical coherence tomography and electroretinography. Mass spectrometry was performed to profile changes in 13C-glucose-derived metabolites in glycolysis and the TCA cycle. We found that knocking down HK2 in rods led to age-related photoreceptor degeneration, evidenced by reduced expression of photoreceptor-specific proteins, age-related reductions of the outer nuclear layer, photoreceptor inner and outer segments and impaired electroretinographic responses. Loss of HK2 in rods led to upregulation of HK1, phosphorylation of pyruvate kinase muscle isozyme 2, mitochondrial stress proteins and enzymes in the TCA cycle. Mass spectrometry found that the deletion of HK2 in rods resulted in accumulation of 13C-glucose along with decreased pyruvate and increased metabolites in the TCA cycle. Our data suggest that HK2-mediated aerobic glycolysis is indispensable for the maintenance of photoreceptor structure and function and that long-term inhibition of glycolysis leads to photoreceptor degeneration.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#266

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#267

 

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Name
Description Although intravenous immunoglobulin (IVIG) can effectively treat Kawasaki disease (KD), 10–20% of KD patients show no beneficial clinical response. Developing reliable criteria to discriminate non-responders is important for early planning of appropriate regimens. To predict the non-responders before IVIG treatment, gene expression dataset of 110 responders and 61 non-responders was obtained from Gene Expression Omnibus. After weighted gene co-expression network analysis, we found that modules positively correlated with the non-responders were mainly associated with myeloid cell activation. Transcripts up-regulated in the non-responders, IL1R2, GK, HK3, C5orf32, CXCL16, NAMPT and EMILIN2, were proven to play key roles via interaction with other transcripts in co-expression network. The crucial transcripts may affect the clinical response to IVIG treatment in acute KD. And these transcripts may serve as biomarkers and therapeutic targets for precise diagnosis and treatment of the non-responders.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#268

 

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Name
Description Autophagy is an intracellular digestive process, which has a crucial role in maintaining cellular homeostasis by self-eating the unnecessary and/or damaged components of the cell at various stress events. ULK1, one of the key elements of autophagy activator complex, together with the two sensors of nutrient and energy conditions, called mTORC1 and AMPK kinases, guarantee the precise function of cell response mechanism. We claim that the feedback loops of AMPK–mTORC1–ULK1 regulatory triangle determine an accurate dynamical characteristic of autophagic process upon cellular stress. By using both molecular and theoretical biological techniques, here we reveal that a delayed negative feedback loop between active AMPK and ULK1 is essential to manage a proper cellular answer after prolonged starvation or rapamycin addition. AMPK kinase quickly gets induced followed by AMPK-P-dependent ULK1 activation, whereas active ULK1 has a rapid negative effect on AMPK-P resulting in a delayed inhibition of ULK1. The AMPK-P → ULK1 ˧ AMPK-P negative feedback loop results in a periodic repeat of their activation and inactivation and an oscillatory activation of autophagy, as well. We demonstrate that the periodic induction of self-cannibalism is necessary for the proper dynamical behaviour of the control network when mTORC1 is inhibited with respect to various stress events. By computational simulations we also suggest various scenario to introduce “delay” on AMPK-P-dependent ULK1 activation (i.e. extra regulatory element in the wiring diagram or multi-phosphorylation of ULK1).

#Medicine & Human body;#Theoretical sciences
Field # Medicine & Human body
Updated 20 October 2020

#269

 

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Name
Description Paraquat (PQ), a widely used herbicide, could cause neurodegenerative diseases, yet the mechanism remains incompletely understood. This study aimed to investigate the direct effect of PQ on NSC in vivo and its possible mechanism. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control once a week for 2 weeks, and sacrificed 1 week after the last PQ injection. Furthermore, extra experiments with Tauroursodeoxycholic Acid (TUDCA) intervention were performed to observe the relationship between ER stress, neuroinflammation and the neural stem cell (NSC) impairment. The results showed that 20 mg/kg PQ caused the NSC number decrease in both subgranular zones (SGZ) and subventricular zone (SVZ). Further analysis indicated that the 20 mg/kg PQ suppressed the proliferation of NSC, without affecting the apoptosis. Moreover, 20 mg/kg PQ also induced ER stress in microglia and caused neuroinflammation in SGZ and SVZ. Interestingly, the ER stress inhibitor could simultaneously ameliorate the neuroinflammation and NSC reduction. These data suggested that increased ER stress in microglia might be a possible pathway for PQ-induced neuroinflammation and NSC impairment. That is a previously unknown mechanism for PQ neurotoxicity.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#270

 

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Name
Description Pancreatic cystic neoplasms (PCNs) are a heterogeneous group with varying risks of malignancy. To explore the clinical utility of liquid biopsy in cyst type classification, we analyzed the GNAS/KRAS mutations in circulating cell-free DNA (cfDNA) obtained from 57 patients with histologically diagnosed PCNs, including 34 with intraductal papillary mucinous neoplasms (IPMNs) and compared the mutant allele prevalence and variant patterns with the paired resected specimens using next-generation sequencing. The positive prevalence of GNAS mutations in cfDNA of patients with IPMN (n = 11, 32%) was significantly higher than that in those with other PCNs (0%, P = 0.002). Conversely, KRAS mutations were detected in cfDNA of only 2 (6%) IPMN patients. The paired-sample comparison revealed highly concordance between the GNAS mutation status of cfDNA and resected IPMN specimens. Similar distributions of GNAS mutation positivity in cfDNA were observed across the different histological grades, whereas IPMNs with intestinal subtype showed a significantly higher prevalence of GNAS mutations than other subtypes (P = 0.030). GNAS mutation positivity in cfDNA was significantly associated with the acellular mucin pool of histological findings in primary IPMN lesions (P = 0.017). Detection of GNAS mutation in cfDNA can serve as a novel biomarker for cyst type classification and differentiation of intestinal subtype IPMN from the other PCNs.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#271

 

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Name
Description Studies on the amyloidogenic N-terminal domain of the E. coli HypF protein (HypF-N) have contributed significantly to a detailed understanding of the pathogenic mechanisms in neurodegenerative diseases characterised by the formation of misfolded oligomers, by proteins such as amyloid-β, α-synuclein and tau. Given that both cell membranes and mitochondria are increasingly recognised as key targets of oligomer toxicity, we investigated the damaging effects of aggregates of HypF-N on mitochondrial membranes. Essentially, we found that HypF-N oligomers characterised by high surface hydrophobicity (type A) were able to trigger a robust permeabilisation of mito-mimetic liposomes possessing cardiolipin-rich membranes and dysfunction of isolated mitochondria, as demonstrated by a combination of mitochondrial shrinking, lowering of mitochondrial membrane potential and cytochrome c release. Furthermore, using single-channel electrophysiology recordings we obtained evidence that the type A aggregates induced currents reflecting formation of ion-conducting pores in mito-mimetic planar phospholipid bilayers, with multi-level conductances ranging in the hundreds of pS at negative membrane voltages. Conversely, HypF-N oligomers with low surface hydrophobicity (type B) could not permeabilise or porate mitochondrial membranes. These results suggest an inherent toxicity of membrane-active aggregates of amyloid-forming proteins to mitochondria, and that targeting of oligomer-mitochondrial membrane interactions might therefore afford protection against such damage.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#272

 

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Name
Description Hypothermic oxygenated machine perfusion (HOPE) was recently tested in preclinical trials in kidney transplantation (KT). Here we investigate the effects of HOPE on extended-criteria-donation (ECD) kidney allografts (KA). Fifteen ECD-KA were submitted to 152 ± 92 min of end-ischemic HOPE and were compared to a matched group undergoing conventional-cold-storage (CCS) KT (n = 30). Primary (delayed graft function-DGF) and secondary (e.g. postoperative complications, perfusion parameters) endpoints were analyzed within 6-months follow-up. There was no difference in the development of DGF between the HOPE and CCS groups (53% vs. 33%, respectively; p = 0.197). Serum urea was lower following HOPE compared to CCS (p = 0.003), whereas the CCS group displayed lower serum creatinine and higher eGFR rates on postoperative days (POD) 7 and 14. The relative decrease of renal vascular resistance (RR) following HOPE showed a significant inverse association with serum creatinine on POD1 (r = − 0.682; p = 0.006) as well as with serum urea and eGFR. Besides, the relative RR decrease was more prominent in KA with primary function when compared to KA with DGF (p = 0.013). Here we provide clinical evidence on HOPE in ECD-KT after brain death donation. Relative RR may be a useful predictive marker for KA function. Further validation in randomized controlled trials is warranted. Trial registration: clinicaltrials.gov (NCT03378817, Date of first registration: 20/12/2017).

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#273

 

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Name
Description To evaluate the imaging features of subungual glomus tumors using 18 MHz high-frequency ultrasound with CDFI (Color Doppler Flow Imaging). 20 patients treated by surgical resection and examined by ultrasound between January 2008 and December 2019. All eligible cases are divided into two groups: Group A used the probe frequency of 9–14 MHz from January 2008 to December 2014, and Group B used the probe frequency of 18 MHz from January 2015 to December 2019. Patient demographics, clinical records, pathologic specimens and sonography features were reviewed. 50% of tumors in Group A and 100% of tumors in Group B showed clear boundary and regular shape. Blood flow signals were identified inside 50% tumors in Group A (3 in 6), all 14 cases with blood flow signals detected in Group B (14 in 14,100%). 2 cases were misdiagnosed and 1 case escaped diagnosis in Group A, no case was misdiagnosed in Group B. The accuracy of diagnosis rate of Group B is significantly higher than that of Group A. 18-MHz ultrasound combined with CDFI may be a practical useful tool for detecting subungual glomus tumors. More importantly 18-MHz ultrasound can obviously improve the diagnostic accuracy.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#274

 

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Name
Description Stroke is a leading cause of long-term disability in adults and a leading cause of death in developed nations. The cascade of cellular events and signalling that occur after cerebral ischemia are complex, however, analyzing global element markers of metabolic state affords the means to monitor stroke severity, status of injury, and recovery. These markers provide a multi-parameter method for assessing changes through the post-stroke time course. We employ synchrotron-based elemental mapping to follow elemental changes in the brain at 1 h, 1-, 2-, and 3-days, and at 1-, 2-, 3-, and 4-weeks post-stroke in a photothrombotic stroke model in mice. Our analysis reveals a highly consistent metabolic penumbra that can be readily identified based on the level of dysregulated potassium and other key elements. Maps of elemental distributions are also useful to demarcate events in the cellular response to the inflammatory cascade, including ion dysregulation, recruitment of cells to the lesion, and glial scar formation.

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 20 October 2020

#275

 

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Name
Description Porcine circovirus 2 (PCV2) is a single stranded DNA virus with one of the highest mutation rates among DNA viruses. This ability allows it to generate a cloud of mutants constantly providing new opportunities to adapt and evade the immune system. This pig pathogen is associated to many diseases, globally called porcine circovirus diseases (PCVD) and has been a threat to pig industry since its discovery in the early 90’s. Although 11 ORFs have been predicted from its genome, only two main proteins have been deeply characterized, i.e. Rep and Cap. The structural Cap protein possesses the majority of the epitopic determinants of this non-enveloped virus. The evolution of PCV2 is affected by both natural and vaccine-induced immune responses, which enhances the genetic variability, especially in the most immunogenic Cap region. Intra-host variability has been also demonstrated in infected animals where long-lasting infections can take place. However, the association between this intra-host variability and pathogenesis has never been studied for this virus. Here, the within-host PCV2 variability was monitored over time by next generation sequencing during an experimental infection, demonstrating the presence of large heterogeneity. Remarkably, the level of quasispecies diversity, affecting particularly the Cap coding region, was statistically different depending on viremia levels and clinical signs detected after infection. Moreover, we proved the existence of hyper mutant subjects harboring a remarkably higher number of genetic variants. Altogether, these results suggest an interaction between genetic diversity, host immune system and disease severity.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#276

 

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Name
Description Zymoseptoria tritici causes Septoria tritici blotch (STB) of wheat, an economically important disease causing yield losses of up to 10% despite the use of fungicides and resistant cultivars. Z. tritici infection is symptomless for around 10 days, during which time the fungus grows randomly across the leaf surface prior to entry through stomata. Wounded leaves show faster, more extensive STB, suggesting that wounds facilitate fungal entry. Wheat leaves also host epiphytic bacteria; these include ice-nucleating (INA+) bacteria, which induce frost damage at warmer temperatures than it otherwise occurs. Here, STB is shown to be more rapid and severe when wheat is exposed to both INA+ bacteria and sub-zero temperatures. This suggests that ice-nucleation-induced wounding of the wheat leaf provides additional openings for fungal entry. INA+ bacterial populations are shown to benefit from the presence of Z. tritici, indicating that this microbial interaction is mutualistic. Finally, control of INA+ bacteria is shown to reduce STB.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#277

 

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Name
Description KRAS mutations are associated with rare cases of neurodevelopmental disorders that can cause intellectual disabilities. Previous studies showed that mice expressing a mutant KRAS have impaired the development and function of GABAergic inhibitory neurons, which may contribute to behavioural deficits in the mutant mice. However, the underlying cellular mechanisms and the role of excitatory neurons in these behavioural deficits in adults are not fully understood. Herein, we report that neuron type-specific expression of a constitutively active mutant KRASG12V in either excitatory or inhibitory neurons resulted in spatial memory deficits in adult mice. In inhibitory neurons, KRASG12V induced ERK activation and enhanced GABAergic synaptic transmission. Expressing KRASG12V in inhibitory neurons also impaired long-term potentiation in the hippocampal Shaffer-collateral pathway, which could be rescued by picrotoxin treatment. In contrast, KRASG12V induced ERK activation and neuronal cell death in excitatory neurons, which might have contributed to the severe behavioural deficits. Our results showed that both excitatory and inhibitory neurons are involved in mutant KRAS-associated learning deficits in adults via distinct cellular mechanisms.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#278

 

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Name
Description SARS-CoV-2 can infiltrate the lower respiratory tract, resulting in severe respiratory failure and a high death rate. Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection. Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, including Ace2. Thus, stem cells can be potentially infected by SARS-CoV-2, which may lead to defects in regeneration capacity partially accounting for the severity of SARS-CoV-2 infection and its consequences.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#279

 

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Name
Description In order to analyze the associations between thyroid cancer and environmental factors, we analyzed the national sample cohort representative of the entire population provided by the Korean National Health Insurance Service database record from 2006 to 2015. The cohort was categorized according to age, body mass index, income, residential areas, frequency of exercise, frequency of alcohol drinking, diet, presence or absence of hyperthyroidism, presence or absence of hypothyroidism, and smoking data. Age ≥ 55 years (HR 0.68, 95% CI 0.53–0.88), lower income (0.57, 0.40–0.80), and current smoking (0.69, 0.55–0.85) were associated with lower thyroid cancer occurrence among men. Body mass index (BMI) ≥ 25 kg/m2 (1.51, 1.26–1.82), higher income (1.44, 1.19–1.76), urban residence (1.24, 1.03–1.49), and presence of hypothyroidism (3.31, 2.38–4.61) or hyperthyroidism (2.46, 1.75–3.46) were associated with higher thyroid cancer occurrence among men. Age ≥ 55 years (0.63, 0.56–0.71), moderate alcohol drinking (0.87, 0.77–0.99), and current smoking (0.56, 0.37–0.85) were associated with lower thyroid cancer occurrence among women. BMI ≥ 25 kg/m2 (1.41, 1.26–1.57), frequent exercise (1.21, 1.07–1.36), higher income (1.18, 1.06–1.32), urban residence (1.17, 1.06–1.29), and presence of hypothyroidism (1.60, 1.40–1.82) or hyperthyroidism (1.38, 1.19–1.61) were associated with higher thyroid cancer occurrence among women. In conclusion, age ≥ 55 years and current smoking were associated with lower thyroid cancer occurrence, while BMI ≥ 25 kg/m2, higher income, urban residence, hypothyroidism, and hyperthyroidism were associated with higher occurrence in both men and women.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#280

 

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Name
Description Polyautoimmunity implicates that some autoimmune diseases share common etiopathogenesis. Some studies have reported an association between multiple sclerosis (MS) and vitiligo; meanwhile, other studies have failed to confirm this association. We performed a systemic review and meta-analysis to examine the association of MS with vitiligo. We searched the MEDLINE and Embase databases on March 8, 2020 for relevant case–control, cross-sectional, and cohort studies. The Newcastle–Ottawa Scale was used to evaluate the risk of bias of the included studies. Where applicable, we performed a meta-analysis to calculate the pooled odds ratio (OR) for case–control/cross-sectional studies and risk ratio for cohort studies with 95% confidence interval (CI). Our search identified 285 citations after removing duplicates. Six case–control studies with 12,930 study subjects met our inclusion criteria. Our meta-analysis found no significant association of MS with prevalent vitiligo (pooled OR 1.33; 95% CI 0.80‒2.22). Analysis of the pooled data failed to display any increase of prevalent vitiligo in MS patients compared with controls. Ethnic and genetic factors may play an important role for sporadically observed associations between MS and vitiligo. Future studies of this association should therefore consider stratification by ethnic or genetic factors.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#281

 

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Name
Description Whilst axial length (AxL) from ultrasound examination is a useful clinical parameter for monitoring progression in younger children with glaucoma, distinguishing AxL changes due to raised intraocular pressure (IOP) from age is often challenging. Existing normograms have included a limited number of children with glaucoma. The aim of this study was to evaluate the relationship between AxL with age and IOP in children with primary congenital glaucoma (PCG) and develop a model for expected AxL increase with age. All children (n = 208; 397 eyes) with PCG who attended our tertiary eye care facility from June 2014 and July 2018 and had AxL and IOP measurements were included. The relationship of AxL with age and IOP was studied by applying a LOWESS fit and then mixed effects models. In the final model, age was the most significant factor influencing the growth of AxL (coefficient age 3.14[95% CI 2.91–3.35, p < 0.001], coefficient age2 − 0.53[95% CI, − 0.59 to − 0.47, p < 0.001]), and this association was influenced by the interaction of IOP with sex (p = 0.098 for girls relative to boys), the number of antiglaucoma medications (AGM [p < 0.001 for ≥ 3 AGM]) and glaucoma surgery (p = 0.015). This model enabled us to derive predicted values for clinical use in children with PCG to predict those with progressive glaucoma.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#282

 

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Name
Description This study aimed to investigate the association between serum concentrations of chemokine (C–C Motif) ligand 18 (CCL-18) and interleukin 23 (IL-23) and clinical parameters of chronic obstructive pulmonary disease (COPD). The serum concentrations of CCL-18 and IL-23 were tested by enzyme linked immunosorbent assay (ELISA). The association between their concentrations and clinical parameters of COPD patients were analyzed by linear regression, logistic regression and ROC curve. The results showed that the serum concentrations of CCL-18 and IL-23 in COPD patients were increased compared with healthy people (P < 0.001) and that patients with acute exacerbation of COPD (AECOPD) had higher serum CCL-18 and IL-23 concentrations than stable patients (P < 0.001). Synergistic increase of CCL-18 and IL-23 in COPD patients was positively correlated with COPD patients' higher GOLD grade (P < 0.001), higher mMRC score (P < 0.001) and longer medical history (P < 0.001), but negatively correlated with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (P < 0.001) and FEV1% predicted (P < 0.001). The serum concentrations of CCL-18 and IL-23 were most related to the GOLD grade (OR = 2.764 for CCL-18 and OR = 4.215 for IL-23) and detection of both showed considerable sensitivity (72.57% for CCL-18 and 76.92% for IL-23) and specificity (92.50% for CCL-18 and 77.5% for IL-23) in identifying COPD. Increased serum concentrations of CCL-18 and IL-23 correlated with the disease progression of COPD and they could be used as biomarkers for disease evaluation of COPD.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#283

 

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Name
Description Recent recurrent outbreaks of Gram-negative bacteria show the critical need to target essential bacterial mechanisms to fight the increase of antibiotic resistance. Pathogenic Gram-negative bacteria have developed several strategies to protect themselves against the host immune response and antibiotics. One such strategy is to remodel the outer membrane where several genes are involved. yejM was discovered as an essential gene in E. coli and S. typhimurium that plays a critical role in their virulence by changing the outer membrane permeability. How the inner membrane protein YejM with its periplasmic domain changes membrane properties remains unknown. Despite overwhelming structural similarity between the periplasmic domains of two YejM homologues with hydrolases like arylsulfatases, no enzymatic activity has been previously reported for YejM. Our studies reveal an intact active site with bound metal ions in the structure of YejM periplasmic domain. Furthermore, we show that YejM has a phosphatase activity that is dependent on the presence of magnesium ions and is linked to its function of regulating outer membrane properties. Understanding the molecular mechanism by which YejM is involved in outer membrane remodeling will help to identify a new drug target in the fight against the increased antibiotic resistance.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#284

 

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Name
Description Golimumab has demonstrated its long-term efficacy and safety in ulcerative colitis in clinical trials, but no data of long-term persistence has been published from real world. To estimate long-term persistence of golimumab, as well as factors associated with longer persistence, in patients with ulcerative colitis in real life. Observational multicentre study including adult patients with ulcerative colitis treated with golimumab and with at least twelve months of follow-up. We included 190 patients, 105 (55.26%) naive to anti-TNF, with mean disease duration of 9.32 ± 8.09 years. Probability of persistence was 63%, 46%, 39% and 27% at 1, 2, 3 and 4 years, respectively. Persistence was lower in patients with primary failure to previous anti-TNF. Eighty-two (43.16%) patients needed dose intensification during follow-up, with a mean time until intensification of 8.03 ± 8.64 months. Dose intensification and lower disease duration predicted higher persistence with golimumab (p = 0.037 and p = 0.008, respectively). During a follow-up of 17.25 ± 15.83 months, 32 (16.5%) patients needed hospitalisation and 11 (6%) underwent colectomy. No unexpected adverse events were reported. Golimumab has demonstrated good persistence and safety profile for long treatment in ulcerative colitis patients.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#285

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#286

 

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Name
Description The ventricular conduction system coordinates heartbeats by rapid propagation of electrical activity through the Purkinje fiber (PF) network. PFs share common progenitors with contractile cardiomyocytes, yet the mechanisms of segregation and network morphogenesis are poorly understood. Here, we apply genetic fate mapping and temporal clonal analysis to identify murine cardiomyocytes committed to the PF lineage as early as E7.5. We find that a polyclonal PF network emerges by progressive recruitment of conductive precursors to this scaffold from a pool of bipotent progenitors. At late fetal stages, the segregation of conductive cells increases during a phase of rapid recruitment to build the definitive PF network through a non-cell autonomous mechanism. We also show that PF differentiation is impaired in Nkx2-5 haploinsufficient embryos leading to failure to extend the scaffold. In particular, late fetal recruitment fails, resulting in PF hypoplasia and persistence of bipotent progenitors. Our results identify how transcription factor dosage regulates cell fate divergence during distinct phases of PF network morphogenesis. Here, the authors apply genetic fate mapping and temporal clonal analysis to study progenitor recruitment and network morphogenesis of murine cardiac Purkinje fibers. Additionally, they characterize how transcription factor dosage regulates cell fate divergence during distinct phases of this process.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#287

 

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Name
Description Telomerase is a specialized reverse transcriptase that adds GGTTAG repeats to chromosome ends and is upregulated in most human cancers to enable limitless proliferation. Here, we uncover two distinct mechanisms by which naturally occurring oxidized dNTPs and therapeutic dNTPs inhibit telomerase-mediated telomere elongation. We conduct a series of direct telomerase extension assays in the presence of modified dNTPs on various telomeric substrates. We provide direct evidence that telomerase can add the nucleotide reverse transcriptase inhibitors ddITP and AZT-TP to the telomeric end, causing chain termination. In contrast, telomerase continues elongation after inserting oxidized 2-OH-dATP or therapeutic 6-thio-dGTP, but insertion disrupts translocation and inhibits further repeat addition. Kinetics reveal that telomerase poorly selects against 6-thio-dGTP, inserting with similar catalytic efficiency as dGTP. Furthermore, telomerase processivity factor POT1-TPP1 fails to restore processive elongation in the presence of inhibitory dNTPs. These findings reveal mechanisms for targeting telomerase with modified dNTPs in cancer therapy. Telomerase enzymes add telomeric repeats to the end of linear chromosomes. Here the authors reveal mechanisms by which oxidized dNTPs and therapeutic dNTPs inhibit telomerase-mediated telomere elongation.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#288

 

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Name
Description Evidence is lacking as to how developing neurons integrate mitogenic signals with microenvironment cues to control proliferation and differentiation. We determine that the Siah2 E3 ubiquitin ligase functions in a coincidence detection circuit linking responses to the Shh mitogen and the extracellular matrix to control cerebellar granule neurons (CGN) GZ occupancy. We show that Shh signaling maintains Siah2 expression in CGN progenitors (GNPs) in a Ras/Mapk-dependent manner. Siah2 supports ciliogenesis in a feed-forward fashion by restraining cilium disassembly. Efforts to identify sources of the Ras/Mapk signaling led us to discover that GNPs respond to laminin, but not vitronectin, in the GZ microenvironment via integrin β1 receptors, which engages the Ras/Mapk cascade with Shh, and that this niche interaction is essential for promoting GNP ciliogenesis. As GNPs leave the GZ, differentiation is driven by changing extracellular cues that diminish Siah2-activity leading to primary cilia shortening and attenuation of the mitogenic response. In neural development, progenitors transition from a proliferative to a differentiated state. Here, the authors show that cerebellar granule neurons retract primary cilia as they exit their proliferative niche upon decreased ECM engagement, enabling radial migration due to loss of Shh sensitivity.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#289

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#290

 

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Name
Description The coronavirus pandemic has made it harder for people in India to access healthcare for tuberculosis and 87,000 additional deaths due to TB are expected this year

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#291

 

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Name
Description In a National Institutes of Health-funded study involving both mice and patients who are part of an NIH Clinical Center trial, researchers discovered that a gene, called PIEZO2, may be responsible for the powerful urge to urinate that we normally feel several times a day. The results, published in N

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#292

 

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Name
Description Humans aren’t born with mature brain circuitry that attaches emotions to the things they see or hear in their environment, a new study shows. Researchers studying brain scans of newborns found that the part of the brain involved in experiencing emotions isn’t functionally connected in a mature wa

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#293

 

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Name
Description Around the world, some 50 million people have epilepsy, with more than 3 million in the United States alone. It’s one of the most common neurological diseases globally, characterized by recurrent seizures in part or all of the body. It’s also quite treatable with daily antiseizure medications. Yet l

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#294

 

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Name
Description Researchers found an acceleration in transmission between the Black Death of 1348 and later epidemics, which culminated in the Great Plague of 1665.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#295

 

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Name
Description Voters will weigh in on more than 100 state initiatives and referenda

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#296

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#297

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#298

 

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Description Cell-free DNA (cfDNA) has been investigated in acute graft-versus-host disease (aGvHD) following allogeneic cell transplantation (HSCT). Identifying the tissue of origin of cfDNA in patients with aGvHD is relevant particularly when a biopsy is not feasible. We investigate the cfDNA tissue of origin in patients with aGvHD using methylated gene biomarkers. Patients with liver, colon, or skin aGvHD (n = 28) were analyzed. Liver- and colon-derived cfDNA was measured using a colon- (SESN3) and liver (PTK2B)-specific methylation marker with digital droplet PCR. A statistically significant difference (p < 0.001) in PTK2B and SESN3 concentration was observed between patients with colon or liver GvHD and the control group. For SESN3 and PTK2B the area under the curve in the receiver-operating characteristic (ROC) space was 0.952 (95% CI, 0.888–1 p < 0.001) and 0.971 (95% CI, 0.964–1 p < 0.001), respectively. Thresholds to differentiate aGvHD from non-aGvHD in colon were 0 (sensitivity: 0.905; specificity: 0.989) and liver 1.5 (sensitivity: 0.928; specificity: 0.910). Clinical improvement of liver or colon aGvHD resulted in PTK2B and SESN3 reduced concentration. Whereas, in those patients without improvement the PTK2B and SESN3 level remained stable or increased. The PTK2B liver-specific marker and the SESN3 colon-specific marker and their longitudinal analysis might improve aGvHD detection.

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#299

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#300

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020

#301

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 20 October 2020