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#1

 

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Description Prophylactic donor lymphocyte infusions (DLI) are used to augment post-transplant immune recovery to reduce both infectious complications and disease recurrence. Preclinical studies implicate the naive T-cell subset as the primary driver of graft-versus-host disease (GvHD). In this phase I dose escalation study, we assessed the safety of a DLI that was depleted of CD45RA+ naive T cells. Sixteen adult patients received a prophylactic DLI at a median of 113 days (range 76–280 days) following an HLA-identical, non-myeloablative allogeneic hematopoietic stem cell transplantation. Three patients each received the naive T-cell depleted DLI with a CD3+ dose of 1 × 105/kg, 1 × 106/kg, and 5 × 106/kg. The maximum dose of 1 × 107/kg was expanded to 7 patients. No dose-limiting grade III/IV acute GvHD or adverse events attributable to the DLI were observed at any dose level. One patient developed grade 2 acute GvHD of skin and upper intestines, and another developed moderate chronic GvHD of the lungs following the DLI. With a median follow-up of 2.8 years, 2-year progression-free and overall survival is 50.0% and 68.8%, respectively. In conclusion, these data suggest that a DLI that has been depleted of CD45RA+ naive T cells is feasible and carries a low risk of acute or chronic GvHD.

#Medicine & Human body
Field # Medicine & Human body
Updated 05 July 2020

#2

 

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Description Allogeneic peripheral blood stem cell transplantation (PBSCT) is associated with an increased risk of severe acute and chronic graft-versus-host disease (GVHD) compared to bone marrow transplantation. Anti-thymocyte globulin (ATG) can reduce severe acute and chronic GVHD in PBSCT; however, an optimal dose of ATG remains undefined. We conducted a multicenter phase II study to investigate safety and efficacy of low-dose ATG (a total of 2 mg/kg Thymoglobulin) in patients undergoing HLA-matched PBSCT after myeloablative conditioning. The primary endpoint was grades III–IV GVHD at 100 days. Seventy-seven patients were enrolled and 72 patients with a median age of 46.5 years were eligible for analysis. The primary endpoint, cumulative incidence of grades III–IV acute GVHD at 100 days was 1.4% (95% CI, 0.1–6.7%), which was greatly less than our pre-defined statistical threshold value (18.0%). The incidence of chronic GVHD at 1 year was also low (all-grade; 15.3%, moderate to severe; 5.6%). Non-relapse mortality, relapse, overall survival, disease-free survival, and GVHD-free, relapse-free survival at 1 year were 4.2%, 20.8%, 84.7%, 75.0%, and 69.4%, respectively. Low dose thymoglobulin is promising to reduce severe acute and chronic GVHD in HLA-matched PBSCT following myeloablative conditioning.

#Medicine & Human body
Field # Medicine & Human body
Updated 05 July 2020

#3

 

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Description Altered dopamine transmission is thought to influence the formation of persecutory delusions. However, despite extensive evidence from clinical studies there is little experimental evidence on how modulating the dopamine system changes social attributions related to paranoia, and the salience of beliefs more generally. Twenty seven healthy male participants received 150mg L-DOPA, 3 mg haloperidol, or placebo in a double-blind, randomised, placebo-controlled study, over three within-subject sessions. Participants completed a multi-round Dictator Game modified to measure social attributions, and a measure of belief salience spanning themes of politics, religion, science, morality, and the paranormal. We preregistered predictions that altering dopamine function would affect (i) attributions of harmful intent and (ii) salience of paranormal beliefs. As predicted, haloperidol reduced attributions of harmful intent across all conditions compared to placebo. L-DOPA reduced attributions of harmful intent in fair conditions compared to placebo. Unexpectedly, haloperidol increased attributions of self-interest about opponents’ decisions. There was no change in belief salience within any theme. These results could not be explained by scepticism or subjective mood. Our findings demonstrate the selective involvement of dopamine in social inferences related to paranoia in healthy individuals.

#Medicine & Human body
Field # Medicine & Human body
Updated 05 July 2020

#4

 

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Description Autism spectrum disorders (ASD) are highly heritable and are characterized by deficits in social communication and restricted and repetitive behaviors. Twin studies on phenotypic subdomains suggest a differing underlying genetic etiology. Studying genetic variation explaining phenotypic variance will help to identify specific underlying pathomechanisms. We investigated the effect of common variation on ASD subdomains in two cohorts including >2500 individuals. Based on the Autism Diagnostic Interview-Revised (ADI-R), we identified and confirmed six subdomains with a SNP-based genetic heritability h2SNP = 0.2–0.4. The subdomains nonverbal communication (NVC), social interaction (SI), and peer interaction (PI) shared genetic risk factors, while the subdomains of repetitive sensory-motor behavior (RB) and restricted interests (RI) were genetically independent of each other. The polygenic risk score (PRS) for ASD as categorical diagnosis explained 2.3–3.3% of the variance of SI, joint attention (JA), and PI, 4.5% for RI, 1.2% of RB, but only 0.7% of NVC. We report eight genome-wide significant hits—partially replicating previous findings—and 292 known and novel candidate genes. The underlying biological mechanisms were related to neuronal transmission and development. At the SNP and gene level, all subdomains showed overlap, with the exception of RB. However, no overlap was observed at the functional level. In summary, the ADI-R algorithm-derived subdomains related to social communication show a shared genetic etiology in contrast to restricted and repetitive behaviors. The ASD-specific PRS overlapped only partially, suggesting an additional role of specific common variation in shaping the phenotypic expression of ASD subdomains.

#Medicine & Human body
Field # Medicine & Human body
Updated 05 July 2020

#5

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 05 July 2020

#6

 

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Description New Scientist's weekly round-up of the best books, films, TV series, games and more that you shouldn’t miss

#Medicine & Human body;#Psychology
Field # Medicine & Human body
Updated 05 July 2020

#7

 

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Description The lenses, made of spider dragline silk, could be used to create high resolution images of human tissue.

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 05 July 2020

#8

 

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Description The virus has sometimes moved from pigs to humans, but not between humans.

#Medicine & Human body
Field # Medicine & Human body
Updated 05 July 2020

#9

 

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Description The transport of proteins across the nuclear membrane is a highly regulated process, essential for the cell function. This transport is actively mediated by members of the karyopherin family, termed importins, or exportins, depending on the direction of transport. These proteins play an active part in tumorigenesis, through aberrant localization of their cargoes, which include oncogenes, tumor-suppressor genes and mediators of key signal transduction pathways. Overexpression of importins and exportins is reported in many malignancies, with implications in cell growth and viability, differentiation, drug resistance, and tumor microenvironment. Given their broad significance across tumors and pathways, much effort is being put to develop specific inhibitors as a novel anticancer therapeutics. Already, selinexor, a specific inhibitor of exportin-1 (XPO1), is approved for clinical use. This review will focus on the role of importins and exportins in hematological malignancies. We will discuss current preclinical and clinical data on importins and exportins, and demonstrate how our growing understanding of their functions has identified new therapeutic targets.

#Medicine & Human body
Field # Medicine & Human body
Updated 05 July 2020

#10

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 05 July 2020

#11

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 05 July 2020

#12

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 05 July 2020

#14

 

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Description Blood glucose becomes just one more telemetry feed to track during a race.

#Medicine & Human body
Field # Medicine & Human body
Updated 04 July 2020

#15

 

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Description Refeeding syndrome (RFS) can occur in severely malnourished or starved populations that are provided with rapid or unbalanced nutrition. International guidelines recommend a cautious approach for managing RFS risk (hypocaloric nutrition for 4–7 days), however emerging evidence supports a more assertive approach. This study aimed to describe nutritional management and RFS-related adverse outcomes in patients at risk of RFS receiving care after implementing updated guidelines reflecting emerging evidence. A retrospective cohort study of inpatients at risk of RFS during admission to a large metropolitan hospital in Queensland, Australia between November 2018 and April 2019 was conducted. Data were collected from medical records on nutritional management (provision of nutrition, electrolyte, and vitamin replacement) and outcomes (incidence of RFS, serum electrolyte decreases, hypo/hyperglycaemia, oedema, and organ function disturbance). Data were analysed descriptively; relationships between serum electrolyte decreases and nutrition management were explored using Fisher’s Exact tests. Of the 70 patients identified at risk of RFS (58.4 ± 16.8 years, 56% male, 94% malnourished), majority of participants received required supplementation prior to the commencement of nutrition (thiamine: 76%; micronutrients: 72–100%; multivitamin: 61%) and a standard initial nutrition management plan (79%; cautious: 13%; liberal: 8%). There were no cases of RFS. Four participants experienced RFS-related adverse outcomes (severe electrolyte decreases: n = 2, hypo/hyperglycaemia: n = 2); however, there was no differences in serum electrolyte decreases based on the nutrition management plan (initial: p = 0.912; goal: p = 0.688). The implementation of more liberal RFS guidelines for the management of RFS risk appears to be safe. Further research examining liberalised refeeding protocols may be useful in updating international guidelines.

#Medicine & Human body
Field # Medicine & Human body
Updated 04 July 2020

#16

 

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Description Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation (HSCT). Sirolimus plus tacrolimus is an accepted regimen for graft-versus-host disease (GVHD) prophylaxis, with both agents implicated as risk factors for SOS. We analyzed 260 consecutive patients who underwent allogeneic HSCT following myeloablative conditioning using total body irradiation (TBI)-based (n = 151) or chemotherapy only (n = 109) regimens, with sirolimus plus tacrolimus for GVHD prophylaxis. SOS occurred in 28 patients at a median of 22 (range, 12–58) days. Mean sirolimus trough levels were higher between days 11 and 20 following transplant in patients who developed SOS (10.3 vs. 8.5 ng/ml, P = 0.008), with no significant difference in mean trough levels between days 0 and 10 (P = 0.67) and days 21–30 (P = 0.37). No differences in mean tacrolimus trough levels during the same time intervals were observed between those developing SOS and others. On multivariable analysis, a mean sirolimus trough level ≥ 9 ng/ml between days 11 and 20 increased the risk of SOS (hazard ratio 3.68, 95% CI: 1.57–8.67, P = 0.003), together with a longer time from diagnosis to transplant (P = 0.004) and use of TBI (P = 0.006). Our results suggest that mean trough sirolimus levels ≥ 9 ng/mL between days 11 and 20 post transplant may increase the risk of SOS and should be avoided.

#Medicine & Human body
Field # Medicine & Human body
Updated 04 July 2020

#17

 

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Description

#Medicine & Human body
Field # Medicine & Human body
Updated 04 July 2020

#18

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 04 July 2020

#19

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 04 July 2020

#20

 

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Description Physical exercising is extremely healthy for your body and mind. However, intense exercising is likely to cause some pains and, sometimes, even injuries. Runners often use non-steroidal anti-inflammatories (NSAIDs)  to ease post-exercise aches, pains or injuries, but scientists from the Queen Mary’s

#Medicine & Human body
Field # Medicine & Human body
Updated 04 July 2020

#22

 

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Description Aberrantly expressed microRNAs (miRNAs) disrupt intracellular RNA networks and contribute to malignant transformation of cancer cells. Utilizing the latest RNA sequencing technology, we newly created the miRNA expression signature of esophageal squamous cell carcinoma (ESCC). A total of 47 miRNAs were downregulated in ESCC tissues, and these miRNAs were candidates for antitumor miRNAs in ESCC cells. Analysis of the signature revealed that several passenger strands of miRNAs were significantly downregulated in ESCC, e.g., miR-28-3p, miR-30a-3p, miR-30c-3p, miR-133a-3p, miR-139-3p, miR-143-5p, and miR-145-3p. Recent studies indicate that some passenger strands of miRNAs closely involved in cancer pathogenesis. In this study, we focused on both strands of pre-miR-143, and investigated their antitumor roles and target oncogenes in ESCC. Ectopic expression of miR-143-5p and miR-143-3p significantly attenuated malignant phenotypes (e.g., proliferation, migration, and invasive abilities) in ESCC cell lines. We revealed that six genes (HN1, HMGA2, NETO2, STMN1, TCF3, and MET) were putative targets of miR-143-5p regulation, and one gene (KRT80) was a putative target of miR-143-3p regulation in ESCC cells. Our ESCC miRNA signature and analysis strategy provided important insights into the molecular pathogenesis of ESCC.

#Medicine & Human body
Field # Medicine & Human body
Updated 04 July 2020

#23

 

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Description A survey by community platform LocalCircles showed that 21% of respondents were ordering essentials and other products through ecommerce platforms, while an additional 19% were opting for home delivery of goods from large retailers and local corner stores.

#Medicine & Human body
Field # Medicine & Human body
Updated 04 July 2020

#24

 

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Description Waymo paused its Waymo One service due to the coronavirus pandemic, but it's ready to welcome back workers and riders, and it expects to keep growing in 2020.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#25

 

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Description Scientists are looking at sewers running under the world’s cities and towns for information they hope will help to stem the spread of the coronavirus.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#26

 

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Description Meet a legless caecilian with a funky mouth that may hide a venomous secret.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#27

 

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Description Bats cope with myriad viruses—including what caused COVID-19—so how do they do it?

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#28

 

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Description A lack of resources has made it hard to keep data secure.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#29

 

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Description The aim of this study is to describe trends in overweight and obesity among Slovenian youth for the period 1989–2018. Nearly all schoolchildren in Slovenia had their height and weight measured annually, which lead to a total of 6,738,510 data-points during the 30-year period. The IOTF cut-off points and Joinpoint regression were used to examine annual percent change (APC) in overweight and obesity prevalence across 3 age groups (7–10, 11–14 and 15–18 years). Obesity approximately tripled, while overweight doubled between 1989 and late 2000s in both genders. Since then overweight has been steadily decreasing in all 3 age groups for boys and in 7–10-year-old girls. Obesity has also been declining since 2009, but only in the youngest boys and girls (APC = − 1.9, 95% CI = − 3.2 to − 0.6 and APC = − 1.6, 95% CI = − 3.0 to − 0.2, respectively). Unfavourable trends were noted only in 15–18-year-old girls, with obesity rising at an unchanged rate over the past 30 years (APC = 4.8, 95% CI = 4.5–5.1). Overweight and obesity among Slovenian youth has increased dramatically over the last 3 decades. Still, during the last decade this rise has been reversed or at least stopped. This reversal of trends was more marked in boys than in girls, and in young children compared to adolescents.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#30

 

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Description Sorafenib was originally identified as an inhibitor of multiple oncogenic kinases and remains the first-line systemic therapy for advanced hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have been reported to play critical roles in the initiation, progression, and drug resistance of HCC. In this study, we aimed to identify sorafenib-induced miRNAs and demonstrate their regulatory roles. First, we identified that the expression of the tumor-suppressive miRNA miR-375 was significantly induced in hepatoma cells treated with sorafenib, and miR-375 could exert its antiangiogenic effect partially via platelet-derived growth factor C (PDGFC) inhibition. Then, we demonstrated that sorafenib inhibited PDGFC expression by inducing the expression of miR-375 and a transcription factor, achaete-scute homolog-1 (ASH1), mediated the induction of miR-375 by sorafeinb administration in hepatoma cells. Finally, we verified that the expression of miR-375 was reduced in sorafenib-resistant cells and that the restoration of miR-375 could resensitize sorafenib-resistant cells to sorafenib partially by the degradation of astrocyte elevated gene-1 (AEG-1). In conclusion, our data demonstrate that miR-375 is a critical determinant of HCC angiogenesis and sorafenib tolerance, revealing a novel miRNA-mediated mechanism underlying sorafenib treatment.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#31

 

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Description Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear. In this retrospective cohort study, tissue specimens of patients with unresectable or recurrent GC and prior or scheduled treatment with nivolumab as third-line or higher therapy between September 2017 and February 2019 were collected from 23 institutions. The tumour-positive score (TPS) and combined positive score (CPS) of PD-L1 expression and mismatch repair (MMR) were analysed by immunohistochemistry. Associations between clinicopathological factors and tumour-response rate, hyperprogressive disease (HPD) rate and survival were assessed. Of 200 eligible patients, 143 had measurable lesions. The response and HPD rates were 17.5% and 22.1%, respectively. The response rate was significantly higher in patients with performance status (PS) 0–1 (P = 0.026), non-peritoneal metastasis (P = 0.021), PD-L1 TPS ≥ 1 (P = 0.012), CPS ≥ 5 (P = 0.007) or ≥ 10 (P < 0.001) or MMR deficiency (P < 0.001). The HPD rate was significantly higher in patients with PS 2–3 (P = 0.026), liver metastasis (P < 0.001) and CPS < 10 (P = 0.048). Multivariate analysis revealed that CPS (P = 0.001) and MMR (P = 0.002) were independent prognostic factors of progression-free survival, as well as liver metastasis (P < 0.001), peritoneal metastasis (P = 0.004) and CRP (P < 0.001). PD-L1 CPS and MMR could be useful biomarkers for nivolumab treatment efficacy in GC. UMIN000032164.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#32

 

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Description The prognosis of HPV- HNSCC was worse than that of HPV+ HNSCC. Analysis of tumours and tumour-infiltrating lymphocytes (TILs) may provide insight into the progression of HPV− HNSCC. The tumour and TIL phenotypic characteristics of 134 HNSCC specimens (HPV− tumours were classified into “Infiltrating” and “Pushing” subtypes based on their different tumour nest configuration and prognosis) were retrospectively analysed. HNSCC data from the Cancer Genome Atlas (n = 263) were analysed for CD8α, HPV and overall survival (OS). A murine HNSCC model was used to verify the antitumour role of PD-1+CD8+ TILs. The “Infiltrating” HPV− subtype showed shorter OS than the “Pushing” subtype. Moreover, there is a tendency from “Pushing” to “Infiltrating” subtype from the primary to the recurrent lesion. Different from total CD8+ TILs, tumour-specific PD-1+CD8+ TILs were fewer in invasive margin (IM) of “Infiltrating” HPV− tumours. PD-1+CD8+ TILs recognised autologous HNSCC cells and showed stronger inhibition of tumour growth in a murine HNSCC model resistant to PD-1 blockade. Coevolution of HPV− HNSCC and TILs is characterised by an “Infiltrating” phenotype and less tumour-specific PD-1+CD8+ TILs, which may provide a framework for further translational studies and patient stratification.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#33

 

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Description This case–control study compared the body composition, resting metabolic rate (RMR), and respiratory quotient (RQ) of narcolepsy patients with those of body mass index (BMI)- gender and age-matched controls. This study included 14 male patients with narcolepsy and 14 matched controls. The narcolepsy patients were subdivided into two subgroups (n = 7/each): those with cataplexy (NT1) and those without cataplexy (NT2). Anthropometric measurements, bioelectric impedance analysis, and indirect calorimetry were used in addition to the calculation of common body-composition indices (conicity index, abdominal volume index, and body adiposity index). Our results showed no significant difference in fat percentage, fat mass, fat-free mass, and TBW among NT1, NT2, and controls (p > 0.05). Compared to matched controls, there was a reduction of muscle mass in both NT1 and NT2 subgroups. The RMR was similar in all groups, while patients in the NT1/NT2 subgroups had a lower RQ, used more fat and fewer carbohydrates during the fasting period. These findings give an insight into the distinctive state of altered metabolism in patients with narcolepsy, especially the resting metabolic rate, which was not altered in NT1 vs. NT2 compared to the controls when matched for BMI, age, and gender.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#34

 

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Description Cross-sectional studies have indicated potential for positron emission tomography (PET) in imaging tau pathology in Alzheimer’s disease (AD); however, its prognostic utility remains unproven. In a longitudinal, multi-modal, prognostic study of cognitive decline, 20 patients with a clinical biomarker-based diagnosis in the AD spectrum (mild cognitive impairment or dementia and a positive amyloid-beta PET scan) were recruited from the Cognitive Clinic at Karolinska University Hospital. The participants underwent baseline neuropsychological assessment, PET imaging with [18F]THK5317, [11C]PIB and [18F]FDG, magnetic resonance imaging, and in a subgroup cerebrospinal fluid (CSF) sampling, with clinical follow-up after a median 48 months (interquartile range = 32:56). In total, 11 patients declined cognitively over time, while 9 remained cognitively stable. The accuracy of baseline [18F]THK5317 binding in temporal areas was excellent at predicting future cognitive decline (area under the receiver operating curve 0.84–1.00) and the biomarker levels were strongly associated with the rate of cognitive decline (β estimate −33.67 to −31.02, p < 0.05). The predictive accuracy of the other baseline biomarkers was poor (area under the receiver operating curve 0.58–0.77) and their levels were not associated with the rate of cognitive decline (β estimate −4.64 to 15.78, p > 0.05). Baseline [18F]THK5317 binding and CSF tau levels were more strongly associated with the MMSE score at follow-up than at baseline (p < 0.05). These findings support a temporal dissociation between tau deposition and cognitive impairment, and suggest that [18F]THK5317 predicts future cognitive decline better than other biomarkers. The use of imaging markers for tau pathology could prove useful for clinical prognostic assessment and screening before inclusion in relevant clinical trials.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#35

 

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Description With the ever-increasing availability of whole-genome sequences, machine-learning approaches can be used as an alternative to traditional alignment-based methods for identifying new antimicrobial-resistance genes. Such approaches are especially helpful when pathogens cannot be cultured in the lab. In previous work, we proposed a game-theory-based feature evaluation algorithm. When using the protein characteristics identified by this algorithm, called ‘features’ in machine learning, our model accurately identified antimicrobial resistance (AMR) genes in Gram-negative bacteria. Here we extend our study to Gram-positive bacteria showing that coupling game-theory-identified features with machine learning achieved classification accuracies between 87% and 90% for genes encoding resistance to the antibiotics bacitracin and vancomycin. Importantly, we present a standalone software tool that implements the game-theory algorithm and machine-learning model used in these studies.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#36

 

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Description The identification of clinically-relevant early diagnostic and prognostic protein biomarkers is essential to maximize therapeutic efficacy and prevent cancer progression. The aim of the current study is to determine whether aberrant plasma protein profile can be applied as a surrogate tool for early diagnosis of bladder carcinoma. Plasma samples from patients with low grade non-muscle invasive bladder cancer and healthy controls were analyzed using combined 2D-DIGE and mass-spectrometry to identify differentially expressed proteins. Validation was performed using western blotting analysis in an independent cohort of cancer patients and controls. Fifteen differentially-expressed proteins were identified of which 12 were significantly up-regulated and three were significantly down-regulated in tumors compared to controls. The Ingenuity Pathways Analysis revealed functional connection between the differentially-expressed proteins and immunological disease, inflammatory disease and cancer mediated through chemokine and cytokine signaling pathway and NF-kB transcription factor. Among the three validated proteins, haptoglobin was able to distinguish between patients with low grade bladder cancer and the controls with high sensitivity and specificity (AUC > 0.87). In conclusion, several biomarker proteins were identified in bladder cancer. Haptoglobin is a potential candidate that merit further investigation to validate its usefulness and functional significance as potential biomarkers for early detection of bladder cancer.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#38

 

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Description Chronic kidney diseases have become a major issue worldwide. The spectrum of biopsy proven renal diseases differs between locations and changes over time. It is therefore essential to describe the local epidemiological trends and the prevalence of renal biopsy in various regions to shine new light on the pathogenesis of various renal diseases and provide a basis for further hypothesis-driven research. We retrospectively analyzed 34,630 hospitalized patients undergoing native renal biopsy between January 1, 2009 and December 31, 2018. Indications for renal biopsy and histological diagnosis were analyzed to describe the prevalence of renal biopsy, and changing prevalence between period 1 (2009–2013) and period 2 (2014–2018) were further analyzed. Nephrotic syndrome (NS) was the most common indication for biopsy. Membranous nephropathy (MN, 24.96%) and IgA nephropathy (IgAN, 24.09%) were the most common primary glomerulonephritis (PGN). MN was most common in adults, with IgAN more prevalent in children. Lupus nephritis (LN) was the most common secondary glomerulonephritis (SGN) in adults, while Henöch–Schönlein purpura nephritis (HSPN) in children. The prevalence of MN increased significantly and nearly doubled from period 1 (15.98%) to period 2 (30.81%) (P = 0.0004). The same trend appeared with membranoproliferative glomerulonephritis (MPGN), diabetic nephropathy (DN) and obesity-related glomerulopathy (ORG), while the frequencies of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), LN and hepatitis B associated glomerulonephritis (HBV-GN) significantly decreased between the two intervals. NS was the most common indication for biopsy across all age groups and genders. MN has overtaken IgAN to become the most common PGN in adults, while IgAN was the most common PGN in children. LN was the most common SGN in adults, and HSPN the most common in children.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#39

 

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Description It is unclear whether smoking interacts with different aspects of Epstein–Barr virus (EBV) infection with regard to multiple sclerosis (MS) risk. We aimed to investigate whether smoking acts synergistically with elevated EBNA-1 antibody levels or infectious mononucleosis (IM) history regarding MS risk. Two Swedish population-based case–control studies were used (6,340 cases and 6,219 matched controls). Subjects with different smoking, EBNA-1 and IM status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Current and past smokers had higher EBNA-1 antibody levels than never smokers (p < 0.0001). There was an additive interaction between current smoking and high EBNA-1 antibody levels (AP 0.3, 95% CI 0.2–0.4), but not between past smoking and high EBNA-1 antibody levels (AP 0.01, 95% CI − 0.1 to 0.1), with regard to MS risk. An interaction also occurred between current smoking and IM history (AP 0.2, 95% CI 0.004–0.4), but not between past smoking and IM history (AP − 0.06, 95% CI − 0.4 to 0.3). Current smoking increases EBNA-1 antibody levels and acts synergistically with both aspects of EBV infection to increase MS risk, indicating that there is at least one pathway to disease in which both risk factors are involved.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#40

 

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Description Polycyclic xanthones are secondary metabolites from actinomycetes and cervinomycin A and B are bioactive 26-membered polycyclic xanthones from Streptomyces sp. CPCC 204980. Herein, we report cervinomycins C1-4 (1–4) from the same strain. The structures of 1–4 were determined by 1D- and 2D-NMR, or single-crystal X-ray diffraction. Compounds 1–4 feature the open or loss of A (oxazolidine) ring in their angular polycyclic framework compared with cervinomycin B. Compounds 1–4 showed potent cytotoxicity against human cancer cell lines HCT116 and BxPC-3, with IC50 at 0.9–801.0 nM and strong anti-Gram-positive bacterial activity.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#41

 

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Description ER stress and apoptosis contribute to the loss of pancreatic β-cells under pro-diabetic conditions of glucolipotoxicity. Although activation of canonical intrinsic apoptosis is known to require pro-apoptotic Bcl-2 family proteins Bax and Bak, their individual and combined involvement in glucolipotoxic β-cell death are not known. It has also remained an open question if Bax and Bak in β-cells have non-apoptotic roles in mitochondrial function and ER stress signaling, as suggested in other cell types. Using mice with individual or combined β-cell deletion of Bax and Bak, we demonstrated that glucolipotoxic β-cell death in vitro occurs by both non-apoptotic and apoptotic mechanisms, and the apoptosis could be triggered by either Bax or Bak alone. In contrast, they had non-redundant roles in mediating staurosporine-induced apoptosis. We further established that Bax and Bak do not affect normal glucose-stimulated β-cell Ca2+ responses, insulin secretion, or in vivo glucose tolerance. Finally, our experiments revealed that combined deletion of Bax and Bak amplified the unfolded protein response in islets during the early stages of chemical- or glucolipotoxicity-induced ER stress. These findings shed new light on roles of the core apoptosis machinery in β-cell survival and stress signals of importance for the pathobiology of diabetes.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#42

 

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Description SAGA (Spt-Ada-Gcn5 acetyltransferase) is a highly conserved transcriptional coactivator that consists of four functionally independent modules. Its two distinct enzymatic activities, histone acetylation and deubiquitylation, establish specific epigenetic patterns on chromatin and thereby regulate gene expression. Whereas earlier studies emphasized the importance of SAGA in regulating global transcription, more recent reports have indicated that SAGA is involved in other aspects of gene expression and thus plays a more comprehensive role in regulating the overall process. Here, we discuss recent structural and functional studies of each SAGA module and compare the subunit compositions of SAGA with related complexes in yeast and metazoans. We discuss the regulatory role of the SAGA deubiquitylating module (DUBm) in mRNA surveillance and export, and in transcription initiation and elongation. The findings suggest that SAGA plays numerous roles in multiple stages of transcription. Further, we describe how SAGA is related to human disease. Overall, in this report, we illustrate the newly revealed understanding of SAGA in transcription regulation and disease implications for fine-tuning gene expression. A protein that helps add epigenetic information to genome, SAGA, controls many aspects of gene activation, potentially making it a target for cancer therapies. To fit inside the tiny cell nucleus, the genome is tightly packaged, and genes must be unpacked before they can be activated. Known to be important in genome opening, SAGA has now been shown to also play many roles in gene activation. Daeyoup Lee at the KAIST, Daejeon, South Korea, and co-workers have reviewed recent discoveries about SAGA’s structure, function, and roles in disease. They report that SAGA’s complex (19 subunits organized into four modules) allows it to play so many roles, genome opening, initiating transcription, and efficiently exporting mRNAs. Its master role means that malfunction of SAGA may be linked to many diseases.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#43

 

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Description The biggest challenge in colorectal cancer therapy is to avoid intestinal drug absorption before reaching the colon, while focusing on tumor specific delivery with high local concentration and minimal toxicity. In our work, thymoquinone (TQ)-loaded polymeric nanocapsules were prepared using the nanoprecipitation technique using Eudragit S100 as polymeric shell. Conjugation of anisamide as a targeting ligand for sigma receptors overexpressed by colon cancer cells to Eudragit S100 was carried out via carbodiimide coupling reaction, and was confirmed by thin layer chromatography and 1H-NMR. TQ nanocapsules were characterized for particle size, surface morphology, zeta potential, entrapment efficiency % (EE%), in vitro drug release and physical stability. A cytotoxicity study on three colon cancer cell lines (HT-29, HCT-116, Caco-2) was performed. Results revealed that the polymeric nanocapsules were successfully prepared, and the in vitro characterization showed a suitable size, zeta potential, EE% and physical stability. TQ exhibited a delayed release pattern from the nanocapsules in vitro. Anisamide-targeted TQ nanocapsules showed higher cytotoxicity against HT-29 cells overexpressing sigma receptors compared to their non-targeted counterparts and free TQ after incubation for 48 h, hence delineating anisamide as a promising ligand for active colon cancer targeting.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#44

 

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Description Isolated hypogonadotropic hypogonadism (IHH), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) constitute a disease spectrum whose etiology remains largely unknown. This study aimed to clarify whether mutations in SMCHD1, an epigenetic regulator gene, might underlie this disease spectrum. SMCHD1 is a causative gene for Bosma arhinia microphthalmia syndrome characterized by arhinia, microphthalmia and IHH. We performed mutation screening of SMCHD1 in patients with etiology-unknown IHH (n = 31) or CPHD (n = 43, 19 of whom also satisfied the SOD diagnostic criteria). Rare variants were subjected to in silico analyses and classified according to the American College of Medical Genetics and Genomics guidelines. Consequently, a rare likely pathogenic variant, p.Asp398Asn, was identified in one patient. The patient with p.Asp398Asn exhibited CPHD, optic nerve hypoplasia, and a thin retinal nerve fiber layer, and therefore satisfied the criteria of SOD. This patient showed a relatively low DNA methylation level of the 52 SMCHD1-target CpG sites at the D4Z4 locus. Exome sequencing for the patient excluded additional variants in other IHH/CPHD-causative genes. In vitro assays suggested functional impairment of the p.Asp398Asn variant. These results provide the first indication that SMCHD1 mutations represent a rare genetic cause of the HH-related disease spectrum.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#45

 

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Description Brain-on-a-chip systems are designed to simulate brain activity using traditional in vitro cell culture on an engineered platform. It is a noninvasive tool to screen new drugs, evaluate toxicants, and elucidate disease mechanisms. However, successful recapitulation of brain function on these systems is dependent on the complexity of the cell culture. In this study, we increased cellular complexity of traditional (simple) neuronal cultures by co-culturing with astrocytes and oligodendrocyte precursor cells (complex culture). We evaluated and compared neuronal activity (e.g., network formation and maturation), cellular composition in long-term culture, and the transcriptome of the two cultures. Compared to simple cultures, neurons from complex co-cultures exhibited earlier synapse and network development and maturation, which was supported by localized synaptophysin expression, up-regulation of genes involved in mature neuronal processes, and synchronized neural network activity. Also, mature oligodendrocytes and reactive astrocytes were only detected in complex cultures upon transcriptomic analysis of age-matched cultures. Functionally, the GABA antagonist bicuculline had a greater influence on bursting activity in complex versus simple cultures. Collectively, the cellular complexity of brain-on-a-chip systems intrinsically develops cell type-specific phenotypes relevant to the brain while accelerating the maturation of neuronal networks, important features underdeveloped in traditional cultures.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#46

 

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Description Rapid whole genome sequencing (rWGS) of peripheral blood has been used to detect microbial DNA in acute infections. Cytomegalovirus (CMV) is a herpesvirus capable of causing severe disease in neonates and immunocompromised patients. We identified CMV in patients undergoing diagnostic rWGS by matching reads that did not align to the human reference genome to a database of microbial genomes. rWGS was conducted on peripheral blood obtained from ill pediatric patients (age 1 day to 18 years). Reads not aligning to the human genome were analyzed using an in-house pipeline to identify DNA consistent with CMV infection. Of 669 patients who received rWGS from July 2016 through July 2019, we identified 28 patients (4.2%) with reads that aligned to the CMV reference genome. Six of these patients had clinical findings consistent with symptomatic CMV infection. Positive results were highly correlated (R2 > 0.99, p < 0.001) to a CMV-qPCR assay conducted on DNA isolated from whole blood samples. In acutely ill children receiving rWGS for diagnosis of genetic disease, we propose analysis of patient genetic data to identify CMV, which could impact treatment of up to 4% of children in the intensive care unit.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#47

 

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Description To study the antimicrobial effects of quaternary ammonium silane (QAS) exposure on Streptococcus mutans and Lactobacillus acidophilus bacterial biofilms at different concentrations. Streptococcus mutans and Lactobacillus acidophilus biofilms were cultured on dentine disks, and incubated for bacterial adhesion for 3-days. Disks were treated with disinfectant (experimental QAS or control) and returned to culture for four days. Small-molecule drug discovery-suite was used to analyze QAS/Sortase-A active site. Cleavage of a synthetic fluorescent peptide substrate, was used to analyze inhibition of Sortase-A. Raman spectroscopy was performed and biofilms stained for confocal laser scanning microscopy (CLSM). Dentine disks that contained treated dual-species biofilms were examined using scanning electron microscopy (SEM). Analysis of DAPI within biofilms was performed using CLSM. Fatty acids in bacterial membranes were assessed with succinic-dehydrogenase assay along with time-kill assay. Sortase-A protein underwent conformational change due to QAS molecule during simulation, showing fluctuating alpha and beta strands. Spectroscopy revealed low carbohydrate intensities in 1% and 2% QAS. SEM images demonstrated absence of bacterial colonies after treatment. DAPI staining decreased with 1% QAS (p < 0.05). Fatty acid compositions of dual specie biofilm increased in both 1% and 2% QAS specimens (p < 0.05). Quaternary ammonium silane demonstrated to be a potent antibacterial cavity disinfectant and a plaque inhibitor and can be of potential significance in eliminating caries-forming bacteria.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#48

 

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Description Carbohydrate antigen 125 (CA125) is a congestion and inflammation biomarker and has been proved to be related to a worse prognosis in heart diseases. However, the precise relationship between elevated CA125 in patients with ST-segment elevation myocardial infarction (STEMI) has not yet been sufficiently studied. We set out to determine the association of CA125 with all-cause mortality at 6 months in STEMI. CA125, N-terminal pro brain natriuretic peptide (NTproBNP) and high sensitive C-reactive protein (hs-CRP) were measured in 245 patients admitted consecutively with STEMI undergoing coronary angioplasty. The mean age in our sample was 63.7 years, 64.9% were males, 28.3% had diabetes and 17.7% presented with acute heart failure (Killip ≥ 2). The median serum level of CA125 was 8.1 U/ml. At 6 months, the rate of all-cause mortality was 18% (44 patients). Receiver operating characteristic curve analysis demonstrated that CA125 presented similar performance to predict mortality as NTproBNP and hs-CRP. Patients with CA125 ≥ 11.48 had a higher rate of mortality (Hazard Ratio = 2.07, 95% confidence interval = 1.13–3.77, p = 0.017) than patients with CA125 < 11.48. This study suggests that elevated CA125 levels might be used to identify patients with STEMI with a higher risk of death at 6 months. CA125 seems to be a similar predictor of mortality compared to NTproBNP and hs-CRP.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#49

 

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Description Tesla would build “microfactories” at Grohmann Automation in Germany. CureVac is also reportedly building a stationary site with an aim to increase the output of the vaccines “to billions of doses”.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#50

 

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Description The objective of the study was to demonstrate the non-inferiority of low-frequency spa therapy combined with rehabilitation (Spa-rehab) versus standard spa therapy at 6 months for symptomatic knee osteoarthritis (KOA). A prospective, randomized, monocenter, non-inferiority trial with recruitment of community-based symptomatic KOA patients was performed. Standard spa therapy comprised standardized spa treatment, 6 days a week for 3 weeks, and Spa-rehab therapy comprised spa sessions, 3 days a week for 3 weeks, followed by a dedicated rehabilitation program, 3 days a week for 3 weeks. The primary endpoint was achieving at 6 months a minimal clinically important improvement (MCII) for pain on a visual analog scale and/or an MCII for function on the WOMAC index and no knee surgery (composite MCII). Secondary endpoints were composite MCII at 3 months and achieving a Patient Acceptable Symptom State (PASS) for pain and function at 3 and 6 months. Among 283 patients included, 145 were allocated to standard spa therapy and 138 to Spa-rehab therapy. We could not demonstrate the non-inferiority of Spa-rehab therapy for the primary endpoint: difference for responders − 0.08 [90% CI (− 0.18 to 0.02), p = 0.14]. However, the difference test between the groups was not significant (p = 0.18). Spa-rehab therapy was not inferior to standard spa therapy for the composite MCII at 3 months or the PASS at 3 and 6 months. Spa-rehab therapy can reasonably be proposed to patients with symptomatic KOA. This protocol may be more cost-effective than standard spa therapy and avoid absenteeism from work and accommodation costs for patients who live close to a centre.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#51

 

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Description Preclinical models that reliably recapitulate the immunosuppressive properties of human gliomas are essential to assess immune-based therapies. GL261 murine glioma cells are widely used as a syngeneic animal model of glioma, however, it has become common practice to transfect these cells with luciferase for fluorescent tumor tracking. The aim of this study was to compare the survival of mice injected with fluorescent or non-fluorescent GL261 cells and characterize the differences in their tumor microenvironment. Mice were intracranially implanted with GL261, GL261 Red-FLuc or GL261-Luc2 cells at varying doses. Cytokine profiles were evaluated by proteome microarray and Kaplan–Meier survival analysis was used to determine survival differences. Median survival for mice implanted with 5 × 104 GL261 cells was 18 to 21 days. The GL261 Red-FLuc implanted mice cells did not reach median survival at any tumor dose. Mice injected with 3 × 105 GL261-Luc2 cells reached median survival at 23 days. However, median survival was significantly prolonged to 37 days in mice implanted with 5 × 104 GL261-Luc2 cells. Additionally, proteomic analyses revealed significantly elevated inflammatory cytokines in the supernatants of the GL261 Red-FLuc cells and GL261-Luc2 cells. Our data suggest that GL261 Red-FLuc and GL261-Luc2 murine models elicit an anti-tumor immune response by increasing pro-inflammatory modulators.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#52

 

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Description The study was aimed at assessing the diagnostic performance of 68Ga-PSMA-617 PET/CT in the detection of prostate cancer (PCa) in patients with a prostate-specific antigen (PSA) level of 4–20 ng/ml and to compare its efficacy with that of multiparametric MRI (mpMRI). We analyzed the data of 67 consecutive patients with PSA levels of 4–20 ng/ml who almost simultaneously underwent 68Ga-PSMA-617 PET/CT and mpMRI. 68Ga-PSMA-617 PET/CT and mpMRI diagnostic performances were compared via receiver operating characteristic (ROC) curve analysis. Of the 67 suspected PCa cases, 33 had pathologically confirmed PCa. 68Ga-PSMA-617 PET/CT showed a patient-based sensitivity, specificity, and positive and negative predictive values (PPVs and NPVs) of 87.88%, 88.24%, 87.88%, and 88.24%, respectively. The corresponding values for mpMRI were 84.85%, 52.94%, 63.64%, and 78.26%. The area under the curve values for 68Ga-PSMA-617 PET/CT and mpMRI were 0.881 and 0.689, respectively. 68Ga-PSMA-617 PET/CT showed a better diagnostic performance than mpMRI in the detection of PCa in patients with PSA levels of 4–20 ng/ml.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#53

 

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Description Cr-LAAO, an l-amino acid oxidase isolated from Calloselasma rhodosthoma snake venom, has been demonstrated as a potent stimulus for neutrophil activation and inflammatory mediator production. However, the mechanisms involved in Cr-LAAO induced neutrophil activation has not been well characterized. Here we investigated the mechanisms involved in Cr-LAAO-induced lipid body (also known as lipid droplet) biogenesis and eicosanoid formation in human neutrophils. Using microarray analysis, we show for the first time that Cr-LAAO plays a role in the up-regulation of the expression of genes involved in lipid signalling and metabolism. Those include different members of phospholipase A2, mostly cytosolic phospholipase A2-α (cPLA2-α); and enzymes involved in prostaglandin synthesis including cyclooxygenases 2 (COX-2), and prostaglandin E synthase (PTGES). In addition, genes involved in lipid droplet formation, including perilipin 2 and 3 (PLIN 2 and 3) and diacylglycerol acyltransferase 1 (DGAT1), were also upregulated. Furthermore, increased phosphorylation of cPLA2-α, lipid droplet biogenesis and PGE2 synthesis were observed in human neutrophils stimulated with Cr-LAAO. Treatment with cPLA2-α inhibitor (CAY10650) or DGAT-1 inhibitor (A922500) suppressed lipid droplets formation and PGE2 secretion. In conclusion, we demonstrate for the first time the effects of Cr-LAAO to regulate neutrophil lipid metabolism and signalling.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#54

 

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Description Irritable bowel syndrome (IBS) is a functional disorder of brain-gut interactions. Differential brain responses to rectal distention between IBS and healthy controls (HCs) have been demonstrated, particularly in the pain matrix and the default mode network. This study aims to compare resting-state functional properties of these networks between IBS patients and HCs using graph analysis in two independent cohorts. We used a weighted graph analysis of the adjacency matrix based on partial correlations between time series in the different regions in each subject to determine subject specific graph measures. These graph measures were normalized by values obtained in equivalent random networks. We did not find any significant differences between IBS patients and controls in global normalized graph measures, hubs, or modularity structure of the pain matrix and the DMN in any of our two independent cohorts. Furthermore, we did not find consistent associations between these global network measures and IBS symptom severity or GI-specific anxiety but we found a significant difference in the relationship between measures of psychological distress (anxiety and/or depressive symptoms) and normalized characteristic path length. The responses of these networks to visceral stimulation rather than their organisation at rest may be primarily disturbed in IBS.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#55

 

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Description IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) may have protective properties in cardiovascular and rheumatic diseases. We here compare these antibodies in systemic rheumatic conditions and study their properties. Anti-PC and anti-MDA was measured using ELISA in patients with SLE (374), RA (354), Mixed connective tissue disease (MCTD, 77), Systemic sclerosis (SSc, 331), Sjögren’s syndrome (SjS, 324), primary antiphospholipid syndrome (PAPs, 65), undifferentiated connective tissue disease (UCTD, 118) and 515 matched healthy controls (HC). Cardiovascular score (CV) was broadly defined based on clinical disease symptoms. Anti-PC and anti-MDA peptide/protein characterization were compared using a proteomics de novo sequencing approach. anti-MDA and anti-PC were extracted from total IgM. The proportion of Treg cells was determined by flow cytometry. The maximal difference between cases and controls was shown for MCTD: significantly lower IgM Anti-PC but not anti-MDA among patients (median 49.3RU/ml vs 70.4 in healthy controls, p(t-test) = 0.0037). IgM low levels were more prevalent in MCTD, SLE, SjS, SSc and UCTD. IgM anti-PC variable region profiles were different from and more homologous than anti-MDA. Anti-PC but not anti-MDA were significantly negatively correlated with CV in the whole patient group. In contrast to IgM anti-PC, anti-MDA did not promote polarization of Tregs. Taken together, Anti-PC is decreased in MCTD and also in SLE, SjS and SSc but not in other studied diseases. Anti-PC may thus differentiate between these. In contrast, anti-MDA did not show these differences between diseases studied. Anti-PC level is negatively correlated with CV in the patient group cohort. In contrast to anti-PC, anti-MDA did not promote Treg polarization. These findings could have both diagnostic and therapeutic implications, one possibility being active or passive immunization with PC in some rheumatic conditions.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#56

 

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Description Numerous essential metal elements (EMEs) are necessary to maintain the proper function of human body. In this case-control study, we investigated the associations of 11 EMEs [Calcium (Ca), potassium (K), magnesium (Mg), sodium (Na), manganese (Mn), selenium (Se), cobalt (Co), Molybdenum (Mo), copper (Cu), zinc (Zn), and iron (Fe)] in serum with the risk of schizophrenia. We recruited first-episode and drug-naïve schizophrenic patients (cases = 99) and age-sex-matched normal subjects (controls = 99) from Tangshan, Hebei Province, China. The 11 EMEs in serum from cases and controls were quantified by inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. We observed that a higher level of Mn (OR = 2.390; 95%CI: 1.504–3.796) and lower levels of Ca (OR = 0.939; 95%CI: 0.890–0.990), Mg (OR = 0.806; 95%CI: 0.669–0.972), Na (OR = 0.995; 95%CI: 0.993–0.998), and Se (OR = 0.954; 95%CI: 0.937–0.972) were associated with an elevated risk of schizophrenia. Dose–response relationships between serum EME concentrations and the risk of schizophrenia were observed in most of the schizophrenia-associated EMEs. Moreover, the serum concentrations of these schizophrenia-associated EMEs in patients were correlated with the severity of their clinical symptoms. Significant correlations were found between EMEs and biomarkers associated with schizophrenia related to metabolic and oxidative stress. This study suggested that the concentration and profile of EMEs were different between schizophrenic patients and normal controls and revealed potential metabolisms associated with EMEs and schizophrenia, suggesting EMEs might act as biomarkers of schizophrenia to improve the current situation of diagnosis and treatment.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#57

 

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Description The proper differentiation and maintenance of regulatory T cells in the gut is coordinated by a neural arc that connects the gut to the brain via liver sensory afferent neurons.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#58

 

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Description As Nature Communications celebrates a 10-year anniversary, the field has witnessed the transition of cancer immunotherapy from a pipe dream to an established powerful cancer treatment modality. Here we discuss the opportunities and challenges for the future.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#59

 

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Description

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#60

 

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Description

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#61

 

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Description Colorectal carcinoma (CRC) with deficient mismatch repair (dMMR) is an etiologically heterogeneous molecular entity. We investigated the genetic profile, focusing on key signaling pathways and molecular diversity of dMMR CRCs. In this study, next-generation sequencing was applied to 156 consecutive dMMR CRCs and 225 randomly selected proficient MMR (pMMR) CRCs diagnosed between July 2015 and December 2019 at Peking Union Medical College Hospital. Genetic alterations and MLH1 promoter hypermethylation (MLH1me+) were analyzed. Among the most frequently mutated genes, RNF43, ARID1A, PIK3CA, ATM, and BRCA2 mutants were enriched in dMMR CRCs, whereas APC and TP53 mutations were enriched in pMMR CRCs. In dMMR group, RNF43, APC, ARID1A, and BRCA2 mutations were largely microsatellite instability events. WNT pathway was commonly altered regardless of MMR status. Compared to pMMR CRCs, dMMR CRCs had remarkably more prevalent PI3K, RTK-RAS, TGFβ, and DNA damage repair pathway alterations and more multiple mutations in WNT and PI3K pathways. Within dMMR tumors, mutual exclusivity occurred between CTNNB1 mutation and APC or RNF43 mutation, while coexistence existed between BRAF and RNF43 mutation, as well as RAS and APC mutation. MLH1me+ dMMR CRCs had significantly more frequent RNF43 mutations but less frequent KRAS, APC, and CTNNB1 mutations comparing to MLH1-unmethylated dMMR CRCs. RNF43/BRAF comutations were detected in MLH1me+ dMMR CRCs, whereas RAS/APC comutations were largely detected in Lynch syndrome-associated cases. RNF43 mutation was independently associated with MLH1me+ rather than BRAF mutations. dMMR CRCs bearing receptor tyrosine kinase fusion demonstrated no additional RTK-RAS mutations, significantly fewer PI3K alterations and more TGFBR2 mutations than other dMMR tumors. Our study revealed that dMMR CRCs had distinctive gene mutation spectra and signaling pathway interaction patterns compared to proficient mismatch repair (pMMR) CRCs, and molecular heterogeneity was evident for these divergent oncogenic pathways. These findings justify the use of individualized therapy targeted to dMMR CRC subgroups.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#63

 

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Description

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#64

 

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Description Mammalian DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B, which exhibit both redundant and distinctive methylation activities. However, the related molecular basis remains undetermined. Through comprehensive structural, enzymology and cellular characterization of DNMT3A and DNMT3B, we here report a multi-layered substrate-recognition mechanism underpinning their divergent genomic methylation activities. A hydrogen bond in the catalytic loop of DNMT3B causes a lower CpG specificity than DNMT3A, while the interplay of target recognition domain and homodimeric interface fine-tunes the distinct target selection between the two enzymes, with Lysine 777 of DNMT3B acting as a unique sensor of the +1 flanking base. The divergent substrate preference between DNMT3A and DNMT3B provides an explanation for site-specific epigenomic alterations seen in ICF syndrome with DNMT3B mutations. Together, this study reveals distinctive substrate-readout mechanisms of the two DNMT3 enzymes, implicative of their differential roles during development and pathogenesis. In mammals, DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B. Here the authors report the crystal structures of DNMT3B in complex with both CpG and CpA DNA, providing insight into the substrate-recognition mechanism underpinning the divergent genomic methylation activities of DNMT3A and DNMT3B.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#65

 

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Description Many of the people behind world-changing medical discoveries wouldn't have got into medical school by today’s standards, thanks to poor grades or misbehaving

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#66

 

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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 03 July 2020

#67

 

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Name
Description TBD

#Medicine & Human body;#Psychology
Field # Medicine & Human body
Updated 03 July 2020

#68

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#69

 

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Description On Feb. 11, 2020, the World Health Organization put a name to the mysterious respiratory disease spreading with alarming speed around the globe: COVID-19.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#70

 

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Description University of Wisconsin–Madison researchers have developed a safer and more efficient way to deliver a promising new method for treating cancer and liver disorders and for vaccination — including a COVID-19 vaccine from Moderna Therapeutics that has advanced to clinical trials with humans. The te

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#71

 

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Description The Americas have become the biggest covid-19 hotspot with almost half of all the world's cases, but some countries in the region have found strategies to buck the trend

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#72

 

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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 03 July 2020

#73

 

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Description Researchers at the University of Alberta have found a way to deliver anti-cancer drugs with more precision, which could increase the effectiveness of many cancer treatments. U of A oncologist Frank Wuest altered the surface of nanoparticles, which are well suited to deliver drugs, with epidermal

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#74

 

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Description Genomics carries great expectations: the power to help health-care providers assess and assist their patients in managing their individualized risks for common, serious medical conditions, such as cancer and heart disease.  However, how to effectively meld genetic risk assessments into health care i

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#75

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#76

 

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Description New research from The University of Queensland has found that women who have hot flushes and night sweats after menopause are 70 per cent more likely to have heart attacks, angina and strokes. School of Public Health PhD student Dr Dongshan Zhu has found women of any age who experience hot fl

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#77

 

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Description Facebook said Thursday it would offer reminders to its users to wear protective masks, responding to the latest surge in US coronavirus cases, which has sparked renewed fears of containing the pandemic.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#78

 

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Description The gut bacteria in some people have acquired genes for digesting seaweed fibres in a transfer from marine bacteria. We don't know what effect this has on health, but it could be harmful

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#79

 

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Description Type 2 diabetes is a major burden on healthcare systems in the entire world. It is especially prevalent among older men, who typically don’t follow healthy diets, don’t exercise and generally don’t take good care of themselves. Now a team of scientists led by the University of Adelaide found that tw

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#80

 

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Description Naked mole-rats can live for an incredibly long time and have an exceptional resistance to cancer thanks to unique conditions in their bodies that stop cancer cells multiplying, according to new research. Understanding how these remarkable animals are almost completely immune to cancer could impr

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#81

 

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Description A new technique could help reduce antibiotic prescribing by predicting which drugs could be effective in fighting bacteria within minutes. Scientists at the University of Exeter have developed the method, which allows users to see whether a bacterium is likely to respond to antibiotics. The res

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#82

 

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Description The genetic variation of the novel coronavirus that dominates the world today infects human cells more readily than the original that emerged in China, according to a new study published in the journal Cell on Thursday.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#83

 

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Description Coronavirus-centric searches have dropped, but volumes remain more than double that of February, Google revealed while detailing search trends in India for the month of June.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#84

 

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Description The condition is now commonly known as multisystem inflammatory syndrome in children or MIS-C.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#85

 

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Description A study found it was not just individuals with COVID-19 who showed T-cell immunity but also many of their exposed asymptomatic family members.

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#86

 

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Name
Description It’s all about the living garden, and garden living

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#87

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 03 July 2020

#88

 

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Name
Description Although the severity of influenza virus infections has been associated with host energy metabolism, the related mechanisms have not yet been clarified. Here we examined the effects of influenza virus infection on host energy metabolism in mice. After infecting mice with intranasal applications of 500 plaque-forming units of A/Puerto Rico/8/34 (H1N1; PR8) virus, the serum levels of most intermediates in the tricarboxylic acid (TCA) cycle and related metabolic pathways were significantly reduced. These data suggest that substrate supply to the TCA cycle is reduced under these conditions, rather than specific metabolic reactions being inhibited. Then, we focused on glucose and fatty acid metabolism that supply substrates to the TCA cycle. Akt phosphorylation following insulin injections was attenuated in the livers of PR8 virus-infected mice. Furthermore, glucose tolerance tests revealed that the PR8 virus-infected mice showed higher blood glucose levels than the vehicle-inoculated control mice. These results suggest that influenza virus infection impairs insulin signaling, which regulates glucose uptake. However, increases in the hepatic expressions of fatty acid-metabolizing enzymes suggest that fatty acids accumulate in liver cells of infected mice. Collectively, our data indicate that influenza virus infection dysregulates host energy metabolism. This line of investigation provides novel insights into the pathogenesis of influenza.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#89

 

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Description Stripe or yellow rust (YR) caused by Puccinia striiformis Westend. f. sp. tritici Erikss. is a persistent biotic-stress threatening global wheat production. To broaden our understanding of the shared genetic basis of YR resistance across multi-site and multi-year evaluations, we performed a large genome-wide association study using 43,706 YR observations on 23,346 wheat lines from the International Maize and Wheat Improvement Center evaluated between 2013 and 2019 at sites in India, Kenya and Mexico, against predominant races prevalent in the countries. We identified 114 repeatable markers tagging 20 quantitative trait loci (QTL) associated with YR on ten chromosomes including 1D, 2A, 2B, 2D, 3A, 4A, 4D, 5A, 5B and 6B, among which four QTL, QYr.cim-2DL.2, QYr.cim-2AS.1, QYr.cim-2BS.2 and QYr.cim-2BS.3 were significant in more than ten datasets. Furthermore, we report YR-associated allelic fingerprints for the largest panel of wheat breeding lines (52,067 lines) till date, creating substantial opportunities for YR favorable allele enrichment using molecular markers. Overall, the markers and fingerprints reported in this study provide excellent insights into the genetic architecture of YR resistance in different geographical regions, time-periods and wheat germplasm and are a huge resource to the global wheat breeding community for accelerating YR resistance breeding efforts.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#90

 

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Description Enriching brain DHA is believed to be beneficial for the prevention and treatment of several neurological diseases, including Alzheimer’s disease. An impediment in assessing the effectiveness of the treatments is the lack of a reliable biomarker for brain DHA. The commonly used erythrocyte omega-3 index is not suitable for brain because of the involvement of unique transporter at the blood brain barrier (BBB). We recently showed that dietary lysophosphatidylcholine (LPC)-DHA significantly increases brain DHA, which results in increase of brain BDNF. Since there is bidirectional transport of BDNF through the BBB, we tested the hypothesis that plasma BDNF may be used as biomarker for brain DHA enrichment. We altered the brain DHA in rats and mice over a wide range using different dietary carriers of DHA, and the correlations between the increase in brain omega-3 index with the increases in plasma BDNF and the erythrocyte index were determined. Whereas the increase in brain omega-3 index positively correlated with the increase in plasma BDNF, it negatively correlated with the erythrocyte index. These results show that the plasma BDNF is more reliable than the erythrocyte index as biomarker for assessing the effectiveness of omega-3 supplements in improving brain function.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#91

 

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Description Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease that often recurs despite aggressive treatment with neoadjuvant chemotherapy and (radical) cystectomy. Basal and luminal molecular subtypes have been identified that are linked to clinical characteristics and have differential sensitivities to chemotherapy. While it has been suggested that epigenetic mechanisms play a role in defining these subtypes, a thorough understanding of the biological mechanisms is lacking. This report details the first genome-wide analysis of histone methylation patterns of human primary bladder tumours by chromatin immunoprecipitations and next-generation sequencing (ChIP-seq). We profiled multiple histone marks: H3K27me3, a marker for repressed genes, and H3K4me1 and H3K4me3, which are indicators of active enhancers and active promoters. Integrated analysis of ChIP-seq data and RNA sequencing revealed that H3K4 mono-methylation demarcates MIBC subtypes, while no association was found for the other two histone modifications in relation to basal and luminal subtypes. Additionally, we identified differentially methylated H3K4me1 peaks in basal and luminal tumour samples, suggesting that active enhancers play a role in defining subtypes. Our study is the first analysis of histone modifications in primary bladder cancer tissue and provides an important resource for the bladder cancer community.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#92

 

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Description Macroautophagy, the degradation of cytoplasmic content by lysosomal fusion, is an evolutionary conserved process promoting homeostasis and intracellular defence. Macroautophagy is initiated primarily by a complex containing ULK1 or ULK2 (two paralogs of the yeast Atg1 protein). To understand the differences between ULK1 and ULK2, we compared the human ULK1 and ULK2 proteins and their regulation. Despite the similarity in their enzymatic domain, we found that ULK1 and ULK2 have major differences in their autophagy-related interactors and their post-translational and transcriptional regulators. We identified 18 ULK1-specific and 7 ULK2-specific protein motifs serving as different interaction interfaces. We found that interactors of ULK1 and ULK2 all have different tissue-specific expressions partially contributing to diverse and ULK-specific interaction networks in various tissues. We identified three ULK1-specific and one ULK2-specific transcription factor binding sites, and eight sites shared by the regulatory region of both genes. Importantly, we found that both their post-translational and transcriptional regulators are involved in distinct biological processes—suggesting separate functions for ULK1 and ULK2. Unravelling differences between ULK1 and ULK2 could lead to a better understanding of how ULK-type specific dysregulation affects autophagy and other cellular processes that have been implicated in diseases such as inflammatory bowel disease and cancer.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#93

 

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Description Irreversible electroporation (IRE) is a non-thermal ablation modality that has been shown to be safe and effective in its application to tumors that are close to risky areas. This study aims to assess the safety and efficacy of IRE for unresectable hilar cholangiocarcinoma. Nine patients from two medical centers in Asia received IRE treatment between June 2015 and July 2017. Before IRE treatment, percutaneous biliary decompressions had been performed on eight patients, and internal stenting had been performed on one patient. All patients tolerated the procedure well without high-grade complications. The ablated tumors had constant size without contrast enhancement for more than three months in eight patients and the level of CA19-9 decreased significantly in all patients. The percutaneous biliary drainage tube was removed from two patients with recanalization of the bile duct. The internal stent in one patient was removed without further stenting. The median overall survival period was 26 months, and the progression-free survival was 18 months. Bile ducts remained narrow in the majority (2/3) of the treated patients. Nevertheless, IRE ablation of unresectable hilar cholangiocarcinoma involving vital structures is a safe and feasible primary treatment for local tumor control and is effective in prolonging survival.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#94

 

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Description Ten distinct cDNAs encoding five different protein phosphatases 1 (PPP1) were cloned from Nilaparvata lugens. NlPPP1α and NlPPP1β are highly conserved whereas NlPPP1-Y, NlPPP1-Y1 and NlPPP1-Y2 are lowly conserved among insects. NlPPP1α and NlPPP1β exhibited a ubiquitous expression, while NlPPP1-Y, NlPPP1-Y1, and NlPPP1-Y2 were obviously detected from the 4th instar nymph to imago developmental stages in males, especially detected in internal reproductive organ and fat bodies of the male. Injection nymphs with dsRNA of NlPPP1α or NlPPP1β was able to reduce the target gene expression in a range of 71.5–91.0%, inducing a maximum mortality rate of 95.2% or 97.2% at 10th day after injection and eclosion ratio down by 65.5–100.0%. Injection with dsNlPPP1Ys targeted to NlPPP1-Y, NlPPP1-Y1and NlPPP1-Y2 was able to induce a maximum mortality rate of 95.5% at 10th day after injection, eclosion ratio down by 86.4%. Knock-down one of the male-biased NlPPP1 genes has no effect on survival and eclosion ratio. Injection of 4th instar nymph with dsNlPPP1Ys led to reduced oviposition amount and hatchability, down by 44.7% and 19.6% respectively. Knock-down of NlPPP1-Y1 or NlPPP1-Y2 gene did not significantly affect oviposition amount but significantly affected hatchability. The results indicate that the male-biased NlPPP1 genes have overlapping functions in N. lugens development, and NlPPP1-Y1 and NlPPP1-Y2 may play important roles in spermatogenesis and fertilization. The dsNlPPP1β and dsNlPPP1Ys in this study could be the preferred sequence in RNAi and low-conserved male-biased NlPPP1 genes could be potential target for N. lugens control.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#95

 

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Name
Description We elucidated the molecular cross-talk between cartilage and synovium in osteoarthritis, the most widespread arthritis in the world, using the powerful tool of single-cell RNA-sequencing. Multiple cell types were identified based on profiling of 10,640 synoviocytes and 26,192 chondrocytes: 12 distinct synovial cell types and 7 distinct articular chondrocyte phenotypes from matched tissues. Intact cartilage was enriched for homeostatic and hypertrophic chondrocytes, while damaged cartilage was enriched for prefibro- and fibro-, regulatory, reparative and prehypertrophic chondrocytes. A total of 61 cytokines and growth factors were predicted to regulate the 7 chondrocyte cell phenotypes. Based on production by > 1% of cells, 55% of the cytokines were produced by synovial cells (39% exclusive to synoviocytes and not expressed by chondrocytes) and their presence in osteoarthritic synovial fluid confirmed. The synoviocytes producing IL-1beta (a classic pathogenic cytokine in osteoarthritis), mainly inflammatory macrophages and dendritic cells, were characterized by co-expression of surface proteins corresponding to HLA-DQA1, HLA-DQA2, OLR1 or TLR2. Strategies to deplete these pathogenic intra-articular cell subpopulations could be a therapeutic option for human osteoarthritis.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#96

 

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Description A cohort study of 6,500,000 human pregnancies showed an increased risk of adverse fetal outcomes following abdominal but not non-abdominal surgery under general anesthesia. This may be the consequence of uterine handling during abdominal surgery. However, there are no data on any effects on the cardiometabolic physiology of the fetus or mother in response to uterine manipulation in otherwise healthy pregnancy. Consequently, 9 sheep in late gestation were anesthetized with isofluorane and maternal and fetal catheters and flow probes were implanted to determine cardiovascular and metabolic changes during uterine handling. Uterine handling led to an acute increase in uterine artery vascular resistance, fetal peripheral vasoconstriction, a reduction in oxygen delivery to the femoral circulation, worsening fetal acidosis. There was no evidence of systemic fetal hypoxia, or changes in fetal heart rate, carotid blood flow or carotid oxygen delivery. Therefore, the data support that uterine handling during abdominal surgery under general anesthesia can impact adversely on fetal cardiometabolic health. This may provide a potential explanation linking adverse fetal outcomes in abdominal compared with non-abdominal surgery during pregnancy. The data have important implications for human fetal surgery where the uterus is handled, as operative procedures during late gestation under general maternal anesthesia become more prevalent.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#97

 

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Description Breast cancer (BC), as one of the leading causes of death among women, comprises several subtypes with controversial and poor prognosis. Considering the TNM (tumor, lymph node, metastasis) based classification for staging of breast cancer, it is essential to diagnose the disease at early stages. The present study aims to take advantage of the systems biology approach on genome wide gene expression profiling datasets to identify the potential biomarkers involved at stage I, stage II, stage III, and stage IV as well as in the integrated group. Three HER2-negative breast cancer microarray datasets were retrieved from the GEO database, including normal, stage I, stage II, stage III, and stage IV samples. Additionally, one dataset was also extracted to test the developed predictive models trained on the three datasets. The analysis of gene expression profiles to identify differentially expressed genes (DEGs) was performed after preprocessing and normalization of data. Then, statistically significant prioritized DEGs were used to construct protein–protein interaction networks for the stages for module analysis and biomarker identification. Furthermore, the prioritized DEGs were used to determine the involved GO enrichment and KEGG signaling pathways at various stages of the breast cancer. The recurrence survival rate analysis of the identified gene biomarkers was conducted based on Kaplan–Meier methodology. Furthermore, the identified genes were validated not only by using several classification models but also through screening the experimental literature reports on the target genes. Fourteen (21 genes), nine (17 genes), eight (10 genes), four (7 genes), and six (8 genes) gene modules (total of 53 unique genes out of 63 genes with involving those with the same connectivity degree) were identified for stage I, stage II, stage III, stage IV, and the integrated group. Moreover, SMC4, FN1, FOS, JUN, and KIF11 and RACGAP1 genes with the highest connectivity degrees were in module 1 for abovementioned stages, respectively. The biological processes, cellular components, and molecular functions were demonstrated for outcomes of GO analysis and KEGG pathway assessment. Additionally, the Kaplan–Meier analysis revealed that 33 genes were found to be significant while considering the recurrence-free survival rate as an alternative to overall survival rate. Furthermore, the machine learning calcification models show good performance on the determined biomarkers. Moreover, the literature reports have confirmed all of the identified gene biomarkers for breast cancer. According to the literature evidence, the identified hub genes are highly correlated with HER2-negative breast cancer. The 53-mRNA signature might be a potential gene set for TNM based stages as well as possible therapeutics with potentially good performance in predicting and managing recurrence-free survival rates at stages I, II, III, and IV as well as in the integrated group. Moreover, the identified genes for the TNM-based stages can also be used as mRNA profile signatures to determine the current stage of the breast cancer.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#98

 

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Description Patients’ prognostication around cardiac surgery is key to better assess risk–benefit balance. Preoperative brain natriuretic peptide (BNP) biomarker has been associated with mortality after cardiac surgery, but its added value with EuroScore 2 remains to be confirmed. In a prospective registry cohort of 4,980 patients undergoing cardiac surgery, the prognostic performance of EuroScore 2 and preoperative BNP was assessed regarding postoperative in-hospital mortality. Discrimination feature was evaluated using receiver-operator-characteristics analysis with area under curve (AUROC). Calibration feature was assessed using Hosmer–Lemeshow test. Multivariable analysis was performed to assess the association between covariates and in-hospital mortality. In-hospital mortality was 3.7%. The AUROC of EuroScore 2 was 0.82 (95% confidence interval (95%CI) 0.79–0.85, p < 0.0001). The AUROC of BNP was 0.66 (95%CI 0.62–0.70, p < 0.0001). The combined model with an AUROC of 0.67 (95%CI 0.63–0.71, p = 0.0001) did not yield better AUROC than EuroScore 2 alone (p < 0.0001 in disfavor of the combined model), nor BNP alone (p = 0.79). In multivariable analysis, EuroScore 2 remained independently associated with mortality (adj.OR of 1.12 (1.10–1.14), p < 0.0001), but BNP was not. Preoperative BNP was not an independent risk factor of postoperative mortality and did not add prognostic information, as compared to EuroScore 2 alone. Clinical trial registry Registry for the Improvement of Postoperative OutcomeS in Cardiac and Thoracic surgEry (RIPOSTE) database (NCT03209674).

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#99

 

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Description The genomic diversity of Plasmodium malariae malaria parasites is understudied, partly because infected individuals tend to present with low parasite densities, leading to difficulties in obtaining sufficient parasite DNA for genome analysis. Selective whole genome amplification (SWGA) increases the relative levels of pathogen DNA in a clinical sample, but has not been adapted for P. malariae parasites. Here we design customized SWGA primers which successfully amplify P. malariae DNA extracted directly from unprocessed clinical blood samples obtained from patients with P. malariae-mono-infections from six countries, and further test the efficacy of SWGA on mixed infections with other Plasmodium spp. SWGA enables the successful whole genome sequencing of samples with low parasite density (i.e. one sample with a parasitaemia of 0.0064% resulted in 44% of the genome covered by ≥ 5 reads), leading to an average 14-fold increase in genome coverage when compared to unamplified samples. We identify a total of 868,476 genome-wide SNPs, of which 194,709 are unique across 18 high-quality isolates. After exclusion of the hypervariable subtelomeric regions, a high-quality core subset of 29,899 unique SNPs is defined. Population genetic analysis suggests that P. malariae parasites display clear geographical separation by continent. Further, SWGA successfully amplifies genetic regions of interest such as orthologs of P. falciparum drug resistance-associated loci (Pfdhfr, Pfdhps, Pfcrt, Pfk13 and Pfmdr1), and several non-synonymous SNPs were detected in these genes. In conclusion, we have established a robust SWGA approach that can assist whole genome sequencing of P. malariae, and thereby facilitate the implementation of much-needed large-scale multi-population genomic studies of this neglected malaria parasite. As demonstrated in other Plasmodia, such genetic diversity studies can provide insights into the biology underlying the disease and inform malaria surveillance and control measures.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#100

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#101

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#102

 

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Description In the modern era, detailed pathologic characteristics of a thyroid tumor are crucial to achieve accurate diagnosis and guide treatment. The presence of capsular invasion (CI) is diagnostic for carcinoma, whereas vascular invasion (VI) and nodal metastasis (NM) are included in risk stratification. However, the very definition of CI and VI is surrounded by controversies and an accurate assessment of NM is lacking. Whole Block Imaging (WBI) by microCT is a new imaging modality to create 3D reconstruction of whole tissue block with microscopic level resolution without the need for tissue sectioning. In this study, we aimed to define CI, VI, and NM volume using WBI by microCT. Twenty-eight paraffin blocks (PBs) from 26 thyroid tumors were scanned. Ten PBs contained CI, whereas 7 had VI. 3D microCT images were compared with whole slide images (WSI) of corresponding H&E slides. In 2 cases with VI and/or CI, WSI of serial H&E slides were obtained and underwent 3D-reconstruction to be compared with the WBI. Satellite tumor nodules beyond tumor capsule were shown to be CI by demonstrating the point of penetration using microCT and 3D reconstruction. Additional foci of CI were detected using microCT. VI was seen using microCT. Fibrin associated with tumor thrombus was not always present on serially sectioned H&E slides. WBI by microCT scanner was able to assess the volume of NM. In conclusion, WBI is able to detect CI, VI, and assess the volume of NM in thyroid carcinoma without tissue sectioning. It is the ultimate method for the complete sampling of the tumor capsule. It has the potential to increase the detection rate of CI, better define criteria for CI and VI, and provide an accurate assessment of the volume of nodal disease. This technology may impact the future practice of surgical pathology.

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 02 July 2020

#103

 

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Description With information on COVID-19 evolving daily, the public is confronted with a mix of partial information, conflicting information and sometimes outright misinformation. Who should they turn to for the truth? In the context of acute uncertainty, I discuss what scientists can do to help mitigate the misinformation about what we do know and give some context to help decision-making in the unfolding story of COVID-19. In this Comment, Heidi Larson discusses the COVID-19 ‘infodemic’ and suggests the ways in which scientists can help to mitigate the spread of misinformation.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#104

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#105

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#106

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#107

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#108

 

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Description BioNTech of Germany and the US pharmaceutical giant Pfizer reported positive preliminary results on Wednesday from a joint project to develop a coronavirus vaccine.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#109

 

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Description Facebook said Thursday it would offer reminders to its users to wear protective masks, responding to the latest surge in US coronavirus cases, which has sparked renewed fears of containing the pandemic.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#110

 

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Description New daily coronavirus cases in the United States soared past 50,000 for the first time Wednesday, as the World Health Organization delivered a grave warning that the global pandemic is accelerating.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#111

 

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Name
Description Graves’ disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism and occurs at all ages but especially in women of reproductive age. Graves’ hyperthyroidism is caused by autoantibodies to the thyroid-stimulating hormone receptor (TSHR) that act as agonists and induce excessive thyroid hormone secretion, releasing the thyroid gland from pituitary control. TSHR autoantibodies also underlie Graves’ orbitopathy (GO) and pretibial myxoedema. Additionally, the pathophysiology of GO (and likely pretibial myxoedema) involves the synergism of insulin-like growth factor 1 receptor (IGF1R) with TSHR autoantibodies, causing retro-orbital tissue expansion and inflammation. Although the aetiology of GD remains unknown, evidence indicates a strong genetic component combined with random potential environmental insults in an immunologically susceptible individual. The treatment of GD has not changed substantially for many years and remains a choice between antithyroid drugs, radioiodine or surgery. However, antithyroid drug use can cause drug-induced embryopathy in pregnancy, radioiodine therapy can exacerbate GO and surgery can result in hypoparathyroidism or laryngeal nerve damage. Therefore, future studies should focus on improved drug management, and a number of important advances are on the horizon. Graves’ disease is an autoimmune disease caused by autoantibodies to the thyroid-stimulating hormone receptor, causing hyperthyroidism. In this Primer, Davies and colleagues discuss the epidemiology, pathophysiology and diagnosis of Graves’ disease and highlight the need for better therapeutics for its management.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#112

 

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Description A new study reveals that the common asthma drug salbutamol may offer potential as a treatment for Alzheimer’s disease. Alzheimer’s disease is the most common form of dementia, affecting 47 million people worldwide and its prevalence is expected to triple to more than 130 million cases by 2050.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#113

 

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Description Nitric oxide is an important signaling molecule in the body, with a role in building nervous system connections that contribute to learning and memory. It also functions as a messenger in the cardiovascular and immune systems. But it has been difficult for researchers to study exactly what its ro

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#114

 

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Description The provincial government is supporting a pair of University of Alberta research initiatives in an effort to combat the toll COVID-19 is inflicting on military, veterans, first responders and their families. The U of A-led Heroes in Mind, Advocacy and Research Consortium (HiMARC) that supports me

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#115

 

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Description Professor John Miles from JCU’s Australian Institute of Tropical Health and Medicine said diseases caused by non-tuberculous mycobacteria (NTM) have been steadily increasing globally. “NTMs are the lesser-known cousins of tuberculosis. They are tiny bacteria that live in the soil, water systems,

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#116

 

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Description For hundreds and hundreds of years people have tried to stop the aging process. However, their efforts have never yielded any positive results - there is no youth elixir. Even with the latest scientific advancement we cannot stop the damage that time does on our bodies. But now scientists from Saarl

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#117

 

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Description Scientists used a combination of advanced microscopy and chemical detection techniques to uncover the structural makeup of human tooth enamel at unprecedented atomic resolution, revealing lattice patterns and unexpected irregularities. The findings could lead to a better understanding of how tooth d

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#118

 

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Description Repeated measurements of the biomarker FIB-4 in the blood every few years can predict the risk of developing severe liver disease, according to a new study from Karolinska Institutet published in the Journal of Hepatology. The risk of liver cirrhosis increases if the levels of this biomarker rise be

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#119

 

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Description Witnesses divulge little on how Trump administration's vaccine push selects candidates for clinical testing or funding

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#120

 

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Description Clinical study has been helped by a simple design, a centralized health care system, and lots of infections

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#121

 

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Description Head of the International AIDS Society says conference organizers hope to retain its unique nature and influence online

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#122

 

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Description Imagine this happening in the UK. Just imagine.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#123

 

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Description Big questions remain about any potential coronavirus immunity — particularly whether those who have been infected are protected from reinfection.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#124

 

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Description Conspiracy theories have driven people to burn cellular equipment. Telecom workers have had to bear the brunt of this.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#125

 

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Name
Description The annual Prime Day sale is typically held in July.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#126

 

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Description Here's a look at Hewlett Packard Enterprise CEO Antonio Neri's recovery from COVID-19 and how it has inspired HPE partners, customers and employees.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#127

 

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Description A sharp downturn in demand for its services is behind Accenture's plan to cut up to 900 jobs in the U.K.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#128

 

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Description To evaluate the quality of planning target volume (PTV) and organs at risk (OAR) generated by the manual Pinnacle planning (manP) and Auto-Planning (AP) modules and discuss the feasibility of AP in the application of radiotherapy for patients with breast cancer. Thirty patients who underwent breast-conserving therapy were randomly selected. The Philips Pinnacle 9.10 treatment planning system was used to design the manP and AP modules for PTV and OAR distribution on the same computed tomography. A physician compared the plans in terms of dosimetric parameters and monitor units (MUs) using blind qualitative scoring. Statistical differences were evaluated using paired two-sided Wilcoxon’s signed-rank test. On comparing the plans of AP and manP modules, the conformal index (P < 0.01) and D50 (P = 0.04) of PTV in the AP group was lower than those in the manP group, while D1 was higher (P = 0.03). In terms of dosimetry of OAR, ipsilateral lung V20 Gy (P < 0.01), V10 Gy (P < 0.01), V5 Gy (P < 0.05), and Dmean (P < 0.01) of the AP group were better than those of the manP group. Heart V40 Gy and Dmean of all patients with breast cancer in the AP group were lower than those in the manP group (P < 0.01). Moreover, 12 patients with left breast cancer had the same results (P < 0.01). The MU value of the intensity-modulated radiation therapy module designed using two different methods was higher in the AP group than in the manP group (P = 0.32), although there was no statistical significance. The AP module almost had an equal quality of PTV and dose distribution as the manP module, and its OAR was less irradiated.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#129

 

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Description Lipedema is a chronic adipose tissue disorder characterized by the disproportional subcutaneous deposition of fat and is commonly misdiagnosed as lymphedema or obesity. The molecular determinants of the lipedema remain largely unknown and only speculations exist regarding the lymphatic system involvement. The aim of the present study is to characterize the lymphatic vascular involvement in established lipedema. The histological and molecular characterization was conducted on anatomically-matched skin and fat biopsies as well as serum samples from eleven lipedema and ten BMI-matched healthy patients. Increased systemic levels of vascular endothelial growth factor (VEGF)-C (P = 0.02) were identified in the serum of lipedema patients. Surprisingly, despite the increased VEGF-C levels no morphological changes of the lymphatic vessels were observed. Importantly, expression analysis of lymphatic and blood vessel-related genes revealed a marked downregulation of Tie2 (P < 0.0001) and FLT4 (VEGFR-3) (P = 0.02) consistent with an increased macrophage infiltration (P = 0.009), without changes in the expression of other lymphatic markers. Interestingly, a distinct local cytokine milieu, with decreased VEGF-A (P = 0.04) and VEGF-D (P = 0.02) expression was identified. No apparent lymphatic anomaly underlies lipedema, providing evidence for the different disease nature in comparison to lymphedema. The changes in the lymphatic-related cytokine milieu might be related to a modified vascular permeability developed secondarily to lipedema progression.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#130

 

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Description Aberrant metabolisms have been hypothesized to precede the occurrence of hepatocellular carcinoma (HCC), therefore, we investigated biomarkers associated with subsequent HCC in peripheral bloods using metabolomic technologies. A cohort of 475 HCC-naïve liver cirrhotic patients were recruited and prospectively followed. A total of 39 patients developed HCC in the follow-up period. Baseline plasma metabolites were explored using untargeted nuclear magnetic resonance. Candidates were then quantified by ultra-performance liquid chromatography. A series of univairiate and multivariate analysis showed that Phenylalanine (Phe) and Glutamine (Gln) levels are associated with time to HCC, independent of viological etiologies and age. A HCC risk score R was then constructed using the polynomial combination of age, Phe and Gln in the units of micromolar (μM): $$egin{aligned} { ext{R }} & = { ext{ Age }}* , left( {0.0694} ight) + { ext{ Phe }}* , left( {0.3399} ight) + { ext{ Phe }^{2}}* , left( { - 0.00188154} ight) hfill \ & quad + { ext{ Gln }}* , left( { - 0.0133} ight) + { ext{ Gln }^{2}}* , left( { , 0.00002244} ight) hfill \ end{aligned}$$ R correlates with the time to HCC significantly (Hazard ratio [HR] = 2.368, 95% confidence interval [CI] 1.760–3.187, P < 0.001). An additional cross-sectional analysis showed that Phe and Gln concentrations both correlates with HCC occurrence in the next 3 years (area under the receiver operating characteristic curve [AUC] = 0.607 and 0.629, P = 0.033 and 0.010 respectively). In conclusion, phenylalanine and glutamine concentrations in the peripheral blood correlate with subsequent HCC.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#131

 

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Name
Description Bronchiolitis manifests as a variety of histological features that explain the complex clinical profiles and imaging aspects. In the period between January 2011 and June 2015, patients with a cryobiopsy diagnosis of bronchiolitis were retrospectively retrieved from the database of our institution. Clinical profiles, imaging features and histologic diagnoses were analysed to identify the role of cryobiopsy in the diagnostic process. Twenty-three patients with a multidisciplinary diagnosis of small airway disease were retrieved (14 females, 9 males; age range 31–74 years old; mean age 54.2 years old). The final MDT diagnoses were post-infectious bronchiolitis (n = 5), constrictive bronchiolitis (n = 3), DIPNECH (n = 1), idiopathic follicular bronchiolitis (n = 3), Sjogren’s disease (n = 1), GLILD (n = 1), smoking-related interstitial lung disease (n = 6), sarcoid with granulomatous bronchiolar disorder (n = 1), and subacute hypersensitivity pneumonitis (n = 2). Complications reported after the cryobiopsy procedure consisted of two cases of pneumothorax soon after the biopsy (8.7%), which were successfully managed with the insertion of a chest tube. Transbronchial cryobiopsy represents a robust and mini-invasive method in the characterization of small airway diseases, allowing a low percentage of complications and good diagnostic confidence.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#132

 

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Description Skin conductance monitoring is one of the promising methods for objectively evaluating pain. However, skin conductance might possibly increase in response to sympathetic stimulation other than pain. In this study, we aimed to test whether skin conductance monitoring can distinguish physical pain stimulation (heat, mechanical and cold stimulation) from other sympathetic stimuli (stimulation by noise and painful images). Twenty-three healthy volunteers participated in this prospective observational study. The number of fluctuations in skin conductance (NFSC) and normalized skin conductance level (nSCL) were measured and compared with pain scores on a self-reported pain scale (numerical pain scale [NPS]). Both NFSC and nSCL increased during mechanical stimulation. Further, nSCL, but not NFSC, well reflected heat stimulus intensity, suggesting its ability to quantitatively evaluate pain. nSCLs during physical pain stimulation were greater than those during other sympathetic stimulations. However, NFSC was not able to completely distinguish between the stimuli. These results suggest that nSCL could better differentiate physical pain stimuli from other sympathetic stimuli than NFSC. In comparisons between subjective and objective pain assessment in the same individual, nSCL correlated better with NPS score, indicating the possibility of being able to monitor the transition of pain. Monitoring changes in skin conductance using nSCL might be useful for objectively detecting physical pain.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#133

 

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Name
Description Neurofilament light chain (NfL) has been demonstrated to correlate with multiple sclerosis disease severity as well as treatment response. Nevertheless, additional serum biomarkers are still needed to better differentiate disease activity from disease progression. The aim of our study was to assess serum glial fibrillary acid protein (s-GFAP) and neurofilament light chain (s-NfL) in a cohort of 129 multiple sclerosis (MS) patients. Eighteen primary progressive multiple sclerosis (PPMS) and 111 relapsing remitting MS (RRMS) were included. We showed that these 2 biomarkers were significantly correlated with each other (R = 0.72, p < 0.001). Moreover, both biomarkers were higher in PPMS than in RRMS even if multivariate analysis only confirmed this difference for s-GFAP (130.3 ± 72.8 pg/ml vs 83.4 ± 41.1 pg/ml, p = 0.008). Finally, s-GFAP was correlated with white matter lesion load and inversely correlated with WM and GM volume. Our results seem to confirm the added value of s-GFAP in the context of multiple sclerosis.

#Medicine & Human body
Field # Medicine & Human body
Updated 02 July 2020

#134

 

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Name
Description A new polymeric heart valve with a life span potentially longer than current artificial valves that would also prevent the need for the millions of patients with diseased heart valves to require life-long blood thinning tablets has been developed by scientists at the universities of Bristol and Camb

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#135

 

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Description French car sales recovered to pre-coronavirus crisis levels in June, the industry said Wednesday, as consumers took advantage of state-backed incentives.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#136

 

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Name
Description Facebook is shutting down Hobbi, its experimental Pinterest-like app focusing on progress shots.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#137

 

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Name
Description On a spring morning in 1955, a pair of press officers greeted a mob of reporters in a stately hall on the University of Michigan campus. The officers had hot news: A clinical trial of the long-awaited polio vaccine had proved it to be safe and effective. The reporters nearly rioted in their scramble

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#138

 

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Name
Description By softening a cell’s nucleus so that it can squeeze its way through dense connective tissues, a group of researchers believes they’ve demonstrated a new way to help the body efficiently repair injuries. The team of researchers from the University of Pennsylvania tested this theory by using medicati

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#139

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#140

 

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Name
Description Google said late on Tuesday it was delaying the reopening of its US offices by around two months because of a surge in the number of coronavirus cases in some states.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#141

 

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Description FDA sets rules for vaccine approval amid concern of hastiness and political pressure.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#142

 

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Name
Description

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 01 July 2020

#143

 

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Name
Description As per the report, a new beta version of Gboard was rolled out via Google Play Store and some users who were on version 9.5.12.317844448 discovered that Google Messages is offering suggestions for completing the sentences through Smart Compose just as it does on Gmail right now.

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 01 July 2020

#144

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#145

 

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Name
Description When will there be a vaccine for COVID-19? A vaccine developed by BioNTech and Pfizer has shown potential.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#146

 

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Name
Description American Airlines resumed trying to fill its planes to full capacity Wednesday, abandoning some coronavirus precautions and drawing criticism from public health officials as the pandemic runs wild in parts of America.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#147

 

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Name
Description About 40 percent of cases were asymptomatic, and viral load didn't seem to matter.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#148

 

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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 01 July 2020

#149

 

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Name
Description The heterogeneity of critical illness complicates both clinical trial design and real-world management. This complexity has resulted in conflicting evidence and opinion regarding the optimal management in many intensive care scenarios. Understanding this heterogeneity is essential to tailoring management to individual patients. Hyperglycaemia is one such complication in the intensive care unit (ICU), accompanied by decades of conflicting evidence around management strategies. We hypothesized that analysis of highly-detailed electronic medical record (EMR) data would demonstrate that patients vary widely in their glycaemic response to critical illness and response to insulin therapy. Due to this variability, we believed that hyper- and hypoglycaemia would remain common in ICU care despite standardised approaches to management. We utilized the Medical Information Mart for Intensive Care III v1.4 (MIMIC) database. We identified 19,694 admissions between 2008 and 2012 with available glucose results and insulin administration data. We demonstrate that hyper- and hypoglycaemia are common at the time of admission and remain so 1 week into an ICU admission. Insulin treatment strategies vary significantly, irrespective of blood glucose level or diabetic status. We reveal a tremendous opportunity for EMR data to guide tailored management. Through this work, we have made available a highly-detailed data source for future investigation.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#150

 

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Description Sarcopenia is an important prognostic factor in patients with gastrointestinal and chronic liver diseases. Computed tomography and bioelectrical impedance analysis are the gold standards for measuring skeletal muscle mass for the diagnosis of decreased muscle mass, but there are some institutions where BIA and CT cannot be carried out. We evaluated the utility of simplified methods for measuring muscle mass; the psoas muscle mass index (PMI) method, simple PMI method, and arm muscle area (AMA) method. This retrospective study included 331 patients with gastrointestinal diseases and 81 patients with chronic liver diseases who were admitted from June 2018 to December 2019 at Municipal Hospital of Kofu. The skeletal muscle mass was measured using the PMI via the volume analyzer SYNAPSE VINCENT ver3.0, simple PMI based on CT imaging, and AMA method. Positive correlations were found between muscle mass measured by PMI and simple PMI, PMI and AMA, and simple PMI and AMA in patients with gastrointestinal diseases (correlation coefficients = 0.76, 0.57, 0.47, respectively, p < 0.001). Positive correlations were observed between muscle mass measured by PMI and simple PMI, PMI and AMA, and simple PMI and AMA in chronic liver diseases (correlation coefficients = 0.77, 0.53, 0.45, respectively, p < 0.001). Measurement of muscle mass by the AMA method showed some correlation with the PMI method. Measurement of muscle mass by the simple PMI method showed correlation with the PMI method. These simplified methods can be alternative methods of evaluating muscle mass in patients with gastrointestinal and chronic liver disease.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#151

 

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Name
Description A major cause of failed drug discovery programs is suboptimal target selection, resulting in the development of drug candidates that are potent inhibitors, but ineffective at treating the disease. In the genomics era, the availability of large biomedical datasets with genome-wide readouts has the potential to transform target selection and validation. In this study we investigate how computational intelligence methods can be applied to predict novel therapeutic targets in oncology. We compared different machine learning classifiers applied to the task of drug target classification for nine different human cancer types. For each cancer type, a set of “known” target genes was obtained and equally-sized sets of “non-targets” were sampled multiple times from the human protein-coding genes. Models were trained on mutation, gene expression (TCGA), and gene essentiality (DepMap) data. In addition, we generated a numerical embedding of the interaction network of protein-coding genes using deep network representation learning and included the results in the modeling. We assessed feature importance using a random forests classifier and performed feature selection based on measuring permutation importance against a null distribution. Our best models achieved good generalization performance based on the AUROC metric. With the best model for each cancer type, we ran predictions on more than 15,000 protein-coding genes to identify potential novel targets. Our results indicate that this approach may be useful to inform early stages of the drug discovery pipeline.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#152

 

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Name
Description Biologicals like anti-tumor necrosis factor (TNF) therapy for Crohn’s disease (CD) are safe and effective but there is a significant rate of primary and secondary nonresponse in the patients. In this study, we applied a computational approach to discover novel drug therapies for anti-TNF refractory CD in silico. We use a transcriptome dataset (GSE100833) for the anti-TNF refractory CD patients from NCBI GEO. After co-expression analysis, we specifically investigated the extent of protein–protein interactions among genes in clusters based on a protein–protein interaction database, STRING. Pathway analysis was performed using the clEnrich function based on KEGG gene sets. Co-expressed genes in cluster 1, 2, 3, 4, up or down-regulated genes and all differentially expressed genes are highly connected. Among them, cluster 1, which is highly enriched for chemokine signaling, also showed enrichment for cytokine–cytokine receptor interaction and identifies several drugs including cyclosporin with known efficacy in CD. Vorinostat, histone deacetylase inhibitors, and piperlongumine, which is known to have inhibitory effect on activity of NF-κB, were also identified. Some alkaloids were also selected as potential therapeutic drugs. These finding suggest that they might serve as a novel therapeutic option for anti-TNF refractory CD and support the use of public molecular data and computational approaches to discover novel therapeutic options for CD.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#153

 

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Name
Description Different point stimulations can induce brain activity in specific regions, and however whether these stimulations affect unique neurotransmitter transmission remains unknown. Therefore, we aimed to investigate the effect of point specificity to the brain by resolving the metabolite profiles. Eighteen Sprague–Dawley rats were randomly divided into three groups: (1) the sham group: sham acupuncture at Zusanli (ST36) without electric stimulation; (2) the Zusanli (ST36) group: electroacupuncture (EA) at ST36; and (3) the Neiguan (PC6) group: EA at PC6. Then, the metabolites from rat brain samples were measured by LC–ESI–MS. The results of a partial least squares discriminant analysis revealed the differences among the sham, ST36, and PC6 groups regarding the relative content of metabolites in the cerebral cortex, hippocampus, and hypothalamus. EA at PC6 resulted in downregulation of adenosine, adrenaline, γ-aminobutyric acid, glycine, and glutamate majorly in hippocampus, and then in cerebral cortex. Otherwise, EA at ST6 resulted in upregulation of adrenaline and arginine in hippocampus, and all stimulations showed barely change of identified neurotransmitters in hypothalamus. These differential metabolite and neurotransmitter profiles prove that brain areas can be modulated by point specificity and may provide a maneuver to understand more details of meridian.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#154

 

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Name
Description Voltage-gated Na+ (NaV) channels regulate homeostasis in bacteria and control membrane electrical excitability in mammals. Compared to their mammalian counterparts, bacterial NaV channels possess a simpler, fourfold symmetric structure and have facilitated studies of the structural basis of channel gating. However, the pharmacology of bacterial NaV remains largely unexplored. Here we systematically screened 39 NaV modulators on a bacterial channel (NaChBac) and characterized a selection of compounds on NaChBac and a mammalian channel (human NaV1.7). We found that while many compounds interact with both channels, they exhibit distinct functional effects. For example, the local anesthetics ambroxol and lidocaine block both NaV1.7 and NaChBac but affect activation and inactivation of the two channels to different extents. The voltage-sensing domain targeting toxin BDS-I increases NaV1.7 but decreases NaChBac peak currents. The pore binding toxins aconitine and veratridine block peak currents of NaV1.7 and shift activation (aconitine) and inactivation (veratridine) respectively. In NaChBac, they block the peak current by binding to the pore residue F224. Nonetheless, aconitine has no effect on activation or inactivation, while veratridine only modulates activation of NaChBac. The conservation and divergence in the pharmacology of bacterial and mammalian NaV channels provide insights into the molecular basis of channel gating and will facilitate organism-specific drug discovery.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#155

 

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Description Studies suggest that semen quality is declining globally, however, the debate remains open due to the possible effects of ethnic and geographical differences. This study aimed to explore whether semen quality of sperm donor candidates has changed in Henan Province, China from 2009 to 2019. In this retrospective study, we included 23,936 sperm donor candidates who were recruited by the Henan Human Sperm Bank of China between 2009 and 2019. To minimize intra-individual bias, we included only the first ejaculate provided by each sperm donor candidate. The following parameters were measured: volume, sperm concentration, total sperm count, progressive motility, and total motility. After adjustment for age, body mass index (BMI), and sexual abstinence duration, we evaluated changes in main semen parameters over time using multiple linear regression analyses. The sperm concentration decreased from 62.0 million/mL in 2009 to 32.0 million/mL in 2019 (P < 0.001), with an average annual rate of 3.9%. The total sperm count decreased from 160.0 million in 2009 to 80.0 million in 2019 (P < 0.001), with an average annual rate of 4.2%. The progressive motility decreased from 54.0% in 2009 to 40.0% in 2019 (P < 0.001), with an average annual rate of 2.5%. The total motility decreased from 60.0% in 2009 to 46.0% in 2019 (P < 0.001), with an average annual rate of 1.9%. Our results indicated that semen quality among sperm donor candidates had decreased during the study period in Henan Province, China.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#156

 

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Name
Description This study was conducted to assess whether levetiracetam (LEV) affects the survival of patients with glioblastoma (GBM) treated with concurrent temozolomide (TMZ) chemotherapy. To this end, from 2004 to 2016, 322 patients with surgically resected and pathologically confirmed isocitrate dehydrogenase (IDH)-wildtype GBM who received TMZ-based chemoradiotherapy were analysed. The patients were divided into two groups based on whether LEV was used as an anticonvulsant both at the time of surgery and the first visit thereafter. The median overall survival (OS) and progression-free survival (PFS) were compared between the groups. The OS was 21.1 and 17.5 months in the LEV (+) and LEV (−) groups, respectively (P = 0.003); the corresponding PFS was 12.3 and 11.2 months (P = 0.017). The other prognostic factors included age, extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and Karnofsky Performance Status (KPS) score. The multivariate analysis showed age (hazard ratio [HR], 1.02; P < 0.001), postoperative KPS score (HR 0.99; P = 0.002), complete tumour resection (HR 0.52; P < 0.001), MGMT promoter methylation (HR 0.75; P < 0.001), and LEV use (HR 0.72; P = 0.011) were significantly associated with OS. In conclusion, LEV use was associated with prolonged survival in patients with GBM treated with concurrent TMZ chemoradiotherapy.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#157

 

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Name
Description We detected disproportionate reports of premature ovarian insufficiency (POI) and related events, including amenorrhea, menstruation irregular, FSH increased, and premature menopause, following human papillomavirus (HPV) vaccine from FDA Vaccine Adverse Event Reporting System (VAERS). The signal was detected by the methods of Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-item Gamma Poisson Shrinker (MGPS). When both methods detected a positive result, a signal was generated. Besides, time-scan map is drawn based on the IC value and 95%CI of BCPNN, if the IC curve showed a steady upward trend and the 95%CI narrowed, the signal was stable and strong association.The results showed that there were not POI reports of HPV vaccine, but VAERS received a total of 2, 389, 27 POI related events for HPV2, HPV4, HPV9 respectively from the year of marketed to 2018. No signal was detected for HPV2. HPV4-POI ralated events were all detected as signals by two methods. There was only one signal of menstruation irregular for HPV9. Time scan of HPV4-POI ralated events showed those signals were stability and strong association, but not for HPV9. Our results only represent statistical association between HPV vaccine and POI related events, causal relationship needs further investigation.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#158

 

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Name
Description L-myo-inositol phosphate synthase (MIPS; EC 5.5.1.4) is involved in abiotic stress tolerance, however its disruption and overexpression has also been associated with enhanced tolerance to pathogens. The molecular mechanism underlying the role of MIPS in growth, immunity and abiotic stress tolerance remains uncharacterized. We explore the molecular mechanism of MIPS action during growth and heat stress conditions. We raised and characterized the TaMIPS over-expressing rice transgenics which showed a reduced reproductive potential. Transcriptome analysis of overexpression transgenics revealed the activation of ET/JA dependent immune response. Pull-down analysis revealed the interaction of TaMIPS-B with ethylene related proteins. Our results suggest an essential requirement of MIPS for mediating the ethylene response and regulate the growth. A model is proposed outlining how fine tuning of MIPS regulate growth and stress tolerance of the plant.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#159

 

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Name
Description Apple is re-closing 30 retail stores in the U.S., including in Florida, California and Georgia.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#160

 

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Name
Description Laparoscopic appendectomy (LA) is a widely used surgical procedure. Patients often suffer from considerable postoperative pain and indigestion, which prolongs their in-hospital stay. Almost 10% of patients develop postoperative complications. The enhanced recovery after surgery (ERAS) program has proven its efficacy in elective surgery and could hypothetically improve LA outcomes. Currently, there is no ERAS program for LA. A modified ERAS (mERAS) protocol was studied in a prospective, randomized nonblinded clinical trial. The mERAS group consisted of 50 patients; the control group, of 54 patients. The mERAS protocol included a patient information brochure; minimizing drain use; local anesthesia; low-pressure pneumoperitoneum; early mobilization and oral diet. The primary outcome was postoperative length of stay (pLOS). Modified protocol reduced median pLOS to 1.25 days vs 2 days in the controls (p < 0.0001). Twenty-one (42%) mERAS patients and 4 (7.4%) controls were discharged within 24 h (p < 0.001) after surgery; 0 readmissions were reported. Postoperative pain intensity assessed on the visual analogue scale was significantly lower in the mERAS group [mERAS vs control 0 h, 2 h, 6 h, 12 h and 24 h after surgery: 2.33 ± 2.12 vs 4.19 ± 2.08 (p < 0.0001), 2.27 ± 1.91 vs 4.02 ± 1.89 (p < 0.0001), 2.28 ± 1.98 vs 3.70 ± 1.57 (p = 0.0001), 1.98 ± 1.72 vs 3.43 ± 1.54 (p < 0.0001) and 1.80 ± 1.74 vs 3.00 ± 1.27 (p = 0.032), respectively)]. The severity of shoulder and neck pain was lower but its incidence was similar. Peristalsis recovery was achieved earlier in the study group (median (min–max))—mERAS 7 (2–34) h vs control 11 (3–43) h; p = 0.009) but did not affect the time of the first flatus 23 (2–72) h vs 29 (6–70) h, respectively; p = 0.499). The modified ERAS program for LA has advantages over the traditional approach. This trial was registered at ClinicalTrials.gov as NCT03754777 (27/11/2018).

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#161

 

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Name
Description Extracellular vesicles derived from mesenchymal stem cells (MSCs) represent a novel approach for regenerative and immunosuppressive therapy. Recently, cytochalasin B-induced microvesicles (CIMVs) were shown to be effective drug delivery mediators. However, little is known about their immunological properties. We propose that the immunophenotype and molecular composition of these vesicles could contribute to the therapeutic efficacy of CIMVs. To address this issue, CIMVs were generated from murine MSC (CIMVs-MSCs) and their cytokine content and surface marker expression determined. For the first time, we show that CIMVs-MSCs retain parental MSCs phenotype (Sca-1+, CD49e+, CD44+, CD45−). Also, CIMVs-MSCs contained a cytokine repertoire reflective of the parental MSCs, including IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12(p40), IL-13, IL-17, CCL2, CCL3, CCL4, CCL5, CCL11, G-CSF, GM-CSF and TNF-α. Next, we evaluated the immune-modulating properties of CIMVs-MSCs in vivo using standard preclinical tests. MSCs and CIMVs-MSCs reduced serum levels of anti-sheep red blood cell antibody and have limited effects on neutrophil and peritoneal macrophage activity. We compared the immunomodulatory effect of MSCs, CIMVs and EVs. We observed no immunosuppression in mice pretreated with natural EVs, whereas MSCs and CIMVs-MSCs suppressed antibody production in vivo. Additionally, we have investigated the biodistribution of CIMVs-MSCs in vivo and demonstrated that CIMVs-MSCs localized in liver, lung, brain, heart, spleen and kidneys 48 h after intravenous injection and can be detected 14 days after subcutaneous and intramuscular injection. Collectively our data demonstrates immunomodulatory efficacy of CIMVs and supports their further preclinical testing as an effective therapeutic delivery modality.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#162

 

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Name
Description Indium compounds have been widely used in manufacturing displays of mobile phones, computers and televisions. However, inhalation exposure to indium compounds causes interstitial pneumonia in exposed workers and lung cancer in experimental animals. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed under inflammatory conditions and may participate in indium-induced carcinogenesis. In this study, we examined 8-nitroG formation in A549 cultured human lung epithelial cells treated with indium compounds, including nanoparticles of indium oxide (In2O3) and indium-tin oxide (ITO), and indium chloride (InCl3). We performed fluorescent immunocytochemistry to examine 8-nitroG formation in indium-exposed A549 cells. All indium compounds significantly increased 8-nitroG formation in A549 cells at 5 ng/ml after 4 h incubation. 8-NitroG formation was largely reduced by 1400 W, methyl-β-cyclodextrin (MBCD) and monodansylcadaverine (MDC), suggesting the involvement of nitric oxide synthase and endocytosis. 8-NitroG formation in A549 cells was also largely suppressed by small interfering RNA (siRNA) for high-mobility group box-1 (HMGB1), receptor for advanced glycation and end products (AGER, RAGE) and Toll-like receptor 9 (TLR9). These results suggest that indium compounds induce inflammation-mediated DNA damage in lung epithelial cells via the HMGB1-RAGE-TLR9 pathway. This mechanism may contribute to indium-induced genotoxicity in the respiratory system.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#163

 

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Name
Description The clinical manifestations of patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis in East China and factors associated with prognosis were analyzed. A retrospective study of 106 patients (58 females; 48 males) with anti-NMDAR encephalitis in East China was carried out from June 2015 to February 2019. Clinical features and factors influencing outcomes were reviewed. Behavioral changes were observed in 74.5% (79/106) of patients, and comprised the initial symptoms in 61.3% (65/106). Seizures were observed in 67% (71/106) of patients, and served as initial symptoms in 31.1% (33/106). A total of 54.9% (39/71) of seizures were focal seizures. More clinical symptoms were observed in female patients than in male patients (P = 0.000). Similarly, background activity (BA) with high cerebrospinal fluid (CSF) antibody titers at the peak stage was more severe in female patients than in male patients (P = 0.000). The Binary logistic regression and receiver operating characteristic (ROC) curve analyses revealed the factors associated with poor outcomes included consciousness disturbance (OR 4.907, 95% CI 1.653–14.562, P = 0.004; area: 65.4%, sensitivity: 44.2%, specificity: 86.5%, P = 0.014), EEG BA (OR 3.743, 95% CI 1.766–7.932, P = 0.001; area: 76.6%, sensitivity: 73%, specificity: 75%, P = 0.000), number of symptoms (OR 2.911, 95% CI 1.811–4.679, P = 0.000; area: 77.1%, sensitivity: 59.5%, specificity: 78.6%, P = 0.000) and CSF antibody titer (OR 31.778, 95% CI 8.891–113.57, P = 0.000; area: 83.9%, sensitivity: 89.2%, specificity: 78.6%, P = 0.000). EEG BA and number of symptoms were associated with CSF antibody titers. Consciousness disturbances, EEG BA, number of symptoms and CSF antibody titers served as predictors of poor outcomes.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#164

 

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Name
Description The surveillance of drug resistance among tuberculosis (TB) patients is central to preventing the spread of antimicrobial resistance. The Democratic Republic of the Congo (DR Congo) is classified by the World Health Organization (WHO) as a country with a high burden of TB and multidrug-resistant TB (MDR-TB), but there are no nationally representative data on drug resistance. In 2016–2017, a national survey of TB patients was conducted in 108 microscopy centres across all 11 provinces of the country using innovative molecular approaches. Sputum samples were collected from 1,545 new and 163 previously treated patients. These were tested by the Xpert MTB/RIF assay, followed by targeted next-generation sequencing performed directly on sputum. The prevalence of rifampicin resistance was low, at 1.8% (95% CI: 1.0–3.2) among new and 17.3% (95% CI: 11.9–24.4) among previously treated patients. Resistance to pyrazinamide, fluoroquinolones and second-line injectables was also low. The prevalence of resistance to isoniazid among rifampicin-susceptible patients was higher, at 6.6% (95% CI: 4.4–9.8) among new and 8.7% (95% : 3.2–21.2) among previously treated patients. Diagnosing and treating isoniazid-resistant patients remains a challenge, given that many will be missed by the current national diagnostic algorithm that is driven by detecting rifampicin resistance by Xpert MTB/RIF. This is the first nationwide survey incorporating targeted sequencing directly on sputum. It serves as a proof-of-concept for other settings that do yet have rapid specimen transport networks or capacity to conduct culture.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#165

 

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Description We present the first ever broadband, calibrated electrical connection to the inside of a cell. The interior of a vital, living cell contains multiple dynamic and electrically active organelles such as mitochondria, chloroplasts, lysosomes, and the endoplasmic reticulum. However, little is known about the detailed electrical activity inside the cell. Here we show an ultra-high bandwidth nano-electronic interface to the interior of living cells with integrated fluorescence readout of metabolic activity. On-chip/on-petri dish nanoscale capacitance calibration standards are used to quantify the electronic coupling from bench to cell from DC to 26 GHz (with cell images at 22 GHz). The interaction of static to high frequency electromagnetic fields with the cell constituents induce currents of free charges and local reorganization of linked charges. As such, this enables a direct, calibrated, quantitative, nanoscale electronic interface to the interior of living cells. The interface could have a variety of applications in interfacing life sciences to nano-electronics, including electronic assays of membrane potential dynamics, nano-electronic actuation of cellular activity, and tomographic, nano-radar imaging of the morphology of vital organelles in the cytoplasm, during all phases of the cell life cycle (from development to senescence), under a variety of physiological environments, and under a broad suite of pharmacological manipulations.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#166

 

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Name
Description Improved prostate cancer prognostic biomarkers are urgently needed. We previously identified the four-miRNA prognostic biomarker panel MiCaP ((miR-23a-3p × miR-10b-5p)/(miR-133a-3p × miR-374b-5p)) for prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Here, we identified an optimal numerical cut-off for MiCaP dichotomisation using a training cohort of 475 RP patients and tested this in an independent cohort of 281 RP patients (PCA281). Kaplan–Meier, uni- and multivariate Cox regression analyses were conducted for multiple endpoints: BCR, metastatic-(mPC) and castration-resistant prostate cancer (CRPC), prostate cancer-specific (PCSS) and overall survival (OS). Functional effects of the four MiCaP miRNAs were assessed by overexpression and inhibition experiments in prostate cancer cell lines. We found the numerical value 5.709 optimal for MiCaP dichotomisation. This was independently validated in PCA281, where a high MiCaP score significantly [and independent of the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score] predicted BCR, progression to mPC and CRPC, and PCSS, but not OS. Harrell’s C-index increased upon addition of MiCaP to CAPRA-S for all endpoints. Inhibition of miR-23a-3p and miR-10b-5p, and overexpression of miR-133a-3p and miR-374b-5p significantly reduced cell survival. Our results may promote future implementation of a MiCaP-based test for improved prostate cancer risk stratification.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#167

 

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Description Malnutrition has been considered to be associated with the prognosis of cancer. The Geriatric Nutritional Risk Index (GNRI), based on serum albumin levels, present body weight, and ideal body weight, is a simple screening tool to predict the risk of nutrition-related morbidity and mortality in elderly patients. We aimed to evaluate whether preoperative GNRI was associated with postoperative complications and prognosis in elderly patients with colorectal cancer (CRC). We retrospectively enrolled 313 CRC patients aged ≥65 years after curative surgery and classified them into an all-risk GNRI (≤98) group and a no-risk GNRI (>98) group. Kaplan-Meier analysis showed overall survival was significantly worse in the all-risk GNRI group than in the no-risk GNRI group (P = 0.009). Multivariable analyses showed low GNRI (≤98) was an independent risk factor for postoperative complications (P = 0.048) and overall survival (P = 0.001) in the patients. Among the complications, the incidence of surgical site infection, in particular, was significantly higher in the all-risk GNRI group (P = 0.008). In conclusion, low preoperative GNRI (≤98) was associated with increased postoperative complications and poor prognosis. Preoperative GNRI can be used as an identifier for potential high-risk group of morbidity and mortality in elderly CRC patients.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#168

 

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Name
Description Whether the clinical trial treatment effect of urate-lowering therapy (ULT) in patient with chronic kidney disease (CKD) is generalizable to real-word settings is unclear. This study aimed to compare febuxostat with allopurinol for uric acid reduction and renal protection in patients with CKD. Adult CKD patients newly treated with ULT were identified using electronic health records from 2010 to 2015 from a large healthcare delivery system in Taiwan. Patients with renal replacement therapy or undergoing ULT for <3 months were excluded. Propensity score–matched cohort study design was conducted to compare outcomes between patients initiated with febuxostat or allopurinol therapy. Cox regression analyses were employed to compare the adjusted hazards ratio (aHR) of incident event of estimated glomerular filtration rate (eGFR) ≥ 30% decrease, and the difference in longitudinal changes in serum uric acid (SUA) and eGFR between groups was analyzed using linear mixed model. Overall, 1050 CKD patients who initiated febuxostat (n = 525) or allopurinol (n = 525) treatment were observed for 2.5 years. Compared with allopurinol, febuxostat use was associated with higher rate of patients maintaining SUA target <6 mg/dL in >80% of follow-up time with a reduction in mean SUA change. There were no significant differences in the mean eGFR changes over time between the febuxostat and allopurinol groups or in the risk of eGFR decline ≥30% of baseline. Febuxostat was associated with greater reduction in SUA level than allopurinol in patients with CKD. However, febuxostat and allopurinol showed no difference in renal function changes during study follow-up. These findings require further investigation with long-term follow up in CKD patients with hyperuricemia.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#169

 

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Name
Description CD96 is a promising candidate for immunotherapy. However, its role and importance in glioma remains unknown. We thus aimed to genetically and clinically characterize CD96 expression in gliomas. For this, we extracted RNA-seq data of 699 glioma samples from the TCGA dataset and validated these findings using the CGGA dataset comprising 325 glioma samples. Clinical and isocitrate dehydrogenase (IDH) mutation status were also analyzed. Various packages in R language were mainly used for statistical analysis. CD96 expression was significantly up-regulated in high-grade, IDH-wildtype, and mesenchymal-molecular subtype gliomas based on TCGA data, which was validated using the CGGA dataset. Subsequent gene ontology analysis of both datasets suggested that genes relevant to CD96 are mainly involved in immune functions in glioma as such genes were positively correlated with CD96 expression. To further explore the relationship between CD96 and immune responses, we selected seven immune-related metagenes and found that CD96 expression was positively correlated with HCK, LCK, and MHC II in the CGGA and TCGA cohorts but negatively associated with IgG. Further, Pearson correlation analysis showed that CD96 is associated with TIGIT, CD226, CRTAM, TIM-3, PD-L1, CTLA-4, and STAT3, indicating the additive antitumoral effects of these checkpoint proteins. CD96 was also suggested to play an important role in immune responses and positively collaborate with other checkpoint members. These findings show that CD96 is promising candidate for immunotherapy, and that such agents could complement current immunotherapy strategies for glioma.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#170

 

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Name
Description We aimed to estimate the optimal gestational weight gain (GWG) in Tibetan women and to evaluate the appropriateness of the Institute of Medicine (IOM) GWG recommendations for Tibetan women. We analyzed data from 1474 Tibetan women from a cross-sectional study conducted in 2019. According to the three different body mass index (BMI) classification criteria (WHO BMI categories, WHO Asian BMI categories, Chinese BMI categories), we estimated the association of GWG with pregnancy outcomes (neonate birthweight and mode of delivery) using a polynomial regression model, and the optimal GWG in each BMI group was calculated. The risk of adverse outcomes showed a U-shaped curve with increasing GWG. The optimal GWG of Tibetan women based on the WHO BMI categories was 17.2 kg (range, 13.3 to 20.9 kg) for underweight, 9.3 kg (5.8 to 12.9 kg) for normal weight, and 5.2 kg (1.3 to 9.1 kg) for overweight. Underweight Tibetan mothers may gain more gestational weight than recommend by the IOM guidelines. However, normal weight Tibetan mothers are likely to benefit from gaining less weight than that recommended by the IOM. The GWG recommendations based on the IOM guidelines might not be appropriate for Tibetan women, and ethnicity-specific recommendations for GWG should be properly addressed.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#171

 

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Name
Description Baksh et al. have delineated a pathway through which serine availability is integrated with stem cell fate decisions and can control the initiation of epidermal squamous cell carcinomas.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#172

 

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Name
Description Gastric epithelial cells (GECs) provide the first point of contact of the host by Helicobacter pylori (H. pylori), and the interaction between H. pylori and GECs plays a critical role in H. pylori-associated diseases. Aberrant expression of transcription factors (TFs) contributes to the pathogenesis of inflammatory disorders, including H. pylori-associated gastritis. ETS (E26 transformation specific) transcription factor family is one of the largest families of evolutionarily conserved TFs, regulating critical functions during cell homeostasis. We screened ETS family gene expression in H. pylori-infected mouse and human GECs and found that ETS1 (ETS proto-oncogene 1, transcription factor) expression was highly affected by H. pylori infection. Then, we reported that ETS1 was induced in GECs by H. pylori via cagA activated NF-κB pathway. Notably, we demonstrated that proinflammatory cytokines IL-1β and TNFα have synergistic effects on ETS1 expression during H. pylori infection in an NF-κB-pathway-dependent manner. RNA-seq assay and Gene-ontology functional analysis revealed that ETS1 positively regulate inflammatory response during H. pylori infection. Increased ETS1 is also detected in the gastric mucosa of mice and patients with H. pylori infection. Collectively, these data showed that ETS1 may play an important role in the pathogenesis of H. pylori-associated gastritis.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#173

 

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Name
Description Public camera footage of how people have responded so far to COVID-19 social distancing guidelines in spaces such as tourist spots and busy street corners could help inform new policies as the pandemic progresses.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#174

 

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Name
Description Toward identifying new strategies to target gastric cancer stem-like cells (CSCs), we evaluated the function of the tumour suppressor CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) in gastric CSC maintenance. We examined the expression of CDK5RAP3 and CD44 in gastric cancer patients. The function and mechanisms of CDK5RAP3 were checked in human and mouse gastric cancer cell lines and in mouse xenograft. We show that CDK5RAP3 is weakly expressed in gastric CSCs and is negatively correlated with the gastric CSC marker CD44. CDK5RAP3 overexpression decreased expression of CSC markers, spheroid formation, invasion and migration, and reversed chemoresistance in gastric CSCs in vitro and vivo. CDK5RAP3 expression was found to be regulated by extracellular-related kinase (ERK) signalling. ERK inhibitors decreased spheroid formation, migration and invasion, and the expression of epithelial-to-mesenchymal transition (EMT)-related proteins in both GA cells and organoids derived from a genetically engineered mouse model of GA. Finally, CDK5RAP3 expression was associated with reduced lymph-node metastasis and better prognosis, even in the presence of high expression of the EMT transcription factor Snail, among patients with CD44-positive GA. Our results demonstrate that CDK5RAP3 is suppressed by ERK signalling and negatively regulates the self-renewal and EMT of gastric CSCs.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#175

 

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Name
Description Triterpenoid saponins (TSs) are common plant defense phytochemicals with potential pharmaceutical properties. Platycodon grandiflorus (Campanulaceae) has been traditionally used to treat bronchitis and asthma in East Asia. The oleanane-type TSs, platycosides, are a major component of the P. grandiflorus root extract. Recent studies show that platycosides exhibit anti-inflammatory, antiobesity, anticancer, antiviral, and antiallergy properties. However, the evolutionary history of platycoside biosynthesis genes remains unknown. In this study, we sequenced the genome of P. grandiflorus and investigated the genes involved in platycoside biosynthesis. The draft genome of P. grandiflorus is 680.1 Mb long and contains 40,017 protein-coding genes. Genomic analysis revealed that the CYP716 family genes play a major role in platycoside oxidation. The CYP716 gene family of P. grandiflorus was much larger than that of other Asterid species. Orthologous gene annotation also revealed the expansion of β-amyrin synthases (bASs) in P. grandiflorus, which was confirmed by tissue-specific gene expression. In these expanded gene families, we identified key genes showing preferential expression in roots and association with platycoside biosynthesis. In addition, whole-genome bisulfite sequencing showed that CYP716 and bAS genes are hypomethylated in P. grandiflorus, suggesting that epigenetic modification of these two gene families affects platycoside biosynthesis. Thus whole-genome, transcriptome, and methylome data of P. grandiflorus provide novel insights into the regulation of platycoside biosynthesis by CYP716 and bAS gene families.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#176

 

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Name
Description The evidence is growing that we can form an immune memory of the coronavirus - but we don't know how strong it is and how long it lasts yet

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#177

 

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Name
Description MdMYB88 and MdMYB124 have been demonstrated to be responsible for lignin accumulation in apple under drought stress. In this study, using a metabolomic approach, we identified differentially accumulated phenylpropanoid and flavonoid metabolites in MdMYB88/124 transgenic RNAi plants under control and long-term drought stress conditions in apple roots. We confirmed the regulation of phenylalanine by MdMYB88 and MdMYB124 via UPLC-MS in apple roots under both control and drought conditions. Using Electrophoretic Mobility Shift Assay (EMSA) and ChIP-quantitative PCR (qPCR) analyses, we found that MdMYB88 positively regulates the MdCM2 gene, which is responsible for phenylalanine biosynthesis, through binding to its promoter region. Under long-term drought conditions, MdMYB88/124 RNAi plants consistently accumulated increased amounts of H2O2 and MDA, while MdMYB88 and MdMYB124 overexpression plants accumulated decreased amounts of H2O2 and MDA. We also examined the accumulation of metabolites in the phenylpropanoid biosynthesis pathway in the leaves of MdMYB88 and MdMYB124 transgenic apple plants after long-term drought stress. We found that metabolites responsible for plant defense, including phenylpropanoids and flavonoids, accumulated less in the RNAi plants but more in the overexpression plants under both control and drought conditions. We further demonstrated that MdMYB88/124 RNAi plants were more sensitive to Alternaria alternata f. sp. mali and Valsa mali, two pathogens that currently severely threaten apple production. In contrast, MdMYB88 and MdMYB124 overexpression plants were more tolerant to these pathogens. The cumulative results of this study provided evidence for secondary metabolite regulation by MdMYB88 and MdMYB124, further explained the molecular roles of MdMYB88 and MdMYB124 in drought resistance, and provided information concerning molecular aspects of their roles in disease resistance.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#178

 

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Name
Description CEO Elon Musk has repeatedly gotten himself into trouble when it comes to the coronavirus.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#179

 

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Name
Description Women who experience high blood pressure during pregnancy are more likely to develop heart disease and heart failure in later life, according to an international team of researchers. Between 1-6% of all pregnancies in Western countries are affected by high blood pressure, which usually returns to

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#180

 

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Name
Description Aging sucks. Your entire body starts deteriorating and it’s sad. There is nothing good about aging. But probably the worst part is the decline of cognitive abilities. Losing the sharpness of your mind is truly heartbreaking, but millions and millions of people are facing the inevitability of dementi

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#181

 

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Name
Description SC researchers peering deep inside a living cell have discovered something surprising: Its system for preventing genetic damage linked to diseases can fail so badly that the cell would be better off without it. It’s a paradoxical finding because it challenges the idea that tiny protein guardians

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#182

 

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Name
Description Researchers say early identification of infection clusters and the isolation of symptomatic and asymptomatic infections can suppress transmission.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#183

 

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Name
Description In these strange times, it can be tough to get definite answers. To compensate, our brains seek solace in conspiracy theories.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#184

 

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Name
Description Depression is one of the common psychiatric disorders in old age. Major depressive disorder (MDD) has been identified as a risk factor or prodrome for neurodegenerative dementias, suggesting neuropathological overlaps and a continuum between MDD and neurodegenerative disorders. In this study, we examined tau and amyloid-β (Aβ) accumulations in the brains of MDD and healthy controls using positron emission tomography (PET) to explore pathological substrates of this illness. Twenty MDD and twenty age-matched, healthy controls were examined by PET with a tau radioligand, [11C]PBB3, and an Aβ radioligand, [11C]PiB. Radioligand retentions were quantified as a standardized uptake value ratio (SUVR). We also assessed clinical manifestations of the patients using the 17-item Hamilton Depression Scale, the Geriatric Depression Scale, and psychotic symptoms. Mean cortical [11C]PBB3 SUVRs in MDD patients were significantly higher than those of healthy controls. These values were higher in MDD patients with psychotic symptoms than in those without any. The present findings indicate that tau depositions may underlie MDD, and especially in patients with psychotic symptoms. PET detection of tau accumulations may provide mechanistic insights into neuronal dysfunctions in these cases and could serve as predictions of their clinical consequences.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#185

 

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Name
Description Without a mask, droplets produced during coughing can travel up to 12 feet. With a mask, this distance is reduced to just a few inches.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#186

 

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Name
Description Insight into how compound kills cells might lead to safer variants of commonly used chemotherapy

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#187

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#188

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#189

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#190

 

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Name
Description Elon Musk is once again posting misleading claims about the coronavirus pandemic in an attempt to downplay the danger it poses.

#Medicine & Human body
Field # Medicine & Human body
Updated 01 July 2020

#191

 

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Name
Description A novel method is developed for predicting the stage of a cancer tissue based on the consistency level between the co-expression patterns in the given sample and samples in a specific stage. The basis for the prediction method is that cancer samples of the same stage share common functionalities as reflected by the co-expression patterns, which are distinct from samples in the other stages. Test results reveal that our prediction results are as good or potentially better than manually annotated stages by cancer pathologists. This new co-expression-based capability enables us to study how functionalities of cancer samples change as they evolve from early to the advanced stage. New and exciting results are discovered through such functional analyses, which offer new insights about what functions tend to be lost at what stage compared to the control tissues and similarly what new functions emerge as a cancer advances. To the best of our knowledge, this new capability represents the first computational method for accurately staging a cancer sample. The R source code used in this study is available at GitHub (https://github.com/yxchspring/CECS).

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#192

 

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Description To estimate the prevalence of Sjögren’s syndrome (SS) in the adult Spanish population we performed a population-based multicenter cross-sectional study. Cases were defined by the American-European Consensus Group criteria proposed in 2002. A total of 4,916 subjects aged 20 years or over were included. The estimated prevalence of SS (including primary and secondary forms) in the adult population in Spain was 0.33% (95% CI 0.21–0.53). Extrapolating to the total population of the country aged ≥ 20 years (around 37.7 million persons), there would be around 125,000 cases of SS in Spain. Considering only primary SS, the estimated prevalence was 0.25% (95% CI 0.15–0.43) or 1 person in 400. The prevalence of primary SS in Spain is comparable to that reported in other European studies with a similar design and diagnostic criteria. Based on these results, primary SS could not be considered a rare (orphan) disease. Only 50% of cases had already been diagnosed with SS prior EPISER 2016 study, confirming the existence of a non-negligible proportion of undiagnosed cases in the general population.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#193

 

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Name
Description Osteoarthritis presents as a change in the chondrocyte phenotype and an imbalance between anabolic and catabolic processes. Age affects its onset and progression. Small nucleolar RNAs (SnoRNAs) direct chemical modification of RNA substrates to fine-tune spliceosomal and rRNA function, accommodating changing requirements for splicing and protein synthesis during health and disease. Articular cartilage from young, old and OA knees was used in a microarray study to identify alterations in snoRNA expression. Changes in snoRNAs in osteoarthritis-like conditions were studied in chondrocytes using interleukin-1 and osteoarthritic synovial fluid. SNORD26 and SNORD96A knockdown and overexpression were undertaken using antisense oligonucleotides and overexpression plasmids. We identified panels of snoRNAs differentially expressed due to ageing (including SNORD96A, SNORD44) and osteoarthritis (including SNORD26 and SNORD116). In vitro experiments using osteoarthritis-like conditions affected snoRNA expression. Knockdown or overexpression of SNORD26 or SNORD96A resulted in changes in chondrogenic, hypertrophic, rRNA and osteoarthritis related gene expression. We demonstrate that snoRNA expression changes in cartilage ageing, and osteoarthritis and in osteoarthritis-like conditions, and when the expression of these snoRNAs is altered this affects chondrogenic and hypertrophic gene expression. Thus, we propose an additional dimension in the molecular mechanisms underlying cartilage ageing and osteoarthritis through the dysregulation of snoRNAs.

#Medicine & Human body;#Ageing
Field # Medicine & Human body
Updated 30 June 2020

#194

 

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Name
Description In patients with heart failure, some organizational and modifiable factors could be prognostic factors. We aimed to assess the association between the in-hospital care pathways during hospitalization for acute heart failure and the risk of readmission. This retrospective study included all elderly patients who were hospitalized for acute heart failure at the Universitary Hospital Lariboisière (Paris) during 2013. We collected the wards attended, length of stay, admission and discharge types, diagnostic procedures, and heart failure discharge treatment. The clinical factors were the specific medical conditions, left ventricular ejection fraction, type of heart failure syndrome, sex, smoking status, and age. Consistent groups of in-hospital care pathways were built using an ascending hierarchical clustering method based on a primary components analysis. The association between the groups and the risk of readmission at 1 month and 1 year (for heart failure or for any cause) were measured via a count data model that was adjusted for clinical factors. This study included 223 patients. Associations between the in-hospital care pathway and the 1 year-readmission status were studied in 207 patients. Five consistent groups were defined: 3 described expected in-hospital care pathways in intensive care units, cardiology and gerontology wards, 1 described deceased patients, and 1 described chaotic pathways. The chaotic pathway strongly increased the risk (p = 0.0054) of 1 year readmission for acute heart failure. The chaotic in-hospital care pathway, occurring in specialized wards, was associated with the risk of readmission. This could promote specific quality improvement actions in these wards. Follow-up research projects should aim to describe the processes causing the generation of chaotic pathways and their consequences.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#195

 

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Name
Description It has been suggested that an age-related loss of cognitive function might be driven by atherosclerotic effects associated with altered lipid patterns. However, the relationship between Lipoprotein (a) [Lp(a)] and healthy cognitive aging has not yet been sufficiently investigated. For the current analysis we used the cross-sectional data of 1,380 Berlin Aging Study II (BASE-II) participants aged 60 years and older (52.2% women, mean age 68 ± 4 years). We employed the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)-Plus test battery to establish latent factors representing continuous measures of domain specific cognitive functions. Regression models adjusted for APOE genotypes, lipid parameters and other risk factors for cognitive impairment were applied to assess the association between Lp(a) and performance in specific cognitive domains. Men within the lowest Lp(a)-quintile showed better cognitive performance in the cognitive domain executive functions and processing speed (p = 0.027). No significant results were observed in women. The results of the current analysis of predominantly healthy BASE-II participants point towards an association between low Lp(a) concentrations and better cognitive performance. However, evidence for this relationship resulting from the current analysis and the employment of a differentiated cognitive assessment is rather weak.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#196

 

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Name
Description Tumour budding in colorectal cancer has become an important prognostic factor. Represented by single cells or small tumour cell clusters at the invasion front of the tumour mass, these tumour buds seem to reflect cells in a ‘hybrid’ state of epithelial–mesenchymal transition, and evidence indicates that the presence of these entities is associated with lymph node metastasis, local recurrence and distant metastatic disease. The International Tumour Budding Consensus Conference (ITBCC) has highlighted a scoring system for the reporting of tumour budding in colorectal cancer, as well as different clinical scenarios that could affect patient management. Other organs are not spared: tumour budding has been described in numerous gastrointestinal and non-gastrointestinal cancers. Here, we give an update on ITBCC validation studies in the context of colorectal cancer and the clinical implications of tumour budding throughout the upper gastrointestinal and pancreatico-biliary tract.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#197

 

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Name
Description HIV-1 protease inhibitors (PIs), such as darunavir (DRV), are the key component of antiretroviral therapy. However, HIV-1 often acquires resistance to PIs. Here, seven novel PIs were synthesized, by introducing single atom changes such as an exchange of a sulfur to an oxygen, scission of a single bond in P2′-cyclopropylaminobenzothiazole (or -oxazole), and/or P1-benzene ring with fluorine scan of mono- or bis-fluorine atoms around DRV’s scaffold. X-ray structural analyses of the PIs complexed with wild-type Protease (PRWT) and highly-multi-PI-resistance-associated PRDRVRP51 revealed that the PIs better adapt to structural plasticity in PR with resistance-associated amino acid substitutions by formation of optimal sulfur bond and adaptation of cyclopropyl ring in the S2′-subsite. Furthermore, these PIs displayed increased cell permeability and extreme anti-HIV-1 potency compared to DRV. Our work provides the basis for developing novel PIs with high potency against PI-resistant HIV-1 variants with a high genetic barrier.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#198

 

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Name
Description Poll and colleagues examined the historical activity of hippocampal CA1 neurons during learning and memory recall using longitudinal two-photon in vivo imaging, providing evidence that extra neural ensemble activity disrupts memory recall in a mouse model of early Alzheimer’s disease.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#199

 

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Name
Description The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages. Eight-plex isobaric tags coupled with two-dimensional liquid chromatography–tandem mass spectrometry were used to analyse the proteome of PDAC tissues with different TNM stages. A loss-of-function study was performed to evaluate the oncogenic roles of WD repeat-containing protein 1 (WDR1) in PDAC. The molecular mechanism by which WDR1 promotes PDAC progression was studied by real-time qPCR, Western blotting, proximity ligation assay and co-immunoprecipitation. A total of 5036 proteins were identified, and 4708 proteins were quantified with high confidence. Compared with normal pancreatic tissues, 37 proteins were changed significantly in PDAC tissues of different stages. Moreover, 64 proteins were upregulated or downregulated in a stepwise manner as the TNM stages of PDAC increased, and 10 proteins were related to tumorigenesis. The functionally uncharacterised protein, WDR1, was highly expressed in PDAC and predicted a poor prognosis. WDR1 knockdown suppressed PDAC tumour growth and metastasis in vitro and in vivo. Moreover, WDR1 knockdown repressed the activity of the Wnt/β-Catenin pathway; ectopic expression of a stabilised form of β-Catenin restored the suppressive effects of WDR1 knockdown. Mechanistically, WDR1 interacted with USP7 to prevent ubiquitination-mediated degradation of β-Catenin. Our study identifies several previous functional unknown proteins implicated in the progression of PDAC, and provides new insight into the oncogenic roles of WDR1 in PDAC development.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#200

 

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Name
Description Genetic robustness is an important characteristic to tolerate genetic or nongenetic perturbations and ensure phenotypic stability. Morphogens, a type of evolutionarily conserved diffusible molecules, govern tissue patterns in a direction-dependent or concentration-dependent manner by differentially regulating downstream gene expression. However, whether the morphogen-directed gene regulatory network possesses genetic robustness remains elusive. In the present study, we collected 4217 morphogen-responsive genes along A-P axis of Drosophila wing discs from the RNA-seq data, and clustered them into 12 modules. By applying mathematical model to the measured data, we constructed a gene modular network (GMN) to decipher the module regulatory interactions and robustness in morphogen-directed development. The computational analyses on asymptotical dynamics of this GMN demonstrated that this morphogen-directed GMN is robust to tolerate a majority of genetic perturbations, which has been further validated by biological experiments. Furthermore, besides the genetic alterations, we further demonstrated that this morphogen-directed GMN can well tolerate nongenetic perturbations (Hh production changes) via computational analyses and experimental validation. Therefore, these findings clearly indicate that the morphogen-directed GMN is robust in response to perturbations and is important for Drosophila to ensure the proper tissue patterning in wing disc.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#201

 

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Name
Description

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#202

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#203

 

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Name
Description In an initial study conducted at the University of Notre Dame, researchers found that least-biased news sources and scientific-based news sources published less than a quarter of all stories currently available about COVID-19. ...

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#204

 

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Name
Description PSA Group unveiled one of its most important new models Tuesday with 20 people physically present and 2,600 watching online - a marketing configuration that the coronavirus seems likely to accelerate across the industry after ...

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#205

 

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Name
Description Scotland may be only weeks away from no new daily cases of coronavirus. As the nation gets close, cases from over the border will become a big problem.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#206

 

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Name
Description Coronavirus cases have surged in several areas thought to have the virus under control, including parts of South Korea, Australia and the US.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#207

 

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Name
Description Tiny lenses made out of spider silk and clear resin can produce a special kind of light beam that makes them perfect for taking images of tiny objects like viruses

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#208

 

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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 30 June 2020

#209

 

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Description The superhydrophobic material, called ElastiDry, repels bacteria, viruses. Personal protective equipment (PPE) has been at the center of the fight against COVID-19. Like rarely before, the unforgiving virus has shown medical providers the essential importance of top-line devices. With this cri

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#210

 

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Description Xiang-Dong Fu, PhD, has never been more excited about something in his entire career. He has long studied the basic biology of RNA, a genetic cousin of DNA, and the proteins that bind it. But a single discovery has launched Fu into a completely new field: neuroscience. For decades, Fu and his tea

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#211

 

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Description Many parts of the world are in the midst of a deadly pandemic of cholera, an extreme form of watery diarrhea. UC Riverside scientists have discovered specific gut bacteria make some people resistant to it — a finding that could save lives. Cholera can kill within hours if left untreated, and it s

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#212

 

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Description Antibiotic resistance is one of the greatest threats to human life, but what can we do about it?

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#213

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#214

 

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Name
Description Earlier rules gave institutions more flexibility in supporting research

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#215

 

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Description To stop the pandemic, the world’s public health experts must win the coming “story war” over vaccine misinformation

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#216

 

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Description The ride-hailing company says drivers in select cities will now have a steady supply of Clorox disinfectant wipes for everyone to use.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#217

 

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Description Surgical excision is the preferred treatment for multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism (PHPT), although controversy regarding the surgical strategy exists. We retrospectively investigated the short-term outcomes of PHPT by various surgical extents. Thirty-three patients who underwent parathyroidectomy due to MEN1-related PHPT at Yonsei Severance Hospital between 2005 and 2018 were included (age [mean ± SD], 43.4 ± 14.1 [range, 23–81] years). Total parathyroidectomy with auto-transplantation to the forearm (TPX) was the most common surgical method (17/33), followed by less-than-subtotal parathyroidectomy (LPX; 12/33) and subtotal parathyroidectomy (SPX; 4/33). There was no postoperative persistent hyperparathyroidism. Recurrence was high in the LPX group without significance (1 in TPX, 2 in SPX, and 3 in LPX, p = 0.076). Permanent and transient hypoparathyroidism were more common in TPX (n = 6/17, 35.3%, p = 0.031; n = 4/17, 23.5%, p = 0.154, respectively). Parathyroid venous sampling (PVS) was introduced in 2013 for preoperative localisation of hyperparathyroidism at our hospital; nine among 19 patients operated on after 2013 underwent pre-parathyroidectomy PVS, with various surgical extents, and no permanent hypoparathyroidism (p = 0.033) or post-LPX recurrence was observed. Although TPX with auto-transplantation is the standard surgery for MEN1-related PHPT, surgical extent individualisation is necessary, given the postoperative hypoparathyroidism rate of TPX and feasibility of PVS.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#218

 

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Description Transforming growth factor-β (TGF-β) promotes tumor invasion and metastasis by inducing epithelial-mesenchymal transition (EMT). EMT is often related with acquisition of stemness characteristics. The objective of this study was to determine whether EMT and stemness characteristics induced by TGF-β might be associated with epigenetic regulation in lung cancer. A human normal lung epithelial cell line and four lung cancer cell lines were treated with TGF-β. Transcriptome analysis of BEAS-2B and A549 cells incubated with TGF-β were analyzed through next-generation sequencing (NGS). Western blotting was carried out to investigate expression levels of epithelial and mesenchymal markers. Wound healing and Matrigel invasion assay, sphere formation assay, and in vivo mice tumor model were performed to evaluate functional characteristics of EMT and stemness acquisition. To investigate whether activation of EMT and stem cell markers might be involved in epigenetic regulation of lung cancer, experiment using a DNA methyltransferase inhibitor (5-azacytidine, AZA), methylation-specific PCR (MSP) and bisulfite sequencing were performed. NGS revealed changes in expression levels of EMT markers (E-cadherin, N-cadherin, fibronectin, vimentin, slug and snail) and stem cell markers (CD44 and CD87) in both BEAS-2B and A549 cells. Functional analysis revealed increased migration, invasion, sphere formation, and tumor development in mice after TGF-β treatment. Expression of slug and CD87 genes was activated following treatment with AZA and TGF-β. MSP and bisulfite sequencing indicated DNA demethylation of slug and CD87 genes. These results suggest that TGF-β induced EMT and cancer stemness acquisition could be associated with activation of slug and CD87 gene by their promoter demethylation.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#219

 

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Description

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#220

 

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Description Renal interstitial fibrosis (RIF) is currently recognized as a crucial mechanism of the pathogenesis of chronic kidney disease (CKD). Kangxianling (KXL, anti-fibrin) is a traditional Chinese medicine that has been proven to significantly reduce the levels of ECM deposition and inhibit renal fibrosis. To characterize the mechanisms and drug targets of KXL, we established a RIF rat model and treated the rats with KXL and losartan. Histological analyses validated the establishment of the RIF model and the treatment effect of KXL. Multiple levels of transcriptomic datasets were generated using lncRNA, mRNA and microRNA sequencing of kidney tissues. Functional annotations and pathway analyses were performed to unravel the therapeutic mechanisms. A multi-level transcriptomic regulatory network was built to illustrate the core factors in fibrosis pathogenesis and therapeutic regulation. KXL and losartan significantly reduced the progression of RIF, and a better therapeutic effect was shown with higher concentrations of KXL. According to the cluster analysis results of the RNA-seq data, the normal control (NC) and high concentration of KXL (HK) treatment groups were the closest in terms of differentially expressed genes. The WNT, TGF-β and MAPK pathways were enriched and dominated the pathogenesis and therapy of RIF. miR-15b, miR-21, and miR-6216 were upregulated and miR-107 was downregulated in the fibrosis model. These small RNAs were shown to play critical roles in the regulation of the above fibrosis-related genes and could be inhibited by KXL treatment. Finally, based on the lncRNA datasets, we constructed a mRNA-lncRNA-miRNA coexpression ceRNA network, which identified key regulatory factors in the pathogenesis of kidney fibrosis and therapeutic mechanisms of KXL. Our work revealed the potential mechanism of the Chinese medicine Kangxianling in inhibiting renal interstitial fibrosis and supported the clinical use of KXL in the treatment of kidney fibrosis.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#221

 

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Description X-rays are widely used in probing inside information nondestructively, enabling broad applications in the medical radiography and electronic industries. X-ray imaging based on emerging lead halide perovskite scintillators has received extensive attention recently. However, the strong self-absorption, relatively low light yield and lead toxicity of these perovskites restrict their practical applications. Here, we report a series of nontoxic double-perovskite scintillators of Cs2Ag0.6Na0.4In1-yBiyCl6. By controlling the content of the heavy atom Bi3+, the X-ray absorption coefficient, radiative emission efficiency, light yield and light decay were manipulated to maximise the scintillator performance. A light yield of up to 39,000 ± 7000 photons/MeV for Cs2Ag0.6Na0.4In0.85Bi0.15Cl6 was obtained, which is much higher than that for the previously reported lead halide perovskite colloidal CsPbBr3 (21,000 photons/MeV). The large Stokes shift between the radioluminescence (RL) and absorption spectra benefiting from self-trapped excitons (STEs) led to a negligible self-absorption effect. Given the high light output and fast light decay of this scintillator, static X-ray imaging was attained under an extremely low dose of ∼1 μGyair, and dynamic X-ray imaging of finger bending without a ghosting effect was demonstrated under a low-dose rate of 47.2 μGyair s−1. After thermal treatment at 85 °C for 50 h followed by X-ray irradiation for 50 h in ambient air, the scintillator performance in terms of the RL intensity and X-ray image quality remained almost unchanged. Our results shed light on exploring highly competitive scintillators beyond the scope of lead halide perovskites, not only for avoiding toxicity but also for better performance. Low-dose X-ray imaging, which relies on scintillators to convert X-ray photons into readily detectable photons of light, has been improved using new varieties of scintillators composed of materials known as double perovskites. Yang Yang and colleagues at Zhejiang University in China made their scintillators from nontoxic elements including caesium, silver, sodium, indium, bismuth and chloride ions. They outperform existing lead halide perovskite scintillators due to greatly increased light-yield, heat stability and low toxicity. Unlike many alternatives, they do not contain toxic lead ions. The researchers maximised the light-yielding efficiency by controlling the content of bismuth ions (Bi3+) in the double perovskite crystals. They demonstrated the potential of their material by achieving exceptionally low-dose static X-ray images and real-time dynamic images of finger bending. The researchers see great scope for further improvements by exploring other types of lead-free perovskites and perovskite derivatives.

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 30 June 2020

#222

 

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Description Post V-shaped recovery in June as online spend picks up; UPI transactions at 1.42 billion highest in a month

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#223

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#224

 

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Description A new effort looks to help unemployed workers gain needed skills for in-demand digital positions.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#225

 

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Description Scammers are sending emails claiming to be government officials giving money for a "Global Empowerment Fund."

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#226

 

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Description Early trial data suggests that vaccine is safe, but efficacy still unclear.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#227

 

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Description US employees get a “thank you” bonus; German warehouse workers are on strike.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#228

 

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Description Researchers have discovered that Mediterranean populations may be more susceptible to an autoinflammatory disease because of evolutionary pressure to survive the bubonic plague. The study, carried out by scientists at the National Human Genome Research Institute (NHGRI), part of the National Institu

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#229

 

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Description UC San Francisco scientists assembled an international research team that has figured out how SARS-CoV-2, the virus that causes COVID-19, hijacks proteins in host cells that serve as master regulators of key cellular processes. By doing so, the virus is able to rewire the cell’s internal circuitry t

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#230

 

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Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#231

 

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Description Google has turned off automatic back up for photos and videos from messaging apps. The development was shared by the search giant on its support blog. The reason for this change is to &ldquo;save internet resources&rdquo; due to the ongoing coronavirus pandemic.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#232

 

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Description Most traditional cancer therapies target either the tumor cells themselves or indiscriminately kill any rapidly dividing cell. New findings by researchers at University of California San Diego School of Medicine indicate that manipulating macrophages, a type of immune cell found abundantly in the ti

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#233

 

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Description Cambridge-led study discovers new genetic causes of rare diseases, potentially leading to improved diagnosis and better patient care. A research programme pioneering the use of whole genome sequencing in the NHS has diagnosed hundreds of patients and discovered new genetic causes of disease. Whol

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#234

 

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Description Problems in how the brain recognizes and processes novel information lie at the root of psychosis, researchers from the University of Cambridge and King’s College London have found. Their discovery that defective brain signals in patients with psychosis could be altered with medication paves the way

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#235

 

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Description Ribonucleic acid, or RNA, is part of our genetic code and present in every cell of our body. The best known form of RNA is a single linear strand, of which the function is well known and characterized. But there is also another type of RNA, so-called “circular RNA”, or circRNA, which forms a continu

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#236

 

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Description This will go down well on politics social media.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#237

 

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Description Tech executives at Intel, Microsoft, GE Digital, PTC and FogHorn Systems discuss how COVID-19 has affected the IoT market, including where new opportunities have popped up.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#238

 

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Description We already know that our brains have a waste disposal system that keeps dead and toxic neurons from clogging up our biological pathways. Now, scientists have managed to capture a video of the process for the first time, in laboratory tests on mice.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#239

 

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Description Molecular biology has helped illuminate long-held questions about flowering plants

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#240

 

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Description An electric toothbrush deal to put a smile on your face

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#241

 

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Description v class="pf-content">

The coronavirus is currently changing slowly. There are only about two dozen mutations....

#Medicine & Human body

Field # Medicine & Human body
Updated 30 June 2020

#242

 

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Description BCL2 overexpression has been reported to be associated with poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL). However, currently there is no consensus on the evaluation of BCL2 expression and only the proportion of BCL2 positive cells are evaluated for the determination of BCL2 positivity. This study aimed to define BCL2 positivity by quantitative analysis integrating both the intensity and proportion of BCL2 expression. BCL2 expression of 332 patients (221 patients for the training set and 111 patients for the validation set) with newly diagnosed DLBCL who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) were analyzed using the tumor-specific automated quantitative analysis (AQUA) scoring method based on multiplex immunofluorescence. In the training set, high BCL2 AQUA score (N = 86, 38.9%) was significantly associated with poor prognosis (p = 0.01, HR 2.00; 95% CI [1.15–3.49]) independent of international prognostic index, cell of origin, and MYC expression. The poor prognostic impact of the high BCL2 AQUA score was validated in the validation set. AQUA scoring of BCL2 expression incorporating both the intensity and proportion of BCL2 positive cells was independently associated with survival outcomes of patients with primary DLBCL treated with R-CHOP.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#243

 

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Description Adolescent alcohol exposure may increase anxiety-like behaviors by altering central monoaminergic functions and other important neuronal pathways. The present study was designed to investigate the anxiolytic effect of 0.5% γ-oryzanol (GORZ) and its neurochemical and molecular mechanisms under chronic 10% ethanol consumption. Five-week-old ICR male mice received either control (14% casein, AIN 93 M) or GORZ (14% casein, AIN 93 M + 0.5% GORZ) diets in this study. We showed that GORZ could potentially attenuate alcohol-induced anxiety-like behaviors by significantly improving the main behavioral parameters measured by the elevated plus maze test. Moreover, GORZ treatment significantly restored the alcohol-induced downregulation of 5-hydroxytryptophan and 5-hydroxyindole acetic acid in the hippocampus and improved homovanillic acid levels in the cerebral cortex. Furthermore, a recovery increase in the level of 3-methoxy-4-hydroxyphenylglycol both in the hippocampus and cerebral cortex supported the anxiolytic effect of GORZ. The significant elevation and reduction in the hippocampus of relative mRNA levels of brain-derived neurotrophic factor and interleukin 1β, respectively, also showed the neuroprotective role of GORZ in ethanol-induced anxiety. Altogether, these results suggest that 0.5% GORZ is a promising neuroprotective drug candidate with potential anxiolytic, neurogenic, and anti-neuroinflammatory properties for treating adolescent alcohol exposure.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#244

 

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Description The control of ovulation helps guarantee the success of reproduction and as such, contributes to the fitness of a species. In mammals, two types of ovulation are observed: induced and spontaneous ovulation. Recent work on camelids, that are induced ovulators, highlighted the role of a factor present in seminal plasma, beta Nerve Growth Factor (β-NGF), as the factor that triggers ovulation in a GnRH dependent manner. In the present work, we characterized alpaca β-NGF (aβ-NGF) and its 3D structure and compared it with human recombinant β-NGF (hβ-NGF). We showed that the β-NGF enriched fraction of alpaca semen and the human recombinant protein, both stimulated spontaneous electrical activity of primary GnRH neurons derived from mouse embryonic olfactory placodes. This effect was dose-dependent and mediated by p75 receptor signaling. P75 receptors were found expressed in vitro by olfactory ensheathing cells (OEC) in close association with GnRH neurons and in vivo by tanycytes in close vicinity to GnRH fibers in adult mouse. Altogether, these results suggested that β-NGF induced ovulation through an increase in GnRH secretion provoked by a glial dependent P75 mediated mechanism.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#245

 

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Description Exposure to pesticides such as rotenone is a risk factor for Parkinson’s disease. Dopaminergic neurons are especially sensitive to the toxicity of compounds that inhibit the mitochondrial respiratory chain such as rotenone and 1-methyl-4-phenylpyridinium (MPP+). However, there is scarce information on their effects on glia. To evaluate whether these neurotoxicants affect the immune response of glia, primary mouse mixed glial and microglial cultures were treated with interleukin (IL) 4 in the absence and presence of MPP+ or rotenone. Using qRTPCR or western blot, we determined the expression of anti-inflammatory markers, the CD200R1 microglial receptor and its ligand CD200, and genes regulating glycolysis and oxidative metabolism. ATP and lactate levels were additionally determined as an index of cell metabolism. Microglial phagocytosis was also evaluated. MPP+ and rotenone clearly abrogated the IL4-induced expression of anti-inflammatory markers in mixed glial cultures. CD200 and CD200R1 expression and microglia phagocytosis were also affected by the neurotoxicants. Changes in the mRNA expression of the molecules regulating glycolysis and oxidative metabolism, as well as in ATP levels and lactate release suggested that metabolic reprogramming in response to MPP+ and rotenone differs between microglial and mixed glial cultures. These findings support the hypothesis that parkinsonian neurotoxicants may impair brain immune response altering glial cell metabolism.

#Medicine & Human body
Field # Medicine & Human body
Updated 30 June 2020

#246

 

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Description Because chronic lung allograft dysfunction (CLAD) develops predominantly on one side after bilateral living-donor lobar lung transplantation (LDLLT), lung perfusion scintigraphy (Q-scinti) was expected to show a perfusion shift to the contralateral unaffected lung with the development of CLAD. Our study examined the potential usefulness of Q-scinti in the diagnosis of CLAD after bilateral LDLLT. We conducted a single-center retrospective cohort study of 58 recipients of bilateral LDLLT. The unilateral shift values on Q-scinti were calculated and compared between the CLAD group (N = 27) and the non-CLAD group (N = 31) from 5 years before to 5 years after the diagnosis of CLAD. The unilateral shift values in Q-scinti were significantly higher in the CLAD group than in the non-CLAD group from 5 years before the diagnosis of CLAD to 5 years after the diagnosis (P < 0.05). The unilateral shift values in Q-scinti were significantly correlated with the percent baseline values of the forced expiratory volume in 1 s (P = 0.0037), the total lung capacity (P = 0.0028), and the forced vital capacity (P = 0.00024) at the diagnosis of CLAD. In patients developing unilateral CLAD after bilateral LDLLT, Q-scinti showed a unilateral perfusion shift to the contralateral unaffected lung. Thus, Q-scinti appears to have the potential to predict unilateral CLAD after bilateral LDLLT.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#247

 

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Description Naïve human pluripotent stem cells (hPSC) resemble the embryonic epiblast at an earlier time-point in development than conventional, ‘primed’ hPSC. We present a comprehensive miRNA profiling of naïve-to-primed transition in hPSC, a process recapitulating aspects of early in vivo embryogenesis. We identify miR-143-3p and miR-22-3p as markers of the naïve state and miR-363-5p, several members of the miR-17 family, miR-302 family as primed markers. We uncover that miR-371-373 are highly expressed in naïve hPSC. MiR-371-373 are the human homologs of the mouse miR-290 family, which are the most highly expressed miRNAs in naïve mouse PSC. This aligns with the consensus that naïve hPSC resemble mouse naive PSC, showing that the absence of miR-371-373 in conventional hPSC is due to cell state rather than a species difference.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#248

 

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Description We aimed to evaluate the association between obesity and the incidence of retinal vein occlusion (RVO) with and without diabetes mellitus (DM).This is a retrospective cohort study using Korean National Health Insurance System data. The participants were 23,061,531 adults older than 20 years who received a health examination at least once between 2009 and 2012, and all patients were observed for RVO development until 2015. We used a multivariate adjusted Cox regression analysis to evaluate the association between RVO and body mass index (BMI) with and without DM. The analysis were evaluated via a hazard ratio (HR) and 95% confidence interval (CI). The age-, sex-, and multivariable-adjusted HRs for RVO were stratified by BMI. This population-based study revealed evidence that obesity has a different effect on the incidence of RVO in the presence and absence of DM.In people with DM, a lower BMI was associated with an increased risk of RVO, and a higher BMI was associated with a lower risk for RVO. In people without DM, the correlation was reversed: a lower BMI was associated with a lower risk for RVO and vice versa.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#249

 

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Description Neuroscientists have identified neurons responsible for making memory-based decisions. Most of us know that feeling of trying to retrieve a memory that does not come right away. You might be watching a romantic comedy featuring that famous character actor who always plays the best friend and finds

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#250

 

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Description Differentiating glaucoma from myopic eye is a challenge to ophthalmologists. We try to develop a new discrete Fourier transform (DFT) model for analyzing optical coherence tomography data for the circumpapillary retinal nerve fiber layer (cpRNFL), and investigate DFT as a new diagnostic tool for glaucomatous myopic eyes. The thicknesses of 12 equidistant cpRNFL points were transformed into 6 signals in the frequency domain, ranging from 1 to 6 Hz. In all 232 eyes, generalized linear model showed that 1 Hz, 2 Hz, and 4 Hz were associated with glaucoma, high myopia, and the interaction between glaucoma and high myopia. The 3 Hz signal was associated with glaucoma and high myopia exclusively. A receiver operating characteristic curve analysis of the 3 Hz signals showed areas under the curves of 0.93 (95% CI 0.90–0.96) and 0.93 (95% CI 0.88–0.98), for diagnosing glaucoma in all subjects and in the highly myopic group, respectively. The DFT model is useful to differentiate glaucoma from non-glaucomatous change and showed potential as a diagnostic tool for glaucomatous myopic eyes.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#251

 

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Description Scientists at LiU’s Laboratory of Organic Electronics have developed an organic transistor that they can use to measure and study in fine detail a phenomenon known as extracellular electron transfer in which bacteria release electrons. The study of bacteria and their significance for the natu

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#252

 

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Description After examining the genes of more than 200,000 people all over the world who have type-2 diabetes, researchers from the Perelman School of Medicine at the University of Pennsylvania and the Veterans Health Administration’s (VHA) Corporal Michael J. Crescenz Veterans Affairs Medical Center (CMCVAMC) 

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#253

 

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Description Ladder is one of the most important tool humans have ever invented. This seemingly simple and cheap device is ubiquitous in construction sites everywhere in the world. Not only that - pretty much every house owner has a ladder or two. And many people fall off of them, suffering life-long consequence

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#254

 

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Description EAEC is a common cause of diarrheal illness worldwide. Pathogenesis is believed to occur in the ileum and colon, where the bacteria adhere and form a robust aggregating biofilm. Among the multiple virulence factors produced by EAEC, the Pic serine protease has been implicated in bacterial colonization by virtue of its mucinolytic activity. Hence, a potential role of Pic in mucus barrier disruption during EAEC infection has been long postulated. In this study, we used human colonoids comprising goblet cells and a thick mucin barrier as an intestinal model to investigate Pic’s roles during infection with EAEC. We demonstrated the ability of purified Pic, but not a protease defective Pic mutant to degrade MUC2. Western blot and confocal microscopy analysis revealed degradation of the MUC2 layer in colonoids infected with EAEC, but not with its isogenic EAECpic mutant. Wild-type and MUC2-knockdown colonoids infected with EAEC strains exposed a differential biofilm distribution, greater penetration of the mucus layer and increased colonization of the colonic epithelium by Wild-type EAEC than its isogenic Pic mutant. Higher secretion of pro-inflammatory cytokines was seen in colonoids infected with EAEC than EAECpic. Although commensal E. coli expressing Pic degraded MUC2, it did not show improved mucus layer penetration or colonization of the colonic epithelium. Our study demonstrates a role of Pic in MUC2 barrier disruption in the human intestine and shows that colonoids are a reliable system to study the interaction of pathogens with the mucus layer.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#255

 

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Description In the largest exercise research program of its kind, researchers are poised to collect and turn data from nearly 2,600 volunteers into comprehensive maps of the molecular changes in the body due to exercise. It is well known that physical activity has substantial health benefits, but we do not full

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#256

 

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Description Entomopathogenic nematodes are effective biocontrol agents against arthropod pests. However, their efficacy is limited due to sensitivity to environmental extremes. The objective of the present study was to establish a foundation of genetic-based selection tools for beneficial traits of heat and desiccation tolerance in entomopathogenic nematodes. Screening of natural populations enabled us to create a diverse genetic and phenotypic pool. Gene expression patterns and genomic variation were studied in natural isolates. Heterorhabditis isolates were phenotyped by heat- and desiccation-stress bioassays to determine their survival rates compared to a commercial line. Transcriptomic study was carried out for the commercial line, a high heat-tolerant strain, and for the natural, low heat-tolerant isolate. The results revealed a higher number of upregulated vs. downregulated transcripts in both isolates vs. their respective controls. Functional annotation of the differentially expressed transcripts revealed several known stress-related genes and pathways uniquely expressed. Genome sequencing of isolates with varied degrees of stress tolerance indicated variation among the isolates regardless of their phenotypic characterization. The obtained data lays the groundwork for future studies aimed at identifying genes and molecular markers as genetic selection tools for enhancement of entomopathogenic nematodes ability to withstand environmental stress conditions.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#257

 

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Description In a new study researchers at Karolinska Institutet and KTH Royal Institute of Technology have developed a new kind of brain atlas based on an innovative method of mapping brain tissue into areas according to their molecular profile. The study is published in Science Advances. Many of the atl

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#258

 

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Name
Description The imbalance in immune tolerance may cause the variety of reproductive failures. An intravenous immunoglobulin infusion (IVIg) therapy is used to improve the live birth rate in women suffering from recurrent pregnancy loss, recurrent spontaneous abortions and recurrent implantation failures. However, the results of IVIg studies are still inconclusive as IVIg infusion in women suffering from pregnancy loss is sometimes ineffective. One of the mechanisms of action of this treatment is inhibition of B cells differentiation and expansion of Tregs and secretion of interleukin 10. It was proposed that immunomodulatory effects of IVIg may be attributed to tregitopes - self-IgG-derived epitopes present in the structure of immunoglobulins. Similarly to IVIg, tregitopes cause the expansion of Tregs and secretion of antigen-specific effector cytokine response. Here, we studied whether the administration of mouse tregitope 167 and/or 289 can prevent abortions in mouse abortion-prone mouse matings. We revealed that tregitopes reduce the foetal death rate. This may be driven by observed higher pool of peripheral Tregs, increased production of IL-10 by Tregs and Bregs and/or maintaining the tolerogenic phenotype of antigen-presenting cells. We believe that our findings may indicate a potential alternative to IVIg for therapeutic intervention in case of pregnancy failures.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#259

 

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Description More children are being vaccinated around the world today than ever before, and the prevalence of many vaccine-preventable diseases has dropped over the last decade. Despite these encouraging signs, however, the availability of essential vaccines has stagnated globally in recent years, according to

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#260

 

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Name
Description After the birth of her third child, Lee ScottLorde experienced postpartum depression, something that affects one in nine mothers. Injuries she’d incurred during the delivery made it hard for her to walk, which exacerbated her unhappiness. “I decided I would start by taking small walks outside,” s

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#261

 

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Name
Description Bone marrow mesenchymal stem cells (BMSCs) have multi-lineage differentiation potential and play an important role in tissue repair. Studies have shown that BMSCs gather at the injured tissue site after granulocyte-colony stimulating factor (G-CSF) administration. In this study, we first investigated whether G-CSF could promote BMSC homing to damaged lung tissue induced by bleomycin (BLM) and then investigated whether SDF-1/CXCR4 chemotaxis might be involved in this process. Next, we further studied the potential inhibitory effect of G-CSF administration in mice with lung fibrosis induced by bleomycin. We examined both the antifibrotic effects of G-CSF in mice with bleomycin-induced pulmonary fibrosis in vivo and its effects on the proliferation, differentiation and chemotactic movement of cells in vitro. Flow cytometry, real-time PCR, transwell and Cell Counting Kit-8 (CCK-8) assays were used in this study. The results showed that both preventative and therapeutic G-CSF administration could significantly inhibit bleomycin-induced pulmonary fibrosis. G-CSF enhanced BMSC migration to lung tissues, but this effect could be alleviated by AMD3100, which blocked the SDF-1/CXCR4 axis. We also found that BMSCs could inhibit fibroblast proliferation and transdifferentiation into myofibroblasts through paracrine actions. In conclusion, G-CSF exerted antifibrotic effects in bleomycin-induced lung fibrosis, in part by promoting BMSC homing to injured lung tissues via SDF-1/CXCR4 chemotaxis.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#262

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#263

 

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Name
Description Numerous studies have shown that children who grow up in more deprived neighbourhoods tend to have worse physical health as adults compared to those raised in more affluent areas.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#264

 

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Name
Description While the brain is composed of two types of cells, glia tend to receive far less attention for their importance in brain function and disease than the more celebrated neurons. But scientists have known for more than a century that special types of glial cells are integral components of neuromuscular

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#265

 

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Name
Description Researchers have developed a method to spur the production of new antibiotic or antiparasitic compounds hiding in the genomes of actinobacteria, which are the source of drugs such as actinomycin and streptomycin and are known to harbor other untapped chemical riches. The scientists reported their fi

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#266

 

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Name
Description When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made. In this process, called organ sparing, resources are preferentially delegated to the nervous system at the cost of l

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#267

 

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Name
Description A method known as CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia. It modifies a patient’s own T-cells by adding a piece of an antibody that recognizes unique features on the surface of cancer cells. In a new study, researchers report that they h

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#268

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#269

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#270

 

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Name
Description The MIT Press has announced the launch of Rapid Reviews: COVID-19 (RR:C19), an open access, rapid-review overlay journal that will accelerate peer review of Covid-19-related research and deliver real-time, verified scientific information.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#271

 

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Name
Description Recently, platelet-rich plasma (PRP) has received attention as a treatment for patients with osteoarthritis of the knee (OAK), a chronic degenerative disease, to bridge the gap between conservative and surgical treatments. Here, we investigated the differences in the humoral factors present in two types of PRP purified using the Autologous Protein Solution (APS) kit (group Z; leucocyte-rich PRP) or the Cellaid Serum Collection Set P type (group J; leucocyte-poor [LP]-PRP). Differences in humoral factors between healthy subjects (n = 10) and OAK patients (n = 12; group Z = 6, group J = 6), and the relationship between humoral factors and clinical outcome scores were investigated. Both anti-inflammatory and inflammatory cytokines were highly enriched in APS. The concentrations of tumour necrosis factor (TNF)-α, platelet-derived growth factor, fibroblast growth factor, soluble TNF-receptor 2, soluble Fas and transforming growth factor-β1 were higher in group Z, while the total amounts were higher in group J. The concentration of interleukin-1 receptor antagonist was positively correlated with the magnitude of change in the clinical outcome score and may contribute to improving knee-joint function. This is the first description of the humoral factors in APS and LP-PRP prepared from healthy subjects or OAK patients of Asian descent.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#272

 

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Name
Description The conserved region of influenza hemagglutinin (HA) stalk (or stem) has gained attention as a potent target for universal influenza vaccines1–5. Although the HA stalk region is relatively well conserved, the evolutionarily dynamic nature of influenza viruses6 raises concerns about the possible emergence of viruses carrying stalk escape mutation(s) under sufficient immune pressure. Here we show that immune pressure on the HA stalk can lead to expansion of escape mutant viruses in study participants challenged with a 2009 H1N1 pandemic influenza virus inoculum containing an A388V polymorphism in the HA stalk (45% wild type and 55% mutant). High level of stalk antibody titers was associated with the selection of the mutant virus both in humans and in vitro. Although the mutant virus showed slightly decreased replication in mice, it was not observed in cell culture, ferrets or human challenge participants. The A388V mutation conferred resistance to some of the potent HA stalk broadly neutralizing monoclonal antibodies (bNAbs). Co-culture of wild-type and mutant viruses in the presence of either a bNAb or human serum resulted in rapid expansion of the mutant. These data shed light on a potential obstacle for the success of HA-stalk-targeting universal influenza vaccines—viral escape from vaccine-induced stalk immunity. High levels of antibodies specific for the stalk region of influenza hemagglutinin protein are associated with expansion of mutant viruses in human volunteers, suggesting potential challenges for influenza vaccine efforts targeting the HA stalk.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#273

 

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Name
Description Evolutionary genetic and experimental analyses suggest that mutations causing familial Mediterranean fever have been positively selected in the Middle East, probably because they confer heightened resistance against Yersinia pestis infection.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#274

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#275

 

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Name
Description Young and colleagues show that anti-cancer compounds can undergo partitioning into biomolecular condensates, affecting their activity.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#276

 

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Name
Description Now more than ever, digital applications are essential to accessing genetics services and optimizing their delivery. At this watershed moment, digital solutions must be balanced with the merits of human interaction, without compromising quality or exacerbating existing genomic and technological disparities. As highlighted by the COVID-19 pandemic, digital solutions are becoming essential for the provision of clinical genetics services. However, as this Comment emphasizes, the use of digital tools alone can exacerbate genomic and technological disparities and must be balanced with the merits of face-to-face interactions.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#277

 

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Name
Description Retrospective descriptive study. To compare histopathological findings and the long-term course of SCI patients with bladder cancer found incidentally at the initial urological workup to those diagnosed with bladder cancer many years after the onset of SCI. Spinal cord injury center in Germany. Data and follow-up of consecutive in- and out-patients with SCI admitted at a tertiary spinal cord injury center between January 1, 1998 and December 31, 2018 were screened retrospectively. All patients with acquired SCI were evaluated for pathological findings in the urinary bladder present at the time of SCI on the initial urological workup. Data of 37 long-term SCI patients from the same center with diagnosed bladder cancer and data of the general German population served as reference groups. Descriptive statistics were applied. In total, four patients with bladder cancer at initial urological workup were assessed. They all had non-muscle invasive bladder cancer. Two of the patients were cystectomized 34 and 106 months after first bladder cancer diagnosis, due to relapsing tumor and progressive renal failure, respectively. In both cases no tumor was found in the resected bladder. All four patients are currently alive with no tumor and a mean follow-up of 105 months. In incidental bladder cancer observed at the initial urological workup after acquired SCI, the duration of SCI, at least in the first 5 years, does not noticeably contribute to a poor prognosis, i.e., progression to muscle invasive bladder cancer (≥T2) or a higher grading (G3).

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#278

 

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Name
Description Simultaneously targeting other pathways could increase the activity of PD-1 blockade in lymphoid malignancies not sensitive to single-agent blockade. We explored the safety and efficacy of combined PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory (R/R) lymphoid malignancies. This phase 1b trial enrolled adult patients with R/R classical Hodgkin lymphoma (cHL), non-Hodgkin lymphoma (NHL), or multiple myeloma (MM). Patients received nivolumab plus ipilimumab (nivo/ipi) or lirilumab (nivo/liri) until complete response (CR), progression, or unacceptable toxicity. The primary endpoint was safety and tolerability, while secondary endpoints included overall (ORR) and CR rates (CRR), progression-free and overall survival. Sixty-five patients were treated with nivo/ipi, and 72 with nivo/liri. Twenty-nine percent of patients experienced grade 3–4 treatment-related adverse events with nivo/ipi, and 15% with nivo/liri. In cHL, ORR was 74% for nivo/ipi and 76% for nivo/liri, CRRs were 23% and 24%, respectively. In B-NHL and T-NHL, ORR range was 9–22% and CRR was 0–6%. No patient with MM had an objective response. While both combinations were active in cHL, the toxicity of nivo/ipi was higher than expected from nivolumab alone. These data suggest no meaningful improvement in the efficacy of the combinations over single-agent nivolumab in the diseases studied.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#279

 

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Name
Description Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation. In 2949 patients not involved in any score development, higher hazard ratios and concordance indices in any comparison demonstrated the best discrimination of long-term survival with the ELTS score. In a second step, of 5154 patients analyzed to investigate risk group classification differences, 23% (n = 1197) were allocated to high-risk by the Sokal score. Of the 1197 Sokal high-risk patients, 56% were non-high-risk according to the ELTS score and had a significantly more favorable long-term survival prognosis than the 526 high-risk patients according to both scores. The Sokal score identified too many patients as high-risk and relatively few (40%) as low-risk (versus 60% with the ELTS score). Inappropriate risk classification jeopardizes optimal treatment selection. The ELTS score outperformed the Sokal score, the Euro, and the EUTOS score regarding risk group discrimination. The recent recommendation of the European LeukemiaNet for preferred use of the ELTS score was supported with significant statistical evidence.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#280

 

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Name
Description Optogenetics is the genetic approach for controlling cellular processes with light. It provides spatiotemporal, quantitative and reversible control over biological signaling and metabolic processes, overcoming limitations of chemically inducible systems. However, optogenetics lags in plant research because ambient light required for growth leads to undesired system activation. We solved this issue by developing plant usable light-switch elements (PULSE), an optogenetic tool for reversibly controlling gene expression in plants under ambient light. PULSE combines a blue-light-regulated repressor with a red-light-inducible switch. Gene expression is only activated under red light and remains inactive under white light or in darkness. Supported by a quantitative mathematical model, we characterized PULSE in protoplasts and achieved high induction rates, and we combined it with CRISPR–Cas9-based technologies to target synthetic signaling and developmental pathways. We applied PULSE to control immune responses in plant leaves and generated Arabidopsis transgenic plants. PULSE opens broad experimental avenues in plant research and biotechnology. PULSE is an optogenetic tool that consists of two modules with different wavelength sensitivities. Their interplay enables optogenetic access to gene expression in plants independently of ambient light.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#281

 

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Name
Description Pachytene Piwi-interacting RNAs (piRNAs) are abundant small non-coding RNAs expressed in mammalian germ lines. A new study indicates that, among the diverse pool of piRNA sequences, a small number act as highly selective guides that induce cleavage of coding and non-coding transcripts, thus promoting piRNA generation and regulating gene expression.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#282

 

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Name
Description COVID-19 is now the leading cause of death in the United States, killing more people each day than either cancer or heart disease.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#283

 

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Name
Description The exposure notification technology jointly developed by Google and Apple has begun rolling out in India through updates on their smartphone operating systems — iOS and Android. Public health authorities in India could now use the API to build a contact tracing app that is integrated deeply with the mobile operating system, thus avoiding technical glitches such as loss of tracking when the app is in the background.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#284

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#285

 

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Name
Description TBD

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#286

 

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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 29 June 2020

#287

 

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Name
Description The way that speech processing differs from the processing of other sounds has long been a major open question in human neuroscience. Researchers at Aalto University have endeavored to answer this by investigating brain representations for naturally spoken words using machine learning models and com

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#288

 

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Name
Description Since its introduction in 2011, functional ultrasound (fUS) imaging is progressively rising as a predominant neuroimaging modality. From this technique, developed by the team of Mickael Tanter (laboratory Physics for Medicine Paris, Inserm/ESPCI Paris-PSL/PSL University/CNRS), has emerged a now fast

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 29 June 2020

#289

 

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Name
Description In the watery inside of a cell, complex processes take place in tiny functional compartments called organelles. Energy-producing mitochondria are organelles, as is the frilly golgi apparatus, which helps to transport cellular materials. Both of these compartments are bound by thin membranes. But

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#290

 

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Name
Description When neurons fire an electrical impulse, they also experience a surge of calcium ions. By measuring those surges, researchers can indirectly monitor neuron activity, helping them to study the role of individual neurons in many different brain functions. One drawback to this technique is the cross

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#291

 

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Name
Description The Indian unit of Amazon.com has eliminated all single-use plastic in its packaging across fulfilment centres in the country, in line with its target to weed out the packaging material by June, the e-commerce giant said on Monday.

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 29 June 2020

#292

 

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Name
Description Researchers at MIT and elsewhere have developed a way to generate the important signaling molecule nitric oxide inside the body on demand, in order to study its functions.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#293

 

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Name
Description No more self-service for you.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#294

 

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Name
Description The global pandemic has not stopped Accenture from buying companies over the last few weeks with a heavy focus in Europe and on manufacturing.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#295

 

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Name
Description U.S. and World Health Organization are already debating how to prioritize the initial distribution of a coveted vaccine

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#296

 

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Name
Description MIT has developed a robot that navigates around spaces to blast the virus with UV light. The team has even ...

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#297

 

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Name
Description OPCML is a highly conserved glycosyl phosphatidylinositol (GPI)-anchored protein belonging to the IgLON family of cell adhesion molecules. OPCML functions as a tumor suppressor and is silenced in over 80% of ovarian cancers by loss of heterozygosity and by epigenetic mechanisms. OPCML inactivation is also observed in many other cancers suggesting a conservation of tumor suppressor function. Although epigenetic silencing and subsequent loss of OPCML expression correlate with poor progression-free and overall patient survival, its mechanism of action is only starting to be fully elucidated. Recent discoveries have demonstrated that OPCML exerts its tumor suppressor effect by inhibiting several cancer hallmark phenotypes in vitro and abrogating tumorigenesis in vivo, by downregulating/inactivating a specific spectrum of Receptor Tyrosine Kinases (RTKs), including EphA2, FGFR1, FGFR3, HER2, HER4, and AXL. This modulation of RTKs can also sensitize ovarian and breast cancers to lapatinib, erlotinib, and anti-AXL therapies. Furthermore, OPCML has also been shown to function in synergy with the tumor suppressor phosphatase PTPRG to inactivate pro-metastatic RTKs such as AXL. Recently, the identification of inactivating point mutations and the elucidation of the crystal structure of OPCML have provided valuable insights into its structure-function relationships, giving rise to its potential as an anti-cancer therapeutic.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#298

 

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Name
Description The protein syntenin-1 is expressed by a variety of cell types, and is upregulated in various malignancies, including melanoma, breast cancer and glioma. Although the mechanism by which elevated syntenin-1 expression contributes to cancer has been described, the exact pathway has not been elucidated. To investigate the involvement of syntenin-1 in colorectal cancer (CRC), we performed immunohistochemical analysis of 139 CRC surgical specimens. We also examined syntenin-1 knockdown in CRC cell lines. High syntenin-1 expression was associated with less differentiated histologic grade and poor prognosis, and was an independent prognostic indicator in CRC. Syntenin-1 knockdown in CRC cells reduced the presence of cancer stem cells (CSCs), oxaliplatin chemoresistance and migration. DNA microarray analysis and quantitative real-time polymerase chain reaction showed decreased prostaglandin E2 receptor 2 (PTGER2) expression in syntenin-1-knockdown cells. PTGER2 knockdown in CRC cells yielded the same phenotype as syntenin-1 knockdown. Celecoxib, which has anti-inflammatory effects by targeting cyclooxygenase-2, reduced CSCs and decreased chemoresistance, while prostaglandin E2 (PGE2) had the opposite effect. Our findings suggested that syntenin-1 enhanced CSC expansion, oxaliplatin chemoresistance and migration capability through regulation of PTGER2 expression. Syntenin-1 may be a promising new prognostic factor and target for anti-cancer therapies.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#299

 

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Name
Description Palbociclib in combination with endocrine therapy increases progression-free survival in patients with ER-positive, HER2-negative advanced breast cancer (BC). In this study, we retrospectively evaluated safety in the first patient treated with concurrent use of palbociclib and radiation therapy (RT) in the Curie Institute. Between April 2017 and August 2019, 30 women with metastatic BC received locoregional and/or symptomatic irradiation at a metastatic site concurrently with palbociclib. The most common acute toxicities were radiodermatitis and neutropenia. Palbociclib had to be discontinued during RT in three locally treated patients who developed grade 3 radiodermatitis and febrile neutropenia, grade 2 dysphagia and metastatic disease progression, respectively. After a follow-up of at least 6 months, none of the patients had late toxicity. Concomitant administration of palbociclib with RT was reasonably well tolerated in our series of 30 patients. More prospective data with longer follow-up are needed to confirm these results.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#300

 

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Name
Description Chinese officials may start administering an early candidate for a COVID-19 vaccine to China's military. Early trials showed it had limited efficacy.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#301

 

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Name
Description Therapeutic cancer vaccines are an attractive approach for treating malignant tumours, and successful tumour eradication depends primarily on controlling tumour immunosuppression status as well as heterogeneity of tumour cells driven by epigenetic alterations. Peptide-loaded dendritic cell (DC) prime and non-infectious peptide booster heterologous immunisations were assessed for the immunogenicity of polo-like kinase-1 (PLK1)-derived peptides. Heterologous vaccination regimen targeting multiple shared tumour antigens simultaneously with PD-L1 blockade was assessed against murine myeloid leukaemia. A synthetic PLK1122 (DSDFVFVVL)-based heterologous vaccination generated large numbers of long-lasting antigen-specific CD8 T-cells eliciting therapeutic effects against various established tumours. The therapeutic efficacy of single antigen-targeting PLK1122-based vaccine with sufficient endurance of PD-L1 blockade toward C1498 leukaemia relied on the heterogeneous clonal levels of MHC-I and PD-L1 expression. A novel multi-peptide-based vaccination targeting PLK1 and survivin simultaneously along with PD1 blockade led to complete tumour eradication and long-term survival in mice with clonally heterologous C1498 myeloid leukaemia. Our findings suggest that PLK1 could be an attractive immunotherapeutic target antigen for cancer immunotherapy, and that similar strategies would be applicable for the optimisation of cancer vaccines for the treatment of numerous viral diseases and malignant tumours.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#302

 

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Name
Description Clever-1 (also known as Stabilin-1 and FEEL-1) is a scavenger receptor expressed on lymphatic endothelial cells, sinusoidal endothelial cells and immunosuppressive monocytes and macrophages. Its role in cancer growth and spread first became evident in Stab1–/– knockout mice, which have smaller primary tumours and metastases. Subsequent studies in mice and humans have shown that immunotherapeutic blockade of Clever-1 can activate T-cell responses, and that this response is mainly mediated by a phenotypic change in macrophages and monocytes from immunosuppressive to pro-inflammatory following Clever-1 inhibition. Analyses of human cancer cohorts have revealed marked associations between the number of Clever-1-positive macrophages and patient outcome. As hardly any reports to date have addressed the role of Clever-1 in immunotherapy resistance and T-cell dysfunction, we performed data mining using several published cancer cohorts, and observed a remarkable correlation between Clever-1 positivity and resistance to immune checkpoint therapies. This result provides impetus and potential for the ongoing clinical trial targeting Clever-1 in solid tumours, which has so far shown a shift towards immune activation when a particular epitope of Clever-1 is blocked.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#303

 

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Name
Description Although numerous studies have shown that the protein α-synuclein (α-Syn) plays a central role in Parkinson’s disease, dementia with Lewy bodies, and other neurodegenerative diseases, the protein’s physiological function remains poorly understood. Furthermore, despite recent reports suggesting that, under the influence of Ca2+, α-Syn can interact with synaptic vesicles, the mechanisms underlying that interaction are far from clear. Thus, we used single-vesicle imaging to quantify the extent to which Ca2+ regulates nanoscale vesicle clustering mediated by α-Syn. Our results revealed not only that vesicle clustering required α-Syn to bind to anionic lipid vesicles, but also that different concentrations of Ca2+ exerted different effects on how α-Syn induced vesicle clustering. In particular, low concentrations of Ca2+ inhibited vesicle clustering by blocking the electrostatic interaction between the lipid membrane and the N terminus of α-Syn, whereas high concentrations promoted vesicle clustering, possibly due to the electrostatic interaction between Ca2+ and the negatively charged lipids that is independent of α-Syn. Taken together, our results provide critical insights into α-Syn’s physiological function, and how Ca2+ regulates vesicle clustering mediated by α-Syn. Calcium plays a critical role in the clustering of synaptic vesicles (which in a neuron store various neurotransmitters released at the synapse) induced by the protein alpha-synuclein, and different calcium concentrations exert different effects on such clustering. Alpha-synuclein is a key element in the development of Parkinson’s disease and other neurodegenerative conditions: it has been shown to interact with synaptic vesicles under the influence of calcium, but its physiological functions are poorly understood. Jiajie Diao of the University of Cincinnati College of Medicine, USA and colleagues used single-vesicle imaging to examine how calcium regulates vesicle clustering mediated by alpha-synuclein. They found that high calcium concentrations promoted vesicle clustering independent of alpha-synuclein, but low calcium concentrations inhibited vesicle clustering in an alpha-synuclein–dependent manner. The authors believe their findings provide insights into alpha-synuclein’s physiological function.

#Medicine & Human body;#Aging
Field # Medicine & Human body
Updated 29 June 2020

#304

 

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Name
Description Global cases of COVID-19, the disease caused by the novel coronavirus, have surpassed 10,000,000 globally as the US cases spike, according to data analysed from Johns Hopkins University.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#305

 

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Name
Description Asymptomatic coronavirus cases are the focus of growing research for their possible role in spreading the virus.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#306

 

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Name
Description The type of suture used to repair perineal injury may be associated with this healing process and subsequent sexual function. This study aims to assess whether the suture technique used (continuous or interrupted) has an impact on a woman’s sexual function following childbirth. A single-blind randomised clinical trial was conducted with primiparous women who had experienced a perineal injury during childbirth. A computer-generated random number table was applied to allocate women to each group. Data were collected on sociodemographic variables, variables associated with childbirth, and outcomes during the 3 months after childbirth. Mean difference was used to assess the influence of the suture type on outcomes. Multivariate analyses were carried out to adjust for unbalanced variables after randomisation. Seventy women participated in the intervention group (continuous suture) and 64 women in the control group (interrupted suture). The women in the intervention group scored high for sexual desire, adjusted mean difference (aMD) = 1.8, 95% CI = 1.1–2.6 (p < 0.001); the same happened with arousal (aMD = 1.7, 95% CI = 0.8–2.5, p < 0.001). In the intervention group, orgasm was more easily reached, aMD = 0.8, 95% CI = 0.4–1.1 (p < 0.001). Women who received a continuous suture indicated they felt less discomfort (p < 0.001). Women who had a continuous suture reported better postpartum sexual function. Trial registration: ClinicalTrials.gov NCT03825211 posted 31/01/ 2019.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#307

 

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Name
Description A team of researchers at the Department of Energy’s Oak Ridge and Argonne national laboratories has performed the first room-temperature X-ray measurements on the SARS-CoV-2 main protease — the enzyme that enables the virus to reproduce. The X-ray measurements mark an important first step in

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#308

 

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Name
Description Traditionally, the practice of the tibial component placement in total knee arthroplasty has focused on achieving maximum coverage without malrotation. However, the concept of maximizing coverage has not been well defined or researched and yet biased results are often produced. This study aimed to evaluate the effect of a prioritizing maximum coverage positioning strategy on the rotational alignment by using a strict computer algorithm. Computed tomographic scans of 103 tibial specimens were used to reconstruct three-dimensional tibia models. A virtual surgery was performed to generate the resection plane with a posterior slope of 7° on the proximal tibia. Symmetrical and anatomical tibial components were placed and analyzed with an automated program designed for approximating the maximum coverage based on the coherent point drift algorithm. We found that the average tibial coverage achieved across all specimens and implants was 85.62 ± 3.65%, ranging from 83.64 ± 4.10% to 86.69 ± 3.07%. When placed for maximal tibial coverage, the mean degree of rotation related to the Insall line was − 0.73° ± 4.53° for all subjects, 23% of the tibial components were malrotated. The average percentage position of the baseplate anteroposterior axis over the patellar tendon was 26.95 ± 14.71% from the medial edge. These results suggest that with specific design and proper placement of the component, approximating the maximum tibial coverage in total knee arthroplasty does not necessarily result in implant malrotation. The current tibial baseplates have shown good performance on the coverage when aligned parallel to the Insall line with the anteroposterior axis positioned between the medial 1/3 and medial 1/6 of the patella tendon.

#Medicine & Human body;#Hardware & Devices
Field # Medicine & Human body
Updated 29 June 2020

#309

 

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Name
Description Serious cutaneous adverse drug reactions [i.e., SJS/TEN with severe ocular complications (SOC)] associated with cold medicine (CM) were reported in several studies. To assess the risks of CM-induced SJS/TEN with SOC, systematic review and meta-analysis were employed. Studies investigating associations between HLA genotypes and CM-induced SJS/TEN with SOC were systematically searched in PubMed, Scopus and the Cochrane Library. Overall odds ratios (ORs) with 95% CIs were calculated using a random-effects model to determine these associations. An initial search of the databases identified 24,011 articles, of which 6 studies met the inclusion criteria. In total from all studies, associations between 81 different HLA genotypes and CM-induced SJS/TEN with SOC (i.e., 22 different HLA-A genotypes, 40 different HLA-B genotypes and 19 different HLA-C genotypes) were investigated. Risk factors to develop SJS/TEN with SOC in patients who used CM were identified from our meta-analysis. HLA-A*0206 (OR = 3.90; 95% CI = 1.96–7.77), HLA-A*3303 (OR = 2.28; 95% CI = 1.31–3.97), HLA-B*4403 (OR = 3.27; 95% CI = 1.52–7.03) and HLA-C*0501 (OR = 2.55; 95% CI = 1.19–5.44) were associated with CM-induced SJS/TEN with SOC. With our results demonstrating a significant association between using of CMs and the severe ADR, a genetic testing can be helpful. However, the CMs are commonly used as an over-the-counter drug in practically almost of people in populations worldwide, the genetic screening prior to use of the CMs might not be cost-effective. Nonetheless, for people with a family history of developing the ADRs with a possible involvement of CMs, a genetic screening may be beneficial.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#310

 

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Name
Description Workers at six Amazon sites in Germany will go on strike on Monday in protest over safety after some staff at logistics centres tested positive for coronavirus, labour union Verdi said.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#311

 

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Name
Description To evaluate the Dutch-English Lambert-Eaton Myasthenic Syndrome (LEMS) Tumour Association Prediction (DELTA-P) score in a prospective cohort of patients with newly diagnosed LEMS to assess the clinical validity of this tool in a real-world setting. Clinical features from 87 patients with LEMS, occurring within three months from disease onset, were collated to produce a DELTA-P score for each patient. Lung cancer was detected in 44/87 (51%) LEMS patients. Weight loss ≥ 5%, tobacco use at LEMS onset and age at onset ≥ 50 years were independent predictors for the development of small-cell lung cancer (SCLC) in LEMS patients in multivariable analysis. Median DELTA-P scores were significantly higher in SCLC-LEMS patients (3.5, 95% CI 3 to 4) compared to non-tumour-LEMS (2, 95% CI 1 to 2) (P < 0.0001). Higher DELTA-P scores increased the risk of SCLC stepwise (score 0 = 0%, 1 = 18.8%, 2 = 45%, 3 = 55.5%, 4 = 85.7%, 5 = 87.5%, 6 = 100%). The area under the curve of the receiver operating curve was 82.5% (95% CI 73.9% to 91%). The DELTA-P cancer prediction score, calculated at the time of LEMS diagnosis, is an effective tool for cancer screening in an independent, prospective study setting.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#312

 

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Name
Description High-altitude Tajiks (HA-Tajiks), Tibetans and Sherpas are three groups of high-altitude native people in China. The differences in the mtDNA genome between the three populations and the role of the mtDNA genome in the high-altitude adaptation of HA-Tajiks were seldom investigated. In this study, 80 HA-Tajiks were enrolled, and their whole mtDNA genomes were sequenced. The haplogroup of each subject was determined by comparison to the revised Cambridge Reference Sequence (rCRS). Ten additional populations from East Asia and Central Asia, including Tibetans and Sherpas, were selected as references. The top haplogroup was U, followed by H, T and J. Principle component analysis and genetic distance analysis indicated that HA-Tajiks showed a close relationship with Wakhi Tajiks, Pamiri Tajiks and Sarikoli Tajiks, indicating that they should be considered one nation scattered around the Pamirs. The difference in the mtDNA genome between HA-Tajiks and Sherpas was significantly greater than that between HA-Tajiks and Tibetans. Among the 13 genes related to the OXPHOS pathway encoded by the mtDNA genome, HA-Tajiks showed more significant differences in ND3 and CYTB compared to Tibetans. Compared to Sherpas, HA-Tajiks showed more significant differences in ND1, ND2, COX1, ATP8, ATP6, ND3, ND4L, ND4, ND5 and CYTB. The associated functional changes and underlying molecular mechanisms should be explored by molecular and biochemical investigations in further studies.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#313

 

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Name
Description Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) had been suggested as a possible glycobiomarker for assessing liver fibrosis. Here, we conducted this updated meta-analysis to systematically investigate the predictive accuracy of WFA+-M2BP for diagnosing liver fibrosis and hepatocellular carcinoma (HCC) by comparing with multiple non-invasive indicators. We searched relevant literatures from Pubmed, Web of Science, EMBASE and Cochrane Library and enrolled 36 eligible studies involving 7,362 patients. Summary results were calculated using bivariate random effects model. The pooled sensitivities, specificities and areas under the summary receiver operating characteristic curves (AUSROCs) of WFA+-M2BP for identifying mild fibrosis, significant fibrosis, advanced fibrosis, cirrhosis, and HCC were 0.70/0.68/0.75, 0.71/0.75/0.79, 0.75/0.76/0.82, 0.77/0.86/0.88, and 0.77/0.80/0.85, respectively. The accuracy of WFA+-M2BP was strongly affected by etiology and it was not better than other non-invasive indicators for predicting early fibrosis. It showed similar diagnostic performance to hyaluronic acid and FibroScan for cirrhosis, but was equivalent to α-fetoprotein for HCC. In conclusion, WFA+-M2BP was suitable to diagnose late stage of liver fibrosis, especially cirrhosis. Individual cutoff value of WFA+-M2BP could be used to grade liver fibrosis in different etiology. Combined diagnostic model was suggested to improve its predictive accuracy for HCC.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#314

 

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Name
Description Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype ‘drug use’ to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces, and their respective associations with drug intake. In addition to describing its strengths, we also discuss limitations of the IMAGEN study. Because of the longitudinal design and related attrition, analyses are underpowered for (epi-) genome-wide approaches due to the limited sample size. Estimating the generalizability of results requires replications in independent samples. However, such densely phenotyped longitudinal studies are still rare and alternative internal cross-validation methods (e.g., leave-one out, split-half) are also warranted. In conclusion, the IMAGEN cohort is a unique, very well characterized longitudinal sample, which helped to elucidate neurobiological mechanisms involved in complex behavior and offers the possibility to further disentangle genotype × phenotype interactions.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020

#315

 

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Name
Description Several pretreatment variables such as elevated glucose and hypoperfusion severity are related to brain hemorrhage after endovascular treatment of acute stroke. We evaluated whether elevated glucose and severe hypoperfusion have synergistic effects in the promotion of parenchymal hemorrhage (PH) after mechanical thrombectomy (MT). We included 258 patients MT-treated who had a pretreatment computed tomography perfusion (CTP) and a post-treatment follow-up MRI. Severe hypoperfusion was defined as regions with cerebral blood volume (CBV) values < 2.5% of normal brain [very-low CBV (VLCBV)-regions]. Median baseline glucose levels were 119 (IQR = 105–141) mg/dL. Thirty-nine (15%) patients had pretreatment VLCBV-regions, and 42 (16%) developed a PH after MT. In adjusted models, pretreatment glucose levels interacted significantly with VLCBV on the prediction of PH (p-interaction = 0.011). In patients with VLCBV-regions, higher glucose was significantly associated with PH (adjusted-OR = 3.15; 95% CI = 1.08–9.19, p = 0.036), whereas this association was not significant in patients without VLCBV-regions. CBV values measured at pretreatment CTP in coregistered regions that developed PH or infarct at follow-up were not correlated with pretreatment glucose levels, thus suggesting the existence of alternative deleterious mechanisms other than direct glucose-driven hemodynamic impairments. Overall, these results suggest that both severe hypoperfusion and glucose levels should be considered in the evaluation of adjunctive neuroprotective strategies.

#Medicine & Human body
Field # Medicine & Human body
Updated 29 June 2020