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Today: 06 July 2020, Monday.

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#1

 

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Heterogeneity with respect to recurrence and survival in high-risk stage II colon cancer patients still exists, and further classification is urgently required. This study aimed to ascertain the prognostic value of DNA ploidy, stroma-tumour fraction and nucleotyping in the prognosis of high-risk stage II colon cancer. A total of 188 high-risk stage II colon cancer patients received radical surgery in Peking University Cancer Hospital, from 2009 to 2015. Status of mismatch repair proteins in tumours was analysed using immunohistochemistry. DNA ploidy, stroma-tumour fraction and nucleotyping were estimated by automated digital imaging systems. Nucleotyping and DNA ploidy were significant prognostic factors, while stroma-tumour fraction were not significantly prognostic in the univariate analysis. In the multivariable model, the dominant contributory factor of disease-free survival was chromatin heterogeneous vs. chromatin homogeneous [HR 3.309 (95% CI: 1.668–6.564), P = 0.001]. Our study indicates that nucleotyping is an independent prognostic factor in high-risk stage II colon cancer. Therefore, it may help subdivide patients into different subgroups and give them different strategies for follow-up and treatment in the future.

#Medicine & Human body
Field # Medicine & Human body
Updated 06 July 2020

#2

 

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Wisteria floribunda agglutinin (WFA)+ Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about the association of M2BPGi with HCC aggressiveness. We aimed to clarify the significance of M2BPGi in HCC. The protein expression of M2BPGi and galectin-3, a ligand of M2BP, and the mRNA expression of M2BP were evaluated in surgically resected human HCC samples. M2BPGi-regulating signals in HCC cells were investigated using transcriptome analysis. The effects of M2BPGi on HCC properties and galectin-3/mTOR signaling were evaluated. M2BPGi and galectin-3 proteins co-localised in HCC cells, while M2BP mRNA was detected in cirrhotic liver stromal cells. mTOR signaling was upregulated in M2BPGi-treated HCC cells. Moreover, M2BPGi treatment induced tumour-promoting effects on HCC in vitro by activated mTOR signaling. In addition, M2BPGi bound to galectin-3 to induce membranous galectin-3 expression in HCC cells. In vivo, M2BPGi enhanced the growth of xenografted HCC. M2BPGi is produced in stromal cells of the cirrhotic liver. Furthermore, M2BPGi enhances the progression of HCC through the galectin-3/mTOR pathway.

#Medicine & Human body
Field # Medicine & Human body
Updated 06 July 2020

#3

 

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A remarkably better prognosis is associated with oropharyngeal squamous cell carcinomas (OPSCC) driven by human papillomaviruses (HPV) compared with HPV-negative OPSCC. Consequently, de-escalation of standard treatment has been suggested. Due to modest specificity rates, debates are ongoing, whether p16INK4a, a surrogate marker for HPV-driven OPSCC, is sufficient to correctly identify those tumours and avoid substantial HPV misattribution and thus undertreatment of patients by de-escalation. Robust data estimating the proportion of potentially undertreated patients are missing. We assessed a large-scale cohort of consecutively included OPSCC diagnosed between 2000 and 2017 for HPV–DNA, HPV genotypes, p16INK4a expression and multiple tumour- and patient-related risk factors, and investigated their impact on patients’ survival in comprehensive uni- and multivariate analyses. Aetiological relevance of HPV (p16INK4a- and high-risk HPV–DNA-positivity) was detected in 27.1% (n = 192) of OPSCC, with HPV16 being the most abundant HPV type (94.6%). In 5.5% patients (n = 39), p16INK4a overexpression but no HPV–DNA was detected. Principal component and survival analyses revealed that 60.6% of these p16INK4a-positive OPSCC lacking HPV–DNA did not resemble HPV16-driven but HPV-negative OPSCC regarding risk-factor profile and overall survival. Notably, this group represented 10.6% of all p16INK4a-overexpressing OPSCC. p16INK4a as a single marker appears insufficient to indicate OPSCC patients suitable for treatment de-escalation.

#Medicine & Human body
Field # Medicine & Human body
Updated 06 July 2020

#4

 

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Recent large-scale genetic studies, particularly genome-wide association studies (GWAS), have emphasised the importance of common genetic variation in endometrial cancer susceptibility. Although each of these variants only confer modest effects on endometrial cancer risk, together they are likely to explain a substantial amount of the familial relative risk of the disease. Therefore, methods to combine genetic risk variants, such as polygenic risk scores (PRS) have gained traction as an attractive method for individualised risk prediction and management. Here, we discuss the benefits of a PRS for endometrial cancer and considerations required for clinical implementation.

#Medicine & Human body
Field # Medicine & Human body
Updated 06 July 2020

#5

 

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Preclinical and epidemiological evidence suggests that vitamin D may have anti-cancer activities in patients with colorectal cancer. A recently completed, randomised Phase 2 trial of vitamin D3 supplementation in patients with metastatic colorectal cancer has shown promising results, and a Phase 3 trial is currently underway.

#Medicine & Human body
Field # Medicine & Human body
Updated 06 July 2020

#6

 

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Patients with non-specific symptoms often experience longer times to diagnosis and poorer clinical outcomes than those with site-specific symptoms. This paper reports initial results from five multidisciplinary diagnostic centre (MDC) projects in England, piloting rapid referral for patients with non-specific symptoms. The evaluation covered MDC activity from 1st December 2016 to 31st July 2018, with projects using a common dataset. Logistical regression analyses were conducted, with a diagnosis of any cancer as the dependent variable. Exploratory analysis was conducted on presenting symptoms and diagnoses of cancer, and on comparisons within these groupings. In total, 2961 patients were referred into the MDCs and 241 cancers were diagnosed. The pathway detected cancers across a broad range of tumour sites, including several rare and less common cancers. An association between patient age and cancer was identified (p < 0.001). GP ‘clinical suspicion’ was identified as a strong predictor of cancer (p = 0.006), with a reduced association with cancer observed in patients with higher numbers of GP consultation before referral (p = 0.008). The MDC model diagnoses cancer in patients with non-specific symptoms, with a conversion rate of 8%, demonstrating the diagnostic potential of a non-site-specific symptomatic referral pathway.

#Medicine & Human body
Field # Medicine & Human body
Updated 06 July 2020

#7

 

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IL-9-producing T cells can harbour potent anti-cancer functions. In this issue of the British Journal of Cancer, Almeida et al. found that the host microbiota enhances in vivo T cell-derived secretion of IL-9, thereby limiting cancer outgrowth.

#Medicine & Human body
Field # Medicine & Human body
Updated 06 July 2020

#8

 

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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

#9

 

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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

#10

 

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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

#11

 

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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

#12

 

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In the biggest news of the week, the government blocked 59 China-linked apps. The week also saw some launches from Vivo, Panasonic, OnePlus, Logitech and Fossil. Reliance Jio launched its video-conferencing app JioMeet. All this and other top tech news of the week.

#Entertainments
Field # Entertainments
Updated 05 July 2020

#13

 

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TBD

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

#14

 

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A wave of protests over law enforcement abuses has highlighted concerns over artificial intelligence programs like facial recognition which critics say may reinforce racial bias.

#Hardware & Devices;#Gadgets
Field # Hardware & Devices
Updated 05 July 2020

#15

 

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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

#16

 

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Picture a Scientist shines a light on gender discrimination in science – and also finds reasons to be hopeful, says Simon Ings

#Social & Corporation affairs
Field # Social & Corporation affairs
Updated 05 July 2020

#17

 

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We once thought Mars had canals built by an advanced society. We've come a long way since then, but there is still much to discover, finds Leah Crane

#Astronautics
Field # Astronautics
Updated 05 July 2020

#18

 

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How much easier life would be after a storm if insurance companies stopped haggling over wind versus water damage! Wind damage, which is covered by insurance, can be identified by combining wind-field models and terrain information. While not something the average homeowner can figure out, this kind

#Environment & Nature
Field # Environment & Nature
Updated 05 July 2020

#19

 

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OnePlus TV 32Y1 model in the newly announced Y series will be going on sale today at 12pm (noon) via Amazon. This will be the first sale of the TV model.

#Entertainments
Field # Entertainments
Updated 05 July 2020

#20

 

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Mi TV 4X price in India is quite low but is that the only reason Xiaomi TVs have succeeded in India?

#Gadgets
Field # Gadgets
Updated 05 July 2020

#21

 

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IIT Bombay Heritage Foundation on Friday announced a grant of Rs. 2.35 crores to IIT Bombay in order to fulfill the needs of students in wake of the COVID-19 pandemic.

#Hardware & Devices
Field # Hardware & Devices
Updated 05 July 2020

#22

 

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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

#23

 

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Wear your masks and you can have an edit button, Twitter says

#Software;#Social & Corporation affairs
Field # Software
Updated 05 July 2020

#24

 

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This London-based watchmaker is turning firefighting materials into unique watches

#Gadgets
Field # Gadgets
Updated 05 July 2020

#25

 

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v class="pf-content">

A meter-class telescope with a coronagraph to block solar light, placed in the strong interference region of the solar gravitational lens (SGL), is capable of imaging an exoplanet at a distance of up to 30 parsecs with a few 10 km-scale resolution on its surface. The picture shows results of a simulation of the effects of the SGL on an Earth-like exoplanet image. Earth diameter is 12724 kilometers. Ten-kilometer resolution would be better than a one-megapixel image....

#Theoretical sciences

Field # Theoretical sciences
Updated 05 July 2020

#26

 

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“This building is not a monument.”

#Astronautics
Field # Astronautics
Updated 05 July 2020

#27

 

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

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

#28

 

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ThiefQuest or EvilQuest can grab passwords and credit card numbers.

#Software;#Security
Field # Software
Updated 05 July 2020

#29

 

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On the 25th anniversary of the SNES game's US release, it feels more relevant than ever.

#Entertainments;#Games
Field # Entertainments
Updated 05 July 2020

#30

 

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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

#31

 

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TBD

#Astronautics
Field # Astronautics
Updated 05 July 2020

#32

 

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TBD

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

#33

 

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TBD

#Chemicals
Field # Chemicals
Updated 05 July 2020

#34

 

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TBD

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

#35

 

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TBD

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

#36

 

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Uber kicked off rideshare operations in Japan's capital city on Friday. Thanks to a partnership with three local taxi services, Tokyo riders can summon one of the 600 cars plugg...

#Social & Corporation affairs;#Vehicles & Special machines
Field # Social & Corporation affairs
Updated 05 July 2020

#37

 

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TwoSeven's group streaming service offers users a wide range of compatibility with Netflix, Hulu, YouTube, HBO, and more. But it's still a work in progress.

#Entertainments
Field # Entertainments
Updated 05 July 2020

#38

 

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A new image from the ESA/NASA Hubble Space Telescope shows an incredibly detailed look at a fluffy-looking spiral galaxy.

#Astronautics
Field # Astronautics
Updated 05 July 2020

#39

 

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In a mobile-first world, it’s easy to think anything related to your brand’s mobile presence should be a top priority.…...

#Social & Corporation affairs
Field # Social & Corporation affairs
Updated 05 July 2020

#40

 

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It’s nice to know that, even in these tumultuous times, some amount of normality will return somewhere.

#Entertainments
Field # Entertainments
Updated 05 July 2020

#41

 

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Researchers have published a list of more than 50 iOS apps that do the same thing.

#Social & Corporation affairs
Field # Social & Corporation affairs
Updated 05 July 2020

#42

 

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Mortal Kombat co-creator Ed Boon hinted that NetherRealm Studios is still trying, but having issues, in bringing Evil Dead's Ash Williams to Mortal Kombat 11.

#Entertainments;#Games
Field # Entertainments
Updated 05 July 2020

#43

 

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TBD

#Entertainments;#Games
Field # Entertainments
Updated 05 July 2020

#44

 

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An assembly line in a Sony factory in Kisarazu, Japan, which features a total of 32 robots, takes only 30 seconds to assemble a complete PlayStation 4 console.

#Entertainments;#Games
Field # Entertainments
Updated 05 July 2020

#45

 

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TBD

#Entertainments;#Games
Field # Entertainments
Updated 05 July 2020

#46

 

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Laura Bailey, the voice actor of Abby in The Last of Us Part II, has bafflingly been receiving abhorrent death threats for what her character did in the game.

#Entertainments;#Games
Field # Entertainments
Updated 05 July 2020

#47

 

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The kid-friendly indoor quadcopter comes with two batteries for extra flight time.

#Drones
Field # Drones
Updated 05 July 2020

#48

 

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The 65-incher costs $1,000 and the 75-incher is $1,800. The sale at Best Buy ends today.

#Entertainments
Field # Entertainments
Updated 05 July 2020

#49

 

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TBD

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

#50

 

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TBD

#Construction
Field # Construction
Updated 05 July 2020

#51

 

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TBD

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

#52

 

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TBD

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

#53

 

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Analysing the hormones in blood can help establish how many eggs a woman has left – but the hormones in hair might provide a more accurate picture of fertility

#Social & Corporation affairs;#Futurism
Field # Social & Corporation affairs
Updated 05 July 2020

#54

 

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Imagine being completely blind but still being able to see. Does that sound impossible? Well, it happens.

#Hardware & Devices;#Games
Field # Hardware & Devices
Updated 05 July 2020

#55

 

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TBD

#Entertainments;#Games
Field # Entertainments
Updated 05 July 2020