We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 ...loci newly associated with PBC (at P<5×10(-8)), increasing the number of known susceptibility loci to 25. The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis. An additional five loci contained nonsynonymous variants in high linkage disequilibrium (LD; r2>0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r2>0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.
Public trust is central to the collection of genomic and health data and the sustainability of genomic research. To merit trust, those involved in collecting and sharing data need to demonstrate they ...are trustworthy. However, it is unclear what measures are most likely to demonstrate this.
We analyse the 'Your DNA, Your Say' online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle- and high-income countries, gathered in 15 languages. We examine how participants perceived the relative value of measures to demonstrate the trustworthiness of those using donated DNA and/or medical information. We examine between-country variation and present a consolidated ranking of measures.
Providing transparent information about who will benefit from data access was the most important measure to increase trust, endorsed by more than 50% of participants across 20 of 22 countries. It was followed by the option to withdraw data and transparency about who is using data and why. Variation was found for the importance of measures, notably information about sanctions for misuse of data-endorsed by 5% in India but almost 60% in Japan. A clustering analysis suggests alignment between some countries in the assessment of specific measures, such as the UK and Canada, Spain and Mexico and Portugal and Brazil. China and Russia are less closely aligned with other countries in terms of the value of the measures presented.
Our findings highlight the importance of transparency about data use and about the goals and potential benefits associated with data sharing, including to whom such benefits accrue. They show that members of the public value knowing what benefits accrue from the use of data. The study highlights the importance of locally sensitive measures to increase trust as genomic data sharing continues globally.
Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic had a devastating effect on college students worldwide. Here, the authors aimed to determine the prevalence of anxiety and its ...related coping strategies, provide a theoretical basis for understanding self-prescription, and identify the factors contributing to stress and anxiety in medical students during the pandemic.
Methods
The authors conducted a cross-sectional study among medical students in Saudi Arabia from September to November 2020. They assessed anxiety using the GAD-7 scale based on seven core symptoms. The authors also examined perceived psychological stress using a single-item measure of stress, the factors contributing to stress during the transition to online learning and examinations, and related coping strategies. The Statistical Package for Social Sciences (SPSS) version 26.0 was used to examine the data for both descriptive and inferential analyses. Chi-square test, one-way ANOVA, and univariate linear regression were used to test the research hypotheses.
Results
The authors collected and analyzed data from 7116 medical students distributed across 38 medical colleges. Among them, 40% reported moderate to severe anxiety symptoms. Pre-clinical and female students experienced more stress than clinical and male students. 12.19% (
n
= 868) of respondents reported using medication during their college years. Among those, 58.9% (
n
= 512) had moderate to severe anxiety, and the most commonly used drug was propranolol (45.4%,
n
= 394). Among the studied sample, 40.4% (
n
= 351) decreased their medication use after switching to online teaching. Most students used these medications during the final exam (35.8%,
n
= 311) and before the oral exam (35.5%,
n
= 308). In terms of coping strategies, males were much more likely to use substances than females, who mainly resorted to other strategies.
Conclusions
This study provides a national overview of the impact of COVID-19 on the mental health of medical students. The results indicated that the pandemic is associated with highly significant levels of anxiety. These findings can provide theoretical evidence for the need for supportive psychological assistance from academic leaders in this regard.
The exploration encompassed the synthesis and characterization of two innovative complexes, namely FePHNS and CuPHNS, employing a diverse array of analytical techniques such as elemental analysis, ...infrared and ultraviolet-visible spectroscopy, mass spectrometry, molar conductivity measurements, magnetic susceptibility assessments, and thermal analysis (TGA). In the spectral domain, infrared spectroscopy substantiated the tridentate ONS coordination of the PHNS ligand to the central metal atom. Thermal analysis offered valuable insights into the distribution and content of water molecules within the complexes. Density functional theory (DFT) calculations were harnessed to validate the molecular structures of both the PHNS ligand and its complex entities, providing an intricate comprehension of their quantum chemical parameters. The investigation extended to an evaluation of the in vitro antibacterial, antifungal, and antioxidant efficacy of the PHNS ligand and its complexes, revealing heightened biological activities for the complexes in comparison to the free PHNS ligand, notably with the CuPHNS complex demonstrating the highest activity, while the PHNS ligand exhibited the lowest. To delve into potential physiological activities, molecular docking studies were conducted, predicting the binding affinity of the compounds to proteins 2vf5 (Glucosamine-6-phosphate synthase in complex with glucosamine-6-phosphate) from Escherichia coli, 3cku (rate oxidase from Aspergillus flavus complexed with its inhibitor 8-azaxanthin and chloride) from Aspergillus flavus, and 5IJT (Crystal structure of Human Peroxiredoxin 2 Oxidized). The ensuing analysis of protein-ligand interactions and binding energies underscored the promising physiological activities of the investigated compounds, warranting further exploration for their potential in novel drug development.
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•Novel Fe(III) and Cu(II) ions in molar ratios of 1:1 and 1:2 with PHNS ligand complexes have been synthesized.•Their in vitro antibacterial, antifungal, and antioxidant efficacy of the PHNS ligand and its complexes has been investigated.•The CuPHNS complex demonstrated the highest biological activity, while the PHNS ligand exhibited the lowest.•DFT and molecular docking results were correlated with in vitro activities
Aims/Introduction
Limited studies have identified risk factors linked to the progression of diabetic peripheral neuropathy (DPN) in type 2 diabetes. This study examined the association of risk ...factors with change in neuropathy measures over 2 years.
Materials and Methods
Participants with type 2 diabetes (n = 78) and controls (n = 26) underwent assessment of clinical and metabolic parameters and neuropathy using corneal confocal microscopy (CCM), vibration perception threshold (VPT), and the DN4 questionnaire at baseline and 2 year follow‐up.
Results
Participants with type 2 diabetes had a lower corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) (P ≤ 0.0001) and a higher VPT (P ≤ 0.01) compared with controls. Over 2 years, despite a modest reduction in HbA1c (P ≤ 0.001), body weight (P ≤ 0.05), and LDL (P ≤ 0.05) the prevalence of DPN (P = 0.28) and painful DPN (P = 0.21) did not change, but there was a significant further reduction in CNBD (P ≤ 0.0001) and CNFL (P ≤ 0.05). CNFD, CNBD, and CNFL decreased significantly in physically inactive subjects (P < 0.05–0.0001), whilst there was no change in CNFD (P = 0.07) or CNFL (P = 0.85) in physically active subjects. Furthermore, there was no change in CNFD (P = 0.82), CNBD (P = 0.08), or CNFL (P = 0.66) in patients treated with glucose lowering medication associated with weight loss, whilst CNBD (P = 0.001) decreased in patients on glucose lowering medication associated with weight gain.
Conclusions
In participants with type 2 diabetes, despite a modest improvement in HbA1c, body weight, and LDL there was a progressive loss of corneal nerve fibers; except in those who were physically active or on glucose lowering medication associated with weight loss.
The aim of this study was to determine how attitudes toward the return of genomic research results vary internationally.
We analyzed the “Your DNA, Your Say” online survey of public perspectives on ...genomic data sharing including responses from 36,268 individuals across 22 low-, middle-, and high-income countries, and these were gathered in 15 languages. We analyzed how participants responded when asked whether return of results (RoR) would motivate their decision to donate DNA or health data. We examined variation across the study countries and compared the responses of participants from other countries with those from the United States, which has been the subject of the majority of research on return of genomic results to date.
There was substantial variation in the extent to which respondents reported being influenced by RoR. However, only respondents from Russia were more influenced than those from the United States, and respondents from 20 countries had lower odds of being partially or wholly influenced than those from the United States.
There is substantial international variation in the extent to which the RoR may motivate people’s intent to donate DNA or health data. The United States may not be a clear indicator of global attitudes. Participants’ preferences for return of genomic results globally should be considered.
This study explores the effect of gamma rays on a new glass and glass–ceramic 10ZnO–34.5B2O3–34.5TeO2–20Bi2O3–1Nd2O3. The samples were exposed to different gamma-ray doses of 2.5, 10, and 50 kGy. The ...impact of gamma-ray irradiation was investigated using different physicochemical methods. The X-ray diffraction (XRD) results for glass samples show that the amorphous nature did not change before and after irradiation, and a shift in the main peak along with a change in the unit cell volume with increasing doses was observed in glass-ceramic matrix. The Fourier transform infrared (FTIR) and Raman spectra (IR) for the glass samples show change in intensity without variation in the band position. The 50 kGy dose hid a high wavenumber peak in the FTIR and Raman spectra for the glass–ceramic sample, indicating a significant change in the glass–ceramic matrix. The reduction in the band gap energy for the glass samples confirms the FTIR results. The durability of the glass samples was gradually enhanced by increasing the dose up to 10 kGy. The up-conversion photoluminescence in the glass samples exhibits an emission peak at 525 nm that decreases in intensity as the dose increases. The mean free path results confirm the shielding features of the glass when compared to other reference glass materials. The results show that the glass is excellently stable and can withstand high gamma-ray doses, making it suitable for radiation applications.
•XRD results affirm the amorphous nature and crystal phase for glasses and glass ceramics.•The radiation doses mainly affect glass ceramics.•The band gap values reduce gradually with increasing gamma-ray doses for glasses.•The photoluminescence intensity shows a reduction with increasing gamma doses for glasses.•The glass durability increases with increasing gamma doses up to 10 kGy.
Semiconductor photocatalysts have been widely used to catalyse photochemical reactions for the remediation of wastewater contaminated with organic dyes. This study aimed to synthesise and ...characterise manganese-doped Dy
2
O
3
(Dy
2
O
3
/Mn) nanostructures as possible catalysts with improved photocatalytic properties. A low-cost hydrothermal method was used to fabricate materials with optimal morphological and structural properties. Before characterisation, Dy
2
O
3
/Mn nanostructures were subjected to heat treatments in the range 300–600 °C. X-ray diffraction analysis revealed that all samples exhibited a cubic phase structure; the crystallite size varied between 30.7 and 40.2 nm with the calcination temperature. Scanning electron microscopy, energy-dispersive spectroscopy, and Fourier transform infrared spectroscopy were used to examine the morphology and chemical content of the nanostructures, and the efficacy of the elaboration approach was validated. Diffuse reflectance spectroscopy demonstrated the visible-light absorption of the samples, and the bandgap energy was determined to be approximately 2.9 eV. Methylene blue (MB) dye was used to examine the photocatalytic activity of the Dy
2
O
3
/Mn nanostructures under visible-light irradiation. After 360 min, 92% of MB was degraded. The doping of Dy
2
O
3
with Mn improved both the photocatalytic activity and the overall properties of the catalyst. Therefore, Dy
2
O
3
/Mn nanostructures could replace current catalysts for the degradation of organic dyes in wastewater.
Graphical abstract
Introduction
PD catheter tip migration is a common complication and a significant cause of catheter malfunction. In this perspective, we present our experience with a new catheter and a new technique ...that involves the use of a new triple cuff PD catheter and a low entry site in an attempt to prevent PD catheter migration.
Methods
A total of 503 incident PD patients have been studied in more than one PD center over a period of 5 years.
Results
During the 5‐year follow up we recorded zero percent catheter migration. Other technical complications were poor drainage in 3.4%, omental wrap in 2.8%, early leakage in 3.4%, and catheter replacement in 2.4%. By the end of the study, the one‐year PD catheter survival was 97.6%.
Conclusion
Our new triple cuff PD catheter and our low‐entry approach seem to be effective in preventing PD catheter migration and minimizing other mechanical complications.
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