Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship between non-alcoholic fatty liver disease and cardiac arrhythmia: a systematic review and meta-analysis

Objective We performed a meta-analysis to create a quantitative estimate of the association between non-alcoholic fatty liver disease (NAFLD) and the risk of cardiac arrhythmia (including atrial fibrillation (AF), prolonged QT interval, premature atrial/ventricular contraction [PAC/PVC] and heart block). Methods A literature review was conducted using PubMed, Embase, Web of Science and the Cochrane Library database to identify observational studies of the link between NAFLD and cardiac arrhythmia. Effect sizes were expressed as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). The method of analysis of AF was also analysed separately, according to the effect estimate (OR or HR). Results Nineteen studies of 7,012,960 individuals were included. NAFLD was independently associated with higher risks of AF (OR 1.71, 95% CI: 1.14–2.57; HR 1.12, 95% CI: 1.11–1.13), prolonged QT interval (OR 2.86, 95% CI: 1.64–4.99), PAC/PVC (OR 2.53, 95% CI: 1.70–3.78) and heart block (OR 2.65, 95% CI: 1.88–3.72). The heterogeneity of the data with respect to AF and prolonged QT was moderate on sensitivity analysis. Conclusions We found a significantly higher risk of cardiac arrhythmia in patients with NAFLD, but the observational design of the studies does not permit conclusions regarding causality.
Performance and paroxetine stability in tablets manufactured by fused deposition modelling-based 3D printing.

OBJECTIVES The objective of this study was to develop a method for the preparation and characterization of paroxetine (PRX) tablets, obtained by coupling hot-melt extrusion and fused deposition modelling (FDM)-based three-dimensional printing (3DP) technology. The impact of the printing process parameters on the drug stability and on the tablets performance was assessed. METHODS Tablets were obtained by FDM of hot-melt extruded PRX-loaded filaments. Physicochemical, thermal, spectroscopic, diffractometric analysis and in-vitro dissolution tests of the intermediate products and the finished dosage forms were performed. KEY FINDINGS The characterization of printed tablets evidenced mass and dimensions uniformity, and consistency of drug content and dissolution profile. The formation of amorphous solid dispersions and interaction of formulation components throughout the manufacturing process were demonstrated. Layer thickness, printing temperature, printing and travelling speeds, and infill were the most impacting process parameters on both the physicochemical properties and the in-vitro performance of the 3D-printed tablets. CONCLUSIONS PRX tablets, meeting compendial limits, were manufactured by 3DP, envisaging their clinical use as individually designed dosage forms. The assessment of the impact of processing parameters on the printed tablets provided insights, which will ultimately allow streamlining of the 3D process set-up for quicker and easier production of patient-centric medicines.
Genetic improvement of two Indian non-basmati aromatic rice landraces through physical and chemical mutagenesis

Abstract Purpose Kala Jirga and Ajara Ghansal are the non-basmati aromatic rice landraces having small grains and good cooking qualities. In spite of huge demand these landraces are cultivated in a few pockets of Kolhapur district of India due to micro-climate required for the development of aroma and grain quality. Both the varieties are late maturing (> 160 days), tall (> 140 cm) and highly susceptible to lodging which resulted into low productivity. To overcome these constraints, induced mutation was attempted to improve the traits in these important rice landraces. Material and methods Seeds of two landraces were treated with three concentrations/doses of Ethyl methanesulphonate (EMS), Sodium Azide (SA) and Gamma (γ) rays. Putative mutants were identified and isolated in M2 generation for desirable traits by comparing with adjacent untreated control. Putative mutants were grown in three replications to test their breeding behavior and other economical traits in M3 generation. Results In the present study, differential response of landraces toward mutagenic treatments was observed which resulted into greater number of putative mutants in Ajara Ghansal (56 putative mutants) as compared to Kala Jirga (24 putative mutants). EMS induced the highest mutation frequency followed by Gamma rays and SA. In M3 generation, fifteen and eighteen mutants of Kala Jirga and Ajara Ghansal respectively exhibited true breeding for mutant traits, while rest of the putative mutants had very poor agronomic traits or reverted back to their normal trait. Desirable mutants of both the landraces viz., dwarf, early, nonlodging and more tillers with high yield were very promising and can be released for commercial cultivation after multi-location testing or used in crossing program as a donor for desirable traits. Conclusions Induced mutations were found to be very useful to improve the specific defect present in both landraces. The desirable mutants with early maturity and high number of tillers may prove useful in the improvement of aromatic rice.
A Multimethod Examination of Medical Students’ Experiences With Bereavement and Complicated Grief

Few studies have examined grief in medical students. This study used a multimethod approach to describe how bereavement and CG may impact medical students’ educational experience and their perspectives on grief support and training. One hundred three medical students completed an online survey with quantitative and qualitative methods. Seventy-three (71%) students reported experiencing bereavement, of which 12 (18%) screened positive for CG. Medical students who screened positive for CG reported significantly more emotional and behavioral challenges (M = 3.58 [SD = 2.64]) compared to medical students without CG (M = 0.93 [SD = 1.58], p < .001). Qualitative analyses revealed that bereaved and nonbereaved students wanted more grief education and bereavement support from medical institutions. Therefore, it is crucial for medical institutions, to acknowledge that grief and bereavement may impact students’ performance due to multifactorial causes.
Critical Domains in the Specific Binding of Radiolabeled Vip3Af Insecticidal Protein to Brush Border Membrane Vesicles from Spodoptera spp. and Cultured Insect Cells

This study shows that Vip3Af binding sites are fully shared with Vip3Aa, only partially shared with Vip3Ca, and not shared with Cry1Ac and Cry1F in two Spodoptera spp. Truncated versions of Vip3Af revealed that only domains I to III were necessary for the specific binding, most likely because they can form the functional tetrameric oligomer and because domain III is supposed to contain the binding epitopes. ABSTRACT Vegetative insecticidal proteins (Vip3) from Bacillus thuringiensis have been used, in combination with Cry proteins, to better control insect pests and as a strategy to delay the evolution of resistance to Cry proteins in Bt crops (crops protected from insect attack by the expression of proteins from B. thuringiensis). In this study, we have set up the conditions to analyze the specific binding of 125I-Vip3Af to Spodoptera frugiperda and Spodoptera exigua brush border membrane vesicles (BBMV). Heterologous competition binding experiments revealed that Vip3Aa shares the same binding sites with Vip3Af, but Vip3Ca does not recognize all of them. As expected, Cry1Ac and Cry1F did not compete for Vip3Af binding sites. By trypsin treatment of selected alanine mutants, we were able to generate truncated versions of Vip3Af. Their use as competitors with 125I-Vip3Af indicated that only those molecules containing domains I to III (DI-III and DI-IV) were able to compete with the trypsin-activated Vip3Af protein for binding and that molecules only containing either domain IV or domains IV and V (DIV and DIV-V) were unable to compete with Vip3Af. These results were further confirmed with competition binding experiments using 125I-DI-III. In addition, the truncated protein 125I-DI-III also bound specifically to Sf21 cells. Cell viability assays showed that the truncated proteins DI-III and DI-IV were as toxic to Sf21 cells as the activated Vip3Af, suggesting that domains IV and V are not necessary for the toxicity to Sf21 cells, in contrast to their requirement in vivo. IMPORTANCE This study shows that Vip3Af binding sites are fully shared with Vip3Aa, only partially shared with Vip3Ca, and not shared with Cry1Ac and Cry1F in two Spodoptera spp. Truncated versions of Vip3Af revealed that only domains I to III were necessary for the specific binding, most likely because they can form the functional tetrameric oligomer and because domain III is supposed to contain the binding epitopes. In contrast to results obtained in vivo (bioassays against larvae), domains IV and V are not necessary for ex vivo toxicity to Sf21 cells.
The Association of Sleep Disturbance and Suicide Risk Among Firefighters: Exploring Emotion Regulation Dimensions

Abstract Aim This study explored the extent to which emotion regulation dimensions statistically mediate the association between sleep disturbance and suicide risk among firefighters. Method Participants were 865 firefighters working for a fire department in an urban area in the southern U.S. Bootstrapping was used to test the indirect effects of sleep disturbance on suicide risk through emotion regulation dimensions, after controlling for depression and trauma exposure Results The effect of sleep disturbance on suicide risk was significantly statistically mediated by emotion regulation difficulties (β= .09, SE = .02, 95% CI: .05, .14). Moreover, each of the five dimensions of emotion regulation difficulties significantly statistically mediated this association, with difficulties in engaging in goal-direct behavior (β = .09, SE = .02, 95% CI: .05, .14) and lack of strategies to reduce distress demonstrating the strongest indirect effects (β = .07, SE = .02, 95% CI: .04, .11), after accounting for depression and trauma exposure. Conclusion Results suggest that suicide interventions for firefighters who suffer from sleep disturbance should focus on the development of emotion regulation strategies.
Voluntary oral methamphetamine increases memory deficits and contextual sensitization during abstinence associated with decreased PKMζ and increased κOR in the hippocampus of female mice

Background: Female populations exhibit vulnerabilities to psychostimulant addiction, as well as cognitive dysfunction following bouts of abuse. Aims: The goal for this study was to advance our understanding of the mechanisms that produce sex disparities in drug addiction. Methods: We used an animal model for voluntary oral methamphetamine administration (VOMA) and focused on male and female mice that consumed 7.6–8.2 mg/kg of methamphetamine (MA) per day during the last 18 days of the paradigm. Results: The VOMA-exposed female mice displayed increased locomotor activity in the drug-administration context compared to male mice, demonstrating sex-specific changes in contextual sensitization. During 2 weeks of forced abstinence, mice underwent further behavioral testing. We show that abstinence increased open-arm entries on the elevated plus maze in both sexes. There were no differences in immobility on the tail suspension test. In a hippocampal-dependent radial arm maze task, VOMA-treated female mice, but not male mice, showed working memory deficits. Hippocampal tissue was collected and analyzed using Western blotting. VOMA-exposed female mice exhibited increased kappa opioid receptor (κOR) expression in the hippocampus compared to male mice, suggesting a vulnerability toward abstinence-induced dysphoria. Female VOMA mice also exhibited a decrease in the memory protein marker, protein kinase M zeta (PKMζ), in the hippocampus. Conclusions: Our study reveals sex-specific effects following abstinence from chronic MA consumption on hippocampal κOR and PKMζ expression, suggesting that these neural changes in female mice may underlie spatial memory deficits and identify an increased susceptibility to dysregulated neural mechanisms. These data validate VOMA as a model sensitive to sex differences in behavior and hippocampal neurochemistry following chronic MA exposure.
Prevalence of Mycoplasma genitalium fluoroquinolone-resistance markers, and dual-class-resistance markers, in asymptomatic men who have sex with men

Introduction Failure of fluoroquinolones, the principal treatment option for macrolide-resistant Mycoplasma genitalium infections, has recently emerged. This is of particular concern for men who have sex with men (MSM), who have high proportions of macrolide-resistant M. genitalium infections. Treatment failure with moxifloxacin is likely the result of single nucleotide polymorphisms (SNPs) in parC, whilst concurrent gyrA mutations may play a role. Gap Statement The levels of fluoroquinolone resistance and dual-class (i.e. macrolide and fluoroquinolone) resistance in M. genitalium among asymptomatic MSM is unknown. Aim To (i) determine the proportion of fluoroquinolone resistance and dual-class resistance in M. genitalium infections among asymptomatic MSM, (ii) explore any clinical and behavioural associations with fluoroquinolone resistance, and (iii) determine the distribution of antibiotic resistance among M. genitalium mgpB sequence types (STs). Methodology M. genitalium positive samples (N=94) were obtained from 1001 asymptomatic MSM enrolled in a study at Melbourne Sexual Health Centre (Carlton, Australia) between August 2016 and September 2017. Sanger sequencing was performed to determine the proportion of M. genitalium infections with SNPs in parC that have previously been associated with failure of moxifloxacin (corresponding to amino changes S83I, D83R, D87Y and D87N) and in gyrA (corresponding to amino acid changes M95I, D99N, D99Y and D99G). Associations between clinical/behavioural factors and parC SNPs were examined. Strain typing was performed by sequencing a portion of the mgpB gene. Results The proportion of MSM with infections harbouring parC and gyrA SNPs was 13.0 % [95 % confidence interval (CI): 6.8–23.2 %] and 4.7 % (95 % CI: 1.1–13.4 %), respectively; dual-class resistance was 13.0 %. No significant clinical/behavioural associations were found. Antibiotic resistance was not restricted to specific mgpB STs. Conclusion One in eight (13 %) of asymptomatic MSM with M. genitalium had an infection with dual-class-resistance mutations. Typing by mgpB sequence suggested fluoroquinolone resistance is arising from independent mutation events. This study illustrates that asymptomatic MSM may act as a reservoir for antibiotic-resistant M. genitalium .
Human microRNA‐182‐5p and kinectin 1: Potential biomarkers for prognosis in oral squamous cell carcinoma

The prognostic impact of hsa‐miRNA‐182‐5p in oral cancer remains unexplored. Therefore, the aim of this study was to investigate the prognostic value of hsa‐miRNA‐182‐5p and its predicted target kinectin 1 (KTN1) in oral squamous cell carcinoma (OSCC).
Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine

Abstract Background The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. Methods In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. Results A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose. Conclusions AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.)
Aberrant global and local dynamic properties in schizophrenia with instantaneous phase method based on Hilbert transform

Abstract Background Emerging functional imaging studies suggest that schizophrenia is associated with aberrant spatiotemporal interaction which may result in aberrant global and local dynamic properties. Methods We investigated the dynamic functional connectivity (FC) by using instantaneous phase method based on Hilbert transform to detect abnormal spatiotemporal interaction in schizophrenia. Based on resting-state functional magnetic resonance imaging, two independent datasets were included, with 114 subjects from COBRE [51 schizophrenia patients (SZ) and 63 healthy controls (HCs)] and 96 from OpenfMRI (36 SZ and 60 HCs). Phase differences and instantaneous coupling matrices were firstly calculated at all time points by extracting instantaneous parameters. Global [global synchrony and intertemporal closeness (ITC)] and local dynamic features [strength of FC (sFC) and variability of FC (vFC)] were compared between two groups. Support vector machine (SVM) was used to estimate the ability to discriminate two groups by using all aberrant features. Results We found SZ had lower global synchrony and ITC than HCs on both datasets. Furthermore, SZ had a significant decrease in sFC but an increase in vFC, which were mainly located at prefrontal cortex, anterior cingulate cortex, temporal cortex and visual cortex or temporal cortex and hippocampus, forming significant dynamic subnetworks. SVM analysis revealed a high degree of balanced accuracy (85.75%) on the basis of all aberrant dynamic features. Conclusions SZ has worse overall spatiotemporal stability and extensive FC subnetwork lesions compared to HCs, which to some extent elucidates the pathophysiological mechanism of schizophrenia, providing insight into time-variation properties of patients with other mental illnesses.
Dietary Protein and Carbohydrate Levels Affect the Gut Microbiota and Clinical Assessment in Healthy Adult Cats

ABSTRACT Background Relative levels of dietary protein and carbohydrate intake influence microbiota and their functional capabilities, but the effect has not been well documented in cats. Objectives The impact of 3 foods with different protein:carbohydrate ratios on the gut microbiota and functional attributes in healthy adult cats was evaluated. Methods Male and female cats (n = 30; mean age: 5.1 y; mean body weight: 5.26 kg) were fed 1 of 3 foods [P28 (28.3% protein, dry matter basis), P35 (35.1%), and P55 (54.8%)] for 90 d in a Williams Latin Square design. Each food had a 1:1 ratio of animal (dried chicken) to plant (pea) protein; protein replaced carbohydrate as protein level increased. Fecal microbiota and their functional capability were assessed with 16S sequencing and the Kyoto Encyclopedia of Genes and Genomes database, respectively. Results Fecal pH, ammonia, and branched-chain fatty acids (BCFAs) were higher when cats consumed P55 food than when they consumed P28 and P35. Clear separation of samples between P28 and P55 based on bacterial genera was observed, with partitioning into saccharolytic and proteolytic functions, respectively. Significantly higher α diversity was seen with P55 than with P28 and P35. Amino acid metabolism, mucin foraging pathways, and urea metabolism were higher with P55 than with P28, whereas feces from cats fed P28 had higher concentrations of carbohydrate-active enzymes and enzymes involved in SCFA pathways than with P55. Bacterial genera that showed positive associations with amino acid catabolism also showed positive associations with mucin degradation. Conclusions Despite higher protein digestibility and less protein arriving to the colon, when healthy adult cats consumed the highest level of protein (P55), their gut microbiota exhibited higher mucin glycan foraging and amino acid metabolism, leading to higher fecal pH, ammonia, and BCFAs. This is likely due to lower availability of carbohydrate substrates and dietary fiber as protein replaced carbohydrate in the food.
Incremental Visual Occlusion During Split-Belt Treadmill Walking Has No Gradient Effect on Adaptation or Retention

Split-belt treadmills have become an increasingly popular means of quantifying ambulation adaptability. Multiple sensory feedback mechanisms, including vision, contribute to task execution and adaptation success. No studies have yet explored visual feedback effects on locomotor adaptability across a spectrum of available visual information. In this study, we sought to better understand the effects of visual information on locomotor adaptation and retention by directly comparing incremental levels of visual occlusion. Sixty healthy young adults completed a split-belt adaptation protocol, including a baseline, asymmetric walking condition (adapt), a symmetric walking condition (de-adapt), and another asymmetric walking condition (re-adapt). We randomly assigned participants into conditions with varied visual occlusion (i.e., complete and lower visual field occlusion, or normal vision). We captured kinematic data, and outcome measures included magnitude of asymmetry, spatial and temporal contributions to step length asymmetry, variability of the final adapted pattern, and magnitude of adaptation. We used repeated measures and four-way MANOVAs to examine the influence of visual occlusion and walking condition. Participants with complete, compared to lower visual field visual occlusion displayed less consistency in their walking pattern, evident via increased step length standard deviation (p = .007, d = 0.89), and compared to normal vision groups (p = .003 d = 0.81). We found no other group differences, indicating that varying levels of visual occlusion did not significantly affect locomotor adaptation or retention. This study offers insight into the role vision plays in locomotor adaptation and retention with clinical utility for improving variability in step control.