Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Candidate Gene Variants in Modulating the Risk and Severity of Alcoholic Hepatitis.

BACKGROUND Alcoholic hepatitis (AH) is a severe and life-threatening form of alcohol-associated liver disease. Only a minority of heavy drinkers acquires AH, suggesting a genetic basis for the susceptibility to and severity of AH. METHODS A cohort consisting of 211 patients with AH and 176 heavy drinking controls was genotyped for five variants in five candidate genes that previously had been associated with chronic liver diseases: rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3), rs72613567 in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), rs58542926 in transmembrane 6 superfamily member 2 (TM6SF2), rs641738 in membrane bound O-acyltransferase domain containing 7 (MBOAT7), and the copy number variant in the haptoglobin (HP) gene. We tested the effects of individual variants and the combined/interacting effects of variants on AH risk and severity. RESULTS We found significant associations between AH risk and the risk alleles of rs738409 (P=0.0081) and HP (P=0.0371), but not rs72613567 (P=0.3132), rs58542926 (P=0.2180), nor rs641738 (P=0.7630), after adjusting for patient's age and sex. A multiple regression model indicated that PNPLA3 rs738409:G [OR=1.59 (95% CI: 1.15-2.22), P=0.0055] and HP*2 [OR=1.38 (95% CI: 1.04-1.82), P=0.0245] combined and adjusted for age and sex also had a large influence on AH risk among heavy drinkers. In the entire cohort, variants in PNPLA3 and HP were associated with increased total bilirubin and Model for End-stage Liver Disease (MELD) score, two measures of AH severity. The HSD17B13 rs72613567:AA allele was not found to reduce risk of AH in patients carrying the G allele of PNPLA3 rs738409 (P=0.0921). CONCLUSION The current study demonstrates that PNPLA3 and HP genetic variants increase AH risk and are associated with total bilirubin and MELD score, surrogates of AH severity.
Vitamin D status and predictors of 25-hydroxyvitamin D levels in patients with heart failure living in a sunny region.

AIMS hypovitaminosis D has frequently been identified in patients with heart failure (HF). However, few studies have been conducted in regions with high solar incidence. Therefore, this study aimed to evaluate vitamin D status and predictors of 25-hydroxyvitamin D (25(OH)D) levels in patients with HF living in a sunny region (5 °- 6 °S). METHODS this cross-sectional study enrolled 70 patients with HF. Biodemographic, clinical, biochemical, dietary, and sun exposure data were collected, and 25(OH)D levels were measured. RESULTS the mean 25(OH)D level was 40.1 (12.4) ng/mL, and 24.3 % (95 % CI: 14.2-33.8) of patients with HF had hypovitaminosis D (25(OH)D < 30 ng/mL). Female patients (p = 0.001), those with ischemic etiology (p = 0.03) and those with high parathyroid hormone levels (> 67 pg/mL) (p = 0.034) were more likely to present hypovitaminosis D. Higher 25(OH)D levels were observed in men than in women (β = 7.78, p = 0.005) and in patients with HF in New York Heart Association (NHYA) functional class I when compared to those in class III/IV (β = 8.23, p = 0.032). CONCLUSIONS the majority of patients with HF had sufficient 25(OH)D levels. Sex and functional classification were identified as independent predictors of 25(OH)D levels. These results highlight the need for increased monitoring of vitamin D status among female patients with heart failure and those with more severe symptoms.
Opioid Literacy of Korean Americans in Rural Alabama: Addressing the Role of Social Determinants of Health

Introduction: Opioid crisis has disproportionately affected Alabamians with the highest opioid prescription rate, and it is subjected to affect Korean Americans (KA) negatively based on common predictors of opioid misuse that KA possess. Method: Cross-sectional data of KA in rural Alabama (N = 230) were analyzed. Opioid literacy was assessed by the Brief Opioid Overdose Knowledge survey. Six social determinants of health factors were considered: financial status, educational attainment, English proficiency, household food insecurity, health literacy, and social contact. Results: Participants had limited opioid literacy (M = 3.56, SD = 3.06). After adjusting for demographics and health covariates, higher levels of overall opioid literacy were associated with higher household income (B = .48, p < .01), higher levels of health literacy (B = .71, p < .01), and less frequent social contact (B = −.40, p < .01). Significant social determinants of health predictors varied across subdomains of opioid literacy. Discussion: The findings suggest that culturally competent and community-level interventions are needed to increase opioid literacy in KA in rural Alabama.
Digestible energy content of meat meals and meat and bone meals for growing pigs

1. The digestible energy content of 14 meat meals and meat and bone meals produced from different regions in eastern Australia was determined using growing pigs. The relationship between digestible energy content and chemical constituents in the meals was investigated. 2. Digestible energy ranged from 9·4 to 13·9MJ/kg (air-dry basis). This variation in digestible energy was best described by the regression equation: 3. Simpler equations, with only gross energy or crude protein and ether extract were: 4. Digestibility of the energy and crude protein in the meals ranged from 0·63 to 0·77 and 0·73 to 0·91 respectively. These variations were not related to any of the major chemical constituents of the meals.
Mitonuclear Coevolution, but not Nuclear Compensation, Drives Evolution of OXPHOS Complexes in Bivalves

Abstract In Metazoa, four out of five complexes involved in oxidative phosphorylation (OXPHOS) are formed by subunits encoded by both the mitochondrial (mtDNA) and nuclear (nuDNA) genomes, leading to the expectation of mitonuclear coevolution. Previous studies have supported coadaptation of mitochondria-encoded (mtOXPHOS) and nuclear-encoded OXPHOS (nuOXPHOS) subunits, often specifically interpreted with regard to the “nuclear compensation hypothesis,” a specific form of mitonuclear coevolution where nuclear genes compensate for deleterious mitochondrial mutations due to less efficient mitochondrial selection. In this study, we analyzed patterns of sequence evolution of 79 OXPHOS subunits in 31 bivalve species, a taxon showing extraordinary mtDNA variability and including species with “doubly uniparental” mtDNA inheritance. Our data showed strong and clear signals of mitonuclear coevolution. NuOXPHOS subunits had concordant topologies with mtOXPHOS subunits, contrary to previous phylogenies based on nuclear genes lacking mt interactions. Evolutionary rates between mt and nuOXPHOS subunits were also highly correlated compared with non-OXPHO-interacting nuclear genes. Nuclear subunits of chimeric OXPHOS complexes (I, III, IV, and V) also had higher dN/dS ratios than Complex II, which is formed exclusively by nuDNA-encoded subunits. However, we did not find evidence of nuclear compensation: mitochondria-encoded subunits showed similar dN/dS ratios compared with nuclear-encoded subunits, contrary to most previously studied bilaterian animals. Moreover, no site-specific signals of compensatory positive selection were detected in nuOXPHOS genes. Our analyses extend the evidence for mitonuclear coevolution to a new taxonomic group, but we propose a reconsideration of the nuclear compensation hypothesis.
Examining the effect of stress on the flexible updating of avoidance responses

Acute stress has been found to impair the flexible updating of stimulus − outcome associations. However, there is a lack of studies investigating the effect of acute stress on the flexible updating of stimulus–response associations, like active avoidance responses. The current study used an avoidance reversal learning paradigm to address this question. Sixty‐one participants learned that a red dot was associated with an aversive sound, whereas a green dot was not (Pavlovian Acquisition phase). Next, they were trained to avoid the aversive stimulus by selectively pressing a button in response to the red, but not the green, dot (Avoidance Acquisition phase). Subsequently, participants either underwent a stress induction task or a no‐stress control task. The flexible updating of expectancies of the US and avoidance responses were assessed after reversal of the original contingencies (Reversal Test). Acute stress did not impair the flexible updating of avoidance responses during the Reversal Test. In contrast, results showed that in the stress group the expectancies of the aversive sound were more in accordance with the reversed contingencies compared to the ratings of control participants. Additionally, cortisol responders avoided less often in comparison to cortisol non‐responders. Increased noradrenergic activity in stressed participants was related to impairments in the flexible updating of avoidance responses after contingency reversal, while this association was absent in the control participants. In conclusion, our results suggest that the autonomic response might account for shifting the balance toward inflexible updating of stimulus–outcome awareness while stress does not impair flexible updating of avoidance responses.
GESTACOVID project: psychological and perinatal effects in Spanish pregnant women subjected to confinement due to the COVID-19 pandemic

Abstract Introduction COVID-19 was declared a pandemic and confinement with movement restriction measures were applied in Spain. Postnatal mental disorders are common but frequently undiagnosed, being a risk period to develop anxiety and depression symptoms. The aim of this study is to evaluate the impact of confinement as depressive and anxiety symptoms in pregnant women (PrW) and puerperal women (PuW) mental health, as well as obstetric and perinatal outcomes during this period. Materials and methods The self-administered survey consists of a total of 28 questions, the first 16 providing contextual information and the following ones corresponding to the GHQ-12 that has been evaluated in a binomial form. A logistic regression model has been used to assess whether the contextual variables acted as a protective or risk factor and its fitting has been represented by a receiver operating curve. Results Of the 754 PrW interviewed, 58.22% were screened positive. Confinement time for these was 54.93 ± 9.75 days. The risk factors that were identified after the refinement have been to have a worse general state of health, to be sadder and to be more nervous. Among the protectors have been found to have a higher Apgar 10 score and induction of labor. The area under the adjusted regression adjustment curve was 0.8056. Conclusions Our results show a high prevalence of depression and anxiety symptoms with strict confinement measures. PrW and PuW must be considered a risk group to develop mental health disorders during disruption circumstances. Using a mental health screening tool could help to identify a group of patients with more risk and to carry out a careful monitoring to allow adequate management.
Efficacy of Transnasal Endoscopic Fine‐Needle Aspiration Biopsy in Diagnosing Submucosal Nasopharyngeal Carcinoma

The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non‐real‐time image‐guided transnasal endoscopic fine‐needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions.
A preliminary clinical trial comparing wet silver dressings versus wet‐to‐dry povidone‐iodine dressings for wound healing in pemphigus vulgaris patients

There is insufficient evidence concerning the efficacy of wet silver‐containing dressings for wound healing in pemphigus vulgaris (PV). In this randomized, controlled clinical trial, 58 patients with PV skin erosions (10%‐70% body surface area) were assigned to receive either wet silver‐containing dressings (n = 28) or wet to dry povidone‐iodine dressings as a control (n = 30). The patients in the treatment group demonstrated a significant improvement in the number of dressing changes, wound healing time, and duration of hospital stay compared with the control group. Patients treated with wet silver dressings had significantly lower NRS pain scores and reported better subjective satisfaction compared with the control group. The only adverse reactions were an occasional abnormal discharge or infection, but there was no difference between the two groups. In our study the wet silver‐containing dressings were safe and effective for the treatment of wound healing in PV patients.
Replication and cross-validation of the personality assessment inventory (PAI) cognitive bias scale (CBS) in a mixed clinical sample

Abstract Objective: This study is a cross-validation of the Cognitive Bias Scale (CBS) from the Personality Assessment Inventory (PAI), a ten-item scale designed to assess symptom endorsement associated with performance validity test failure in neuropsychological samples. The study utilized a mixed neuropsychological sample of consecutively referred patients at a large academic medical center in the Midwest. Participants and Methods: Participants were 332 patients who completed embedded and free-standing performance validity tests (PVTs) and the PAI. Pass and fail groups were created based on PVT performance to evaluate classification accuracy of the CBS. Results: The results were generally consistent with the initial study for overall classification accuracy, sensitivity, and cut-off score. Consistent with the validation study, CBS had better classification accuracy than the original PAI validity scales and a comparable effect size to that obtained in the original validation publication; however, the Somatic Complaints scale (SOM) and the Conversion subscale (SOM-C) also demonstrated good classification accuracy. The CBS had incremental predictive ability compared to existing PAI scales. Conclusions: The results supported the CBS, but further research is needed on specific populations. Findings from this present study also suggest the relationship between conversion tendencies and PVT failure may be stronger in some geographic locations or population types (forensic versus clinical patients).
Genetic architecture of Tourette syndrome: our current understanding

Abstract Tourette syndrome (TS) is a severe neuropsychiatric disorder characterized by recurrent, involuntary physical and verbal tics. With a prevalence as high as 1% in children, a deeper understanding of the etiology of the disorder and contributions to risk is critical. Here, we cover the current body of knowledge in scientific literature regarding the genetics of TS. We first review the history and diagnostic criteria for TS cases. We then cover the prevalence, and begin to address the etiology of the disorder. We highlight long-standing evidence for a genetic contribution to TS risk from epidemiology studies focused on twins, families, and population-scale data. Finally, we summarize current large-scale genetic studies of TS along specific classes of genetic variation, including common variation, rare copy number variation, and de novo variation that impact protein-coding sequence. Although these variants do not account for the entirety of TS genetic risk, current evidence is clear that each class of variation is a factor in the overall risk architecture across TS cases.
Effects of copy number variations on brain structure and risk for psychiatric illness: Large‐scale studies from the ENIGMA working groups on CNVs

The Enhancing NeuroImaging Genetics through Meta‐Analysis copy number variant (ENIGMA‐CNV) and 22q11.2 Deletion Syndrome Working Groups (22q‐ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA‐CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q‐ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest‐ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi‐site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene‐dosage effects on distinct brain regions also emerged, providing further insight into genotype–phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This “genotype‐first” approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
Contraceptive use and pregnancy plans among women of reproductive age during the first Australian COVID-19 lockdown: findings from an online survey

Abstract Purpose Australia introduced ‘lockdown’ measures to control COVID-19 on 22 March 2020 which continued for a period of two months. We aimed to investigate the impact this had on sexual and reproductive health (SRH). Materials and Methods Australians aged 18+ were eligible to participate in an online survey from 23 April to 11 May 2020. We report on the experiences of 518 female participants aged <50 years. Pregnancy intentions and contraceptive use were analysed using descriptive statistics. Odds ratios and 95% confidence intervals were calculated to investigate difficulty accessing SRH products and services. Qualitative data were analysed using conventional content analysis. Results Most participants were aged 18–24 years, and indicated they were trying to avoid pregnancy. The oral contraceptive pill was the most common single method used however nearly 20% reported they were not using contraception. Women who were employed had less trouble accessing contraception during lockdown. Participants reported delaying childbearing or deciding to remain childfree due to COVID-19. Conclusion COVID-19 lockdown impacted the SRH of Australian women. Findings highlight the importance of continued access to SRH services and products during global emergencies.
Extracellular microvesicles promote microglia‐mediated pro‐inflammatory responses to ethanol

Alcohol use disorder (AUD) pathology features pro‐inflammatory gene induction and microglial activation. The underlying cellular processes that promote this activation remain unclear. Previously considered cellular debris, extracellular vesicles (EVs) have emerged as mediators of inflammatory signaling in several disease states. We investigated the role of microvesicles (MVs, 50 nm–100 µm diameter EVs) in pro‐inflammatory and microglial functional gene expression using primary organotypic brain slice culture (OBSC). Ethanol caused a unique immune gene signature that featured: temporal induction of pro‐inflammatory TNF‐α and IL‐1β, reduction of homeostatic microglia state gene Tmem119, progressive increases in purinergic receptor P2RY12 and the microglial inhibitory fractalkine receptor CX3CR1, an increase in the microglial presynaptic gene C1q, and a reduction in the phagocytic gene TREM2. MV signaling was implicated in this response as reduction of MV secretion by imipramine blocked pro‐inflammatory TNF‐α and IL‐1β induction by ethanol, and ethanol‐conditioned MVs (EtOH‐MVs) reproduced the ethanol‐associated immune gene signature in naïve OBSC slices. Depletion of microglia prior to ethanol treatment prevented pro‐inflammatory activity of EtOH‐MVs, as did incubation of EtOH‐MVs with the HMGB1 inhibitor glycyrrhizin. Ethanol caused HMGB1 secretion from cultured BV2 microglia in MVs through activation of PI3 kinase. In summary, these studies find MVs modulate pro‐inflammatory gene induction and microglial activation changes associated with ethanol. Thus, MVs may represent a novel therapeutic target to reduce neuroinflammation in the setting of alcohol abuse or other diseases that feature a neuroimmune component. [Correction added on 5 April 2021, after first online publication: The copyright line was changed. ]
Impact of Pemafibrate in Patients with Hypertriglyceridemia and Metabolic Dysfunction-associated Fatty Liver Disease Pathologically Diagnosed with Non-alcoholic Steatohepatitis: A Retrospective, Single-arm Study

Objective The therapeutic effect of pemafibrate on metabolic dysfunction-associated fatty liver disease (MAFLD) remains unknown. This retrospective, single-arm study investigated the efficacy and safety of pemafibrate in MAFLD patients with hypertriglyceridemia. Methods A total of 10 patients who received pemafibrate (oral, 0.1 mg, twice a day) at Gunma Saiseikai Maebashi Hospital between September 2018 and September 2019 were included. All patients underwent a liver biopsy, and the disease grade and stage were pathologically assessed based on the FLIP algorithm. Results The median age was 66.0 (53.8-74.8) years old, and 5 patients (50.0%) were men. All patients were diagnosed with non-alcoholic steatohepatitis (NASH). The fasting and non-fasting triglyceride (TG) levels were 175 (149-247) mg/dL and 228 (169-335) mg/dL, respectively. The AST and ALT values at 6 months were significantly lower than at baseline [AST: 28.0 (22.0-33.8) U/L vs. 43.5 (24.0-55.0) U/L, p=0.008, ALT: 23.0 (14.8-26.5) U/L vs. 51.5 (23.0-65.3) U/L, p=0.005, respectively], especially in NASH patients with significant activity and advanced fibrosis (p=0.040 and 0.014, respectively). Fasting TG levels were significantly lower and HDL-C levels significantly higher at 6 months than at baseline (p=0.005 and 0.032, respectively). At six months, FIB-4, the aspartate aminotransferase-to-platelet ratio index, and the macrophage galactose-specific lectin-2 binding protein glycosylation isomer level were significantly improved compared with baseline (p=0.041, 0.005 and 0.005, respectively). Treatment-related adverse events were not observed. Conclusion Pemafibrate treatment may be safe and effective for MAFLD patients with hypertriglyceridemia.