Miracle-dz/UniFAR-FTUs huggingface dataset:
A longitudinal, epigenome-wide study of DNA methylation in anorexia nervosa: results in actively ill, partially weight-restored, long-term remitted and non-eating-disordered women

Background This study explored state-related tendencies in DNA methylation in people with anorexia nervosa. Methods We measured genome-wide DNA methylation in 75 women with active anorexia nervosa (active), 31 women showing stable remission of anorexia nervosa (remitted) and 41 women with no eating disorder (NED). We also obtained post-intervention methylation data from 52 of the women from the active group. Results Comparisons between members of the active and NED groups showed 58 differentially methylated sites (Q < 0.01) that corresponded to genes relevant to metabolic and nutritional status (lipid and glucose metabolism), psychiatric status (serotonin receptor activity) and immune function. Methylation levels in members of the remitted group differed from those in the active group on 265 probes that also involved sites associated with genes for serotonin and insulin activity, glucose metabolism and immunity. Intriguingly, the direction of methylation effects in remitted participants tended to be opposite to those seen in active participants. The chronicity of Illness correlated (usually inversely, at Q < 0.01) with methylation levels at 64 sites that mapped onto genes regulating glutamate and serotonin activity, insulin function and epigenetic age. In contrast, body mass index increases coincided (at Q < 0.05) with generally increased methylation-level changes at 73 probes associated with lipid and glucose metabolism, immune and inflammatory processes, and olfaction. Limitations Sample sizes were modest for this type of inquiry, and findings may have been subject to uncontrolled effects of medication and substance use. Conclusion Findings point to the possibility of reversible epigenetic alterations in anorexia nervosa, and suggest that an adequate pathophysiological model would likely need to include psychiatric, metabolic and immune components.
Adaption of body zinc pools in weaned piglets challenged with subclinical zinc deficiency.

The effects of subclinical Zn deficiency on depletion and redistribution of body Zn were studied in weaned piglets. Forty-eight weaned piglets (German-Large-White×Land-Race×Piétrain; 50 % female, 50 % male-castrated; body weight 8·5 (sd 0·27) kg) were fed restrictively (450 g/d) a basal maize-soyabean meal-based diet supplemented with varying amounts of ZnSO4.7H2O (analysed dietary Zn: 28·1, 33·6, 38·8, 42·7, 47·5, 58·2, 67·8, 88·0 mg/kg diet) for an experimental period of 8 d. Analyses comprised Zn concentrations in soft tissues. Statistical analyses included regression models and k-means cluster analysis. Jejunum and kidney Zn correlated positively with dietary Zn (P<0·05). Other Zn pools responded in a non-linear fashion by declining (colon, epidermis, spleen) or increasing (mesenteric lymph follicles, thymus, skeletal muscle) below 63·6, 48·0, 47·5, 68·0, 43·0 and 53·1 mg Zn/kg diet, respectively (P<0·01). Above these thresholds, Zn concentrations in epidermis, mesenteric lymph follicles and skeletal muscle plateaued (P<0·0001), whereas they exhibited a decrease in colon and thymus (P<0·01) as well as a numerical increase in spleen. Clustering by dietary Zn concentration indicated clusters of varying Zn supply status and pathophysiological status. Clustering by biological matrices revealed a discrimination between storage, transport and excretion media as well as soft tissues. Taken together, novel response patterns indicated compensation reactions in tissues that are essential for the acute survival of growing animals (heart, skeletal muscle, immune tissues). Furthermore, this is to our knowledge the first study that mapped the gross Zn requirement by clustering tissue Zn concentrations between treatment groups.
Voice in Digital Education: The Impact of Instructor's Perceived Age and Gender on Student Learning and Evaluation

Instructor evaluations are influenced by implicit age and gender bias, with lower ratings and negative feedback given to instructors believed to stray from stereotypical age and gender norms. Female instructors exhibiting typically male‐associated qualities such as leadership and authority, are often negatively impacted. Implicit bias also influences evaluation of digital resources and instructors, regardless of students' positive learning outcomes. As digital learning resources become the norm in education, it is crucial to explore the impact of implicit bias at various educational levels. In this study, undergraduate and graduate students were randomly exposed to one of five digital tutorials; four experimental tutorials presenting identical anatomy content with narrators of different gender and age, and a control tutorial featuring origami (paper folding) instructions without audio. Learning outcomes were measured by pre‐quiz vs. post‐quiz comparisons using repeated measures MANOVA. Implicit bias was analyzed by evaluation response comparisons using repeated measures MANOVA and three‐way MANOVA. Post‐quiz scores increased significantly in the four experimental groups (P < 0.05) but not in the control (P = 0.99). The increased performance was not statistically different across the four experimental groups (P > 0.26), suggesting that learning occurred irrespective of the instructor gender and age. Students' evaluations were consistently higher for the experimental resources than the control. There was no significant difference in evaluations across the four experimental groups but compared to the control, younger male and younger female narrators received significantly higher ratings for approachability, acceptance, inclusivity, and care for student learning. The study highlights important considerations for digital resources development and interpretation of student evaluations.
Results of surgical management of infective endocarditis associated with Staphylococcus aureus.

OBJECTIVES Staphylococcus aureus (SA) is a leading cause of infective endocarditis (IE), and such cases are on the rise. Our objective was to evaluate the clinical outcomes of surgical intervention in patients with SA-associated IE and to identify the factors associated with outcomes. METHODS Between 2009 and 2017, 585 patients underwent valve surgery for definitive left-sided IE at 14 affiliated hospitals. Their medical records were retrospectively reviewed, and the preoperative variables and clinical results of patients with (n = 117) or without SA infection (n = 468) were compared. RESULTS The SA group had a more critical preoperative condition with higher rates of chronic haemodialysis, preoperative embolic events and preoperative inflammation levels, as well as worse renal function. In-hospital mortality was 20% and 7% in the patients with or without SA infection, respectively. The overall survival rate at 1 year and 5 years was 72% and 62% in the SA group, and 88% and 81% in the non-SA group, respectively (P < 0.001). The Cox hazard analysis revealed that methicillin-resistant SA infection was an independent risk factor for overall mortality in the SA group. The rate of freedom from recurrence of endocarditis at 1 year and 5 years was 95% and 90% in the SA group and 96% and 92% in the non-SA group, respectively (P = 0.43). CONCLUSIONS The short- and mid-term outcomes after valve surgery for active IE in patients with SA are still challenging. Methicillin-resistant SA infection is an independent predictor of mid-term mortality.
EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT/β‐catenin pathway

Epidermal growth factor‐like protein 6 (EGFL6) serves as an exocrine protein promoting proliferation and migration during carcinogenesis in ovarian cancer. However, its function and mechanisms in colorectal cancer (CRC) have not been completely explored. To investigate the role of EGFL6 in CRC cell growth, in vitro CCK8, colony formation assays, flow cytometric analysis of the cell cycle and apoptosis, and an in vivo tumor xenograft model were utilized. Additionally, Western blotting and luciferase reporter assays were used to investigate the underlying mechanisms of EGFL6 function on the WNT/β‐catenin signaling pathway. Immunohistochemical staining showed that EGFL6 is overexpressed in CRCs and this overexpression was highly correlated with advanced T classification, N classification, distant metastasis, and poor survival. Knocking down EGFL6 in CRC cell lines induced the inhibition of cell growth, cell cycle arrest at the G0/G1 phase, and apoptosis. Further, knockdown of EGFL6 blocked WNT/β‐catenin signaling as measured by Western blotting and luciferase reporter assay. Results also showed that recombinant EGFL6 (rEGFL6) induced β‐catenin in a concentration‐ and time‐dependent manner. Further experiments showed that administration of rEGFL6 to cell cultures with EGFL6 knocked down or treated with the WNT/β‐catenin inhibitor ICG‐001 increased β‐catenin and its downstream protein CyclinD1. The CCK8 assay showed that EGFL6 promoted CRC cell growth partly by the promotion of TCF7L2 expression. These findings suggest that EGFL6 plays a crucial role in the progression of CRC by regulation of the WNT/β‐catenin signaling pathway.
A Candidate-Gene Approach Identifies Novel Associations Between Common Variants in/Near Syndromic Obesity Genes and BMI in Pediatric and Adult European Populations

We hypothesized that monogenic syndromic obesity genes are also involved in the polygenic variation of BMI. Single-marker, tag single nucleotide polymorphism (tagSNP) and gene-based analysis were performed on common variants near 54 syndromic obesity genes. We used publicly available data from meta-analyses of European BMI genome-wide association studies conducted by the Genetic Investigation of ANthropometric Traits (GIANT) Consortium and the UK Biobank (UKB) (N = 681,275 adults). A total of 33 loci were identified, of which 19 of 33 (57.6%) were located at SNPs previously identified by the GIANT Consortium and UKB meta-analysis, 11 of 33 (33.3%) were located at novel SNPs, and 3 of 33 (9.1%) were novel genes identified with gene-based analysis. Both single-marker and tagSNP analyses mapped the previously identified 19 SNPs by the GIANT Consortium and UKB meta-analysis. Gene-based analysis confirmed 15 of 19 (78.9%) of the novel SNPs’ associated genes. Of the 11 novel loci, 8 were identified with single-marker analysis and the remaining 3 were identified with tagSNP analysis. Gene-based analysis confirmed 4 of 11 (36.3%) of these loci. Meta-analysis with the Early Growth Genetics (EGG) Consortium (N = 35,668 children) was conducted post hoc for top SNPs, confirming 17 of 33 (51.5%) loci, of which 5 were novel. This study supports evidence for a continuum between rare monogenic syndromic and common polygenic forms of obesity.
The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity

As the most commonly used plasticizer, Di-(2-ethylhexyl)-phthalate (DEHP) exists everywhere in the environment due to the widespread use of polyvinyl chloride (PVC) in human life, and it is also a recognized environmental pollutant. Studies have proved the hepatotoxicity of DEHP, however the mechanism has not been adequately explored, especially the role of the reactive oxygen species (ROS) in it. In the present study, 21 day-old ICR mice were administered DEHP with dose of 0, 125, 250, and 375 mg/kg/day for 28 days by intragastrical gavage. After contamination, histopathology displayed that liver tissue were damaged mildly with the effect of DEHP; a significant increase of the serum liver function index (including aspartate transaminase (AST) and alanine transaminase (ALT)) were observed. Additionally, the level of lipid peroxidation markedly rise, especially ROS and malondialdehyde (MDA), but the activation of superoxide dismutase (SOD) was obviously decreased in mice liver. In addition, DEHP promoted the phosphorylation of JNK and p38MAPK proteins in mice liver, as well as increased the expression of p53 protein and decreased the level of DNA methylation in the p53 gene promoter region. These results indicated that the hepatotoxicity of mice caused by DEHP may be through activating the JNK/p38MAPK/p53 signaling pathway and further promoting the generation of ROS to induce lipid peroxidation in liver, and the role of DNA methylation may be inevitable.
Prior Anticoagulation and Short‐ or Long‐Term Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients With Nonvalvular Atrial Fibrillation

Background We aimed to clarify associations between prior anticoagulation and short‐ or long‐term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio (INR) <2 on admission, 28 (2.4%) received prior warfarin treatment with an INR ≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation (INR <2: adjusted odds ratio: 0.58; 95% CI, 0.42–0.81; P=0.001; INR ≥2: adjusted odds ratio: 0.40; 95% CI, 0.16–0.97; P=0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20–6.15; P=0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL: http://www.clinicaltrials. gov. Unique identifier: NCT01581502.
Effect of Rosmarinic Acid on the Serum Parameters of Glucose and Lipid Metabolism and Oxidative Stress in Estrogen-Deficient Rats

Rosmarinic acid is found in medicinal and spice plants such as rosemary, lemon balm, and mint. The aim of the study was to investigate the effect of rosmarinic acid on parameters of glucose and lipid metabolism and parameters of oxidative stress in rats in the early phase of estrogen deficiency. The study was carried out on mature female Wistar rats divided into the following groups: sham-operated control rats, ovariectomized control rats, and ovariectomized rats treated orally with rosmarinic acid at a dose of 10 mg/kg or 50 mg/kg daily for 28 days. The concentration of sex hormones, parameters related to glucose and lipid metabolism as well as parameters of antioxidant abilities and oxidative damage were determined in the blood serum. In the ovariectomized control rats, the homeostasis model assessment of insulin resistance (HOMA-IR) index and cholesterol concentration increased, the superoxide dismutase activity increased, and the reduced glutathione concentration decreased. Administration of rosmarinic acid at both doses induced decreases in the fructosamine concentration and HOMA-IR, an increase in the concentration of reduced glutathione, and a decrease in the concentration of advanced oxidation protein products in ovariectomized rats. Moreover, rosmarinic acid at a dose of 50 mg/kg induced a decrease in the total cholesterol and triglyceride concentrations. The results indicate that rosmarinic acid may be useful in the prevention of metabolic disorders associated with estrogen deficiency, however further studies are necessary.
A Systematic Review of the Symptom Profile and Course of Methamphetamine-Associated Psychosis

Abstract Objectives: The psychiatric symptom profile of methamphetamine-associated psychosis (MAP) has varied considerably across studies of different research designs. We performed a systematic review to examine the available evidence for specific psychotic symptoms associated with MAP, including the clinical course and longitudinal changes in this symptom profile. Methods: Five key electronic databases were searched to identify studies that examined the symptom profile or clinical course of MAP in individuals identified as having MAP. The reporting of specific psychiatric symptoms, and duration of symptoms where available, was recorded for each study. Results: Ninety-four articles were identified (n = 7387), including case-control (k = 29), cross-sectional (k = 20), experimental (k = 6), case report (k = 29), and longitudinal (k = 20) studies. Persecutory delusions, auditory and visual auditory hallucinations were by far the most commonly reported symptoms (reported in 65–84% of studies). Hostility, conceptual disorganization, and depression were reported in a large proportion of studies (31–53%). Negative symptoms were mostly absent (<20%). The median percentage of participants with persistent psychotic symptoms (>1 month duration) across studies was 25% (excluding case reports). Conclusion: Persecutory delusions, auditory and visual hallucinations, hostility, depression and conceptual disorganization are central to MAP, whereas negative psychotic symptoms are typically absent. An overrepresentation of institutionalized or male participants may have overemphasized negative symptoms and underreported affective symptoms in past research. Symptoms of MAP may persist beyond one month after drug cessation in some individuals. Clinicians are encouraged to manage affective symptoms in MAP individuals, and monitor for the development of chronic psychotic symptoms.
Metabolic Syndrome and Its Associations with Components of Sarcopenia in Overweight and Obese Older Adults

Ageing, obesity and the metabolic syndrome (MetS) may all contribute to poor muscle health (sarcopenia). This study aimed to determine the cross-sectional associations between MetS (International Diabetes Federation classification) and sarcopenia (revised European Working Group on Sarcopenia in Older People definition) in 84 overweight and obese older adults. Components of sarcopenia included muscle strength (hand grip and leg extension), physical performance (stair climb test and short physical performance battery (SPPB), including gait speed and repeated chair stands time), muscle mass (appendicular lean mass (ALM), dual-energy X-ray absorptiometry), muscle size (peripheral quantitative computed tomography-determined calf and forearm cross-sectional area (CSA)) and muscle quality (muscle density and strength normalised to lean mass). Waist circumference was associated with greater muscle size, but poorer leg extension strength, chair stands and stair climb time, gait speed, SPPB scores and muscle quality measures (all p < 0.05). MetS was positively associated with ALM and forearm muscle CSA, and negatively associated with muscle quality measures and chair stands time (all p < 0.05). MetS is associated with larger muscle size, yet poorer muscle quality in overweight and obese older adults. Assessments of muscle function and quality should be considered for obese older adults and those with MetS.
Empagliflozin as an adjunctive therapy for type 1 diabetes.

Long-term complications of type 1 diabetes (T1D) due to exposure to chronic hyperglycaemia, including blindness, amputations, cardiovascular disease and kidney failure, remain a fear for many people living with T1D. Intensive insulin therapy reduces the risk of complications, but the majority of people with T1D fail to achieve recommended glycaemic targets (1-3). Furthermore, long-term intensive insulin therapy is associated with weight gain, a relevant side-effect as a significant proportion of people with T1D are now overweight (4).
Raccoons accumulate PrPSc after intracranial inoculation of the agents of chronic wasting disease or transmissible mink encephalopathy but not atypical scrapie

Prion diseases are neurodegenerative diseases characterized by the accumulation of misfolded prion protein (PrPSc) in the brain and other tissues. Animal prion diseases include scrapie in sheep, chronic wasting disease (CWD) in cervids, and transmissible mink encephalopathy (TME) in ranch-raised mink. We investigated the susceptibility of raccoons to various prion disease agents and compared the clinicopathologic features of the resulting disease. Raccoon kits were inoculated intracranially with the agents of raccoon-passaged TME (TMERac), bovine-passaged TME (TMEBov), hamster-adapted drowsy (TMEDY) or hyper TME (TMEHY), CWD from white-tailed deer (CWDWtd) or elk (CWDElk), or atypical (Nor98) scrapie. Raccoons were euthanized when they developed clinical signs of prion disease or at study endpoint (<82 mo post-inoculation). Brain was examined for the presence of spongiform change, and disease-associated PrPSc was detected using an enzyme immunoassay, western blot, and immunohistochemistry. All raccoons inoculated with the agents of TMERac and TMEBov developed clinical disease at ~6.6 mo post-inoculation, with widespread PrPSc accumulation in central nervous system tissues. PrPSc was detected in the brain of 1 of 4 raccoons in each of the CWDWtd-, CWDElk-, and TMEHY-inoculated groups. None of the raccoons inoculated with TMEDY or atypical scrapie agents developed clinical disease or detectable PrPSc accumulation. Our results indicate that raccoons are highly susceptible to infection with raccoon- and bovine-passaged TME agents, whereas CWD isolates from white-tailed deer or elk and hamster-adapted TMEHY transmit poorly. Raccoons appear to be resistant to infection with hamster-adapted TMEDY and atypical scrapie agents.
FDA Approval Summary: Ivosidenib for Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation

The FDA approved ivosidenib (Tibsovo; Agios), a small-molecule inhibitor of isocitrate dehydrogenase (IDH)1 on July 20, 2018, for treatment of adults with relapsed or refractory acute myeloid leukemia (R/R AML) with susceptible IDH1 mutation as detected by an FDA-approved test. The efficacy of ivosidenib was established on the basis of complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR + CRh, and conversion from transfusion dependence (TD) to transfusion independence (TI) in Study AG120-C-001, a single-arm trial. With median follow-up of 8.3 months for 174 adults with IDH1-mutated R/R AML treated with 500 mg ivosidenib daily, the CR + CRh rate was 33% [95% confidence interval (CI), 26–40], median duration of response was 8.2 (95% CI, 5.6–12) months, and conversion from TD to TI occurred in 37% of patients. These endpoints reflect short-term benefit in patients with an unmet medical need; long-term efficacy outcomes were not assessed. Serious adverse reactions (AR) in ≥5% of patients were differentiation syndrome (10%), leukocytosis (10%), and QT interval prolongation (7%). Common (≥20%) ARs of any grade were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, QT interval prolongation, rash, pyrexia, cough, and constipation. Assessment of long-term safety of ivosidenib is a condition of this approval.