Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of Moderate Alcohol Consumption on Circulating Metabolites and Gut Microbiota in Patients With Coronary Artery Disease

Background: Epidemiological studies confirmed that moderate alcohol consumption was associated with a reduced risk of adverse cardiovascular events. It is increasingly recognized that the composition of gut microbiota and metabolites is involved in modulating the cardiovascular health of the host. However, the association of moderate alcohol consumption with serum metabolites and gut microbiome and its impact on coronary artery disease (CAD) is not fully investigated. Method: Serum untargeted metabolomics analysis and fecal 16S rRNA sequencing were performed on 72 male patients with CAD having various alcohol consumption (36 non-drinkers, 18 moderate drinkers, and 18 heavy drinkers) and 17 matched healthy controls. MetaboAnalyst and PICRUSt2 were utilized to analyze the possible involved metabolic pathways. Multi-omics analysis was achieved by Spearman correlation to reveal the interactions of alcohol consumption with gut microbiome and serum metabolites in patients with CAD. Results: We noted distinct differences between patients with CAD, with varying levels of alcohol consumption and healthy controls in aspects of serum metabolome and the gut microbiome. Moderate alcohol consumption significantly changed the lipidomic profiles, including reductions of sphingolipids and glycerophospholipids in moderate drinkers with CAD when compared with non and heavy drinkers with CAD. Moreover, we also found the reduction of microbial-derived metabolites in moderate drinkers with CAD, such as 2-phenylacetamide and mevalonic acid. To be noted, the gut microbiota of moderate drinkers with CAD tended to resemble that of healthy controls. Compared with non-drinkers, the relative abundance of genus Paraprevotella, Lysinibacillus was significantly elevated in moderate drinkers with CAD, while the genus Bifidobacterium, Megasphaera, and Streptococcus were significantly reduced in moderate drinkers with CAD. Multi-omics analysis revealed that specific metabolites and microbes associated with moderate alcohol consumption were correlated with the severity of CAD. Conclusions: Our study revealed that the impact of moderate alcohol consumption on serum metabolites and gut microbiota in patients with CAD seemed to be separated from that of heavy and non-alcohol consumption. Moderate drinking tended to have more positive effects on metabolic profiles and commensal flora, which may explain its beneficial effects on cardiovascular health. Overall, our study provides a novel insight into the effects of moderate alcohol consumption in patients with CAD.
Racial Disparities in 30-Day Outcomes Following Index Admission for COVID-19

We investigated racial disparities in a 30-day composite outcome of readmission and death among patients admitted across a 5-hospital health system following an index COVID-19 admission. A dataset of 1,174 patients admitted between March 1, 2020 and August 21, 2020 for COVID-19 was retrospectively analyzed for odds of readmission among Black patients compared to all other patients, with sequential adjustment for demographics, index admission characteristics, type of post-acute care, and comorbidities. Tabulated results demonstrated a significantly greater odds of 30-day readmission or death among Black patients (18.0% of Black patients vs. 11.3% of all other patients; Univariate Odds Ratio: 1.71, p = 0.002). Sequential adjustment via logistic regression revealed that the odds of 30-day readmission or death were significantly greater among Black patients after adjustment for demographics, index admission characteristics, and type of post-acute care, but not comorbidities. Stratification by type of post-acute care received on discharge revealed that the same disparity in odds of 30-day readmission or death existed among patients discharged home without home services, but not those discharged to home with home services or to a skilled nursing facility or acute rehab facility. Collectively, the findings suggest that weighing comorbidity burdens in post-acute care decisions may be relevant in addressing racial disparities in 30-day outcomes following discharge from an index COVID-19 admission.
pH Stress Mediated Alteration in Protein Composition and Reduction in Cytotoxic Potential of Gardnerella vaginalis Membrane Vesicles

The vagina of healthy women is predominantly colonized by lactobacilli but it also harbors a limited proportion of certain anaerobes such as Gardnerella vaginalis. An increase in G. vaginalis along with other anaerobes on account of perturbation in the vaginal microbiota is associated with bacterial vaginosis (BV). Although strategies adopted by G. vaginalis for survival and pathogenesis in a conducive environment (i.e., high vaginal pH, characteristic of BV) have been previously studied, the approaches potentially employed for adaptation to the low pH of the healthy vagina are unknown. In the present study, we investigated the effect of acidic stress on the modulation of the production and function of membrane vesicles (MVs) of G. vaginalis. pH stress led to a distortion of the bacterial cell morphology as well as an altered biogenesis of MVs, as revealed by transmission electron microscopy (TEM). Both qualitative and quantitative differences in protein content of MVs produced in response to pH stress were observed by flow cytometry. A significant change in the protein composition characterized by presence of chaperones despite a reduction in number of proteins was also noted in the stress induced MVs. Further, these changes were also reflected in the reduced cytotoxic potential toward vaginal epithelial cells. Although, these findings need to be validated in the in vivo settings, the modulation of G. vaginalis MV biogenesis, composition and function appears to reflect the exposure to acidic conditions prevailing in the host vaginal mileu in the absence of vaginal infection.
Socioeconomic Status, Parental Involvement and Implications for Subjective Well-Being During the Global Pandemic of Covid-19

School closures prompted by the global outbreak of COVID-19 have impacted children’s subjective well-being. In this context, a growing number of studies has pointed out that the experience of learning at home is an essential factor influencing their subjective well-being, raising the importance of parental involvement in the educational process of their children. This article explores the formal and informal parental practices of home learning during school closures period in 19 countries and their explanatory factors, with the further aim of discussing their implications for children’s subjective well-being. The study uses the International COVID-19 Impact on Parental Engagement Study (ICIPES) database and develops a regression analysis of family, child, and school factors predicting parental involvement in homeschooling. The main findings show that parents’ socioeconomic status is a critical predictor of both formal and informal parental practices. In addition, the results denote the impact of other factors, such as the level of parental confidence with the use of technology and children’s age and gender (in the case of informal activities). Based on these findings, the article discusses policy implications to promote parental involvement and children’s subjective well-being.
Recurrent Wheeze Exacerbations Following Acute Bronchiolitis—A Machine Learning Approach

Introduction: Acute bronchiolitis is one of the most common respiratory infections in infancy. Although most infants with bronchiolitis do not get hospitalized, infants with hospitalized bronchiolitis are more likely to develop wheeze exacerbations during the first years of life. The objective of this prospective cohort study was to develop machine learning models to predict incidence and persistence of wheeze exacerbations following the first hospitalized episode of acute bronchiolitis. Methods: One hundred thirty-one otherwise healthy term infants hospitalized with the first episode of bronchiolitis at a tertiary pediatric hospital in Athens, Greece, and 73 age-matched controls were recruited. All patients/controls were followed up for 3 years with 6-monthly telephone reviews. Through principal component analysis (PCA), a cluster model was used to describe main outcomes. Associations between virus type and the clusters and between virus type and other clinical characteristics and demographic data were identified. Through random forest classification, a prediction model with smallest classification error was identified. Primary outcomes included the incidence and the number of caregiver-reported wheeze exacerbations. Results: PCA identified 2 clusters of the outcome measures (Cluster 1 and Cluster 2) that were significantly associated with the number of recurrent wheeze episodes over 3-years of follow-up (Chi-Squared, p < 0.001). Cluster 1 included infants who presented higher number of wheeze exacerbations over follow-up time. Rhinovirus (RV) detection was more common in Cluster 1 and was more strongly associated with clinical severity on admission (p < 0.01). A prediction model based on virus type and clinical severity could predict Cluster 1 with an overall error 0.1145 (sensitivity 75.56% and specificity 91.86%). Conclusion: A prediction model based on virus type and clinical severity of first hospitalized episode of bronchiolitis could predict sensitively the incidence and persistence of wheeze exacerbations during a 3-year follow-up. Virus type (RV) was the strongest predictor.
Influence of Obstructive Sleep Apnea on Systemic Inflammation in Pregnancy

Background: Obstructive sleep apnea (OSA) is prevalent in pregnancy and it is associated with adverse pregnancy-related outcomes such as gestational diabetes, pre-eclampsia, and low birth weight. Maternal systemic inflammation is proposed to be one of the main intermediate mechanisms. However, the effects of OSA on systemic inflammation are unknown in normal pregnancy. Methods: Women in the 3rd trimester underwent hospital polysomnography to evaluate whether OSA increases systemic inflammation in normal pregnancy and its potential association with adverse fetal outcomes. OSA was defined as an apnea–hypopnea index (AHI) of ≥ 5 h−1. Plasma cytokines levels (TNF-α, IL-1β, IL-6, IL-8, and IL-10) were determined by multiple immunoassays. Results: We included 11 patients with OSA and 22 women with AHI < 5 h−1, who were homogeneous in age, and body mass index (BMI). Women with OSA had significant higher levels of TNF-α, IL-1β, IL-8, and IL-10. We found significant correlations between AHI during REM and TNF-α (r = 0.40), IL-1β (r = 0.36), IL-6 (r = 0.52), IL-8 (r = 0.43), between obstructive apnea index and TNF-α (r = 0.46) and between AHI and IL-1β (r = 0.43). We also found that CT90% was related to IL-8 (r = 0.37). There were no significant differences in neonatal characteristics; however, we found inverse correlations between TNF-α and IL-8 with birth weight (both r = −0.48), while IL-8 showed a significant inverse relationship with neonatal gestational age (r = −0.48). Conclusions: OSA in our normal pregnancy population was associated with higher systemic inflammation, which was related to obstructive events, especially during REM sleep. Moreover, systemic inflammation was inversely correlated with neonatal birth weight and age.
Therapeutic Effects of Melatonin on Ocular Diseases: Knowledge Map and Perspective

Melatonin plays a critical role in the pathophysiological process including circadian rhythm, apoptosis, and oxidative stress. It can be synthesized in ocular tissues, and its receptors are also found in the eye, triggering more investigations concentrated on the role of melatonin in the eye. In the past decades, the protective and therapeutic potentials of melatonin for ocular diseases have been widely revealed in animal models. Herein, we construct a knowledge map of melatonin in treating ocular diseases through bibliometric analysis and review its current understanding and clinical evidence. The overall field could be divided into twelve topics through keywords co-occurrence analysis, in which the glaucoma, myopia, and retinal diseases were of greatest research interests according to the keywords burst detection. The existing clinical trials of melatonin in ocular diseases mainly focused on the glaucoma, and more research should be promoted, especially for various diseases and drug administration. We also discuss its bioavailability and further research topics including developing melatonin sensors for personalized medication, acting as stem cell therapy assistant drug, and consuming food-derived melatonin for facilitating its clinical transformation.
SEAGLE: A Scalable Exact Algorithm for Large-Scale Set-Based Gene-Environment Interaction Tests in Biobank Data

The explosion of biobank data offers unprecedented opportunities for gene-environment interaction (GxE) studies of complex diseases because of the large sample sizes and the rich collection in genetic and non-genetic information. However, the extremely large sample size also introduces new computational challenges in G×E assessment, especially for set-based G×E variance component (VC) tests, which are a widely used strategy to boost overall G×E signals and to evaluate the joint G×E effect of multiple variants from a biologically meaningful unit (e.g., gene). In this work, we focus on continuous traits and present SEAGLE, a Scalable Exact AlGorithm for Large-scale set-based G×E tests, to permit G×E VC tests for biobank-scale data. SEAGLE employs modern matrix computations to calculate the test statistic and p-value of the GxE VC test in a computationally efficient fashion, without imposing additional assumptions or relying on approximations. SEAGLE can easily accommodate sample sizes in the order of 105, is implementable on standard laptops, and does not require specialized computing equipment. We demonstrate the performance of SEAGLE using extensive simulations. We illustrate its utility by conducting genome-wide gene-based G×E analysis on the Taiwan Biobank data to explore the interaction of gene and physical activity status on body mass index.
A Rare Manifestation of a Presumed Non-Osteophilic Brain Neoplasm: Extensive Axial Skeletal Metastases From Glioblastoma With Primitive Neuronal Components

Background Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system. GBM with primitive neuronal component (GBM-PNC) is an aggressive variant identified in 0.5% of GBMs. Extracranial metastasis from GBM-PNC is a rare and challenging situation. Methods A special case of early-onset GBM with systemic bone metastasis was enrolled. Clinical data, including patient characteristics, disease course, and serial radiological images were retrieved and analyzed. Tumor tissues were obtained by surgical resections and were made into formalin-fixed paraffin-embedded sections. Histopathological examinations and genetic testing were performed for both the primary and metastatic tumor specimens. Results A 20-year-old man suffered from GBM with acute intratumoral hemorrhage of the left temporal lobe. He was treated by gross total resection and chemoradiotherapy following the Stupp protocol. Seven months later, he returned with a five-week history of progressive neck pain and unsteady gait. The radiographic examinations identified vertebral collapse at C4 and C6. Similar osteolytic lesions were also observed at the thoracolumbar spine, pelvic, and left femur. Anterior spondylectomy of C4 and C6 was performed. The resected vertebral bodies were infiltrated with greyish, soft, and ill-defined tumor tissue. One month later, he developed mechanical low-back pain and paraplegia caused by thoracolumbar metastases. Another spine surgery was performed, including T10 total en-bloc spondylectomy, T7-9, L2-3, and L5-S1 laminectomy. After the operation, the patient’s neurological function and spinal stability remained stable. However, he finally succumbed to the rapidly increased tumor burden and died 15 months from onset because of cachexia and multiple organ failure. In addition to typical GBM morphology, the histological examinations identified monomorphic small-round cells with positive immunohistochemical staining of synaptophysin and CD99, indicating the coexistence of PNC. The next-generation sequencing detected pathogenic mutations in TP53 and DNMT3A. Based on above findings, a confirmed diagnosis of systemic metastases from GBM-PNC (IDH-wild type, WHO grade IV) was made. Conclusions The present case highlights the occurrence and severity of extensive axial skeletal metastases from GBM-PNC. This rare variant of GBM requires aggressive multimodal treatment including surgery and chemoradiotherapy targeting PNC. The pathological screening of PNC is recommended in patients with early-onset GBM and intratumoral hemorrhage. Surgery for spinal metastasis is appropriate in patients with chemoradioresistance and relatively good general status, with the objectives of restoring spinal stability and relieving spinal cord compression.
Longshot or Favorite: The Ending Effect in Investment Decisions

The ending effect describes the phenomenon that at the end of a series of repeated risky decision-making tasks, participants become more likely to engage in risk-taking behavior. Past research has suggested that the ending effect might be caused by a motivational shift induced by changes in time perception. Previous studies mainly tested this phenomenon in a binary decision-making setting (e.g., a decision-making task usually includes two alternatives). However, none of these prior studies included safe options and risky options that differed in risk levels. To address this knowledge gap, the present study replicated the ending effect in a repeated decision-making task that included both a safe option and risky options that differed in risk levels (N = 104). We found that at the end of the decision-making task, participants became more likely to engage in risk-taking and to favor the option with the highest risk. Further, we found that the investment likelihood and investment amount of high-risk options both increased significantly at the ending. In addition, a shift in favoring the safe option emerged in the noninformed condition at the end. We also found that the emotional motivation in the last round could predict the increased preference for high-risk at the ending. This study extended previous findings on the ending effect by adopting a more complex decision-making scenario and, more broadly, helped further our understanding of the psychological consequences of perceived endings.
Real-World Data of Tigecycline-Associated Drug-Induced Liver Injury Among Patients in China: A 3-year Retrospective Study as Assessed by the Updated RUCAM

Background: Tigecycline, a glycylcycline antibiotic, is increasingly used clinically for the treatment of severe infections caused by multidrug-resistant bacteria, but it is also associated with hepatotoxicity. However, the incidence and risk factors of tigecycline-associated drug-induced liver injury (DILI) are unclear. We conducted this study to investigate the incidence, characteristics and risk factors of tigecycline-associated DILI in the real-world clinic setting. Patients and Methods: A retrospective analysis was conducted in inpatients who received tigecycline treatment from January 2018 to January 2020. Based on the biochemical criteria of DILI and the causality assessment by Roussel Uclaf Causality Assessment Method (RUCAM) using cases with a probable or highly probable causality grading, two clinical pharmacists and one clinician worked together to screen patients for tigecycline-associated DILI. Then patients with DILI were randomly matched by gender in a ratio of 1:2 to the remaining patients in the tigecycline cohort without biochemical abnormalities to identify risk factors. Results: A total of 973 patients from 1,250 initial participants were included. The incidence of tigecycline-associated DILI was 5.7% (55/973). Among 55 DILI patients, 10 cases presented with the hepatocellular pattern, 4 cases belonged to the mixed pattern, and 41 presented with the cholestatic pattern. Most cases reached the severity of grade 1 and 2. The rate of recovery in hepatocellular pattern, mixed pattern, and cholestatic pattern was 70.0, 50.0, and 41.5%, respectively. The proportion of the DILI cases treated with high dose (100 mg) and prolonged duration (>14 days) was significantly higher than standard dose and routine duration (100.0% vs. 18.1%, p < 0.05). Logistic regression analysis showed that high maintenance dose (OR = 1.028, p = 0.002), prolonged duration (OR = 1.208, p = 0.000), and number of hepatotoxic drugs (OR = 2.232, p = 0.000) were independent factors of tigecycline-associated DILI. Conclusion: Tigecycline was associated with liver injury, with a slightly higher incidence (5.7%) than the frequency of “frequent” (5%) defined by the Medical Dictionary for Regulatory Activities. Patients with a high maintenance dose and prolonged tigecycline regimen, as well as concomitant use of multiple hepatotoxic drugs should be paid more attention.
Rapid Identification of Secondary Structure and Binding Site Residues in an Intrinsically Disordered Protein Segment

Mycobacterium tuberculosis harbours nine toxin-antitoxin (TA) systems of the MazEF family. MazEF TA modules are of immense importance due to the perceived role of the MazF toxin in M. tuberculosis persistence and disease. The MazE antitoxin has a disordered C-terminal domain that binds the toxin, MazF and neutralizes its endoribonuclease activity. However, the structure of most MazEF TA complexes remains unsolved till date, obscuring structural and functional information about the antitoxins. We present a facile method to identify toxin binding residues on the disordered antitoxin. Charged residue scanning mutagenesis was used to screen a yeast surface displayed MazE6 antitoxin library against its purified cognate partner, the MazF6 toxin. Binding residues were deciphered by probing the relative reduction in binding to the ligand by flow cytometry. We have used this to identify putative antitoxin interface residues and local structure attained by the antitoxin upon interaction in the MazEF6 TA system and the same methodology is readily applicable to other intrinsically disordered protein regions.
Monoclonal Antibodies Targeting IL-5 or IL-5Rα in Eosinophilic Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Background: Although the predominant airway inflammation in chronic obstructive pulmonary disease (COPD) is neutrophilic, approximately 20–40% of COPD patients present with eosinophilic airway inflammation. Compared with non-eosinophilic COPD patients, eosinophilic COPD patients are characterized by a greater number of total exacerbations and higher hospitalization rates. Furthermore, anti-interleukin-5 (IL-5) therapy, consisting of monoclonal antibodies (mAbs) targeting IL-5 or IL-5 receptor α (IL-5Rα), has been proven to be effective in severe eosinophilic asthma. This meta-analysis aimed to determine the efficacy and safety of anti-IL-5 therapy in eosinophilic COPD. Methods: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases from inception to August 2020 (updated in June 2021) to identify studies comparing anti-IL-5 therapy (including mepolizumab, benralizumab, and reslizumab) with placebo in eosinophilic COPD patients. Results: Anti-IL-5 therapy was associated with a decrease in acute exacerbation rate (RR 0.89; 95% CI 0.84 to 0.95, I 2 = 0%) and the severe adverse events (RR 0.90; 95% CI 0.84 to 0.97, I 2 = 0%). However, no significant improvement was observed in pre-bronchodilator forced expiratory volume in 1 s (FEV1) (WMD 0.01; 95% CI −0.01 to 0.03, I 2 = 25.9%), SGRQ score (WMD −1.17; 95% CI −2.05 to −0.29, I 2 = 0%), and hospital admission rate (RR 0.91; 95% CI 0.78 to 1.07, I 2 = 20.8%). Conclusion: Anti-IL-5 therapy significantly reduced the annual acute exacerbation rate and severe adverse events in eosinophilic COPD patients. However, it did not improve lung function, quality of life, and hospitalization rate.