Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Epidemiology of Pediatric COVID-19 Delta Variant Cases From North Sumatra, Indonesia

The Delta variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) dominated the coronavirus disease 2019 (COVID-19) pandemic in 2021. Here we report the Delta variant among pediatric cases in North Sumatra, Indonesia, from June to July 2021. Whole-genome sequencing (WGS) from 18 new COVID-19 pediatric patients showed that six were B.1. 459 and six were B.1. 466.2, known variants in Indonesia in clade 20A. Six were the Delta variant B.1. 617.2 of clade 21A, with five on one branch and one on a distant branch consistent with that patient's geographic separation, suggesting at least two introductions to the region. Variants tended to be spatially clustered, and four children with Delta variant had an adult infected household member, all of whom had lower real-time polymerase chain reaction cycle threshold (Ct) values compared with the child. No temporal trends were observed for Ct. These data support a paradigm shift with children being highly susceptible to the Delta variant and a priority for vaccination.
Methylated Cytochrome P450 and the Solute Carrier Family of Genes Correlate With Perturbations in Bile Acid Metabolism in Parkinson’s Disease

Parkinson’s disease (PD) is second most prevalent neurodegenerative disorder following Alzheimer’s disease. Parkinson’s disease is hypothesized to be caused by a multifaceted interplay between genetic and environmental factors. Herein, and for the first time, we describe the integration of metabolomics and epigenetics (genome-wide DNA methylation; epimetabolomics) to profile the frontal lobe from people who died from PD and compared them with age-, and sex-matched controls. We identified 48 metabolites to be at significantly different concentrations (FDR q < 0.05), 4,313 differentially methylated sites [5’-C-phosphate-G-3’ (CpGs)] (FDR q < 0.05) and increased DNA methylation age in the primary motor cortex of people who died from PD. We identified Primary bile acid biosynthesis as the major biochemical pathway to be perturbed in the frontal lobe of PD sufferers, and the metabolite taurine (p-value = 5.91E-06) as being positively correlated with CpG cg14286187 (SLC25A27; CYP39A1) (FDR q = 0.002), highlighting previously unreported biochemical changes associated with PD pathogenesis. In this novel multi-omics study, we identify regulatory mechanisms which we believe warrant future translational investigation and central biomarkers of PD which require further validation in more accessible biomatrices.
The Limits of Sharenting: Exploring Parents’ and Adolescents’ Sharenting Boundaries Through the Lens of Communication Privacy Management Theory

Parents sharing information about their children on social network sites (SNSs) (i.e., sharenting) is common today. However, previous work confronting parents’ and adolescents’ views on sharenting and related privacy concerns is limited. Therefore, the present study scrutinizes parents’ motives for sharenting and adolescents’ attitudes toward sharenting and negotiated privacy management strategies. Communication Privacy Management (CPM) was used as a theoretical framework. Based on 30 semi-structured interviews, two motives for sharenting were identified. Parents share information about their adolescent children because they are proud of their offspring or to inform family and friends. In turn, adolescents’ approval of their parents’ sharenting behavior depends on the content parents disclose online. Adolescents perceive sharenting as positive as long as they are nicely portrayed and positive events are shared. Additionally, both adolescents and parents are concerned about the child’s online privacy. They adopt several strategies to respect privacy boundaries and to avoid privacy turbulence.
Identifying the Leadership Challenges of K-12 Public Schools During COVID-19 Disruption: A Systematic Literature Review

Globally, the COVID-19 pandemic is triggering a public health emergency and crisis on a large scale, with far-reaching effects and severe damage to all aspects of politics, economy, cultural and social life, and health. Consecutive outbreaks over the past nearly 2 years of “living with COVID-19” have forced most schools to physically close, resulting in the largest educational disruption in human history. In turbulent times of the COVID-19 crisis, school leaders are facing numerous major challenges germane to school governance and leadership. The key objective of the study is to fully explore the prospective challenges principals are encountering in public schools in times of COVID-19. To fulfill the research purpose, a systematic literature review (SLR) was carried out to investigate the leadership challenges. As a result, a total of 24 challenges were explored through SLR approach. Frequency analysis approach was initially applied to figure out the most significant challenges. Accordingly, seven challenges were found statistically significant as showing frequency ≥ 50 each. Irrevocably, the study works as a contribution to K-12 school leadership by providing guidance for current and future leaders in crisis based on practical investigation, experiences, and recommendations. Policy makers can leverage these findings to make necessary adjustments to school policy to better prepare school leaders for crisis. Additionally, the findings of the current study are believed to have profound implications for future research. These findings expand our current understanding on school leadership in time of crisis that needs further investigation. Subsequent studies can quantitatively and/or qualitatively validate these leadership challenges findings regarding a particular school context.
Dihuang-Yinzi Alleviates Cognition Deficits via Targeting Energy-Related Metabolism in an Alzheimer Mouse Model as Demonstrated by Integration of Metabolomics and Network Pharmacology

Energy metabolism disturbance and the consequent reactive oxygen species (ROS) overproduction play a key and pathogenic role in the onset and progression of Alzheimer’s disease (AD). Dihuang-Yinzi (DHYZ) is a traditional Chinese herbal prescription clinically applied to treat AD and other neurodegenerative diseases for a long time. However, the systematical metabolic mechanism of DHYZ against AD remains largely unclear. Here we aimed to explore the mechanism of DHYZ in the treatment of AD comprehensively in an in vivo metabolic context by performing metabolomics analysis coupled with network pharmacology study and experimental validation. The network pharmacology was applied to dig out the potential target of DHYZ against AD. The metabolomics analysis based on UPLC-HRMS was carried out to profile the urine of 2× Tg-AD mice treated with DHYZ. By integrating network pharmacology and metabolomics, we found DHYZ could ameliorate 4 key energy-related metabolic pathways, including glycerophospholipid metabolism, nicotinate/nicotinamide metabolism, glycolysis, and tricarboxylic acid cycle. Besides, we identified 5 potential anti-AD targets of DHYZ, including DAO, HIF1A, PARP1, ALDH3B2, and ACHE, and 14 key differential metabolites involved in the 4 key energy-related metabolic pathways. Furthermore, DHYZ depressed the mitochondrial dysfunction and the resultant ROS overproduction through ameliorating glycerophospholipid metabolism disturbance. Thereby DHYZ increased nicotinamide adenine dinucleotide (NAD+) content and promoted glycolysis and tricarboxylic acid (TCA) cycle, and consequently improved oxidative phosphorylation and energy metabolism. In the present study, we provided a novel, comprehensive and systematic insight into investigating the therapeutic efficacy of DHYZ against AD via ameliorating energy-related metabolism.
Pro-Angiogenesis Role of LINC00662 From Esophageal Squamous Cell Carcinoma Cells-Derived Extracellular Vehicles

Objective: LINC00662 is oncogenic in some human cancers, but no much was revealed concerning to its specific action in tumor angiogenesis. Given that, our study investigated the role of LINC00662 from esophageal squamous cell carcinoma (ESCC) cells-derived extracellular vehicles (EVs) in angiogenesis through microRNA (miR)-195-5p/vascular endothelial growth factor A (VEGFA) axis. Methods: Clinical tissue samples were collected from patients with ESCC, in which LINC00662, miR-195-5p and VEGFA expression was analyzed. ESCC cells were transfected, from which EVs were isolated. Human umbilical vein endothelial cells (HUVECs) were co-cultured with the pretreated EVs. After that, viability, colony formation ability, invasion, migration and tube formation ability of HUVECs were observed. Tumor xenograft in nude mice was performed to detect the effect of LINC00662, miR-195-5p or EV specific inhibitor GW4869 on tumor development. Results: LINC00662 and VEGFA were upregulated while miR-195-5p was downregulated in the cancer tissue of patients with ESCC. EVs derived from ESCC cells promoted viability, colony formation ability, invasion and tube formation ability of HUVECs. Downregulation of LINC00662 or upregulation of miR-195-5p reversed the promotion of EVs derived from ESCC cells on the viability, colony formation ability, invasion and tube formation ability of HUVECs in vitro and in vivo. VEGFA overexpression reversed EVs carrying restored miR-195-5p induced effects on HUVECs in vitro. Conclusion: In summary, elevated LINC00662 transferred by ESCC cells-derived EVs induces angiogenesis through downregulating miR-195-5p and upregulating VEGFA.
Animal Crossing and COVID-19: A Qualitative Study Examining How Video Games Satisfy Basic Psychological Needs During the Pandemic

The COVID-19 pandemic has affected the way many people live their lives. The increasing amount of time spent indoors and isolated during periods of lockdown has been accompanied by an increase in the time people spend playing video games. One such game which soared in popularity during the early stages of the pandemic was Animal Crossing: New Horizons. Through semi-structured interviews with players from different parts of the world, and using a theory-informed qualitative analysis, we document and examine players’ motivations and experiences playing Animal Crossing: New Horizons during the pandemic. Findings suggest that playing the game helped satisfy various psychological needs—autonomy, relatedness, and competence—as described by Self-Determination Theory. Conversely, players stopped playing the game when they found that their psychological needs were thwarted or better met through other activities. Our findings offer support that video games can offer psychological relief in stressful contexts by providing opportunities for people to satisfy key psychological needs. Theoretical and practical implications are discussed.
Effect of Metformin on Myocardial Injury Induced by Hepatic Ischemia-Reperfusion in Rats

Background: There is no effective medication for treatment or prevention of hepatic ischemia-reperfusion (HIR) injury caused by liver transplantation and hepatectomy. This study aimed to investigate the therapeutic effects of metformin on HIR injury and related myocardial injury in rats. Methods: Wistar male rats were randomly divided into four groups: sham group, ischemia-reperfusion group, and IR group treated with metformin 150 mg/kg and 100 mg/kg. Wistar male rats were administered metformin 150 mg/kg, 100 mg/kg or saline 30 min pre-operative and underwent 15 min ischemia and 6 h reperfusion (n = 4). Results: Metformin significantly alleviates the injury caused by HIR. Administration of metformin resulted in a significant reduction in the serum levels of alanine transaminase and aspartate transaminase and the activity of malondialdehyde, creatine kinase-MB, and lactate dehydrogenase but maintained high catalase and superoxide dismutase activity. Metformin significantly inhibited the IR-induced elevation of tumor necrosis factor-α in liver and heart tissue. Conclusion: Metformin can alleviate hepatic and myocardial injury induced by IR by inhibiting oxidative stress.
Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials

Objective This study aims to confirm the prognostic value of baseline serum neurofilament light chain (sNfL) for on-study disease activity and worsening in patients with relapsing MS (RMS). Background Previous post-hoc studies suggested that sNfL could be a prognostic biomarker in RMS. In the phase 3 ASCLEPIOS I/II trials in which ofatumumab demonstrated better efficacy outcomes than teriflunomide, treatment with ofatumumab also led to significantly reduced sNfL levels compared to teriflunomide treatment. Design/Methods In this study, we report protocol-planned analyses from the pooled ASCLEPIOS I/II trials (N=1882). Per protocol, patients were stratified by median baseline sNfL levels (9.3 pg/ml) into high (>median) and low (≤median) categories to prognosticate: annualized rate of new/enlarging T2 (neT2) lesions in year 1 and 2, annualized relapse rate, annual percentage change in whole brain (WB) and regional brain volume [thalamus, white matter (WM), cortical gray matter (cGM)], and disability outcomes. Similar analyses were performed for the recently diagnosed (within 3 years), treatment-naive patients (no prior disease-modifying therapy) subgroup. Results High versus low sNfL at baseline was prognostic of increased on-study T2 lesion formation at year 1 (relative increase: ofatumumab +158%; teriflunomide +69%, both p<0.001), which persisted in year 2 (+65%, p=0.124; +46%, p=0.003); of higher annual percentage change of WB volume (ofatumumab, −0.32% vs. −0.24%, p=0.044, and teriflunomide, −0.43% vs. −0.29%, p=0.002), thalamic volume (−0.56% vs. −0.31%, p=0.047 and −0.94% vs. −0.49%, p<0.001), and WM volume (−0.30% vs. −0.19%, p=0.083 and −0.38% vs. −0.18%, p=0.003) but not of cGM volume (−0.39% vs. −0.32%, p=0.337 and −0.49% vs. −0.46%, p=0.563). A single sNfL assessment at baseline was not prognostic for on-study relapses or disability worsening. Results were similar in the subgroup of recently diagnosed, treatment-naive patients. Conclusion This study confirms that baseline sNfL levels are prognostic of future on-study lesion formation and whole brain and regional atrophy in all RMS patients, including recently diagnosed, treatment-naive patients.
Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans

This secondary analysis sought to determine if plasma menthol glucuronide (MG) concentrations predict changes in three outcomes, subjective drug effects, urges to smoke, and heart rate, following concurrent inhaled menthol and intravenous nicotine. A total of 45 menthol and non-menthol cigarettes smokers (36 male, nine female, 20 Black, and 23 White) were included in this double-blind, placebo-controlled study. Across three test sessions, participants were assigned to a different flavor condition for each session: 0% (no menthol), 0.5%, or 3.2% menthol. In each test session, participants received in a random order one intravenous delivery of saline and two intravenous deliveries of nicotine (0.25 mg/70 kg and 0.5 mg/70 kg), each 1 h apart, concurrent with menthol delivery by e-cigarettes. The main outcomes were subjective drug effects, urges to smoke, and heart rate. The results showed that following e-cigarette inhalation, changes in plasma MG concentrations or “menthol boost” increased proportionally to the menthol concentration in the e-liquids. While changes in plasma MG concentrations were not predictive of increases in heart rate or subjective drug effects that are reflective of acute effects from nicotine (i.e., feel good effects, stimulated, aversive effects), they were predictive of cooling effect, a typical effect of menthol, but only in menthol smokers in the absence of concurrent active nicotine infusion. These findings demonstrate the utility of plasma MG as a biomarker both for acute menthol exposure by e-cigarette inhalation and for the examination of the concentration-dependent behavioral and physiological effects of menthol in humans.
Case Report: Vortioxetine in the Treatment of Depressive Symptoms in Patients With Epilepsy—Case Series

Epilepsy and depression are both serious and potentially disabling conditions which often coexist—bidirectional relationship between the two disorders has been observed. Comorbidity between depression and epilepsy can be attributed to: underlying common pathophysiological mechanisms, psychiatric side effect of antiepileptic medications and psychological response to stress in people with chronic, neurological condition. Despite high prevalence of depressive symptoms in patients with epilepsy, current evidence of the effectiveness of antidepressant therapy in this group of patients is very limited. Vortioxetine is an antidepressant with multimodal activity, very good treatment tolerability, low risk of inducing pharmacokinetic interactions, relative safety of treatment in patients with somatic comorbidities, low risk of causing: sedation, sexual dysfunctions and metabolic side effects. Vortioxetine seems to be a promising treatment option for depressed patients with cognitive dysfunctions, anhedonia and anxiety. In this case series, we report nine cases of patients with epilepsy and depressive symptoms treated with vortioxetine. Seven cases are patients with secondary focal and generalized epilepsy and two with unclassified epilepsy. Three patients presented with depressive episode in the course of bipolar disorder and six patients had depressive symptoms due to organic mood disorder. The dose range of vortioxetine was between 10 and 20 mg. In all of the presented cases effectiveness and tolerability of treatment were very good. Remission of depressive symptoms was achieved in all patients. No epilepsy seizures after switch to vortioxetine were observed in seven cases. In two patients seizures occurred during the first months of vortioxetine treatment but this most probably was due to suboptimal antiepileptic treatment—satisfactory seizure control was achieved after optimization of antiepileptic pharmacotherapy. Vortioxetine was discontinued in two of the presented cases due to pregnancy planning. The duration of observation period during vortioxetine therapy ranged from 2 to 48 months. In conclusion, vortioxetine can be a promising treatment option in patients with epilepsy and comorbid depressive symptoms.
Effects of Dietary Lipid Sources on Alleviating the Negative Impacts Induced by the Fishmeal Replacement With Clostridium autoethanogenum Protein in the Diet of Pacific White Shrimp (Litopenaeus vannamei)

This study evaluated the effects of lipid sources on the replacement of fishmeal with Clostridium autoethanogenum protein (CAP) in the diet of Pacific white shrimp (Litopenaeus vannamei). By using CAP to replace 40% fishmeal in the basal diet (contains 25% fishmeal), four diets (PC as the control diet, LSO as the low soybean oil level, MSO as the middle soybean oil level, and HSO as the high soybean oil level) were formulated by adding different proportions of fish oil and soybean oil. Each diet was assigned to four replicates (40 shrimps per replicate, initial weight = 1.79 ± 0.02 g). A 7-day Vibrio parahaemolyticus challenge test was conducted at the end of the 50-day feeding experiment. Weight gain was significantly higher and the cumulative mortality after challenge was lower in HSO treatment. The total antioxidant capacity (T-AOC) in hepatopancreas was significantly raised with increasing dietary soybean oil based on CAP substitution. After challenge, Pen3 mRNA expression was significantly higher in hepatopancreas and NF-κB pathway-related mRNA (dorsal, relish, and IKKβ) expression was higher in the intestine in HSO treatment. The height of mucosal folds and the thickness of the muscle layer were positively correlated with the level of dietary soybean oil. Transmission electron microscopy (TEM) analysis showed that the microvilli were damaged and the endoplasmic reticulum was swollen in shrimp fed the LSO diet. Diversity of intestinal microbiota was increased in shrimp fed the LSO diet, with a significant increase in beneficial bacteria such as Halocynthiibacter and Ruegeria as well as less harmful bacteria such as Vibrio. These results suggested that the replacement of fishmeal with CAP and the high proportion of soybean oil in the diet could improve the growth performance, disease resistance, and intestinal structure of Pacific white shrimp, and high fish oil in a low-FM diet raised the percentage of beneficial bacteria in the intestine of shrimp.
Prevention Effect of Protopanaxadiol-Type Saponins Saponins and Protopanaxatriol-Type Saponins on Myelosuppression Mice Induced by Cyclophosphamide

Ginsenosides from ginseng are used as a therapeutic agent for various diseases. They enhance the immunomodulatory effect in cyclophosphamide (CP)-treated tumor disease. The structural characteristics of steroidal saponins are mainly divided into protopanaxadiol-type saponin (PDS) and protopanaxatriol-type saponin (PTS). At present, few researchers have studied which kind of saponin plays a more important role, thus, we compared the prevention effect of PDS and PTS on myelosuppression mice induced by CP. The components and contents of saponin and monosaccharide were analyzed by using ultra high performance liquid chromatography-charged aerosol detector (UPLC-CAD) and reversed phase-high performance liquid chromatography (RP-HPLC), respectively. Thirty-two mice were randomly divided into four groups, including control, model (CP), CP+PDS, and CP+PTS. The mice were orally administered with PDS or PTS for 28 days and then injected with CP saline solution on 25, 26, 27, and 28 days at a dose of 50 mg × kg−1. After the end of modeling, the whole blood of mice from the ophthalmic venous plexus was collected to detect routine blood tests, inflammatory cytokines, and hematopoiesis-related cytokines. Cell cycle and the apoptosis of bone marrow in the right femur were detected. The spleen and thymus were used to calculate the organ index and histological examination, and splenocytes were used to detect the percentage of CD4+ and CD25+ T cells. In the saponins analysis, PDS mainly included the Rb1, Rc, Rb2, and Rd of protopanaxadiol-type ginsenosides (accounted for 91.64%), and PTS mainly included the Re, Rg1, and Rf of protopanaxatriol-type ginsenosides (accounted for 75.46%). The animal results showed that both PDS and PTS improved the most indicators of myelosuppression mice induced by CP, including increased weight, blood cell numbers, hematopoiesis-related cytokines, and inflammatory cytokines; promoted the cell cycle of bone marrow and inhibited the apoptosis of bone marrow; elevated the spleen and thymus indexes and CD4+ count of splenocytes. The prevention effect of PDS was better than PTS in some indicators, such as red blood cells, hemoglobin, interleukin (IL)-1β, IL-4, IL-10, tumor necrosis factor-α, CD4+, and thymus index. These results suggest both PDS and PTS can prevent myelosuppression of mice induced by CP. Meanwhile, PDS and its metabolite showed higher bioavailability and bioactivity compared with PTS. Graphical Abstract