Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical predictors of in‐hospital mortality in venoarterial extracorporeal membrane oxygenation

Venoarterial extracorporeal membrane oxygenation (VA‐ECMO) is utilized as a life‐saving procedure and bridge to myocardial recovery for patients in refractory cardiogenic shock. Despite technical advancements, VA‐ECMO retains high mortality. This study aims to identify the clinical predictors of in‐hospital mortality after VA‐ECMO to improve risk stratification for this tenuous patient population.
Identification of potential proteases for abdominal aortic aneurysm by weighted gene coexpression network analysis.

Proteases are involved in the degradation of the extracellular matrix, which contributes to the formation of abdominal aortic aneurysm (AAA). To identify new disease targets in addition to the results of previous microarray studies, we performed next-generation sequencing (NGS) of the whole transcriptome of Angiotensin II-treated Apo E-/- male mice (n=4) and control mice (n=4) to obtain differentially expressed genes (DEGs). Identified DEGs of proteases were analyzed using weighted gene coexpression network analysis (WGCNA). RT-qPCR was conducted to validate the differential expression of selected hub genes. We found that 43 DEGs were correlated with the expression of the protease profile, and most were clustered in immune response module. Among 26 hub genes, we found that Mmp16 and Mmp17 were significantly downregulated in AAA mice, while Ctsa, Ctsc and Ctsw were upregulated. Our functional annotation analysis of genes coexpressed with the five hub genes indicated that Ctsw and Mmp17 were involved in T cell regulation and Cell adhesion molecule pathway, respectively, and that both were involved in general regulation of the cell cycle and gene expression. Overall, our data suggest that these ectopic genes are potentially crucial to AAA formation and may act as biomarkers for the diagnosis of AAA.
Construct and discriminative validity and reliability of the Selective Control of the Upper Extremity Scale (SCUES) in children with unilateral cerebral palsy

ABSTRACT Aims One of the impairments evaluated in children with cerebral palsy (CP), which perhaps has been least investigated, is reduced selective motor control. The aim of the present study was to determine construct validity, discriminative validity, and intra- and interrater reliability of the Selective Control of the Upper Extremity Scale (SCUES). Methods Thirty-three children with unilateral CP, with a mean age of 11.5 ± 3.3 years, at level I to IV according to the Manual Ability Classification System (MACS), participated. The children were video-recorded and scored using the SCUES. The videos were scored twice to determine the intra- and interrater reliability. Reliability was assessed using the intraclass correlation coefficient, the standard error of the measurement (SEM), and the smallest real difference (SRD). Differences in the SCUES scores were determined between the less- and more-affected arm and across all MACS levels for discriminative validity. Construct validity of the SCUES was established by the MACS, and the Jebsen Taylor Hand Function Test (JTT). Results SCUES scores were significantly different between the less- and more-affected arm (p < .001) and between the arm joints. SCUES scores were also significantly different among MACS levels (p < .001). The SCUES was strongly correlated with the JTT (Spearman’s rho = −0.80, p < .001) and MACS (rho = −0.78, p < .001). Intra- and interrater reliability were excellent (intraclass correlation coefficient [ICC] > 0.75) for all joints of the more-affected extremity. The SRDs at the 95% confidence level for intra- and interrater reliability were 2.11 and 1.16, respectively. Conclusions The SCUES is a valid and reliable tool to assess selective motor control of the upper extremity in children with unilateral CP.
Quantification of bronchoalveolar neutrophil extracellular traps and phagocytosis in murine pneumonia.

The past two decades have witnessed a resurgence in neutrophil research, inspired in part by the discovery of neutrophil extracellular traps (NETs) and their myriad roles in health and disease. Within the lung, dysregulation of neutrophils and NETosis have been linked to an array of diseases including pneumonia, cystic fibrosis, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and severe asthma. However, our understanding of pathologic neutrophil responses in the lung remains incomplete. Two methodologic issues have contributed to this gap: first, an emphasis on studying neutrophils from blood rather than the lung; and second, the technical difficulties of interrogating neutrophil responses in mice, which has largely restricted basic murine research to specialized laboratories. To address these limitations, we have developed a suite of techniques for studying neutrophil effector functions specifically in the mouse lung. These include ex vivo assays for phagocytosis and NETosis using bronchoalveolar neutrophils, and in situ evaluation of NETosis in a murine model of pneumonia. Throughout, we have prioritized technical ease and robust, quantitative readouts. We hope these assays will help to standardize research on lung neutrophils and improve accessibility to this burgeoning field.
Antimicrobial and phytotoxicity activities of aqueous crude extract from the Amazonian ethnomedicinal plant Bellucia grossularioides (L.) Triana

The use of plants or their parts as alternative therapies for disease is very common in many countries worldwide. Secondary metabolites present in the extracts of certain plants can inhibit or halt the development of certain pathogen species. The present study assessed the possible antimicrobial activities of a popular crude aqueous extract. The aerial parts of the Amazon tree Bellucia grossularioides (L) Triana (popularly known as Muuba or Angry-Jambo) were prepared according to folk recommendations and tested against four microorganisms related to health concerns in three concentrations (20, 10 and 5 mg/ml). The results showed no antimicrobial potential against Staphylococcus aureus, Candida albicans and Candida krusei, which cause furunculosis and leukorrhea, respectively. Additionally, growth inhibition of the toxigenic fungus Aspergillus parasiticus was assayed in vitro and the results showed no inhibitory activity for any of the tested concentrations. These findings contradict the traditional knowledge and may assist the targeting of future therapeutics practices. However, an inhibitory effect was observed for all forms of the preparations and concentrations tested on the roots of Allium cepa, indicating phytotoxic effects. Key words: Medicinal plants, antifungal, antibacterial, Allium cepa.
Populations exposed to seasonal variability: from individual-level energetics to community dynamics

Seasonality strongly affects ecological dynamics, especially in the temperate zone. In most animal populations, ontogenetic development results in large differences in body size and ecological role between individuals. Individuals in different ontogenetic life stages are therefore differentially affected by seasonality. Yet, the effect of seasonality has been little explored in models that incorporate ontogenetic development. This thesis investigates the importance of seasonality for predictions regarding commercial exploitation and species interactions in biological communities using newly derived and recently developed models that incorporate ontogenetic structure. Existing ecological theory that is based on models with ontogenetic structure and continuous dynamics is shown to be robust against seasonal variability. This thesis furthermore describes effects of seasonality and harvesting on multispecies systems that differ fundamentally from classic insights derived from models that ignore ontogenetic development. The results show that harvesting of prey fish may have a beneficial effect on large predatory fish and that seasonality may promote the persistence of predatory species.
Extracellular heparan sulfate proteoglycans and glycan-binding lectins orchestrate trans-synaptic signaling

ABSTRACT The exceedingly narrow synaptic cleft (<20 nm) and adjacent perisynaptic extracellular space contain an astonishing array of secreted and membrane-anchored glycoproteins. A number of these extracellular molecules regulate intercellular trans-synaptic signaling by binding to ligands, acting as co-receptors or modulating ligand–receptor interactions. Recent work has greatly expanded our understanding of extracellular proteoglycan and glycan-binding lectin families as key regulators of intercellular signaling at the synapse. These secreted proteins act to regulate the compartmentalization of glycoprotein ligands and receptors, crosslink dynamic extracellular and cell surface lattices, modulate both exocytosis and endocytosis vesicle cycling, and control postsynaptic receptor trafficking. Here, we focus closely on the Drosophila glutamatergic neuromuscular junction (NMJ) as a model synapse for understanding extracellular roles of the many heparan sulfate proteoglycan (HSPG) and lectin proteins that help determine synaptic architecture and neurotransmission strength. We particularly concentrate on the roles of extracellular HSPGs and lectins in controlling trans-synaptic signaling, especially that mediated by the Wnt and BMP pathways. These signaling mechanisms are causally linked to a wide spectrum of neurological disease states that impair coordinated movement and cognitive functions. Summary: A Review of the multitude of extracellular proteoglycans, glycan-binding lectins and secreted enzymes regulating trans-synaptic signaling at the Drosophila neuromuscular junction.
Pilot Testing of a Nudge-Based Digital Intervention (Welbot) to Improve Sedentary Behaviour and Wellbeing in the Workplace

Welbot is a nudge-based digital intervention that aims to reduce sedentary behaviour and improve physical and mental wellbeing at work. The purpose of this study was to pilot test the Welbot intervention. Forty-one (6M/35F) University staff (M age = 43-years) participated in this study, which was a single arm repeated measures trial conducted over three weeks of intervention. The primary outcome was sedentary behaviour (measured subjectively and objectively) and secondary outcomes included: mental wellbeing, procrastination, depression, anxiety and stress, and work engagement. A subset of participants (n = 6) wore an ActivPAL to objectively measure activity data, while another subset of participants (n = 6) completed a qualitative semi-structured interview to ascertain experiences of using Welbot. Following the intervention, a Friedman non-parametric test revealed that participants self-reported significantly less time sitting and more time standing and objectively recorded more steps at the week-1 follow-up. A series of paired t-tests exhibited that changes in all secondary outcomes were in the expected direction. However, only improvements in depression, anxiety, and stress were significant. After using Welbot, thematic analysis demonstrated that participants perceived they had a positive behaviour change, increased awareness of unhealthy behaviours at work, and provided suggestions for intervention improvement. Overall, findings provided indications of the potential positive impact Welbot may have on employees’ wellbeing, however, limitations are noted. Recommendations for intervention improvement including personalisation (e.g., individual preferences for nudges and the option to sync Welbot with online calendars) and further research into how users engage with Welbot are provided.
Multivariate association between brain function and eating disorders using sparse canonical correlation analysis

Eating disorder is highly associated with obesity and it is related to brain dysfunction as well. Still, the functional substrates of the brain associated with behavioral traits of eating disorder are underexplored. Existing neuroimaging studies have explored the association between eating disorder and brain function without using all the information provided by the eating disorder related questionnaire but by adopting summary factors. Here, we aimed to investigate the multivariate association between brain function and eating disorder at fine-grained question-level information. Our study is a retrospective secondary analysis that re-analyzed resting-state functional magnetic resonance imaging of 284 participants from the enhanced Nathan Kline Institute-Rockland Sample database. Leveraging sparse canonical correlation analysis, we associated the functional connectivity of all brain regions and all questions in the eating disorder questionnaires. We found that executive- and inhibitory control-related frontoparietal networks showed positive associations with questions of restraint eating, while brain regions involved in the reward system showed negative associations. Notably, inhibitory control-related brain regions showed a positive association with the degree of obesity. Findings were well replicated in the independent validation dataset (n = 34). The results of this study might contribute to a better understanding of brain function with respect to eating disorder.
Evaluating the Relative Vaccine Effectiveness of Adjuvanted Trivalent Influenza Vaccine Compared to High-Dose Trivalent and Other Egg-Based Influenza Vaccines among Older Adults in the US during the 2017–2018 Influenza Season

The influenza-related disease burden is highest among the elderly. We evaluated the relative vaccine effectiveness (rVE) of adjuvanted trivalent influenza vaccine (aTIV) compared to other egg-based influenza vaccines (high-dose trivalent (TIV-HD), quadrivalent (QIVe-SD), and standard-dose trivalent (TIVe-SD)) against influenza-related and cardio-respiratory events among subjects aged ≥65 years for the 2017–2018 influenza season. This retrospective cohort analysis used prescription claims, professional fee claims, and hospital charge master data. Influenza-related hospitalizations/ER visits and office visits and cardio-respiratory events were assessed post-vaccination. Inverse probability of treatment weighting (IPTW) and Poisson regression were used to evaluate the adjusted rVE of aTIV compared to other vaccines. In an economic analysis, annualized follow-up costs were compared between aTIV and TIV-HD. The study was composed of 234,313 aTIV, 1,269,855 TIV-HD, 212,287 QIVe-SD, and 106,491 TIVe-SD recipients. aTIV was more effective in reducing influenza-related office visits and other respiratory-related hospitalizations/ER visits compared to the other vaccines. For influenza-related hospitalizations/ER visits, aTIV was associated with a significantly higher rVE compared to QIVe-SD and TIVe-SD and was comparable to TIV-HD. aTIV was also associated with a significantly higher rVE compared to TIVe-SD against hospitalizations/ER visits related to pneumonia and asthma/COPD/bronchial events. aTIV and TIV-HD were associated with comparable annualized all-cause and influenza-related costs. Adjusted analyses demonstrated a significant benefit of aTIV against influenza- and respiratory-related events compared to the other egg-based vaccines.
Genetic Mutations That Drive Evolutionary Rescue to Lethal Temperature in Escherichia coli

Abstract Evolutionary rescue occurs when adaptation restores population growth against a lethal stressor. Here, we studied evolutionary rescue by conducting experiments with Escherichia coli at the lethal temperature of 43.0 °C, to determine the adaptive mutations that drive rescue and to investigate their effects on fitness and gene expression. From hundreds of populations, we observed that ∼9% were rescued by genetic adaptations. We sequenced 26 populations and identified 29 distinct mutations. Of these populations, 21 had a mutation in the hslVU or rpoBC operon, suggesting that mutations in either operon could drive rescue. We isolated seven strains of E. coli carrying a putative rescue mutation in either the hslVU or rpoBC operon to investigate the mutations’ effects. The single rescue mutations increased E. coli’s relative fitness by an average of 24% at 42.2 °C, but they decreased fitness by 3% at 37.0 °C, illustrating that antagonistic pleiotropy likely affected the establishment of rescue in our system. Gene expression analysis revealed only 40 genes were upregulated across all seven mutations, and these were enriched for functions in translational and flagellar production. As with previous experiments with high temperature adaptation, the rescue mutations tended to restore gene expression toward the unstressed state, but they also caused a higher proportion of novel gene expression patterns. Overall, we find that rescue is infrequent, that it is facilitated by a limited number of mutational targets, and that rescue mutations may have qualitatively different effects than mutations that arise from evolution to nonlethal stressors.
SARS-CoV-2 and the pandemic of COVID-19

SARS-CoV-2 is a virus that is the cause of a serious life-threatening disease known as COVID-19. It was first noted to have occurred in Wuhan, China in November 2019 and the WHO reported the first case on December 31, 2019. The outbreak was declared a global pandemic on March 11, 2020 and by May 30, 2020, a total of 5 899 866 positive cases were registered including 364 891 deaths. SARS-CoV-2 primarily targets the lung and enters the body through ACE2 receptors. Typical symptoms of COVID-19 include fever, cough, shortness of breath and fatigue, yet some atypical symptoms like loss of smell and taste have also been described. 20% require hospital admission due to severe disease, a third of whom need intensive support. Treatment is primarily supportive, however, prognosis is dismal in those who need invasive ventilation. Trials are ongoing to discover effective vaccines and drugs to combat the disease. Preventive strategies aim at reducing the transmission of disease by contact tracing, washing of hands, use of face masks and government-led lockdown of unnecessary activities to reduce the risk of transmission.
Baseline Characteristics of Study Participants in the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) Trial

Abstract. Recurrent enteric infections and micronutrient deficiencies, including deficiencies in the tryptophan–kynurenine–niacin pathway, have been associated with environmental enteric dysfunction, potentially contributing to poor child growth and development. We are conducting a randomized, placebo-controlled, 2 × 2 factorial interventional trial in a rural population in Haydom, Tanzania, to determine the effect of 1) antimicrobials (azithromycin and nitazoxanide) and/or 2) nicotinamide, a niacin vitamer, on attained length at 18 months. Mother/infant dyads were enrolled within 14 days of the infant’s birth from September 2017 to September 2018, with the follow-up to be completed in February 2020. Here, we describe the baseline characteristics of the study cohort, risk factors for low enrollment weight, and neonatal adverse events (AEs). Risk factors for a low enrollment weight included being a firstborn child (−0.54 difference in weight-for-age z-score [WAZ] versus other children, 95% CI: −0.71, −0.37), lower socioeconomic status (−0.28, 95% CI: −0.43, −0.12 difference in WAZ), and birth during the preharvest season (November to March) (−0.22, 95% CI: −0.33, −0.11 difference in WAZ). The most common neonatal serious AEs were respiratory tract infections and neonatal sepsis (2.2 and 1.4 events per 100 child-months, respectively). The study cohort represents a high-risk population for whom interventions to improve child growth and development are urgently needed. Further analyses are needed to understand the persistent impacts of seasonal malnutrition and the interactions between seasonality, socioeconomic status, and the study interventions.
Current Landscape of NRF2 Biomarkers in Clinical Trials

The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by NFE2L2) plays a critical role in the maintenance of cellular redox and metabolic homeostasis, as well as the regulation of inflammation and cellular detoxication pathways. The contribution of the NRF2 pathway to organismal homeostasis is seen in many studies using cell lines and animal models, raising intense attention towards targeting its clinical promise. Over the last three decades, an expanding number of clinical studies have examined NRF2 inducers targeting an ever-widening range of diseases. Full understanding of the pharmacokinetic and pharmacodynamic properties of drug candidates rely partly on the identification, validation, and use of biomarkers to optimize clinical applications. This review focuses on results from clinical trials with four agents known to target NRF2 signaling in preclinical studies (dimethyl fumarate, bardoxolone methyl, oltipraz, and sulforaphane), and evaluates the successes and limitations of biomarkers focused on expression of NRF2 target genes and others, inflammation and oxidative stress biomarkers, carcinogen metabolism and adduct biomarkers in unavoidably exposed populations, and targeted and untargeted metabolomics. While no biomarkers excel at defining pharmacodynamic actions in this setting, it is clear that these four lead clinical compounds do touch the NRF2 pathway in humans.
Assessment of Coagulation Parameters in Women Affected by Endometriosis: Validation Study and Systematic Review of the Literature

The presence of endometriosis determines an inflammatory response locally. The objective of this validation study and systematic review was to assess systemic levels of coagulation and inflammatory parameters in women with or without the disease. We conducted a retrospective analysis of a database prospectively collected from January 2017 to February 2020 including n = 572 women who underwent laparoscopic surgery for endometriosis (cases, n = 324) or other benign gynecologic diseases (controls, n = 248). Inflammatory markers and coagulation parameters were determined. An advanced systematic search of the literature on the same parameters was conducted up to April 2020. A significantly higher neutrophil count was found in endometriosis patients. Patients with endometriomas and stage III–IV disease had a significantly lower absolute lymphocyte count and shortened activated partial thromboplastin time (aPTT) values. In the final regression model, aPTT retained significant predictive value for stage III–IV endometriosis (odds ratio (OR) = 0.002, 95% confidence interval (CI) = 0.00–0.445; p = 0.024). Results from the n = 14 included studies in the systematic review are characterized by a high variability, but some consistency has been found for alterations in thrombin time, platelet-to-lymphocyte ratio, and neutrophil count associated with endometriosis. Modest systemic changes of some inflammatory and coagulation parameters are associated with endometriosis. Indeed, all the modifications detected are still within the normal reference intervals, explaining the high heterogeneity among studies.