Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiovascular health and mitochondrial function: testing an association.

BACKGROUND Although mitochondrial dysfunction appears to be a contributing factor in the pathogenesis of cardiovascular and metabolic diseases, empirical data on this association are still lacking. This study evaluSated whether mitochondrial oxidative capacity, as assessed by phosphorus magnetic resonance spectroscopy, was associated with cardiovascular risk, as estimated by the Framingham Risk Score (FRS), and with a clinical history of cardiovascular disease (CVD), in community-dwelling adults. METHODS 616 subjects from the Baltimore Longitudinal Study on Aging (mean age 66 years) underwent a comprehensive clinical evaluation. Mitochondrial oxidative capacity in skeletal muscle was assessed as post-exercise phosphocreatine recovery time constant by phosphorus magnetic resonance spectroscopy. Multivariate regression models were employed to determine the cross-sectional association of mitochondrial oxidative capacity with FRS and history of CVD. RESULTS decreased mitochondrial oxidative capacity was strongly associated with higher FRS independent of age, body composition and physical activity. Lower oxidative capacity was also associated with a history of positive of CVD and higher number of CVD events. CONCLUSIONS we speculate that the observed association could reflect the effect of an excessive production of oxidative species by dysfunctional mitochondria. Furthermore, decreased energy production could hamper the functionality of heart and vessels. In turn, a malfunctioning cardiovascular apparatus could fail to deliver the oxygen necessary for optimal mitochondrial energy production, therefore creating a vicious cycle. Longitudinal studies are necessary to ascertain the directionality of the association and the eventual presence of common pathogenetic roots. In conclusion, mitochondria could represent an important target for intervention in cardiovascular health.
Maternal HIV and child anthropometric outcomes over time: An analysis of Zimbabwe demographic health surveys from 2005-2015.

OBJECTIVE(S) To understand the association between children's anthropometric measures and maternal HIV status in Zimbabwe and to determine whether these relationships changed over time. DESIGN Data from Demographic Health Surveys in Zimbabwe rounds 2005, 2010, and 2015 were used to conduct cross-sectional analyses of child anthropometric measures (stunting, underweight, and wasting). METHODS Using separate logistic regression models for each of the anthropometric measures, we estimated the adjusted prevalence odds ratio of stunting, underweight, and wasting in children according to maternal HIV status. Moreover, we evaluated an interaction by survey year to evaluate change over time. RESULTS Children of mothers with HIV had 32% greater odds (OR = 1.32, 95% CI 1.16 to 1.5) of stunting, 27% greater odds (OR = 1.27, 95% CI 1.1 to 1.48) of underweight status and 7% greater odds (OR = 1.07, 95% CI 0.81 to 1.42) of wasting status, than children of mothers without HIV. These associations between maternal HIV status and child undernutrition did not differ by year (p > 0.05 for all interaction terms). CONCLUSION In Zimbabwe, having a mother who tested positive for HIV at the time of the survey has been associated with greater child undernutrition over the last two decades with no significant change by survey round. This emphasizes the need for continued programming to address nutritional deficiencies, sanitation, and infectious disease prevention in this high-risk population. The greatest impact of maternal HIV status has been on child stunting and underweight, associated with poor long-term child development.
Calculated stacking-fault energies in α-Al2O3

Abstract Atomistic lattice simulation was used to calculate the energies of stacking faults in the aluminium sublattice of α-Al2O3. Three potentials were employed. The first two were derived by first ascribing formal charges to aluminium and oxygen (3.0 + and 2.0– respectively), and then by using two different methods to determine a short-range two-body interaction; the third was extracted from ab initio Hartree-Fock calculations. Stacking faults on the (0001) planes with a fault vector of are high in energy (1.2-4.6 J m−2) and are sensitive to the potential model used. The energies of stacking faults on the and planes with a fault vector of are lower in energy (0.3-0.9 J m−2) and compare favourably with experiment.
Biofilm of Candida albicans: formation, regulation and resistance

Candida albicans is the most common human fungal pathogen, causing infections that range from mucous membranes to systemic infections. The present article provides an overview of C. albicans, with the production of biofilms produced by this fungus, as well as reporting the classes of antifungals used to fight such infections, together with the resistance mechanisms to these drugs. Candida albicans is highly adaptable, enabling the transition from commensal to pathogen due to a repertoire of virulence factors. Specifically, the ability to change morphology and form biofilms is central to the pathogenesis of C. albicans. Indeed, most infections by this pathogen are associated with the formation of biofilms on surfaces of hosts or medical devices, causing high morbidity and mortality. Significantly, biofilms formed by C. albicans are inherently tolerant to antimicrobial therapy, so the susceptibility of C. albicans biofilms to current therapeutic agents remains low. Therefore, it is difficult to predict which molecules will emerge as new clinical antifungals. The biofilm formation of C. albicans has been causing impacts on susceptibility to antifungals, leading to resistance, which demonstrates the importance of research aimed at the prevention and control of these clinical microbial communities.
Perturbing the energy landscape for improved packing during computational protein design

The FastDesign protocol in the molecular modeling program Rosetta iterates between sequence optimization and structure refinement to stabilize de novo designed protein structures and complexes. FastDesign has been used previously to design novel protein folds and assemblies with important applications in research and medicine. To promote sampling of alternative conformations and sequences, FastDesign includes stages where the energy landscape is smoothened by reducing repulsive forces. Here, we discover that this process disfavors larger amino acids in the protein core because the protein compresses in the early stages of refinement. By testing alternative ramping strategies for the repulsive weight, we arrive at a scheme that produces lower energy designs with more native‐like sequence composition in the protein core. We further validate the protocol by designing and experimentally characterizing over 4000 proteins and show that the new protocol produces higher stability proteins.
Predictors of Water Lead Levels in Drinking Water of Homes With Domestic Wells in 3 Illinois Counties

Supplemental Digital Content is Available in the Text. Context: Millions of US homes receive water from private wells, which are not required to be tested for lead (Pb). An approach to prioritizing high-risk homes for water lead level (WLL) testing may help focus outreach and screening efforts, while reducing the testing of homes at low risk. Objective: To (1) characterize distribution of WLLs and corrosivity in tap water of homes with private residential wells, and (2) develop and evaluate a screening strategy for predicting Pb detection within a home. Design: Cross-sectional. Setting: Three Illinois counties: Kane (northern), Peoria (central), and Jackson (southern). Participants: 151 private well users from 3 Illinois counties. Intervention: Water samples were analyzed for WLL and corrosivity. Main Outcome Measures: (1) WLL and corrosivity, and (2) the sensitivity, specificity, and predictive value of a strategy for prioritizing homes for WLL testing. Results: Pb was detected (>0.76 ppb) in tap water of 48.3% homes, and 3.3% exceeded 15 ppb, the US Environmental Protection Agency action level for community water systems. Compared with homes built in/after 1987 with relatively low corrosivity, older homes with more corrosive water were far more likely to contain measurable Pb (odds ratio = 11.07; 95% confidence interval, 3.47-35.31). The strategy for screening homes with private wells for WLL had a sensitivity of 88%, specificity of 42%, positive predictive value of 58%, and negative predictive value of 80%. Conclusions: Pb in residential well water is widespread. The screening strategy for prioritizing homes with private wells for WLL testing is greater than 85% sensitive.
Pheochromocytoma/paraganglioma preclinical models: which to use and why?

Pheochromocytomas/paragangliomas (PPGLs) are rare neuroendocrine tumours linked to more than 15 susceptibility genes. PPGLs present with very different genotype/phenotype correlations. Certainly, depending on the mutated gene, and the activated intracellular signalling pathways, as well as their metastatic potential, each tumour is immensely different. One of the major challenges in in vitro research, whatever the study field, is to choose the best cellular model for that study. Unfortunately, most of the time there is not ‘a best’ cell model. Thus, in order to avoid observations that could be related to and/or dependent on a specific cell line, researchers often perform the same experiments using different cell lines simultaneously. The situation is even more complicated when there are only very few cell models obtained in different species for a disease. This is the case for PPGLs. In this review, we will describe the characteristics of the different cell lines and of mouse models, trying to understand if there is one that is more appropriate to use, depending on which aspect of the tumours one is trying to investigate.
Self-management and independence guidelines for the care of people with spina bifida

Self-management and independence behaviors are associated with improved health conditions common to spina bifida such as skin integrity and bowel and bladder management. While most children with spina bifida ultimately achieve basic self-care behaviors, (e.g., dressing appropriately, planning activities with peers, or cooking pre-planned meals), they often lag 2–5 years behind their typically-developing peers in these activities [1]. Valid and reliable condition-specific assessments of self-management and independence are critical to optimizing outcomes for this population. Partnerships among parents, clinicians, and youths with spina bifida are essential to implementing tailored interventions based on these assessments. The guidelines delineated in this article are informed by current self-management research for people with spina bifida and offer recommendations to promote self-management and independence across the lifespan.
Effectiveness of Botulinum Toxin A Injection in Managing Mobility-Related Outcomes in Adult Patients With Cerebral Palsy

Supplemental digital content is available in the text. Purpose Intramuscular botulinum toxin A (BTX-A) is used in the management of focal spasticity in cerebral palsy (CP). The aim was to conduct a systematic review to assess current literature on the use of BTX-A in the management of mobility-related outcomes among adult persons with spastic CP. Methods All studies reporting on the use of BTX-A in the management of spastic CP among adult persons were identified by searching the following electronic databases: PubMed, CINAHL, the Cochrane Library, and EMBASE. Results Six studies were included in the review. Most studies were conducted in mixed patient groups comprising patients with movement disorders, traumatic brain injury, CP, and other disorders requiring therapy for spasticity. BTX-A was shown to be effective in improving spasticity-related outcomes among persons with CP, but mixed results were shown for functional outcomes. Conclusions More studies are required on exclusive CP cohorts using recommended and currently used scales, incorporating quality of life and patient satisfaction scales. Results from long-term follow-up studies will be valuable for better evaluation of the effectiveness of BTX-A in the management of spasticity-related outcomes among adult persons with CP.
Characteristics of social media ‘detoxification’ in university students

ABSTRACT The multiplication of social networking sites has led to increased frequency of use among young adults. While the association with mental wellbeing is still controversial, high levels of social media use were correlated with problematic behaviours, low self-esteem and depressive symptoms. ‘Social Media Detoxification’ (Detox) is the term used to describe voluntary attempts at reducing or stopping social media use to improve wellbeing. We conducted a pilot study to explore the characteristics of social media detoxification applied by 68 university students in their social media activity. Descriptive analysis revealed that most students reported a positive change in mood, reduced anxiety and improved sleep during and in the immediate aftermath of the detoxification period. These preliminary findings show that ‘social media detoxification’ is a phenomenon understood and used by university students to moderate their social media use. Wide variability in its application and effects is noted in our sample.
Computational guided identification of novel potent inhibitors of N-terminal domain of nucleocapsid protein of severe acute respiratory syndrome coronavirus 2

Abstract The Coronavirus Disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 is an exceptionally contagious disease that leads to global epidemics with elevated mortality and morbidity. There are currently no efficacious drugs targeting coronavirus disease 2019, therefore, it is an urgent requirement for the development of drugs to control this emerging disease. Owing to the importance of nucleocapsid protein, the present study focuses on targeting the N-terminal domain of nucleocapsid protein from severe acute respiratory syndrome coronavirus 2 to identify the potential compounds by computational approaches such as pharmacophore modeling, virtual screening, docking and molecular dynamics. We found three molecules (ZINC000257324845, ZINC000005169973 and ZINC000009913056), which adopted a similar conformation as guanosine monophosphate (GMP) within the N-terminal domain active site and exhibiting high binding affinity (>−8.0 kcalmol−1). All the identified compounds were stabilized by hydrogen bonding with Arg107, Tyr111 and Arg149 of N-terminal domain. Additionally, the aromatic ring of lead molecules formed π interactions with Tyr109 of N-terminal domain. Molecular dynamics and Molecular mechanic/Poisson–Boltzmann surface area results revealed that N-terminal domain – ligand(s) complexes are less dynamic and more stable than N-terminal domain – GMP complex. As the identified compounds share the same corresponding pharmacophore properties, therefore, the present results may serve as a potential lead for the development of inhibitors against severe acute respiratory syndrome coronavirus 2. Communicated by Ramaswamy H. Sarma
New Horizons: Does Mineralocorticoid Receptor Activation by Cortisol Cause ATP Release and COVID-19 Complications?

Abstract This paper attempts to explain how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes the complications that make coronavirus disease 2019 (COVID-19) a serious disease in specific patient subgroups. It suggests that cortisol-associated activation of the mineralocorticoid receptor (MR) in epithelial and endothelial cells infected with the virus stimulates the release of adenosine 5′-triphosphate (ATP), which then acts back on purinergic receptors. In the lung this could produce the nonproductive cough via purinergic P2X3 receptors on vagal afferent nerves. In endothelial cells it could stimulate exocytosis of Weibel-Palade bodies (WPBs) that contain angiopoietin-2, which is important in the pathogenesis of acute respiratory distress syndrome (ARDS) by increasing capillary permeability and von Willebrand factor (VWF), which mediates platelet adhesion to the endothelium and hence clotting. Angiopoietin-2 and VWF levels both are markedly elevated in COVID-19–associated ARDS. This paper offers an explanation for the sex differences in SARS-CoV-2 complications and also for why these are strongly associated with age, race, diabetes, and body mass index. It also explains why individuals with blood group A have a higher risk of severe infection than those with blood group O. Dexamethasone has been shown to be of benefit in coronavirus ARDS patients and has been thought to act as an anti-inflammatory drug. This paper suggests that a major part of its effect may be due to suppression of cortisol secretion. There is an urgent need to trial the combination of dexamethasone and an MR antagonist such as spironolactone to more effectively block the MR and hence the exocytosis of WPBs.
Numerical analysis of the effects of ossicular chain malformations on bone conduction stimulation

Abstract To assess the effects of ossicular chain malformations on the performance of bone conduction hearing aids, a human ear finite-element model that includes an ear canal, a middle ear, and a spiral cochlea incorporating the third windows was established. This finite element model was built based on micro-computed tomography scanning and reverse modelling techniques, and the reliability of the finite element model was verified by comparison with reported experimental data. Based on this model, two main types of ossicular chain malformations, i.e., the incudostapedial disconnection and the ossicles fixation, were simulated, and their influences on bone conduction were analyzed by comparing the trans-cochlear-partition differential pressures. The results indicate that the incudostapedial disconnection mainly deteriorates the bone conduction response at mid frequencies. The stapes fixation has the largest effect among the ossicles fixation with the bone conduction stimulation, which also mainly decreases the mid-frequency response of the bone conduction, especially at 2 kHz. As the speech intelligibility has the most important frequency range at the range between 1 kHz and 2.5 kHz, the mid-frequency deterioration caused by ossicular chain malformations should be compensated in optimizing the design of the bone conduction hearing aids. For treating patients with the ossicular chain malformations, especially for the patients who suffer from the stapes fixation, the output of bone conduction hearing aids’ actuator in the middle frequency band should be improved.
Pharmacokinetics of tenofovir alafenamide with and without cobicistat in pregnant and postpartum women living with HIV: Results from IMPAACT P1026s.

OBJECTIVE To evaluate the pharmacokinetics of tenofovir alafenamide (TAF) 10 mg with cobicistat and 25 mg without boosting in pregnant and postpartum women with HIV and to characterize TAF placental transfer and infant washout pharmacokinetics. DESIGN Open-label, multicenter phase IV prospective study of TAF pharmacokinetics during pregnancy, postpartum, delivery and infant washout. METHODS Pregnant women receiving TAF 10 mg with cobicistat or TAF 25 mg without boosting as part of clinical care had intensive pharmacokinetic assessments performed during the second and third trimesters, and 6-12 weeks postpartum. Maternal and infant blood samples were collected at delivery, and washout pharmacokinetic samples were collected in infants. TAF concentrations were quantified using LC/MS. Comparisons between pregnancy and postpartum were made using geometric mean ratios (90% confidence intervals) and Wilcoxon signed-rank tests. RESULTS Thirty-one pregnant women receiving TAF 10 mg with cobicistat-boosting and 27 women receiving TAF 25 mg without boosting were enrolled. TAF exposures did not significantly differ between pregnancy and postpartum when administered as 10 mg with cobicistat. Antepartum TAF exposures with the 25 mg dose were 33-43% lower in comparison to postpartum, but comparable to those measured in non-pregnant adults. TAF was below the lower limit of quantitation in 43/44 cord blood, 41/45 maternal blood at delivery, and all infant washout samples. CONCLUSIONS TAF exposures were comparable or higher than those measured in non-pregnant adults during pregnancy and postpartum. These findings provide reassurance on adequate TAF exposures during pregnancy, and support efforts to expand the use of TAF in pregnant women with HIV.
Switching to Progressively Reduced Nicotine Content Cigarettes in Smokers with Low Socioeconomic Status: A Double-Blind Randomized Clinical Trial.

INTRODUCTION The Food and Drug Administration issued an advanced notice of proposed rulemaking for setting a product standard for nicotine levels in cigarettes, with an emphasis on minimally or non-addicting very low nicotine content (VLNC). METHODS A 33-week, two-arm, double-blind randomized trial conducted in Hershey, Pennsylvania, USA and Washington, DC, USA included adult daily cigarette smokers (≥5 cigarettes per day) with less than a college degree, and who had no plans to quit within the next 6 months. Participants were randomized to either Reduced Nicotine Content (RNC) study cigarettes tapered every 3 weeks to a final VLNC (0.2 mg/cigarette) for six weeks or to Usual Nicotine Content (UNC) study cigarettes (11.6 mg/cigarette). Outcomes included acceptability of study cigarettes measured by attrition (primary outcome), compliance, reduction in cigarette dependence and tobacco biomarkers, and post-intervention cessation. RESULTS The RNC (n= 122) vs. UNC (n=123) group had higher attrition (adjusted Hazard Ratio 3.4; 95% confidence interval [CI] 1.99-5.81). At the end of the intervention, cotinine levels were 50% lower in the RNC group (mean group difference -137 ng/mL; 95% CI -172, -102). The RNC group smoked fewer CPD (-4.1; 95% CI -6.44, -1.75) and had lower carbon monoxide levels (-4.0 ppm; 95% CI -7.7, -0.4). Forty seven percent (29/62) of the RNC group were biochemically-confirmed compliant with smoking VLNC cigarettes (mean cotinine= 8.9 ng/ml). At three month follow-up, only compliant VLNC smokers quit with an assisted quit attempt (N=6/22, 27%). CONCLUSIONS This study supports a VLNC standard in cigarettes. IMPLICATIONS Differential dropout and noncompliance indicate some smokers had difficulty transitioning to cigarettes with reduced nicotine. These smokers will benefit from supplemental nicotine in medicinal or noncombustible tobacco products if a nicotine reduction standard is established. Other smokers in the study were able to successfully transition to VLNC cigarettes exclusively and substantially reduced their exposure to nicotine.
Effect of leaf temperature on the estimation of photosynthetic and other traits of wheat leaves from hyperspectral reflectance.

A growing number of leaf traits can be estimated from hyperspectral reflectance data. These include structural and compositional traits, such as leaf mass per area (LMA), nitrogen and chlorophyll content, but also physiological traits such a Rubisco carboxylation activity, electron transport rate and respiration rate. Since physiological traits vary with leaf temperature, how does this impact on predictions made from reflectance measurements? We investigated this with two wheat varieties, by repeatedly measuring each leaf through a sequence of temperatures imposed by varying the air temperature in a growth room. Leaf temperatures ranging from 20 to 35°C did not alter the estimated Rubisco capacity normalised to 25°C (Vcmax25), chlorophyll or nitrogen contents per unit leaf area. Models estimating LMA and Vcmax25/N were both slightly influenced by leaf temperature: estimated LMA increased by 0.27% °C -1 and Vcmax25/N increased by 0.46% °C -1. A model estimating Rubisco activity closely followed variation associated with leaf temperature. Reflectance spectra change with leaf temperature and therefore contain a temperature signal.