Miracle-dz/UniFAR-FTUs huggingface dataset:
“Earth angels” and parking spots: qualitative perspectives on healthy aging with spinal cord injury

Abstract Purpose People aging with spinal cord injury (SCI) can experience the premature onset of comorbid conditions, as well as the development and progression of secondary health conditions. The aim of this study was to understand the subjective experiences of persons aging with SCI in relation to their surrounding social and physical environments, including the impact of barriers and facilitators. Material/Methods: Eleven individuals who had an SCI for more than ten years and were 45 years or older participated in a semi-structured phone interview about their experiences with healthy aging, social participation, social supports, and community barriers. Results Four main themes emerged in the qualitative data that captured the subjective experience of aging with SCI. These were: (1) Maintaining Physical Independence; (2) Importance of Resources and Special Equipment; (3) Planning Ahead; and (4) Finding Ways to Adapt. Conclusions The findings from this study highlight the importance of looking beyond individual factors to consider the social and environmental factors that support continued independence and participation in society as people living with long term SCI experience their aging process. Qualitative research that delves further into the dynamics behind this process is needed to fully anticipate the needs of this growing population. IMPLICATIONS FOR REHABILITATION People aging with spinal cord injury (SCI) who are engaged in their social and physical environments have become increasingly adaptive when faced with accelerating and secondary comorbidities. Programs and facilities should ensure universal access to prevention and self-management programs that target physical activity and health habits when considered in the context of a patient’s socio-environmental constraints and resources. Clinical healthcare providers need to engage with their patients to develop an early intervention approach to preserve functional capacity while navigating potential future health problems. Clinicians should act as advocates for ongoing policy changes that help promote an environment more inclusive towards people aging with SCI.
Secukinumab provided significant and sustained improvement in the signs and symptoms of ankylosing spondylitis: results from the 52-week, Phase III China-centric study, MEASURE 5

Supplemental Digital Content is available in the text Abstract Background Secukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis (AS) through 5 years in pivotal Phase III studies. Here, we present efficacy and safety results (52-week) of secukinumab in patients with AS from the MEASURE 5 study. Methods MEASURE 5 was a 52-week, Phase III, China-centric study. Eligible patients were randomly assigned (2:1) to receive subcutaneous secukinumab 150 mg or placebo weekly for the first five doses and then once every 4 weeks (q4w). All placebo patients switched to secukinumab 150 mg q4w starting at Week 16. Primary endpoint was Assessments of SpondyloArthritis international Society (ASAS) 20 at Week 16. Randomization was stratified by region (China vs. non-China). Results Of 458 patients (secukinumab 150 mg, N = 305; placebo, N = 153) randomized, 327 (71.4%) were from China and 131 (28.6%) were not from China. Of these, 97.7% and 97.4% patients completed Week 16 and 91.1% and 95.3% (placebo-secukinumab) patients completed Week 52 of treatment. The primary endpoint was met; secukinumab significantly improved ASAS20 response at Week 16 vs. placebo (58.4% vs. 36.6%; P < 0.0001); corresponding rate in the Chinese population was 56.0% vs. 38.5% (P < 0.01). All secondary efficacy endpoints significantly improved with secukinumab 150 mg in the overall population at Week 16; responses were maintained with a trend toward increased efficacy from Week 16 to 52. No new or unexpected safety signals were reported up to Week 52. Conclusions Secukinumab 150 mg demonstrated rapid and significant improvement in signs and symptoms of AS. Secukinumab was well tolerated and the safety profile was consistent with previous reports. Efficacy and safety results were comparable between the overall and Chinese populations. Trial registration ClinicalTrials.gov, NCT02896127; https://clinicaltrials.gov/ct2/show/NCT02896127? term=NCT02896127&draw=2&rank=1.
Vascular Risk Factors of Hippocampal Subfield Volumes in Persons without Dementia: The Medea 7T Study

Background: Vascular risk factors have been associated with risk of Alzheimer’s disease (AD) and volume loss of the hippocampus, but the associations with subfields of the hippocampus are understudied. Knowing if vascular risk factors contribute to hippocampal subfield atrophy may improve our understanding of vascular contributions to neurodegenerative diseases. Objective: To investigate the associations between age, sex, and vascular risk factors with hippocampal subfields volumes on 7T MRI in older persons without dementia. Methods: From the Medea 7T study, 283 participants (67±9 years, 68% men) without dementia had 7T brain MRI and hippocampal subfield segmentation. Subfields were automatically segmented on the 3D T2-weighted 7T images with ASHS software. Using linear mixed models, we estimated adjusted associations of age, sex, and vascular risk factors with z-scores of volumes of the entorhinal cortex (ERC), subiculum (SUB), Cornu Ammonis (CA)1, CA2, CA3, CA4, and dentate gyrus (DG), and tail as multivariate correlated outcomes. Results: Increasing age was associated with smaller volumes in all subfields, except CA4/DG. Current smoking was associated with smaller ERC and SUB volumes; moderate alcohol use with smaller CA1 and CA4/DG, obesity with smaller volumes of ERC, SUB, CA2, CA3, and tail; and diabetes mellitus with smaller SUB volume. Sex, former smoking, and hypertension were not associated with subfield volumes. When formally tested, no risk factor affected the subfield volumes differentially. Conclusion: Several vascular risk factors were associated with smaller volumes of specific hippocampal subfields. However, no statistical evidence was found that subfields were differentially affected by these risk factors.
Optimizing Pharmacology Studies in Pregnant and Lactating Women Using Lessons From HIV: A Consensus Statement

Information on the extent of drug exposure to mothers and infants during pregnancy and lactation normally becomes available years after regulatory approval of a drug. Clinicians face knowledge gaps on drug selection and dosing in pregnancy and infant exposure during breastfeeding. Physiological changes during pregnancy often result in lower drug exposures of antiretrovirals, and in some cases a risk of reduced virologic efficacy. The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network and the World Health Organization (WHO)–convened Pediatric Antiretrovirals Working Group collaboratively organized a workshop of key stakeholders in June 2019 to define key standards to generate pharmacology data for antiretrovirals to be used among pregnant and lactating women; review the antiretroviral product pipeline; describe key gaps for use in low‐income and middle‐income countries; and identify opportunities to undertake optimal studies allowing for rapid implementation in the clinical field. We discussed ethical and regulatory principles, systemic approaches to obtaining data for pregnancy pharmacokinetic/pharmacodynamic (PK/PD) studies, control groups, optimal sampling times during pregnancy, and pharmacokinetic parameters to be considered as primary end points in pregnancy PK/PD studies. For lactation studies, the type of milk to collect, ascertainment of maternal adherence, and optimal PK methods to estimate exposure were discussed. Participants strongly recommended completion of preclinical reproductive toxicology studies prior to phase III, to allow study protocols to include pregnant women or to allow women who become pregnant after enrolment to continue in the trial. The meeting concluded by developing an algorithm for design and interpretation of results and noted that recruitment of pregnant and lactating women into clinical trials is critical.
A Telemedicine Approach to Covid-19 Assessment and Triage

Covid-19 is a new highly contagious RNA viral disease that has caused a global pandemic. Human-to-human transmission occurs primarily through oral and nasal droplets and possibly through the airborne route. The disease may be asymptomatic or the course may be mild with upper respiratory symptoms, moderate with non-life-threatening pneumonia, or severe with pneumonia and acute respiratory distress syndrome. The severe form is associated with significant morbidity and mortality. While patients who are unstable and in acute distress need immediate in-person attention, many patients can be evaluated at home by telemedicine or videoconferencing. The more benign manifestations of Covid-19 may be managed from home to maintain quarantine, thus avoiding spread to other patients and health care workers. This document provides an overview of the clinical presentation of Covid-19, emphasizing telemedicine strategies for assessment and triage of patients. Advantages of the virtual visit during this time of social distancing are highlighted.
Trend of COVID-19 spreads and status of household handwashing practice and its determinants in Bangladesh – situation analysis using national representative data

ABSTRACT The objective of the study was to assess the prevalence and factors associated with household (HH) handwashing practice in Bangladesh and draw a trend of COVID-19 spreads and compare that with the countrywide HH handwashing practice. The study is based on the two national representative publicly available datasets (MICS 2019, and confirmed cases of COVID-19). Of 61,209 (weighted) HH, the overall prevalence of HH handwashing was found 56.3%, and the prevalence was significantly varied across the socio-economic status of the HH. Map comparison suggested that the gradual increasing trend of COVID-19 cases in areas where HH handwashing practice is low. The northern part of Bangladesh had the highest handwashing practice, whereas it had less effected by COVID-19 cases. However, central Bangladesh had the hardest hit by COVID-19 cases, and it had around 50% handwashing practice coverage. Large-scale observational study is necessary to establish the causality.
Discovery of Dual FGFR4 and EGFR Inhibitors by Machine Learning and Biological Evaluation

Kinase inhibitors are widely used in antitumor research, but there are still many problems such as drug resistance and off-target toxicity. A more suitable solution is to design a multi-target inhibitor with certain selectivity. Herein, computational and experimental studies were applied to the discovery of dual inhibitors against FGFR4 and EGFR. A quantitative structure-property relationship (QSPR) study was carried out to predict FGFR4 and EGFR activity of a data set consisting of 843 and 5088 compounds, respectively. Four different machine learning methods including support vector machine (SVM), random forest (RF), gradient boost regression tree (GBRT), and XGBoost (XGB) were built using the most suitable features selected by mutual information algorithm. As for FGFR4 and EGFR, SVM showed the best performance with R2test-FGFR4 = 0.80, R2test-EGFR = 0.75, demonstrating excellent model stability, which was used to predict the activity of some compounds from an in-house database. Finally, compound 1 was selected which exhibits inhibitory activity against FGFR4 (IC50 = 86.2nM) and EGFR (IC50 = 83.9nM) kinase, respectively. Furthermore, molecular docking and molecular dynamics simulations were performed to identify key amino acids for the interaction of compound 1 with FGFR4 and EGFR. In this paper, the machine learning based QSAR models were established and effectively applied to the discovery of dual-target inhibitors against FGFR4 and EGFR, demonstrating the great potential of machine learning strategies in dual inhibitor discovery.
Common Eider and Herring Gull as Contaminant Indicators of Different Ecological Niches of an Urban Fjord System

Seabirds like gulls are common indicators in contaminant monitoring. The herring gull (Larus argentatus) is a generalist with a broad range of dietary sources, possibly introducing a weakness in its representativeness of aquatic contamination. To investigate the herring gull as an indicator of contamination in an urban‐influenced fjord, the Norwegian Oslofjord, we compared concentrations of a range of lipophilic and protein‐associated organohalogen contaminants (OHCs), Hg, and dietary markers in blood (n = 15), and eggs (n = 15) between the herring gull and the strict marine‐feeding common eider (Somateria mollissima) in the breeding period of May 2017. Dietary markers showed that the herring gull was less representative of the marine food web than the common eider. We found higher concentrations of lipophilic OHCs (wet weight and lipid weight) and Hg (dry weight) in the blood of common eider (mean ± SE ∑PCB = 210 ± 126 ng/g ww, 60 600 ± 28 300 ng/g lw; mean Hg = 4.94 ± 0.438 ng/g dw) than of the herring gull (mean ± SE ∑PCB = 19.0 ± 15.6 ng/g ww, 1210 ± 1510 ng/g lw; mean Hg = 4.26 ± 0.438 ng/g dw). Eggs gave opposite results; higher wet weight and lipid weight OHC concentrations in the herring gull (mean ± SE ∑PCB = 257 ± 203 ng/g ww, 3240 ± 2610 ng/g lw) than the common eider (mean ± SE ∑PCB = 18.2 ± 20.8 ng/g ww, 101 ± 121 ng/g lw), resulting in higher OHC maternal transfer ratios in gulls than eiders. We suggest that the matrix differences are due to fasting during incubation in the common eider. We suggest that in urban areas, herring gull might not be representative as an indicator of marine contamination but rather urban contaminant exposure. The common eider is a better indicator of marine pollution in the Oslofjord. The results are influenced by the matrix choice, as breeding strategy affects lipid dynamics regarding the transfer of lipids and contaminants to eggs and remobilization of contaminants from lipids to blood during incubation, when blood is drawn from the mother. Our results illustrate the benefit of a multispecies approach for a thorough picture of contaminant status in urban marine ecosystems. Integr Environ Assess Manag 2021;17:422–433. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Culture-dependent and -independent methods revealed an abundant myxobacterial community shaped by other bacteria and pH in Dinghushan acidic soils

Myxobacteria are one of the most promising secondary metabolites producers. However, they are difficult to isolate and cultivate. To obtain more myxobacteria and know the effects of environmental factors on myxobacterial community, we characterized myxobacterial communities in Dinghushan acidic forest soils of pH 3.6–4.5 with culture-dependent and -independent techniques, and analyzed environmental factors shaping myxobacterial communities. A total of 21 myxobacteria were isolated using standard cultivation methods, including eleven isolates of Corallococcus, nine isolates of Myxococcus and one isolate of Archangium, and contained three potential novel species. In addition, a total of 67 unknown myxobacterial operational taxonomic units (OTUs) were obtained using high-throughput sequencing method. The abundance of Myxococcales account for 0.9–2.2% of bacterial communities, and Sorangium is the most abundant genus (60.1%) in Myxococcales. Correlation analysis demonstrated that bacterial diversity and soil pH are the key factors shaping myxobacterial community. These results revealed an abundant myxobacterial community which is shaped by other bacteria and pH in Dinghushan acidic forest soils.
AC-DC Electropenetrography: Fundamentals, Controversies, and Perspectives for Arthropod Pest Management.

Studying the intimate association of arthropods with their physical substrate is both important and challenging. It is important because substrate is a key determinant for organism fitness; challenging because the intricacies of this association are dynamic, and difficult to record and resolve. The advent of electropenetrography (EPG) and subsequent developments allowed researchers to overcome this challenge. Nonetheless, EPG research has been historically restricted to piercing-sucking hemipteran plant pests. Recently, its potential use has been greatly broadened for additional pests with instrument advances. Thus, blood-feeding arthropods and chewing feeders, as well as non-feeding behaviors like oviposition by both pests and parasitoids, are novel new targets for EPG research, with critical consequences for IPM. EPG can explain mechanisms of crop damage, plant or animal pathogen transmission, and the effects of insecticides, antifeedants, repellents, or transgenic plants and animals, on specific behaviors of damage or transmission. The present review broadly covers the principles and development of EPG technology, emphasizing controversies and challenges remaining with suggested research to overcome them. In addition, it summarizes 60+ years of basic and applied EPG research, and previews future directions for pest management. The goal is to stimulate new applications for this unique enabling technology. This article is protected by copyright. All rights reserved.
Blunted opioid regulation of the HPA stress response during nicotine withdrawal: therapeutic implications

Abstract Endogenous opioids regulate pain, drug reward, and stress responses. We have previously shown reduced hypothalamic-pituitary-adrenal (HPA) responses to psychological stress and to opioid blockade among dependent smokers. In this study, we examined the extent to which biologically confirmed nicotine withdrawal alters endogenous opioid regulation of HPA axis functioning during rest and in response to acute stress. Smokers were randomly assigned to one of two conditions; 24 h withdrawal from all nicotine-containing products (n = 62) or smoking ad libitum (n = 44). A nonsmoking comparison group (n = 43) was also included. Participants (85 males and 64 females) completed two acute stress sessions during which a placebo or 50 mg of naltrexone (opioid antagonist) were administered using a double-blind design. Blood and saliva samples (assayed for cortisol and adrenocorticotropic hormone, i.e. ACTH) and mood measures were obtained during a resting absorption period, after acute stress (public speaking, mental arithmetic, and cold pressor tasks), and during an extended recovery period. Results indicated that opioid blockade (naltrexone) was associated with increased ACTH and cortisol responses to stress, and tobacco withdrawal was associated with blunted hormonal responses. A pattern of sex differences also emerged, with women exhibiting reduced ACTH responses to stress and higher ACTH and plasma cortisol responses to opioid blockade. These results indicated that compared to ad libitum smoking, nicotine withdrawal is associated with blunted opioid modulation of the HPA axis. Sex may modulate these effects. Blunted endogenous opioid regulation may underlie an incentive process that reinforces smoking behavior and may warrant therapeutic attention.
Silk fibroin reactive inks for 3D printing crypt-like structures

A reactive silk fibroin ink formulation designed for extrusion three-dimensional (3D) printing of protein-based hydrogels at room temperature is reported. This work is motivated by the need to produce protein hydrogels that can be printed into complex shapes with long-term stability using extrusion 3D printing at ambient temperature without the need for the addition of nanocomposites, synthetic polymers, or sacrifical templates. Silk fibroin from the Bombyx mori silkworm was purified and synthesized into reactive inks by enzyme-catalyzed dityrosine bond formation. Rheological and printing studies showed that tailoring the peroxide concentration in the reactive ink enables the silk to be extruded as a filament and printed into hydrogel constructs, supporting successive printed layers without flow of the construct or loss of desired geometry. To enable success of longer-term in vitro studies, 3D printed silk hydrogels were found to display excellent shape retention over time, as evidenced by no change in construct dimensions or topography when maintained for nine weeks in culture medium. Caco-2 (an intestinal epithelial cell line) attachment, proliferation, and tight junction formation on the printed constructs was not found to be affected by the geometry of the constructs tested. Intestinal myofibroblasts encapsulated within reactive silk inks were found to survive shearing during printing and proliferate within the hydrogel constructs. The work here thus provides a suitable route for extrusion 3D printing of protein hydrogel constructs that maintain their shape during printing and culture, and is expected to enable longer-term cellular studies of hydrogel constructs that require complex geometries and/or varying spatial distributions of cells on demand via digital printing.
ON THE SINGULARLY PERTURBED SEMILINEAR REACTION-DIFFUSION PROBLEM AND ITS NUMERICAL SOLUTION

We obtain improved derivative estimates for the solution of the semilinear singularly perturbed reaction-diffusion problem in one dimension. This enables us to modify the transition points between the fine and coarse parts of the Shishkin discretization mesh. We prove that the numerical solution, obtained by using the central finite-difference scheme on the modified mesh, retains the same order of convergence uniform in the perturbation parameter as on the standard Shishkin mesh. However, the modified mesh may be denser in the layers than the standard one, and, when this is the case, numerical results show an improvement in the accuracy of the computed solution.
An potential MRI agent and an anticancer drug encapsulated within CPMV virus-like particles.

BACKGROUND Virus nanoparticles have been extensively studied over the past decades for theranostics applications. Viruses are well-characterized, naturally occurring nanoparticles that can be produced in high quantity with a high degree of similarity in both structure and composition. OBJECTIVES The plant virus cowpea mosaic virus (CPMV) has been innovatively used as a nanoscaffold. Utilization of the internal cavity of empty virus-like particles (VLPs) for the inclusion of therapeutics within the capsid has opened many opportunities in drug delivery and imaging applications. METHODS The encapsidation of magnetic materials and anticancer drugs was achieved. SuperscriptCPMV denotes molecules attached to the external surface of CPMV and CPMVSubscript denotes molecules within the interior of the capsid. RESULTS Here, the generation of novel VLPs incorporating iron-platinum nanoparticles TCPMVFePt and cisplatin (Cis) (TCPMVCis) is reported. TCPMVCis have a cytotoxic IC50 of TCPMVCis on both A549 and MDA-MB-231 cell lines of 1.8 μM and 3.9 µM respectively after 72 hours of incubation. The TCPMVFePt were prepared as potential MRI contrast agents. CONCLUSIONS Cisplatin loaded VLP (TCPMVCis) is shown to enhance cisplatin cytotoxicity in cancer cell lines, and its potency increased 2.3-folds.