Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Validation of a Nomogram for Prediction of QT Interval Prolongation in Patients Administered Bedaquiline-Containing Regimens in China: a Modeling Study

Corrected QT duration (QTc) interval prolongation is the most frequent adverse event associated with bedaquiline (BDQ) use. It may affect the safety of antituberculosis therapy, which leads to the consequent demands of needing to monitor during therapy. ABSTRACT Corrected QT duration (QTc) interval prolongation is the most frequent adverse event associated with bedaquiline (BDQ) use. It may affect the safety of antituberculosis therapy, which leads to the consequent demands of needing to monitor during therapy. Our objective was to establish and validate a prediction model for estimating the risk of QTc prolongation after initiation of BDQ-containing regimens to multidrug-resistant tuberculosis (MDR-TB) patients. We constructed an individualized nomogram model based on baseline demographic and clinical characteristics of each patient within a Chinese cohort during BDQ treatment. The generalizability of this model was further validated through use of externally acquired data obtained from Beijing Chest Hospital from 2019 to 2020. Overall, 1,215 and 165 patients were included in training and external validation cohorts, respectively, whereby during anti-TB drug treatment, QTc prolongation was observed in 273 (22.5%) and 29 (17.6%) patients within these respective cohorts, for whom QTc values were >500 ms in 86 (31.5%) and 10 (34.7%) patients, respectively. Next, a total of four Cox proportional hazards models were created and assessed; then, nomograms derived from the models were plotted based on independent predictors of clofazimine, baseline QTc interval, creatinine, extensive drug-resistance (XDR), moxifloxacin, levofloxacin, and sex. Nomogram analysis revealed concordance index values of 0.723 (95% confidence interval [CI], 0.695 to 0.750) for the training cohort and 0.710 (95% CI, 0.627 to 0.821) for the external validation cohort, thus indicating relatively fair agreement between predicted and observed probabilities of QTc prolongation occurrence based on data obtained during 8-week, 16-week, and 24-week anti-TB treatment of both cohorts. Taken together, results obtained using these models demonstrated that coadministration of clofazimine and abnormal baseline QTc interval significantly contributed to QTc prolongation development during MDR-TB patient treatment with a BDQ-containing anti-TB treatment regimen.
Constitutive bone marrow adipocytes suppress local bone formation

BM adipocytes (BMAd) are a unique cell population derived from BM mesenchymal progenitors and marrow adipogenic lineage precursors. Although they have long been considered to be a space filler within bone cavities, recent studies have revealed important physiological roles in hematopoiesis and bone metabolism. To date, the approaches used to study BMAd function have been confounded by contributions by nonmarrow adipocytes or by BM stromal cells. To address this gap in the field, we have developed a BMAd-specific Cre mouse model to deplete BMAds by expression of diphtheria toxin A (DTA) or by deletion of peroxisome proliferator-activated receptor gamma (Pparg). We found that DTA-induced loss of BMAds results in decreased hematopoietic stem and progenitor cell numbers and increased bone mass in BMAd-enriched locations, including the distal tibiae and caudal vertebrae. Elevated bone mass appears to be secondary to enhanced endosteal bone formation, suggesting a local effect caused by depletion of BMAd. Augmented bone formation with BMAd depletion protects mice from bone loss induced by caloric restriction or ovariectomy, and it facilitates the bone-healing process after fracture. Finally, ablation of Pparg also reduces BMAd numbers and largely recapitulates high–bone mass phenotypes observed with DTA-induced BMAd depletion.
Three-Dimensional Organoids as a Model to Study Nonalcoholic Fatty Liver Disease

Despite the rising prevalence of nonalcoholic fatty liver disease (NAFLD), the underlying disease pathophysiology remains unclear. The need is great for an efficient and reliable 'human' in vitro model to study NAFLD and the progression to nonalcoholic steatohepatitis (NASH), which will soon become the leading indication for liver transplantation. Here, we review the recent developments in the use of 3D liver organoids as a model to study NAFLD and NASH pathophysiology and possible treatments. Various techniques that are currently used to make liver organoids are discussed, such as the use of induced pluripotent stem cells vs. primary cell lines and human vs. murine cells. Moreover, methods for inducing lipid droplet accumulation and fibrosis to model NAFLD are explored. Finally, the limitations specific to the 3D organoid model for NAFLD/NASH are reviewed, highlighting the need for further development of multilineage models to include hepatic nonparenchymal cells and immune cells. The ultimate goal is to be able to accurately recapitulate the complex liver microenvironment in which NAFLD develops and progresses to NASH.
Effect of telemonitoring and telerehabilitation on physical activity, exercise capacity, health-related quality of life and healthcare use in patients with chronic lung diseases or COVID-19: A scoping review

Background Telemonitoring and telerehabilitation can support home-based pulmonary rehabilitation (PR) and benefit patients with lung diseases or COVID-19. This study aimed to (1) identify which telemonitoring and telerehabilitation interventions (e.g. videoconferencing) are used to provide telehealth care for people with chronic respiratory conditions or COVID-19, and (2) provide an overview of the effects of telemonitoring and telerehabilitation on exercise capacity, physical activity, health-related QoL (HRQoL), and healthcare use in patients with lung diseases or COVID-19. Methods A search was performed in the electronic databases of Ovid MEDLINE, EMBASE, and Cinahl through 15 June 2021. Subject heading and keywords were used to reflect the concepts of telemonitoring, telerehabilitation, chronic lung diseases, and COVID-19. Studies that explored the effect of a telerehabilitation and/or telemonitoring intervention, in patients with a chronic lung disease such as asthma, chronic obstructive pulmonary diseases (COPD), or COVID-19, and reported the effect of the intervention in one or more of our outcomes of interest were included. Excluding criteria included evaluation of new technological components, teleconsultation or one-time patient assessment. Results This scoping review included 44 publications reporting the effect of telemonitoring (25 studies), telerehabilitation (8 studies) or both (11 studies) on patients with COPD (35 studies), asthma (5 studies), COPD and asthma (1 study), and COVID-19 (2 studies). Patients who received telemonitoring and/or telerehabilitation had improvements in exercise capacity in 9 out of 11 (82%) articles, better HRQoL in 21 out of 25 (84%), and fewer health care use in 3 out of 3 (100%) articles compared to pre-intervention. Compared to controls, no statistically significant differences were found in the intervention groups’ exercise capacity in 5 out 6 (83%) articles, physical activity in 3 out of 3 (100%) articles, HRQoL in 21 out of 25 (84%) articles, and healthcare use in 15 out of 20 (75%) articles. The main limitation of the study was the high variability between the characteristics of the studies, such as the number and age of the patients, the outcome measures, the duration of the intervention, the technological components involved, and the additional elements included in the interventions that may influence the generalization of the results. Conclusion Telemonitoring and telerehabilitation interventions had a positive effect on patient outcomes and appeared to be as effective as standard care. Therefore, they are promising alternatives to support remote home-based rehabilitation in patients with chronic lung diseases or COVID-19.
Dietary supplementation of 25-hydroxycholecalciferol as an alternative to cholecalciferol in swine diets: A review.

25-hydroxycholecalciferol (25-OHD3 ) formed via hepatic hydroxylation from vitamin D, cholecalciferol, represents the precursor of the biologically active vitamin D hormone, 1,25-dihydroxyvitamin D. Due to a higher absorption rate and the omission of one hydroxylation, dietary supplementation of 25-OHD3 instead of vitamin D3 is considered to be more efficient as plasma concentrations of 25-OHD3 are increased more pronounced. The present review summarises studies investigating potential beneficial effects on mineral homeostasis, bone metabolism, health status and performance in sows, piglets and fattening pigs. Results are inconsistent. While most studies could not demonstrate any or only a slight impact of partial or total replacement of vitamin D3 by 25-OHD3 , some experiments indicated that 25-OHD3 might alter physiological processes when animals are challenged, for example, by a restricted mineral supply.
Glucocorticoid Receptor Function and Cognitive Performance in Women With HIV

ABSTRACT Objective Alterations in glucocorticoid receptor (GCR) function may be a risk factor for cognitive complications among older people with human immunodeficiency virus (HIV). We evaluated whether HIV serostatus and age modify the GCR function-cognition association among women. Methods Eighty women with HIV (n = 40, <40 years of age [younger]; n = 40, >50 years of age [older]) and 80 HIV-uninfected women (n = 40 older, n = 40 younger) enrolled in the Women’s Interagency HIV Study completed a comprehensive neuropsychological test battery. Peripheral blood mononuclear cells collected concurrent with neuropsychological testing were assessed for GCR function. Multivariable linear regression analyses were conducted to examine whether a) HIV serostatus and age were associated with GCR function, and b) GCR function-cognition associations are moderated by HIV serostatus and age adjusting for relevant covariates. Results Among older women, higher baseline FKBP5 expression level was associated with lower attention/working memory performance among women with HIV (B = 6.4, standard error = 1.7, p = .0003) but not in women without HIV infection (B = −1.7, standard error = 1.9, p = .37). There were no significant HIV serostatus by age interactions on dexamethasone (DEX)-stimulated expression of the genes regulated by the GCR or lipopolysaccharide-stimulated tumor necrosis factor α levels (with or without DEX stimulation; p values > .13). HIV serostatus was associated with GC target genes PER1 (p = .006) and DUSP1 (p = .02), but not TSC22D3 (p = .32), after DEX stimulation. Conclusions Collectively, these data suggest that HIV serostatus and age may modify the influence of the GCR, such that the receptor is likely engaged to a similar extent, but the downstream influence of the receptor is altered, potentially through epigenetic modification of target genes.
Scaling of radial turbulent structure velocities in the tokamak SOL

It is a well known feature of turbulence that it displays intermittency, i.e. large-amplitude fluctuation events, which are ascribed to the formation of turbulent spatiotemporal patterns. This structure formation is of particular importance for magnetically confined plasmas due to the associated transport processes. In the last few years advanced diagnostics of tokamak scrape-off layers (SOLs) revealed that turbulent structures propagate coherently across the magnetic field over distances larger than the structure size [1, 2]. The structures form close to the separatrix and propagate into the far SOL, thereby impacting key reactor issues like helium ’ash’ pumping, first wall sputtering of impurities, and first wall recycling. Several models have been proposed to address the radial propagation of turbulent structures in tokamak SOL. They commonly rely on the curvature of the magnetic field, either due to polarization of density structures and contact to material surfaces [3, 4] or due to interchange mode drive [5, 6]. Although those model approaches differ fundamentally, they are in rather good agreement with experimental results. Furthermore, the models make predictions of the radial structure speed, based on characteristic structure feature like relative fluctuation amplitude and spatial size, and configurational parameters like the magnetic field strength and curvature and connection length to material boundaries. However, the predicted scalings differ significantly and are sometimes contradictory. In the present paper we address the scaling properties of turbulent structures in the SOL of the NSTX and Alcator C-Mod tokamak. The basic configuration of the considered situations is a lower single null Ohmic discharge in Alcator C-Mod and an inner wall limited discharge in NSTX. It has been shown that radially propagating structures can be observed in both devices [7, 8]. The SOL plasma, however, differs strongly in collisionality and the magnetic field strength, which are important quantities for scaling considerations in the models. For the discharges considered here the magnetic field was 5.4T for Alcator C-Mod and 0.4T for NSTX. The SOL plasma pressure fluctuations are observed with gas puff imaging diagnostics [9]. The Da emission intensity of a localized gas puff is observed at the outer midplane with a fast framing camera. The camera view is tangentially along the local magnetic field, such that a radialpoloidal cross-section is imaged. The spatial area imaged is for C-Mod (Dr, Dz) = (6,6)cm and is larger for NSTX with (Dr, Dz) = (23,23)cm. The camera frame rate for the present experiments
Identifying targets for interventions to support public use of face coverings

Abstract Objectives Interventions to promote the wearing of face coverings if required in the future can only be developed if we know why people do or do not wear them. Study aims were, therefore, to assess public adherence to wearing face coverings to reduce transmission of SARS‐CoV‐2 and to gauge why people were or were not wearing face coverings in work, public transport, and indoor leisure settings. Design Cross‐sectional survey. Methods 10,622 adults (25 January–6 February 2022) who were representative of the UK population were asked about their (a) wearing of face coverings in work, public transport, and leisure settings; (b) sociodemographic characteristics; and (c) perceptions of capabilities, opportunities, and motivations (“COM‐B"). Data were analysed descriptively, using within‐participants ANOVA and multiple linear regression. Results Participants reported mostly wearing face coverings in public transport settings (>80%), but substantially less in work (<50%) and leisure (<30%) contexts. Perceptions of capabilities, opportunities, and motivations to wear face coverings were consistently associated with the actual wearing of face coverings across the three settings, but there were marked deficits in automatic motivation and social opportunity. People living in England, describing themselves as White, and men were least likely to wear face coverings. Conclusions Interventions targeted at men, people living in England, and those describing themselves as White that focus on increasing capabilities, providing greater opportunities and boosting motivations are suggested to promote the wearing of face coverings, with particular focus on addressing automatic motivation and social opportunity.
A Kinetic Model for the Generation and Annihilation of Thermally Induced Carrier Donors in a Semiconducting Metal-Oxide Thin Film.

Based on a kinetic model involving oxidant diffusion and an oxidation-reduction reaction, a 3-parameter equation is derived relating the change in the concentration of thermally induced carrier donors in common metal-oxide semiconductors (such as indium-gallium-zinc oxide and indium-tin-zinc oxide) to heat-treatment time. The change in the concentration of such donors is characterized by measuring the shift in the turn-on voltage of a thin-film transistor subjected to heat treatments in different atmospheres for different durations. The model parameters are extracted using optimal curve-fitting techniques, leading to the determination of relevant activation energies from the temperature dependence of the extracted parameters. The proposed model is found to be applicable to metal-oxide semiconductors of different compositions. It is discovered that the generation of donors in a non-oxidizing atmosphere is largely suppressed at a temperature below 250 °C, but the effective annihilation of the donors spans over a wider temperature range in an oxidizing atmosphere.
Myocardial development in crocodylians

Recent reports confirmed the notion that there exists a rudimentary cardiac conduction system (CCS) in the crocodylian heart, and development of its ventricular part is linked to septation. We thus analyzed myocardial development with the emphasis on the CCS components and vascularization in two different crocodylian species.
Inclusion of children with disabilities in qualitative health research: A scoping review

Background Children with disabilities have the right to participate in health research so their priorities, needs, and experiences are included. Health research based primarily on adult report risks misrepresenting children with disabilities and their needs, and contributes to exclusion and a lack of diversity in the experiences being captured. Prioritizing the participation of children with disabilities enhances the relevance, meaningfulness, and impact of research. Methods A scoping review was conducted to critically examine the participation of children with disabilities in qualitative health research. The electronic databases PubMed, PsychInfo, Embase, and Google Scholar were searched. Inclusion criteria included qualitative health studies conducted with children with disabilities, published between 2007 and 2020, and written in English. Articles were screened by two reviewers and the synthesis of data was performed using numeric and content analysis. Results A total of 62 studies met inclusion criteria. Rationales for including children with disabilities included child-focused, medical model of disability, and disability rights rationales. Participation of children with disabilities in qualitative health research was limited, with the majority of studies conducting research on rather than in partnership with or by children. Findings emphasize that children with disabilities are not participating in the design and implementation of health research. Conclusion Further effort should be made by health researchers to incorporate children with a broad range of impairments drawing on theory and methodology from disability and childhood studies and collaborating with people who have expertise in these areas. Furthermore, an array of multi-method inclusive, accessible, adaptable, and non-ableist methods should be available to enable different ways of expression.
Aircraft wake turbulence and its detection : proceedings

Keynote Address. - Aircraft Wakes: A New Look at a Classical Problem. - Fundamental Problems. - The Velocity of Viscous Vortex Rings. - Studies in the Motion and Decay of Vortices. - Transport of a Vortex Wake in a Stably Stratified Atmosphere. - Experimental Methods. - Split-Film Anemometer Sensors for Three-Dimensional Velocity-Vector Measurement. - Sub-Scale Modeling of Aircraft Trailing Vortices. - The Utility of Doppler Radar in the Study of Aircraft Wing-Tip Vortices. - Application of Laser Doppler Systems to Vortex Measurement and Detection. - Wake Formation and Character. - An Analysis of Flight Measurements in the Wake of a Jet Transport Aircraft. - Vortex Control. - The Effect of a Drooped Wing Tip on Its Trailing Vortex System. - Some Work at the Royal Aircraft Establishment on the Behaviour of Vortex Wakes. - Span Loading and Formation of Wake. - An Experimental Investigation of Trailing Vortices Behind a Wing with a Vortex Dissipator. - Vortex Wake Development and Aircraft Dynamics. - Measurements of Boeing 747, Lockheed C5A and Other Aircraft Vortex Wake Characteristics by Tower Fly-by Technique. - Flight Evaluation of the Wing Vortex Wake Generated by Large Jet Transports. - Stability and Decay. - An Assessment of Dominant Mechanisms in Vortex-Wake Decay. - Theoretical and Experimental Study of the Stability of a Vortex Pair. - Structure of a Line Vortex in an Imposed Strain. - A New Look at the Dynamics of Vortices with Finite Cores. - Decay of an Isolated Vortex. - Decay of a Vortex Pair Behind an Aircraft. - Results of Trailing Vortex Studies in a Towing Tank. - Interactions with Vortex Wakes. - Results of the Boeing Company Wake Turbulence Test Program. - Aircraft Response to Turbulence Including Wakes. - Airloads and Moments on an Aircraft Flying Over a Pair of Inclined Trailing Vortices. - Aircraft Wake Turbulence Controllability Experiment. - Fog Formation and Dispersal by Trailing Vortices. - An Estimate of the Power Required to Eliminate Trailing Vortices by Suction. - Panel Discussion. - Conclusions. - Author Index.
Ameliorating the antitumor activity of gemcitabine against breast tumor using αvβ3 integrin-targeting lipid nanoparticles

Abstract Objective The main objective is to formulate solid lipid nanoparticles conjugated with cyclic RGDfk peptide encapsulated with gemcitabine hydrochloride drug for targeting breast cancer. Significance The hydrophilic nature of gemcitabine hampers passive transport by cell membrane permeation that may lead to drug resistance as it has to enter the cells via nucleoside transporters. The art of encapsulating the drug in a nanovesicle and then anchoring it with a targeting ligand is one of the present areas of research in cancer chemotherapy. Methods In this study, solid lipid nanoparticles were prepared by double emulsification and solvent evaporation method. Cyclic RGDfk and gemcitabine hydrochloride were used as targeting ligands and chemotherapeutic drugs, respectively, for targeting breast cancer. The prepared nanoparticles were evaluated for in vitro and in vivo performance to showcase the targeting efficiency and therapeutic benefits of the gemcitabine-loaded ligand conjugated nanoparticles. Results When compared with gemcitabine (GEM) and GEM loaded nanoparticles (GSLN), the ligand conjugated GEM nanoparticles (cGSLN) showed superior cytotoxicity, apoptosis, and inhibition of 3D multicellular spheroids in human breast cancer cells (MDA MB 231). The in vivo tumor regression studies in orthotopic breast cancer induced Balb/C mice showed that cGSLN displayed superior tumor suppression and also the targeting potential of the cGSLN toward induced breast cancer. Conclusion Prepared nanoformulations showed enhanced anticancer activity in both 2D and 3D cell culture models along with antitumor efficacy in orthotopic breast cancer mouse models. Graphical Abstract