Miracle-dz/UniFAR-FTUs huggingface dataset:
A structural framework for unidirectional transport by a bacterial ABC exporter

Significance A specific ATP-binding cassette (ABC) transporter is generally viewed to function as either an exporter or an importer, but in principle ABC transporters can transport substrates in both directions across the membrane. Structural studies of the prokaryotic ABC exporter NaAtm1 demonstrate that progression through the transport cycle is accompanied by changes in transmembrane helix 6 (TM6) that modulate the binding cavity for transported substrate. Significantly, kinking of TM6 in a post-ATP hydrolysis state stabilized by MgADPVO4 eliminates the substrate-binding cavity. The presence of this cavity during the transition from the inward-facing to outward-facing conformational states, and its absence in the reverse direction, thereby provide an elegant and conceptually simple mechanism for enforcing the export directionality of transport. The ATP-binding cassette (ABC) transporter of mitochondria (Atm1) mediates iron homeostasis in eukaryotes, while the prokaryotic homolog from Novosphingobium aromaticivorans (NaAtm1) can export glutathione derivatives and confer protection against heavy-metal toxicity. To establish the structural framework underlying the NaAtm1 transport mechanism, we determined eight structures by X-ray crystallography and single-particle cryo-electron microscopy in distinct conformational states, stabilized by individual disulfide crosslinks and nucleotides. As NaAtm1 progresses through the transport cycle, conformational changes in transmembrane helix 6 (TM6) alter the glutathione-binding site and the associated substrate-binding cavity. Significantly, kinking of TM6 in the post-ATP hydrolysis state stabilized by MgADPVO4 eliminates this cavity, precluding uptake of glutathione derivatives. The presence of this cavity during the transition from the inward-facing to outward-facing conformational states, and its absence in the reverse direction, thereby provide an elegant and conceptually simple mechanism for enforcing the export directionality of transport by NaAtm1. One of the disulfide crosslinked NaAtm1 variants characterized in this work retains significant glutathione transport activity, suggesting that ATP hydrolysis and substrate transport by Atm1 may involve a limited set of conformational states with minimal separation of the nucleotide-binding domains in the inward-facing conformation.
Recent advances in sarcoidosis genomics: epigenetics, gene expression, and gene by environment (G × E) interaction studies.

PURPOSE OF REVIEW We aim to review the most recent findings in genomics of sarcoidosis and highlight the gaps in the field. RECENT FINDINGS Original explorations of sarcoidosis subphenotypes, including cases associated with the World Trade Center and ocular sarcoidosis, have identified novel risk loci. Innovative gene--environment interaction studies utilizing modern analytical techniques have discovered risk loci associated with smoking and insecticide exposure. The application of whole-exome sequencing has identified genetic variants associated with persistent sarcoidosis and rare functional variations. A single epigenomics study has provided background knowledge of DNA methylation mechanisms in comparison with gene expression data. The application of machine-learning techniques has suggested new drug repositioning for the treatment of sarcoidosis. Several gene expression studies have identified prominent inflammatory pathways enriched in the affected tissue. SUMMARY Certainly, sarcoidosis research has recently advanced in the exploration of disease subphenotypes, utilizing novel analytical techniques, and including measures of clinical variation. Nevertheless, large-scale and diverse cohorts investigated with advanced sequencing methods, such as whole-genome and single-cell RNA sequencing, epigenomics, and meta-analysis coupled with cutting-edge analytic approaches, when employed, will broaden and translate genomics findings into clinical applications, and ultimately open venues for personalized medicine.
Simulation-Based Mastery Learning of Bronchoscopy-Guided Percutaneous Dilatational Tracheostomy: Competency Acquisition and Skills Transfer to a Cadaveric Model.

INTRODUCTION Although simulation-based training has demonstrated improvement of procedural skills and clinical outcomes in different procedures, there are no published training protocols for bronchoscopy-guided percutaneous dilatational tracheostomy (BG-PDT). The objective of this study was to assess the acquisition of BG-PDT procedural competency with a simulation-based mastery learning training program, and skills transfer into cadaveric models. METHODS Using a prospective interventional design, 8 trainees naive to the procedure were trained in a simulation-based mastery learning BG-PDT program. Students were assessed using a multimodal approach, including blind global rating scale (GRS) scores of video-recorded executions, total procedural time, and hand-motion tracking-derived parameters. The BG-PDT mastery was defined as proficient tracheostomy (successful procedural performance, with less than 3 puncture attempts, and no complications) with GRS scores higher than 21 points (of 25). After mastery was achieved in the simulator, residents performed 1 BG-PDT execution in a cadaveric model. RESULTS Compared with baseline, in the final training session, residents presented a higher procedural proficiency (0% vs. 100%, P < 0.001), with higher GRS scores [8 (6-8) vs. 25 (24-25), P = 0.01] performed in less time [563 (408-600) vs. 246 (214-267), P = 0.01] and with higher movement economy. Procedural skills were further transferred to the cadaveric model. CONCLUSIONS Residents successfully acquired BG-PDT procedural skills with a simulation-based mastery learning training program, and skills were effectively transferred to a cadaveric model. This easily replicable program is the first simulation-based BG-PDT training experience reported in the literature, enhancing safe competency acquisition, to further improve patient care.
Diet of the eastern chestnut mouse (Pseudomys gracilicaudatus). II Seasonal and successional patterns

The seasonal and successional changes of the diet of P. gracilicaudatus was examined by microscopic analysis of faecal pellets collected in a coastal heathland of New South Wales. Overall, five major dietary items (leaf, stem, seed, fungi and insect), which accounted for more than 95% of the total diet, showed significant seasonal changes. The Mantel test demonstrated that the diet of P. gracilicaudatus significantly differed between all seasons. At different successional stages of the habitat, the consumption of the dietary items leaf, stem and insect were significantly different. The overall diet at the middle successional stage was significantly different from those at the other two stages, between which the diet was not significantly different. However, when the comparison was made in summer, the differences between the young and old stages were significant for most dietary items and overall. As a result, a significant interaction of season and regeneration age on the diet of P. gracilicaudatus occurred. Such an interaction also extended to dietary diversity and among-individual variation. These results indicate that P. gracilicaudatus possesses an opportunistic foraging strategy that has evolved in a variable environment. They also have important take-home messages that any interpretation of observed ecological patterns and the design of future research for any species that appear to have evolved with such fire regimes must take into account such an interaction of season and vegetation succession.
A comparison of online and in-person counseling outcomes using solution-focused brief therapy for college students with anxiety

Abstract Objective This study compared online, synchronous video counseling to in-person counseling using solution-focused brief therapy for college students with mild to moderate anxiety. Participants: Participants were 49 undergraduate students who were seeking counseling for mild to moderate anxiety. The study was conducted from November, 2017 to December 2018. Methods: In a randomized, non-inferiority design, undergraduate participants were randomly assigned to online, synchronous video counseling or in-person treatment for anxiety using solution-focused brief therapy (SFBT). Participants completed the Beck’s Anxiety Inventory (BAI) and College Counseling Assessment of Psychological Symptoms (CCAPS) to assess outcomes. Results: The results showed significant changes in scores on the BAI and the CCAPS Generalized Anxiety and Social Anxiety subscales for participants in both study conditions, and no significant differences in effectiveness of the two delivery methods. Conclusions: The findings provide support for the treatment of college students with anxiety with SFBT through online, synchronous video counseling. Limitations related to sample size and diversity are discussed.
Management of immunosuppression in kidney transplant recipients with COVID‐19 pneumonia: A summary of 41 confirmed cases reported worldwide

There is no consensus on immunosuppression management for kidney transplant recipients (KTRs) with SARS‐CoV‐2 pneumonia. Therefore, we conducted a search in English database from October 2019 to July 2020 and extracted data from cases with treatment details worldwide, and total of 41 recipients with a median age of 50 years were enrolled in this study. Most of them were males (75.8%). The most common presenting symptoms were fever (80.5%), cough (63.4%), and fatigue (41.5%). Patients were classified into three catalogs according to severity of pneumonia: 17 (41.5%) were mild, 15 (36.6%) severe, and 9 (21.9%) critical disease. Laboratory tests revealed that serum creatinine of critical patients was significantly higher than that of mild or severe patients. 68.3% received oxygen support; all patients received antiviral therapy, and 15 (36.6%) recipients were additionally treated with intravenous immunoglobulin and interferon‐α. 19.5% of patients maintained immunosuppressive therapy; 36.6% suspended antimetabolite; and 43.9% only treated with corticosteroid. Six (14.6%) patients died (severe: 2, critical: 4); high creatinine with low lymphocyte count was the biggest challenge of immunosuppression management. In all, it is necessary to pay close attention to renal function and lymphocyte count in KTRs infected with COVID‐19 and choose appropriate medication programs according to the specific situations.
Margaret G. Bradbury (1927–2010)

M ARGARET (‘‘MAGGIE’’) BRADBURY was born in Chicago, Illinois on 15 July 1927 to Margaret and Gerald Bradbury. She had one sibling, a younger brother Gerald, Jr., who had a daughter Jarill Ristine and son Robert. Margaret attended public schools in Chicago and Evanston, Illinois. Her father, an architect, died when she was young, but left her with a great interest in architecture. Jarill Ristine (in litt., 4 Dec. 2010) relates that Margaret’s ‘‘father died when she was probably 11, my dad was 9. He was sent off to boarding school while Maggie lived at home . when Aunt Maggie [came] for a visit . usually Christmas . I was always enchanted. To me she was larger than life, beautiful and exciting to listen to . telling wonderful stories about Te Vega and places she had been. ’’ In 1947 Margaret entered the field of science as Staff Artist of the Department of Zoology at the Chicago Natural History Museum (now Field Museum of Natural History, FMNH), providing illustrations for (among others) herpetologists Robert F. Inger (1954, 1956) and Karl P. Schmidt, and ichthyologists Robert H. Kanazawa (1952) and Loren P. Woods (Woods and Kanazawa, 1951). The amphibian drawings she did for Inger’s Philippine Amphibia (1954) and the squirrelfish genus Holocentrus for Woods (1955; also Woods and Sonoda, 1973) displayed her early artistic skills. During part of her years at FMNH, she was enrolled at Roosevelt College [now University] in Chicago, at that time a new (opened 1945) college dedicated to equal access to education and to progressive causes. She received her B.S. degree in Zoology in 1955. During the summer of 1955, she collected fishes in the Bahamas on an expedition of the Academy of Natural Sciences, Philadelphia, after which she matriculated as a graduate student at Stanford University (SU). DMC recalls Margaret saying that she entered the SU graduate program as a student of George S. Myers at the urging of FMNH ichthyologists Marion Grey and Loren Woods, and herpetologist Karl P. Schmidt. DMC first met her as a fellow graduate student at SU during one of her Turkish coffee parties—such events perhaps a prelude to a life as a supremely gracious hostess entertaining a constant stream of friends, visitors, and associates.
Building an Analytics Culture to Boost a Data-Driven Entrepreneur's Business Model

This chapter treats the movement that marks, affects, and transforms any part of business and society. It is about big data that is creating, and the value generating that companies, startups, and entrepreneurs have to derive through sophisticated methods and advanced tools. This chapter suggests that analytics can be of crucial importance for business and entrepreneurial practices if correctly aligned with business process needs and can also lead to significant improvement of their performance and quality of the decisions they make. So, the main purpose of this chapter are exploring why small business, entrepreneur, and startups have to use data analytics and how they can integrate, operationally, analytics methods to extract value and create new opportunities.
The effect of dietary nitrate supplementation on the speed-duration relationship in mice with sickle cell disease.

Sickle cell disease (SCD) causes exercise intolerance likely due to impaired skeletal muscle function and low nitric oxide (NO) bioavailability. Dietary nitrate improves hemodynamic and metabolic control during exercise in humans and animals. The purpose of this investigation was to assess the impact of nitrate supplementation on exercise capacity as measured by the running speed to exercise duration relationship (critical speed (CS)) in mice with SCD. We tested the hypothesis that nitrate supplementation via beetroot juice (BR) would attenuate the exercise intolerance observed in mice with SCD. Ten wild-type (WT) and 18 Berkley sickle-cell mice (BERK) received water (WT: n=10, BERK: n=10) or nitrate-rich BR (BERK+BR: n=8, nitrate dose 1 mmol/kg/day) for five days. Following the supplementation period, all mice performed 3-5 constant-speed treadmill tests that resulted in exhaustion within 1.5 to 20 min. Time to exhaustion vs. treadmill speed was fit to a hyperbolic model to determine CS. CS was significantly lower in BERK vs. WT and BERK+BR with no significant difference between WT and BERK+BR (WT: 36.6 ± 1.6, BERK: 23.8 ± 1.5, BERK+BR: 31.1 ± 2.1 m/min, p<0.05). Exercise tolerance, measured via CS, was significantly lower in BERK mice relative to WT. However, BERK mice receiving 5 days of nitrate supplementation exhibited no difference in exercise tolerance when compared to WT. These results support the potential utility of a dietary nitrate intervention to improve functionality in SCD patients.
Children and advergame: the role of presence, flow and persuasion knowledge

Entertainment offered in advergame can make it difficult for children to understand the message conveyed. Therefore, further investigation on its effectiveness as marketing tool is needed. In this study, we analyse the role of presence, flow, and persuasion knowledge on children's attitudes and intention to buy product advertised in the advergame. Two hundred 10-12-year-old children from public and private schools in Jakarta and Surabaya have participated in this study. The results show that presence has a positive impact on advergame attitude. The prediction stating that flow has a positive impact on advergame and brand attitude is not proven. The increasing persuasion knowledge only shows the impact on brand attitude. Advergame attitude shows a positive impact on brand attitude and not in purchase intention; whereas brand attitude shows a positive impact on children's intention to buy. Based on the findings, suggestions concerning future research and managerial implications are proposed.
Physiological characteristics associated with increased resistance to decompression sickness in male and female rats.

Decompression sickness (DCS) is a complex and poorly understood systemic disease with wide inter-individual resistance variability. We selectively bred rats with a 3-fold greater resistance to DCS than standard ones. To investigate possible physiological mechanisms underlying the resistance to DCS, including sex-related differences in these mechanisms, 15 males and 15 females resistant to DCS were compared with aged-matched standard Wistar males (n=15) and females (n=15). None of these individuals had been previously exposed to hyperbaric treatment. Comparison of the allelic frequencies of SNPs showed a difference of one SNP located on the X chromosome. Compared with non-resistant rats, the neutrophil-to-lymphocyte ratio and the plasmatic activity of coagulation Factor X were significantly higher in DCS-resistant individuals regardless of their sex. The maximal relaxation elicited by sodium nitroprusside was lower in DCS-resistant individuals regardless of their sex. Males but not females resistant to DCS exhibited higher neutrophil and lymphocyte counts, higher prothrombin time whereas lower mitochondrial basal O2 consumption and citrate synthase activity. Principal Components Analysis showed that two principal components discriminate the DCS-resistant males but not females from the non-resistant ones. These components were loaded with aPTT, MLR, PT, FX, Fib, for PC1, and ARBC and ANC for PC2. In conclusion, the mechanisms which drive the resistance to DCS appear different between males and females; lower coagulation tendency and enhanced inflammatory response to decompression stress might be key for resistance in males. The involvement of these physiological adaptations in resistance to DCS must now be confirmed.
Predicting eating disorders from Internet activity.

OBJECTIVE Eating disorders (EDs) compromise the health and functioning of affected individuals, but it can often take them several years to acknowledge their illness and seek treatment. Early identification of individuals with EDs is a public health priority, and innovative approaches are needed for such identification and ultimate linkage with evidence-based interventions. This study examined whether Internet activity data can predict ED risk/diagnostic status, potentially informing timely interventions. METHOD Participants were 936 women who completed a clinically validated online survey for EDs, and 231 of them (24.7%) contributed their Internet browsing history. A machine learning algorithm used key attributes from participants' Internet activity histories to predict their ED status: clinical/subclinical ED, high risk for an ED, or no ED. RESULTS The algorithm reached an accuracy of 52.6% in predicting ED risk/diagnostic status, compared to random decision accuracy of 38.1%, a relative improvement of 38%. The most predictive Internet search history variables were the following: use of keywords related to ED symptoms and websites promoting ED content, participant age, median browsing events per day, and fraction of daily activity at noon. DISCUSSION ED risk or clinical status can be predicted via machine learning with moderate accuracy using Internet activity variables. This model, if replicated in larger samples where it demonstrates stronger predictive value, could identify populations where further assessment is merited. Future iterations could also inform tailored digital interventions, timed to be provided when target online behaviors occur, thereby potentially improving the well-being of many individuals who may otherwise remain undetected.
Understanding Nurse-led Case Management in Patients with Chronic Illnesses: A Realist Review

This realist review aims, with evidence from recent studies, to understand both how nurse-led case management interventions are implemented in the management of chronic illnesses, and in what circumstances these interventions are successful. The review followed the realist review methodology. From four electronic databases, twenty empirical and primary nurse-led case management intervention studies published between January 2011 and February 2020 were included. For each study, causality was explored, and findings were integrated. Three contexts, five mechanisms, and three major outcomes were found, and several context–mechanism–outcome strings were identified. Further analysis and synthesis of the studies showed that when duration of intervention, service delivery mode, and types of services are appropriate, as well as number of services with patients considering care is provided, case managment interventions change outcomes for patients with chronic illnesses. Finally, an explanatory conceptual framework based on the review results was developed to guide nurse managers and researchers.
Gap Analysis for the Conversion to Area Under the Curve Vancomycin Monitoring in a Small Rural Hospital.

Objective Consensus guidelines for vancomycin monitoring now recommend area under the curve (AUC) calculations for optimal vancomycin efficacy and safety. This will be a major practice change for many facilities. Implementation guidance is available but has not been reported in smaller, primary care hospitals. The objective of this study was to measure the uptake of AUC monitoring implementation in a rural facility. Methods This is a gap analysis evaluating the appropriateness of vancomycin levels tests after the April 1, 2019 transition. All vancomycin levels between April 2019 and June 2019 after the go-live date were included with no exclusions in a retrospective chart review. The primary outcome was the proportion of levels in the appropriate time frame: peaks 1 to 2 hours after infusion with troughs at least 1 half-life after initial dose and prior to the next dose. Secondary outcomes included reasons identified for inappropriate levels and the proportion of AUC24 calculations within therapeutic range (400-600 mg.h/L). Descriptive statistics were used to measure the scope and outcomes of this transition. Results The transition was effective with 97% of cases utilizing AUC-based methods. There were 65 vancomycin levels in the 3-month study period with 86% deemed appropriate. Of the 9 inappropriate levels, 4 had to be repeated for accurate monitoring. There were 28 two-level couplets used for AUC24 calculations, 17 (61%) fell within therapeutic range. Conclusion Implementation strategies for the AUC transition described in tertiary medical centers can be successfully utilized in primary facilities.