Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Qigong Exercise on Physical and Psychological Health among African Americans

Interventions are needed to address physical and psychological health in middle-aged and older African Americans (AAs). The purpose of this pilot study was to evaluate the feasibility and potential benefits of an eight-week Qigong exercise on physical ability and function, balance, frailty, depression and anxiety, and spiritual well-being in AAs using a single-group design. Fifteen AAs with a mean age of 64 years received Qigong exercise over 16 semi-weekly, one-hour sessions. The majority were female (93.3%) and college-level educated (53.3%). Repeat chair stands, physical function, and spiritual well-being improved significantly (p < .05) with effect sizes ranging from . 45 to . 87. Over 52% of participants showed improved depression scores, fast gait speed, and standing balance. Nearly 42% demonstrated some frailty improvement over baseline. No adverse events were reported. Qigong exercise potentially improves the physical ability and function, and spiritual well-being of AAs and needs further testing in a randomized clinical trial.
Ethanol-Impaired Myogenic Differentiation is Associated with Decreased Myoblast Glycolytic Function.

BACKGROUND Myopathy affects nearly half of individuals with alcohol use disorder (AUD), and impaired skeletal muscle regenerative potential is a probable contributing factor. Previous findings from our laboratory indicate that chronic in vivo and in vitro ethanol treatment decrease myogenic potential of skeletal muscle myoblasts. Myogenesis, a highly coordinated process, requires shifts in cellular metabolic state allowing for myoblasts to proliferate and differentiate into mature myotubes. The objective of this study was to determine whether alcohol interferes with myoblast mitochondrial and glycolytic metabolism and impairs myogenic differentiation. METHODS Myoblasts were isolated from vastus lateralis muscle excised from alcohol-naïve adult male (n=5) and female (n=5) rhesus macaques. Myoblasts were proliferated for 3 days (day 0 differentiation; D0) and differentiated for 5 days (D5) with or without 50 mM ethanol. Metabolism was assessed using a Mitochondrial Stress Test to measure oxygen consumption (OCR) and extracellular acidification (ECAR) rates at D0. Differentiation was examined at D5. Expression of mitochondrial and glycolytic genes and mitochondrial DNA (mtDNA) were measured at D0 and D5. RESULTS Ethanol significantly (p<0.05) increased myoblast maximal OCR and decreased ECAR at D0, and decreased fusion index, myotubes per field, and total nuclei at D5. The ethanol-induced decrease in ECAR was associated with the ethanol-mediated decreases in fusion index and myotubes per field. Ethanol did not alter the decrease in glycolytic gene expression and increase in mtDNA from D0 to D5. CONCLUSION During myoblast proliferation, ethanol decreased glycolytic metabolism and increased maximal OCR, suggesting that myoblast metabolic phenotype was dysregulated with ethanol. The ethanol-induced decrease in ECAR was associated with decreased differentiation. These findings suggest that ethanol-mediated shifts in metabolic phenotype may underlie impaired differentiation, which has important clinical implications for myogenesis in those affected by alcoholic myopathy.
Zinc supplementation alleviates endoplasmic reticulum stress during porcine oocyte in vitro maturation by upregulating zinc transporters

Endoplasmic reticulum (ER) stress is a major contributor to embryonic development failure. Mammalian oocytes have a high risk of exposure to cellular stress during in vitro embryo production. We investigated the effects of zinc supplementation during in vitro maturation under ER stress. We evaluated cumulus expansion, embryonic development derived by parthenogenetic activation, reactive oxygen species, protein expression of X‐box binding protein 1 (XBP1), and expression of genes related to ER stress. Supplementation with 1 μg/ml zinc significantly increased the nuclear maturation of oocytes, cleavage and blastocyst formation rates, and total blastocyst cell number (p < .05). Under ER stress, zinc significantly reduced protein expression of XBP1, and increased cleavage and blastocyst rates (p < .05). Concomitantly, zinc supplementation upregulated the expression of zinc transporters (SLC39A14 and SLC39A10), PTGS2, and downregulated ER stress‐related genes (sXBP1, uXBP1, ATF4, and PTPN1/PTP1B), and caspase 3. These results suggest that zinc supplementation alleviates ER stress by providing essential metal‐ion transporters for oocyte maturation and subsequent embryonic development.
Age and Perioperative Outcomes After Implementation of an Enhanced Recovery After Surgery Pathway in Women Undergoing Major Prolapse Repair Surgery.

OBJECTIVE As perioperative care pathways are developed to improve recovery, there is a need to explore the impact of age. The aim of this study was to compare the impact of a urogynecology-specific enhanced recovery after surgery (ERAS) pathway on perioperative outcomes across 3 age categories: young, middle age, and elderly. METHODS A retrospective cohort study was conducted assessing same-day discharge, opioid administration, pain scores, and complications differences across and within 3 age categories, young (<61 years), middle age (61-75 years), elderly (>75 years), before and after ERAS implementation. RESULTS Among 98 (25.7%) young, 202 (52.9%) middle-aged, and 82 (21.5%) elderly women, distribution before and after ERAS implementation was similar. In each age category, we found a commensurate increase in same-day discharge and decrease in length of stay independent of age. Age was associated with a variable response to opioid administration after ERAS. In women who received opioids, we found there was a greater reduction in opioids in elderly. Young women received 22.5 mg more than middle-aged women, whereas elderly women received 24.3 mg less than middle-aged women (P < 0.0001, P < 0.0001) for a mean difference of 46.8 mg between the youngest and oldest group. We found no significant differences in postanesthesia care unit pain scores with ERAS implementation. Complications did not increase after ERAS implementation in any age group, although younger and elderly women were more likely to experience complications independent of ERAS. CONCLUSIONS Elderly women had similar outcomes compared with their younger counterparts after implementation of an ERAS pathway. Further research is needed to assess whether our age-related observations are generalizable.
Gallic acid as a key substance to inhibit proliferation and adipogenesis in bovine subcutaneous adipocyte

Abstract Gallic acid (GA) is a widespread naturally occurring phenolic acid and one of the main active monomers that forms polyphenols such as tannins. In recent years, GA has been found as a potential regulator in lipid metabolism. However, effects and possible mechanisms of GA on cell growth and lipid metabolism of bovine subcutaneous adipocytes remain unknown. In this study, we investigated whether GA could affect proliferation and adipogenesis of subcutaneous adipocyte in beef cattle. We found that GA possesses inhibitive effects on proliferation and adipogenesis of bovine subcutaneous adipocyte via activating the metabolic master factor AMP-activated protein kinase alpha (AMPKα) to promote programmed cell death and lipolysis. The findings prove GA is a key substance to inhibit proliferation and adipogenesis of bovine subcutaneous adipocyte in vitro. Further in vivo study needs conducted to verify the reductive effects of GA on subcutaneous fat in beef cattle.
Adherence and persistence among patients with type 2 diabetes initiating dulaglutide compared with semaglutide and exenatide BCise: 6‐month follow‐up from US real‐world data

To compare 6‐month adherence, persistence and treatment patterns among patients initiating once‐weekly glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), dulaglutide versus semaglutide, and dulaglutide versus exenatide BCise, using claims from the HealthCore Integrated Research Database.
Deep amplicon sequencing for culture-free prediction of susceptibility or resistance to 13 anti-tuberculous drugs

Conventional molecular tests for detecting Mycobacterium tuberculosis complex (MTBC) drug resistance on clinical samples cover a limited set of mutations. Whole-genome sequencing (WGS) typically requires culture. Here, we evaluated the Deeplex Myc-TB targeted deep-sequencing assay for prediction of resistance to 13 anti-tuberculous drugs/drug classes, directly applicable on sputum. With MTBC DNA tests, the limit of detection was 100–1000 genome copies for fixed resistance mutations. Deeplex Myc-TB captured in silico 97.1–99.3% of resistance phenotypes correctly predicted by WGS from 3651 MTBC genomes. On 429 isolates, the assay predicted 92.2% of 2369 first- and second-line phenotypes, with a sensitivity of 95.3% and a specificity of 95.0% (95.4% and 97.1%, respectively, when excluding ethionamide). 83 out of 102 (81.4%) residual discrepancies with phenotypic results involved pyrazinamide, ethambutol and ethionamide, and low-level rifampicin or isoniazid resistance mutations, all notoriously prone to phenotypic testing variability. Only two out of 96 (2.1%) resistance phenotypes undetected by Deeplex Myc-TB had known resistance-associated mutations by WGS analysis outside Deeplex Myc-TB targets. Phenotype predictions from Deeplex Myc-TB analysis directly on 109 sputa from a Djibouti survey matched those of MTBSeq/PhyResSE/Mykrobe, fed with WGS data from subsequent cultures, with a sensitivity of 93.5/98.5/93.1% and a specificity of 98.5/97.2/95.3%, respectively. Most residual discordances involved gene deletions/indels and 3–12% heteroresistant calls undetected by WGS analysis or natural pyrazinamide resistance of globally rare “Mycobacterium canettii” strains then unreported by Deeplex Myc-TB. On 1494 arduous sputa from a Democratic Republic of the Congo survey, 14 902 out of 19 422 (76.7%) possible susceptible or resistance phenotypes could be predicted culture-free. Deeplex Myc-TB may enable fast, tailored tuberculosis treatment. The novel Deeplex Myc-TB molecular assay shows a high degree of accuracy for extensive prediction of susceptibility and resistance to 13 anti-tuberculous drugs, directly achievable without culture, which may enable fast, tailored tuberculosis treatment https://bit.ly/3bAvcAt
Nano-Enhanced Cancer Immunotherapy: Immunology Encounters Nanotechnology

Cancer immunotherapy utilizes the immune system to fight cancer and has already moved from the laboratory to clinical application. However, and despite excellent therapeutic outcomes in some hematological and solid cancers, the regular clinical use of cancer immunotherapies reveals major limitations. These include the lack of effective immune therapy options for some cancer types, unresponsiveness to treatment by many patients, evolving therapy resistance, the inaccessible and immunosuppressive nature of the tumor microenvironment (TME), and the risk of potentially life-threatening immune toxicities. Given the potential of nanotechnology to deliver, enhance, and fine-tune cancer immunotherapeutic agents, the combination of cancer immunotherapy with nanotechnology can overcome some of these limitations. In this review, we summarize innovative reports and novel strategies that successfully combine nanotechnology and cancer immunotherapy. We also provide insight into how nanoparticular combination therapies can be used to improve therapy responsiveness, to reduce unwanted toxicity, and to overcome adverse effects of the TME.
Primary Care Pre-Visit Electronic Patient Questionnaire for Asthma: Uptake Analysis and Predictor Modeling

Background mHealth tablet-based interventions are increasingly being studied and deployed in various health care settings, yet little knowledge exists regarding patient uptake and acceptance or how patient demographics influence these important implementation metrics. Objective To determine which factors influence the uptake and successful completion of an mHealth tablet questionnaire by analyzing its implementation in a primary care setting. Methods We prospectively studied a patient-facing electronic touch-tablet asthma questionnaire deployed as part of the Electronic Asthma Management System. We describe tablet uptake and completion rates and corresponding predictor models for these behaviors. Results The tablet was offered to and accepted by patients in 891/1715 (52.0%) visits. Patients refused the tablet in 33.0% (439/1330) visits in which it was successfully offered. Patients aged older than 65 years of age (odds ratio [OR] 2.30, 95% CI 1.33-3.95) and with concurrent chronic obstructive pulmonary disease (OR 2.22, 95% CI 1.05-4.67) were more likely to refuse the tablet, and those on an asthma medication (OR 0.55, 95% CI 0.30-0.99) were less likely to refuse it. Once accepted, the questionnaire was completed in 784/891 (88.0%) instances, with those on an asthma medication (OR 0.53, 95% CI 0.32-0.88) being less likely to leave it incomplete. Conclusions Older age predicted initial tablet refusal but not tablet questionnaire completion, suggesting that perceptions of mHealth among older adults may negatively impact uptake, independent of usability. The influence of being on an asthma medication suggests that disease severity may also mediate mHealth acceptance. Although use of mHealth questionnaires is growing rapidly across health care settings and diseases, few studies describe their real-world acceptance and its predictors. Our results should be complemented by qualitative methods to identify barriers and enablers to uptake and may inform technological and implementation strategies to drive successful usage.
Types, Safety, and Efficacy of Limb Distalization for Inadequate Weight Loss After Roux-en-Y Gastric Bypass

Supplemental Digital Content is available in the text Objective: Comprehensive classification and evaluation of the outcome of limb distalization (LD) for inadequate weight loss after roux-en-y gastric bypass (RYGB) Background: Limb distalization is a revisional malabsorptive procedure for the management of inadequate weight loss after RYGB. Multiple studies with small sample sizes reported the outcome of LD. This meta-analysis aims to reach a higher level of evidence regarding the safety and efficacy of the procedure. Methods: A systematic search, including all studies on LD for management of inadequate weight loss after RYGB. The search engines included were PubMed, Embase, Web of Science, Cochrane Library, Scopus, and EBSCOhost. Results: Fourteen studies were included. The pooled estimates of the mid-term percentage of excess weight loss (%EWL), diabetic, and hypertension remission were 50.8%, 69.9%, and 59.8%, respectively. The rate of surgical revision for the management of protein-energy malnutrition (PEM) was 17.1%. The %EWL was significantly higher with older age and good response to index surgery (P = 0.01, 0.04, respectively). Less total alimentary limb length was not associated with better %EWL (P = 0.9), but it was significantly associated with severe PEM (P = 0.01). Conclusions: LD has an encouraging rate of resolution of comorbidities. A judicious patient selection is essential for better weight loss after LD. Type I LD with total alimentary limb length ≥350 cm was associated with less risk of malnutrition. PEM is a life-threatening complication that may require revisional surgery years after LD. Future studies on LD, adopting standardized surgical practice and terminology, will allow a more conclusive assessment of the outcome of the procedure.
Prediction of hepatitis E using machine learning models

Background Accurate and reliable predictions of infectious disease can be valuable to public health organizations that plan interventions to decrease or prevent disease transmission. A great variety of models have been developed for this task. However, for different data series, the performance of these models varies. Hepatitis E, as an acute liver disease, has been a major public health problem. Which model is more appropriate for predicting the incidence of hepatitis E? In this paper, three different methods are used and the performance of the three methods is compared. Methods Autoregressive integrated moving average(ARIMA), support vector machine(SVM) and long short-term memory(LSTM) recurrent neural network were adopted and compared. ARIMA was implemented by python with the help of statsmodels. SVM was accomplished by matlab with libSVM library. LSTM was designed by ourselves with Keras, a deep learning library. To tackle the problem of overfitting caused by limited training samples, we adopted dropout and regularization strategies in our LSTM model. Experimental data were obtained from the monthly incidence and cases number of hepatitis E from January 2005 to December 2017 in Shandong province, China. We selected data from July 2015 to December 2017 to validate the models, and the rest was taken as training set. Three metrics were applied to compare the performance of models, including root mean square error(RMSE), mean absolute percentage error(MAPE) and mean absolute error(MAE). Results By analyzing data, we took ARIMA(1, 1, 1), ARIMA(3, 1, 2) as monthly incidence prediction model and cases number prediction model, respectively. Cross-validation and grid search were used to optimize parameters of SVM. Penalty coefficient C and kernel function parameter g were set 8, 0.125 for incidence prediction, and 22, 0.01 for cases number prediction. LSTM has 4 nodes. Dropout and L2 regularization parameters were set 0.15, 0.001, respectively. By the metrics of RMSE, we obtained 0.022, 0.0204, 0.01 for incidence prediction, using ARIMA, SVM and LSTM. And we obtained 22.25, 20.0368, 11.75 for cases number prediction, using three models. For MAPE metrics, the results were 23.5%, 21.7%, 15.08%, and 23.6%, 21.44%, 13.6%, for incidence prediction and cases number prediction, respectively. For MAE metrics, the results were 0.018, 0.0167, 0.011 and 18.003, 16.5815, 9.984, for incidence prediction and cases number prediction, respectively. Conclusions Comparing ARIMA, SVM and LSTM, we found that nonlinear models(SVM, LSTM) outperform linear models(ARIMA). LSTM obtained the best performance in all three metrics of RSME, MAPE, MAE. Hence, LSTM is the most suitable for predicting hepatitis E monthly incidence and cases number.
Readthrough of stop codons under limiting ABCE1 concentration involves frameshifting and inhibits nonsense-mediated mRNA decay

Abstract To gain insight into the mechanistic link between translation termination and nonsense-mediated mRNA decay (NMD), we depleted the ribosome recycling factor ABCE1 in human cells, resulting in an upregulation of NMD-sensitive mRNAs. Suppression of NMD on these mRNAs occurs prior to their SMG6-mediated endonucleolytic cleavage. ABCE1 depletion caused ribosome stalling at termination codons (TCs) and increased ribosome occupancy in 3′ UTRs, implying enhanced TC readthrough. ABCE1 knockdown indeed increased the rate of readthrough and continuation of translation in different reading frames, providing a possible explanation for the observed NMD inhibition, since enhanced readthrough displaces NMD activating proteins from the 3′ UTR. Our results indicate that stalling at TCs triggers ribosome collisions and activates ribosome quality control. Collectively, we show that improper translation termination can lead to readthrough of the TC, presumably due to ribosome collisions pushing the stalled ribosomes into the 3′ UTR, where it can resume translation in-frame as well as out-of-frame.
Context-dependent functional compensation between Ythdf m6A reader proteins

Here, Lasman et al. sought to understand the role of three homologous m6A-binding proteins (Ythdf1, Ythdf2, and Ythdf3) and systematically knocked out the Mettl3 writer, each of the Ythdf readers, and the three readers together (triple-KO). Their findings suggest a novel model for the Ythdf reader function, in which there is profound dosage-dependent redundancy when all three readers are equivalently coexpressed in the same cell types.
CRISPR/Cas9-Mediated Point Mutation in Nkx3.1 Prolongs Protein Half-Life and Reverses Effects Nkx3.1 Allelic Loss

These findings show that prolonging the half-life of Nkx3.1 reduces proliferation, enhances DNA end-labeling, and protects from DNA damage, ultimately blocking the proneoplastic effects of Nkx3.1 allelic loss. NKX3.1 is the most commonly deleted gene in prostate cancer and is a gatekeeper suppressor. NKX3.1 is haploinsufficient, and pathogenic reduction in protein levels may result from genetic loss, decreased transcription, and increased protein degradation caused by inflammation or PTEN loss. NKX3.1 acts by retarding proliferation, activating antioxidants, and enhancing DNA repair. DYRK1B-mediated phosphorylation at serine 185 of NKX3.1 leads to its polyubiquitination and proteasomal degradation. Because NKX3.1 protein levels are reduced, but never entirely lost, in prostate adenocarcinoma, enhancement of NKX3.1 protein levels represents a potential therapeutic strategy. As a proof of principle, we used CRISPR/Cas9-mediated editing to engineer in vivo a point mutation in murine Nkx3.1 to code for a serine to alanine missense at amino acid 186, the target for Dyrk1b phosphorylation. Nkx3.1S186A/−, Nkx3.1+/−, and Nkx3.1+/+ mice were analyzed over one year to determine the levels of Nkx3.1 expression and effects of the mutant protein on the prostate. Allelic loss of Nkx3.1 caused reduced levels of Nkx3.1 protein, increased proliferation, and prostate hyperplasia and dysplasia, whereas Nkx3.1S186A/− mouse prostates had increased levels of Nkx3.1 protein, reduced prostate size, normal histology, reduced proliferation, and increased DNA end labeling. At 2 months of age, when all mice had normal prostate histology, Nkx3.1+/− mice demonstrated indices of metabolic activation, DNA damage response, and stress response. These data suggest that modulation of Nkx3.1 levels alone can exert long-term control over premalignant changes and susceptibility to DNA damage in the prostate. Significance: These findings show that prolonging the half-life of Nkx3.1 reduces proliferation, enhances DNA end-labeling, and protects from DNA damage, ultimately blocking the proneoplastic effects of Nkx3.1 allelic loss.
Circulating cell‐free DNA improves the molecular characterisation of Ph‐negative myeloproliferative neoplasms

Genetic studies in patients with Philadelphia‐negative myeloproliferative neoplasms (MPNs) are essential to establish the correct diagnosis and to optimise their management. Recently, it has been demonstrated that it is possible to detect molecular alterations analysing cell‐free DNA (cfDNA) in plasma samples, which is known as liquid biopsy. We have assessed the molecular profile of a cohort of 107 MPN patients [33 polycythaemia vera (PV), 56 essential thrombocythaemia (ET), 14 primary myelofibrosis (PMF) and 4 unclassifiable MPN] by next‐generation sequencing (NGS) using cfDNA and paired granulocyte DNA. A high concentration of cfDNA in plasma was observed in patients with high molecular complexity, in MPL‐mutated cases, and in PMF patients. Targeted sequencing of cfDNA showed a comparable mutational profile (100% accuracy) to the one obtained in granulocytic DNA and a strong correlation was observed between the variant allele frequency (VAF) of gene mutations in both DNA sources. The median VAF detected in cfDNA (29·0%; range: 0·95–91·73%) was significantly higher than the VAF detected in granulocytes (median 25·2%; range: 0·10–95·5%), especially for MPL mutations (44·3% vs. 22·5%). In conclusion, our data support the use of cfDNA as a fast, sensitive and accurate strategy for performing molecular characterisation of MPN patients.