Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term follow-up of a randomized clinical trial comparing glycemic excursion minimization (GEM) to weight loss (WL) in the management of type 2 diabetes

Introduction We previously reported the physical, psychological and behavioral 3-month post-treatment results of a randomized controlled trial comparing glycemic excursion minimization (GEM) versus conventional weight loss (WL) therapy in the management of type 2 diabetes (T2D). GEM is a paradigm shift in the lifestyle management of T2D that focuses on reducing postnutrient glucose excursions, rather than reducing weight. We now present the 13-month follow-up results. Research design and methods The initial study sample of 172 were 30–80 years old, had T2D for ≤10 years, an HbA1c ≥6.8% (51 mmol/mol), and were not using insulin. Participants were randomized to 6 hours of group treatment, either to WL or one of three versions of GEM. GEM groups differed in degree of blood glucose (BG) feedback provided during treatment: no recommended feedback, systematic capillary BG feedback before and after nutrient intake and physical activity, or continuous glucose monitoring. Since these GEM groups did not differ in pre-post improvement they were combined for initial and current analyses. Of those who completed the 3-month postassessment, 100% and 96% of the WL and GEM participants completed the 13-month follow-up assessment. Results Pre to follow-up within-group comparisons indicated WL participants sustained improvement in body mass index (BMI) (−0.9±1.4, p=0.001). GEM participants continued to benefit in their HbA1c (−0.5±1.4, p<0.001), BMI (−1±1, p<0.001), high-density lipoprotein (p<0.001), reduction of carbohydrate ingestion (p<0.001), self-monitoring of blood glucose satisfaction (p<0.001) and frequency (p<0.001), diabetes knowledge (p<0.001), diabetes empowerment (p<0.001), and both diabetes distress emotional (p=0.009) and regimen (p=0.001) subscales. Forty-two percent and 52% of WL and GEM participants, respectively, were classified as responders (individuals whose A1c dropped by at least −0.5%), with a mean HbA1c reduction of −1.2% and −1.5%. Neither WL nor GEM responders differed from non-responders in baseline demographics, psychological or disease severity variables. While WL responders could not be predicted, 73% of GEM responders were predicted by post minus pretreatment reductions of HbA1c, diabetes medication and BMI. Conclusions While WL sustained improvement in BMI, GEM sustained benefits across a broad range of physical, behavioral and psychological parameters, beneficial for clinicians and adults with T2D. This may be especially relevant for primary care physicians who manage about 90% of patients with T2D. Trial registration number NCT03196895.
Efficacy and cost-effectiveness of Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis: protocol for a randomised placebo-controlled trial (the SCUlpTOR trial)

Introduction Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease. Intra-articular stem cell therapy is increasingly being used for treating KOA with little high-quality evidence to support its use. The aim of this study is to investigate the efficacy, safety and cost-effectiveness of allogeneic mesenchymal stem cells (Cymerus MSCs) for treating symptomatic tibiofemoral KOA and improving knee structure over 24 months. Methods and analysis The Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis study is a phase III, multi-centre, parallel, superiority, randomised, double-blind, placebo-controlled trial, which will be conducted in Sydney and Hobart, Australia. 440 participants (220 per arm) aged over 40 years with painful KOA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) with medial minimum joint space width between 1 and 4 mm in the study knee will be recruited from the community and randomly allocated to receive either intra-articular MSCs or saline at baseline, week 3 and week 52. The coprimary outcomes will be the proportion of participants achieving patient-acceptable symptom state for knee pain at 24 months and quantitative central medial femorotibial compartment cartilage thickness change from baseline to 24 months. Main secondary outcomes include change in knee pain, Patient Global Assessment, physical function, quality of life and other structural changes. Additional data for cost-effectiveness analysis will also be recorded. Adverse events will be monitored throughout the study. The primary analysis will be conducted using modified intention-to-treat. Ethics and dissemination This protocol has been approved by The University of Sydney (USYD) Human Research Ethics Committee (HREC) #: 2020/119 and The University of Tasmania (UTAS) HREC #: H0021868. All participants will be required to provide informed consent. Dissemination will occur through conferences, social media, and scientific publications. Trial registration numbers Australian New Zealand Clinical Trials Registry (ACTRN12620000870954); U1111-1234-4897.
Double-masked, sham and placebo-controlled trial of corneal cross-linking and topical difluprednate in the treatment of bacterial keratitis: Steroids and Cross-linking for Ulcer Treatment Trial (SCUT II) study protocol

Introduction Although antibiotics are successful at achieving microbiological cure in infectious keratitis, outcomes are often poor due to corneal scarring. Ideal treatment of corneal ulcers would address both the infection and the inflammation. Adjunctive topical steroid treatment may improve outcomes by reducing inflammation. Corneal cross-linking (CXL) is a novel prospective therapy that may simultaneously reduce both inflammatory cells and bacterial pathogens. The purpose of this study is to determine differences in 6-month visual acuity between standard medical therapy with antibiotics versus antibiotics with adjunctive early topical steroid therapy versus antibiotic treatment plus CXL and early topical steroids. Methods and analysis This international, randomised, sham and placebo-controlled, three-arm clinical trial randomises patients with smear positive bacterial ulcers in a 1:1:1 fashion to one of three treatment arms: (1) topical 0.5% moxifloxacin plus topical placebo plus sham CXL; (2) topical 0.5% moxifloxacin plus difluprednate 0.05% plus sham CXL; or (3) the CXL group: topical 0.5% moxifloxacin plus difluprednate 0.05% plus CXL. Ethics and dissemination We anticipate that both adjunctive topical steroids and CXL will improved best spectacle corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings and journal publications. Our data will also be available on reasonable request. Trial registration number NCT04097730.
Augmenting Adoptive T-cell Immunotherapy by Targeting the PD-1/PD-L1 Axis

Cancer immunotherapy utilizing checkpoint blockade antibodies or adoptive cellular therapy (ACT) with tumor-specific T cells has led to unprecedented clinical responses in patients with cancer and has been considered one of the most significant breakthroughs in cancer treatment in the past decade. Nevertheless, many cancers remain refractory to these therapies due to the presence of an immunosuppressive tumor microenvironment. This has led to the innovative idea of combining ACT with checkpoint inhibition. A landmark 2004 study by Blank and colleagues published in Cancer Research was one of the original demonstrations that adoptive transfer of T cells lacking the negative T-cell regulator, PD-1, was able to restore functional T-cell antitumor activity, resulting in rapid regression of established tumors in a preclinical model. This work was instrumental in not only driving clinical studies utilizing checkpoint inhibition but also a new wave of recent trials involving checkpoint blockade in the setting of ACT. See related article by Blank and colleagues, Cancer Res 2004;64:1140–5
Applied Incremental Dynamic Analysis

We are presenting a practical and detailed example of how to perform incremental dynamic analysis (IDA), interpret the results and apply them to performance-based earthquake engineering. IDA is an emerging analysis method that offers thorough seismic demand and capacity prediction capability by using a series of nonlinear dynamic analyses under a multiply scaled suite of ground motion records. Realization of its opportunities requires several steps and the use of innovative techniques at each one of them. Using a nine-story steel moment-resisting frame with fracturing connections as a test bed, the reader is guided through each step of IDA: (1) choosing suitable ground motion intensity measures and representative damage measures, (2) using appropriate algorithms to select the record scaling, (3) employing proper interpolation and (4) summarization techniques for multiple records to estimate the probability distribution of the structural demand given the seismic intensity, and (5) defining limit-states, such as the dynamic global system instability, to calculate the corresponding capacities. Finally, (6) the results can be used to gain intuition for the structural behavior, highlighting the connection between the static pushover (SPO) and the dynamic response, or (7) they can be integrated with conventional probabilistic seismic hazard analysis (PSHA) to estimate mean annual frequencies of limit-state exceedance. Building upon this detailed example based on the nine-story structure, a complete commentary is provided, discussing the choices that are available to the user, and showing their implications for each step of the IDA.
Corporate Social Responsibility and Financial Performance of the Firms Listed on the Pakistan Stock Exchange

Received: May 08 , 2021 Corporate Social Responsibility (CSR)has emerged as aprominent topic for researchers that has helped firms to gain goodwill, social welfare returns andbetter financial performance. The present research, therefore, studies the influence of corporate social responsibility (CSR) on the profitability of firms listed on the KSE 100 index of the Pakistan Stock Exchange (PSX). The sample for the study is the top 100 firms of the country based on market capitalization. Secondary data was collected from the annual reports of the firms starting from 2015 to 2019. Donations were used to measure CSR whereas, Net Profit Margin (NPM) Return on Equity (ROE) and Return on Asset (ROA) were the measures of financial performance. The results of the study discovered that CSR does affect the financial performance of the listed companies in the PSX. The study concluded that businesses must engage more in performing CSR activities. Accepted: October12 , 2021
Evidence Around the Impact of Pulmonary Rehabilitation and Exercise on Redox Status in COPD: A Systematic Review

Introduction: Oxidative stress is increasingly recognized as a significant factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation, a major component of which is prescribed exercise, is essential in COPD care. Regular exercise has been proposed to increase antioxidant defenses and overall enhance the ability of the body to counteract oxidative stress. However, the mechanisms through which it improves COPD outcomes remain unclear. Objectives: We aimed to appraise the current evidence around the impact of pulmonary rehabilitation on redox status, compared with other exercise interventions, to gain an understanding of optimal exercise interventions to modify this pathophysiological mechanism. Methods: We performed a systematic review through searching CENTRAL, MEDLINE, PubMed, Scopus, and Web of Science. Results were independently reviewed and relevant studies were selected by two independent assessors. Studies were assessed by two independent people using the modified RoB 2 tool and discrepancies were resolved through discussion. Results: We identified 1,710 records and 1,117 records after duplicate removal. Six studies were included in the final analysis. The evidence available was low quality and four studies had high risk of bias and two studies had unclear risk of bias. Studies were small (15–56 participants); only two included details of randomization and patient cohorts were of varying ages and poorly described. Differences in smoking status and previous exercise levels, which are known to impact redox status, were not well documented. Studies were not standardized and used different exercise doses and measured different outcomes. One study reported lower malondialdehyde levels, a marker of lipid peroxidation, after pulmonary rehabilitation, compared with control. However, one study saw no difference following whole-body vibration training and another study showed higher malondialdehyde levels following supervised modified arm swing exercise compared with control. Conclusion: Understanding the impact of exercise on oxidative stress in COPD could lead to tailored exercise programs and modification of pathological mechanisms. However, we identify a lack of high-quality evidence to determine this. Larger, standardized, and high quality randomized controlled trials (RCTs) are essential, which use carefully clinically characterized and controlled cohorts to determine the relative impact of different exercise interventions on redox status to guide COPD management. We propose an idealized RCT design, which could be used to try and meet this need.
Ground Movements – A Hidden Source of Loading on Deep Foundations

Abstract Ground movements can arise from a large number of sources and can have a significant effect on nearby piles and deep foundations. The loading of the piles by ground movements is a different mechanism to that arising from direct applied loading to the pile head, and consequently it is not generally possible to adequately analyze the effects of ground movements simply by applying some type of equivalent loading to the pile head. The main effects of ground movements are the development of additional movements, axial forces and bending moments in the piles, and thus the key design aspects are related to movements and to the structural integrity of the pile. However, the ultimate geotechnical load carrying capacity is generally not affected by the ground movements themselves. This paper will describe an approach to the analysis of ground movement effects on piles, considering axial and lateral movements separately. Some of the main features of pile response will be discussed for three specific problems involving ground movements: 1. Piles near and within embankments;2. Piles near an excavation for a pile cap;3. Piles subjected to seismic ground motions.
Combined Stress Conditions in Melon Induce Non-additive Effects in the Core miRNA Regulatory Network

Climate change has been associated with a higher incidence of combined adverse environmental conditions that can promote a significant decrease in crop productivity. However, knowledge on how a combination of stresses might affect plant development is still scarce. MicroRNAs (miRNAs) have been proposed as potential targets for improving crop productivity. Here, we have combined deep-sequencing, computational characterization of responsive miRNAs and validation of their regulatory role in a comprehensive analysis of response of melon to several combinations of four stresses (cold, salinity, short day, and infection with a fungus). Twenty-two miRNA families responding to double and/or triple stresses were identified. The regulatory role of the differentially expressed miRNAs was validated by quantitative measurements of the expression of the corresponding target genes. A high proportion (ca. 60%) of these families (mainly highly conserved miRNAs targeting transcription factors) showed a non-additive response to multiple stresses in comparison with that observed under each one of the stresses individually. Among those miRNAs showing non-additive response to stress combinations, most interactions were negative, suggesting the existence of functional convergence in the miRNA-mediated response to combined stresses. Taken together, our results provide compelling pieces of evidence that the response to combined stresses cannot be easily predicted from the study individual stresses.
Vaccine Hesitancy Is a Barrier to Achieving Equitable Herd Immunity Among Racial Minorities

Introduction: Racial minority groups have been disproportionately affected by the 2019 novel coronavirus disease (COVID-19). Vaccine hesitancy may be a major barrier to achieving equitable herd immunity and must be addressed to reduce the excess morbidity and mortality of COVID-19 in disproportionately affected communities. This study aimed to determine if COVID-19 vaccine hesitancy, and its factors vaccine complacency and confidence, are more prominent among disproportionately affected racial minority groups. Methods:We collected data from participants aged 18 years or older from the four most populous U.S. states, including New York, California, Florida, and Texas, and Canada. Data were collected using a web-based survey platform. Data are available at http://www.covid19-database.com. Results:Data from 4,434 participants were included [mean (SD) age = 48.7 (17.2) and 50.4% women]. Vaccine hesitancy was higher in Black, Indigenous (Native American and Indigenous People of Canada, including First Nations, Inuit and Métis), and Latinx compared to White participants, while no difference was found between East Asian and White participants. The group differences in vaccine hesitancy for Indigenous and Black compared to White participants remained after controlling for sociodemographic factors. Determinants of vaccine complacency were equivalent between disproportionately affected racial groups and white participants. Vaccine confidence (i.e., trust in vaccine benefit) was generally lower in all racial groups compared to White participants. Differences in vaccine mistrust comparing Black and East Asian to White participants remained after controlling for sociodemographic factors. Discussion:Disproportionately affected racial minorities may have higher vaccine hesitancy and lower confidence in COVID-19 vaccines. Public health and other relevant government services should address vaccine hesitancy among racial minorities using a culturally sensitive, community-centered approach to attain equitable herd immunity.
Effects of Dietary Supplementation With Bacillus subtilis, as an Alternative to Antibiotics, on Growth Performance, Serum Immunity, and Intestinal Health in Broiler Chickens

Bacillus subtilis (B. subtilis) as in-feed probiotics is a potential alternative for antibiotic growth promoters (AGP) in the poultry industry. The current study investigated the effects of B. subtilis on the performance, immunity, gut microbiota, and intestinal barrier function of broiler chickens. A 42-day feeding trial was conducted with a total of 600 1-day-old Arbor Acres broilers with similar initial body weight, which was randomly divided into one of five dietary treatments: the basal diet (Ctrl), Ctrl + virginiamycin (AGP), Ctrl + B. subtilis A (BSA), Ctrl + B. subtilis B (BSB), and Ctrl + B. subtilis A + B (1:1, BSAB). The results showed significantly increased average daily gain in a step-wise manner from the control, B. subtilis, and to the AGP groups. The mortality rate of the B. subtilis group was significantly lower than the AGP group. The concentrations of serum immunoglobulin (Ig) G (IgG), IgA, and IgM in the B. subtilis and AGP groups were higher than the control group, and the B. subtilis groups had the highest content of serum lysozyme and relative weight of thymus. Dietary B. subtilis increased the relative length of ileum and the relative weight of jejunum compared with the AGP group. The villus height (V), crypt depth (C), V/C, and intestinal wall thickness of the jejunum in the B. subtilis and AGP groups were increased relative to the control group. Dietary B. subtilis increased the messenger RNA (mRNA) expression of ZO-1, Occludin, and Claudin-1, the same as AGP. The contents of lactic acid, succinic acid, and butyric acid in the ileum and cecum were increased by dietary B. subtilis. Dietary B. subtilis significantly increased the lactobacillus and bifidobacteria in the ileum and cecum and decreased the coliforms and Clostridium perfringens in the cecum. The improved performance and decreased mortality rate observed in the feeding trial could be accrued to the positive effects of B. subtilis on the immune response capacity, gut health, and gut microflora balance, and the combination of two strains showed additional benefits on the intestinal morphology and tight junction protein expressions. Therefore, it can be concluded that dietary B. subtilis A and B could be used as alternatives to synthetic antibiotics in the promotion of gut health and productivity index in broiler production.
A unified analytical fully depleted and partially depleted SOI MOSFET model

In this paper we present a unified analytical drain current model for fully depleted and partially depleted SOI MOSFETs. The analytical model is based on a nonpinned surface potential approach and is valid in all regions of operation. It was developed by starting from a two-dimensional Poisson equation, and its accuracy has been verified with the experimental data of SOI MOSFETs.
Men’s Help-Seeking for Distress: Navigating Varied Pathways and Practices

There is a widely accepted dominant narrative surrounding men’s mental health help-seeking, that men are less likely to pursue formal mental health support on account of hegemonic masculine ideals that limit emotional expression and vulnerability. Across the literature, little attention has been given to the varied ways in which men can and will seek out help when experiencing mental health troubles. This paper reports findings from a qualitative study of men’s experiences of distress, specifically focused on their help-seeking and everyday coping and management of distress. Between 2016 and 2017, 38 individual interviews were carried out in South Wales, United Kingdom, with men of a range of ages (21–74 years of age) and social backgrounds. Analysis identifies nuanced help-seeking practices and pathways, emphasizing ways in which men can and will engage with mental health support. Some men struggled with articulating personal issues in mental health terms, and some portrayed ambivalence to help-seeking, yet at the same time reconstructed help-seeking to positively align with masculine values. The paper further highlights the significant influence of familial and friendship networks in the help-seeking process as well as the value of therapy for men experiencing mental health difficulties, challenging the idea that masculinity inhibits the disclosure of emotional problems. Awareness of the diversity of ways in which men can actively engage with their mental health is needed so that mental health support interventions and practitioners can best reach out to men experiencing distress and provide gender-sensitive support suitable to a range of different men.