bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuromuscular rehabilitation – what to do?
Authors: Mandarakas Melissa R. , Young Peter , Burns Joshua 
Published: August 2021

Purpose of review
Rehabilitation for patients with neuromuscular disorders (NMDs) has undisputed health benefits and is potentially therapeutic for targeting impairments, improving quality of life, and enabling activities of daily living. Whilst rehabilitation is commonly prescribed, unequivocal evidence and disease-related guidelines are lacking. This review highlights recent studies of exercise, assistive devices, respiratory management and manual therapy and stretching for patients with NMDs.

Recent findings
Randomised controlled trials of neuromuscular rehabilitation are scant, often underpowered and lack a control group. Recent case studies, clinical trials and cohort studies support rehabilitative therapies such as exercise, respiratory muscle training, assistive devices, and manual therapy and stretching, to provide systemic health benefits, with the possibility to retain or improve function. No evidence of overwork weakness or muscle damage have been reported in exercise trials, and rehabilitative exercise programs in many cases lead to positive psychosocial impacts. Tele-rehab is an emerging area of interest, as a response to the COVID-19 pandemic.

Summary
Robust evidence for the benefits of neuromuscular rehabilitation is lacking, and clinical trial quality can be improved. Tele-rehab is a tantalising development to improve access to neuromuscular rehabilitation in both metropolitan and remote settings during and beyond the COVID-19 pandemic.
Dysregulation of energy homeostasis in amyotrophic lateral sclerosis
Authors: Guillot Simon J. , Bolborea Matei , Dupuis Luc 
Published: August 2021

Purpose of review
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting upper and lower motor neurons, inexorably leading to an early death. Defects in energy metabolism have been associated with ALS, including weight loss, increased energy expenditure, decreased body fat mass and increased use of lipid nutrients at the expense of carbohydrates. We review here recent findings on impaired energy metabolism in ALS, and its clinical importance.

Recent findings
Hypothalamic atrophy, as well as alterations in hypothalamic peptides controlling energy metabolism, have been associated with metabolic derangements. Recent studies showed that mutations causing familial ALS impact various metabolic pathways, in particular mitochondrial function, and lipid and carbohydrate metabolism, which could underlie these metabolic defects in patients. Importantly, slowing weight loss, through high caloric diets, is a promising therapeutic strategy, and early clinical trials indicated that it might improve survival in at least a subset of patients. More research is needed to improve these therapeutic strategies, define pharmacological options, and refine the population of ALS patients that would benefit from these approaches.

Summary
Dysfunctional energy homeostasis is a major feature of ALS clinical picture and emerges as a potential therapeutic target.
Advances in the genetic classification of amyotrophic lateral sclerosis
Authors: Cooper-Knock Johnathan , Harvey Calum , Zhang Sai , Moll Tobias , Timpanaro Ilia Sarah , Kenna Kevin P. , Iacoangeli Alfredo , Veldink Jan H. 
Published: August 2021

Purpose of review
Amyotrophic lateral sclerosis (ALS) is an archetypal complex disease wherein disease risk and severity are, for the majority of patients, the product of interaction between multiple genetic and environmental factors. We are in a period of unprecedented discovery with new large-scale genome-wide association study (GWAS) and accelerating discovery of risk genes. However, much of the observed heritability of ALS is undiscovered and we are not yet approaching elucidation of the total genetic architecture, which will be necessary for comprehensive disease subclassification.

Recent findings
We summarize recent developments and discuss the future. New machine learning models will help to address nonlinear genetic interactions. Statistical power for genetic discovery may be boosted by reducing the search-space using cell-specific epigenetic profiles and expanding our scope to include genetically correlated phenotypes. Structural variation, somatic heterogeneity and consideration of environmental modifiers represent significant challenges which will require integration of multiple technologies and a multidisciplinary approach, including clinicians, geneticists and pathologists.

Summary
The move away from fully penetrant Mendelian risk genes necessitates new experimental designs and new standards for validation. The challenges are significant, but the potential reward for successful disease subclassification is large-scale and effective personalized medicine.
Efficacy and Safety of Intranasal Dexmedetomidine During Recovery From Sevoflurane Anesthesia in Children: A Systematic Review and Meta-analysis
Authors: Xu Chengfeng , Zhang Yanyuan , Zhang Taomei , Wu Duozhi , Zhang Kexian 
Published: August 2021

Background
Intranasal drip of dexmedetomidine in children with sevoflurane anesthesia can reduce anesthesia and restlessness. However, there is still some controversy. We conducted a meta-analysis to explore the effect of intranasal infusion of dexmedetomidine on the quality of recovery during the recovery period, to provide certain guidance for clinical application.

Methods
Web of Science, PubMed, Embase, and the Cochrane Library were used for literature search. Systematic reviews were based on PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analysis).

Results
A total of 14 articles and 1123 patients were included. The results of the meta-analysis showed that the incidence of emergence agitation [risk ratio (RR), 0.32; 95% confidence interval (CI), 0.20–0.50; P < 0.0001], satisfactory sedation at parent separation (RR, 1.41; 95% CI, 1.031–93; P = 0.034), incidence of nausea and vomiting (RR, 0.41; 95% CI, 0.21–0.78; P = 0.007), and incidence of laryngospasm (RR, 0.23; 95% CI, 0.08–0.65; P = 0.006) of the intranasal dexmedetomidine group were different compared with the control group. However, the satisfactory sedation at mask induction in the intranasal dexmedetomidine group (RR, 1.16; 95% CI, 0.87–1.54; P = 0.319), postanesthesia care unit (PACU) stay time (standardized mean deviation, 0.51; 95% CI, −0.11 to 1.12; P = 0.107), and extubation time (standardized mean deviation, 1.64; 95% CI, −1.07 to 4.35; P = 0.235) were not statistically significant compared with those of the control group.

Conclusion
Intranasal dexmedetomidine anesthesia with sevoflurane in children can reduce the incidence of emergence agitation, provide more satisfactory sedation when the parents are separated, reduce the incidence of nausea and vomiting, and reduce the incidence of laryngospasm. In addition, the 2 μg/kg dose of dexmedetomidine may be the best dose for clinical application.
Hydroxychloroquine Prophylaxis against Coronavirus Disease-19: Practice Outcomes among Health-Care Workers
Authors: Bhatt Parloop , Patel Vishva , Shah Prachi , Parikh Keyur 
Published: August 2021

ABSTRACTBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus responsible for the ongoing Covid-19 pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine(HCQ) could prevent SARS CoV-2 in healthcare workers(HCW) at high-risk of exposure.MethodThis voluntary observational study for the prevention and treatment of COVID-19 was conducted at a tertiary care center, from 12th June to 12th October 2020(total 16 weeks). All consented asymptomatic HCW’s of CIMS hospital were administered 400 mg HCQ twice a day on day one followed by 400 mg once weekly to be taken with meals up to 16 weeks. Data collected included OPD registration, risk assessment, medical and family history (related to COVID), physical examination and vitals, pulse oximetry, ECG (pre and post HCQ), drug adherence, side effects, adverse drug reactions.ResultThe study enrolled 927 full-time, hospital-based HCWs ((including doctors, nurses, paramedical, lab technicians, sanitary workers and others), of whom 731(78.85%) initially started HCQ while 196 (21.14%) did not volunteer. The median age and weight of the study population was 27.5 years and 69.5 kg respectively. No major associated co-morbidities were present in these HCW’s. There was an increased trend towards non adherence to HCQ with each proceeding week more so after week 11. Of the 731 HCW’s taking HCQ a total of 167(22.8%) tested COVID positive at different intervals of time as against 30 HCW (15.3%) out of 196 not taking HCQ. The rate of COVID-19 positive was statistically significantly higher in the HCW’s taking HCQ (p=0.0220; 95% CI: 1.14% to 12.94%), as compared to those not on HCQ. Thus HCQ was not prophylactically effective against COVID 19 infection. No participants in this study experienced grade 3 or 4 adverse events. No significant difference in the median of ECG changes in QTc between pre and post HCQ administration of 46 HCW’s was observed.ConclusionsThis clinical study did not detect a reduction in SARS CoV-2 transmission with prophylactic administration of 400 mg/HCQ in HCW’s. All participants who did contract SARSCoV-2 were either asymptomatic or had mild disease courses with full recoveries. All adverse events were self-limiting and no serious cardiovascular events were reported with use of HCQ. In the absence of robust data, it seems premature to recommend HCQ as a prophylactic panacea for COVID-19.
Estimating the contribution of transmission in primary healthcare clinics to community-wide TB disease incidence, and the impact of infection prevention and control interventions, in KwaZulu-Natal, South Africa
Authors: McCreesh Nicky , Karat Aaron S , Govender Indira , Baisley Kathy , Diaconu Karin , Yates Tom A , Houben Rein MGJ , Kielmann Karina , Grant Alison D , White Richard G 
Published: August 2021

AbstractBackgroundThere is a high risk of Mycobacterium tuberculosis (Mtb) transmission in healthcare facilities in high burden settings. Recent World Health Organization guidelines on tuberculosis infection prevention and control (IPC) recommend a range of measures to reduce transmission in healthcare and institutional settings. These were evaluated primarily based on evidence for their effects on transmission to healthcare workers in hospitals. To estimate the overall impact of IPC interventions, it is necessary to also consider their impact on community-wide tuberculosis incidence and mortality.MethodsWe developed an individual-based model of Mtb transmission between household members, in primary healthcare clinics (PHCs), and in other congregate settings; drug sensitive and multidrug resistant tuberculosis disease development and resolution; and HIV and antiretroviral therapy (ART) and their effects on tuberculosis. The model was parameterised using data from a high HIV prevalence, rural/peri-urban community in KwaZulu-Natal, South Africa, including data on social contact in clinics and other settings by sex, age group, and HIV/ART status; and data on the prevalence of tuberculosis in clinic attendees and the general population. We estimated the proportion of disease in adults that resulted from transmission in PHC clinics in 2019, and the impact of a range of IPC interventions in clinics on community-wide TB incidence and mortality.ResultsWe estimate that 7.6% (plausible range 3.9-13.9%) of drug sensitive and multidrug resistant tuberculosis in adults resulted from transmission in PHC clinics in the study community in 2019. The proportion is higher in HIV-positive people, at 9.3% (4.8%-16.8%), compared to 5.3% (2.7%-10.1%) in HIV-negative people. We estimate that IPC interventions could reduce the number of incident TB cases in the community in 2021-2030 by 3.4-8.0%, and the number of deaths by 3.0-7.2%.ConclusionsA non-trivial proportion of tuberculosis results from transmission in PHC clinics in the study communities, particularly in HIV-positive people. Implementing IPC interventions could lead to moderate reductions in disease burden. We therefore recommend that IPC measures in clinics should be implemented both for their benefits to staff and patients, but also for their likely effects on TB incidence and mortality in the surrounding community.
A Sustainable Development Goal framework to guide multisectoral action on NAFLD through a societal approach
Authors: Lazarus Jeffrey V , Mark Henry E , Colombo Massimo , Demaio Sandro , Dillon John F , George Jacob , Hagström Hannes , Hocking Samantha , Lee Nancy , Nieuwenhuijsen Mark J , Rinella Mary E , Romero-Gomez Manuel , Soriano Joan B , Schattenberg Jörn M , Tacke Frank , Tsochatzis Emmanuel A. , Valenti Luca , Zelber-Sagi Shira , Dirac M. Ashworth , Huang Terry T-K 
Published: August 2021

AbstractNon-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition that requires a comprehensive and coordinated response across sectors and disciplines. In the absence of a multisectoral framework, we developed a NAFLD-Sustainable Development Goals (SDG) framework to converge thinking about the design and delivery of NAFLD public health responses. A multidisciplinary group identified SDG targets and indicators for inclusion in the NAFLD-SDG framework through a two-stage process. Firstly, a core team of three researchers independently reviewed the 169 SDG targets and 231 unique indicators proposed by the Inter-Agency and Expert Group on SDG to select a shortlist. Over two Delphi rounds, a multidisciplinary group of 12 experts selected which of the shortlisted targets and indicators to include in the NAFLD-SDG framework. Respondents also provided written feedback on their selection. Targets and indicators with 75% or greater agreement were included in the final NAFLD-SDG framework. The final framework comprises 16 targets–representing 9% of all SDG targets and 62% (16/26) of the shortlisted targets–and seven indicators, accounting for 50% (7/14) of the shortlisted indicators and 3% of all SDG indicators. The selected targets and indicators cover a broad range of factors, from health, food and nutrition to education, the economy and the built environment. Addressing the challenge of NAFLD will require re-envisioning the liver health landscape, with a greater focus on joined-up systems thinking and action. The NAFLD-SDG framework can help guide this process, including by outlining the key stakeholders with whom the liver health community needs to engage.
Association of chronic kidney disease, ethnicity and socioeconomic status with COVID-19 hospitalisation and mortality: a UK Biobank study
Authors: Wilkinson Thomas J , Lightfoot Courtney J , Smith Alice C. , Yates Thomas , Khunti Kamlesh , Zaccardi Francesco 
Published: August 2021

AbstractIn individuals with chronic kidney disease (CKD), Black and South Asian ethnic groups are twice as likely to have severe COVID-19 compared to White participants, whilst the most socially deprived groups are at a 50-60% increased risk of severe COVID-19.This study is the first to highlight the association between ethnicity and socioeconomic deprivation and the risk of severe COVID-19 among those with CKD in the UK.Interventions to reduce morbidity and mortality amongst these groups and policy and practice improvements are needed to address the broad disparity among CKD patients.
SARS-CoV-2 antibody binding and neutralization in dried blood spot eluates and paired plasma
Authors: Itell Hannah L. , Weight Haidyn , Fish Carolyn S. , Logue Jennifer K. , Franko Nicholas , Wolf Caitlin R. , McCulloch Denise J. , Galloway Jared , Matsen Frederick A. , Chu Helen Y. , Overbaugh Julie 
Published: August 2021

ABSTRACTWidescale assessment of SARS-CoV-2-specific antibodies is critical to understanding population seroprevalence, correlates of protection, and the longevity of vaccine-elicited responses. Most SARS-CoV-2 studies characterize antibody responses in plasma/sera. While reliable and broadly used, these samples pose several logistical restrictions such as requiring venipuncture for collection and cold chain for transportation and storage. Dried blood spots (DBS) overcome these barriers as they can be self-collected by fingerstick and mailed and stored at ambient temperature. Here, we evaluate the suitability of DBS for SARS-CoV-2 antibody assays by comparing several antibody responses between paired plasma and DBS from SARS-CoV-2 convalescent and vaccinated individuals. We found that DBS not only reflected plasma antibody binding by ELISA and epitope profiles using phage-display, but also yielded SARS-CoV-2 neutralization titers that highly correlated with paired plasma. Neutralization measurement was further streamlined by adapting assays to a high-throughput 384-well format. This study supports the adoption of DBS for numerous SARS-CoV-2 binding and neutralization assays.
Targeted in silico characterization of fusion transcripts in tumor and normal tissues via FusionInspector
Authors: Haas Brian J. , Dobin Alexander , Ghandi Mahmoud , Van Arsdale Anne , Tickle Timothy , Robinson James T. , Gillani Riaz , Kasif Simon , Regev Aviv 
Published: August 2021

MotivationGene fusions play a key role as driver oncogenes in tumors, and their reliable discovery and detection are important for cancer research, diagnostics, prognostics and guiding personalized therapy. While discovering gene fusions from genome sequencing can be laborious and costly, the resulting “fusion transcripts” can be recovered from RNA-seq data of tumor and normal samples. However, alleged and putative fusion transcripts can also arise from multiple sources other than chromosomal rearrangements, including cis- or trans-splicing events, experimental artifacts during RNA-seq or computational errors of transcriptome reconstruction methods. Understanding how to discern, interpret, categorize, and verify predicted fusion transcripts is essential for consideration in clinical settings and prioritization for further research.SummaryHere, we present FusionInspector for in silico characterization and interpretation of candidate fusion transcripts from RNA-seq and exploration of their sequence and expression characteristics. We applied FusionInspector to thousands of tumor and normal transcriptomes, and identified statistical and experimental features enriched among biologically impactful fusions. Through clustering and machine learning, we identified large collections of fusions potentially relevant to tumor and normal biological processes. We show that biologically relevant fusions are enriched for relatively high expression of the fusion transcript, imbalanced fusion allelic ratios, and canonical splicing patterns, and are deficient in sequence microhomologies detected between partner genes. We demonstrate that FusionInspector accurately validates fusion transcripts in silico, and helps identify and characterize numerous understudied fusions in tumor and normal tissues samples. FusionInspector is freely available as open source for screening, characterization, and visualization of candidate fusions via RNA-seq, and helps with transparent explanation and interpretation of machine learning predictions and their experimental sources.HighlightsFusionInspector software for supervised analysis of candidate fusion transcriptsClustering of recurrent fusion transcripts resolves biologically relevant fusionsIdentification of distinguishing characteristics of known and novel fusion transcripts in tumor and normal tissues
The Ca2+ concentration in vitro impacts the cytokine production of mouse and human lymphoid cells and the polarization of human macrophages
Authors: Eskiocak Yusuf Cem , Ayyildiz Zeynep Ozge , Gunalp Sinem , Korkmaz Asli , Helvaci Derya Goksu , Dogan Yavuz , Sag Duygu , Wingender Gerhard 
Published: August 2021

AbstractVarious aspects of the in vitro culture conditions can impact the functional response of immune cells. For example, it was shown that a Ca2+ concentration of at least 1.5 mM during in vitro stimulation is needed for optimal cytokine production by conventional αβ T cells. Here we extend these findings by showing that also unconventional T cells (invariant Natural Killer T cells, mucosal-associated invariant T cells, γδ T cells), as well as B cells, show an increased cytokine response following in vitro stimulation in the presence of elevated Ca2+ concentrations (approx. 1.8 mM). This effect appeared more pronounced with mouse than with human lymphoid cells and did not influence their survival. A similarly increased cytokine response due to elevated Ca2+ levels was observed with primary human monocytes. In contrast, primary human monocyte-derived macrophages, either unpolarized (M0) or polarized into M1 or M2 macrophages, displayed increased cell death in the presence of elevated Ca2+ concentrations. Furthermore, elevated Ca2+ concentrations promoted phenotypic M1 differentiation by increasing M1 markers on M1 and M2 macrophages and decreasing M2 markers on M2 macrophages. However, the cytokine production of macrophages, again in contrast to the lymphoid cells, was unaltered by the Ca2+ concentration. In summary, our data demonstrate that the Ca2+ concentration during in vitro cultures is an important variable to be considered for functional experiments and that elevated Ca2+ levels can boost cytokine production by both mouse and human lymphoid cells.
Biomorphogenic feedbacks and the spatial organisation of a dominant grass steer dune development
Authors: Bonte Dries , Batsleer Femke , Provoost Sam , Reijers Valérie , Vandegehuchte Martijn L. , Van De Walle Ruben , Dan Sebastian , Matheve Hans , Rauwoens Pieter , Strypsteen Glenn , Suzuki Tomohiro , Verwaest Toon , Hillaert Jasmijn 
Published: August 2021

AbstractNature-based solutions to mitigate the impact of future climate change depend on restoring biological diversity and natural processes. Coastal foredunes represent the most important natural flood barriers along coastlines worldwide, but their area has been squeezed dramatically because of a continuing urbanisation of coastlines, especially in Europe. Dune development is steered by the development of vegetation in interaction with sand fluxes from the beach. Marram grass (Calamagrostis arenaria, formerlyAmmophila arenaria) is the main dune building species along most European coasts, but also in other continents where the species was introduced. Engineering of coastal dunes, for instance by building dunes in front of dikes, needs to be based on a solid understanding of the species’ interactions with the environment. Only quantitative approaches enable the further development of mechanistic models and coastal management strategies that encapsulate these biomorphogenic interactions. We here provide a quantitative review of the main biotic and physical interactions that affect marram grass performance, their interactions with sand fluxes and how they eventually shape dune development. Our review highlights that the species’ spatial organisation is central to dune development. We further demonstrate this importance by means of remote sensing and a mechanistic model and provide an outlook for further research on the use of coastal dunes as a nature-based solution for coastal protection.