bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipose-Derived Stem Cells, Obesity, and Inflammation
Authors: Miller Dana , Grant Austin , Durgam Sushmitha , El-Hayek Kevin , Flanigan David C. , Malanga Gerard , Vasileff William Kelton , Baria Michael R. 
Published: November 2021

Abstract
Adipose is a known source of mesenchymal stem cells that can be used to treat musculoskeletal disorders, such as osteoarthritis. Because obesity often coexists with osteoarthritis, excess adiposity may be a useful source of mesenchymal stem cells. However, obesity is associated with systemic inflammation, which may influence the quality of adipose-derived stem cells. We performed a systematic review of the literature examining adipose-derived stem cell behavior, cytokine, and growth factor profiles from obese and nonobese patients. Two independent reviewers applied the inclusion/exclusion criteria and independently extracted data including mesenchymal stem cell count/viability/behavior, growth factor, and/or cytokine expression. Twenty-two articles met criteria for inclusion. Samples from obese patients had increased mesenchymal stem cell content (n = 6), but decreased proliferative ability (n = 3), and increased expression of interleukin 1 (n = 3), interleukin 6 (n = 3), and tumor necrosis factor α (n = 6). There was also greater macrophage content (n = 4). Weight loss normalized cellular function. In vitro behavior and quality of adipose-derived stem cell are significantly different between obese and nonobese patients. Samples from obese patients had greater adipose-derived stem cell content, lower proliferative ability, increased senescence, and increased proinflammatory cytokine expression. Differences in cellular function should be considered when using adipose to treat musculoskeletal pathology in obese and nonobese patients.
Frailty in people living with HIV: an update
Authors: Jones Howell T. , Levett Tom , Barber Tristan J. 
Published: November 2021

Purpose of review
The HIV population is ageing with rising rates of frailty though strategies of how best to manage it remain ill-defined. It also remains unclear what the prevalence of frailty is within this cohort, how best to diagnose it and what factors are associated.

Recent findings
The prevalence of frailty remains unclear because of heterogenous results. Routine screening in those 50+ is recommended and whilst the Fried Frailty Phenotype is currently preferred the Clinical Frailty Scale could be considered. No biomarkers are currently recommended. Looking at associated factors, HIV neurocognitive impairment and long-term alcohol usage has been shown to be associated with developing frailty whilst those who are frail have been shown to be less active and more likely to fall. NAFLD with fibrosis has been shown to be an indicator of metabolic age and the Pooled Cohort Equations has been shown to be more effective in diagnosing cardiovascular risk in frail people living with HIV.

Summary
Whilst the prevalence of frailty differs between countries, with the addition of prefrailty, this represents a large proportion of people living with HIV. Services must ensure strategies are in place to support those living with HIV and frailty. Further longitudinal studies are required.
Challenges of sexually transmitted infections and sexual health among people who inject drugs
Authors: Dumchev Kostyantyn 
Published: November 2021

Purpose of review
This review provides a summary of recently published research on sexually transmitted infections (STI) and related behaviors among people who inject drugs (PWID), covering three major areas: sexual behavior and its role in STI transmission among PWID, multilevel factors associated with STI risk, and strategies addressing sexual health of PWID. This review is timely given the growing priority of combination prevention approaches and integrated care for PWID.

Recent findings
Modern research improves the understanding that PWID have an increased risk of STI, which varies by gender, setting, type of substance used, and presence of mental disorders. Major socioeconomic and structural factors, specific and nonspecific to PWID, facilitate inequality and sexual risk behavior. Sexual transmission continues to contribute substantially to the spread of bloodborne infections among PWID, accounting for at least 10% of new HIV cases according to epidemiological modeling. Despite the substantial evidence that behavioral interventions can improve sexual health and reduce sex-related risks among PWID, there is a research-practice gap, reflected in the scarcity of implementation studies published recently.

Summary
Integration of sexual health into prevention programs for PWID is essential to curb transmission of STI, including HIV, among PWID and their sexual partners.
Intravenous thrombolysis for acute ischemic stroke: why not?
Authors: Psychogios Klearchos , Tsivgoulis Georgios 
Published: November 2021

Purpose of review
The aim of this study was to summarize available evidence regarding the safety and efficacy of intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA) in acute ischemic stroke (AIS) patients with specific comorbidities and potential contraindications to systemic reperfusion therapy. Recent advances in IVT implementation in wake-up stroke and in extended time window using advanced neuroimaging will also be highlighted.

Recent findings
Despite theoretical concerns of a higher bleeding risk with IVT, there are no data showing increased risk of symptomatic intracerebral haemorrhage (sICH) in patients with stroke mimics, including seizures, increasing age and dual antiplatelet pretreatment. In addition, recent randomized evidence allows us to expand the time window of IVT for AIS using advanced neuroimaging both in wake-up stroke patients and in patients presenting within 4.5–9 h from symptom onset fulfilling certain neuroimaging criteria (based on DWI/FLAIR mismatch or perfusion mismatch).

Summary
IVT is a highly effective systemic reperfusion therapy that counts 25 years of everyday clinical experience but still presents several challenges in its application. Appropriate patient selection and adherence to rt-PA protocol is paramount in terms of safety. The effort to simplify the indications, expand the therapeutic time window and eliminate specific initial contraindications is continuously evolving.
Network dysfunction in pre and postsurgical epilepsy: connectomics as a tool and not a destination
Authors: Johnson Graham W. , Doss Derek J. , Englot Dario J. 
Published: November 2021

Purpose of review
Patients with focal drug-resistant epilepsy (DRE) sometimes continue to have seizures after surgery. Recently, there is increasing interest in using advanced network analyses (connectomics) to better understand this problem. Connectomics has changed the way researchers and clinicians view DRE, but it must be applied carefully in a hypothesis-driven manner to avoid spurious results. This review will focus on studies published in the last 18 months that have thoughtfully used connectomics to advance our fundamental understanding of network dysfunction in DRE – hopefully for the eventual direct benefit to patient care.

Recent findings
Impactful recent findings have centered on using patient-specific differences in network dysfunction to predict surgical outcome. These works span functional and structural connectivity and include the modalities of functional and diffusion magnetic resonance imaging (MRI) and electrophysiology. Using functional MRI, many groups have described an increased functional segregation outside of the surgical resection zone in patients who fail surgery. Using electrophysiology, groups have reported network characteristics of resected tissue that suggest whether a patient will respond favorably to surgery.

Summary
If we can develop accurate models to outline functional and structural network characteristics that predict failure of standard surgical approaches, then we can not only improve current clinical decision-making; we can also begin developing alternative treatments including network approaches to improve surgical success rates.
Symptomatic and asymptomatic transmission of SARS-CoV-2 in K-12 schools, British Columbia, April to June 2021
Authors: Choi Alex , Mâsse Louise C. , Bardwell Samantha , Zhao Yanjie , Xu Yang Xin Zi , Markarian Ani , Coombs Daniel , Watts Allison , Macdonald Adrienne , Dhillon Nalin , Irvine Michael , O’Reilly Collette , Lavoie Pascal M. , Goldfarb David 
Published: November 2021

AbstractWe prospectively studied SARS-CoV-2 transmission at schools in an era of Variants of Concern (VoCs), offering all close contacts serial viral asymptomatic testing up to 14 days. Of 229 school close contacts, 3 tested positive (1.3%), of which 2 were detected through asymptomatic testing. Most secondary transmission (90%) occurred in households. Routine asymptomatic testing of close contacts should be examined in the context of local testing rates, preventive measures, programmatic costs, and health impacts of asymptomatic transmission.
Developmental Deconvolution for Classification of Cancer Origin
Authors: Moiso Enrico , Farahani Alexander , Marble Hetal , Hendricks Austin , Mildrum Samuel , Levine Stuart , Lennerz Jochen , Garg Salil 
Published: November 2021

AbstractCancer is a disease manifesting in abrogation of developmental programs, and malignancies are named based on their cell or tissue of origin. However, a systematic atlas of tumor origins is lacking. Here we map the single cell organogenesis of 56 developmental trajectories to the transcriptomes of over 10,000 tumors across 33 cancer types. We use this map to deconvolute individual tumors into their constituent developmental trajectories. Based on these deconvoluted developmental programs, we construct a Developmental Multilayer Perceptron (D-MLP) classifier that outputs cancer origin. The D-MLP classifier (ROC-AUC: 0.974 for top prediction) outperforms classification based on expression of either oncogenes or highly variable genes. We analyze tumors from patients with cancer of unknown primary (CUP), selecting the most difficult cases where extensive multimodal workup yielded no definitive tumor type. D-MLP revealed insights into developmental origins and diagnosis for most patient tumors. Our results provide a map of tumor developmental origins, provide a tool for diagnostic pathology, and suggest developmental classification may be a useful approach for otherwise unclassified patient tumors.
Cumulative Effects of Resting-state Connectivity Across All Brain Networks Significantly Correlate with ADHD Symptoms
Authors: Mooney Michael A. , Hermosillo Robert J.M. , Feczko Eric , Miranda-Dominguez Oscar , Moore Lucille A. , Perrone Anders , Byington Nora , Grimsrud Gracie , Rueter Amanda , Nousen Elizabeth , Antovich Dylan , Feldstein Ewing Sarah W. , Nagel Bonnie J. , Nigg Joel T. , Fair Damien A. 
Published: November 2021

ABSTRACTBackgroundThe clinical utility of MRI neuroimaging studies of psychopathology has been limited by a constellation of factors—small sample sizes, small effect sizes, and heterogeneity of methods and samples across studies—that hinder generalizability and specific replication. An analogy is early genomics studies of complex traits, wherein a move to large, multi-site samples and a focus on cumulative effects (polygenic scores) led to reproducible and clinically applicable effects from genome-wide association studies. A similar logic in MRI may provide a way to improve reproducibility, precision, and clinical utility for brain-wide MRI association studies.MethodsPolyneuro scores (PNS) represent the cumulative effect of brain-wide measures—in the present case, resting-state functional connectivity (rs-fcMRI) associated with ADHD symptoms. These scores were constructed and validated using baseline data from the Adolescent Brain Cognitive Development (ABCD, N=5666) study, with a reproducible matched subset as the discovery cohort (N=2801). Association between the PNS and ADHD symptoms was further tested in an independent case-control cohort, the Oregon-ADHD-1000 (N=533).ResultsThe ADHD PNS was significantly associated with ADHD symptoms in both the ABCD and Oregon cohorts after accounting for relevant covariates (p-values < 0.001). While the strongest effects contributing to the PNS were concentrated among connections involving the default mode and cingulo-opercular networks, the most predictive PNS involved connectivity across all brain networks. These findings were robust to stringent motion thresholds. In the longitudinal Oregon-ADHD-1000, non-ADHD comparison youth had significantly lower ADHD PNS (β=-0.309, p=0.00142) than children with persistent ADHD (met diagnostic criteria at two or more time points from age 7 to 19). The ADHD PNS, however, did not reliably mediate polygenic risk for ADHD. Instead, the PNS and an ADHD polygenic score were independently associated with ADHD symptoms.ConclusionsA polyneuro risk score representing cumulative ADHD-associated resting-state connectivity was robustly associated with ADHD symptoms in two independent cohorts using distinct sampling designs, yet was independent of polygenic liability for ADHD, suggesting the need to examine environmental influences. The polyneuro score approach holds promise for improving the reproducibility of neuroimaging studies, identifying their clinical utility, and unraveling the complex relationships between brain connectivity and the etiology of behavioral disorders.
Shotgun metagenomics of soil invertebrate communities reflects taxonomy, biomass and reference genome properties
Authors: Schmidt Alexandra , Schneider Clément , Decker Peter , Hohberg Karin , Römbke Jörg , Lehmitz Ricarda , Bálint Miklós 
Published: November 2021

AbstractMetagenomics - shotgun sequencing of all DNA fragments from a community DNA extract - is routinely used to describe the composition, structure and function of microorganism communities. Advances in DNA sequencing and the availability of genome databases increasingly allow the use of shotgun metagenomics on eukaryotic communities. Metagenomics offers major advances in the recovery of biomass relationships in a sample, in comparison to taxonomic marker gene based approaches (metabarcoding). However, little is known about the factors which influence metagenomics data from eukaryotic communities, such as differences among organism groups, the properties of reference genomes and genome assemblies.We evaluated how shotgun metagenomics records composition and biomass in artificial soil invertebrate communities. We generated mock communities of controlled biomass ratios from 28 species from all major soil mesofauna groups: mites, springtails, nematodes, tardigrades and potworms. We shotgun-sequenced these communities and taxonomically assigned them with a database of over 270 soil invertebrate genomes.We recovered 90% of the species, and observed relatively high false positive detection rates. We found strong differences in reads assigned to different taxa, with some groups (e.g. springtails) consistently attracting more hits than others (e.g. enchytraeids). Original biomass could be predicted from read counts after considering these taxon-specific differences. Species with larger genomes, and with more complete assemblies consistently attracted more reads than species with smaller genomes. The GC content of the genome assemblies had no effect on the biomass-read relationships.The results show considerable differences in taxon recovery and taxon specificity of biomass recovery from metagenomic sequence data. The properties of reference genomes and genome assemblies also influence biomass recovery, and they should be considered in metagenomic studies of eukaryotes. We provide a roadmap for investigating factors which influence metagenomics-based eukaryotic community reconstructions. Understanding these factors is timely as accessibility of DNA sequencing, and momentum for reference genomes projects show a future where the taxonomic assignment of DNA from any community sample becomes a reality.
The natural compound TMYX reduces SAN cells rate by antagonizing the cAMP modulation of f-channels
Authors: Piantoni Chiara , Paina Manuel , Molla David , Liu Sheng , Bertoli Giorgia , Jiang Hongmei , Wang Yanyan , Wang Yi , Wang Yi , DiFrancesco Dario , Barbuti Andrea , Bucchi Annalisa , Baruscotti Mirko 
Published: November 2021

AbstractTongmai Yangxin (TMYX), is a complex compound of a Traditional Chinese Medicine (TCM) used to treat several cardiac rhythm disorders; however, no information regarding its mechanism of action is available. In this study we provide a detailed characterization of the effects of TMYX on the electrical activity of pacemaker cells and unravel its mechanism of action.Single-cell electrophysiology revealed that TMYX elicits a reversible and dose-dependent (2/6 mg/ml) slowing of spontaneous action potentials rate (−20.8/-50.2%) by a selective reduction of the diastolic phase (−50.1/-76.0%). This action is mediated by a negative shift of the If activation curve (−6.7/-11.9 mV) and is caused by a reduction of the cAMP-induced stimulation of pacemaker channels. We provide evidence that TMYX acts by directly antagonizes the cAMP-induced allosteric modulation of the pacemaker channels. Noticeably, this mechanism functionally resembles the pharmacological actions of muscarinic stimulation or β-blockers, but it does not require generalized changes in cytoplasmic cAMP levels thus ensuring a selective action on rate.In agreement with a competitive inhibition mechanism, TMYX exerts its maximal antagonistic action at submaximal cAMP concentrations and then progressively becomes less effective thus ensuring a full contribution of If to pacemaker rate during high metabolic demand and sympathetic stimulation.Funding sourcesThis work was supported by grants from Tianjin Zhongxin Pharmaceutical Group Co., Ltd. Le Ren Tang Pharmaceutical Factory P.R. China. The financial supporter played no role in the study design, data collection and analysis, decision to publish, or the preparation of the manuscript.
A prospective study of asymptomatic SARS-CoV-2 infection among individuals involved in academic research under limited operations during the COVID-19 pandemic
Authors: Pettifor Audrey , DiPrete Bethany L. , Shook-Sa Bonnie E. , Premkumar Lakshmanane , Kuczynski Kriste , Dittmer Dirk , Aiello Allison , Wallet Shannon , Maile Robert , Tan Joyce , Jadi Ramesh , Pluta Linda , de Silva Aravinda M. , Weber David J. , Kim Min , Seña Arlene C. , Jones Corbin D. 
Published: November 2021

ABSTRACTBackgroundEarly in the pandemic, transmission risk from asymptomatic infection was unclear making it imperative to monitor infection in workplace settings. Further, data on SARS-CoV-2 seroprevalence within university populations has been limited.MethodsWe performed a longitudinal study of University research employees on campus July-December 2020. We conducted questionnaires on COVID-19 risk factors, RT-PCR testing, and SARS-CoV-2 serology using an in-house spike RBD assay, laboratory-based Spike NTD assay, and standard nucleocapsid platform assay. We estimated prevalence and cumulative incidence of seroconversion with 95% confidence intervals using the inverse of the Kaplan-Meier estimator.Results910 individuals were included in this analysis. At baseline, 6.2% (95% CI 4.29-8.19) were seropositive using the spike RBD assay; four (0.4%) were seropositive using the nucleocapsid assay, and 44 (4.8%) using the Spike NTD assay. Cumulative incidence was 3.61% (95% CI: 2.04-5.16). Six asymptomatic individuals had positive RT-PCR results.ConclusionsPrevalence and incidence of SARS-CoV-2 infections was low; however differences in target antigens of serological tests provided different estimates. Future research on appropriate methods of serological testing in unvaccinated and vaccinated populations is needed. Frequent RT-PCR testing of asymptomatic individuals is required to detect acute infections, and repeated serosurveys are beneficial for monitoring subclinical infection.
Experiences of staff providing specialist palliative care during COVID-19A multiple qualitative case study
Authors: Bradshaw Andy , Dunleavy Lesley , Garner Ian , Preston Nancy , Bajwah Sabrina , Cripps Rachel , Fraser Lorna K , Maddocks Matthew , Hocaoglu Mevhibe , Murtagh Fliss EM , Oluyase Adejoke O , Sleeman Katherine E , Higginson Irene J , Walshe Catherine 
Published: November 2021

AbstractObjectivesTo explore the experiences of, and impact on, staff working in palliative care during the COVID-19 pandemic.DesignQualitative multiple case study using semi-structured interviews between November 2020 and April 2021 as part of the CovPall study. Data were analysed using thematic framework analysis.SettingOrganisations providing specialist palliative services in any setting.ParticipantsStaff working in specialist palliative care, purposefully sampled by the criteria of role, care setting and COVID-19 experience.Main outcome measuresExperiences of working in palliative care during the COVID-19 pandemic.ResultsFive cases and 24 participants were recruited (n=12 nurses, 4 clinical managers, 4 doctors, 2 senior managers, 1 healthcare assistant, 1 allied healthcare professional). Central themes demonstrate how infection control constraints prohibited and diluted participants’ ability to provide care that reflected their core values, resulting in experiences of moral distress. Despite organisational, team, and individual support strategies, continually managing these constraints led to a ‘crescendo effect’ in which the impacts of moral distress accumulated over time, sometimes leading to burnout. Solidarity with colleagues and making a valued contribution provided ‘moral comfort’ for some.ConclusionsThis study provides a unique insight into why and how healthcare staff have experienced moral distress during the pandemic, and how organisations have responded. Despite their experience of dealing with death and dying, the mental health and well-being of palliative care staff was affected by the pandemic. Organisational, structural, and policy changes are urgently required to mitigate and manage these impacts.
Evaluation of a novel direct capture method for virus concentration n wastewater from COVID-19 infectious ward and correlation analysis with the number of inpatients
Authors: Inaba Manami , Nakao Ryohei , Imamura Fumiko , Nakashima Yutaka , Miyazono Seiji , Akamatsu Yoshihisa 
Published: November 2021

ABSTRACTThe global outbreak of the SARS-CoV-2 pandemic has increased the focus of Wastewater-based epidemiology (WBE) studies as a tool for understanding the epidemic and risk management. A highly sensitive and rapid method for the virus concentration from wastewater is needed to obtain the accurate information for early detection of SARS-CoV-2 outbreak and epidemic. In this study, we evaluated the efficiency of the direct capture method provided from Promega, based on column adsorption using the wastewater from actual infectious diseases ward. The efficiency of the nucleic acid extraction-purification process was also evaluated by Maxwell® RSC instrument (fully automated extraction) and QIAamp Viral RNA mini kit (manual extraction). The obtained SARS-CoV-2 data from wastewater were analyzed with the number of inpatients which is the consideration of the severity and the days of onset. The combination of direct capture and Maxwell’s method (DC-MW) was suggested to be a highly sensitive and simple method with better concentration efficiency and quantification than other methods. Moreover, the inpatient conditions (severity and days of after onset) should be considered to accurately understand the actual status of the correlation between the number of inpatients and SARS-CoV-2 concentration in wastewater. The highly sensitive method of DC-MW was suggested to assess more actual situation of SARS-CoV-2 shedding into the wastewater.