bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of work loss on mental and physical health during the COVID-19 pandemic: Findings from a prospective cohort study
Authors: Griffiths Daniel , Sheehan Luke , van Vreden Caryn , Petrie Dennis , Grant Genevieve , Whiteford Peter , R Sim Malcolm , Collie Alex 
Published: September 2020

AbstractObjectiveTo determine if losing work during the COVID-19 pandemic is associated with mental and physical health. To determine if social interactions and financial resources moderate the relationship between work loss and health.DesignBaseline data from a prospective longitudinal cohort study.SettingAustralia, 27th March to 12th June 2020.ParticipantsAustralians aged 18+ years, employed in a paid job prior to the COVID-19 pandemic who responded to an online or telephone survey.Main Outcome MeasuresKessler-6 score > 18 indicating high psychological distress. Short Form 12 (SF-12) mental health or physical health component score < = 45 indicating poor mental or physical health.Results2,603 respondents including groups who had lost their job (N = 541), were not working but remained employed (N = 613), were working less (N = 789) and whose work was unaffected (N = 789). Three groups experiencing work loss had greater odds of high psychological distress (AOR = 2.22–3.66), poor mental (AOR = 1.78–2.27) and physical health (AOR = 2.10–2.12) than the unaffected work group. Poor mental health was more common than poor physical health. The odds of high psychological distress (AOR = 5.43–8.36), poor mental (AOR = 1.92–4.53) and physical health (AOR = 1.93–3.90) were increased in those reporting fewer social interactions or less financial resources.ConclusionLosing work during the COVID-19 pandemic is associated with mental and physical health problems, and this relationship is moderated by social interactions and financial resources. Responses that increase financial security and enhance social connections may partially alleviate the health impacts of work loss.RegistrationAustralian New Zealand Clinical Trials Registry: ACTRN12620000857909.
A novel and potent thrombolytic fusion protein consisting of anti-insoluble fibrin antibody and mutated urokinase
Authors: Hanaoka Shingo , Saijou Shinji , Matsumura Yasuhiro 
Published: September 2020

AbstractBecause the risk of thromboembolism increases with age, as well as due to infectious diseases, safer and more effective thrombolytic agents are in greater demand. Tissue plasminogen activator (tPA) is currently used clinically because it has higher binding specificity for insoluble fibrin (IF) than urokinase (UK), but even pro-tPA has catalytic activity in places other than IF. Meanwhile, UK has the advantage that it is specifically activated on IF, but it only binds IF weakly. Unlike the anti-IF monoclonal antibody (mAb) established in the past, our anti-IF mAb recognizes a pit structure formed only in IF. Here, we developed a new mAb against the pit, 1101, that does not affect coagulation or fibrinolysis, and prepared a fusion protein of UK with humanized 1101 Fab to transport UK selectively to IF. In IF-containing lesions, UK is cleaved by plasmin at two sites, Lys158/Ile159 and Lys135/Lys136. Cleavage of the former leads to activation of UK; however, because activated UK is linked by S-S bonds before and after cleavage, it is not released from the fusion. Cleavage at the latter site causes UK to leave the fusion protein; hence, we mutated Lys135/Lys136 to Gly135/Gly136 to prevent release of UK. This engineered UK-antibody fusion, AMU1114, significantly decreased the systemic side effects of UKin vivo. In a mouse thrombus formation experiment, the vascular patency rate was 0% (0/10) in the control, 50% (5/10) in the tPA, and 90% (9/10) in the AMU1114 treatment group. These data support future clinical development of AMU1114.
Celastrol directly inhibits PFKM to induce weight loss and leptin sensitization
Authors: Wang Kang , Wu Xiaobo , Zhuang Yinghua , Sun Huan , Wang Fengchao , Wang Tao , Zhang Zhiyuan 
Published: September 2020

AbstractDespite the prevalence of obesity and related health consequences around the globe, effective treatments for inducing healthy weight loss are still lacking. Celastrol is a pentacyclic triterpene that was recently identified as a potent anti-obesity agent. Celastrol increases sensitivity to leptin, but the molecular target of celastrol is unknown. Therefore, the mechanisms by which this agent exerts its anti-obesity effect remain elusive. Using tissue-specific ABPP (activity-based protein profiling), we found that PFKM, a rate-limiting enzyme for glycolysis in skeletal muscle, is a direct target of celastrol. Celastrol inhibited PFKM enzymatic activity, andPfkmknockout mice were resistant to a high fat diet, were hypersensitive to exogenous leptin, and were unresponsive to celastrol. PFKM inhibition led to activation of AMPK and inactivation of ACC in cultured myotubes and mouse skeletal muscle. Specific loss of AMPK in muscle significantly attenuated the anti-obesity effects of celastrol. Further, PFKM inhibition and subsequent activation of the AMPK/ACC signaling pathway reduced levels of free fatty acids by switching energy expenditure and consequently decreasing levels of SOCS1 expression, which are both required for leptin sensitization in 293t/hLepRb cells and mice. Finally, using a high throughput compound screen we identified an alternative PFKM inhibitor, 3-79, which exhibits a strong anti-obesity effect and non-covalent binding capacity. This compound is a promising agent for treating obesity in the clinic.
EARLY VIRAL CLEARANCE AMONG COVID-19 PATIENTS WHEN GARGLING WITH POVIDONE-IODINE AND ESSENTIAL OILS – A CLINICAL TRIAL
Authors: Mohamed Nurul Azmawati , Baharom Nizam , Sulaiman Wan Shahida Wan , Rashid Zetti Zainol , Ken Wong Kon , Ali Umi Kalsom , Othman Siti Norlia , Samat Muttaqillah Najihan , Kori Najma , Periyasamy Petrick , Zakaria Nor Azizan , Sugurmar Agni Nhirmal Kumar , Kazmin Nur Ezzaty Mohammad , Khee Cheong Xiong , Saniman Siti Mariyam , Isahak Ilina 
Published: September 2020

AbstractBackgroundGargling had been reported to have significant roles in the prevention and treatment of respiratory tract infections. The purpose of this study was to assess the ability of regular gargling to eliminate SARS-CoV-2 in the oropharynx and nasopharynx.MethodologyThis pilot, open labeled, randomized, parallel study compared the effect of 30 seconds, 3 times/day gargling using 1% povidone-iodine (PVP-I), essential oils and tap water on SARS-CoV-2 viral clearance among COVID-19 patients in a tertiary hospital in Kuala Lumpur. Progress was monitored by day 4,6 and 12 PCR (Ct value), gargling and symptoms diary as well as clinical observations.ResultsFive confirmed Stage 1 COVID-19 patients were recruited for each arm. The age range was from 22 to 56 years old. The majority were males. Two respondents had co-morbidities, which were asthma and obesity. Viral clearance was achieved at day 6 in 100%, 80%, 20% and 0% for 1% PVP-I, essential oils, tap water and control group respectively. Analysis of 1% PVP-I group versus control group showed significant p-value for comparison of PCR results on Day 4, Day 6 and Day 12.ConclusionsThis preliminary study showed that gargling with 1% PVP-I and essential oils show great potential to be part of the treatment and management of Stage 1 COVID-19. Larger studies are required to ascertain the benefit of gargling for different stages of COVID-19 patients. This study was registered in clinicaltrial.gov (NCT04410159).
Implementing a program to improve handoffs and reduce adverse events in Paediatric Intensive Care Units in Argentina: a stepped wedge trial
Authors: Facundo Jorro-Barón , Inés Suarez-Anzorena , Rodrigo Burgos-Pratx , Noelia Demaio , Matias Penazzi , Gisela Rodriguez , Paula Rodriguez Ana , Daniel Velardez , Silvina Ábalos , Silvina Lardone , Joaquín Olivieri , Rocío Gallagher , Rocio Rodriguez , Luz Gibbons , Martin Landry Luis , Ezequiel Garcia-Elorrio 
Published: September 2020

ABSTRACTIntroductionAn effective and standardized communication anticipates and limits the appearance of possible adverse events.ObjectiveTo evaluate the effect of the implementation of a handoff program in reducing the frequency of adverse events (AE) in Paediatric Intensive Care Units (PICUs).MethodsFacility-based, cluster randomised stepped wedge trial in six Argentine PICUs, with more than 20 admissions per month. The intervention comprised a Spanish version on the I-PASS Handoff Bundle consisting of a written and verbal handoff using mnemonics, an introductory workshop with teamwork training, an advertising campaign, simulation exercises and observation and standardized feedback of handoffs.ResultsWe recruited 6 cluster PICUs in 5 hospitals. We reviewed 1465 medical records (MR). We did not observed differences in the rates of preventable AE per 1000 days of hospitalization (control 60.4 [37.5 - 97.4] vs. intervention 60.4 [33.2 - 109.9], p = 0.3568, RR:1.21 [CI95%:0.80 - 1.83]), and no changes in the categories or types of AE. We evaluated 847 handoffs. Compliance with all items in verbal and written handoff was significantly higher in the intervention group. We observed a longer time per patient to complete the handoff in the intervention group (7.29 minutes [5.77 - 8.81] vs. 5.96 [4.69 - 7.23]; p < 0.0002, RR:1.33 [CI95%:0.64 - 2.02]), without changes in the whole time used for handoff (control: 35.7 [29.6 - 41.8] vs. intervention: 34.7 [26.5 - 42.1]; p = 0.4900, RR:1.43 [CI95%:-2.63 - 5.49]). Perception of improved communication from provider didn’t show changes.ConclusionsAfter the implementation of the I-PASS bundle, improvement in the quality of handoffs was observed. Nevertheless, no differences were observed in the frequency of AE, nor in the perception of improved communication.
Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19
Authors: Aamodt Anne Hege , Høgestøl Einar August , Popperud Trine Haug , Holter Jan Cato , Dyrhol-Riise Anne Ma , Tonby Kristian , Stiksrud Birgitte , Quist-Paulsen Else , Berge Tone , Barratt-Due Andreas , Aukrust Pål , Heggelund Lars , Blennow Kaj , Zetterberg Henrik , Harbo Hanne Flinstad 
Published: September 2020

AbstractObjectiveTo test the hypotheses that blood concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients.MethodsForty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa). Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects.ResultsIn total, 21 % (n = 10) of the patients were admitted to an intensive care unit, whereas the overall mortality rate was 13 % (n = 6). Non-survivors had higher serum concentrations of NfL than patients who were discharged alive both in adjusted analyses (p = 2.6 × 10−7) and unadjusted analyses (p = 0.001). Serum concentrations of GFAp were significantly higher in non-survivors than survivors in adjusted analyses (p = 0.02). The NfL concentrations in non-survivors increased over repeated measurements, whereas the concentrations in survivors were stable. Significantly higher concentrations of NfL were found in patients reporting fatigue, while reduced concentrations were found in patients experiencing cough, myalgia and joint pain.ConclusionIncreased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
Care dependency among older women in Austrian nursing homes: The role of outdoor temperatures
Authors: Schuettengruber Gerhilde , Grossschaedl Franziska , Hoedl Manuela 
Published: September 2020

ABSTRACTThe aim of this study was to investigate the associations between outdoor temperatures and care dependency degree among female nursing home residents. A secondary data analysis of data from a cluster-randomized controlled trial was conducted. Data from 345 female nursing home residents in two federal states in southern Austria were collected. Data on the degree of care dependency, dementia and age were collected from the participating female residents. Outdoor temperature data were provided by the Austrian Central Institute for Meteorology and Geodynamics. The results of the regression analysis show that the outdoor temperatures significantly affect the degree of care dependency. As the outdoor temperature decreases, the CDS score increases, which indicates that the number of independent woman enhance. For nursing home practice, we strongly recommend establishing heat plans. Representative prospective studies need to be carried out to investigate the causality between temperature and the degree of care dependency.
Cholesteryl Ester Transfer Protein as a Drug Target for Cardiovascular Disease
Authors: Schmidt Amand F , Hunt Nicholas B , Gordillo-Marañón Maria , Charoen Pimphen , Drenos Fotios , Casas Juan-Pablo , Kivimaki Mika , Lawlor Deborah A , Giambartolomei Claudia , Papacosta Olia , Chaturvedi Nishi , Bis Joshua C ,   UCLEB consortium, O’Donnell Christopher , Wannamethee Goya , Wong Andrew , Price Jackie F , Hughes Alun D , Gaunt Tom R , Franceschini Nora , Mook-Kanamori Dennis O , Zwierzyna Magdalena , Sofat Reecha , Hingorani Aroon D , Finan Chris 
Published: September 2020

AbstractDrug development of cholesteryl ester transfer protein (CETP) inhibition to prevent coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and Mendelian randomization (MR) results. Findings from meta-analyses of CETP inhibitor trials (≥ 24 weeks follow-up) were used to judge between-compound heterogeneity in treatment effects. Genetic data were extracted on 190+ pharmacologically relevant outcomes; spanning 480,698-21,770 samples and 74,124-4,373 events. Drug target MR of protein concentration was used to determine the on-target effects of CETP inhibition and compared to that of PCSK9 modulation. Fifteen eligible CETP inhibitor trials of four compounds were identified, enrolling 79,961 participants. There was a high degree of heterogeneity in effects on lipids, lipoproteins, blood pressure, and clinical events. For example, dalcetrapib and evacetrapib showed a neutral effect, torcetrapib increased, and anacetrapib decreased cardiovascular disease (CVD); heterogeneity p-value < 0.001. In drug target MR analysis, lower CETP concentration (per μg/ml) was associated with CHD (odds ratio 0.95; 95%CI 0.91; 0.99), heart failure (0.95; 95%CI 0.92; 0.99), chronic kidney disease (0.94 95%CI 0.91; 0.98), and age-related macular degeneration (1.69; 95%CI 1.44; 1.99). Lower PCSK9 concentration was associated with a lower risk of CHD, heart failure, atrial fibrillation and stroke, and increased risk of Alzheimer’s disease and asthma. In conclusion, previous failures of CETP inhibitors are likely compound related. CETP inhibition is expected to reduce risk of CHD, heart failure, and kidney disease, but potentially increase risk of age-related macular disease.
COVID-19 transmission in a university setting: a rapid review of modelling studies
Authors: Christensen Hannah , Turner Katy , Trickey Adam , Booton Ross D. , Hemani Gibran , Nixon Emily , Relton Caroline , Danon Leon , Hickman Matthew , Brooks-Pollock Ellen ,   Part of the University of Bristol UNCOVER group
Published: September 2020

AbstractManaging COVID-19 within a university setting presents unique challenges. At the start of term, students arrive from geographically diverse locations and potentially have higher numbers of social contacts than the general population, particularly if living in university halls of residence accommodation. Mathematical models are useful tools for understanding the potential spread of infection and are being actively used to inform policy about the management of COVID-19. Our aim was to provide a rapid review and appraisal of the literature on mathematical models investigating COVID-19 infection in a university setting. We searched PubMed, Web of Science, bioRxiv/ medRxiv and sought expert input via social media to identify relevant papers. BioRxiv/ medRxiv and PubMed/Web of Science searches took place on 3 and 6 July 2020, respectively. Papers were restricted to English language. Screening of peer-reviewed and pre-print papers and contact with experts yielded five relevant papers – all of which were pre-prints. All models suggest a significant potential for transmission of COVID-19 in universities. Testing of symptomatic persons and screening of the university community regardless of symptoms, combined with isolation of infected individuals and effective contact tracing were critical for infection control in the absence of other mitigation interventions. When other mitigation interventions were considered (such as moving teaching online, social/physical distancing, and the use of face coverings) the additional value of screening for infection control was limited. Multiple interventions will be needed to control infection spread within the university setting and the interaction with the wider community is an important consideration. Isolation of identified cases and quarantine of contacts is likely to lead to large numbers of students requiring educational, psychological and behavioural support and will likely have a large impact on the attendance of students (and staff), necessitating online options for teaching, even where in-person classes are taking place. Models were highly sensitive to assumptions in the parameters, including the number and type of individuals’ contacts, number of contacts traced, frequency of screening and delays in testing. Future models could aid policy decisions by considering the incremental benefit of multiple interventions and using empirical data on mixing within the university community and with the wider community where available. Universities will need to be able to adapt quickly to the evolving situation locally to support the health and wellbeing of the university and wider communities.
Maternal and child genetic liability for smoking and caffeine consumption and
child mental health: An intergenerational genetic risk score analysis in the
ALSPAC cohort
Authors: Schellhas Laura , Haan Elis , Easey Kayleigh E , Wootton Robyn E , Sallis Hannah M , Sharp Gemma C , Munafò Marcus R , Zuccolo Luisa 
Published: September 2020

ABSTRACT

Background and aims
Previous studies suggest an association between maternal tobacco and
caffeine consumption during and outside of pregnancy and offspring mental
health. We aimed to separate effects of the maternal environment
(intrauterine or postnatal) from pleiotropic genetic effects.

Design
Secondary analysis of a longitudinal study. We 1) validated smoking and
caffeine genetic risk scores (GRS) derived from published GWAS for use
during pregnancy, 2) compared estimated effects of maternal and offspring
GRS on childhood mental health outcomes, and 3) tested associations between
maternal and offspring GRS on their respective outcomes.

Setting
We used data from a longitudinal birth cohort study from England, the
Avon Longitudinal Study of Parents and Children (ALSPAC).

Participants
Our sample included 7921 mothers and 7964 offspring.

Measurements
Mental health and non-mental health phenotypes were derived from
questionnaires and clinical assessments: 79 maternal phenotypes assessed
during and outside of pregnancy, and 71 offspring phenotypes assessed in
childhood (<10 years) and adolescence (11-18 years).

Findings
The maternal smoking and caffeine GRS were associated with maternal
smoking and caffeine consumption during pregnancy (2nd
trimester: Psmoking = 3.0×10−7,
Pcaffeine = 3.28×10−5). Both
the maternal and offspring smoking GRS showed evidence of association with
reduced childhood anxiety symptoms (βmaternal = -0.033;
βoffspring= -0.031) and increased conduct disorder
symptoms (βmaternal= 0.024;
βoffspring= 0.030), after correcting for multiple
testing. Finally, the maternal and offspring smoking GRS were associated
with phenotypes related to sensation seeking behaviours in mothers and
adolescence (e.g., increased symptoms of externalising disorders,
extraversion, and monotony avoidance). The caffeine GRS showed weaker
evidence for associations with mental health outcomes.

Conclusions
We did not find strong evidence that maternal smoking and caffeine
genetic risk scores (GRS) have a causal effect on offspring mental health
outcomes. Our results confirm that the smoking GRS also captures liability
for sensation seeking personality traits.
Insufficient fibrinolysis in COVID-19: a systematic review of thrombolysis based on meta-analysis and meta-regression
Authors: Ji Hong-Long , Su Zhenlei , Zhao Runzhen , Komissarov Andrey A. , Yi Guohua , Liu Shan-Lu , Idell Steven , Matthay Michael A. 
Published: September 2020

SummaryBackgroundHow aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists. To investigate whether abnormal fibrinolysis is a culprit or protector or both, we associated elevated plasma D-dimer with clinical variables to identify a panoramic view of the derangements of fibrinolysis that contribute to the pathogenesis of COVID-19 based on studies available in the literature.MethodsWe performed this systematic review based on both meta-analysis and meta-regression to compute the correlation of D-dimer at admission with clinical features of COVID-19 patients in retrospective studies or case series. We searched the databases until Aug 18, 2020, with no limitations by language. The first hits were screened, data extracted, and analyzed in duplicate. We did the random-effects meta-analyses and meta-regressions (both univariate and multivariate). D-dimer associated clinical variables and potential mechanisms were schematically reasoned and graphed.FindingsOur search identified 42 observational, or retrospective, or case series from six countries (n=14,862 patients) with all races and ages from 1 to 98-year-old. The weighted mean difference of D-dimer was 0.97 μg/mL (95% CI 0.65, 1.29) between relatively mild (or healthy control) and severely affected groups with significant publication bias. Univariate meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels, including 3 demographics, 5 comorbidities, 22 laboratory tests, 18 organ injury biomarkers, 8 severe complications, and 2 outcomes (discharge and death). Of these, 11 readouts were negatively associated with the level of plasma D-dimer. Further, age and gender were confounding factors for the identified D-dimer associated variables. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K+, glucose, SpO2, BUN, bilirubin, ALT, AST, systolic blood pressure, and CK. We thus propose that insufficient hyperfibrinolysis (fibrinolysis is accelerated but unable to prevent adverse clinical impact for clinical deterioration COVID-19) as a peculiar mechanism.InterpretationThe findings of this meta-analysis- and meta-regression-based systematic review supports elevated D-dimer as an independent predictor for mortality and severe complications. D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and locally (i.e., in the lung) hyperactive derangements of fibrinolysis. D-dimer and associated clinical biomarkers and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.FundingNational Institute of Health.