bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seropositivity of SARS-CoV-2 in an unvaccinated cohort in British Columbia, Canada: a cross-sectional survey with dried blood spot samples
Authors: Racey C Sarai , Booth Amy , Albert Arianne , Smith Laurie W , Krajden Mel , Murray Melanie C M , Côté Hélène C F , Gottschlich Anna , Goldfarb David M , Sadarangani Manish , Galea Liisa A M , Kaida Angela , Brotto Lori A , Ogilvie Gina S 
Published: August 2022

ObjectivesGathering population-based data on prevalence of SARS-CoV-2 infection is vital to the public health response and planning. Current seroprevalence data in BC are limited with respect to considerations of how socioeconomic and demographic factors, such as age, sex, gender, income, identifying as a visibility minority and occupation, are related to SARS-CoV-2 antibody detection due to infection-acquired immunity. We aimed to estimate the SARS-CoV-2 seropositivity in a cohort of British Columbians, using at-home self-collected dried blood spot (DBS) samples.DesignThis cross-sectional study included online surveys that collected sociodemographic and COVID-19 vaccine receipt information, and an at-home DBS collection kit.SettingBritish Columbia (BC), Canada.ParticipantsEligible participants were aged 25–69 years and residents of BC.Primary outcome measureSARS-CoV-2 anti-spike IgG antibody detection in unvaccinated individuals. Adjusted incidence rate ratios (aIRR) explored factors associated with seropositivity.ResultsSARS-CoV-2 serology was performed on a total of 4048 unvaccinated participants 25–69 years of age who submitted DBS samples taken from November 2020 to June 2021. A total of 118 seropositive cases were identified, for an estimated overall seropositivity of 2.92% (95% CI 2.42% to 3.48%). Participants identifying as a visible minority had a higher seropositivity, 5.1% vs 2.6% (p=0.003), compared with non-visible minority participants. After adjustment by age and sex, identifying as a visible minority (aIRR=1.85, 95% CI 1.20 to 2.84) remained the only significant factor associated with SARS-CoV-2 antibody detection in this cohort of unvaccinated individuals.ConclusionsSARS-CoV-2 seropositivity in the BC population due to infection-acquired immunity was low. Seropositivity indicated that among those unvaccinated, visible minority communities have been most impacted. Continued monitoring of SARS-CoV-2 serology due to both infection-acquired and vaccine-acquired immunity will be vital in public health planning and pandemic response.
Qualitative study exploring the well-being experiences of paediatric critical care consultants working in the UK during the COVID-19 pandemic
Authors: Butcher Isabelle , Saeed Sumayyah , Morrison Rachael , Donnelly Peter , Shaw Rachel 
Published: August 2022

ObjectivesThe aim of this study was to examine the well-being experiences of consultants working in paediatric critical care (PCC) settings in the UK during the COVID-19 pandemic.DesignQualitative design using individual interviews and thematic analysis.SettingPCC.ParticipantsEleven medical consultants working in PCC in a range of PCC settings/transport teams in the UK from nine units participated. Participants ranged in years of experience as a consultant from four to 23 years.MethodsA set of open semistructured questions were used to elicit information about participants’ experiences of workplace well-being. Interviews were audiorecorded and transcribed.FindingsThematic analysis identified six themes and data saturation was reached. These were as follows: (1) positive and negative impact of working during COVID-19, (2) job satisfaction and public scrutiny in the unique environment of PCC, (3) supporting the workforce through modified shift work, (4) perceptions of support and recognition offered from the hospital management, (5) successful coping strategies are personal and adaptive, and (6) importance of civility and good teamworkConclusionFindings show that consultants’ well-being is challenged in a number of ways and that the solutions to the problem of burn-out are multifaceted. Action is required from individual consultants, clinical teams, hospital management and national regulatory bodies. Our work corroborates the recent General Medical Council report highlighting doctors’ core needs for well-being: autonomy, belonging, competence. Burn-out is a long-term problem, requiring sustainable solutions. Future research needs to develop and evaluate the effectiveness of evidence-based interventions to improve consultants’ well-being. Trials of effectiveness need to present evidence that will persuade hospital management to invest in their consultants’ well-being within the economic context of reduced budgets and limited PCC workforce.
Comparison of obstructive sleep apnoea prevalence and severity across WHO pulmonary hypertension groups
Authors: Simonson Joseph L , Pandya Dhwani , Khan Sara , Greenberg Harly E , Talwar Arunabh 
Published: August 2022

IntroductionPulmonary hypertension is classified into five groups in the WHO classification system. Patients with pulmonary hypertension often have comorbid obstructive sleep apnoea (OSA), yet the prevalence and severity of OSA in each of the WHO pulmonary hypertension groups have not been well established.MethodsTo compare the prevalence and severity of OSA between WHO pulmonary hypertension groups, we performed a retrospective cohort study, including patients who had polysomnography or a home sleep study and confirmed pulmonary hypertension on right heart catheterisation. The primary outcomes of OSA prevalence and severity were measured by median apnoea hypopnea index (AHI) or respiratory event index (REI) and were compared by WHO pulmonary hypertension group. Multivariable negative binomial regression was used to evaluate the association between the outcome of OSA severity by AHI or REI and WHO group.ResultsAmong the cohort of 132 patients, OSA was common in all WHO pulmonary hypertension groups but was most common and most severe in WHO group II pulmonary hypertension. Median AHI or REI in WHO group II was 12.0 events/hour compared with 2.8 in group I, 3.7 in group III, 10.0 in group IV and 6.4 in group V. Multivariable negative binomial regression showed about a twofold increase in AHI or REI in WHO group II compared with WHO group I pulmonary hypertension.DiscussionOur findings demonstrate that OSA deserves greater consideration as a treatable comorbidity that may affect pulmonary haemodynamics and quality of life in patients with pulmonary hypertension across all WHO groups.
Pressure–flow responses to exercise in aortic stenosis, mitral regurgitation and diastolic dysfunction
Authors: Andersen Mads J , Wolsk Emil , Bakkestrøm Rine , Christensen Nicolaj , Carter-Storch Rasmus , Omar Massar , Dahl Jordi S , Frederiksen Peter H , Borlaug Barry , Gustafsson Finn , Hassager Christian , Moller Jacob E 
Published: August 2022

BackgroundHaemodynamic exercise testing is important for evaluating patients with dyspnoea on exertion and preserved ejection fraction. Despite very different pathologies, patients with pressure (aortic stenosis (AS)) and volume (mitral regurgitation (MR)) overload and diastolic dysfunction after recent acute myocardial infarction (AMI) reach similar filling pressure levels with exercise. The pressure–flow relationships (the association between change in cardiac output (∆CO) and change in pulmonary arterial wedge pressure (∆PAWP) may provide insight into haemodynamic adaptation to exercise in these groups.Methods and resultsOne hundred sixty-eight subjects aged >50 years with a left ventricular ejection fraction of ≥50% underwent invasive exercise testing. They were enrolled in four different studies: AS (40 patients), AMI (52 patients), MR (43 patients) and 33 healthy subjects. Haemodynamic data were measured at rest, at 25 W, 75 W and at peak exercise. In all groups, PAWP increased with exercise. The greatest increase was observed in patients with AMI (from 12.7±3.9 mm Hg to 33.1±8.2 mm Hg, p<0.0001) and patients with AS (from 11.8±3.9 mm Hg to 31.4±6.1 mm Hg, p<0.0001), and the smallest was observed in healthy subjects (from 8.3±2.4 mm Hg to 21.1±7.5 mm Hg, p<0.0001). In all groups, the relative pressure increase was greatest at the beginning of the exercise. CO increased most in healthy patients (from 5.3±1.1 to 16.0±3.0 L/min, p<0.0001) and least in patients with AS (from 5.3±1.2 L/min to 12.4±2.6 L/min, p<0.0001). The pressure–flow relationships (∆PAWP/∆CO) and differed among groups (p=0.02). In all groups, the pressure–flow relationship was steepest in the initial phase of the exercise test. The AMI and AS groups (2.3±1.2 mm Hg/L/min and 3.0±1.3 mm Hg/L/min, AMI and AS, respectively) had the largest overall pressure–flow relationship; the healthy group had the smallest initially and at peak exercise (1.3±1.1 mm Hg/L/min) followed by MR group (1.9±1.4 mm Hg/L/min).ConclusionThe pressure–flow relationship was steepest in the initial phase of the exercise test in all groups. The pressure–flow relationship differs between groups.Trial registration numbersNCT01974557,NCT01046838,NCT02961647andNCT02395107.
First estimates of diffuse gastric cancer risks for carriers ofCTNNA1germline pathogenic variants
Authors: Coudert Marie , Drouet Youenn , Delhomelle Hélène , Svrcek Magali , Benusiglio Patrick R , Coulet Florence , Clark Dana Farengo , Katona Bryson W , van Hest Liselotte P , van der Kolk Lizet E , Cats Annemieke , van Dieren Jolanda M , Nehoray Bita , Slavin Thomas , Spier Isabel , Hüneburg Robert , Lobo Silvana , Oliveira Carla , Boussemart Lise , Masson Laure , Chiesa Jean , Schwartz Mathias , Buecher Bruno , Golmard Lisa , Bouvier Anne-Marie , Bonadona Valérie , Stoppa-lyonnet Dominique , Lasset Christine , Colas Chrystelle 
Published: August 2022

BackgroundPathogenic variants (PV) ofCTNNA1are found in families fulfilling criteria for hereditary diffuse gastric cancer (HDGC) but no risk estimates were available until now. The aim of this study is to evaluate diffuse gastric cancer (DGC) risks for carriers of germlineCTNNA1PV.MethodsData from published CTNNA1 families were updated and new families were identified through international collaborations. The cumulative risk of DGC by age for PV carriers was estimated with the genotype restricted likelihood (GRL) method, taking into account non-genotyped individuals and conditioning on all observed phenotypes and genotypes of the index case to obtain unbiased estimates. A non-parametric (NP) and the Weibull functions were used to model the shape of penetrance function with the GRL. Kaplan-Meier incidence curve and standardised incidence ratios were also computed. A ‘leave-one-out’ strategy was used to evaluate estimate uncertainty.ResultsThirteen families with 46 carriers of PV were included. The cumulative risks of DGC at 80 years for carriers ofCTNNA1PV are 49% and 57%, respectively with the Weibull GRL and NP GRL methods. Risk ratios to population incidence reach particularly high values at early ages and decrease with age. At 40 years, they are equal to 65 and 833, respectively with the Weibull GRL and NP GRL.ConclusionThis is the largest series ofCTNNA1families that provides the first risk estimates of GC. These data will help to improve management and surveillance for these patients and support inclusion ofCTNNA1in germline testing panels.
Sustained Supratherapeutic Paclitaxel Delivery Enhances Irreversible Sarcoma Cell Death
Authors: Blessing William A. , Digesu Christopher S. , Liu Rong , Mahvi David A. , Tal-mason Aya , Kumar Anil , Hachey Krista J. , Colby Aaron H. , Korunes-Miller Jenny T. , Agar Natalie , Regan Michael S. , Shih Angela , Raut Chandrajit P. , Grinstaff Mark W. , Colson Yolonda L. 
Published: August 2022

Abstract
Risk of locoregional recurrence after sarcoma resection is high, increasing both morbidity and mortality. Intraoperative implantation of paclitaxel (PTX)-eluting polymer films locally delivers sustained, supratherapeutic PTX concentrations to the tumor bed that are not clinically feasible with systemic therapy, thereby reducing recurrence and improving survival in a murine model of recurrent sarcoma. However, the biology underlying increased efficacy of PTX-eluting films is unknown and provides the impetus for this work. In vitro PTX efficacy is time and dose dependent with prolonged exposure significantly decreasing PTX IC50 values for human chondrosarcoma (CS-1) cells (153.9 nmol/L at 4 hours vs. 14.2 nmol/L at 30 hours, P = 0.0001). High-dose PTX significantly inhibits proliferation with in vivo PTX films delivering a dose &gt;130 μmol/L directly to the tumor thereby irreversibly arresting cell cycle and inducing apoptosis in CS-1 as well as patient-derived liposarcoma (LP6) and leiomyosarcoma (LMS20). Supratherapeutic PTX upregulates the expression of p21 in G2–M arrested cells, and irreversibly induces apoptosis followed by cell death, within 4 hours of exposure. Microarray analyses corroborate the finding of poor DNA integrity commonly observed as a final step of apoptosis in CS-1 cells and tumor. Unlike low PTX concentrations at the tumor bed during systemic delivery, supratherapeutic concentrations achieved with PTX-eluting films markedly decrease sarcoma lethality in vivo and offer an alternative paradigm to prevent recurrence.
Relações entre a judicialização de cobertura e a incorporação de tecnologia na saúde suplementar: o caso dos quimioterápicos
Authors: Kozan Julian Ferreira , Magalhães Marina de Almeida 
Published: August 2022

A negativa de cobertura de tratamentos é o principal fator que leva beneficiários de planos de saúde a buscar a justiça, e o motivo central alegado pelas empresas do setor para essa recusa é o fato do tratamento pleiteado não ser contemplado no Rol de Procedimentos e Eventos em Saúde da Agência Nacional de Saúde Suplementar. Este artigo analisou a incorporação de tecnologias em saúde no Brasil, especialmente no setor de saúde suplementar, e a regulação da cobertura de tratamento para câncer pelos planos de saúde, identificando possíveis influências, bem como o sentido da atuação do Poder Judiciário na incorporação de quimioterápicos na saúde suplementar. Para tanto, utilizaram-se dois bancos de dados que, somados, contêm informações sobre todos os acórdãos (1.368), proferidos em segunda instância entre 2015 e 2019 pelo Tribunal de Justiça do Estado de São Paulo, em ações judiciais ajuizadas na Comarca da Capital que demandaram tratamentos quimioterápicos contra operadoras de planos de saúde. Foram explorados em maior detalhe os casos dos dez quimioterápicos mais demandados no escopo considerado. Os resultados do estudo mostraram que, apesar da regulação setorial da saúde suplementar determinar a cobertura de sete dos dez quimioterápicos mais demandados, isso não impediu que ela fosse, ainda assim, negada aos beneficiários. Há, portanto, indicativos de que a atuação do Poder Judiciário, que julgou favoravelmente 96,3% das demandas analisadas, cumpre uma função de enforcement da regulação setorial da incorporação de tecnologias, em contraposição à hipótese de que seria uma via ilegítima para o acesso a tecnologias não cobertas. Trata-se, a partir dessa perspectiva, de uma importante instância de garantia do direito à saúde dos beneficiários de planos privados de saúde.
Routine Pressure Wire Assessment Versus Conventional Angiography in the Management of Patients With Coronary Artery Disease: The RIPCORD 2 Trial
Authors: Stables Rodney H. , Mullen Liam J. , Elguindy Mostafa , Nicholas Zoe , Aboul-Enien Yousra H. , Kemp Ian , O’Kane Peter , Hobson Alex , Johnson Thomas W. , Khan Sohail Q. , Wheatcroft Stephen B. , Garg Scot , Zaman Azfar G. , Mamas Mamas A. , Nolan James , Jadhav Sachin , Berry Colin , Watkins Stuart , Hildick-Smith David , Gunn Julian , Conway Dwayne , Hoye Angels , Fazal Iftikhar A. , Hanratty Colm G. , De Bruyne Bernard , Curzen Nick 
Published: August 2022

Background:
Measurement of fractional flow reserve (FFR) has an established role in guiding percutaneous coronary intervention. We tested the hypothesis that, at the stage of diagnostic invasive coronary angiography, systematic FFR-guided assessment of coronary artery disease would be superior, in terms of resource use and quality of life, to assessment by angiography alone.

Methods:
We performed an open-label, randomized, controlled trial in 17 UK centers, recruiting 1100 patients undergoing invasive coronary angiography for the investigation of stable angina or non–ST-segment–elevation myocardial infarction. Patients were randomized to either angiography alone (angiography) or angiography with systematic pressure wire assessment of all epicardial vessels >2.25 mm in diameter (angiography+FFR). The coprimary outcomes assessed at 1 year were National Health Service hospital costs and quality of life. Prespecified secondary outcomes included clinical events.

Results:

In the angiography+FFR arm, the median number of vessels examined was 4 (interquartile range, 3–5). The median hospital costs were similar: angiography, £4136 (interquartile range, £2613–£7015); and angiography+FFR, £4510 (£2721–£7415;
P
=0.137). There was no difference in median quality of life using the visual analog scale of the EuroQol EQ-5D-5L: angiography, 75 (interquartile range, 60–87); and angiography+FFR, 75 (interquartile range, 60–90;
P
=0.88). The number of clinical events was as follows: deaths, 5 versus 8; strokes, 3 versus 4; myocardial infarctions, 23 versus 22; and unplanned revascularizations, 26 versus 33, with a composite hierarchical event rate of 8.7% (48 of 552) for angiography versus 9.5% (52 of 548) for angiography+FFR (
P
=0.64).

Conclusions:
A strategy of systematic FFR assessment compared with angiography alone did not result in a significant reduction in cost or improvement in quality of life.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01070771.
Cardiomyocyte-Specific Long Noncoding RNA Regulates Alternative Splicing of the Triadin Gene in the Heart
Authors: Zhao Yuanbiao , Riching Andrew S. , Knight Walter E. , Chi Congwu , Broadwell Lindsey J. , Du Yanmei , Abdel-Hafiz Mostafa , Ambardekar Amrut V. , Irwin David C. , Proenza Catherine , Xu Hongyan , Leinwand Leslie A. , Walker Lori A. , Woulfe Kathleen C. , Bristow Michael R. , Buttrick Peter M. , Song Kunhua 
Published: August 2022

Background:

Abnormalities in Ca
2+
homeostasis are associated with cardiac arrhythmias and heart failure. Triadin plays an important role in Ca
2+
homeostasis in cardiomyocytes. Alternative splicing of a single
triadin
gene produces multiple triadin isoforms. The cardiac-predominant isoform, mouse MT-1 or human Trisk32, is encoded by
triadin
exons 1 to 8. In humans, mutations in the
triadin
gene that lead to a reduction in Trisk32 levels in the heart can cause cardiac dysfunction and arrhythmias. Decreased levels of Trisk32 in the heart are also common in patients with heart failure. However, mechanisms that maintain triadin isoform composition in the heart remain elusive.

Methods:

We analyzed triadin expression in heart explants from patients with heart failure and cardiac arrhythmias and in hearts from mice carrying a knockout allele for
Trdn-as
, a cardiomyocyte-specific long noncoding RNA encoded by the antisense strand of the
triadin
gene, between exons 9 and 11. Catecholamine challenge with isoproterenol was performed on
Trdn-as
knockout mice to assess the role of
Trdn-as
in cardiac arrhythmogenesis, as assessed by ECG. Ca
2+
transients in adult mouse cardiomyocytes were measured with the IonOptix platform or the GCaMP system. Biochemistry assays, single-molecule fluorescence in situ hybridization, subcellular localization imaging, RNA sequencing, and molecular rescue assays were used to investigate the mechanisms by which
Trdn-as
regulates cardiac function and triadin levels in the heart.

Results:

We report that
Trdn-as
maintains cardiac function, at least in part, by regulating alternative splicing of the
triadin
gene. Knockout of
Trdn-as
in mice downregulates cardiac triadin, impairs Ca
2+
handling, and causes premature death.
Trdn-as
knockout mice are susceptible to cardiac arrhythmias in response to catecholamine challenge. Normalization of cardiac triadin levels in
Trdn-as
knockout cardiomyocytes is sufficient to restore Ca
2+
handling. Last,
Trdn-as
colocalizes and interacts with serine/arginine splicing factors in cardiomyocyte nuclei and is essential for efficient recruitment of splicing factors to
triadin
precursor mRNA.

Conclusions:
These findings reveal regulation of alternative splicing as a novel mechanism by which a long noncoding RNA controls cardiac function. This study indicates potential therapeutics for heart disease by targeting the long noncoding RNA or pathways regulating alternative splicing.
Association Between Device-Measured Physical Activity and Incident Heart Failure: A Prospective Cohort Study of 94 739 UK Biobank Participants
Authors: Ho Frederick K. , Zhou Ziyi , Petermann-Rocha Fanny , Para-Soto Solange , Boonpor Jirapitcha , Welsh Paul , Gill Jason M.R. , Gray Stuart R. , Sattar Naveed , Pell Jill P. , Celis-Morales Carlos 
Published: August 2022

Background:
Studies of objectively measured physical activity (PA) have investigated acute cardiovascular outcomes but not heart failure (HF), an emerging chronic condition. This study aimed to investigate the dose-response relationship between device-measured PA and HF by intensity of PA.

Methods:
This was a prospective cohort study of 94 739 UK Biobank participants who had device-measured PA in 2013 to 2015 and were free from myocardial infarction and HF. PA was measured with a wrist-worn accelerometer, and time spent on light-, moderate-, and vigorous-intensity PA was extracted. Incident HF was ascertained from linked hospital and death records. Cox proportional hazard models with cubic penalized splines were used to study the associations, which were adjusted for sociodemographic and lifestyle factors. Competing risk was handled with cause-specific hazard ratios.

Results:
The overall incidence of HF was 98.5 per 10 000 person-years over a median 6.1 years of follow-up. Compared with participants who undertook no moderate- to vigorous-intensity PA, those who performed 150 to 300 min/wk of moderate-intensity PA (hazard ratio, 0.37 [95% CI, 0.34–0.41]) and 75 to 150 min/wk of vigorous-intensity PA (hazard ratio, 0.34 [95% CI, 0.25–0.46]) were at lower HF risk. The association between vigorous-intensity PA and HF was reverse-J shaped with a potentially lower risk reduction above 150 min/wk.

Conclusions:
Device-measured PA, especially moderate-intensity PA, was associated with a lower risk of HF. Current vigorous-intensity PA recommendations should be encouraged but not increased. In contrast, increasing moderate-intensity PA may be beneficial even among those meeting current recommendations.