bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of total pre-existing comorbidities with stroke risk: a large-scale community-based cohort study from China
Authors: Zhang Ya , Wang Cuicui , Liu Dong , Zhou Zhengyuan , Gu Shujun , Zuo Hui 
Published: October 2021

Abstract
Background
Comorbidities, any other coexisting diseases in patients with a particular index disease, are known to increase the mortality of a stroke. However, the association of pre-existing comorbidities with stroke risk has not been fully studied.

Methods
This study included 16,246 adults from a prospective community-based cohort with a baseline survey conducted in 2013 in China. Participants were followed up with hospitalization records and the Cause of Death Registry. The association of eight pre-existing comorbidities (coronary heart disease, hyperlipidemia, hypertension, diabetes, previous stroke, chronic obstructive pulmonary disease, nephropathy, and cancer) with stroke risk was analyzed using the Cox proportional hazard model in 2020.

Results
At a median follow-up of 5.5 years, a total of 449 participants (206 men and 243 women) developed a stroke. Four pre-existing comorbidities (hypertension, congenital heart disease, previous stroke, and diabetes) were independently and positively associated with the risk for all types of stroke. The adjusted hazard ratios for participants with only 1 and ≥ 2 pre-existing comorbidities compared with those without pre-existing conditions were 1.96 (95% CI: 1.44, 2.67; P < 0.001) and 2.87 (95% CI; 2.09, 3.94; P < 0.001) for total stroke, respectively. Moreover, male and female participants with a combination of increased age and a higher number of pre-existing comorbidities experienced the greatest risk of stroke.

Conclusions
The number of pre-existing comorbidities was independently associated with an increased risk of stroke. There was a synergic effect between increased age and a higher number of pre-existing comorbidities on stroke occurrence. Our novel findings emphasize the importance and potential application of pre-existing comorbidities as a risk indicator in stroke prevention.
Barriers and strategies to successful tuberculosis treatment in a high-burden tuberculosis setting: a qualitative study from the patient’s perspective
Authors: Pradipta Ivan S. , Idrus Lusiana R. , Probandari Ari , Lestari Bony W. , Diantini Ajeng , Alffenaar Jan-Willem C. , Hak Eelko 
Published: October 2021

Abstract
Background
Previously treated tuberculosis (TB) patients are a widely reported risk factor for multidrug-resistant tuberculosis. Identifying patients’ problems during treatment is necessary to control TB, especially in a high-burden setting. We therefore explored barriers to successful TB treatment from the patients’ perspective, aiming to identify potential patient-centred care strategies to improve TB treatment outcome in Indonesia.

Methods
A qualitative study was conducted in a province of Indonesia with high TB prevalence. Participants from various backgrounds (i.e., TB patients, physicians, nurses, pharmacists, TB activist, TB programmers at the district and primary care levels) were subject to in-depth interviews and focus group discussions (FGDs). All interviews and FGDs were transcribed verbatim from audio and visual recordings and the respective transcriptions were used for data analysis. Barriers were constructed by interpreting the codes’ pattern and co-occurrence. The information’s trustworthiness and credibility were established using information saturation, participant validation and triangulation approaches. Data were inductively analysed using the Atlas.ti 8.4 software and reported following the COREQ 32-items.

Results
We interviewed 63 of the 66 pre-defined participants and identified 15 barriers. The barriers were classified into three themes, i.e., socio-demography and economy; knowledge and perception and TB treatment. Since the barriers can be interrelated, we determined five main barriers across all barrier themes, i.e., lack of TB knowledge, stigmatisation, long distance to the health facility, adverse drug reaction and loss of household income.

Conclusion
The main treatment barriers can be considered to strengthen patient-centred care for TB patients in Indonesia. A multi-component approach including TB patients, healthcare providers, broad community and policy makers is required to improve TB treatment success.
Uses of equipoise in discussions of the ethics of randomized controlled trials of COVID-19 therapies
Authors: Nix Hayden P. , Weijer Charles 
Published: October 2021

Abstract
Background
Early in the COVID-19 pandemic, the urgent need to discover effective therapies for COVID-19 prompted questions about the ethical problem of randomization along with its widely accepted solution: equipoise. In this scoping review, uses of equipoise in discussions of randomized controlled trials (RCT) of COVID-19 therapies are evaluated to answer three questions. First, how has equipoise been applied to COVID-19 research? Second, has equipoise been employed accurately? And third, do concerns about equipoise pose a barrier to the ethical conduct of COVID-19 RCTs?

Methods
Google Scholar and Pubmed were searched for articles containing substantial discussion about equipoise and COVID-19 RCTs. 347 article titles were screened, 91 full text articles were assessed, and 48 articles were included. Uses of equipoise were analyzed and abstracted into seven categories.

Results and discussion
Approximately two-thirds of articles (33/48 articles) used equipoise in a way that is consistent with the concept. They invoked equipoise to support (1) RCTs of specific therapies, (2) RCTs in general, and (3) the early termination of RCTs after achieving the primary outcome. Approximately one-third of articles (15/48 articles) used equipoise in a manner that is inconsistent with the concept. These articles argued that physician preference, widespread use of unproven therapies, patient preference, or expectation of therapeutic benefit may undermine equipoise and render RCTs unethical. In each case, the purported ethical problem can be resolved by correcting the use of equipoise.

Conclusions
Our findings highlight the continued relevance of equipoise as it supports the conduct of well-conceived RCTs and provides moral guidance to physicians and researchers as they search for effective therapies for COVID-19.
Improving mental health care transitions through information capture during admission to inpatient mental health services: a quality improvement study
Authors: Tyler Natasha , Wright Nicola , Gregoriou Kyriakos , Waring Justin 
Published: October 2021

Abstract
Background
Many interventions aim to improve the transition from ward to community at the time of discharge, with varying success. Guidelines suggest that discharge planning should begin at admission, but in reality this is ideal rather than standard practice. We aimed to develop a novel information capture tool during admission that facilitates and accelerates discharge.

Methods
A quality improvement study to develop, implement and evaluate a novel tool that improves information capture upon admission to acute mental health wards within a single English National Health Service (NHS) trust. We developed the tool by synthesising existing evidence and working with multi-agency and multi-disciplinary professionals in two co-design workshops. During implementation the tool was piloted on three wards. Ethnographic observations (145 h) and interviews (45) were used to evaluate the implementation of the tool across the three wards. Thematic synthesis was used to consolidate the findings.

Results
The tool developed considerably as the process evolved. The finished product is a list of 10 information categories that should be captured from external agencies upon admission to hospital to facilitate discharge planning to community settings. Reported advantages of the tool were: (1) facilitating confidence in junior staff to legitimately question the suitability of a patient for an acute ward (2) collecting and storing essential information in a single accessible place that can be used throughout the care pathway and (3) collecting information from the services/agencies to which patients will eventually be discharged.

Conclusions
Improving the quality of information at admission has the potential to facilitate and accelerate discharge. The novel tool provides a framework for capturing this information that can be incorporated into existing information systems. However, the introduction of the tool exacerbated complex, fragile distributed team dynamics, highlighting the importance of sociocultural context in information flow transitional interventions within distributed teams.
Respiratory function declines in children with asthma associated with chemical species of fine particulate matter (PM2.5) in Nagasaki, Japan
Authors: Kim Yoonhee , Park Eun Ha , Ng Chris Fook Sheng , Chung Yeonseung , Hashimoto Kunio , Tashiro Kasumi , Hasunuma Hideki , Doi Masataka , Tamura Kei , Moriuchi Hiroyuki , Nishiwaki Yuji , Kim Hwajin , Yi Seung-Muk , Kim Ho , Hashizume Masahiro 
Published: October 2021

Abstract
Background
The differential effects of PM2.5 fractions on children’s lung function remain inconclusive. This study aimed to examine whether lung function in asthmatic children was associated with increased PM2.5 fractions in urban areas in Nagasaki prefecture, Japan, where the air pollution level is relatively low but influenced by transboundary air pollution.

Methods
We conducted a multiyear panel study of 73 asthmatic children (boys, 60.3%; mean age, 8.2 years) spanning spring 2014–2016 in two cities. We collected self-measured peak expiratory flow (PEF) twice a day and daily time-series data for PM2.5 total mass and its chemical species. We fitted a linear mixed effects model to examine short-term associations between PEF and PM2.5, adjusting for individual and time-varying confounders. A generalized linear mixed effects model was also used to estimate the association for worsening asthma defined by severe PEF decline. Back-trajectory and cluster analyses were used to investigate the long-range transboundary PM2.5 in the study areas.

Results
We found that morning PEFs were adversely associated with higher levels of sulfate (− 1.61 L/min; 95% CI: − 3.07, − 0.15) in Nagasaki city and organic carbon (OC) (− 1.02 L/min; 95% CI: − 1.94, − 0.09) in Isahaya city, per interquartile range (IQR) increase at lag1. In addition, we observed consistent findings for worsening asthma, with higher odds of severe PEF decline in the morning for sulfate (odds ratio (OR) = 2.31; 95% CI: 1.12, 4.77) and ammonium (OR = 1.73; 95% CI: 1.06, 2.84) in Nagasaki city and OC (OR = 1.51; 95% CI: 1.06, 2.15) in Isahaya city, per IQR increase at lag1. The significant chemical species were higher on days that could be largely attributed to the path of Northeast China origin (for sulfate and ammonium) or both the same path and local sources (for OC) than by other clusters.

Conclusions
This study provides evidence of the differential effects of PM2.5 fractions on lung function among asthmatic children in urban areas, where the Japanese national standards of air quality have been nearly met. Continuous efforts to promote mitigation actions and public awareness of hazardous transboundary air pollution are needed to protect susceptible children with asthma.
A case of ectopic pancreas of the stomach accompanied by intraductal papillary mucinous neoplasm with GNAS mutation
Authors: Nambu Naoko , Yamasaki Takashi , Nakagomi Nami , Kumamoto Tsutomu , Nakamura Tatsuro , Tamura Akio , Tomita Toshihiko , Miwa Hiroto , Shinohara Hisashi , Hirota Seiichi 
Published: October 2021

Abstract
Background
Ectopic pancreas is basically a benign disease and is not always necessary to be removed. However, all types of neoplasms occurring in the normal pancreas such as ductal adenocarcinomas and intraductal papillary mucinous neoplasms (IPMNs) may develop even within ectopic pancreas. We recently encountered an extremely rare case of ectopic pancreas in the gastric antrum associated with IPMN possessing a GNAS mutation.

Case presentation
A 71-year-old Japanese woman complained of epigastric pain. Computed tomography and upper gastrointestinal endoscopy showed an intramural cystic mass in the antrum of the stomach. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy did not give a definitive diagnosis, and the patient underwent resection of the lesion. Histology of the resected specimen showed that the gastric intramural lesion was ectopic pancreas. Moreover, the lesion contained dilated duct components with tubulo-villous epithelial proliferation consistent with pancreatic IPMN. Since the covering epithelial cells had highly atypical nuclei, the lesion was diagnosed as IPMN with high grade dysplasia. Immunohistochemistry showed that the IPMN component showed to be MUC2-, MUC5AC-, and CDX2-positive but MUC1- and MUC6-negative. Mutational analyses using genomic DNA revealed that the IPMN component had a mutation of GNAS at exon 8 (Arg201Cys).

Conclusion
We finally diagnosed this case as gastric ectopic pancreas accompanied by intestinal type IPMN with high grade dysplasia possessing GNAS mutation. Although there were 17 cases of ectopic pancreas with IPMN including 6 cases of gastric ones reported in the English literature, this is the first case of ectopic pancreas with IPMN which was proved to have GNAS mutation. Intimate preoperative examinations including imaging analyses and EUS-FNA biopsy/cytology are recommended to decide whether the lesion has to be resected or not even if they are not effective for getting the right diagnosis.
RSV: perspectives to strengthen the need for protection in all infants
Authors: Navarro Alonso Jose Antonio , Bont Louis J. , Bozzola Elena , Herting Egbert , Lega Federico , Mader Silke , Nunes Marta C. , Ramilo Octavio , Valiotis George , Olivier Catherine Weil , Yates Ann , Faust Saul N. 
Published: October 2021

AbstractRespiratory syncytial virus (RSV)—the most common viral cause of bronchiolitis—is a significant cause of serious illness among young children between the ages of 0–5 years and is especially concerning in the first year of life. Globally, RSV is a common cause of childhood acute lower respiratory illness (ALRI) and a major cause of hospital admissions in young children and infants and represents a substantial burden for health-care systems. This burden is strongly felt as there are currently no effective preventative options that are available for all infants. However, a renaissance in RSV prevention strategies is unfolding, with several new prophylactic options such as monoclonal antibodies and maternal vaccinations that are soon to be available. A key concern is that health decision makers and systems may not be ready to take full advantage of forthcoming technological innovations. A multi-stakeholder approach is necessary to bridge data gaps to fully utilise upcoming options. Knowledge must be made available at multiple levels to ensure that parents and doctors are aware of preventative options, but also to ensure that stakeholders and policymakers are given the necessary information to best advise implementation strategies.
Revisiting kinorhynch segmentation: variation of segmental patterns in the nervous system of three aberrant species
Authors: Herranz Maria , Park Taeseo , Di Domenico Maikon , Leander Brian S. , Sørensen Martin V. , Worsaae Katrine 
Published: October 2021

AbstractBackgroundKinorhynch segmentation differs from the patterns found in Chordata, Arthropoda and Annelida which have coeloms and circulatory systems. Due to these differences and their obsolete status as ‘Aschelminthes’, the microscopic kinorhynchs are often not acknowledged as segmented bilaterians. Yet, morphological studies have shown a conserved segmental arrangement of ectodermal and mesodermal organ systems with spatial correspondence along the anterior-posterior axis. However, a few aberrant kinorhynch lineages present a worm-like body plan with thin cuticle and less distinct segmentation, and thus their study may aid to shed new light on the evolution of segmental patterns within Kinorhyncha.ResultsHere we found the nervous system in the aberrantCateria styxandFranciscideres kalenesosto be clearly segmental, and similar to those of non-aberrant kinorhynchs; hereby not mirroring their otherwise aberrant and posteriorly shifted myoanatomy. InZelinkaderes yong, however, the segmental arrangement of the nervous system is also shifted posteriorly and misaligned with respect to the cuticular segmentation.ConclusionsThe morphological disparity together with the distant phylogenetic positions ofF. kalenesos,C. styxandZ. yongsupport a convergent origin of aberrant appearances and segmental mismatches within Kinorhyncha.
Novel alterations in IFT172 and KIFAP3 may induce basal cell carcinoma
Authors: Onodera Shoko , Morita Nana , Nakamura Yuriko , Takahashi Shinichi , Hashimoto Kazuhiko , Nomura Takeshi , Katakura Akira , Kosaki Kenjiro , Azuma Toshifumi 
Published: October 2021

AbstractBackgroundBasal cell carcinoma (BCC) is the most commonly occurring neoplasm in patients with Gorlin syndrome. It is widely accepted that multiple basal cell carcinomas simultaneously develop in middle-aged patients with this syndrome. However, the presence of driver genes other than thePTCH1in Gorlin syndrome has not been explored. This study aimed to identify common gene mutations other thanPTCH1in simultaneously occurring basal cell carcinomas in patients with Gorlin syndrome via exome sequencing analysis.MethodsNext-generation sequencing analysis was performed using four basal cell carcinoma samples, one dental keratinocyte sample, and two epidermoid cyst samples, which were surgically resected from one patient with Gorlin syndrome on the same day.ResultsOverall, 282 somatic mutations were identified in the neoplasms. No additional somatic mutations inPTCH1,PTCH2,TP53, andSMOwere identified. However, enrichment analysis showed that multiple genes, such asIFT172andKIFAP3,could regulate ciliary functions important for Hedgehog signaling.ConclusionThe development of BCCs in patients with Gorlin syndrome may be triggered by mutations that cause substantial dysfunction of cilia.
The Youth Aware of Mental Health program in Australian Secondary Schools: 3- and 6-month outcomes
Authors: McGillivray Lauren , Shand Fiona , Calear Alison L. , Batterham Philip J. , Rheinberger Demee , Chen Nicola A. , Burnett Alexander , Torok Michelle 
Published: October 2021

AbstractObjectiveThe evidence base for suicide prevention programs in Australian schools is limited. The aim of this study was to examine the impact of a universal, mental health promotion and suicide prevention program—Youth Aware of Mental Health (YAM)—on suicidal ideation, mental health, and help-seeking in Australian secondary school students from baseline to post-intervention and 6-month follow up.MethodsUsing a single-arm design, the YAM program was delivered to Year 9 students (13–16 years) in secondary schools located within four regions across New South Wales, Australia. A structured self-report questionnaire using validated scales was administered at each time point. Linear mixed-effects modelling was used to examine differences in suicidal ideation scores across time, while accounting for random effects of individual schools.ResultsSuicidal ideation reduced significantly from baseline to post, and from baseline to follow-up (p < 0.001). Depression severity declined (p < 0.001) and help-seeking intentions increased (p < 0.001) at post-intervention and 6- months following the intervention period. No suicide deaths were reported for any study participants.ConclusionThe current findings provide preliminary evidence that the YAM program is a promising preventive intervention for Australian schools, particularly for reducing suicidal ideation, depression and increasing help-seeking intentions in young people. The implementation of YAM in a large number of schools across New South Wales demonstrates the feasibility, and acceptability by schools, of implementing this program at scale.Trial registration:ANZCTR, ACTRN12619000338167. Registered 5 March 2019—Retrospectively registered,http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376989&isReview=true.
Innovative clinical trial design and delivery: a phase 3 COVID-19 post-exposure prophylaxis study in skilled nursing and assisted living facilities (BLAZE-2)
Authors: Knorr Jack , Tuttle Jay L. , Sabo Janelle A. , East Dawn H. , Price Karen L. , Shen Lei 
Published: October 2021

AbstractThe efficient community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the current pandemic of coronavirus disease-2019 (COVID-19), which in severe and critical cases results in progressive pulmonary infection, complicated by respiratory failure, with a high prevalence of acute respiratory distress syndrome. Of all age groups, older adults have the greatest risk of severe COVID-19 and the associated complications. Globally, there are many reports of the rapid spread of COVID-19 among residents of skilled nursing facilities, with high associated rates of morbidity and mortality. With over 1.3 million residents in nursing home care in the USA, there is an urgent need for therapeutic strategies to prevent COVID-19 in these populations.Lilly, in collaboration with the National Institute of Allergy and Infectious Diseases, conducted the BLAZE-2 trial to evaluate the efficacy and safety of the monoclonal antibody bamlanivimab (LY3819253) in preventing SARS-CoV-2 infection and COVID-19, defined as symptomatic infection, in skilled nursing and assisted living facilities. It is a phase 3 randomized, double-blind, placebo-controlled trial, where participants were randomized to bamlanivimab (4200 mg) or placebo and then followed up for 24 weeks. Conducting a trial in the midst of a pandemic in these facilities poses several challenges, including a vulnerable elderly population, travel restrictions, supply chain interruptions, and defining the target population. The operational challenges were addressed by the innovative use of mobile research units which are customized, equipped, and staffed to support BLAZE-2 randomization and participant dosing within the skilled nursing and assisted living facilities. Herein, we describe the design of the study, the analytics behind facility selection, and an innovative operational model.