bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy ofN-acetylcysteine on idiopathic or postinfective non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis protocol
Authors: Luo Ai , Liu Xuemei , Hu Qiongqiong , Yang Mei , Jiang Hongli , Liu Wei 
Published: March 2022

IntroductionNon-cystic fibrosis (non-CF) bronchiectasis is a chronic pulmonary disorder that causes destruction and permanent dilatation of the airways, resulting in excessive sputum production, repeated infection and inflammation. A need for high-quality and specialised care has been highlighted in recent years.N-acetylcysteine (NAC) is a widely used mucolytic agent in respiratory diseases that not only possesses a property to enhance secretion clearance, but also exhibits antioxidant and anti-inflammatory effects. However, the efficacy and safety of NAC are not well described in idiopathic or postinfective non-CF bronchiectasis.ObjectiveThis study aims to evaluate the efficacy and safety of NAC in patients with idiopathic or postinfective non-CF bronchiectasis.Methods and analysisPubMed/Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials will be searched from inception to 1 March 2022 for eligible randomised controlled trials that investigating the effects of NAC on exacerbations, health-related quality of life, lung functions, sputum volume and colour, inflammation markers, exercise capacity and adverse events in patients with idiopathic or postinfective non-CF bronchiectasis, with ongoing trials being identified by searches on the websites of Chinese Clinical Trial Registry and ClinicalTrials.gov. Two independent reviewers will identify eligible studies, two will fulfil the data extraction and three will perform the quality appraisal. To generate more accurate analyses, the Grading of Recommendations Assessment, Development and Evaluation will be used to grade the evidence. χ2test and I2statistic will be used to assess heterogeneity. Subgroup analyses and meta-regression will be used to explore potential sources of heterogeneity. The potential publication bias will be examined using funnel plots.Ethics and disseminationNo research ethics approval is required in this study because it is a systematic review. The results of this study are expected to be disseminated through peer-reviewed journals and conferences.Trial registration numberCRD42021239438.
Predicting the impact of climate change on the re-emergence of malaria cases in China using LSTMSeq2Seq deep learning model: a modelling and prediction analysis study
Authors: Kamana Eric , Zhao Jijun , Bai Di 
Published: March 2022

ObjectivesMalaria is a vector-borne disease that remains a serious public health problem due to its climatic sensitivity. Accurate prediction of malaria re-emergence is very important in taking corresponding effective measures. This study aims to investigate the impact of climatic factors on the re-emergence of malaria in mainland China.DesignA modelling study.Setting and participantsMonthly malaria cases for four Plasmodium species (P. falciparum, P. malariae, P. vivax and other Plasmodium) and monthly climate data were collected for 31 provinces; malaria cases from 2004 to 2016 were obtained from the Chinese centre for disease control and prevention and climate parameters from China meteorological data service centre. We conducted analyses at the aggregate level, and there was no involvement of confidential information.Primary and secondary outcome measuresThe long short-term memory sequence-to-sequence (LSTMSeq2Seq) deep neural network model was used to predict the re-emergence of malaria cases from 2004 to 2016, based on the influence of climatic factors. We trained and tested the extreme gradient boosting (XGBoost), gated recurrent unit, LSTM, LSTMSeq2Seq models using monthly malaria cases and corresponding meteorological data in 31 provinces of China. Then we compared the predictive performance of models using root mean squared error (RMSE) and mean absolute error evaluation measures.ResultsThe proposed LSTMSeq2Seq model reduced the mean RMSE of the predictions by 19.05% to 33.93%, 18.4% to 33.59%, 17.6% to 26.67% and 13.28% to 21.34%, for P. falciparum, P. vivax, P. malariae, and other plasmodia, respectively, as compared with other candidate models. The LSTMSeq2Seq model achieved an average prediction accuracy of 87.3%.ConclusionsThe LSTMSeq2Seq model significantly improved the prediction of malaria re-emergence based on the influence of climatic factors. Therefore, the LSTMSeq2Seq model can be effectively applied in the malaria re-emergence prediction.
Psychological barriers to the use of opioid analgesics for treating pain in patients with advanced recurrent cancer (BAROC): protocol for a multicentre cohort study
Authors: Tsuno Takehiko , Fujimiya Tatsuhiro , Kawaguchi Takashi , Yanaizumi Ryota , Kojima Keiko , Miyasato Akime , Azuma Kanako , Saeki Tomoya , Mawatari Hironori , Igarashi Takashi , Miura Tomofumi , Ogura Hiroyuki , Kondo Junichi , Tanoue Tadashi , Hamada Hiroshi , Oyama Yu , Kotani Akira , Yamaguchi Takuhiro , Hakamata Hideki 
Published: March 2022

IntroductionOpioid analgesics are essential for treating cancer pain. However, patients are sometimes reluctant to use them because of concerns about addiction and dependence. Rapid pain relief following opioid administration may help overcome the psychological barriers to opioid analgesic use. This study aims to determine the relationship between psychological resistance to strong opioid analgesic use and pain amelioration speed in patients with advanced recurrent cancer.Methods and analysisThis ongoing, multicentre, observational study enrols patients aged 20 years or older with distant metastasis or advanced recurrent cancer receiving strong opioid analgesics for cancer pain for the first time. All participants, both inpatient and outpatient, were recruited from five Japanese hospitals. We are investigating the relationship between psychological barriers at the start of treatment and pain relief during the first week of treatment in these patients. The primary outcome is the Japanese version of the Barriers Questionnaire-II score at baseline. The secondary outcomes are the relationships between psychological barriers to strong opioid analgesic use and changes in pain over time. The participants are asked to fill out an electronic patient-reported outcome daily during the first week of treatment. The sample size was determined based on the number of patients in the year prior to study commencement who used strong opioid analgesics, met the eligibility criteria and could be expected to consent to participate in the study.Ethics and disseminationThe study protocol was approved by the ethics committee (approval ID B200600091) of Yokohama City University on 24 August 2020. The protocol has been reviewed by the institutional review boards at the four participating study sites. The results will be published in a peer-reviewed journal and will be presented at a relevant meeting.Trial registration numberUMIN000042443.
How are adults with capacity-affecting conditions and associated communication difficulties included in ethically sound research? A documentary-based survey of ethical review and recruitment processes under the research provisions of the Mental Capacity Act (2005) for England and Wales
Authors: Bunning Karen , Jimoh Oluseyi Florence , Heywood Rob , Killett Anne , Ryan Hayley , Shiggins Ciara , Langdon Peter E 
Published: March 2022

ObjectivesThis study aimed to determine the characteristics of ethical review and recruitment processes, concerning the inclusion of adults with capacity-affecting conditions and associated communication difficulties in ethically sound research, under the provisions of the Mental Capacity Act (MCA, 2005) for England and Wales.DesignA documentary-based survey was conducted focusing on adults with capacity-affecting conditions and associated communication difficulties. The survey investigated: (1) retrospective studies during the implementation period of the MCA (2007–2017); (2) prospective applications to MCA-approved Research Ethics Committees (RECs) during a 12-month period (2018–19); (3) presentational and linguistic content of participant information sheets used with this population.SettingStudies conducted and approved in England and Wales.SampleStudies focused on adults with the following capacity-affecting conditions: acquired brain injury; aphasia after stroke; autism; dementia; intellectual disabilities; mental health conditions. The sample comprised: (1) 1605 studies; (2) 83 studies; (3) 25 participant information sheets.Primary and secondary outcome measuresThe primary outcome was the inclusion/exclusion of adults with capacity-affecting conditions from studies. The secondary outcome was the provisions deployed to support their inclusion.ResultsThe retrospective survey showed an incremental rise in research applications post-MCA implementation from 2 (2012) to 402 (2017). The prospective survey revealed exclusions of people on the bases of: ‘lack of capacity’ (n=21; 25%); ‘communication difficulties’ (n=5; 6%); ‘lack of consultee’ (n=11; 13%); and ‘limited English’ (n=17; 20%). REC recommendations focused mainly on participant-facing documentation. The participant information sheets were characterised by inconsistent use of images, typography and layout, volume of words and sentences; some simplified language content, but variable readability scores.ConclusionsPeople with capacity-affecting conditions and associated communication difficulties continue to be excluded from research, with recruitment efforts largely concentrated around participant-facing documentation. There is a need for a more nuanced approach if such individuals are to be included in ethically sound research.
Management of patients presenting to the emergency department with sudden onset severe headache: systematic review of diagnostic accuracy studies
Authors: Walton Matthew , Hodgson Robert , Eastwood Alison , Harden Melissa , Storey James , Hassan Taj , Randall Marc Stuart , Hassan Abu , Williams John , Wade Ros 
Published: March 2022

ObjectiveAdvances in imaging technologies have precipitated uncertainty and inconsistency in the management of neurologically intact patients presenting to the Emergency Department (ED) with non-traumatic sudden onset severe headache with a clinical suspicion of subarachnoid haemorrhage (SAH). The objective of this systematic review was to evaluate diagnostic strategies in these patients.MethodsStudies assessing any decision rule or diagnostic test for evaluating neurologically intact adults with a severe headache, reaching maximum intensity within 1 hour, were eligible. Eighteen databases (including MEDLINE and Embase) were searched. Quality was assessed using QUADAS-2. Where appropriate, hierarchical bivariate meta-analysis was used to synthesise diagnostic accuracy results.ResultsThirty-seven studies were included. Eight studies assessing the Ottawa SAH clinical decision rule were pooled; sensitivity 99.5% (95% CI 90.8 to 100), specificity 24% (95% CI 15.5 to 34.4). Four studies assessing CT within 6 hours of headache onset were pooled; sensitivity 98.7% (95% CI 96.5 to 100), specificity 100% (95% CI 99.7 to 100). The sensitivity of CT beyond 6 hours was considerably lower (≤90%; 2 studies). Three studies assessing lumbar puncture (LP; spectrophotometric analysis) following negative CT were pooled; sensitivity 100% (95% CI 100 to 100), specificity 95% (95% CI 86.0 to 98.5).ConclusionThe Ottawa SAH Rule rules out further investigation in only a small proportion of patients. CT undertaken within 6 hours (with expertise of a neuroradiologist or radiologist who routinely interprets brain images) is highly accurate and likely to be sufficient to rule out SAH; CT beyond 6 hours is much less sensitive. The CT–LP pathway is highly sensitive for detecting SAH and some alternative diagnoses, although LP results in some false positive results.
Mental health research in the Arab region in response to the COVID-19 pandemic: a scoping review
Authors: Hassan Mohamed Hussein Mahmoud Osman , Abdelhafez Ibrahim Hamdy Ezzat , Ouanes Sami , Al-Janahi Eiman , Zoghbi Yuri , Wadoo Ovais 
Published: March 2022

BackgroundThe ongoing pandemic has led to a global surge in coronavirus disease 2019 (COVID-19)-related mental health research. However, most related publications come from Western countries or China, and their findings cannot always be extrapolated to Arab countries.AimsThis study provides a quantitative and qualitative analysis of mental health research pertaining to Arab countries' response to the COVID-19 pandemic.MethodsA scoping review of the World Health Organization (WHO) COVID-19 database for publications on mental health was conducted by authors affiliated with Arab institutions, including articles from inception to 24 October 2020. The included publications were evaluated for their national distribution, international collaboration, publication type, and main research themes. Methodological quality analysis of the included research studies was performed using the original and modified versions of the Newcastle–Ottawa Scale.ResultsIn total, 102 articles were included in this study, averaging 4.6 articles per Arab country. Most of the articles emerged from the Kingdom of Saudi Arabia, Jordan, and Egypt. A majority of publications demonstrated international collaboration. Most of the publications were original research studies and cross-sectional in design. The predominant research theme was examining the pandemic’s mental health effects on the general population and healthcare workers. Only 28.0% of the studies were of high methodological quality, whereas 41.5% were moderate and 30.5% were low in quality.ConclusionsMental health research in response to the COVID-19 pandemic in the Arab region has quantitative and qualitative shortfalls. Arab institutions need to respond to the pandemic promptly in order to address the delineated research gap and to generate higher-quality research output.
Beta-blockers are associated with better long-term survival in patients with Takotsubo syndrome
Authors: Silverio Angelo , Parodi Guido , Scudiero Fernando , Bossone Eduardo , Di Maio Marco , Vriz Olga , Bellino Michele , Zito Concetta , Provenza Gennaro , Radano Ilaria , Baldi Cesare , D'Andrea Antonello , Novo Giuseppina , Mauro Ciro , Rigo Fausto , Innelli Pasquale , Salerno-Uriarte Jorge , Cameli Matteo , Vecchione Carmine , Antonini Canterin Francesco , Galasso Gennaro , Citro Rodolfo 
Published: March 2022

ObjectiveThe advantage of beta-blockers has been postulated in patients with Takotsubo syndrome (TTS) given the pathophysiological role of catecholamines. We hypothesised that beta-blocker treatment after discharge may improve the long-term clinical outcome in this patient population.MethodsThis was an observational, multicentre study including consecutive patients with TTS diagnosis prospectively enrolled in the Takotsubo Italian Network (TIN) register from January 2007 to December 2018. TTS was diagnosed according to the TIN, Heart Failure Association and InterTAK Diagnostic Criteria. The primary study outcome was the occurrence of all-cause death at the longest available follow-up; secondary outcomes were TTS recurrence, cardiac and non-cardiac death.ResultsThe study population included 825 patients (median age: 72.0 (63.0–78.0) years; 91.9 % female): 488 (59.2%) were discharged on beta-blockers and 337 (40.8%) without beta-blockers. The median follow-up was 24.0 months. The adjusted Cox regression analysis showed a significantly lower risk for all-cause death (adjusted HR: 0.563; 95% CI: 0.356 to 0.889) and non-cardiac death (adjusted HR: 0.525; 95% CI: 0.309 to 0.893) in patients receiving versus those not receiving beta-blockers, but no significant differences in terms of TTS recurrence (adjusted HR: 0.607; 95% CI: 0.311 to 1.187) and cardiac death (adjusted HR: 0.699; 95% CI: 0.284 to 1.722). The positive survival effect of beta-blockers was higher in patients with hypertension than in those without (pinteraction=0.014), and in patients who developed cardiogenic shock during the acute phase than in those who did not (pinteraction=0.047).ConclusionsIn this real-world register population, beta-blockers were associated with a significantly higher long-term survival, particularly in patients with hypertension and in those who developed cardiogenic shock during the acute phase.
Evaluation of the causes of sex disparity in heart failure trials
Authors: Morgan Holly , Sinha Aish , Mcentegart Margaret , Hardman Suzanna Marie , Perera Divaka 
Published: March 2022

ObjectivesCardiovascular disease is one of the leading causes of mortality and morbidity in women. Despite this, even in contemporary research, female patients are poorly represented in trials. This study aimed to explore reasons behind the sex disparity in heart failure (HF) trials.MethodsHF trials published in seven high-impact clinical journals (impact factor >20), between 2000 and 2020, were identified. Trials with over 300 participants of both sexes were included. Large HF registries, as well as population statistics, were also identified using the same criteria.ResultsWe identified 146 HF trials, which included 248 620 patients in total. The median proportion of female patients was 25.8%, with the lowest proportions seen in trials enrolling patients with ischaemic cardiomyopathy (17.9%), severe systolic dysfunction (left ventricular ejection fraction (LVEF) <35%) (21.4%) and those involving an invasive procedure (21.1%). The highest proportion of women was seen in trials assessing HF with preserved LVEF (51.6%), as well as trials including older participants (40.5%). Significant differences were seen between prevalence of female trial participants and population prevalence in all LVEF categories (25.8% vs 49.0%, p<0.01).ConclusionsA significant sex disparity was identified in HF trials, most visible in trials assessing patients with severely reduced LVEF and ischaemic aetiology. This is likely due to a complex interplay between enrolment bias and biological variation. Furthermore, the degree of both these aspects may vary according to trial type. Going forward, we should encourage all HF trials to appraise their recruitment log and suggest reasons for any reported sex disparity.
Targeting the tumor mutanome for personalized vaccination in a TMB low non-small cell lung cancer
Authors: McCann Katy , von Witzleben Adrian , Thomas Jaya , Wang Chuan , Wood Oliver , Singh Divya , Boukas Konstantinos , Bendjama Kaidre , Silvestre Nathalie , Nielsen Finn Cilius , Thomas Gareth , Sanchez-Elsner Tilman , Greenbaum Jason , Schoenberger Stephen , Peters Bjoern , Vijayanand Pandurangan , Savelyeva Natalia , Ottensmeier Christian 
Published: March 2022

BackgroundCancer is characterized by an accumulation of somatic mutations, of which a significant subset can generate cancer-specific neoepitopes that are recognized by autologous T cells. Such neoepitopes are emerging as important targets for cancer immunotherapy, including personalized cancer vaccination strategies.MethodsWe used whole-exome and RNA sequencing analysis to identify potential neoantigens for a patient with non-small cell lung cancer. Thereafter, we assessed the autologous T-cell reactivity to the candidate neoantigens using a long peptide approach in a cultured interferon gamma ELISpot and tracked the neoantigen-specific T-cells in the tumor by T-cell receptor (TCR) sequencing. In parallel, identified gene variants were incorporated into a Modified Vaccinia Ankara-based vaccine, which was evaluated in the human leucocyte antigen A*0201 transgenic mouse model (HHD).ResultsSequencing revealed a tumor with a low mutational burden: 2219 sequence variants were identified from the primary tumor, of which 23 were expressed in the transcriptome, involving 18 gene products. We could demonstrate spontaneous T-cell responses to 5/18 (28%) mutated gene variants, and further analysis of the TCR repertoire of neoantigen-specific CD4+and CD8+T cells revealed TCR clonotypes that were expanded in both blood and tumor tissue. Following vaccination of HHD mice, de novo T-cell responses were generated to 4/18 (22%) mutated gene variants; T cells reactive against two variants were also evident in the autologous setting. Subsequently, we determined the major histocompatibility complex restriction of the T-cell responses and used in silico prediction tools to determine the likely neoepitopes.ConclusionsOur study demonstrates the feasibility of efficiently identifying tumor-specific neoantigens that can be targeted by vaccination in tumors with a low mutational burden, promising successful clinical exploitation, with trials currently underway.
Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy
Authors: Sidler Daniel , Born Alexander , Schietzel Simeon , Horn Michael P , Aeberli Daniel , Amsler Jennifer , Möller Burkhard , Njue Linet M , Medri Cesare , Angelillo-Scherrer Anne , Borradori Luca , Seyed Jafari S. Morteza , Radonjic-Hoesli Susanne , Chan Andrew , Hoepner Robert , Bacher Ulrike , Mani Laila-Yasmin , Iype Joseena Mariam , Suter-Riniker Franziska , Staehelin Cornelia , Nagler Michael , Hirzel Cedric , Maurer Britta , Moor Matthias B 
Published: March 2022

BackgroundThe majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients.MethodsWe investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6–4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression.Results5.6 months (IQR: 5.1–6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0–7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants.ConclusionThis study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.Trial registration numberNCT04877496; ClinicalTrials.gov number.