bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining tennis elbow characteristics – The assessment of magnetic resonance imaging defined tendon pathology in an asymptomatic population
Authors: Paluch Anthony J , Burden Eleanor G , Batten Timothy J , Knight Beatrice , Anaspure Rahul , Aboelmagd Sharief , Evans Jonathan Peter , Smith Christopher D 
Published: December 2022

Background This radiological study aims to assess the prevalence of lateral elbow pathology in an asymptomatic population using 3.0T magnetic resonance imaging (MRI). Methods Bilateral elbow MRI was undertaken in 30 asymptomatic volunteers. Exclusion criteria included elbow pain within 3 months, elbow trauma or previous diagnosis of lateral epicondylar tendinopathy. Baseline patient-reported outcome measures were recorded along with age and body mass index (BMI). Two musculoskeletal radiologists independently graded the degree of abnormality at the common extensor tendon. Results Thirty volunteers were categorised according to age; 35–44 ( n = 10), 45–54 ( n = 11), and 55–65 ( n = 9) with a 1:1 male-to-female ratio. Radiological evidence of tendon abnormality was found in 37% of volunteers. The proportion with abnormal findings increased with age; 35–44 (10%), 45–54 (36%), 55–65 (67%) and BMI; 18–24.9 (23%), 25–29.9 (43%), > 30 (67%). Changes were generally ‘mild’ or ‘moderate’, with a single volunteer showing ‘severe’ pathology. Kappa for the radiographic agreement was 0.91 (0.83–0.98). Discussion This study has demonstrated MRI findings suggestive of pathology at the common extensor tendon to be prevalent in an asymptomatic population, increasing with age and BMI. This draws into question the diagnostic and prognostic value of MRI imaging in lateral epicondylar tendinopathy, especially in older patients.
CCN4/WISP1 Promotes Migration of Human Primary Osteoarthritic Chondrocytes
Authors: Timmermans Ritchie G.M. , Blom Arjen B. , Bloks Niek G.C. , Nelissen Rob. G.H.H. , van der Linden Enrike H.M.J. , van der Kraan Peter M. , Meulenbelt Ingrid , Ramos Yolande F.M. , van den Bosch Martijn H.J. 
Published: December 2022

Objectives Previously, we have shown the involvement of cellular communication network factor 4/Wnt-activated protein Wnt-1-induced signaling protein 1 (CCN4/WISP1) in osteoarthritic (OA) cartilage and its detrimental effects on cartilage. Here, we investigated characteristics of CCN4 in chondrocyte biology by exploring correlations of CCN4 with genes expressed in human OA cartilage with functional follow-up. Design Spearman correlation analysis was performed for genes correlating with CCN4 using our previously established RNA sequencing dataset of human preserved OA cartilage of the RAAK study, followed by a pathway enrichment analysis for genes with ρ ≥|0.6.| Chondrocyte migration in the absence or presence of CCN4 was determined in a scratch assay, measuring scratch size using a live cell imager for up to 36 h. Changes in expression levels of 12 genes, correlating with CCN4 and involved in migratory processes, were determined with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results Correlation of CCN4 with ρ ≥|0.6| was found for 58 genes in preserved human OA cartilage. Pathway analysis revealed “neural crest cell migration” as most significant enriched pathway, containing among others CORO1C, SEMA3C, and SMO. Addition of CCN4 to primary chondrocytes significantly enhance chondrocyte migration as demonstrated by reduced scratch size over the course of 36 h, but at the timepoints measured no effect was observed on mRNA expression of the 12 genes. Conclusion CCN4 increases cell migration of human primary OA chondrocytes. Since WISP1 expression is known to be increased in OA cartilage, this may serve to direct chondrocytes toward cartilage defects and orchestrate repair.
How I prevent and treat central nervous system disease in adults with acute lymphoblastic leukemia
Authors: Kopmar Noam E. , Cassaday Ryan D. 
Published: December 2022

Abstract
The central nervous system (CNS) is the most important site of extramedullary disease in adults with acute lymphoblastic leukemia (ALL). Although CNS disease is identified only in a minority of patients at the time of diagnosis, subsequent CNS relapses (either isolated or concurrent with other sites) occur in some patients even after the delivery of prophylactic therapy targeted to the CNS. Historically, prophylaxis against CNS disease has included intrathecal (IT) chemotherapy and radiotherapy (RT), although the latter is being used with decreasing frequency. Treatment of a CNS relapse usually involves intensive systemic therapy and cranial or craniospinal RT along with IT therapy and consideration of allogeneic hematopoietic cell transplant. However, short- and long-term toxicities can make these interventions prohibitively risky, particularly for older adults. As new antibody-based immunotherapy agents have been approved for relapsed/refractory B-cell ALL, their use specifically for patients with CNS disease is an area of keen interest not only because of the potential for efficacy but also concerns of unique toxicity to the CNS. In this review, we discuss data-driven approaches for these common and challenging clinical scenarios as well as highlight how recent findings potentially support the use of novel immunotherapeutic strategies for CNS disease.
Novel insights into Hodgkin lymphoma biology by single-cell analysis
Authors: Aoki Tomohiro , Steidl Christian 
Published: December 2022

Abstract
The emergence and rapid development of single-cell technologies mark a paradigm shift in cancer research. Various technology implementations represent powerful tools to understand cellular heterogeneity, identify minor cell populations that were previously hard to detect and define, and make inferences about cell-to-cell interactions at single-cell resolution. Applied to lymphoma, recent advances in single-cell RNA sequencing have broadened opportunities to delineate previously underappreciated heterogeneity of malignant cell differentiation states and presumed cell of origin, and to describe the composition and cellular subsets in the ecosystem of the tumor microenvironment (TME). Clinical deployment of an expanding armamentarium of immunotherapy options that rely on targets and immune cell interactions in the TME emphasizes the requirement for a deeper understanding of immune biology in lymphoma. In particular, classic Hodgkin lymphoma (CHL) can serve as a study paradigm because of its unique TME, featuring infrequent tumor cells among numerous nonmalignant immune cells with significant interpatient and intrapatient variability. Synergistic to advances in single-cell sequencing, multiplexed imaging techniques have added a new dimension to describing cellular cross talk in various lymphoma entities. Here, we comprehensively review recent progress using novel single-cell technologies with an emphasis on the TME biology of CHL as an application field. The described technologies, which are applicable to peripheral blood, fresh tissues, and formalin-fixed samples, hold the promise to accelerate biomarker discovery for novel immunotherapeutic approaches and to serve as future assay platforms for biomarker-informed treatment selection, including immunotherapies.
Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19
Authors: Daines Luke , Zheng Bang , Elneima Omer , Harrison Ewen , Lone Nazir I. , Hurst John R. , Brown Jeremy S. , Sapey Elizabeth , Chalmers James D. , Quint Jennifer K. , Pfeffer Paul , Siddiqui Salman , Walker Samantha , Poinasamy Krisnah , McAuley Hamish , Sereno Marco , Shikotra Aarti , Singapuri Amisha , Docherty Annemarie B. , Marks Michael , Toshner Mark , Howard Luke S. , Horsley Alex , Jenkins Gisli , Porter Joanna C. , Ho Ling-Pei , Raman Betty , Wain Louise V. , Brightling Christopher E. , Evans Rachael A. , Heaney Liam G. , De Soyza Anthony , Sheikh Aziz 
Published: December 2022

BackgroundPersistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation.MethodsPHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0–10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness.ResultsWe included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14–2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06–2.35), female sex (adjusted OR 1.56, 95% CI 1.21–2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00–1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35–0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14–0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63–0.69) and good calibration (calibration slope 1.00, 95% CI 0.80–1.21).ConclusionsPost-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.
Real-life effectiveness of indacaterol/glycopyrronium/mometasone for symptomatic relief of cough after switching from inhaled corticosteroid/long-acting β2-agonist therapy in patients with asthma: REACH study design
Authors: Niimi Akio , Kanemitsu Yoshihiro , Tajiri Tomoko , Sumi Kazuya , Mikami Toshiaki , Kondo Norihiko 
Published: December 2022

Cough is a major symptom in patients with asthma and poses a significant burden compared with other asthma symptoms. However, there are no approved treatments in Japan, developed to specifically treat cough in patients with asthma. We present the design of REACH, an 8-week real-life study, which will evaluate the efficacy of a combination of indacaterol acetate, glycopyrronium bromide and mometasone furoate (IND/GLY/MF) in asthmatic patients with cough refractory to medium-dose inhaled corticosteroid/long-acting β2-agonist (ICS/LABA).Patients with asthma (age ≥20 to <80 years) with a cough visual analogue scale (VAS) ≥40 mm will be randomised 2:1:1 to receive IND/GLY/MF medium-dose 150/50/80 μg once daily or step-up to a high-dose regimen of fluticasone furoate/vilanterol trifenatate (FF/VI) 200/25 µg once daily or budesonide/formoterol fumarate (BUD/FM) 160/4.5 µg four inhalations twice daily during the 8-week treatment period. The primary objective is to demonstrate the superiority of IND/GLY/MF medium-dose over high-dose ICS/LABA in terms of cough-specific quality of life after 8 weeks. The key secondary objective is to demonstrate the superiority of IND/GLY/MF in terms of subjective assessment of cough severity.Cough frequency (VitaloJAK cough monitor) and capsaicin cough receptor sensitivity will be evaluated in eligible patients. Cough VAS scores, fractional exhaled nitric oxide, spirometry and blood tests, and the Asthma Control Questionnaire-6, Cough and Sputum Assessment Questionnaire, and Japanese version of the Leicester Cough Questionnaire will be evaluated.REACH will provide valuable evidence on whether a switch to IND/GLY/MF medium-dose or step-up to high-dose ICS/LABA is beneficial for patients with persistent cough despite treatment with medium-dose ICS/LABA.
Airway clearance treatments in bronchiectasis: feasibility of linking survey results to registry data and a survey of patients’ and physiotherapists’ practices
Authors: McLeese Rebecca H. , O'Neill Katherine , O'Neill Brenda , Chalmers James D. , Boyd Jeanette , De Soyza Anthony , McChrystal Ryan , Crichton Megan L. , Bradley Judy M. 
Published: December 2022

Background and objectiveThere are limited data on airway clearance treatment (ACT) practices. This study aimed to: 1) assess the feasibility of collecting online surveys on ACTs from patients and physiotherapists and linking the patient survey data to outcome data in the Bronch-UK/EMBARC Registry; 2) assess the association between ACT practices and outcome data; and 3) ascertain the factors affecting physiotherapist ACT practices.MethodsSurvey methodology was used to collect data from patients with bronchiectasis and physiotherapists in Northern Ireland. Associations between patient survey data and linked Bronch-UK/EMBARC Registry patient outcome data were explored.ResultsIt was feasible to conduct an online survey with patients with bronchiectasis and link the data to the Bronch-UK/EMBARC Registry. 13% of patients did not perform ACTs. ACTs were used more often by patients who were symptomatic/had more severe disease compared to those with milder symptoms/disease. Patients used ACTs when they were symptomatic rather than as a preventative management strategy. Physiotherapists generally followed the bronchiectasis guidelines, using the stepwise approach to management.ConclusionOur survey provided information about the feasibility of linking online survey and patient registry data. This study provides up-to-date information on ACT practice throughout the course of the disease trajectory as well as insight into the implementation of bronchiectasis guidelines by physiotherapists. Future work should explore how to optimise ACT data collection to maximise the use of real-world ACT data in bronchiectasis research and inform priority ACT research questions.
Healthcare experiences of adults with COPD across community care settings: a meta-ethnography
Authors: Madawala Sanduni , Osadnik Christian Robert , Warren Narelle , Kasiviswanathan Karthika , Barton Chris 
Published: December 2022

BackgroundStudies investigating lived experiences of patients with COPD raise important concerns about interactions with healthcare professionals. Patients often describe feelings of guilt and shame associated with their COPD and may experience stigma and poor patient experience of care. The aims and objectives of the present study were to systematically scope and synthesise findings from peer-reviewed qualitative studies describing healthcare experiences of patients living with COPD across community care settings.MethodsA meta-ethnography was undertaken. Database searches were performed in Ovid MEDLINE, PsychINFO, Ovid Emcare, CINAHL Plus and Sociological Abstracts. Eligible qualitative studies were included. Study screening and data extraction was performed by two independent reviewers. A “line-of-argument” synthesis and deductive and inductive analysis was used to identify key themes, where the deductive element aligned to Wong and Haggerty's six key dimensions of patient experiences.ResultsData from 23 studies were included. Experiences and their meaning to patients were explored within the context of six domains of patient experience including access, interpersonal communication, continuity and coordination, comprehensiveness and trust. Inductive coding revealed emotion, stigma, identity and vulnerability shaped healthcare experiences of adults with COPD.ImplicationsExperiences often fell short of what was expected and needed in community settings. Adopting strategies to improve experiences of care in the community can be expected to improve self-management and contribute to improved health outcomes and quality of life. These strategies should take account of vulnerability, stigma and emotions such as guilt and blame that are potent affective drivers of the experience of care for patients with COPD.
Diversity of bacterial communities in the plasmodia of myxomycetes
Authors: Li Shu , Qi Bao , Wang Wan , Peng Xueyan , Gontcharov Andrey A , Liu Bao , Wang Qi , Li Yu 
Published: December 2022

Abstract
Background
Myxomycetes are a group of eukaryotes belonging to Amoebozoa, which are characterized by a distinctive life cycle, including the plasmodium stage and fruit body stage. Plasmodia are all found to be associated with bacteria. However, the information about bacteria diversity and composition in different plasmodia was limited. Therefore, this study aimed to investigate the bacterial diversity of plasmodia from different myxomycetes species and reveal the potential function of plasmodia-associated bacterial communities.

Results
The bacterial communities associated with the plasmodia of six myxomycetes (Didymium iridis, Didymium squamulosum, Diderma hemisphaericum, Lepidoderma tigrinum, Fuligo leviderma, and Physarum melleum) were identified by 16S rRNA amplicon sequencing. The six plasmodia harbored 38 to 52 bacterial operational taxonomic units (OTUs) that belonged to 7 phyla, 16 classes, 23 orders, 40 families, and 53 genera. The dominant phyla were Bacteroidetes, Firmicutes, and Proteobacteria. Most OTUs were shared among the six myxomycetes, while unique bacteria in each species only accounted for a tiny proportion of the total OTUs.

Conclusions
Although each of the six myxomycetes plasmodia had different bacterial community compositions, a high similarity was observed in the plasmodia-associated bacterial communities' functional composition. The high enrichment for gram-negative (> 90%) and aerobic (> 99%) bacteria in plasmodia suggest that myxomycetes may positively recruit certain kinds of bacteria from the surrounding environment.
Hypothetical interventions on emergency ambulance and prehospital acetylsalicylic acid administration in myocardial infarction patients presenting without chest pain
Authors: Møller Amalie Lykkemark , Rytgaard Helene Charlotte Wiese , Mills Elisabeth Helen Anna , Christensen Helle Collatz , Blomberg Stig Nikolaj Fasmer , Folke Fredrik , Kragholm Kristian Hay , Lippert Freddy , Gislason Gunnar , Køber Lars , Gerds Thomas Alexander , Torp-Pedersen Christian 
Published: December 2022

AbstractBackgroundMyocardial infarction (MI) patients presenting without chest pain are a diagnostic challenge. They receive suboptimal prehospital management and have high mortality. To elucidate potential benefits of improved management, we analysed expected outcome among non-chest pain MI patients if hypothetically they (1) received emergency ambulances/acetylsalicylic acid (ASA) as often as observed for chest pain patients, and (2) all received emergency ambulance/ASA.MethodsWe sampled calls to emergency and non-emergency medical services for patients hospitalized with MI within 24 h and categorized calls as chest pain/non-chest pain. Outcomes were 30-day mortality and a 1-year combined outcome of re-infarction, heart failure admission, and mortality. Targeted minimum loss-based estimation was used for all statistical analyses.ResultsAmong 5418 calls regarding MI patients, 24% (1309) were recorded with non-chest pain. In total, 90% (3689/4109) of chest pain and 40% (525/1309) of non-chest pain patients received an emergency ambulance, and 73% (2668/3632) and 37% (192/518) of chest pain and non-chest pain patients received prehospital ASA. Providing ambulances to all non-chest pain patients was not associated with improved survival. Prehospital administration of ASA to all emergency ambulance transports of non-chest pain MI patients was expected to reduce 30-day mortality by 5.3% (CI 95%: [1.7%;9%]) from 12.8% to 7.4%. No significant reduction was found for the 1-year combined outcome (2.6% CI 95% [− 2.9%;8.1%]). In comparison, the observed 30-day mortality was 3% among ambulance-transported chest pain MI patients.ConclusionsOur study found large differences in the prehospital management of MI patients with and without chest pain. Improved prehospital ASA administration to non-chest pain MI patients could possibly reduce 30-day mortality, but long-term effects appear limited. Non-chest pain MI patients are difficult to identify prehospital and possible unintended effects of ASA might outweigh the potential benefits of improving the prehospital management. Future research should investigate ways to improve the prehospital recognition of MI in the absence of chest pain.
Intervention effect estimates in randomised controlled trials conducted in primary care versus secondary or tertiary care settings: a meta-epidemiological study
Authors: Dugard Amandine , Tavernier Elsa , Caille Agnès , Dechartres Agnès , Hoang Adeline , Giraudeau Bruno , Dibao-Dina Clarisse 
Published: December 2022

Abstract
Background
Many clinical practice guidelines are based on randomised controlled trials conducted in secondary or tertiary care setting and general practitioners frequently question their relevance for primary care patients. Our aim was to compare the intervention effect estimates between primary care setting randomised controlled trials (PC-RCTs) and secondary or tertiary care setting randomised controlled trials (ST-RCTs).

Methods
Meta-epidemiological study of meta-analyses (MAs) of a binary outcome including at least one PC-RCT and one ST-RCT. PC-RCTs were defined as trials recruiting patients in general practices, primary care practices, family practices, community centers or community pharmacies. ST-RCTs were defined as trials recruiting in hospitals, including hospitalized patients, hospital outpatients and patients from emergency departments. For each MA, we estimated a ratio of odds ratio (ROR) by using random-effects meta-regression, with an ROR less than 1 indicating lower estimates of the intervention effect in PC-RCTs than ST-RCTs. Finally, we estimated a combined ROR across MAs by using a random-effects meta-analysis. We performed subgroup analyses considering the type of outcomes (objective vs subjective), type of experimental intervention (pharmacological vs non-pharmacological), and control group (active vs inactive) as well as analyses adjusted on items of the Cochrane Risk of Bias tool.

Results
Among 1765 screened reviews, 76 MAs with 230 PC-RCTs and 384 ST-RCTs were selected. The main medical fields were pneumology (13.2%) and psychiatry or addictology (38.2%). Intervention effect estimates did not significantly differ between PC-RCTs and ST-RCTs (ROR = 0.97, 95% confidence interval 0.88 to 1.08), with moderate heterogeneity across MAs (I2 = 45%). Subgroup and adjusted analyses led to consistent results.

Conclusion
We did not observe any significant difference in intervention effect estimates between PC-RCTs and ST-RCTs. Nevertheless, most of the medical fields in this meta-epidemiological study were not representative of the pathologies encountered in primary care. Further studies with pathologies more frequently encountered in primary care are needed.