bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with risk of major adverse cardiovascular events in patients with rheumatoid arthritis: a nationwide, population-based, case-control study
Authors: Chen Yen-Ju , Liu Shih-Chia , Lai Kuo-Lung , Tang Kuo-Tung , Lin Ching-Heng , Chen Yi-Ming , Tseng Chih-Wei , Chang Yu-Mei , Gotcher Donald F. , Chiou Chuang-Chun , Weng Shao-Jen , Chen Hsin-Hua 
Published: August 2021

Objectives: To investigate factors associated with major adverse cardiovascular events (MACEs) in patients with rheumatoid arthritis (RA). Methods: We conducted a nationwide, population-based, case-control study using Taiwan’s National Health Insurance Research Database for 2003–2013. From 2004 to 2012, we identified 108,319 newly diagnosed RA patients without previous MACEs, of whom 7,580 patients (7.0%) developed MACEs during follow-up. From these incident RA patients, we included 5,994 MACE cases and 1:4 matched 23,976 non-MACE controls for analysis. The associations of MACEs with comorbidities and use of anti-rheumatic medications within 1 year before the index date were examined using conditional logistic regression analyses. Results: Using multivariable conditional logistic regression analysis, the risk of MACE in RA patients was associated with use of golimumab [odd’s ratio (OR), 0.09; 95% confidence interval (CI), 0.01-0.67], abatacept (OR, 0.13; 95% CI, 0.02–0.93), hydroxychloroquine (OR, 0.90; 95% CI, 0.82-0.99), methotrexate (OR, 0.72; 95% CI, 0.64–0.81), cyclosporin (OR, 1.43; 95% CI, 1.07–1.91), nonsteroidal anti-inflammation drugs (NSAIDs) (OR, 1.36; 95% CI, 1.27–1.46), antiplatelet agent (OR, 2.47; 95% CI, 2.31-2.63), hypertension (without anti-hypertensive agents: OR, 1.04; 95% CI, 0.96-1.12; with anti-hypertensive agents: OR, 1.47; 95% CI, 1.36-1.59), diabetes (OR, 1.27; 95% CI, 1.18-1.37), hyperlipidemia without lipid-lowering agents (OR, 1.09; 95% CI, 1.01-1.17), ischemic heart disease (OR, 1.20; 95% CI, 1.10-1.31), and chronic obstructive pulmonary disease (COPD) (OR, 1.12; 95% CI, 1.03-1.23) in the parsimonious model. The risk of MACE in RA patients also increased markedly in participants younger than 65 years with some comorbidities. Conclusions: This population-based case-control study revealed that the use of golimumab, abatacept, hydroxychloroquine, and methotrexate were associated with a decreased risk of MACE development in newly diagnosed RA patients, while the use of cyclosporin, NSAIDs, and antiplatelet agents, and comorbidities, including hypertension, diabetes, hyperlipidemia without lipid-lowering agent therapy, ischemic heart disease, and COPD, were associated with an increased risk of MACE development in RA patients.
Conspiracy beliefs and attitudes toward COVID-19 vaccinations
Authors: Pivetti Monica , Di Battista Silvia , Paleari Francesca Giorgia , Hakoköngäs Eemeli 
Published: August 2021

During the coronavirus pandemic, this study aimed to investigate the impact of conspiracy beliefs on Finnish attitudes toward vaccinations in general and COVID-19 vaccinations in particular. This study was a conceptual replication in Finland of a study by Pivetti et al. (2021) . Some 529 Finnish participants responded to a self-report questionnaire during the partial lockdown in Finland in spring 2020. The hypothesized relationships between variables of interest were integrated in a serial multiple mediation model via structural equation modelling. Results showed that endorsing general conspiracy beliefs directly predicted (1) general attitudes toward vaccines and (2) COVID-19 conspiracy beliefs, and indirectly predicted (3) attitudes toward COVID-19 vaccines via the serial mediation of COVID-19 conspiracy beliefs and general attitudes toward vaccines. As for the antecedents of beliefs in conspiracy theories, political orientation and moral purity predicted beliefs in COVID-19 conspiracy theories. Trust in science was inversely related to general conspiracy beliefs. As for the consequences of conspiracy beliefs, COVID-19 conspiracy beliefs directly predicted support for governmental restrictions (negatively) and the perception of informational contamination (positively).
Do ACL Injury Risk Reduction Exercises Reflect Common Injury Mechanisms? A Scoping Review of Injury Prevention Programs
Authors: Dischiavi Steven L. , Wright Alexis A , Heller Rachel A. , Love Claire E. , Salzman Adam J. , Harris Christian A. , Bleakley Chris M. 
Published: August 2021

Context: Anterior cruciate ligament (ACL) injury risk reduction programs have become increasingly popular. As ACL injuries continue to reflect high incidence rates, the continued optimization of current risk reduction programs, and the exercises contained within them, is warranted. The exercises must evolve to align with new etiology data, but there is concern that the exercises do not fully reflect the complexity of ACL injury mechanisms. It was outside the scope of this review to address each possible inciting event, rather the effort was directed at the elements more closely associated with the end point of movement during the injury mechanism. Objective: To examine if exercises designed to reduce the risk of ACL injury reflect key injury mechanisms: multiplanar movement, single limb stance, trunk and hip dissociative control, and a flight phase. Data Sources: A systematic search was performed using PubMed, Medline, EBSCO (CINAHL), SPORTSDiscus, and PEDro databases. Study Selection: Eligibility criteria were as follows: (1) randomized controlled trials or prospective cohort studies, (2) male and/or female participants of any age, (3) exercises were targeted interventions to prevent ACL/knee injuries, and (4) individual exercises were listed and adequately detailed and excluded if program was unable to be replicated clinically. Study Design: Scoping review. Level of Evidence: Level 4. Data Extraction: A total of 35 studies were included, and 1019 exercises were extracted for analysis. Results: The average Consensus on Exercise Reporting Template score was 11 (range, 0-14). The majority of exercises involved bilateral weightbearing (n = 418 of 1019; 41.0%), followed by single limb (n = 345 of 1019; 33.9%) and nonweightbearing (n = 256 of 1019; 25.1%). Only 20% of exercises incorporated more than 1 plane of movement, and the majority of exercises had sagittal plane dominance. Although 50% of exercises incorporated a flight phase, only half of these also involved single-leg weightbearing. Just 16% of exercises incorporated trunk and hip dissociation, and these were rarely combined with other key exercise elements. Only 13% of exercises challenged more than 2 key elements, and only 1% incorporated all 4 elements (multiplanar movements, single limb stance, trunk and hip dissociation, flight phase) simultaneously. Conclusion: Many risk reduction exercises do not reflect the task-specific elements identified within ACL injury mechanisms. Addressing the underrepresentation of key elements (eg, trunk and hip dissociation, multiplanar movements) may optimize risk reduction in future trials.
I Want Some Freedom for My People: Baptists, Great Texts, and Honors Education
Authors: Mitchell Philip 
Published: August 2021

I thought the Baptists had finally given up and become Methodist. We Methodists are heart people. Baptists have no hearts at all. Instead Baptists have the Bible which they use as a club to beat one another into submission. In this respect, I am on the side of the Baptists…. Hopefully Baptists are just too mean (and I mean that as a compliment) to make the mistakes the Methodists have made. (Hauerwas, 2007, pp. 110–111) The true liberty of man is to know, obey, and enjoy his Creator and to do all the good unto, and enjoy the happiness with and in, his fellow-creatures that he is capable of…. To love ourselves, and truly to seek our own welfare, is both liberty and our indispensable duty. But the conceit that man could advance either his honor or happiness by disobedience instead of obedience was first injected by the father of lies, and all such conceits ever since are as false as he is. (Backus, 1773)
Patient Satisfaction Using a Home-Based Rehabilitation Protocol for the Non-Surgical Treatment of Proximal Humeral Fractures: A Prospective Longitudinal Cohort Study
Authors: Aguado Héctor J. , Ventura-Wichner Paula S. , Perez-Hickman Laura , Polo-Pérez Isabel , Alonso-Olmo Juan A. , Bragado María , Pereda-Manso Adela , Martínez-Zarzuela Mario , García-Virto Virginia , Simón-Pérez Clarisa , Barajas Emilio J. , Martín-Ferrero Miguel A. 
Published: August 2021

Supervised, center-based, daily physiotherapy presents limitations: transport, need for an accompanying person, or risk of infection. Home-based rehabilitation protocols (HBRP) can be effective alternatives. We use a HBRP for the non-surgically treated proximal humeral fractures (PHF) in older patients. Objectives To assess patient satisfaction and preferences of using a booklet, videos, or an app to guide physiotherapy. Patients and methods Prospective, single-center observational study of patients ≥55 years old who sustained a non-surgically treated PHF. The HBRP consisted of immediate mobilization, followed by 5 physiotherapist-guided, weekly sessions of rehabilitation and standard physiotherapy after 3 months, if needed. A booklet with images, videos, or a smartphone application were offered to guide the patients. Results Mean degree of satisfaction (1-5) was 4.66 ± .9: 84 patients (82.4%) were very satisfied, 11 patients (10.8%) were satisfied, and 5 patients (4.9%) were not satisfied at all. Mean Oxford Shoulder Score achieved was 40.5 ± 6.6. 59.8% patients preferred the booklet and 29.4% the videos. Exercise compliance was considered very high in 87.3% of patients, while 4% hardly never followed the HBRP. Only 17.7% patients needed center-based physiotherapy after the HBRP. Discussion Reasons for satisfaction were good final functional outcome, no need for transportation, being away from hospital, immediate rehabilitation availability and being capable of maintaining independence. Adherence is a major concern. Videos are more didactic explaining the exercises. Conclusion If standard physiotherapy is not available, the HBRP can be a valid treatment option for PHF management in older patients, with a high degree of patient satisfaction. Older patients preferred the booklet to guide physiotherapy.
Physiologic IGFBP7 levels prolong IGF1R activation in acute lymphoblastic leukemia
Authors: Artico Leonardo Luís , Laranjeira Angelo Brunelli Albertoni , Campos Livia Weijenborg , Corrêa Juliana Ronchi , Zenatti Priscila Pini , Carvalheira José Barreto Campello , Brambilla Sandra Regina , Nowill Alexandre Eduardo , Brandalise Silvia Regina , Yunes José Andrés 
Published: August 2021

Abstract
Insulin and insulin-like growth factors (IGFs) are mitogenic and prosurvival factors to many different cell types, including acute lymphoblastic leukemia (ALL). Circulating IGFs are bound by IGF binding proteins (IGFBPs) that regulate their action. IGFBP7 is an IGFBP-related protein (IGFBP-rP) that in contrast to other IGFBPs/IGFBP-rPs features higher affinity for insulin than IGFs and was shown to bind the IGF1 receptor (IGF1R) as well. The role of IGFBP7 in cancer is controversial: on some tumors, it functions as an oncogene, whereas in others, it functions as a tumor suppressor. In childhood ALL, higher IGFBP7 expression levels were associated with worse prognosis. Here we show that IGFBP7 exerts mitogenic and prosurvival autocrine effects on ALL cells that were dependent on insulin/IGF. IGFBP7 knockdown or antibody-mediated neutralization resulted in significant attenuation of ALL cell viability in vitro and leukemia progression in vivo. IGFBP7 was shown to prolong the surface retention of the IGF1R under insulin/IGF1 stimulation, resulting in sustained IGF1R, insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) phosphorylation. Conversely, the insulin receptor was readily internalized and dephosphorylated on insulin stimulation, despite IGFBP7 addition. The affinity of homodimeric IGF1R for insulin is reportedly &gt;100 times lower than for IGF1. In the presence of IGFBP7, however, 25 ng/mL insulin resulted in IGF1R activation levels equivalent to that of 5 ng/mL IGF1. In conclusion, IGFBP7 plays an oncogenic role in ALL by promoting the perdurance of IGF1R at the cell surface, prolonging insulin/IGF stimulation. Preclinical data demonstrate that IGFBP7 is a valid target for antibody-based therapeutic interventions in ALL.
In-hospital and midterm post-discharge complications of adults hospitalised with respiratory syncytial virus infection in France, 2017–2019: an observational study
Authors: Descamps Alexandre , Lenzi Nezha , Galtier Florence , Lainé Fabrice , Lesieur Zineb , Vanhems Philippe , Amour Sélilah , L'Honneur Anne-Sophie , Fidouh Nadhira , Foulongne Vincent , Lagathu Gisèle , Duval Xavier , Merle Corinne , Lina Bruno , Carrat Fabrice , Launay Odile , Loubet Paul 
Published: August 2021

ObjectivesThe purpose of this study was to describe the clinical characteristics and in-hospital and post-discharge outcomes of respiratory syncytial virus (RSV) infection among adults hospitalised with influenza-like illness (ILI) and compared against patients admitted for influenza.MethodsAdults hospitalised with ILI were prospectively included from five French university hospitals over two consecutive winter seasons (2017/2018 and 2018/2019). RSV and influenza virus were detected by multiplex reverse transcription PCR on nasopharyngeal swabs. RSV-positive patients were compared to RSV-negative and influenza-positive hospitalised patients. Poisson regression models were used to estimate the adjusted prevalence ratio (aPR) associated with in-hospital and post-discharge outcomes between RSV and influenza infections. The in-hospital outcome was a composite of the occurrence of at least one complication, length of stay ≥7 days, intensive care unit admission, use of mechanical ventilation and in-hospital death. Post-discharge outcome included 30- and 90-day all-cause mortality and 90-day readmission rates.ResultsOverall, 1428 hospitalised adults with ILI were included. RSV was detected in 8% (114 of 1428) and influenza virus in 31% (437 of 1428). Patients hospitalised with RSV were older than those with influenza (mean age 73.0versus68.8 years, p=0.015) with a higher frequency of chronic respiratory or cardiac disease (52%versus39%, p=0.012, and 52%versus41%, p=0.039, respectively) and longer hospitalisation duration (median stay 8versus6 days, p<0.001). Anti-influenza therapies were less prescribed among RSV patients than influenza patients (20%versus66%, p<0.001). In-hospital composite outcome was poorer in RSV patients (aPR 1.5, 95% CI 1.1–2.1) than in those hospitalised with influenza. No difference was observed for the post-discharge composite outcome (aPR 1.1, 95% CI 0.8–1.6).ConclusionRSV infection results in serious respiratory illness, with worse in-hospital outcomes than influenza and with similar midterm post-discharge outcomes.
VEGF-C/VEGFR-3 signalling in macrophages ameliorates acute lung injury
Authors: Yamashita Masahiro , Niisato Miyuki , Kawasaki Yasushi , Karaman Sinem , Robciuc Marius R. , Shibata Yuji , Ishida Yoji , Nishio Ryosuke , Masuda Tomoyuki , Sugai Tamotsu , Ono Masao , Tuder Rubin M. , Alitalo Kari , Yamauchi Kohei 
Published: August 2021

BackgroundSuccessful recovery from acute lung injury requires inhibition of neutrophil influx and clearance of apoptotic neutrophils. However, the mechanisms underlying recovery remain unclear. We investigated the ameliorative effects of vascular endothelial growth factor (VEGF)-C/VEGF receptor 3 (VEGFR-3) signalling in macrophages in lipopolysaccharide (LPS)-induced lung injury.MethodsLPS was intranasally injected into wild-type and transgenic mice. Gain and loss of VEGF-C/VEGFR-3 signalling function experiments employed adenovirus-mediated intranasal delivery of VEGF-C (Ad-VEGF-C vector) and soluble VEGFR-3 (sVEGFR-3) or anti-VEGFR-3 blocking antibodies and mice with a deletion of VEGFR-3 in myeloid cells.ResultsThe early phase of lung injury was significantly alleviated by the overexpression of VEGF-C with increased levels of bronchoalveolar lavage (BAL) fluid interleukin-10 (IL-10), but worsened in the later phase by VEGFR-3 inhibition upon administration of Ad-sVEGFR-3 vector. Injection of anti-VEGFR-3 antibodies to mice in the resolution phase inhibited recovery from lung injury. The VEGFR-3-deleted mice had a shorter survival time than littermates and more severe lung injury in the resolution phase. Alveolar macrophages in the resolution phase digested most of the extrinsic apoptotic neutrophils and VEGF-C/VEGFR-3 signalling increased efferocytosisviaupregulation of integrin αvin the macrophages. We also found that incubation with BAL fluid from acute respiratory distress syndrome (ARDS) patients, but not from controls, decreased VEGFR-3 expression and the efficiency of IL-10 expression and efferocytosis in human monocyte-derived macrophages.ConclusionsVEGF-C/VEGFR-3 signalling in macrophages ameliorates experimental lung injury. This mechanism may also provide an explanation for ARDS resolution.
Identification of asthma-associated microRNAs in bronchial biopsies
Authors: Roffel Mirjam P. , Boudewijn Ilse M. , van Nijnatten Jos L.L. , Faiz Alen , Vermeulen Corneel J. , van Oosterhout Antoon J. , Affleck Karen , Timens Wim , Bracke Ken R. , Maes Tania , Heijink Irene H. , Brandsma Corry-Anke , van den Berge Maarten 
Published: August 2021

BackgroundChanges in microRNA (miRNA) expression can contribute to the pathogenesis of many diseases, including asthma. We aimed to identify miRNAs that are differentially expressed between asthma patients and healthy controls, and explore their association with clinical and inflammatory parameters of asthma.MethodsDifferentially expressed miRNAs were determined by small RNA sequencing on bronchial biopsies of 79 asthma patients and 82 healthy controls using linear regression models. Differentially expressed miRNAs were associated with clinical and inflammatory asthma features. Potential miRNA–mRNA interactions were analysed using mRNA data available from the same bronchial biopsies, and enrichment of pathways was identified with Enrichr and g:Profiler.ResultsIn total, 78 differentially expressed miRNAs were identified in bronchial biopsies of asthma patients compared with controls, of which 60 remained differentially expressed after controlling for smoking and inhaled corticosteroid treatment. We identified several asthma-associated miRNAs, including miR-125b-5p and miR-223-3p, based on a significant association with multiple clinical and inflammatory asthma features and their negative correlation with genes associated with the presence of asthma. The most enriched biological pathway(s) affected by miR-125b-5p and miR-223-3p were inflammatory response and cilium assembly/organisation. Of interest, we identified that lower expression of miR-26a-5p was linked to more severe eosinophilic inflammation as measured in blood, sputum as well as bronchial biopsies.ConclusionCollectively, we identified miR-125b-5p, miR-223-3p and miR-26a-5p as potential regulators that could contribute to the pathogenesis of asthma.
Blood leukocyte transcriptomes in Gram-positive and Gram-negative community-acquired pneumonia
Authors: Pereverzeva Liza , Uhel Fabrice , Peters Sengers Hessel , Butler Joe , van Vught Lonneke A. , Burnham Katie L. , Davenport Emma E. , Knight Julian C. , Cremer Olaf L. , Schultz Marcus J. , Bonten Marc M.J. , Scicluna Brendon P. , van der Poll Tom 
Published: August 2021

BackgroundGram-positive and Gram-negative bacteria are the most common causative pathogens in community-acquired pneumonia (CAP) on the intensive care unit (ICU). The aim of this study was to determine whether the host immune response differs between Gram-positive and Gram-negative CAP upon ICU admission.Methods16 host response biomarkers providing insight into pathophysiological mechanisms implicated in sepsis and blood leukocyte transcriptomes were analysed in patients with CAP upon ICU admission in two tertiary hospitals in the Netherlands.Results309 patients with CAP with a definite or probable likelihood (determined by predefined criteria) were included. A causative pathogen was determined in 74.4% of admissions. Patients admitted with Gram-positive CAP (n=90) were not different from those admitted with Gram-negative CAP (n=75) regarding demographics, chronic comorbidities, severity of disease and mortality. Host response biomarkers reflective of systemic inflammation, coagulation activation and endothelial cell function, as well as blood leukocyte transcriptomes, were largely similar between Gram-positive and Gram-negative CAP. Blood leukocyte transcriptomes were also similar in Gram-positive and Gram-negative CAP in two independent validation cohorts. On a pathogen-specific level,Streptococcus pneumoniaeandEscherichia coliinduced the most distinct host immune response.ConclusionOutcome and host response are similar in critically ill patients with CAP due to Gram-positive bacteria compared with Gram-negative bacteria.
Exhaled volatile organic compounds and lung microbiome in COPD: a pilot randomised controlled trial
Authors: Mohan Divya , Keir Holly R. , Richardson Hollian , Mayhew David , Boyer Joseph , van der Schee Marc P. , Allsworth Max D. , Miller Bruce E. , Tal-Singer Ruth , Chalmers James D. 
Published: August 2021

BackgroundBreath analysis is a burgeoning field, with interest in volatile organic compounds (VOCs) as a noninvasive diagnostic tool or an outcome measure, but no randomised controlled trials (RCTs) have yet evaluated this technology in a clinical trial longitudinally. In a pilot RCT, our exploratory objectives were feasibility of measuring VOCsviamultiple techniques, assessing relationships between VOCs andHaemophiluscolonisation and whether CXCR2 antagonism with danirixin altered lung microbiome composition in individuals with COPD.Method43 participants had VOCs and sputum biomarkers evaluated. VOCs and induced sputum were collected after 6 h of fasting at screening and at days 1, 7 and 14. VOCs were analysedviagas chromatography mass spectrometry (GC-MS), field asymmetric ion mobility spectrometry (FAIMS) and eNose. The primary outcome for these analyses was the relationship between VOCs andHaemophilusabundance determined by 16S rRNA sequencing.ResultsA joint-effects model demonstrated a modest relationship between four exhaled VOCs andHaemophilusrelative abundance (R2=0.55) measured only by GC-MS, but not as measured using gas chromtaography FAIMS or eNose. There was considerable variability in absolute quantities of individual VOCs longitudinally.ConclusionsVOC measurement in clinical trials to identify subsets of COPD is feasible, but assessment of new VOC technologies must include concurrent GC-MS validation. Further work to standardise collection of VOCs and measuring a background or “housekeeper” VOC is required to understand and normalise individual VOC quantities.