bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated histopathological evaluation of pterygium using artificial intelligence
Authors: Kim Jong Hoon , Kim Young Jae , Lee Yeon Jeong , Hyon Joon Young , Han Sang Beom , Kim Kwang Gi 
Published: January 2022

PurposeThis study aimed to evaluate the efficacy of a new automated method for the evaluation of histopathological images of pterygium using artificial intelligence.MethodsAn in-house software for automated grading of histopathological images was developed. Histopathological images of pterygium (400 images from 40 patients) were analysed using our newly developed software. Manual grading (I–IV), labelled based on an established scoring system, served as the ground truth for training the four-grade classification models. Region of interest segmentation was performed before the classification of grades, which was achieved by the combination of expectation-maximisation andk-nearest neighbours. Fifty-five radiomic features extracted from each image were analysed with feature selection methods to examine the significant features. Five classifiers were evaluated for their ability to predict quantitative grading.ResultsAmong the classifier models applied for automated grading in this study, the bagging tree showed the best performance, with a 75.9% true positive rate (TPR) and 75.8% positive predictive value (PPV) in internal validation. In external validation, the method also demonstrated reproducibility, with an 81.3% TPR and 82.0% PPV for the average of four classification grades.ConclusionsOur newly developed automated method for quantitative grading of histopathological images of pterygium may be a reliable method for quantitative analysis of histopathological evaluation of pterygium.
Changing operating room practices: the effect on postoperative endophthalmitis rates following cataract surgery
Authors: Haripriya Aravind , Ravindran Ravilla D , Robin Alan L , Shukla Aakriti Garg , Chang David F 
Published: January 2022

PurposeTo determine whether four new operating room (OR) protocols instituted because of COVID-19 reduced the cataract surgical postoperative endophthalmitis rate (POE).DesignRetrospective, sequential, clinical registry study.Methods85 552 sequential patients undergoing cataract surgery at the Aravind Eye Hospitals between 1 January 2020 and 25 March 2020 (56 551 in group 1) and 3 May 2020 and 31 August 2020 (29 011 in group 2). In group 1, patients were not gowned, surgical gloves were disinfected but not changed between cases, OR floors were not cleaned between every case, and multiple patients underwent preparation and surgery in the same OR. In group 2, each patient was gowned, surgical gloves were changed between each case, OR floors and counters were cleaned between patients, and only one patient at a time underwent preparation and surgery in the OR.ResultsGroup 1 was older, had slightly more females, and better preoperative vision. More eyes in group 2 underwent phacoemulsification (p=0.18). Three eyes (0.005%) in group 1 and 2 eyes (0.006%) in group 2 developed POE (p=0.77). Only one eye that underwent phacoemulsification developed POE; this was in group 1. There was no difference in posterior capsule rupture rate between the two groups.ConclusionsAdopting a set of four temporary OR protocols that are often mandatory in the Western world did not reduce the POE rate. Along with previously published studies, these results challenge the necessity of these common practices which may be needlessly costly and wasteful, arguing for the reevaluation of empiric and potentially unnecessary guidelines that govern ophthalmic surgeries.
Rethinking pain education from the perspectives of people experiencing pain: a meta-ethnography to inform physiotherapy training
Authors: Thompson Kate , Johnson Mark I , Milligan James , Briggs Michelle 
Published: January 2022

BackgroundPain is a complex, global and multidimensional phenomena that impacts the lives of millions of people. Chronic pain (lasting more than 3 months) is particularly burdensome for individuals, health and social care systems. Physiotherapists have a fundamental role in supporting people who are experiencing pain. However, the appropriateness of pain education in pre-registration physiotherapy training programmes has been questioned.Recent research reports identify the need to integrate the voice of patients to inform the development of the pre-registration curriculum. The aim of this meta-ethnography was to develop new conceptual understanding of patients' needs when accessing physiotherapy for pain management. The concepts were viewed through an educational lens to create a patient needs-based model to inform physiotherapy training.MethodsNoblit and Hare’s seven-stage meta-ethnography was used to conduct this qualitative systematic review. Five databases (MEDLINE, CINAHL Complete, ERIC, PsycINFO and AMED) were searched with eligibility criteria: qualitative methodology, reports patient experience of physiotherapy, adult participants with musculoskeletal pain, reported in English. Databases were searched to January 2018. Emerge reporting guidelines guided the preparation of this manuscript.ResultsA total of 366 citations were screened, 43 full texts retrieved and 18 studies included in the final synthesis. Interpretive qualitative synthesis resulted in six distinct categories that represent patients’ needs when in pain. Analysing categories through an education lens resulted in three overall lines of argument to inform physiotherapy training. The categories and lines of argument are represented in a ‘needs-based’ model to inform pre-registration physiotherapy training.DiscussionThe findings provide new and novel interpretations of qualitative data in an area of research that lacks patient input. This is a valuable addition to pain education research. Findings support the work of others relative to patient centredness in physiotherapy.
Vertical integration of primary care practices with acute hospitals in England and Wales: why, how and so what? Findings from a qualitative, rapid evaluation
Authors: Sidhu Manbinder , Pollard Jack , Sussex Jon 
Published: January 2022

ObjectivesTo understand the rationale, implementation and early impact of vertical integration between primary care medical practices and the organisations running acute hospitals in the National Health Service in England and Wales.Design and settingA qualitative, cross-comparative case study evaluation at two sites in England and one in Wales, consisting of interviews with stakeholders at the sites, alongside observations of strategic meetings and analysis of key documents.ResultsWe interviewed 52 stakeholders across the three sites in the second half of 2019 and observed four meetings from late 2019 to early 2020 (further observation was prevented by the onset of the COVID-19 pandemic). The single most important driver of vertical integration was found to be to maintain primary care local to where patients live and thereby manage demand pressure on acute hospital services, especially emergency care. The opportunities created by maintaining local primary care providers—to develop patient services in primary care settings and better integrate them with secondary care—were exploited to differing degrees across the sites. There were notable differences between sites in operational and management arrangements, and in organisational and clinical integration. Closer organisational integration was attributed to previous good relationships between primary and secondary care locally, and to historical planning and preparation towards integrated working across the local health economy. The net impact of vertical integration on health system costs is argued by local stakeholders to be beneficial.ConclusionsVertical integration is a valuable option when primary care practices are at risk of closing, and may be a route to better integration of patient care. But it is not the only route and vertical integration is not attractive to all primary care physicians. A future evaluation of vertical integration is intended; of patients’ experience and of the impact on secondary care service utilisation.
Chinese patients with hereditary spastic paraplegias (HSPs): a protocol for a hospital-based cohort study
Authors: Qiu Yu-Sen , Zeng Yi-Heng , Yuan Ru-Ying , Ye Zhi-Xian , Bi Jin , Lin Xiao-Hong , Chen Yi-Jun , Wang Meng-Wen , Liu Ying , Yao Shao-Bo , Chen Yi-Kun , Jiang Jun-Yi , Lin Yi , Lin Xiang , Wang Ning , Fu Ying , Chen Wan-Jin 
Published: January 2022

IntroductionHereditary spastic paraplegias (HSPs) are uncommon but not rare neurodegenerative diseases. More than 100 pathogenic genes and loci related to spastic paraplegia symptoms have been reported. HSPs have the same core clinical features, including progressive spasticity in the lower limbs, though HSPs are heterogeneous (eg, clinical signs, MRI features, gene mutation). The age of onset varies greatly, from infant to adulthood. In addition, the slow and variable rates of disease progression in patients with HSP represent a substantial challenge for informative assessment of therapeutic efficacy. To address this, we are undertaking a prospective cohort study to investigate genetic–clinical characteristics, find surrogates for monitoring disease progress and identify clinical readouts for treatment.Methods and analysisIn this case-control cohort study, we will enrol 200 patients with HSP and 200 healthy individuals in parallel. Participants will be continuously assessed for 3 years at 12-month intervals. Six aspects, including clinical signs, genetic spectrum, cognitive competence, MRI features, potential biochemical indicators and nerve electrophysiological factors, will be assessed in detail. This study will observe clinical manifestations and disease severity based on different molecular mechanisms, including oxidative stress, cholesterol metabolism and microtubule dynamics, all of which have been proposed as potential treatment targets or modalities. The analysis will also assess disease progression in different types of HSPs and cellular pathways with a longitudinal study using t tests and χ2 tests.Ethics and disseminationThe study was granted ethics committee approval by the first affiliated hospital of Fujian Medical University (MRCTA, ECFAH of FMU (2019)194) in 2019. Findings will be disseminated via presentations and peer-reviewed publications. Dissemination will target different audiences, including national stakeholders, researchers from different disciplines and the general public.Trial registration numberNCT04006418.
Persistent reduction of retinal microvascular vessel density in patients with moderate and severe COVID-19 disease
Authors: Banderas García Sandra , Aragón David , Azarfane Brahim , Trejo Fernando , Garrell-Salat Xavier , Sánchez-Montalvá Adrián , Otero-Romero Susana , Garcia-Arumi Jose , Zapata Miguel Angel 
Published: January 2022

ObjectiveThis study aims to analyse the possible recovery or worsening in retinal microvasculature after 8 months in a previously studied COVID-19 cohort.Methods and analysisA cross-sectional case–control study and a prospective longitudinal cohort study. Participants were the subjects of our previous study who re-enrolled for a new examination including a fundus photograph (retinography), an optical coherence tomography (OCT) scan and an OCT angiography. COVID-19 diagnosed patients were divided into three groups: group 1: mild disease, asymptomatic/paucisymptomatic subjects who received outpatient care; group 2: moderate disease and group 3: severe disease, both of which required hospital admission because of pneumonia. Statistical analyses were performed using SPSS software (V.23.0). Cross-sectional intergroup differences were analysed by means of analysis of variance for normally distributed variables and the Kruskal-Wallis test for non-normally distributed ones. In reference to the prospective part of the study (intragroup differences, baseline with 8-month comparison), a paired t-test was used for normally distributed data and Wilcoxon signed ranks sum for non-normally distributed data.ResultsThe fovea-centered superficial and deep vascular densities were significantly diminished in severe cases compared with mild cases (p=0.004; p=0.003, respectively, for superficial and deep) and to controls (p=0.014; p=0.010), also in moderate cases to mild group (p=0.004; p=0.003) and to controls (p=0.012; p=0.024). In the longitudinal study, no significant statistical differences were found between baseline and 8-month follow-up vessel density values.ConclusionWe demonstrated persistent reduction in the central vascular area over time in patients with moderate and severe COVID-19.
The association between vital signs and clinical outcomes in emergency department patients of different age categories
Authors: Candel Bart GJ , Duijzer Renée , Gaakeer Menno I , ter Avest Ewoud , Sir Özcan , Lameijer Heleen , Hessels Roger , Reijnen Resi , van Zwet Erik W , de Jonge Evert , de Groot Bas 
Published: January 2022

BackgroundAppropriate interpretation of vital signs is essential for risk stratification in the emergency department (ED) but may change with advancing age. In several guidelines, risk scores such as the Systemic Inflammatory Response Syndrome(SIRS) and Quick Sequential Organ Failure Assessment (qSOFA) scores, commonly used in emergency medicine practice (as well as critical care) specify a single cut-off or threshold for each of the commonly measured vital signs. Although a single cut-off may be convenient, it is unknown whether a single cut-off for vital signs truly exists and if the association between vital signs and in-hospital mortality differs per age-category.AimsTo assess the association between initial vital signs and case-mix adjusted in-hospital mortality in different age categories.MethodsObservational multicentre cohort study using the Netherlands Emergency Department Evaluation Database (NEED) in which consecutive ED patients ≥18 years were included between 1 January 2017 and 12 January 2020. The association between vital signs and case-mix adjusted mortality were assessed in three age categories (18-65; 66-80; >80 years) using multivariable logistic regression. Vital signs were each divided into five to six categories, for example, systolic blood pressure (SBP) categories (≤80, 81–100, 101–120, 121–140, >140 mm Hg).ResultsWe included 101 416 patients of whom 2374 (2.3%) died. Adjusted ORs for mortality increased gradually with decreasing SBP and decreasing peripheral oxygen saturation (SpO2). Diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) had quasi-U-shaped associations with mortality. Mortality did not increase for temperatures anywhere in the range between 35.5°C and 42.0°C, with a single cut-off around 35.5°C below which mortality increased. Single cut-offs were also found for MAP <70 mm Hg and respiratory rate >22/min. For all vital signs, older patients had larger increases in absolute mortality compared with younger patients.ConclusionFor SBP, DBP, SpO2and HR, no single cut-off existed. The impact of changing vital sign categories on prognosis was larger in older patients. Our results have implications for the interpretation of vital signs in existing risk stratification tools and acute care guidelines.
Gut microbiota regulate Alzheimer’s disease pathologies and cognitive disorders via PUFA-associated neuroinflammation
Authors: Chen Chun , Liao Jianming , Xia Yiyuan , Liu Xia , Jones Rheinallt , Haran John , McCormick Beth , Sampson Timothy Robert , Alam Ashfaqul , Ye Keqiang 
Published: January 2022

ObjectiveThis study is to investigate the role of gut dysbiosis in triggering inflammation in the brain and its contribution to Alzheimer’s disease (AD) pathogenesis.DesignWe analysed the gut microbiota composition of 3×Tg mice in an age-dependent manner. We generated germ-free 3×Tg mice and recolonisation of germ-free 3×Tg mice with fecal samples from both patients with AD and age-matched healthy donors.ResultsMicrobial 16S rRNA sequencing revealed Bacteroides enrichment. We found a prominent reduction of cerebral amyloid-β plaques and neurofibrillary tangles pathology in germ-free 3×Tg mice as compared with specific-pathogen-free mice. And hippocampal RNAseq showed that inflammatory pathway and insulin/IGF-1 signalling in 3×Tg mice brain are aberrantly altered in the absence of gut microbiota. Poly-unsaturated fatty acid metabolites identified by metabolomic analysis, and their oxidative enzymes were selectively elevated, corresponding with microglia activation and inflammation. AD patients’ gut microbiome exacerbated AD pathologies in 3×Tg mice, associated with C/EBPβ/asparagine endopeptidase pathway activation and cognitive dysfunctions compared with healthy donors’ microbiota transplants.ConclusionsThese findings support that a complex gut microbiome is required for behavioural defects, microglia activation and AD pathologies, the gut microbiome contributes to pathologies in an AD mouse model and that dysbiosis of the human microbiome might be a risk factor for AD.
CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment
Authors: Seyfrid Mathieu , Maich William Thomas , Shaikh Muhammad Vaseem , Tatari Nazanin , Upreti Deepak , Piyasena Deween , Subapanditha Minomi , Savage Neil , McKenna Dillon , Mikolajewicz Nicholas , Han Hong , Chokshi Chirayu , Kuhlmann Laura , Khoo Amanda , Salim Sabra Khalid , Archibong-Bassey Blessing , Gwynne William , Brown Kevin , Murtaza Nadeem , Bakhshinyan David , Vora Parvez , Venugopal Chitra , Moffat Jason , Kislinger Thomas , Singh Sheila 
Published: January 2022

PurposeGlioblastoma (GBM) patients suffer from a dismal prognosis, with standard of care therapy inevitably leading to therapy-resistant recurrent tumors. The presence of cancer stem cells (CSCs) drives the extensive heterogeneity seen in GBM, prompting the need for novel therapies specifically targeting this subset of tumor-driving cells. Here, we identify CD70 as a potential therapeutic target for recurrent GBM CSCs.Experimental designIn the current study, we identified the relevance and functional influence of CD70 on primary and recurrent GBM cells, and further define its function using established stem cell assays. We use CD70 knockdown studies, subsequent RNAseq pathway analysis, andin vivoxenotransplantation to validate CD70’s role in GBM. Next, we developed and tested an anti-CD70 chimeric antigen receptor (CAR)-T therapy, which we validatedin vitroandin vivousing our established preclinical model of human GBM. Lastly, we explored the importance of CD70 in the tumor immune microenvironment (TIME) by assessing the presence of its receptor, CD27, in immune infiltrates derived from freshly resected GBM tumor samples.ResultsCD70 expression is elevated in recurrent GBM and CD70 knockdown reduces tumorigenicityin vitroandin vivo. CD70 CAR-T therapy significantly improves prognosisin vivo. We also found CD27 to be present on the cell surface of multiple relevant GBM TIME cell populations, notably putative M1 macrophages and CD4 T cells.ConclusionCD70 plays a key role in recurrent GBM cell aggressiveness and maintenance. Immunotherapeutic targeting of CD70 significantly improves survival in animal models and the CD70/CD27 axis may be a viable polytherapeutic avenue to co-target both GBM and its TIME.
Trade-off of major bleeding versus myocardial infarction on mortality after percutaneous coronary intervention
Authors: Ng Andrew Kei-Yan , Ng Pauline Yeung , Ip April , Lam Lap Tin , Siu Chung-Wah 
Published: January 2022

BackgroundThe choice of antithrombotic therapy after percutaneous coronary intervention (PCI) is heavily dependent on the relative trade-off between major bleeding (MB) and myocardial infarction (MI). However, the mortality trade-off was mostly described in Western populations and remained unknown in East Asians.MethodThis was a retrospective cohort study from 14 hospitals under the Hospital Authority of Hong Kong between 2004 and 2017. Participants were patients undergoing first-time PCI and survived for the first year. Patients were stratified by the presence of MB and MI during the first year. The primary endpoint was all-cause mortality between 1 and 5 years after PCI. The secondary endpoint was cardiovascular mortality.ResultsA total of 32 180 patients were analysed. After adjustment for baseline characteristics and using patients with neither events as reference, the risks of all-cause mortality were increased in patients with MI only (HR, 1.63; 95% CI 1.45 to 1.84; p<0.001), further increased in those with MB only (HR, 2.11, 95% CI 1.86 to 2.39; p<0.001) and highest in those with both (HR, 2.92; 95% CI 2.39 to 3.56; p<0.001). In both Cox regression and propensity score analyses, MB had a stronger impact on all-cause mortality than MI, but similar impact on cardiovascular mortality.ConclusionsBoth MB and MI within the first year after PCI were associated with increase in all-cause and cardiovascular mortality in Chinese patients, but the impact was stronger with MB.
Identifying best modelling practices for tobacco control policy simulations: a systematic review and a novel quality assessment framework
Authors: Huang Vincy , Head Anna , Hyseni Lirije , O'Flaherty Martin , Buchan Iain , Capewell Simon , Kypridemos Chris 
Published: January 2022

BackgroundPolicy simulation models (PSMs) have been used extensively to shape health policies before real-world implementation and evaluate post-implementation impact. This systematic review aimed to examine best practices, identify common pitfalls in tobacco control PSMs and propose a modelling quality assessment framework.MethodsWe searched five databases to identify eligible publications from July 2013 to August 2019. We additionally included papers from Feirmanet alfor studies before July 2013. Tobacco control PSMs that project tobacco use and tobacco-related outcomes from smoking policies were included. We extracted model inputs, structure and outputs data for models used in two or more included papers. Using our proposed quality assessment framework, we scored these models on population representativeness, policy effectiveness evidence, simulated smoking histories, included smoking-related diseases, exposure-outcome lag time, transparency, sensitivity analysis, validation and equity.FindingsWe found 146 eligible papers and 25 distinct models. Most models used population data from public or administrative registries, and all performed sensitivity analysis. However, smoking behaviour was commonly modelled into crude categories of smoking status. Eight models only presented overall changes in mortality rather than explicitly considering smoking-related diseases. Only four models reported impacts on health inequalities, and none offered the source code. Overall, the higher scored models achieved higher citation rates.ConclusionsWhile fragments of good practices were widespread across the reviewed PSMs, only a few included a ‘critical mass’ of the good practices specified in our quality assessment framework. This framework might, therefore, potentially serve as a benchmark and support sharing of good modelling practices.