bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital at home: a systematic review of how medication management is conceptualised, described and implemented in practice – a study protocol
Authors: McGlen Sophie , Lasserson Daniel , Crowley Clare , Qamariat Zahra AL , Lim Rosemary H 
Published: May 2022

AbstractIntroductionHospital at Home (H@H) is a method of healthcare delivery, where hospital level interventions are conducted in the patient’s usual place of residence, offering an alternative to hospital admission. This often includes the ability to perform point of care diagnostics and treat conditions using a range of treatments traditionally associated with hospital admission, including intravenous medicines and oxygen. H@H services have been established worldwide but there is a wide variation in definition and delivery models and currently no documented evidence supporting the delivery of medicines and medicines management within the H@H model. Therefore, this study aims to 1) describe how medication management in H@H is conceptulised, 2) describe and identify key components of medication management in H@H and 3) describe and identify variability in the implementation of medication management services within H@H modelsMethods and AnalysisWe will search a range of databases (PubMed, Medline, Embase, CINAHL), publicly accessible documents and expert recommendations. Studies, reports and policy documents published between 1st January 2000 and 31st January 2022 will be included. Two independent reviewers will 1) screen and select studies based on a priori inclusion/exclusion, 2) conduct quality assessment using the Mixed Methods Appraisal Tool on included studies and 3) extract data. Inductive thematic analysis (objectives 1 and 2), the SEIPS 2.0 model (objective 2) and the Consolidated Framework for Implementation Research (objective 3) will be used to synthesise data.Ethics and disseminationThis systematic review will use secondary data sources from published documents, and as such research ethical approval was not required. We will disseminate the findings of this study in a peer-reviewed journal and national/international conference(s).PROSPERO registration numberCRD42022300691Strengths and limitations of this studyThe search will be performed on a comprehensive range of databases and relevant information sources to capture a global perspective relating to Hospital at Home (H@H).A wide range of search terms will be used in our search, however due to the changing nature of H@H, some terms may be unintentionally missed.Only published literature will be synthesized in this systematic review, and it is recognised that in a rapidly changing environment not all practices will be captured in written form.A combination of thematic synthesis, a work systems model (Systems Engineering Initiative for Patient Safety 2.0) and the Consolidated Framework for Implementation Research will be used to provide a system-level analysis of studies.The study team consists of four pharmacists from a range of practice and research backgrounds and a H@H consultant, therefore, will benefit from different perspectives on the topic area.
Reconstruction of Full-length scFv Libraries with the Extended Range Targeted Sequencing Method
Authors: Wei Christopher , Criner Sarah , Sridhar Bharat , Shultzaberger Ryan , Looney Timothy , Fabani Martin M , Glezer Eli N 
Published: May 2022

AbstractSingle chain fragment variable (scFv) phage display libraries of randomly paired VH-VL antibody domains are a powerful and widely adopted tool for the discovery of antibodies of a desired specificity. Characterization of full length VH-VL constructs using synthetic long read assemblies of short read next-generation sequencing data has emerged as a powerful approach to identify antibody candidates with greater speed and sensitivity than classical screening methods. Here we introduce a new version of the synthetic long read approach, which we denote the Extended Range Targeted Sequencing method. We apply the method to demonstrate accurate and high throughput analysis of full-length VH-VL constructs from a commercial scFv combinatorial display library.
Radiological Imaging of Viral Pneumonia Cases Identified Before the COVİD-19 Pandemic Period and COVİD-19 Pneumonia Cases Comparison of Characteristics
Authors: Cömert Rana Günöz , Cingöz Eda , Meşe Sevim , Durak Görkem , Tunacı Atadan , Ağaçfidan Ali , Önel Mustafa , Ertürk Şükrü Mehmet 
Published: May 2022

AbstractBackgroundThoracic CT imaging is widely used as a diagnostic method in the diagnosis of COVID-19 pneumonia. Radiological differential diagnosis and isolation of other viral agents causing pneumonia in patients gained importance, especially during the pandemic period.AimsWe aimed to investigate whether there is a difference between the CT imaging findings characteristically defined in COVID-19 pneumonia and the findings detected in pneumonia due to other viral agents, and which finding may be more effective in the diagnosis.Study DesignThe study included 249 adult patients with pneumonia found in thorax CT examination and positive COVID-19 RT-PCR test and 94 patients diagnosed with non-COVID pneumonia (viral PCR positive, no bacterial/fungal agents were detected in other cultures) from the last 5 years before the pandemic. It was retrospectively analyzed using the PACS System. CT findings were evaluated by two radiologists with 5 and 20 years of experience who did not know to which group the patient belonged, and it was decided by consensus.MethodsDemographic data (age, gender, known chronic disease) and CT imaging findings (percentage of involvement, number of lesions, distribution preference, dominant pattern, ground-glass opacity distribution pattern, nodule, tree in bud sign, interstitial changes, crazy paving sign, reversed halo sign, vacuolar sign, halo sign, vascular enlargement, linear opacities, traction bronchiectasis, peribronchial wall thickness, air trapping, pleural retraction, pleural effusion, pericardial effusion, cavitation, mediastinal/hilar lymphadenopathy, dominant lesion size, consolidation, subpleural curvilinear opacities, air bronchogram, pleural thickening) of the patients were evaluated. CT findings were also evaluated with the RSNA consensus guideline and the CORADS scoring system. Data were divided into two main groups as non-COVID-19 and COVID-19 pneumonia and compared statistically with chi-square tests and multiple regression analysis of independent variables.ResultsTwo main groups; RSNA and CORADS classification, percentage of involvement, number of lesions, distribution preference, dominant pattern, nodule, tree in bud, interstitial changes, crazy paving, reverse halo vascular enlargement, peribronchial wall thickness, air trapping, pleural retraction, pleural/pericardial effusion, cavitation and mediastinal/hilar lymphadenopathy were compared, significant differences were found between the groups (p < 0.01). Multiple linear regression analysis of independent variables found a significant effect of reverse halo sign (β = 0.097, p <0.05) and pleural effusion (β = 10.631, p <0.05) on COVID-19 pneumonia.ConclusionPresence of reverse halo and absence of pleural effusion was found to be efficient in the diagnosis of COVID-19 pneumonia.
Autoimmune interactions between the HLA-DQβ157polymorphism, T cell receptors, and microbial mimics of insulin in type 1 diabetes
Authors: García Arcadio Rubio , Paterou Athina , Powell Doherty Rebecca D. , Landry Laurie G. , Lee Mercede , Anderson Amanda M. , Scudder Claire L. , Slawinski Hubert , Ferreira Ricardo C. , Trzupek Dominik , Szypowska Agnieszka , Teyton Luc , Ternette Nicola , Nakayama Maki , Wicker Linda S. , Todd John A. , Pekalski Marcin L. 
Published: May 2022

AbstractInsulin autoimmunity and pancreatic islet β-cell destruction, mediated by T cells, underlie the pathogenesis of type 1 diabetes (T1D). However, the mechanisms by which genetic and environmental risk factors interact to cause T1D remain incompletely understood. Here, we show how variation in the human leukocyte antigen (HLA) class II region, notably DQβ157, the strongest T1D genetic risk factor, induces a positive thymic selection bias that favors amino acid motifs with negatively charged side chains in the peptide-binding CDR3β region of CD4+T cell receptors (TCRs). This bias was enriched in TCRs from T1D patients and predicted the proportion of anti-insulin infiltrates in pancreatic islets. We link host genetics and immunity to the environment by identifying over 100 gut bacterial proteins with significantly similar sequences to a primary epitope in T1D, insulin B9–25peptide. We show that CD4+T cells isolated from the pancreas of a newly diagnosed child with T1D recognised both insulin and a bacterial mimotope peptide, restricted by the most predisposing DQ molecule. Our results point to the evolution of certain microbial antigens towards mimicry in the regulation of immune tolerance to insulin.
Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection
Authors: Yu Qiuning , Xia Namei , Zhao Yanteng , Jin Huifang , Chen Renyin , Ye Fanglei , Chen Liyinghui , Xie Ying , Wan Kangkang , Zhou Jun , Zhou Dihan , Lv Xianping 
Published: May 2022

AbstractBackgroundNumerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease.MethodsThe current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC and multiple cancer types.ResultsWe obtained 438,558 DMCs, 15,462 DMRs, and 1,568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC and nine other cancer types. The HOXL-score estimated by HOXC10 and HOXD1 methylation showed good ability in discriminating ESCC from normal samples, while the methylation of GSX1 displayed potential utility for pan-cancer detection.ConclusionsWe observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of multiple cancer types.
Prenatal alcohol exposure alters axon formation and Robo/Slit guidance cue expression in the internal capsule at E15.5
Authors: Chi Peter , Dewees Kevyn , Scoville Jennifer , Deak Terrence , Favero Carlita 
Published: May 2022

AbstractWe previously showed the prenatal alcohol exposure (PAE) induced precocious growth of E15.5 internal capsule axons. We set out to further delineate which axon tracts were affected and a potential mechanism for this phenomenon. Pregnant Swiss Webster mice were exposed to saline or 20% ethanol via subcutaneous injection from embryonic days (E) 7.5 until E14.5. E15.5 embryos were captured via C-section and brains were either fixed for immunostaining or flash frozen for tissue punches. To identify internal capsule axons we performed immunohistochemistry using L1 antibody to visualize all internal capsule axons and NetrinG1 antibody to identify thalamocortical axons specifically. mRNA was extracted from tissue punches to visualize Slit1, Robo1, Slit2, and Robo2 gene expression levels via real time RT PCR. We found that L1-expressing axons exhibited increased axon crossing in females with the opposite effect in males and no difference in Netrin-G1-expressing axons. We also found PAE increased Robo1 mRNA. Taken together, our results indicate that PAE elicits specific effects on axon trajectories, potentially via the Slit/Robo guidance family of repellents and receptors. These findings add to the growing body of evidence demonstrating alcohol disruptions of axon growth and guidance during embryonic development that may contribute to connectivity errors that characterize Fetal Alcohol Spectrum Disorders.
Mapping the landscape of anti-phage defense mechanisms in the E. coli pangenome
Authors: Vassallo Christopher , Doering Christopher , Littlehale Megan L. , Teodoro Gabriella , Laub Michael T. 
Published: May 2022

SummaryThe ancient, ongoing coevolutionary battle between bacteria and their viral predators, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Dozens of additional anti-phage systems have been identified based on their co-location within so-called defense islands, but whether these computational screens are exhaustive is unclear. Here, we developed an experimental selection scheme agnostic to genomic context to identify defense systems encoded in 71 diverse E. coli strains. Our results unveil 21 new and conserved defense systems, none of which were previously detected as enriched in defense islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defense systems in E. coli, with defense systems typically carried in specific locations, or hotspots. These hotspots in homologous prophages and mobile genetic elements encode dozens of additional, as-yet uncharacterized defense system candidates. Collectively, our findings reveal an extended landscape of antiviral immunity in E. coli and provide a generalizable approach for mapping defense systems in other species.
Comprehensive Analysis of the Expression and Prognosis for PSMBs in Clear Cell Renal Cell Carcinoma
Authors: Jiang Ning , Zhang Yulin , Zhao Zihan , Li Tianhang , Liu Tianyao , Guo Hongqian , Yang Rong 
Published: May 2022

AbstractBackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common malignances with an ever-increasing incidence and high mortality. Although comprehensive therapy has made great progress in recent years, the prognosis of most ccRCC patients is still poor. The proteasome β subunits (PSMBs) are a group of genes composing the ubiquitin–proteasome pathway, which is the principal mechanism of protein catabolism in mammalian cytoplasm and nucleus and is essential for the regulation of almost all cellular processes. Growing evidence show s that the PSMBs play an important role in the occurrence and progression of various cancers. However, the expression and prognostic value of PSMBs in ccRCC have not been evaluated.MethodsTo solve this issue, ONCOMINE, UALCAN, Human Protein Atlas, cBioPortal, Metascape, GeneMANIA, STRING, DAVID 6.8, TIMER were used in this study.ResultsThe transcriptional expression levels of PSMB2/4/7/8/9/10 in ccRCC tissues were found to be significantly upregulated, and the mRNA expression levels of PSMB1/2/3/4/8/9/10 were associated with advanced tumor stage and tumor grade. Besides, higher mRNA expression of PSMB1/2/3/4/5/6/7/10 were associated with a shorter overall survival (OS). Furthermore, the protein expression level of PSMB4/7/8/9/10 in ccRCC was higher than normal renal tissues. Significant relationships were also found between the expression of PSMBs and the infiltration of immune-related cells.ConclusionsThe present study implied that PSMB4 and PSMB10 might act as potential therapy targets and prognostic biomarkers in ccRCC, which may contribute to available knowledge, improve the treatment designs, and enhance the accuracy of prognosis for patients with ccRCC.
DOXYCYCLINE TO TREAT LEVODOPA-INDUCED DYSKINESIAS IN PARKINSON’S DISEASE: A PROOF-OF-CONCEPT STUDY
Authors: Santos-Lobato Bruno Lopes , Brito Manuelina Mariana Capellari Macruz , Pimentel Ângela Vieira , Cavalcanti Rômulo Torres Oliveira , Del-Bel Elaine , Tumas Vitor 
Published: May 2022

ABSTRACTBackgroundLevodopa-induced dyskinesia (LID) is a common motor complication of levodopa therapy in patients with Parkinson’s disease (PD). Doxycycline is a widely used and inexpensive tetracycline with anti-inflammatory properties.ObjectiveEvaluate the efficacy and safety of doxycycline in patients with PD and LID.MethodsThis was an open-label, single-center, phase 2 proof-of-concept study in patients with PD with mild functional impact of dyskinesia, which used levodopa three times daily, in a movement disorders clinic in Brazil. Participants were treated with doxycycline 200 mg/day for 12 weeks, with evaluations in baseline, week 4, and week 12 of treatment. The primary outcome measure was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) total score at week 12, evaluated by two blinded raters. Key secondary outcomes measures were OFF time and ON time with troublesome dyskinesia in the PD home diary.ResultsEight patients with PD were treated and evaluated. Doxycycline 200 mg/day reduced the UDysRS total score in week 12, compared with baseline (Friedman’s X2= 9.6, p = 0.008). Further, doxycycline reduced the ON time with troublesome dyskinesia (Friedman’s X2= 10.8, p = 0.004) without worsening parkinsonism. There were no severe adverse events, and dyspepsia was the commonest event.ConclusionsDoxycycline was effective in reducing LID and safe after a 12-week treatment. Further well-designed placebo-controlled clinical trials with a longer duration and a larger number of participants are needed.
Surface changes of clinical target volume and its sublocations in nasopharyngeal cancer with image-guided radiation therapy
Authors: Tan Wenyong , Yang Ming , Hu Desheng 
Published: May 2022

ABSTRACTPURPOSEWe aimed to quantify the sublocal geometric uncertainties of the neck prophylactic clinical target volume (CTVprophy) during image-guided radiotherapy for nasopharyngeal cancer (NPC).MATERIALS AND METHODSTwenty patients with locally advanced NPC underwent one planning computed tomography (CTplan) followed by six weekly CT (CTrepeat) scans during chemotherapy and intensity-modulated radiation therapy. The sternocleidomastoid muscle (SCM) and its anterior, middle, and posterior parts, as well as the body contours at the 1st (C1) and 2nd (C2) cervical vertebrae, hyoid bone (HB), and cricoid cartilage (CC) in transverse CT sections, were manually delineated in the CTplan and each CTrepeat. The residual error and 2D or 3D vector displacements of each sublocation were calculated, and the planning target volume (PTV) margins were estimated using the PTV margin formula.RESULTSThe left- and right-sided SCM volume decreased by 3.7 ± 9.6% (1.9–5.4%) and 5.1 ± 6.7% (3.9–6.3%), respectively, and the center of mass shifted medially 0.8–0.9 mm. An anisotropic PTV margin of 2–4 and 1–5 mm was needed in the left-right and anterior-posterior directions, respectively. The geometric changes in the upper neck at the C1 and C2 sections were smaller than those in the middle-lower neck at the HB and CC levels. At the same sublocation, the margin needed in the anterior-middle part was smaller than that needed in the posterior part of the neck. The rigid imaging registration-induced anatomical errors in the upper neck were < 1.9%, and those in the middle and lower neck level were 0.6–3.8%.CONCLUSIONSThe surface geometrical changes of the neck prophylactic CTV in the sublocations are substantial and an anisotropic PTV margin of 1–5 mm is needed in the context of image-guided radiotherapy for NPC.
Reweighting the UK Biobank to reflect its underlying sampling population substantially reduces pervasive selection bias due to volunteering
Authors: van Alten Sjoerd , Domingue Benjamin W. , Galama Titus , Marees Andries T. 
Published: May 2022

AbstractThe UK Biobank (UKB) is a large cohort study of considerable empirical importance to fields such as medicine, epidemiology, statistical genetics, and the social sciences, due to its very large size (∼ 500,000 individuals) and its wide availability of variables. However, the UKB is not representative of its underlying sampling population. Selection bias due to volunteering (volunteer bias) is a known source of confounding. Individuals entering the UKB are more likely to be older, to be female, and of higher socioeconomic status. Using representative microdata from the UK Census as a reference, we document significant bias in estimated associations due to non-random selection into the UKB. For some associations, volunteer bias in the UKB is so severe that estimates have the opposite sign. E.g., older individuals in the UKB tend to be in better health. To aid researchers in correcting for volunteer bias in the UKB, we construct inverse probability weights based on UK census microdata. The use of these weights in weighted regressions reduces 78% of volunteer bias on average. Our inverse probability weights will be made available.
Representation of evidence-based clinical practice guideline recommendations on FHIR
Authors: Lichtner Gregor , Jurth Carlo , Alper Brian S , Spies Claudia , Boeker Martin , Meerpohl Joerg J , von Dincklage Falk 
Published: May 2022

AbstractBackgroundVarious formalisms have been developed to represent clinical practice guideline recommendations in a computer-interpretable way. However, none of the existing formalisms leverage the structured and computable information that emerge from the evidence-based guideline development process. Thus, we here propose a FHIR-based guideline representation format that is structurally aligned to the knowledge artifacts emerging during the process of evidence-based guideline development.MethodsWe identified the information required to represent evidence-based clinical practice guideline recommendations and reviewed the knowledge artifacts emerging during the evidence-based guideline development process. Then we conducted a consensus-based design process with domain experts to develop an information model for guideline recommendation representation that is structurally aligned to the evidence-based guideline recommendation development process and a corresponding representation based on evidence-based medicine (EBM)-on-FHIR resources.ResultsThe information model of clinical practice guideline recommendations and its EBMonFHIR-based representation contain the clinical contents of individual guideline recommendations, a set of metadata for the recommendations, the ratings for the recommendations (e.g., strength of recommendation, certainty of overall evidence), the ratings of certainty of evidence for individual outcomes (e.g., risk of bias) and links to the underlying evidence (systematic reviews based on primary studies). We created profiles and an implementation guide for all FHIR resources required to represent a complete clinical practice guideline and used the profiles to implement an exemplary clinical guideline recommendation.ConclusionsOur EBMonFHIR-based representation of clinical practice guideline recommendations allows to directly link the evidence assessment process through systematic reviews and evidence grading, and the underlying evidence from primary studies to the resulting guideline recommendations. This not only allows to evaluate the evidence on which recommendations are based on transparently and critically, but also allows for a more direct and in future automatable way to generate computer-interpretable guideline recommendations based on computable evidence.