bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased histological severity and chronicity of interface inflammation in anti‐MDA5 dermatomyositis—A comparative dermatopathological analysis
Authors: Chan Agnes Wai Sze , Cheung Christina Man‐Tung , Wong Priscilla Ching‐Han , Choi Paul Cheung Lung , Ng Joanna Ka Man , Li Joshua Jing Xi 
Published: August 2023

AbstractAnti‐melanoma differentiation‐associated gene 5 (MDA5) dermatomyositis is characterized by serological detection of anti‐MDA5 antibody and rapidly progressive interstitial lung disease. In this study, the largest cohort of skin biopsies to date of anti‐MDA5 dermatomyositis was reviewed and compared with cases of dermatomyositis with negative serology. Findings contribute to the histological diagnosis and evaluation of the severity of cutaneous inflammation in anti‐MDA5 dermatomyositis. Skin biopsies collected over a 7‐year period from individuals with clinically and histologically confirmed dermatomyositis with anti‐MDA5 serology were reviewed. A total of 46 cases with 17 anti‐MDA5 positive cases were retrieved. Patients with positive antibody were younger (53.7 vs. 60.6 years, p = .013). No differences in epidermal changes (p > .05) were observed. Pertaining to interface changes, anti‐MDA5 dermatomyositis showed a higher degree of pigmentary incontinence (p = .014), suggesting increased and sustained cutaneous inflammation. Periodic acid–Schiff (PAS) stain demonstrated a greater degree of basement membrane thickening (p = .045). Other parameters, including dermal inflammation, dermal mucin deposition and vasculitic/vasculopathic features did not show statistical difference between anti‐MDA5 positive and negative dermatomyositis (p > .05). Findings suggest increased cutaneous inflammation for anti‐MDA5 dermatomyositis. In skin biopsies, marked pigmentary incontinence or basement membrane thickening should raise suspicion of anti‐MDA5 dermatomyositis.
Institutional investor horizons, ownership structure and investment efficiency in China
Authors: Wang Zhihao , Liao Kezhi , Wang Sisi 
Published: August 2023

AbstractThis paper investigates the effects of institutional investor horizons on investment efficiency in China. By analysing 26,831 firm‐year observations from Chinese listed companies, we find that long‐term (short‐term) institutional ownership is negatively (positively) associated with the level of inefficient investments. A battery of robustness tests indicates causality. Further analyses reveal that the rise in environmental uncertainty and information asymmetry are transmission channels for increased inefficient investments. Moreover, we find that the single controlling shareholder and state owner can curb the management myopia induced by short‐term institutional investors while they do not impede the monitoring effort of long‐term institutional investors.
Epigenetic responses to rhinovirus exposure in airway epithelial cells are correlated with key transcriptional pathways in chronic rhinosinusitis
Authors: Soliai Marcus M. , Kato Atsushi , Naughton Katherine A. , Norton James E. , Klinger Aiko I. , Kern Robert C. , Tan Bruce K. , Nicolae Dan L. , Schleimer Robert P. , Ober Carole , Pinto Jayant M. 
Published: August 2023

AbstractBackgroundViruses may drive immune mechanisms responsible for chronic rhinosinusitis with nasal polyposis (CRSwNP), but little is known about the underlying molecular mechanisms.ObjectivesTo identify epigenetic and transcriptional responses to a common upper respiratory pathogen, rhinovirus (RV), that are specific to patients with CRSwNP using a primary sinonasal epithelial cell culture model.MethodsAirway epithelial cells were collected at surgery from patients with CRSwNP (cases) and from controls without sinus disease, cultured, and then exposed to RV or vehicle for 48 h. Differential gene expression and DNA methylation (DNAm) between cases and controls in response to RV were determined using linear mixed models. Weighted gene co‐expression analysis (WGCNA) was used to identify (a) co‐regulated gene expression and DNAm signatures, and (b) genes, pathways, and regulatory mechanisms specific to CRSwNP.ResultsWe identified 5585 differential transcriptional and 261 DNAm responses (FDR <0.10) to RV between CRSwNP cases and controls. These differential responses formed three co‐expression/co‐methylation modules that were related to CRSwNP and three that were related to RV (Bonferroni corrected p < .01). Most (95%) of the differentially methylated CpGs (DMCs) were in modules related to CRSwNP, whereas the differentially expressed genes (DEGs) were more equally distributed between the CRSwNP‐ and RV‐related modules. Genes in the CRSwNP‐related modules were enriched in known CRS and/or viral response immune pathways.ConclusionRV activates specific epigenetic programs and correlated transcriptional networks in the sinonasal epithelium of individuals with CRSwNP. These novel observations suggest epigenetic signatures specific to patients with CRSwNP modulate response to viral pathogens at the mucosal environmental interface. Determining how viral response pathways are involved in epithelial inflammation in CRSwNP could lead to therapeutic targets for this burdensome airway disorder.
Immunoregulatory mechanisms between epithelial clear cells and mononuclear phagocytes in the epididymis
Authors: Battistone Maria Agustina , Elizagaray Maia L , Barrachina Ferran , Ottino Kiera , Mendelsohn Alexandra C , Breton Sylvie 
Published: August 2023

AbstractIntroductionOne of the most intriguing aspects of male reproductive physiology is the ability of the epididymis to prevent the mounting of immune responses against the onslaught of foreign antigens carried by spermatozoa while initiating very efficient immune responses versus stressors. Epithelial clear cells are strategically positioned to work in a concerted manner with region‐specific heterogeneous subsets of mononuclear phagocytes to survey the epididymal barrier and regulate the balance between inflammation and immune tolerance in the post‐testicular environment.ObjectiveThis review aims to describe how clear cells communicate with mononuclear phagocytes to contribute to the unique immune environment in which sperm mature and are stored in the epididymis.Materials/methodsA comprehensive systematic review was performed. PubMed was searched for articles specific to clear cells, mononuclear phagocytes, and epididymis. Articles that did not specifically address the target material were excluded.ResultsIn this review, we discuss the unexpected roles of clear cells, including the transfer of new proteins to spermatozoa via extracellular vesicles and nanotubes as they transit along the epididymal tubule; and we summarize the immune phenotype, morphology, and antigen capturing, processing, and presenting abilities of mononuclear phagocytes. Moreover, we present the current knowledge of immunoregulatory mechanisms by which clear cells and mononuclear phagocytes may contribute to the immune‐privileged environment optimal for sperm maturation and storage.Discussion and conclusionNotably, we provide an in‐depth characterization of clear cell‐mononuclear phagocyte communication networks in the steady‐state epididymis and in the presence of injury. This review highlights crucial concepts of mucosal immunology and cellcell interactions, all of which are critical but understudied facets of human male reproductive health.
Genetic variant annotation scores in congenital long QT syndrome
Authors: Younis Arwa , Bodurian Christopher , Arking Dan E. , Bragazzi Nicola Luigi , Tabaja Chadi , Zareba Wojciech , McNitt Scott , Aktas Mehmet K. , Polonsky Bronislava , Lopes Coeli M. , Sotoodehnia Nona , Kudenchuk Peter J. , Goldenberg Ilan 
Published: August 2023

AbstractBackgroundCongenital Long QT Syndrome (LQTS) is a hereditary arrhythmic disorder. We aimed to assess the performance of current genetic variant annotation scores among LQTS patients and their predictive impact.MethodsWe evaluated 2025 patients with unique mutations for LQT1–LQT3. A patient‐specific score was calculated for each of four established genetic variant annotation algorithms: CADD, SIFT, REVEL, and PolyPhen‐2. The scores were tested for the identification of LQTS and their predictive performance for cardiac events (CE) and life‐threatening events (LTE) and then compared with the predictive performance of LQTS categorization based on mutation location/function. Score performance was tested using Harrell's C‐index.ResultsA total of 917 subjects were classified as LQT1, 838 as LQT2, and 270 as LQT3. The identification of a pathogenic variant occurred in 99% with CADD, 92% with SIFT, 100% with REVEL, and 86% with PolyPhen‐2. However, none of the genetic scores correlated with the risk of CE (Harrell's C‐index: CADD = 0.50, SIFT = 0.51, REVEL = 0.50, and PolyPhen‐2 = 0.52) or LTE (Harrell's C‐index: CADD = 0.50, SIFT = 0.53, REVEL = 0.54, and PolyPhen‐2 = 0.52). In contrast, high‐risk mutation categorization based on location/function was a powerful independent predictor of CE (HR = 1.88; p < .001) and LTE (HR = 1.89, p < .001).ConclusionIn congenital LQTS patients, well‐established algorithms (CADD, SIFT, REVEL, and PolyPhen‐2) were able to identify the majority of the causal variants as pathogenic. However, the scores did not predict clinical outcomes. These results indicate that mutation location/functional assays are essential for accurate interpretation of the risk associated with LQTS mutations.
The diagnostic utility of the basal and post‐exercise QRS‐T angle in patients with stable coronary artery disease
Authors: Günay Tufan , Karakus Alper 
Published: August 2023

AbstractBackgroundTo evaluate the diagnostic utility of basal and post‐exercise QRS‐T angle in patients with stable coronary artery disease (CAD).MethodsThis cross‐sectional and observational study analyzed 190 patients with stable angina. The QRS‐T angle is measured on the 12‐lead electrocardiograms at baseline and just after stopping the treadmill stress test in patients undergoing conventional coronary angiography (CAG). The pre‐ and post‐exercise QRS‐T angle and ΔQRS‐T angle were analyzed.ResultsOf the 190 patients, 66 (34.7%) were assigned to group 1 (patients with coronary lesion) and 124 (65.3%) to group 2 (patients without coronary lesion) after CAG. There was no statistically significant difference in QRS‐T angle between groups at baseline (pre‐exercise) (30.7 ± 17 vs. 27.8 ± 12.8, p = .233). The QRS‐T angle value was significantly higher in group 1 than in group 2 (68.8 ± 40.3 vs. 22.7 ± 21.5, p = .01) after exercise (post‐exercise). The ΔQRS‐T angle was also significantly higher in group 1 than in group 2 (38.1 ± 37.6 vs. −5.1 ± 22.9, p = .01). Receiver operating characteristic curve revealed that the cut‐off value of QRS‐T angle (post‐exercise) for the coronary obstruction was >51.5° with 81% of sensitivity and 66% of specificity (AUC: 0.832, p = .001, CI: 0.769–0.894). Duke treadmill score for coronary stenosis was >1.5 with 77% of sensitivity and 69% of specificity (AUC: 0.814, p = .001, CI: 0.749–0.878).ConclusionIt could be proposed that post‐exercise QRS‐T angle and Δ QRS‐T angle are significantly associated with coronary obstruction in patients with stable angina and appear to be more sensitive than the Duke treadmill score and traditional electrocardiographic parameters.
STAR SIGN study: Evaluation of COVID‐19 vaccine efficacy against the SARS‐CoV‐2 variants BQ.1.1 and XBB.1.5 in patients with inflammatory bowel disease
Authors: Woelfel Simon , Dütschler Joel , König Marius , Dulovic Alex , Graf Nicole , Junker Daniel , Oikonomou Vasileios , Krieger Claudia , Truniger Samuel , Franke Annett , Eckhold Annika , Forsch Kristina , Koller Seraina , Wyss Jacqueline , Krupka Niklas , Oberholzer Melanie , Frei Nicola , Geissler Nora , Schaub Peter ,   STAR SIGN Study Investigators, Albrich Werner C. , Friedrich Matthias , Schneiderhan‐Marra Nicole , Misselwitz Benjamin , Korte Wolfgang , Bürgi Justus J. , Brand Stephan 
Published: August 2023

SummaryBackgroundVaccine‐elicited immune responses are impaired in patients with inflammatory bowel disease (IBD) treated with anti‐TNF biologics.AimsTo assess vaccination efficacy against the novel omicron sublineages BQ.1.1 and XBB.1.5 in immunosuppressed patients with IBD.MethodsThis prospective multicentre case–control study included 98 biologic‐treated patients with IBD and 48 healthy controls. Anti‐spike IgG concentrations and surrogate neutralisation against SARS‐CoV‐2 wild‐type, BA.1, BA.5, BQ.1.1, and XBB.1.5 were measured at two different time points (2–16 weeks and 22–40 weeks) following third dose vaccination. Surrogate neutralisation was based on antibody‐mediated blockage of ACE2‐spike protein–protein interaction. Primary outcome was surrogate neutralisation against tested SARS‐CoV‐2 sublineages. Secondary outcomes were proportions of participants with insufficient surrogate neutralisation, impact of breakthrough infection, and correlation of surrogate neutralisation with anti‐spike IgG concentration.ResultsSurrogate neutralisation against all tested sublineages was reduced in patients with IBD who were treated with anti‐TNF biologics compared to patients treated with non‐anti‐TNF biologics and healthy controls (each p ≤ 0.001) at visit 1. Anti‐TNF therapy (odds ratio 0.29 [95% CI 0.19–0.46]) and time since vaccination (0.85 [0.72–1.00]) were associated with low, and mRNA‐1273 vaccination (1.86 [1.12–3.08]) with high wild‐type surrogate neutralisation in a β‐regression model. Accordingly, higher proportions of patients treated with anti‐TNF biologics had insufficient surrogate neutralisation against omicron sublineages at visit 1 compared to patients treated with non‐anti‐TNF biologics and healthy controls (each p ≤ 0.015). Surrogate neutralisation against all tested sublineages decreased over time but was increased by breakthrough infection. Anti‐spike IgG concentrations correlated with surrogate neutralisation.ConclusionsPatients with IBD who are treated with anti‐TNF biologics show impaired neutralisation against novel omicron sublineages BQ.1.1 and XBB.1.5 and may benefit from prioritisation for future variant‐adapted vaccines.
Bortezomib in relapsed/refractory immune thrombotic thrombocytopenic purpura: A single‐centre retrospective cohort and systematic literature review
Authors: Lee Nicholas C. J. , Yates Sean , Rambally Siayareh , Sarode Ravi , Ibrahim Ibrahim F. , Shen Yu‐Min , Hofmann Sandra L. , Bavli Natalie R. 
Published: August 2023

SummaryImmune thrombotic thrombocytopenic purpura (iTTP) is a rare and life‐threatening haematological condition. Initial treatment involves plasma exchange (PLEX), corticosteroids, caplacizumab and rituximab. In relapsed and refractory cases despite initial treatments, further immune‐modulating therapy includes the proteasome inhibitor, bortezomib. Evidence for bortezomib in this setting is limited to case reports and case series. We report our experience and perform a systematic review of the literature. We identified 21 publications with 28 unique patients in addition to our cohort of eight patients treated with bortezomib. The median age of patients was 44 years (IQR: 27–53) and 69% female. They were usually in an initial, refractory presentation of iTTP where they had received PLEX, corticosteroids, rituximab and another line of therapy. After bortezomib administration, 72% of patients had a complete response, with 85% maintaining a durable response without relapse at the last follow‐up.
Emollients for preventing atopic eczema: Cost‐effectiveness analysis of the BEEP trial
Authors: Sach Tracey H. , Lartey Stella T. , Davies Charlotte , Chalmers Joanne R. , Haines Rachel H. , Bradshaw Lucy E. , Montgomery Alan A. , Thomas Kim S. , Brown Sara J. , Ridd Matthew J. , Lawton Sandra , Cork Mike J. , Flohr Carsten , Mitchell Eleanor , Swinden Richard , Wyatt Laura , Tarr Stella , Davies‐Jones Susan , Jay Nicola , Kelleher Maeve M. , Perkin Michael R. , Boyle Robert J. , Williams Hywel C. ,   the BEEP Study Team
Published: August 2023

AbstractBackgroundRecent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy.ObjectiveTo determine the cost‐effectiveness of daily all‐over‐body application of emollient during the first year of life for preventing atopic eczema in high‐risk children at 2 years from a health service perspective. We also considered a 5‐year time horizon as a sensitivity analysis.MethodsA within‐trial economic evaluation using data on health resource use and quality of life captured as part of the BEEP trial alongside the trial data. Parents/carers of 1394 infants born to families at high risk of atopic disease were randomised 1:1 to the emollient group, which were advised to apply emollient (Doublebase Gel or Diprobase Cream) to their child at least once daily to the whole body during the first year of life or usual care. Both groups received advice on general skin care. The main economic outcomes were incremental cost‐effectiveness ratio (ICER), defined as incremental cost per percentage decrease in risk of eczema in the primary cost‐effectiveness analysis. Secondary analysis, undertaken as a cost‐utility analysis, reports incremental cost per Quality‐Adjusted Life Year (QALY) where child utility was elicited using the proxy CHU‐9D at 2 years.ResultsAt 2 years, the adjusted incremental cost was £87.45 (95% CI −54.31, 229.27) per participant, whilst the adjusted proportion without eczema was 0.0164 (95% CI −0.0329, 0.0656). The ICER was £5337 per percentage decrease in risk of eczema. Adjusted incremental QALYs were very slightly improved in the emollient group, 0.0010 (95% CI −0.0069, 0.0089). At 5 years, adjusted incremental costs were lower for the emollient group, −£106.89 (95% CI −354.66, 140.88) and the proportion without eczema was −0.0329 (95% CI −0.0659, 0.0002). The 5‐year ICER was £3201 per percentage decrease in risk of eczema. However, when inpatient costs due to wheezing were excluded, incremental costs were lower and incremental effects greater in the usual care group.ConclusionsIn line with effectiveness endpoints, advice given in the BEEP trial to apply daily emollient during infancy for eczema prevention in high‐risk children does not appear cost‐effective.
Recurrent Motion Refiner for Locomotion Stitching
Authors: Kim Haemin , Cho Kyungmin , Hong Seokhyeon , Noh Junyong 
Published: August 2023

AbstractStitching different character motions is one of the most commonly used techniques as it allows the user to make new animations that fit one's purpose from pieces of motion. However, current motion stitching methods often produce unnatural motion with foot sliding artefacts, depending on the performance of the interpolation. In this paper, we propose a novel motion stitching technique based on a recurrent motion refiner (RMR) that connects discontinuous locomotions into a single natural locomotion. Our model receives different locomotions as input, in which the root of the last pose of the previous motion and that of the first pose of the next motion are aligned. During runtime, the model slides through the sequence, editing frames window by window to output a smoothly connected animation. Our model consists of a two‐layer recurrent network that comes between a simple encoder and decoder. To train this network, we created a sufficient number of paired data with a newly designed data generation. This process employs a K‐nearest neighbour search that explores a predefined motion database to create the corresponding input to the ground truth. Once trained, the suggested model can connect various lengths of locomotion sequences into a single natural locomotion.
BNT162b2‐vaccine‐induced neutralization responses are immune correlates of clinical protection against SARS‐CoV‐2 in heart transplant recipients
Authors: Peled Yael , Patel Jignesh K. , Raanani Ehud , Eilon Ram , Fardman Alexander , Beigel Roy , Atari Nofar , Kliker Limor , Elkader Bayan Abd , Mandelboim Michal , Afek Arnon 
Published: August 2023

AbstractBackgroundDefining immune correlates of protection against COVID‐19 is pivotal for optimizing the use of COVID‐19 vaccines, predicting the impact of novel variants on clinical outcomes, and advancing the development of immunotherapies and next‐generation vaccines. We aimed to identify vaccine‐induced immune correlates of protection against COVID‐19‐related hospitalizations in a highly vaccinated heart transplant (HT) cohort.MethodsIn a case‐control study of HT recipients vaccinated with the BNT162b2 vaccine, patients were prospectively assessed for vaccine‐induced neutralization of the wild‐type virus, and the Delta and Omicron BA.1, BA.2, BA.4, and BA.5 variants. Comparative analyses with controls were conducted to identify correlates of protection against COVID‐19 hospitalization. ROC analyses were performed. Primary outcomes were COVID‐19 hospitalizations and severity of SARS‐CoV‐2 breakthrough infection.ResultsThe study cohort comprised 59 HT recipients aged 58 (49,65) years with breakthrough infections after three or four monovalent BNT162b2 doses; 41 (69.5%) were men. Thirty‐six (61%) patients with COVID‐19 were hospitalized; most cases were non‐severe (58, 98%). For hospitalized (vs. non‐hospitalized) COVID‐19 patients, vaccine‐induced neutralization titers were significantly lower against all SARS‐CoV‐2 variants (p < .005). Vaccine‐induced neutralization of the wild‐type virus and delta and omicron BA.1, BA.2, BA.4, and BA.5 variants was associated with a reduced risk for COVID‐19‐related hospitalization. The optimal neutralization titer thresholds that were predictive of COVID‐19 hospitalizations were 96 (wild‐type), 48 (delta), 12 (BA.1), 96 (BA.2), 96 (BA.4), and 48 (BA.5).ConclusionsBNT162b2‐vaccine‐induced neutralization responses are immune correlates of protection and confer clinical protection against COVID‐19 hospitalizations.
Implementierung eines Dermatoskopie‐Curriculums in der Facharztausbildung am Universitätsklinikum Augsburg
Authors: Schuh Sandra , Schiele Stefan , Thamm Janis , Kranz Stefanie , Welzel Julia , Blum Andreas 
Published: August 2023

ZusammenfassungHintergrund und ZieleBislang gibt es in Deutschland kein strukturiertes Programm für die Dermatoskopieausbildung während der Facharztausbildung. Es bleibt der Initiative des einzelnen Assistenzarztes überlassen, ob und in welchem Umfang er sich in der Dermatoskopie weiterbildet, obwohl die Dermatoskopie zu den Kernkompetenzen der dermatologischen Ausbildung und der täglichen Praxis gehört. Ziel der Studie war die Etablierung eines strukturierten Dermatoskopie‐Curriculums während der dermatologischen Facharztausbildung am Universitätsklinikum Augsburg.Patienten und MethodikEs wurde eine Online‐Plattform mit Dermatoskopie‐Modulen geschaffen, auf die von überall und jederzeit zugegriffen werden kann. Praktische Fertigkeiten wurden unter individueller Anleitung eines Dermatoskopie‐Experten erworben. Die Teilnehmer wurden vor und nach Abschluss der Module auf ihren Wissensstand getestet. Die Testergebnisse zum therapeutischen Management und zur korrekten dermatoskopischen Diagnose wurden analysiert.ErgebnisseDie Ergebnisse der 28 Teilnehmer verbesserten sich vom Eingangs‐ zum Abschlusstest bei der Managemententscheidung (74,0% vs. 89,4%) und bei der dermatoskopischen Genauigkeit (65,0% vs. 85,6%). Die Unterschiede zwischen Eingangs‐ und Abschlusstest bei der Gesamtpunktzahl (7,05/10 vs. 8,94/10 Punkte) und bei der richtigen Diagnose waren signifikant (p < 0,001).SchlussfolgerungenDas Dermatoskopie‐Curriculum verbessert die Managemententscheidungen und die dermatoskopische Diagnostik der Teilnehmer. Das wird dazu führen, dass mehr Hautkrebsfälle erkannt werden und weniger gutartige Läsionen reseziert werden müssen. Das Curriculum kann anderen dermatologischen Ausbildungszentren und Gesundheitsberufen angeboten werden.