bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial Cell Phenotypic Plasticity in Cardiovascular Physiology and Disease: Mechanisms and Therapeutic Prospects
Authors: de Queiroz Diego B , Parente Juliana M , Pernomian Laena , Waigi Emily W , Alfaidi Mabruka , Tan Wenbin , McCarthy Cameron G , Wenceslau Camilla F 
Published: February 2025

Abstract
Endothelial cells (ECs) are a highly specialized and heterogeneous population that plays a fundamental role in maintaining vascular homeostasis, immune regulation, and blood flow control. Beyond serving as a physical barrier, ECs exhibit remarkable plasticity, undergoing phenotypic transitions, including endothelial-to-mesenchymal (EndMT), endothelial-to-hematopoietic (EndHT), endothelial-to-osteoblast (EndOT) and endothelial-to-immune-cell-like (EndICLT). These transitions allow ECs to adapt to developmental, physiological, and pathological conditions. Advances in single-cell RNA sequencing (scRNA-seq), and associated technologies, have provided deeper insights into the molecular diversity of ECs across different vascular beds and stages of development, revealing their transcriptional heterogeneity and specialized functions. For example, ECs within the aortic arch display distinct phenotypic variations depending on their location, reflecting adaptations to regional differences in blood flow and shear stress. Activated EndMT has been implicated in the progression of various cardiovascular diseases, including hypertension, atherosclerosis, and vascular malformations by contributing to endothelial dysfunction, vascular wall inflammation, and remodeling. Recent therapeutic approaches aim to mitigate EndMT-associated vascular damage through interventions such as endothelial reprogramming, statins, and autophagy enhancers. Partial reprogramming of ECs has shown promise in restoring endothelial function, reducing vascular stiffness, and lowering blood pressure in hypertensive models. Understanding the complexity of EC heterogeneity and plasticity is critical for developing targeted therapies to prevent and treat cardiovascular diseases. By leveraging emerging genomic technologies and reprogramming strategies, future research may offer novel regenerative medicine approaches to restore vascular health and improve clinical outcomes for patients with cardiovascular diseases.
Potential outcome simulation for efficient head-to-head comparison of adaptive dose-finding designs
Authors: Sweeting Michael , Slade Daniel , Jackson Dan , Brock Kristian 
Published: February 2025

ABSTRACT
Dose-finding trials are a key component of the drug development process and rely on a statistical design to help inform dosing decisions. Triallists wishing to choose a design require knowledge of operating characteristics of competing methods. This is often assessed using a large-scale simulation study with multiple designs and configurations investigated, which can be time-consuming and therefore limits the scope of the simulation. We introduce a new approach to the design of simulation studies of dose-finding trials. The approach simulates all potential outcomes that individuals could experience at each dose level in the trial. Datasets are simulated in advance and then applied to each of the competing methods to enable a more efficient head-to-head comparison. Furthermore, individual trial datasets can be interrogated to understand when designs deviate in their decision making. In three case-studies, we show sizeable reductions in Monte Carlo error for comparing a performance metric between two competing designs. Efficiency gains depend on the similarity of the designs. Comparing two Phase I/II design variants, with high correlation of recommending the same optimal biologic dose, we show that the new approach requires a simulation study that is approximately 48 times smaller than the conventional approach. Furthermore, advance-simulated trial datasets can be reused to assess the performance of designs across multiple configurations. We recommend researchers consider this more efficient simulation approach in their dose-finding studies and we have updated the R package escalation to help facilitate implementation.
The subtype-free average causal effect for heterogeneous disease etiology
Authors: Sasson A , Wang M , Ogino S , Nevo D 
Published: February 2025

ABSTRACT
Studies have shown that the effect an exposure may have on a disease can vary for different subtypes of the same disease. However, existing approaches to estimate and compare these effects largely overlook causality. In this paper, we study the effect smoking may have on having colorectal cancer subtypes defined by a trait known as microsatellite instability (MSI). We use principal stratification to propose an alternative causal estimand, the Subtype-Free Average Causal Effect (SF-ACE). The SF-ACE is the causal effect of the exposure among those who would be free from other disease subtypes under any exposure level. We study non-parametric identification of the SF-ACE and discuss different monotonicity assumptions, which are more nuanced than in the standard setting. As is often the case with principal stratum effects, the assumptions underlying the identification of the SF-ACE from the data are untestable and can be too strong. Therefore, we also develop sensitivity analysis methods that relax these assumptions. We present 3 different estimators, including a doubly robust estimator, for the SF-ACE. We implement our methodology for data from 2 large cohorts to study the heterogeneity in the causal effect of smoking on colorectal cancer with respect to MSI subtypes.
Prevalence and pathogenic activity of anti-desmocollin-3 antibodies in patients with pemphigus vulgaris and pemphigus foliaceus
Authors: Maho-Vaillant Maud , Lemieux Alexandre , Arnoult Christophe , Lebourgeois Léopoldine , Hébert Vivien , Jaworski Thara , Tedbirt Billal , Jouen Fabienne , Boyer Olivier , Calbo Sébastien , Joly Pascal , Golinski Marie-Laure 
Published: February 2025

Abstract

Background
Desmocollin-3 (DSC3) is a calcium-dependent desmosomal cadherin that plays an essential role in cell–cell adhesion. IgG antibodies (Abs) directed against the extracellular (EC) domain of DSC3 have occasionally been detected in rare types of pemphigus. Investigations into the prevalence of anti-EC-DSC3 IgG Abs and those targeting the intracellular (IC) domain of DSC3 in pemphigus vulgaris and pemphigus foliaceus sera, and their potential pathogenic activity, have yielded conflicting results.

Objectives
To assess the prevalence and pathogenicity of Abs directed against the EC and IC domains of DSC3 in patients with pemphigus.

Methods
Anti-DSC3 IgG and IgA directed against the EC and IC domains of DSC3 were assayed in 146 patients with pemphigus using a newly developed addressable laser bead immunoassay. The pathogenicity of these autoAbs was first tested in vitro using a keratinocyte dissociation assay with patients’ sera or from C57BL/6 mice immunized with recombinant IC-DSC3. In vivo pathogenicity was tested by passive transfer of an anti-IC-DSC3 monoclonal Ab (mAb) derived from a hybridoma (A9) into neonatal mice.

Results
Anti-EC-DSC3 or anti-IC-DSC3 IgG and/or IgA Abs were detected in 21.2% of sera from patients with pemphigus vs. 4.0% (P &lt; 0.001) and 5.0% (P &lt; 0.001) of sera from healthy donors, respectively. Most anti-DSC3 Abs corresponded to IgA. Anti-IC-DSC3 Abs were detected in 44% of patients with pemphigus whose serum anti-desmoglein (DSG) 1–3 Ab profile was inconsistent with their clinical and histological features, according to compensation theory. Anti-IC-DSC3 IgG and IgA Abs induced a dissociation of the keratinocyte monolayer in vitro, which was abolished by preadsorption of these IgG or IgA fractions with recombinant IC-DSC3. In addition, IgG from mice immunized with recombinant IC-DSC3 induced acantholysis in vitro. Finally, in neonatal mice, the passive transfer of an anti-IC-DSC3 mAb in combination with anti-DSG1–3 Abs exacerbated blister formation.

Conclusions
Our findings suggest that anti-IC-DSC3 Abs are pathogenic and explain the discordance seen in some patients with regard to their clinical phenotype and their anti-DSG1–3 Ab profile.
Quadriceps muscle injuries in athletes: a narrative review
Authors: Ariyaratne Sisith P , Shirodkar Kapil , Botchu Rajesh , James Steven L J 
Published: February 2025

Abstract
The quadriceps muscles are a large group of four muscles in the anterior compartment of the thigh, comprising the rectus femoris, vastus medialis, vastus intermedius and vastus lateralis, which in combination act as the primary extensors of the knee joint. The rectus femoris is also responsible for hip joint flexion. Quadriceps muscle injuries are frequently encountered in sports and athletic activities, and present a significant challenge in the realm of sports medicine, impacting athletes across various disciplines and levels of competition. A spectrum of sporting injuries and imaging findings can affect this muscle group, including strains and tears, avulsions, contusions, degloving injuries, and exercise related signal abnormalities (ERSA). A thorough understanding of these various pathologies and imaging features is crucial to guide appropriate diagnosis, management and rehabilitation, as well as ensure safe and prompt return to play, minimise risk of re-injury or long term adverse sequela, optimise performance and improve career longevity of these athletes. This comprehensive review article aims to review the unique anatomy of the quadriceps muscle group and integrate current knowledge of the various forms of sporting injuries affecting it, with a specific emphasis on the imaging features.
35 Management and aortic reconstruction in patients with infrarenal aortic graft infection. A UK vascular networks’ 10-year experience
Authors: Gamtkitsulashvili Gvantsa , Enemosah Ibrahim , Hatem R , Cowan H , Patterson Benjamin , Nordon Ian , Baxter Stephan 
Published: February 2025

Abstract

Aim
Aortic graft infections (AGI) are rare with no global consensus for diagnosis and management, we report our experience of management and complex in situ reconstruction.

Methods
Retrospective cohort study of 49 patients who developed AGI following EVAR and open aortic intervention from January 2010 to December 2020.

Results
Primary intervention was open aortic repair in 40 (81.6%) patients (7 ruptured aneurysm (rAAA), 22 aneurysmal disease and 11 aortoiliac-occlusive disease). Nine (18.4%) patients had an EVAR (3 for rAAA). AGI was identified at a median of 18 months post primary intervention. All patients were commenced on long term antibiotics. 22 (45%) patients were unfit for explantation, 8 (16.3%) were on surveillance for low grade infection, while 15 (30.6%) had an explant and aortic graft in situ reconstruction, with 2 (13.3%) requiring interval aortic stent prior to explant. Femoral vein (53%) and bovine pericardium (20%) were most commonly used conduit. Post-operative 30 day mortality was 13.3% (2 patients). Survival post-explant was 69% and 65% at 2 years and 5 years respectively versus 43% and 29% in the non-operative group.

Conclusion
Infrarenal aortic graft in situ reconstruction is safe following AGI with a reasonable 5 year survival rate. Patient fitness assessment is pertinent due to high perioperative risk.
19 Functional hydrogel for the treatment of abdominal wall defects: a review
Authors: Liu Ye , Wu Xiuwen , Ren Jianan 
Published: February 2025

Abstract
The abdominal wall serves as a crucial barrier safeguarding the internal organs of body. Abdominal wall defects, resulting from various reasons such as surgery, infection, and trauma, are familiar clinical condition. Complex defects of the abdominal wall have limited self-healing capacity and require external intervention to promote tissue repair and regeneration. Traditional clinical treatment approaches including tension-free patch repair, component separation technique, autologous tissue transplantation, abdominal wall expansion techniques, and abdominal cavity reduction techniques have been widely employed. However, their respective drawbacks restrict their clinical application. Despite the development of diverse biomaterials, the expected therapeutic effects have not been fully achieved. Hydrogel have emerged as promising strategies extensively studied and applied in promoting tissue regeneration by filling or repairing damaged tissue due to their unique properties. This review summaries and discusses the five prominent functions and advances in the application of hydrogels for promoting repair and reconstruction of abdominal wall defects: (1) good biocompatibility with host tissues that reduces adverse reactions and immune responses while supporting cell adhesion migration proliferation; (2) tunable mechanical properties matching those of the abdominal wall that adapt to normal movements deformations while reducing tissue stress thereby influencing regulating cell behavior tissue regeneration; (3) drug carriers continuously delivering drugs and bioactive molecules to sites optimizing healing processes enhancing tissue regeneration; (4) promotion of cell interactions by simulating hydrated extracellular matrix (ECM) environments, providing physical support, space, and cues for cell migration, adhesion, and proliferation. (5) easy manipulation and application in surgical procedures, allowing precise placement and close adhesion to the defective abdominal wall, providing mechanical support. Additionally, the advancements of hydrogels in the repair of abdominal wall defects are also mentioned. Finally, the existing challenges and limitations faced by hydrogels are concluded, and the future directions of hydrogel for abdominal wall reconstruction are further proposed.
Shifts in Medical Liability in the Macau SAR
Authors: Cascão Rui 
Published: February 2025

Abstract
The Macau SAR has a civil law legal system, historically connected to the Portuguese legal system included in the Roman-German family of legal systems. Until Law 5/2016 (Medical Error Act), medical malpractice claims could be framed in tort and/or contract. Certain aspects of administrative law related to treatment provided by public healthcare providers, in particular as regards their duties and liability, have a bearing on the applicable substantive and procedural legal regime and entail the jurisdiction of administrative courts. Aggrieved patients faced the challenge of navigating an uneven level playing field and the burden of proving fault, damages, and causation. The approval of Law 5/2016 was protracted, and there was a lack of consensus in society. Nevertheless, it has unique features: a public committee is created and charged with providing forensic expertise in cases of alleged medical malpractice and another public committee is created to handle and conciliate medical malpractice claims, award just satisfaction, and prevent lawsuits. The aim of this contribution is to explain this legislative shift, critically examine the challenges that it has brought forth, and analyse it in a comparative law context. Building on existing scholarship, this article presents Macau’s novel medical liability system, which has unique features, to a wider global audience: it identifies the aspects that can be perfected in future revisions of the law and highlights the merits of the missed chance, envisaged in the 2005 Green Paper, to move away from fault-based liability towards a no-fault compensation system.
Low psychosocial burden in patients with paraganglioma syndrome. Results from the Head and Neck Paraganglioma Registry in a single center
Authors: de Bresser Carolijn J M , Rijken Johannes A , van Treijen Mark J C , van Nesselrooij Bernadette P M , de Ridder M , de Bree Remco , de Borst Gert J , Petri Bart-Jeroen , van Leeuwaarde Rachel S 
Published: February 2025

Abstract

Objective
Autosomal dominant variants in the succinate dehydrogenase gene (SDHx) are responsible for approximately 50% of the development of hereditary paragangliomas and pheochromocytomas (PPGLs). Limited research has been conducted on the psychosocial impact of possessing a hereditary tumor syndrome. In this study, the psychological impact of harboring a genetic variant associated with familial paraganglioma syndrome was assessed. Secondary objectives included the analysis of potential variations in quality of life in (pre)symptomatic stage and comparison with the general Dutch population and other hereditary tumor syndromes.

Methods
The first 100 patients from the Head and Neck PGL Registry in the University Medical Center Utrecht were selected. Psychosocial outcomes were assessed cross-sectionally using five validated health-related questionnaires: EuroQol 5D-5L, Cancer Worry Scale, Hospital Anxiety and Depression Scale, Modified Fatigue Impact Scale and EORTC QLQ-C30.

Results
No significant differences were observed when stratified for (pre)symptomatic status or genetic variant status. Hereditary PPGLs tended to express greater concern about development of PPGLs in family members. Complaints in the physical domains were more frequently observed in the sporadic group. The PPGL cohort demonstrated better outcomes when compared to other hereditary tumor syndromes and aligned with the Dutch tariff.

Conclusion
The psychosocial impact of harboring a PPGL seems to align with the general healthy Dutch population. Clinical care management involving a multidisciplinary approach and comprehensive counseling on PPGLs and their genetic origins, effectively supports patients. Routine psychological support in the care for these patients does not seem imperative and should be offered indicated on a case-by-case basis.
How is digital technology used to facilitate shared decision-making between healthcare professionals and patients in cardiovascular care? A scoping review
Authors: Leysen Dirk , Propst Eva , McGowan Hannah , Pfannerstill Franziska , Crutzen Rik , Kulnik Stefan Tino 
Published: February 2025

Abstract

Aims
To (1) identify characteristics of digital technologies (DTs) used to facilitate shared decision-making (SDM) within the field of cardiovascular care, (2) examine conceptualizations of SDM underpinning these DTs, and (3) summarize designs and outcomes of evaluation studies concerning these DTs.

Methods and results
We conducted a scoping review following methodological guidelines by the Joanna Briggs Institute. Ten scientific databases were searched. We selected peer-reviewed articles in cardiovascular care, with SDM and DT in the title and/or abstract published between January 2000 and March 2023. We extracted data on the type of DT, intended user(s), timepoint and mode of use, purpose, decision topic, underlying SDM model, and designs and outcomes of evaluation studies. Data were analyzed descriptively in a narrative synthesis.
From 4,432 search results, 48 articles reporting on 31 DTs were included. Half of the articles were published after 2018, with most published in 2022. Most DTs are web-based applications for interactive use before and during the encounter between patient and healthcare professional, to convey information on cardiovascular care, calculate personal risk and/or recommend treatment options. SDM conceptualizations refer to the International Patient Decision Aid Standards and authors in the field. Thirty-seven evaluation studies report on 31 DTs, with heterogeneous results related to variation in intervention designs, measurement timepoints, and outcome measures.

Conclusion
A recent increase in the reporting of DTs to facilitate SDM in cardiovascular care indicates their potential. This scoping review offers researchers, developers, and clinicians a comprehensive overview of this literature.

Registration
Open Science Framework, https://doi.org/10.17605/OSF.IO/TRGQ5
Allometry of sound reception structures and evidence for a mandibular middle ear in non-mammalian synapsids
Authors: Olroyd Savannah L , Kopperud Bjørn T 
Published: February 2025

Abstract
The origin of sensory structures provides an excellent framework for studying how constraints and selective pressures affect the evolution of complex features. The evolution of the mammalian middle ear from the jaw hinge of non-mammalian synapsids offers a deep-time perspective on sensory evolution but is limited by a poor understanding of early synapsid hearing. This work tests the hypothesis that the size of the reflected lamina of the angular bone in non-mammalian synapsids followed a strict, negative allometric trend that may be expected for a sound receiver. Allometry is first investigated in the pterygoid bone of chameleons, which was co-opted for hearing in some species and represents a possible analog for the synapsid reflected lamina. Results indicate that chameleons with a pterygoid ear exhibit a similar allometric slope, while species without a pterygoid ear have variable slopes, suggesting an optimum allometric pattern in sound receivers. In the reflected lamina, we find reduced variation around the allometric trend in therocephalians and non-bidentalian anomodonts, and evolutionary modeling suggests constraint in these groups. These results are consistent with a mandibular middle ear in non-mammalian synapsids, adding valuable new insights to the hypothesis that selective pressures for hearing ability were present long before the evolution of the mammalian middle ear.
Dynamic Changes in Gene Expression Through Aging in Drosophila melanogaster Heads
Authors: Hanson Katherine M , Macdonald Stuart J 
Published: February 2025

Abstract
Work in many systems has shown large-scale changes in gene expression during aging. However, many studies employ just two, arbitrarily-chosen timepoints at which to measure expression, and can only observe an increase or a decrease in expression between “young” and “old” animals, failing to capture any dynamic, non-linear changes that occur throughout the aging process. We used RNA sequencing to measure expression in male head tissue at 15 timepoints through the lifespan of an inbred Drosophila melanogaster strain. We detected &gt;6,000 significant, age-related genes, nearly all of which have been seen in previous Drosophila aging expression studies, and which include several known to harbor lifespan-altering mutations. We grouped our gene set into 28 clusters via their temporal expression change, observing a diversity of trajectories; some clusters show a linear change over time, while others show more complex, non-linear patterns. Notably, re-analysis of our dataset comparing the earliest and latest timepoints – mimicking a two-timepoint design – revealed fewer differentially-expressed genes (around 4,500). Additionally, those genes exhibiting complex expression trajectories in our multi-timepoint analysis were most impacted in this re-analysis; their identification, and the inferred change in gene expression with age, was often dependent on the timepoints chosen. Informed by our trajectory-based clusters, we executed a series of gene enrichment analyses, identifying enriched functions/pathways in all clusters, including the commonly seen increase in stress- and immune-related gene expression with age. Finally, we developed a pair of accessible Shiny apps to enable exploration of our differential expression and gene enrichment results.