bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial
Authors: Misset Benoît , Diep Anh Nguyet , Bertrand Axelle , Piagnerelli Michael , Hoste Eric , Michaux Isabelle , De Waele Elisabeth , Dumoulin Alexander , Jorens Philippe G. , van der Hauwaert Emmanuel , Vallot Frédéric , Swinnen Walter , De Schryver Nicolas , de Mey Nathalie , Layios Nathalie , Mesland Jean-Baptiste , Robinet Sébastien , Cavalier Etienne , Donneau Anne-Françoise , Moutschen Michel , Laterre Pierre-François 
Published: October 2024

Abstract
Background
Convalescent plasma (CP) reduced the mortality in COVID-19 induced ARDS (C-ARDS) patients treated in the CONFIDENT trial. As patients are immunologically heterogeneous, we hypothesized that clusters may differ in their treatment responses to CP.

Methods
We measured 20 cytokines, chemokines and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients of centers having accepted to participate in this secondary study. We performed descriptive statistics, unsupervised hierarchical cluster analysis, and examined the association between the clusters and CP effect on day-28 mortality.

Results
Of the 475 patients included in CONFIDENT, 391 (82%) were sampled, and 196/391 (50.1%) had been assigned to CP. We identified four sub-phenotypes representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients. The most contributing biomarkers in the principal component analysis were IL-1β, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 displayed a lower immune response, sub-phenotype-2 a higher adaptive response, sub-phenotype-3 the highest innate antiviral, pro and anti-inflammatory response, and adhesion molecule activation, and sub-phenotype-4 a higher pro and anti-inflammatory response, migration protein and adhesion molecule activation. Sub-phenotype-2 and sub-phenotype-4 had higher severity at the time of inclusion. The effect of CP treatment on mortality appeared higher than standard care in each sub-phenotype, without heterogeneity between sub-phenotypes (p = 0.97).

Conclusion
In patients with C-ARDS, we identified 4 sub-phenotypes based on their immune response. These sub-phenotypes were associated with different clinical profiles. The response to CP was similar across the 4 sub-phenotypes.
Trial registration: Ethics Committee of the University Hospital of Liège CE 2020/239. Clinicaltrials.gov NCT04558476. Registered 2020-09-11, https://www.clinicaltrials.gov/study/NCT04558476.
The role of eco-anxiety in the presentation of bulimia nervosa: a case report
Authors: Runfola Cristin D. , Safer Debra L. 
Published: October 2024

Abstract
Background
Despite a growing literature demonstrating the significant impacts of climate change on mental health, research is urgently needed to investigate how climate change-related concerns may contribute to the development, exacerbation, or re-emergence of eating disorders, as well as affect the effectiveness of existing interventions. This case report contributes to this scant knowledge base by offering empirical evidence for how responses to climate change can influence eating disorder symptoms and, importantly, limit the effectiveness of evidence-based treatments such as Cognitive Behavior Therapy-Enhanced (CBT-E).

Case presentation
A 24-year-old female graduate student studying environmental science presented to a specialized eating disorder clinic with worsening bulimia nervosa. Her symptoms initially improved with CBT-E; however, after three months, concerns about food waste significantly impeded further progress. The therapist, identifying symptoms of eco-anxiety, adapted standard CBT-E strategies to include psychoeducation about eco-anxiety, cognitive restructuring of beliefs about food waste and other eating-related eco-concerns, relevant exposures related to such concerns, and problem-solving to increase social support. These adaptations led to resumed progress, with the patient achieving nutritional adequacy by treatment end (38 sessions) and maintaining treatment gains through one year follow-up.

Conclusions
To our awareness, this is the first case report on the co-occurrence of eco-anxiety and eating disorders. This case underscores the importance of screening for concurrent eco-anxiety, suggests ways in which eating disorders and eco-anxiety can influence one another longitudinally, describes how coexisting eco-anxiety can limit standard CBT-E’s effectiveness, and provides examples of successful treatment adaptations tailored to address eco-anxiety-related concerns.
Linear epitopes of PRRSV-1 envelope proteins ectodomains are not correlated with broad neutralization
Authors: Castillo-Pérez Jaime , Martínez-Lobo Francisco Javier , Frómeta Raquel , Castro José María , Simarro Isabel , Prieto Cinta 
Published: October 2024

Abstract
Background
Neutralizing antibodies against PRRSV are capable of conferring protection against viral reinfection, but they tend to be strain specific and usually have poor cross-reactivity. Nonetheless, it has been described that there are individuals capable of efficiently neutralizing viruses of different origin, so it is expected that there are conserved neutralizing epitopes relevant for broad neutralization. However, although immunodominant regions and neutralizing epitopes have been described in different envelope proteins, their role in broad neutralization is unknown. The main objective of this study was to determine whether the linear epitopes existing in the ectodomains of PRRSV envelope proteins play a role in cross-neutralization.

Results
A pepscan analysis was carried out using synthetic peptides against the ectodomains of PRRSV envelope proteins and PRRSV-hyperimmune sera of different cross-reactivity. The results obtained confirm the existence of antigenic regions in the ectodomains of the GP2, GP3, GP4 and GP5 that tend to be relatively conserved among different PRRSV isolates. Nonetheless, these antigenic regions have poor immunogenicity since they are only recognized by a limited number of sera. Furthermore, no differences were found between the reactivity of sera with broad cross-neutralization capacity and sera with poor heterologous neutralization activity, which indicate that linear epitopes existing in the ectodomains of PRRSV envelope proteins are not relevant for the development of broadly reactive neutralizing antibodies. Subsequently, some selected peptides were used in competition assays with the virus for binding to the cell receptors and in seroneutralization inhibition assays by incubation with hyperimmune sera. Firstly, some peptides that interfere with virus infectivity were identified in competition assays, but only in the case of one viral isolate, which points to the possible existence of a strain-dependent inhibition. However, the results of the seroneutralization inhibition assay indicate that, under the conditions of our study, none of the peptides used was capable of inhibiting virus neutralization by the hyperimmune sera.

Conclusions
The results obtained indicate that the linear peptides analyzed in this study do not play a major role in the induction of broadly reactive neutralizing antibodies, which could probably depend on conformational neutralizing.
Exploring in vivo and in vitro models for heart failure with biomarker insights: a review
Authors: Prajapati Anil Kumar , Shah Gaurang 
Published: October 2024

Abstract
Background
Heart failure (HF) is a condition characterized by the heart’s inability to meet the body’s demands, resulting in various complications. Two primary types of HF exist, namely HF with preserved left ventricular ejection fraction (LVEF) and HF reduced with LVEF. The progression of HF involves compensatory mechanisms such as cardiac hypertrophy, fibrosis, and alterations in gene expression. Pressure overload and volume overload are common etiologies of HF, with pressure overload often stemming from conditions like hypertension, leading to left ventricular hypertrophy and fibrosis. In contrast, volume overload can arise from chronic valvular regurgitant disease, also inducing left ventricular hypertrophy.

Main body
In vitro cell culture techniques serve as vital tools in studying HF pathophysiology, allowing researchers to investigate cellular responses and potential therapeutic targets. Additionally, biomarkers, measurable biological characteristics, play a crucial role in diagnosing and predicting HF. Some notable biomarkers include adrenomedullin, B-type natriuretic peptide, copeptin, galectin-3, interleukin-6, matrix metalloproteinases (MMPs), midregional pro-atrial natriuretic peptide, myostatin, procollagen type I C-terminal propeptide, procollagen type III N-terminal propeptide and tissue inhibitors of metalloproteinases (TIMPs). These biomarkers aid in HF diagnosis, assessing its severity, and monitoring treatment response, contributing to a deeper understanding of the disease and potentially leading to improved management strategies and outcomes.

Conclusions
This review provides comprehensive insights into various in vivo models of HF, commonly utilized cell lines in HF research, and pivotal biomarkers with diagnostic relevance for HF. By synthesizing this information, researchers gain valuable resources to further explore HF pathogenesis, identify novel therapeutic targets, and enhance diagnostic and prognostic approaches.
Toxicity Adaptive Lists Design: A Practical Design for Phase I Drug Combination Trials in Oncology
Authors: Russo Massimiliano , Mariani Francesco , Cleary James M. , Shapiro Geoffrey I. , Coté Gregory M. , Trippa Lorenzo 
Published: October 2024

PURPOSE
We introduce a novel algorithmic approach to design phase I trials for oncology drug combinations.

METHODS
Our proposed Toxicity Adaptive Lists Design (TALE) is straightforward to implement, requiring the prespecification of a small number of parameters that define rules governing dose escalation, de-escalation, or reassessment of previously explored dose levels. These rules effectively regulate dose exploration and control the number of toxicities. A key feature of TALE is the possibility of simultaneous assignment of multiple-dose combinations that are deemed safe by previously accrued data.

RESULTS
A numerical study shows that TALE shares comparable operative characteristics, in terms of identification of the maximum tolerated dose (MTD), to alternative approaches such as the Bayesian optimal interval design, the COPULA, the product of independent beta probabilities escalation, and the continual reassessment method for partial ordering designs while reducing the risk of overdosing patients.

CONCLUSION
The proposed TALE design provides a favorable balance between maintaining patient safety and accurately identifying the MTD. To facilitate the use of TALE, we provide a user-friendly R Shiny application and an R package for computing relevant operating characteristics, such as the risk of assigning highly toxic dose combinations.
Technical Feasibility of Delineating the Thalamic Gustatory Tract Using Tractography
Authors: Sakakura Kazuki , Pertsch Nathan , Mueller Julia , Borghei Alireza , Rubert Nicholas , Sani Sepehr 
Published: October 2024

BACKGROUND AND OBJECTIVES:
Magnetic resonance–guided focused ultrasound (MRgFUS) has been increasingly performed in recent years as a minimally invasive treatment of essential tremor and tremor-dominant Parkinson disease. One of the side effects after treatment is dysgeusia. Some centers use tractography to facilitate the treatment planning. However, there have been no reports of identifying gustatory tracts so far. Our aim was to investigate the technical feasibility of isolating and visualizing the gustatory tracts, as well as to explore the relationship between the gustatory tract and the MRgFUS lesion using actual patient data.

METHODS:
We used 20 randomly selected individuals from the Human Connectome Project database to perform tractography of the gustatory tracts. We defined region of interest as the dorsal region of the brainstem, Brodmann area 43 associated with taste perception, and a sphere with a 3-mm radius centered around the ventral intermediate nucleus in the anterior commissure-posterior commissure plane. We also examined the position of the gustatory tract in relation with other tracts, including the medial lemniscus, the pyramidal tract, and the dentatorubrothalamic tract. In addition, using the data of real patients with essential tremor, we investigated the distance between MRgFUS lesions and the gustatory tract and its association with the development of dysgeusia.

RESULTS:
We delineated a mean of 15 streamlines of the gustatory tracts per subject in each hemisphere. There was no statistical difference in the localization of the gustatory tracts between the left and right cerebral hemispheres. The gustatory tract was located anteromedial to the medial lemniscus and posteromedial to the dentatorubrothalamic tract in the anterior commissure-posterior commissure plane. The distance from the MRgFUS lesion to the gustatory tract was significantly shorter in the case where dysgeusia occurred compared with nondysgeusia cases (P-value: .0068).

CONCLUSION:
The thalamic gustatory tracts can be reliably visualized using tractography.
Glutaraldehyde-enhanced autofluorescence as a general tool for 3D morphological imaging
Authors: Niemeläinen Miika , Haapanen-Saaristo Anna-Mari , Koskinen Leena M. , Gullmets Josef , Peuhu Emilia , Meinander Annika , Calhim Sara , Paatero Ilkka 
Published: October 2024

ABSTRACT
Routine histochemical techniques are capable of producing vast amount of information from diverse sample types, but these techniques are limited in their ability to generate 3D information. Autofluorescence imaging can be used to analyse samples in 3D but it suffers from weak/low signal intensities. Here, we describe a simple chemical treatment with glutaraldehyde to enhance autofluorescence for 3D fluorescence imaging and to generate detailed morphological images on whole-mount samples. This methodology is straightforward and cost-effective to implement, suitable for a wide range of organisms and sample types. Furthermore, it can be readily integrated with standard confocal and fluorescence microscopes for analysis. This approach has the potential to facilitate the analysis of biological 3D structures and research in developmental biology, including studies on model and non-model organisms.
40 years since the Heidelberg genetic screen that revolutionized developmental and cell biology
Authors: Peifer Mark 
Published: October 2024

ABSTRACT
Our current understanding of the molecular basis of embryonic development and the shared machinery underlying this remarkable process has its roots in three papers published 40 years ago, which summarize the results of the Nobel Prize-winning ‘Heidelberg screen’. The genesis of these experiments that empowered us and the stories behind the experiments are worth revisiting.
Effects of hemodynamic load on cardiac remodeling in fish and mammals: the value of comparative models
Authors: Shaftoe Jared B. , Gillis Todd E. 
Published: October 2024

ABSTRACT
The ability of the vertebrate heart to remodel enables the cardiac phenotype to be responsive to changes in physiological conditions and aerobic demand. Examples include exercise-induced cardiac hypertrophy, and the significant remodeling of the trout heart during thermal acclimation. Such changes are thought to occur in response to a change in hemodynamic load (i.e. the forces that the heart must work against to circulate blood). Variations in hemodynamic load are caused by either a volume overload (high volume of blood returning to the heart, impairing contraction) or a pressure overload (elevated afterload pressure that the heart must contract against). The changes observed in the heart during remodeling are regulated by multiple cellular signaling pathways. The cardiac response to these regulatory mechanisms occurs across levels of biological organization, affecting cardiac morphology, tissue composition and contractile function. Importantly, prolonged exposure to pressure overload can cause a physiological response – that improves function – to transition to a pathological response that causes loss of function. This Review explores the role of changes in hemodynamic load in regulating the remodeling response, and considers the cellular signals responsible for regulating remodeling, incorporating knowledge gained from studying biomedical models and comparative animal models. We specifically focus on the renin–angiotensin system, and the role of nitric oxide, oxygen free radicals and transforming growth factor beta. Through this approach, we highlight the strong conservation of the regulatory pathways of cardiac remodeling, and the specific conditions within endotherms that may be conducive to the development of pathological phenotypes.
Rank-and-File Employee Stock Options and Workplace Safety
Authors: Chen Yangyang , Ofosu Emmanuel , O’Sullivan Don , Veeraraghavan Madhu , Zolotoy Leon 
Published: October 2024

We provide robust evidence that rank-and-file employee stock options (R&F options) lead to lower work-related injury rates. This finding is consistent with the view that R&F options improve workplace safety by facilitating employee retention and cooperation. To establish causality, we employ difference-in-differences analysis around the passage of FAS 123R option expensing regulation and instrumental variable estimation. In cross-sectional analysis, we find that the documented effect is amplified among firms with higher labor mobility rates and among firms with greater scope for employee free riding. The results of supplemental analysis suggest that work-related injuries adversely impact firm performance and rule out reduced employee whistleblowing about workplace safety issues as an alternative mechanism driving our findings. This paper was accepted by Victoria Ivashina, finance. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2022.02072 .
Impact of storage on sterility of surgical instruments in autoclave bags
Authors: Hart Katherine , Cartlidge Helen 
Published: October 2024

Background: There is no published veterinary research to support an optimal storage duration and method of sterile surgical instrumentation (SI) when using self-seal autoclave bags (SSABs), although aspects of research from human healthcare are transferable. Multiple pieces of research in human healthcare have demonstrated the ability of sterilisation packaging materials to maintain barrier integrity and sterility for several months poststerilisation. Research on an optimal storage method is inconclusive. Aims: To determine an ideal storage duration and method of single SI, packaged in SSABs and sterilised via an autoclave. To determine the current practice of sterilisation, storage methods and durations using SSABs in small animal practice. Methods: This mixed methods study consisted of an online questionnaire to investigate the current procedures for autoclave sterilisation in veterinary practice. Alongside this, a non-randomised control study was conducted to assess the sterility of single SI, packaged in SSABs and sterilised via autoclave, to determine an ideal storage duration and method. SI was sterilised and stored for one, three and six months, in open (on a shelf) and closed (in a box) environments. Results: The questionnaire indicated veterinary professionals are adopting a cautious approach to storage durations with 75.5% (n=40) storing sterile single SI for between one and three months, prior to reprocessing. The experimental study did not identify an optimal storage method and either open or closed could be used for effective storage in undisturbed conditions. It is highly probable that most SI were sterile at the end of the storage durations and for up to 6 months. Conclusions: Laboratory findings are mostly consistent with those in existing literature. Results suggest the storage of sterile SI, in either open or closed environments for up to 6 months was not detrimental to the sterility of the instruments. To encourage good sustainability performance, practices could extend the storage times of sterilised SI prior to reprocessing.
The degenerated glenohumeral joint
Authors: Toegel Stefan , Martelanz Luca , Alphonsus Juergen , Hirtler Lena , Gruebl-Barabas Ruth , Cezanne Melanie , Rothbauer Mario , Heuberer Philipp , Windhager Reinhard , Pauzenberger Leo 
Published: October 2024

AimsThis study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated.MethodsSpecimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA).ResultsCartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found.ConclusionThis study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy.Cite this article: Bone Joint Res 2024;13(10):596–610.