bluuebunny/crossref_metadata_2025_split huggingface dataset:
CryptoBench: cryptic protein–ligand binding sites dataset and benchmark
Authors: Škrhák Vít , Novotný Marian , Feidakis Christos P , Krivák Radoslav , Hoksza David 
Published: December 2024

Abstract

Motivation
Structure-based methods for detecting protein–ligand binding sites play a crucial role in various domains, from fundamental research to biomedical applications. However, current prediction methodologies often rely on holo (ligand-bound) protein conformations for training and evaluation, overlooking the significance of the apo (ligand-free) states. This oversight is particularly problematic in the case of cryptic binding sites (CBSs) where holo-based assessment yields unrealistic performance expectations.

Results
To advance the development in this domain, we introduce CryptoBench, a benchmark dataset tailored for training and evaluating novel CBS prediction methodologies. CryptoBench is constructed upon a large collection of apo–holo protein pairs, grouped by UniProtID, clustered by sequence identity, and filtered to contain only structures with substantial structural change in the binding site. CryptoBench comprises 1107 structures with predefined cross-validation splits, making it the most extensive CBS dataset to date. To establish a performance baseline, we measured the predictive power of sequence- and structure-based CBS residue prediction methods using the benchmark. We selected PocketMiner as the state-of-the-art representative of the structure-based methods for CBS detection, and P2Rank, a widely-used structure-based method for general binding site prediction that is not specifically tailored for cryptic sites. For sequence-based approaches, we trained a neural network to classify binding residues using protein language model embeddings. Our sequence-based approach outperformed PocketMiner and P2Rank across key metrics, including area under the curve, area under the precision-recall curve, Matthew’s correlation coefficient, and F1 scores. These results provide baseline benchmark results for future CBS and potentially also non-CBS prediction endeavors, leveraging CryptoBench as the foundational platform for further advancements in the field.

Availability and implementation
The CryptoBench dataset, including the benchmark model, is available on Open Science Framework—https://osf.io/pz4a9/. The code and tutorial are available at the GitHub repository—https://github.com/skrhakv/CryptoBench/.
Prevalence of two endosymbionts in range-expanding Zodarion spiders (Araneae: Zodariidae)
Authors: Viel Nathan , Wijacki Tamara , Pétillon Julien , Pekár Stano 
Published: December 2024

Abstract
Major changes in species geographical ranges are usually explained by climatic changes or human activities. Intrinsic causes, such as endosymbiotic agents, have not yet been considered thoroughly, despite their potential to affect profoundly the biology of organisms such as arthropods and their aim to maximize their own transmission, e.g. by altering the dispersal abilities of their host. Here, we describe on a large scale the prevalence of two widespread endosymbionts, Wolbachia and Cardinium, in the rapidly range-expanding spider Zodarion rubidumSimon, 1914. Using standard PCR, we screened for the presence of both endosymbionts in specimens collected from 40 populations across Europe. We interpolated the prevalence of the endosymbionts over the study area using ordinary kriging, looking for spatial patterns corresponding to the putative expansion pathway of Z. rubidum. We found that both endosymbionts are widely present throughout Z. rubidum populations, with Wolbachia showing low prevalences with a few patches of high incidence, and with Cardinium being almost at fixation across the study area. Furthermore, in seven additional Zodarion species we investigated the relationship between the prevalence of endosymbionts and spider geographical ranges. We failed to find any significant relationship between these two parameters. We discuss possible explanations for such wide endosymbiont distributions and question their potential impact on Zodarion populations.
Can brain network connectivity facilitate the clinical development of disease-modifying anti-Alzheimer drugs?
Authors: Pini Lorenzo , Lista Simone , Griffa Alessandra , Allali Gilles , Imbimbo Bruno P 
Published: December 2024

Abstract
The preclinical phase of Alzheimer’s disease represents a crucial time window for therapeutic intervention but requires the identification of clinically relevant biomarkers that are sensitive to the effects of disease-modifying drugs. Amyloid peptide and tau proteins, the main histological hallmarks of Alzheimer’s disease, have been widely used as biomarkers of anti-amyloid and anti-tau drugs. However, these biomarkers do not fully capture the multiple biological pathways of the brain. Indeed, robust amyloid-target engagement by anti-amyloid monoclonal antibodies has recently translated into modest cognitive and clinical benefits in Alzheimer’s disease patients, albeit with potentially life-threatening side effects. Moreover, targeting the tau pathway has yet to result in any positive clinical outcomes. Findings from computational neuroscience have demonstrated that brain regions do not work in isolation but are interconnected within complex network structures. Brain connectivity studies suggest that misfolded proteins can spread through these connections, leading to the hypothesis that Alzheimer’s disease is a pathology of network disconnectivity. Based on these assumptions, here we discuss how incorporating brain connectivity outcomes could better capture global brain functionality and, in conjunction with traditional Alzheimer’s disease biomarkers, could facilitate the clinical development of new disease-modifying anti-Alzheimer’s disease drugs.
Investigation of crack initiation during the burst test of hydrogen storage composite overwrapped pressure vessels
Authors: Liu Changchen , Ouyang Zhihui , Yu Jiexiang , Ma Li 
Published: December 2024

Abstract
Hydrogen storage composite overwrapped pressure vessels (COPVs), as a core component of fuel cells, are widely used in the new energy vehicles and other fields. However, the service performance of COPVs, especially the burst pressure, has a great dispersion, which may come from the microscopic defects inside the vessels. In this paper, the industrial computed tomography scan was carried out on a type III hydrogen storage COPV with an aluminum alloy liner and a carbon fiber wound layer, and it was found that many delamination defects with random sizes and locations exist inside the fiber wound layer. Among these defects, there are 164 delamination defects with an area of &lt;500 mm2 (accounting for 87.7% of the total number of defects), but the area of the defects only comprises 19.14% of the entire defects area. Delamination defects were the predominant type of manufacturing defect in the fiber wound layer of COPVs. Then the burst test of the COPV was carried out, which showed that the aggregated area of large-sized delamination defects located in the composite layer of the cylindrical part triggered the crack initiation during the burst test. Thus, in turn, directly affected both the burst pressure and the post-burst morphology. Finally, a 3D equivalent model of the laminated structure is proposed to model the expansion of the composite cylinder. By carrying out a finite element simulation of the COPV, the most dangerous area during the loading process of the COPV is confirmed. The experimentally measured burst pressure of the cylinder is 115.5 MPa, which deviates by 18.6% from the pristine model prediction and by 9.09% from the model with delamination defects.
School Social Work and Mental Health Funding
Authors: Kelly Caroline H 
Published: December 2024

Abstract
School social workers provide mental health services to millions of students each year. However, few studies focus on how social workers generate funding and other support for school mental health. The purpose of this study is to identify the continuum of school mental health supports and how social workers advocate for and generate these supports. This study examines variation in school social worker experiences across three school types: Chicago neighborhood schools, Chicago charter schools, and Chicago-area suburban schools. This study uses the ecological systems framework to structure the interview guide and inform coding. This study finds three major themes: (1) schools improve student access to mental health services, (2) social workers advocate for mental health supports differently depending on their school type, and (3) schools sideline social workers through inadequate support of their positions. Findings suggest greater support for school social work positions and greater collaboration between administrators and school social workers to fully leverage available resources and meet student mental health needs.
Disruption of Epithelial Barrier Integrity via Altered GILZ/c-Rel/RACK1 Signaling in Inflammatory Bowel Disease
Authors: Buoso Erica , Masi Mirco , Limosani Roberta Valeria , Fagiani Francesca , Oliviero Chiara , Colombo Giorgia , Cari Luigi , Gentili Marco , Lusenti Eleonora , Rosati Lucrezia , Pisati Federica , Pasini Alessandra , Lenti Marco Vincenzo , Di Sabatino Antonio , Mobbs Claire Louise , Przyborski Stefan , Ronchetti Simona , Travelli Cristina , Racchi Marco 
Published: December 2024

Abstract

Background and Aims
Given the role of Receptor for Activated C Kinase 1 (RACK1) in both immune cell activation and in the maintenance of the intestinal epithelial barrier integrity, we investigated whether it was involved in inflammatory bowel disease (IBD).

Methods
RACK1 expression was analyzed in intestinal mucosal samples of healthy and IBD patients, in mice with chemically induced colitis, and in diseased in vitro 2D and 3D coculture models by luciferase assay, reverse transcription-quantitative PCR, Western blotting, immunofluorescence, and immunohistochemistry. Based on our finding that glucocorticoid-induced leucine zipper (GILZ or tsc22d3) positively correlates with RACK1 expression in IBD patients, GILZ knockout mice and cell silencing experiments were performed.

Results
RACK1 was significantly decreased in IBD, especially in ulcerative colitis. This was associated with an NF-κB/c-Rel-related mechanism, correlating with decreased GILZ protein expression. GILZ depletion confirmed a decrease in RACK1 expression, which favored SRC activation and led to a significant reduction in E-cadherin, resulting in impaired epithelial barrier integrity. Finally, our data highlighted that this novel mechanism could be considered to develop new therapies since dexamethasone, the first line of treatment in IBD, restored RACK1 expression through the glucocorticoid receptor in a c-Rel/GILZ-independent manner.

Conclusions
We provide the first evidence that an alteration of RACK1/SRC/E-cadherin regulatory mechanism, correlating with decreased GILZ protein expression, is involved in epithelial barrier disruption. The clinical relevance is based on the fact that this mechanism involving GILZ/c-Rel-related RACK1 expression could be considered to improve IBD therapies, particularly in patients with low or no response to glucocorticoid treatment.
Paradoxical improvement in exercise tolerance and peak VO2 consumption after treatment with ivabradine and beta-blockers in a patient with mild dilated cardiomyopathy and inappropriate sinus tachycardia—a case report
Authors: Graziano Francesca , Pizzolato Matteo , Bondarev Sergei , Corrado Domenico , Zorzi Alessandro 
Published: December 2024

Abstract

Background
Left bundle branch block (LBBB) is a rare conduction disorder in athletes associated with ventricular dyssynchrony, which can lead to left ventricular systolic dysfunction and exercise intolerance. Inappropriate sinus tachycardia (IST) is characterized by an excessive heart rate (HR) that is not related to physiological needs, often resulting in reduced exercise capacity. Managing these conditions in athletes can be challenging, as standard treatments like beta-blockers and ivabradine, while effective in controlling HR, are described to be associated with a reduction in maximal exercise performance.

Case summary
A 50-year-old amateur athlete presented with exercise intolerance, LBBB, and mild dilated cardiomyopathy due to ventricular dyssynchrony. Resting electrocardiogram and 24-h monitoring confirmed IST. Initial cardiopulmonary exercise testing (CPET) off-therapy showed rapid HR increase during exertion, an early plateau in oxygen pulse, and reduced peak oxygen consumption (VO2, 22.1 mL/kg/min, 76% of the predicted value). After 1 month of ivabradine 5 mg b.i.d., there was some improvement in these parameters. At the third follow-up, with combined therapy of ivabradine (5 mg b.i.d.) and metoprolol (50 mg b.i.d.), the HR response during exercise normalized, and CPET parameters significantly improved, with peak VO2 reaching 29.2 mL/kg/min (101% of the predicted value).

Discussion
This case highlights a paradoxical improvement in exercise tolerance and peak VO2 with combined ivabradine and beta-blocker therapy in a patient with IST. The treatment optimized the HR response during exercise, suggesting that individualized strategies can enhance exercise performance in patients with IST and mild cardiomyopathy, despite the expected limitations of these medications.
Anomalous origin of the left coronary artery from pulmonary artery mimicking antero-lateral ST-elevation myocardial infarction: a case report
Authors: Arow Ziad , Zilberman Liaz , Koifman Edward , Assali Abid , Arnson Yoav 
Published: December 2024

Abstract

Background
Anomalous origin of the left coronary artery (LCA) from the pulmonary artery (PA) (ALCAPA) is a rare congenital abnormality. We present a case of an ALCAPA in a 25-year-old man.

Case summary
A 25-year-old male with no past medical history was admitted to our intensive cardiac care unit after sudden cardiac arrest due to ventricular fibrillation and suspected acute coronary syndrome. After being treated with shock by automated external defibrillator, an electrocardiogram (ECG) demonstrated sinus tachycardia with antero-lateral ST-segment elevation. Initial transthoracic echocardiography showed severe and diffuse left ventricular dysfunction and dilatation. Coronary angiography revealed anomalous origin of the LCA from the PA and extensive collateral circulation from a giant RCA. An ECG-gated cardiac computed tomography confirmed the diagnosis of anomalous left main originating from the left PA. Cardiac magnetic resonance demonstrated an enlarged left ventricle with globally reduced function and extensive sub-endocardial scarring of the anterior, antero-lateral, and lateral walls. Following a multidisciplinary heart team discussion, the patient successfully underwent repair of aberrant LCA with direct LCA re-implantation to the aorta and subcutaneous implantable cardioverter defibrillator implantation. Optimal medical therapy for heart failure with reduced ejection fraction was initiated, and the patient was discharged home for a close clinical and echocardiographic follow-up.

Discussion
In conclusion, ALCAPA in the adulthood is a very rare congenital anomaly that clinicians should be aware of. The preferred treatment, when diagnosed in time, is direct re-implantation of the LCA to the aorta.
Evaluating neurological outcomes of and risk factors for hypoattenuated leaflet thickening following aortic root replacement and arch surgery
Authors: Radner Caroline , Peterss Sven , Buech Joscha , Grefen Linda , Hagl Christian , Pichlmaier Maximilian 
Published: December 2024

Abstract

OBJECTIVES
In this retrospective study, we aimed to assess incidence, possible causes and clinical consequences of hypoattenuated leaflet thickening (HALT) following aortic root replacement with valved composite grafts and concomitant aortic arch repair.

METHODS
Between January 2016 and December 2022, 454 patients underwent Bentall procedures with arch replacements in hypothermic circulatory arrest at the University Aortic Centre MunichLMU, Germany. Sequential postoperative ECG-gated, high-resolution computed tomography angiographies were analyzed, and the presence of HALT correlated with neurologic events and transvalvular gradients over time. Furthermore, attention was given to intraoperative hemostatic product use and postoperative anticoagulation regimes.

RESULTS
327 out of 454 patients were included. The follow-up period averaged to 3.27 years. 28% of the patients showed radiographic signs of HALT, which was correlated with a significantly higher incidence of transient neurological events as compared to those without (38 vs 8 events, P &lt; 0.01). However, there were no significant differences with respect to the postoperative anticoagulation regimen or transvalvular gradients between the two groups. Only the intraoperative administration of prothrombin complex concentrate was significantly higher in patients with postoperative HALT.

CONCLUSIONS
HALT is observed in a high percentage of cases following aortic root replacement combined with complex aortic procedures. Furthermore, it is associated with an increased risk of neurological events but only a weak correlation was demonstrated with the perioperative coagulation management. While no long-term implications were noted, these findings suggest the necessity for further investigations, longer follow-up periods, and more comprehensive diagnostic approaches.
The maintenance of genetic polymorphism underlying sexually antagonistic traits
Authors: Flintham Ewan , Savolainen Vincent , Otto Sarah P , Reuter Max , Mullon Charles 
Published: December 2024

Abstract
Selection often favors different trait values in males and females, leading to genetic conflicts between the sexes when traits have a shared genetic basis. Such sexual antagonism has been proposed to maintain genetic polymorphism. However, this notion is based on insights from population genetic models of single loci with fixed fitness effects. It is thus unclear how readily polymorphism emerges from sex-specific selection acting on continuous traits, where fitness effects arise from the genotype-phenotype map and the fitness landscape. Here, we model the evolution of a continuous trait that has a shared genetic basis but different optima in males and females, considering a wide variety of genetic architectures and fitness landscapes. For autosomal loci, the long-term maintenance of polymorphism requires strong conflict between males and females that generates uncharacteristic sex-specific fitness patterns. Instead, more plausible sex-specific fitness landscapes typically generate stabilizing selection leading to an evolutionarily stable state that consists of a single homozygous genotype. Except for sites tightly linked to the sex-determining region, our results indicate that genetic variation due to sexual antagonism should arise only rarely and often be transient, making these signatures challenging to detect in genomic data.
People With Dementia Disclosing Their Diagnosis to Social Networks: A Systematic Review and Meta-Synthesis
Authors: Kohl Gianna , Molinari Ulate Mauricio , Bhatt Jem , Lynch Jennifer , Scior Katrina , Charlesworth Georgina 
Published: December 2024

Abstract

Background and Objectives
Given the stigma of dementia, individuals with the condition may be wary to disclose their diagnosis to other people, both in face-to-face and digital settings. While sharing one’s dementia diagnosis with others is essential for accessing valuable support for social, cognitive, and physical well-being, this area of research has largely been neglected. In this meta-synthesis, we aimed to systematically review qualitative research on the factors associated with online and offline self-disclosure in people with dementia.

Research Design and Methods
We conducted a systematic search in 6 electronic databases. Inclusion criteria comprised qualitative and mixed-methods studies describing experiences with self-disclosure in people with any type of dementia. Quality of the included studies was assessed using the Mixed Methods Appraisal Tool. The meta-synthesis was conducted in NVivo using a thematic synthesis approach.

Results
28 studies were included. 3 analytical themes were generated: “Concealment,” “Stigma and fear,” and “Taking control,” the latter 2 with subthemes. Findings from this review were corroborated with people with dementia and family carers as part of Patient and Public Involvement meetings. Our findings reveal that while stigma plays a pivotal role, people with dementia can take control of the meaning of their diagnosis through self-disclosure.

Discussion and Implications
Self-disclosure is complex and multifaceted. People with dementia, particularly those experiencing stigma, can benefit from post-diagnostic support that encompasses resources and interventions for self-disclosure. Further research is required to investigate people with dementia’s disclosure decision-making process.
Reduced predation and competition from herring may have contributed to the increase of three-spined stickleback in the Baltic Sea
Authors: Donadi Serena , Olin Agnes , Casini Michele , Eklöf Johan , Erlandsson Mårten , Fredriksson Ronny , Kaljuste Olavi , Larson Niklas , Nilsson Jonas , Bergström Ulf 
Published: December 2024

Abstract
In many areas of the Baltic Sea, three-spined stickleback (Gasterosteus aculeatus) has increased several fold since the early 2000s. Two major planktivores of the Baltic Sea, Atlantic herring (Clupea harengus) and European sprat (Sprattus sprattus), may interact with stickleback via competition for food and predation, but the potential implications at the population level are still unknown. Here, we explored interactions between stickleback, herring, and sprat using (i) herring diet analyses and (ii) fish biomass estimates from hydroacoustics for 2001–2019 covering the largest Baltic Sea basins—the Central Baltic and the Bothnian Sea. The diet analyses revealed that stickleback is an important prey for large herring along the Swedish Baltic Sea coast, comprising up to 64% of the diet of individuals &gt;22 cm. We found a negative influence of large herring (&gt;18 cm) on stickleback in the Central Baltic, and a negative relationship between sprat and small herring (&lt;18 cm) (pooled) and stickleback in the Bothnian Sea. The decline in herring and sprat population after the mid-1990s could have contributed to the increase in stickleback population via reduced predation and competition. Overall, herring may be an underappreciated piscivore, and high fishing pressure on herring could generate cascading effects on lower trophic levels.
The effect of addressing the top 10 global causes of death on life expectancy in 2019: a global and regional analysis
Authors: Shahbazi Fatemeh , Moslehi Samad , Mirzaei Zahra , Mohammadi Younes 
Published: December 2024

Abstract

Background
The life expectancy (LE) index reflects health changes in society, highlighting trends in health quality and quantity. This study focused on analysing the impact of the top 10 causes of death on the global increase in LE in 2019.

Methods
Data on the top 10 causes of death in 2019 were obtained from the Global Burden of Disease website and a period life table was used to assess how eliminating these causes would impact LE.

Results
At the global level, eliminating deaths from ischaemic heart disease, stroke, chronic obstructive pulmonary disease, lower respiratory infections, neonatal conditions, lung cancers, Alzheimer's disease, diarrheal diseases, diabetes mellitus and kidney diseases resulted in an increase in LE at birth of 2.44, 1.64, 0.75, 0.80, 4.06, 0.48, 0.36, 0.52, 0.36 and 0.35 y, respectively.

Conclusions
The analysis reveals a gender gap in LE influenced by specific causes of death and regional differences. Therefore, public health policies should be customized for each area to target reductions in deaths that significantly improve LE.