bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is There a Hamstring Autograft Diameter Threshold for Anterior Cruciate Ligament Reconstruction?
Authors: Mirzayan Raffy , Chang Richard N. , Royse Kathryn E. , Reyes Chelsea E. , Prentice Heather A. , Maletis Gregory B. 
Published: February 2025

Background: Hamstring autograft (HA) is a popular graft for anterior cruciate ligament reconstruction (ACLR). Although multiple studies have demonstrated that increasing the graft diameter decreases the risk of failure or revision surgery, the exact minimum graft diameter remains controversial, with the unofficial standard being 8 mm. Purpose: To evaluate the risk of aseptic revision after HA-ACLR in patients aged ≤25 years, comparing graft diameters of (1) <8 versus ≥8 mm and (2) ≤8 versus >8 mm. A secondary purpose was to determine whether there was a threshold for graft diameter that best identifies patients at a higher risk of aseptic revision. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 5972 primary HA-ACLRs were identified using data from the ACLR registry of Kaiser Permanente. Propensity score–weighted Cox regression was used to evaluate revision risk for HAs with <8 versus ≥8 mm diameter and with ≤8 versus >8 mm diameter. An effect plot and receiver operating characteristic curve and area under the curve (AUC) analysis were also created to model the probability of revision based on the HA diameter to determine whether there was a specific diameter threshold to minimize revision risk. Results: In the propensity score–weighted Cox model, <8 mm autografts had a higher risk of aseptic revision compared with ≥8 mm autografts (hazard ratio [HR], 1.32 [95% CI, 1.01-1.71]; P = .039); a higher risk was also observed when comparing ≤8 to >8 mm grafts (HR, 1.32 [95% CI, 1.06-1.66]; P = .015). In receiver operating characteristic analysis, an HA diameter that best identified patients at a higher risk for revision after ACLR could not be identified (AUC, 0.56). However, the adjusted effect plot showed a direct decrease in revision risk with each increasing increment in graft size. Conclusion: A 32% higher risk of revision was observed in smaller graft diameter groups (<8 or ≤8 mm) compared with larger graft sizes (≥8 or >8 mm), regardless of specific diameter cutoff. In a cohort of almost 6000 HA-ACLR, the authors were unable to determine a definitive minimum graft diameter threshold that should be used.
Interaction of genetic variants and methylation in transcript-level expression regulation in Alzheimer’s disease by multi-omics data analysis
Authors: Han Seonggyun , Cho Soo-ah , Choi Wongyung , Eilbeck Karen , Coon Hilary , Nho Kwangsik , Lee Younghee 
Published: February 2025

Abstract

Background
Alzheimer’s disease (AD) presents a significant public health problem and major cause of dementia. Not only genetic but epigenetic factors contribute to complex and heterogeneous molecular mechanisms underlying AD risk; in particular, single nucleotide polymorphisms (SNPs) and DNA methylation can lead to dysregulation of gene expression in the AD brain. Each of these regulators has been independently studied well in AD progression, however, their interactive roles, particularly when they are located differently, still remains unclear. Here, we aimed to explore the interplay between SNPs and DNA methylation in regulating transcript expression levels in the AD brain through an integrative analysis of whole-genome sequencing, RNA-seq, and methylation data measured from the dorsolateral prefrontal cortex.

Results
We identified 179 SNP-methylation combination pairs that showed statistically significant interactions associated with the expression of 67 transcripts (63 unique genes), enriched in functional pathways, including immune-related and post-synaptic assembly pathways. Particularly, a number of HLA family genes (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB5, HLA-DPA1, HLA-K, HLA-DQB1, and HLA-DMA) were observed as having expression changes associated with the interplay.

Conclusions
Our findings especially implicate immune-related pathways as targets of these regulatory interactions. SNP-methylation interactions may thus contribute to the molecular complexity underlying immune-related pathogenies in AD patients. Our study provides a new molecular knowledge in the context of the interplay between genetic and epigenetic regulations, in that it concerns transcript expression status in AD.
Identification of key genes controlling anthocyanin biosynthesis in the fruits of a bud variety of Tarocco blood-orange
Authors: Zhang Peian , Zhao Quan , Song Yang , Jin Huanchun , Liu Yingyao , Hu Dan , Liu Dongfeng 
Published: February 2025

Abstract
Tarocco is a prevalent blood-orange variety in China, has a bud variant identified in Wenzhou City. To characterize the quality traits and molecular mechanisms underlying inhibition of anthocyanin synthesis in this variety, we collected fruits of Tarocco (WT) and the bud variant Ouya (MT) at nine developmental stages. Their anthocyanin, soluble sugar, and organic acid profiles were examined, and transcriptomes and metabolites were analyzed at three developmental stages. The results revealed that MT is a new blood orange variety with weak anthocyanins and a better sugar-acid ratio than the WT. The content of anthocyanin in MT fruits were significantly lower than those in WT fruits, especially cyanidin-like anthocyanins, while the flavone contents exhibited no remarkable variation. A total of 64 differentially expressed genes (DEGs), including five transcription factors (TFs), five methylation-related genes, and one flavonoid biosynthesis gene, were identified between WT and MT at three fruit developmental stages. The potential regulatory networks of these TFs were further constructed using weighted gene co-expression network analysis.Furthermore, in MT fruit treated with the 5-azacytidine, we observed hypomethylation of anthocyanins accumulated in the pulp and the promoters and genebodies of some anthocyanin synthesis-related genes. These results provide new insights into the influence of DNA methylation on anthocyanin accumulation in MT and also provide support for the promotion of MT as a new variety.
GATA3 amplification is associated with high grade disease in non-invasive urothelial bladder cancer but unrelated to patient prognosis
Authors: Plage Henning , Frericks Adrian , Hofbauer Sebastian , Furlano Kira , Weinberger Sarah , Roßner Florian , Schallenberg Simon , Elezkurtaj Sefer , Lennartz Maximilian , Marx Andreas , Samtleben Henrik , Fisch Margit , Rink Michael , Slojewski Marcin , Kaczmarek Krystian , Ecke Thorsten , Koch Stefan , Simon Ronald , Sauter Guido , Zecha Henrik , Weischenfeldt Joachim , Klatte Tobias , Minner Sarah , Horst David , Schlomm Thorsten , Kluth Martina 
Published: February 2025

Abstract

Purpose
We aimed to assess the impact of GATA3 binding protein (GATA3) gene copy number alterations on tumor aggressiveness, patient prognosis, and GATA3 protein expression in a large urothelial bladder cancer cohort.

Methods
A tissue microarray containing over 2,700 urothelial bladder cancers (pTa-pT4) was analyzed retrospectively using dual-labeling fluorescence in-situ hybridization (FISH) with probes for GATA3 (10p14) and centromere 10. GATA3 copy number gains were categorized as GATA3 elevation (ratio GATA3/centromere ≥ 2/≤4), low-level amplification (ratio > 4/≤12), and high-level amplification (ratio > 12) and deletions were divided between homozygous and heterozygous.

Results

GATA3 copy number gain was detected in 9.9% of 2,213 interpretable tumors, including 2.0% with GATA3 elevation, 3.2% with low-level amplification, and 4.7% with high-level amplification. The frequency of high-level amplification increased from pTa G2 low (0%) to pTa G3 tumors (12% [CI 0.07;0.21]; p < 0.0001 pTa G2 low vs. pTaG2 high) but decreased in advanced-stage carcinomas pT2-4 with 5.4% [CI 0.07;0.21] (p < 0.0001, pTa vs. pT2-4). In muscle-invasive carcinomas, GATA3 amplification was not linked to tumor aggressiveness or patient survival. Overall, no homozygous GATA3 deletion was detected and heterozygous GATA3 deletion was only observed in 1.1%; of 1,432 pT2-4 tumors without any association to cancer progression. While GATA3 copy number was significantly correlated with GATA3 expression (p < 0.0001), the relationship was not strong. Only 2.3% of GATA3-negative cancers had a deletion, and 42.1% of strong GATA3-expressing cancers exhibited high-level amplification.

Conclusion
High-level GATA3 amplification is common in urothelial bladder cancer and correlates with grade progression in pTa tumors, while GATA3 deletion is rare. Neither amplification nor deletion appears to be the primary driver of GATA3 expression dysregulation.

Clinical trial number
Not applicable.
Increasing challenges of general practitioner-oncologist interaction in end-of-life communication: a qualitative study
Authors: Villalobos Matthias , Korezelidou Anastasia , Unsöld Laura , Deis Nicole , Thomas Michael , Siegle Anja 
Published: February 2025

Abstract

Background
The timely initiation of end-of-life (EOL) conversations is considerered best practice for patients with advanced cancer and therefore recommended in oncological guidelines. General practitioners (GPs) play a key role in the coordination of EOL-care and often claim that they have also the responsibility to initiate the necessary conversations. Nonetheless, the content of these conversations is rarely a subject of communication between GPs and oncology specialists but crucial for timely integration of palliative care. The aim of this study is to explore the GPs‘ perspectives on initiation and conduction of EOL-conversations in patients with metastatic lung cancer and how they perceive the interaction with the oncologists of a cancer center.

Methods
Qualitative design with in-depth interviews with GPs that refer patients with metastatic lung cancer to a cancer center; thematic analysis following Braun and Clarke.

Results
We identified three main themes: timing and conduction of EOL-conversations, factors influencing EOL-conversations, and modes of GP-oncologist interaction. All themes showed important and increasing challenges in regard to communication strategies or procedures within the cancer center and between general practitioners and oncologists. Aside from the elucidated challenges of EOL-communication, new problems arise from the difficulties in keeping pace with advances in oncology and the increasing prognostic uncertainty. Additionally, the lack of standardized communication in EOL-topics between GPs and oncologists is underlined. Options in the mode of interaction include written information in reports or digital platforms and direct phone calls.

Conclusions
Because of the growing complexity in modern oncology, strategies for improvement in GP-oncologist interaction have to consider information about therapeutic advances and prognosis of patients. The increasing prognostic uncertainty hazards the adequate provision and conduction of EOL-conversations and thus, the timely integration of palliative care. As a consequence, a trustful personal interaction that includes direct contact via phone calls between GPs and oncologists should be encouraged.
Emotions and feelings in neuroscience education across career stages: a qualitative study with views from alumni, junior and senior academics
Authors: Sandrone Stefano 
Published: February 2025

Abstract

Introduction
Emotions and feelings are crucial components of our lives. However, their role in medical education scholarship, including in neuroscience education, has been overlooked. Moreover, their impact has been understudied in academia, especially across career stages. We explored emotions and feelings in the context of neuroscience education and across different career stages.

Methods
This work is based on a project exploring the value of learning in postgraduate education, drawing on data from nineteen semi-structured interviews with university alumni and academics. Eight alumni (six females and two males) and eleven academics from a UK-based STEM-intensive institution participated in the study. Alumni refers to former students who have completed the MSc in neuroscience at a STEM-intense institution within the last six years. Lecturers and Senior Lecturers in neuroscience have been labelled as junior academics, whereas Readers and Professors have been labelled senior academics.

Results
The alumni recognised their master experience was intense and challenging, yet acknowledged that enjoyment and stress are two faces of the same coin. Many cited their peers as an inspiration to go beyond the limits but only one student mentioned gratitude, which was never mentioned by the academics. At least one alumnus and one junior academic mentioned trust and confidence, but not the senior academics. Anxiety and confidence (and lack of) dominated the interviews with junior academics, who used intense words when discussing the pleasures of science. Conversely, the senior academics dedicated few words to emotions and feelings, never talked about anxiety, trust or gratitude, and very briefly mentioned the reward linked to sharing their knowledge with the next generations.

Discussion
This work epitomises the importance of exploring emotions and feelings in neuroscience education. Talking more openly about emotions and reducing the pervasive narration of ‘success stories’ might be directions to follow, along with stressing the importance of cultivating self-efficacy, trust and gratitude since the early stages. Meetings between students and supervisors can play a key role in developing self-trust among the students. More focus should be placed on supporting the transition process between postgraduate studies and the subsequent steps of the academic ladder.
Mandatory verses voluntary self-tests for new online casino customers: effect on engagement, quality, gambling behavior and use of responsible gambling measures
Authors: Jonsson Jakob , Lakew Nathan , Lindner Philip 
Published: February 2025

Abstract

Background
To combat the public health concern that is problem gambling, gambling operators are increasingly being required by legislation to exercise a duty of care obligation, including the provision of Responsible Gambling (RG) tools. Self-test assessments have long been a popular RG tool implemented by many operators, yet there has been scant empirical research on self-tests, including on how the method of delivery impacts engagement, quality, and subsequent gambling behavior. The main objective of the current study was to examine if the level of voluntariness to perform a self-test moderated these key outcomes.

Method
Participants in the study, 1800 new online customers at a leading Swedish gambling company, were randomized to one of three arms: No message (control), up to four messages inviting them to do a self-test, and one message with a mandatory (but technically possible to circumvent) self-test. The interventions were presented when the customer logged in.

Results
The results showed that 38.9% in the mandatory group and 4.8% in the voluntary group completed the self-test, with indications of a somewhat lower quality of the test by the mandatory group. There was no difference in customer churn or gambling behavior, and only minor differences in use of RG-measures post intervention.

Conclusions
We conclude that presentation format matters and can affect the use and quality of tests: gambling operators should exercise caution when interpreting non-risk assessment results derived solely from self-test tools, particularly mandatory ones, as it can result in inaccurate risk assessments that may mislead duty of care obligations. The balance between achieving high participation and maintaining quality (and thereby meaningfulness) is discussed.
Inclusive health for people with disabilities in Chile: a national health system assessment
Authors: Rodríguez Gatta Danae , Piriz Tapia Constanza , Tagle Schmidt Elvira , Luna Benavides Jimena , Vivar Jara Daniel , Moreno Celis Rodrigo , Tobar Carrizo Gonzalo , Vilaró Cáceres Judit , Heydt Phyllis , Banks Lena Morgon , Kuper Hannah 
Published: February 2025

Abstract

Background
Globally, one in six people have disabilities. They often experience health inequities and many of them arise from system-level failures. This study aimed to assess the inclusion of people with disabilities in the health system of Chile and define recommendations for improvement on the basis of the evidence.

Methods
A health system assessment was conducted between June and November 2023 following the Missing Billion Disability-Inclusive Health Systems Framework and System Level Assessment Toolkit. The assessment was led by the Ministry of Health and conducted by a task team, including organizations of people with disabilities. Mixed methods were used to collect data on nine system-level and service delivery components for a set of 33 indicators, including through a health policy review, systematic review, key informant interviews and a scoping review. Scores were assigned to indicators, components and the overall health system. With this assessment, key recommendations were developed and agreed upon on the basis of a prioritization analysis of impact and feasibility during workshops.

Results
The Chilean health system was assessed to have a low progress towards disability-inclusive health. Among system-level components, intermediate progress has been made in governance, health financing and data and evidence. However, progress in leadership on disability seems low. Among service delivery components, the accessibility of health facilities and rehabilitation and assistive technology showed the best results. However, there were notable gaps in the autonomy and awareness and ability to afford care by people with disabilities, and the capacity of human resources to support this group. The task team defined priority actions in governance, leadership, and human resources.

Conclusions
Short-term actions for the country should involve foundational governance on inclusive health, strengthened leadership of people with disabilities, and mandatory training of healthcare workers to improve healthcare access among this population. Future reassessments should be conducted to monitor and evaluate progress on effective healthcare coverage and health status among people with disabilities.
Automated pipeline for leaf spot severity scoring in peanuts using segmentation neural networks
Authors: Larsen Joshua , Dunne Jeffrey , Austin Robert , Newman Cassondra , Kudenov Michael 
Published: February 2025

Abstract

Background
Late and early leaf spot in peanuts is a foliar disease contributing to a significant amount of lost yield globally. Peanut breeding programs frequently focus on developing disease-resistant peanut genotypes. However, existing phenotyping protocols employ subjective rating scales, performed by human raters, who determine the severity of leaf spot infection. The objective of this study was to develop an objective end-to-end pipeline that can serve to replace an expert human scorer in the field. This was accomplished using image capture protocols and segmentation neural networks that extracted lesion areas from plot-level images to determine an appropriate rating for infection severity.

Results
The pipeline incorporated a neural network that accurately determined the infected leaf surface area and identified dead leaves from plot-level cellphone imagery. Image processing algorithms then convert these labels into quality metrics that can efficiently score these images based on infected versus non-infected area. The pipeline was evaluated using field data from plots with varying leaf spot severity, creating a dataset of thousands of images that spanned conventional visual severity scores ranging from 1–9. These predictions were based on the amount of infected leaf area and the presence of defoliated leaves in the surrounding area. We were able to demonstrate automated scoring, as compared to expert visual scoring, with a root mean square error of 0.996 visual scores, on individual images (one image per plot), and 0.800 visual scores when three images were captured of each plot.

Conclusion
Results indicated that the model and image processing pipeline can serve as an alternative to human scoring. Eliminating human subjectivity for the scoring protocols will allow non-experts to collect scores and may enable drone-based data collection. This could reduce the time needed to obtain new lines or identify new genes responsible for leaf spot resistance in peanut.
Two dramatically different clinical scenarios of neonatal Echovirus-11 infection in late preterm male twins: a case report and review of the literature
Authors: Perniciaro Simona , Proietti Caterina , Bossi Angela , Maragliano Roberta , Facco Carla , Novazzi Federica , Mancini Nicasio , Agosti Massimo Agostino 
Published: February 2025

Abstract

Background
Enterovirus is a well-known cause of infection in all age groups, with particular importance for neonates with both vertically and horizontally transmission. Neonatal clinical manifestations are highly variable and mostly is asymptomatic, but severe infections are described such as myocarditis, meningitis, encephalitis, hepatitis, coagulopathy, pneumonia and viral sepsis. Since 2022, The World Health Organization has recently reported an increasing number of severe neonatal infection associated with a new variant of Echovirus-11 (E-11). Many of the infants described with E-11 infections in a case reports series were preterm, male and twins. Despite the criticality of neonatal disease, the clinical management remains primarily supportive and therapeutic options are unfortunately few.

Case presentation
We present the case of male dichorionic diamniotic late-preterm twins, born in December 2023 at Filippo del Ponte Hospital in Varese (Northen Italy) with early Echovirus-11 infection. They had two dramatically different clinical scenarios and one of them developed a severe and fatal hemorrhage-hepatitis syndrome.

Conclusions
Our experience has the purpose to emphasize public health attention to Echovirus-11 neonatal infections and their rare dramatically neonatal clinical presentations. Prematurity, host genetic predisposition and vertical transmission seem to be strong risk factors for severe infections, but it still need to be elucidated. According to previous Italian report, a surveillance protocols in all cases with unexpected clinical presentations and sequencing complete genome in order to better understand typing and molecular characterization of emerging and re-emerging pathogenic variants and new strains are strongly recommend in Italy.