bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal driver neoantigen loss under EGFR TKI and immune selection pressures
Authors: Al Bakir Maise , Reading James L. , Gamble Samuel , Rosenthal Rachel , Uddin Imran , Rowan Andrew , Przewrocka Joanna , Rogers Amber , Wong Yien Ning Sophia , Bentzen Amalie K. , Veeriah Selvaraju , Ward Sophia , Garnett Aaron T. , Kalavakur Paula , Martínez-Ruiz Carlos , Puttick Clare , Huebner Ariana , Cook Daniel E. , Moore David A. , Abbosh Chris , Hiley Crispin T. , Naceur-Lombardelli Cristina , Watkins Thomas B. K. , Petkovic Marina , Schwarz Roland F. , Gálvez-Cancino Felipe , Litchfield Kevin , Meldgaard Peter , Sorensen Boe Sandahl , Madsen Line Bille , Jäger Dirk , Forster Martin D. , Arkenau Tobias , Domingo-Vila Clara , Tree Timothy I. M. , Kadivar Mohammad , Hadrup Sine Reker , Chain Benny , Quezada Sergio A. , McGranahan Nicholas , Swanton Charles 
Published: February 2025

Abstract
Neoantigen vaccines are under investigation for various cancers, including epidermal growth factor receptor (EGFR)-driven lung cancers1,2. We tracked the phylogenetic history of an EGFR mutant lung cancer treated with erlotinib, osimertinib, radiotherapy and a personalized neopeptide vaccine (NPV) targeting ten somatic mutations, including EGFR exon 19 deletion (ex19del). The ex19del mutation was clonal, but is likely to have appeared after a whole-genome doubling (WGD) event. Following osimertinib and NPV treatment, loss of the ex19del mutation was identified in a progressing small-cell-transformed liver metastasis. Circulating tumour DNA analyses tracking 467 somatic variants revealed the presence of this EGFR wild-type clone before vaccination and its expansion during osimertinib/NPV therapy. Despite systemic T cell reactivity to the vaccine-targeted ex19del neoantigen, the NPV failed to halt disease progression. The liver metastasis lost vaccine-targeted neoantigens through chromosomal instability and exhibited a hostile microenvironment, characterized by limited immune infiltration, low CXCL9 and elevated M2 macrophage levels. Neoantigens arising post-WGD were more likely to be absent in the progressing liver metastasis than those occurring pre-WGD, suggesting that prioritizing pre-WGD neoantigens may improve vaccine design. Data from the TRACERx 421 cohort3 provide evidence that pre-WGD mutations better represent clonal variants, and owing to their presence at multiple copy numbers, are less likely to be lost in metastatic transition. These data highlight the power of phylogenetic disease tracking and functional T cell profiling to understand mechanisms of immune escape during combination therapies.
Integrating the environmental and genetic architectures of aging and mortality
Authors: Argentieri M. Austin , Amin Najaf , Nevado-Holgado Alejo J. , Sproviero William , Collister Jennifer A. , Keestra Sarai M. , Kuilman Midas M. , Ginos Bigina N. R. , Ghanbari Mohsen , Doherty Aiden , Hunter David J. , Alvergne Alexandra , van Duijn Cornelia M. 
Published: February 2025

Abstract
Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock (n = 45,441), identifying 25 independent exposures associated with mortality and proteomic aging. These exposures were also associated with incident age-related multimorbidity, aging biomarkers and major disease risk factors. Compared with information on age and sex, polygenic risk scores for 22 major diseases explained less than 2 percentage points of additional mortality variation, whereas the exposome explained an additional 17 percentage points. Polygenic risk explained a greater proportion of variation (10.3–26.2%) compared with the exposome for incidence of dementias and breast, prostate and colorectal cancers, whereas the exposome explained a greater proportion of variation (5.5–49.4%) compared with polygenic risk for incidence of diseases of the lung, heart and liver. Our findings provide a comprehensive map of the contributions of environment and genetics to mortality and incidence of common age-related diseases, suggesting that the exposome shapes distinct patterns of disease and mortality risk, irrespective of polygenic disease risk.
COVID-19 affected elite track-and-field athletes’ Olympic preparation before Tokyo 2020 compared to Rio 2016
Authors: Banning Alexander , van Meurs Edda , Dreiskämper Dennis 
Published: February 2025

Abstract
The COVID-19 pandemic has had a significant impact on elite sport by postponing the Olympic Games Tokyo 2020 four months before the original start. This impacted athletes’ macro-cycle periodization, psychological stressors and resources. We analyse whether track-and-field athletes were able to maintain their performance levels successfully across the last two Olympic cycles, controlling for age, gender and doping prevalence. For this, worldwide competition results (excluding multi-events & relays) of at least national level since London 2012 and up to Tokyo 2020 were retrieved. Individual performance curves were analysed using hierarchical multilevel modelling. Individual baselines (random intercept) and developments (random slope) were analysed. 2,383 athletes (52% male) recorded 15,766 outcomes since London 2012. The final conditional growth model (ICC = 48%) shows that performances increased in the wake of Olympic games, dropped significantly in 2020 and recovered beyond previous form in 2021. There was no significant difference between men’s and women’s developments. Age was a significant predictor (b = 0.17, SE = 0.02), but doping violations was not (b = 0.01, SE = 0.03). These results showcase performance trends in international athletics and their variability, present an overall successful periodization to achieve peak performance at Tokyo 2020, and discuss predictions for track and field at Paris 2024.
Hemodynamics are associated with subsequent lumen remodeling and clinical maturation of hemodialysis arteriovenous fistula
Authors: He Yong , Wei Guo , Greene Tom , Imrey Peter B. , Northrup Hannah , Radeva Milena K. , Beck Gerald J. , Gassman Jennifer J. , Kraiss Larry W. , Robbin Michelle , Roy-Chaudhury Prabir , Cheung Alfred K. , Berceli Scott A. , Shiu Yan-Ting ,   the Hemodialysis Fistula Maturation (HFM) Study Group, Huber T. , Berceli S. , Jansen M. , McCaslin G. , Trahan Y. , Cheung A. , Kraiss L. , Greene T. , Kinikini D. , Treiman G. , Ihnat D. , Sarfati M. , Lavasani I. , Maloney M. , Schlotfeldt L. , Beck G. , Gassman J. , Imrey P. , Li L. , Alster J. , Li M. , MacKrell J. , Radeva M. , Weiss B. , Wiggins K. , Feldman H. , Dember L. , Farber A. , Kaufman J. , Stern L. , LeSage P. , Kivork C. , Soares D. , Malikova M. , Vita J. , Hamburg N. , Duess M. , Levit A. , Allon M. , Young C. , Taylor M. , Woodard L. , Mangadi K. , Roy-Chaudhury P. , Munda R. , Lee T. , Alloway R. , El-Khatib M. , Canaan T. , Pflum A. , Thieken L. , Campos-Naciff B. , Vazquez M. , Vongpatanasin W. , Davidson I. , Hwang C. , Lightfoot T. , Livingston C. , Valencia A. , Dolmatch B. , Fenves A. , Hawkins N. , Himmelfarb J. , Alpers C. , Hudkins K. , Wietecha T. , Buchanan C. , Clark C. , Crawford C. , Hamlett J. , Kundzins J. , Manahan L. , Wise J. , Higgins H. , Ke S. , Mandaci O. , Snell C. , Gravley J. , Behnken S. , Mortensen R. , Kusek J. , Star R. , Chertow G. , Besarab A. , Brayman K. , Diener-West M. , Louis T. , Harrison D. , Inker L. , McClellan W. , Rubin J. 
Published: February 2025

Abstract
The pathogenesis of arteriovenous fistula (AVF) maturation failure is unclear. We evaluated the associations of wall shear stress (WSS) with subsequent AVF remodeling and clinical maturation using regression models in this prospective cohort study. Participants underwent duplex ultrasound at postoperative Day 1, Week 2, and Week 6 to measure AVF blood flow rate and diameter of the draining vein and proximal artery. The median vein WSS of 602 participants decreased from Day 1 to Week 6 (from 33.4 to 21.6 dyne/cm2) but did not change noticeably for the artery (from 58.4 to 55.1 dyne/cm2). WSS was positively associated with subsequent lumen expansion, with doubling of Day-1 WSS presaging a 9% (95% confidence interval (CI) 5%-14%; P < 0.001) greater Day 1-to-Week 6 increase in vein lumen cross-sectional area and a 5% (95% CI: 1%-10%; P = 0.020) greater increase in artery lumen area. The odds of unassisted clinical maturation increased by 45% (95% CI: 11%-89%; P = 0.006) with each doubling of Day-1 vein WSS, and by 82% (95% CI: 39%-250%; P < 0.001) with each doubling of Day-1 artery WSS. These findings show that WSS was positively associated with subsequent lumen expansion and AVF unassisted clinical maturation.
Insights into leprosy epidemiology from an isolated population located in the Brazilian Amazon
Authors: de Oliveira Mackert Ciane Cristina , Lázaro Fernando Panissa , Olandowski Márcia , D’Espindula Helena Regina Salomé , dos Santos Andressa Mayra , Sartori Priscila Verchai Uaska , de Andrade Rodrigues Rafael Saraiva , Cambri Geison , Xavier Marília Brasil , Schurr Erwin , Alcaïs Alexandre , Mira Marcelo Távora 
Published: February 2025

Abstract
Leprosy, a chronic infectious disease caused mainly by Mycobacterium leprae (M. leprae), is still an important public health problem in countries such as Brazil and India. Here, we estimate key epidemiological parameters in the Prata Village, a unique, hyper-endemic, former leprosy colony isolated in the Brazilian Amazon. This is a population-based study in which the entire Prata Village population has been enrolled. Clinical, socioeconomic, and demographic data were obtained and validated by cross-checking using three independent information sources. Validated data was used for descriptive epidemiological analysis. From a total of 2,005 inhabitants by the time of the enrollment, 1,084 (56.2%) were born in the Village and, therefore, likely under lifelong exposure to leprosy cases. We observed differences between the sub-populations born and not born in the village in the cumulative prevalence of leprosy (5.9% vs. 22.9%, respectively) and the median age at diagnosis (15 years vs. 28 years, respectively). In contrast, there was no difference in the distribution of cases between males and females. Although extrapolating our findings to more open populations must be done carefully, we believe we used a unique population as a model to provide additional insights into the epidemiology of leprosy.
Molecular mechanism of Cinnamomum zeylanicum and Citrus aurantium essential oils against the root-knot nematode, Meloidogyne incognita
Authors: Fanelli Elena , Vovlas Alessio , D’Addabbo Trifone , De Luca Francesca 
Published: February 2025

Abstract
The root-knot nematode Meloidogyne incognita is the most harmful and destructive nematode species due to its widespread distribution and its ability to destroy a wide range of agriculturally and economically important crops. Plant-derived essential oils (EO) are one of the promising strategies for nematode management showing high nematicidal potential. Very little is known about the molecular mechanisms activated by EOs in M. incognita. In our study, we assessed the effects of Cinnamomum zeylanicum, Citrus aurantium and the chemical nematicide Oxamyl on the mortality of M. incognita juveniles (J2) at different doses and exposure. The toxicity of C. zeylanicum and C. aurantium EOs to M. incognita J2 was largely different, peaking 94.7 and 26.7% mortality rates after a 24-hour exposure to 100 µg mL− 1 EO concentrations, respectively. The different nematicidal activity of the two EOs was also confirmed by their LC50 values, ranging between 0.1 and 399 mg mL− 1 concentrations for the 24-hour treatment, respectively.
The sublethal dose (0.78 µg mL− 1), the concentration that does not cause mortality but still triggers physiological responses, was chosen for both EOs and Oxamyl to investigate the expression levels of Mi-ace-1, Mi-ace-2, and Mi-hsp90, involved in host finding processes, and Mi-far-1, involved in the cuticle protection, by using real time PCR. Our results reveal that C. zeylanicum is toxic at lower doses than C. aurantium. The different expression level of Mi-far-1 in J2s treated with C. zeylanicum suggests a different action mode compared to C. aurantium and Oxamyl. Understanding the action mode of these compounds at molecular level will help to develop more potent and effective nematicides safer for environment and humans.
The Peer Effect Is “Utterly Profound”: A Social-ABI-lity Pilot Study of a Multicomponent, Peer-Moderated Social Media Skills Intervention for People With Acquired Brain Injury
Authors: Brunner Melissa , Rietdijk Rachael , Southwell Kylie , Baker James , Cooper Stephen , Avramovic Petra , Brassel Sophie , Power Emma , Rushworth Nick , Togher Leanne 
Published: February 2025

Purpose:
People who have an acquired brain injury (ABI) experience challenges in using social media. However, rehabilitation clinicians report feeling inadequately prepared to support them in its use. We aimed to evaluate the outcomes of a multicomponent, peer-moderated social media skills intervention for people with ABI.

Method:
This study utilized a mixed-methods, pre–post intervention design. Two people with ABI were invited to be research co-investigators and participated as peer moderators. A total of seven adults with an ABI were recruited to participate in the intervention and completed a short self-guided course about social media skills (social-ABI-lity course) and then took part in a private, peer-moderated Facebook group over an 8-week period (social-ABI-lity Facebook group). Data were analyzed with mixed methods, collected via observation of group activity, weekly surveys, social media use and quality of life questionnaires (pre-intervention, postintervention, and after 3 months), and postintervention interview.

Results:
Small improvements in social media skills were observed, although no significant changes were noted on quantitative measures for quality of life or confidence and enjoyment of Facebook use. Following a thematic analysis of interview data and incorporating reflections from peer moderators, we generated eight themes: loss, isolation, return, confidence, choice, identity, connection to community, and the “peer” effect. The intervention was identified as being feasible, acceptable, and engaging for all, with the role of the peer moderators perceived as being highly relevant and relatable by the participants. The peer moderators reported a positive influence on their confidence and sense of self-identity following the intervention.

Conclusions:
The intervention was feasible and acceptable, with peer moderators also benefitting from their involvement. Future research is warranted to determine the fidelity and efficacy of this intervention on a larger scale and to develop clinical resources to support goal setting and individualized approaches to support people with ABI to use social media safely and meaningfully.
Non‐Linearity Incremental Ensemble Learning Based Depth Explorations of Latent Individual Contributions
Authors: Deng Xiaozheng , Zhang Yuanyuan , Mao Shasha , Liu Peng 
Published: February 2025

ABSTRACTIn ensemble learning, individual accuracy and diversities are two key factors for improving the ensemble performance, and most existing methods have been designed from the view of boosting individual diversities. Whereas stronger individual diversities inevitably result in decreasing accuracies of partial individuals, it brings a great challenge for improving the ensemble performance. In fact, we observe that the contribution of individuals should be a crucial factor for ensemble learning, which can effectively alleviate the problem of balancing diversity and accuracy, but it is ignored in most existing studies. Based on this, we propose a new incremental non‐linearity deep ensemble learning method that effectively combines multiple individuals based on the exploration of individual contributions by utilizing deep learning. In the proposed method, a characterization matrix is first constructed to represent the original individuals. Then, a deep ensemble network is constructed to explore the potential contribution of individuals in conjunction with the optimization objective of ensemble learning. Interestingly, a special layer is designed to achieve the minimization of ensemble error. Finally, experimental results on public datasets illustrate that the proposed method achieves the average 0.66–4.8% performance improvements compared to existing typical ensemble methods.
Well-differentiated Adenocarcinoma Arising from Gastric Cystica Profunda Treated by Endoscopic Submucosal Dissection: A case report and literature review
Authors: Huang Cao , Liu Jiang 
Published: February 2025

AbstractGastritis cystica profunda (GCP) is a rare disease that is often observed at the stoma site of patients undergoing
gastric surgery. Specific symptoms are often lacking, making it difficult to diagnose. GCP may
develop into cancer. Endoscopic resection is a good method to reduce surgical injury, and the
therapeutic effect depends on the status of the primary disease.The patient was a 77-year-old male who was admitted to the hospital for repeated
epigastric distention. The man had never undergone gastric surgery and did not have Helicobacter pylori infection. Physical and laboratory tests showed no
abnormality. Computed tomography showed no significant abnormality. Endoscopy revealed
multiple ulcers on the posterior wall of the gastric body, but biopsy showed no evidence of
malignancy. The patient subsequently underwent ESD surgery with a lesion of 1.5 cm×2.3 cm.
Pathological results showed the cystic dilatation of gastric glands in the submucosa, with
some well-differentiated adenocarcinoma. The final diagnosis was GCP with well-differentiated
gastric adenocarcinoma.Herein, we describe a case of ESD therapy for GCP with well-differentiated gastric
adenocarcinoma. When gastric mucosal lesions are difficult to diagnose, further treatment and
diagnosis with EMR or ESD can be considered. For patients with early gastric cancer, long-term
postoperative monitoring should be carried out.
Aktueller Stand zur Reform der Gebührenordnung für Ärzte (GOÄ) und Veranstaltung des BDDH auf der 69. Tagung der Gesellschaft für Thrombose- und Hämostaseforschung (GTH) in Lausanne 2025
Authors: Koscielny Jürgen , Kappert Günther , Sucker Christoph 
Published: February 2025

Abstract
Aktueller Stand zur Reform der Gebührenordnung für Ärzte (GOÄ)
Nach langwierigen und gründlichen Verhandlungen wurde, auch wieder mit dem Vorstand der GTH, der neue Änderungsvertrag mit dem VDEK verabschiedet und ist sofort abschließbar. Nachfolgend finden Sie die wichtigsten Änderungen, auch bezüglich der ambulanten Gentherapie der Hämophilie:
GTH 2025 ARTE: The Art in Science – Curiosity and Creativity
Authors: Albisetti Manuela , Alberio Lorenzo 
Published: February 2025

AbstractThe 2025 Annual Congress of the Society of Thrombosis and Haemostasis Research (GTH) takes its inspiration from ARTE—Advances, Research, Technology, and Education in the field of thrombosis and hemostasis. The numerous scientific contributions of the congress highlight the most recent progresses in this field, and reveal the profound connection between the rigor of science and the beauty of human creativity. ARTE, the Italian word for “art,” refers to the deep synergy existing between analytical precision and imaginative expression, which is vividly reflected in this year's contributions to our themed congress issue.
The Use of DOACs in Pediatrics: Current Therapeutic and Prophylactic Indications, Cardiac Indications, and Real-World Evidence—A Review
Authors: Bosch Alessandra , Olivieri Martin , Holzhauer Susanne 
Published: February 2025

AbstractBased on clinical trials that have been conducted and published in the past decade, direct oral anticoagulants (DOACs) are increasingly being used as an antithrombotic treatment in children with venous thrombotic events and to prevent thrombotic events in children at risk. In this review, current indications and standards for the initiation of DOACs in children are summarized for the treatment of venous thrombotic events and for the primary and secondary prevention in children at risk of developing thromboses based on the published randomized controlled trials (RCT). Similarly, indications for DOACs in children with underlying cardiac disease are portrayed based on RCT findings. Lastly, available real-world data are reviewed for the use of DOACs in pediatric patients with a focus on patients at higher risk of both thrombosis and bleeding who were primarily excluded from the RCTs. DOACs contribute largely to the evolving individualization of care of thrombotic events in children, but at-risk patient populations remain underrepresented regarding DOAC experience, such as preterm infants, and children with severe renal or hepatic disease. Real-world data from observational studies and registries will continue to be necessary to establish DOACs' effectiveness and safety in children in everyday clinical use.
Basic Concepts and Indications of CAR T Cells
Authors: van den Berg Jana , Läubli Heinz , Khanna Nina , Jeker Lukas T. , Holbro Andreas 
Published: February 2025

AbstractChimeric antigen receptor (CAR) T cell therapy has revolutionized cancer immunotherapy, particularly for hematological malignancies. This personalized approach is based on genetically engineering T cells derived from the patient to target antigens expressed—among others—on malignant cells. Nowadays they offer new hope where conventional therapies, such as chemotherapy and radiation, have often failed. Since the first FDA approval in 2017, CAR T cell therapy has rapidly expanded, proving highly effective against previously refractory diseases with otherwise a dismal outcome. Despite its promise, CAR T cell therapy continues to face significant challenges, including complex manufacturing, the management of toxicities, resistance mechanisms that impact long-term efficacy, and limited access as well as high costs, which continue to shape ongoing research and clinical applications. This review aims to provide an overview of CAR T cell therapy, including its fundamental concepts, clinical applications, current challenges, and future directions in hematological malignancies.