bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of BCG vs upfront radical cystectomy for high‐risk non‐muscle‐invasive bladder cancer
Authors: Scilipoti Pietro , Longoni Mattia , de Angelis Mario , Zaurito Paolo , Ślusarczyk Aleksander , Soria Francesco , Pradere Benjamin , Krajewski Wojciech , D'Andrea David , Mari Andrea , Del Giudice Francesco , Pichler Renate , Subiela José Daniel , Marcq Gautier , Gallioli Andrea , Afferi Luca , Mastroianni Riccardo , Simone Giuseppe , Albisinni Simone , Mertens Laura S. , Laukhtina Ekaterina , Oberneder Katharina , Rodríguez Elena José Luis , Aranda Javier , Puentedura Alfonso Lafuente , Caño Velasco Jorge , Contieri Roberto , Hurle Rodolfo , Mori Keiichiro , Radziszewski Piotr , Shariat Shahrokh F. , Gontero Paolo , Necchi Andrea , Rouprêt Morgan , Montorsi Francesco , Salonia Andrea , Briganti Alberto , Moschini Marco ,   the European Association of Urology – Young Academic Urologists (EAU‐YAU), Urothelial carcinoma working group
Published: February 2025

ObjectiveTo assess the oncological outcomes of patients with high‐risk (HR) and very high‐risk (VHR) non‐muscle‐invasive bladder cancer (NMIBC) treated with upfront radical cystectomy (RC) vs Bacillus Calmette–Guérin (BCG) instillations from a contemporary European multicentre cohort.Patients and MethodsWe conducted a retrospective analysis of 1491 patients diagnosed with HR‐ or VHR‐NMIBC from a European multicentre database between 2015 and 2024. Patients were included if they received either upfront RC or at least five doses of BCG. A 1:1 propensity score matching (PSM) according to clinically relevant variables was applied. Progression was defined as muscle‐invasive or metastatic disease. Cumulative incidence plots and multivariable competing risk regression models addressing cancer‐specific mortality (CSM) were fitted.ResultsAmong the 1221 patients with HR‐ (n = 1221 [90%]) or VHR‐NMIBC (n = 121 [10%]), 87 (7.1%) underwent upfront RC. The median follow‐up was 2.6 years. After PSM (87 vs 87 patients), the 5‐year CSM rate was similar in patients treated with BCG (13%) vs their upfront RC counterparts (16%) (hazard ratio: 1.77, 95% confidence interval [CI] 0.66–4.73; P = 0.3). Of the 1134 patients who initially received BCG, 73 (6.6%) eventually required delayed RC, with 34 (47%) progressing to muscle‐invasive bladder cancer before delayed RC. The 3‐year CSM rate was comparable in upfront RC (13%) vs delayed RC (11%) among non‐progressing patients (P = 0.3). However, patients who progressed before delayed RC had worse 3‐year CSM relative to those who did not (13% vs 31%, hazard ratio: 0.32, 95% CI 0.13–0.83; P = 0.018).ConclusionWithin a European cohort of patients with HR‐ and VHR‐NMIBC, upfront RC was rarely performed. Patients treated with BCG did not exhibit a CSM disadvantage relative to their upfront RC counterparts. After matching, long‐term CSM was similar between BCG therapy and upfront RC. Delayed RC, led to worse outcomes if performed after progression, but matched upfront RC when performed before progression, underscoring importance of timely surgery.
Evaluating interactions of patients with large language models for medical information
Authors: Carl Nicolas , Haggenmüller Sarah , Wies Christoph , Nguyen Lisa , Winterstein Jana Theres , Hetz Martin Joachim , Mangold Maurin Helen , Hartung Friedrich Otto , Grüne Britta , Holland‐Letz Tim , Michel Maurice Stephan , Brinker Titus Josef , Wessels Frederik 
Published: February 2025

ObjectivesTo explore the interaction of real‐world patients with a chatbot in a clinical setting, investigating key aspects of medical information provided by large language models (LLMs).Patients and methodsThe study enrolled 300 patients seeking urological counselling between February and July 2024. First, participants voluntarily conversed with a Generative Pre‐trained Transformer 4 (GPT‐4) powered chatbot to ask questions related to their medical situation. In the following survey, patients rated the perceived utility, completeness, and understandability of the information provided during the simulated conversation as well as user‐friendliness. Finally, patients were asked which, in their experience, best answered their questions: LLMs, urologists, or search engines.ResultsA total of 292 patients completed the study. The majority of patients perceived the chatbot as providing useful, complete, and understandable information, as well as being user‐friendly. However, the ability of human urologists to answer medical questions in an understandable way was rated higher than of LLMs. Interestingly, 53% of participants rated the question‐answering ability of LLMs higher than search engines. Age was not associated with preferences. Limitations include social desirability and sampling biases.DiscussionThis study highlights the potential of LLMs to enhance patient education and communication in clinical settings, with patients valuing their user‐friendliness and comprehensiveness for medical information. By addressing preliminary questions, LLMs could potentially relieve time constraints on healthcare providers, enabling medical personnel to focus on complex inquiries and patient care.
Imatinib aggravates pressure‐overload‐induced right ventricle failure via JNK/Runx2 pathway
Authors: Zeng Xiaohui , Ma Zhuoji , Wen Shanshan , Zhou Liang , Hong Wanxian , Wu Zhixiong , Cen Chunxian , Bai Qianwen , Ding Shangwei , Chen Xin , Wang Jian , Chen Lingdan , Lu Wenju , Wang Tao 
Published: February 2025

AbstractBackground and PurposeRight ventricular (RV) function is the key prognostic determinant of pulmonary hypertension (PH). In PH patients, imatinib treatment decreases pulmonary vascular resistance and improves exercise capacity, but does not change mortality or duration to clinical worsening. Imatinib has been reported to be cardiotoxic in the left heart. We hypothesise that imatinib damages the pressure overloaded RV via its direct effects within the heart, which may counteract its therapeutic effects in haemodynamic improvement of PH.Experimental ApproachA pulmonary arterial banding (PAB) rat model with fixed pulmonary artery narrowing was performed to avoid changes in RV afterload.Key ResultsIn PAB rats, imatinib treatment decreased the survival rate and exacerbated RV dysfunction, myocardial hypertrophy, apoptosis and fibrosis. In vitro, imatinib increased cardiomyocyte hypertrophy and did not change cardiac fibroblasts activation; however, imatinib‐treated conditioned medium from cardiomyocytes promoted fibroblast activation. Mechanistically, imatinib increased the phosphorylation of c‐jun N‐terminal kinase (JNK) and the expression of RUNX family transcription factor 2 (Runx2), and subsequently promoted the transcription of thrombospondin 4 (THBS4) and connective tissue growth factor (CTGF) in RV cardiomyocytes. Finally, SP600125, a JNK inhibitor, significantly alleviated imatinib‐induced RV failure in PAB rats and enhanced the effects of imatinib on RV function improvement in SU5416 + hypoxia‐induced PH rats without affecting pulmonary artery narrowing.Conclusion and ImplicationsWe demonstrate for the first time that imatinib aggravates RV failure under pressure overload through JNK/Runx2 pathway, and JNK inhibition improves the therapeutic effects of imatinib on RV function in PH.
Psychosocial Functioning for Preschool‐Aged Siblings of Children With Chronic Disorders: A Scoping Review
Authors: Prentice Caitlin M. , Fjermestad Krister , Haukeland Yngvild Bjartveit , Vatne Torun M. 
Published: February 2025

ABSTRACTBackgroundSchool‐aged siblings of children with chronic disorders, including somatic, neurodevelopmental and psychological diagnoses, are at a small but significant risk of experiencing psychosocial difficulties. It is unclear whether this is the case for such siblings when they are preschool age.ObjectiveThis scoping review examined research describing psychosocial challenges and adaptation among preschool‐aged children who have a sibling with a chronic disorder, and interventions aimed to serve this population.DesignWe searched online databases for peer‐reviewed studies published between 1998 and 2024 and identified 18 studies that reported psychosocial functioning such as psychological states, mental health variables and descriptions of experiences for 3‐ to 6‐year‐olds who were siblings of children with a neurodevelopmental disorder, somatic illness, mental illness or rare genetic disorder.ResultsOf the 18 studies included, 15 were related to siblings of autistic children, and 12 of these aimed to study the development of autism in infants. Only two intervention studies were identified, and these had very small samples with maximum three participants in the 3‐ to 6‐year‐old age range.ConclusionsResults across the included studies suggest that preschool‐aged siblings may be at an increased risk of psychosocial difficulties, but it was difficult to draw definitive conclusions due to the large proportion of included studies related to the development of autism and the heterogeneity of study types represented. Future research should focus on the psychosocial functioning of preschool‐aged siblings and target preschool‐aged siblings of children with chronic disorders beyond autism.
Bridging Gaps in Oncology: Comparative Analysis of Development and Approval Pathways for Anticancer Drugs and Companion Diagnostic in the United States and Japan
Authors: Saito Kaku , Narukawa Mamoru 
Published: February 2025

ABSTRACTCompanion diagnostics (CDxs) are essential in personalized medicine for oncology, where specific genetic mutations drive treatment decisions. Some differences remain in the regulatory frameworks and approval processes for CDx between the United States (U.S.) and Japan. Data were collected from public databases for CDxs and anticancer drugs approved between January 1, 2014, and August 15, 2024, in both countries. The analysis included both initial drug approvals and supplemental approvals to examine the characteristics of approved CDxs and anticancer drugs, identify regional differences, compare development and approval timelines of CDxs and associated anticancer drugs in both countries, and assess the factors influencing approval timelines. CDx approval has increased significantly in both countries since 2014, driven by next‐generation sequencing technologies, with 96 anticancer drug indications approved with CDx in the U.S. and 61 in Japan. In the U.S., drug approvals often preceded CDx approvals, influenced by post‐marketing commitments (PMCs), whereas Japan tended to approve CDxs and drugs almost simultaneously. The median gap between CDx and drug approvals in the U.S. was 0 days (interquartile range (IQR): 0–391), indicating a broader range and often longer delay compared to 18 days (IQR: −52 to 0) in Japan, with a statistically significant difference between the two countries (p < 0.0001). Logistic regression analysis revealed orphan drug designation was significantly associated with CDx‐related PMC in the U.S. (p = 0.042). These results highlight the need for greater regulatory harmonization between the U.S. and Japan to streamline approval processes and improve patient access to personalized treatments.
The risk of epilepsy after neonatal seizures
Authors: Tinggaard Jeanette , Pedersen Signe V. , Larsen Mads L. , Jensen Andreas K. , Greisen Gorm , Hansen Bo M. , Hoei‐Hansen Christina E. 
Published: February 2025

AbstractAimTo estimate the cumulative risk of epilepsy after neonatal seizures and identify subpopulations at increased risk.MethodThis was a nationwide register‐based cohort study including all children born in Denmark between 1997 and 2018. The cumulative risk of epilepsy in children with and without neonatal seizures was compared. Furthermore, neonatal seizures were stratified according to aetiology.ResultsWe followed 1 294 377 children and identified 1998 neonatal survivors with neonatal seizures. The cumulative risk of epilepsy was 20.4% (95% confidence interval [CI] = 18.5–22.3) among children with neonatal seizures, compared to 1.15% (95% CI = 1.12–1.18) among children without. Epilepsy was diagnosed before 1 year of age in 11.4% of children with neonatal seizures, in an additional 4.5% between 1 year and 5 years, 3.1% between 5 years and 10 years, and 1.4% between 10 years and 22 years. The aetiologies of neonatal cerebral infarction, haemorrhage, or malformations (adjusted hazard ratio = 2.49, 95% CI = 1.98–3.14) and low Apgar score (1.49, 95% CI = 1.12–1.98) were associated with the highest risk of epilepsy, compared to children with seizures of unknown aetiology.InterpretationEpilepsy after neonatal seizures is common and remains a substantial risk throughout childhood. Aetiological risk factors are identifiable and relevant when planning appropriate information for parents and follow‐up.
Take a Look: Naturalistic Composition of the Maternal Nest in the European Rabbit Oryctolagus cuniculus Contributes to Offspring Growth and Survival
Authors: Barrios‐Montiel Rodrigo , Arteaga Lourdes , Zepeda José Alfredo , Bautista Amando , Hudson Robyn 
Published: February 2025

ABSTRACTSometimes we should take a closer look at the natural behaviour of even the most familiar domestic mammals. An example is the nesting behaviour of the female European rabbit Oryctolagus cuniculus and her offspring. After giving birth in a nest of dry grass and fur, mothers return to briefly nurse once a day and deposit faecal pellets there. In domestic rabbits, we examined the temporal pattern of mothers' defecation in the nest, the response of pups to these faeces and the effect of these and nest hay on pups' pre‐ and postweaning growth and survival. In Experiment 1, we tested primiparous and multiparous mothers given a nest box and hay and allowed access to their pups once a day to nurse. We recorded daily the number of faecal pellets deposited in the nest and the number nibbled by the pups until weaning on postnatal day 30. Mothers defecated in the nest until around postnatal day 12. The pellets and hay then started to be nibbled by the pups, and histological analysis showed that pups ingested plant material. We found no difference in maternal behaviour between primiparous and multiparous females. In Experiment 2, we investigated the growth and survival of pups before and after weaning: (1) with hay and mother's faeces present in the nest; (2) without hay; (3) without mother's faeces; and (4) without hay or mother's faeces. In condition 1, pups transitioned to solid food with little sign of digestive pathology, whereas in conditions 2 and 3, and particularly in condition 4, pups developed diarrhoea and several died. Thus, the presence of nest hay and mother's faeces appear to contribute to pups' transition to solid food. We conclude that rabbits show a well‐coordinated pattern of behaviour between mothers and their preweaning offspring, likely relevant to the appropriate management of domestic rabbits.
Mixed‐Mode Timoshenko‐Based Peridynamics for Dynamic Crack Propagation in Functionally Graded Materials
Authors: Bautista Victor , Shahbazian Behnam , Mirsayar Mirmilad 
Published: February 2025

ABSTRACTA recently developed Timoshenko‐based peridynamic model with a variable micropolar shear influence factor is extended to study the behavior of dynamic crack propagation in functionally graded materials (FGMs). To this end, first, the proposed model is validated against two experimental three‐point bending benchmark problems with different material functions as well as varying loading rates and durations. Then, numerous additional cases with different boundary conditions and material distribution are studied to predict crack initiation and propagation in such mediums. The examples consist of three‐point bending and Kalthoff–Winkler specimens with various material functions under dynamic loads. Finally, the effects of material anisotropy induced by functionally varying material properties on crack propagation path are addressed. It is shown that this new model is advantageous because of its capability to account for shear deformation effects in the bonds previously ignored by the original bond‐based peridynamic models. Moreover, comparing the proposed modified bond‐based model to more complex methods, such as state‐based peridynamics, reveals that the simplicity of the current approach results in lower computational costs while still achieving comparable results.
Continent‐Wide Patterns of Climate and Mast Seeding Entrain Boreal Bird Irruptions
Authors: Widick Ivy V. , Strong Courtenay , LaMontagne Jalene M. , Young Matthew A. , Zuckerberg Benjamin 
Published: February 2025

ABSTRACTAvian irruptions are facultative, often periodic, migrations of thousands of birds outside of their resident range. Irruptive movements produce regional anomalies of abundance that oscillate over time, forming ecological dipoles (geographically disjunct regions of low and high abundance) at continental scales. Potential drivers of irruptions include climate and food variability, but these relationships are rarely tested over broad geographic scales. We used community science data on winter bird abundance (1989–2021) to identify spatiotemporal patterns of irruption for nine boreal birds across the United States and Canada and compared them to time series of winter climate and annual tree seed production. We hypothesized that, during irruption, bird abundance would decrease in regions experiencing colder winter climates (climate variability hypothesis) or low seed production resulting from the boom‐and‐bust of widespread mast‐seeding patterns (resource variability hypothesis). Across all species, we detected latitudinal or longitudinal irruption modes, or both, demonstrating north–south and east–west migration dynamics across the northern United States and southern Canada. Seven of nine species displayed associations consistent with the climate variability hypothesis and six with the resource variability hypothesis. While irruption dynamics are likely entrained by multiple environmental drivers, future climate change could alter the spatial and temporal characteristics of avian irruption.
From Clinics to Communities: Understanding Public Perceptions of Dental Services in Pakistan
Authors: Ali Kamran , Zahra Daniel , Bashir Ulfat , Raja Hina Zafar , Alkhtib Asmaa , Younas Minahil Arujj , Manzoor Ummara , Shakoor Asma , Khalid Mariya , Mansoor Amna , Hakeem Saman , Mumtaz Maryam , Raja Mahwish 
Published: February 2025

ABSTRACTIntroductionAccess to dental services is a core component of public healthcare. The aim of this study was to evaluate the perceptions and experiences of the public regarding access, quality and affordability of dental services in Pakistan.MethodsIt was an analytical cross‐sectional study based on an online survey. The data collection instrument was based on eight items related to participant perceptions and experiences of dental services in public and private sectors. Pretesting of the survey questionnaire was done, and the target participants were approached through social media, and dental service providers.ResultsA total of 1007 participants representing all provinces of the country responded to the study questionnaire including 54.32% (n = 547) females and 45.68% (n = 460) males. Education and financial status showed the largest effect on perceptions. Although all groups agreed that dental professionals contribute positively to improving public health, those in the ‘No Education’ or ‘Poor’ groups showed fewer positive perceptions about the accessibility, quality, and affordability of dental services. Perceptions of dental services between genders showed minimal differences. Chi‐squared tests of association showed significant (p < 0.001) relationships between personal awareness of oral health and respondent characteristics such as education, employment, financial status and location.ConclusionsThis study provides useful insights into the public perceptions and experiences of dental health services in Pakistan. The findings reveal disparities in access, quality, and affordability of dental services among disadvantaged groups, particularly within the public sector. Oral health awareness was also reported to be low amongst people with low educational and financial status. Given the limitations of the current study, further research using qualitative methods may provide a more in‐depth understanding of the facilitators and barriers to dental services to inform a major reform to improve public dental services in the country.Patient and Public Involvement and Engagement (PPIE)Members of the public with previous experience of using dental services were involved in pretesting of the study questionnaire Pretesting of the survey questionnaire was done in two phases: In the first phase, cognitive interviews were conducted with eight members of the public including four participants each with proficiency in English and Urdu. The purpose of the cognitive interviews was to determine that the participants were able to comprehend all items of the questionnaire accurately. In the second phase the questionnaire was piloted with 15 members of the public who were given a choice to answer the questionnaire in English or Urdu based on their individual preference.
Association Between Recurrent Aphthous Ulcers and Oral Biodiversity: A Systematic Review and Meta‐Analysis
Authors: Zhao Lin , Xie Hongyu , Kang Lunwei , Liao Ga 
Published: February 2025

ABSTRACTObjectiveThis study aimed to investigate the relationship between recurrent aphthous ulcers (RAU) and dysbiosis of the oral microbiota.MethodsA systematic search was conducted across several databases, including the Cochrane Library, PubMed, Web of Science Core Collection, Embase, Scopus, CBM, CNKI, WanFang, and VIP, to identify relevant studies from the inception of the library until September 20, 2024. All included studies were evaluated for quality using the Newcastle–Ottawa scale. These studies assessed the diversity and abundance of oral microorganisms in patients with RAU in comparison to healthy individuals. Results were synthesized via random‐effects meta‐analysis (I2 statistic for heterogeneity). Mean differences (MD) and 95% confidence intervals (CI) were applied to evaluate the pooled effects of outcomes. The systematic review was registered in PROSPERO (CRD42024615516).ResultsA total of 10 studies involving 343 patients and 348 controls were included in this study, 7 of these were utilized for meta‐analysis to conduct a quantitative assessment. The meta‐analysis showed that in terms of alpha diversity, saliva samples collected from patients with RAU exhibited a significantly lower Chao 1 index of alpha diversity (MD = –41.22, 95% CI –64.34 to –18.09, p < 0.01), and that patients with ulcerated sites in the oral mucosa demonstrated a higher Chao 1 index when compared to healthy sites within the oral mucosa (MD = 27.48, 95% CI 2.98 to 51.97, p = 0.03).ConclusionsSignificant differences in the Chao 1 index between patients and healthy controls, along with variations in beta diversity and the relative abundance of taxa, indicate that microbial dysbiosis may play a crucial role in the development of RAU.