bluuebunny/crossref_metadata_2025_split huggingface dataset:
NanoAbLLaMA: construction of nanobody libraries with protein large language models
Authors: Wang Xin , Chen Haotian , Chen Bo , Liang Lixin , Mei Fengcheng , Huang Bingding 
Published: February 2025

IntroductionTraditional methods for constructing synthetic nanobody libraries are labor-intensive and time-consuming. This study introduces a novel approach leveraging protein large language models (LLMs) to generate germline-specific nanobody sequences, enabling efficient library construction through statistical analysis.MethodsWe developed NanoAbLLaMA, a protein LLM based on LLaMA2, fine-tuned using low-rank adaptation (LoRA) on 120,000 curated nanobody sequences. The model generates sequences conditioned on germlines (IGHV3-301 and IGHV3S5301). Training involved dataset preparation from SAbDab and experimental data, alignment with IMGT germline references, and structural validation using ImmuneBuilder and Foldseek.ResultsNanoAbLLaMA achieved near-perfect germline generation accuracy (100% for IGHV3-301, 95.5% for IGHV3S5301). Structural evaluations demonstrated superior predicted Local Distance Difference Test (pLDDT) scores (90.32 ± 10.13) compared to IgLM (87.36 ± 11.17), with comparable TM-scores. Generated sequences exhibited fewer high-risk post-translational modification sites than IgLM. Statistical analysis of CDR regions confirmed diversity, particularly in CDR3, enabling the creation of synthetic libraries with high humanization (&gt;99.9%) and low risk.DiscussionThis work establishes a paradigm shift in nanobody library construction by integrating LLMs, significantly reducing time and resource demands. While NanoAbLLaMA excels in germline-specific generation, limitations include restricted germline coverage and framework flexibility. Future efforts should expand germline diversity and incorporate druggability metrics for clinical relevance. The model’s code, data, and resources are publicly available to facilitate broader adoption.
Cerebrospinal fluid profiles of targeted metabolomics on neurotransmitters in patients with post-neurosurgical bacterial meningitis
Authors: Mei Zhaojun , Guan Liao , Xu Ziao , Cheng Hongwei , Ye Lei 
Published: February 2025

BackgroundPost-neurosurgical bacterial meningitis (PNBM) is a severe complication in patients receiving neurosurgical treatments. Pathogens and neuroinflammation have been reported to influence metabolites in the microenvironment of the central nervous system. However, information about the relationship between neurotransmitter levels and PNBM is still limited. In this study, we aimed to investigate the diagnostic potential of neurotransmitters for PNBM in the patients with stroke.MethodsIn this study, a total of 66 stroke patients were recruited. Among them, 40 patients were complicated with PNBM. We profiled cerebrospinal fluid (CSF) levels of neurotransmitter precursors and metabolites using the targeted metabolomics method, which contained 26 precursors and metabolites of neurotransmitters, using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC/MS).ResultsWe found that 14 biomarkers were downregulated but 3,4-dihydroxyphenylacetic acid (DOPAC) was upregulated in the CSF of PNBM patients. Among the biomarkers, D-glutamine (AUC=1.000), Boc-D-Tyr-OH (AUC=0.9447), L(+)-arginine (AUC=0.9418), and DOPAC (AUC=0.9173) had strong diagnostic efficiency for PNBM. Bioinformatic analysis showed that tyrosine metabolism, butanoate metabolism, histidine metabolism, alanine, aspartate and glutamate metabolism, glycerophospholipid metabolism, arginine and proline metabolism, and tryptophan metabolism might be involved in the pathogenesis of PNBM. After reviewing previous studies, we found a probable diverse pathophysiological alteration between PNBM and community-acquired bacterial meningitis.ConclusionsIn summary, we identified downregulated levels of D-glutamine, Boc-D-Tyr-OH, L(+)-arginine, and phenprobamate, and an upregulated level of DOPAC in CSF to have strong diagnostic efficiencies. The results also offered potential targets for the treatment of PNBM.
Empowering pediatric, adolescent, and young adult patients with cancer utilizing generative AI chatbots to reduce psychological burden and enhance treatment engagement: a pilot study
Authors: Hasei Joe , Hanzawa Mana , Nagano Akihito , Maeda Naoko , Yoshida Shinichirou , Endo Makoto , Yokoyama Nobuhiko , Ochi Motoharu , Ishida Hisashi , Katayama Hideki , Fujiwara Tomohiro , Nakata Eiji , Nakahara Ryuichi , Kunisada Toshiyuki , Tsukahara Hirokazu , Ozaki Toshifumi 
Published: February 2025

BackgroundPediatric and adolescent/young adult (AYA) cancer patients face profound psychological challenges, exacerbated by limited access to continuous mental health support. While conventional therapeutic interventions often follow structured protocols, the potential of generative artificial intelligence (AI) chatbots to provide continuous conversational support remains unexplored. This study evaluates the feasibility and impact of AI chatbots in alleviating psychological distress and enhancing treatment engagement in this vulnerable population.MethodsTwo age-appropriate AI chatbots, leveraging GPT-4, were developed to provide natural, empathetic conversations without structured therapeutic protocols. Five pediatric and AYA cancer patients participated in a two-week intervention, engaging with the chatbots via a messaging platform. Pre- and post-intervention anxiety and stress levels were self-reported, and usage patterns were analyzed to assess the chatbots’ effectiveness.ResultsFour out of five participants reported significant reductions in anxiety and stress levels post-intervention. Participants engaged with the chatbot every 2–3 days, with sessions lasting approximately 10 min. All participants noted improved treatment motivation, with 80% disclosing personal concerns to the chatbot they had not shared with healthcare providers. The 24/7 availability particularly benefited patients experiencing nighttime anxiety.ConclusionsThis pilot study demonstrates the potential of generative AI chatbots to complement traditional mental health services by addressing unmet psychological needs in pediatric and AYA cancer patients. The findings suggest these tools can serve as accessible, continuous support systems. Further large-scale studies are warranted to validate these promising results.
Perspectives from science teacher educators on the potential contribution of Sámi traditional knowledge to sustainable development
Authors: Melis Claudia , Kvivesen Mona , Munkebye Eli 
Published: February 2025

IntroductionThis study investigates how Sámi traditional knowledge is integrated in science teacher education in Norway, and what teacher educators declare about its potential contribution to sustainable development.MethodsData was collected through an anonymous electronic survey and analyzed by means of both qualitative and quantitative methods. Thirty-nine respondents from 15 teacher education institutions in Norway participated in the study.ResultsAccording to the respondents, most science courses explicitly mentioned Sámi traditional knowledge. The most common Sámi topics taught in science in kindergarten education, were the seasons, preparing traditional food, constellations and reflecting about how traditional knowledge can contribute to sustainability. For primary school teacher education, the most common Sámi topics were the constellations, conflicts with building of windmills parks in traditional reindeer grazing areas, traditional use of plants and seasons. The self-declared level of knowledge on Sámi traditional knowledge was rather low and the majority of respondents expressed the intention to improve their competence by reading or attending courses. The thematic analysis of the answers to the question about how Sámi traditional knowledge could contribute to sustainable development, identified four main Sámi themes: traditional use of resources, view of nature, local knowledge versus Sámi traditional knowledge, and social sustainability. Our results confirmed that teaching Sámi traditional knowledge poses a significant challenge for science teacher educators, both as consequence of their perceived knowledge and the limited amount of time available for teaching. Some respondents found the subject not relevant for the students, whereas other were challenged by its sensitivity or by the availability of culture bearers. The contrast between traditional knowledge and western science as different views of knowledge was also mentioned.DiscussionBased on teacher educators’ perspectives, we propose that adopting a Two-Eyed Seeing approach in science teaching could promote critical thinking, by enabling a reflection on our resource utilization and on our human-nature relationship. Some of the challenges associated with lack of time and knowledge could be addressed by promoting further education for science teacher educators, building a network of knowledge bearer that could be invited in the teacher courses, or reevaluating the courses content to make place for Sámi themes. This would also promote decolonization and inclusion of the Sámi people, thus contributing to several aspects of sustainability.
Quality of care and challenges in medical convoy transfers during Hajj season 2023: a cross-sectional study
Authors: Alsaleh Ghadah , Khan Anas , Alabdulatif Lamis , Alhazmi Jumana , Althobaiti Amira 
Published: February 2025

BackgroundThe Hajj pilgrimage, a significant spiritual journey for Muslims, occurs annually in Mecca, Saudi Arabia, attracting millions of participants from diverse backgrounds worldwide. This surge in pilgrims poses substantial challenges for healthcare services, as many face health risks due to physical exertion, dehydration, and exposure to infectious diseases. The unique healthcare demands during Hajj necessitate a thorough understanding of the quality of care provided and the challenges faced by medical convoys.ObjectivesThis study aims to assess the quality of care provided by medical convoys to medical conditions transferred to secondary or tertiary healthcare facilities during the Hajj season in 2023, while also examining the difficulties and challenges encountered by healthcare providers throughout the trip.Methods and materialsThis observational retrospective cross-sectional study involved 295 patients transferred from Makkah and Madinah hospitals to Arafat via a specialized medical convoy service during the 2023 Hajj season. Data were collected from electronic patient data sheets, documenting demographic characteristics, comorbidities, clinical diagnoses, transfer details, and the Risk Score for Transported Patients (RSTP). Ethical approval was obtained under IRB log Number: 23-452E from the Research Ethics Committee at King Fahad Medical City.ResultsAmong the 295 patients, the majority were males with an average age of 63.16 years. The most common nationalities were Asian (48.1%) and African (28.5%). Significant comorbidities included hypertension (34.2%) and diabetes mellitus (33.2%). RSTP indicated that 96.6% of patients had scores below 6. Nearly half were discharged within 72 h post-transfer, while a small percentage experienced deterioration or mortality. Most patients (58.3%) did not receive any medications or anesthesia, although 31.2% were administered analgesics. Common diagnoses included fractures (15.3%) and heat stroke (10.5%). Univariate logistic regression analysis revealed significant associations between higher RSTP and factors such as older age, presence of arrhythmias, need for respiratory support, lower Glasgow Coma Scale scores, total score, and blood pressure.ConclusionThis study highlights the diverse demographic characteristics and significant comorbidities of patients transferred during the Hajj season, indicating the need for tailored healthcare strategies that address the complexities of managing these patients. The strong association between higher RSTP scores and factors such as older age and arrhythmias underscores the importance of enhanced monitoring during transport. It is crucial to develop protocols that ensure patient safety and optimize outcomes in future healthcare delivery during Hajj.
Effect of fat distribution on left ventricular structure and function in different sexes: a Mendelian randomization study
Authors: Li Hang , Yin Guangjiao , Zhang Yanfang , Wang Ziwei , Lv Fang , Li Rui , Qin Juanjuan , Ye Xujun 
Published: February 2025

BackgroundAlthough there is an interaction between sex, body fat distribution, and cardiac structure and function, these relationships have not been fully elucidated yet. This study aims to reveal the causal relationship between genetic determinants of fat distribution pattern and function of the left ventricular structure in different sexes.MethodsGenetic variants for waist circumference, hip circumference, waist-to-hip ratio (WHR), and body mass index (BMI) were selected from genome-wide association studies conducted in European samples. The dataset for left ventricular (LV) parameters was obtained from over 35,000 European samples in the UK Biobank Cardiovascular Magnetic Resonance sub-study. Two-sample Mendelian randomization (MR) analysis was employed to explore causal relationships.ResultsAfter adjusting for BMI, WHR shows a positive causal relationship with LV hypertrophy and a significant negative causal relationship with LV volume and diastolic function. In further subgroup analysis, we only found similar results in WHR among the female population (FWHR), while in the male population, there was no significant causal relationship between MWHR and LV hypertrophy and diastolic function. Additionally, in our MR analysis, no causal relationship was found between WHR and LVEF.ConclusionsThis study indicates that the fat distribution pattern has unique effects on the structure and function of the LV, and these effects vary by sex. This study provides evidence for a causal relationship between fat distribution and LV structure and function across both sexes.
Causal inference of inflammatory proteins in infertility: a Mendelian randomization study
Authors: Chen Peng , Ni Sha , Ou-Yang Ling 
Published: February 2025

BackgroundInfertility affects 8-12% of couples globally, manifesting as a complex reproductive disorder with varied causes, negatively impacting emotional, physical, and social well-being. Inflammation is implicated in many diseases, including male and female infertility.MethodsThis study employed Mendelian randomization (MR) with two-sample, bidirectional, and mediation approaches to explore the relationship between circulating inflammatory proteins and infertility. Causal analysis was conducted using inverse variance-weighted (IVW) and MR-Egger regression, supplemented by enrichment analysis, protein-protein interaction (PPI) network exploration, and drug signature analysis.ResultsOur findings identified a significant positive correlation between C-X-C motif chemokine 6 (CXCL6) and male infertility, positioning CXCL6 as a potential therapeutic target or biomarker. No causal links were detected between circulating inflammatory proteins and female infertility post-FDR adjustment. Minor mediation effects were observed for metabolites such as androstenediol monosulfate, arachidonoylcholine, and serum phosphate to glycerol ratio. Cytokine-related pathways emerged as significant in both male and female infertility. Gene-drug interaction analysis highlighted the need for further investigation of pioglitazone in treating female infertility.ConclusionThis study establishes a potentially causal relationship between CXCL6 and male infertility, suggesting its potential as a drug target or molecular biomarker. The integrative approach combining causal inference with molecular pathway and drug interaction analysis opens new avenues for understanding and treating infertility.
Dynamics and interactions of soil moisture and temperature during degradation and restoration of alpine swamp meadow on the Qinghai-Tibet plateau
Authors: Ma Guankui , Zhang Yongkun , Li Hang , Yang Yongsheng , Li Runjie 
Published: February 2025

Soil temperature (ST) and soil moisture (SM) are two fundamental land surface variables that directly or indirectly affect the processes and functions of alpine ecosystems. To clarify dynamics and interactions of SM and ST during degradation and restoration of alpine swamp meadow, four successional stages of alpine swamp meadow (non-degraded, NG; Kobresia humilis-dominated degraded, DG1; bare soil/weed-type degraded, DG2; artificially restored, RE) were selected to measure SM and ST at 10, 20 and 30 cm depths with 30-minute time interval in 2021 and 2022. Results showed that: (1) With the degradation and restoration of alpine swamp meadow, SM at 10 cm depth decreased at first, and then increased significantly (p &lt; 0.05), which was attributed to the role of vegetation coverage and soil organic carbon in soil evaporation and water holding capacity, respectively; (2) ST at various depths did not respond to diverse degradation and restoration stages of alpine swamp meadow (p &gt; 0.05); (3) The relationships between ST and SM varied with seasons, with positive and negative linear correlation in spring and summer, and positive exponential correlation in autumn and winter (p &lt; 0.01). The study of SM and ST at different degradation and restoration stages of alpine swamp meadow will provide theoretical support for the research of related ecological processes and functions of such ecosystem.
Proposed research classification criteria for Lyme disease in infection associated chronic illness studies
Authors: Fallon Brian A. , Kuvaldina Mara , Zubcevik Nevena , DeBiasi Roberta , Mulkey Sarah B. , Chiu Charles , Chow Felicia , Paolino Kristopher , Lai Randy , Putrino David , Proal Amy , Pavlicova Martina , Aucott John 
Published: February 2025

BackgroundResearch on patients with persistent symptoms despite prior treatment for Lyme disease can be challenging to interpret given the diversity of criteria selected to characterize Lyme disease and to define the syndrome of those with persistent symptoms. Because most research studies only include patients with well-documented prior Lyme disease, the generalizability of the study results is limited, excluding the larger group of patients often seen in community practice who do not meet these stringent enrollment criteria. Researchers at the Lyme and other Tick-borne Diseases Clinical Trials Network (LTD-CTN) recognized early on that a research classification system was needed to facilitate the design of studies that are more inclusive. This paper presents a proposed research classification system.MethodsCriteria used in published clinical research on previously treated Lyme disease were reviewed. Clinical expertise was provided by principal investigators in the LTD-CTN. Further input was obtained from a diverse panel of stakeholders in the field, including clinicians, academic researchers, and patient advocates. This classification system was developed based on feedback collected from all these sources.ResultsThe new research classification system proposes criteria for Lyme disease at different levels of diagnostic certainty: well-defined, probable, possible, and uncertain. Criteria for ascertainment for each classification level and additional factors to be considered in patient selection for research are described.ConclusionThe proposed research classification system should improve the quality and generalizability of clinical research by providing clear case definitions for enrollment of a more diverse group of patients with sequelae from Lyme disease.
Effects and potential pathways of goose astrovirus infection on gosling hepatic lipid metabolism
Authors: Yin Chao , Shi Yun , Li Haiqin , Lu Zhihua , Gao Xiaona , Hu Guoliang , Guo Xiaoquan 
Published: February 2025

IntroductionThe adverse effects of goose astrovirus (GoAstV) on avian growth and health have been widely reported previously, while the stress reactions and corresponding mechanism of gosling liver responding to GoAstV infection remain not entirely clear.MethodsOne-day-old goslings inoculated subcutaneously with 2 × 10−6 TCID50 of GoAstV were employed as an experimental model, and the potential effects and pathways of GoAstV infection on gosling liver functions were investigated by combining the morphological, biochemical and RNA sequencing (RNA-seq) techniques.ResultsStructural and functional impairments were found in gosling livers post the virus infection, as characterized by the histological alterations in liver index and morphology of hepatic cord and sinuses, as well as the abnormal expression patterns of the cellular antioxidant, inflammation and apoptosis-related genes. RNA sequencing analysis were performed to investigate the underlying mechanism. Results showed that the analysis of screened 1949 differentially expressed genes (DEGs) were mainly enriched in GO terms related to organic immune defense and substance metabolism, and their corresponding KEGG pathways represented by PPAR signaling pathway, intestinal immune network for IgA production, and fatty acid metabolism and degradation, suggesting that the functions of avian immunity and lipid metabolism were greatly changed after the GoAstV infection. Finally, the lipid deposition in gosling hepatocytes were further demonstrated by the subsequent Oil red O staining, biochemical detection of serum TG and HDL-C, and the gene expression analysis including PPARα, PPARγ, ACSBG2, ACSL5, CPT1A and PCK1.DiscussionThough limitations exist, the findings of this study are helpful to expand our understanding about the negative effects of GoAstV on goslings, and provide us with new clues for the salvaging of GoAstV-induced liver dysfunctions in poultry industry.
Enhancing the diagnostic efficacy of right-to-left shunt using robot-assisted transcranial Doppler: a quality improvement project
Authors: Shah Ruchir , Devlin Christian , Gao Lan , Ledford Samuel , Ramjee Vimal , Madan Vinay , Patterson Jennifer , Daniel Lauren , Devlin Thomas 
Published: February 2025

BackgroundStroke is the leading cause of adult disability worldwide, with approximately 30% of strokes remaining cryptogenic. One potential important etiology is a patent foramen ovale (PFO), which may contribute to stroke through paradoxical thromboembolism or in situ thromboembolus formation. Recent advancements in robot-assisted transcranial Doppler (raTCD) have shown increased sensitivity in detecting right-to-left shunt (RLS) compared to transthoracic echocardiography (TTE), particularly in detecting the large shunts which are associated with higher stroke risk.MethodsWe conducted a retrospective quality improvement project at our regional stroke center to compare the performance of TTE and raTCD in identifying RLS in ischemic stroke patients. The study involved 148 patients admitted between February 2021 and February 2023. All patients underwent TTE and raTCD with agitated saline bubble contrast, with additional transesophageal echocardiography (TEE) at the treatment team’s discretion. The primary metrics analyzed included differences in overall RLS detection and large RLS detection rates for raTCD, TTE and TEE.ResultsraTCD detected RLS in 60.1% of patients compared to 37.2% with TTE (p &lt; 0.001), with a 42.6% detection rate for large shunts on raTCD versus 23.0% on TTE (p &lt; 0.001). The sensitivity and specificity of raTCD were 92 and 87.5%, respectively, compared to 78.57 and 71.43% for TTE, using TEE as the gold standard. Nine patients underwent PFO closure, all correctly identified with large shunts by raTCD, while TTE missed or underestimated the PFO size in 44% of the cases.ConclusionraTCD significantly outperforms TTE in detecting RLS and large shunts, suggesting its integration into standard PFO workup protocols may enhance secondary stroke prevention. These findings support the adoption of raTCD as a complementary diagnostic tool alongside TTE and TEE for more accurate PFO detection and risk stratification.