bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping of dI3 neuron sensorimotor circuits across the cervical and lumbar spinal cord
Authors: Nasiri Shahriar , Laliberte Alex M. , Bui Tuan V. 
Published: November 2024

AbstractFrom the fine control of hand movements to the dynamic corrective adjustments during locomotion, spinal circuits integrate descending supraspinal and sensory inputs to modulate diverse motor functions. The integration of such a wide range of signals across the spinal cord is primarily mediated by propriospinal interneurons. In this study, we investigate the connectivity of a population of propriospinal interneurons marked by the expression ofIsl1, called dI3 neurons. These dI3s integrate supraspinal and sensory signals to facilitate many important functions, such as hand grasp, locomotion, and motor recovery after spinal cord injury; however, we have a limited understanding of how subpopulations of dI3s modulate network activity across the spinal cord to contribute to these behaviors. Their functional connectivity to motor circuits across the cervical and lumbar spinal cord was assessed through optogenetic activation of dI3s localized in different spinal segments. Our data demonstrates that cervical and lumbar dI3 subpopulations can form local, commissural, intersegmental, and long propriospinal pathways. Furthermore, dI3 subpopulations can be tonically stimulated to elicit locomotor activity. These extensive projection patterns of dI3s across the cervical and lumbar spinal cord suggest that dI3 subpopulations can modulate the activity of multiple motor networks within their respective spinal cord segments or across distant forelimb and hindlimb segments to facilitate a wide variety of motor functions.
Trends in hoaxes of academic communication
Authors: Faulkes Zen 
Published: November 2024

AbstractAcademic journals use peer review to weed out false information, but peer review and other editorial processes are normally confidential. Therefore, individuals sometimes create hoaxes to test whether editorial processes are as robust as they are claimed, or whether they are done at all. This article tracks the occurrence of hoaxes aimed at scholarly publishers and academic conferences since 2000. Since 2009, successful hoaxes usually appeared at a year of one or more a year, usually motivated by academics or journalists exposing so-called “predatory” journals. The apparent rise in the number of hoaxes reflects a lack of transparency in editorial processes at both legitimate and “predatory” journals. Reaction of academic communities to hoaxes varies widely depending on the perceived intent of the target of the hoaxes and whether the hoax demonstrates what the hoaxer claims.
The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity
Authors: Chatterjee Emeli , Betti Michael J. , Sheng Quanhu , Lin Phillip , Emont Margo P , Li Guoping , Amancherla Kaushik , Limpitikul Worawan B , Whittaker Olivia Rosina , Luong Kathy , Azzam Christopher , Gee Denise , Hutter Matthew , Flanders Karen , Sahu Parul , Garcia-Contreras Marta , Gokulnath Priyanka , Flynn Charles R. , Brown Jonathan , Yu Danxia , Rosen Evan D. , Jensen Kendall Van-Keuren , Gamazon Eric R. , Shah Ravi , Das Saumya 
Published: November 2024

ABSTRACTWe characterized circulating extracellular vesicles (EVs) in obese and lean humans, identifying transcriptional cargo differentially expressed in obesity. Since circulating EVs may have broad origin, we compared this obesity EV transcriptome to expression from human visceral adipose tissue derived EVs from freshly collected and cultured biopsies from the same obese individuals. Using a comprehensive set of adipose-specific epigenomic and chromatin conformation assays, we found that the differentially expressed transcripts from the EVs were those regulated in adipose by BMI-associated SNPs from a large-scale GWAS. Using a phenome-wide association study of the regulatory SNPs for the EV-derived transcripts, we identified a substantial enrichment for inflammatory phenotypes, including type 2 diabetes. Collectively, these findings represent the convergence of the GWAS (genetics), epigenomics (transcript regulation), and EV (liquid biopsy) fields, enabling powerful future genomic studies of complex diseases.
Multidisciplinary teamwork among healthcare workers in the provision of Prevention of Mother-to-child transmission services in the three tertiary hospitals in Fiji: A qualitative perspective
Authors: Razzaq Amina , Worth Heather , Alam Neeloy Ashraful 
Published: November 2024

AbstractIntroductionTeamwork is considered as an effective strategy in the provision of quality patient care including the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV). Multidisciplinary teamwork (collaborative practice) among healthcare workers has widely accepted as a source of optimising healthcare provision and improving patient safety. The World Health Organisation [WHO] endorsed the need to establish effective teamwork within healthcare settings, in a quest to address the challenges of fragmented health systems to improve the utilisation of an efficient and effective workforce and deliver high quality patient care.AimWe aim to understand the key contributory factors in establishing effective multidisciplinary teamwork among healthcare workers in providing prevention of mother-to-child transmission services to HIV-positive pregnant women and their infants.MethodsData was collected using in-depth interviews. Interviews were conducted in the three tertiary hospitals and associated health clinics in Fiji between April-May 2013 and February-March 2014. Ethical approvals were obtained. A total of 58 healthcare providers were interviewed including doctors (n=12), midwives (n=19), nurses (n= 14), laboratory technicians (n=5) and counsellors (n=8) were interviewed. The data was analysed using thematic analysis.ResultsWe found that multidisciplinary teamwork was an overarching theme followed by three sub-themes in discussing what constitutes effective multidisciplinary teamwork among these healthcare providers in delivering PMTCT services to HIV-positive pregnant women and their infants. The three sub themes included: integration of PMTCT services, effective communication and supportive colleagues.ConclusionOur findings would be useful in developing strategies to foster teamwork and improve working relationships between healthcare workers in other similar settings.
Gut microbiome dysbiosis and immune activation correlate with somatic and neuropsychiatric symptoms in COVID-19 patients
Authors: Scalzo Paula L. , Marshall Austin , Soriano Sirena , Curry Kristen , Dulay Mario , Hodics Timea , Quigley Eamonn MM , Treangen Todd J. , Piskorz María M. , Villapol Sonia 
Published: November 2024

AbstractCOVID-19 patients often exhibit altered immune responses and neuropsychiatric symptoms during hospitalization. However, the potential interactions with gut microbiome profiles have not been fully characterized. Here, COVID-19 disease severity was classified as low (27.4%), moderate (29.8%), and critical (42.8%). Fever (66.1%) and cough (55.6%) were common symptoms. Additionally, 27.3% reported somatic symptoms, 27.3% experienced anxiety, 39% had depressive symptoms, and 80.5% reported stress. Gut microbiome profiling was performed using full-length 16S rRNA gene sequencing. Elevated interleukin-6 levels were observed in the most severe cases, indicating systemic inflammation. Reduced gut bacterial diversity was more pronounced in women and obese patients and correlated with higher disease severity. The presence of the genusMitsuokellawas significantly associated with increased physical, stress, anxiety, and depressive symptoms, andGranulicatellawith critically ill patients. These findings suggest a link between mental health status, systemic inflammation, and gut dysbiosis in COVID-19 patients, emphasizing the potential of microbiome-targeted therapies to improve recovery and reduce severe complications.
Cross-ancestral GWAS identifies 29 novel variants across Head and Neck Cancer subsites
Authors: Ebrahimi E , Sangphukieo A , Park HA , Gaborieau V , Ferreiro-Iglesias A , Diergaarde B , Ahrens W , Alemany L , Arantes LMRB , Betka J , Bratman SV , Canova C , Conlon MSC , Conway DI , Cuello M , Curado M , de Carvalho A , de Oliviera J , Gormley M , Hadji M , Hargreaves S , Healy CM , Holcatova I , Hung RJ , Kowalski LP , Lagiou P , Lagiou A , Liu G , Macfarlane GJ , Olshan AF , Perdomo S , Pinto LF , Podesta JV , Polesel J , Pring M , Rashidian H , Gama RR , Richiardi L , Robinson M , Rodriguez-Urrego PA , Santi SA , Saunders DP , Soares-Lima SC , Timpson N , Vilensky M , von Zeidler SV , Waterboer T , Zendehdel K , Znaor A , Brennan P ,   HEADSpAcE Consortium, McKay J , Virani S , Dudding T 
Published: November 2024

AbstractIn this multi-ancestry genome-wide association study (GWAS) and fine mapping study of head and neck squamous cell carcinoma (HNSCC) subsites, we analysed 19,073 cases and 38,857 controls and identified 29 independent novel loci. We provide robust evidence that a 3’ UTR variant inTP53(rs78378222, T>G) confers a 40% reduction in odds of developing overall HNSCC. We further examine the gene-environment relationship ofBRCA2andADH1Bvariants demonstrating their effects act through both smoking and alcohol use. Through analyses focused on the human leukocyte antigen (HLA) region, we highlight that although human papilloma virus (HPV)(+) oropharyngeal cancer (OPC), HPV(-) OPC and oral cavity cancer (OC) all show GWAS signal at 6p21, each subsite has distinct associations at the variant, amino acid, and 4-digit allele level. We also defined the specific amino acid changes underlying the well-known DRB1*13:01-DQA1*01:03-DQB1*06:03 protective haplotype for HPV(+) OPC. We show greater heritability of HPV(+) OPC compared to other subsites, likely to be explained by HLA effects. These findings advance our understanding of the genetic architecture of head and neck squamous cell carcinoma, providing important insights into the role of genetic variation across ancestries, tumor subsites, and gene-environment interactions.
Systematic comparison of phenome-wide admixture mapping and genome-wide association in a diverse biobank
Authors: Cullina Sinead , Shemirani Ruhollah , Asgari Samira , Kenny Eimear E. 
Published: November 2024

AbstractBiobank-scale association studies that include Hispanic/Latino(a) (HL) and African American (AA) populations remain underrepresented, limiting the discovery of disease associated genetic factors in these groups. We present here a systematic comparison of phenome-wide admixture mapping (AM) and genome-wide association (GWAS) using data from the diverse BioMebiobank in New York City. Our analysis highlights 77 genome-wide significant AM signals, 48 of which were not detected by GWAS, emphasizing the complementary nature of these two approaches. AM-tagged variants show significantly higher minor allele frequency and population differentiation (Fst) while GWAS demonstrated higher odds ratios, underscoring the distinct genetic architecture identified by each method. This study offers a comprehensive phenome-wide AM resource, demonstrating its utility in uncovering novel genetic associations in underrepresented populations, particularly for variants missed by traditional GWAS approaches.
Implementing a consultation service for translating genomic research findings into the clinic: lessons from the SickKids Genome Board
Authors: Pan Amy , Pulsifer Kenzie , Axford Michelle , Dolman Lena , Gallinger Bailey , Liston Eriskay , Stephenson Elizabeth , Szuto Anna , Zahavich Laura , Costain Gregory 
Published: November 2024

ABSTRACTObjectivesGenome-wide sequencing (GWS) is now used across the breadth of paediatric research. There is a greater potential to identify unexpected, clinically relevant findings with GWS than with the targeted genetic techniques used in prior decades. Individual research teams may not have the expertise to evaluate and manage these findings. The Hospital for Sick Children (SickKids) Genome Board is a no-cost consultation service for researchers with questions arising from genetic aspects of their studies.MethodsWe reviewed all submissions to and recommendations from the Genome Board over the first four years, to identify common questions, themes, and trends.ResultsThere were 67 submissions, and a year-over-year increase in volumes. The most common request (60%) was to assess variants identified by GWS for pathogenicity, clinical actionability, and returnability to a study participant. Overall, 23 of 48 reviewed variants were recommended for clinical confirmation and return with genetic counselling. Other categories of submissions included requests to researchers from study participants to release their “raw” genomic data, and for input on protocols related to clinical translation of findings.ConclusionThe Genome Board provides a generalizable model for centralized triage of clinical questions arising from genomic research at a paediatric centre. Clinicians should be aware that patient participation in genetic research studies can have downstream consequences for their healthcare.
Advancing Question-Answering in Ophthalmology with Retrieval-Augmented Generation (RAG): Benchmarking Open-source and Proprietary Large Language Models
Authors: Nguyen Quang , Nguyen Duy-Anh , Dang Khang , Liu Siyin , Nguyen Khai , Wang Sophia Y. , Woof William , Thomas Peter , Patel Praveen J. , Balaskas Konstantinos , Thygesen Johan H. , Wu Honghan , Pontikos Nikolas 
Published: November 2024

AbstractPurposeTo evaluate the application of Retrieval-Augmented Generation (RAG), a technique that combines information retrieval with text generation, to benchmark the performance of open-source and proprietary generative large language models (LLMs) in medical question-answering tasks within the ophthalmology domain.MethodsOur dataset comprised 260 multiple-choice questions sourced from two question-answer banks designed to assess ophthalmic knowledge: the American Academy of Ophthalmology’s Basic and Clinical Science Course (BCSC) Self-Assessment program and OphthoQuestions. Our RAG pipeline involved initial retrieval of documents in the BCSC companion textbook using ChromaDB, followed by reranking with Cohere to refine the context provided to the LLMs. We benchmarked four models, including GPT-4 and three open-source models (Llama-3-70B, Gemma-2-27B, and Mixtral-8×7B, all under 4-bit quantization), under three settings: zero-shot, zero-shot with Chain-of-Thought and RAG. Model performance was evaluated using accuracy on the two datasets. Quantization was applied to improve the efficiency of the open-source models. Effects of quantization level was also measured.ResultsUsing RAG, GPT-4-turbo’ s accuracy increased from 80.38% to 91.92% on BCSC and from 77.69% to 88.65 % on OphthoQuestions. Importantly, the RAG pipeline greatly enhanced overall performance of Llama-3 from 57.50% to 81.35% (23.85% increase), Gemma-2 62.12% to 79.23% (17.11% increase), and Mixtral-8×7B 52.89% to 75% (22.11% increase). Zero-shot-CoT had overall no significant improvement on the models’ performance. Quantization using 4 bit was shown to be as effective as using 8 bits while requiring half the resources.ConclusionOur work demonstrates that integrating RAG significantly enhances LLM accuracy, especially for privacy-preserving smaller open-source LLMs that can be run in sensitive and resource-constrained environments such within hospitals, offering a viable alternative to cloud-based LLMs like GPT-4-turbo.
Cross-dataset Evaluation of Dementia Longitudinal Progression Prediction Models
Authors: Zhang Chen , An Lijun , Wulan Naren , Nguyen Kim-Ngan , Orban Csaba , Chen Pansheng , Chen Christopher , Zhou Juan Helen , Liu Keli , Yeo B.T. Thomas ,   the Alzheimer’s Disease Neuroimaging Initiative,   the Australian Imaging Biomarkers and Lifestyle Study of Aging
Published: November 2024

AbstractAccurate Alzheimer’s Disease (AD) progression prediction is essential for early intervention. The TADPOLE challenge, involving 92 algorithms, used multimodal biomarkers to predict future clinical diagnosis, cognition, and ventricular volume. The winning algorithm, FROG, utilized a Longitudinal-to-Cross-sectional (L2C) transformation to convert variable longitudinal histories into fixed-length feature vectors, which contrasted with most existing approaches that fitted models to entire longitudinal histories, e.g., AD Course Map (AD-Map) and minimal recurrent neural networks (MinimalRNN). The TADPOLE challenge only utilized the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. To evaluate FROG’s generalizability, we trained it on the ADNI dataset and tested it on three external datasets covering 2,312 participants and 13,200 timepoints. We also introduced two FROG variants. One variant, L2C feedforward neural network (L2C-FNN), unified all XGBoost models used by the original FROG with an FNN. Across external datasets, L2C-FNN and AD-Map were the best for predicting cognition and ventricular volume. For clinical diagnosis prediction, L2C-FNN was the best, while AD-Map was the worst. L2C-FNN compared favorably with other approaches regardless of the number of observed timepoints, and when predicting from 0 to 6 years into the future, underscoring its potential for long-term dementia progression prediction. Pretrained ADNI models are publicly available: GITHUB_LINK.
A single center cross-sectional study on the efficacy of low-dose cytarabine and aclramycin combined with granulocyte colony-stimulating factor (CAG regimen) in elder adults with acute myeloid leukemia
Authors: MinXu  , He Chunxiao , Wen Xuemei , Lan Chen , Li Xintong , Hong Yaqun , Li Xiaofan 
Published: November 2024

AbstractBackgroundNowadays, the combination of CAG regimen with targeted therapy and immunotherapy has greatly improved the prognosis of AML patients, but there are controversies about the prognostic factors of CAG regimen alone, especially in AML elders.ObjectiveBy investigating the survival status of elder patients who received induction CAG regimen in our hospital at the beginning of this century and analyzing the factors affecting survival, we aim to provide scientific evidence for improving the survival of current patients.MethodThe AML elder patients treated with induction CAG regimen including low-dose cytarabine (10 mg/m2per 12 hours, day 1 to 14), aclarubicin(14 mg/m2per day, day 1 to 4), and G-CSF priming (200 ug / m2per day, day 1 to 14) in Fujian Medical University Union Hospital from January 2001 to December 2009 were involved in this research.ResultsAmong 92 elderly AML patients, 44 (47.8%) showed clinical efficacy, while 48 (52.2%) experienced treatment failure (including 12 deaths (13.0%)). The main adverse reactions of chemotherapy were bone marrow suppression, with mild non hematological adverse reactions. The median recurrence time was 7 months. The risk factors related efficacy were high blasts, elevated LDH and HBDH.ConclusionThe CAG regimen is suitable for elderly patients and can be used for the treatment of relapsed refractory AML and secondary AML. The CAG regimen has mild non hematological adverse reactions. After chemotherapy, there is a longer bone marrow suppression period and a higher infection rate; The reason for the improved efficacy of CAG regimen in current patients may be related to the effective reduction of tumor burden during induction combined with target or immunotherapy.
Generating snoRNA-guided Programmable 2’-O-methylation
Authors: Zhao Justin , Cockman Eric , Yin Xinhe , Chao Yvonne , Pecot Chad , Holley Christopher L. 
Published: November 2024

AbstractSmall nucleolar RNAs (snoRNAs) are critical in guiding post-transcriptional modifications like 2’-O-methylation (Nm), which play crucial roles in downstream processes such as splicing and translation. This study tests a novel method for Nm validation, addressing a significant gap in modern Nm research, and offers insight into the intricacies of snoRNA-guided Nm. While mapping of Nm modifications has seen significant improvement within the past decade, no major techniques have been able to validate these potential sites. Additionally, many mapping techniques lack consensus among proposed Nm sites, especially on mRNAs. Without a proper validation technique, Nm research lags compared to its peer post-transcriptional modifications. The RNase H-based Nm-VAQ assay used here quantifies 2’-O-methylation at single nucleotide resolution across various RNA species including rRNA, snRNA, and mRNA. Its optimization for mRNA allows for an unprecedented way to study the effects of Nm modifications in low abundance transcripts. Utilizing this, the study also explores the potential of creating synthetic snoRNAs to guide Nm modifications. Exogenous snoRNAs are shown to rescue Nm in genetic knockout models and can be mutated to guide Nm at any location along the target RNA transcript. Preliminary work indicates that synthetic snoRNAs demonstrate the ability to modify luciferase, impacting translation efficiency. Targeting an exon increases mRNA abundance but decreases protein expression, consistent with previous findings onPxdnmRNA. These findings set the scene for novel understanding of the relationship between snoRNA abundance, 2’-O-methylation efficiency, and Nm’s impact on gene expression.
Accuratede novodesign of high-affinity protein binding macrocycles using deep learning
Authors: Rettie Stephen A. , Juergens David , Adebomi Victor , Bueso Yensi Flores , Zhao Qinqin , Leveille Alexandria N. , Liu Andi , Bera Asim K. , Wilms Joana A. , Üffing Alina , Kang Alex , Brackenbrough Evans , Lamb Mila , Gerben Stacey R. , Murray Analisa , Levine Paul M. , Schneider Maika , Vasireddy Vibha , Ovchinnikov Sergey , Weiergräber Oliver H. , Willbold Dieter , Kritzer Joshua A. , Mougous Joseph D. , Baker David , DiMaio Frank , Bhardwaj Gaurav 
Published: November 2024

ABSTRACTThe development of macrocyclic binders to therapeutic proteins typically relies on large-scale screening methods that are resource-intensive and provide little control over binding mode. Despite considerable progress in physics-based methods for peptide design and deep-learning methods for protein design, there are currently no robust approaches forde novodesign of protein-binding macrocycles. Here, we introduce RFpeptides, a denoising diffusion-based pipeline for designing macrocyclic peptide binders against protein targets of interest. We test 20 or fewer designed macrocycles against each of four diverse proteins and obtain medium to high-affinity binders against all selected targets. Designs against MCL1 and MDM2 demonstrate KDbetween 1-10 μM, and the best anti-GABARAP macrocycle binds with a KDof 6 nM and a sub-nanomolar IC50in vitro. For one of the targets, RbtA, we obtain a high-affinity binder with KD< 10 nM despite starting from the target sequence alone due to the lack of an experimentally determined target structure. X-ray structures determined for macrocycle-bound MCL1, GABARAP, and RbtA complexes match very closely with the computational design models, with three out of the four structures demonstrating Ca RMSD of less than 1.5 Å to the design models. In contrast to library screening approaches for which determining binding mode can be a major bottleneck, the binding modes of RFpeptides-generated macrocycles are known by design, which should greatly facilitate downstream optimization. RFpeptides thus provides a powerful framework for rapid and custom design of macrocyclic peptides for diagnostic and therapeutic applications.