bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploratory Randomised Trial of Tranexamic Acid to Decrease Postoperative Delirium in Adults Undergoing Lumbar Fusion: A trial stopped early
Authors: Hindman Bradley J. , Olinger Catherine R. , Woodroffe Royce W. , Zanaty Mario , Streese Carolina Deifelt , Zacharias Zeb R. , Houtman Jon C. D. , Wendt Linder H. , Ten Eyck Patrick P. , O’Connell-Moore Debra J. , Ray Emanuel J. , Lee Sarah J. , Waldschmidt Daniel F. , Havertape Lauren G. , Nguyen Lanchi B. , Chen Pei-fu , Banks Matthew I. , Sanders Robert D. , Howard Matthew A. 
Published: October 2024

AbstractBackgroundPostoperative delirium may be mediated by perioperative systemic- and neuro-inflammation. By inhibiting the pro-inflammatory actions of plasmin, tranexamic acid (TXA) may decrease postoperative delirium. To explore this hypothesis, we modified an ongoing randomised trial of TXA, adding measures of postoperative delirium, cognitive function, systemic cytokines, and astrocyte activation.MethodsAdults undergoing elective posterior lumbar fusion randomly received intraoperative intravenous TXA (n=43: 10 mg kg-1loading dose, 2 mg kg-1h-1infusion) or Placebo (n=40). Blood was collected pre- and at 24 h post-operatively (n=32) for biomarkers of systemic inflammation (cytokines) and astrocyte activation (S100B). Participants had twice daily delirium assessments using the 3-minute diagnostic interview for Confusion Assessment Method (n=65). Participants underwent 4 measures of cognitive function preoperatively and during post-discharge follow-up.ResultsDelirium incidence in the TXA group (7/32=22%) was not significantly less than in the Placebo group (11/33=33%);P=0.408, absolute difference=11%, relative difference=33%, effect size = −0.258 (95% CI −0.744 to 0.229). In the Placebo group (n=16), delirium severity was associated with the number of instrumented vertebral levels (P=0.001) and with postoperative interleukin −8 and −10 concentrations (P=0.00008 andP=0.005, respectively) and these associations were not significantly modified by TXA. In the Placebo group, delirium severity was associated with S100B concentration (P=0.0009) and the strength of the association was decreased by TXA (P=0.002).ConclusionsA potential 33% relative decrease in postoperative delirium incidence justifies an adequately powered clinical trial to determine if intraoperative TXA decreases delirium in adults undergoing lumbar fusion.
Modelling the potential spread of Clade Ib MPXV in Asian cities
Authors: Jin Shihui , Gan Gregory , Endo Akira , Prem Kiesha , Jin Tan Rayner Kay , Lim Jue Tao , Ejima Keisuke , Dickens Borame L 
Published: October 2024

ABSTRACTBackgroundThe ongoing 2023–2024 mpox outbreak in several African countries, driven by the novel Clade Ib strain, has resulted in imported cases reported in Sweden, Thailand, and India. The potentially high transmissibility of this new strain and shifts in transmission modes may make territories in Asia, which were minimally affected by previous mpox waves, vulnerable to community-wide transmission following importation. While this highlights the importance of early preparedness, current knowledge of the virus’s transmission dynamics remains too limited to effectively inform policy-making and resource planning.MethodsA compartmental model was constructed to characterise the potential mpox transmission dynamics. Importation- triggered outbreaks were simulated in 37 Asian cities under scenarios with one, three, and five initial local infections. The impacts of various non-pharmaceutical interventions (NPIs), including isolation and quarantine, were projected and compared.FindingsOur simulations revealed substantial disparities in outbreak sizes among the 37 Asian cities, with large-scale outbreaks expected in territories with a high proportion of sexually active individuals at risk or low immunity from smallpox vaccination. Total case count in one year following initial local infections would increase linearly with initial infection size. In the scenario with three initial local infections, up to 340 cases per million residents were expected without interventions. Isolation for diagnosed cases was projected to lower the outbreak size by 43.8% (interquartile range [IQR]: 42.7%–44.5%), 67.8% (IQR: 66.5%–68.9%), 80.8% (IQR: 79.5%–82.0%), and 88.0% (IQR: 86.8%–89.1%) when it reduced interpersonal contacts by 25%, 50%, 75%, and 100%, respectively. Quarantining close contacts would contribute to a further decrease in cases of up to 22 percentage points over one year.InterpretationThe potential mpox outbreak in an Asian setting could be alleviated through strong surveillance and timely response from stakeholders. NPIs are recommended for outbreak management due to their demonstrated effectiveness and practicability.
Genetic architecture of lumbar spinal stenosis
Authors: Salo Ville , Määttä Juhani , Takala Jasmin , Heikkilä Anni , FinnGen  , Reimann Ene , Mägi Reedik ,   Estonian Biobank Research Team, Reis Kadri , G.Elhanas Abdelrahman , Reigo Anu , Palta Priit , Esko Tõnu , Leinonen Ville , Karppinen Jaro , Sliz Eeva , Kettunen Johannes 
Published: October 2024

Introductory paragraphOver 100 million people worldwide suffer from lumbar spinal stenosis (LSS) with increasing incidence with ageing population, yet little is known about the LSS genetic background. Given the high cost of treating LSS, a deeper understanding of LSS pathogenesis may eventually result in the development of novel preventative and treatment methods, potentially leading to reductions in related societal costs. Our aim is to gain a better understanding of the genetic components underlying LSS. In the FinnGen, Estonian, and UK biobanks, we conduct a genome-wide association study (GWAS) of LSS and merge the results in the genome-wide meta-analysis. In addition to the seven known risk loci, our meta-analysis reveals 47 loci that have not been associated with LSS in previous studies. Many downstream analyses and multiple candidate genes discovered from the LSS-associated loci suggest that spinal degeneration plays a major role in the pathogenesis of LSS.
Creating a biomedical knowledge base by addressing GPT inaccurate responses and benchmarking context
Authors: Darnell S. Solomon , Overall Rupert W. , Guarracino Andrea , Colonna Vicenza , Villani Flavia , Garrison Erik , Isaac Arun , Muli Priscilla , Muriithi Frederick Muriuki , Kabui Alexander , Kilyungi Munyoki , Lisso Felix , Kibet Adrian , Muhia Brian , Nijveen Harm , Yousefi Siamak , Ashbrook David , Huang Pengzhi , Suh G. Edward , Umar Muhammad , Batten Christopher , Chen Hao , Sen Śaunak , Williams Robert W. , Prins Pjotr 
Published: October 2024

We created GNQA, a generative pre-trained transformer (GPT) knowledge base driven by a performant retrieval augmented generation (RAG) with a focus on aging, dementia, Alzheimer’s and diabetes. We uploaded a corpus of three thousand peer reviewed publications on these topics into the RAG. To address concerns about inaccurate responses and GPT ‘hallucinations’, we implemented a context provenance tracking mechanism that enables researchers to validate responses against the original material and to get references to the original papers. To assess the effectiveness of contextual information we collected evaluations and feedback from both domain expert users and ‘citizen scientists’ on the relevance of GPT responses.A key innovation of our study is automated evaluation by way of a RAG assessment system (RAGAS). RAGAS combines human expert assessment with AI-driven evaluation to measure the effectiveness of RAG systems. When evaluating the responses to their questions, human respondents give a “thumbs-up” 76% of the time. Meanwhile, RAGAS scores 90% on answer relevance on questions posed by experts. And when GPT-generates questions, RAGAS scores 74% on answer relevance. With RAGAS we created a benchmark that can be used to continuously assess the performance of our knowledge base.Full GNQA functionality is embedded in the freeGeneNetwork.orgweb service, an open-source system containing over 25 years of experimental data on model organisms and human. The code developed for this study is published under a free and open-source software license athttps://git.genenetwork.org/gn-ai/tree/README.md.
Genetic diversity and fine-scale structure of two populations of a subterranean rodent,Ellobius talpinus
Authors: Rudyk Anna I. , Kuprina Kristina V. , Bergaliev Arman M. , Galkina Svetlana A. , Romanovich Anna E. , Novikov Eugene A. , Volodina Elena V. , Smorkatcheva Antonina V. 
Published: October 2024

ABSTRACTSubterranean rodents represent an interesting model system for molecular ecologists. Their lifestyle is associated with fragmented environments, limited dispersal ability, and low fecundity. These characteristics all are expected to increase inter- and intrapopulation differentiation and reduce intra- population genetic diversity, yet the published empirical data revealed the lack of generality of this pattern. This emphasizes the importance of accumulating more data on individual species to understand what factors shape the genetic dynamics of populations. This study represents the first characterization of the population genetic diversity and fine-scale genetic structure of a highly specialized subterranean vole,Ellobius talpinus. We used nine microsatellite loci and a fragment of the mitochondrial D-loop to investigate genetic patterns of two distant populations: the Novosibirsk population at the extreme northeastern edge of the species range, and the sub-peripheral Saratov population. As a result, the two populations exhibit distinct patterns of genetic structure. The Novosibirsk population showed a low nuclear diversity with an observed heterozygosity (Ho) of 0.34 and an unbiased expected heterozygosity (uHe) of 0.55. Mitochondrial D-loop was nearly monomorphic with over 90% of the observed haplotypes being identical, resulting in a haplotype diversity (Hd) of 0.14 and nucleotide diversity (π) of 0.0004. In contrast, the Saratov population displayed moderate nuclear (Ho= 0.64;uHe= 0.76) and high mitochondrial variation (Hd= 0.83;π= 0.034), compared to the surface-dwelling voles. Nine haplotypes representing four well-differentiated mitochondrial clades were found in the Saratov population. In a heterogeneous landscape, significant genetic differentiation was revealed at both intermediate (dozens of kilometers) and fine (several kilometers) scales. However, within the continuous suitable habitat, no fine-scale spatial structure was observed apart from that caused by kin clustering. The spatial genetic patterns revealed inE. talpinusappear to reflect a combination of effects of strong social structure, local natural and anthropogenic barriers limiting dispersal opportunities, and occasional long-distance dispersal.
Identification and Expression of the peach TNLRMiagenes for the Resistance to the Root-knot NematodeMeloidogyne incognita
Authors: Duval Henri , Heurtevin Laure , Dlalah Naïma , Caravel Claire , Callot Caroline , Van Ghelder Cyril 
Published: October 2024

AbstractRoot-Knot Nematodes (RKN) are major pests for world agriculture. As RKN are polyphagous endoparasites, present in various climates and able to multiply rapidly, the quest to discover new natural resistances in plants is essential. InPrunusspecies, several major resistance genes to RKN that belong to the NLR family, have been detected in recent years. In Peach, the RMia gene, which confers resistance to the RKNMeloidogyne incognita, M. arenaria, andM. ethiopica, was localized on the chromosome 2. In this study, we used short-and long-read sequencing technologies to identify the RMia gene in two independent RKN-resistant peach varieties. We characterized three candidate genes and studied their expression profile upon RKN infection. Our study identified and characterized these candidates that are most likely involved in the RKN resistance. Ultimately, we developed new molecular markers associated to this resistance that can be used in breeding programs.
Decoding m6Am by simultaneous transcription-start mapping and methylation quantification
Authors: Liu Jianheng Fox , Hawley Ben R. , Nicholson Luke S. , Jaffrey Samie R. 
Published: October 2024

ABSTRACTN6,2’-O-dimethyladenosine (m6Am) is a modified nucleotide located at the first transcribed position in mRNA and snRNA that is essential for diverse physiological processes. m6Am mapping methods assume each gene uses a single start nucleotide. However, gene transcription usually involves multiple start sites, generating numerous 5’ isoforms. Thus, gene levels annotations cannot capture the diversity of m6Am modification in the transcriptome. Here we describe CROWN-seq, which simultaneously identifies transcription-start nucleotides and quantifies m6Am stoichiometry for each 5’ isoform that initiates with adenosine. Using CROWN-seq, we map the m6Am landscape in nine human cell lines. Our findings reveal that m6Am is nearly always a high stoichiometry modification, with only a small subset of cellular mRNAs showing lower m6Am stoichiometry. We find that m6Am is associated with increased transcript expression and provide evidence that m6Am may be linked to transcription initiation associated with specific promoter sequences and initiation mechanisms. These data suggest a potential new function for m6Am in influencing transcription.
Deoxysphingolipids activate cGAS-STING in colon cancer cells and enhance tumor immunity
Authors: Saha Suchandrima , Valezquez Fabiola N. , Dehpanah Fatemeh , Mao Cungui , Montrose David C. 
Published: October 2024

AbstractBioactive sphingolipids (SLs) play critical roles in cellular function, including modifying the oncogenic potential of cancer cells. Depletion of the non-essential amino acid serine induces an intracellular shift from the generation of canonical SLs to non-canonical SLs known as deoxySLs, which can exert antitumor effects. Recent evidence has shown that restricting endogenous and exogenous sources of serine from cancer cells promotes antitumor immunity by activating the cyclic GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) pathway. However, it is not known whether deoxySLs play a role in mediating this antitumor immune response. In this study, we demonstrated that depleting both externally supplied and internally synthesized serine from CT26 colon cancer cells maximally increased the levels of deoxySLs compared to removing either source alone. The ability of serine restriction to induce cytosolic accumulation of mitochondrial DNA (mtDNA) and subsequent activation of cGAS-STING components, including downstream Type I interferons (IFNs) was prevented by blocking deoxySL generation with the serine-palmitoyl transferase (SPT) inhibitor, myriocin. Direct administration of deoxysphinganine to cells induced mitochondrial dysfunction, in association with accumulation of cytosolic mtDNA, and increased expression of cGAS-STING components and Type I IFNs. A similar increase in IFNs was observed following mutation of SPT or supplementation of WT cells with alanine. Increasing deoxySLs in tumors through SPT mutation or feeding an alanine-enriched diet suppressed tumor growth in mice, while combining SPT mutation with a high alanine diet accentuated the antitumor effects. The observed tumor growth suppression was associated with increased infiltration of activated dendritic and cytotoxic T cells. Collectively, these findings reveal a novel role for deoxySLs in mediating antitumor immunity and provide support for the potential of using diet modification as an anticancer approach.
A human brain network linked to restoration of consciousness after deep brain stimulation
Authors: Warren Aaron E.L , Raguž Marina , Friedrich Helen , Schaper Frederic L.W.V.J. , Tasserie Jordy , Snider Samuel B. , Li Jian , Chua Melissa M.J. , Butenko Konstantin , Friedrich Maximilian U. , Jha Rohan , Iglesias Juan E. , Carney Patrick W. , Fischer David , Fox Michael D. , Boes Aaron D. , Edlow Brian L. , Horn Andreas , Chudy Darko , Rolston John D. 
Published: October 2024

ABSTRACTDisorders of consciousness (DoC) are states of impaired arousal or awareness. Deep brain stimulation (DBS) is a potential treatment, but outcomes vary, possibly due to differences in patient characteristics, electrode placement, or stimulation of specific brain networks. We studied 40 patients with DoC who underwent DBS targeting the thalamic centromedian-parafascicular complex. Better-preserved gray matter, especially in the striatum, correlated with consciousness improvement.Stimulation was most effective when electric fields extended into parafascicular and subparafascicular nuclei—ventral to the centromedian nucleus, near the midbrain— and when it engaged projection pathways of the ascending arousal network, including the hypothalamus, brainstem, and frontal lobe. Moreover, effective DBS sites were connected to networks similar to those underlying impaired consciousness due to generalized absence seizures and acquired lesions. These findings support the therapeutic potential of DBS for DoC, emphasizing the importance of precise targeting and revealing a broader link between effective DoC treatment and mechanisms underlying other conscciousness-impairing conditions.
A new AI-assisted data standard accelerates interoperability in biomedical research
Authors: Long Rodney Alan , Ballard Shannon , Shah Syed , Bianchi Owen , Jones Lietsel , Koretsky Mathew J. , Kuznetsov Nicole , Marsan Elise , Jen Bryant , Chiang Philip , Mukherjee Abhradeep , Blauwendraat Cornelis , Leonard Hampton , Vitale Dan , Levine Kristin , Bandres-Ciga Sara , Jarreau Paige , Brannelly Patrick , Pantazis Caroline , Screven Laurel , Andersh Kate , Kapasi Alifiya , Crary John F. , Gutman David , Dugger Brittany N. , Biber Sarah , Hohman Timothy , Faghri Faraz , Griswold Michael , Sargent Lana , van Keuren-Jensen Kendall , Singleton Andrew B. , Fann Yang , Nalls Mike A. , Iwaki Hirotaka 
Published: October 2024

AbstractIn this paper, we leveraged Large Language Models(LLMs) to accelerate data wrangling and automate labor-intensive aspects of data discovery and harmonization. This work promotes interoperability standards and enhances data discovery, facilitating AI-readiness in biomedical science with the generation of Common Data Elements (CDEs) as key to harmonizing multiple datasets. Thirty-one studies, various ontologies, and medical coding systems served as source material to create CDEs from which available metadata and context was sent as an API request to 4th-generation OpenAI GPT models to populate each metadata field. A human-in-the-loop (HITL) approach was used to assess quality and accuracy of the generated CDEs. To regulate CDE generation, we employed ElasticSearch and HITL to avoid duplicate CDEs and instead, added them as potential aliases for existing CDEs. The generated CDEs are foundational to assess the interoperability potential of datasets by determining how many data set column headers can be correctly mapped to CDEs as well as quantifying compliance with permissible values and data types. Subject matter experts reviewed generated CDEs and determined that 94.0% of generated metadata fields did not require manual revisions. Data tables from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Global Parkinson’s Genetic Program (GP2) were used as test cases for interoperability assessments. Column headers from all test cases were successfully mapped to generated CDEs at a rate of 32.4% via elastic search.The interoperability score, a metric for dataset compatibility to CDEs and other connected datasets, based on relevant criteria such as data field completeness and compliance with common harmonization standards averaged 53.8 out of 100 for test cases. With this project, we aim to automate the most tedious aspects of data harmonization, enhancing efficiency and scalability in biomedical research while decreasing activation energy for federated research.
Immune response induced by the Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (Ad5-nCoV) in persons living with HIV (PLWH)
Authors: Cahn P. , Barreto L. , Figueroa M.I. , Fink V. , Rolón M.J. , Lopardo G. , Casetti I. , Ceschel M. , Patterson P. , Gambardella L. , Miernes G. , Nava A. , Gou J. , Wang R. , Zhu T. , Halperin S.A. 
Published: October 2024

SummaryBackgroundDespite higher risk of poorer outcomes and potential sub-optimal vaccine effectiveness, people living with HIV (PLWH) are underrepresented in SARS-CoV-2 vaccine trials. We evaluated the safety and immunogenicity of the Ad5-nCoV vaccine (CanSino Biologics Inc./The Beijing Institute of Biotechnology) in PLWH.MethodsIn this single arm, open-label Phase 2b trial, PLWH were enrolled in Argentina. Participants received two doses of Ad5-nCoV vaccine (intramuscular, dosage 5×1010viral particles) at days 0 and 56. The primary outcomes were safety as serious adverse events [SAE], solicited and unsolicited local and systemic adverse events, impact on HIV viral load and CD4 counts and immunogenicity measured by S-RBD IgG and pseudo-virus neutralizing antibodies (nAbs) up to 52 weeks (ClinicalTrials.gov:NCT05005156).FindingsBetween June 2021-January 2022, 140 PLWH received at least one dose of Ad5-nCoV vaccine. At baseline, the majority were on antiretroviral therapy (99.3%), virologically suppressed (93.6%), with a median (IQR) CD4-cell count:736 (531-946) cells/ul. At baseline, 38 (27%) participants were seropositive for S-RBD antibodies, and 40 (28%) for nAbs. There were no SAEs related to the vaccine. Solicited AE within 7 days after first and second dose occurred in 93 (69%) and 75 (60%) participants, mostly grade 1, included pain, drowsiness and headache. The incidence of unsolicited AE within 28 days of vaccination was 10.7%. There were no significant changes in plasma viral load, CD4, CD4/CD8 ratio and no new AIDS-defining illnesses were reported. There were significant increases in the geometric mean titers (GMT) of S-RBD and nAbs between baseline to week 52. Seroconversion rates 28 days after the first and second doses (day 84) were 80% and 94% for S-RBD, and 35% and 78% for nAbs.InterpretationTwo doses of the Ad5-nCoV vaccine were safe and induced an adequate immune response in virologically suppressed PLWH, maintaining high antibody titers at least during the first year post-vaccination.FundingCanSino Biologics Inc, Tianjin, China