bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fusobacterium nucleatumdetermines the expression of amphetamine-induced behavioral responses through an epigenetic phenomenon
Authors: Mabry Samuel J. , Cao Xixi , Zhu Yanqi , Rowe Caleb , Patel Shalin , González-Arancibia Camila , Romanazzi Tiziana , Saleeby David P. , Elam Anna , Lee Hui-Ting , Turkmen Serhat , Lauzon Shelby N. , Hernandez Cesar E. , Sun HaoSheng , Wu Hui , Carter Angela M. , Galli Aurelio 
Published: January 2025

AbstractAmphetamines (AMPHs) are psychostimulants commonly used for the treatment of neuropsychiatric disorders. They are also misused (AMPH use disorder; AUD), with devastating outcomes. Recent studies have implicated dysbiosis in the pathogenesis of AUD. However, the mechanistic roles of microbes in AUD are unknown.Fusobacterium nucleatum(Fn) is a bacterium that increases in abundance in both rats and humans upon AMPH exposure.Fnreleases short-chain fatty acids (SCFAs), bacterial byproducts thought to play a fundamental role in the gut-brain axis as well as the pathogenesis of AUD. We demonstrate that in gnotobioticDrosophila melanogaster,colonization withFnor dietary supplementation of the SCFA butyrate, a potent inhibitor of histone deacetylases (HDACs), enhances the psychomotor and rewarding properties of AMPH as well as its ability to promote male sexual motivation. Furthermore, solely HDAC1 RNAi targeted inhibition recapitulates these enhancements, pointing to a specific process underlying thisFnphenomenon. Of note is that the expression of these AMPH behaviors is determined by the increase in extracellular dopamine (DA) levels that result from AMPH-induced reversal of DA transporter (DAT) function, termed non-vesicular DA release (NVDR). The magnitude of AMPH-induced NVDR is dictated, at least in part, by DAT expression levels. Consistent with our behavioral data, we show thatFn, butyrate, and HDAC1 inhibition enhance NVDR by elevating DAT expression. Thus, the participation ofFnin AUD stems from its ability to release butyrate and inhibit HDAC1. These data offer a microbial target and probiotic interventions for AUD treatment.
Prior use-dependent plasticity triggers different individual corticomotor responses during persistent musculoskeletal pain
Authors: Zamorano Anna M. , Kleber Boris , De Martino Enrico , Insausti-Delgado Ainhoa , Vuust Peter , Flor Herta , Graven-Nielsen Thomas 
Published: January 2025

ABSTRACTMovement repetition is crucial for pain interventions. It facilitates the rehabilitation of motor patterns, the acquisition of motor skills and the genesis of adaptive use-dependent plasticity. However, the influence of prior motor experience and pre-existing use-dependent plasticity on pain severity and progression remains poorly investigated. This study investigated the effects of pre-existing use-dependent plasticity during the development of prolonged experimental musculoskeletal pain. Using transcranial magnetic stimulation, corticospinal excitability was assessed by measuring the rest-motor thresholds (RMTs), motor-evoked potential (MEP), representational area of the motor map, volume, and center of gravity of the first dorsal interosseous (FDI) muscle in musicians (n=19), a well-known ecological model of use-dependent plasticity, and in non-musicians (n=20). All participants attended three sessions (Day1, Day3, Day8). Prolonged pain for several days was induced by intramuscular injection of nerve growth factor (NGF) into the right FDI muscle at the end of Day1. Compared to Day1, prolonged pain uniquely led to reduced motor map volume in non-musicians on Day3 (p=0.004), who also showed higher NGF-related pain intensity compared to musicians. The motor maps of musicians, which were already smaller in pain-free conditions (Day1) compared to non-musicians (p=0.021), remained non-significantly different across days. Notably, corticomotor responses (map volume, MEP amplitude, and RMTs) at Day1 were correlated to weekly and accumulated musical training. These findings demonstrate that pre-existing use-dependent plasticity associated with motor training may counteract the effects of prolonged pain in the motor system. Moreover, it confirms that prior motor experience acts as a source of individual variability to pain.
NUBP2deficiency disrupts the centrosome-check point in the brain and causes primary microcephaly
Authors: Rushforth Rebekah , Shamseldin Hanan E , Costantino Nicole , Michaels JES-Rite , Sawyer Sarah L , Osmond Matthew , Kurdi Wesam , Abdulwahab Firdous , DiStasio Andrew ,   Care4Rare Canada Consortium, Boycott Kym M. , Alkuraya Fowzan S. , Stottmann Rolf W. 
Published: January 2025

AbstractMicrocephaly affects 1 in 2,500 babies per year. Primary microcephaly results from aberrant neurogenesis leading to a small brain at birth. This is due to altered patterns of proliferation and/or early differentiation of neurons. Premature differentiation of neurons is associated with defects in the centrosome and/or primary cilia. In this study, we report on the first patients identified withNUBP2-deficiency and utilize a conditional mouse model to ascertain the molecular mechanisms associated withNUBP2-deficient primary microcephaly. We identified homozygousNUBP2variants in these patients who displayed profound primary microcephaly in addition to intrauterine growth restriction, cervical kyphosis, severe contractures of joints, and facial dysmorphia. We then generated a mouse model usingEmx1-Creto ablateNubp2from the forebrain. The mice presented with severe microcephaly starting at E18.5. Neurospheres generated from the forebrain ofEmx1-Cre; Nubp2flox/floxconditional deletion mice were used to support the pathogenicity of the patient variants. We show that loss ofNubp2increases both canonical and non-canonical cell death, but that loss ofp53fails to rescue microcephaly in the mouse model. Examination of neurogenesis inEmx1-Cre; Nubp2flox/floxmice revealed distinct alterations in proliferation and cellular migration accompanied by supernumerary centrosomes and cilia. We therefore propose thatNUBP2is a novel primary microcephaly-related gene and that the role ofNubp2in centrosome and cilia regulation is crucial for proper neurogenesis.
Trio-Based Whole-Genome Sequencing for Critically Ill Pediatric Patients in Korea
Authors: Lee Seungbok , Koh June-Young , Lim Joonoh , Cho Jaeso , Kim Woojoong , Lee Yuna , Yi Boram , Joo Eunjung , Jung Dawoon , Lim Byung Chan , Kim Soo Yeon , Chae Jong-Hee 
Published: January 2025

AbstractThis study aimed to implement genome sequencing using an automated pipeline for critically ill pediatric patients within a real-world healthcare system. Twenty patients under 36 months of age, admitted to the NICU/PICU or suspected of having rapidly progressive genetic disorders, were enrolled. Trio-based genome sequencing was performed using an optimized processing pipeline, which automatically performed mapping, variant calling, annotation, and in silico pathogenicity assessment. Among 20 enrolled patients, 11 (55%) were from the NICU, and 16 (80%) presented with neurological manifestations as their chief complaint. The median time from symptom onset to study enrollment was 73 days for 18 patients referred from other hospitals and less than a week for 2 in-hospital patients. The median turnaround time (TAT) for rWGS was 10 days, with the shortest being 5 days. A definite or presumed genetic diagnosis was made in 11 patients (55%), including 10 of 16 with neurological symptoms (62.5%) and 1 of 4 with non-neurologic symptoms (25%). Management plans were modified for 8 of the 11 patients (72.7%), including medication changes, diet modifications, and preimplantation genetic testing for future pregnancies. This study highlights the feasibility and clinical utility of WGS in critically ill pediatric patients in Korea, demonstrating a high diagnostic yield and significant impact on patient management, particularly among those presenting with neurologic symptoms. Establishing a nationwide fast-track system and providing detailed testing indications are required for effective implementation. Further automation and resource optimization could reduce the TAT and improve the efficacy of rWGS in critical care settings.
Assessing Supervised Natural Language Processing (NLP) Classification of Violent Death Narratives: Development and Assessment of a Compact Large Language Model (LLM) Approach
Authors: Parker Susan T. 
Published: January 2025

AbstractObjectiveThe recent availability of law enforcement and coroner/medical examiner reports for nearly every violent death in the US expands the potential for natural language processing (NLP) research into violence. The objective of this work is to assess applications of supervised NLP to unstructured narrative data in the National Violent Death Reporting System (NVDRS).Materials and MethodsThis analysis applied distilBERT, a compact LLM, to unstructured narrative data to simulate the impacts of pre-processing, volume and composition of training data on model performance, evaluated by F1-scores, precision, recall and the false negative rate. Model performance was evaluated for bias by race, ethnicity, and sex by comparing F1-scores across subgroups.ResultsA minimum training set of 1,500 cases was necessary to achieve an F1-score of 0.6 and a false negative rate of .01-.05 with a compact LLM. Replacement of domain-specific jargon improved model performance while oversampling positive class cases to address class imbalance did not substantially improve F1 scores. Between racial and ethnic groups, F1-score disparities ranged from 0.2 to 0.25, and between male and female victims differences ranged from 0.12 to 0.2.DiscussionFindings demonstrate that compact LLMs with sufficient training data can be applied to supervised NLP tasks to events with class imbalance in NVDRS unstructured police and coroner/medical examiner reports.ConclusionSimulations of supervised text classification across the model-fitting process of pre-processing and training a compact LLM informed NLP applications to unstructured death narrative data.
Acute cortical stroke alters neural activity in subthalamic nucleus, which correlates with motor disability in rats
Authors: Deng Zhengdao , Laughlin Myles MC , Kilic Ugur , Asamoah Boateng , Nuttin Bart 
Published: January 2025

AbstractObjectivesWe aimed to investigate the impact of acute cortical stroke (ACS) on neural activity in subthalamic nucleus (STN). We then examined the correlation between changes in STN activity and motor disability.MethodsForty-four Sprague-Dawley rats were used. While rats were anesthetized, we inserted electrodes in STN and induced an ACS by creating photothrombotic lesion in ipsilateral motor cortex. Local field potentials were recorded before and after ACS. The motor behavior was assessed before and after ACS using single pellet reaching task.ResultsRats experienced significant motor disability after ACS. STN firing rate significantly decreased after ACS. Additionally, delta (0.5-4 Hz) and gamma (50-140 Hz) power significantly decreased after ACS. Furthermore, the decrease in delta mean power correlated with decreases in success rate (r =0.77,p=0.009) and first try success rate (r =0.69,p=0.028). The decreases in gamma mean power (r =0.68,p=0.029) and gamma peak power (r =0.74,p=0.015) correlated with the decrease in success rate. The decrease in gamma power significantly correlated with the decreased STN firing rate. However, decreased delta power exhibited no correlation with decreased gamma power.InterpretationACS causes abnormal STN activity, which correlated with motor disability. Post-stroke STN inhibition may partially compensate for ACS. However, it could also lead to pathological consequences. This STN abnormal activity may serve as a biomarker for motor disability severity after ACS. Furthermore, our findings may provide a possibility for developing neuromodulation strategies, allowing to mitigate post-stroke motor disability through modulating abnormal STN activity.
Delineation and monitoring of the T cell repertoire of adoptive cell transfer product during the treatment of advanced melanoma
Authors: Kerr Cameron , Soleimani Shirin , Mulder David T. , Nabbi Arash , Gray Diana , Pedersen Stephanie , Sotov Valentin , Sudhaman Sumedha , Nguyen Linh , Hirano Naoto , Ohashi Pamela S. , Butler Marcus O. , Pugh Trevor J. 
Published: January 2025

ABSTRACTBackgroundAdoptive cell transfer (ACT) of Tumour-infiltrating lymphocytes (TIL) is an investigational treatment for solid tumours, with preliminary results showing objective clinical responses in some metastatic melanoma patients. The ability to sequence and track the T cell repertoire throughout ACT of TILs provides a method to identify T cell repertoire features associated with patients’ benefit from ACT. Identification of response biomarkers for patients receiving ACT of TILs has been limited. Conflicting evidence is observed in biomarkers such as the number of TILs in the infusion product, with some studies suggesting a relationship with response and others not. Meanwhile, certain potential biomarkers, such as the diversity of the post- infusion peripheral repertoire, have not yet been studied.MethodsIn this study, we sought to determine 1) the efficacy of using CapTCR-seq to track TILs in serial blood draws over the course of ACT immunotherapy 2) whether peripheral T cell repertoire statistics are associated with ACT response. In this study, 9 patients with cutaneous (n = 7) or mucosal (n = 2) melanoma received TIL ACT after chemotherapeutic depletion. Hybrid- capture CapTCR-seq was conducted on pre-/post-transfer peripheral blood mononuclear cells (PBMC) and cell-free DNA.ResultsComparison between PBMC DNA, PBMC RNA, and circulating free DNA (cfDNA) repertoires demonstrated an increased presence of shared T cell clonotypes post-infusion when compared with baseline samples. Higher abundance of TIL clonotypes in the PBMC baseline and post-infusion DNA T cell repertoires and the presence of shared DNA T cell clonotypes between timepoints was seen in responders when compared with non-responders according to RECIST criteria.ConclusionThese results demonstrate effective tracking methodologies and suggest a predictive role for baseline repertoire statistics in response to the ACT of TILs.Trial registrationUniversity Health Network Research Ethics Board #11-0683
Intra-arterial transplantation of autologous mesoangioblasts in m.3243A>G mutation carriers is safe – first phase I/II human clinical study
Authors: van Tienen Florence H.J. , Hoeijmakers Janneke G.J. , van der Leij Christiaan , Timmer Erika , Wanders Nikki , Lindsey Patrick J. , Yi Fangzheng , Lin Fong , Kortekaas Susanne P.M. , Roelofs Helene , Westra Inge M. , Meij Pauline , Wijnen Lambert A.C.M. , de Coo Irenaeus F.M. , Smeets Hubert J.M. 
Published: January 2025

AbstractProgressive myopathy and exercise intolerance significantly impair quality of life in over 50% of m.3243A>G mutation carriers, with no curative therapy currently available. We hypothesize that intra-arterial administration of autologous, mtDNA mutation-free myogenic stem cells, mesoangioblasts, can reduce mutation load, enhance oxidative phosphorylation, and improve muscle function. To test this, the tibialis anterior muscles of three m.3243A>G mutation carriers were damaged by eccentric exercise before infusion of 50 million /kg autologous mesoangioblasts into the left anterior tibial artery. The right tibialis anterior muscle served as control. Expanded mesoangioblasts had a mutation load of <15%, though culturing increased this by 7–15%. Infusion caused mild, transient discomfort without serious adverse events or vascular obstructions, as confirmed by angiography. Blood and muscle biopsies revealed no systemic or local inflammation at 24 hours and 4 weeks post-transplantation. Biopsies of the treated muscle suggested mesoangioblast migration and early signs of regeneration. This first-in-human study demonstrates that intra-arterial administration of autologous mesoangioblasts is safe, with promising, though inconclusive, evidence for muscle regeneration and mesoangioblast homing. These findings support further investigation into the therapeutic potential of mesoangioblasts for treating myopathy in m.3243A>G mutation carriers.
Recipient Cells Are the Source of Hematologic Malignancies After Graft Failure and Mixed Chimerism in Adults with SCD
Authors: Ali Mohamed A. E. , Limerick Emily M. , Hsieh Matthew M. , Upadhyaya Kalpana , Xu Xin , Phang Oswald , Mukendi Jean Pierre Kambala , Calvo Katherine R. , Lopez-Ocasio Maria , Dagur Pradeep , Fitzhugh Courtney D. 
Published: January 2025

AbstractNon-myeloablative hematopoietic cell transplantation (HCT) is a curative option for individuals with sickle cell disease (SCD). Our traditional goal with this approach has been to achieve a state of mixed donor/recipient chimerism. Recently, we reported an increased risk of hematologic malignancies (HMs) in adults with SCD following graft failure or mixed chimerism. To evaluate the origin of HMs, we performed chimerism analyses of 5 patients with SCD who developed HMs after non-myeloablative HCT. DNA was extracted from sorted peripheral blood or bone marrow cells representing mature cell lineages or leukemic blasts and subjected to chimerism analysis by PCR amplification of polymorphic short tandem repeats. Unlike mature cell lineages in patients with mixed chimerism, which still showed a donor-derived fraction of cells, leukemic blast cells were found to be 99-100% recipient-derived in all patients. Non-myeloablative conditioning allows for the survival of patients’ cells that might harbor pre-leukemic clones that possess the capacity to evolve under genotoxic or environmental stress into malignancies; therefore, we have modified our HCT protocols with the goal of full donor chimerism to mitigate the risk of HM development.
Understanding Data Differences across the ENACT Federated Research Network
Authors: Wang Taowei D , Henderson Darren W , Weber Griffin M , Morris Michele , Sadhu Eugene M , Murphy Shawn N , Visweswaran Shyam , Klann Jeff G 
Published: January 2025

ABSTRACTObjectiveFederated research networks, like Evolve to Next-Gen Accrual of patients to Clinical Trials (ENACT), aim to facilitate medical research by exchanging electronic health record (EHR) data. However, poor data quality can hinder this goal. While networks typically set guidelines and standards to address this problem, we developed an organically evolving, data-centric method using patient counts to identify data quality issues, applicable even to sites not yet in the network.Materials and MethodsWe distribute high-performance patient counting scripts as part of Integrating Biology at the Bedside (i2b2), which all ENACT sites operate. They produce counts of patients associated with ENACT ontology terms for each site. At the ENACT Hub, our pipeline aggregates site-contributed counts to produce network statistics, which our self-service web application, Data Quality Explorer (DQE), ingests to help sites conduct data quality investigation relative to the network.ResultsThirteen ENACT sites have contributed their patient counts, and currently seven sites have signed up to use DQE to analyze data quality issues. We announced a call to all ENACT sites to contribute additional patient counts.DiscussionIdentifying site data quality problems relative to the network is novel. Using a metric based on evolving network statistics complements rigid data quality checks. It is adaptable to any network and has low barriers of entry, with patient counting being the sole requirement.ConclusionWe implemented a metric for conducting data quality investigation in ENACT using patient counting and network statistics. Our end-to-end pipeline is privacy-preserving and the underlying design is generalizable.
The Pandemic Journaling Project: A new dataset of first-person accounts of the COVID-19 pandemic
Authors: Willen Sarah S. , Mason Katherine A. , Wurtz Heather M. , Karcher Sebastian 
Published: January 2025

ABSTRACTBackgroundThe rapid global spread of the COVID-19 pandemic affected different regions, communities, and individuals in vastly different ways that interdisciplinary social scientists are well-positioned to document and investigate. This paper describes an innovative mixed-methods dataset generated by a research study that was designed to chronicle and preserve evidence of the pandemic’s divergent effects: the Pandemic Journaling Project (PJP). The dataset was generated by leveraging digital technology to invite ordinary people around the world to document the impact of the COVID-19 pandemic on their everyday lives over a two-year period (May 2020-May 2022) using text, images, and audio.Methods and FindingsPJP’s weekly, online, bilingual (English/Spanish) journaling platform was open to anyone with access to a smartphone or computer, including teens aged 15–17 with permission of a parent or guardian. Participants first completed a baseline quantitative survey, after which they were invited to create two journal entries in response to suggested narrative prompts. In each subsequent week, participants received weekly invitations to contribute via their choice of email or SMS (text message). Each invitation included a link to that week’s journaling prompts and accompanying survey questions.Participants could join the project at any point between May 2020 and May 2022. PJP employed a cohort design. Regardless of when they joined, all received the narrative prompts and accompanying survey questions in the same order. Participants could stop participating at any point, and they could later restart if they wished. The project welcomed any interested participant and sought to capture as broad a range of perspectives as possible, while also taking measures to include voices that might not otherwise be preserved in the historical record.The project launched in May 2020. In the two years it operated as a weekly journaling platform, PJP generated nearly 27,000 individual journal entries from over 1,800 people in 55 countries around the world. Data from PJP’s first phase (PJP-1) are now accessible at the Qualitative Data Repository (QDR) at Syracuse University.ConclusionsThe first phase of the Pandemic Journaling Project has produced an innovative multimedia dataset that can support studies of how the COVID-19 pandemic has affected a wide range of communities across a wide range of outcomes including mental health, reproductive health, vaccine hesitancy, and trust in health professionals, among others. The dataset is available to researchers who follow established data protection protocols and procedures. These data protection measures will be in place for 25 years, through 2049, after which all PJP-1 data will become a fully accessible public archive via QDR.