bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Age and Noise Exposure History on Auditory Nerve Response Amplitudes: A Systematic Review, Study, and Meta-Analysis
Authors: Dias James W. , McClaskey Carolyn M. , Alvey April P. , Lawson Abigail , Matthews Lois J. , Dubno Judy R. , Harris Kelly C. 
Published: March 2024

AbstractAuditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r=-0.407), but noise-exposure effects are weak (r=-0.152). We conclude that noise-exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem.
Mitochondrial stress in GABAergic neurons non-cell autonomously regulates organismal health and aging
Authors: Rathor Laxmi , Curry Shayla , Park Youngyong , McElroy Taylor , Robles Briana , Sheng Yi , Chen Wei-Wen , Min Kisuk , Xiao Rui , Lee Myon Hee , Han Sung Min 
Published: March 2024

AbstractMitochondrial stress within the nervous system can trigger non-cell autonomous responses in peripheral tissues. However, the specific neurons involved and their impact on organismal aging and health have remained incompletely understood. Here, we demonstrate that mitochondrial stress in γ-aminobutyric acid-producing (GABAergic) neurons inCaenorhabditis elegans(C. elegans) is sufficient to significantly alter organismal lifespan, stress tolerance, and reproductive capabilities. This mitochondrial stress also leads to significant changes in mitochondrial mass, energy production, and levels of reactive oxygen species (ROS). DAF-16/FoxO activity is enhanced by GABAergic neuronal mitochondrial stress and mediates the induction of these non-cell-autonomous effects. Moreover, our findings indicate that GABA signaling operates within the same pathway as mitochondrial stress in GABAergic neurons, resulting in non-cell-autonomous alterations in organismal stress tolerance and longevity. In summary, these data suggest the crucial role of GABAergic neurons in detecting mitochondrial stress and orchestrating non-cell-autonomous changes throughout the organism.
Animal group size variation in a minimal attraction-repulsion agent-based model
Authors: Eikelboom Jasper A.J. , Doelman Arjen , van Langevelde Frank , de Knegt Henrik J. 
Published: March 2024

AbstractGrouping behaviour of prey animals is thought to be mainly driven by fear of predation and resource scarcity. Fear of predation often leads to small inter-individual distances, while resource scarcity leads to the opposite. Consequently, it is believed that the number of individuals in a group (group size) is an emergent property of the trade-off between acquiring scarce resources and preventing predation. We analysed whether group size can be reliably used as a proxy for this trade-off, using a deterministic attraction-repulsion agent-based model in a homogeneous area. In our model, each individual experiences distancedependent attraction and repulsion to all others in the area, where varying degrees of grouping behaviour emerge from the number and distance of intersections between the attraction and repulsion functions. We show that the coefficient of variation of group size generally lies between 50 and 150%, depending on both animal density and the trade-off between resource scarcity and predation. Given that the variations of group size are already this large in homogeneous and deterministic scenarios, we urge researchers to be cautious in using group size as a proxy for the resources/predation trade-off and consider inter-individual distance as a more direct and potentially more reliable alternative.
A method for focused ultrasound (FUS) neuromodulation with simultaneous electroencephalogram recordings in awake, head-fixed mice with temporal lobe epilepsy
Authors: Cornelssen Carena , Brown Braden , Finlinson Eli , Blair Skyler , Senthilkumar Sharayu , Kubanek Jan , Wilcox Karen S. 
Published: March 2024

AbstractTranscranial focused ultrasound (FUS) may be a promising neuromodulation technology for treating people with epilepsy whose seizures are drug resistant. Prior studies have shown seizure suppression in animal studies using FUS. However, most of these studies were performed in evoked seizure models and not in animal models of epilepsy. Evoked seizure models do not exhibit the pathophysiology of epilepsy and do not exhibit spontaneous recurrent seizures, which define epilepsy. For translation to humans, there is a critical need to determine the specific FUS stimulation parameters that reduce spontaneous recurrent seizures in a chronic disease model of epilepsy. To achieve this goal, we developed and optimized an approach to determine the effects of ultrasonic stimulation on metrics of seizure-like events (SLEs) in awake, head-fixed mice within the intrahippocampal kainate (IHK) mouse model of temporal lobe epilepsy (TLE). A proof-of-principle study demonstrated that two target (bilateral and contralateral to the kainic acid injection site) stimulation conditions and two FUS parameter sets (low and high pressure) could be combined with the ability to simultaneously record hippocampal electroencephalograms. We also provide a method for analysis of the effects of FUS stimulation on the metrics of SLEs (interevent duration, SLE duration, and spike frequency).
Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage inC. elegans
Authors: Yan Junran , Bhanshali Forum , Shuzenji Chiaki , Mendenhall Tsultrim T. , Cheng Xuanjin , Bai Pamela , Diwan Gahan , Seraj Donna , Meyer Joel N. , Sorensen Poul H. , Hartman Jessica H. , Taubert Stefan 
Published: March 2024

AbstractCells and organisms frequently experience starvation. To adapt and survive, they mount an evolutionarily conserved stress response. A vital component in the mammalian starvation response is eukaryotic elongation factor 2 (eEF2) kinase (eEF2K), which responds to starvation by phosphorylating and inactivating the translation elongation driver eEF2, thus shutting down translation and facilitating survival.C. elegans efk-1/eEF2Kphosphorylates EEF-2/eEF2 on a conserved residue and is required for starvation survival, but how it promotes survival remains unclear. Surprisingly, we found that eEF2 phosphorylation is unchanged in starvedC. elegans, suggesting thatefk-1promotes survival via a noncanonical pathway. We show thatefk-1upregulates transcription of the DNA repair pathways, nucleotide excision repair (NER) and base excision repair (BER), to promote starvation survival. Furthermore,efk-1suppresses oxygen consumption and ROS production in starvation to prevent oxidative stress. Thus,efk-1enables starvation survival by protecting animals from starvation-induced oxidative damage through a translation-independent pathway.
Detection of Drug Effect Signals Associated with Adverse Pregnancy Outcomes Using Propensity Score Matching at Scale
Authors: Hwang Yeon Mi , Piekos Samantha N. , Wei Qi , Price Nathan D. , Hood Leroy , Hadlock Jennifer J. 
Published: March 2024

ABSTRACTObjectiveWe applied propensity score matching method at scale on patient records to confirm signals of known drug effects on preterm birth and detect previously unidentified potential drug effects.Materials and MethodsThis was a retrospective study on women who had continuity of care at Providence St. Joseph Health (PSJH) both before and after pregnancy and delivered live births between 2013/01/01 and 2022/12/31 (n=365,075). Our exposures of interest were all outpatient medications prescribed during pregnancy. We limited our analyses to medication that met the minimal sample size (n=600). The primary outcome of interest was preterm birth. Secondary outcomes of interest were small for gestational age and low birth weight. We used propensity score matching at scale to evaluate the risk of these adverse pregnancy outcomes associated with drug exposure after adjusting for demographics, pregnancy characteristics, and comorbidities.ResultsThe total medication prescription rate increased from 58.5% to 75.3% (P<0.0001) from 2013 to 2022. The prevalence rate of preterm birth was 7.7%. 175 out of 1329 prenatally prescribed outpatient medications met the minimum sample size. We identified 58 medications statistically significantly associated with the risk of preterm birth (P≤0.1; decreased: 12, increased: 46).DiscussionWe narrowed down from 1329 medications to 58 medications that showed statistically significant association with the risk of preterm birth even after addressing numerous covariates through propensity score matching.ConclusionThis data-driven approach demonstrated that multiple testable hypotheses in pregnancy pharmacology can be prioritized at scale, laying the foundation for application in other pregnancy outcomes.
A Novel Sentence Transformer-based Natural Language Processing Approach for Schema Mapping of Electronic Health Records to the OMOP Common Data Model
Authors: Zhou Xinyu , Dhingra Lovedeep Singh , Aminorroaya Arya , Adejumo Philip , Khera Rohan 
Published: March 2024

AbstractMapping electronic health records (EHR) data to common data models (CDMs) enables the standardization of clinical records, enhancing interoperability and enabling large-scale, multi-centered clinical investigations. Using 2 large publicly available datasets, we developed transformer-based natural language processing models to map medication-related concepts from the EHR at a large and diverse healthcare system to standard concepts in OMOP CDM. We validated the model outputs against standard concepts manually mapped by clinicians. Our best model reached out-of-box accuracies of 96.5% in mapping the 200 most common drugs and 83.0% in mapping 200 random drugs in the EHR. For these tasks, this model outperformed a state-of-the-art large language model (SFR-Embedding-Mistral, 89.5% and 66.5% in accuracy for the two tasks), a widely-used software for schema mapping (Usagi, 90.0% and 70.0% in accuracy), and direct string match (7.5% and 7.5% accuracy). Transformer-based deep learning models outperform existing approaches in the standardized mapping of EHR elements and can facilitate an end-to-end automated EHR transformation pipeline.
Cost-effectiveness of RSVpreF vaccine and nirsevimab for the prevention of respiratory syncytial virus disease in Canadian infants
Authors: Gebretekle Gebremedhin B. , Yeung Man Wah , Ximenes Raphael , Cernat Alexandra , Simmons Alison E. , Killikelly April , Siu Winnie , Rafferty Ellen , Brousseau Nicholas , Tunis Matthew , Tuite Ashleigh R. 
Published: March 2024

AbstractBackgroundHealth Canada recently authorized the RSVpreF pregnancy vaccine and nirsevimab to protect infants against respiratory syncytial virus (RSV) disease.ObjectiveAssess the cost-effectiveness of RSVpreF and nirsevimab programs in preventing RSV disease in infants, compared to a palivizumab program.MethodsWe used a static cohort model of a Canadian birth cohort during their first RSV season to estimate sequential incremental cost-effectiveness ratios (ICERs) in 2023 Canadian dollars per quality-adjusted life year (QALY) for nine strategies implemented over a one-year time period, from the health system and societal perspectives. Sensitivity and scenario analyses were conducted to explore the impact of uncertainties on the results.ResultsAll-infants nirsevimab programs averted more RSV-related outcomes than year-round RSVpreF programs, with the most RSV cases averted in seasonal nirsevimab programs. Assuming list prices for these immunizing agents, all-infants nirsevimab and year-round RSVpreF programs were never cost-effective, with ICERs far exceeding commonly used cost-effectiveness thresholds. Seasonal nirsevimab with catch-up was cost-effective if prioritized for infants at moderate/high-risk (ICER <$28,000 per QALY) or those living in settings with higher RSV burden and healthcare costs (ICER of $5,700 per QALY). Using a $50,000 per QALY threshold, an all-infants nirsevimab program could be optimal if nirsevimab is priced at <$110-190 per dose. A year-round RSVpreF for all pregnant women/pregnant people plus nirsevimab for infants at high-risk was optimal if nirsevimab is priced at >$110-190 and RSVpreF priced at <$60-125.InterpretationProphylactic interventions can substantially reduce RSV disease in infants, and targeted nirsevimab programs are the most cost-effective option at current product prices.
Axonal degeneration serum markers and temporal lobe atrophy in Alzheimer’s dementia continuum: a longitudinal study of plasma neurofilament light and tensor-based morphometry
Authors: Khodadadi Amirhossein , Amirkhani Nikan , Nouri Zahra , Adlparvar Tanin , Eskandari Sanaz , Barzgar Rezvan , Sojoudi Pouya , Mayeli Mahsa 
Published: March 2024

AbstractThe plasma neurofilament light chain (NfL), an axonal cytoskeleton protein, increases in Alzheimer’s disease and was therefore proposed as a blood-based biomarker of the disease. Tensor-based morphometry (TBM) is an MR based modality that identifies local volume changes in the brain. Herein, we aimed to investigate whether plasma NfL measures can predict TBM findings derived from temporal lobe of brain in a one-year follow-up and which biomarker can predict cognitive function. A total of 480 participants with Alzheimer’s disease (AD), mild cognitive impairment (MCI), and normal cognition (CN) were found eligible for inclusion from The Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. There was a significant negative association between plasma NfL and TBM only when all subjects were pooled together at baseline (β = -0.139,P=0.004). After one-year follow-up, 30 subjects with MCI converted to AD (MCI-AD) and others remained unchanged (CN, MCI, AD). Plasma NfL levels elevated significantly only in MCI group after one year (P<0.001). We found a significant reduction in TBM measurements at first-year compared to baseline in all groups (P<0.001 for all groups). Additionally, TBM average change rate was significantly higher in MCI-AD and AD groups (P<0.001 for both); however, plasma NfL average change rate was not significantly different between groups. TBM was significantly correlated with MMSE, MoCA, ADAS-11 and ADAS-13 scores in both MCI and AD patients at baseline and after one year, whereas plasma NfL was not. Overall, our findings indicate that plasma NfL is not reliably associated with TBM, and is less effective and sensitive than TBM in predicting dementia progression and cognitive performance. Hence, TBM reduction is not reflected in plasma NfL increment after one year follow-up.
The Functional Communication Checklist for People Living with Primary Progressive Aphasia: Study Protocol
Authors: Gallée Jeanne , Cartwright Jade , Henry Maya L , Mooney Aimee , Stark Brielle C , Volkmer Anna , Nakano Connie , Fredericksen Rob J , Domoto-Reilly Kimiko , Crane Paul K 
Published: March 2024

AbstractThis study protocol describes the development of the first instrument of functional communication for people living with primary progressive aphasia (PPA), with future applications to other progressive conditions, with expert validation, item-level reliability analyses, and stakeholder input and outcomes. Progressive conditions like PPA require monitoring, and as such, re-assessment. Re-assessment poses the high risk of being burdensome, destructive, and of little use to the patient. As such, there is a significant need to establish a validated and reliable measure that (1) poses minimal patient burden and (2) captures communication ability in a strengths-based manner that is representative of daily communication needs and challenges. A strengths-based approach to assessment is widely recognized as the optimal way to promote patient autonomy, minimize harm, and implement functional treatment protocols and strategies. To date, there are no strengths-based assessment tools that were developed for people living with PPA. This study protocol describes our work to address this gap in clinical practice and research.
Paraneoplastic renal dysfunction in fly cancer models driven by inflammatory activation of stem cells
Authors: Kwok Sze Hang , Liu Yuejiang , Bilder David , Kim Jung 
Published: March 2024

ABSTRACTTumors can induce systemic disturbances in distant organs, leading to physiological changes that enhance host morbidity. In Drosophila cancer models, tumors have been known for decades to cause hypervolemic ‘bloating’ of the abdominal cavity. Here we use allograft and transgenic tumors to show that hosts display fluid retention associated with autonomously defective secretory capacity of fly renal tubules, which function analogous to those of the human kidney. Excretion from these organs is blocked by abnormal cells that originate from inappropriate activation of normally quiescent renal stem cells (RSCs). Blockage is initiated by IL-6-like oncokines that perturb renal water-transporting cells, and trigger a damage response in RSCs that proceeds pathologically. Thus, a chronic inflammatory state produced by the tumor causes paraneoplastic fluid dysregulation by altering cellular homeostasis of host renal units.Significance StatementTumors cause pathophysiological changes to host tissues, including distant organs. Here we use fruit fly cancer models to uncover mechanisms underlying paraneoplastic renal dysfunction. IL-6-like signaling from the tumor induces inflammatory signaling in renal tubule cells. Defects in these cells are sensed by normally quiescent renal stem cells, leading to inappropriate proliferation in a damage-like response. Chronic activation in the tumor context results in physical obstruction of tubule ducts and thus failures in fluid clearance. This fly work can prompt investigation of analogous mechanisms underlying renal dysfunction in cancer patients.
Overview of prognostic factors in adult glioma; a 10-year experience at a single institution
Authors: Behrooz Amir Barzegar , Ramandi Hadi Darzi , Latifi-Navid Hamid , Peymani Payam , Tarharoudi Rahil , Momeni Nasrin , Sabaghpour Azarian Mohammad Mehdi , Eltonsy Sherif , Pour-Rashidi Ahmad , Ghavami Saeid 
Published: March 2024

AbstractObjectiveThe most prevalent central nervous system (CNS) neoplasm arising from glial cells is glioma, which diffusely invades brain tissue. Among gliomas, Glioblastoma (GBM) is a glioma of the highest grade and associated with a grim prognosis, with a median overall survival of 15 months with and 3-4 months without therapy. We examined how clinical variables and molecular profiles may have affected overall survival (OS) at Sina Hospital in Tehran over the past ten years.MethodsA retrospective study was conducted at Sina Hospital in Tehran, Iran, and examined patients ≥ 11 years with confirmed glioma diagnoses between 2012 and 2020. We evaluated the correlation between OS in GBM patients and sociodemographic as well as clinical factors, including age, gender, extent of tumor resection, tumor location, chemo/radiotherapy, and molecular profiling based on IDH1, MGMT, TERT, and EGFR status. Kaplan-Meier and multivariate Cox regression models were used to assess patient survival.ResultsFollowing a comprehensive evaluation of medical records, 186 patients were enrolled in the study. The median OS was 20 months, with a 2-year survival rate of 62.5%. Among the 132 patients with available IDH measurements, 105 (79.5%) exhibited IDH1 wild-type tumors. Of the 132 patients with assessed MGMT methylation, 94 (71.2%) had MGMT methylated tumors. TERT promoter methylation was detected in 112 out of 132 cases (84.8%), while no methylation was observed in 20 cases (15.2%). Analyses using multivariable models revealed that age at histological grade (P< 0.0001), adjuvant radiotherapy (P< 0.014), IDH1 status (P< 0.026), and TERT promoter status (P< 0.030) were independently associated with OS.ConclusionThe findings of this study demonstrate that patients with higher tumor histological grades who had received adjuvant radiotherapy, exhibited IDH1 mutations, or presented with TERT promoter mutations, experienced improved OS. The median survival time was 20 months, with 15.6% and 46.9% of patients surviving at 12 and 24 months, respectively.
Polygenic susceptibility for multiple sclerosis is associated with working memory in low-performing young adults
Authors: Petrovska J. , Coynel D. , Freytag V. , de Quervain D. J.-F. , Papassotiropoulos A. 
Published: March 2024

AbstractBackgroundMultiple sclerosis (MS) is a genetically complex disease with substantial heritability estimates. Besides typical clinical manifestations such as motor and sensory deficits, and fatigue, MS is characterized by structural and functional brain abnormalities, and by cognitive impairment such as decreased working memory (WM) performance.ObjectivesThis study investigates the possible link between the polygenic risk for MS and WM performance in healthy adults aged 18 – 35 years. Additionally, it addresses in the same population the relationship between polygenic risk for MS and brain white matter properties, as represented by measures of fractional anisotropy (FA).MethodsWe generated a polygenic risk score (PRS) of MS and investigated its association with WM performance in a population of 3282 healthy adults, which consisted of two subsamples (N1=1803,N2=1479). The association between MS-PRS and FA was studied in the second subsample.ResultsMS-PRS was significantly associated with WM performance within the 10% lowest WM-performing individuals (p= 0.001;pFDR= 0.018). It was not significantly associated with any of the investigated FA measurements.ConclusionsBy identifying a genetic link between MS and WM performance, this study contributes to the understanding of the genetic complexity of MS, and hopefully to the possible identification of molecular pathways linked to cognitive deficits in MS.