bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Intracranial EEG Lateralization of Epileptogenicity in Patients With Confirmed or Suspected Bilateral Mesial Temporal Lobe Onsets During Epilepsy Surgical Evaluation
Authors: Arain Amir M. , Mirro Emily A. , Brown Dan , Peters Angela , Newman Blake , Richards Sindhu , Rolston John D. 
Published: November 2023

Purpose:
The data resulting from epilepsy surgical evaluation are occasionally unclear in cases of mesial temporal lobe (MTL) epilepsy. Long-term intracranial EEG (iEEG) collected by the Responsive Neurostimulation (RNS) System may be an approach for capturing additional seizure data while treating patients with neurostimulation. We reviewed iEEG seizure lateralization and clinical outcomes in bilateral MTL patients at University of Utah.

Methods:
Long-term RNS System iEEG seizure lateralization was compared with pre-RNS System lateralization obtained during surgical evaluation. Safety and clinical outcomes were extracted retrospectively from patient records.

Results:
Twenty-six patients received an RNS System with bilateral MTL leads. Fifteen of the patients had adequate follow-up to report clinical outcomes (>1 year), and 25 patients had enough recorded data (>6 months) to perform iEEG analysis. Median percent reduction in clinical seizures at last follow-up was 58%, and 40% reported being seizure-free at last follow-up, for variable durations. The electrographic seizure lateralization (unilateral vs. bilateral) differed between surgical evaluation and long-term iEEG in 44% of our patients. In the subset of eight patients (32%) who had only unilateral seizures recorded during surgical evaluation, but were implanted with bilateral MTL leads based on bilateral interictal epileptiform discharges, 62% (5/8) had bilateral seizures recorded on long-term iEEG. Interestingly, in the 18 patients who had bilateral seizures recorded during surgical evaluation, 28% (5/18) were found to be unilateral on long-term iEEG.

Conclusions:
Our data suggest that RNS System implantation in suspected bilateral MTL cases may be an option to assess a patient's true seizure lateralization on long-term iEEG. Responsive neuromodulation should be considered before resection or ablation in cases that have evaluation data suggesting bilaterality.
Association of Scalp High-Frequency Oscillation Detection and Characteristics With Disease Activity in Pediatric Epilepsy
Authors: Maeda Keisuke , Hosoda Nami , Fukumoto Junichi , Kawai Shun , Hayafuji Mizuki , Tsuboi Himari , Fujita Shiho , Ichino Naohiro , Osakabe Keisuke , Sugimoto Keiko , Ishihara Naoko 
Published: November 2023

Purpose:
High-frequency oscillation (HFO) in scalp electroencephalography is a promising new noninvasive prognostic epilepsy biomarker, but further data are needed to ascertain the utility of this parameter. The present work investigated the association between epileptic activity and scalp HFO in pediatric patients with various types of epilepsy, using multivariable regression models to correct for possible confounding factors.

Methods:
The authors analyzed 97 subjects who were divided into groups with active epilepsy (within 1 year of seizure), seizure-free epilepsy (>1 year without seizure), and nonepilepsy. Regarding the frequency of seizure occurrence as an indicator of epileptic activity, we categorized subjects into four groups (Daily/Weekly, Monthly, Yearly, and Rarely).

Results:
Multiple linear regression analysis showed that the scalp HFO detection rate was significantly higher in patients with active epilepsy than in those with nonepilepsy (β [95% confidence interval] = 2.77 [1.79–4.29]; P < 0.001). The association between scalp HFO detection rate and frequency of seizure occurrence was highest in the Daily/Weekly group (β [95% confidence interval] = 3.38 [1.57–7.27]; P = 0.002), followed by Monthly and Yearly groups (β [95% confidence interval] = 2.42 [1.02–5.73]; P = 0.046 and 0.36 [0.16–0.83]; P = 0.017). In addition, HFO duration, number of peaks, and number of channels detected were significantly higher in patients with active epilepsy.

Conclusions:
Pediatric patients with active epilepsy and high frequency of seizure occurrence exhibited a higher scalp HFO detection rate. These results may help to establish HFO detectable by noninvasive scalp electroencephalography as a biomarker of active epilepsy in pediatric patients.
Neurophysiological and Clinical Outcomes in Episodic Migraine Without Aura: A Cross-Sectional Study
Authors: Deodato Manuela , Granato Antonio , Martini Miriam , Buoite Stella Alex , Galmonte Alessandra , Murena Luigi , Manganotti Paolo 
Published: November 2023

Purpose:
The aim of this study was to assess differences between people with episodic migraine and healthy controls in some neurophysiological and clinical outcomes, which, in turn, may highlight the differences in sensory processing, especially in cortical excitability, pain processing, and executive function.

Methods:
A cross-sectional study was performed, including the following outcomes: pressure pain thresholds with algometry; resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation with transcranial magnetic stimulation; and executive functions with the trail making test and the frontal assessment battery.

Results:
Thirty adults with migraine (36 ± 10 years) and 30 healthy controls (29 ± 14 years) were included in this study. Compared with the healthy controls, participants with migraine presented lower pressure pain thresholds values in all the assessed muscles (P < 0.001), lower resting motor threshold (−10.5% of the stimulator output, 95% CI: −16.8 to −4.2, P = 0.001, Cohen d = 0.869) and higher short-interval intracortical inhibition motor-evoked potential's amplitude at 3 ms (0.25, 95% CI: 0.05 to 0.46, P = 0.015, Cohen d = 0.662), and worse performances both in trail making test (7.1, 95% CI: 0.9 to 13.4, P = 0.027, Cohen d = 0.594) and frontal assessment battery (−1.1, 95% CI: −1.7 to −0.5, P = 0.001, Cohen d = 0.915).

Conclusions:
Participants with migraine presented significant differences in cortical excitability, executive functions, and pressure pain thresholds, compared with healthy controls.
Publication, Funding, and Experimental Data in Support of Human Reference Atlas Construction and Usage
Authors: Kong Yongxin , Börner Katy 
Published: November 2023

AbstractExperts from 18 consortia are collaborating on the Human Reference Atlas (HRA) which aims to map the 37 trillion cells in the healthy human body. Information relevant for HRA construction and usage is held by experts (clinicians, pathologists, anatomists, single-cell experts), published in scholarly papers, and captured in experimental data. However, these data sources use different metadata schemes and cannot be cross-searched efficiently. This paper documents the compilation of a dataset, called HRAlit, that links the 136 HRA v1.4 digital objects (31 organs with 2,689 anatomical structures, 590 cell types, 1,770 biomarkers) to 583,117 experts; 7,103,180 publications; 896,680 funded projects, and 1,816 experimental datasets. The resulting HRAlit represents 23 tables with 21,704,001 records including 7 junction tables with 13,042,188 relationships. We demonstrate how HRAlit can be mined to identify leading experts, major papers, funding trends, or alignment with existing ontologies in support of systematic HRA construction and usage. Data and code are athttps://github.com/cns-iu/hra-literature.
Microbial functional pathways based on metatranscriptomic profiling enable effective saliva-based health assessments for precision wellness
Authors: Patridge Eric , Gorakshakar Anmol , Molusky Matthew M. , Ogundijo Oyetunji , Janevski Angel , Julian Cristina , Hu Lan , Vuyisich Momchilo , Banavar Guruduth 
Published: November 2023

AbstractIt is increasingly recognized that an important step towards improving overall health is to accurately measure biomarkers of health from the molecular activities prevalent in the oral cavity. We present a general methodology for computationally quantifying the activity of microbial functional pathways using metatranscriptomic data. We describe their implementation as a collection of eight oral pathway scores using a large salivary sample dataset (n=9,350), and we evaluate score associations with oropharyngeal disease phenotypes within an unseen independent cohort (n=14,129). As clinical validation, we show that the relevant oral pathway scores are significantly worse in individuals with periodontal disease, acid reflux, and nicotine addiction, compared with controls. Given these associations, we make the case to use these oral pathway scores to provide molecular health insights from simple, non-invasive saliva samples, and as molecular endpoints for actionable interventions to address the associated conditions.HighlightsMicrobial functional pathways in the oral cavity are quantified as eight oral scoresScores are significantly worse for individuals with oropharyngeal disease phenotypesThis methodology may be generalized to other pathways and other sample typesThese scores provide longitudinal health insights in a precision wellness applicationGraphical Abstract
The circulating immune cell landscape stratifies metastatic burden in breast cancer patients
Authors: Mangiola S , Brown R , Berthelet J , Guleria S , Liyanage C , Ostrouska S , Wilcox J , Merdas M , Larsen PF , Bell C , Schroder J , Mielke L , Mariadason J , Chang-Hao Tsao S , Chen Y , Yadav VK , Anderson RL , Vodala S , Merino D , Behren A , Yeo B , Papenfuss AT , Pal B 
Published: November 2023

AbstractAdvanced breast cancers show varying degrees of metastasis; however, reliable biomarkers of metastatic disease progression remain unknown. In circulation, immune cells are the first line of defence against tumour cells. Herein, using >109,591 peripheral blood mononuclear cells from healthy individuals and breast cancer patients, we tested whether molecular traits of the circulating immune cells, probed with single-cell transcriptomics, can be used to segregate metastatic profiles. Our analyses revealed significant compositional and transcriptional differences in PBMCs of patients with restricted or high metastatic burden versus healthy subjects. The abundance of T cell and monocyte subtypes segregated cancer patients from healthy individuals, while memory and unconventional T cells were enriched in low metastatic burden disease. The cell communication axes were also found to be tightly associated with the extent of metastatic burden. Additionally, we identified a PBMC-derived metastatic gene signature capable of discerning metastatic condition from a healthy state. Our study provides unique molecular insights into the peripheral immune system operating in metastatic breast cancer, revealing potential new biomarkers of the extent of the metastatic state. Tracking such immune traits associated with metastatic spread could complement existing diagnostic tools.
Long-term serial passaging of SARS-CoV-2 reveals signatures of convergent evolution
Authors: Foster Charles S.P. , Walker Gregory J. , Jean Tyra , Wong Maureen , Brassil Levent , Isaacs Sonia R. , Lyu Yonghui , Turville Stuart , Kelleher Anthony , Rawlinson William D. 
Published: November 2023

AbstractUnderstanding viral evolutionary dynamics is crucial to pandemic responses, informing prediction of virus adaptation over time, virus adaptation to antiviral and immune pressures, design of effective therapies, and virus surveillance for public health strategies. Whole-genome sequencing (WGS) of SARS-CoV-2 has enabled fine-grained studies of virus evolution in the human population. Serial passagingin vitrooffers a complementary controlled environment to investigate the emergence and persistence of genetic variants that may confer selective advantage. In this study, nine virus lineages, including four "variants of concern" and three former "variants under investigation", were sampled over ≥33 serial passages (range 33-100) in Vero E6 cells. WGS was used to examine virus evolutionary dynamics and identify key mutations with implications for fitness and/or transmissibility. Mutations accumulated regularly during serial passaging. Many low-frequency variants were lost but others became fixed, suggesting eitherin vitrobenefits, or at least a lack of deleterious effect. Mutations arose convergently both across passage lines and compared with contemporaneous SARS-CoV-2 clinical sequences, including some hypothesised to drive lineage success through host immune evasion (e.g. S:A67V, S:H655Y). The appearance of these mutationsin vitrosuggested key mutations can arise convergently even in the absence of a multicellular host immune response through mechanisms other than immune-driven mutation. Such mutations may provide other benefits to the virusesin vitro, or arise stochastically. Our quantitative investigation into SARS-CoV-2 evolutionary dynamics spans the greatest number of serial passages to date, and will inform measures to reduce the effects of SARS-CoV-2 infection on the human population.ImportanceThe ongoing evolution of SARS-CoV-2 has challenged public health efforts to minimise the health impacts of the virus during the COVID-19 pandemic. Carrying out whole-genome sequencing of outbreak cases has enabled global contact tracing efforts and the identification of mutations of concern within the virus’ genome. Here, we use a complementary approach of charting the evolution of the virus within a controlled cell culture environment, focusing on nine different virus lineages. Our approach demonstrates how SARS-CoV-2 continues to evolve readily in vitro, with many changes mirroring those seen in outbreak cases globally. Findings of the study are important for investigating how important mutations arise, and considering the future evolutionary trajectory of SARS-CoV-2.
Blood transcriptomics analysis offers insights into variant-specific immune response to SARS-CoV-2
Authors: Hoffmann Markus , Willruth Lina-Liv , Dietrich Alexander , Lee Hye Kyung , Knabl Ludwig , Trummer Nico , Baumbach Jan , Furth Priscilla A. , Hennighausen Lothar , List Markus 
Published: November 2023

AbstractBulk RNA sequencing (RNA-seq) of blood is typically used for gene expression analysis in biomedical research but is still rarely used in clinical practice. In this study, we argue that RNA-seq should be considered a routine diagnostic tool, as it offers not only insights into aberrant gene expression and splicing but also delivers additional readouts on immune cell type composition as well as B-cell and T-cell receptor (BCR/TCR) repertoires. We demonstrate that RNA-seq offers vital insights into a patient’s immune status via integrative analysis of RNA-seq data from patients infected with various SARS-CoV-2 variants (in total 240 samples with up to 200 million reads sequencing depth). We compare the results of computational cell-type deconvolution methods (e.g., MCP-counter, xCell, EPIC, quanTIseq) to complete blood count data, the current gold standard in clinical practice. We observe varying levels of lymphocyte depletion and significant differences in neutrophil levels between SARS-CoV-2 variants. Additionally, we identify B and T cell receptor (BCR/TCR) sequences using the tools MiXCR and TRUST4 to show that - combined with sequence alignments and pBLAST - they could be used to classify a patient’s disease. Finally, we investigated the sequencing depth required for such analyses and concluded that 10 million reads per sample is sufficient. In conclusion, our study reveals that computational cell-type deconvolution and BCR/TCR methods using bulk RNA-seq analyses can supplement missing CBC data and offer insights into immune responses, disease severity, and pathogen-specific immunity, all achievable with a sequencing depth of 10 million reads per sample.Key PointsComputational deconvolution of transcriptomes can estimate immune cell abundances in SARS-CoV-2 patients, supplementing missing CBC data.10 million RNA sequencing reads per sample suffice for analyzing immune responses and disease severity, including BCR/TCR identification.
Cross-phenotype associations between Alzheimer’s Disease and its comorbidities may provide clues to progression
Authors: Moore Anni , Ritchie Marylyn D. 
Published: November 2023

AbstractAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide, with one in nine people over the age of 65 living with the disease in 2023. In this study, we used a phenome wide association study (PheWAS) approach to identify cross-phenotype associations between previously identified genetic AD and for electronic health record (EHR) diagnoses from the UK Biobank (UKBB) (n=361,194 of European ancestry) and the eMERGE Network (n=105,108 of diverse ancestry). Based on 497 previously identified AD-associated variants from the Alzheimer’s Disease Variant Portal (ADVP), we found significant associations primarily in immune and cardiac related diseases in our PheWAS. Replicating variants have widespread impacts on immune genes in diverse tissue types. This study demonstrates the potential of using the PheWAS strategy to improve our understanding of AD progression as well as identify potential drug repurposing opportunities for new treatment and disease prevention strategies.
Combining models to generate consensus medium-term projections of hospital admissions, occupancy and deaths relating to COVID-19 in England
Authors: Manley Harrison , Bayley Thomas , Danelian Gabriel , Burton Lucy , Finnie Thomas , Charlett André , Watkins Nicholas A , Birrel Paul , De Angelis Daniela , Keeling Matt , Funk Sebastian , Medley Graham , Pellis Lorenzo , Baguelin Marc , Ackland Graeme J , Hutchinson Johanna , Riley Steven , Panovska-Griffiths Jasmina 
Published: November 2023

AbstractMathematical modelling has played an important role in offering informed advice during the COVID-19 pandemic. In England, a cross government and academia collaboration generated Medium-Term Projections (MTPs) of possible epidemic trajectories over the future 4-6 weeks from a collection of epidemiological models.In this paper we outline this collaborative modelling approach and evaluate the accuracy of the combined and individual model projections against the data over the period November 2021-December 2022 when various Omicron subvariants were spreading across England. Using a number of statistical methods, we quantify the predictive performance of the model projections for both the combined and individual MTPs, by evaluating the point and probabilistic accuracy. Our results illustrate that the combined MTPs, produced from an ensemble of heterogeneous epidemiological models, were a closer fit to the data than the individual models during the periods of epidemic growth or decline, with the 90% confidence intervals widest around the epidemic peaks. We also show that the combined MTPs increase the robustness and reduce the biases associated with a single model projection. Learning from our experience of ensemble modelling during the COVID-19 epidemic, our findings highlight the importance of developing cross-institutional multi-model infectious disease hubs for future outbreak control.
Endogenous Retroelement Expression in the Gut Microenvironment of People Living with HIV-1
Authors: Dopkins Nicholas , Fei Tongyi , Michael Stephanie , Liotta Nicholas , Guo Kejun , Mickens Kaylee L. , Barrett Brad S. , Bendall Matthew L. , Dillon Stephanie M. , Wilson Cara C. , Santiago Mario L. , Nixon Douglas F. 
Published: November 2023

SummaryBackgroundEndogenous retroelements (EREs), including human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs), comprise almost half of the human genome. HIV-1 infects a target cell already possessing ancient retroviral genetic material, and exogenous HIV-1 infection modulates the expression of cell associated EREs. Following initial HIV-1 infection, there is a rapid destruction of CD4+ cells in the gut associated lymphoid tissue (GALT). Our previous studies of the interferome in the gut suggest potential mechanisms regarding how IFNb may drive HIV-1 gut pathogenesis. As ERE activity is suggested to partake in type 1 immune responses and is incredibly sensitive to viral infections, we sought to elucidate underlying interactions between ERE expression and GALT dynamics in PLWH.MethodsERE expression profiles from bulk RNA sequencing of colon biopsies and PBMC were compared between a cohort of PLWH prior to or within 7 days of initiating antiretroviral therapy (ART) (n=19) and uninfected controls (n=13). Individual EREs were then compared with the profiling of uninfected gut CD4+ T cells activated with type 1 interferons (IFN-Is) (n=3) to elucidate potential mechanisms for their induction in PLWH.Findings59 EREs were differentially expressed in the colon of PLWH when compared to uninfected controls (Wald’s Test with Benjamin-Hochberg correction: padj < 0.05 and FC ≤ −1 or ≥ 1). Of these 59, 12 EREs were downregulated in PLWH and 47 were upregulated. Colonic expression of the ERE loci LTR19_12p13.31 and L1FLnI_1q23.1s showed significant correlations with CD8+ T Cells and dendritic cell subset frequencies in the GI tract (Spearman’s Correlation: p value < 0.05). Furthermore L1FLnI_1q23.1s showed a significant upregulation in the blood of PLWH when compared to uninfected controls (T test: p <0.05) suggesting a common mechanism of differential ERE expression in PBMC and GALT.InterpretationERE activity has been largely understudied in genomic characterizations of human pathologies. We show that the activity of certain EREs in the GI tract of PLWH is deregulated, supporting our hypotheses that their underlying activity could function as (bio)markers and potential mediators of pathogenesis in HIV-1 reservoirs.FundingNCI CA260691 (DFN) and NIAID UM1AI164559 (DFN).
Anorexia nervosa polygenic risk, beyond diagnoses: relationship with adolescent disordered eating and behaviours in an Australian female twin population
Authors: Curtis Madeleine , Colodro-Conde Lucia , Medland Sarah E. , Gordon Scott , Martin Nicholas G. , Wade Tracey D. , Cohen-Woods Sarah 
Published: November 2023

AbstractBackgroundIt is well established that there is a substantial genetic component to eating disorders. Polygenic risk scores (PRS) can be used to quantify cumulative genetic risk for a trait at an individual level. Recent studies suggest PRS for Anorexia Nervosa (AN) may also predict risk for other disordered eating behaviours, but no study has examined if PRS for AN can predict disordered eating as a global continuous measure. This study aimed to investigate whether PRS for AN predicted overall levels of disordered eating, or specific lifetime disordered eating behaviours, in an Australian adolescent female population.MethodsPRS were calculated based on summary statistics from the largest Psychiatric Genomics Consortium AN genome-wide association study to date. Analyses were performed using GCTA to test the associations between AN PRS and disordered eating global scores, avoidance of eating, objective bulimic episodes, self-induced vomiting, and driven exercise in a sample of Australian adolescent female twins recruited from the Australian Twin Registry (N = 383).ResultsAfter applying the false discovery rate correction, the AN PRS was significantly associated with all disordered eating outcomes.ConclusionsFindings suggest shared genetic aetiology across disordered eating presentations and provide insight into the utility of AN PRS for predicting disordered eating behaviours, and individuals at risk, in the general population. In the future, PRSs for eating disorders may have clinical utility in early disordered eating risk identification, prevention, and intervention.