bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding ruminative states from neurophysiological patterns
Authors: Welkerling Jana , Schneeweiss Patrick , Wolf Sebastian , Rohe Tim 
Published: May 2024

AbstractIndividuals with depression often engage in iterative “rumination” about challenging situations and potential outcomes. Although the state of rumination has been associated with diverse univariate neurophysiological features, the potential to use multivariate patterns to decode it remains uncertain. In this study, we trained linear support vector machines to differentiate state rumination from distraction using patterns in the alpha, beta, and theta bands, as well as inter-channel connectivity. We used validated tasks to induce rumination or distraction for eight minutes in 24 depressed individuals in six runs over three sessions. During inductions, we recorded 64-channel EEG data and measured self-reported levels of rumination. Participants reported strongly increased rumination, and we decoded state rumination from EEG patterns with significant accuracy. However, the informative features were not consistent across participants, demonstrating that while ruminative states can indeed be decoded from EEG data, these states appear to reflect processes unique to each individual.
Anandamide is an Early Blood Biomarker of Hermansky-Pudlak Syndrome Pulmonary Fibrosis
Authors: Cinar Resat , Basu Abhishek , Arif Muhammad , Park Joshua K. , Zawatsky Charles N. , Zuo Ben Long G. , Zuo Mei Xing G. , O’Brien Kevin J. , Behan Molly , Introne Wendy , Iyer Malliga R. , Gahl William A. , Malicdan May Christine V. , Gochuico Bernadette R. 
Published: May 2024

AbstractHermansky-Pudlak syndrome (HPS) is a group of rare genetic disorders, with several subtypes leading to fatal adult-onset pulmonary fibrosis (PF) and no effective treatment. Circulating biomarkers detecting early PF have not been identified. We investigated whether endocannabinoids could serve as blood biomarkers of PF in HPS. We measured endocannabinoids in the serum of HPS, IPF, and healthy human subjects and in a mouse model of HPSPF. Pulmonary function tests (PFT) were correlated with endocannabinoid measurements. In a pale ear mouse model of bleomycin-induced HPSPF, serum endocannabinoid levels were measured with and without treatment with zevaquenabant (MRI-1867), a peripheral CB1R and iNOS antagonist. In three separate cohorts, circulating anandamide levels were increased in HPS-1 patients with or without PF, compared to healthy volunteers. This increase was not observed in IPF patients or in HPS-3 patients, who do not have PF. Circulating anandamide (AEA) levels were negatively correlated with PFT. Furthermore, a longitudinal study over the course of 5-14 years with HPS-1 patients indicated that circulating AEA levels begin to increase with the fibrotic lung process even at the subclinical stages of HPSPF. In pale ear mice with bleomycin-induced HpsPF, serum AEA levels were significantly increased in the earliest stages of PF and remained elevated at a later fibrotic stage. Zevaquenabant treatment reduced the increased AEA levels and attenuated progression in bleomycin-induced HpsPF. Circulating AEA may be a prognostic blood biomarker for PF in HPS-1 patients. Further studies are indicated to evaluate endocannabinoids as potential surrogate biomarkers in progressive fibrotic lung diseases.
Stenotrophomonas muris- First discovered as an urgent human pathogen with strong virulence associated with bloodstream infections
Authors: Liu Jiaying , Dong Xu , Yu Yuyun , Wu Tiantian , Xiang Yanghui , Yuan Xin , Cao Dan , Bi Kefan , Zhang Hanyin , Zhu Lixia , Zhang Ying 
Published: May 2024

AbstractFor the first time,Stenotrophomonas muris(S. muris) has been identified to be associated with human infections while studying the virulence ofStenotrophomonas maltophilia(S. maltophilia) clinical isolates. Previously,S. muriswas only isolated from the intestines of mice but its pathogenic potential for humans has never been reported. In this work, the phenotype ofS. murisvirulence, the potential genes that encode higher virulence ofS. muris, and host responses toS. murisinfection were investigated for the first time. It was found that S9 (S. murisno.9, isolated from patient’s bloodstream infection) was more virulent than both S8 (S. murisno.8, isolated from patient’s sputum) and S1 (S. maltophilia), where S8 and S9 were subsequently identified asS. murisby whole genome sequencing analysis. Candidate genes which may encode higher virulence of S9 were identified, includingvirB6, dcm, hlyD, and 14 other genes involved in porphyrin metabolism, pyrimidine metabolism, DNA methylation, two component system, and biofilm formation. Transcriptome analysis of host cells (THP-1 cells) infected by S8 and S9 (S9 with strong virulence over S8 with weak virulence) showed that 12 candidate genes involved in ion transport function and calcium signaling pathway were down-regulated and require special attention. Antibiotic susceptibility testing indicated that compared withS. maltophilia, theS. murisstrains, though more susceptible to minocycline, are highly resistant to last resort antibitoics colistin and polymyxin B and are also resistant to cephalosporin and fluoroquinolone. Because of the above differences in virulence properties and antibiotic susceptibility, it is critical thatS. murisbe distinguished fromS. maltophiliain clinical setting for improved care. This work provides the basis for future studies on pathogenic mechanisms ofS. murisand for developing improved treatment in the future.
Cost-effectiveness of respiratory syncytial virus vaccination strategies for older Canadian adults: a multi-model comparison
Authors: Rudd Monica , Simmons Alison E. , Gebretekle Gebremedhin B. , Tuite Ashleigh R. 
Published: May 2024

ABSTRACTBackgroundTwo respiratory syncytial virus (RSV) vaccines are currently approved for use in adults aged 60 years and older in Canada. Economic analyses have shown that adult RSV vaccination programs may be cost-effective, particularly when focused on people at increased risk of RSV disease due to increased age or presence of chronic medical conditions (CMCs). We conducted a multi-model comparison to explore the impact of alternate model structural and methodological assumptions on the cost-effectiveness of RSV vaccination programs.MethodsWe compared three static cost-utility models developed by the Public Health Agency of Canada, GSK, and Pfizer using a common set of input parameters. Each model evaluated sequential incremental cost-effectiveness ratios (ICERs) in 2023 Canadian dollars per quality-adjusted life year (QALY) for a set of policy alternatives, with vaccine eligibility determined by combinations of age and CMC status. Results were calculated for each vaccine separately for scenarios assuming two or three years of vaccine protection using the health system perspective and a 1.5% annual discount rate.ResultsThe three cost-utility models were broadly concordant across the scenarios modeled. In all scenarios, focusing on vaccination of people with CMCs was preferred over broader age-based policies. RSV vaccination for people with CMCs over the age of 70 years was most commonly identified as the optimal policy when using a cost-effectiveness threshold of $50,000/QALY. When only considering policies based on age criteria, vaccinating people over 80 years was cost-effective at this threshold.DiscussionA multi-model comparison of Canadian cost-utility models shows that RSV vaccination programs for RSV are likely cost-effective for some groups of older adults in Canada. These findings were consistent across models, despite differences in model structure.
A new lineage nomenclature to aid genomic surveillance of dengue virus
Authors: Hill Verity , Cleemput Sara , Fonseca Vagner , Tegally Houriiyah , Brito Anderson F. , Gifford Robert , Tran Vi Thuy , Kien Duong Thi Hue , Huynh Tuyen , Yacoub Sophie , Dieng Idrissa , Ndiaye Mignane , Balde Diamilatou , Diagne Moussa M. , Faye Oumar , Salvato Richard , Wallau Gabriel Luz , Gregianini Tatiana S. , Godinho Fernanda M.S. , Vogels Chantal B.F. , Breban Mallery I. , Leguia Mariana , Jagtap Suraj , Roy Rahul , Hapuarachchi Chanditha , Mwanyika Gaspary , Giovanetti Marta , Alcantara Luiz C.J. , Faria Nuno R. , Carrington Christine V.F. , Hanley Kathryn A. , Holmes Edward C. , Dumon Wim , de Oliveira Tulio , Grubaugh Nathan D. 
Published: May 2024

AbstractDengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system. Here we propose adding two sub-genotypic levels of virus classification, named major and minor lineages. These lineages have high thresholds for phylogenetic distance and clade size, rendering them stable between phylogenetic studies. We present an assignment tool to show that the proposed lineages are useful for regional, national and sub-national discussions of relevant DENV diversity. Moreover, the proposed lineages are robust to classification using partial genome sequences. We provide a standardized neutral descriptor of DENV diversity with which we can identify and track lineages of potential epidemiological and/or clinical importance. Information about our lineage system, including methods to assign lineages to sequence data and propose new lineages, can be found at:dengue-lineages.org.
Biomarkers of RV dysfunction in HFrEF identified by direct tissue proteomics: extracellular proteins fibromodulin and fibulin-5
Authors: Běhounek Matěj , Lipcseyová Denisa , Vít Ondřej , Žáček Petr , Talacko Pavel , Husková Zuzana , Kikerlová Soňa , Tykvartová Tereza , Wohlfahrt Peter , Melenovský Vojtěch , Beneš Jan , Petrák Jiří 
Published: May 2024

AbstractBACKGROUNDRight ventricular dysfunction (RVD) is a commonly accompanying condition in patients with heart failure with reduced ejection fraction (HFrEF), and is associated with poor prognosis. However, no specific biomarker of RVD is available for clinical routine.METHODSWe performed a label-free proteomic analysis of myocardium from the left and right ventricles of HFrEF patients with and without RVD who underwent heart transplantation (n=20). Concentrations of two extracellular matrix proteins with highest myocardial upregulation in RVD – fibromodulin (FMOD) and fibulin-5 (FBLN5) - were assayed in the blood, compared to controls (n=65) and tested in separate large cohort of HFrEF patients (n=232) to test association of the two proteins with RV function and long-term outcome.RESULTSFMOD and FBLN5 plasma concentrations progressively increased with worsening RV function (p = 0.0001 and 0.004), while there was no association with LV dysfunction, BMI or kidney function. In survival analysis, plasma levels of both FMOD and FBLN5 were significantly associated with patient outcome (p = 0.005 and 0.0004). Using reclassification analysis, addition of plasma FBLN5 to right ventricle function assessment led to an improvement in AUC after 4 years compared to RV function assessment only. Similarly, adding plasma fibromodulin to the multi-parametric MAGGIC score showed a significantly higher AUC after 4 years. Importantly, the prognostic value of both biomarkers was additive.CONCLUSIONOur study proposes that circulating levels of FMOD and FBLN5 may serve as a new biomarkers of RVD in HFrEF patients.
Left and Right Ventricular Diameters Independently Predict Outcome in Intermediate and High-Risk Pulmonary Embolisms
Authors: Spevack Daniel , Bali Atul D. , Kanwal Arjun , Isath Ameesh , Sharma Tanya , Ahsan Syed , Malekan Ramin , Goldberg Joshua B. 
Published: May 2024

BackgroundThe right to left ventricular diameter ratio (RV/LV) is a key imaging parameter used in risk stratification of pulmonary embolism. While having RV/LV above a cutoff value of 0.9 is usually attributed to pathological RV dilatation, we hypothesized that increased RV/LV may also be attributable to reduced LV filling. We aimed to examine RV and LV diameters as independent predictors of PE outcomes in patients presenting with intermediate or high-risk PE.MethodsWe measured RV and LV diameters on pre-intervention echocardiograms performed on 164 subjects presenting at or referred to our center for large PE requiring surgical thrombectomy, venoarterial extracorporeal membrane oxygenation (VA-ECMO), or catheter directed thrombectomy.ResultsThe primary outcome of death (n=3) or survival of cardiopulmonary resuscitation (CPR) (n=11) was met in 14 subjects. Smaller LV diameter and larger RV diameter were each demonstrated to be independent predictors of the primary outcome. LV diameter of <3.6 cm, RV diameter >5.0 cm, and RV/LV ratio of >1.2 were the cutoff values for each parameter most associated with the primary outcome.ConclusionThis study demonstrates that, in addition to dilated RV, small LV is an independent risk factor of death or need for CPR in hemodynamically significant PE treated with advanced therapies. This finding suggests that the predictive value of RV/LV for PE outcomes may be attributed to both RV enlargement and reduced LV filling.
Driver gene detection via causal inference on single cell embeddings
Authors: Fu Chengbo , Cheng Lu 
Published: May 2024

AbstractDriver genes are pivotal in different biological processes. Current methods generally identify driver genes by associative analysis. Leveraging on the development of current large language models (LLM) in single cell genomics, we propose a causal inference based approach called CID to identify driver genes from scRNA-seq data. Through experiments on three different datasets, we show that CID can (1) identify biologically meaningful driver genes that have not been captured by current associative-analysis based methods, and (2) accurately predict the change directions of target genes if a driver gene is knocked out.
Neuronal migration depends on blood flow in the adult brain
Authors: Ogino Takashi , Saito Akari , Sawada Masato , Takemura Shoko , Nagase Jiro , Kawase Honomi , Inada Hiroyuki , Herranz-Pérez Vicente , Mukouyama Yoh-suke , Ema Masatsugu , García-Verdugo José Manuel , Nabekura Junichi , Sawamoto Kazunobu 
Published: May 2024

AbstractIn animal tissues, several cell types migrate along blood vessels, raising the possibility that blood flow influences cell migration. Here, we show that blood flow promotes the migration of new olfactory-bulb neurons in the adult brain. Neuronal migration is facilitated by blood flow, leading to accumulation of new neurons near blood vessels with abundant blood flow. Blood flow inhibition attenuates blood vessel-guided neuronal migration, suggesting that blood contains factors beneficial to neuronal migration. We found that ghrelin, which is increased in blood by hunger, directly influences neuronal migration. Ghrelin signaling promotes somal translocation by activating actin cytoskeleton contraction at the rear of the cell soma. New neurons mature in the olfactory bulb and contribute to the olfactory function for sensing odorants from food. Finally, we show that neuronal migration is increased by calorie restriction, and that ghrelin signaling is involved in the process. This study suggests that blood flow promotes neuronal migration through blood-derived ghrelin signaling in the adult brain, which could be one of the mechanisms that improve the olfactory function for food-seeking behavior during starvation.
Examining speech-brain tracking during early bidirectional, free-flowing caregiver-infant interactions
Authors: Phillips E.A.M. , Goupil L. , Ives J. E. , Labendzki P. , Whitehorn M. , Marriott Haresign I. , Wass S.V. 
Published: May 2024

AbstractNeural entrainment to slow modulations in the amplitude envelope of infant-directed speech is thought to drive early language learning. Most previous research with infants examining speech-brain tracking has been conducted in controlled, experimental settings, which are far from the complex environments of everyday interactions. Whilst recent work has begun to investigate speech-brain tracking to naturalistic speech, this work has been conducted in semi-structured paradigms, where infants listen to live adult speakers, without engaging in free-flowing social interactions. Here, we test the applicability of mTRF modelling to measure speech-brain tracking in naturalistic and bidirectional free-play interactions of 9-12-month-olds with their caregivers. Using a backwards modelling approach, we test individual and generic training procedures, and examine the effects of data quantity and quality on model fitting. We show model fitting is most optimal using an individual approach, trained on continuous segments of interaction data. Corresponding to previous findings, individual models showed significant speech-brain tracking at delta modulation frequencies, but not in alpha and theta bands. These findings open new methods for studying the interpersonal micro-processes that support early language learning. In future work, it will be important to develop a mechanistic framework for understanding how our brains track naturalistic speech during infancy.
RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability
Authors: Provasek Vincent E. , Bacolla Albino , Rangaswamy Suganya , Mitra Joy , Kodavati Manohar , Yusuf Issa O. , Malojirao Vikas H. , Vasquez Velmarini , Britz Gavin W. , Li Guo-Min , Xu Zuoshang , Mitra Sankar , Garruto Ralph M. , Tainer John A. , Hegde Muralidhar L. 
Published: May 2024

AbstractTAR DNA-binding protein 43 (TDP43) is increasingly recognized for its involvement in neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP43 proteinopathy, characterized by dysregulated nuclear export and cytoplasmic aggregation, is present in most ALS/FTD cases and is associated with a loss of nuclear function and genomic instability in neurons. Building on prior evidence linking TDP43 pathology to DNA double-strand breaks (DSBs), this study identifies a novel regulatory role for TDP43 in the DNA mismatch repair (MMR) pathway. We demonstrate that depletion or overexpression of TDP43 affects the expression of key MMR genes, including MLH1, MSH6, MSH2, MSH3, and PMS2. Specifically, TDP43 modulates the expression of MLH1 and MSH6 proteins through alternative splicing and transcript stability. These findings are validated in ALS mice models, patient-derived neural progenitor cells and autopsied brain tissues from ALS patients. Furthermore, MMR depletion showed a partial rescue of TDP43-induced DNA damage in neuronal cells. Bioinformatics analysis of TCGA cancer database reveals significant correlations between TDP43 and MMR gene expressions and mutational burden across various cancer subtypes. These results collectively establish TDP43 as a critical regulator of the MMR pathway, with broad implications for understanding the genomic instability underlying neurodegenerative and neoplastic diseases.
The phylogenetic position of the Yunxian cranium elucidates the origin of Dragon Man and the Denisovans
Authors: Feng Xiaobo , Lu Dan , Gao Feng , Fang Qin , Feng Yilu , Huang Xuchu , Tan Chen , Zhou Hanwen , Li Qiang , Zhang Chi , Stringer Chris , Ni Xijun 
Published: May 2024

AbstractDiverse Middle Pleistocene forms ofHomocoexisted in Africa, Europe, and Asia. It is very controversial whether these fossil humans represent different species or lineages. The ∼1 Ma old Yunxian 2 fossil from China is crucial for understanding the cladogenesis ofHomoand the origin ofHomo sapiens. Here, we restored and reconstructed the distorted Yunxian 2 cranium using new technology. The results show that this cranium displays mosaic features of plesiomorphy and apomorphy. Phylogenetic analyses and Bayesian tip-dating including the reconstructed Yunxian 2 suggest that it is an early member of the Asian ‘Dragon Man’ lineage, which probably includes the Denisovans, and is the sister group of theHomo sapienslineage. Both theH. sapiensand Dragon Man lineages had deep roots extending beyond the Middle Pleistocene, and the basal position of the Yunxian fossil cranium suggests it represents a population lying close to the last common ancestor of the two lineages.One-Sentence SummaryThe newly-reconstructed Yunxian 2 cranium represents a basal member of the Dragon Man and Denisovan lineage, and probably lies close to the last common ancestor of that lineage and the lineage ofH. sapiens.
Kinetic Analysis of Lanthipeptide Cyclization by Substrate-Tolerant ProcM
Authors: Desormeaux Emily K. , van der Donk Wilfred A. 
Published: May 2024

AbstractLanthipeptides are ribosomally synthesized and post-translationally modified peptides characterized by the presence of thioether crosslinks. Class II lanthipeptide synthetases are bifunctional enzymes responsible for the multistep chemical modification of these natural products. ProcM is a class II lanthipeptide synthetase known for its remarkable substrate tolerance and ability to install diverse (methyl)lanthionine rings with high accuracy. Previous studies suggested that the final ring pattern of the lanthipeptide product may be determined by the substrate sequence rather than by ProcM, and that ProcM operates by a kinetically controlled mechanism, wherein the ring pattern is dictated by the relative rates of the individual cyclization reactions. This study utilizes kinetic assays to determine if rates of isolated modifications can predict the final ring pattern present in prochlorosins. Changes in the core substrate sequence resulted in changes to the reaction rates of ring formation as well as a change in the order of modifications. Additionally, individual chemical reaction rates were significantly impacted by the presence of other modifications on the peptide. These findings indicate that the rates of isolated modifications are capable of predicting the final ring pattern but are not necessarily a good predictor of the order of modification in WT ProcA3.3 and its variants.
Highly heterogeneous human herpes virus-8 oral shedding kinetics among people with and without Kaposi sarcoma and HIV- co-infection
Authors: Krantz Elizabeth M. , Mutyaba Innocent , Nankoma Janet , Okuku Fred , Casper Corey , Orem Jackson , Swan David A. , Phipps Warren , Schiffer Joshua T. 
Published: May 2024

AbstractBackgroundAn improved understanding of oral human herpesvirus-8 (HHV-8) viral dynamics could provide insights into transmission risk and guide vaccine development.MethodsWe evaluated HHV-8 oral shedding dynamics in Ugandan adults stratified by Kaposi sarcoma (KS) and HIV status. Participants were followed for ≥4 weeks, with daily home oral swab collection to quantify HHV-8 using Polymerase Chain Reaction. Shedding rates were defined by the number of days with HHV-8 detected divided by the total days with swabs and compared by group using hurdle models.Results295 participants were enrolled; median age was 35 years (range 18-71), 134 (45%) were male. HHV-8 was detected more frequently among participants with KS (HIV+/KS+ 56/76, 74%; HIV-/KS+ 9/18, 50%) than those without KS (HIV+/KS-36/125, 29%; HIV-/KS-16/76, 21%); odds of shedding did not differ significantly by HIV status. Among participants with HHV-8 detected, shedding rates did not differ significantly by group. Median per-participant viral loads among positive samples were lowest in HIV+/KS+ (3.1 log10copies/mL) and HIV-/KS+ participants (3.3 log10copies/mL) relative to HIV+/KS-(3.8 log10copies/mL) and HIV-/KS-participants (4.0 log10copies/mL). All groups had participants with low-viral load intermittent shedding and those with high-viral load persistent shedding. Within each group, individual HHV-8 shedding rate positively correlated with median HHV-8 log10copies/mL, and episode duration positively correlated with peak viral load.ConclusionsOral HHV-8 shedding is highly heterogeneous across Ugandan adults with and without KS and HIV. Persistent shedding is associated with higher median viral loads regardless of HIV and KS status.