bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cumulative Social Disadvantage and Health-Related Quality of Life: National Health Interview Survey 2013-2017
Authors: Hagan Kobina , Javed Zulqarnain , Cainzos-Achirica Miguel , Hyder Adnan A. , Mossialos Elias , Yahya Tamer , Acquah Isaac , Valero-Elizondo Javier , Pan Alan , Nwana Nwabunie , Taha Mohamad , Nasir Khurram 
Published: August 2022

ABSTRACTBackgroundEvidence of the association between social determinants of health (SDoH) and health-related quality of life (HRQoL) is largely based on single SDoH measures, with limited evaluation of cumulative social disadvantage. We examined the association between cumulative social disadvantage and the Health and Activity Limitation Index (HALex).MethodsWe used data of respondents from the 2013-2017 National Health Interview Survey. A cumulative SDoH index was created by aggregating 46 SDoH from 6 domains, and respondents were grouped by quartiles (SDoH-Q1 to Q4). A higher SDoH index or quartile indicates greater disadvantage. Two outcomes were assessed: HALex score using two-part models, and a binary “poor HALex” (HALex score < 0.79 [20th percentile]) using logistic regression. Regression analyses adjusted for demographics and comorbidities and were performed in the overall sample, and by age, sex, and race/ethnicity categories.ResultsAmong 156,182 adults (mean age 46 years; 51.7% women), higher SDoH quartile groups averaged lower HALex scores and had higher proportions with poor HALex. A unit increase in SDoH index was associated with 0.01 decrease in HALex score (β = −0.01; 95% CI [−0.01, −0.01]) and 14% higher odds of poor HALex (odds ratio, OR = 1.14; 95% CI [1.14, 1.15]). Relative to SDoH-Q1, SDoH-Q4 was associated with HALex score decrease of −0.13 (95% CI [−0.13, −0.13]) and OR 8.67 (95% CI [8.08, 9.30]) for poor HALex. Hispanic persons, despite a relatively higher burden of cumulative social disadvantage, had a weaker SDoH-HALex association than their counterparts.ConclusionHigher cumulative social disadvantage was independently associated with lower HRQoL in an incremental fashion. The more favorable HRQoL profile observed in the Hispanic could be related to a resilient concept of health derived from cultural values and acceptance, and this highlights the need for population “wellness” interventions to be responsive to such phenomenon.
Transcriptomic profiling of cerebrospinal fluid predicts shunt surgery responses in patients with Normal Pressure Hydrocephalus
Authors: Levin Zachary , Leary Owen P. , Mora Victor , Kant Shawn , Brown Sarah , Svokos Konstantina , Akbar Umer , Serre Thomas , Klinge Petra , Fleischmann Alexander , Ruocco Maria Grazia 
Published: August 2022

AbstractMolecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal Pressure Hydrocephalus (NPH) is a neurodegenerative disorder characterized by progressive gait impairment, urinary incontinence, and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess cerebrospinal fluid (CSF). A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles that can predict shunt surgery response with high accuracy. The transcriptomic signatures we identified have important implications for improving NPH diagnosis and treatment and for understanding disease etiology.
Ngfr suppresses Lcn2/Slc22a17 signaling, induces neurogenesis and reduces amyloid pathology in the hippocampus of APP/PS1dE9 mouse
Authors: Siddiqui Tohid , Cosacak Mehmet Ilyas , Popova Stanislava , Bhattarai Prabesh , Lee Annie J. , Min Yuhao , Wang Xue , Allen Mariet , İş Özkan , Atasavum Zeynep Tansu , Vardarajan Badri N. , Santa-Maria Ismael , Tosto Giuseppe , Mayeux Richard , Ertekin-Taner Nilüfer , Kizil Caghan 
Published: August 2022

AbstractNeurogenesis relates to the brain resilience and is reduced in Alzheimer’s disease (AD). Restoring healthy levels of neurogenesis could have beneficial effects for coping with neurodegeneration. However, molecular mechanisms that could enhance neurogenesis from astroglial progenitors in AD pathology are largely unknown. We used lentiviruses to expressNgfrin the hippocampus of the APP/PS1dE9 mouse model of AD, histologically analyzed the changes in proliferation of neural stem cells and neurogenesis; performed single-cell transcriptomics, spatial proteomics, and functional knockdown studies. We found that expression ofNgfr, a neurogenic determinant in pathology-induced neuroregeneration in zebrafish, stimulated proliferative and neurogenic outcome in the APP/PS1dE9 AD mouse model. Ngfr suppressed reactive astrocyte marker Lipocalin-2 (Lcn2) in astroglia. Blockage of Lcn2 receptor, Slc22a17, recapitulated the neurogenic effects of NGFR, and long-term Ngfr expression reduced amyloid plaques and Tau phosphorylation. Furthermore, immunostaining on postmortem human hippocampi with AD or primary age-related Tauopathy and 3D human astroglial cultures showed that elevated LCN2 levels correlate with gliosis. By comparing transcriptional changes in mouse hippocampus, zebrafish brain, and human AD brains in terms of cell intrinsic differential gene expression analyses as well as weighted gene co-expression network analysis, we observed common potential downstream effectors of NGFR signaling,C4BandPFKP, that are relevant to AD. Our study links the regulatory role of an autocrine molecular mechanism in astroglia to the neurogenic ability and modulatory effects on amyloid and tau phosphorylation, opening new research avenues and suggesting that neurogenesis-oriented therapeutic approaches could be a potential clinical intervention for AD.
Age-dependent changes in the dynamic functional organization of the brain at rest – a cross-cultural replication approach
Authors: Yang Xi , Zhou Xinqi , Xin Fei , Becker Benjamin , Linden David , Hernaus Dennis 
Published: August 2022

AbstractAge-associated changes in brain function play an important role in the development of neurodegenerative diseases. Although previous work has examined age-related changes in static functional connectivity (FC), accumulating evidence suggests that advancing age is especially associated with alterations in the dynamic interactions and transitions between different brain states, which hitherto has received less attention. Moreover, conclusions of previous studies in this domain are limited by suboptimal replicability of resting state fMRI and culturally homogenous cohorts. Here, we investigate the robustness of age-associated changes in dynamic functional connectivity (dFC) by capitalizing on the availability of fMRI cohorts from two cultures (Western European and Chinese). In both cohorts we consistently identify two distinct connectivity states: a more frequent segregated within-network connectivity state (state I) and a less frequent integrated between-network connectivity state (state II). In both cohorts, older (55-80 years) compared to younger participants (20-35 years) exhibited lower occurrence of and spent less time in state I. Moreover, older participants tended to exhibit more transitions between networks and greater variance in global efficiency. Overall, our cross-cultural replication of age-associated changes in key dFC metrics implies that advancing age is robustly associated with a reorganization of dynamic brain activation that favors the use of less functionally-specific networks.HighlightsAging is associated with a reorganization of dynamic functional brain connectivity.Age-dependent dynamic functional connectivity changes are relatively stable across cultures.Dynamic properties are promising neural indexes for brain aging in older healthy populations.
Honokiol and alfa-Mangostin inhibit Mayaro virus replication by stimulating the type I interferon pathway
Authors: Valdés-Torres Patricia , Campos Dalkiria , Bhakta Madhvi , Galán-Jurado Paola Elaine , Durant-Archibold Armando A. , González-Santamaría José 
Published: August 2022

ABSTRACTMayaro virus (MAYV) is an emerging arbovirus with increasing circulation across the Americas. In the present study, we evaluated the potential antiviral activity of the following natural compounds against MAYV and other arboviruses: Sanguinarine, (R)-Shikonin, Fisetin, Honokiol, Tanshinone IIA and α-Mangostin. Sanguinarine and Shikonin showed significant cytotoxicity, whereas Fisetin, Honokiol, Tanshinone IIA and α-Mangostin were well-tolerated in all the cell lines tested. Honokiol and α-Mangostin treatment protected Vero-E6 cells against MAYV-induced damage and resulted in a dose-dependent reduction in viral progeny yields for each of the MAYV strains and human cell lines assessed. Also, Honokiol and α-Mangostin disrupted MAYV infection at different stages of the virus life cycle. Moreover, these compounds decreased Una, Chikungunya and Zika viral titers and downmodulated the expression of E1 and nsP1 viral proteins from MAYV, Una and Chikungunya. Finally, in Honokiol- and α-Mangostin-treated cells, we observed an upregulation in the expression of type I interferon and specific interferon-stimulated genes, including IFNα, IFNβ, MxA, ISG15, OAS2, MDA-5, TNFα and IL-1β, which may promote an antiviral cellular state. Our results indicate that Honokiol and α-Mangostin present potential broad-spectrum activity against different arboviruses through a possible modulation of the interferon pathway.
Size-dependence of food intake and mortality interact with temperature and seasonality to drive diversity in fish life histories
Authors: Kindsvater Holly K. , Juan-Jordá Maria-José , Dulvy Nicholas K. , Horswill Cat , Matthiopoulos Jason , Mangel Marc 
Published: August 2022

AbstractUnderstanding how growth and reproduction will adapt to changing environmental conditions is a fundamental question in evolutionary ecology, but predicting the responses of specific taxa is challenging. Analyses of the physiological effects of climate change upon life history evolution rarely consider alternative hypothesized mechanisms, such as size-dependent foraging and the risk of predation, simultaneously shaping optimal growth patterns. To test for interactions between these mechanisms, we embedded a state-dependent energetic model in an ecosystem size-spectrum to ask whether prey availability (foraging) and risk of predation experienced by individual fish can explain observed diversity in life histories of fishes. We found that asymptotic growth emerged from size-based foraging and reproductive and mortality patterns in the context of ecosystem food web interactions. While more productive ecosystems led to larger body sizes, the effects of temperature on metabolic costs had only small effects on size. To validate our model, we ran it for abiotic scenarios corresponding to the ecological lifestyles of three tuna species, considering environments that included seasonal variation in temperature. We successfully predicted realistic patterns of growth, reproduction, and mortality of all three tuna species. We found that individuals grew larger when environmental conditions varied seasonally and spawning was restricted to part of the year (corresponding to their migration from temperate to tropical waters). Growing larger was advantageous because foraging and spawning opportunities were seasonally constrained. This mechanism could explain the evolution of gigantism in temperate tunas. Our approach addresses variation in food availability and individual risk as well as metabolic processes and offers a promising approach to understand fish life-history responses to changing ocean conditions.
Testing the ion-current model for flagellar length sensing and IFT regulation
Authors: Ishikawa Hiroaki , Moore Jeremy , Diener Dennis R. , Delling Markus , Marshall Wallace F. 
Published: August 2022

AbstractEukaryotic cilia and flagella are microtubule-based organelles whose relatively simple shape makes them ideal for investigating the fundamental question of organelle size regulation. Most of the flagellar materials are transported from the cell body via an active transport process called intraflagellar transport (IFT). The rate of IFT entry into flagella, known as IFT injection, has been shown to negatively correlate with flagellar length. However, it remains unknown how the cell measures the length of its flagella and controls IFT injection. One of the most-discussed theoretical models for length sensing to control IFT is the ion-current model, which posits that there is a uniform distribution of Ca2+channels along the flagellum and that the Ca2+current from the flagellum into the cell body increases linearly with flagellar length. In this model, the cell uses the Ca2+current to negatively regulate IFT injection. The recent discovery that IFT entry into flagella is regulated by the phosphorylation of kinesin through a calcium-dependent protein kinase has provided further impetus for the ion-current model. To test this model, we measured and manipulated the levels of Ca2+inside ofChlamydomonasflagella and quantified IFT injection. Although the concentration of Ca2+inside of flagella was weakly correlated with the length of flagella, we found that IFT injection was reduced in calcium-deficient flagella, rather than increased as the model predicted, and that variation in IFT injection was uncorrelated with the occurrence of flagellar Ca2+spikes. Thus, Ca2+does not appear to function as a negative regulator of IFT injection, hence it cannot form the basis of a stable length control system.
scPerturb: Harmonized Single-Cell Perturbation Data
Authors: Peidli Stefan , Green Tessa D. , Shen Ciyue , Gross Torsten , Min Joseph , Garda Samuele , Yuan Bo , Schumacher Linus J. , Taylor-King Jake P. , Marks Debora S. , Luna Augustin , Blüthgen Nils , Sander Chris 
Published: August 2022

AbstractRecent biotechnological advances led to growing numbers of single-cell perturbation studies, which reveal molecular and phenotypic responses to large numbers of perturbations. However, analysis across diverse datasets is typically hampered by differences in format, naming conventions, and data filtering. In order to facilitate development and benchmarking of computational methods in systems biology, we collect a set of 44 publicly available single-cell perturbation-response datasets with molecular readouts, including transcriptomics, proteomics and epigenomics. We apply uniform pre-processing and quality control pipelines and harmonize feature annotations. The resulting information resource enables efficient development and testing of computational analysis methods, and facilitates direct comparison and integration across datasets. In addition, we introduce E-statistics for perturbation effect quantification and significance testing, and demonstrate E-distance as a general distance measure for single cell data. Using these datasets, we illustrate the application of E-statistics for quantifying perturbation similarity and efficacy. The data and a package for computing E-statistics is publicly available at scperturb.org. This work provides an information resource and guide for researchers working with single-cell perturbation data, highlights conceptual considerations for new experiments, and makes concrete recommendations for optimal cell counts and read depth.
Peptaibol Production and Characterization from Trichoderma asperellum and their Action as Biofungicide
Authors: Alfaro-Vargas Pamela , Bastos-Salas Alisson , Muñoz-Arrieta Rodrigo , Pereira-Reyes Reinaldo , Redondo-Solano Mauricio , Fernández Julián , Mora-Villalobos Aníbal , López-Gómez José Pablo 
Published: August 2022

AbstractPeptaibols (Paib), are a class of biologically active peptides isolated from soil, fungi and molds, which have interesting properties as antimicrobial agents. Paib production was optimized in flasks by adding sucrose as a carbon source, Aib as an additive amino acid, and F. oxysporum cell debris as an elicitor. Paib were purified, sequenced and identified by HPLC coupled to mass spectrometry. Afterward, a Paib prototype was prepared with the extracts obtained from the optimized fermentations. The biological activity of these prototypes was evaluated using in vitro and in vivo methods. The prototype inhibited the growth of specific plant pathogens, and it showed inhibition rates similar to those from commercially available fungicides. Growth inhibition rates were 92.2, 74.2, 58.4 and 36.2% against Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria alternata and Fusarium oxysporum, respectively. Furthermore, the antifungal activity was tested in tomatoes inoculated with A. alternata, the incidence of the disease in tomatoes treated with the prototype was 0%, while the untreated fruit showed a 92.5% of infection. Scanning electron microscopy images showed structural differences between fungi treated with or without Paib. The most visual alterations were sunk and shriveled morphology in spores, while the hyphae appeared to be fractured, rough, and dehydrated.
Humoral and cellular immune correlates of protection against COVID-19 in kidney transplant recipients
Authors: Kemlin D. , Gemander N. , Depickère S. , Olislagers V. , Georges D. , Waegemans A. , Pannus P. , Lemy A. , Goossens M. E. , Desombere I. , Michiels J. , Vandevenne M. , Heyndrickx L. , Ariën K.K. , Matagne A. , Ackerman M.E. , Moine A. Le , Marchant A. 
Published: August 2022

AbstractAs solid organ recipients are at high risk of severe COVID-19 and respond poorly to primary SARS-CoV-2 mRNA vaccination, they have been prioritized for booster vaccination. However, an immunological correlate of protection has not been identified in this vulnerable population. We conducted a prospective monocentric cohort study of 65 kidney transplant recipients who received three doses of SARS-CoV-2 BNT162b2 mRNA vaccination. Associations between symptomatic breakthrough infection (BTI) and vaccine responses, patient demographic and clinical characteristics were explored. Symptomatic COVID-19 was diagnosed in 32% of kidney transplant recipients during a period of six months after the administration of the third vaccine dose. During this period, SARS-CoV-2 delta and omicron were the dominant variants in the general population. Univariate analyzes identified avidity of SARS-CoV-2 receptor binding domain (RBD) binding IgG, neutralizing antibodies and SARS-CoV-2 S2 domain-specific IFN-γ responses as correlates of protection against BTI. Some demographic and clinical parameters correlated with vaccine responses, but none correlated with the risk of BTI. In multivariate analysis, the risk of BTI was best predicted by neutralizing antibody and S2-specific IFN-γ responses, adjusting for age, graft function and mycophenolate mofetil use. In conclusion, both antibody and T cell responses predict the risk of BTI in kidney transplant recipients who received three doses of SARS-CoV-2 mRNA vaccine. T cell responses may help compensate for the suboptimal antibody response to vaccination in this vulnerable population.One Sentence SummaryAntibody and T cell responses to booster SARS-CoV-2 vaccination predict the risk of symptomatic breakthrough infection in kidney transplant recipients
A pilot analysis of circulating cfRNA transcripts for the detection of lung cancer
Authors: Seneviratne Chamindi , Shetty Amol C. , Geng Xinyan , McCracken Carrie , Cornell Jessica , Mullins Kristin , Jiang Feng , Stass Sanford 
Published: August 2022

AbstractLung cancers are the leading cause of cancer-related deaths worldwide. Studies have shown that non-small cell lung cancer (NSCLC) which constitutes majority of lung cancers, are significantly more responsive to early-stage interventions. However, the early stages are often asymptomatic, and current diagnostic methods are limited in their precision and safety. The cell-free RNAs (cfRNA) circulating in plasma (Liquid biopsies) offer non-invasive detection of spatial and temporal changes occurring in primary tumors since early stages. To address gaps in current cfRNA knowledgebase, we conducted a pilot study for comprehensive analysis of transcriptome-wide changes in plasma cfRNA in NSCLC patients. Total cfRNA was extracted from archived plasma collected from NSCLC patients (N=12), cancer-free former smokers (N=12) and non-smoking healthy volunteers (N=12). Plasma cfRNA expression levels were quantified by using a tagmentation-based library preparation and sequencing. The comparisons of cfRNA expression levels between patients and the two control groups revealed a total of 2357 differentially expressed cfRNA enriched in 123 pathways. Of these, 251 transcripts were previously reported in primary NSCLCs. A small subset of genes (N=5) was validated in an independent sample (N=50) using qRT-PCR. Our study provides a framework for developing blood-based assays for early detection of NSCLC and warrants further validation.
SARS-CoV-2 IgM and IgG serology and clinical outcomes in COVID-19 patients
Authors: Mohan S , Kumar Pratap , Panda Prasan Kumar , Jain Vikram , Raina Rohit , Saha Sarama , Vivekandan S , Omar Balram J 
Published: August 2022

AbstractBackgroundThe SARS-CoV-2 virus has become pandemic for the last 2 years. Inflammatory response to the virus leads to organ dysfunction and death. Predicting the severity of inflammatory response helps in managing critical patients using serology tests IgG and IgM. We conducted a longitudinal study to correlate serum SARS-CoV-2 IgM and IgG serology with clinical outcomes in COVID-19 patients.MethodsWe analyzed patient data from March to December of 2020 for those who were admitted at AIIMS Rishikesh. Clinical and laboratory data of these patients were collected from the e-hospital portal and analysed. Correlation was seen with clinical outcomes and was assessed using MS Excel 2010 and SPSS software.ResultsOut of 494 patients, the mean age of patients was 48.95 ± 16.40 years and there were more male patients in the study (66.0%). The patients were classified into 4 groups; mild-moderate 328 (67.1%), severe 131 (26.8%) and critical 30 (6.1%). The mean duration from symptom onset to serology testing was 19.87 ± 30.53 days. In-hospital mortality was observed in 25.1% patients. The seropositivity rate (i.e., either IgG or IgM >10 AU) was 50%. There was a significant difference between the 2 groups in terms of IgM Levels (AU/mL) (W = 33428.000, p = <0.001) and IgG Levels (AU/mL) (W = 39256.500, p = <0.001), with the median IgM/ IgG Levels (AU/mL) being highest in the RT-PCR-Positive group. There was no significant difference between the groups in terms of IgM Levels and IgG levels with all other clinical outcomes (disease severity, septic shock, Intensive care admission, mechanical ventilation and mortality).ConclusionSerology (IgM and IgG) levels are high in RTPCR positive group compared to clinical COVID-19. However, serology cannot be useful for the prediction of disease outcomes except few situations. The study also highlights the importance of doing serology at a particular time as antibody titres vary with the duration of the disease.