bluuebunny/crossref_metadata_2025_split huggingface dataset:
NetAllergen, a random forest model integrating MHC-II presentation propensity for improved allergenicity prediction
Authors: Li Yuchen , Sackett Peter Wad , Nielsen Morten , Barra Carolina 
Published: September 2022

ABSTRACTAllergy is a pathological immune reaction towards innocuous protein antigens. Although only a narrow fraction of plant or animal proteins induce allergy, atopic disorders affect millions of children and adults and cost billions in healthcare systems worldwide. In-silico predictors can aid in the development of more innocuous food sources. Previous allergenicity predictors used sequence similarity, common structural domains, and amino acid physicochemical features. However, these predictors strongly rely on sequence similarity to known allergens and fail to predict protein allergenicity accurately when similarity diminishes. In addition, ‘allergen’ is a broad terminology that may include different compounds, hindering the classification task. To overcome these limitations, we collected allergens from AllergenOnline, a curated database of IgE-inducing allergens, carefully removed allergen redundancy with a novel protein partitioning pipeline, and developed a new allergen prediction method, introducing MHC presentation propensity as a novel feature. NetAllergen outperformed a sequence similarity-based BLAST baseline approach, and previous allergenicity predictor AlgPred 2 when similarity to known allergens is limited. NetAllergen is available as a web service (services.healthtech.dtu.dk/service.php?NetAllergen-1.0) and can predict allergenicity from a protein sequence.
Differential representation of natural and manmade images in the human ventral visual stream
Authors: Gopnarayan Mrugsen Nagsen , Rathore Deeksha R. , Bauer Fabio S. , Hillard Jasper , Chawla Prerita 
Published: September 2022

AbstractThe human visual cortex processes visual stimuli hierarchically. Early visual areas (V1, V2) of the ventral visual stream feed crude visual features (like orientation and edges) into later visual areas (V4, lateral occipital (Lat Occ), inferior temporal (IT)) that then encode complex visual features (like object form). Previous studies have reported a difference in fMRI responses between natural and urban landscapes in certain parts of the brain. Here we asked if this distinction in the representation of complex natural and man-made visual stimuli extends to the ventral visual stream and if state-of-the-art convolutional neural networks (CNN) provide a map to this categorical distinction. To assess this, we used an open source fMRI data set of V1-4 and LatOcc BOLD responses to 1750 passively viewed natural and man-made grayscale images. The same images were fed into the pre-trained CORnet-S, a CNN designed to model hierarchical human visual processing layer-wise. To identify differences in representations within and between the human visual cortex and the CNN, we computed representational dissimilarity matrices. The BOLD response to the manmade and natural images shows correlation differences for the two categories, which increase across V4 and LatOcc. Such differences were also observed in the model CORnet-S for the layers V4 and IT. Our results suggest that the human visual cortex processes natural and manmade images differently starting from V4 and that this representational difference is modeled in CORnet-S. In both, categorical representation is progressively established in the later processing stages. This might indicate that the brain has perhaps developed two-distinct systems for their representations which can be directed through evolution. Further analysis may elucidate the contributory role of evolution towards this paradigm.
Neuronal pentraxin Nptx2 regulates complement activity in the brain
Authors: Zhou Jiechao , Wade Sarah D. , Graykowski David , Xiao Mei-Fang , Zhao Binhui , Giannini Lucia AA , Hanson Jesse E. , van Swieten John C , Sheng Morgan , Worley Paul F. , Dejanovic Borislav 
Published: September 2022

AbstractComplement overactivation mediates microglial synapse elimination in neurological diseases like Alzheimer’s disease and frontotemporal dementia (FTD), but how complement activity is regulated in the brain remains largely unknown. We identified that the secreted neuronal pentraxin Nptx2 binds complement C1q and thereby regulates its activity in the brain. Nptx2-deficient mice show increased complement activity and C1q-dependent microglial synapse engulfment and loss of excitatory synapses. In a neuroinflammation culture model and in aged TauP301S mice, AAV-mediated neuronal overexpression of Nptx2 was sufficient to restrain complement activity and ameliorate microglia-mediated synapse loss. Analysis of human CSF samples from a genetic FTD cohort revealed significantly reduced levels of Nptx2 and Nptx2-C1q protein complexes in symptomatic patients, which correlated with elevated C1q and activated C3. Together, these results show that Nptx2 regulates complement activity and microglial synapse elimination in the healthy and diseased brain and that diminished Nptx2 levels might exacerbate complement-mediated neurodegeneration in FTD patients.
Cytosolic condensates enriched in polyserine repeats are preferred sites of tau fiber propagation
Authors: Lester Evan , Alstyne Meaghan Van , McCann Kathleen L. , Reddy Spoorthy , Cheng Li Yi , Kuo Jeff , Pratt James , Parker Roy 
Published: September 2022

AbstractTau aggregates are a hallmark of multiple neurodegenerative diseases and can contain RNAs and RNA binding proteins, including SRRM2 and PNN. How these resident nuclear proteins mislocalize and their influence on the prion-like propagation of tau fibers remains unknown. We demonstrate that polyserine repeats in SRRM2 and PNN are necessary and sufficient for recruitment to tau aggregates. Moreover, we demonstrate tau fibers preferentially grow in association with endogenous cytoplasmic assemblies – mitotic interchromatin granules and cytoplasmic speckles – which contain SRRM2 and PNN. Polyserine undergoes self-assemblyin vitroand in cells, where polyserine-assemblies are sites of tau fiber propagation. Modulating the levels of polyserine containing proteins results in a corresponding change in tau aggregation. These findings define a specific protein motif, and cellular condensates, that promote tau fiber propagation. As cytoplasmic speckles form in iPSC neurons under inflammatory or hyperosmolar stress, they may promote tau fiber propagation in various neurodegenerative diseases.
Consideration of within-patient diversity highlights transmission pathways and antimicrobial resistance gene variability in vancomycin resistantEnterococcus faecium
Authors: McHugh Martin P , Pettigrew Kerry A , Taori Surabhi , Evans Thomas J , Leanord Alistair , Gillespie Stephen H , Templeton Kate E , Holden Matthew TG 
Published: September 2022

SynopsisBackgroundWhole genome sequencing (WGS) is increasingly applied to healthcare-associated vancomycin-resistantEnterococcus faecium(VREfm) outbreaks. Within-patient diversity could complicate transmission resolution if single colonies are sequenced from identified cases.ObjectivesDetermine the impact of within-patient diversity on transmission resolution of VREfmMethodsFourteen colonies were collected from VREfm positive rectal screens, single colonies were collected from clinical samples, and Illumina WGS performed. Two isolates were selected for Oxford Nanopore sequencing and hybrid genome assembly to generate lineage-specific reference genomes. Mapping to closely related references was used to identify genetic variations and closely related genomes. A transmission network was inferred for the entire genome set using Phyloscanner.ResultsIn total, 229 isolates from 11 patients were sequenced. Carriage of 2-3 sequence types was detected in 27% of patients. Presence of antimicrobial resistance genes and plasmids was variable within genomes from the same patient and sequence type. We identified two dominant sequence types (ST80 and ST1424), with two putative transmission clusters of two patients within ST80, and a single cluster of six patients within ST1424. We found transmission resolution was impaired using fewer than 14 colonies.ConclusionsPatients can carry multiple sequence types of VREfm, and even within related lineages the presence of mobile genetic elements and antimicrobial resistance genes can vary. VREfm within-patient diversity should be considered to ensure accurate resolution of transmission networks.
The variability of nociplastic and central pain definition in literature: a scoping review
Authors: Margelli Michele , Enrico Bonas , Giovanni Obinu , Gianluca De Marco , Andrea Baroni , Carlo Sartorio 
Published: September 2022

AbstractBackgroundCurrently, the concept of pain is widely discussed in the scientific community, particularly chronic musculoskeletal pain.One important classification concerns the mechanisms of pain generation, according to which pain is divided into nociceptive pain, neuropathic pain, nociplastic pain (NP), and central sensitization (CS).Often the terms nociplastic pain and central sensitization are used incorrectly, as synonyms, or improperly; this can make data transmission complicated.The aim of this review will be to provide a clearer overview of the concept of pain in the scientific literature, describe the variability on the use of the terms nociplastic pain and central sensitization, and describe the mechanisms in relation to musculoskeletal pain syndromes.Inclusion CriteriaEvery study describing the mechanisms of nociplastic pain or central sensitization in a population of adults (> 18 years old), with acute or chronic musculoskeletal pain, in one or more anatomic regions. This scoping review will consider studies conducted in any context. Articles in English or Italian will be considered.MethodsThe proposed scoping review will be conducted in accordance with the Joanna Briggs Institute methodology (JBI) for scoping reviews.The search will be carried out on 5 databases: MEDLINE, Cochrane Central, Scopus, Embase, and PEDro.Selection and data extraction will be conducted by two blind independent researchers and inconsistencies will be resolved by a third reviewer.The results will be presented in a schematic, tabular and descriptive format that will line up with the objectives and scope of the review.ConclusionsThis will be the first scoping review to provide a comprehensive overview of the topic. The results will add meaningful information for clinicians. Furthermore, any knowledge gaps of the topic will be identified. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.
The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy
Authors: Prins H.A.B. , Crespo R. , Lungu C. , Rao S. , Li L. , Overmars R.J. , Papageorgiou G. , Mueller Y.M. , Hossain T. , Kan T.W. , Rijnders B.J.A. , Bax H.I. , van Gorp E.C.M. , Nouwen J.L. , de Vries-Sluijs T.E.M.S. , Schurink C.A.M. , de Mendonça Melo M. , van Nood E. , Colbers A. , Burger D. , Palstra R-J. , van Kampen J.J.A. , van de Vijver D.A.M.C. , Mesplède T. , Katsikis P.D. , Gruters R.A. , Koch B.C.P. , Verbon A. , Mahmoudi T. , Rokx C. 
Published: September 2022

AbstractA major barrier towards HIV-1 cure is the presence of a replication-competent latent reservoir that, upon treatment cessation, can spark viral rebound leading to disease progression. Pharmacological reactivation of the latent HIV-1 reservoir with Latency reversing agents (LRAs) is a first step toward triggering reservoir decay. Inhibitors of the BAF-complex, a key repressor of HIV-1 transcription were identified to act as LRAs, and enhanced the effect of other LRAs such as histone deacetylase inhibitors ex-vivo. We repurposed the licensed drug pyrimethamine as a BAF-inhibitor to investigate its in vivo impact on the HIV-1 reservoir of people living with HIV-1 (PLWH). Twenty eight PLWH on suppressive antiviral therapy were randomized in a 1:1:1:1 ratio to receive pyrimethamine; high dose valproic acid; both valproic acid and pyrimethamine; or no intervention for 14 days. The primary endpoint was change in HIV-1 reactivation measured as cell associated (CA)HIV-1 RNA at treatment initiation and at the end of treatment. We observed a rapid, modest and significant increase in CAHIV-1 RNA in CD4+T-cells in response to pyrimethamine exposure, which persisted throughout the 14 day treatment, concomitant with induction of BAF target genes as biomarkers of pyrimethamine activity as well as detected plasma pyrimethamine levels. Valproic acid treatment alone did not lead to increase in CAHIV-1 RNA, nor did valproic acid augment the latency reversal effect of pyrimethamine. Despite demonstrated latency reversal, pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir as determined by a tat/rev limiting dilution assay. Serious adverse events were not observed, although physician-directed treatment adjustments occurred, particularly when combining valproic acid with pyrimethamine. These data underline the need for pharmacovigilance in combinatorial clinical strategies and demonstrate that the BAF inhibitor pyrimethamine reverses HIV-1 latency in vivo in PLWH, substantiating its potential in advancement in clinical studies to target the proviral reservoir. Clinicaltrials.gov:NCT03525730One sentence summaryThis clinical trial shows that the BAF inhibitor pyrimethamine reverses HIV-1 latency in vivo which supports repurposing this drug for cure studies.
Post-COVID-19 syndrome: retinal microcirculation as a potential marker for chronic fatigue
Authors: Schlick Sarah , Lucio Marianna , Bartsch Alexander , Skornia Adam , Hoffmanns Jakob , Szewczykowski Charlotte , Schröder Thora , Raith Franziska , Rogge Lennart , Heltmann Felix , Moritz Michael , Beitlich Lorenz , Schottenhamml Julia , Herrmann Martin , Harrer Thomas , Ganslmayer Marion , Kruse Friedrich E. , Lämmer Robert , Mardin Christian , Hohberger Bettina 
Published: September 2022

AbstractPost-COVID-19 syndrome (PCS) summarizes persisting sequelae after infection with the severe-acute-respiratory-syndrome-Coronavirus-2 (SARS-CoV-2). PCS can affect patients of all covid-19 disease severities. As previous studies revealed impaired blood flow as a provoking factor for triggering PCS, it was the aim of the present study to investigate a potential association of self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker.A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT-Angiography (OCT-A) and quantified by the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic Fatigue (CF) was assessed with the variables ‘Bell score’, age and gender. The VD in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed considering the repetitions (12 times). Taking in account of such repetitions a mixed model was performed to detect possible differences in the least square means between different groups of analysis.An age effect on VD was observed between patients and controls (p<0.0001). Gender analysis yielded that women with PCS showed lower VD levels in SVP compared to male patients (p=0.0015). The PCS patients showed significantly lower VD of ICP as compared to the controls (p=0.0001, [CI: 0.32; 1]). Moreover, considering PCS patients, the mixed model reveals a significant difference between chronic fatigue (CF) and without CF in VD of SVP (p=0.0033, [CI: -4.5; -0.92]). The model included age, gender and the variable ‘Bell score’, representing a subjective marker for CF. Consequently, the retinal microcirculation might be an objective biomarker in subjective-reported chronic fatigue of patients with PCS.
Determinants of self-reported health status during COVID-19 lockdown among surveyed Ecuadorian population: a cross sectional study
Authors: Dueñas-Espín Iván , Jacques-Aviñó Constanza , Egas-Reyes Verónica , Larrea Sara , Torres-Castillo Ana Lucía , Trujillo Patricio , Peralta Andrés 
Published: September 2022

AbstractObjectiveTo examine the associations of sociodemographic, socioeconomic, and behavioral factors with depression, anxiety, and self-reported health status during the COVID-19 lockdown in Ecuador. We also assessed the differences in these associations between women and men.Design, setting, and participantsWe conducted a cross-sectional study of adults living in Ecuador between July and October 2020. All data were collected through an online survey. We ran descriptive and bivariate analyses and fitted sex-stratified multivariate logistic regression models to assess the association between explanatory variables and self-reported health status.Results1801 women and 1123 men completed the survey. Their median (IQR) age was 34 (27–44) years, most participants had a university education (84%) and a full-time public or private job (63%); 16% of participants had poor health self-perception. Poor self-perceived health was associated with severe depression, COVID-19 infection, and chronic diseases. For women, and self-employment, having cohabitants requiring care, having COVID-19 and having a chronic disease increased the likelihood of having poor self-reported health status. For men, poor self-reported health status was associated with perceived poor or inadequate housing and depression.ConclusionBeing female, having solely public healthcare system access, perceiving housing conditions as inadequate, living with cohabitants requiring care, perceiving difficulties in coping with work or managing household chores, COVID-19 infection, chronic disease, and depression symptoms were significantly and independently associated with poor self-reported health status in Ecuadorian population.
The impact of COVID-19 vaccination in the US: averted burden of SARS-COV-2-related cases, hospitalizations and deaths
Authors: Yamana Teresa K. , Galanti Marta , Pei Sen , Di Fusco Manuela , Angulo Frederick J. , Moran Mary M. , Khan Farid , Swerdlow David L. , Shaman Jeffrey 
Published: September 2022

AbstractBy August 1, 2022, the SARS-CoV-2 virus had caused over 90 million cases of COVID-19 and one million deaths in the United States. Since December 2020, SARS-CoV-2 vaccines have been a key component of US pandemic response; however, the impacts of vaccination are not easily quantified. Here, we use a dynamic county-scale metapopulation model to estimate the number of cases, hospitalizations, and deaths averted due to vaccination during the first six months of vaccine availability. We estimate that COVID-19 vaccination was associated with over 8 million fewer confirmed cases, over 120 thousand fewer deaths, and 700 thousand fewer hospitalizations during the first six months of the campaign.
Associations of ABO and Rhesus D Blood Groups with Phenome-Wide Disease Incidence: A 41-year Retrospective Cohort Study of 482,914 Patients
Authors: Bruun-Rasmussen Peter , Dziegiel Morten Hanefeld , Banasik Karina , Johansson Pär Ingemar , Brunak Søren 
Published: September 2022

AbstractBackgroundThe natural selection responsible for the observed blood group frequency differences between populations remains debatable. The ABO system has been associated with several diseases and recently also with susceptibility to COVID-19 infection. Associative studies of the RhD system and diseases are sparser. A large disease-wide risk analysis may further elucidate the relationship between the ABO/RhD blood groups and disease incidence.MethodsWe performed a systematic log-linear quasi-Poisson regression analysis of the ABO/RhD blood groups across 1,312 phecode diagnoses. Unlike prior studies, we determined the uniqueness of each individual ABO blood group as opposed to using blood group O as the reference. Moreover, we used up to 41-years of nationwide Danish follow-up data, and a disease categorization scheme specifically developed for diagnosis-wide analysis. Further, we determined associations between the ABO/RhD blood groups and the age at the first diagnosis. Estimates were adjusted for multiple testing.ResultsThe retrospective cohort included 482,914 Danish patients (60.4% females). The incidence rate ratios (IRRs) of 101 phecodes were found statistically significant between the ABO blood groups, while the IRRs of 28 phecodes were found statistically significant for the RhD blood group. The associations included cancers and musculoskeletal-, genitourinary-, endocrinal-, infectious-, cardiovascular-, and gastrointestinal diseases.ConclusionsWe found associations of disease-wide susceptibility differences between the blood groups of the ABO and RhD systems, including cancer of the tongue, monocytic leukemia, cervical cancer, osteoarthrosis, asthma, and HIV- and hepatitis B infection. This may indicate that the ABO/RhD blood groups are the results of a selective pressure driven partly by robustness to disease. We found marginal evidence of associations between the blood groups and disease onset.FundingNovo Nordisk Foundation and the Innovation Fund Denmark
Genetic Analysis of Activin/Inhibin β Subunits in Zebrafish Development and Reproduction
Authors: Zhao Cheng , Zhai Yue , Geng Ruijing , Wu Kun , Song Weiyi , Ai Nana , Ge Wei 
Published: September 2022

AbstractActivin and inhibin are both dimeric proteins sharing the same β subunits that belong to the TGF-β superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs. However, their functions in development and reproduction of other species are poorly defined. In this study, we disrupted all three activin/inhibin β subunits (βAa,inhbaa; βAb,inhbab; and βB,inhbb) in zebrafish using CRISPR/Cas9. The loss of βAa/b but not βB led to a high mortality rate in the post-hatching stage. Surprisingly, the expression offshbbut notlhbin the pituitary increased in the female βA mutant together with aromatase (cyp19a1a) in the ovary. The single mutant of βAa/b showed normal folliculogenesis in young females; however, their double mutant (inhbaa−/−;inhbab−/−) showed delayed follicle activation, granulosa cell hypertrophy, stromal cell accumulation and tissue fibrosis. The ovary ofinhbaa−/−deteriorated progressively after 180 dpf with reduced fecundity and the folliculogenesis ceased completely around 540 dpf. In addition, tumor- or cyst-like tissues started to appear in theinhbaa−/−ovary after about one year. In contrast to females, activin βAa/b mutant males showed normal spermatogenesis and fertility. As for activin βB subunit, theinhbb−/−mutant exhibited normal folliculogenesis, spermatogenesis and fertility in both sexes; however, the fecundity of mutant females decreased dramatically at 270 dpf with accumulation of early follicles. In summary, the activin-inhibin system plays an indispensable role in fish reproduction, in particular folliculogenesis and ovarian homeostasis.