bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating inflammatory proteins may be potential drug targets for Idiopathic Membranous Nephropathy: proteome-wide Mendelian Randomization and colocalization analysis
Authors: Su Zhihang , Rao Qingqing , Wu Di , Yin Zheng , Liu Wen , Wan Qijun 
Published: December 2023

AbstractBackgroundIdiopathic membranous nephropathy (IMN) is a predominant cause of nephrotic syndrome among adults. Existing drugs are ineffective in about one-third of IMN patients, and the high recurrence rate makes them far from satisfactory. Therefore, it is imperative to find new therapeutic targets for membranous nephropathy. Circulating inflammatory proteins in plasma have been found to be related to the disease and prognosis of IMN patients, yet the causal relationship between them still remains unclear. A better understanding of the inflammatory response of IMN can help us better understand the occurrence of IMN, as well as a good way to find new therapeutic targets. In this study, we aim to use proteome-wide Mendelian Randomization and colocalization analysis to identify plasma inflammatory proteins as potential therapeutic targets for IMN.MethodsWe selected the genetic instrumental variables (IVs) of 91 plasma inflammatory protein quantitative trait locus (pQTL) data obtained from 14824 European population samples by Zhao JH et al. in 2023 as exposure factors. The outcome variable was obtained from the Genome-Wide Association Study (GWAS) data on IMN, which involved 2150 cases and 5829 controls across five European cohorts. To investigate the associations between inflammatory proteins and IMN risk, we conducted a two-sample bi-directional MR analysis, sensitivity analysis, Bayesian colocalization, phenotype scanning, and analysis of the Protein-Protein Interaction (PPI) network.ResultsThe MR analysis uncovered 2 inflammatory factors associated with IMN. TNF-beta [(Tumor Necrosis Factor-beta) (IVW, OR=1.483, 95%CI=1.186-1.853, P=0.0005, PFDR=0.046)] was associated with an increased risk of IMN. IL-5 [(Interleukin-5) (IVW, OR=0.482, 95%CI=0.302-0.770, P=0.002, PFDR=0.097)] was associated with protective effects against IMN. After False Discovery Rate multiple correction and sensitivity analysis, they remain significant. None of these proteins exhibited a reverse causal relationship. Bayesian colocalization analysis provided evidence that TNF-beta share variants with IMN [posterior probability of hypothesis 4 (PPH4) = 0.88]. Utilizing the PPI network, we identified several proteins associated with the previously mentioned inflammatory proteins. Notably, TNF-beta and IL-5 were found to be linked to Nuclear Factor Kappa B Subunit 1 (NFKB1).ConclusionsOur exhaustive analysis suggests a causative impact of TNF-beta and IL-5 levels on the genetically predisposed risk of IMN. These proteins hold potential as promising therapeutic targets for IMN treatment, thus necessitating further clinical investigation.
A probabilistic graphical model for estimating selection coefficient of missense variants from human population sequence data
Authors: Zhao Yige , Zhong Guojie , Hagen Jake , Pan Hongbing , Chung Wendy K. , Shen Yufeng 
Published: December 2023

AbstractAccurately predicting the effect of missense variants is a central problem in interpretation of genomic variation. Commonly used computational methods does not capture the quantitative impact on fitness in populations. We developedMisFitto estimate missense fitness effect using biobank-scale human population genome data.MisFitjointly models the effect at molecular level (d) and population level (selection coefficient,s), assuming that in the same gene, missense variants with similardhave similars. MisFitis a probabilistic graphical model that integrates deep neural network components and population genetics models efficiently with inductive bias based on biological causality of variant effect. We trained it by maximizing probability of observed allele counts in 236,017 European individuals. We show thatsis informative in predicting frequency across ancestries and consistent with the fraction of de novo mutations givens. Finally,MisFitoutperforms previous methods in prioritizing missense variants in individuals with neurodevelopmental disorders.
Combined Effect of Inflammation and Malnutrition for Long-term Prognosis in Patients with Acute Coronary Syndrome: A Cohort Study
Authors: Yuxiu Yang , Ma Xiaoteng , Gao Fei , Liu Tao , Deng Jianping , Li Qiuxuan , Liu Zaiqiang , Wang Yufei , Zheng Yang , Yang Jingyao , Wang Zhijian 
Published: December 2023

AbstractBackgroundDysregulated inflammation with superimposed malnutrition may constitute a significant threat in acute coronary syndrome (ACS), which needs to be elucidated. We aimed to explore the prevalence and combined predictive value of inflammation and malnutrition in ACS patients.MethodsPatients presenting with ACS undergoing percutaneous coronary intervention (PCI) were retrospectively included and stratified into four groups: nourished without elevated high-sensitivity C-reactive protein (hs-CRP), nourished with elevated hs-CRP, malnourished without elevated hs-CRP, and malnourished with elevated hs-CRP. Elevated hs-CRP was determined as over 2.2mg/L, and malnutrition was defined according to the nutritional risk index (NRI). The primary outcome was major adverse cardiovascular events (MACEs), the composite of cardiac mortality, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization.ResultsA total of 1,743 patients were ultimately included; 646 (37%) presented elevated hs-CRP, and 119 (7%) were considered malnourished. During a median follow-up of 30 months, 351 (20.1%) MACEs occurred. The coexistence of malnutrition and elevated hs-CRP correlated with the worst outcomes among the four phenotypes, with a significantly increased risk of MACEs (adjusted hazard ratio: 2.446; 95% confidence interval: 1.464 - 4.089; p <0.001). In the subgroup analysis, NRI displayed MACEs-predicting value merely among patients with elevated hs-CRP rather than those without (p for interaction = 0.005), suggesting the modifying effect of inflammation; simultaneously, the prognostic implications of hs-CRP were influenced by patients’ baseline nutritional status, as it only existed in malnourished patients (p for interaction < 0.001).ConclusionsAmong patients with ACS undergoing PCI, the double burden of inflammation and malnutrition signifies poorer outcomes, and their prognostic implications may be amplified by each other, which would provide implications to facilitate more individualized ACS care.
Early COVID-19 vaccine effectiveness of XBB.1.5 vaccine against hospitalization and ICU admission, the Netherlands, 9 October - 5 December 2023
Authors: van Werkhoven C. Henri , Valk Anne-Wil , Smagge Bente , de Melker Hester E. , Knol Mirjam J. , Hahné Susan J.M. , van den Hof Susan , de Gier Brechje 
Published: December 2023

AbstractWe present early vaccine effectiveness (VE) estimates of the 2023 seasonal COVID-19 vaccination campaign using XBB.1.5 vaccine against COVID-19 hospitalization and ICU admission in previously vaccinated adults ≥60 years old in the Netherlands. We compared vaccination status of 2050 hospitalizations including 92 ICU admissions with age group-, sex-, region- and date-specific population vaccination coverage between 9 October and 5 December 2023. VE against hospitalization was 70.7% (95% CI: 66.6; 74.3), VE against ICU admission was 73.3% (95% CI: 42.2; 87.6).
Cervical Cancer Screening Outcomes for HIV-positive Women in the Lubombo and Manzini regions of Eswatini – Prevalence and Predictors of a Positive Visual Inspection with Acetic Acid (VIA) Screen
Authors: Mapaona Rufaro , Williams Victor , Musarapasi Normusa , Kibwana Sharon , Maseko Thokozani , Chekenyere Rhinos , Gumbo Sidumo , Mdluli Phetsile , Byarugaba Hugben , Galagedera Dileepa , Mafukidze Arnold , de Mendoza Alejandra , Adsul Prajakta , Bongomin Pido , Loffredo Christopher , Dlamini Xolisile , Bazira Deus , Ojoo Sylvia , Haumba Samson 
Published: December 2023

AbstractThis study aimed to describe the prevalence and predictors of a positive VIA (visual inspection with acetic acid) cervical cancer screening test in women living with human immunodeficiency virus (HIV). We retrospectively analysed data from women aged ≥15 who accessed VIA screening from health facilities in the Lubombo and Manzini regions of Eswatini. Sociodemographic and clinical data from October 2020 to June 2023 were extracted from the client management information system. VIA screening outcome was categorised into negative, positive, or suspicious. A logistic regression model estimated the adjusted odds ratio (AOR) of the predictors of a positive VIA screen at p<0.05 with 95% confidence intervals. Of 23,657 participants, 60.8% (n=14,397) were from the Manzini region. The mean age was 33.3 years (standard deviation 7.0), and 33% (n=7,714) were first-time screens. The prevalence of a positive VIA was 2.6% (95% CI: 2.2%, 3.0%): 2.8% (95% CI: 2.2%, 3.5%) in Lubombo and 2.4% (95% CI: 2.0%, 2.9%) in Manzini (p=0.096). Screening at mission-owned (OR 1.40; p=0.001), NGO-owned (OR 3.08; p<0.001) and industrial/workplace-owned health facilities (OR 2.37; p=0.044) were associated with positive test results compared to government-owned health facilities, and being within the 35–44 age group (OR 1.26; p=0.017) compared to 25-34 years age group was a positive predictor of a positive VIA screen. Negative predictors of positive VIA test were: being on anti-retroviral therapy (ART) for 5-9 years (OR 0.76; p=0.004) and ≥10 years (OR 0.66; p=0.002) compared to <5 years; and having an undetectable viral load (OR 0.39; p<0.001) compared to unsuppressed. Longer duration on ART and an undetectable viral load reduced the odds, while middle-aged women and screening at non-public health facilities increased the odds of a positive VIA screen.
The somato-cognitive action network links diverse neuromodulatory targets for Parkinson’s disease
Authors: Ren Jianxun , Zhang Wei , Dahmani Louisa , Hu Qingyu , Jiang Changqing , Bai Yan , Ji Gong-Jun , Zhou Ying , Zhang Ping , Wang Weiwei , Wang Kai , Wang Meiyun , Li Luming , Wang Danhong , Liu Hesheng 
Published: December 2023

AbstractThe newly-recognized somato-cognitive action network (SCAN) is posited to be important in movement coordination. Functional disruptions in Parkinson’s disease (PD) correspond with complex, non-effector-specific motor symptoms, indicating that SCAN dysfunction may underlie these symptoms. Along the same lines, the SCAN may link multiple neuromodulatory targets used for PD treatment. To investigate the role of the SCAN in PD, we leveraged resting-state precision functional mapping, analyzing data from 673 individuals across 6 independent datasets and 5 types of neuromodulation. Our findings revealed functional abnormalities within the SCAN in PD patients and the selective involvement of the SCAN in diverse neuromodulatory targets. Moreover, our data suggests causal links between SCAN connectivity changes and motor symptom alleviation following both invasive and non-invasive neuromodulation. Collectively, these findings underscore the critical role of the SCAN in the pathophysiology of PD and its brain stimulation treatments, and suggest the SCAN as a promising candidate target for neuromodulation.
Near chromosome-level and highly repetitive genome assembly of the snake pipefishEntelurus aequoreus(Syngnathiformes: Syngnathidae)
Authors: Wolf Magnus , Ferrette Bruno Lopes da Silva , Coimbra Raphael T. F. , de Jong Menno , Nebenfuehr Marcel , Prochotta David , Schöneberg Yannis , Zapf Konstantin , Rosenbaum Jessica , Mc Intyre Hannah A. , Maier Julia , de Souza Clara C.S. , Gehlhaar Lucas M. , Werner Melina J. , Oechler Henrik , Wittekind Marie , Sonnewald Moritz , Nilsson Maria A. , Janke Axel , Winter Sven 
Published: December 2023

AbstractThe snake pipefish,Entelurus aequoreus(Linnaeus, 1758), is a slender, up to 60 cm long, northern Atlantic fish that dwells in open seagrass habitats and has recently expanded its distribution range. The snake pipefish is part of the family Syngnathidae (seahorses and pipefish) that has undergone several characteristic morphological changes, such as loss of pelvic fins and elongated snout. Here, we present a highly contiguous, near chromosome-scale genome of the snake pipefish assembled as part of a university master’s course. The final assembly has a length of 1.6 Gbp in 7,391 scaffolds, a scaffold and contig N50 of 62.3 Mbp and 45.0 Mbp and L50 of 12 and 14, respectively. The largest 28 scaffolds (>21 Mbp) span 89.7% of the assembly length. A BUSCO completeness score of 94.1% and a mapping rate above 98% suggest a high assembly completeness. Repetitive elements cover 74.93% of the genome, one of the highest proportions so far identified in vertebrate genomes. Demographic modeling using the PSMC framework indicates a peak in effective population size (50 – 100 kya) during the last interglacial period and suggests that the species might largely benefit from warmer water conditions, as seen today. Our updated snake pipefish assembly forms an important foundation for further analysis of the morphological and molecular changes unique to the family Syngnathidae.
Self-inhibiting percolation and viral spreading in epithelial tissue
Authors: Xu Xiaochan , Nielsen Bjarke Frost , Sneppen Kim 
Published: December 2023

AbstractSARS-CoV-2 induces delayed type-I/III interferon production, allowing it to escape the early innate immune response. The delay has been attributed to a deficiency in the ability of cells to sense viral replication upon infection, which in turn hampers activation of the antiviral state in bystander cells. Here, we introduce a cellular automaton model to investigate the spatiotemporal spreading of viral infection as a function of virus and host-dependent parameters. The model suggests that the considerable person-to-person heterogeneity in SARS-CoV-2 infections is a consequence of high sensitivity to slight variations in biological parameters near a critical threshold. It further suggests that within-host viral proliferation can be curtailed by the presence of remarkably few cells that are primed for IFN production. Thus the observed heterogeneity in defense readiness of cells reflects a remarkably cost-efficient strategy for protection.
Plant plasmodesmata bridges form through ER-dependent incomplete cytokinesis
Authors: Li Ziqiang P. , Moreau Hortense , Petit Jules D. , Souza-Moraes Tatiana , Smokvarska Marija , Perez-Sancho Jessica , Petrel Melina , Decoeur Fanny , Brocard Lysiane , Chambaud Clément , Grison Magali , Paterlini Andrea , Glavier Marie , Hoornaert Lucie , Joshi Amit S. , Gontier Etienne , Prinz William A. , Jaillais Yvon , Taly Antoine , Campelo Felix , Caillaud Marie-Cécile , Bayer Emmanuelle M. 
Published: December 2023

AbstractDiverging from conventional cell division models, plant cells undergo incomplete division to generate plasmodesmata communication bridges between daughter cells. While fundamental for plant multicellularity, the molecular events leading to bridge stabilization, as opposed to severing, remain unknown. Using electron tomography, we mapped the transition from cell plate fenestrae to plasmodesmata. We show that the ER connects daughter cells across fenestrae, and as the cell plate matures, fenestrae contract, causing the PM to mold around constricted ER tubes. The ER’s presence prevents fenestrae fusion, forming plasmodesmata, while its absence results in closure. The ER-PM tethers MCTP3, 4, and 6 further stabilize nascent plasmodesmata during fenestrae contraction. Genetic deletion inArabidopsisreduces plasmodesmata formation. Our findings reveal how plants undergo incomplete division to promote intercellular communication.One-Sentence SummaryThe ER is important for stabilizing nascent plasmodesmata, a process integral to incomplete cytokinesis in plants.
Contrasting levels of transcriptome-wide SNP diversity and decoupled patterns of molecular and functional adaptive variation in conifers
Authors: Pavy Nathalie , Gérardi Sébastien , Prunier Julien , Rigault Philippe , Laroche Jérôme , Daigle Gaétan , Boyle Brian , Mackay John , Bousquet Jean 
Published: December 2023

ABSTRACTAdaptive convergence can arise when response to natural selection involves shared molecular or functional mechanisms among multiple taxa. Conifers are of ancient origin with delayed sexual maturity related to their woody perennial nature. Thus, they represent a relevant plant group to assess if convergence from selection may have become disconnected between molecular and functional levels. In this purpose, transcriptome-wide SNP diversity was assessed in seven partially sympatric and reproductively isolated conifer species populating the temperate and boreal forests of northeastern North America. SNP diversity was found highly heterogeneous among species, which would relate to variation in species-specific demography and history. Rapidly evolving genes with signatures of positive selection were identified, and their relative abundance among species reflected differences in transcriptome-wide SNP diversity. Their analysis also revealed very limited convergence among taxa in spite of sampling same tissues at same age. However, convergence increased gradually at the levels of gene families and biological processes, which were largely related to stress response and regulatory mechanisms in all species. Given their multiple small to large gene families and long time since inception, conifers may have had sufficient gene network flexibility and gene functional redundancy for evolving alternative adaptive genes for similar metabolic responses to environmental selection pressures. Despite a long divergence time of ∼350 Mya between conifers and Angiosperms, we also uncovered a set of 20 key genes presumably under positive selection in both lineages.
In vivo mapping of protein-protein interactions of schizophrenia risk factors generates an interconnected disease network
Authors: McClatchy Daniel B. , Powell Susan B. , Yates John R. 
Published: December 2023

AbstractGenetic analyses of Schizophrenia (SCZ) patients have identified thousands of risk factors. In silico protein-protein interaction (PPI) network analysis has provided strong evidence that disrupted PPI networks underlie SCZ pathogenesis. In this study, we performedin vivoPPI analysis of several SCZ risk factors in the rodent brain. Using endogenous antibody immunoprecipitations coupled to mass spectrometry (MS) analysis, we constructed a SCZ network comprising 1612 unique PPI with a 5% FDR. Over 90% of the PPI were novel, reflecting the lack of previous PPI MS studies in brain tissue. Our SCZ PPI network was enriched with known SCZ risk factors, which supports the hypothesis that an accumulation of disturbances in selected PPI networks underlies SCZ. We used Stable Isotope Labeling in Mammals (SILAM) to quantitate phencyclidine (PCP) perturbations in the SCZ network and found that PCP weakened most PPI but also led to some enhanced or new PPI. These findings demonstrate that quantitating PPI in perturbed biological states can reveal alterations to network biology.
Simple and Highly Specific Targeting of Resident Microglia with Adeno-Associated Virus
Authors: Serrano Carolina , Cananzi Sergio , Shen Tianjin , Wang Lei-Lei , Zhang Chun-Li 
Published: December 2023

ABSTRACTMicroglia, as the immune cells of the central nervous system (CNS), play dynamic roles in both health and diseased conditions. The ability to genetically target microglia using viruses is crucial for understanding their functions and advancing microglia-based treatments. We here show that resident microglia can be simply and specifically targeted using adeno-associated virus (AAV) vectors containing a 466-bp DNA fragment from the humanIBA1(hIBA1) promoter. This targeting approach is applicable to both resting and reactive microglia. When combining the shorthIBA1promoter with the target sequence of miR124, up to 95% of transduced cells are identified as microglia. Such a simple and highly specific microglia-targeting strategy may be further optimized for research and therapeutics.Significance StatementBrain microglia play critical roles in human health and diseases. Genetic manipulation of these cells will offer numerous therapeutic opportunities. However, there is a lack of relevant strategies to target these cells with high specificity since they are traditionally considered to be refractory to virus transduction. Through in vivo screening of many promoters, this study identified a short promoter from the humanIBA1gene. When incorporated into lentivirus or adeno-associated virus vectors, this promoter proves effective in driving gene expression with high specificity for brain microglia. Such a simple strategy will facilitate specific approaches for microglia-based research.
Effects of auditory noise intensity and color on the dynamics of upright stance
Authors: Carey Sam , Ross Jessica M. , Abney Drew , Balasubramaniam Ramesh 
Published: December 2023

SummaryPrevious work assessing the effect of additive noise on the postural control system has found a positive effect of white noise on postural dynamics. This study covers two separate experiments that were run sequentially to better understand how the structure of the additive noise signal affects postural dynamics, while also furthering our knowledge of how the intensity of auditory stimulation of noise may elicit this phenomenon. Across the two experiments, we introduced three auditory noise stimulations of varying structure (white, pink, and brown noise). Experiment 1 presented the stimuli at 35 dB while Experiment 2 was presented at 75 dB. Our findings demonstrate a decrease in variability of the postural control system regardless of the structure of the noise signal presented, but only for high intensity auditory stimulation.
Unfolding and De-confounding: Biologically meaningful causal inference from longitudinal multi-omic networks usingMETALICA
Authors: Ruiz-Perez Daniel , Gimon Isabella , Sazal Musfiqur , Mathee Kalai , Narasimhan Giri 
Published: December 2023

ABSTRACTA key challenge in the analysis of microbiome data is the integration of multi-omic datasets and the discovery of interactions between microbial taxa, their expressed genes, and the metabolites they consume and/or produce. In an effort to improve the state-of-the-art in inferring biologically meaningful multi-omic interactions, we sought to address some of the most fundamental issues in causal inference from longitudinal multi-omics microbiome data sets. We developed METALICA, a suite of tools and techniques that can infer interactions between microbiome entities. METALICA introduces novelunrollingandde-confoundingtechniques used to uncover multi-omic entities that are believed to act as confounders for some of the relationships that may be inferred using standard causal inferencing tools. The results lend support to predictions about biological models and processes by which microbial taxa interact with each other in a microbiome. Theunrollingprocess helps to identify putative intermediaries (genes and/or metabolites) to explain the interactions between microbes; thede-confoundingprocess identifies putative common causes that may lead to spurious relationships to be inferred. METALICA was applied to the networks inferred by existing causal discovery and network inference algorithms applied to a multi-omics data set resulting from a longitudinal study of IBD microbiomes. The most significant unrollings and de-confoundings were manually validated using the existing literature and databases.ImportanceWe have developed a suite of tools and techniques capable of inferring interactions between microbiome entities. METALICAintroduces novel techniques called unrolling and de-confounding that are employed to uncover multi-omic entities considered to be confounders for some of the relationships that may be inferred using standard causal inferencing tools. To evaluate our method, we conducted tests on the Inflammatory Bowel Disease (IBD) dataset from the iHMP longitudinal study, which we pre-processed in accordance with our previous work.