bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal and comparative analysis of humoral response upon COVID-19 vaccination
Authors: Romero-Pinedo Salvador , Quesada Marina , Álvarez-Fernández Stela , Olmo Asunción , Abia David , Alarcón Balbino , Delgado Pilar 
Published: October 2021

ABSTRACTThe emergence of COVID-19 has led to a worldwide challenge for the rapid development of vaccines. Several types of safe and effective vaccines have been available in a time frame never seen before. Comparative studies to know the extent of protection and the immune response elicited by the different vaccines are of outstanding utility. Here, as a correlate for protection, we perform a comparative study of the humoral response to three vaccines, ChAdOx1 (Oxford-AstraZeneca), mRNA-1273 (Moderna), and BNT162b2 (Pfizer-BioNTech) by applying a flow cytometry-based highly sensitive method that we had previously developed. We have found that mRNA vaccines (mRNA-1273 and BNT162b2) induce a stronger humoral response that lasts for at least 6 months after vaccination. We also show that only one dose of BNT162b2 is enough to achieve the maximum response in seropositive pre-vaccination donors.
δ1 variant of SARS-COV-2 acquires spike V1176F and yields a highly mutated subvariant in Europe
Authors: Yang Xiang-Jiao 
Published: October 2021

ABSTRACTGenomic surveillance of SARS-COV-2 has revealed that in addition to many variants of interests, this virus has yielded four variants of concern, α, β, γ and δ, as designated by the World Health Organization. δ variant has recently become the predominant pandemic driver around the world and yielded four different subvariants (δ1, δ2, δ3 and δ4). Among them, δ1 has emerged as the key subvariant that drives the pandemic in India, Europe and the USA. A relevant question is whether δ1 subvariant continues to evolve and acquires additional mutations. Related to this, this subvariant has acquired spike V1176F, a signature substitution of γ variant, and yielded a new sublineage, δ1F. The substitution alters heptad repeat 2 of spike protein and is expected to improve interaction with heptad repeat 1 and enhance virus entry. Moreover, there are δ1F sublineages encoding spike N501Y, A783S, Q836E and V1264L. While N501Y is a signature substitution shared by α, β and γ variants, V1264L is a key substitution in a δ1 sublineage that is a major pandemic driver in Southeast Asia. The Q836E-encoding lineage carries an average of 50 mutations per genome, making it the most mutated variant identified so far. Similar to δ1 subvariant, δ2 subvariant has also acquired spike V1176F and yielded new sublineages. Together, these results suggest that V1176F is a recurrent spike substitution that is frequently acquired by SARS-COV-2 variants to improve viral fitness. It is thus important to track the evolutionary trajectory of related variants for considering and instituting the most effective public health measures.
Genomics-based identification of a potential causal role for acylcarnitine metabolism in depression
Authors: Milaneschi Yuri , Arnold Matthias , Kastenmüller Gabi , Dehkordi Siamak Mahmoudian , Krishnan Ranga R. , Dunlop Boadie W. , Rush A. John , Penninx Brenda W. J. H. , Kaddurah-Daouk Rima ,   for the Mood Disorders Precision Medicine Consortium (MDPMC)
Published: October 2021

ABSTRACTBackgroundAltered metabolism of acylcarnitines – transporting fatty acids to mitochondria – may link cellular energy dysfunction to depression. We examined the potential causal role of acylcarnitine metabolism in depression by leveraging genomics and Mendelian randomization.MethodsSummary statistics were obtained from large GWAS: the Fenland Study (N= 9,363), and the Psychiatric Genomics Consortium (246,363 depression cases and 561,190 controls). Two-sample Mendelian randomization analyses tested the potential causal link of 15 endogenous acylcarnitines with depression.ResultsIn univariable analyses, genetically-predicted lower levels of short-chain acylcarnitines C2 (Odds Ratio [OR] 0.97, 95% Confidence Intervals [CIs] 0.95-1.00) and C3 (OR 0.97, 95%CIs 0.96-0.99) and higher levels of medium-chain acylcarnitines C8 (OR 1.04, 95%CIs 1.01-1.06) and C10 (OR 1.04, 95%CIs 1.02-1.06) were associated with increased depression risk. No reverse potential causal role of depression genetic liability on acylcarnitines levels was found. Multivariable analyses showed that the association with depression was driven by the medium-chain acylcarnitines C8 (OR 1.04, 95%CIs 1.02-1.06) and C10 (OR 1.04, 95%CIs 1.02-1.06), suggesting a potential causal role in the risk of depression. Causal estimates for C8 (OR=1.05, 95%CIs=1.02-1.07) and C10 (OR=1.05, 95%CIs=1.02-1.08) were confirmed in follow-up analyses using genetic instruments derived from a GWAS meta-analysis including up to 16,841 samples.DiscussionAccumulation of medium-chain acylcarnitines is a signature of inborn errors of fatty acid metabolism and age-related metabolic conditions. Our findings point to a link between altered mitochondrial energy production and depression pathogenesis. Acylcarnitine metabolism represents a promising access point for the development of novel therapeutic approaches for depression.
Proteomic and clinical biomarkers for acute mountain sickness diagnosis, prognosis, protection, and pathogenesis in a longitudinal cohort
Authors: Yang Jing , Jia Zhilong , Song Xinyu , Shi Jinlong , Zhao Xiaojing , He Kunlun 
Published: October 2021

AbstractAcute mountain sickness (AMS) is frequently experienced by non-high-altitude natives at high altitudes, which affects the quality of health and productivity of humans. The diagnosis of the disease mainly depends on a self-questionnaire, which reveals our insufficient understanding of AMS and the necessity of developing reliable biomarkers for AMS. In addition to 65 clinical indexes and 22 AMS symptom phenotypes, we profiled the plasma proteomic profiles of AMS via a combination of proximity extension assay with multiple reaction monitoring for a longitudinal cohort of 53 individuals divided into discovery and validation stages. Through differential analysis, machine learning models with high accuracy and protein-symptom-clinical index functional network analysis, we identified proteomic and clinical biomarkers for AMS diagnosis, prognosis, protection, and pathogenesis. RET, a top-weighted protein in the pathogenesis model, showed opposite regulations between individuals with AMS and those without AMS ascending to a high altitude. The downregulation of ADAM15 may play a protective role at high altitude in individuals without AMS. These results suggest that RET and ADAM15 could be promising therapeutic targets for AMS. Moreover, PHGDH and TRAF2 could be candidate predictive and diagnostic biomarkers for AMS, respectively. Additionally, C-peptide was found to be actively involved in the pathogenesis and could aid the assistant diagnosis of AMS. Notably, individuals with AMS showed higher gluconeogenesis activity at the plain than those without AMS. Our findings shed light on the proteomic and clinical biomarkers of AMS, provide a wealth of biological insights into AMS, and thereby promote precision medicine for AMS.
Theta-band phase locking during encoding leads to coordinated entorhinal-hippocampal replay
Authors: Santos-Pata Diogo , Barry Caswell , Freyja Ólafsdóttir H. 
Published: October 2021

AbstractPrecisely timed interactions between hippocampal and cortical neurons during replay epochs are thought to support memory consolidation. Indeed, research has shown replay is associated with heightened hippocampal-cortical synchrony. Yet, many caveats remain in our understanding. Namely, it remains unclearhowthis offline synchrony comes about, whether it is specific to particular behavioural states and how - if at all - it relates to learning. In this study, we sought to address these questions by analysing coordination between CA1 cells and neurons of the deep layers of the medial entorhinal cortex (dMEC) while rats learned a novel spatial task. During movement, we found a subset of dMEC cell which were particularly locked to hippocampal LFP theta-band oscillations and which were preferentially coordinated with hippocampal replay during offline periods. Further, dMEC synchrony with CA1 replay peaked ∼10ms after replay initiation in CA1, suggesting the distributed replay reflects extra-hippocampal information propagation, and was specific to ‘offline’ periods.Finally, theta-modulated dMEC cells only became coordinated with replay after an animal’s first encounter with a novel spatial environment and then showed a striking experience-dependent increase in synchronisation with hippocampal replay trajectories, mirroring the animals’ acquisition of the novel task and coupling to the hippocampal local field. Together, these findings provide strong support for the hypothesis that synergistic hippocampal-cortical replay supports the consolidation of new memories and highlights phase locking to hippocampal theta oscillations as a potential mechanism by which such cross-structural synchrony comes about. Importantly, as CA1 phase-locking to theta is implicated in the generation of theta sequences, thought to be required for replay expression, we speculate the dMEC theta phase-locking reflects the emergence of distributed hippocampal-dMEC theta sequences and that these may support the commission of memories to long-term cortical storage.
Identification of Significant Gene Expression Changes in Multiple Perturbation Experiments using Knockoffs
Authors: Zhao Tingting , Zhu Guangyu , Flaherty Patrick 
Published: October 2021

AbstractMotivationLarge-scale multiple perturbation experiments have the potential to reveal a more detailed understanding of the molecular pathways that respond to genetic and environmental changes. A key question in these studies is which gene expression changes are important for the response to the perturbation.ResultsWe present here a method based on the model-X knockoffs framework to identify significant gene expression changes in multiple perturbation experiments. This approach makes no assumptions on the functional form of the dependence between the responses and the perturbations and provides finite sample false discovery rate control for the set of important gene expression responses. In a large-scale multiple perturbation gene expression data set from the Library of Integrated Network-Based Cellular Signature (LINCS) NIH program, we identified important genes whose expression is modulated in response to perturbation with anthracycline, vorinostat, trichostatin-a, geldanamycin, and sirolimus. Furthermore, we compared the set of important genes that respond to these small molecules to identify co-responsive pathways.Availability and Implementationhttps://github.com/flahertylab/deepYknockoffContactpflaherty@umass.eduandzhaott0416@gmail.comSupplementary informationSupplementary data are available atBioinformaticsonline.
High Resolution Nanostructure with Two-stages of Exponential Energy Dissipation at the Ultrathin Osteochondral Interface Tissue of Human Knee Joint
Authors: Wang Xiaozhao , Lin Junxin , Li Zonghao , Ma Yuanzhu , Zhang Xianzhu , He Qiulin , Wu Qin , Wei Wei , Yao Xudong , Li Chenglin , Li Wenyue , Xie Shaofang , Hu Yejun , Zhang Shufang , Hong Yi , Li Xu , Chen Weiqiu , Duan Wangping , Ouyang Hongwei 
Published: October 2021

ABSTRACTCartilage adheres to subchondral bone via a specific osteochondral interface tissue where forces are transferred from soft cartilage to hard bone without fatigue damage over a lifetime of load cycles. However, the fine structure and mechanical properties of osteochondral interface tissue remain unclear. Here, we identified an ultrathin ∼20-30 μm calcified region with two-layered micro-nano structures of osteochondral interface tissue in human knee joint, which exhibited characteristic biomolecular compositions and complex nanocrystals assembly. Within this region, an exponential increase of modulus (3 orders of magnitude) was conducive to the force transmission which was verified by finite element simulations. The nanoscale heterogeneity of hydroxyapatite, along with enrichment of elastic-responsive protein-titin which is usually present in muscle, endowed the osteochondral tissue with excellent energy dissipation and fatigue resistance properties. Our results provide potential design for high-performance interface materials for osteochondral interface regeneration and functional coatings.
Monoclonal Antibody Treatment of Breakthrough COVID-19 in Fully Vaccinated Individuals with High-Risk Comorbidities
Authors: Bierle Dennis M. , Ganesh Ravindra , Tulledge-Scheitel Sidna , Hanson Sara N. , Arndt Lori L. , Wilker Caroline G. , Razonable Raymund R. 
Published: October 2021

AbstractBreakthrough COVID-19 may occur in fully vaccinated persons. In this cohort of 1395 persons (mean age, 54.3 years; 60% female; median body mass index, 30.7) who developed breakthrough COVID-19, there were 107 (7.7%) who required hospitalization by day 28. Hospitalization was significantly associated with the number of medical comorbidities. Anti-spike monoclonal antibody treatment was significantly associated with a lower risk of hospitalization (Odds Ratio: 0.227; 95% confidence interval, 0.128 - 0.403; p<0.001). The number needed to treat to prevent one hospitalization was 225 among the lowest-risk patient group compared to 4 among the groups with highest numbers of medical comorbidity.summaryBreakthrough COVID-19 may occur among vaccinated individuals with a high number of medical comorbidities, especially during the surge of SARS-CoV-2 Delta variant. Treatment with anti-spike monoclonal antibody was associated with significantly lower rates of hospitalization and oxygen supplementation.
ZipHiC: a novel Bayesian framework to identify enriched interactions and experimental biases in Hi-C data
Authors: Osuntoki Itunu G. , Harrison Andrew , Dai Hongsheng , Bao Yanchun , Zabet Nicolae Radu 
Published: October 2021

AbstractSeveral computational and statistical methods have been developed to analyse data generated through the 3C-based methods, especially the Hi-C. Most of existing methods do not account for dependency in Hi-C data. Here, we present ZipHiC, a novel statistical method to explore Hi-C data focusing on detection of enriched contacts. ZipHiC implements a Bayesian method based on a hidden Markov random field (HMRF) model and the Approximate Bayesian Computation (ABC) to detect interactions in two-dimensional space based on Hi-C contact frequency matrix. ZipHiC uses data on the sources of biases related to contact frequency matrix, allows borrowing information from neighbours using the Potts model and improves computation speed by using the ABC model. In addition to outperforming existing tools on both simulated and real data, our model also provides insights into different sources of biases that affects Hi-C data. We show that some datasets display higher biases from DNA accessibility or Transposable Elements content. Furthermore, approximately half of the detected significant interactions connect promoters with other parts of the genome indicating a functional biological role. Finally, we found that the micro-C datasets display higher biases from DNA accessibility compared to a similar Hi-C experiment, but this can be corrected by ZipHiC.
Identification of bacterial drug-resistant cells by the convolutional neural network in transmission electron microscope images
Authors: Hayashi-Nishino Mitsuko , Aoki Kota , Kishimoto Akihiro , Takeuchi Yuna , Fukushima Aiko , Uchida Kazushi , Echigo Tomio , Yagi Yasushi , Hirose Mika , Iwasaki Kenji , Shin’ya Eitaro , Washio Takashi , Furusawa Chikara , Nishino Kunihiko 
Published: October 2021

AbstractThe emergence of bacteria that are resistant to antibiotics is common in areas where antibiotics are used widely. The current standard procedure for detecting bacterial drug resistance is based on bacterial growth under antibiotic treatments. Here we describe the morphological changes in enoxacin-resistant Escherichia coli cells and the computational method used to identify these resistant cells in transmission electron microscopy (TEM) images without using antibiotics. Our approach was to create patches from TEM images of enoxacin-sensitive and enoxacin-resistant E. coli strains, use a convolutional neural network for patch classification, and identify the strains on the basis of the classification results. The proposed method was highly accurate in classifying cells, achieving an accuracy rate of 0.94. Using a gradient-weighted class activation mapping to visualize the region of interest, enoxacin-resistant and enoxacin-sensitive cells were characterized by comparing differences in the envelope. Moreover, Pearson’s correlation coefficients suggested that four genes, including lpp, the gene encoding the major outer membrane lipoprotein, were strongly associated with the image features of enoxacin-resistant cells.
Clonally expanded CD38hi cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor-associated arthritis
Authors: Wang Runci , Singaraju Anvita , Marks Kathryne E. , Shakib Lorien , Dunlap Garrett , Cunningham-Bussel Amy , Chen Lin , Tirpack Aidan , Fein Miriam R. , Todd Derrick J. , MacFarlane Lindsey , Goodman Susan M. , DiCarlo Edward F. , Massarotti Elena M. , Sparks Jeffrey A. , Hamnvik Ole-Petter R. , Min Le , Jonsson A. Helena , Brenner Michael B. , Chan Karmela K. , Bass Anne R. , Donlin Laura T. , Rao Deepak A. 
Published: October 2021

AbstractImmune checkpoint inhibitor (ICI) therapies that promote T cell activation have improved outcomes for advanced malignancies yet also elicit harmful autoimmune reactions. The T cell mechanisms mediating these iatrogenic autoimmune events remain unclear. Here we assayed T cells from joints of patients affected by ICI-induced inflammatory arthritis (ICI-arthritis), which can present clinically indistinguishable from rheumatoid arthritis (RA). Compared to the autoimmune arthritides RA and psoriatic arthritis (PsA), ICI-arthritis joints contained an expanded CD38hi CD127− CD8+ T cell subset that displays cytotoxic, effector, and interferon (IFN) response signatures. The abundance of CD38hi CD8 T cells in ICI-arthritis resulted from a limited number of clones that could be found proliferating in the joint. Exposure of synovial T cells to Type I IFN, more so than IFN-γ, induces the CD38hi cytotoxic phenotype. Relative to other CD8+ T cell subsets in the joints, the CD38hi population is distinct from a dysfunctional population and clonally most related to TCF7+ memory populations. Examination of synovial tissue from bilateral knee arthroplasty demonstrated considerable sharing of TCR clonotypes in the CD38hi CD8 T cell fraction from both knees. These results define a distinct CD8 T cell subset that may be directly activated by ICI therapy and mediate a tissue-specific autoimmune cellular reaction in patient joints.
VSS-Hi-C: Variance-stabilized signals for chromatin contacts
Authors: Kenari Neda Shokraneh , Bayat Faezeh , Libbrecht Maxwell 
Published: October 2021

AbstractMotivationThe genome-wide chromosome conformation capture assay Hi-C is widely used to study chromatin 3D structures and their functional implications. Read counts from Hi-C indicate the strength of chromatin contact between each pair of genomic loci. These read counts are heteroskedastic: that is, a difference between the interaction frequency of 0 and 100 is much more significant than a difference between the interaction frequency of 1000 and 1100. This property impedes visualization and downstream analysis because it violates the Gaussian variable assumption of many computational tools. Thus heuristic transformations aimed at stabilizing the variance of signals like the shifted-log transformation are typically applied to data before its visualization and inputting to models with Gaussian assumption. However, such heuristic transformations cannot fully stabilize the variance because of their restrictive assumptions about the mean-variance relationship in the data.ResultsHere we present VSS-Hi-C, a data-driven variance stabilization method for Hi-C data. We show that VSS-Hi-C signals have a unit variance improving visualization of Hi-C, for example in heatmap contact maps. VSS-Hi-C signals also improve the performance of subcompartment callers relying on Gaussian observations. VSS-Hi-C is implemented as an R package and can be used for variance stabilization of different genomic and epigenomic data types with two replicates available.Availabilityhttps://github.com/nedashokraneh/vssHiCContactmaxwl@sfu.ca
Immunogenicity of BNT162b2 Vaccine in Patients with Inflammatory Bowel Disease on Infliximab Combination Therapy: A Multicenter Prospective Study
Authors: Shehab Mohammad , Abu-Farha Mohamed , Alrashed Fatema , Alfadhli Ahmad , AlOtaibi Khazna , AlSahli Abdulla , Thanaraj Thangavel Alphonse , Channanath Arshad , Ali Hamad , Abubaker Jehad , Al-Mulla Fahd 
Published: October 2021

AbstractBackgroundVaccination is a promising strategy to protect vulnerable groups like inflammatory bowel disease (IBD) patients against COVID-19 and associated severe outcomes. COVID-19 Vaccines clinical trials excluded IBD patients taking infliximab with azathioprine or 6-mercaptopurine (infliximab combination). Therefore, we sought to evaluate serologic responses to COVID-19 vaccination with the mRNA vaccine, BNT162b2 in IBD patients receiving infliximab combination therapy compared to healthy participants.MethodsThis is a multicenter prospective study. IBD patients were recruited at the time of attendance at infusion center between August 1st, 2021, and September 15th, 2021. Our primary outcome was the concentrations of SARS-CoV-2 antibodies 4-10 weeks after vaccination with two doses of BNT162b2 vaccine in IBD patients taking infliximab combination therapy (study group) compared to healthy participants group (control group). Both study and healthy participants groups were matched for age, sex and time-since-last-vaccine-dose using optimal pair matching method.ResultsIn total 116 participants were recruited in the study, 58 patients in the study group and 58 in the control group. Median (IQR) IgG concentrations were lower in the study group [99 BAU/mL (40, 177)] than the control group [139 BAU/mL (120, 188)], following vaccination (p = 0.0032). Neutralizing antibodies was also lower in the study group compared to the control group [64% (23, 94) vs 91% (85, 94), p <0.001]. The median IgA levels in the study group was also significantly lower when compared to the control group [6 U/ml (3, 34) vs 13 U/ml (7, 30), p =0.0097]. In the study group, the percentage of patients who achieved positive IgG, neutralizing antibody and IgA levels were 81%, 75% and 40% respectively. In the control group, all participants (100%) had positive IgG and neutralizing antibody levels while 62% had positive IgA levels.ConclusionIn patients with IBD receiving infliximab combination therapy, IgG, IgA and neutralizing antibody levels after BNT162b2 vaccine were lower compared to healthy participants. However, most patients treated with infliximab combination therapy seroconverted after two doses of the vaccine.