bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is the Association Between Smoking and Depression Mediated by Inflammation? A Mendelian Randomization Study
Authors: Galan D. , Perry B.I. , Warrier V. , Easton D. , Khandaker G.M. , Murray G.K. 
Published: February 2021

AbstractSmoking, inflammation and depression commonly co-occur and may be mechanistically linked. However, key questions remain around the direction of association and the influence of residual confounding. We aimed to characterize the association between lifetime smoking and depression, as well as to assess the role that genetically-predicted C-reactive protein (CRP) level, an archetypal inflammatory marker, as a potential mediator for this association. We performed inverse variance weighted Mendelian randomization (MR) analyses using recently published summary-level GWAS data for lifetime smoking index, CRP levels, and depression. A subset of inflammatory-related genetic variants from the lifetime smoking GWAS were also used to assess the potential inflammatory causal pathways between smoking and depression. The analysis indicated significant reciprocal relationships between lifetime smoking and both depression (ORSmk-Dep = 2.01, 95% CI 1.71-2.37, p < 0.001; O RDep-Smk = 1.09, 95% CI 1.06-1.13, p < 0.001) and CRP levels (ORSmk-CRP = 1.40, 95% CI 1.21-1.55, p < 0.001; ORCRP-Smk = 1.03, 95% CI 1.02-1.05, p < 0.001). These significant and positive associations were also supported by the majority of the robust MR methods performed. The reciprocal relationships between CRP levels (using >500 genetic instruments for CRP) and depression were not significant (ORCRP-Dep = 1.01, 95% CI 0.99-1.04; ORDep-CRP = 1.03, 95% CI 0.99-1.07). We observed little variation in the IVW estimates between smoking and depression when we limited the genetic variants assessed to those related to inflammation or when we adjusted the analysis by CRP-levels in multivariable analysis. Our study supports potential causal associations between lifetime smoking and depression, as well as between lifetime smoking and CRP levels, but not between CRP and depression. No evidence was found that CRP mediates the relationship between smoking and depression.
Distinct microRNA expression signatures of primary and secondary central nervous system lymphomas
Authors: Sebestyén Endre , Nagy Ákos , Marosvári Dóra , Rajnai Hajnalka , Kajtár Béla , Deák Beáta , Matolcsy András , Brandner Sebastian , Storhoff James , Chen Ning , Bagó Attila G. , Bödör Csaba , Reiniger Lilla 
Published: February 2021

AbstractCentral nervous system (CNS) lymphoma is a rare and aggressive non-Hodgkin lymphoma that might arise in the CNS (primary CNS lymphoma, PCNSL) or disseminates from a systemic lymphoma to the CNS (secondary CNS lymphoma, SCNSL). Dysregulated expression of microRNAs (miRNAs) is associated with various pathological processes and miRNA expression patterns may have diagnostic, prognostic and therapeutic implications. However, miRNA expression is understudied in CNS lymphomas. Here, we performed expression analysis of 798 miRNAs in 73 CNS lymphoma samples using the NanoString platform, followed by a detailed statistical analysis to identify potential novel biomarkers characterizing subgroups and to examine differences based on their primary and secondary nature, molecular subtype, mutational patterns and survival. We describe the general expression patterns of miRNAs across CNS lymphoma samples and identified 31 differentially expressed miRNAs between primary and secondary groups. Additionally, we identified 7 more miRNAs associated with a molecular subtype and 25 associated with mutation status. Using unsupervised clustering methods, we defined a small but distinct primary CNS lymphoma subgroup, with characteristically different expression patterns compared to the rest of the cases. Finally, we identified differentially regulated pathways in the above comparisons and assessed the utility of miRNA expression patterns in predicting survival. Our study identifies a novel CNS lymphoma subgroup defined by distinct miRNAs, proves the importance of specific miRNAs and pathways in their pathogenesis, and provides the basis for future research.
Acute Medical Unit Healthcare workers’ interaction in a developing country: Social Network Analysis
Authors: Belayachi Jihane , Benammi Sarah , Bennis Rhita Nechba , Madani Naoufel , Abouqal Redouane 
Published: February 2021

INTRODUCTIONSocial network analysis is used to increase the awareness of leaders about the power of networks, to further catalyze relationships and connections, and to strengthen the capacity of the network to act collectively. We focus on understanding and measuring the communication patterns in an acute medical unit team. We sought to use Social Network Analysis to describe the patterns of communications in teamwork of an acute medical unit.METHODSNetwork Analysis was conducted to examine network structure in 58 teamwork professional communication in an AMU. Team members reported the frequency (0 to 10+ times) of professional discussion with every other coworker during the last 48-hoursk, density, degree and betweenness centralization, degree and betweenness centrality; and homophily were calculated. P-value was obtained based on 1000 quadratic assignment procedure QAP permutations of the network. The network analysis was used to construct network maps using multidimentional scaling and generates a visual representation of networks through network diagrams.RESULTSthere were 460 connections (density=28%). The whole network has a moderate degree centralization (37%) and lower betweenness centralization (8%). Three senior physicians, the head nurse, the physiotherapist, the medical secretary and the archive manager were most central in network. There was evidence regarding heterophily in a network indicated by high level of E-I index value 0.34 (P<0.01, by QAP).CONCLUSIONSNA provided a description of patterns of communications in teamwork in an acute medical unit. We used SNA statistics to reveal variation in patterns of team communication and teammate interconnectedness by shift.
Sero-surveillance for IgG to SARS-CoV-2 at antenatal care clinics in two Kenyan referral hospitals
Authors: Lucinde R. , Mugo D. , Bottomley C. , Aziza R , Gitonga J. , Karanja H. , Nyagwange J. , Tuju J. , Wanjiku P. , Nzomo E. , Kamuri E. , Thuranira K. , Agunda S. , Nyutu G. , Etyang A. , Adetifa I. M. O. , Kagucia E. , Uyoga S. , Otiende M. , Otieno E. , Ndwiga L. , Agoti C. N. , Aman R. , Mwangangi M. , Amoth P. , Kasera K. , Nyaguara A. , Ng’ang’a W. , Ochola L. B. , Barasa E. , Bejon P. , Tsofa B. , Ochola-Oyier L. I. , Warimwe G. M. , Agweyu A. , Scott J. A. G. , Gallagher K. E. 
Published: February 2021

AbstractThe high proportion of SARS-CoV-2 infections that remain undetected presents a challenge to tracking the progress of the pandemic and implementing control measures in Kenya. We determined the prevalence of IgG to SARS-CoV-2 in residual blood samples from mothers attending antenatal care services at 2 referral hospitals in Kenya. We used a validated IgG ELISA for SARS-Cov-2 spike protein and adjusted the results for assay sensitivity and specificity. In Kenyatta National Hospital, Nairobi, seroprevalence in August 2020 was 49.9% (95% CI 42.7-58.0). In Kilifi County Hospital seroprevalence increased from 1.3% (95% CI 0.04-4.7) in September to 11.0% (95% CI 6.2-16.7) in November 2020. There has been substantial, unobserved transmission of SARS-CoV-2 in parts of Nairobi and Kilifi Counties.
Longitudinal Metabolomics of Human Plasma Reveals Robust Prognostic Markers of COVID-19 Disease Severity
Authors: Sindelar Miriam , Stancliffe Ethan , Schwaiger-Haber Michaela , Anbukumar Dhanalakshmi S. , Albrecht Randy A. , Liu Wen-Chun , Travis Kayla Adkins , García-Sastre Adolfo , Shriver Leah P. , Patti Gary J. 
Published: February 2021

AbstractThere is an urgent need to identify which COVID-19 patients will develop life-threatening illness so that scarce medical resources can be optimally allocated and rapid treatment can be administered early in the disease course, when clinical management is most effective. To aid in the prognostic classification of disease severity, we performed untargeted metabolomics profiling of 341 patients with plasma samples collected at six longitudinal time points. Using the temporal metabolic profiles and machine learning, we then built a predictive model of disease severity. We determined that the levels of 25 metabolites measured at the time of hospital admission successfully predict future disease severity. Through analysis of longitudinal samples, we confirmed that these prognostic markers are directly related to disease progression and that their levels are restored to baseline upon disease recovery. Finally, we validated that these metabolites are also altered in a hamster model of COVID-19. Our results indicate that metabolic changes associated with COVID-19 severity can be effectively used to stratify patients and inform resource allocation during the pandemic.
C-bouton components on rat extensor digitorum longus motoneurons are resistant to chronic functional overload
Authors: Kissane Roger W.P. , Ghaffari-Rafi Arash , Tickle Peter G. , Chakrabarty Samit , Egginton Stuart , Brownstone Robert M. , Smith Calvin C. 
Published: February 2021

AbstractMammalian motor systems adapt to the demands of their environment. For example, muscle fibre types change in response to increased load or endurance demands. However, for adaptations to be effective, motoneurons must adapt such that their properties match those of the innervated muscle fibres. We used a rat model of chronic functional overload to assess adaptations to both motoneuron size and a key modulatory synapse responsible for amplification of motor output, C-boutons. Overload of Extensor Digitorum Longus (EDL) muscles was induced by removal of their synergists, Tibialis Anterior (TA) muscles. Following 21 days survival, EDL muscles showed an increase in fatigue resistance and a decrease in force output, indicating a shift to a slower phenotype. These changes were reflected by a decrease in motoneuron size. However, C-bouton complexes remained largely unaffected by overload. The C-boutons themselves, quantified by expression of vesicular acetylcholine transporter, were similar in size and density in the control and overload conditions. Expression of the post-synaptic voltage-gated potassium channel (KV2.1) was also unchanged. Small conductance calcium activated potassium channels (SK3) were expressed in most EDL motoneurons, despite this being an almost exclusively fast motor pool. Overload induced a decrease in the proportion of SK3+cells, however there was no change in density or size of clusters. We propose that reductions in motoneuron size may promote early recruitment of EDL motoneurons, but that C-bouton plasticity is not necessary to increase the force output required in response to muscle overload.
Two interconnected patterning loops are required for body axis and head organizer formation inHydra
Authors: Mercker Moritz , Tursch Anja , Veerman Frits , Kazarnikov Alexey , Höger Stefanie , Lengfeld Tobias , Özbek Suat , Holstein Thomas W , Marciniak-Czochra Anna 
Published: February 2021

ABSTRACTThe formation of body axes and apical termini is crucial for animal development. InHydra, nuclearβ-catenin and Wnt3 play key roles and were previously thought to be part of a single mechanism for axis and head formation. This study challenges this view by combining mathematical modeling with experimental data. We show thatβ-catenin and Wnt3 patterning in Hydra operate at two different scales, requiring distinct inhibitory mechanisms.β-catenin, possibly interacting with other Wnts, co-ordinates axis formation, whereas Wnt3 is involved in small-scale head patterning. A double-loop reaction-diffusion model was developed, demonstrating the ability to describe patterns with divergent shapes, which single-loop models could not achieve. The previously proposed threshold mechanism for Wnt3 expression based onβ-catenin prepatterns could not explain the data. Our results suggest a more complex patterning mechanism in other animals, where axis and head formation may not be controlled by a single process.
Optical analysis of the action range of glutamate in the neuropil
Authors: Matthews E.A. , Sun W. , McMahon S.M. , Doengi M. , Halka L. , Anders S. , Müller J.A. , Steinlein P. , Vana N. , van Dyk G. , Pitsch J. , Becker A.J. , Pfeifer A. , Kavalali E.T. , Lamprecht A. , Henneberger C. , Stein V. , Schoch S. , Dietrich D. 
Published: February 2021

AbstractThe wiring scheme of neurons is key to the function of the brain. Neurons are structurally wired by synapses and it is a long-held view that most synapses in the CNS are sufficiently isolated to avoid cross-talk to AMPA receptors of neighboring synapses. Here we report in hippocampal brain slices that quantal glutamate release activated optical reporter proteins >1.5 µm distant to the releasing synapse. 2P-glutamate uncaging was used to quantitatively probe glutamate spread in the neuropil. Releasing ∼35000 molecules of glutamate (∼5 vesicles) at a distance of 500 nm to a spine generated an uncaging EPSC reaching ∼30% of the quantal amplitude at synaptic AMPA-Rs. The same stimulus activated ∼70% of the quantal amplitude at NMDA-Rs and still generated clear current and calcium responses when applied at >= 2 µm remote to the spine. Extracellular spread of glutamate on the sub-micrometer scale appeared cooperative and caused supra-additive activation of AMPA-Rs in a spine. These observations are not predicted by previously used models of glutamate diffusion in the neuropil. An extracellular glutamate scavenger system weakly reduced field potential responses but not the quantal amplitude, indicating that a cross-talk component regularly contributes to synaptic transmission. Our data suggest that slight synaptic crosstalk responses at AMPA receptors of ∼2-4 adjacent synapses may be common (>70 synapses for NMDA receptors). Such broadcasting of synaptic signals to very local neighborhoods could stabilize network learning performance and allow for integration of synaptic activity within the extracellular space.
A human antibody with blocking activity to RBD proteins of multiple SARS-CoV-2 variants including B.1.351 showed potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus macaques
Authors: Gu Chunyin , Cao Xiaodan , Wang Zongda , Hu Xue , Yao Yanfeng , Zhou Yiwu , Liu Peipei , Liu Xiaowu , Gao Ge , Hu Xiao , Zhang Yecheng , Chen Zhen , Gao Li , Peng Yun , Jia Fangfang , Shan Chao , Yu Li , Liu Kunpeng , Li Nan , Guo Weiwei , Jiang Guoping , Min Juan , Zhang Jianjian , Yang Lu , Shi Meng , Hou Tianquan , Li Yanan , Liang Weichen , Lu Guoqiao , Yang Congyi , Wang Yuting , Xia Kaiwen , Xiao Zheng , Xue Jianhua , Huang Xueyi , Chen Xin , Ma Haixia , Song Donglin , Pan Zhongzong , Wang Xueping , Guo Haibing , Liang Hong , Yuan Zhiming , Guan Wuxiang , Deng Su-Jun 
Published: February 2021

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein for infection. After the virus sequence was published, we identified two potent antibodies against SARS-CoV-2 RBD from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a phase I clinical trial, showed broad-spectrumin vitroblocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.
Insulin-Like Growth Factor I Couples Metabolism With Circadian Activity Through Hypothalamic Orexin Neurons
Authors: Pignatelli J. , de Sevilla E. Fernandez , Sperber J. , Horrillo J.D. , Medina-Gomez G. , Aleman I. Torres 
Published: February 2021

AbstractUncoupling of metabolism and circadian activity is associated with an increased risk of various pathologies, including neurodegeneration. Recently, insulin and the closely related insulin-like growth factor I (IGF-I) were shown to entrain feeding patterns with circadian rhythms. Moreover, both hormones act centrally to modulate peripheral glucose metabolism; however, whereas central targets of insulin actions are intensely scrutinized, those mediating the actions of IGF-I remain undefined. We analyzed whether IGF-I targets orexin neurons in the lateral hypothalamus, as these neurons are involved in circadian rhythms and energy allocation, and are modulated by IGF-I. Mice with disrupted IGF-IR activity in orexin neurons show phase shifts in circadian feeding behavior, loss of circadian orexin expression, and gradually develop sex-dependent metabolic alterations. In addition, modulation by IGF-I of hepatic KLF transcription factors involved in peripheral glucose metabolism is mediated by orexin neurons. Thus, IGF-I entrains energy metabolism and circadian rhythms through hypothalamic orexin neurons.
Decoding nucleosome positions with ATAC-seq data at single-cell level
Authors: Xu Bingxiang , Li Xiaoli , Gao Xiaomeng , Jia Yan , Li Feifei , Zhang Zhihua 
Published: February 2021

AbstractAs the basal bricks, the dynamics and arrangement of nucleosomes orchestrate the higher architecture of chromatin in a fundamental way, thereby affecting almost all nuclear biology processes. Thanks to its rather simple protocol, ATAC-seq has been rapidly adopted as a major tool for chromatin-accessible profiling at both bulk and single-cell level. However, to picture the arrangement of nucleosomesper seremains a challenge with ATAC-seq. In the present work, we introduce a novel ATAC-seq analysis toolkit, named deNOPA, to predict nucleosome positions. Assessments showed that deNOPA not only outperformed state-of-the-art tools, but it is the only tool able to predict nucleosome position precisely with ultrasparse ATAC-seq data. The remarkable performance of deNOPA was fueled by the reads from short fragments, which compose nearly half of sequenced reads and are normally discarded from nucleosome position detection. However, we found that the short fragment reads enrich information on nucleosome positions and that the linker regions were predicted by reads from both short and long fragments using Gaussian smoothing. We applied deNOPA to a single-cell ATAC-seq dataset and deciphered the intrapopulation heterogeneity of the human erythroleukemic cell line (K562). Last, using deNOPA, we showed that the dynamics of nucleosome organization may not directly couple with chromatin accessibility in the cis-regulatory regions when human cells respond to heat shock stimulation. Our deNOPA provides a powerful tool with which to analyze the dynamics of chromatin at nucleosome position level in the single-cell ATAC-seq age.
A new test suggests that balancing selection maintains hundreds of non-synonymous polymorphisms in the human genome
Authors: Soni Vivak , Vos Michiel , Eyre-Walker Adam 
Published: February 2021

AbstractThe role that balancing selection plays in the maintenance of genetic diversity remains unresolved. Here we introduce a new test, based on the McDonald-Kreitman test, in which the number of polymorphisms that are shared between populations is contrasted to those that are private at selected and neutral sites. We show that this simple test is robust to a variety of demographic changes, and that it can also give a direct estimate of the number of shared polymorphisms that are directly maintained by balancing selection. We apply our method to population genomic data from humans and conclude that more than a thousand non-synonymous polymorphisms are subject to balancing selection.
Comparison of Janus kinase inhibitors to block the type I interferon pathway in human skeletal muscle cells
Authors: Kinder Travis B. , Inglese James 
Published: February 2021

AbstractThe family of Janus kinases (JAK1, JAK2, JAK3, TYK2) mediate signal transduction from cytokine receptors by phosphorylation and activation of intracellular signaling pathways and transcription factors. Small molecule antagonists of JAKs (Jakinibs) have been developed with varying selectivity for the use in malignancies and immune regulation. There is growing recognition of the effectiveness of jakinibs in autoimmunity of the skeletal muscle called myositis, but which of these drugs is most effective is unknown. We have assayed a library of 48 jakinibs for their ability to inhibit the JAK1/TYK2-dependent type I interferon (IFN) - major histocompatibility complex (MHC) class I pathway using human skeletal muscle cells genome-engineered to fuse a pro-luminescent HiBiT peptide to endogenous MHC class I. The most effective compounds were upadacitinib (JAK1/2 inhibitor, FDA approved) and deucravacitinib (TYK2 inhibitor, phase III). These active jakinibs warrant further clinical evaluation to show their safety and efficacy in patients.Graphical Abstract
Vegan cheeses vs processed cheeses – traceability issues and monitoring countermeasures
Authors: Haddad Moawiya A. , Omar Sharaf S. , Parisi Salvatore 
Published: February 2021

PurposeThe purpose of this study comes from the need of defining improved durability values and the realization of a good traceability management for selected vegan cheeses has suggested the comparison between a processed cheese and its analogous version without animal-origin raw materials. The durability should be studied at a well-defined temperature, probably agreed among the food producer and the food processor. In addition, the traceability system should consider many components and related suppliers.Design/methodology/approachA supply chain risk assessment analysis has been carried out with relation to two different products: an analogue cheese and a vegan cheese-like preparation. Raw materials and ingredients have been evaluated (production method and origin; geographical identification), with the aim of identifying simplified food.FindingsAn assessment of food supply networks has been carried out. In the first situation (analogue cheeses), the ingredient “cheeses” shows an important complexity: five suppliers with a related six-interconnection hub. On the other side, vegan cheeses are obtained from 11 ingredients (a challenging hub); four of them may be produced from 2–5 components of different origin (five total hubs). Tested processed cheeses are represented by means of a linear food supply network with two hubs (cheeses and “arrival” show degrees 6 and 9, respectively). Networks concerning vegan cheeses include five different hubs: four complex raw materials (degree: 2, 3, 4 and 5) and the “arrival” step (degree: 12).Originality/valueThe information load of vegan cheeses (two hubs, degrees >> average degree) appears high if compared with processed cheeses (two hubs), although the complexity of networks appears similar. Vegan cheeses may seem technologically simpler than processed cheeses and be sometimes questioned because of important traceability issues. Adequate traceability countermeasures in terms of preventive monitoring actions should be recommended when speaking of vegan cheeses. Anyway, a centralized manager would be always required.