bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers of Cytokine Release Syndrome Predict Disease Severity and Mortality From COVID-19 in Kidney Transplant Recipients
Authors: Benotmane Ilies , Perrin Peggy , Vargas Gabriela Gautier , Bassand Xavier , Keller Nicolas , Lavaux Thomas , Ohana Mickael , Bedo Dimitri , Baldacini Clément , Sagnard Mylene , Bozman Dogan-Firat , Chiesa Margaux Della , Cognard Noëlle , Olagne Jérôme , Delagreverie Héloïse , Marx David , Heibel Françoise , Braun Laura , Moulin Bruno , Fafi-Kremer Samira , Caillard Sophie 
Published: October 2020

Background.
Data on coronavirus disease 2019 (COVID-19) in immunocompromised kidney transplant recipients (KTR) remain scanty. Although markers of inflammation, cardiac injury, and coagulopathy have been previously associated with mortality in the general population of patients with COVID-19, their prognostic impact amongst KTR with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has not been specifically investigated.

Methods.
We conducted a cohort study of 49 KTR who presented with COVID-19. Clinical and laboratory risk factors for severe disease and mortality were prospectively collected and analyzed with respect to outcomes. The study participants were divided into 3 groups: (1) mild disease manageable in an outpatient setting (n = 8), (2) nonsevere disease requiring hospitalization (n = 21), and (3) severe disease (n = 20).

Results.
Gastrointestinal manifestations were common at diagnosis. The 30-day mortality rate in hospitalized patients was 19.5%. Early elevations of C-reactive protein (>100 mg/L) and interleukin-6 (>65 ng/L) followed by increases in high-sensitivity troponin I (>30 ng/L) and D-dimer (>960 ng/mL) were significantly associated with severe disease and mortality. Viral load did not have prognostic significance in our sample, suggesting that outcomes were chiefly driven by a cytokine release syndrome (CRS).

Conclusions.
Regular monitoring of CRS biomarkers in KTR with COVID-19 is paramount to improve clinical outcomes.
Synergistic interactions between detritivores disappear under reduced rainfall
Authors: Joly François-Xavier , McAvoy Euan , Subke Jens-Arne 
Published: October 2020

AbstractUnderstanding the consequences of altered rainfall patterns on litter decomposition is critical to predicting the feedback effect of climate change on atmospheric CO2concentrations. While their effect on microbial decomposition received considerable attention, their effect on litter fragmentation by detritivores, the other dominant decomposition pathway, remains largely unexplored. Particularly, it remains unclear how different detritivore species and their interactions respond to changes in rainfall quantity and frequency. To fill this knowledge gap, we determined the contribution to litter decomposition of two detritivore species (millipede and isopod), separately and in combination, under contrasting rainfall quantity and frequency in a temperate forest. Although halving rainfall quantity and frequency decreased top-soil moisture by 7.8 and 13.1%, respectively, neither millipede- nor isopod-driven decomposition were affected by these changes. In contrast, decomposition driven by both detritivore species in combination was 65.5% higher than expected based on monospecific treatments under high rainfall quantity, but unchanged or even lower under low rainfall quantity. This indicates that while detritivore activity is relatively insensitive to changes in rainfall patterns, large synergistic interactions between detritivore species may disappear under future rainfall patterns. Incorporating interspecific interactions between decomposers thus seems critical to evaluate the sensitivity of decomposition to altered rainfall patterns.
The Nature ofEspeletiaSpecies
Authors: Pineda Yam M. , Cortés Andrés J. , Madriñán Santiago , Jiménez Iván 
Published: October 2020

AbstractSpecies are often regarded as basic units of study in biology, following the presumption that they are real and discrete natural entities. But several biologists wonder if species are arbitrary divisions that do not correspond to discrete natural groups of organisms. Two issues must be addressed to solve this controversy, but few studies seem to do so. The first is whether organisms form sympatric and synchronic groups that are distinct in terms of phenotypes and genome-wide allele frequencies, often called “good species.” Alternatives to “good species” include “cryptic species,” syngameons and, more generally, cases in which phenotypes and genome-wide allele frequencies reflect contrasting evolutionary histories. The second issue is the degree to which species taxa (i.e., taxonomic classification at the species level) reflect natural groups of organisms or constitute arbitrary divisions of biological diversity. Here, we empirically addressed both issues by studying plants of the Andean genusEspeletia(Asteraceae). We collected a geographically dense sample of 538 specimens from the paramo de Sumapaz, in the Cordillera Oriental of Colombia. Additionally, we examined 165 herbarium specimens previously collected by other researchers in this region, or from taxa known to occur there. We tested for the existence of phenotypic groups using normal mixture models and data on 13 quantitative characters. Among 307 specimens with all 13 measurements, we found six distinct phenotypic groups in sympatry. We also tested for the existence of groups defined by genome-wide allele frequencies, using ancestry models and data on 2,098 single nucleotide polymorphisms. Among 77 specimens with complete genomic data, we found three groups in sympatry, with high levels of admixture. Concordance between groups defined by phenotype and genome-wide allele frequencies was low, suggesting that phenotypes and genome-wide allele frequencies reflect contrasting evolutionary histories. Moreover, the high levels of admixture suggest thatEspeletiaplants form a syngameon in the paramo de Sumapaz. To determine the extent to which species taxa corresponded to phenotypic and genomic groups, we used data on 12 phenotypic characters to assign 307 specimens to species taxa, according to descriptions of species taxa in the most recent monograph ofEspeletia. This sample included 27 specimens cited in the monograph. Remarkably, only one out of 307 specimens in our sample fell inside any of the phenotypic ranges reported in the monograph for the species taxa known to occur in the paramo de Sumapaz. These results show that species taxa inEspeletiaare delineations of largely empty phenotypic space that miss biological diversity.
A chaotic viewpoint-based approach to solve haplotype assembly using hypergraph model
Authors: Olyaee Mohammad Hossein , Khanteymoori Alireza , Khalifeh Khosrow 
Published: October 2020

AbstractDecreasing the cost of high-throughput DNA sequencing technologies, provides a huge amount of data that enables researchers to determine haplotypes for diploid and polyploid organisms. Although various methods have been developed to reconstruct haplotypes in diploid form, their accuracy is still a challenging task. Also, most of the current methods cannot be applied to polyploid form. In this paper, an iterative method is proposed, which employs hypergraph to reconstruct haplotype. The proposed method by utilizing chaotic viewpoint can enhance the obtained haplotypes. For this purpose, a haplotype set was randomly generated as an initial estimate, and its consistency with the input fragments was described by constructing a weighted hypergraph. Partitioning the hypergraph specifies those positions in the haplotype set that need to be corrected. This procedure is repeated until no further improvement could be achieved. Each element of the finalized haplotype set is mapped to a line by chaos game representation, and a coordinate series is defined based on the position of mapped points. Then, some positions with low qualities can be assessed by applying a local projection. Experimental results on both simulated and real datasets demonstrate that this method outperforms most other approaches, and is promising to perform the haplotype assembly.
The stage specific plasticity of descending modulatory controls in a rodent model of cancer induced bone pain
Authors: Kucharczyk Mateusz Wojciech , Derrien Diane , Dickenson Anthony Henry , Bannister Kirsty 
Published: October 2020

AbstractPain resulting from metastatic bone disease is a major unmet clinical need. Studying spinal processing in rodent models of cancer pain is desirable since the percept of pain is influenced in part by modulation at the level of the transmission system in the dorsal horn of the spinal cord. Here a rodent model of cancer induced bone pain (CIBP) was generated following syngenic rat mammary gland adenocarcinoma cell injection in the tibia of male Sprague Dawley rats. Disease progression was classified as ‘early’ or ‘late’ stage according to bone destruction. Even though wakeful CIBP rats showed progressive mechanical hypersensitivity, subsequentin vivoelectrophysiological measurement of mechanically evoked deep dorsal horn spinal neuronal responses revealed no change. Rather, a dynamic reorganization of spinal neuronal modulation by descending controls was observed, and this was maladaptive only in the early stage of CIBP. Interestingly, this latter observation corresponded with the degree of damage to the primary afferents innervating the cancerous tissue. Plasticity in the modulation of spinal neuronal activity by descending control pathways reveals a novel opportunity for targeting CIBP in a stage-specific manner. Finally, the data herein has translational potential since the descending control pathways measured are present also in man.Simple SummaryThe mechanisms that underlie pain resulting from metastatic bone disease remain elusive. This translates to a clinical and socioeconomic burden; targeted therapy is not possible, and patients do not receive adequate analgesic relief. Complicating matters is the heterogeneous nature of metastatic bone disease. Early stage cancers are molecularly very different to their late stage counterparts and so too is the pain associated with infant and advanced tumours. Thus, analgesic approaches should differ according to disease stage. In this article we demonstrate that a unique form of brain inhibitory control responsible for modulation of incoming pain signals at the level of the spinal cord changes with the progression of bone tumours, This corresponds with the degree of damage to the primary afferents innervating the cancerous tissue. Plasticity in the modulation of spinal neuronal activity by descending control pathways reveals a novel opportunity for targeting bone cancer pain in a stage-specific manner.
SARS-CoV-2 Spike protein promotes hyper-inflammatory response that can be ameliorated by Spike-antagonistic peptide and FDA-approved ER stress and MAP kinase inhibitorsin vitro
Authors: Hsu Alan C-Y. , Wang Guoqiang , Reid Andrew T. , Veerati Punnam Chander , Pathinayake Prabuddha S. , Daly Katie , Mayall Jemma R. , Hansbro Philip M. , Horvat Jay C. , Wang Fang , Wark Peter A. 
Published: October 2020

SummarySARS-CoV-2 infection causes an inflammatory cytokine storm and acute lung injury. Currently there are no effective antiviral and/or anti-inflammatory therapies. Here we demonstrate that 2019 SARS-CoV-2 spike protein subunit 1 (CoV2-S1) induces high levels of NF-κB activations, production of pro-inflammatory cytokines and mild epithelial damage, in human bronchial epithelial cells. CoV2-S1-induced NF-κB activation requires S1 interaction with human ACE2 receptor and early activation of endoplasmic reticulum (ER) stress, and associated unfolded protein response (UPR), and MAP kinase signalling pathways. We developed an antagonistic peptide that inhibits S1-ACE2 interaction and CoV2-S1-induced productions of pro-inflammatory cytokines. The existing FDA-approved ER stress inhibitor, 4-phenylburic acid (4-PBA), and MAP kinase inhibitors, trametinib and ulixertinib, ameliorated CoV2-S1-induced inflammation and epithelial damage. These novel data highlight the potentials of peptide-based antivirals for novel ACE2-utilising CoVs, while repurposing existing drugs may be used as treatments to dampen elevated inflammation and lung injury mediated by SARS-CoV-2.
SC-JNMF: Single-cell clustering integrating multiple quantification methods based on joint non-negative matrix factorization
Authors: Shiga Mikio , Seno Shigeto , Onizuka Makoto , Matsuda Hideo 
Published: October 2020

AbstractUnsupervised cell clustering is important in discovering cell diversity and subpopulations. Single-cell clustering using gene expression profiles is known to show different results depending on the method of expression quantification; nevertheless, most single-cell clustering methods do not consider the method.In this article, we propose a robust and highly accurate clustering method using joint non-negative matrix factorization (joint NMF) based on multiple gene expression profiles quantified using different methods. Matrix factorization is an excellent method for dimension reduction and feature extraction of data. In particular, NMF approximates the data matrix as the product of two matrices in which all factors are non-negative. Our joint NMF can extract common factors among multiple gene expression profiles by applying each NMF to them under the constraint that one of the factorized matrices is shared among the multiple NMFs. The joint NMF determines more robust and accurate cell clustering results by leveraging multiple quantification methods compared to the conventional clustering methods, which uses only a single quantification method. In conclusion, our study showed that our clustering method using multiple gene expression profiles is more accurate than other popular methods.
Conserved human effector Treg signature is reflected in transcriptomic and epigenetic landscape
Authors: Mijnheer Gerdien , Lutter Lisanne , Mokry Michal , van der Wal Marlot , Fleskens Veerle , Scholman Rianne , Pandit Aridaman , Tao Weiyang , Wekking Mark , Vervoort Stephin , Roberts Ceri , Petrelli Alessandra , Peeters Janneke G.C. , Knijff Marthe , de Roock Sytze , Vastert Sebastiaan , Taams Leonie S. , van Loosdregt Jorg , van Wijk Femke 
Published: October 2020

AbstractTreg are critical regulators of immune homeostasis, and increasing evidence demonstrates that environment-driven Treg differentiation into effector (e)Treg is crucial for optimal functioning. However, human Treg programming under inflammatory conditions remains poorly understood. Here, we combine transcriptional and epigenetic profiling to identify the human eTreg core signature. Functional autoimmune inflammation-derived Treg display a unique transcriptional profile characterized by upregulation of both a core Treg (FOXP3, CTLA-4, TIGIT) and effector program (GITR, BLIMP-1, BATF). We identified a specific human eTreg signature that includes the vitamin D receptor (VDR) as predicted key-regulator in eTreg differentiation. H3K27ac/H3K4me1 occupancy revealed pronounced changes in the (super-)enhancer landscape, including enrichment of the binding motif for VDR and BATF. The observed Treg profile showed striking overlap with tumor-infiltrating Treg. Our data demonstrate that human inflammation-derived Treg acquire a specific eTreg profile guided by epigenetic changes. The core eTreg profile is conserved, and fine-tuned by environment-specific adaptations.
FANCD2 Alleviates Physiologic Replication Stress in Fetal Liver HSC
Authors: Mochizuki-Kashio Makiko , me Yoon Young , Menna Theresa , Grompe Markus , Kurre Peter 
Published: October 2020

ABSTRACTBone marrow failure (BMF) in Fanconi Anemia (FA) results from exhaustion of hematopoietic stem cells (HSC), but the physiological role of FA proteins in HSC pool integrity remains unknown. Herein we demonstrate that FANCD2, a core component of the FA pathway, counters replication stress during developmental HSC expansion in the fetal liver (FL). Rapid rates of proliferation and FANCD2 deficient result in excess RPA-coated ssDNA, and provoke pChk1 activation andCdkn1a(p21)nuclear localization in fetalFancd2−/−HSC. Checkpoint mediated S-phase delays induced byCdkn1a(p21)are rescued by Tgf-βinhibition, but pChk1 activation is further aggravated. Our observations reveal the mechanism and physiological context by which FANCD2 safeguards HSC pool formation during development.
Transcriptional differences for COVID-19 Disease Map genes between males and females indicate a different basal immunophenotype relevant to the disease
Authors: Liu Tianyuan , Nogueira Leandro Balzano , Lleo Ana , Conesa Ana 
Published: October 2020

AbstractWorldwide COVID-19 epidemiology data indicate clear differences in disease incidence among sex and age groups. Specifically, male patients are at a higher death risk than females. However, whether this difference is the consequence of a pre-existing sex-bias in immune genes or a differential response to the virus has not been studied yet. We created DeCovid, an R shiny app that combines gene expression data of different human tissue from the Genotype-Tissue Expression (GTEx) project and the COVID-19 Disease Map gene collection to explore basal gene expression differences across healthy demographic groups. We used this app to study differential gene expression between men and women for COVID-19 associated genes. We identified that healthy women present higher levels in the expression of interferon genes and the JAK-STAT pathway leading to cell survival.
Proteoglycan 4 (PRG4) expression and function in dry eye associated inflammation
Authors: Menon Nikhil G. , Goyal Ruchi , Lema Carolina , Woods Paige S. , Jay Gregory D. , Shapiro Linda H. , Redfern Rachel L. , Ghosh Mallika , Schmidt Tannin A. 
Published: October 2020

AbstractPurposeDry eye disease (DED) affects hundreds of millions worldwide. Proteoglycan 4 (PRG4) has been shown to improve signs and symptoms of DED in humans. The objectives of this study were to characterize endogenous PRG4 expression by telomerase-immortalized human corneal epithelial (hTCEpi) cells, examine how exogenous recombinant human PRG4 (rhPRG4) modulates cytokine and chemokine secretion in response to TNFα and IL-1β, explore rhPRG4 as a potential substrate and/or inhibitor of MMP-9, and to understand how experimental dry (EDE) in mice affects PRG4 expression.MethodsPRG4 secretion was quantified by Western blotting and PRG4 expression by immunocytochemistry. Cytokine/chemokine release was measured by ELISA, and MMP-9 inhibition was quantified using an MMP-9 inhibitor kit. EDE was induced in mice, and PRG4 was visualized by immunohistochemistry in the cornea and Western blotting in lacrimal gland lysate.ResultshTCEpi cells synthesize and secrete PRG4in vitro, which is inhibited by TNFα and IL-1β. TNFα and IL-1β significantly increased secretion of cytokine IL-6 and chemokines IL-8, IP-10, RANTES, and ENA-78, and several of these chemokines were downregulated after cotreatment with rhPRG4. Fluorescently-labelled rhPRG4 was internalized by hTCEpi cells. rhPRG4 was not digested by MMP-9 and inhibitedin vitroactivity of exogenous MMP-9 both in solution and in the presence of human tears. Finally, EDE decreased corneal and lacrimal gland expression of PRG4.ConclusionsThese results demonstrate rhPRG4’s anti-inflammatory properties in the corneal epithelium and its contribution to ocular surface homeostasis, furthering our understanding of PRG4’s immunomodulatory properties in the context of DED inflammation.
High Definition transcranial Direct Current Stimulation (HD-tDCS) for chronic tinnitus: outcomes from a prospective longitudinal large cohort study
Authors: Jacquemin Laure , Mertens Griet , Shekhawat Giriraj Singh , Van de Heyning Paul , Vanderveken Olivier M. , Topsakal Vedat , De Hertogh Willem , Michiels Sarah , Beyers Jolien , Moyaert Julie , Van Rompaey Vincent , Gilles Annick 
Published: October 2020

AbstractBackgroundTranscranial Direct Current Stimulation (tDCS) aims to induce cortical plasticity by modulating the activity of brain structures. The broad stimulation pattern, which is one of the main limitations of tDCS, can be overcome with the recently developed technique called High-Definition tDCS (HD-TDCS).ObjectiveInvestigation of the effect of HD-tDCS on tinnitus in a large patient cohort.MethodsThis prospective study included 117 patients with chronic, subjective, non-pulsatile tinnitus who received six sessions of anodal HD-tDCS of the right Dorsolateral Prefrontal Cortex (DLPFC). Therapy effects were assessed by use of a set of standardized tinnitus questionnaires filled out at the pre-therapy (Tpre), post-therapy (T3w) and follow-up visit (T10w). Besides collecting the questionnaire data, the perceived effect (i.e. self-report) was also documented at T10w.ResultsThe Tinnitus Functional Index (TFI) and Tinnitus Questionnaire (TQ) total scores improved significantly over time (pTFI < .01; pTQ < .01), with the following significant post-hoc comparisons: Tpre vs. T10w (pTFI < .05; pTQ < .05) and T3w vs. T10w (pTFI < .01 ; pTQ < .01). The percentage of patients reporting an improvement of their tinnitus at T10w was 47%. Further analysis revealed a significant effect of gender with female patients showing a larger improvement on the TFI and TQ (pTFI < .01; pTQ < .05).ConclusionsThe current study reported the effects of HD-tDCS in a large tinnitus population. HD-tDCS of the right DLPFC resulted in a significant improvement of the tinnitus perception, with a larger improvement for the female tinnitus patients.
Sex differences in lifespan trajectories and variability of human sulcal and gyral morphology
Authors: Díaz-Caneja Covadonga M. , Alloza Clara , Gordaliza Pedro M. , Pena Alberto Fernández , de Hoyos Lucía , Santonja Javier , Buimer Elizabeth E.L. , van Haren Neeltje E.M. , Cahn Wiepke , Arango Celso , Kahn René S. , Hulshoff Pol Hilleke E. , Schnack Hugo G. , Janssen Joost 
Published: October 2020

AbstractSex differences in development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants two scans, 104 three scans, age range: 16-70 years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40 years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. While hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and thickness and lower variability for sulcal width. Across sexes, variability decreased with age for all measures except for cortical volume and thickness. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions.