bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCL2 produced by CD68+/CD163+ macrophages as a promising clinical biomarker of microscopic polyangiitis-interstitial lung disease
Authors: Matsuda Shogo , Kotani Takuya , Kuwabara Hiroko , Suzuka Takayasu , Kiboshi Takao , Fukui Keisuke , Ishida Takaaki , Fujiki Youhei , Shiba Hideyuki , Hata Kenichiro , Shoda Takeshi , Hirose Yoshinobu , Takeuchi Tohru 
Published: January 2021

Abstract

Objectives
Microscopic polyangiitis (MPA) is often complicated by interstitial lung disease (ILD); however, biomarkers that can be used to diagnose and predict the progression of MPA-ILD have not been identified. In this study, we evaluated various serum biomarkers in MPA-ILD to assess their diagnostic and predictive performance.

Methods
We enrolled 49 patients with anti-neutrophil cytoplasmic antibody (ANCA)+ MPA and 10 healthy controls, with 32 of the MPA patients also presenting ILD. The presence of ILD was assessed by high-resolution CT and evaluated by ground-glass opacity and fibrosis score. We compared 16 biomarker profiles among MPA-ILD patients, those without ILD, and healthy controls and extracted biomarkers with higher levels in MPA-ILD groups to determine correlations with disease activity and other biomarkers. Three lung biopsies were examined by haematoxylin-eosin staining and immunostaining.

Results
Initial serum C–C motif chemokine ligand 2 (CCL2) levels were significantly higher in the MPA-ILD group than those of the MPA group, and were significantly higher in MPA-ILD patients 1 year after immunosuppressive therapy than those before treatment. Initial serum CCL2 levels positively correlated with an increased fibrosis score during the year after treatment and with initial serum platelet-derived growth factor levels. Immunohistochemical staining showed intense CCL2 signals in CD68+/CD163+ macrophages and metaplastic epithelial cells in MPA-ILD lungs.

Conclusion
CCL2 is associated with MPA-ILD pathogenesis and suggested its potential efficacy as a useful marker for diagnosing and predicting MPA-ILD progression. Therefore, targeting CCL2 in alveolar CD68+/CD163+ macrophages might represent a therapeutic intervention in ANCA+ MPA-ILD.
Discriminating Palates: Evaluation and Ethnoracial Inequality in American Fine Dining
Authors: Gualtieri Gillian 
Published: January 2021

AbstractElite cultural fields are often not diverse. Existing studies have examined how marginalized cultural producers are actively discriminated against or excluded from positions of prestige, but less is known about how ethnoracial inequality affects the evaluative processes used to assess products in fields of cultural production. This article analyzes 120 in-depth interviews with critically-recognized chefs in New York City and the San Francisco Bay Area and 1,380 Michelin restaurant reviews to uncover the system of insidious racial inequality that shapes evaluation in the American fine dining field. I find that there are three logics of evaluation—of (1) technique, (2) creativity, and (3) authenticity—that are differentially enacted for distinct ethnoracial categories of restaurants in the field. I show how these different, racialized evaluative processes result in the systematic devaluation of culinary products categorically associated with non-whiteness, what I call Ethnic restaurants, and disproportionate consecration of products associated with whiteness, which I term Classic and Flexible restaurants. I bring the race/ethnicity and sociology of culture literatures together to illuminate the ways in which inequality infiltrates the logics that organize systems of value in fields of cultural production.
Descriptions of eleven new species of squat lobsters (Crustacea: Anomura) from seamounts around the Yap and Mariana Trenches with notes on DNA barcodes and phylogeny
Authors: Dong Dong , Gan Zhibin , Li Xinzheng 
Published: January 2021

AbstractSeamounts are well known for the high biodiversity and endemism of their macrobenthic fauna. Hundreds of squat lobster species from seamount environments have been reported in recent years, but squat lobster fauna on the seamount groups around ocean trenches in the tropical West Pacific are still poorly known. In this paper, we describe 11 new species (two Munida, three Munidopsis, one Sternostylus, one Uroptychodes and four Uroptychus) based on specimens collected during expeditions to seamounts around the Yap Trench and Mariana Trench. Of these species, six belong to the superfamily Chirostyloidea and five belong to Galatheoidea. We also provide DNA barcode data for three genes to support the taxonomic status of these new species. The morphological variations, genetic differentiation and phylogenetic relationships of these species are discussed.
Eribulin Mesylate for the Treatment of Metastatic Hormone-refractory and Triple-negative Breast Cancer
Authors: Valerio Maria R. , Arrivas Bajardi Eugenia , Arcara Carmelo C. , Borsellino Nicolo’ , Lo Mauro Mario , Cipolla Calogero , Santarpia Mariacarmela , Firenze Alberto , Motta Gianmarco , Vigneri Paolo , Gebbia Vittorio 
Published: January 2021

Objective:
Eribulin mesylate (EM) is a fully synthetic macrocyclic ketone analogue of the marine natural product halichondrin. EM has been reported to be active in metastatic breast cancer. In this paper, we report efficacy and safety of data of EM in a retrospective, real-world series of patients with poor prognosis, hormone-refractory, or triple-negative metastatic breast cancer.

Materials and Methods:
The analysis was carried out at 4 interrelated oncology centers. EM was delivered at the dose of 1.4 mg/m2 in 100 mL of normal saline over 2 to 5 minutes on days 1 and 8 every 21 days. EM was continued until disease progression or unacceptable toxicity. Side effects were reported every cycle as per standard clinical practice and graded according to NCI-CTCAE, version 4.0. Time-to-progression and overall survival were reported.

Results:
In this series of 90 patients the overall response rate was 22%, and 21% and 23% in the hormonal-resistant group and the triple-negative one, respectively. Stable disease was recorded in 24%, 21%, and 27%, respectively, in the whole series, the hormonal-resistant group, and the triple-negative one, respectively. Time-to-progression was 3.5 months (range, 1 to 22 mo) in the whole series and 3.0 months (range, 1 to 14.7 mo) and 3.4 months (range, 2.2 to 16.2 mo) in the hormonal-resistant group and the triple-negative one, respectively. Overall survival reached a median of 11.4 months.

Conclusions:
This multicenter study, albeit retrospective, demonstrates the activity of this combination as third-line chemotherapy option in a challenging clinical setting such as triple-negative or hormone-resistant patients with breast cancer progressing after several lines of hormonal manipulations.
Mortality of Drug-resistant Tuberculosis in High-burden Countries: Comparison of Routine Drug Susceptibility Testing with Whole-genome Sequencing
Authors: Reichmuth Martina L. , Zürcher Kathrin , Ballif Marie , Loiseau Chloé , Borrell Sonia , Reihnhard Miriam , Skrivankova Veronika , Hömke Rico , Sander Peter , Avihingsanon Anchalee , Abimiku Alash’le G , Marcy Olivier , Collantes Jimena , Carter E. Jane , Wilkinson Robert J. , Cox Helen , Yotebieng Marcel , Huebner Robin , Fenner Lukas , Böttger Erik C. , Gagneux Sebastien , Egger Matthias 
Published: January 2021

AbstractBackgroundDrug-resistant Mycobacterium tuberculosis (Mtb) strains threaten tuberculosis (TB) control. We compared data on drug resistance obtained at clinics in seven high TB burden countries during routine care with whole-genome sequencing (WGS) carried out centrally.MethodsWe collected pulmonary Mtb isolates and clinical data from adult TB patients in Africa, Latin America, and Asia, stratified by HIV status and drug resistance, from 2013 to 2016. Participating sites performed drug susceptibility testing (DST) locally, using routinely available methods. WGS was done using Illumina HiSeq 2500 at laboratories in the USA and Switzerland. We used TBprofiler to analyse the genomes. We used multivariable logistic regression adjusted for sex, age, HIV-status, history of TB, sputum positivity, and Mtb-lineage to analyse mortality.FindingsWe included 582 TB patients. The median age was 32 years (interquartile range: 27-43 years), 225 (39%) were female, and 247 (42%) were HIV-positive. Based on WGS, 339 (58%) isolates were pan-susceptible, 35 (6%) monoresistant, 146 (25%) multidrug-resistant, and 24 (4%) pre-/ extensively drug-resistant (pre-XDR/XDR-TB). The local DST results were discordant compared to WGS results in 130/582 (22%) of patients. All testing methods identified isoniazid and rifampicin resistance with relatively high agreement (kappa 0.69 for isoniazid and 0.88 rifampicin). Resistance to ethambutol, pyrazinamide, and second-line drugs was rarely tested locally. Of 576 patients with known treatment, 86 (15%) patients received inadequate treatment according to WGS results and the World Health Organization treatment guidelines. The analysis of mortality was based on 530 patients; 63 patients (12%) died and 77 patients (15%) received inadequate treatment. Mortality ranged from 6% in patients with pan-susceptible Mtb (18/310) to 39% in patients with pre-XDR/XDR-TB (9/23). The adjusted odds ratio for mortality was 4.82 (95% CI 2.43-9.44) for under-treatment and 0.52 (95% CI 0.03-2.73) for over-treatment.InterpretationIn seven high-burden TB countries, we observed discrepancies between drug resistance patterns from local DST and WGS, which resulted in inadequate treatment and higher mortality. WGS can provide accurate and detailed drug resistance information, which is required to improve the outcomes of drug-resistant TB in high burden settings. Our results support the WHO’s call for point-of-care tests based on WGS.
Mobile brain/body imaging of landmark-based navigation with high-density EEG
Authors: Delaux Alexandre , de Saint Aubert Jean-Baptiste , Ramanoël Stephen , Bécu Marcia , Gehrke Lukas , Klug Marius , Chavarriaga Ricardo , Sahel José-Alain , Gramann Klaus , Arleo Angelo 
Published: January 2021

AbstractCoupling behavioral measures and brain imaging in naturalistic, ecological conditions is key to comprehend the neural bases of spatial navigation. This highly-integrative function encompasses sensorimotor, cognitive, and executive processes that jointly mediate active exploration and spatial learning. However, most neuroimaging approaches in humans are based on static, motion constrained paradigms and they do not account for all these processes, in particular multisensory integration. Following the Mobile Brain/Body Imaging approach, we aimed to explore the cortical correlates of landmark-based navigation in actively behaving young adults, solving a Y-maze task in immersive virtual reality. EEG analysis identified a set of brain areas matching state-of-the-art brain imaging literature of landmark-based navigation. Spatial behavior in mobile conditions additionally involved sensorimotor areas related to motor execution and proprioception usually overlooked in static fMRI paradigms. Expectedly, we located a cortical source in or near the posterior cingulate, in line with the engagement of the retrosplenial complex in spatial reorientation. Consistent with its role in visuo-spatial processing and coding, we observed an alpha power desynchronization while participants gathered visual information. We also hypothesized behavior-dependent modulations of the cortical signal during navigation. Despite finding few differences between the encoding and retrieval phases of the task, we identified transient time-frequency patterns attributed, for instance, to attentional demand, as reflected in the alpha/gamma range, or memory workload in the delta/theta range. We confirmed that combining mobile high-density EEG and biometric measures can help unravel the brain structures and the neural modulations subtending ecological landmark-based navigation.
MolRep: A Deep Representation Learning Library for Molecular Property Prediction
Authors: Rao Jiahua , Zheng Shuangjia , Song Ying , Chen Jianwen , Li Chengtao , Xie Jiancong , Yang Hui , Chen Hongming , Yang Yuedong 
Published: January 2021

AbstractSummaryRecently, novel representation learning algorithms have shown potential for predicting molecular properties. However, unified frameworks have not yet emerged for fairly measuring algorithmic progress, and experimental procedures of different representation models often lack rigorousness and are hardly reproducible. Herein, we have developed MolRep by unifying 16 state-of-the-art models across 4 popular molecular representations for application and comparison. Furthermore, we ran more than 12.5 million experiments to optimize hyperparameters for each method on 12 common benchmark data sets. As a result, CMPNN achieves the best results ranked the 1st in 5 out of 12 tasks with an average rank of 1.75. Relatively, ECC has good performance in classification tasks and MAT good for regression (both ranked 1st for 3 tasks) with an average rank of 2.71 and 2.6, respectively.AvailabilityThe source code is available at:https://github.com/biomed-AI/MolRepSupplementary informationSupplementary data are available online.
Integrating protein networks and machine learning for disease stratification in the Hereditary Spastic Paraplegias
Authors: Vavouraki Nikoleta , Tomkins James E. , Kara Eleanna , Houlden Henry , Hardy John , Tindall Marcus J. , Lewis Patrick A. , Manzoni Claudia 
Published: January 2021

AbstractThe Hereditary Spastic Paraplegias are a group of neurodegenerative diseases characterized by spasticity and weakness in the lower body. Despite the identification of causative mutations in over 70 genes, the molecular aetiology remains unclear. Due to the combination of genetic diversity and variable clinical presentation, the Hereditary Spastic Paraplegias are a strong candidate for protein-protein interaction network analysis as a tool to understand disease mechanism(s) and to aid functional stratification of phenotypes. In this study, experimentally validated human protein-protein interactions were used to create a protein-protein interaction network based on the causative Hereditary Spastic Paraplegia genes. Network evaluation as a combination of both topological analysis and functional annotation led to the identification of core proteins in putative shared biological processes such as intracellular transport and vesicle trafficking. The application of machine learning techniques suggested a functional dichotomy linked with distinct sets of clinical presentations, suggesting there is scope to further classify conditions currently described under the same umbrella term of Hereditary Spastic Paraplegias based on specific molecular mechanisms of disease.
Overburdening of peer reviewers. A multi-disciplinary and multi-stakeholder perspective on causes, effects and potential policy implications
Authors: Severin Anna , Chataway Joanna 
Published: January 2021

AbstractPeer review of manuscripts is labour-intensive and time-consuming. Individual reviewers often feel themselves overburdened with the amount of reviewing they are requested to do. Aiming to explore how stakeholder groups perceive reviewing burden and what they believe to be the causes of a potential overburdening of reviewers, we conducted focus groups with early-, mid-, and senior career scholars, editors, and publishers. By means of a thematic analysis, we aimed to identify the causes of overburdening of reviewers. First, we show that, across disciplines and roles, stakeholders believed that the reviewing workload has become so enormous that the academic community is no longer able to supply the reviewing resources necessary to address its demand for peer review. Second, the reviewing workload is distributed unequally across the academic community, thereby overwhelming small groups of scholars. Third, stakeholders believed the overburdening of reviewers to be caused by (i) an increase in manuscript submissions; (ii) insufficient editorial triage; (iii) a lack of reviewing instructions; (iv) difficulties in recruiting reviewers; (v) inefficiencies in manuscript handling and (vi) a lack of institutionalisation of peer review. These themes were assumed to mutually reinforce each other and to relate to an inadequate incentive structure in academia that favours publications over peer review. In order to alleviate reviewing burden, a holistic approach is required that addresses both the increased demand for and the insufficient supply of reviewing resources.
satuRn:Scalable Analysis of differential Transcript Usage for bulk and single-cell RNA-sequencing applications
Authors: Gilis Jeroen , Vitting-Seerup Kristoffer , Van den Berge Koen , Clement Lieven 
Published: January 2021

AbstractAlternative splicing produces multiple functional transcripts from a single gene. Dysregulation of splicing is known to be associated with disease and as a hallmark of cancer. Existing tools for differential transcript usage (DTU) analysis either lack in performance, cannot account for complex experimental designs or do not scale to massive scRNA-seq data. We introduce satuRn, a fast and flexible quasi-binomial generalized linear modelling framework that is on par with the best performing DTU methods from the bulk RNA-seq realm, while providing good false discovery rate control, addressing complex experimental designs and scaling to scRNA-seq applications.
Dissociable mechanisms of reward learning co-mature during human adolescence as predicted by macaque lesion models
Authors: Wittmann Marco K. , Scheuplein Maximilian , Gibbons Sophie G. , Noonan MaryAnn P. 
Published: January 2021

AbstractReward-guided learning and decision-making is a fundamental adaptive ability and depends on a number of component processes. We investigate how such component processes mature during human adolescence. Our approach was guided by analyses of the effects of lateral orbitofrontal lesions in macaque monkeys, as this part of the brain shows clear developmental maturation in humans during adolescence. Using matched tasks and analyses in humans (n=388, 11-35yrs), we observe developmental changes in two key learning mechanisms as predicted from the monkey data. First, choice-reward credit assignment – the ability to link a specific outcome to a specific choice – is reduced in adolescents. Second, the effects of the global reward state – how good the environment is overall recently − exerts a distinctive pattern of influence on learning in humans compared to other primates and across adolescence this pattern becomes more pronounced. Both mechanisms were correlated across participants suggesting that associative learning of correct reward assignments and GRS based learning constitute two complementary mechanisms of reward-learning that co-mature during adolescence.
Mitochondrial function is essential for humoral immunity by controlling flux of the TCA cycle, phosphatidic acid and mTOR activity in B cells
Authors: Urbanczyk Sophia , Baris Olivier R. , Hofmann Jörg , Golombek Florian , Castiglione Kathrin , Meng Xianyi , Bozec Aline , Mougiakakos Dimitrios , Schulz Sebastian R. , Schuh Wolfgang , Schlötzer-Schrehardt Ursula , Steinmetz Tobit D. , Brodesser Susanne , Wiesner Rudolf J. , Mielenz Dirk 
Published: January 2021

AbstractThe function of mitochondrial respiration during B cell fate decisions and differentiation remains equivocal. This study reveals that selection for mitochondrial fitness occurs during B cell activation and is essential for subsequent plasma cell differentiation. By expressing a mutated mitochondrial helicase in transitional B cells, we depleted mitochondrial DNA during B cell maturation, resulting in reduced oxidative phosphorylation. Although no changes in follicular B cell development were evident, germinal centers, class switch recombination to IgG, plasma cell generation and humoral immunity were diminished. Defective oxidative phosphorylation led to aberrant flux of the tricarboxylic acid cycle and lowered the amount of saturated phosphatidic acid. Consequently, MTOR activity and BLIMP-1 induction were curtailed whereas HIF1α, glycolysis and AMPK activity were amplified. Exogenous phosphatidic acid increased mTOR activity in activated B cells. Hence, mitochondrial function is required and selected for in activated B cells for the successful generation of functional plasma cells.
Locally confined IFNγproduction by CD4+T cells provides niches for murine cytomegalovirus replication in the salivary gland
Authors: Oderbolz Josua , Zangger Nathan , Zimmermann Lea , Sandu Ioana , Starruß Jörn , Graw Frederik , Oxenius Annette 
Published: January 2021

AbstractCytomegalovirus (CMV) has evolved a unique virus-host relationship in the salivary glands (SGs) to sustain prolonged viral replication and hence chances for horizontal transmission. Previous reports have established a decisive role for IFNγproducing CD4+T cells to control murine CMV (MCMV) infection in the SGs; however, micro-anatomical information regarding their mode of action is largely missing. Here, we provide a spatiotemporal analysis of defined antiviral immune actions that eventually culminate in control of lytic MCMV replication in this preferred mucosal niche. CXCR3-mediated guidance of CD4+T cells towards CXCL9 and CXCL10 expressing cells resulted in discrete clusters close to infection foci where they reported TCR engagement and produced IFNγ. Of note, these clusters occasionally contained CD11c+antigen-presenting cells with engulfed virus-associated remnants, most likely apoptotic bodies derived from previously infected cells, enabling antigen presentation to CD4+T cells. The induced IFNγproduction within these CD4+T cell accumulations triggered IFNγR signaling in a confined perimeter, thereby inducing local, but not organ-wide protection, and allowing MCMV replication to continue at not yet protected sites. Combining experimental data with a mathematical model of the spatiotemporal dynamics of infection and CD4+T cell dynamics revealed a scenario, in which ultimate MCMV control is achieved through accumulating sites of regionally-confined tissue protection.
Atopic Biomarker Changes after Exposure toPorphyromonas gingivalisLipopolysaccharide: A Small Experimental Study in Wistar Rat
Authors: Nelwan Sindy Cornelia , Nugraha Ricardo Adrian , Endaryanto Anang , Meizarini Asti , Tedjosasongko Udijanto , Pradopo Seno , Utomo Haryono 
Published: January 2021

BackgroundIgE and IgG4are implicated in atopic development and clinically utilized as major biomarkers. Atopic responses following certain pathogens such asPorphyromonas gingivalisis currently an area of interest for further research.PurposeThe aim of this study is to measure the level of IgE, IgG4, and IgG4/IgE ratio periodically after exposure of periodontal pathogenPorphyromonas gingivalis(Pg) lipopolysaccharide (LPS).MethodsWe used 16 wistar rats (Rattus norvegicus) randomly subdivided into 4 groups, group 1 were injected by placebo, group 2 by LPS Pg 0.3 μg/mL,group 3 by LPS Pg 1 μg/mL, and group 4 by LPS Pg 3 μg/mL. Sera from both groups were taken from retro-orbital plexus before and after exposure.ResultsLevel of IgE and IgG4increased significantly following exposure of LPS Pg at day-4 and day-11. Greater increase of IgE rather than IgG4contributes to rapid decline of IgG4/IgE ratio, detected in the peripheral blood at day-4 and day-11.ConclusionModulation of atopic responses following exposure to LPS Pg is reflected by decrease in IgG4/IgE ratio that accompanies an increase of IgE.Clinical significancePorphyromonas gingivalis, a keystone pathogen during periodontal disease, may have a tendency to disrupt atopic biomarkers.