bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding Digital Capital as a Factor of Transformation of Professional Communities
Authors: Yarmak V. Е. 
Published: April 2023

Introduction. To date, in the scientific discourse, an approach to the definition of digital capital as an object of research in sociology is only being formed. Sociological analysis is important for the study of digital capital because it is able to reveal its specifics, features, material and non-material components.Methodology and sources. The study and theorization of digital capital is based on theoretical and methodological positions and studies of the processes of digitalization and digital capital proposed by researchers earlier. Based on this, the author proposed her own definition of digital capital and research methodology and conducted a pilot empirical study.Results and discussion. It is revealed that, on the one hand, the development of society under the influence of digitalization and the presence of digital capital among representatives of various socio-demographic and professional groups contributes to the development of society. But on the other hand, the simplification of structural processes in connection with the introduction of digital technologies entails a number of objective problems: a shortage of specialists with the necessary competencies, a decrease in the quality of qualifications existing specialists, inequality among professional groups, unemployment, etc.Conclusion. In one way or another, digitalization has affected either the working conditions or influenced the transformation of the profession, including new specialties and requirements. The main advantage of digitalization is to increase the productivity of the enterprise by reducing the time required to develop a new product, release it to the market and deliver it to the consumer, as well as to optimize the company's resources, which increases the efficiency of its work as a whole. Respondents employed at IT enterprises noted that the process of digitalization minimally affected their field of activity, since it was always “in numbers” anyway. At the same time, the IT profession has really transformed. This lies in the fact, that earlier it included only those who are engaged, for example, in programming, and now this profession includes everyone who is somehow connected with a digital product.
Anoikis-related genes combined with single cell sequencing: Insights into model specification of lung adenocarcinoma and applicability for prognosis and therapy
Authors: Zhou Yiyi , Hu Zhenli 
Published: April 2023

Background: Anoikis has therapeutic potential against different malignancies including lung adenocarcinoma. This study used anoikis and bioinformatics to construct a prognostic model for lung adenocarcinoma and explore new therapeutic strategies.Methods: Several bioinformatic algorithms (co-expression analysis, univariate Cox analysis, multivariate Cox analysis, and cross-validation) were used to screen anoikis-related genes (ARGs) to construct a risk model. Lung adenocarcinoma patients were divided into training and testing groups at a ratio of 1:1. The prognostic model was validated by risk score comparison between high- and low-risk groups using receiver operating characteristic curve (ROC), nomograms, independent prognostic analysis and principal component analysis. In addition, two anoikis-related genes patterns were classified utilizing consensus clustering method and were compared with each other in survival time, immune microenvironment, and regulation in pathway. Single cell sequencing was applied to analyze anoikis-related genes constructed the model.Results: This study demonstrated the feasibility of the model based on seven anoikis-related genes, as well as identifying axitinib, nibtinib and sorafenib as potential therapeutic strategies for LUAD. Risk score based on this model had could be used as an independent prognostic factor for lung adenocarcinoma (HR &gt; 1; p &lt; 0.001) and had the highest accuracy to predict survival compared with the clinical characteristics. Single cell sequencing analysis discovered Keratin 14 (KRT14, one of the seven anoikis-related genes) was mainly expressed in malignant cells in various cancers.Conclusion: We identified seven anoikis-related genes and constructed an accurate risk model based on bioinformatics analysis that can be used for prognostic prediction and for the design of therapeutic strategies in clinical practice.
Research-based flow cytometry assays for pathogenic assessment in the human B-cell biology of gene variants revealed in the diagnosis of inborn errors of immunity: a Bruton’s tyrosine kinase case-study
Authors: del Pino-Molina L. , Bravo Gallego L. Y. , Soto Serrano Y. , Reche Yebra K. , Marty Lobo J. , González Martínez B. , Bravo García-Morato M. , Rodríguez Pena R. , van der Burg M. , López Granados E. 
Published: April 2023

IntroductionInborn errors of immunity (IEI) are an expanding group of rare diseases whose field has been boosted by next-generation sequencing (NGS), revealing several new entities, accelerating routine diagnoses, expanding the number of atypical presentations and generating uncertainties regarding the pathogenic relevance of several novel variants.MethodsResearch laboratories that diagnose and provide support for IEI require accurate, reproducible and sustainable phenotypic, cellular and molecular functional assays to explore the pathogenic consequences of human leukocyte gene variants and contribute to their assessment. We have implemented a set of advanced flow cytometry-based assays to better dissect human B-cell biology in a translational research laboratory. We illustrate the utility of these techniques for the in-depth characterization of a novel (c.1685G&gt;A, p.R562Q) de novo gene variant predicted as probably pathogenic but with no previous insights into the protein and cellular effects, located in the tyrosine kinase domain of the Bruton’s tyrosine kinase (BTK) gene, in an apparently healthy 14-year-old male patient referred to our clinic for an incidental finding of low immunoglobulin (Ig) M levels with no history of recurrent infections.Results and discussionA phenotypic analysis of bone marrow (BM) revealed a slightly high percentage of pre-B-I subset in BM, with no blockage at this stage, as typically observed in classical X-linked agammaglobulinemia (XLA) patients. The phenotypic analysis in peripheral blood also revealed reduced absolute numbers of B cells, all pre-germinal center maturation stages, together with reduced but detectable numbers of different memory and plasma cell isotypes. The R562Q variant allows Btk expression and normal activation of anti-IgM-induced phosphorylation of Y551 but diminished autophosphorylation at Y223 after anti IgM and CXCL12 stimulation. Lastly, we explored the potential impact of the variant protein for downstream Btk signaling in B cells. Within the canonical nuclear factor kappa B (NF-κB) activation pathway, normal IκBα degradation occurs after CD40L stimulation in patient and control cells. In contrast, disturbed IκBα degradation and reduced calcium ion (Ca2+) influx occurs on anti-IgM stimulation in the patient’s B cells, suggesting an enzymatic impairment of the mutated tyrosine kinase domain.
ATRA treatment slowed P-selectin-mediated rolling of flowing HL60 cells in a mechano-chemical-dependent manner
Authors: Dong Xiaoting , Peng Shiping , Ling Yingchen , Huang Bing , Tu Wenjian , Sun Xiaoxi , Li Quhuan , Fang Ying , Wu Jianhua 
Published: April 2023

All-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) toward granulocytes may trigger APL differentiation syndrome (DS), but there is less knowledge about the mechano-chemical regulation mechanism of APL DS under the mechano-microenvironment. We found that ATRA-induced changes in proliferation, morphology, and adhesive molecule expression levels were either dose or stimulus time dependent. An optimal ATRA stimulus condition for differentiating HL60 cells toward neutrophils consisted of 1 × 10-6 M dose and 120 h of stimulus time. Under wall shear stresses, catch–slip bond transition governs P-selectin-mediated rolling for neutrophils and untreated or ATRA-treated (1 × 10-6 M, 120 h) HL60 cells. The ATRA stimuli slowed down the rolling of HL60 cells on immobilized P-selectin no matter whether ICAM-1 was engaged. The β2 integrin near the PSGL-1/P-selectin axis would be activated within sub-seconds for each cell group mentioned above, thus contributing to slow rolling. A faster β2 integrin activation rate and the higher expression levels of PSGL-1 and LFA-1 were assigned to induce the over-enhancement of ATRA-treated HL60 adhesion in flow, causing APL DS development. These findings provided an insight into the mechanical–chemical regulation for APL DS development via ATRA treatment of leukemia and a novel therapeutic strategy for APL DS through targeting the relevant adhesion molecules.
Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies
Authors: Mai Hoa Le , Degauque Nicolas , Lorent Marine , Rimbert Marie , Renaudin Karine , Danger Richard , Kerleau Clarisse , Tilly Gaelle , Vivet Anaïs , Le Bot Sabine , Delbos Florent , Walencik Alexandre , Giral Magali , Brouard Sophie 
Published: April 2023

IntroductionThe human immune system contains cells with either effector/memory or regulatory functions. Besides the well-established CD4+CD25hiCD127lo regulatory T cells (Tregs), we and others have shown that B cells can also have regulatory functions since their frequency and number are increased in kidney graft tolerance and B cell depletion as induction therapy may lead to acute rejection. On the other hand, we have shown that CD28-CD8+ T cells represent a subpopulation with potent effector/memory functions. In the current study, we tested the hypothesis that kidney allograft rejection may be linked to an imbalance of effector/memory and regulatory immune cells.MethodsBased on a large cohort of more than 1000 kidney graft biopsies with concomitant peripheral blood lymphocyte phenotyping, we investigated the association between kidney graft rejection and the percentage and absolute number of circulating B cells, Tregs, as well as the ratio of B cells to CD28-CD8+ T cells and the ratio of CD28-CD8+ T cells to Tregs. Kidney graft biopsies were interpreted according to the Banff classification and divided into 5 biopsies groups: 1) normal/subnormal, 2) interstitial fibrosis and tubular atrophy grade 2/3 (IFTA), 3) antibody-mediated rejection (ABMR), 4) T cell mediated-rejection (TCMR), and 5) borderline rejection. We compared group 1 with the other groups as well as with a combined group 3, 4, and 5 (rejection of all types) using multivariable linear mixed models.Results and discussionWe found that compared to normal/subnormal biopsies, rejection of all types was marginally associated with a decrease in the percentage of circulating B cells (p=0.06) and significantly associated with an increase in the ratio of CD28-CD8+ T cells to Tregs (p=0.01). Moreover, ABMR, TCMR (p=0.007), and rejection of all types (p=0.0003) were significantly associated with a decrease in the ratio of B cells to CD28-CD8+ T cells compared to normal/subnormal biopsies. Taken together, our results show that kidney allograft rejection is associated with an imbalance between immune cells with effector/memory functions and those with regulatory properties.
Hydroxychloroquine improves pregnancy outcomes of women with positive antinuclear antibody spectrum test results
Authors: Ye Shenglong , Liu Yuanying , Zhao Xueqing , Ma Yue , Wang Yongqing 
Published: April 2023

Background:Empirical use of Hydroxychloroquine (HCQ) in patients with positive antinuclear antibody spectrum (ANAs) test result is controversial regarding its impact on improving perinatal outcomes. This study aimed to investigate the effect of HCQ on adverse pregnancy outcomes associated with placental dysfunction in ANAs-positive patients.Methods:The study included pregnant women with positive ANAs test result from 2016 to 2020 in our center, and divided into a weakly positive and a positive group in just ANA positive patients among them. Univariate and multivariate analyses were conducted to determine the effect of HCQ on pregnancy outcomes in each subgroup. Stratified and interactive analyses were performed to assess the value of HCQ in improving pregnancy outcomes.Results:(i) A total of 261 cases were included, accounting for 30.60% of pregnancy complicated with autoimmune abnormalities, and 65.12% of them used HCQ during pregnancy. (ii) The application of HCQ significantly reduced the incidence of early-onset preeclampsia (1.18% vs. 12.09%, p = 0.040) and small-for-gestational-age infants (10.06% vs. 25.84%, p = 0.003) in the ANAs-positive population, increased birth weight (3075.87 ± 603.91 g vs. 2847.53 ± 773.73 g, p = 0.025), and prolonged gestation (38.43 ± 2.31 vs. 36.34 ± 5.45 weeks, p &lt; 0.001). (iii) A total of 185 just ANA-positive patients were stratified according to titers. Among them, the rate of HCQ usage was significantly higher than that in the weakly positive group (81.03% vs. 58.27%, p = 0.003). (vi) Stratified univariate analysis showed that HCQ usage in the ANA-positive group could reduce the incidence of preeclampsia (2.13% vs. 27.27%, p = 0.019) and prolong gestation (38.29 ± 2.54 vs. 34.48 ± 7.68 weeks, p = 0.006). In the ANA-weakly positive group, HCQ significantly reduced the incidence of preeclampsia (6.76% vs. 28.30%, p = 0.002), early-onset preeclampsia (1.35% vs. 13.21%, p = 0.027), and small-for-gestational-age infants (7.89% vs. 35.19%, p &lt; 0.001). Multivariate regression analysis showed that HCQ significantly reduced the incidence of preeclampsia in both groups. Intergroup interaction analysis showed no significant difference in the value of HCQ in reducing the incidence of preeclampsia between the two groups.Conclusion:ANAs positivity is an important abnormal autoimmunity type in pregnancy. HCQ can be considered as a choice for improving adverse pregnancy outcomes related to placental dysfunction, such as preeclampsia, in this population.
Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome
Authors: Augustin Max , Heyn Ferdinand , Ullrich Stella , Sandaradura de Silva Ute , Albert Marie-Christine , Linne Viktoria , Schlotz Maike , Schommers Philipp , Pracht Elisabeth , Horn Carola , Suarez Isabelle , Simonis Alexander , Picard Lea Katharina , Zoufaly Alexander , Wenisch Christoph , Fätkenheuer Gerd , Gruell Henning , Klein Florian , Hallek Michael , Walczak Henning , Rybniker Jan , Theobald Sebastian J. , Lehmann Clara 
Published: April 2023

BackgroundSymptoms lasting longer than 12  weeks after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection are called post-coronavirus disease (COVID) syndrome (PCS). The identification of new biomarkers that predict the occurrence or course of PCS in terms of a post-viral syndrome is vital. T-cell dysfunction, cytokine imbalance, and impaired autoimmunity have been reported in PCS. Nevertheless, there is still a lack of conclusive information on the underlying mechanisms due to, among other things, a lack of controlled study designs.MethodsHere, we conducted a prospective, controlled study to characterize the humoral and cellular immune response in unvaccinated patients with and without PCS following SARS-CoV-2 infection over 7 months and unexposed donors.ResultsPatients with PCS showed as early as 6 weeks and 7 months after symptom onset significantly increased frequencies of SARS-CoV-2-specific CD4+ and CD8+ T-cells secreting IFNγ, TNF, and expressing CD40L, as well as plasmacytoid dendritic cells (pDC) with an activated phenotype. Remarkably, the immunosuppressive counterparts type 1 regulatory T-cells (TR1: CD49b/LAG-3+) and IL-4 were more abundant in PCS+.ConclusionThis work describes immunological alterations between inflammation and immunosuppression in COVID-19 convalescents with and without PCS, which may provide potential directions for future epidemiological investigations and targeted treatments.
Assessment of the competence in electrocardiographic interpretation among Arabic resident doctors at the emergency medicine and internal medicine departments: A multi-center online cross-sectional study
Authors: Rakab Amine , Swed Sarya , Alibrahim Hidar , Bohsas Haidara , Abouainain Yasmeen , Abbas Kirellos Said , Khair Eldien Jabban Yazan , Sawaf Bisher , Rageh Bushra , Alkhawaldeh Majd , Al-Fayyadh Israa , Rakab Mohamad Saad , Fathey Sherihan , Hafez Wael , Gerbil Amr , El-Shafei Emad Hassan Hassan 
Published: April 2023

BackgroundThis study aims to assess the electrocardiographic interpretation abilities of resident doctors at internal medicine and emergency medicine departments in eight Arabic countries.MethodsAn online cross-sectional study was conducted between October 7, 2022 and October 21, 2022 in eight Arabic countries. The questionnaire consisted of two main sections: the first section included sociodemographic information, while the second section contained 12 clinical case questions of the most severe cardiac abnormalities with their electrocardiography (ECG) recordings.ResultsOut of 2,509 responses, 630 were eligible for the data analysis. More than half of the participants were males (52.4%). Internal medicine residents were (n = 530, 84.1%), whereas emergency medicine residents were (n = 100, 15.9%). Almost participants were in their first or second years of residency (79.8%). Only 36.2% of the inquired resident doctors had attended an ECG course. Most participants, 85.6%, recognized the ECG wave order correctly, and 50.5% of the participants scored above 7.5/10 on the ECG interpretation scale. The proportions of participants who were properly diagnosed with atrial fibrillation, third-degree heart block, and atrial tachycardia were 71.1, 76.7, and 56.6%, respectively. No statistically significant difference was defined between the internal and emergency medicine residents regarding their knowledge of ECG interpretation (p value = 0.42). However, there was a significant correlation between ECG interpretation and medical residency year (p value &lt; 0.001); the fourth-year resident doctors had the highest scores (mean = 9.24, SD = 1.6). As well, participants in the third and second years of postgraduate medical residency have a probability of adequate knowledge of ECG interpretation more than participants in the first year of residency (OR = 2.1, p value = 0.001) and (OR = 1.88, p value = 0.002), respectively.ConclusionAccording to our research findings, resident doctors in departments of internal medicine and emergency medicine in Arabic nations have adequate ECG interpretation abilities; nevertheless, additional development is required to avoid misconceptions about critical cardiac conditions.
Haemophilus influenzae carriage and antibiotic resistance profile in Belgian infants over a three-year period (2016–2018)
Authors: Ekinci Esra , Willen Laura , Rodriguez Ruiz Juan Pablo , Maertens Kirsten , Van Heirstraeten Liesbet , Serrano Gabriela , Wautier Magali , Deplano Ariane , Goossens Herman , Van Damme Pierre , Beutels Philippe , Malhotra-Kumar Surbhi , Martiny Delphine , Theeten Heidi 
Published: April 2023

BackgroundNon-typeable Haemophilus influenzae has become increasingly important as a causative agent of invasive diseases following vaccination against H. influenzae type b. The emergence of antibiotic resistance underscores the necessity to investigate typeable non-b carriage and non-typeable H. influenzae (NTHi) in children.MethodsNasopharyngeal swab samples were taken over a three-year period (2016–2018) from 336 children (6–30 months of age) attending daycare centers (DCCs) in Belgium, and from 218 children with acute otitis media (AOM). Biotype, serotype, and antibiotic resistance of H. influenzae strains were determined phenotypically. Mutations in the ftsI gene were explored in 129 strains that were resistant or had reduced susceptibility to beta-lactam antibiotics. Results were compared with data obtained during overlapping time periods from 94 children experiencing invasive disease.ResultsOverall, NTHi was most frequently present in both carriage (DCC, AOM) and invasive group. This was followed by serotype “f” (2.2%) and “e” (1.4%) in carriage, and “b” (16.0%), “f” (11.7%), and “a” (4.3%) in invasive strains. Biotype II was most prevalent in all studied groups, followed by biotype III in carriage and I in invasive strains. Strains from both groups showed highest resistance to ampicillin (26.7% in carriage vs. 18.1% in invasive group). A higher frequency of ftsI mutations were found in the AOM group than the DCC group (21.6 vs. 14.9% – p = 0.056). Even more so, the proportion of biotype III strains that carried a ftsI mutation was higher in AOM compared to DCC (50.0 vs. 26.3% – p &lt; 0.01) and invasive group.ConclusionIn both groups, NTHi was most frequently circulating, while specific encapsulated serotypes for carriage and invasive group were found. Biotypes I, II and III were more frequently present in the carriage and invasive group. The carriage group had a higher resistance-frequency to the analyzed antibiotics than the invasive group. Interestingly, a higher degree of ftsI mutations was found in children with AOM compared to DCC and invasive group. This data helps understanding the H. influenzae carriage in Belgian children, as such information is scarce.
Identification of cuproptosis-related biomarkers in dilated cardiomyopathy and potential therapeutic prediction of herbal medicines
Authors: Bian Rutao , Wang Yakuan , Li Zishuang , Xu Xuegong 
Published: April 2023

Background: Dilated cardiomyopathy (DCM) is one of the significant causes of heart failure, and the mechanisms of metabolic ventricular remodelling due to disturbances in energy metabolism are still poorly understood in cardiac pathology. Understanding the biological mechanisms of cuproptosis in DCM is critical for drug development.Methods: The DCM datasets were downloaded from Gene Expression Omnibus, their relationships with cuproptosis-related genes (CRGs) and immune signatures were analyzed. LASSO, RF, and SVM-RFE machine learning algorithms were used to identify signature genes and the eXtreme Gradient Boosting (XGBoost) model was used to assess diagnostic efficacy. Molecular clusters of CRGs were identified, and immune Infiltration analysis was performed. The WGCNA algorithm was used to identify specific genes in different clusters. In addition, AUCell was used to analyse the cuproptosis scores of different cell types in the scRNA-seq dataset. Finally, herbal medicines were predicted from an online database, and molecular docking and molecular dynamics simulations were used to support the confirmation of the potential of the selected compounds.Results: We identified dysregulated cuproptosis genes and activated immune responses between DCM and healthy controls. Two signature genes (FDX1, SLC31A1) were identified and performed well in an external validation dataset (AUC = 0.846). Two molecular clusters associated with cuproptosis were further defined in DCM, and immune infiltration analysis showed B-cell naive, Eosinophils, NK cells activated and T-cell CD4 memory resting is significant immune heterogeneity in the two clusters. AUCell analysis showed that cardiomyocytes had a high cuproposis score. In addition, 19 and 3 herbal species were predicted based on FDX1 and SLC31A1. Based on the molecular docking model, the natural compounds Rutin with FDX1 (-9.3 kcal/mol) and Polydatin with SLC31A1 (-5.5 kcal/mol) has high stability and molecular dynamics simulation studies further validated this structural stability.Conclusion: Our study systematically illustrates the complex relationship between cuproptosis and the pathological features of DCM and identifies two signature genes (FDX1 and SLC31A1) and two natural compounds (Rutin and Polydatin). This may enhance our diagnosis of the disease and facilitate the development of clinical treatment strategies for DCM.