bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning and bioinformatics analysis to identify autophagy-related biomarkers in peripheral blood for rheumatoid arthritis
Authors: Dong Guoqi , Gao Hui , Chen Yingqi , Yang Huayuan 
Published: September 2023

Background: Although rheumatoid arthritis (RA) is a common autoimmune disease, the precise pathogenesis of the disease remains unclear. Recent research has unraveled the role of autophagy in the development of RA. This research aims to explore autophagy-related diagnostic biomarkers in the peripheral blood of RA patients.Methods: The gene expression profiles of GSE17755 were retrieved from the gene expression ontology (GEO) database. Differentially expressed autophagy-related genes (DE-ARGs) were identified for the subsequent research by inserting autophagy-related genes and differentially expressed genes (DEGs). Three machine learning algorithms, including random forest, support vector machine recursive feature elimination (SVM-RFE), and least absolute shrinkage and selection operator (LASSO), were employed to identify diagnostic biomarkers. A nomogram model was constructed to assess the diagnostic value of the biomarkers. The CIBERSORT algorithm was performed to investigate the correlation of the diagnostic biomarkers with immune cells and immune factors. Finally, the diagnostic efficacy and differential expression trend of diagnostic biomarkers were validated in multiple cohorts containing different tissues and diseases.Results: In this study, 25 DE-ARGs were identified between RA and healthy individuals. In addition to “macroautophagy” and “autophagy-animal,” DE-ARGs were also associated with several types of programmed cell death and immune-related pathways according to GO and KEGG analysis. Three diagnostic biomarkers, EEF2, HSP90AB1 and TNFSF10, were identified by the random forest, SVM-RFE, and LASSO. The nomogram model demonstrated excellent diagnostic value in GSE17755 (AUC = 0.995, 95% CI: 0.988–0.999). Furthermore, immune infiltration analysis showed a remarkable association between EEF2, HSP90AB1, and TNFSF10 expression with various immune cells and immune factors. The three diagnostic biomarkers also exhibited good diagnostic efficacy and demonstrated the same trend of differential expression in multiple validation cohorts.Conclusion: This study identified autophagy-related diagnostic biomarkers based on three machine learning algorithms, providing promising targets for the diagnosis and treatment of RA.
Comparative effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in immunocompromised individuals: a systematic review and meta-analysis using the GRADE framework
Authors: Wang Xuan , Haeussler Katrin , Spellman Anne , Phillips Leslie E. , Ramiller Allison , Bausch-Jurken Mary T. , Sharma Pawana , Krivelyova Anna , Vats Sonam , Van de Velde Nicolas 
Published: September 2023

IntroductionDespite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response after vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) vs BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework.MethodsThe systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals ≥18 years of age; outcomes of interest were symptomatic, laboratory-confirmed SARS-CoV-2 infection, SARS-CoV-2 infection, severe SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies. Evidence was evaluated using the GRADE framework.ResultsOverall, 17 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.75–0.97]; P=0.0151; I2 = 67.7%), severe SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.77–0.93]; P=0.0009; I2 = 0%), COVID-19–associated hospitalization (RR, 0.88 [95% CI, 0.79–0.97]; P&lt;0.0001; I2 = 0%), and COVID-19–associated mortality (RR, 0.63 [95% CI, 0.44–0.90]; P=0.0119; I2 = 0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials. Based on nonrandomized studies, evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies.ConclusionThis GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2.
Complement inhibition can decrease the haemostatic response in a microvascular bleeding model at multiple levels
Authors: Golomingi Murielle , Kohler Jessie , Lamers Christina , Pouw Richard B. , Ricklin Daniel , Dobó József , Gál Péter , Pál Gábor , Kiss Bence , Dopler Arthur , Schmidt Christoph Q. , Hardy Elaissa Trybus , Lam Wilbur , Schroeder Verena 
Published: September 2023

BackgroundHaemostasis is a crucial process by which the body stops bleeding. It is achieved by the formation of a platelet plug, which is strengthened by formation of a fibrin mesh mediated by the coagulation cascade. In proinflammatory and prothrombotic conditions, multiple interactions of the complement system and the coagulation cascade are known to aggravate thromboinflammatory processes and increase the risk of arterial and venous thrombosis. Whether those interactions also play a relevant role during the physiological process of haemostasis is not yet completely understood. The aim of this study was to investigate the potential role of complement components and activation during the haemostatic response to mechanical vessel injury.MethodsWe used a microvascular bleeding model that simulates a blood vessel, featuring human endothelial cells, perfusion with fresh human whole blood, and an inducible mechanical injury to the vessel. We studied the effects of complement inhibitors against components of the lectin (MASP-1, MASP-2), classical (C1s), alternative (FD) and common pathways (C3, C5), as well as a novel triple fusion inhibitor of all three complement pathways (TriFu). Effects on clot formation were analysed by recording of fibrin deposition and the platelet activation marker CD62P at the injury site in real time using a confocal microscope.ResultsWith the inhibitors targeting MASP-2 or C1s, no significant reduction of fibrin formation was observed, while platelet activation was significantly reduced in the presence of the FD inhibitor. Both common pathway inhibitors targeting C3 or C5, respectively, were associated with a substantial reduction of fibrin formation, and platelet activation was also reduced in the presence of the C3 inhibitor. Triple inhibition of all three activation pathways at the C3-convertase level by TriFu reduced both fibrin formation and platelet activation. When several complement inhibitors were directly compared in two individual donors, TriFu and the inhibitors of MASP-1 and C3 had the strongest effects on clot formation.ConclusionThe observed impact of complement inhibition on reducing fibrin clot formation and platelet activation suggests a role of the complement system in haemostasis, with modulators of complement initiation, amplification or effector functions showing distinct profiles. While the interactions between complement and coagulation might have evolved to support haemostasis and protect against bleeding in case of vessel injury, they can turn harmful in pathological conditions when aggravating thromboinflammation and promoting thrombosis.
Correlations between gut microbiota and lichen planus: a two-sample Mendelian randomization study
Authors: Yan Ming , Ouyang Yu-Long , Xiao Li-Yuan , Ao Man , Gosau Martin , Friedrich Reinhard E. , Smeets Ralf , Fu Ling-Ling , Feng Hong-chao , Burg Simon 
Published: September 2023

PurposeSeveral existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota and LP was analyzed using the Mendelian randomization (MR) method.MethodsThrough the two-sample MR method, single nucleotide polymorphisms (SNPs) relevant to gut microbiota were selected as instrument variables (IVs) to evaluate the causal association between gut microbiota and the risk of LP.ResultsAccording to the selection criteria of inverse-variance weighted (IVW), six bacterial genera were found to be significantly linked to the initiation of LP; The IVW results suggested that Oxalobacteraceae, Victivallaceae, and Actinobacteria could restrain the initiation of LP, showing protective effects against LP. Desulfovibrio, Veillonella, and Ruminococcus gauvreauii groups were demonstrated to have casual correlations with the onset of LP.ConclusionThe relationship between gut microbiota and LP was not a single positive or inverse relationship. Investigation of the causal relationship of these gut microbiota with LP could further provide evidence for the intestine-skin axis theory. However, the specific mechanism of microorganisms affecting the skin remains to be clarified. In this paper, the protective effects and mechanisms of Oxalobacteraceae, Victivallaceae, and Actinobacteria on LP require further exploration.
Multi-omics segregate different transcriptomic impacts of anti-IL-17A blockade on type 17 T-cells and regulatory immune cells in psoriasis skin
Authors: Kim Jaehwan , Lee Jongmi , Li Xuan , Kunjravia Norma , Rambhia Darshna , Cueto Inna , Kim Katherine , Chaparala Vasuma , Ko Younhee , Garcet Sandra , Zhou Wei , Cao Junyue , Krueger James G. 
Published: September 2023

Durable psoriasis improvement has been reported in a subset of psoriasis patients after treatment withdrawal of biologics blocking IL-23/Type 17 T-cell (T17) autoimmune axis. However, it is not well understood if systemic blockade of the IL-23/T17 axis promotes immune tolerance in psoriasis skin. The purpose of the study was to find translational evidence that systemic IL-17A blockade promotes regulatory transcriptome modification in human psoriasis skin immune cell subsets. We analyzed human psoriasis lesional skin 6 mm punch biopsy tissues before and after systemic IL-17A blockade using the muti-genomics approach integrating immune cell-enriched scRNA-seq (n = 18), microarray (n = 61), and immunohistochemistry (n = 61) with repository normal control skin immune cell-enriched scRNA-seq (n = 10) and microarray (n = 8) data. For the T17 axis transcriptome, systemic IL-17A blockade depleted 100% of IL17A+ T-cells and 95% of IL17F+ T-cells in psoriasis skin. The expression of IL23A in DC subsets was also downregulated by IL-17A blockade. The expression of IL-17-driven inflammatory mediators (IL36G, S100A8, DEFB4A, and DEFB4B) in suprabasal keratinocytes was correlated with psoriasis severity and was downregulated by IL-17A blockade. For the regulatory DC transcriptome, the proportion of regulatory semimature DCs expressing regulatory DC markers of BDCA-3 (THBD) and DCIR (CLEC4A) was increased in posttreatment psoriasis lesional skin compared to pretreatment psoriasis lesional skin. In addition, IL-17A blockade induced higher expression of CD1C and CD14, which are markers of CD1c+ CD14+ dendritic cell (DC) subset that suppresses antigen-specific T-cell responses, in posttreatment regulatory semimature DCs compared to pretreatment regulatory semimature DCs. In conclusion, systemic IL-17A inhibition not only blocks the entire IL-23/T17 cell axis but also promotes regulatory gene expression in regulatory DCs in human psoriasis skin.
Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses
Authors: Uzcategui Nestor L. , Güçer Sena , Richter Cris , Speidel Annika , Zirdum Elizabeta , Duszenko Michael , Garaschuk Olga , Figarella Katherine 
Published: September 2023

IntroductionInvasion of the central nervous system (CNS) is the most serious consequence of Trypanosoma brucei infection, which causes sleeping sickness. Recent experimental data have revealed some more insights into the disease during the meningoencephalitic stage. However, detailed cellular processes befalling the CNS during the disease are poorly understood.MethodsTo further address this issue, we implanted a cranial window on the cortex of B6.129P2(Cg)-Cx3cr1tm1Litt/J mice, infected them with Trypanosoma brucei expressing RFP via intraperitoneal injection, and monitored microglial cells and parasites longitudinally over 30 days using in vivo 2-photon imaging. We correlated the observed changes with histological analyses to evaluate the recruitment of peripheral immune cells.Results and discussionWe uncovered an early involvement of microglia that precedes invasion of the CNS by the parasite. We accomplished a detailed characterization of the progressive sequence of events that correlates with microglial morphological changes and microgliosis. Our findings unveiled a heterogeneous microglial response in places of initial homeostatic disruption near brain barriers and pointed out an exceptional capability of microglia to hamper parasite proliferation inside the brain. We also found early signs of inflammation in the meninges, which synchronize with the microglial response. Moreover, we observed a massive infiltration of peripheral immune cells into the parenchyma as a signature in the final disease stage. Overall, our study provides new insights into the host-pathogen immune interactions in the meningeal and parenchymal compartments of the neocortex.
Application of the Team Emergency Assessment Measure Scale in undergraduate medical students and interprofessional clinical teams: validity evidence of a Spanish version applied in Chile
Authors: Armijo-Rivera Soledad , Ferrada-Rivera Sandra , Aliaga-Toledo Marcela , Pérez Leonardo A. 
Published: September 2023

BackgroundTeamwork is one of the competencies necessary for physicians to work effectively in health systems and is a competency that can be developed with simulation in professionals and medicine students. The Team Emergency Assessment Measurement (TEAM) was created to evaluate the non-technical performance of team members during resuscitation events in real teams. The TEAM scale includes items to assess leadership, teamwork, situational awareness, and task management. An objective evaluation tool in Spanish is valuable for training health professionals at all undergraduate and continuing education levels. This study aimed to generate evidence of the validity of the Team Emergency Assessment Measure (TEAM) in Spanish to measure the performance of medical students and adult, pediatric, and obstetric emergency clinical teams in simulated emergencies as a self-assessment tool.MethodsTo develop the Spanish version of the instrument, a forward and backward translation process was followed by independent translators, native and fluent in English and Spanish, and a review by a panel of Chilean experts comprising three trained simulation instructors to verify semantics and cultural equivalence. High-fidelity simulations with debriefing were conducted with 5th-year medical students, in which students and instructors applied the Spanish version of the TEAM scale. In the second stage, adult, pediatric, and obstetric emergency management simulations were conducted using the TEAM scale for real clinical teams as a self-assessment tool.FindingsBy applying the overall TEAM scale to medicine students and clinical teams, Cronbach's alpha was 0.921. For medical students' self-assessment, we obtained Cronbach's alpha of 0.869. No significant differences were found between the overall scores and the scores by dimensions evaluated by instructors and students (p &gt; 0.05). In the case of clinical team training, Cronbach's alpha was 0.755 for adult emergency teams, 0.797 for pediatric emergency teams, and 0.853 for obstetric emergency teams.ConclusionThe validated instrument is adequate for evaluating teamwork in medical student simulations by instructors and peers and for self-assessment in adult, pediatric, and obstetric emergency clinical teams.
Functional proteins in breast milk and their correlation with the development of the infant gut microbiota: a study of mother-infant pairs
Authors: Xi Menglu , Liang Dong , Yan Yalu , Duan Sufang , Leng Houxi , Yang Haibing , Shi Xiaojin , Na Xiaona , Yang Yucheng , Yang Celi , Szeto Ignatius Man-Yau , Zhao Ai 
Published: September 2023

IntroductionProteins in breast milk play an important role in the growth and development of infants. This study aims to explore the correlation between functional proteins in breast milk and the infant gut microbiota.MethodsTwenty-three mothers and their infants were enrolled and breast milk samples and infant fecal samples were collected. Breast milk protein content was determined by UPLC-MS/MS, and 16S rRNA sequencing was employed to analyze the gut microbiota of infant.ResultsThe results indicated that the secretory immunoglobulin A (sIgA) content in breast milk was positively correlated with the abundance of Veillonella parvula. The κ-casein content was positively correlated with the abundance of Clostridium butyricum. The osteopontin (OPN) and lactalbumin contents were positively correlated with the abundance of Parabacteroides distasonis at 42 days. Functional pathway analysis showed that the OPN and κ-casein contents in breast milk were significantly correlated with amino acid, pyruvate, propionic acid, linoleic acid, and alpha-linolenic acid metabolic pathways in early life.DiscussionThe results of this study suggest that specific proteins in breast milk can influence the abundance of certain gut microbes in infants, playing an important role in early immune and metabolic development.
Archaeome structure and function of the intestinal tract in healthy and H1N1 infected swine
Authors: Meene Alexander , Gierse Laurin , Schwaiger Theresa , Karte Claudia , Schröder Charlotte , Höper Dirk , Wang Haitao , Groß Verena , Wünsche Christine , Mücke Pierre , Kreikemeyer Bernd , Beer Martin , Becher Dörte , Mettenleiter Thomas C. , Riedel Katharina , Urich Tim 
Published: September 2023

BackgroundMethanogenic archaea represent a less investigated and likely underestimated part of the intestinal tract microbiome in swine.Aims/MethodsThis study aims to elucidate the archaeome structure and function in the porcine intestinal tract of healthy and H1N1 infected swine. We performed multi-omics analysis consisting of 16S rRNA gene profiling, metatranscriptomics and metaproteomics.Results and discussionWe observed a significant increase from 0.48 to 4.50% of archaea in the intestinal tract microbiome along the ileum and colon, dominated by genera Methanobrevibacter and Methanosphaera. Furthermore, in feces of naïve and H1N1 infected swine, we observed significant but minor differences in the occurrence of archaeal phylotypes over the course of an infection experiment. Metatranscriptomic analysis of archaeal mRNAs revealed the major methanogenesis pathways of Methanobrevibacter and Methanosphaera to be hydrogenotrophic and methyl-reducing, respectively. Metaproteomics of archaeal peptides indicated some effects of the H1N1 infection on central metabolism of the gut archaea.Conclusions/Take home messageFinally, this study provides the first multi-omics analysis and high-resolution insights into the structure and function of the porcine intestinal tract archaeome during a non-lethal Influenza A virus infection of the respiratory tract, demonstrating significant alterations in archaeal community composition and central metabolic functions.
Elevated white blood cell counts in ischemic stroke patients are associated with increased mortality and new vascular events
Authors: Vo Thao Phuong , Kristiansen Marie Hvelplund , Hasselbalch Hans Carl , Wienecke Troels 
Published: September 2023

Background and purposeHigh levels of white blood cells (WBC) in ischemic stroke have been shown to increase the risk of new vascular events and mortality in short and intermediate follow-up studies, but long-term effects remain unknown. We studied whether elevated levels of WBC in ischemic stroke patients are associated with new vascular events and mortality in a 10-year follow-up period.MethodsWe included ischemic stroke patients hospitalized between 2011 and 2012, categorizing their WBC counts within 48 h of stroke onset as high or normal (3.5–8.8 × 109 mmol/L; &gt;8.8 × 109 mmol/L). Using Aahlen Johansen and Cox proportional hazard models with competing risk, we analyzed the association between WBC levels and new vascular events. Kaplan–Meier and standard Cox proportional hazard models were used to assess the risk of all-cause mortality.ResultsAmong 395 patients (median age 69, [IQR: 63, 78], female patients 38,0%), 38.5% had elevated WBC at admission. During the 10-year follow-up, 113 vascular events occurred, with 46% in patients with elevated WBC and 54% in patients with normal WBC. After adjusting for relevant factors, elevated WBC levels were independently associated with increased risk of new vascular events (HR: 1.61, CI: 1.09–2.39 p &lt; 0.05) and death (HR: 1.55, CI: 1.15–2.09, p &lt; 0.05).ConclusionElevated WBC levels in ischemic stroke patients are linked to a higher risk of new vascular events and mortality. Thus, ischemic stroke patients with elevated WBC without clinical infection need special attention to investigate possible underlying conditions to prevent future vascular events and reduce mortality. The interpretation of our results is limited by the absence of adjustment to premorbid functional status, stroke severity, and stroke treatment.