bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of resistance to phagocytosis and pulmonary persistence in mucoid Pseudomonas aeruginosa
Authors: Rowe Warren J. , Lebman Deborah A. , Ohman Dennis E. 
Published: March 2023

IntroductionPseudomonas aeruginosa is known for its ability to form biofilms, which are dependent on the production of exopolysaccharides. During chronic colonization of the airway and biofilm formation, P. aeruginosa converts to a mucoid phenotype, indicating production of the exopolysaccharide alginate. The mucoid phenotype promotes resistance to phagocytic killing, but the mechanism has not been established.Methods and ResultsTo better understand the mechanism of phagocytic evasion conferred by alginate production, Human (THP-1) and murine (MH-S) macrophage cell lines were used to determine the effects of alginate production on macrophage binding, signaling and phagocytosis. Phagocytosis assays using mucoid clinical isolate FRD1 and its non-mucoid algD mutant showed that alginate production inhibited opsonic and non-opsonic phagocytosis, but exogenous alginate was not protective. Alginate caused a decrease in binding to murine macrophages. Blocking antibodies to CD11b and CD14 showed that these receptors were important for phagocytosis and were blocked by alginate. Furthermore, alginate production decreased the activation of signaling pathways required for phagocytosis. Mucoid and non-mucoid bacteria induced similar levels of MIP-2 from murine macrophages.DiscussionThis study demonstrated for the first time that alginate on the bacterial surface inhibits receptor-ligand interactions important for phagocytosis. Our data suggest that there is a selection for alginate conversion that blocks the earliest steps in phagocytosis, leading to persistence during chronic pulmonary infections.
Deaths and disability-adjusted life years of hypertension in China, South Korea, and Japan: A trend over the past 29 years
Authors: Qiu Yan , Ma Junzhuang , Zhu Jiahong , Liu Ying , Ren Wen , Zhang Shuaishuai , Ren Jingjing 
Published: March 2023

BackgroundHypertension has been confirmed as an independent risk factor for cardiovascular disease and death. Few data were analyzed on deaths and disability-adjusted life years (DALYs) caused by hypertension in East Asia. We aimed to provide an overview of burden attributable to high blood pressure in China in the past 29 years, compared with those in Japan and South Korea.MethodsData were collected from the 2019 Global Burden of Disease study on diseases due to high systolic blood pressure (SBP). We retrieved the age-standardized mortality rate (ASMR) and DALYs rate (ASDR) by gender, age, location, and sociodemographic index. The death and DALY trends were evaluated by estimated annual percentage change, with 95% confidence interval.FindingsConsiderable differences were detected in the diseases attributable to high SBP in China, Japan, and South Korea. In 2019, the ASMR and ASDR of diseases due to high SBP in China were 153.34 (126.19, 182.49) per 100,000 population and 2,844.27 (2,391.91, 3,321.12) per 100,000 population, respectively, which was about 3.50-fold of those in another two countries. The elders and males had higher ASMR and ASDR in the three countries. Between 1990 and 2019, the declining trends were less pronounced in China for both the deaths and DALYs.ConclusionsThe deaths and DALYs due to hypertension declined in China, Japan, and South Korea in the past 29 years, with China having the greatest burden.
The clusterin connectome: Emerging players in chondrocyte biology and putative exploratory biomarkers of osteoarthritis
Authors: Kovács Patrik , Pushparaj Peter Natesan , Takács Roland , Mobasheri Ali , Matta Csaba 
Published: March 2023

IntroductionClusterin is a moonlighting protein that has many functions. It is a multifunctional holdase chaperone glycoprotein that is present intracellularly and extracellularly in almost all bodily fluids. Clusterin is involved in lipid transport, cell differentiation, regulation of apoptosis, and clearance of cellular debris, and plays a protective role in ensuring cellular survival. However, the possible involvement of clusterin in arthritic disease remains unclear. Given the significant potential of clusterin as a biomarker of osteoarthritis (OA), a more detailed analysis of its complex network in an inflammatory environment, specifically in the context of OA, is required. Based on the molecular network of clusterin, this study aimed to identify interacting partners that could be developed into biomarker panels for OA.MethodsThe STRING database and Cytoscape were used to map and visualize the clusterin connectome. The Qiagen Ingenuity Pathway Analysis (IPA) software was used to analyze and study clusterin associated signaling networks in OA. We also analyzed transcription factors known to modulate clusterin expression, which may be altered in OA.ResultsThe top hits in the clusterin network were intracellular chaperones, aggregate-forming proteins, apoptosis regulators and complement proteins. Using a text-mining approach in Cytoscape, we identified additional interacting partners, including serum proteins, apolipoproteins, and heat shock proteins.DiscussionBased on known interactions with proteins, we predicted potential novel components of the clusterin connectome in OA, including selenoprotein R, semaphorins, and meprins, which may be important for designing new prognostic or diagnostic biomarker panels.
Antibody response in children with multisystem inflammatory syndrome related to COVID-19 (MIS-C) compared to children with uncomplicated COVID-19
Authors: Thiriard Anaïs , Meyer Benjamin , Eberhardt Christiane S. , Loevy Natasha , Grazioli Serge , Adouan Wafae , Fontannaz Paola , Marechal Fabienne , L’Huillier Arnaud G. , Siegrist Claire-Anne , Georges Daphnée , Putignano Antonella , Marchant Arnaud , Didierlaurent Arnaud M. , Blanchard-Rohner Geraldine 
Published: March 2023

ObjectivesTo comprehensively analyze the quality of the antibody response between children with Multisystem inflammatory syndrome (MIS-C) and age-matched controls at one month after SARS-CoV-2 exposure, and infected in the same time-period.MethodsSerum from 20 MIS-C children at admission, and 14 control children were analyzed. Antigen specific antibody isotypes and subclasses directed against various antigens of SARS-CoV-2 as well as against human common coronavirus (HCoVs) and commensal or pathogenic microorganisms were assessed by a bead-based multiplexed serological assay and by ELISA. The functionality of these antibodies was also assessed using a plaque reduction neutralization test, a RBD-specific avidity assay, a complement deposition assay and an antibody-dependent neutrophil phagocytosis (ADNP) assay.ResultsChildren with MIS-C developed a stronger IgA antibody response in comparison to children with uncomplicated COVID-19, while IgG and IgM responses are largely similar in both groups. We found a typical class-switched antibody profile with high level of IgG and IgA titers and a measurable low IgM due to relatively recent SARS-CoV-2 infection (one month). SARS-CoV-2-specific IgG antibodies of MIS-C children had higher functional properties (higher neutralization activity, avidity and complement binding) as compared to children with uncomplicated COVID-19. There was no difference in the response to common endemic coronaviruses between both groups. However, MIS-C children had a moderate increase against mucosal commensal and pathogenic strains, reflecting a potential association between a disruption of the mucosal barrier with the disease.ConclusionEven if it is still unclear why some children develop a MIS-C, we show here that MIS-C children produce higher titers of IgA antibodies, and IgG antibodies with higher functionality, which could reflect the local gastro-intestinal mucosal inflammation potentially induced by a sustained SARS-CoV-2 gut infection leading to continuous release of SARS-CoV-2 antigens.
Assessment of local and systemic signature of eosinophilic esophagitis (EoE) in children through multi-omics approaches
Authors: Adel-Patient Karine , Campeotto Florence , Grauso Marta , Guillon Blanche , Moroldo Marco , Venot Eric , Dietrich Céline , Machavoine François , Castelli Florence A. , Fenaille François , Molina Thierry Jo , Barbet Patrick , Delacourt Christophe , Leite-de-Moraes Maria , Lezmi Guillaume 
Published: March 2023

BackgroundEosinophilic oesophagitis (EoE) is a chronic food allergic disorder limited to oesophageal mucosa whose pathogenesis is still only partially understood. Moreover, its diagnosis and follow-up need repeated endoscopies due to absence of non-invasive validated biomarkers. In the present study, we aimed to deeply describe local immunological and molecular components of EoE in well-phenotyped children, and to identify potential circulating EoE-biomarkers.MethodsBlood and oesophageal biopsies were collected simultaneously from French children with EoE (n=17) and from control subjects (n=15). Untargeted transcriptomics analysis was performed on mRNA extracted from biopsies using microarrays. In parallel, we performed a comprehensive analysis of immune components on both cellular and soluble extracts obtained from both biopsies and blood, using flow cytometry. Finally, we performed non-targeted plasma metabolomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Uni/multivariate supervised and non-supervised statistical analyses were then conducted to identify significant and discriminant components associated with EoE within local and/or systemic transcriptomics, immunologic and metabolomics datasets. As a proof of concept, we conducted multi-omics data integration to identify a plasmatic signature of EoE.ResultsFrench children with EoE shared the same transcriptomic signature as US patients. Network visualization of differentially expressed (DE) genes highlighted the major dysregulation of innate and adaptive immune processes, but also of pathways involved in epithelial cells and barrier functions, and in perception of chemical stimuli. Immune analysis of biopsies highlighted EoE is associated with dysregulation of both type (T) 1, T2 and T3 innate and adaptive immunity, in a highly inflammatory milieu. Although an immune signature of EoE was found in blood, untargeted metabolomics more efficiently discriminated children with EoE from control subjects, with dysregulation of vitamin B6 and various amino acids metabolisms. Multi-blocks integration suggested that an EoE plasma signature may be identified by combining metabolomics and cytokines datasets.ConclusionsOur study strengthens the evidence that EoE results from alterations of the oesophageal epithelium associated with altered immune responses far beyond a simplistic T2 dysregulation. As a proof of concept, combining metabolomics and cytokines data may provide a set of potential plasma biomarkers for EoE diagnosis, which needs to be confirmed on a larger and independent cohort.
Overlapping cytokines in H. pylori infection and gastric cancer: A tandem meta-analysis
Authors: Yu Bingting , Xiang Luochengling , Peppelenbosch Maikel P. , Fuhler Gwenny M. 
Published: March 2023

BackgroundPrevious evidence indicated that Helicobacter pylori-induced inflammation is the first step towards gastric carcinogenesis. However, investigations of the immunological factors driving this process have shown inconsistencies. We aimed to present a thorough summary of all researched cytokines in relation to H. pylori infection and GC and relate these to global GC risk.MethodsWe performed a systematic review and tandem meta-analysis identifying all published studies reporting on serum cytokine levels in H. pylori-infected cases vs. non-infected controls and gastric cancer cases vs. non-gastric cancer controls, with sub-analyses performed to identify global regional differences in cytokine induction and their correlation with GC incidence.ResultsOnly levels of systemic IL-6 (standardized mean difference [SMD]:0.95, 95%CI [0.45;1.45]) and TNF-α (SMD:0.88, 95%CI [0.46; 1.29]) were significantly increased upon H. pylori infection. Sub-analysis showed that of IL-6 levels were increased upon H. pylori infection in East Asian, Middle Eastern and Southeast Asian cohorts, but not in North America, Europe, Russia and Africa. Serum levels of IL-6, IL-7, IL-10, IL-12, and TNF-α were significantly raised in GC. Exploration of the relationship between serum cytokines changes upon H. pylori infection and regional differences in risk of GC development indicated that the SMD of IL-6 serum levels presents a significant correlation with the relative incidence of GC (r=0.81, p=0.00014).ConclusionThis study shows that H. pylori infection and GC are associated with increased IL-6 and TNF-α levels. Particularly, IL-6 shows region-specific increases that correlate with GC incidence, making it a key contender for the cause of this disease.
Mixed muco-cutaneous pemphigoid: Clinical and immunological features of 15 cases
Authors: Janela Raphaël , Ishii Norito , Castel Marion , Jouen Fabienne , Cellier Lucie , Courville Philippe , Joly Pascal , Hébert Vivien 
Published: March 2023

IntroductionWe describe a series of patients whose auto-immune bullous skin disease (AIBD) of the dermal-epidermal junction (DEJ) was characterized by clinical, immunological and ultrastructural features intermediate between bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP), and a recalcitrant course.Patients and MethodsFrom the database of the French reference centre for AIBD, we screened all the patients who were referred for an AIBD of the DEJ with a mucosal involvement, who neither met the diagnostic criteria for the diagnosis of BP, nor were typical of MMP. Sera were analysed by NC16A-ELISA and immunobloting against the C-terminal and LAD-1 parts of BP180. Skin biopsies were studied by direct immunoelectron microscopy (IEM).ResultsFifteen patients (4 males, 11 females) of mean age 70.8 ± 11.8 years were included. The mucosal involvement was localized in oral cavity in all cases and in pharyngeal/laryngeal or genital area in 8 (53%), and 6 patients (40%), respectively. No patient had ocular involvement, nor atrophic or fibrosing scars. All patients had extensive skin lesions (mean BPDAI score =65.9 ± 24.4), which predominated on the upper body part. Direct IEM performed on 8 patients showed IgG deposits on the lamina lucida in all cases, and the lamina densa in 5 cases. All sera recognized NC16A, while none recognized BP-230 in ELISA. 10 out of the 13 tested sera (76.9%) contained IgG which recognized the C-terminal domain of BP180 and 10 sera (76.9%) the LAD-1 domain of BP180. Patients poorly responded to super potent topical corticosteroids and were treated with oral corticosteroids ± immunosuppressant in 13 cases (86.6%).ConclusionThis mixed muco-cutaneous pemphigoid differs from BP by the younger age of patients, multiple mucosae involvement, circulating antibodies against both the C- and N-terminal part of BP180, and very poor response to topical CS. It differs from MMP by extensive inflammatory skin lesions, absence of ocular involvement and atrophic/fibrosing scars.
Optimal time for COVID-19 vaccination in rituximab-treated dermatologic patients
Authors: Seree-aphinan Chutima , Ratanapokasatit Yanisa , Suchonwanit Poonkiat , Rattanakaemakorn Ploysyne , O-Charoen Pichaya , Pisitkun Prapaporn , Suangtamai Thanitta , Setthaudom Chavachol , Chirasuthat Sonphet , Chanprapaph Kumutnart 
Published: March 2023

BackgroundBy depleting circulating B lymphocytes, rituximab time-dependently suppresses coronavirus disease 2019 (COVID-19) vaccines’ humoral immunogenicity for a prolonged period. The optimal time to vaccinate rituximab-exposed immune-mediated dermatologic disease (IMDD) patients is currently unclear.ObjectiveTo estimate the vaccination timeframe that equalized the occurrence of humoral immunogenicity outcomes between rituximab-exposed and rituximab-naïve IMDD patients.MethodsThis retrospective cohort study recruited rituximab-exposed and age-matched rituximab-naïve subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity post-vaccination. Baseline clinical and immunological data (i.e., immunoglobulin levels, lymphocyte immunophenotyping) and SARS-CoV-2-specific immunity levels were extracted. The outcomes compared were the percentages of subjects who produced neutralizing antibodies (seroconversion rates, SR) and SARS-CoV-2-specific IgG levels among seroconverters. The outcomes were first analyzed using multiple regressions adjusted for the effects of corticosteroid use, steroid-spearing agents, and pre-vaccination immunological status (i.e., IgM levels, the percentages of the total, naïve, and memory B lymphocytes) to identify rituximab-related immunogenicity outcomes. The rituximab-related outcome differences with a 95% confidence interval (CI) between groups were calculated, starting by including every subject and then narrowing down to those with longer rituximab-to-vaccination intervals (≥3, ≥6, ≥9, ≥12 months). The desirable cut-off performances were &lt;25% outcome inferiority observed among rituximab-exposed subgroups compared to rituximab-naïve subjects, and the positive likelihood ratio (LR+) for the corresponding outcomes ≥2.FindingsForty-five rituximab-exposed and 90 rituximab-naive subjects were included. The regression analysis demonstrated a negative association between rituximab exposure status and SR but not with SARS-CoV-2-specific IgG levels. Nine-month rituximab-to-vaccination cut-off fulfilled our prespecified diagnostic performance (SR difference between rituximab-exposed and rituximab-naïve group [95%CI]: -2.6 [-23.3, 18.1], LR+: 2.6) and coincided with the repopulation of naïve B lymphocytes in these patients.ConclusionsNine months of rituximab-to-vaccination interval maximize the immunological benefits of COVID-19 vaccines while avoiding unnecessary delay in vaccination and rituximab treatment for IMDD patients.
Subculturing and Gram staining of blood cultures flagged negative by the BACTEC™ FX system: Optimizing the workflow for detection of Cryptococcus neoformans in clinical specimens
Authors: Liu Lingli , Du Lijun , He Shuquan , Sun Tianshu , Kong Fanrong , Liu Yali , Xu Yingchun 
Published: March 2023

ObjectiveTo investigate whether an incubation time of 5 days (Aerobic/F, Anaerobic/F) and 14 days (Myco/F) blood culture bottles is sufficient to prevent false-negative results.MethodsWe evaluated 1,244 blood bottles (344 patients) defined as negative by the BACTEC™ FX system. We also reviewed published cases and our own cases of bloodstream infection caused by Cryptococcus neoformans and simulated different scenarios, including different inoculation concentrations, bottle types, and clinical isolates.ResultsTwo bottles (0.16%) were found to contain C. neoformans when subcultured and Gram stained. A 5-day protocol with Aerobic/F bottles was insufficient for the growth of C. neoformans in some cases, and C. neoformans grew better in Myco/F bottles than in Aerobic/F bottles.ConclusionSubculturing and Gram staining after a 5-day protocol were important for the detection of C. neoformans, and Myco/F bottles should be collected for the blood culture of C. neoformans.
A study of auxiliary screening for Alzheimer’s disease based on handwriting characteristics
Authors: Qi Hengnian , Zhang Ruoyu , Wei Zhuqin , Zhang Chu , Wang Lina , Lang Qing , Zhang Kai , Tian Xuesong 
Published: March 2023

Background and objectivesAlzheimer’s disease (AD) has an insidious onset, the early stages are easily overlooked, and there are no reliable, rapid, and inexpensive ancillary detection methods. This study analyzes the differences in handwriting kinematic characteristics between AD patients and normal elderly people to model handwriting characteristics. The aim is to investigate whether handwriting analysis has a promising future in AD auxiliary screening or even auxiliary diagnosis and to provide a basis for developing a handwriting-based diagnostic tool.Materials and methodsThirty-four AD patients (15 males, 77.15 ± 1.796 years) and 45 healthy controls (20 males, 74.78 ± 2.193 years) were recruited. Participants performed four writing tasks with digital dot-matrix pens which simultaneously captured their handwriting as they wrote. The writing tasks consisted of two graphics tasks and two textual tasks. The two graphics tasks are connecting fixed dots (task 1) and copying intersecting pentagons (task 2), and the two textual tasks are dictating three words (task 3) and copying a sentence (task 4). The data were analyzed by using Student’s t-test and Mann–Whitney U test to obtain statistically significant handwriting characteristics. Moreover, seven classification algorithms, such as eXtreme Gradient Boosting (XGB) and Logistic Regression (LR) were used to build classification models. Finally, the Receiver Operating Characteristic (ROC) curve, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Area Under Curve (AUC) were used to assess whether writing scores and kinematics parameters are diagnostic.ResultsKinematic analysis showed statistically significant differences between the AD and controlled groups for most parameters (p &lt; 0.05, p &lt; 0.01). The results found that patients with AD showed slower writing speed, tremendous writing pressure, and poorer writing stability. We built statistically significant features into a classification model, among which the model built by XGB was the most effective with a maximum accuracy of 96.55%. The handwriting characteristics also achieved good diagnostic value in the ROC analysis. Task 2 had a better classification effect than task 1. ROC curve analysis showed that the best threshold value was 0.084, accuracy = 96.30%, sensitivity = 100%, specificity = 93.41%, PPV = 92.21%, NPV = 100%, and AUC = 0.991. Task 4 had a better classification effect than task 3. ROC curve analysis showed that the best threshold value was 0.597, accuracy = 96.55%, sensitivity = 94.20%, specificity = 98.37%, PPV = 97.81%, NPV = 95.63%, and AUC = 0.994.ConclusionThis study’s results prove that handwriting characteristic analysis is promising in auxiliary AD screening or AD diagnosis.