bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Frequency of Activated Switched Memory B Cells and Its Association With the Presence of Pulmonary Fibrosis in Diffuse Cutaneous Systemic Sclerosis Patients
Authors: Simon Diána , Balogh Péter , Erdő-Bonyár Szabina , Böröcz Katalin , Minier Tünde , Czirják László , Berki Tímea 
Published: June 2021

Disease-associated, high-affinity pathological autoantibody production is a well-described consequence of immune dysregulation affecting B cells in systemic sclerosis (SSc), including the distribution of B-cell subsets. We have previously shown that the increased relative frequency of CD19+CD27+IgD− switched memory B cells is associated with the severe form of SSc. This study sought to analyze memory B cell subsets using an extended range of markers for further subdivision based on CD19, IgD, CD27, CD38 and CD95 phenotype, to define relationship between the alterations of memory B cell subsets and the clinical features of SSc. Peripheral blood samples were obtained from 21 SSc patients, including 14 diffuse (dcSSc) and 7 limited (lcSSc) cutaneous SSc patients, with disease duration of 2.7 ( ± 1.6) years. After purification of CD19+ B cells, multiparametric flow cytometry was performed and the frequencies of CD19+IgD−CD27−CD38+ double negative (DN) 1, CD19+IgDloCD27+CD38+ unswitched, CD19+IgD−CD27+CD38+CD95− resting switched and CD19+IgD−CD27+CD38−CD95+ activated switched memory (ASM) B cells were determined, and correlated with clinical features of SSc. The dcSSc patients had a higher frequency of ASM B cells (p = 0.028) compared to lcSSc patients. The percentage of ASM B cells was elevated in anti-Scl-70 (anti-topoisomerase I) antibody positive patients compared to negative patients (p = 0.016). Additionally, the frequency of ASM B cells was also increased in patients with pulmonary fibrosis (p = 0.003) suggesting that patients with severe form of SSc have higher ASM B cell ratios. Furthermore, the ratio of DN1 B cells was decreased (p = 0.029), while the level of anti-citrate synthase IgG natural autoantibody was elevated (p = 0.028) in patients with active disease. Our observations on the increase of ASM B cells in dcSSc and in patients with pulmonary fibrosis may point to the association of this alteration with the severe form of the disease. Functionally the correlation of ASM B cells as effector memory-plasma cell precursors with anti-topoisomerase I antibody positivity could reflect their contribution to pathological autoantibody production, whereas the decrease of memory precursor DN B cells and the increase of anti-citrate synthase IgG autoantibody may have potential significance in the assessment of disease activity.
Comparison of Surrogate Markers of the Type I Interferon Response and Their Ability to Mirror Disease Activity in Systemic Lupus Erythematosus
Authors: Enocsson Helena , Wetterö Jonas , Eloranta Maija-Leena , Gullstrand Birgitta , Svanberg Cecilia , Larsson Marie , Bengtsson Anders A. , Rönnblom Lars , Sjöwall Christopher 
Published: June 2021

ObjectivesType I interferons (IFNs) are central and reflective of disease activity in systemic lupus erythematosus (SLE). However, IFN-α levels are notoriously difficult to measure and the type I IFN gene signature (IGS) is not yet available in clinical routine. This study evaluates galectin-9 and an array of chemokines/cytokines in their potential as surrogate markers of type I IFN and/or SLE disease activity.MethodsHealthy controls and well-characterized Swedish SLE patients from two cross-sectional cohorts (n=181; n=59) were included, and a subgroup (n=21) was longitudinally followed. Chemokine/cytokine responses in immune complex triggered IFN-α activity was studied in healthy donor peripheral blood mononuclear cells (PBMC). Levels of chemokines/cytokines and galectin-9 were measured by immunoassays. Gene expression was quantified by qPCR.ResultsThe IGS was significantly (p&lt;0.01) correlated with galectin-9 (rho=0.54) and CXCL10 (rho=0.37) levels whereas serum IFN-α correlated with galectin-9 (rho=0.36), CXCL10 (rho=0.39), CCL19 (rho=0.26) and CCL2 (rho=0.19). The strongest correlation was observed between galectin-9 and TNF (rho=0.56). IFN-α and disease activity (SLEDAI-2K) were correlated (rho=0.20) at cross-sectional analysis, but no significant associations were found between SLEDAI-2K and galectin-9 or chemokines. Several inflammatory mediators increased at disease exacerbation although CCL19, CXCL11, CXCL10, IL-10 and IL-1 receptor antagonist were most pronounced. Immune complex-stimulation of PBMC increased the production of CCL2, CXCL8 and TNF.ConclusionGalectin-9 and CXCL10 were associated with type I IFN in SLE but correlated stronger with TNF. None of the investigated biomarkers showed a convincing association with disease activity, although CXCL10 and CCL19 performed best in this regard.
Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis
Authors: Schrezenmeier Eva , Bergfeld Leon , Hillus David , Lippert Joerg-Detlev , Weber Ulrike , Tober-Lau Pinkus , Landgraf Irmgard , Schwarz Tatjana , Kappert Kai , Stefanski Ana-Luisa , Sattler Arne , Kotsch Katja , Dörner Thomas , Sander Leif Erik , Budde Klemens , Halleck Fabian , Kurth Florian , Corman Victor Max , Choi Mira 
Published: June 2021

Patients with kidney failure have notoriously weak responses to common vaccines. Thus, immunogenicity of novel SARS-CoV-2 vaccines might be impaired in this group. To determine immunogenicity of SARS-CoV-2 vaccination in patients with chronic dialysis, we analyzed the humoral and T-cell response after two doses of mRNA vaccine Tozinameran (BNT162b2 BioNTech/Pfizer). This observational study included 43 patients on dialysis before vaccination with two doses of Tozinameran 21 days apart. Overall, 36 patients completed the observation period until three weeks after the second dose and 32 patients were further analyzed at week 10. Serum samples were analyzed by SARS-CoV-2 specific IgG and IgA antibodies ~1, ~3–4 and ~10 weeks after the second vaccination. In addition, SARS-CoV-2-specific T-cell responses were assessed at ~3–4 weeks by an interferon-gamma release assay (IGRA). Antibody and T cell outcomes at this timepoint were compared to a group of 44 elderly patients not on dialysis, after immunization with Tozinameran. Median age of patients on chronic dialysis was 74.0 years (IQR 66.0, 82.0). The proportion of males was higher (69.4%) than females. Only 20/36 patients (55.6%, 95%CI: 38.29–71.67) developed SARS-CoV-2-IgG antibodies at the first sampling, whereas 32/36 patients (88.9%, 95%CI: 73.00–96.38) demonstrated IgG detection at the second sampling. In a longitudinal follow-up at ~10 weeks after the second dose, the proportion of dialysis patients reactive for anti-SARS-CoV-2-IgG decreased to 27/32 (84.37%, 95%CI: 66.46–94.10) The proportion of anti-SARS-CoV-2 S1 IgA decreased from 33/36 (91.67%; 95%CI: 76.41–97.82) at weeks 3–4 down to 19/32 (59.38; 95%CI: 40.79–75.78). Compared to a cohort of vaccinees with similar age but not on chronic dialysis seroconversion rates and antibody titers were significantly lower. SARS-CoV-2-specific T-cell responses 3 weeks after second vaccination were detected in 21/31 vaccinated dialysis patients (67.7%, 95%CI: 48.53–82.68) compared to 42/44 (93.3%, 95%CI: 76.49–98.84) in controls of similar age. Patients on dialysis demonstrate a delayed, but robust immune response three to four weeks after the second dose, which indicates effective vaccination of this vulnerable group. However, the lower immunogenicity of Tozinameran in these patients needs further attention to develop potential countermeasures such as an additional booster vaccination.
24-Month Clinical, Immuno-Virological Outcomes, and HIV Status Disclosure in Adolescents Living With Perinatally-Acquired HIV in the IeDEA-COHADO Cohort in Togo and Côte d'Ivoire, 2015–2017
Authors: Dassi Tchoupa Revegue Marc Harris , Takassi Unoo Elom , Tanoh Eboua François , Desmonde Sophie , Amoussou-Bouah Ursula Belinda , Bakai Tchaa Abalo , Jesson Julie , Dahourou Désiré Lucien , Malateste Karen , Aka-Dago-Akribi Hortense , Raynaud Jean-Philippe , Arrivé Elise , Leroy Valériane 
Published: June 2021

Background: Adolescents living with perinatally-acquired HIV (APHIV) face challenges including HIV serostatus disclosure. We assessed their 24-month outcomes in relation to the disclosure of their own HIV serostatus.Methods: Nested within the International epidemiologic Database to Evaluate AIDS pediatric West African prospective cohort (IeDEA pWADA), the COHADO cohort included antiretroviral (ART)-treated APHIV aged 10–19 years, enrolled in HIV care before the age of 10 years, in Abidjan (Côte d'Ivoire) and Lomé (Togo) in 2015. We measured the HIV serostatus disclosure at baseline and after 24 months and analyzed its association with a favorable combined 24-month outcome using logistic regression. The 24-month combined clinical immuno-virological outcome was defined as unfavorable when either death, loss to follow-up, progression to WHO-AIDS stage, a decrease of CD4 count &gt;10% compared to baseline, or a detectable viral load (VL &gt; 50 copies/mL) occurred at 24 months.Results: Overall, 209 APHIV were included (51.6% = Abidjan, 54.5% = females). At inclusion, the median CD4 cell count was 521/mm3 [IQR (281–757)]; 29.6% had a VL measurement, of whom, 3.2% were virologically suppressed. APHIV were younger in Lomé {median age: 12 years [interquartile range (IQR): 11–15]} compared to Abidjan [14 years (IQR: 12–15, p = 0.01)]. Full HIV-disclosure increased from 41.6% at inclusion to 74.1% after 24 months. After 24 months of follow-up, six (2.9%) died, eight (3.8%) were lost to follow-up, and four (1.9%) were transferred out. Overall, 73.7% did not progress to the WHO-AIDS stage, and 62.7% had a CD4 count above (±10%) of the baseline value (48.6% in Abidjan vs. 69.0% in Lomé, p &lt; 0.001). Among the 83.7% with VL measurement, 48.8% were virologically suppressed (Abidjan: 45.4%, Lomé: 52.5%, p &lt;0.01). The 24-month combined outcome was favorable for 45% (29.6% in Abidjan and 61.4% in Lomé, p &lt; 0.01). Adjusted for baseline variables, the 24-month outcome was worse in Lomé in those who had been disclosed for &gt;2 years compared to those who had not been disclosed to [aOR = 0.21, 95% CI (0.05–0.84), p = 0.03].Conclusions: The frequency of HIV-disclosure improved over time and differed across countries but remained low among West African APHIV. Overall, the 24-month outcomes were poor. Disclosure before the study was a marker of a poor 24-month outcome in Lomé. Context-specific responses are urgently needed to improve adolescent care and reach the UNAIDS 90% target of virological success.
The Relationship of the Test for Respiratory and Asthma Control in Kids Initial Score on the Prognosis of Pre-school Children With Asthma: A Prospective Cohort Study
Authors: Liu Lu , Zhang Jing , Zhang Lei , Yuan Shu-Hua , Wu Jin-Hong , Tang Ming-Yu , Chen Jian-De , Zhang Fen , Qi Xin-Yi , Yin Yong 
Published: June 2021

Objective: The test for respiratory and asthma control in kids (TRACK) is currently the only standard follow-up tool for children under 5 years of age with asthma. The purpose of this study was to investigate the relationship between the TRACK initial score (Ti) and their prognosis after 6 months of follow-up in pre-schoolers with asthma.Design: A prospective cohort study.Methods: The study included pre-schoolers diagnosed with asthma at the Shanghai Children's Medical Center between January 2019 and June 2020, and follow-up for 6 months. TRACK scores, frequency of wheezing and respiratory infections, number of Emergency Department (ED) visits and treatment regimen were collected. According to the TRACK initial score, the children were divided into “Ti &lt; 60 group” and “Ti ≥ 60 group,” and the two groups were compared in terms of TRACK score related indicators, clinical manifestations and treatment.Results: There are 102 pre-schoolers included in the analysis [78 boys (76.5%) and 24 girls (23.5%); mean (SD) age, 28.05 (11.63) months]. After 6 months of follow-up, the TRACK score was improved in both groups, and the “Ti ≥ 60 group” had a higher score, lower rate of uncontrolled asthma and fewer reassessments were required. There was no difference in the number of wheezing attacks between the two groups in terms of clinical presentation, but the “Ti &lt; 60 group” had more respiratory infections and ED visits. Regarding the use of ICSs, in the “Ti &lt; 60 groups,” the dose of ICSs was higher and reduced slowly, and the dose difference between the two groups began to appear after 5 months of follow-up.Conclusion: TRACK is essential for pre-schoolers with asthma at the time they are diagnosed. In addition, if the TRACK initial score is &lt; 60, the probability of poor prognosis is higher.
Computational Drug Repurposing for Alzheimer’s Disease Using Risk Genes From GWAS and Single-Cell RNA Sequencing Studies
Authors: Xu Yun , Kong Jiming , Hu Pingzhao 
Published: June 2021

Background:Traditional therapeutics targeting Alzheimer’s disease (AD)-related subpathologies have so far proved ineffective. Drug repurposing, a more effective strategy that aims to find new indications for existing drugs against other diseases, offers benefits in AD drug development. In this study, we aim to identify potential anti-AD agents through enrichment analysis of drug-induced transcriptional profiles of pathways based on AD-associated risk genes identified from genome-wide association analyses (GWAS) and single-cell transcriptomic studies.Methods:We systematically constructed four gene lists (972 risk genes) from GWAS and single-cell transcriptomic studies and performed functional and genes overlap analyses in Enrichr tool. We then used a comprehensive drug repurposing tool Gene2Drug by combining drug-induced transcriptional responses with the associated pathways to compute candidate drugs from each gene list. Prioritized potential candidates (eight drugs) were further assessed with literature review.Results:The genomic-based gene lists contain late-onset AD associated genes (BIN1, ABCA7, APOE, CLU, and PICALM) and clinical AD drug targets (TREM2, CD33, CHRNA2, PRSS8, ACE, TKT, APP, and GABRA1). Our analysis identified eight AD candidate drugs (ellipticine, alsterpaullone, tomelukast, ginkgolide A, chrysin, ouabain, sulindac sulfide and lorglumide), four of which (alsterpaullone, ginkgolide A, chrysin and ouabain) have shown repurposing potential for AD validated by their preclinical evidence and moderate toxicity profiles from literature. These support the value of pathway-based prioritization based on the disease risk genes from GWAS and scRNA-seq data analysis.Conclusion:Our analysis strategy identified some potential drug candidates for AD. Although the drugs still need further experimental validation, the approach may be applied to repurpose drugs for other neurological disorders using their genomic information identified from large-scale genomic studies.
Variable Secondary Metabolite Profiles Across Cultivars of Curcuma longa L. and C. aromatica Salisb.
Authors: Kulyal Poonam , Acharya Satyabrata , Ankari Aditya B. , Kokkiripati Praveen K. , Tetali Sarada D. , Raghavendra Agepati S. 
Published: June 2021

Background:Curcuma spp. (Zingiberaceae) are used as a spice and coloring agent. Their rhizomes and essential oils are known for medicinal properties, besides their use in the flavoring and cosmetic industry. Most of these biological activities were attributed to volatile and nonvolatile secondary metabolites present in the rhizomes of Curcuma spp. The metabolite variations among the species and even cultivars need to be established for optimized use of Curcuma spp.Objectives: We compared the phytochemical profiles of rhizomes and their essential oils to establish the variability among seven cultivars: five of Curcuma longa L. (Alleppey Supreme, Duggirala Red, Prathibha, Salem, Suguna) and two of C. aromatica Salisb. (Kasturi Araku, Kasturi Avidi). The GC-MS and LC-MS-based analyses were employed to profile secondary metabolites of these selected cultivars.Methods: Rhizomes of Curcuma spp. were subjected to hydro-distillation to collect essential oil and analyzed by GC-MS. The methanol extracts of fresh rhizomes were subjected to LC-MS analyses. The compounds were identified by using the relevant MS library databases as many compounds as possible.Results: The essential oil content of the cultivars was in the range of 0.74–1.62%. Several compounds were detected from the essential oils and rhizome extracts by GC-MS and LC-MS, respectively. Of these, 28 compounds (13 from GCMS and 15 from LCMS) were common in all seven cultivars, e.g., α-thujene, and diarylheptanoids like curcumin. Furthermore, a total of 39 new compounds were identified from C. longa L. and/or C. aromatica Salisb., most of them being cultivar-specific. Of these compounds, 35 were detected by GC-MS analyses of essential oils, 1,2-cyclohexanediol, 1-methyl-4-(1-methylethyl)-, and santolina alcohol, to name a few. The other four compounds were detected by LC-MS of the methanolic extracts of the rhizomes, e.g., kaempferol-3,7-O-dimethyl ether and 5,7,8-trihydroxy-2′,5′-dimethoxy-3′,4′-methylene dioxyisoflavanone.Conclusions: We identified and recorded the variability in the metabolite profiles of essential oils and whole rhizome extracts from the seven cultivars of Curcuma longa L. and C. aromatica Salisb. As many as 39 new metabolites were detected in these seven Indian cultivars of Curcuma spp. Many of these compounds have health benefits.
Polarization: What Do We Know and What Can We Do About It?
Authors: Casal Bértoa Fernando , Rama José 
Published: June 2021

Polarization is not new in Europe. Looking at electoral support for radical political forces after the Second World War, one can observe how polarization has been on the rise since the 1960s. Still, it is in the 1990s, with the thaw of European party systems and the subsequent emergence of (populist) radical parties, that the percentage of votes for anti-political establishment parties reached unprecedented levels. In this article, we not only show the general (country-level) picture but also highlight both the consequences and causes of polarization, proposing at the same time some potential remedies to combat it. Using an aggregate, longitudinal unique dataset, containing 47 European countries across more than 170 years from 1848 to 2020 (Casal Bértoa, 2021;Casal Bértoa and Enyedi, 2021), we try to shed light here on the perils of polarization for the quality of democracy, how traditional political parties are to be blamed, and how we can tackle the problem.
Child Development and Early Interaction: PERL Research Protocol, a Preventive Home Visiting Program, Randomized Controlled Trial in France
Authors: Buchheit Sophie , Kabuth Bernard , Colombo Marie-Christine , Ligier Fabienne 
Published: June 2021

Background: Early childhood is a key period for reducing the social inequalities that affect health. Some parenting support and home visitation programs have proven to be effective in assisting parents during this period. France's Protection Maternelle et Infantile (maternal and child welfare) services (PMIs) are at the heart of this primary prevention and may adapt their intervention to improve parenting support. In this manuscript, we describe the protocol of the PERL study, an intervention based on a home visiting program.Method and design: The PERL study is a single-center, randomized, controlled interventional trial. The aim was to assess the impact of a preventive home visiting program on the development of young children and parent-baby interaction. Visits were made by PMI nurses to 64 randomly recruited families from the general population. All families who had a baby born after 37 weeks of pregnancy between September 2018 and December 2019, and who resided in the trial area were eligible. Participants were randomly allocated to the intervention group or the control group. The PMI nurses made 12 home visits in the first year, 6 in the second year, and 4 in the third and fourth years of the child's life. Primary and secondary outcomes were measured when the child was 4 and 24 months old. These measurements recorded (i) the child's developmental milestones, in particular, language and socio emotional skills, (ii) early interaction, maternal sensitivity, and attachment patterns, (iii) maternal psychopathology including depression.Discussion: This study aims to assess the impact of home visits, made by specifically-trained and supervised nurses, on the child's development and parent-child interactions. Such interventions are complementary to other preventive programs addressing the impact of social inequalities on perinatal health. Placing nurses' professional skills at the center of this project may prove an effective and cost-saving intervention compared to existing programs. The study proposes a prevention model that is in keeping with the principle of reducing social inequalities in health by providing support from the earliest age through public service.Clinical Trial Registration: The clinical trial number is NCT03506971, registered on April 24, 2018.
Real-World Evidence: The Low Validity of Temperature Screening for COVID-19 Triage
Authors: Pană Bogdan C. , Lopes Henrique , Furtunescu Florentina , Franco Diogo , Rapcea Anca , Stanca Mihai , Tănase Alina , Coliţă Anca 
Published: June 2021

Background: The COVID-19 pandemic forced health-related organizations to rapidly launch country-wide procedures that were easy to use and inexpensive. Body temperature measurement with non-contact infrared thermometers (NCITs) is among the most common procedures, both in hospital settings and in many other entities. However, practical hospital experiences have raised great doubts about the procedure's validity.Aim: This study aimed to evaluate the validity of the body temperature measured using NCITs among oncological and transplant patients who took the polymerase chain reaction test for SARS-Cov-2 PCR+ and PCR- in a Romanian Hospital.Methods: Body temperature was measured for 5,231 inpatients using NCITs. The cutoff point for fever was equal to or above 37.3°C. Patients then completed a questionnaire about their symptoms, contact, and travel history.Findings: Fever was detected in five of 53 persons with PCR+, resulting in a sensitivity of 9.43% (95% CI, 3.13–20.66%). No fever was verified in 5,131 of 5,171 persons with PCR-, resulting in a specificity of 99.15% (95% CI, 98.86–99.38%). A defensive vision of NCIT procedure (maximum standard error only in favor) had a sensitivity of 15.09% (95% CI, 6.75–27.59%).Conclusions: The use of NCITs in a triage provides little value for detection of COVID-19. Moreover, it provides a false sense of protection against the disease while possibly discriminating individuals that could present fever due to other reasons, such as oncologic treatments, where fever is a common therapeutical consequence. The consumption of qualified human resources should be considered, especially in the context of the shortage of healthcare professionals worldwide.