bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of omalizumab for seasonal allergic rhinoconjunctivitis: a retrospective cohort study
Authors: Tang Rui , Lei Shubin , Zhu Liping , Lv Yuzhen , Li Hong 
Published: July 2022

BackgroundAllergic rhinoconjunctivitis (ARC) is an allergic disease that is characterized by conjunctival and nasal symptoms such as edema and congestion of conjunctiva, rhinorrhea, sneezing, and blocked nose. Seasonal ARC (SARC) is usually induced by seasonal allergens and often occurs at specific times during the year. Traditional treatments of SARC include nasal corticosteroids, antihistamines, and mast cell membrane stabilizers. Biological agents such as omalizumab have also been proved effective in the treatment of SARC.ObjectivesWe aim to certify the preventative efficacy of omalizumab for SARC and explore its influence factors.MethodsMedical records of 64 SARC patients were retrospectively analyzed, and generalized linear models were used to analyze influence factors of efficacy of omalizumab.ResultsCompared with forepassed pollen season without omalizumab treatment, the combined symptom and medication score (CSMS) of ARC with pre-seasonal omalizumab was significantly lower (with omalizumab: 0.67[0.00,1.83], without omalizumab: 4.00[2.83,4.96], p&lt;0.001, max score=6). Subgroup analysis was conducted to explore the influence factor of preventative efficacy of omalizumab. The CSMS with omalizumab treatment were not significantly different among different age, gender, dosage, number of injections, and injection date subgroups (p&gt;0.05).ConclusionPre-seasonal omalizumab treatment could significantly relieve SARC related symptoms and reduce medication use. This preventative efficacy would not be influenced by the dosage and number of injections of omalizumab. A single dose of 150mg omalizumab could achieve a satisfactory outcome.
Increased frequency of TIGIT+ CD4 T Cell subset in autoantibody-positive first-degree relatives of patients with rheumatoid arthritis
Authors: Anaparti Vidyanand , Tanner Stacy , Zhang Christine , O’Neil Liam , Smolik Irene , Meng Xiaobo , Marshall Aaron J. , El-Gabalawy Hani 
Published: July 2022

BackgroundDespite immune cell dysregulation being an important event preceding the onset of rheumatoid arthritis (RA), the phenotype of T and B cells in preclinical RA is less understood. The aim of this study was to characterize T and B cell populations in RA patients and their autoantibody (aAb) negative and positive first-degree relatives (FDR).MethodsCryopreserved peripheral blood mononuclear cells (PBMCs) collected at scheduled visits from aAb-(n=25), and aAb+ FDR (n=10) and RA patients (n=13) were thawed and stained using optimized antibody cocktails as per a specific 13-color T or B cell panel. Immunophenotyping was performed using a Cytoflex LX (Beckman-Coulter) flow cytometer and FlowJo software was used for analyzing the frequency of immune cell populations.ResultsMulticolor flow cytometry experiments identified an increased TIGIT expression in circulating lymphocytes of aAb+ FDR and RA patients, relative to aAb- FDR (P&lt;0.01). These TIGIT+ T cells exhibited a memory phenotype and expressed high levels of PD-1, ICOS, HLA-DR, CXCR3 and CXCR5. Moreover, increased TIGIT+ CD4 T cell frequency correlated with the frequency of PD-1+ CD4 T cells (r = 0.4705: P = 0.0043) and circulating levels of ACPA and RF. We also identified a decreased frequency of CD27+IgD- switched memory B cells in RA patients (P &lt; 0.01), while increased frequency of TIGIT+ CD4 T cells in FDR correlated with the frequency of PD1+PTEN+ B cells (r = 0.6838, P = 0.0004) and autoantibody positivity (P = 0.01).ConclusionWe demonstrate TIGIT as a distinct CD4 T cell marker for differentiating aAb- FDR from aAb+FDR and might play a critical role in regulating T and B cell crosstalk in preclinical RA.
Antibody response following the third and fourth SARS-CoV-2 vaccine dose in individuals with common variable immunodeficiency
Authors: Nielsen Bibi Uhre , Drabe Camilla Heldbjerg , Barnkob Mike Bogetofte , Johansen Isik Somuncu , Hansen Anne Kirstine Kronborg , Nilsson Anna Christine , Rasmussen Line Dahlerup 
Published: July 2022

BackgroundThe antibody response after vaccination is impaired in common variable immunodeficiency (CVID).ObjectiveWe aimed to study the spike receptor-binding domain IgG antibody (anti-S-RBD) levels during a four-dose SARS-CoV-2 vaccination strategy and after monoclonal antibody (mAB) treatment in CVID. Moreover, we assessed the anti-S-RBD levels in immunoglobulin replacement therapy (IgRT) products.MethodsIn an observational study, we examined anti-S-RBD levels after the second, third, and fourth dose of mRNA SARS-CoV-2 vaccines. Moreover, we measured anti-S-RBD after treatment with mAB. Finally, anti-S-RBD was assessed in common IgRT products. Antibody non-responders (anti-S-RBD &lt; 7.1) were compared by McNemar’s test and anti-S-RBD levels were compared with paired and non-paired Wilcoxon signed rank tests as well as Kruskal–Wallis tests.ResultsAmong 33 individuals with CVID, anti-S-RBD levels increased after the third vaccine dose (165 BAU/ml [95% confidence interval: 85; 2280 BAU/ml], p = 0.006) and tended to increase after the fourth dose (193 BAU/ml, [−22; 569 BAU/ml], p = 0.080) compared to the previous dose. With increasing number of vaccinations, the proportion of patients who seroconverted (anti-S-RBD ≥ 7.1) increased non-significantly. mAB treatment resulted in a large increase in anti-S-RBD and a higher median level than gained after the fourth dose of vaccine (p = 0.009). IgRT products had varying concentrations of anti-S-RBD (p &lt; 0.001), but none of the products seemed to affect the overall antibody levels (p = 0.460).ConclusionMultiple SARS-CoV-2 vaccine doses in CVID seem to provide additional protection, as antibody levels increased after the third and fourth vaccine dose. However, anti-S-RBD levels from mAB outperform the levels mounted after vaccination.Clinical ImplicationsBoosting with SARS-CoV-2 vaccines seems to improve the antibody response in CVID patients.Capsule summaryThe third and possibly also the fourth dose of mRNA SARS-CoV-2 vaccine in CVID improve the antibody response as well as stimulate seroconversion in most non-responders.
Identification of pyroptosis-related subtypes and establishment of prognostic model and immune characteristics in asthma
Authors: Yang Fan , Wang Tieshan , Yan Peizheng , Li Wanyang , Kong Jingwei , Zong Yuhan , Chao Xiang , Li Weijie , Zhao Xiaoshan , Wang Ji 
Published: July 2022

BackgroundAlthough studies have shown that cell pyroptosis is involved in the progression of asthma, a systematic analysis of the clinical significance of pyroptosis-related genes (PRGs) cooperating with immune cells in asthma patients is still lacking.MethodsTranscriptome sequencing datasets from patients with different disease courses were used to screen pyroptosis-related differentially expressed genes and perform biological function analysis. Clustering based on K-means unsupervised clustering method is performed to identify pyroptosis-related subtypes in asthma and explore biological functional characteristics of poorly controlled subtypes. Diagnostic markers between subtypes were screened and validated using an asthma mouse model. The infiltration of immune cells in airway epithelium was evaluated based on CIBERSORT, and the correlation between diagnostic markers and immune cells was analyzed. Finally, a risk prediction model was established and experimentally verified using differentially expressed genes between pyroptosis subtypes in combination with asthma control. The cMAP database and molecular docking were utilized to predict potential therapeutic drugs.ResultsNineteen differentially expressed PRGs and two subtypes were identified between patients with mild-to-moderate and severe asthma conditions. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes. Poor control subtypes were closely related to glucocorticoid resistance and airway remodeling. BNIP3 was identified as a diagnostic marker and associated with immune cell infiltration such as, M2 macrophages. The risk prediction model containing four genes has accurate classification efficiency and prediction value. Small molecules obtained from the cMAP database that may have therapeutic effects on asthma are mainly DPP4 inhibitors.ConclusionPyroptosis and its mediated immune phenotype are crucial in the occurrence, development, and prognosis of asthma. The predictive models and drugs developed on the basis of PRGs may provide new solutions for the management of asthma.
Immunosuppressive landscape in hepatocellular carcinoma revealed by single-cell sequencing
Authors: Bai Yi , Chen Dapeng , Cheng Chuanliang , Li Zhongmin , Chi Hao , Zhang Yuliang , Zhang Xiaoyu , Tang Shaohai , Zhao Qiang , Ang Bing , Zhang Yamin 
Published: July 2022

Background/AimsHepatocellular carcinoma (HCC), accounting for 75-85% of primary liver cancer cases, is the third leading cause of cancer-related death worldwide. The purpose of this research was to examine the tumor immune microenvironment (TIME) in HCC.MethodsWe investigated the HCC TIME by integrated analysis of single-cell and bulk-tissue sequencing data to reveal the landscape of major immune cell types.ResultsRegulatory T(Treg) cells were found to be specifically distributed in the TIME of HCC. Several immune checkpoints, including TNFRSF4, TIGIT and CTLA4, were found to be uniquely overexpressed in Treg cells, and the glycolysis/gluconeogenesis pathway was enriched in Treg cells. We also discovered the presence of two NK-cell subsets with different cytotoxic capacities, one in an activated state with antitumor effects and another with an exhausted status. In addition, memory B cells in HCC were found to exist in a unique state, with high proliferation, low differentiation, and low activity, which was induced by overexpression of PRAP1 and activation of the MIF-CD74 axis.ConclusionsWe revealed the TIME landscape in HCC, highlighting the heterogeneity of major immune cell types and their potential mechanisms in the formation of an immunosuppressive environment. Hence, blocking the formation of the TIME could be a useful therapeutic strategy for HCC.
Vertical patterns of chlorophyll a in the euphotic layer are related to mesoscale eddies in the South China Sea
Authors: Wu Mei-Lin , Wang You-Shao , Wang Yu-Tu , Sun Fu-Lin , Li Xiaomei , Gu Fang-Fang , Xiang Jing-Chang 
Published: July 2022

Phytoplankton closely connects with the hydrodynamics and biogeochemical environment of the ocean. While research focusing on both the physiochemical factors and hydrodynamics regulating phytoplankton has already been conducted, the coupling mechanism between mesoscale eddies and the vertical distribution of phyto	plankton in the South China Sea (SCS) is still not well understood. Here, phytoplankton was studied under one weak-cold and two warm eddies along the 18°N transect in the SCS. The results show that the vertical distribution of chlorophyll (chl-a) presented a similar pattern at all four sampling stations. The mixed layer is less than 50 m. It is the same as the meridional salinity gradients that may be distinguished above a depth of 60 m. The subsurface chlorophyll maximum at the edge of a warm (WI) and cold eddy (CI) at E413 and E411 was shallower than that at the edge of a warm eddy (WII) at E407 and E409, indicating that temperature and salinity may be the important driving factors. On the whole, mesoscale eddies had a significant influence on the vertical pattern of chl-a in the SCS during the study period.
Long-term effect of a short pulse of dietary supplementation with algae on the quality of turbot (Scophthalmus maximus) frozen fillets
Authors: Sáez M. Isabel , Galafat Alba , Vizcaíno Antonio J. , Rodríguez Cristina , Hernández de Rojas Alma , Alarcón F. Javier , Martínez Tomás F. 
Published: July 2022

This study raises the question of the potential long-term effects of a feeding pulse with diets containing algal biomass on the quality of frozen turbot (Scophthalmus maximus) fillets. A feeding trial was carried out with this aim, in which juvenile turbot were fed during 60 d with six different experimental diets, two of which were enriched with the macroalgaeUlva rigida(U diets), the other two with a microalgae blend (M diets), plus a non-supplemented control diet (CT), and finally, a commercial aquafeed (COM). Two inclusion levels were considered in algae-enriched diets (50 and 100 g kg-1) so that they were designed as U5 and U10 forU. rigida, and M5 and M10 for microalgae-enriched diets. The duration of the feeding pulse with the functional diets was 60 days, and then, all specimens were fed with a COM diet for a further 150-d period until reaching a body size close to the commercial standard (approximately 750 g). Subsequently, fish were sacrificed; fillets were removed from the pigmented flank and kept at -20 °C for 5 months. Then, fillets were thawed and the muscle proximal composition and fatty acid profile were analyzed, and fillet quality parameters were assessed during a 10-d co\ld storage period at 4°C. The possible deferred effects of algae-enriched diets on fillet quality were compared with a control diet without algae (CT) and with a commercial diet (COM). Roughly, the results obtained indicated that a 60-d administration pulse of algae-enriched diets induced some long-term changes in both the nutritional and organoleptic quality of turbot fillets. In this regard, the algae-enriched aquafeeds improved the muscle antioxidant response throughout the cold storage period, prolonging the shelf life of thawed turbot fillets. In addition, in terms of consumers’ acceptability, this feeding pulse on pre-growing stage of the productive cycle was able to modify the skin and muscle pigmentation of fish of commercial size. Namely, the U10 diet increased the protein content, improved muscle texture, reduced fillet total lipid content, and favored muscle selective retention of n-3 polyunsaturated fatty acids. On the other hand, the strategy based on the early administration of a diet rich in fishmeal (CT) for 60 d, followed by feeding with commercial feed, also affected positively the quality of fillets, with values comparable to U10 specimens. Thus, the results obtained indicate that a two-month feeding pulse with algae-supplemented diets during pre-growing phase may represent a promising strategy to improve the nutritional and organoleptic quality of frozen turbot fillet, as well as to extend their shelf life during the post-thawing cold storage.
Altered Lung Microbiome and Metabolome Profile in Children With Pulmonary Arterial Hypertension Associated With Congenital Heart Disease
Authors: Ma Runwei , Cheng Liming , Song Yi , Sun Yi , Gui Wenting , Deng Yao , Xie Chao , Liu Min 
Published: July 2022

BackgroundsPulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular functional and structural changes, resulting in increased pulmonary vascular resistance and eventually right heart failure and death. Congenital Left-to-Right shunts (LTRS) is one type of congenital heart disease (CHD) and PAH associated with the congenital Left-to-Right shunt (PAH-LTRS) is a severe disease in children. However, changes in the lung microbiome and their potential impact on PAH-LTRS have not been not fully studied. We hypothesized that lung microbiota and their derived metabolites have been disturbed in children with PAH-LTRS, which might contribute to the progression and outcomes of PAH-LTRS.MethodsIn this study, 68 age- and sex-matched children of three different groups (patients with PAH-LTRS cohort, patients with LTRS but have no pathologic features of PAH cohort, and healthy reference cohort) were enrolled in the current study. Bronchoalveolar lavage fluid samples from these participants were conducted for multi-omics analysis, including 16S rRNA sequencing and metabolomic profiling. Data progressing and integration analysis were performed to identify pulmonary microbial and metabolic characteristics of PAH-LTRS in children.ResultsWe found that microbial community density was not significantly altered in PAH-LTRS based on α-diversity analysis. Microbial composition analysis indicated phylum of Bacteroidetes was that less abundant while Lactobacillus, Alicycliphilus, and Parapusillimonas were significantly altered and might contribute to PAH in children with LTRS. Moreover, metabolome profiling data showed that metabolites involved in Purine metabolism, Glycerophospholipid metabolism, Galactose metabolism, and Pyrimidine metabolism were also significantly disturbed in the PAH-LTRS cohort. Correlation analysis between microbes and metabolites indicated that alterations in the microbial composition from the lung microbiota could eventually result in the disturbance in certain metabolites, and might finally contribute to the pathology of PAH-LTRS.ConclusionLung microbial density was not significantly altered in patients with PAH-LTRS. Composition analysis results showed that the relative microbiome abundance was different between groups. Metabolome profiling and correlation analysis with microbiota showed that metabolome also altered in children with PAH-LTRS. This study indicated that pulmonary microbes and metabolites disturbed in PAH-LTRS could be potentially effective biomarkers and provides valuable perspectives on clinical diagnosis, treatment, and prognosis of pediatric PAH-LTRS.
Severity of depressive but not anxiety symptoms impacts glucose metabolism among patients with type 2 diabetes in primary care
Authors: Hargittay Csenge , Eöry Ajándék , Márkus Bernadett , Mohos András , Ferenci Tamás , Vörös Krisztián , Rihmer Zoltán , Gonda Xenia , Torzsa Péter 
Published: July 2022

BackgroundData from primary care regarding the prevalence of symptoms of depression and anxiety, and their effect on glycemic control among people with diabetes is lacking in Hungary. The recently introduced Patient Health Record (PHR) requires family doctors to screen for depressive symptoms.ObjectivesWe aimed to investigate the prevalence of depressive and anxiety symptoms among patients with type 2 diabetes in the general practice, and the relationship between these affective disorders and glycated hemoglobin (HbA1c) level.MethodsWe included 338 consecutive patients with type 2 diabetes from six primary care practices in this cross-sectional study. A self-administered questionnaire (patient history, anthropometric, socioeconomic, laboratory parameters), the Beck Depression Inventory (BDI) and the Hamilton Anxiety Scale (HAM-A) were used.ResultsThe mean age of the sample was 64.0 ± 11.5 (years ± SD), 61% of participants were female. The prevalence of depressive symptoms was 21%, mainly moderate/severe symptoms (13%). Anxiety symptoms were more common (35%). We found significant univariate association between the depressive symptoms and HbA1c (p = 0.001), suicide attempt (p &lt; 0.001), anxiety (p &lt; 0.001), micro- and macrovascular complication (p = 0.028 and p &lt; 0.001), education (p = 0.001) and place of residence (p = 0.002). In multivariate analysis, however, only BDI score had significant (p = 0.03191) association with glycemic control.ConclusionAmong primary care patients with type 2 diabetes, the prevalence of depressive symptoms was less frequent than anxiety symptoms. More severe depressive symptoms were associated with worse glycemic control.
Enlarged perivascular spaces and white matter hyperintensities in patients with frontotemporal lobar degeneration syndromes
Authors: Wang Ming-Liang , Sun Zheng , Li Wen-Bin , Zou Qiao-Qiao , Li Peng-Yang , Wu Xue , Li Yue-Hua ,   the 4-Repeat Tau Neuroimaging Initiative and the Frontotemporal Lobar Degeneration Neuroimaging Initiative
Published: July 2022

ObjectiveThe aim of this study was to investigate the distribution characteristics of enlarged perivascular spaces (EPVS) and white matter hyperintensities (WMH) and their associations with disease severity across the frontotemporal lobar degeneration (FTLD) syndromes spectrum.MethodsThis study included 73 controls, 39 progressive supranuclear palsy Richardson’s syndrome (PSP-RS), 31 corticobasal syndrome (CBS), 47 behavioral variant frontotemporal dementia (bvFTD), 36 non-fluent variant primary progressive aphasia (nfvPPA), and 50 semantic variant primary progressive aphasia (svPPA). All subjects had brain magnetic resonance imaging (MRI) and neuropsychological tests, including progressive supranuclear palsy rating scale (PSPRS) and FTLD modified clinical dementia rating sum of boxes (FTLD-CDR). EPVS number and grade were rated on MRI in the centrum semiovale (CSO-EPVS), basal ganglia (BG-EPVS), and brain stem (BS-EPVS). Periventricular (PWMH) and deep (DWMH) were also graded on MRI. The distribution characteristics of EPVS and WMH were compared between control and disease groups. Multivariable linear regression analysis was performed to evaluate the association of EPVS and WMH with disease severity.ResultsCompared with control subjects, PSP-RS and CBS had more BS-EPVS; CBS, bvFTD, and nfvPPA had less CSO-EPVS; all disease groups except CBS had higher PWMH (p &lt; 0.05). BS-EPVS was associated with PSPRS in PSP-RS (β = 2.395, 95% CI 0.888–3.901) and CBS (β = 3.115, 95% CI 1.584–4.647). PWMH was associated with FTLD-CDR in bvFTD (β = 1.823, 95% CI 0.752–2.895), nfvPPA (β = 0.971, 95% CI 0.030–1.912), and svPPA (OR: 1.330, 95% CI 0.457–2.204).ConclusionBS-EPVS could be a promising indicator of disease severity in PSP-RS and CBS, while PWMH could reflect the severity of bvFTD, nfvPPA, and svPPA.