bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recognition of fold- and function-specific sites in the ligand-binding domain of the thyroid hormone receptor-like family
Authors: Verma Sonia , Chakraborti Soumyananda , Singh Om P. , Pande Veena , Dixit Rajnikant , Pandey Amit V. , Pandey Kailash C. 
Published: September 2022

BackgroundThe thyroid hormone receptor-like (THR-like) family is the largest transcription factors family belonging to the nuclear receptor superfamily, which directly binds to DNA and regulates the gene expression and thereby controls various metabolic processes in a ligand-dependent manner. The THR-like family contains receptors THRs, RARs, VDR, PPARs, RORs, Rev-erbs, CAR, PXR, LXRs, and others. THR-like receptors are involved in many aspects of human health, including development, metabolism and homeostasis. Therefore, it is considered an important therapeutic target for various diseases such as osteoporosis, rickets, diabetes, etc.MethodsIn this study, we have performed an extensive sequence and structure analysis of the ligand-binding domain (LBD) of the THR-like family spanning multiple taxa. We have use different computational tools (information-theoretic measures; relative entropy) to predict the key residues responsible for fold and functional specificity in the LBD of the THR-like family. The MSA of THR-like LBDs was further used as input in conservation studies and phylogenetic clustering studies.ResultsPhylogenetic analysis of the LBD domain of THR-like proteins resulted in the clustering of eight subfamilies based on their sequence homology. The conservation analysis by relative entropy (RE) revealed that structurally important residues are conserved throughout the LBDs in the THR-like family. The multi-harmony conservation analysis further predicted specificity in determining residues in LBDs of THR-like subfamilies. Finally, fold and functional specificity determining residues (residues critical for ligand, DBD and coregulators binding) were mapped on the three-dimensional structure of thyroid hormone receptor protein. We then compiled a list of natural mutations in THR-like LBDs and mapped them along with fold and function-specific mutations. Some of the mutations were found to have a link with severe diseases like hypothyroidism, rickets, obesity, lipodystrophy, epilepsy, etc.ConclusionOur study identifies fold and function-specific residues in THR-like LBDs. We believe that this study will be useful in exploring the role of these residues in the binding of different drugs, ligands, and protein-protein interaction among partner proteins. So this study might be helpful in the rational design of either ligands or receptors.
Integrated transcriptomic and metabolomic analyses of pak choi [Brassica pekinensis (Lour.) Rupr] response to combined stress of acid rain and cadmium-containing atmospheric fine particulate matter
Authors: Zha Yan , Zhao Bo , Qiu Jieren , Li Xuqing 
Published: September 2022

Heavy metal-containing atmospheric particulate matter (PM) and acid rain (AR) trigger molecular alteration in plants, perturbing metabolites and damaging plant growth. However, the molecular mechanisms of plants under AR along with Cd-containing atmospheric fine particulate matter (PM2.5-Cd) stress remain unknown. In this study, integrated transcriptomics and metabolomics analyses of pak choi (Brassica pekinensis (Lour.) Rupr) exposed to AR (pH3.5) and PM2.5-Cd (500 μg·m−3) stress were performed. Metabolomics analyses revealed that AR-Cd stress mainly affected 42 metabolic pathways, including 451 differentially expressed metabolites (DEMs). RNA-seq identified 735 common differentially expressed genes (DEGs: 557 upregulated and 178 downregulated). Further analysis found several important DEGs (transcription factors, metabolic pathways genes, and signal transduction genes), including WRKY11, WRKY53, WRKY41, MYB73, NAC062, NAC046, HSFA4A, ABCC3, CAXs, GSTs, AZFs, PODs, PME41, CYP707A2, and CDPK32 implying that Cd chelate sequestration into the vacuoles, the antioxidant system, cell wall biosynthesis pathway, and calcium signaling play a critical role in AR damage and Cd detoxification. Conjoint revealed phenylpropanoid and flavonoid biosynthesis pathways with different metabolism patterns, including the key DEM, chlorogenic acids. The results obtained using multiple approaches provide a molecular-scale perspective on plant response to AR-Cd stress.
24 h movement behavior and metabolic syndrome study protocol: A prospective cohort study on lifestyle and risk of developing metabolic syndrome in undergraduate students from low-income regions during a pandemic
Authors: Nascimento-Ferreira Marcus Vinicius , Marin Kliver Antonio , Abrão Ferreira Ruhena Kelber , Oliveira Luiz Fernando , Bandeira Ana Caroline , Silva Sousa Paula , Miranda de Sousa Josilene , de Almeida Cardoso Antonio Gibran , Conceição da Silva Lorrane Cristine , Rosa Ana Clara Arrais , de Carvalho Millena Vaz , Pereira de Carvalho Silva Ithamara Sthefanny , Franco Alaiana Marinho , Torres-Leal Francisco Leonardo , Barbosa de Carvalho Heráclito , Ferreira de Moraes Augusto César 
Published: September 2022

IntroductionObesity and its comorbidities are increasingly prevalent in Latin America, with a more rapid growth in individuals with lower income. The composition of movement behaviors within a 24 h period may have important implications for obesity, metabolic and mental health in cross-sectional data. However, a longitudinal study is needed to confirm the findings from the primarily cross-sectional evidence. The COVID-19 pandemic has been associated with cardiometabolic outcomes and has impeded healthy behavior.ObjectivesThe first objective is to evaluate the time elapsed since the diagnosis of not meeting 24 h movement guidelines and the potential subsequent onset of metabolic syndrome in undergraduate students from low-income regions within 4 years of follow up. The second objective is to test the association between 24 h movement, mental wellbeing, eating behaviors, and abdominal obesity in the period of this pandemic.MethodsThe 24 h movement behavior and metabolic syndrome (24 h-MESYN) study is a multicentre cohort study that will include participants from two Brazilian cities within the 2022–2025 period to asses the first objective, and also a nested case-control study at the baseline will be carried out to evaluate the second objective. Previously, we conducted a feasibility study in the academic year of 2021 to assessing the psychometric properties of subjective tools, refine our study protocol, and adjust the epidemiological conditions of the cohort's subsequent phases (like as prevalence of exposure of interest, sampling process, and study adherence). Statistical tests as Cohen's kappa agreement; factorial analysis; logistic, Poisson and linear regression; and Kaplan-Meier analysis will be performed, in accordance with the objectives.
Landscape of circulating metabolic fingerprinting for keloid
Authors: Hu Yu , Zhou Xuyue , Chen Lihao , Li Rong , Jin Shuang , Liu Lingxi , Ju Mei , Luan Chao , Chen Hongying , Wang Ziwei , Huang Dan , Chen Kun , Zhang Jiaan 
Published: September 2022

BackgroundKeloids are a fibroproliferative disease characterized by unsatisfactory therapeutic effects and a high recurrence rate.ObjectiveThis study aimed to investigate keloid-related circulating metabolic signatures.MethodsUntargeted metabolomic analysis was performed to compare the metabolic features of 15 keloid patients with those of paired healthy volunteers in the discovery cohort. The circulating metabolic signatures were selected using the least absolute shrinkage. Furthermore, the selection operators were quantified using multiple reaction monitoring-based target metabolite detection methods in the training and test cohorts.ResultsMore than ten thousand metabolic features were consistently observed in all the plasma samples from the discovery cohort, and 30 significantly different metabolites were identified. Four differentially expressed metabolites including palmitoylcarnitine, sphingosine, phosphocholine, and phenylalanylisoleucine, were discovered to be related to keloid risk in the training and test cohorts. In addition, using linear and logistic regression models, the respective risk scores for keloids based on a 4-metabolite fingerprint classifier were established to distinguish keloids from healthy volunteers.ConclusionsIn summary, our findings show that the characteristics of circulating metabolic fingerprinting manifest phenotypic variation in keloid onset.
Evaluating the role of IDO1 macrophages in immunotherapy using scRNA-seq and bulk-seq in colorectal cancer
Authors: Liu Xingwu , Yan Guanyu , Xu Boyang , Yu Han , An Yue , Sun Mingjun 
Published: September 2022

BackgroundMacrophage infiltration is crucial for colorectal cancer (CRC) immunotherapy. Detailed classification of macrophage subsets will facilitate the selection of patients suitable for immunotherapy. However, the classification of macrophages in CRC is not currently detailed.MethodsIn this study, we combined single-cell RNA sequencing (scRNA-seq) and bulk-seq to analyze patients with colorectal cancer. scRNA-seq data were used to study cell-cell communication and to differentiate immune-infiltrating cells and macrophage subsets. Bulk-seq data were used to further analyze immune infiltration, clinical features, tumor mutational burden, and expression of immune checkpoint molecules in patients with CRC having different macrophage subsets.ResultsSeven macrophage subpopulations were identified, among which indoleamine 2,3 dioxygenase 1 (IDO1) macrophages had the most significant difference in the degree of infiltration among normal, microsatellite-unstable, and microsatellite-stable populations. We then performed gene set variation analysis using 12 marker genes of IDO1 macrophages and divided the patients into two clusters: high-IDO1 macrophages (H-IDO1M) and low-IDO1 macrophages (L-IDO1M). H-IDO1M showed higher infiltration of immune cells, higher expression of immune checkpoints, and less advanced pathological stages than L-IDO1M (p &lt; 0.05).ConclusionsThis study elucidated that IDO1-macrophage-based molecular subtypes can predict the response to immunotherapy in patients with CRC. The results provide new insights into tumor immunity and help in clinical decisions regarding designing effective immunotherapy for these patients.
Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis
Authors: Ruiz Maria Julia , Siracusano Gabriel , Cottignies-Calamarte Andréa , Tudor Daniela , Real Fernando , Zhu Aiwei , Pastori Claudia , Capron Claude , Rosenberg Arielle R. , Temperton Nigel , Cantoni Diego , Liao Hanqing , Ternette Nicola , Moine Pierre , Godement Mathieu , Geri Guillaume , Chiche Jean-Daniel , Annane Djillali , Cramer Bordé Elisabeth , Lopalco Lucia , Bomsel Morgane 
Published: September 2022

The role of the mucosal pulmonary antibody response in coronavirus disease 2019 (COVID-19) outcome remains unclear. Here, we found that in bronchoalveolar lavage (BAL) samples from 48 patients with severe COVID-19-infected with the ancestral Wuhan virus, mucosal IgG and IgA specific for S1, receptor-binding domain (RBD), S2, and nucleocapsid protein (NP) emerged in BAL containing viruses early in infection and persist after virus elimination, with more IgA than IgG for all antigens tested. Furthermore, spike-IgA and spike-IgG immune complexes were detected in BAL, especially when the lung virus has been cleared. BAL IgG and IgA recognized the four main RBD variants. BAL neutralizing titers were higher early in COVID-19 when virus replicates in the lung than later in infection after viral clearance. Patients with fatal COVID-19, in contrast to survivors, developed higher levels of mucosal spike-specific IgA than IgG but lost neutralizing activities over time and had reduced IL-1β in the lung. Altogether, mucosal spike and NP-specific IgG and S1-specific IgA persisting after lung severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance and low pulmonary IL-1β correlate with COVID-19 fatal outcome. Thus, mucosal SARS-CoV-2-specific antibodies may have adverse functions in addition to protective neutralization.HighlightsMucosal pulmonary antibody response in COVID-19 outcome remains unclear. We show that in severe COVID-19 patients, mucosal pulmonary non-neutralizing SARS-CoV-2 IgA persit after viral clearance in the lung. Furthermore, low lung IL-1β correlate with fatal COVID-19. Altogether, mucosal IgA may exert harmful functions beside protective neutralization.
Analysis of chromatin data supports a role for CD14+ monocytes/macrophages in mediating genetic risk for juvenile idiopathic arthritis
Authors: Crinzi Elizabeth A. , Haley Emma K. , Poppenberg Kerry E. , Jiang Kaiyu , Tutino Vincent M. , Jarvis James N. 
Published: September 2022

IntroductionGenome wide association studies (GWAS) have identified multiple regions that confer genetic risk for the polyarticular/oligoarticular forms of juvenile idiopathic arthritis (JIA). However, genome-wide scans do not identify the cells impacted by genetic polymorphisms on the risk haplotypes or the genes impacted by those variants. We have shown that genetic variants driving JIA risk are likely to affect both innate and adaptive immune functions. We provide additional evidence that JIA risk variants impact innate immunity.Materials and methodsWe queried publicly available H3K4me1/H3K27ac ChIP-seq data in CD14+ monocytes to determine whether the linkage disequilibrium (LD) blocks incorporating the SNPs that tag JIA risk loci showed enrichment for these epigenetic marks. We also queried monocyte/macrophage GROseq data, a functional readout of active enhancers. We defined the topologically associated domains (TADs) encompassing enhancers on the risk haplotypes and identified genes within those TADs expressed in monocytes. We performed ontology analyses of these genes to identify cellular processes that may be impacted by these variants. We also used whole blood RNAseq data from the Genotype-Tissue Expression (GTEx) data base to determine whether SNPs lying within monocyte GROseq peaks influence plausible target genes within the TADs encompassing the JIA risk haplotypes.ResultsThe LD blocks encompassing the JIA genetic risk regions were enriched for H3K4me1/H3K27ac ChIPseq peaks (p=0.00021 and p=0.022) when compared to genome background. Eleven and sixteen JIA were enriched for resting and activated macrophage GROseq peaks, respectively risk regions (p=0.04385 and p=0.00004). We identified 321 expressed genes within the TADs encompassing the JIA haplotypes in human monocytes. Ontological analysis of these genes showed enrichment for multiple immune functions. Finally, we found that SNPs lying within the GROseq peaks are strongly associated with expression levels of plausible target genes in human whole blood.ConclusionsThese findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.
Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy
Authors: Suber Jada , Zhang Yugen , Ye Ping , Guo Rishu , Burks A. Wesley , Kulis Michael D. , Smith Scott A. , Iweala Onyinye I. 
Published: September 2022

Background10% of US residents have food allergies, including 2% with peanut allergy. Mast cell mediators released during the allergy effector phase drive allergic reactions. Therefore, targeting sensitized mast cells may prevent food allergy symptoms.ObjectiveWe used novel, human, allergen-specific, IgE monoclonal antibodies (mAbs) created using human hybridoma techniques to design anin vitrosystem to evaluate potential therapeutics targeting sensitized effector cells.MethodsTwo human IgE mAbs specific for peanut, generated through human hybridoma techniques, were used to sensitize rat basophilic leukemia (RBL) SX-38 cells expressing the human IgE receptor (FcϵRI). Beta-hexosaminidase release (a marker of degranulation), cytokine production, and phosphorylation of signal transduction proteins downstream of FcϵRI were measured after stimulation with peanut. Degranulation was also measured after engaging inhibitory receptors CD300a and Siglec-8.ResultsPeanut-specific human IgE mAbs bound FcϵRI, triggering degranulation after stimulation with peanut in RBL SX-38 cells. Sensitized RBL SX-38 cells stimulated with peanut increased levels of phosphorylated SYK and ERK, signal transduction proteins downstream of FcϵRI. Engaging inhibitory cell surface receptors CD300a or Siglec-8 blunted peanut-specific activation.ConclusionAllergen-specific human IgE mAbs, expressed from human hybridomas and specific for a clinically relevant food allergen, passively sensitize allergy effector cells central to thein vitromodels of the effector phase of food allergy. Peanut reproducibly activates and induces degranulation of RBL SX-38 cells sensitized with peanut-specific human IgE mAbs. This system provides a unique screening tool to assess the efficacy of therapeutics that target allergy effector cells and inhibit food allergen-induced effector cell activation.
Pan-cancer analysis of AIM2 inflammasomes with potential implications for immunotherapy in human cancer: A bulk omics research and single cell sequencing validation
Authors: Qin Yan , Pan Liuxian , Qin Tianyu , Ruan Hanyi , Zhang Yujie , Zhang Yan , Li Jianli , Yang Jianrong , Li Wei 
Published: September 2022

BackgroundThe absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic double-stranded DNA(dsDNA) and induces cytokine maturation, release, and pyroptosis. Some studies found that the AIM2 inflammasome was a double-edged sword in many cancers. However, there have been fewer studies on AIM2 inflammasomes in pan-cancer.MethodsGene expression was analyzed using The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) database. Immunohistochemistry (IHC) was used to validate the expression of the AIM2. We used the survival curve to explore the prognostic significance of the AIM2 inflammasomes in pan-cancer. Mutations and methylation of AIM2 inflammasome-related genes (AIM2i-RGs) were also comprehensively analyzed. Single sample gene set enrichment analysis was used to calculate the AIM2 inflammasomes score and explore the correlation of the AIM2 inflammasomes score with immune-related genes and immune infiltrations. The function of AIM2 inflammasomes in pan-cancer was analyzed at the single-cell level. Single-cell transcriptome sequencing (scRNA-seq) data was used to assess the activation state of the AIM2 inflammasomes in the tumor microenvironment.ResultsWe found that AIM2i-RGs were aberrantly expressed in tumors and were strongly associated with prognosis. In pan-cancer, the expression of AIM2i-RGs was positively associated with copy number variation and negatively associated with methylation. In AIM2i-RGs, missense mutations were the predominant type of single nucleotide polymorphism. Moreover, we found that the drugs dimethyloxallyl glycine (DMOG) and Z-LNle-CHO may be sensitive to the AIM2 inflammasomes. The AIM2 inflammasomes score was significantly and positively correlated with the tumor immunity score and the stroma score. In most tumors, the AIM2 inflammasomes score was significantly and positively correlated with CD8+ T cell abundance in the tumor microenvironment. Additionally, the AIM2 inflammasomes score was significantly correlated with immune checkpoint genes in pan-cancer as well as immune checkpoint therapy-related markers including tumor mutational burden (TMB), microsatellite instability(MSI), and tumor immune dysfunction and exclusion(TIDE). scRNA-seq analysis suggested that AIM2 inflammasomes differ significantly among different cells in the tumor microenvironment. IHC confirmed low expression of AIM2 in colorectal cancer.DiscussionAIM2 inflammasomes may be a new target for future tumor therapy It is likely involved in tumor development, and its high expression may serve as a predictor of tumor immunotherapy efficacy.
Cytokine levels as predictors of mortality in critically ill patients with severe COVID-19 pneumonia: Case-control study nested within a cohort in Colombia
Authors: Molina Francisco José , Botero Luz Elena , Isaza Juan Pablo , Cano Luz Elena , López Lucelly , Hoyos Lina Marcela , Correa Elizabeth , Torres Antoni 
Published: September 2022

BackgroundHigh levels of different cytokines have been associated in COVID-19 as predictors of mortality; however, not all studies have found this association and its role to cause multi-organ failure and death has not been fully defined. This study aimed to investigate the association of the levels of 10 cytokines with mortality in patients with COVID-19 admitted to the intensive care unit (ICU).Materials and methodsThis is a case-control study nested within a cohort of patients with COVID-19 who were on mechanical ventilation and were not hospitalized for more than 48 h across nine ICUs in Medellín, Colombia. Serum samples were collected upon admission to the ICU and 7 days later and used to measure cytokine levels.ResultsUpon admission, no differences in mortality between the cytokine levels were observed when comparisons were made quantitatively. However, in the multivariate analysis, patients with median IL-1β levels &lt;1.365 pg/ml showed an increase in mortality (OR = 3.1; 1.24&lt;7.71; p = 0.015). On day 7 in the ICU, IL-1β median levels were lower (0.34 vs. 2.41 pg/ml, p = 0.042) and IL-10 higher (2.08 vs. 1.05 pg/ml, p = 0.009) in patients who died. However, in the multivariate analysis, only IL-12p70 was associated with mortality (OR = 0.23; 0.07&lt;0.73; p = 0.012). The mean difference in the levels between day 1 and day 7 decreased in both IFN-γ (3.939 pg/ml, p &lt; 0.039) and in IL-18 (16.312 pg/ml, p &lt; 0.014) in the patients who died. A low IL-1β/IL-10 ratio was associated with mortality on both day 1 and day 7, while an IL-1β/IL-10 ratio below the cut-off on day 7 was associated with decreased survival. The lowest TNFα/IL-10 ratio was associated with mortality only on day 7.ConclusionAt the time of admission, patients with median IL-1β levels lower than 1.365 pg/ml had increased mortality. An IL-1β/IL-10 ratio &lt;2 at day 7 and IL-12p70 levels &gt;1.666 pg/ml was associated with decreased survival.
Effect of fetoscopic laser surgery on the placental characteristics and birth-weight discordance of twins with twin-to-twin transfusion syndrome
Authors: Wang Xueju , Li Luyao , Yuan Pengbo , Zhao Yangyu , Wei Yuan 
Published: September 2022

ObjectiveThis study explored the effect of fetoscopic laser surgery on the placental structure and birth-weight discordance of twin-to-twin transfusion syndrome (TTTS).MethodsA retrospective cohort study was conducted in TTTS patients who were admitted to the Peking University Third Hospital between April 2014 and April 2020. The patients were divided into two groups: laser group and control group. Placentas with twin survival were injected, and pregnancy outcomes and placental characteristics of the two groups were compared. The correlation between the birth-weight discordance and placental characteristics in each group was analyzed.ResultsThe gestational age at first diagnosis in the laser group was significantly smaller than that in the control group (21.6 ± 2.8 weeks vs. 27.7 ± 3.0 weeks, p &lt; 0.001). The proportion of patients with TTTS stage-I in the laser group was significantly lower than the control group (9.4 vs. 64.0%, p &lt; 0.001). The gestational age at delivery in the laser group was significantly larger than that in the control group (33.6 ± 2.1 weeks vs. 31.4 ± 2.5 weeks, p = 0.001). In the laser group, the birth-weight discordance ratio was positively correlated with the placental territory discordance ratio (Spearman coefficient = 0.556; p = 0.001).ConclusionThe birth-weight discordance is positively correlated with placental territory discordance in TTTS patients after FLS.