bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy
Authors: Portokallidou Konstantina , Dovrolis Nikolas , Ragia Georgia , Atzemian Natalia , Kolios George , Manolopoulos Vangelis G. 
Published: February 2023

IntroductionHeart failure (HF) is a complex clinical syndrome leading to high morbidity. In this study, we aimed to identify the gene expression and protein signature of HF main causes, namely dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM).MethodsOmics data were accessed through GEO repository for transcriptomic and PRIDE repository for proteomic datasets. Sets of differentially expressed genes and proteins comprising DCM (DiSig) and ICM (IsSig) signatures were analyzed by a multilayered bioinformatics approach. Enrichment analysisviathe Gene Ontology was performed through the Metascape platform to explore biological pathways. Protein-protein interaction networks were analyzedviaSTRING db and Network Analyst.ResultsIntersection of transcriptomic and proteomic analysis showed 10 differentially expressed genes/proteins in DiSig (AEBP1,CA3,HBA2,HBB,HSPA2,MYH6,SERPINA3,SOD3,THBS4,UCHL1) and 15 differentially expressed genes/proteins in IsSig (AEBP1,APOA1,BGN,CA3,CFH,COL14A1,HBA2,HBB,HSPA2,LTBP2,LUM,MFAP4,SOD3,THBS4,UCHL1). Common and distinct biological pathways between DiSig and IsSig were retrieved, allowing for their molecular characterization. Extracellular matrix organization, cellular response to stress and transforming growth factor-beta were common between two subphenotypes. Muscle tissue development was dysregulated solely in DiSig, while immune cells activation and migration in IsSig.DiscussionOur bioinformatics approach sheds light on the molecular background of HF etiopathology showing molecular similarities as well as distinct expression differences between DCM and ICM. DiSig and IsSig encompass an array of “cross-validated” genes at both transcriptomic and proteomic level, which can serve as novel pharmacological targets and possible diagnostic biomarkers.
Relationship of iodine excess with thyroid function in 6-year-old children living in an iodine-replete area
Authors: Lee Yun Jeong , Cho Sun Wook , Lim Youn-Hee , Kim Bung-Nyun , Kim Johanna Inhyang , Hong Yun-Chul , Park Young Joo , Shin Choong Ho , Lee Young Ah 
Published: February 2023

BackgroundAdequate iodine intake is essential for growing children, as both deficient and excessive iodine status can result in thyroid dysfunction. We investigated the iodine status and its association with thyroid function in 6-year-old children from South Korea.MethodsA total of 439 children aged 6 (231 boys and 208 girls) were investigated from the Environment and Development of Children cohort study. The thyroid function test included free thyroxine (FT4), total triiodothyronine (T3), and thyroid-stimulating hormone (TSH). Urine iodine status was evaluated using urine iodine concentration (UIC) in morning spot urine and categorized into iodine deficient (&lt; 100 μg/L), adequate (100–199 μg/L), more than adequate (200–299 μg/L), mild excessive (300–999 μg/L), and severe excessive (≥ 1000 μg/L) groups. The estimated 24-hour urinary iodine excretion (24h-UIE) was also calculated.ResultsThe median TSH level was 2.3 μIU/mL, with subclinical hypothyroidism detected in 4.3% of patients without sex differences. The median UIC was 606.2 μg/L, with higher levels in boys (684 μg/L vs. 545 μg/L, p = 0.021) than girls. Iodine status was categorized as deficient (n = 19, 4.3%), adequate (n = 42, 9.6%), more than adequate (n = 54, 12.3%), mild excessive (n = 170, 38.7%), or severe excessive (n = 154, 35.1%). After adjusting for age, sex, birth weight, gestational age, body mass index z-score, and family history, both the mild and severe excess groups showed lower FT4 (β = − 0.04, p = 0.032 for mild excess; β = − 0.04, p = 0.042 for severe excess) and T3 levels (β = − 8.12, p = 0.009 for mild excess; β = − 9.08, p = 0.004 for severe excess) compared to the adequate group. Log-transformed estimated 24h-UIE showed a positive association with log-transformed TSH levels (β = 0.04, p = 0.046).ConclusionExcess iodine was prevalent (73.8%) in 6-year-old Korean children. Excess iodine was associated with a decrease in FT4 or T3 levels and an increase in TSH levels. The longitudinal effects of iodine excess on later thyroid function and health outcomes require further investigation.
The gene spectrum of thalassemia in Yangjiang of western Guangdong Province
Authors: Liang Hong-Feng , Liang Wei-Min , Xie Wen-Guang , Lin Fen , Liu Li-Li , Li Lie-Jun , Ge Yi-Yuan , Lu Min , Liao Yu-Wei , Zeng Guang-Kuan , Yao Jin-Xiu , Situ Jing-Wei , Yang Li-Ye 
Published: February 2023

Background: Thalassemia presents a higher incidence in southern China. The objective of this study is to analyze the genotype distribution of thalassemia in Yangjiang, a western city of Guangdong Province in China.Methods: The genotypes of suspected cases with thalassemia were tested by PCR and reverse dot blot (RDB). Unidentified rare thalassemia genotypes of the samples were further ascertained by PCR and direct DNA sequencing.Results: Among 22467 suspected cases with thalassemia, 7658 cases were found with thalassemia genotypes using our PCR-RDB kit. Among these 7658 cases, 5313 cases were found with α-thalassemia (α-thal) alone, --SEA/αα was the most common genotype, accounting for 61.75% of α-thal genotypes, and the following mutations were found: α3.7/αα, -α4.2/αα, αCSα/αα, αWSα/αα, and αQSα/αα. A total of 2032 cases were found with β-thalassemia (β-thal) alone. βCD41-42/βN, βIVS−II−654/βN, and β−28/βN accounted for 80.9% of all β-thal genotypes, and the following genotypes were found: βCD17/βN, βCD71-72/βN, and βE/βN. Compound heterozygotes of β-thal and β-thalassemia homozygotes were identified in 11 and five cases, respectively, in this study. α-thal combined with β-thal was identified in 313 cases, showing 57 genotype combinations of the coincidence of both Hb disorders; one extreme patient had a genotype of --SEA/αWSα and βCD41-42/β−28. In addition, four rare α-mutations (--THAI, HKαα, Hb Q-Thailand, and CD31 AGG&gt;AAG) and six rare β-mutations (CD39 CAG&gt;TAG, IVS-Ⅱ-2 (−T), −90(C&gt;T), Chinese Gγ+(Aγδβ)0, CD104 (-G), and CD19 A&gt;G) were also found in this study population.Conclusion: This study provided detailed genotypes of thalassemia in Yangjiang of western Guangdong Province in China and reflected the complexity of genotypes in this high-prevalence region, and this would be valuable for diagnosis and counseling for thalassemia in this area.
Immunosuppressive capacity of circulating MDSC predicts response to immune checkpoint inhibitors in melanoma patients
Authors: Petrova Vera , Groth Christopher , Bitsch Rebekka , Arkhypov Ihor , Simon Sonja C. S. , Hetjens Svetlana , Müller Verena , Utikal Jochen , Umansky Viktor 
Published: February 2023

PurposeAlthough the treatment of advanced melanoma patients with immune checkpoint inhibitors (ICI) significantly increased the therapeutic efficiency, many patients remain resistant to ICI that could be due to immunosuppression mediated by myeloid-derived suppressor cells (MDSC). These cells are enriched and activated in melanoma patients and could be considered as therapeutic targets. Here we studied dynamic changes in immunosuppressive pattern and activity of circulating MDSC from melanoma patients treated with ICI.Experimental designMDSC frequency, immunosuppressive markers and function were evaluated in freshly isolated peripheral blood mononuclear cells (PBMC) from 29 melanoma patients receiving ICI. Blood samples were taken prior and during the treatment and analyzed by flow cytometry and bio-plex assay.ResultsMDSC frequency was significantly increased before the therapy and through three months of treatment in non-responders as compared to responders. Prior to the ICI therapy, MDSC from non-responders displayed high levels of immunosuppression measured by the inhibition of T cell proliferation assay, whereas MDSC from responding patients failed to inhibit T cells. Patients without visible metastasis were characterized by the absence of MDSC immunosuppressive activity during the ICI treatment. Moreover, non-responders showed significantly higher IL-6 and IL-8 concentrations before therapy and after the first ICI application as compared to responders.ConclusionsOur findings highlight the role of MDSC during melanoma progression and suggest that frequency and immunosuppressive activity of circulating MDSC before and during the ICI treatment of melanoma patients could be used as biomarkers of response to ICI therapy.
Epstein-Barr virus DNA seropositivity links distinct tumoral heterogeneity and immune landscape in nasopharyngeal carcinoma
Authors: Li Wangzhong , Lv Shuhui , Liu Guoying , Lu Nian , Jiang Yaofei , Liang Hu , Xia Weixiong , Xiang Yanqun , Xie Changqing , He Jianxing 
Published: February 2023

BackgroundEpstein-Barr virus (EBV) DNA seronegative (Sero-) and seropositive (Sero+) nasopharyngeal carcinoma (NPC) are distinctly different disease subtypes. Patients with higher baseline EBV DNA titers seem to benefit less from anti-PD1 immunotherapy, but underlying mechanisms remain unclear. Tumor microenvironment (TME) characteristics could be the important factor affecting the efficacy of immunotherapy. Here, we illuminated the distinct multicellular ecosystems of EBV DNA Sero- and Sero+ NPCs from cellular compositional and functional perspectives at single-cell resolution.MethodWe performed single-cell RNA sequencing analyses of 28,423 cells from ten NPC samples and one non-tumor nasopharyngeal tissue. The markers, function, and dynamics of related cells were analyzed.ResultsWe found that tumor cells from EBV DNA Sero+ samples exhibit low-differentiation potential, stronger stemness signature, and upregulated signaling pathways associated with cancer hallmarks than that of EBV DNA Sero- samples. Transcriptional heterogeneity and dynamics in T cells were associated with EBV DNA seropositivity status, indicating different immunoinhibitory mechanisms employed by malignant cells depending on EBV DNA seropositivity status. The low expression of classical immune checkpoints, early-triggered cytotoxic T-lymphocyte response, global activation of IFN-mediated signatures, and enhanced cell-cell interplays cooperatively tend to form a specific immune context in EBV DNA Sero+ NPC.ConclusionsCollectively, we illuminated the distinct multicellular ecosystems of EBV DNA Sero- and Sero+ NPCs from single-cell perspective. Our study provides insights into the altered tumor microenvironment of NPC associated with EBV DNA seropositivity, which will help direct the development of rational immunotherapy strategies.
3D genome-selected microRNAs to improve Alzheimer's disease prediction
Authors: Li Keyi , Chi Runqiu , Liu Liangjie , Feng Mofan , Su Kai , Li Xia , He Guang , Shi Yi 
Published: February 2023

IntroductionAlzheimer's disease (AD) is a type of neurodegenerative disease that has no effective treatment in its late stage, making the early prediction of AD critical. There have been an increase in the number of studies indicating that miRNAs play an important role in neurodegenerative diseases including Alzheimer's disease via epigenetic modifications including DNA methylation. Therefore, miRNAs may serve as excellent biomarkers in early AD prediction.MethodsConsidering that the non-coding RNAs' activity may be linked to their corresponding DNA loci in the 3D genome, we collected the existing AD-related miRNAs combined with 3D genomic data in this study. We investigated three machine learning models in this work under leave-one-out cross-validation (LOOCV): support vector classification (SVC), support vector regression (SVR), and knearest neighbors (KNNs).ResultsThe prediction results of different models demonstrated the effectiveness of incorporating 3D genome information into the AD prediction models.DiscussionWith the assistance of the 3D genome, we were able to train more accurate models by selecting fewer but more discriminatory miRNAs, as witnessed by several ML models. These interesting findings indicate that the 3D genome has great potential to play an important role in future AD research.
Sociodemographic inequalities in vegetables, fruits, and animal source foods consumption in children aged 6–23 months from 91 LMIC
Authors: Ricardo Luiza I. C. , Gatica-Domínguez Giovanna , Neves Paulo A. R. , Vaz Juliana dos Santos , Barros Aluisio J. D. , Wehrmeister Fernando C. 
Published: February 2023

IntroductionNo multi-country analysis described patterns and inequalities for the brand-new feeding indicators proposed by WHO/UNICEF: zero consumption of vegetables and fruits (ZVF) and consumption of eggs and/or flesh (EFF). Our aim was to describe patterns in the prevalence and social inequalities of ZVF and EFF among children aged 6–23 months in low-and middle-income countries.MethodsData from nationally representative surveys (2010–2019) in 91 low-and middle-income countries were used to investigate within-country disparities in ZVF and EFF by place of residence, wealth quintiles, child sex and child age. The slope index of inequality was used to assess socioeconomic inequalities. Analyses were also pooled by World Bank income groups.ResultsThe prevalence of ZVF was 44.8% and it was lowest in children from upper-middle income countries, from urban areas, and those 18–23 months. The slope index of inequality showed that socioeconomic inequalities in the prevalence of ZVF were higher among poor children in comparison to richest children (mean SII = −15.3; 95%CI: −18.5; −12.1). Overall, 42.1% of children consumed egg and/or flesh foods. Being a favorable indicator, findings for EFF were generally in the opposite direction than for ZVF. The prevalence was highest in children from upper-middle income countries, from urban areas, and those 18–23 months of age. The slope index of inequality showed pro-rich patterns in most countries (mean SII = 15.4; 95%CI: 12.2; 18.6).DiscussionOur findings demonstrate that inequalities exist in terms of household wealth, place of residence, and age of the child in the prevalence of the new complementary feeding indicators. Moreover, children from low-and lower-middle countries had the lowest consumption of fruits, vegetables, eggs, and flesh foods. Such findings provide new insights towards effective approaches to tackle the malnutrition burden through optimal feeding practices.
Prevalence of hypertension in endemic and non-endemic areas of Keshan disease: A cross-sectional study in rural areas of China
Authors: Hou Jie , Zhu Lifang , Jin Shuran , Li Jinshu , Xing Zhifeng , Wang Yanling , Wan Xiaoyan , Guo Xianni , Wang Anwei , Wang Xiuhong , Liu Jinming , Ma Jing , Zhou Shuang , Zhang Xiangdong , Zheng Heming , Wang Jianhui , Feng Hongqi , Sun Shuqiu , Wang Tong 
Published: February 2023

BackgroundHypertension is a major public health concern that strongly influences the quality of life of people worldwide. Keshan disease (KD) is an endemic cardiomyopathy related to low selenium, threatening residents in rural areas of 16 provinces in China. Furthermore, the prevalence of hypertension in the KD-endemic areas has been increasing annually. However, hypertension research associated with KD has only focused on endemic regions, and no studies have compared hypertension prevalence between endemic and non-endemic areas. Therefore, this study investigated the prevalence of hypertension to provide a basis for preventing and controlling hypertension in the KD-endemic areas, even in rural areas.MethodsWe extracted blood pressure information from cardiomyopathy investigation data from a cross-sectional study of the KD-endemic and non-endemic areas. The hypertension prevalence between the two groups was compared using the Chi-square test or Fisher s exact test. Additionally, Pearson’s correlation coefficient was employed to evaluate the relationship between the per capita gross domestic product (GDP) and hypertension prevalence.ResultsThere was a statistically significant increase of hypertension prevalence in the KD-endemic areas (22.79%, 95% confidence interval [CI]: 22.30–23.27%) over the non-endemic areas (21.55%, 95% CI: 21.09–22.02%). In the KD-endemic areas, more men had hypertension than women (23.90% vs. 21.65%, P &lt; 0.001). Furthermore, the hypertension prevalence was higher in the north than in the south in the KD-endemic areas (27.52% vs. 18.76%, P &lt; 0.001), non-endemic areas (24.86% vs. 18.66%, P &lt; 0.001), and overall (26.17% vs. 18.68%, P &lt; 0.001). Finally, the prevalence of hypertension positively correlated with per capita GDP at province level.ConclusionsThe increasing hypertension prevalence is a public health problem in the KD-endemic areas. Healthy diets, such as high consumption of vegetables and seafoods, and foods that are rich in selenium, might help prevent and control hypertension in the KD-endemic areas and other rural areas in China.
Elevated triglyceride-glucose index predicts mortality following endovascular abdominal aortic aneurysm repair
Authors: Li Tan , Yang Chao , Yang Jun , Jing Jingjing , Ma Chunyan 
Published: February 2023

BackgroundTriglyceride-glucose (TyG) index has been increasingly studied as a simple and reliable predictor of adverse events of some cardiovascular disorders. However, its prognostic effect on postoperative outcomes in patients with abdominal aortic aneurysm (AAA) is still unknown. The current study aimed to explore the potential role of TyG index in predicting mortality of AAA patients following endovascular aneurysm repair (EVAR).Materials and methodsThis retrospective cohort study analyzed the preoperative TyG index in a total of 188 AAA patients who underwent EVAR with the follow-up of 5 years. Data were analyzed with SPSS software Version 23.0. Association between the TyG index and all-cause mortality was evaluated using Cox regression models and Kaplan-Meier method.ResultsCox regression analyses showed that per 1-unit increment of TyG index was significantly associated with an increased risk of postoperative 30-day, 1-year, 3-year, and 5-year mortality, even after adjustment for potential confounders (all P&lt;0.05). Kaplan-Meier analysis suggested that patients with high TyG index (≥8.68) had a worse overall survival (P = 0.007).ConclusionThe elevated TyG index could be a promising predictive factor of postoperative mortality in AAA patients after EVAR.
Identification of TSGA10 and GGNBP2 splicing variants in 5′ untranslated region with distinct expression profiles in brain tumor samples
Authors: Kazerani Reihane , Salehipour Pouya , Shah Mohammadi Mohammadreza , Amanzadeh Jajin Elnaz , Modarressi Mohammad Hossein 
Published: February 2023

IntroductionBrain tumors (BTs) are perceived as one of the most common malignancies among children. The specific regulation of each gene can play a critical role in cancer progression. The present study aimed to determine the transcripts of the TSGA10 and GGNBP2 genes, considering the alternative 5′UTR region, and investigating the expression of these different transcripts in BTs.Material and methodsPublic data on brain tumor microarray datasets in GEO were analyzed with R software to evaluate the expression levels of TSGA10 and GGNBP2 genes (the Pheatmap package in R was also used to plot DEGs in a heat map). In addition, to validate our in-silico data analysis, RT-PCR was performed to determine the splicing variants of TSGA10 and GGNBP2 genes in testis and brain tumor samples. The expression levels of splice variants of these genes were analyzed in 30 brain tumor samples and two testicular tissue samples as a positive control.ResultsIn silico results show that the differential expression levels of TSGA10 and GGNBP2 were significant in the GEO datasets of BTs compared to normal samples (with adjusted p-value&lt;0.05 and log fold change &gt; 1). This study’s experimental results showed that the TSGA10 gene produces four different transcripts with two distinct promoter regions and splicing exon 4. The relative mRNA expression of transcripts without exon 4 was higher than transcripts with exon 4 in BT samples (p-value&lt;001). In GGNBP2, exon 2 in the 5′UTR region and exon 6 in the coding sequence were spliced. The expression analysis results showed that the relative mRNA expression of transcript variants without exon 2 was higher than other transcript variants with exon 2 in BT samples (p-value&lt;001).ConclusionThe decreased expression levels of transcripts with longer 5′UTR in BT samples than in testicular or low-grade brain tumor samples may decrease their translation efficiency. Therefore, decreased amounts of TSGA10 and GGNBP2 as potential tumor suppressor proteins, especially in high-grade brain tumors, may cause cancer development by angiogenesis and metastasis.
UBE2S and UBE2C confer a poor prognosis to breast cancer via downregulation of Numb
Authors: Guo Yanjing , Chen Xinyu , Zhang Xiaowei , Hu Xichun 
Published: February 2023

PurposeUbiquitin-conjugating enzymes E2S (UBE2S) and E2C (UBE2C), which mediate the biological process of ubiquitination, have been widely reported in various cancers. Numb, the cell fate determinant and tumor suppressor, was also involved in ubiquitination and proteasomal degradation. However, the interaction between UBE2S/UBE2C and Numb and their roles in the clinical outcome of breast cancer (BC) are not widely elucidated.MethodsOncomine, Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas (HPA) database, qRT-PCR, and Western blot analyses were utilized to analyze UBE2S/UBE2C and Numb expression in various cancer types and their respective normal controls, breast cancer tissues, and breast cancer cell lines. The expression of UBE2S, UBE2C, and Numb in BC patients with different ER, PR, and HER2 status, grades, stages, and survival status was compared. By Kaplan–Meier plotter, we further evaluated the prognostic value of UBE2S, UBE2C, and Numb in BC patients. We also explored the potential regulatory mechanisms underlying UBE2S/UBE2C and Numb through overexpression and knockdown experiments in BC cell lines and performed growth and colony formation assays to assess cell malignancy.ResultsIn this study, we showed that UBE2S and UBE2C were overexpressed while Numb was downregulated in BC, and in BC of higher grade, stage, and poor survival. Compared to hormone receptor negative (HR−) BC cell lines or tissues, HR+ BC demonstrated lower UBE2S/UBE2C and higher Numb, corresponding to better survival. We also showed that increased UBE2S/UBE2C and reduced Numb predicted poor prognosis in BC patients, as well as in ER+ BC patients. In BC cell lines, UBE2S/UBE2C overexpression decreased the level of Numb and enhanced cell malignancy, while knocking down UBE2S/UBE2C demonstrated the opposite effects.ConclusionUBE2S and UBE2C downregulated Numb and enhanced BC malignancy. The combination of UBE2S/UBE2C and Numb could potentially serve as novel biomarkers for BC.