bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of potential biomarkers of inflammation-related genes for ischemic cardiomyopathy
Authors: Wang Jianru , Xie Shiyang , Cheng Yanling , Li Xiaohui , Chen Jian , Zhu Mingjun 
Published: August 2022

ObjectiveInflammation plays an important role in the pathophysiology of ischemic cardiomyopathy (ICM). We aimed to identify potential biomarkers of inflammation-related genes for ICM and build a model based on the potential biomarkers for the diagnosis of ICM.Materials and methodsThe microarray datasets and RNA-Sequencing datasets of human ICM were downloaded from the Gene Expression Omnibus database. We integrated 8 microarray datasets via the SVA package to screen the differentially expressed genes (DEGs) between ICM and non-failing control samples, then the differentially expressed inflammation-related genes (DEIRGs) were identified. The least absolute shrinkage and selection operator, support vector machine recursive feature elimination, and random forest were utilized to screen the potential diagnostic biomarkers from the DEIRGs. The potential biomarkers were validated in the RNA-Sequencing datasets and the functional experiment of the ICM rat, respectively. A nomogram was established based on the potential biomarkers and evaluated via the area under the receiver operating characteristic curve (AUC), calibration curve, decision curve analysis (DCA), and Clinical impact curve (CIC).Results64 DEGs and 19 DEIRGs were identified, respectively. 5 potential biomarkers (SERPINA3, FCN3, PTN, CD163, and SCUBE2) were ultimately selected. The validation results showed that each of these five potential biomarkers showed good discriminant power for ICM, and their expression trends were consistent with the bioinformatics results. The results of AUC, calibration curve, DCA, and CIC showed that the nomogram demonstrated good performance, calibration, and clinical utility.ConclusionSERPINA3, FCN3, PTN, CD163, and SCUBE2 were identified as potential biomarkers associated with the inflammatory response to ICM. The proposed nomogram could potentially provide clinicians with a helpful tool to the diagnosis and treatment of ICM from an inflammatory perspective.
Lower ghrelin levels does not impact the metabolic benefit induced by Roux-en-Y gastric bypass
Authors: Liang Yuan , Yu Ruili , He Rui , Sun Lijun , Luo Chao , Feng Lu , Chen Hong , Yin Yue , Zhang Weizhen 
Published: August 2022

ObjectiveRoux-en-Y gastric bypass is an effective intervention for metabolic disorder. We aim to elucidate whether ghrelin contributes to weight reduction, and glycemic and lipid control after Roux-en-Y gastric bypass (RYGB).DesignFour-week-old WT and Ghrl-TSC1-/- mice were fed high fat diet for 12 weeks before surgery, and continued to be on the same diet for 3 weeks after surgery. Body weight, food intake, glycemic and lipid metabolism were analyzed before and after surgery.ResultsGastric and circulating ghrelin was significantly increased in mice with RYGB surgery. Hypoghrelinemia elicited by deletion of TSC1 to activate mTOR signaling in gastric X/A like cells demonstrated no effect on weight reduction, glycemic and lipid control induced by Roux-en-Y gastric bypass surgery.ConclusionLower ghrelin levels does not impact the metabolic benefit induced by Roux-en-Y gastric bypass.
Association of gestational hypertension and preeclampsia with offspring adiposity: A systematic review and meta-analysis
Authors: Yan Shiyu , Lyu Jinlang , Liu Zheng , Zhou Shuang , Ji Yuelong , Wang Haijun 
Published: August 2022

BackgroundThe association of gestational hypertension (GH) and preeclampsia (PE) with offspring adiposity outcomes had controversial results in different studies.ObjectiveWe conducted a systematic review and meta-analysis to evaluate the relationship between maternal GH/PE and offspring adiposity outcomes.Search strategyStudies were identified in PubMed, Embase, and Cochrane databases, with keywords including “gestational hypertension”, “preeclampsia”, “offspring”, “weight”, “cohort study”, etc., without year restriction. This study was registered with PROSPERO, CRD42022292084.Selection criteriaWe set the selection criteria for six aspects: population, outcome, time frame, study design, and availability. For the studies included in the meta-analysis, we required the potential confounders in these studies have been adjusted.Data collection and analysisTwo reviewers independently evaluated the data from the included studies. The meta-analyses included mean differences, regression coefficients, and corresponding 95% confidence intervals. Results were performed using RevMan software (version 5.4; Cochrane Collaboration). Heterogeneity among the included studies was assessed using the I2 statistic.Main resultsA total of 16 studies were included in our review, 15 of which were evaluated as high quality. In all offspring, during the early life (28 days-36 months), GH/PE exposure was found to be not or inversely associated with offspring obesity, then become positively associated at larger ages (3-19 years old). In offspring with adverse birth outcomes, the maternal GH/PE-exposed group had a lower weight in the short term (28 days to 18 months), but there was a trend of rapid weight gain as they grew older, compared with the non-exposed group. The meta-analysis showed that the BMI of the female offspring in the maternal PE-exposed group was significantly higher than that of the non-exposed offspring (MD=1.04, 95% CI: 0.67~1.42, P &lt; 0.05).ConclusionsThe systematic review suggested that maternal exposure to de novo hypertension disorders of pregnancy (HDP) was associated with obesity in offspring, extending from early childhood to adolescence. The meta-analysis showed that PE was associated with higher BMI in female offspring. More studies are needed to conduct stratified analyses by PE/GH, the severity of HDP, or gender.Systematic review registrationPROSPERO, identifier CRD42022292084.
Blood hemoglobin A1c might predict adverse differences in heart rate variability in a diabetic population: Evidence from the Midlife in the United States (MIDUS) study
Authors: Huang Ying , Chen Hong , Hu Dongxia , Wan Rong 
Published: August 2022

BackgroundCardiac autonomic neuropathy in population with diabetes mellitus (DM) is frequent and linked with high risk of cardiovascular mortality. However, studies on whether blood hemoglobin A1c (HbA1c) levels are related to adverse differences in heart rate variability (HRV) in individuals with DM are scarce.AimWe aimed to investigate the association of blood HbA1c levels with adverse differences in HRV, which is an indicator of cardiac autonomic control, in adult individuals with and without DM.MethodsData were collected from the Midlife in the United States (MIDUS) study, and 928 individuals were analyzed for the relationship between blood HbA1c levels and HRV through a cross-sectional analysis.ResultsParticipants with DM had significantly higher HRV than those without DM. The smooth curve suggested inverse relationships between blood HbA1c levels and HF- and LF-HRV seen in participants with DM but not in those without DM after controlling for all covariates (age, sex, BMI, smoking, number of drinking years and exercise). Furthermore, linear regression analysis demonstrated that elevated blood HbA1c levels did contribute to adverse differences in HF-HRV (Sβ= -0.118; 95% CI -0.208, -0.027; P=0.012) and LF-HRV (Sβ= -0.097; 95% CI -0.177, -0.017; P=0.019) after controlling for these covariates in participants with DM, while in participants without DM, blood HbA1c was not significantly related to adverse differences in HF-HRV (Sβ=0.095; 95% CI -0.059, 0.248; P=0.228) or LF-HRV (Sβ=0.043; 95% CI -0.103, 0.189; P=0.565). DM has a significant modifying effect on associations between blood HbA1c and adverse differences in HF-HRV (P for interaction=0.019) and LF-HRV (P for interaction=0.029).ConclusionsWe reported strong evidence that elevated blood levels of HbA1c were associated with adverse differences in HRV in the diabetic population but not in the nondiabetic population. This finding supported that long-term hyperglycemia is related to autonomic nerve injury in the diabetic population. Blood HbA1c might be a good indicator of cardiac autonomic neuropathy.
Novel topical esmolol hydrochloride improves wound healing in diabetes by inhibiting aldose reductase, generation of advanced glycation end products, and facilitating the migration of fibroblasts
Authors: Kulkarni Sudhir A. , Deshpande Supreet K. , Rastogi Ashu 
Published: August 2022

Aims/ObjectivesWound healing in people with diabetes is delayed secondary to impaired nitric oxide generation, advanced glycation end products (AGE), and poor migration of epithelial cells. We developed a novel topical esmolol hydrochloride (Galnobax) and assessed its efficacy for wound healing in streptozocin-induced diabetic hairless rat.MethodsAll experiments were performed at an animal laboratory and tertiary-care research facility. Ex vivo aldose reductase inhibition was assessed from enzymes obtained from a bacterial culture (spectrophotometer), sorbitol content in homogenized red blood cells, and AGE in glucose and bovine serum by fluorometry following the addition of esmolol in varying concentrations. A scratch assay of human fibroblasts, endothelial cells, and keratinocytes was assessed under a high-glucose environment and after esmolol by phase-contrast microscopy. The efficacy evaluation of the topical application of Galnobax (14 and 20%) or vehicle was conducted in streptozotocin-induced diabetic hairless rats, and endogenous nitrite and hydroxyproline from homogenized wound tissue were measured along with pharmacokinetic and dermal toxicity in Hanford miniature swine.ResultsEsmolol inhibited the formation of sorbitol by 59% in erythrocytes in comparison to glucose-induced sorbitol levels. AGE generation in bovine serum albumin was reduced at 1 mM esmolol concentrations (2.6 ± 1.7) compared with control (p &lt; 0.05) and similar to that of diclofenac (2.5 ± 1.3). Esmolol at 1 and 10 µM enhanced the migration of fibroblasts, epithelial cells, and keratinocytes compared with control. The nitric oxide levels (day 7) were 44 and 112% higher with Galnobax (14%) than those of the diabetic group (p &lt; 0.05) and the vehicle control group (p &lt; 0.05), respectively. The days 7 and 14 hydroxyproline in the wound was higher by 22 and 44% following Galnobax (14%) compared with the diabetic and vehicle control groups. The wound area exhibited better reduction with Galnobax at 14% up to day 10 follow-up compared with the controls. The pharmacokinetic and dermal toxicity in miniature swine suggested no significant adverse event with Galnobax.ConclusionsTopical esmolol hydrochloride is a novel, safe, and effective treatment modality that acts through pleotropic mechanisms to hasten wound healing in diabetes.
Causal relationships of obesity on musculoskeletal chronic pain: A two-sample Mendelian randomization study
Authors: Chen Xiaoqing , Tang Haifeng , Lin Jinding , Zeng Rongdong 
Published: August 2022

BackgroundThe association between obesity and musculoskeletal chronic pain has attracted much attention these days; however, the causal relationship between them is uncertain. Hence, this study performed a Mendelian randomization (MR) analysis to investigate the causal effects of body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) on knee pain, hip pain, and back pain.Materials and methodsThe summary data for obesity and musculoskeletal chronic pain came from the genome-wide association study datasets. Significant and independent (p &lt; 5 × 10−8; r2 &lt; 0.001, kb = 10,000) single-nucleotide polymorphisms were extracted for MR analysis. The inverse variance weighted (IVW) and other methods were used for MR analysis, while sensitivity analyses were conducted to test the reliability and stability.ResultsThe positive causal effects of BMI on knee pain (odds ratio (OR) = 1.049; 95% CI: 1.034 to 1.063; p = 9.88 × 10−12), hip pain (OR = 1.034; 95% CI: 1.024 to 1.044; p = 1.38 × 10−12), and back pain (OR = 1.022; 95% CI: 1.007 to 1.038; p = 0.004) were observed. WC and HC were also positively associated with knee pain (WC: OR = 1.057; 95% CI: 1.041 to 1.072; p = 1.54 × 10−13; HC: OR = 1.034; 95% CI: 1.017 to 1.052; p = 1.32 × 10−4) and hip pain (WC: OR = 1.031; 95% CI: 1.020 to 1.042; p = 2.61 × 10−8; HC: OR = 1.027; 95% CI: 1.018 to 1.035; p = 5.48 × 10−10) but not back pain. No causal relationship was found between WHR and musculoskeletal chronic pain. The results were robust according to sensitivity tests.ConclusionsThis study revealed that BMI was positively related to knee, hip, and back pain and that WC and HC were positively associated with knee and hip pain, while WHR was not related to any type of musculoskeletal chronic pain.
Xanthan gum as a water-based binder for P3-Na2/3Ni1/3Mn2/3O2
Authors: Zilinskaite Silvija , Reeves-McLaren Nik , Boston Rebecca 
Published: August 2022

P3-Na2/3Ni1/3Mn2/3O2 (P3-NNM) is a promising cathode material for Na-ion batteries, although large volume expansions during cycling mean that challenges around suitable binders still remain. This study reports the use of xanthan gum as a water-soluble, easy to handle, and sustainable biopolymer binder in conjunction with a P3-Na2/3Ni1/3Mn2/3O2-positive electrode material. The conditions for recovering pristine P3-NNM powders, following water-based processing, are established, and the electrochemical performance of cells prepared using the xanthan gum binder are compared to the more traditional polyvinylidene fluoride. Comparable discharge capacities are observed regardless of the binder choice, at ca. 115 mA h g−1 (77 mAh g−1 after 50 cycles; 0.1 C between 2.0 and 4.2 V). The xanthan gum binder cells also show a similar rate capability and slightly higher capacities at faster c-rates vs. polyvinylidene fluoride, making xanthan gum a viable alternative to the traditional organic binders for water-stable cathode materials.
Comprehensive analysis of nine m7G-related lncRNAs as prognosis factors in tumor immune microenvironment of hepatocellular carcinoma and experimental validation
Authors: Wang Tao , Zhou Zhijia , Wang Xuan , You Liping , Li Wenxuan , Zheng Chao , Zhang Jinghao , Wang Lingtai , Kong Xiaoni , Gao Yueqiu , Sun Xuehua 
Published: August 2022

Background: Hepatocellular carcinoma (HCC) remains the most prevalent gastrointestinal malignancy worldwide, with robust drug resistance to therapy. N7-methylguanosine (m7G) mRNA modification has been significantly related to massive human diseases. Considering the effect of m7G-modified long non-coding RNAs (lncRNAs) in HCC progression is unknown, the study aims at investigating a prognostic signature to improve clinical outcomes for patients with HCC.Methods: Two independent databases (TCGA and ICGC) were used to analyze RNAseq data of HCC patients. First, co-expression analysis was applied to obtain the m7G-related lncRNAs. Moreover, consensus clustering analysis was employed to divide HCC patients into clusters. Then, using least absolute shrinkage and selection operator-Cox regression analysis, the m7G-related lncRNA prognostic signature (m7G-LPS) was first tested in the training set and then confirmed in both the testing and ICGC sets. The expression levels of the nine lncRNAs were further confirmed via real-time PCR in cell lines, principal component analysis, and receiver operating characteristic curve. The m7G-LPS could divide HCC patients into two different risk groups with the optimal risk score. Then, Kaplan–Meier curves, tumor mutation burden (TMB), therapeutic effects of chemotherapy agents, and expressions of immune checkpoints were performed to further enhance the availability of immunotherapeutic treatments for HCC patients.Results: A total of 1465 lncRNAs associated with the m7G genes were finally selected from the TCGA database, and through the univariate Cox regression, the expression levels of 22 m7G-related lncRNAs were concerning HCC patients’ overall survival (OS). Then, the whole patients were grouped into two subgroups, and the OS in Cluster 1 was longer than that of patients in Cluster 2. Furthermore, nine prognostic m7G-related lncRNAs were identified to conduct the m7G-LPS, which were further verified. A prognostic nomogram combined age, gender, HCC grade, stage, and m7G-LPS showed strong reliability and accuracy in predicting OS in HCC patients. Finally, immune checkpoint expression, TMB, and several chemotherapy agents were remarkably associated with risk scores. More importantly, the OS of the TMB-high patients was the worst among the four groups.Conclusion: The prognostic model we established was validated by abundant algorithms, which provided a new perspective on HCC tumorigenesis and thus improved individualized treatments for patients.
Peripheral enthesitis assessed by whole-body MRI in axial spondyloarthritis: Distribution and diagnostic value
Authors: Guo Zikang , Li Boya , Zhang Yimeng , Kong Chunyu , Liu Yang , Qu Jin , Zhan Ying , Shen Zhiwei , Lei Xinwei 
Published: August 2022

ObjectiveTo determine the distribution and diagnostic value of peripheral enthesitis detected by whole-body MRI (WBMRI) in axial spondyloarthritis (axSpA) diagnosis, and to determine the value of the peripheral enthesitis score in axSpA assessment.MethodsSixty axSpA patients [mean age of 33.2 (24.8–40.6) years] and 50 controls with chronic low back pain (LBP) [mean age of 34.7 (28.3–41.1) years] were enrolled. The gold standard was physician’s comprehensive diagnosis based on current classification criteria and physical examination. All subjects underwent WBMRI, and 47 peripheral entheses were assessed for each patient with scores of 0–188.ResultsWBMRI identified 155 enthesitis sites in 78.3% (n = 47) patients with axSpA. Meanwhile, 23 enthesitis sites were identified in 32% (n = 16) controls. The pelvis had the maximum number of enthesitis sites (52, 33.5%) in axSpA patients. Pelvic and anterior chest wall enthesitis had the highest sensitivity (51.67%) and specificity (100%) in axSpA diagnosis, respectively. There were different manifestations of enthesitis subtypes between axSpA patients and the control group. Osteitis was more present than soft-tissue inflammation in axSpA patients. The AUC for the number of enthesitis sites was 0.819 (95% CI 0.739–0.899), and that for the enthesitis score was 0.833 (95% CI 0.755–0.910), indicating statistically significant differences (P = 0.025). Based on the Youden index and clinical need, three enthesitis sites (sensitivity of 53.33, specificity of 98, and Youden index of 0.51) and enthesitis score (sensitivity of 58.33, specificity of 98, and Youden index of 0.56) may have the greatest value for axSpA diagnosis.ConclusionThe distribution of peripheral enthesitis can be adequately assessed by whole-body MRI, which could help diagnose axial spondyloarthritis. The enthesitis score may provide a more accurate assessment and diagnostic tool in axSpA compared with enthesitis site counting.
Starch accumulation dynamics and transcriptome analysis of Chlorella sorokiniana during transition of sulfur nutritional status
Authors: Xu Haiqing , Yang Jinzhi , Wang Xu , Peng Qing , Han Yanxia , Liu Xudong , Liu Kexin , Dou Shijuan , Li Liyun , Liu Guozhen , Yang Ming 
Published: August 2022

Microalgae can effectively accumulate starch by using nutritional limitation methods in the context of bioalcohol fuel production. However, relatively few studies have focused on starch accumulation in microalgae and its molecular basis, especially under sulfur limitation conditions. In this study, the starch accumulation dynamics and physiological responses ofChlorella sorokinianaunder sulfur starvation (SS) and sulfur replenishment (SR) conditions were investigated, and the genes involved in the transcriptional regulation were explored using RNA-seq. The starch content inC. sorokinianacells significantly increased from 1.6% to 55.0% of dry weight within 24 h under SS conditions, and then, it decreased to 3.4% within 12 h after transition to SR conditions. However, cell growth was inhibited, and pigment content decreased under SS conditions. Using RNA-seq analysis, a total of 9720 differentially expressed genes (DEGs) induced by sulfur status were obtained. These genes were narrowed down to 454 starvation and replenishment cross-validated (SRV)-DEGs, among which 283 SRV-DEGs were significantly up-regulated and 171 SRV-DEGs were down-regulated under SS conditions, and returned to their previous state under SR conditions. The SRV-DEGs enriched in the sulfate metabolism pathway were all up-regulated under SS conditions after 6 h to speed up the sulfur metabolic cycle, and the transcriptional abundance of a sulfate transporter (SULTR4), cysteine synthase[O-acetylserine(thiol)-lyase] (OASTL), serine acetyltransferase (SAT), and methanethiol oxidase (SELENBP1) increased 8.6-fold, 12.6-fold, 8.7-fold, and 12.4-fold, respectively. Protein synthesis was correspondingly inhibited, which resulted in the reallocation of carbon and elevated the starch synthesis pathway, in which the expressions of glycogen branching enzyme (GBE) and starch synthase (SS) were up-regulated 12.0- and 3.0-fold, respectively. The fatty acid desaturase (FAD) and phosphatidic acid phosphatase (PAP) in the lipid synthesis pathway were strongly up-regulated 8.8- and 16.2-fold, respectively, indicating the competitive synthesis of lipids. The down-regulation of SRV-DEGs associated with carbon fixation, such as those in the Calvin cycle, possibly affected cell growth. The time-resolved transcriptional analysis identified the SRV-DEGs, revealing the underlying starch accumulation mechanism, as well as the relationship with cell growth and lipid synthesis.