bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of weight loss on pregnancy outcomes, neuronal-reproductive-metabolic hormones and gene expression profiles in granulosa cells in obese infertile PCOS patients undergoing IVF-ET
Authors: Wu Limin , Fang Qunying , Wang Mengli , Wang Yurui , Zhu Xinyi , Fang Zhaohui , Lu Fangting , Xu Bo , Jin Rentao , Han Hui , Tong Xianhong 
Published: September 2022

ObjectiveTo investigate the effect of weight loss on pregnancy outcomes, PCOS related neuronal-reproductive-metabolic hormones and ovarian granulosa cell gene expression profiles in obese PCOS infertile patients undergoing in vitro fertilization-embryo transfer (IVF-ET).Methods75 patients undergoing IVF-ET due to tubal factors alone collected as the control group (group A), and 352 patients with obese PCOS infertility were divided into four groups according to the amount of weight loss before IVF: 0 kg (group B), 1-5 kg (group C), 5-10 kg (group D), and &gt;10 kg (group E). Six cases of ovarian granulosa cells were collected randomly with the random number table method in each group for detecting mRNA profiling. Pathway networks and biological functions of the differentially expressed genes were analyzed. Validation by RT-PCR was performed.Results(1) The levels of luteinizing hormone(LH), testosterone(T) and homeostasis model assessment insulin resistance(HOMA-IR) in group E were significantly lower than those in groups B and C (P&lt;0.05). (2) Compared with groups A and E, groups B and C showed increased total gonadotropin (Gn) and days of Gn stimulation (P&lt;0.05), and the E2 level on trigger day and number of oocytes obtained in group B was significantly less than that in group E (P&lt;0.05 or 0.01). Embryo implantation rate, clinical pregnancy rate and live birth rate were increased and miscarriage rate was decreased in groups A, D and E compared with group B (P&lt;0.05 or 0.01). (3) There were significant differences among the control group and PCOS groups in some genes that are involved in neuronal-reproductive-metabolic endocrine, transcriptional regulation, cell proliferation and differentiation, etc (P&lt;0.05). RNA-Seq results were validated by real time PCR analysis for the expression of follicle stimulating hormone receptor (FSHR), drosophila mothers against decapentaplegic protein 7(Smad7) and glutathione peroxidase 3(GPX3) genes that are known to have an important role in follicular development. Functional alterations were confirmed by the improvement in the ovarian responsiveness to Gn and embryo quality.ConclusionWeight loss more than 5kg may regulate the neuroreproductive endocrine hormone secretion, insulin resistance and gene expression profiles of ovarian granulosa cells, so as to improve the ovarian responsiveness to Gn, the embryo quality, embryo implantation rate, clinical pregnancy rate, live birth rate, and reduce the spontaneous abortion rate in obese infertile PCOS patients undergoing IVF-ET.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR1800018298.
Renal fat fraction is significantly associated with the risk of chronic kidney disease in patients with type 2 diabetes
Authors: Shen Yan , Xie Lianghua , Chen Xiangjun , Mao Lina , Qin Yao , Lan Rui , Yang Shumin , Hu Jinbo , Li Xue , Ye Hanwen , Luo Wenjin , Gong Lilin , Li Qifu , Mao Yun , Wang Zhihong 
Published: September 2022

BackgroundsEctopic fat deposition is closely related to chronic kidney disease (CKD). Currently, there are few population studies that have been conducted to determine the relationship between renal parenchyma fat deposition and the risk of CKD among patients with type 2 diabetes mellitus (T2DM). Therefore, we employed magnetic resonance imaging (MRI) to detect renal parenchyma fat content in individuals with T2DM, expressed as renal fat fraction (FF), to explore whether renal FF is an important risk factor for CKD in patients with T2DM.MethodsIn this cross-sectional study, 189 subjects with T2DM were enrolled. CKD was defined as the estimated glomerular filtration rate (eGFR)&lt;60 mL/min/1.73m2. Measurement of the renal FF was performed on a 3.0-T MRI (MAGNETOM Skyra, Siemens, Erlangen, Germany). Binary logistic regression was used to determine the association between tertiles of renal FF and risk of CKD. Receiver-operator characteristic (ROC) curves were constructed to evaluate the sensitivity and specificity of renal FF in detecting CKD in T2DM patients.ResultsThe patients were divided into three groups according to tertiles of the renal FF level (2.498 - 7.434). As renal FF increases, patients tend to be older, and more abdominally obese, with a decreased eGFR (p&lt;0.05). After adjustment for potential confounders, patients in the highest tertile of renal FF had a significantly increased risk of CKD than those in the lowest tertile (odds ratio (OR) = 3.98, 95% confidence interval (CI) = 1.12 - 14.09, p = 0.032), and the area under the ROC curve for this model was 0.836 (0.765–0.907).ConclusionsThe renal FF is significantly independently associated with CKD in patients with T2DM.
Development of a clinically validated in vitro functional assay to assess pathogenicity of novel GAA variants in patients with Pompe disease identified via newborn screening
Authors: Goomber Shelly , Huggins Erin , Rehder Catherine W. , Cohen Jennifer L. , Bali Deeksha S. , Kishnani Priya S. 
Published: September 2022

Purpose: The addition of Pompe disease (Glycogen Storage Disease Type II) to the Recommended Uniform Screening Panel in the United States has led to an increase in the number of variants of uncertain significance (VUS) and novel variants identified in the GAA gene. This presents a diagnostic challenge, especially in the setting of late-onset Pompe disease when symptoms are rarely apparent at birth. There is an unmet need for validated functional studies to aid in classification of GAA variants. Methods: We developed an in vitro mammalian cell expression and functional analysis system based on guidelines established by the Clinical Genome Resource (ClinGen) Sequence Variant Interpretation Working Group for PS3/BS3. We validated the assay with 12 control variants and subsequently analyzed eight VUS or novel variants in GAA identified in patients with a positive newborn screen for Pompe disease without phenotypic evidence of infantile-onset disease.Results: The control variants were analyzed in our expression system and an activity range was established. The pathogenic controls had GAA activity between 0% and 11% of normal. The benign or likely benign controls had an activity range of 54%–100%. The pseudodeficiency variant had activity of 17%. These ranges were then applied to the variants selected for functional studies. Using the threshold of &lt;11%, we were able to apply PS3_ supporting to classify two variants as likely pathogenic (c.316C &gt; T and c.1103G &gt; A) and provide further evidence to support the classification of likely pathogenic for two variants (c.1721T &gt; C and c.1048G &gt; A). One variant (c.1123C &gt; T) was able to be reclassified based on other supporting evidence. We were unable to reclassify three variants (c.664G &gt; A, c.2450A &gt; G, and c.1378G &gt; A) due to insufficient or conflicting evidence.Conclusion: We investigated eight GAA variants as proof of concept using our validated and reproducible in vitro expression and functional analysis system. While additional work is needed to further refine our system with additional controls and different variant types in order to apply the PS3/BS3 criteria at a higher level, this tool can be utilized for variant classification to meet the growing need for novel GAA variant classification in the era of newborn screening for Pompe disease.
Identification and validation of an inflammation-related lncRNAs signature for improving outcomes of patients in colorectal cancer
Authors: Huang Mengjia , Ye Yuqing , Chen Yi , Zhu Junkai , Xu Li , Cheng Wenxuan , Lu Xiaofan , Yan Fangrong 
Published: September 2022

Background: Colorectal cancer is the fourth most deadly cancer worldwide. Although current treatment regimens have prolonged the survival of patients, the prognosis is still unsatisfactory. Inflammation and lncRNAs are closely related to tumor occurrence and development in CRC. Therefore, it is necessary to establish a new prognostic signature based on inflammation-related lncRNAs to improve the prognosis of patients with CRC.Methods: LASSO-penalized Cox analysis was performed to construct a prognostic signature. Kaplan-Meier curves were used for survival analysis and ROC curves were used to measure the performance of the signature. Functional enrichment analysis was conducted to reveal the biological significance of the signature. The R package “maftool” and GISTIC2.0 algorithm were performed for analysis and visualization of genomic variations. The R package “pRRophetic”, CMap analysis and submap analysis were performed to predict response to chemotherapy and immunotherapy.Results: An effective and independent prognostic signature, IRLncSig, was constructed based on sixteen inflammation-related lncRNAs. The IRLncSig was proved to be an independent prognostic indicator in CRC and was superior to clinical variables and the other four published signatures. The nomograms were constructed based on inflammation-related lncRNAs and detected by calibration curves. All samples were classified into two groups according to the median value, and we found frequent mutations of the TP53 gene in the high-risk group. We also found some significantly amplificated regions in the high-risk group, 8q24.3, 20q12, 8q22.3, and 20q13.2, which may regulate the inflammatory activity of cancer cells in CRC. Finally, we identified chemotherapeutic agents for high-risk patients and found that these patients were more likely to respond to immunotherapy, especially anti-CTLA4 therapy.Conclusion: In short, we constructed a new signature based on sixteen inflammation-related lncRNAs to improve the outcomes of patients in CRC. Our findings have proved that the IRLncSig can be used as an effective and independent marker for predicting the survival of patients with CRC.
Gene-specific machine learning model to predict the pathogenicity of BRCA2 variants
Authors: Khandakji Mohannad N. , Mifsud Borbala 
Published: September 2022

Background: Existing BRCA2-specific variant pathogenicity prediction algorithms focus on the prediction of the functional impact of a subtype of variants alone. General variant effect predictors are applicable to all subtypes, but are trained on putative benign and pathogenic variants and do not account for gene-specific information, such as hotspots of pathogenic variants. Local, gene-specific information have been shown to aid variant pathogenicity prediction; therefore, our aim was to develop a BRCA2-specific machine learning model to predict pathogenicity of all types of BRCA2 variants.Methods: We developed an XGBoost-based machine learning model to predict pathogenicity of BRCA2 variants. The model utilizes general variant information such as position, frequency, and consequence for the canonical BRCA2 transcript, as well as deleteriousness prediction scores from several tools. We trained the model on 80% of the expert reviewed variants by the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium and tested its performance on the remaining 20%, as well as on an independent set of variants of uncertain significance with experimentally determined functional scores.Results: The novel gene-specific model predicted the pathogenicity of ENIGMA BRCA2 variants with an accuracy of 99.9%. The model also performed excellently on predicting the functional consequence of the independent set of variants (accuracy was up to 91.3%).Conclusion: This new, gene-specific model is an accurate method for interpreting the pathogenicity of variants in the BRCA2 gene. It is a valuable addition for variant classification and can prioritize unreviewed variants for functional analysis or expert review.
Aberrant lncRNA–mRNA expression profile and function networks during the adipogenesis of mesenchymal stem cells from patients with ankylosing spondylitis
Authors: Cen Shuizhong , Cai Mingxi , Wang Yihan , Lu Xiuyi , Chen Zhipeng , Chen Haobo , Fang Yingdong , Wu Changping , Qiu Sujun , Liu Zhenhua 
Published: September 2022

Objective: We have already demonstrated that mesenchymal stem cells from patients with ankylosing spondylitis (ASMSCs) exhibited greater adipogenic differentiation potential than those from healthy donors (HDMSCs). Here, we further investigated the expression profile of long noncoding RNA (lncRNA) and mRNA, aiming to explore the underlying mechanism of abnormal adipogenic differentiation in ASMSCs.Methods: HDMSCs and ASMSCs were separately isolated and induced with adipogenic differentiation medium for 10 days. Thereafter, lncRNAs and mRNAs that were differentially expressed (DE) between HDMSCs and ASMSCs were identified via high-throughput sequencing and confirmed by quantitative real-time PCR (qRT–PCR) assays. Then, the DE genes were annotated and enriched by GO analysis. In addition, protein interaction network was constructed to evaluate the interactions between DE mRNAs and to find hub nodes and study cliques. Besides, co-expression network analysis was carried out to assess the co-expressions between DE mRNA and DE lncRNAs, and competing endogenous RNA (ceRNA) network analysis were conducted to predict the relationships among lncRNAs, mRNAs and miRNAs. The signaling pathways based on the DE genes and the predicted DE genes were enriched by KEGG analysis.Results: A total of 263 DE lncRNAs and 1376 DE mRNAs were found during adipogenesis in ASMSCs. qRT–PCR indicated that the expression of the top 20 mRNAs and the top 10 lncRNAs was consistent with the high-throughput sequencing data. Several lncRNAs (NR_125386.1, NR_046473.1 and NR_038937.1) and their target genes (SPN and OR1AIP2), together with the significantly co-expressed pairs of DE lncRNAs and DE mRNAs (SLC38A5-ENST00000429588.1, TMEM61-ENST00000400755.3 and C5orf46-ENST00000512300.1), were closely related to the enhanced adipogenesis of ASMSCs by modulating the PPAR signaling pathway.Conclusion: Our study analyzed the expression profiles of DE lncRNAs and DE mRNAs during adipogenesis in ASMSCs and HDMSCs. Several DE lncRNAs, DE mRNAs and signaling pathways that probably participate in the aberrant adipogenesis of ASMSCs were selected for future study. These results will likely provide potential targets for our intervention on fat metaplasia and subsequent new bone formation in patients with AS in the future.
Phosphate and IL-10 concentration as predictors of long-covid in hemodialysis patients: A Brazilian study
Authors: Corrêa Hugo L. , Deus Lysleine A. , Araújo Thaís B. , Reis Andrea L. , Amorim Carlos E. N. , Gadelha André B. , Santos Rafael L. , Honorato Fernando S. , Motta-Santos Daisy , Tzanno-Martins Carmen , Neves Rodrigo V. P. , Rosa Thiago S. 
Published: September 2022

BackgroundThe global burden of persistent COVID-19 in hemodialysis (HD) patients is a worrisome scenario worth of investigation for the critical care of chronic kidney disease (CKD). We performed an exploratory post-hoc study from the trial U1111-1237-8231 with two specific aims: i) to investigate the prevalence of COVID-19 infection and long COVID symptoms from our Cohort of 178 Brazilians HD patients. ii) to identify whether baseline characteristics should predict long COVID in this sample.Methods247 community-dwelling older (&gt;60 years) patients (Men and women) undergoing HD (glomerular filtration rate &lt; 15 mL/min/1.73m2) with arteriovenous fistula volunteered for this study. All patients presented hypertension and diabetes. Patients were divided in two groups: without long-COVID and with long-COVID. Body composition, handgrip strength, functional performance, iron metabolism, phosphate, and inflammatory profile were assessed. Patients were screened for 11-months after COVID-19 infection. Results were considered significant at P &lt; 0.05.ResultsWe found that more than 85% of the COVID-19 infected patients presented a severe condition during the infection. In our sample, the mortality rate over 11-month follow was relatively low (8.4%) when compared to worldwide (approximately 36%). Long COVID was highly prevalent in COVID-19 survivors representing more than 80% of all cases. Phosphate and IL-10 were higher in the long COVID group, but only phosphate higher than 5.35 mg/dL appears to present an increased prevalence of long COVID, dyspnea, and fatigue.ConclusionThere was a high prevalence of COVID-19 infection and long COVID in HD patients from the Brazilian trial ‘U1111-1237-8231’. HD clinics should be aware with phosphate range in HD patients as a possible target for adverse post-COVID events.
Metabolic-related gene pairs signature analysis identifies ABCA1 expression levels on tumor-associated macrophages as a prognostic biomarker in primary IDHWT glioblastoma
Authors: Wang Shiqun , Li Lu , Zuo Shuguang , Kong Lingkai , Wei Jiwu , Dong Jie 
Published: September 2022

BackgroundAlthough isocitrate dehydrogenase (IDH) mutation serves as a prognostic signature for routine clinical management of glioma, nearly 90% of glioblastomas (GBM) patients have a wild-type IDH genotype (IDHWT) and lack reliable signatures to identify distinct entities.MethodsTo develop a robust prognostic signature for IDHWT GBM patients, we retrospectively analyzed 4 public datasets of 377 primary frozen tumor tissue transcriptome profiling and clinical follow-up data. Samples were divided into a training dataset (204 samples) and a validation (173 samples) dataset. A prognostic signature consisting of 21 metabolism-related gene pairs (MRGPs) was developed based on the relative ranking of single-sample gene expression levels. GSEA and immune subtype analyses were performed to reveal differences in biological processes between MRGP risk groups. The single-cell RNA-seq dataset was used to examine the expression distribution of each MRG constituting the signature in tumor tissue subsets. Finally, the association of MRGs with tumor progression was biologically validated in orthotopic GBM models.ResultsThe metabolic signature remained an independent prognostic factor (hazard ratio, 5.71 [3.542-9.218], P &lt; 0.001) for stratifying patients into high- and low-risk levels in terms of overall survival across subgroups with MGMTp methylation statuses, expression subtypes, and chemo/ratio therapies. Immune-related biological processes were significantly different between MRGP risk groups. Compared with the low-risk group, the high-risk group was significantly enriched in humoral immune responses and phagocytosis processes, and had more monocyte infiltration and less activated DC, NK, and γδ T cell infiltration. scRNA-seq dataset analysis identified that the expression levels of 5 MRGs (ABCA1, HMOX1, MTHFD2, PIM1, and PTPRE) in TAMs increased with metabolic risk. With tumor progression, the expression level of ABCA1 in TAMs was positively correlated with the population of TAMs in tumor tissue. Downregulation of ABCA1 levels can promote TAM polarization towards an inflammatory phenotype and control tumor growth.ConclusionsThe metabolic signature is expected to be used in the individualized management of primary IDHWT GBM patients.
Long non-coding RNA NBAT1, TUG1, miRNA-335, and miRNA-21 as potential biomarkers for acute ischemic stroke and their possible correlation to thyroid hormones
Authors: Mohammed Asmaa , Shaker Olfat G. , Khalil Mahmoud A. F. , Gomaa Mohammed , Fathy Shaimaa A. , Abu-El-Azayem Abeer K. , Samy Amira , Aboelnor Mahmoud I. , Gomaa Mohamed S. , Zaki Othman M. , Erfan Randa 
Published: September 2022

Objective: RNA-based mechanisms of epigenetic modification related to acute ischemic stroke (AIS) have been widely studied recently. The current work aimed to determine the potential roles of four ncRNAs (TUG1 and its target miR-21, NBAT1, and miR-335) as promising diagnostic biomarkers in AIS as well as their involvement in the disease pathogenesis.Methods: The levels of the studied lncRNAs and miRNAs were measured in the serum for two different groups, including patients with AIS (60) and healthy controls (60). All individuals were subjected to a full history investigation and clinical examination. Blood samples were tested for FBS, 2HPP, TAG, HDL, LDL, TSH, T3, and T4 levels.Results: The serum levels of TUG1 were significantly increased in AIS patients compared to control subjects. It is worthwhile to note that serum TUG1 levels were positively correlated with cholesterol, triglycerides, LDL, carotid IMT (Intima-media thickness), and miR-21, while they were negatively correlated with HDL levels. Our study showed that NBAT1 serum expression levels were elevated in AIS patients compared to controls. NBAT1 expression levels were observed to be positively correlated with triglycerides, TUG1, and miR-21. NBAT1 could distinguish between AIS patients and controls with a sensitivity of 100% and specificity of 100% at a cut-off point of 1.45. Regarding miR-335, we found that its expression levels were downregulated in AIS patients compared with healthy controls. It could distinguish between AIS patients and controls with a sensitivity of 73.3% and a specificity of 100% at a cut-off point of 0.796.Conclusion: Our results revealed that serum TUG1, miR-21, NBAT1, and miR-335 could be promising molecular diagnostic markers for AIS as these biomarkers could discriminate between AIS patients and healthy controls.
Impaired ankle inversion proprioception during walking is associated with fear of falling in older adults
Authors: Shao Xuerong , Wang Zheng , Luan Lijiang , Sheng Yilan , Yu Ruoni , Pranata Adrian , Adams Roger , Zhang Anren , Han Jia 
Published: September 2022

BackgroundAnkle proprioception plays a critical role in lower limb movement control. However, the relationship between ankle proprioception and fear of falling (FOF) in older people is still unclear.Objective(1) This study aims to develop a new device for measuring ankle inversion proprioceptive discrimination sensitivity during walking, i.e., the Ankle Inversion Discrimination Apparatus–Walking (AIDAW), and assess the test–retest reliability of the AIDAW in both young and older adults; (2) to evaluate the discriminant validity of the measure by comparing ankle proprioception during walking between the two groups; and (3) to explore convergent validity by determining to what extent the AIDAW proprioceptive scores correlate with Fall Efficacy Scale-International (FES-I) scores.Materials and methodsThe AIDAW was purpose-built to test ankle inversion proprioceptive discrimination sensitivity during walking. The area under the receiver operating curve (AUC) was calculated as the proprioceptive discrimination score. In total, 54 adults volunteered. Test–retest reliability was evaluated in 12 young and 12 older adults, and another 15 young and 15 older adults completed the comparison study. FOF was assessed by using the FES-I.ResultsThe test–retest reliability intraclass correlation coefficient ICC (3,1) value for the whole group was 0.76 (95% CI: 0.52–0.89). The ICC values of the young and older groups were 0.81 (95% CI: 0.46–0.94) and 0.71 (95% CI: 0.26–0.91), respectively. The Minimal Detectable Change with 90% confidence (MDC90) values for the young and older groups were 0.03 and 0.11, respectively. There was a significant difference between the AIDAW proprioceptive sensitivity scores for the young and older groups (0.78 ± 0.04 vs. 0.72 ± 0.08, F = 5.06, p = 0.033). Spearman’s correlation analysis showed that the FES-I scores were significantly and negatively correlated with the AIDAW scores (rho = −0.61, p = 0.015), with higher FOF associated with worse ankle proprioception.ConclusionThe AIDAW is a reliable and valid device for measuring ankle proprioception during walking in both young and older adults. Ankle inversion proprioceptive discrimination sensitivity during walking was found to be impaired in the elderly compared to young adults. This impairment was found to be strongly associated with FOF, suggesting that assessment and intervention for ankle proprioception in this population are needed to reduce the risk of falls.