bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning identifies exosome features related to hepatocellular carcinoma
Authors: Zhu Kai , Tao Qiqi , Yan Jiatao , Lang Zhichao , Li Xinmiao , Li Yifei , Fan Congcong , Yu Zhengping 
Published: September 2022

Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors with a poor prognosis. There is still a lack of effective biomarkers to predict its prognosis. Exosomes participate in intercellular communication and play an important role in the development and progression of cancers.Methods: In this study, two machine learning methods (univariate feature selection and random forest (RF) algorithm) were used to select 13 exosome-related genes (ERGs) and construct an ERG signature. Based on the ERG signature score and ERG signature-related pathway score, a novel RF signature was generated. The expression of BSG and SFN, members of 13 ERGs, was examined using real-time quantitative polymerase chain reaction and immunohistochemistry. Finally, the effects of the inhibition of BSG and SFN on cell proliferation were examined using the cell counting kit-8 (CCK-8) assays.Results: The ERG signature had a good predictive performance, and the ERG score was determined as an independent predictor of HCC overall survival. Our RF signature showed an excellent prognostic ability with the area under the curve (AUC) of 0.845 at 1 year, 0.811 at 2 years, and 0.801 at 3 years in TCGA, which was better than the ERG signature. Notably, the RF signature had a good performance in the prediction of HCC prognosis in patients with the high exosome score and high NK score. Enhanced BSG and SFN levels were found in HCC tissues compared with adjacent normal tissues. The inhibition of BSG and SFN suppressed cell proliferation in Huh7 cells.Conclusion: The RF signature can accurately predict prognosis of HCC patients and has potential clinical value.
Coronary artery disease risk factors affected by RNA modification-related genetic variants
Authors: Li Ru , Zhang Huan , Tang Fan , Duan Chengcheng , Liu Dan , Wu Naqiong , Zhang Yonghong , Wang Laiyuan , Mo Xingbo 
Published: September 2022

BackgroundSingle nucleotide polymorphisms that affect RNA modification (RNAm-SNPs) may have functional roles in coronary artery disease (CAD). The aim of this study was to identify RNAm-SNPs in CAD susceptibility loci and highlight potential risk factors.MethodsCAD-associated RNAm-SNPs were identified in the CARDIoGRAMplusC4D and UK Biobank genome-wide association studies. Gene expression and circulating protein levels affected by the RNAm-SNPs were identified by QTL analyses. Cell experiments and Mendelian randomization (MR) methods were applied to test whether the gene expression levels were associated with CAD.ResultsWe identified 81 RNAm-SNPs that were associated with CAD or acute myocardial infarction (AMI), including m6A-, m1A-, m5C-, A-to-I- and m7G-related SNPs. The m6A-SNPs rs3739998 in JCAD, rs148172130 in RPL14 and rs12190287 in TCF21 and the m7G-SNP rs186643756 in PVT1 were genome-wide significant. The RNAm-SNPs were associated with gene expression (e.g., MRAS, DHX36, TCF21, JCAD and SH2B3), and the expression levels were associated with CAD. Differential m6A methylation and differential expression in FTO-overexpressing human aorta smooth muscle cells and peripheral blood mononuclear cells of CAD patients and controls were detected. The RNAm-SNPs were associated with circulating levels of proteins with specific biological functions, such as blood coagulation, and the proteins (e.g., cardiotrophin-1) were confirmed to be associated with CAD and AMI in MR analyses.ConclusionThe present study identified RNAm-SNPs in CAD susceptibility genes, gene expression and circulating proteins as risk factors for CAD and suggested that RNA modification may play a role in the pathogenesis of CAD.
Confirmation of human ovulation in assisted reproduction using an adhesive axillary thermometer (femSense®)
Authors: Weiss Gregor , Strohmayer Karl , Koele Werner , Reinschissler Nina , Schenk Michael 
Published: September 2022

ObjectiveTiming for sexual intercourse is important in achieving pregnancy in natural menstrual cycles. Different methods of detecting the fertile window have been invented, among them luteinization hormone (LH) to predict ovulation and biphasic body basal temperature (BBT) to confirm ovulation retrospectively. The gold standard to detect ovulation in gynecology practice remains transvaginal ultrasonography in combination with serum progesterone. In this study we evaluated a wearable temperature sensing patch (femSense®) using continuous body temperature measurement to confirm ovulation and determine the end of the fertile window.Methods96 participants received the femSense® system consisting of an adhesive axillary thermometer patch and a smartphone application, where patients were asked to document information about their previous 3 cycles. Based on the participants data, the app predicted the cycle length and the estimated day of ovulation. From these predictions, the most probable fertile window and the day for applying the patch were derived. Participants applied and activated the femSense® patch on the calculated date, from which the patch continuously recorded their body temperature throughout a period of up to 7 days to confirm ovulation. Patients documented their daily urinary LH test positivity, and a transvaginal ultrasound was performed on day cycle day 7, 10, 12 and 14/15 to investigate the growth of one dominant follicle. If a follicle reached 15 mm in diameter, an ultrasound examination was carried out every day consecutively until ovulation. On the day ovulation was detected, serum progesterone was measured to confirm the results of the ultrasound. The performance of femSense® was evaluated by comparing the day of ovulation confirmation with the results of ovulation prediction (LH test) and detection (transvaginal ultrasound).ResultsThe femSense® system confirmed ovulation occurrence in 60 cases (81.1%) compared to 48 predicted cases (64.9%) with the LH test (p = 0.041). Subgroup analysis revealed a positive trend for the femSense® system of specific ovulation confirmation within the fertile window of 24 h after ovulation in 42 of 74 cases (56.8%). Cycle length, therapy method or infertility reason of the patient did not influence accuracy of the femSense® system.ConclusionsThe femSense® system poses a promising alternative to the traditional BBT method and is a valuable surrogate marker to transvaginal ultrasound for confirmation of ovulation.
Genetic testing of sperm donors at a human sperm bank in China
Authors: Huang Chuan , Wu Hui-Lan , Zhou Wen-Jun , Huang Zeng-Hui , Luo Xue-Feng , Tang Yu-Ling , Liu Qian , Fan Li-Qing , Nie Hong-Chuan , Zhu Wen-Bing 
Published: September 2022

BackgroundIn China, numerous human sperm banks only perform three-generation family history evaluation to exclude genetic diseases with clinical symptoms; therefore, many inherited risks cannot be detected before donor qualification even when a thorough genetic family history evaluation has been performed. Hence, the risk of recessive disease inheritance persists with the current eligibility guidelines in China regarding the donor selection process.MethodsRetrospective study that reviewed the genetic test analyses and clinical outcomes of young adult men who were qualified sperm donors at the Hunan Province Human Sperm Bank of China from January 1, 2018, to May 1, 2021. We included a total of 3231 qualified sperm donors: all donors underwent primary screening for thalassemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Whereafter, 278 of donors underwent genetic testing for specific genes, and 43 donors underwent whole exome sequencing.Results2.4% of 3231 qualified sperm donors might have thalassemia and 1.4% might have G6PD deficiency. Sperm donors with thalassemia and G6PD deficiency would be eliminated. Specific gene testing identified 7 of the 278 donors (2.5%) as carriers of at least one pathogenic or likely pathogenic variant in a gene, including 1.9% of 154 donors (3/154) as carrier variants in α-Like or β-Like globin genes, 17.6% of 17 donors (3/17) as carrier variants in GJB2, 12.5% of 8 donors (1/8) as carrier variants in SMN1. In addition, among the 43 sperm donors carrying the 111 pathogenic/likely pathogenic variants, eight (18.6%) were carriers of pathogenic variants of the GJB2 gene. The frequency, therefore, was approximately 1 in 5.ConclusionsThe data suggest that used blood routine and RDT can make a preliminary screening of sperm donors, and special gene testing should be performed for sperm donors according to the regional incidence of specific genetic diseases. Meanwhile, whole exome sequencing can be used as a supplementary application in sperm donor genetic testing, and aid a successful and healthy pregnancy. However, industry guidelines must be modified to incorporate its use.
Development and validation of a novel diagnostic tool for predicting the malignancy probability of thyroid nodules: A retrospective study based on clinical, B-mode, color doppler and elastographic ultrasonographic characteristics
Authors: Xu Shangyan , Ni Xiaofeng , Zhou Wei , Zhan Weiwei , Zhang Huan 
Published: September 2022

BackgroundClinicians estimate the risk of thyroid nodules and make subsequently decision on the basis of clinical and ultrasonographic findings. Currently, there is no comprehensive diagnostic tool for predicting the malignancy rates of thyroid nodules. Our aim was to develop and validate a novel integrate diagnostic tool for predicting the malignancy probability of thyroid nodules based on clinical, B-mode, Color Doppler and elastographic ultrasonographic characteristics.MethodsA total of 1016 nodules in 1016 patients who underwent thyroid ultrasonography and surgery from July 2021 to December 2021 were included in this retrospective study. All nodules were confirmed by pathology and randomly classified into the training and validation groups. Clinical, B-mode, Color Doppler and elastographic (CBCE) ultrasonographic characteristics of nodules were recorded. Univariate and multivariate analyses were performed to screen independent predictors associated with thyroid cancer. A multivariate model containing the extracted predictors was constructed and presented in the form of a nomogram. The validation and applicability of the CBCE nomogram was evaluated using the receiver operating characteristic (ROC) curve. Diagnostic performances were calculated to compare the CBCE nomogram with ACR-TIRADS (Thyroid Imaging Reporting Data System by American College of Radiology) and EU-TIRADS (Thyroid Imaging Reporting Data System by European Thyroid Association).ResultsThe following factors were included in the CBCE nomogram: patient gender, age, shape, margin, composition and echogenicity, calcification, vascularization distribution, vascularization degree, suspicious lymph node metastases and elastography. The area under the curve (AUC) values were 0.978 and 0.983 for the training and validation groups, respectively. Compared with ACR-TIRADS and EU-TIRADS, the CBCE nomogram showed improved accuracy (0.944) and specificity (0.913) without sacrificing sensitivity (0.963) and showed the highest AUC with an optimal cutoff value of 0.55.ConclusionThe CBCE nomogram has good and high clinical practicability in predicting the malignancy probability of thyroid nodules.
Effectiveness of core needle biopsy in the diagnosis of thyroid lymphoma and anaplastic thyroid carcinoma: A systematic review and meta-analysis
Authors: Vander Poorten Vincent , Goedseels Nathan , Triantafyllou Asterios , Sanabria Alvaro , Clement Paul M. , Cohen Oded , Golusinski Pawel , Guntinas-Lichius Orlando , Piazza Cesare , Randolph Gregory W. , Rinaldo Alessandra , Ronen Ohad , Cabanillas Maria E. , Shaha Ashok R. , Teng Yong , Tufano Ralph P. , Williams Michelle D. , Zafereo Mark , Ferlito Alfio 
Published: September 2022

BackgroundBoth anaplastic thyroid carcinoma (ATC) and thyroid lymphoma (TL) clinically present as rapidly enlarging neck masses. Unfortunately, in this situation, like in any other thyroid swelling, a routine fine-needle aspiration (FNA) cytology is the first and only diagnostic test performed at the initial contact in the average thyroid practice. FNA, however, has a low sensitivity in diagnosing ATC and TL, and by the time the often “inconclusive” result is known, precious time has evolved, before going for core-needle biopsy (CNB) or incisional biopsy (IB) as the natural next diagnostic steps.ObjectivesTo determine the diagnostic value of CNB in the clinical setting of a rapidly enlarging thyroid mass, via a systematic review and meta-analysis of the available data on CNB reliability in the differential diagnosis of ATC and TL.MethodsA PubMed, Embase and Web of Science database search was performed on June 23th 2021. Population of interest comprised patients who underwent CNB for clinical or ultrasonographical suspicion of ATC or TL, patients with a final diagnosis of ATC or TL after CNB, or after IB following CNB.ResultsFrom a total of 17 studies, 166 patients were included. One hundred and thirty-six were diagnosed as TL and 14 as ATC following CNB. CNB, with a sensitivity and positive predictive value of 94,3% and 100% for TL and 80,1% and 100% for ATC respectively, proved to be superior to FNA (reported sensitivity for TL of 48% and for ATC of 61%). Furthermore, the need for additional diagnostic surgery after CNB was only 6.2% for TL and 17.6% for ATC.ConclusionsImmediately performing CNB for a suspected diagnosis of ATC and TL in a rapidly enlarging thyroid mass is more appropriate and straightforward than a stepped diagnostic pathway using FNA first and awaiting the result before doing CNB.
Quantitative assessment of lumbar spine bone marrow in patients with different severity of CKD by IDEAL-IQ magnetic resonance sequence
Authors: Xiong Yan , He Tongxiang , Liu Weiyin Vivian , Zhang Yao , Hu Shuang , Wen Donglin , Wang Yanan , Zhang Peisen , He Fan , Li Xiaoming 
Published: September 2022

BackgroundChronic kidney disease (CKD) has a significant negative impact on bone health. Bone marrow is an essential component of bone, mainly composed of trabecular bone and fat. The IDEAL-IQ sequence of MRI allows indirect quantification of trabecular bone mass by R2* and direct quantification of bone marrow fat content by FF map, respectively.ObjectiveOur objective was to explore the association of CKD severity with bone marrow using IDEAL-IQ and whether mineral and bone metabolism markers alter this association.MethodWe recruited 68 CKD patients in this cross-sectional research (15 with CKD stages 3-4, 26 with stage 5, and 27 with stage 5d). All patients underwent lumbar spine IDEAL-IQ, BMD, and several bone metabolism markers (iPTH, 25-(OH)-VitD, calcium and phosphorus). Multiple linear regression analysis was used to examine the association of CKD severity with MRI measurements (R2* and FF).ResultsMore severe CKD was associated with a higher R2* value [CKD 5d versus 3-4: 30.077 s-1 (95% CI: 12.937, 47.217), P for trend &lt; 0.001], and this association was attenuated when iPTH was introduced [CKD 5d versus 3-4: 19.660 s-1 (95% CI: 0.205, 39.114), P for trend = 0.042]. Furthermore, iPTH had an association with R2* value [iPTH (pg/mL): 0.033 s-1 (95% CI: 0.001, 0.064), P = 0.041]. Besides, FF was mainly affected by age and BMI, but not CKD.ConclusionsThe bone marrow R2* value measured by IDEAL-IQ sequence is associated with CKD severity and iPTH. The R2* of IDEAL-IQ has the potential to reflect lumbar bone changes in patients with CKD.
Trends in hospital admissions for adrenal insufficiency in adolescents and young adults in the 21st century
Authors: Chrisp Georgina L. , Quartararo Maria , Torpy David J. , Falhammar Henrik , Rushworth R. Louise 
Published: September 2022

BackgroundVery little is known about the epidemiology of adrenal crises (AC) and adrenal insufficiency (AI) in adolescents and young adults.MethodsData on all admissions to Australian hospitals between 2000/1 to 2019/20 for a principal diagnosis of AI (including AC) in 10-24 year olds were extracted from a national repository. Age and sex-specific rates and age-adjusted rates were compared.FindingsOver the study, there were 3386 admissions for a principal diagnosis of AI; 24.0% (n=812) were for an AC and 50·7% (n=1718) were for secondary AI. Age-adjusted AI admissions increased from 31·70/million in 2000/1 to 54·68/million in 2019/20 (p&lt;0·0001). Age-adjusted AC admissions also increased, most notably in the second decade (from 5·80/million in 2010/11 to 15·75/million in 2019/20) (p&lt;0·00001). Average AI and AC admission rates were comparable between the sexes, but rates increased significantly in females, especially in those aged 20 to 24 years, whose AC rate in 2019/20 (39·65/million) was significantly higher than the corresponding rate in 2000/1 (3·15/million) (p&lt;0·00001). Average age-adjusted SAI admission rates were higher in males (23·92/million) than females (15·47/million) (p&lt;0·00001). However, SAI admission rates increased only among females (from 11·81/million to 22·12/million in 2019/20), with an increase in 20-24 year old females in the second decade from 5·07/million in 2010 to 20·42/million (p&lt;0·00001). Age adjusted admissions for congenital adrenal hyperplasia, primary AI (PAI) and drug-induced AI did not change significantly over the study.InterpretationAC/AI admissions increased over the first two decades of this century in the emerging adult population, particularly among females who also experienced a marked increase in AC admission rates, most evident in the second decade. Although uncertain, possible explanations include: dose of glucocorticoid replacement; non-adherence to therapy; psychosocial factors; and difficulty in transition to adult services. Admissions for SAI also increased, while rates of PAI and CAH remained constant.
Identification and validation of ferroptosis-related lncRNA signatures as a novel prognostic model for glioma
Authors: Huang Liang , Zhang Juan , Gong Fanghua , Han Yuhua , Huang Xing , Luo Wanxiang , Cai Huaan , Zhang Fan 
Published: September 2022

Background: Ferroptosis is a newly discovered form of regulated cell death with distinct properties and recognizing functions involved in physical conditions or various diseases, including cancers. However, the relationship between gliomas and ferroptosis-related lncRNAs (FRLs) remains unclear.Methods: We collected a total of 1850 samples from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEX) databases, including 698 tumor and 1,152 normal samples. A list of ferroptosis-related genes was downloaded from the Ferrdb website. Differentially expressed FRLs (DEFRLS) were analyzed using the “limma” package in R software. Subsequently, prognosis-related FRLs were obtained by univariate Cox analysis. Finally, a prognostic model based on the 3 FRLs was constructed using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm. The prognostic power of the model was assessed using receiver operating characteristic (ROC) curve analysis and Kaplan-Meier (K-M) survival curve analysis. In addition, we further explored the relationship of the immune landscape and somatic mutations to prognostic model characteristics. Finally, we validated the function of LINC01426 in vitro.Results: We successfully constructed a 3-FRLs signature and classified glioma patients into high-risk and low-risk groups based on the risk score calculated from this signature. Compared with traditional clinicopathological features [age, sex, grade, isocitrate dehydrogenase (IDH) status], the prognostic accuracy of this model is more stable and stronger. Additionally, the model had stable predictive power for overall survival over a 5-year period. In addition, we found significant differences between the two groups in cellular immunity, the numbers of many immune cells, including NK cells, CD4+, CD8+ T-cells, and macrophages, and the expression of many immune-related genes. Finally, the two groups were also significantly different at the level of somatic mutations, especially in glioma prognosis-related genes such as IDH1 and ATRX, with lower mutation rates in the high-risk group leading to poorer prognosis. Finally, we found that the ferroptosis process of glioma cells was inhibited after knocking down the expression of LINC01426.Conclusion: The proposed 3-FRL signature is a promising biomarker for predicting prognostic features in glioma patients.
Microfibrillar-associated protein 2 is a prognostic marker that correlates with the immune microenvironment in glioma
Authors: Xu Wanzhen , Geng Ren , Zhao Yao , Ma Xiaoshan , Bai Yang , Jiang Yining , Zhao Liyan , Li Yunqian 
Published: September 2022

Aims: microfibrillar-associated protein 2 (MFAP2), a component of the extracellular matrix, plays key roles in regulating growth factor signal transduction and various malignant tumors. However, the clinicopathological features of microfibrillar-associated protein 2 in gliomas have not been elucidated to date.Methods: TCGA and CGGA databases were used to study the expression of microfibrillar-associated protein 2 in glioma and its relationship with clinicopathological features of patients with glioma. Western blotting was performed to detect the expression of microfibrillar-associated protein 2 protein in tissue samples from glioma patients. Gene set enrichment analysis (GSEA) was applied to detect biological processes and signal pathways related to microfibrillar-associated protein 2. Single-sample gene set enrichment analysis, TIMER 2.0, and TISIDB databases were used to evaluate the role of microfibrillar-associated protein 2 in tumor immune characteristics. The prognostic role of microfibrillar-associated protein 2 in glioma was analyzed using the Kaplan-Meier method and Cox regression. Survival data were used to establish a nomogram prediction model.Results: microfibrillar-associated protein 2 expression was significantly elevated in gliomas. receiver operating characteristic analysis revealed good discrimination of microfibrillar-associated protein 2 between glioma and normal tissues. High expression of microfibrillar-associated protein 2 was associated with malignant phenotypes, such as histological type. Based on gene set enrichment analysis, we identified pathways associated with high microfibrillar-associated protein 2 expression. High microfibrillar-associated protein 2 expression was related to the infiltration of tumor immune cells, including Th2 cells and macrophages, and correlated with key markers of T-cell exhaustion. Based on the TISIDB database, microfibrillar-associated protein 2 was observed to be associated with chemokines, chemokine receptors, and multiple immunoinhibitors in glioma. Kaplan–Meier survival analyses revealed that high microfibrillar-associated protein 2 expression predicted poor overall survival, DSS, and PFS in patients with glioma. By combining microfibrillar-associated protein 2 and other prognostic factors, a nomogram prognostic prediction model was constructed, which demonstrated an ideal prediction effect.Conclusion: microfibrillar-associated protein 2 is a potential prognostic marker that plays a key role in glioma development given its association with malignant phenotypes, cancer-related pathways and tumor immunity.