bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction
Authors: Su Jia , Cheng Ji , Hu Yingchu , Yu Qinglin , Li Zhenwei , Li Jiyi , Zheng Nan , Zhang Zhaoxia , Yang Jin , Li Xiaojing , Zhang Zeqin , Wang Yong , Zhu Keqi , Du Weiping , Chen Xiaomin 
Published: September 2022

BackgroundIt has been reported that sacubitril/valsartan can improve cardiac function in acute myocardial infarction (AMI) patients complicated by heart failure (HF). However, a number of patients cannot be treated successfully; this phenomenon is called sacubitril/valsartan resistance (SVR), and the mechanisms remain unclear.MethodsIn our present research, the expression profiles of transfer RNA (tRNA)-derived small RNAs (tsRNAs) in SVR along with no sacubitril/valsartan resistance (NSVR) patients were determined by RNA sequencing. Through bioinformatics, quantitative real-time PCR (qRT-PCR), and cell-based experiments, we identified SVR-related tsRNAs and confirmed their diagnostic value, predicted their targeted genes, and explored the enriched signal pathways as well as regulatory roles of tsRNAs in SVR.ResultsOur research indicated that 36 tsRNAs were upregulated and that 21 tsRNAs were downregulated in SVR. Among these tsRNAs, the expression of tRF-59:76-Tyr-GTA-2-M3 and tRF-60:76-Val-AAC-1-M5 was upregulated, while the expression of tRF-1:29-Gly-GCC-1 was downregulated in the group of SVR. Receiver operating characteristic (ROC) curve analysis demonstrated that these three tsRNAs were potential biomarkers of the therapeutic heterogeneity of sacubitril/valsartan. Moreover, tRF-60:76-Val-AAC-1-M5 might target Tnfrsf10b and Bcl2l1 to influence the observed therapeutic heterogeneity through the lipid and atherosclerosis signaling pathways.ConclusionHence, tsRNA might play a vital role in SVR. These discoveries provide new insights for the mechanistic investigation of responsiveness to sacubitril/valsartan.
Magnetic resonance imaging of the supra-cervical fetal membrane detects an increased risk of prelabor rupture of membranes
Authors: Qi Wenxu , Zhao Peinan , Wang Wei , Wen Zichao , Sun Zhexian , Wu Wenjie , Woodard Pamela Karen , Wang Qing , McKinstry Robert C. , Wang Yong 
Published: September 2022

ObjectiveIn 10% of term deliveries and 40% of preterm deliveries, the fetal membrane (FM) ruptures before labor. However, the ability to predict these cases of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) is very limited. In this paper, our objective was to determine whether a prediction method based on T2 weighted magnetic resonance imaging (MRI) of the supra-cervical FM could predict PROM and PPROM.MethodsThis prospective cohort study enrolled 77 women between the 28th and 37th weeks of gestation. Two indicators of fetal membrane defects, including prolapsed depth &gt;5 mm and signal abnormalities, are investigated for our prediction. Fisher’s exact test was used to determine whether prolapsed depth &gt;5 mm and/or signal abnormalities were associated with PROM and PPROM. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for prolapsed depth &gt;5 mm, signal abnormalities, and the combination of prolapsed depth &gt;5 mm and signal abnormalities.ResultAmong 12 women with PROM (5 preterm and 7 term, prior to labor onset), 9 had membrane prolapse &gt;5 mm and 5 had FM signal abnormalities. Among 65 women with rupture of membranes at term, 2 had membrane prolapse &gt;5 mm and 1 had signal abnormalities. By Fisher’s exact test both indicators, membrane prolapse &gt;5 mm and signal abnormalities, were associated with PROM (P&lt;0.001, P&lt;0.001) and PPROM (P=0.001, P&lt;0.001). Additionally, membrane prolapse &gt;5 mm, signal abnormalities, and the combination of the two indicators all demonstrated high specificity for predicting PROM (96.9%, 98.5%, and 100%, respectively) and PPROM (90.3%, 97.2%, and 100%, respectively).ConclusionMRI can distinguish the supra-cervical fetal membrane in vivo and may be able to identify women at high risk of PPROM.
Exploring the risk factors of impaired fasting glucose in middle-aged population living in South Korean communities by using categorical boosting machine
Authors: Byeon Haewon 
Published: September 2022

ObjectiveThis epidemiological study (1) identified factors associated with impaired fasting glucose using 3,019 subjects (≥30 years old and &lt;60 years old) without diabetes mellitus from national survey data and (2) developed a nomogram that could predict groups vulnerable to impaired fasting glucose by using machine learning.MethodsThis study analyzed 3,019 adults between 30 and 65 years old who completed blood tests, physical measurements, blood pressure measurements, and health surveys. Impaired fasting glucose, a dependent variable, was classified into normal blood glucose (glycated hemoglobin&lt;5.7% and fasting blood glucose ≤ 100mg/dl) and impaired fasting glucose (glycated hemoglobin is 5.7-6.4% and fasting blood glucose is 100-125mg/dl). Explanatory variables included socio-demographic factors, health habit factors, anthropometric factors, dietary habit factors, and cardiovascular disease risk factors. This study developed a model for predicting impaired fasting glucose by using logistic nomogram and categorical boosting (CatBoost).ResultsIn this study, the top eight variables with a high impact on CatBoost model output were age, high cholesterol, WHtR, BMI, drinking more than one shot per month for the past year, marital status, hypertension, and smoking.ConclusionIt is necessary to improve lifestyle and continuously monitor subjects at the primary medical care level so that we can detect non-diabetics vulnerable to impaired fasting glucose living in the community at an early stage and manage their blood glucose.
Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio: A valuable predictor of type 2 diabetes mellitus incidence
Authors: Xie Wangcheng , Liu Bin , Tang Yansong , Yang Tingsong , Song Zhenshun 
Published: September 2022

BackgroundGamma-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) have been proven to be valuable predictors of type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the association between GGT/HDL-C ratio and incident T2DM.MethodsThe study retrospectively analyzed 15453 participants from 2004 to 2015. Cox proportional hazards regression models and Kaplan-Meier curves were used to elucidate the effect of GGT/HDL-C ratio on T2DM. Restricted cubic spline (RCS) analysis was performed to explore any non-linear correlation between GGT/HDL-C ratio and the risk of T2DM. The predictive performance of GGT, HDL-C and GGT/HDL-C ratio for T2DM was evaluated utilizing receiver-operating-characteristic (ROC) curves.ResultsDuring a median follow-up of 5.39 years, 373 cases of incident T2DM were observed. Kaplan-Meier curves showed that the cumulative probabilities of T2DM increased in the participants with higher GGT/HDL-C ratio significantly (P &lt; 0.001). Cox models further clarified that high GGT/HDL-C ratio was an independent risk factor for T2DM (HR = 1.01, 95% CI = 1.00-1.01, P = 0.011). Linear positive correlation between GGT/HDL-C ratio and the risk of T2DM was demonstrated through RCS analysis. In the ROC analysis, GGT/HDL-C ratio (AUC = 0.75, 95% CI = 0.73-0.77) showed competitive role in the prediction of T2DM compared with single GGT and HDL-C.ConclusionsThe GGT/HDL-C ratio could serve as a valuable predictor of T2DM, and the risk of T2DM increases in the condition of higher GGT/HDL-C ratio.
The evolving roles of alarin in physiological and disease conditions, and its future potential clinical implications
Authors: Abebe Endeshaw Chekol , Mengstie Misganaw Asmamaw , Seid Mohammed Abdu , Malik Tabarak , Dejenie Tadesse Asmamaw 
Published: September 2022

Alarin is a member of the galanin family of neuropeptides that is widely expressed in the central nervous system and peripheral tissues in humans and rodents. It was initially isolated fifteen years ago in ganglionic cells of human neuroblastoma. Subsequently, it was demonstrated to be broadly distributed in the blood vessels, skin, eyes, peripheral and central nervous systems, thymus, gastrointestinal tract, and endocrine organs of different species. Alarin is a 25 amino acid neuropeptide derived from the alternative splicing of the GALP gene, missing exon 3. It is found to be involved in several physiological functions that include feeding behavior, energy homeostasis, glucose homeostasis, body temperature, and reproduction. It has also vasoactive, anti-inflammatory, anti-edema, and antimicrobial activities. However, the physiological effects of alarin have not been fully elucidated and the receptors that mediate these effects are not currently known. Unearthing the novel biological effects of alarin and its unidentified receptors will therefore be a task in future biomedical research.In addition, alarin is involved in various disease conditions, such as metabolic syndrome, obesity, insulin resistance, type 2 diabetes, diabetic retinopathy, hypertension, cardiac fibrosis, polycystic ovarian syndrome, and depression. Thus, alarin may serve as a promising tool for future pharmacological treatment and diagnosis. But further research is awaited to confirm whether alarin has a protective or pathological role in these diseases. This article provides a comprehensive review on the evolving implications of alarin in a variety of physiological and disease conditions, and its future perspectives.
REV1: A novel biomarker and potential therapeutic target for various cancers
Authors: Zhu Ning , Zhao Yingxin , Mi Mi , Lu Yier , Tan Yinuo , Fang Xuefeng , Weng Shanshan , Yuan Ying 
Published: September 2022

Background: REV1 is a member of the translesion synthesis DNA polymerase Y family. It is an essential player in a variety of DNA replication activities, and perform major roles in the production of both spontaneous and DNA damage-induced mutations. This study aimed to explore the role of REV1 as a prognostic biomarker and its potential function regulating the sensitivity of anti-tumor drugs in various cancers.Methods: We analyzed the impact of REV1 gene alterations on patient prognosis and the impact of different REV1 single nucleotide polymorphisms (SNP) on protein structure and function using multiple online prediction servers. REV1 expression was assessed using data from Oncomine, TCGA, and TIMER database. The correlation between REV1 expression and patient prognosis was performed using the PrognoScan and Kaplan-Meier plotter databases. The IC50 values of anti-cancer drugs were downloaded from the Genomics of Drug Sensitivity in Cancer database and the correlation analyses between REV1 expression and each drug pathway’s IC50 value in different tumor types were conducted.Results: Progression free survival was longer in REV1 gene altered group comparing to unaltered group [Median progression free survival (PFS), 107.80 vs. 60.89 months, p value = 7.062e-3]. REV1 SNP rs183737771 (F427L) was predicted to be deleterious SNP. REV1 expression differs in different tumour types. Low REV1 expression is associated with better prognosis in colorectal disease specific survival (DSS), disease-free survival (DFS), gastric overall survival (OS), post progression survival (PPS) and ovarian (OS, PPS) cancer while high REV1 expression is associated with better prognosis in lung [OS, relapse free survival (RFS), first progession (FP), PPS] and breast (DSS, RFS) cancer. In colon adenocarcinoma and rectum adenocarcinoma and lung adenocarcinoma, low expression of REV1 may suggest resistance to drugs in certain pathways. Conversely, high expression of REV1 in acute myeloid leukemia, brain lower grade glioma, small cell lung cancer and thyroid carcinoma may indicate resistance to drugs in certain pathways.Conclusion: REV1 plays different roles in different tumor types, drug susceptibility, and related biological events. REV1 expression is significantly correlated with different prognosis in colorectal, ovarian, lung, breast, and gastric cancer. REV1 expression can be used as predictive marker for various drugs of various pathways in different tumors.
Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation
Authors: Pan Shengyuan , Hu Bo , Sun Jicheng , Yang Zun , Yu Wenliang , He Zangmin , Gao Xiang , Song Jinlin 
Published: September 2022

PurposeThere is a bidirectional relationship between periodontitis and type 2 diabetes mellitus (T2DM). The aim of this study was to further explore the pathogenesis of this comorbidity, screen out ferroptosis-related genes involved in the pathological process, and predict potential drug targets to develop new therapeutic strategies.MethodsCommon cross-talk genes were identified from periodontitis datasets (GSE16134, GSE10334 and GSE106090) and T2DM databases (DisGeNET and GeneCard). Then, GO and KEGG enrichment analyses, PPI network analysis and hub gene identification were performed. The association between ferroptosis and periodontitis with T2DM was investigated by Pearson correlation analysis. Core ferroptosis-related cross-talk genes were identified and verified by qRT-PCR. Potential drugs targeting these core genes were predicted via DGIDB.ResultsIn total, 67 cross-talk genes and two main signalling pathways (immuno-inflammatory pathway and AGE-RAGE signalling pathway) were identified. Pearson correlation analysis indicated that ferroptosis served as a crucial target in the pathological mechanism and treatment of periodontitis with T2DM. IL-1β, IL-6, NFE2L2 and ALOX5 were identified as core ferroptosis-related genes and the qRT-PCR detection results were statistically different. In total, 13 potential drugs were screened out, among which, Echinacea and Ibudilast should be developed first.ConclusionsThis study contributes to a deeper understanding of the common pathogenesis of periodontitis and T2DM and provides new insights into the role of ferroptosis in this comorbidity. In addition, two drugs with potential clinical application value were identified. The potential utility of these drugs requires further experimental investigation.
Enlarged perivascular spaces, neuroinflammation and neurological dysfunction in NMOSD patients
Authors: Yao Xiao-Ying , Gao Mei-Chun , Bai Shu-Wei , Xie Li , Song Ya-Ying , Ding Jie , Wu Yi-Fan , Xue Chun-Ran , Hao Yong , Zhang Ying , Guan Yang-Tai 
Published: September 2022

Background and objectivesCerebrospinal fluid (CSF) and interstitial fluid exchange along a brain-wide network of perivascular spaces (PVS) termed the ‘glymphatic system’. The aquaporin-4 (AQP4) water channels abundantly expressed on astrocytic endfeet play a key role in the CSF circulation in the glymphatic system. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) featured with a specific autoantibody directed against AQP4 in most of patients. Anti-AQP4 antibodies are likely resulting in the impairment of the brain glymphatic system and the enlargement of PVS in NMOSD patients. In the current study, we aimed to demonstrate the features of EPVS detected by MRI and its association with the CSF anti-AQP4 antibody titer, CNS inflammatory markers, and disease severity in NMOSD patients.MethodsWe conducted a retrospective review of a consecutive cohort of 110 patients with NMOSD who had brain MRI. We assessed the correlation of EPVS with markers of neuroinflammation, blood-brain barrier (BBB) function and severity of neurological dysfunction in patients. We used multivariate logistic regression analysis to determine the independent variables associated with disease severity.ResultsThe median number of total-EPVS was 15.5 (IQR, 11-24.2) in NMOSD patients. The number of total-EPVS was significantly related to EDSS score after correcting for the effects of age and hypertension (r=0.353, p&lt;0.001). The number of total-EPVS was also significantly associated with the titer of CSF anti-AQP4 antibody, the albumin rate (CSF/serum ratios of albumin), the CSF albumin, IgG and IgA levels. Logistic regression analysis showed that total-EPVS and serum albumin level were two independent factors to predict disease severity in NMOSD patients (OR=1.053, p=0.028; OR=0.858, p=0.009 respectively). Furthermore, ROC analysis achieved AUC of 0.736 (0.640-0.831, p&lt;0.001) for total-EPVS to determine severe NMOSD (EDSS 4.5-9.5).DiscussionIn our cohort, we found a relationship between EPVS and neuroinflammation and BBB function in NMOSD. Moreover, EPVS might independently predict neurological dysfunction in patients with NMOSD.
Neutralization effect of plasma from vaccinated COVID-19 convalescents on SARS-CoV-2 Omicron variants
Authors: Xie Yudi , Liu Lei , Wang Jue , Zheng Yaqiong , Luo Chen , Ni Wenxu , He Zhihang , Zhao Xin , Liu Yan , He Yingyu , Zheng Shangen , Li Ling , Liu Zhong 
Published: September 2022

BackgroundCOVID-19 has caused a global pandemic and the death toll is increasing. With the coronavirus continuously mutating, Omicron has replaced Delta as the most widely reported variant in the world. Studies have shown that the plasma of some vaccinated people does not neutralize the Omicron variant. However, further studies are needed to determine whether plasma neutralizes Omicron after one- or two-dose vaccine in patients who have recovered from infection with the original strain.MethodsThe pseudovirus neutralization assays were performed on 64 plasma samples of convalescent COVID-19 patients, which were divided into pre-vaccination group, one-dose vaccinated group and two-dose vaccinated group.ResultsIn the three groups, there were significant reductions of sera neutralizing activity from WT to Delta variant (B.1.617.2), and from WT to Omicron variant (B.1.1.529) (ps&lt;0.001), but the difference between Delta and Omicron variants were not significant (p&gt;0.05). The average neutralization of the Omicron variant showed a significant difference between pre-vaccination and two-dose vaccinated convalescent individuals (p&lt;0.01).ConclusionsAmong the 64 plasma samples of COVID-19 convalescents, whether vaccinated or not, Omicron (B.1.1.529) escaped the neutralizing antibodies, with a significantly decreased neutralization activity compared to WT. And two-dose of vaccine could significantly raise the average neutralization of Omicron in convalescent individuals.
Antithrombin activity levels for predicting long-term outcomes in the early phase of isolated traumatic brain injury
Authors: Takahashi Masaki , Wada Takeshi , Nakae Ryuta , Fujiki Yu , Kanaya Takahiro , Takayama Yasuhiro , Suzuki Go , Naoe Yasutaka , Yokobori Shoji 
Published: September 2022

Coagulopathy management is an important strategy for preventing secondary brain damage in patients with traumatic brain injury (TBI). Antithrombin (AT) is a natural anticoagulant that controls coagulation and inflammation pathways. However, the significance of AT activity levels for outcomes in patients with trauma remains unclear. This study aimed to investigate the relationship between AT activity levels and long-term outcomes in patients with TBI; this was a sub-analysis of a prior study that collected blood samples of trauma patients prospectively in a tertiary care center in Kawaguchi City, Japan. We included patients with isolated TBI (iTBI) aged ≥16 years admitted directly to our hospital within 1 h after injury between April 2018 and March 2021. General coagulofibrinolytic and specific molecular biomarkers, including AT, were measured at 1, 3, 6, 12, and 24 h after injury. We analyzed changes in the AT activity levels during the study period and the impact of the AT activity levels on long-term outcomes, the Glasgow Outcome Scale-Extended (GOSE), 6 months after injury. 49 patients were included in this study; 24 had good neurological outcomes (GOSE 6–8), and 25 had poor neurological outcomes (GOSE 1–5). Low AT activity levels were shown within 1 h after injury in patients in the poor GOSE group; this was associated with poor outcomes. Furthermore, AT activity levels 1 h after injury had a strong predictive value for long-term outcomes (area under the receiver operating characteristic curve of 0.871; 95% CI: 0.747–0.994). Multivariate logistic regression analysis with various biomarkers showed that AT was an independent factor of long-term outcome (adjusted odds ratio: 0.873; 95% CI: 0.765–0.996; p=0.043). Another multivariate analysis with severity scores showed that low AT activity levels were associated with poor outcomes (adjusted odds ratio: 0.909; 95% CI: 0.822–1.010; p=0.063). We demonstrated that the AT activity level soon after injury could be a predictor of long-term neurological prognosis in patients with iTBI.
PTPRD/PTPRT mutation as a predictive biomarker of immune checkpoint inhibitors across multiple cancer types
Authors: Shang Xiaoling , Zhang Wengang , Zhang Xun , Yu Miao , Liu Jingwen , Cheng Yufeng , Cheng Bo 
Published: September 2022

BackgroundImmune checkpoint inhibitors (ICIs) are dramatically changing the treatment landscape of a variety of cancers. Nevertheless, the variability in ICI responses highlight the importance in identifying predictive biomarkers. PTPRD and PTPRT (PTPRD/PTPRT) are the phosphatases of JAK-STAT signaling, a critical pathway in anti-cancer immunity regulation. However, the pan-cancer association between PTPRD/PTPRT mutation and the efficacy of ICIs remains unclear across pan-cancer patients.MethodsWe analyzed the association between PTPRD/PTPRT mutations and patient outcomes using clinical data and genomic mutations from TCGA pan-cancer cohort. Furthermore, the ICI-treatment cohort was used to evaluate the relationship between PTPRD/PTPRT mutation and the efficacy of ICIs. Another ICIs-treatment cohort was used to validate the findings. The TCGA pan-cancer dataset was analyzed to explore the correlation between PTPRD/PTPRT mutations and immune signatures. Moreover, we combined four factors to construct a nomogram model that could be used to predict the survival of pan-cancer patients receiving ICI treatment. The calibration curves and area under the curve were applied to assess the performance of the model.ResultsPTPRD/PTPRT mutations were shown to be associated with a worse prognosis in TCGA cohort (P &lt; 0.05). In the Samstein cohort, prolonged overall survival (OS) was observed in PTPRD/PTPRT mutant cancers, compared with wild-type cancers (mOS: 40.00 vs 16.00 months, HR = 0.570, 95%CI: 0.479-0.679, P &lt; 0.0001). In the validation cohort, significant OS advantage was observed in PTPRD/PTPRT mutant patients (mOS: 31.32 vs 15.53 months, HR = 0.658, 95%CI: 0.464-0.934, P = 0.0292). Furthermore, PTPRD/PTPRT mutations were associated with a higher tumor mutational burden, MSI score, and TCR score (P &lt; 0.0001). Enhanced immune signatures were found in the PTPRD/PTPRT mutant cancers (P &lt; 0.05). Finally, we successfully established a nomogram model that could be used to predict the survival of NSCLC patients who received ICI treatment. Based on the risk score of the model, patients in the low-risk group showed a better mOS than those in the high-risk group (mOS: 2.75 vs 1.08 years, HR = 0.567, 95%CI: 0.492-0.654; P &lt; 0.001).ConclusionsPTPRD/PTPRT mutations may be a potential biomarker for predicting ICI treatment responsiveness in multiple cancer types.