bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between triglyceride glucose index, coronary artery calcification and multivessel coronary disease in Chinese patients with acute coronary syndrome
Authors: Wang Jiayu , Huang Xianwei , Fu Caihua , Sheng Qiping , Liu Ping 
Published: September 2022

Abstract
Background
Multivessel coronary disease (MVCD) is the common type of coronary artery disease in acute coronary syndrome (ACS). Coronary artery calcification (CAC) has been confirmed the strong predictor of major adverse cardiovascular events (MACEs). Several studies have validated that triglyceride glucose (TyG) index can reflect the degree of coronary calcification or predict MACEs. However, no evidence to date has elucidated and compared the predictive intensity of TyG index or/and coronary artery calcification score (CACS) on multi-vascular disease and MACEs in ACS patients.

Methods
A total of 935 patients, diagnosed with ACS and experienced coronary computed tomography angiography (CCTA) from August 2015 to March 2022 in the Second Hospital of Shandong University, were selected for retrospective analysis. The subjects were divided into TyG index quartile 1–4 groups (Q1-Q4 groups), non-multivessel coronary disease (non-MVCD) and multivessel coronary disease (MVCD) groups, respectively. The general data, past medical or medication history, laboratory indicators, cardiac color Doppler ultrasound, CACS, and TyG indexes were respectively compared among these groups. The ROC curve preliminarily calculated and analyzed the diagnostic value of TyG index, CACS, and the combination of the two indicators for MVCD. Univariate and multivariate logistic regression analysis discriminated the independent hazard factors for forecasting MVCD.

Results
Compared with the lower TyG index and non-MVCD groups, the higher TyG index and MVCD groups had higher values of age, smoking history, waist circumference, systolic blood pressure, low-density lipoprotein cholesterol(LDL-C), fasting blood glucose and glycosylated hemoglobin, and CACS, but lower values of high-density lipoprotein cholesterol(HDL-C) (all P < 0.01). Coronary artery calcification is more common in the left anterior descending artery. Compared with non-MVCD, each unit increase in TyG index was associated with a 1.213-fold increased risk of MVCD. Logistic regression analysis adjusted for potential confounders indicated that TyG index is an independent risk factor for MVCD. With the increase of TyG index, the incidence of MACEs, apart from all-cause death, cardiac death, unexpected re-hospitalization of heart failure, recurrent ACS or unplanned revascularization, and non-fatal stroke in coronary artery increased (P log-rank < 0.001).

Conclusion
TyG index could completely substitute for CACS as a reliable, practical, and independent indicator for predicting the severity and prognosis of MVCD in patients with ACS.
HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET
Authors: Zhang Tongyue , Wang Yijun , Xie Meng , Ji Xiaoyu , Luo Xiangyuan , Chen Xiaoping , Zhang Bixiang , Liu Danfei , Feng Yangyang , Sun Mengyu , Huang Wenjie , Xia Limin 
Published: September 2022

Abstract
Background
Metastasis is a major determinant of death in patients with hepatocellular carcinoma (HCC). Dissecting key molecular mediators that promote this malignant feature may help yield novel therapeutic insights. Here, we investigated the role of E-twenty-six transformation-specific variant 1 (ETV1), a member of the E-twenty-six transformation-specific (ETS) family, in HCC metastasis.

Methods
The clinical significance of ETV1 and its target genes in two independent cohorts of HCC patients who underwent curative resection were assessed by Kaplan–Meier analysis and Multivariate Cox proportional hazards model. Luciferase reporter assay and chromatin immunoprecipitation assay were used to detect the transcriptional regulation of target gene promoters by ETV1. The effect of ETV1 on invasiveness and metastasis of HCC were detected by transwell assays and the orthotopically metastatic model.

Results
ETV1 expression was frequently elevated in human HCC specimens. Increased ETV1 expression was associated with the malignant biological characteristics and poor prognosis of HCC patients. ETV1 facilitated invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, ETV1 promoted HCC metastasis via upregulating metastasis-related genes, including protein tyrosine kinase 2 (PTK2) and MET. Down-regulated the expression of PTK2 or tyrosine protein kinase Met (c-MET) decreased ETV1-mediated HCC metastasis. Hepatocyte growth factor (HGF) upregulated ETV1 expression through activating c-MET-ERK1/2-ELK1 pathway. Notably, in two independent cohorts, patients with positive coexpression of ETV1/PTK2 or ETV1/c-MET had worse prognosis. Furthermore, the combination of PTK2 inhibitor defactinib and c-MET inhibitor capmatinib significantly suppressed HCC metastasis induced by ETV1.

Conclusion
This study uncovers functional and prognostic roles for ETV1 in HCC and exposes a positive feedback loop of HGF-ERK1/2-ETV1-c-MET. Targeting this pathway may provide a potential therapeutic intervention for ETV1-overexpressing HCC.
Non-coding RNAs and epithelial mesenchymal transition in cancer: molecular mechanisms and clinical implications
Authors: Khanbabaei Hashem , Ebrahimi Saeedeh , García-Rodríguez Juan Luis , Ghasemi Zahra , Pourghadamyari Hossein , Mohammadi Milad , Kristensen Lasse Sommer 
Published: September 2022

AbstractEpithelial-mesenchymal transition (EMT) is a fundamental process for embryonic development during which epithelial cells acquire mesenchymal characteristics, and the underlying mechanisms confer malignant features to carcinoma cells such as dissemination throughout the organism and resistance to anticancer treatments. During the past decades, an entire class of molecules, called non-coding RNA (ncRNA), has been characterized as a key regulator of almost every cellular process, including EMT. Like protein-coding genes, ncRNAs can be deregulated in cancer, acting as oncogenes or tumor suppressors. The various forms of ncRNAs, including microRNAs, PIWI-interacting RNAs, small nucleolar RNAs, transfer RNA-derived RNA fragments, long non-coding RNAs, and circular RNAs can orchestrate the complex regulatory networks of EMT at multiple levels. Understanding the molecular mechanism underlying ncRNAs in EMT can provide fundamental insights into cancer metastasis and may lead to novel therapeutic approaches. In this review, we describe recent advances in the understanding of ncRNAs in EMT and provide an overview of recent ncRNA applications in the clinic.
Ovarian neoplasia in adolescence: a retrospective chart review of girls with neoplastic ovarian tumors in Saudi Arabia
Authors: AlDakhil Lateefa , Aljuhaimi Asma , AlKhattabi Mashael , Alobaid Saleh , Mattar Rafif E. , Alobaid Abdulaziz 
Published: September 2022

Abstract
Background
Ovarian neoplasia in children and adolescents is a rare tumor. The diagnosis and management of such tumors is often difficult and delayed due to non-specific symptoms and low suspicion. Surgical management that preserves fertility and ovarian function should be the goal.

Objective
This study aimed to review the clinical presentation, tumor characteristics, and management of Saudi Arabian adolescents.

Methods
A retrospective chart review was conducted on adolescent girls aged 19 or less admitted to tow referral hospital in Riyadh, Saudi Arabia, diagnosed with adnexal mass over an 8 years’ period; patients who were older than 19 were excluded.
The data collected from patients’ charts included age, presenting symptoms, radiologic findings, type of surgery, specialist who performed the surgery, and histopathology of the tumors.
We classified patients according to age using the three WHO developmental stages: early adolescence (10–13 years old), middle adolescence (14–16 years old), and late adolescence (16–17 years old).
The statistical study used SPSS version 18.0 to determine the data’s frequency, distributions, and means (SPSS Inc., Chicago, IL).

Results
We analyzed 164 patients, between 10 and 19 years old, admitted to two hospitals between 2009 and 2017. We found that 85% of these patients underwent surgery for adnexal mass removal, and 90.2% were symptomatic or emergency cases. The majority of our patients were post-menarche (96.95%), and were between the ages of 14 and 19. The most common surgical procedure for tumor removal was laparoscopic cystectomy (74.4%).
An adnexal mass with a solid component on ultrasound is the most commonly found indicator of malignancy. The majority of tumors were benign (32.3%). Germ cell tumors were the most common (68.7%) malignant tumor, and yolk sac tumors were the most common subgroup of germ cell tumors. When managed by a gynecologist, surgical intervention can be a successful method of preserving fertility.

Conclusions
Our results confirm that the majority of neoplastic ovarian tumors in children and adolescents are benign, and surgical intervention can be used to maintain fertility, especially when managed by a gynecologist. This is one of the largest reported series and the first from our area.
Identification and validation of a gene-based signature reveals SLC25A10 as a novel prognostic indicator for patients with ovarian cancer
Authors: Li Qi-jia , Wang Juan , Jiang Jing , Lin Bing 
Published: September 2022

Abstract
Background
Ovarian cancer is a common gynecological cancer with poor prognosis and poses a serious threat to woman life and health. In this study, we aimed to establish a prognostic signature for the risk assessment of ovarian cancer.

Methods
The Cancer Genome Atlas (TCGA) dataset was used as the training set and the International Cancer Genome Consortium (ICGC) dataset was set as an independent external validation. A multi-stage screening strategy was used to determine the prognostic features of ovarian cancer with R software. The relationship between the prognosis of ovarian cancer and the expression level of SLC25A10 was selected for further analysis.

Results
A total of 16 prognosis-associated genes were screened to construct the risk score signature. Survival analysis showed that patients in the high-risk score group had a poor prognosis compared to the low-risk group. Accuracy of this prognostic signature was confirmed by the receiver operating characteristic (ROC) curve and decision curve analysis (DCA), and validated with ICGC cohort. This signature was identified as an independent factor for predicting overall survival (OS). Nomogram constructed by multiple clinical parameters showed excellent performance for OS prediction. Finally, it’s found that patients with low expression of SLC25A10 generally had poor survival and higher resistance to most chemotherapeutic drugs.

Conclusions
In sum, we developed a 16-gene prognostic signature, which could serve as a promising tool for the prognostic prediction of ovarian cancer, and the expression level of SLC25A10 was tightly associated with OS of the patients.
DNA methylation and aeroallergen sensitization: The chicken or the egg?
Authors: Kilanowski Anna , Merid Simon Kebede , Abrishamcar Sarina , Feil Dakotah , Thiering Elisabeth , Waldenberger Melanie , Melén Erik , Peters Annette , Standl Marie , Hüls Anke 
Published: September 2022

AbstractBackgroundDNA methylation (DNAm) is considered a plausible pathway through which genetic and environmental factors may influence the development of allergies. However, causality has yet to be determined as it is unknown whether DNAm is rather a cause or consequence of allergic sensitization. Here, we investigated the direction of the observed associations between well-known environmental and genetic determinants of allergy, DNAm, and aeroallergen sensitization using a combination of high-dimensional and causal mediation analyses.MethodsUsing prospectively collected data from the German LISA birth cohort from two time windows (6–10 years:N = 234; 10–15 years:N = 167), we tested whether DNAm is a cause or a consequence of aeroallergen sensitization (specific immunoglobulin E > 0.35kU/l) by conducting mediation analyses for both effect directions using maternal smoking during pregnancy, family history of allergies, and a polygenic risk score (PRS) for any allergic disease as exposure variables. We evaluated individual CpG sites (EPIC BeadChip) and allergy-related methylation risk scores (MRS) as potential mediators in the mediation analyses. We applied three high-dimensional mediation approaches (HIMA, DACT, gHMA) and validated results using causal mediation analyses. A replication of results was attempted in the Swedish BAMSE cohort.ResultsUsing high-dimensional methods, we identified five CpGs as mediators of prenatal exposures to sensitization with significant (adjustedp < 0.05) indirect effects in the causal mediation analysis (maternal smoking: two CpGs, family history: one, PRS: two). None of these CpGs could be replicated in BAMSE. The effect of family history on allergy-related MRS was significantly mediated by aeroallergen sensitization (proportions mediated: 33.7–49.6%), suggesting changes in DNAm occurred post-sensitization.ConclusionThe results indicate that DNAm may be a cause or consequence of aeroallergen sensitization depending on genomic location. Allergy-related MRS, identified as a potential cause of sensitization, can be considered as a cross-sectional biomarker of disease. Differential DNAm in individual CpGs, identified as mediators of the development of sensitization, could be used as clinical predictors of disease development.
MRI outcome evaluation in patients with IB2 and IIA2 squamous cervical cancer stages: preliminary results
Authors: Song Qingling , Pang Huiting , Tong Rui , Zhu Yanmei , Luo Yahong , Yu Tao , Liu Fan , Dong Yue 
Published: September 2022

Abstract
Objectives
To evaluate the therapeutic effect of neoadjuvant therapy (NAT) followed by radical hysterectomy and concurrent chemoradiotherapy (CCRT) in stage IB2 and IIA2 squamous cervical cancer (SCC) and investigate the value of apparent diffusion coefficient (ADC) in outcome evaluation of different treatment strategies in the patients.

Methods
A total of 149 patients with IB2 and IIA2 SCC who underwent pretreatment MRI and DWI scan were included. Patients were treated with NAT + RH or CCRT. Clinical indices and pathological factors were recorded. The imaging indices were measured including tumor size and tumor ADC values. Intraclass correlation coefficient was employed to evaluate the consistency of the indices measured by two observers. ROC curves were used to evaluate the cutoff values of clinical and imaging indices. Kaplan–Meier and Cox proportional hazard model were used to analyze the independent factors of disease-free survival (DFS).

Results
The median follow-up period was 42.3 months. SCC-Ag, ADCmax and ADCmin were independent factors for DFS in the entire cohort. SCC-Ag, ADCmin and vascular invasion were independent factors for DFS in NAT + RH group. ADCmax and ADCmin were independent factors for DFS in CCRT group. ADCmin was the strongest independent factor for DFS in NAT + RH group, while ADCmax was that in CCRT group.

Conclusion
The NAT + RH patients had similar DFS to that of CCRT in IB2 and IIA2 SCC, which could be a potential feasible alternative treatment. ADCmin and ADCmax were more valuable in evaluating the outcome of patients who underwent NAT + RH or CCRT, respectively.
Retinoic acid delays initial photoreceptor differentiation and results in a highly structured mature retinal organoid
Authors: Sanjurjo-Soriano Carla , Erkilic Nejla , Damodar Krishna , Boukhaddaoui Hassan , Diakatou Michalitsa , Garita-Hernandez Marcela , Mamaeva Daria , Dubois Gregor , Jazouli Zhour , Jimenez-Medina Carla , Goureau Olivier , Meunier Isabelle , Kalatzis Vasiliki 
Published: September 2022

Abstract
Background
Human-induced pluripotent stem cell-derived retinal organoids are a valuable tool for disease modelling and therapeutic development. Many efforts have been made over the last decade to optimise protocols for the generation of organoids that correctly mimic the human retina. Most protocols use common media supplements; however, protocol-dependent variability impacts data interpretation. To date, the lack of a systematic comparison of a given protocol with or without supplements makes it difficult to determine how they influence the differentiation process and morphology of the retinal organoids.

Methods
A 2D-3D differentiation method was used to generate retinal organoids, which were cultured with or without the most commonly used media supplements, notably retinoic acid. Gene expression was assayed using qPCR analysis, protein expression using immunofluorescence studies, ultrastructure using electron microscopy and 3D morphology using confocal and biphoton microscopy of whole organoids.

Results
Retinoic acid delayed the initial stages of differentiation by modulating photoreceptor gene expression. At later stages, the presence of retinoic acid led to the generation of mature retinal organoids with a well-structured stratified photoreceptor layer containing a predominant rod population. By contrast, the absence of retinoic acid led to cone-rich organoids with a less organised and non-stratified photoreceptor layer.

Conclusions
This study proves the importance of supplemented media for culturing retinal organoids. More importantly, we demonstrate for the first time that the role of retinoic acid goes beyond inducing a rod cell fate to enhancing the organisation of the photoreceptor layer of the mature organoid.
TGF-β2 enhances expression of equine bone marrow-derived mesenchymal stem cell paracrine factors with known associations to tendon healing
Authors: Koch Drew W. , Schnabel Lauren V. , Ellis Ilene M. , Bates Rowan E. , Berglund Alix K. 
Published: September 2022

Abstract
Background
Mesenchymal stem cells (MSCs) secrete paracrine factors and extracellular matrix proteins that contribute to their ability to support tissue healing and regeneration. Both the transcriptome and the secretome of MSCs can be altered by treating the cells with cytokines, but neither have been thoroughly investigated following treatment with the specific cytokine transforming growth factor (TGF)-β2.

Methods
RNA-sequencing and western blotting were used to compare gene and protein expression between untreated and TGF-β2-treated equine bone marrow-derived MSCs (BM-MSCs). A co-culture system was utilized to compare equine tenocyte migration during co-culture with untreated and TGF-β2-treated BM-MSCs.

Results
TGF-β2 treatment significantly upregulated gene expression of collagens, extracellular matrix molecules, and growth factors. Protein expression of collagen type I and tenascin-C was also confirmed to be upregulated in TGF-β2-treated BM-MSCs compared to untreated BM-MSCs. Both untreated and TGF-β2-treated BM-MSCs increased tenocyte migration in vitro.

Conclusions
Treating equine BM-MSCs with TGF-β2 significantly increases production of paracrine factors and extracellular matrix molecules important for tendon healing and promotes the migration of tenocytes in vitro.
Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma
Authors: Cao Haibo , Zhuo Ran , Zhang Zimu , Wang Jianwei , Tao Yanfang , Yang Randong , Guo Xinyi , Chen Yanling , Jia Siqi , Yao Ye , Yang Pengcheng , Yu Juanjuan , Jiao Wanyan , Li Xiaolu , Fang Fang , Xie Yi , Li Gen , Wu Di , Wang Hairong , Feng Chenxi , Xu Yunyun , Li Zhiheng , Pan Jian , Wang Jian 
Published: September 2022

Abstract
Background
Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neuroblastoma (NB) and is improperly controlled by super enhancers, a mammalian genome region that has been shown to control the expression of NB cell identity genes. However, the specific molecular pathways by which INSM2 leads to NB disease development are unknown.

Results
We identified INSM2 as a gene regulated by super enhancers in NB. In addition, INSM2 expression levels were significantly upregulated in NB and correlated with poor prognosis in patients. We found that INSM2 drives the growth of NB cell lines both in vitro and in vivo. Knocking down INSM2 inhibited fatty acid metabolism in NB cells. Mechanistically, INSM2 regulates the expression of SREBP1 by regulating the mTOR signaling pathway, which in turn affects lipid metabolism, thereby mediating the occurrence and development of neuroblastoma.

Conclusion
INSM2 as a super-enhancer-associated gene could regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma.
Formal mindfulness practice predicts reductions in PTSD symptom severity following a mindfulness-based intervention for women with co-occurring PTSD and substance use disorder
Authors: Somohano Vanessa C. , Kaplan Josh , Newman Aurora G. , O’Neil Maya , Lovejoy Travis 
Published: September 2022

Abstract
Background
Women with co-occurring posttraumatic stress disorder (PTSD) and substance use disorder (SUD) experience systemic barriers that place them in danger of poorer treatment outcomes. Some mindfulness-based interventions (MBIs) have demonstrated efficacy in reducing PTSD and SUD symptoms. Mindfulness practice is a core component of MBIs, thought to elicit and maintain positive behavioral change; however, no research to our knowledge has assessed the role of mindfulness practice on sustained treatment gains among women with co-occurring PTSD-SUD. Such research is necessary to better inform MBIs for dually diagnosed women.

Methods
This secondary analysis assessed whether post-intervention formal and informal mindfulness practice predicted reductions in PTSD symptoms and substance craving 6 months following an 8-session mindfulness-based relapse prevention intervention for women diagnosed with co-occurring PTSD-SUD (N = 23). Data were derived from a pilot randomized controlled trial evaluating the feasibility and preliminary efficacy of a trauma-integrated mindfulness-based relapse prevention program for women with co-occurring PTSD-SUD.

Results
Greater duration of formal mindfulness practice (i.e., minutes per practice) predicted reduced total PTSD symptoms ($$\upbeta$$
β
= − .670, p < .00), trauma-related avoidance ($$\upbeta$$
β
= − .564, p = .01), arousal and reactivity ($$\upbeta$$
β
= − .530, p = .02), and negative cognitions and mood ($$\upbeta$$
β
= − .780, p < .01) six months following treatment. Informal practice did not predict any outcomes.

Conclusions
This research highlights the potential role of formal mindfulness practice in sustaining reductions in PTSD symptoms over time among women with co-occurring PTSD-SUD. Further study of strategies to promote ongoing formal mindfulness practice in this population following a MBI are warranted.
Trial registration The parent trial was registered with ClinicalTrials.gov (Identifier: NCT03505749).