scholarly journals Is HNF4A gene, a risk factor or protection against coronary artery disease?

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Temtem ◽  
M Serrao ◽  
M I Mendonca ◽  
M Santos ◽  
A Sousa ◽  
...  
Keyword(s):  
Regression Model ◽  
Genetic Model ◽  
Hepatic Lipase ◽  
Bivariate Analysis ◽  
Event Analysis ◽  
Loss Of Function ◽  
Atherosclerosis Progression ◽  
Lipid Disorders ◽  
Kaplan Meier ◽  
Survival Regression

Abstract Background Hepatocyte nuclear factor4 A (HNF4A) gene was considered by GWAS associated with atherosclerosis and CAD susceptibility. Loss-of-function mutations in human hepatocyte nuclear factor 4α (HNF4α), a transcriptor factor encoded by the HNF4A gene, are associated with maturity-onset diabetes of the young and lipid disorders. However, the mechanisms underlying the lipid disorders are poorly understood. Aim We propose identifying the genetic predisposition to atherosclerosis progression and events occurrence or regression and better prognosis, through a cohort study from GENEMACOR population. Methods We investigated a cohort of 1,712 patients who underwent coronary angiography with more than 70% stenosis of at least one main coronary vessel. 33 SNPs associated with the risk of CAD in previous GWAS were genotyped by TaqMan assays methodology. We evaluated the best genetic model associated with CAD prognosis (events) with a 95% CI in bivariate analysis. The hazard function was performed by a Cox survival regression model adjusted for age, sex, type 2 diabetes, hypertension, and hypercholesterolemia, to evaluate their relationship with the event's incidence. Finally, we constructed Kaplan–Meier cumulative-event curves for the significant genetic variants. Results Our evaluation revealed a SNP paradoxically associated with protection from atherosclerosis progression and events occurrence: rs1884613 C>G in the HNF4A gene on chromosome 20 dominant model [OR=0.653; 95% CI (0.522–0.817); p=0.0002]. Cox survival regression model showed a CAD protective effect of HNF4A with a Hazard ratio (HR) of 0.771; p=0.007. The Kaplan-Meier cumulative event analysis disclosed that the CG+GG vs CC genotype of rs1884613 HNF4α was associated with a better prognosis (Breslow test, p=0.004) at the end of the follow-up. Conclusion We identified, in this study, one SNPs paradoxically associated with a better CAD prognosis rs1884613 in HNF4A. The HNF4A gene variants could induce loss of HNF4α function, modifying and modulating hepatic lipase and lipid metabolism conferring a beneficial effect on atherosclerosis progression and events occurrence. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

scholarly journals Review of Outcomes after Diagnosis of Malignancy in Kidney Transplant Patients: UNOS Database

2021 ◽  
Vol 2 (3) ◽  
pp. 253-263
Author(s):  
Het Patel ◽  
Nikhil Agrawal ◽  
Voravech Nissaisorakarn ◽  
Ridhi Gupta ◽  
Francesca Cardarelli
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Event Analysis ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Time To Event ◽  
Transplant Patients ◽  
Kaplan Meier ◽  
Lung Malignancy ◽  
Kidney Transplant Patients

Malignancy is the third major cause of death among transplant recipients. Patient and kidney transplant outcomes after the diagnosis of malignancy are not well described. We reviewed incidences and outcomes of colorectal, lung, PTLD, and renal malignancy after transplant among patients who received a transplant from January 2000 to December 2018 using the UNOS/OPTN database. Incidence of each malignancy was measured at 5 years and 10 years of transplant. The Kaplan–Meier curve was used for time-to-event analysis (graft and patient outcomes). Additionally, we sought to identify the causes of graft failure among these recipients. We found that 12,764 (5.5%) patients suffered malignancy, excluding squamous and basal cell skin carcinoma after transplant. During the first 5 years of transplant, incidence of colorectal, lung, PTLD, and renal malignancies was 2.99, 9.21, 15.61, and 8.55 per 10,000 person-years, respectively. Rates of graft failure were 10.3%, 7.6%, 19.9%, and 18.8%, respectively, among these patients at 5 years. Mortality rate was highest among patients who suffered lung malignancy (84%), followed by colorectal (61.5%), PTLD (49.1%), and renal (35.5%) at 5 years after diagnosis of malignancy. In conclusion, kidney transplant recipients diagnosed with lung malignancy have the lowest graft survival, compared to PTLD, colorectal, and renal malignancy. PTLD has the highest incidence rate in the first 5 years of transplant.

Sustainability Time and Its Determinant Factors of Small and Medium-scale Enterprises in East Gojjam Zone: Parametric Survival Regression Model

2021 ◽  
pp. 097215092098865
Author(s):  
Amare Wubishet Ayele ◽  
Abebaw Bizuayehu Derseh
Keyword(s):  
Regression Model ◽  
Marketing Channel ◽  
Educational Status ◽  
Weibull Regression ◽  
Service Sectors ◽  
Weibull Regression Model ◽  
Parametric Survival ◽  
Prospective Study Design ◽  
Significant Factors ◽  
Survival Regression

The contributions of small and medium-sized enterprises (SMEs) to socio-economic development are generally recognized, but they have faced several obstacles that impede their sustainability. This manuscript seeks to identify factors for the survival of SMEs in the East Gojjam Zone, Ethiopia. The prospective study design was employed. Both descriptive and inferential statistics, particularly families of parametric survival regression models, have been used. Of the 650 enterprises included in this study, 330 (50.8%) were censored (sustained enterprises) and the remaining 320 (49.2%) were events or withdrawn enterprises. The findings of this study revealed that the incidence of termination or withdrawal of SMEs in the study area is relatively common. The results from multivariable Weibull regression model revealed that woreda, sector, manger profile (gender, age, educational status, experience (in year) and source of experience), working place, marketing channel and profitability district status of enterprise were found to be statistically significant factors for the sustainability of enterprises in the study area. The bodies concerned, in particular the enterprise administrative offices at various levels, should work with collaborative organizations to develop a strong marketing platform (network), should be able to make workplaces accessible with the required infrastructure at minimal rental costs, and should prioritize the type of sector that has the highest customer needs at the onset, for instance, agriculture and service sectors.

Combination of quantitative features from H&E biopsies and CT scans predicts response to chemotherapy and overall survival in small cell lung cancer (SCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8572-8572
Author(s):  
Cristian Barrera ◽  
Mohammadhadi Khorrami ◽  
Prantesh Jain ◽  
Pingfu Fu ◽  
Kate Butler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Regression Model ◽  
Risk Score ◽  
Risk Group ◽  
Image Features ◽  
Small Cell ◽  
Ct Scans ◽  
Small Cell Lung ◽  
Kaplan Meier ◽  
Response To Chemotherapy

8572 Background: Small Cell Lung Cancer (SCLC) is an aggressive malignancy with a rapid growth, and Chemotherapy remains mainstay of treatment. Identifying therapeutic targets in SCLC presents a challenge, partially due to a lack of accurate and consistently predictive biomarkers. In this study we sought to evaluate the utility of a combination of computer-extracted radiographic and pathology features from pretreatment baseline CT and H&E biopsy images to predict sensitivity to platinum-based chemotherapy and overall survival (OS) in SCLC. Methods: Seventy-eight patients with extensive and limited-stage SCLC who received platinum-doublet chemotherapy were selected. Objective response to chemotherapy (RECIST criteria) and overall survival (OS) as clinical endpoints were available for 51 and 78 patients respectively. The patients were divided randomly into two sets (Training (Sd), Validation (Sv)) with a constraint (equal number of responders and nonresponders in Sd)—Sd comprised twenty-one patients with SCLC. Sv included thirty patients. CT scans and digitized Hematoxylin Eosin-stained (H&E) biopsy images were acquired for each patient. A set of CT derived (46%) and tissue derived (53%) image features were captured. These included shape and textural patterns of the tumoral and peritumoral regions from CT scans and of tumor regions on H&E images. A random forest feature selection and linear regression model were used to identify the most predictive CT and H&E derived image features associated with chemotherapy response from Sd. A Cox proportional hazard regression model was used with these features to compute a risk score for each patients in Sd. Patients in Sv were stratified into high and low-risk groups based on the median risk score. Kaplan-Meier survival analysis was used to assess the prognostic ability of the risk score on Sv. Results: The risk score comprised nine CT (intra and peri-tumoral texture) and six H&E derived (cancer cell texture and shape) features. A linear regression model in conjunction with these 15 features was significantly associated with chemo-sensitivity in Sv (AUC = 0.76, PRC = 0.81). A multivariable model with these 15 features was significantly associated with OS in Sv (HR = 2.5, 95% CI: 1.3-4.9, P = 0.0043). Kaplan-Meier survival analysis revealed a significantly reduced OS in the high-risk group compared to the low-risk group. Conclusions: A combined CT and H&E tissue derived image signature model predicted response to chemotherapy and improved OS in SCLC patients. Image features from baseline CT scans and H&E tissue slide images may help in better risk stratification of SCLC patients. Additional independent validation of these quantitative image-based biomarkers is warranted.

Deciphering Links Between Sexual Violence and Castes in India

2021 ◽  
pp. 2455328X2110325
Author(s):  
Yogendra Musahar
Keyword(s):  
Regression Model ◽  
Sexual Violence ◽  
Economic Status ◽  
Family Health ◽  
Uttar Pradesh ◽  
Binary Logistic Regression ◽  
Wealth Index ◽  
Bivariate Analysis ◽  
Binary Logistic Regression Model ◽  
Explanatory Variables

The recent incident, the gang rape and murder of a 19-year-old woman in Hathras, a small village in Uttar Pradesh of India, once again sparks a debate on links between sexual violence and castes in India. This article aims to examine the links between sexual violence and castes in India. This study utilizes the national representative National Family Health Survey 4 (NFHS-4, 2015–16) data. A bivariate analysis was carried out to analyse the data. A binary logistic regression model was applied to predict the effect of explanatory variables, viz. type of place of residence, years of schooling complete, economic status in terms of wealth index and finally castes on predicted variable, i.e. sexual violence. The binary regression model indicates that there were links between sexual violence and castes. For secured and dignified life of women, caste-based sexual violence must be annihilated.

scholarly journals Colonization with Extensively Drug-Resistant Acinetobacter Baumannii and Prognosis in Critically Ill Patients: An Observational Cohort Study

2021 ◽  
Author(s):  
Yue Zheng ◽  
Nana Xu ◽  
Jiaojiao Pang ◽  
Hui Han ◽  
Hongna Yang ◽  
...  
Keyword(s):  
Regression Model ◽  
Acinetobacter Baumannii ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Drug Resistant ◽  
Short Term ◽  
Term Survival ◽  
Extensively Drug Resistant ◽  
Kaplan Meier

Abstract Background: Acinetobacter baumannii is one of the most often isolated opportunistic pathogens in intensive care units (ICUs). Extensively drug-resistant A. baumannii (XDR-AB) strains lack susceptibility to almost all antibiotics and pose a heavy burden on healthcare institutions. In this study, we evaluated the impact of XDR-AB colonization on both the short-term and long-term survival of critically ill patients.Methods: We prospectively enrolled patients from two adult ICUs in Qilu Hospital of Shandong University from April 2018 through December 2018. Using nasopharyngeal and perirectal swabs, we evaluated the presence of XDR-AB colonization. Participants were followed up for six months. Primary endpoints were 28-day and six-month mortality after ICU admission. For survival analysis, we used the Kaplan-Meier curve. We identified risk factors associated with 28-day and six-month mortality using the logistic regression model and Cox proportional-hazards survival regression model, respectively. Results: Out of 431 patients, 77 were colonized with XDR-AB. Based on the Kaplan-Meier curve results, the survival before 28 days did not differ by colonization status; however, a significant lower survival rate was obtained at six months in colonized patients. Univariate and multivariate results confirmed that XDR-AB colonization was not associated with 28-day mortality, but was an independent risk factor of lower survival days at six months, resulting in a 1.97 times higher risk of death at six months.Conclusions: XDR-AB colonization has no effect on short-term mortality but is associated with lower long-term survival in critically ill patients.

scholarly journals Cox proportion hazard model for patients with hepatitis disease in Iraq

2009 ◽  
Vol 6 (3) ◽  
pp. 612-617
Author(s):  
Baghdad Science Journal
Keyword(s):  
Regression Model ◽  
Survival Time ◽  
Cox Regression ◽  
Survival Function ◽  
Hazard Model ◽  
Cox Regression Model ◽  
Hepatic Diseases ◽  
Kaplan Meier

Cox regression model have been used to estimate proportion hazard model for patients with hepatitis disease recorded in Gastrointestinal and Hepatic diseases Hospital in Iraq for (2002 -2005). Data consists of (age, gender, survival time terminal stat). A Kaplan-Meier method has been applied to estimate survival function and hazerd function.

Survival analysis

2020 ◽  
pp. 181-218
Author(s):  
Bendix Carstensen
Keyword(s):  
Survival Analysis ◽  
Competing Risks ◽  
Cox Model ◽  
Survival Function ◽  
Event Analysis ◽  
Time To Event ◽  
Poisson Models ◽  
Kaplan Meier ◽  
Analysis Survival ◽  
Event Rates

This chapter describes survival analysis. Survival analysis concerns data where the outcome is a length of time, namely the time from inclusion in the study (such as diagnosis of some disease) till death or some other event — hence the term 'time to event analysis', which is also used. There are two primary targets normally addressed in survival analysis: survival probabilities and event rates. The chapter then looks at the life table estimator of survival function and the Kaplan–Meier estimator of survival. It also considers the Cox model and its relationship with Poisson models, as well as the Fine–Gray approach to competing risks.

scholarly journals Overexpression of CLEC18B Associates With the Proliferation, Migration, and Prognosis of Glioblastoma

ASN NEURO ◽  
2018 ◽  
Vol 10 ◽  
pp. 175909141878194 ◽  
Author(s):  
Rui-Ming Guo ◽  
Cheng-Bin Zhao ◽  
Peng Li ◽  
Liang Zhang ◽  
Su-Hua Zang ◽  
...  
Keyword(s):  
Inverse Correlation ◽  
The Cancer Genome Atlas ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Lectin Domain ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Interfering Rna

C-type lectin domain family 18 member B (CLEC18B), encoding a superfamily of CLEC, has been found to be expressed in some of cancer cells, which possibly indicates it associated with cancer. However, the defined functional characterizations of CLEC18B in glioblastoma multiforme (GBM) progression still remain unclear. To this end, clinical relevance of CLEC18B expression with GBM patients’ prognosis was analyzed both in The Cancer Genome Atlas dataset of 174 tissues and 40 GBM tumor tissues collected from our hospital by using the Kaplan–Meier survival and the Cox proportional hazard model. The role of CLEC18B in GBM was determined by loss-of-function assay using small interfering RNA approach in vitro. Functional and signaling analyses were also performed to understand how CLEC18B facilitated the aggressiveness of GBM at molecular and cellular levels using Cell Counting Kit-8 assay, wound-healing, transwell, and Western blot analyses. Results from our analyses showed that CLEC18B was markedly elevated in both GBM tissues and cells, and exhibited strong inverse correlation with overall survival in GBM patients. Moreover, CLEC18B was identified as an independent predictor of patient survival. Functionally, knockdown of CLEC18B inhibited the growth, migration, and invasion of GBM cells. Mechanistic studies revealed that silencing of CLEC18B resulted in downregulation of Wnt/β-catenin signaling activity. Collectively, our findings provide clinical, molecular, and cellular evidence of CLEC18B as a promising prognostic biomarker and therapeutic target for GBM.

Sign in / Sign up

Export Citation Format

Share Document