bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole Genome Copy Number Analyses Reveal a Highly Aberrant Genome in TP53 Mutant Lung Adenocarcinoma Tumors
Authors: Bjaanaes Maria Moksnes , Nilsen Gro , Halvorsen Ann Rita , Russens Hege G. , Solberg Steinar , Jørgensen Lars , Brustugun Odd Terje , Lingjaerde Ole Christian , Helland Åslaug 
Published: May 2021

Abstract
Background: Genetic alterations are common in non-small cell lung cancer (NSCLC), and DNA mutations and translocations are targets for therapy. Copy number aberrations occur frequently in NSCLC tumors and may influence gene expression and further alter signaling pathways. In this study we aimed to characterize the genomic architecture of NSCLC tumors and to identify genomic differences between tumors stratified by histology and mutation status. Furthermore, we sought to integrate DNA copy number data with mRNA expression to find genes with expression putatively regulated by copy number aberrations and the oncogenic pathways associated with these affected genes. Methods: Copy number data were obtained from 190 resected early-stage NSCLC tumors and gene expression data were available from 113 of the adenocarcinomas. Clinical and histopathological data were known, and EGFR-, KRAS- and TP53 mutation status was determined. Allele-specific copy number profiles were calculated using ASCAT, and regional copy number aberration were subsequently obtained and analyzed jointly with the gene expression data.Results:The NSCLC tumors tissue displayed overall complex DNA copy number profiles with numerous recurrent aberrations. Despite histological differences, tissue samples from squamous cell carcinomas and adenocarcinomas had remarkably similar copy number patterns. The TP53-mutated lung adenocarcinomas displayed a highly aberrant genome, with significantly altered copy number profiles including gains, losses and focal complex events. The EGFR-mutant lung adenocarcinomas had specific arm-wise aberrations particularly at chromosome7p and 9q. A large number of genes displayed correlation between copy number and expression level, and the PI(3)K-mTOR pathway was highly enriched for such genes.Conclusions: The genomic architecture in NSCLC tumors is complex, and particularly TP53-mutated lung adenocarcinomas displayed highly aberrant copy number profiles. We suggest to always include TP53-mutation status when studying copy number aberrations in NSCLC tumors. Copy number may further impact gene expression and alter cellular signaling pathways.
A Nomogram Based On A-To-I RNA Editing Predicting The Overall Survival of Patients With Lung Squamous Carcinoma
Authors: Liu Li , Liu Jun , Tu Li , Zhao Zhuxiang , Xie Chenli , Yang Lei 
Published: May 2021

Abstract
Background: A-to-I RNA editing has been recognized as a novel hallmark of cancer, while little is known about its contribution to cancer prognosis. We aimed to develop a prognostic nomogram with A-to-I editing events in lung squamous cell carcinoma (LUSC). Methods: The TCGA A-to-I editing profile, corresponding clinical and gene expression data of LUSC were analyzed. Patients were randomly divided into a training (n = 134) and validation group (n = 94). An A-to-I risk biosignature was generated by univariate Cox regression and followed Lasso regression. Results: We identified a seven A-to-I sites-based risk biosignature that includes TMEM120B(A2588I), HMOX2(A224I), CALCOCO2(A2603I), MIR548AE2(A113641I), ZNF440(A3942I), CLCC1(A2315I), and CHMP3(A23735I). High risk was significantly associated with worse overall survival (OS) in both the training (HR = 7.30; 95%CI = 3.48-15.3) and validation groups (HR = 2.13; 95%CI = 1.09-4.15). Patients with advanced T (P = 0.021) or clinical stages (P = 0.021) had higher risk scores than the counterparters. We then developed a nomogram incorporating the A-to-I biosignature and clinicopathological features, which exerted well performance on predicting probability of LUSC OS with C-indexes as 0.808 and 0.685 in both sets. Moreover, the editing levels of ZNF440(A3942I), CLCC1(A2315I), HMOX2(A224I) are correlated with expressions of their host genes, while the levels of TMEM120B(A2588I), CLCC1(A2315I), and CALCOCO2(A2603I) differed between tumor tissues and normal tissues. Conclusions: Our results for the first time provided insight into the development of A-to-I editing‑based nomogram for predicting OS of LUSC patients.
Haemodynamic Characteristics And Factors Influencing The Head-Up Tilt Test In Patients With Orthostatic Hypotension
Authors: Jiayu Wang , Yueyang Wu , Yongjun Wang , Xingquan Zhao , Yilong Wang , Yinghui Li , Bin Wu , Linjie Wang , Lina Qu , Zhaoxia Li , Xiaomeng Yang , Aubert Andre , Jiexin Liu 
Published: May 2021

Abstract
Background: Failure to activate autonomic neural and hormonal reflex mechanisms could result in orthostatic hypotension. Patients with orthostatic hypotension often experience symptoms of cerebral hypoperfusion, including syncope. The purpose of this study was to investigate the haemodynamic characteristics of patients with orthostatic hypotension and the factors affecting blood pressure regulation.Methods: This retrospective study enrolled 45 patients who were diagnosed with typical orthostatic hypotension by the head-up tilt test at Beijing Tiantan Hospital, Capital Medical University from June 2019 to December 2020. Changes in haemodynamic parameters in these patients were compared in the supine and tilted upright positions.Results: For all patients, haemodynamic parameters in the supine and tilted upright positions were compared, and systolic blood pressure, diastolic blood pressure, mean blood pressure, cardiac output and stroke volume were all significantly decreased per minute. Heart rate significantly increased per minute, but systemic vascular resistance did not significantly change. The absolute value, percentage and rate of increases in heart rate and the absolute value, percentage and rate of decreases in stroke volume from the supine to the titled upright position were significantly lower in patients 60 years and older than in patients under 60 years old. Linear regression analyses found that the changes in heart rate, stroke volume and systemic vascular resistance were related to changes in systolic blood pressure, while the changes in stroke volume and systemic vascular resistance had more important effects on systolic blood pressure.Conclusions: In patients with orthostatic hypotension, we observed no significant increase in systemic vascular resistance from the supine position to the tilted upright position. Nevertheless, an increase in systemic vascular resistance had a significant impact on the maintenance of systolic blood pressure. In addition, in orthostatic hypotension patients younger than 60 years of age, heart rate increased while stroke volume decreased significantly after tilting upright compared with orthostatic hypotension patients older than 60 years of age and older.
The Longer The Decision-TAE Time, The Higher The Risk of Mortality: A Retrospective Study Of Trans-Arterial Embolization In Pelvic Fracture
Authors: Miyake Takahito , Okada Hideshi , Ishihara Takuma , Kanda Norihide , Mizuno Yosuke , Ichihashi Masahiro , Kamidani Ryo , Fukuta Tetsuya , Nachi Sho , Yoshida Takahiro , Nagata Shoma , Kawada Hiroshi , Matsuo Masayuki , Yoshida Shozo , Ogura Shinji 
Published: May 2021

Abstract
Early administration of hemostasis strategies, such as transcatheter arterial embolization (TAE), is critical in pelvic injury patients because they often experience hemorrhagic shock and other fatal injuries. We investigated the influence of delays in TAE administration on mortality. Patients admitted to the Advanced Critical Care Center at Gifu University with pelvic injury between January 2008 and December 2019 who underwent acute TAE were retrospectively enrolled. The time from when the doctor decided to administer TAE to the start of TAE (needling time) was defined as “decision-TAE time.” We included 162 patients. The median decision-TAE time was 59.5 min. Twenty-five patients died. Kaplan-Meier curves for overall survival were compared, with a significant difference observed between the patients above and below the median cutoff value for decision-TAE time (p=0.02). The age and sex-adjusted multivariable Cox proportional hazards regression model revealed that the longer the decision-TAE time, the higher the risk of mortality (p=0.01). The interaction between TAE duration (procedure time) and decision-TAE time was statistically significant (p=0.044), indicating that TAE duration modified the effect of decision-TAE time on mortality. Decision-TAE time may play a key role in establishing resuscitation in pelvic fracture patients, and efforts to shorten this time should be pursued.
Evaluation of Preoperative Diagnostic Methods for Resectable Pancreatic Cancer
Authors: Maruta Akinori , Iwashita Takuji , Yoshida Kensaku , Uemura Shinya , Yasuda Ichiro , Shimizu Masahito 
Published: May 2021

Abstract
Background: In pancreatic cancer clinical practice guideline 2016, it is recommended to perform pathological diagnosis as much as possible, but priorities and algorithms for diagnostic methods have not yet been established. In recent years, EUS-FNA has become mainstream as a method of collecting tissues from pancreatic disease, but the effect of EUS-FNA on surgical results and prognosis has not been clarified.Aims: To evaluate the diagnostic ability of EUS-FNA and preoperative diagnosis affects surgical outcome and prognosis of pancreatic cancer.Methods: Between January 2005 and June 2017, 293 patients who had surgical resection for pancreatic cancer were retrospectively evaluated. The interested outcomes were diagnostic ability of EUS-FNA and the influence for surgical result and prognosis.Results: The diagnostic sensitivity of EUS-FNA was 94.4%, which was significantly higher than ERCP (45.5%) (p<0.001). The adverse event rate in ERCP was 10.2%, which was significantly higher than EUS-FNA (1.3%) (p=0.001). Patients were divided into FNA group (N=160) and non-FNA group (N=133) for each preoperative diagnostic method. In the study of surgical curability R0 between two groups, there was no significant difference in FNA group: 65.0% (104/160) and non-FNA group: 64.7% (86/133), (p=1.000). In the prognostic study, the total of 256 patients with curability R0 or R1, the recurrence rate was 54.3% (70/129) in the FNA group and 57.4% (73/127) in non-FNA group. Moreover peritoneal dissemination occurred 34.3% (24/70) in the FNA group and 21.9% (16/73) in the non-FNA group, neither of which showed significant difference. The median survival time of FNA group and non-FNA group were 955 days and 799 days, respectively, and there was no significant difference between the two groups (Log rank p=0.735). In the Cox proportional hazards model examining factors influencing prognosis, staging, curability and adjuvant chemotherapy were dominant factors, but preoperative diagnostic method(EUS-FNA) itself was not.Conclusions: As a preoperative examination of pancreatic cancer, EUS-FNA was shown to be a safe procedure with high diagnostic ability. It was considered to be the first choice without the influence of surgical curability, postoperative recurrence, peritoneal dissemination and prognosis.
Aggregative trans-eQTL analysis detects trait-specific target gene sets in whole blood
Authors: Dutta Diptavo , He Yuan , Saha Ashis , Arvanitis Marios , Battle Alexis , Chatterjee Nilanjan 
Published: May 2021

Abstract
Large scale genetic association studies have identified many trait-associated variants and understanding the role of these variants in downstream regulation of gene-expressions can uncover important mediating biological mechanisms. In this study, we propose Aggregative tRans assoCiation to detect pHenotype specIfic gEne-sets (ARCHIE), as a method to establish links between sets of known genetic variants associated with a trait and sets of co-regulated gene-expressions through trans associations. ARCHIE employs sparse canonical correlation analysis based on summary statistics from trans-eQTL mapping and genotype and expression correlation matrices constructed from external data sources. A resampling based procedure is then used to test for significant trait-specific trans-association patterns in the background of highly polygenic regulation of gene-expression. Simulation studies show that compared to standard trans-eQTL analysis, ARCHIE is better suited to identify “core”-like genes through which effects of many other genes may be mediated and which can explain disease specific patterns of genetic associations. By applying ARCHIE to available trans-eQTL summary statistics reported by the eQTLGen consortium, we identify 71 gene networks which have significant evidence of trans-association with groups of known genetic variants across 29 complex traits. Around half (50.7%) of the selected genes do not have any strong trans-associations and could not have been detected by standard trans-eQTL mapping. We provide further evidence for causal basis of the target genes through a series of follow-up analyses. These results show ARCHIE is a powerful tool for identifying sets of genes whose trans regulation may be related to specific complex traits. The method has potential for broader applications for identification of networks of various types of molecular traits which mediates complex traits genetic associations.
Combined evaluation of long-lasting insecticidal nets, house screening and push-pull technology as appropriate interventions for integrated management of malaria vectors and cereal pests in Ethiopia: study protocol for household randomized controlled trial
Authors: Asale Abebe , Kassie Menale , Abro Zewdu , Enchalew Bayu , Belay Aklilu , Sangoro Peter O , Tchouassi David , Mutero Clifford M 
Published: May 2021

Abstract
Introduction: The combined application of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) has led to mixed results (Significant reduction vs no impact) on malaria burden. Other studies have attempted to study the combined effects of house screening (HS) and LLINs have demonstrated a reduction in indoor vector densities and malaria when the interventions are combined. In addition to malaria vectored by mosquitoes, farmers living in rural settings face challenges from crop pests, which significantly reduce agricultural productivity and negatively impact their food security. Thus, addressing the coexisting risks of malaria and crop pests could contribute to the improved livelihood of communities. Design: A three-armed household, cluster-randomized, controlled study will be conducted to assess the impact of HS, LLINs, and PPT against clinical malaria in children than LLINs alone in Ethiopia. The unit of randomization will be the household, which includes a house and its occupants. A total of 663 households will be enrolled in this study. All the households will receive the LLINs. Then other treatments will be overlaid according to the randomization sequence. Thus, 246 households will receive HS, and 250 households will receive HS and PPT before the commencement of clinical follow-up. The rest 167 houses that received LLINs only will be used as control. One child aged not more than 14 years will be enrolled from each household and followed for clinical malaria using active case detection to estimate malaria incidence for two malaria transmission seasons. Results: Episodes of clinical malaria, the prevalence of anaemia, density of malaria vector mosquitoes, sporozoite infection rate, crop infestation rate due to stem borer and fall armyworm, crop yield gain, livestock productivity, and cost-effectiveness analysis will be the endpoints of this study. Socio-economic, social demographic, cost-effectiveness analysis will be conducted using qualitative and participatory methods to explore the acceptability of HS and PPT. Conclusion Documenting the combined impact of LLINs, HS, and PPT on the prevalence of clinical malaria and crop pest damage will be the first of its kind and will provide deep insight and evidence base for forging collaborations between health and agriculture sectors. Trial Registration: The protocol was registered online on Date 28/05/2020 on sight www.pactr.org With registration No: PACTR202006878245287.
Diagnostic Value of Serum miR-25-3p in Hypertensive Disorders in Pregnancy
Authors: Zhou Dexia , Qu Bin , Zhang Xuan 
Published: May 2021

Abstract
Objective: Hypertensive disorders in pregnancy (HDIP) are a variety of heterogeneous conditions. microRNA (miR)-25-3p is involved in HDIP diagnosis. This study explored the clinical effects of miR-25-3p on HDIP patients.Methods: A total of 190 HDIP patients including 65 cases of gestation hypertension (GH), 67 cases of mild preeclampsia (mPE) and 58 cases of severe preeclampsia (sPEz), and 60 normal pregnant women were selected as the control. Serum miR-25-3p expression in HDIP patients and controls was detected. Diagnostic efficacy of miR-25-3p on HDIP was analyzed. HDIP patients were assigned into high/low miR-25-3p expression groups. sPEz patients assigned into high/low miR-25-3p expression group were followed up until delivery. Gestational weeks and pregnancy outcomes were recorded at delivery. The effect of miR-25-3p expression on pregnancy outcomes of sPE patients was analyzed.Results: Compared with the controls, miR-25-3p expression in GH, mPE and sPEz patients was upregulated. miR-25-3p expression was highest in sPE patients, then in mPE patients and then in GH patients. Area under the curve of miR-25-3p for sPEz diagnosis was 0.946, with 87.93% sensitivity and 98.33% specificity, which were higher than those for GH and mPE diagnosis. In sPEz patients, systolic and diastolic blood pressure, 24-h urine protein, AST, ALT, GGT and Scr were increased, and PLT was decreased in high expression group. High miR-25-3p expression increased risks of adverse pregnancy outcome in sPEz patients.Conclusions: High miR-25-3p expression helps HDIP diagnosis and is related to increased risks of adverse pregnancy outcomes in sPEz patients.
Bivariate Multilevel Modeling of Modern Contraceptive Use and Knowledge of HIV/AIDS Prevention of Women in Ethiopia
Authors: Bekele Daniel , Kebede Essey 
Published: May 2021

Abstract
Background: Ethiopia is one of the most populous countries in Africa and has the highest number of new HIV infections. Therefore, the main objectives of this study were to demonstrate the joint predictors and association between modern contraceptive use and knowledge of HIV prevention in women aged 15-49 across clusters in Ethiopia.Methods: This study considered a weighted sample of 10,223 married women aged 15-49 years, extracted from the 2016 EDHS data. The bivariate multilevel logistics regression model was used in this study.Results: In Ethiopia, 64.75%, 54.58% of the women didn’t use the modern contraceptive method and didn’t know about HIV prevention, respectively. A positive relationship between the use of modern contraceptives and knowledge of HIV prevention of women across the clusters was found, which implies that modern contraceptive use has positive implications on women's knowledge of HIV prevention techniques across the clusters.Conclusions: Predictor visiting a health facility, wealth index, media exposure, religion, place of residence, and the contextual region are statistically related with the use of modern contraceptive use and knowledge of HIV prevention of women across the clusters. Those women who use the modern contraceptive method have more likelihood of knowing about HIV prevention. The study result confirmed that modern contraceptive use has a spillover effect on women's knowledge of HIV prevention across the clusters. Therefore, the integration of the two programs with taking into account their joint predictors was an advantage in terms of clinical benefit, cost, and for seeking care individuals in the communities. The integration of two programs with due consideration of community-specific was recommended.
A Simulation of Nonlinear Thermally Radiative Hydrodynamic Stagnation Point Flow of Nanomaterial in View of a Stretchable Surface
Authors: Rasheed Haroon Ur , Islam Saeed , Khan Zeeshan , Khan Waris 
Published: May 2021

Abstract
This article aims to explore the mathematical and computational communication of transverse magnetic field interaction to stagnation point viscoelastic nanofluid flow over convectively heated stretching surface accompanied with a heat source, magnetohydrodynamics, and viscous dissipation. The mathematical framework is established for mass conservation, momentum, energy conservation, and concentration of nanoparticles is implemented. The constitutive nonlinear partial differential flow expressions are reduced by utilizing compatible similarity transformations. The non-dimensionless flow laws of (PDEs) are changed into nonlinear dimensionless governing ordinary differential flow laws and then the bvph2 numerical technique is employed for its solution. The consequences of innumerable governing flow parameters are explicitly deliberated and plotted graphically. The physical such as drag force and heat transfer rate are taken into the account and evaluated accordingly. To confirmed the legitimacy and reliability of the upcoming numerical results were compared with homotopic solution (HAM) and an outstanding promise was perceived.
Allele-Specific PCR and Next Generation Sequencing based genetic screening for Congenital Adrenal Hyperplasia in India
Authors: Ravichandran Lavanya , Korula Sophy , H.S. Asha , Varghese Deny , R Parthiban , Johnson Jabasteen , Ishwarya Janani , Shetty Sahana , Cherian Kripa Elizabeth , Jebasingh Felix , Kapoor Nitin , Pachat Divya , Mathai Sarah , Simon Anna , Rajaratnam Simon , Paul Thomas V , Thomas Nihal , Chapla Aaron 
Published: May 2021

Abstract
Purpose
Genotyping CYP21A2 gene is known to be extremely challenging and is not utilized as a first tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating extended panel of genes implicated in CAH. This study aims to establish a comprehensive genetic screening strategy for five genes in CAH.
Methods
Allele-Specific Polymerase Chain Reaction (ASPCR) for hotspot mutations in CYP21A2 gene followed by targeted Next-Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes were carried out to screen 72 clinically diagnosed CAH subjects from India.
Results
Utilizing ASPCR, 88.7% (n = 55/62) of the subjects suspected with 21 hydroxylase deficiency were positive for CYP21A2 hotspot mutations. Utilizing NGS, the ASPCR assay was found to highly sensitive and specific for screening these hotspot mutations. Additionally, through targeted NGS, six study subjects were positive for other CYP21A2 variants: one with a novel c.1274G > T, three with c.1451G > C and one with c.143A > G variant. One subject was compound heterozygous for c.955C > T/c.1042G > A variants identified using ASPCR and NGS. One subject suspected for a simple virilizing 21-hydroxylase deficiency was positive for a CYP19A1:c.1142A > T variant. CYP11B1 variants (c.1201-1G > A, c.1200 + 1delG, c.412C > T, c.1024C > T, c.1012dup, c.623G > A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency.
Conclusion
With an overall mutation-positivity rate of 97.2% (140/144 alleles), ASPCR followed by a multigene targeted NGS assay has shown to be highly sensitive and specific as a cost-effective and comprehensive diagnostic tool for CAH in a clinical setting.