bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel 14-gene signature for overall survival in lung adenocarcinoma based on the Bayesian hierarchical Cox proportional hazards model
Authors: Sun Na , Chu Jiadong , Hu Wei , Chen Xuanli , Yi Nengjun , Shen Yueping 
Published: January 2022

AbstractThere have been few investigations of cancer prognosis models based on Bayesian hierarchical models. In this study, we used a novel Bayesian method to screen mRNAs and estimate the effects of mRNAs on the prognosis of patients with lung adenocarcinoma. Based on the identified mRNAs, we can build a prognostic model combining mRNAs and clinical features, allowing us to explore new molecules with the potential to predict the prognosis of lung adenocarcinoma. The mRNA data (n = 594) and clinical data (n = 470) for lung adenocarcinoma were obtained from the TCGA database. Gene set enrichment analysis (GSEA), univariate Cox proportional hazards regression, and the Bayesian hierarchical Cox proportional hazards model were used to explore the mRNAs related to the prognosis of lung adenocarcinoma. Multivariate Cox proportional hazard regression was used to identify independent markers. The prediction performance of the prognostic model was evaluated not only by the internal cross-validation but also by the external validation based on the GEO dataset (n = 437). With the Bayesian hierarchical Cox proportional hazards model, a 14-gene signature that included CPS1, CTPS2, DARS2, IGFBP3, MCM5, MCM7, NME4, NT5E, PLK1, POLR3G, PTTG1, SERPINB5, TXNRD1, and TYMS was established to predict overall survival in lung adenocarcinoma. Multivariate analysis demonstrated that the 14-gene signature (HR 3.960, 95% CI 2.710–5.786), T classification (T1, reference; T3, HR 1.925, 95% CI 1.104–3.355) and N classification (N0, reference; N1, HR 2.212, 95% CI 1.520–3.220; N2, HR 2.260, 95% CI 1.499–3.409) were independent predictors. The C-index of the model was 0.733 and 0.735, respectively, after performing cross-validation and external validation, a nomogram was provided for better prediction in clinical application. Bayesian hierarchical Cox proportional hazards models can be used to integrate high-dimensional omics information into a prediction model for lung adenocarcinoma to improve the prognostic prediction and discover potential targets. This approach may be a powerful predictive tool for clinicians treating malignant tumours.
Baseline predictors for subretinal fibrosis in neovascular age-related macular degeneration
Authors: Roberts Philipp K. , Schranz Markus , Motschi Alice , Desissaire Sylvia , Hacker Valentin , Pircher Michael , Sacu Stefan , Buehl Wolf , Hitzenberger Christoph K. , Schmidt-Erfurth Ursula M. 
Published: January 2022

AbstractTo find baseline predictors for subretinal fibrosis (SF) in neovascular age-related macular degeneration (nAMD). Forty-five eyes of 45 participants with treatment-naïve nAMD were consecutively enrolled and treated according to a standardized treat-and-extend protocol. Spectral-domain optical coherence tomography (OCT), color fundus photography and fluorescein angiography as well as novel imaging modalities polarization-sensitive OCT and OCT angiography (OCTA) were performed to detect SF after 1 year and find baseline predictors for SF development. Baseline OCTA scans were evaluated for quantitative features such as lesion area, vessel area, vessel junctions, vessel length, vessel endpoints and mean lacunarity. Additionally, the type of macular neovascularization, the presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), retinal hemorrhage as well as best-corrected visual acuity (BCVA) were evaluated. After 12 months 8 eyes (18%) developed SF. Eyes with SF had worse baseline BCVA (p = .001) and a higher prevalence of IRF (p = .014) and SHRM at baseline (p = .017). There was no significant difference in any of the evaluated quantitative OCTA parameters (p > .05) between eyes with and without SF. There were no quantitative baseline microvascular predictors for SF in our study. Low baseline BCVA, the presence of IRF and SHRM, however, are easily identifiable baseline parameters indicating increased risk.
Statistical analysis for explosives detection system test and evaluation
Authors: Lukow Stefan , Weatherall James C. 
Published: January 2022

AbstractThe verification of trace explosives detection systems is often constrained to small sample sets, so it is important to support the significance of the results with statistical analysis. As binary measurements, the trials are assessed using binomial statistics. A method is described based on the probability confidence interval and expressed in terms of the upper confidence interval bound that reports the probability of successful detection and its level of statistical confidence. These parameters provide useful measures of the system’s performance. The propriety of combining statistics for similar tests—for example in trace detection trials of an explosive on multiple surfaces—is examined by statistical tests. The use of normal statistics is commonly applied to binary testing, but the confidence intervals are known to behave poorly in many circumstances, including small sample numbers. The improvement of the normal approximation with increasing sample number is shown not to be substantial for the typical numbers used in this type of explosives detection system testing, and binary statistics are preferred. The methods and techniques described here for testing trace detection can be applied as well to performance testing of explosives detection systems in general.
Risk factors for hemorrhoidal disease among healthy young and middle-aged Korean adults
Authors: Hong Yun Soo , Jung Kyung Uk , Rampal Sanjay , Zhao Di , Guallar Eliseo , Ryu Seungho , Chang Yoosoo , Kim Hyung Ook , Kim Hungdai , Chun Ho-Kyung , Sohn Chong Il , Shin Hocheol , Cho Juhee 
Published: January 2022

AbstractHemorrhoidal disease is a highly prevalent anorectal condition causing substantial discomfort, disability, and decreased quality of life. Evidence on preventable risk factors for hemorrhoidal disease is limited. We conducted a cross-sectional study of 194,620 healthy men and women who completed a health screening exam including colonoscopy in 2011–2017. We evaluated potential risk factors of hemorrhoidal disease, including lifestyle factors, medical history, birth history, gastrointestinal symptoms, and anthropometric measurements. The prevalence of hemorrhoidal disease was 16.6%, and it was higher in females than in males (17.2 vs. 16.3%; P < 0.001). Compared to men, the prevalence of hemorrhoidal disease was higher in parous women (adjusted odds ratio [OR] 1.06; 95% confidence interval [CI] 1.02–1.10), and lower in nulliparous women (adjusted OR 0.92; 95% CI 0.86–0.98). In the adjusted analyses, older age, female sex, smoking, overweight, and being hypertensive were independently associated with the presence of hemorrhoidal disease. The prevalence of hemorrhoidal disease was positively associated with body mass index and waist circumference in parous women. The prevalence of hemorrhoidal disease was higher in older age, females, ever-smokers, and hypertensive participants. The association of excess adiposity with the prevalence of hemorrhoidal disease differed by sex and parity.
Field deployable impedance-based corrosion sensor
Authors: Li Jiajun , Jiang Xiaoxue , Khan Faheem , Ye Xuanjie , Wang Shuren , Chen Jie 
Published: January 2022

AbstractElectrochemical impedance spectroscopy (EIS) has been used in various applications, such as metal corrosion monitoring. However, many conventional corrosion monitoring setups are bulky and inconvenient for in-situ testing. The purpose of this work is to reduce the size of the whole corrosion monitoring system. We utilized EIS to design a field deployable impedance-based corrosion sensor (FDICS), capable of performing in-situ EIS analysis. Experiments verified the sensor’s accuracy, and the results showed that the sensor performed similarly to a bench-top EIS machine when we tested on circuit models. Furthermore, we used the proposed FDICS to monitor a metal corrosion experiment and performed EIS. The result showed that the proposed FDICS is able to obtain the sample’s impedance spectroscopy, which could help researchers test its corrosion severity on a metallic sample in-situ. Compared to other bulky conventional setups, our device eliminates the design complexity while still showing insights into the corrosion reaction.
SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity
Authors: Berdyński Mariusz , Miszta Przemysław , Safranow Krzysztof , Andersen Peter M. , Morita Mitsuya , Filipek Sławomir , Żekanowski Cezary , Kuźma-Kozakiewicz Magdalena 
Published: January 2022

AbstractMutations in superoxide dismutase 1 gene (SOD1) are linked to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder predominantly affecting upper and lower motor neurons. The clinical phenotype of ALS shows inter- and intrafamilial heterogeneity. The aim of the study was to analyze the relations between individual SOD1 mutations and the clinical presentation using in silico methods to assess the SOD1 mutations severity. We identified SOD1 causative variants in a group of 915 prospectively tested consecutive Polish ALS patients from a neuromuscular clinical center, performed molecular modeling of mutated SOD1 proteins and in silico analysis of mutation impact on clinical phenotype and survival analysis of associations between mutations and hazard of clinical end-points. Fifteen SOD1 mutations were identified in 21.1% familial and 2.3% sporadic ALS cases. Their effects on SOD1 protein structure and functioning inferred from molecular modeling and in silico analyses correlate well with the clinical data. Molecular modeling results support the hypothesis that folding intermediates rather than mature SOD1 protein give rise to the source of cytotoxic conformations in ALS. Significant associations between type of mutation and clinical end-points were found.
Interrelationship between 2019-nCov receptor DPP4 and diabetes mellitus targets based on protein interaction network
Authors: Gao Qian , Zhang Wenjun , Li Tingting , Yang Guojun , Zhu Wei , Chen Naijun , Jin Huawei 
Published: January 2022

AbstractPatients with diabetes are more likely to be infected with Coronavirus disease 2019 (COVID-19), and the risk of death is significantly higher than ordinary patients. Dipeptidyl peptidase-4 (DPP4) is one of the functional receptor of human coronavirus. Exploring the relationship between diabetes mellitus targets and DPP4 is particularly important for the management of patients with diabetes and COVID-19. We intend to study the protein interaction through the protein interaction network in order to find a new clue for the management of patients with diabetes with COVID-19. Diabetes mellitus targets were obtained from GeneCards database. Targets with a relevance score exceeding 20 were included, and DPP4 protein was added manually. The initial protein interaction network was obtained through String. The targets directly related to DPP4 were selected as the final analysis targets. Importing them into String again to obtain the protein interaction network. Module identification, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were carried out respectively. The impact of DPP4 on the whole network was analyzed by scoring the module where it located. 43 DPP4-related proteins were finally selected from the diabetes mellitus targets and three functional modules were found by the cluster analysis. Module 1 was involved in insulin secretion and glucagon signaling pathway, module 2 and module 3 were involved in signaling receptor binding. The scoring results showed that LEP and apoB in module 1 were the highest, and the scores of INS, IL6 and ALB of cross module associated proteins of module 1 were the highest. DPP4 is widely associated with key proteins in diabetes mellitus. COVID-19 may affect DPP4 in patients with diabetes mellitus, leading to high mortality of diabetes mellitus combined with COVID-19. DPP4 inhibitors and IL-6 antagonists can be considered to reduce the effect of COVID-19 infection on patients with diabetes.
Artificial intelligence predicts clinically relevant atrial high-rate episodes in patients with cardiac implantable electronic devices
Authors: Kim Min , Kang Younghyun , You Seng Chan , Park Hyung-Deuk , Lee Sang-Soo , Kim Tae-Hoon , Yu Hee Tae , Choi Eue-Keun , Park Hyoung-Seob , Park Junbeom , Lee Young Soo , Kang Ki-Woon , Shim Jaemin , Sung Jung-Hoon , Oh Il-Young , Park Jong Sung , Joung Boyoung 
Published: January 2022

AbstractTo assess the utility of machine learning (ML) algorithms in predicting clinically relevant atrial high-rate episodes (AHREs), which can be recorded by a pacemaker. We aimed to develop ML-based models to predict clinically relevant AHREs based on the clinical parameters of patients with implanted pacemakers in comparison to logistic regression (LR). We included 721 patients without known atrial fibrillation or atrial flutter from a prospective multicenter (11 tertiary hospitals) registry comprising all geographical regions of Korea from September 2017 to July 2020. Predictive models of clinically relevant AHREs were developed using the random forest (RF) algorithm, support vector machine (SVM) algorithm, and extreme gradient boosting (XGB) algorithm. Model prediction training was conducted by seven hospitals, and model performance was evaluated using data from four hospitals. During a median follow-up of 18 months, clinically relevant AHREs were noted in 104 patients (14.4%). The three ML-based models improved the discrimination of the AHREs (area under the receiver operating characteristic curve: RF: 0.742, SVM: 0.675, and XGB: 0.745 vs. LR: 0.669). The XGB model had a greater resolution in the Brier score (RF: 0.008, SVM: 0.008, and XGB: 0.021 vs. LR: 0.013) than the other models. The use of the ML-based models in patient classification was associated with improved prediction of clinically relevant AHREs after pacemaker implantation.
Genomic studies controvert the existence of the CUX1 p75 isoform
Authors: Krishnan Manisha , Senagolage Madhavi D. , Baeten Jeremy T. , Wolfgeher Donald J. , Khan Saira , Kron Stephen J. , McNerney Megan E. 
Published: January 2022

AbstractCUX1, encoding a homeodomain-containing transcription factor, is recurrently deleted or mutated in multiple tumor types. In myeloid neoplasms, CUX1 deletion or mutation carries a poor prognosis. We have previously established that CUX1 functions as a tumor suppressor in hematopoietic cells across multiple organisms. Others, however, have described oncogenic functions of CUX1 in solid tumors, often attributed to truncated CUX1 isoforms, p75 and p110, generated by an alternative transcriptional start site or post-translational cleavage, respectively. Given the clinical relevance, it is imperative to clarify these discrepant activities. Herein, we sought to determine the CUX1 isoforms expressed in hematopoietic cells and find that they express the full-length p200 isoform. Through the course of this analysis, we found no evidence of the p75 alternative transcript in any cell type examined. Using an array of orthogonal approaches, including biochemistry, proteomics, CRISPR/Cas9 genomic editing, and analysis of functional genomics datasets across a spectrum of normal and malignant tissue types, we found no data to support the existence of the CUX1 p75 isoform as previously described. Based on these results, prior studies of p75 require reevaluation, including the interpretation of oncogenic roles attributed to CUX1.
Spontaneous mutation rate estimates for the principal malaria vectors Anopheles coluzzii and Anopheles stephensi
Authors: Rashid Iliyas , Campos Melina , Collier Travis , Crepeau Marc , Weakley Allison , Gripkey Hans , Lee Yoosook , Schmidt Hanno , Lanzaro Gregory C. 
Published: January 2022

AbstractUsing high-depth whole genome sequencing of F0 mating pairs and multiple individual F1 offspring, we estimated the nuclear mutation rate per generation in the malaria vectors Anopheles coluzzii and Anopheles stephensi by detecting de novo genetic mutations. A purpose-built computer program was employed to filter actual mutations from a deep background of superficially similar artifacts resulting from read misalignment. Performance of filtering parameters was determined using software-simulated mutations, and the resulting estimate of false negative rate was used to correct final mutation rate estimates. Spontaneous mutation rates by base substitution were estimated at 1.00 × 10−9 (95% confidence interval, 2.06 × 10−10—2.91 × 10−9) and 1.36 × 10−9 (95% confidence interval, 4.42 × 10−10—3.18 × 10−9) per site per generation in A. coluzzii and A. stephensi respectively. Although similar studies have been performed on other insect species including dipterans, this is the first study to empirically measure mutation rates in the important genus Anopheles, and thus provides an estimate of µ that will be of utility for comparative evolutionary genomics, as well as for population genetic analysis of malaria vector mosquito species.
Genome-wide association study identifies tumor anatomical site-specific risk variants for colorectal cancer survival
Authors: Labadie Julia D. , Savas Sevtap , Harrison Tabitha A. , Banbury Barb , Huang Yuhan , Buchanan Daniel D. , Campbell Peter T. , Gallinger Steven J. , Giles Graham G. , Gunter Marc J. , Hoffmeister Michael , Hsu Li , Jenkins Mark A. , Lin Yi , Ogino Shuji , Phipps Amanda I. , Slattery Martha L. , Steinfelder Robert S. , Sun Wei , Van Guelpen Bethany , Hua Xinwei , Figuieredo Jane C. , Pai Rish K. , Nassir Rami , Qi Lihong , Chan Andrew T. , Peters Ulrike , Newcomb Polly A. 
Published: January 2022

AbstractIdentification of new genetic markers may improve the prediction of colorectal cancer prognosis. Our objective was to examine genome-wide associations of germline genetic variants with disease-specific survival in an analysis of 16,964 cases of colorectal cancer. We analyzed genotype and colorectal cancer-specific survival data from a consortium of 15 studies. Approximately 7.5 million SNPs were examined under the log-additive model using Cox proportional hazards models, adjusting for clinical factors and principal components. Additionally, we ran secondary analyses stratifying by tumor site and disease stage. We used a genome-wide p-value threshold of 5 × 10–8 to assess statistical significance. No variants were statistically significantly associated with disease-specific survival in the full case analysis or in the stage-stratified analyses. Three SNPs were statistically significantly associated with disease-specific survival for cases with tumors located in the distal colon (rs698022, HR = 1.48, CI 1.30–1.69, p = 8.47 × 10–9) and the proximal colon (rs189655236, HR = 2.14, 95% CI 1.65–2.77, p = 9.19 × 10–9 and rs144717887, HR = 2.01, 95% CI 1.57–2.58, p = 3.14 × 10–8), whereas no associations were detected for rectal tumors. Findings from this large genome-wide association study highlight the potential for anatomical-site-stratified genome-wide studies to identify germline genetic risk variants associated with colorectal cancer-specific survival. Larger sample sizes and further replication efforts are needed to more fully interpret these findings.
Histological assessment, anti-quorum sensing, and anti-biofilm activities of Dioon spinulosum extract: in vitro and in vivo approach
Authors: Elekhnawy Engy , Negm Walaa A. , El-Aasr Mona , Kamer Amal Abo , Alqarni Mohammed , Batiha Gaber El-Saber , Obaidullah Ahmad J. , Fawzy Heba M. 
Published: January 2022

AbstractPseudomonas aeruginosa is an opportunistic bacterium causing several health problems and having many virulence factors like biofilm formation on different surfaces. There is a significant need to develop new antimicrobials due to the spreading resistance to the commonly used antibiotics, partly attributed to biofilm formation. Consequently, this study aimed to investigate the anti-biofilm and anti-quorum sensing activities of Dioon spinulosum, Dyer Ex Eichler extract (DSE), against Pseudomonas aeruginosa clinical isolates. DSE exhibited a reduction in the biofilm formation by P. aeruginosa isolates both in vitro and in vivo rat models. It also resulted in a decrease in cell surface hydrophobicity and exopolysaccharide quantity of P. aeruginosa isolates. Both bright field and scanning electron microscopes provided evidence for the inhibiting ability of DSE on biofilm formation. Moreover, it reduced violacein production by Chromobacterium violaceum (ATCC 12,472). It decreased the relative expression of 4 quorum sensing genes (lasI, lasR, rhlI, rhlR) and the biofilm gene (ndvB) using qRT-PCR. Furthermore, DSE presented a cytotoxic activity with IC50 of 4.36 ± 0.52 µg/ml against human skin fibroblast cell lines. For the first time, this study reports that DSE is a promising resource of anti-biofilm and anti-quorum sensing agents.
DNA binding by the antimalarial compound artemisinin
Authors: Slavkovic Sladjana , Shoara Aron A. , Churcher Zachary R. , Daems Elise , de Wael Karolien , Sobott Frank , Johnson Philip E. 
Published: January 2022

AbstractArtemisinin (ART) is a vital medicinal compound that is used alone or as part of a combination therapy against malaria. ART is thought to function by attaching to heme covalently and alkylating a range of proteins. Using a combination of biophysical methods, we demonstrate that ART is bound by three-way junction and duplex containing DNA molecules. Binding of ART by DNA is first shown for the cocaine-binding DNA aptamer and extensively studied using this DNA molecule. Isothermal titration calorimetry methods show that the binding of ART is both entropically and enthalpically driven at physiological NaCl concentration. Native mass spectrometry methods confirm DNA binding and show that a non-covalent complex is formed. Nuclear magnetic resonance spectroscopy shows that ART binds at the three-way junction of the cocaine-binding aptamer, and that binding results in the folding of the structure-switching variant of this aptamer. This structure-switching ability was exploited using the photochrome aptamer switch assay to demonstrate that ART can be detected using this biosensing assay. This study is the first to demonstrate the DNA binding ability of ART and should lay the foundation for further work to study implications of DNA binding for the antimalarial activity of ART.
Genome-wide aberrant methylation in primary metastatic UM and their matched metastases
Authors: Smit Kyra N. , Boers Ruben , Vaarwater Jolanda , Boers Joachim , Brands Tom , Mensink Hanneke , Verdijk Robert M. , van IJcken Wilfred F. J. , Gribnau Joost , de Klein Annelies , Kilic Emine 
Published: January 2022

AbstractUveal melanoma (UM) is an aggressive intra-ocular cancer with a strong tendency to metastasize. Metastatic UM is associated with mutations in BAP1 and SF3B1, however only little is known about the epigenetic modifications that arise in metastatic UM. In this study we aim to unravel epigenetic changes contributing to UM metastasis using a new genome-wide methylation analysis technique that covers over 50% of all CpG’s. We identified aberrant methylation contributing to BAP1 and SF3B1-mediated UM metastasis. The methylation data was integrated with expression data and surveyed in matched UM metastases from the liver, skin and bone. UM metastases showed no commonly shared novel epigenetic modifications, implying that epigenetic changes contributing to metastatic spreading and colonization in distant tissues occur early in the development of UM and epigenetic changes that occur after metastasis are mainly patient-specific. Our findings reveal a plethora of epigenetic modifications in metastatic UM and its metastases, which could subsequently result in aberrant repression or activation of many tumor-related genes. This observation points towards additional layers of complexity at the level of gene expression regulation, which may explain the low mutational burden of UM.