bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline Determinants of Humoral Immune Response To HPV-16 Protect Against Oropharyngeal Cancer
Authors: Ferreiro-Iglesias Aida , McKay James , Brenner Nicole , Virani Shama , Lesseur Corina , Gaborieau Valérie , Ness Andrew , Hung Rayjean , Liu Geoffrey , Diergaarde Brenda , Olshan Andrew , Hayes D , Weissler Mark , Schroeder Lea , Bender Noemi , Pawlita Michael , Thomas Steven , Pring Miranda , Dudding Tom , Kanterewicz Beatriz , Ferris Robert , Thomas Sera , Brhane Yonathan , Díez-Obrero Virginia , Milojevic Maja , Smith-Byrne Karl , Mariosa Daniela , Johansson Mattias , Herrero Rolando , Boccia Stefania , Cadoni Gabriella , Lacko Martin , Holcátová Ivana , Ahrens Wolfgang , Lagiou Pagona , Lagiou Areti , Polesel Jerry , Simonato Lorenzo , Merletti Franco , Healy Claire , Hansen Bo , Nygård Mari , Conway David , Wright Sylvia , Macfarlane Tatiana , Robinson Max , Alemany Laia , Agudo Antonio , Znaor Ariana , Amos Christopher , Waterboer Tim , Brennan Paul 
Published: December 2020

Abstract
Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conducted a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer(OCC)) and 5,256 controls. Four novel susceptibility loci were detected pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, revealed two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.
Weaning from Mechanical Ventilation: On the Improvement of the Prediction of Patients' Readiness with Cardiopulmonary Coupling Indices
Authors: Armañac-Julián Pablo , Hernando David , Lázaro Jesús , de Haro Candelaria , Magrans Rudys , Morales John , Moeyersons Jonathan , Sarlabous Leonardo , López-Aguilar Josefina , Subirà Carles , Fernández Rafael , Orini Michele , Laguna Pablo , Varon Carolina , Gil Eduardo , Bailón Raquel , Blanch Lluís 
Published: December 2020

Abstract
The ideal moment to withdraw respiratory supply of patients under Mechanical Ventilation (MV) at Intensive Care Units (ICU), is not easy to be determined for clinicians. Although the Spontaneous Breathing Trial (SBT) provides a measure of the patients’ readiness, there is still around 15-20% of predictive failure rate. This work explores both Heart Rate Variability (HRV) and Cardiopulmonary Coupling (CPC) estimates as complementary information for readiness prediction. The CPC is related to how the mechanisms regulating respiration and cardiac pumping are working simultaneously, and it is defined from HRV in combination with respiratory information. Three different techniques are used to measure CPC, including Orthogonal Subspace Projections, Dynamic Mutual Information and Time-Frequency Coherence. 22 patients undergoing SBT in pressure support ventilation are analysed in the 24 hours previous to the SBT. 13 had a successful weaning and 9 failed the SBT or needed reintubation –being both considered as failed weaning. Results illustrate that traditional variables such as heart rate, respiratory frequency, and the parameters derived from HRV do not differ in patients with successful or failed weaning. However, significant statistical differences are found for the novel CPC parameters, throughout the whole recordings, comparing the values of the two groups. In addition, the night prior to SBT is the moment where differences are higher, probably because patients with failed weaning might be experiencing more respiratory episodes, e.g. apneas during the night, which is directly related to a reduced RSA. Therefore, results suggest that the traditional measures could be used in combination with these novel CPC biomarkers to help clinicians better predict if patients are ready to be weaned.
Transcriptome signatures reveal candidate key genes in the peripheral blood mononuclear cells of patients with coronary artery disease and prediction of small drug molecules
Authors: Kolur Vijayakrishna , Vastrad Basavaraj , Tengli Anandkumar , Vastrad Chanabasayya , Kotturshetti Iranna 
Published: December 2020

Abstract
Coronary artery disease (CAD) is one of the most common disorders in the cardiovascular system. This study aims to explore potential signaling pathways and important biomarkers that drive CAD development. The CAD GEO Dataset GSE113079 was featured to screen differentially expressed genes (DEGs). The pathway and Gene Ontology (GO) enrichment analysis of DEGs were analyzed using the ToppGene. We screened hub and target genes from protein-protein interaction (PPI) networks, target gene - miRNA regulatory network and target gene - TF regulatory network, and Cytoscape software. Validations of hub genes were performed to evaluate their potential prognostic and diagnostic value for CAD. A final, molecular docking study was performed. 1,036 DEGs were captured according to screening criteria (525upregulated genes and 511downregulated genes). Pathway and Gene Ontology (GO) enrichment analysis of DEGs revealed that these up and down regulated genes are mainly enriched in thyronamine and iodothyronamine metabolism, cytokine-cytokine receptor interaction, nervous system process, cell cycle and nuclear membrane. Hub genes were validated to find out potential prognostic biomarkers, diagnostic biomarkers and novel therapeutic target for CAD. A small drug molecule was predicted. In summary, our findings discovered pivotal gene expression signatures and signaling pathways in the progression of CAD. CAPN13, ACTBL2, ERBB3, GATA4, GNB4, NOTCH2, EXOSC10, RNF2, PSMA1 and PRKAA1 might contribute to the progression of CAD, which could have potential as biomarkers or therapeutic targets for CAD.
Efficacy of S-1 after Pemetrexed in Patients with Non-small Cell Carcinoma: A Retrospective Multi-institutional Analysis
Authors: Takemoto Shinnosuke , Akagi Kazumasa , Ono Sawana , Tomono Hiromi , Honda Noritaka , Suyama Takayuki , Umeyama Yasuhiro , Dotsu Yosuke , Taniguchi Hirokazu , Ogawara Daiki , Senju Hiroaki , Gyotoku Hiroshi , Sugasaki Nanae , Yamaguchi Hiroyuki , Nakatomi Katsumi , Fukuda Minoru , Mukae Hiroshi 
Published: December 2020

Abstract
Back ground: This study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment. Methods: This retrospective study included patients with advanced (c-stage III or IV, UICC 7th) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at 6 hospitals in Japan. Primary endpoint: Overall response rate (ORR). Secondary endpoint: Disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). Results: A total of 53 NSCLC patients met the criteria. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidential interval (CI): 0.00-10.1%). Median TTF, PFS, and OS were 65 days, 84 days, and 385 days, respectively. Conclusion: Although there were several limitations in this study, the ORR of S-1 after PEM in patients with non-SQ NSCLC was low compared to the historical control. It might be one of the choices to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.
Identification of Mutation Resistance Coldspots for Targeting the SARS-CoV2 Main Protease
Authors: Krishnamoorthy Navaneethakrishnan , Fakhro Khalid 
Published: December 2020

Abstract
Most attempts to target the novel coronavirus SARS-CoV2 are focusing on the main protease (Mpro) 1-9. However, >19,000 mutations in the Mpro have already been reported 10. The mutations encompassing 282 amino acid positions and these “hotspots” might change the Mpro structure and activity, potentially rendering novel antivirals and vaccines ineffective. Here we identified 24 mutational “coldspots” that have resisted mutation since the virus was first detected. We compared the structure-function relationship of these coldspots with several SARS-CoV2 Mpro X-ray crystal structures. We found that three coldspot residues (Leu141, Phe185 and Gln192) help to form the active site, while six (Gly2, Arg4, Tyr126, Lys137, Leu141 and Leu286) contribute to dimer formation that is required for Mpro activity. The surface of the dimer interface is more resistant to mutations compared to the active site. Interestingly, 16 coldspots are found in conserved patterns when compared with other coronaviruses. Importantly, several conserved coldpots are available on the surface of the active site and at the dimer interface for targeting. The identification and short list of these coldspots offers a new perspective to target the SARS-CoV2 Mpro while avoiding mutation-based drug resistance.
Selenomethionine&nbsp;Alleviates&nbsp;Intestinal Ischemia Reperfusion&nbsp;Injury&nbsp;by Inhibiting Mitochondrion-mediated Apoptosis&nbsp;in&nbsp;Mice&nbsp;
Authors: Liu Zhe , Mou Guangze , Li Yang , Zhong Yangsheng , Zhao Rui , Zhang Hua , Wu Rui , Jin Chenghao 
Published: December 2020

Abstract
The mechanism of supplement selenomethionine (SeMet) mitigates ischemia reperfusion (I/R)- damage remains to be elucidated in the intestinal tissues of mice. In this study, a model of intestinal I/R injury was established. The levels of redox factors, such as the activities of glutathione peroxidase-1(Gpx1), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) content, were detected using ELISA assays in the intestinal tissues of mice. Several apoptosis-related markers (cytochrome c (Cyt-c), Bcl-2, Bax, and caspase-3) were detected using qPCR and Western blot. The results showed that SeMet alleviated I/R damage by increasing the activities of Gpx1, CAT, SOD and reducing MDA content. Our data demonstrated that SeMet reduced I/R induced mitochondrial damage and inhibited the expression of Cyt-c. SeMet also increased the Bcl-2 /Bax ratio and reduced the expression of Bax and caspase-3 in the mice intestinal tissues. Thus our data reveals that I/R could lead to increased apoptosis, and SeMet alleviated I/ R-induced apoptosis via maintaining REDOX homeostasis and attenuating mitochondrial pathway in the mice intestinal tissues.
Geographical Distribution and Regional Differences in 532 Clinical Isolates of Rapidly Growing Mycobacterial Species in Japan
Authors: Kamada Keisuke , Yoshida Atsushi , Iguchi Shigekazu , Arai Yuko , Uzawa Yutaka , Konno Satoshi , Shimojima Masahiro , Kikuchi Ken 
Published: December 2020

Abstract
Infectious diseases caused by nontuberculous mycobacteria (NTM) are increasingly becoming a major global problem. Additionally, Mycobacteroides abscessus subsp. abscessus (MAB) infections are refractory to macrolides. This study was conducted to investigate the epidemiology of rapidly growing mycobacteria (RGM) species isolated from clinical specimens in Japan and assess differences in the regional distribution of lower respiratory specimens (LRS)- and non-lower respiratory specimens (NLRS)-derived species. 532 strains (427 LRS, 92 NLRS and 15 unknown specimens) were isolated in nine areas of Japan. Their epidemiological differences were examined according to the specimen type, region and climate. Fifteen species were identified. The top three RGM species from LRS and NLRS were identical. The proportion of M. abscessus group (MAG) strains was significantly lower in NLRS than in LRS (35.9% vs. 68.4%). The proportion of MAG strains was higher in northern Japan than in other regions (83.7% vs. 60.5%). Variations in strain abundance among RGM species was evident in regions with a mean annual temperature below 15 °C. We conclude that the proportions of MAG strains differed between NLRS and LRS in Japan. In addition, the mean annual temperature likely influenced the distribution of RGM species.
Estimation of Years of Life Lost by Sweden's Relaxed COVID-19 Mitigation Strategy
Authors: Rypdal Martin , Rypdal Kristoffer , Løvsletten Ola , Sørbye Sigrunn , Ytterstad Elinor , Bianchi Filippo Maria 
Published: December 2020

Abstract
Objective: To estimate the weekly excess all-cause mortality in Norway and Sweden, and to estimate the years of life lost (YLL) attributed to COVID-19 in Sweden and the significance of mortality displacement. Methods: We found expected mortality by taking the declining trend and the seasonality in mortality into account. From the excess mortality in Sweden in 2019/20, we estimated the YLL attributed to COVID-19 using the life expectancy in different age groups. We adjusted this estimate for possible displacement using an auto-regressive model for the year-to-year variations in excess mortality. Results: We found that excess all-cause mortality over the epidemic year (July to July) 2019/20 was 517 (95%CI -12, 1074) in Norway and 4329 (3331, 5325) in Sweden. There were reported 255 COVID-19 related deaths in Norway, and 5741 in Sweden, that year. During the epidemic period March 11 – November 11, there were 6247 reported COVID-19 deaths and 5517 (4701, 6330) excess deaths in Sweden. The estimated number of life-years lost attributed to the more relaxed Swedish strategy was 45850 (13915, 80276) without adjusting for mortality displacement and 43073 (12160, 85451) after adjusting for possible displacement.
Does Generative Adversarial Network Ensure Diversity in Data? Morphologic Evaluation of Synthetic Isocitrate Dehydrogenase-Mutant Glioblastomas in A Clinical Diagnostic Model
Authors: Park Ji Eun , Eun Dain , Kim Ho Sung , Lee Da Hyun , Jang Ryoung Woo , Kim Namkug 
Published: December 2020

Abstract
Generative adversarial network (GAN) creates synthetic images to increase data quantity, but whether GAN ensures diversity is still unknown. We investigated whether GAN-based synthetic images provide sufficient morphologic variability to improve molecular-based prediction, as a rare disease of isocitrate dehydrogenase (IDH)-mutant glioblastomas. GAN was initially trained on 500 normal brains and 110 IDH-mutant high-grade astocytomas, and paired contrast-enhanced T1-weighted and FLAIR MRI data were generated. Diagnostic models were developed from real IDH-wild type (n = 80) with real IDH-mutant glioblastomas (n = 38), or with synthetic IDH-mutant glioblastomas, or augmented by adding both real and synthetic IDH-mutant glioblastomas. Turing tests showed synthetic data showed reality (classification rate of 55%). Both the real and synthetic data showed that a more frontal or insular location (odds ratio [OR], 1.34 vs. 1.52; P = .04) and distinct non-enhancing tumor margins (OR, 2.68 vs. 3.88; P <.001), which become significant predictors of IDH-mutation. In an independent validation set, diagnostic accuracy was higher for the augmented model (90.9% [40/44] and 93.2% [41/44] for each reader, respectively) than for the real model (84.1% [37/44] and 86.4% [38/44] for each reader, respectively). The GAN-based synthetic images yield morphologically variable, realistic-seeming IDH-mutant glioblastomas. GAN will be useful to create a realistic training set in terms of diversity and quality, thereby improving diagnostic performance in a clinical model.
Key Features of the Anatomy and Topography of the Sphenoid Sinus in Different Age Periods
Authors: Aliyeva Merey , Bathalla Mahmoud Farid Mahrous , Balmagambetova Aru , Zhurabekova Gulmira 
Published: December 2020

Abstract
For the period of 2019, magnetic resonance imaging of the head of patients aged 20–71 years was performed. The majority of males have mezocran the shape of the skull, in contrast to females. There was no universal type of pneumatization for both sexes. In young men, the sellar type prevails, but at the age of 60, this type is 2 times less common and there are no protrusions of the channels of the optic nerves and internal carotid arteries. However, only the protrusion of the internal carotid artery channel is more common in women over 60 years of age than in men. In men, there were no cases of canal protrusion, and 49% of young women had a depression in the wall of the sphenoid sinus. In men under the age of 60, the protrusion of the optic nerve channels and internal carotid arteries occurs in approximately the same way as in women over 80 years of age. Due to the variability of the anatomical configuration of the sphenoid sinuses, the impact on access to the cell through the nose can be serious. The surgeon must be aware of these results before surgery in order to reach the cell safely and effectively.
Percutaneous Nephrostomy Versus Retrograde Ureteral Stenting for Acute Obstructive Uropathy: A Systematic Review and Meta-Analysis
Authors: ISMAIL ZUL KHAIRUL AZWADI , NOOR NORHAYATI MOHD , ABDULLAH MOHD SHAFIE 
Published: December 2020

Abstract
Acute obstructive uropathy is associated with significant morbidity among patients with any condition that leads to urinary tract obstruction. Immediate urinary diversion is necessary to prevent further damage to the kidneys. In many centres, the two main treatment options include percutaneous nephrostomy (PCN) and retrograde ureteral stenting (RUS). The purpose of this study if to compare the efficacy and safety of PCN and RUS for the treatment of acute obstructive uropathy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, EMBASE, the World Health Organisation International Clinical Trials Registry Platform and ClinicalTrials.gov. We also searched the reference lists of included studies to identify any additional trials. We included randomised controlled trials and controlled clinical trials comparing the outcomes of clinical improvement (septic parameters and hospitalisation duration), quality of life, urinary-related symptoms, failure rates, post-procedural pain [measured using a visual analogue scale (VAS)] and analgesics use. We conducted statistical analyses using random effects models and expressed the results as risk ratio (RR) and risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). Seven trials were identified that included 667 patients. Meta-analysis of the data revealed no difference in the two methods in improvement of septic parameters, quality of life, failure rates, post-procedural pain (VAS), or analgesics use. Patients receiving PCN had lower rates of haematuria and dysuria post-operatively and longer hospitalisation duration than those receiving RUS. PCN and RUS are effective for the decompression of an obstructed urinary system, with no significant difference in most outcomes. However, PCN is preferable to RUS because of its reduced impact on the patient’s post-operative quality of life due to haematuria and dysuria, although it is associated with slightly longer hospitalisation duration.
Genetic Variants Modifying the Risk of Lung Cancer and Its Subtypes: A Comprehensive Meta-analysis and a Case-control Study
Authors: Sengupta Debmalya , Banerjee Souradeep , Mitra Ritabrata , Chaudhuri Tamohan , Sarkar Abhijit , Bhattacharjee Gautam , Nath Somsubhra , Roychoudhury Susanta , Bhattacharjee Samsiddhi , Sengupta Mainak 
Published: December 2020

Abstract
Association studies on lung cancer have often yielded conflicting and inconclusive results. We performed a comprehensive meta-analysis to dissect the precise effects of the candidate variants. We searched for association studies on lung cancer from the Indian subcontinent. Cochran’s Q-test assessed heterogeneity. Both overall and histotype-stratified meta-analysis was done using fixed-effect and random-effects models. Smoking status stratified subgroup analysis and effect modification tests were done. An associated variant with significant heterogeneity was genotyped in an eastern Indian population to investigate the contribution of potential confounders followed by a comprehensive meta-analysis across world populations. Significant heterogeneity was observed for the 8 variants. Both fixed-effect and random-effects meta-analysis of 24 variants showed FDR-corrected associations of rs3547/XRCC1 and rs1048943/CYP1A1 with lung cancer along with 5 nominal associations. del1/GSTT1, rs4646903/CYP1A1, and rs10488943/CYP1A1 were associated with adenocarcinoma, squamous cell carcinoma, and both, respectively. rs4646903/CYP1A1 was associated with lung cancer among smokers with significant effect modification by smoking. rs10488943/CYP1A1 was associated with lung adenocarcinoma in the East Indian case-control study. rs1048943/CYP1A1 was associated with lung cancer across world populations. Our work confirms the risk loci for lung cancer and its subtypes in the context of smoking and other aetiological factors, which could aid in personalised treatment.
Serum Epidermal Growth Factor-like domain 7 Serves as a Novel Diagnostic Marker for Early Hepatocellular Carcinoma
Authors: Yang Meng-Yuan , Wu Fan , Fang Feng , Yang Hao , Zhang Jing-Fan , Chen Guo-Dong , Yang Lian-Yue 
Published: December 2020

Abstract
Background: Epidermal growth factor-like domain 7 (Egfl7), a recently identified secreted protein, was significantly increased in patients with HCC by our previous studies. However, its efficacy in diagnosis of early HCC remains unknown. In this study we evaluate the efficacy of serum Egfl7 for early HCC diagnosis and compare it with alpha-fetoprotein (AFP).Methods: Serum Egfl7 levels in testing cohort (1065 participants) and validation cohort (464 participants) were measured by a sandwich enzyme-linked immunoassay (ELISA). The efficacies of Egfl7 and AFP in diagnosing early HCC were estimated by receiver operating characteristic (ROC).Results: Serum Egfl7 was significantly elevated in patients with early HCC than all non-HCC controls. At the cut-off value of 2610 ng/mL, the area under ROC, sensitivity, specificity and accuracy of Egfl7 were 0.800, 75.2 %, 71.7% and 73.5% in discriminating early HCC from chronic liver disease (CLD), compared with 0.675, 61.8%, 62.0% and 61.9% for AFP using 20 ng/mL as a cut-off value. Egfl7 also exhibited a significant higher sensitivity and accuracy than AFP in differentiating early HCC patients from non-HCC individuals including healthy individuals and patients with CLD (76.6% vs. 64.0%, 79.9% vs. 66.1%). Additionally, 70.8% of early HCC patients with negative AFP could be diagnosed by Egfl7 and the combined use of Egfl7 and AFP increased the sensitivity to 91.0%. These results were confirmed by a validation cohort.Conclusion: Egfl7 is a valuable serum marker in early diagnosis of HCC with a better sensitivity and accuracy than AFP.