bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-biopsy cell-free DNA from blood: an open window on primary prostate cancer genetics and biology
Authors: Corbetta Marinella , Chiereghin Chiara , simone Ilaria De , Soldà Giulia Maria Emilia Antonietta , Zuradelli Monica , Giunta Michele , Lughezzani Giovanni , Buffi Nicolò Maria , Hurle Rodolfo , Saita Alberto , Casale Paolo , Asselta Rosanna , Lazzeri Massimo , Guazzoni Giorgio , Duga Stefano 
Published: January 2021

Abstract
BackgroundCirculating cell-free DNA (ccfDNA), released from normal and cancerous cells, is a promising biomarker for cancer detection as in neoplastic patients it is enriched in tumor-derived DNA (ctDNA). ctDNA contains cancer-specific mutations and epigenetic modifications, which can have diagnostic/prognostic value. However, in primary tumors, and in particular in localized prostate cancer (PCa), the fraction of ctDNA is very low and conventional strategies to study ccfDNA are unsuccessful.MethodsccfDNA was isolated from plasma before and after prostate biopsy by using the Maxwell RSC ccfDNA Plasma Kit and quantitatively and qualitatively analyzed by a fluorometer and by the Agilent High Sensitivity D5000 ScreenTape System. Somatic mutations were searched for by targeted RNAseq on prostate biopsies, sequencing libraries were prepared using the TruSight RNA Pan-Cancer Panel from Illumina. Detection of selected somatic mutations in ccfDNA was performed by ultra-deep sequencing of amplicons, using the NEBNext® Ultra™ II DNA Library Prep Kit for library preparation. All libraries were sequenced on the NextSeq550 platform.ResultsHere we demonstrate that prostate biopsy, by causing multiple injuries to the organ, leads to a significant increase in plasma concentration of ccfDNA (P < 0.0024) in primary PCa patients. By calculating the minor allele fraction at patient-specific somatic mutations pre- and post-biopsy, we show that ctDNA is significantly enriched (from 3.9 to 164 fold) after biopsy, representing a transient “molecular window” to access and analyze ctDNA. Moreover, we show that newly released ccfDNA contains a larger fraction of di-, tri- and multi-nucleosome associated DNA fragments. This feature could be exploited to further enrich prostate-derived ccfDNA and to analyze epigenetic markers.ConclusionOur data represent a proof-of-concept that liquid tumor profiling from peripheral blood performed just after the biopsy procedure can open a “valuable molecular metastatic window” giving access to the tumor genetic asset, thus providing an opportunity for early cancer detection and individual genomic profiling in the view of PCa precision medicine.
Genome-wide analysis of DNA methylation identifies the apoptosis-related gene UQCRH in renal cancer
Authors: Miyakuni Kosuke , Nishida Jun , Koinuma Daizo , Nagae Genta , Aburatani Hiroyuki , Miyazono Kohei , Ehata Shogo 
Published: January 2021

Abstract
Background

DNA hypermethylation is frequently observed in clear cell renal cell carcinoma (ccRCC) and correlates with poor clinical outcomes. However, the detailed function is not fully uncovered.
Methods

A target for DNA methyltransferases (DNMTs) was explored in ccRCC cells. Highly malignant derivatives of human ccRCC cells were established via serial orthotopic inoculation in mice. Then, DNA methylated sites were genome-widely analyzed using methylation array in reference to RNA-sequencing data.
Results

We found that DNMT3B upregulation contributes to renal cancer progression and identified the ubiquinol cytochrome c reductase hinge protein (UQCRH) as a methylation target in advanced ccRCC. The expression of UQCRH in human ccRCC tissues was lower than that in normal adjacent tissues. Furthermore, its silencing attenuated cytochrome c release in response to apoptotic stimuli, resulting in enhanced primary tumor formation in vivo. Moreover, DNA demethylation enhanced the therapeutic efficiency of the mammalian target of rapamycin (mTOR) inhibitor everolimus in vivo.
Conclusions

These findings suggest that the DNMT3B-induced UQCRH methylation may contribute to renal cancer progression and that DNMT inhibitors exhibit potential clinical significance for ccRCC treatment.
Knowledge, Attitude, Practice and Associated Factors of Health Professionals Towards Podoconiosis in Gamo Zone, Ethiopia, 2019
Authors: Churko Chuchu , Asnakew Mekuria , Tunje Abayneh , Girma Eyayou , Zerdo Zerihun 
Published: January 2021

Abstract
Background: Podoconiosis is entirely preventable, non-communicable disease with high potential of elimination. One of the pillars for elimination of podoconiosis is morbidity control and management. Therefore, the present study was aimed to assess the knowledge, attitude, practices and associated factors of health professionals towards podoconiosis cause, prevention and treatments. Methods: facility based cross-sectional study was conducted. The source population was all health professionals currently working in public health facilities. The final estimated sample size was 349. A pretested self-administrated structured questionnaire was used to collect the data. The data were coded, entered, and cleaned by using Epi.info version7, and analyzed by using SPSS version 20. Result: a total of 320 health professionals were participated in the study. Sixty eight (23.1%) health professionals had poor knowledge towards podoconiosis. Seventy (21.9%) responded as podoconiosis is infectious disease. Profession, address of health facility, service year and attitude of participants became significantly associated with knowledge towards podoconiosis. More than half (56%) had favorable attitude towards podoconiosis patients. Knowledge score (95%CI: 1.389, 4.059, p-value= 0.002) was the independent predictor for attitude status. Very few (11.6%) respondents ever treated podoconiosis patients. Age group 45 years old and above and training on LMMDP was significantly associate with practice, (AOR=17.345; 95%CI: 4.62, 65.119) and (AOR=7.385; 95%CI: 2.5, 21.797), respectively. Conclusion: Despite, high percent of good knowledge and favorable attitude of health professionals towards podoconiosis, practice of study subjects was very low. In-service trainings will be given for health professionals to improve practice. In podoconiosis endemic districts hygiene supplies and other referencing materials should be made available for podoconiosis case management.
Characterization of the 5′ Regulatory Region of the Human RGS4 Gene In Vitro
Authors: Xu Feng-ling , Ding Mei , Li Ya , Xing Jia-xin , Xuan Jin-feng , Yao Jun , Wang Bao-jie 
Published: January 2021

Abstract
Background: In order to detect function of three SNPs (rs12041948, rs6678136 and rs7515900) in 5′ regulatory region of the human RGS4 gene, fragments of 5′ regulatory region of RGS4 (-1112–+365, TSS+1) was cloned into pGL3-Basic vector, and dual-luciferase reporter assay was conducted. We compared and analyzed the relative fluorescence intensities of eight haplotype recombined vectors. Results: In HEK-293 and SK-N-SH cells, the relative fluorescence intensities of haplotype 2 (ATA) was significantly increased when it was compared with haplotype 3 (ACA), 5 (ACC), 7 (GCA), and 8 (GCC). Therefore, haplotypes with C of rs6678136 decreased expression than theses with T. However, no significant difference was assessed in comparation among eight haplotypes, in the U87 cells. Conclusions: The mutant of T>C of rs6678136 might alter the binding of transcription factors to 5′ regulatory region of RGS4 gene, then change the expression. It was predicated that the rs6678136 might alter the binding region of GSX1, ALX3, BARHL1, and BARHL2. The binding is still worthy of further investigation.
Effects of Chlorpheniramine on Emergence Agitation After General Anesthesia for Ureteroscopic Stone Surgery: a Retrospective Cohort Study
Authors: Cho Choon-Kyu , Chang Minhye , Lee Seok-Jin , Sung Tae-Yun , Jee Young Seok 
Published: January 2021

Abstract
Background: The presence of a urinary catheter, postoperative pain, and postoperative nausea and vomiting are risk factors for emergence agitation (EA). Antimuscarinic agents have been the primary agents used for urinary catheter-related bladder discomfort prevention and treatment. Chlorpheniramine has antimuscarinic, antinociceptive, and antiemetic effects. This retrospective study investigated the effect of chlorpheniramine on EA prevention in patients following ureteroscopic stone surgery. Methods: Of 110 adult patients who underwent ureteroscopic stone surgery under general anesthesia between January and December 2019, the medical records of 93 patients were analyzed retrospectively. The patients were divided into control (n = 52) and chlorpheniramine (n = 41) groups according to they receipt of intravenous chlorpheniramine before the induction of anesthesia. The incidence and severity of EA were compared between the groups as primary and secondary endpoints, respectively. The effects of chlorpheniramine on the requirement for inhalation anesthetic (desflurane) during surgery, changes in mean blood pressure and heart rate during emergence, and adverse events were also compared. Results: The incidence (21.2% in the control group, 24.4% in the chlorpheniramine group) and severity of EA did not differ between groups. The intraoperative requirement for desflurane, changes in mean blood pressure and heart rate during emergence, and adverse events were also similar between groups. Conclusion: Chlorpheniramine did not affect EA in patients after ureteroscopic stone surgery.Trial registration: CRiS Registration number KCT0004879. Initial registration date was 3 April 2020 (Retrospectively registered).
Application of Gel to the Transducer of Cartilage Conduction Hearing Aids Improves Their Benefits
Authors: Nishimura Tadashi , Hosoi Hiroshi , Saito Osamu , Shimokura Ryota , Okayasu Tadao , Morimoto Chihiro , Kitahara Tadashi 
Published: January 2021

Abstract
Gel is a conduction medium used to improve signal transmission and is applied in ultrasonography to obtain high-quality images; however, it is rarely used in hearing devices. The application of gel to couple the transducer to the ear could potentially improve the benefits of hearing aids, particularly cartilage conduction (CC) hearing aids, which deliver signals by vibration. The aim of this study was to investigate the impact of gel application on the efficacy of CC hearing aids in 23 patients (30 ears). The aided thresholds, maximum speech recognition scores (SRSs), and hearing level at which the maximum SRS was observed were compared before and after the application of gel to the transducer of CC hearing aids. Subjective impressions of hearing improvement, on applying the gel, were also evaluated. The aided thresholds above 1 kHz significantly improved on applying the gel to the transducer. The effectiveness of gel application was better for patients who reported improvement in hearing. The audiometric results were consistent with subjective evaluations. The application of gel has minimal risk, and its benefits can be verified easily with subjective evaluation. Gel application can be considered an effective option for improving the benefits of CC hearing aids.
Discovery of Biomarkers for Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration From Human Cerebrospinal Fluid Using Mass Spectrometry-Based Proteomics
Authors: Oh Sungtaek , Jang Yura , VandeVrede Lawren , Boxer Adam L , Sockanathan Shanthini , Na Chan-Hyun 
Published: January 2021

Abstract
BackgroundAmyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are progressive neurodegenerative diseases that share clinical and neuropathologic features. Critical to the mission of developing effective therapies for ALS and FTLD is the discovery of biomarkers that can illuminate shared mechanisms of neurodegeneration, which can then be evaluated for diagnostic, prognostic or pharmacodynamic value across the disease spectrums. MethodsHere, we merged unbiased discovery-based approaches and targeted quantitative comparative analyses between ALS and FTLD cerebrospinal fluid (CSF) to identify proteins that are altered in ALS and FTLD. ResultsDiscovery mass spectrometry (MS)-based proteomic approaches combined with tandem mass tags (TMT) quantification methods from 40 CSF samples comprising 20 patients with ALS and 20 healthy control (HC) individuals identified 19 differentially expressed candidate biomarker proteins after CSF fractionation. Notably, these candidate biomarkers included novel and previously identified proteins, thus validating our approach. Candidate biomarkers were subsequently examined using parallel reaction monitoring (PRM) MS methods on 80 unfractionated CSF samples comprising 30 patients with ALS, 19 patients with FTLD, and 31 HC individuals. Two candidate biomarkers (CNTNAP2 and CLSTN1) were downregulated in both ALS and FTLD compared to healthy controls, and 11 further candidate proteins were significantly downregulated in FTLD compared to HC. ConclusionsTaken together, this study identifies multiple novel proteins that are altered in ALS and FTLD, which provides the foundation for their evaluation and development as biomarkers for these diseases.
Effects of Infections of Helicobacter Pylori With Different Virulent Factors on Severity of Gastrointestinal Diseases
Authors: Zhang Yan , Fang Xiang-ming , Tian Kui 
Published: January 2021

Abstract
Background: Helicobacter Pylori (H. pylori) infection, one of the most common chronic bacterial infections, has been considered as a major cause of diseases such as lymphoma, gastritis, peptic ulcers, and stomach cancer. Here, we aimed to determine whether H. pylori strains with different virulence contribute to the gastrointestinal diseases differentially in clinical settings, which may provide future direction for eradication of H. pylori infection. Methods: We recruited 501 patients with gastrointestinal disorders for analysis of antibody types of H. pylori infection. Correlation analysis was done to determine the association of different virulence of H. pylori with patients’ baseline parameters and personal disease history. Next, subjects with each type of anti- H. pylori infection antibody were subjected to esophagogastro duodenoscopy（EGD) and colonoscopy examinations. The pathological diagnosis was also conducted in endoscopic samples. Chi-squared test was employed to compare the differences in endoscopic assessments and pathological findings among three types of H. pylori infection determined by the presence of antibodies to virulent factors. Results: There were 296 cases with Type I H. pylori infection, 120 cases with Type II H. pylori infection, and 85 cases without H. pylori infection (negative, Type III). No correlation was found between different virulence of H. pylori and participants’ baseline data (P > 0.05). EGD results showed that the incidences of peptic ulcer, bleeding and malignant lesions in Type I group were significantly higher than that in Type II and Type III (P＜0.05). Despite of increased trends of incidences of precancerous alterations and the malignance in Type I group compared with type II and III groups, there was no significant difference (P > 0.05). In addition, coloscopic features were similar among three groups. On the other hand, infections of H. pylori with cytotoxin-associated gene A (CagA) and/or vacuolating cytotoxin A (VacA) virulent factors resulted in more severe histopathological diseases than that with only Ure A/B factor and without infection (P < 0.05). Conclusions: Infections of H. pylori strains with CagA/VacA are likely to cause development of severe gastrointestinal diseases. These results are helpful to treat for H. pylori infection clinically.
Adverse Histological Features Alone Was Not Sufficient for Decision of Adjuvant Chemotherapy in T3N0M0 colonic cancer: A Propensity Score Matching Study Based on Population Analysis
Authors: Wang Qinghua , Zheng Hongjuan , Chen Xiaoxiao , Zhang Xia , Jin Xiayun , Tang Wanfen , Xu Xifeng , Zhou Shishi , Du Jinlin , Fu Jianfei 
Published: January 2021

Abstract
Purpose: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Approximately 25% of patients with AJCC stage II suffered recurrence after radical surgery, but the role of adjuvant chemotherapy in Stage II CRC is controversial. We aimed to evaluate the benefit from chemotherapy for T3N0M0 patients with adverse histological features. Methods: An analysis of the Surveillance, Epidemiology, and End Results (SEER) 18 databases was performed to identify patients underwent radical resection 20-80 years old with colonic carcinoma diagnosed during year 2004 to 2012. Poorly differentiated, undifferentiated, mucinous adenocarcinoma and signet ring cell carcinoma (SRCC) were defined as adverse histological features, and well or moderately differentiated adenocarcinoma as good histological features. Multivariate analyses were used to adjust the effects of other covariates. The survival benefit of adjuvant chemotherapy was demonstrated in the propensity score matching cohort. Results: The adjuvant chemotherapy brought no survival benefit (good histological features HR, 1.076; 95% CI, 0.957-1.211; P=0.220; adverse histological features HR, 0.995; 95% CI, 0.777-1.274; P=0.967); Neither mucinous adenocarcinoma nor signet ring cell carcinoma brought a significance on survival (mucinous adenocarcinoma HR, 0.699; 95% CI, 0.488-1.002; P=0.051; signet ring cell carcinoma HR, 0.750; 95% CI, 0.386-1.459; P=0.397) compared to adenocarcinoma. Left-side colon was associated with a poorer survival in good histological features group (HR, 1.136; 95% CI, 1.034-1.248; P=0.008). Conclusions: The adverse histological features don’t influence on survival for patients with T3N0M0 staging, and adjuvant chemotherapy is invalid to improve the survival for these patients, indicating adverse histological features alone was not sufficient for decision of adjuvant chemotherapy in this situation rather than the recommendation of the guidelines.
Comprehensive analysis of the transcriptional expressions and prognostic value of S100A family in pancreatic ductal adenocarcinoma
Authors: Li Hongbin , Wang Jianli , Jin Xiaodong , Zhao Lei , Ye Huili , Ma Yong , Jiang Xiangyan , yu zeyuan 
Published: January 2021

Abstract
Background

Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory malignancy with poor prognosis. It is urgent to identify novel and valid biomarkers to predict the progress and prognosis of PDAC. The S100A family have been identified as being involved in cell proliferation, migration and differentiation progression of various cancer types. However, the expression patterns and prognostic values of S100As in PDAC remain to be analyzed.
Methods

We investigated the transcriptional expressions, methylation level and prognostic value of S100As in PDAC patients from the Oncomine, GEPIA2, Linkedomics, and cBioPortal databases. Real-time PCR was used to detect the expressions of S100A2/4/6/10/14/16 in four pancreatic cancer cell lines and pancreatic cancer tissues from PDAC patients undergoing surgery. To verify the results further, immunohistochemistry was used to measure the expression of S100A2/4/6/10/14/16 in 43 PDAC patients’ tissue samples. The drug relations of S100As were also analyzed by using Drugbank.
Results

The results suggested that, the expression levels of S100A2/4/6/10/14/16 were elevated to PDAC tissues than in normal pancreatic tissues, and the promoter methylation levels of S100A S100A2/4/6/10/14/16 in PDAC (n = 10) were lower compared with normal tissue (n = 184) (P < 0.05). In addition, their expressions were negatively correlated with PDAC patient survival.
Conclusions

Taken together, these results suggest that S100A2/4/6/10/14/16 might be served as prognostic biomarkers for survivals of PDAC patients.
Association of PICK1 and BDNF Variations with Increased Risk of Methamphetamine Dependence Among Iranian Population; A Case-Control Study
Authors: Tajbakhsh Amir , Alimardani Maliheh , Asghari Mahla , Abedini Soheila , Khadem Sohrab Saghafi , Bajestani Abolfazl Nesaei , Alipoor Forough , Alidoust Maryam , Savardashtaki Amir , Hashemian Peyman , Pasdar Alireza 
Published: January 2021

Abstract
Background
Genetic factors play an important role in susceptibility to methamphetamine dependency. In this line, protein that interact with C-kinase-1 (PICK1) and brain-derived neurotrophic factor (BDNF) genes are linked to methamphetamine dependence (substance use disorder). Thus, in a case-control study, we investigated the association between polymorphisms of PICK1 and BDNF genes and methamphetamine dependence in an Iranian population.
Methods
Total of 235 cases and 204 controls were recruited in a period between 2015 to 2018. The PICK1-rs713729, -rs2076369 and BDNF-rs6265 genotypes were determined via ARMS-PCR assay. Statistical analysis was performed, using SPSS 20.0, PHASE 2.1.1 program as well as SNP Analyzer 2.0.
Results
In the present study, two polymorphisms including PICK1-rs713729 (OR: 1.38 (CI: 1.08–1.52; P-value: 0.004) in multiplicative and dominant models, and PICK1-rs2076369 (OR: 1.31 (CI: 1.10–1.56; P-value: 0.002) in multiplicative, dominant and co-dominant models were associated with the risk of methamphetamine abuse. Moreover, haplotype analysis showed a significant association of haplotype AG (OR: 2.50 (CI: 1.50–4.16; P-value: 0.0002) in dominant, recessive and co-dominant models, and haplotype TT (OR: 0.67 (CI: 0.50–0.91; P-value: 0.009) in dominant and co-dominant models with the risk of methamphetamine abuse. None of the polymorphisms in this study had a high level of linkage disequilibrium.
Conclusion
Our findings indicate that the PICK1 gene polymorphism might affect the risk of methamphetamine dependency in our population.