bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoreductive radiotherapy combined with abiraterone in metastatic castration-resistance prostate cancer: a single center experience
Authors: Liu Yang , Long Wen , Zhang Zitong , Mai Lixin , Huang Sijuan , Liu Boji , Cao Wufei , Wu Jianhua , Zhou Fangjian , Li Yonghong , He Liru 
Published: November 2020

Abstract
Background: To investigate the potential benefit of cytoreductive radiotherapy (cRT) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving abiraterone.Methods: From February 2014 to February 2019, 149 mCRPC patients treated with abiraterone were identified. Patients receiving cRT before abiraterone failure (AbiRT group) were matched by one-to-two propensity score to patients without cRT before abiraterone failure (non-AbiRT group).Results: The median follow-up was 23.5 months. Thirty patients (20.1%) were in the AbiRT group, whereas 119 patients (79.9%) were in the non-AbiRT group. The 2-year OS of patients managed by AbiRT and non-AbiRT were 89.5% and 73.5%, respectively (P = 0.0003). On multivariate analysis, only AbiRT (HR, 0.17; 95%CI, 0.05–0.58; P = 0.004) and prognostic index (HR 2.71; 95% CI, 1.37–5.35; P = 0.004) were significant factors. After matching, AbiRT continued to be associated with improved OS (median OS not reached vs. 44.0 months, P = 0.009). Subgroup analysis revealed that patients aged ≤65 years (HR, 0.09; 95%CI, 0.01–0.65; P = 0.018), PSA ≤20 ng/mL (HR 0.29; 95% CI, 0.09–0.99; P = 0.048), chemotherapy-naïve upon abiraterone treatment (HR 0.20; 95% CI, 0.06–0.66; P = 0.008) and in intermediate prognosis groups by COU-AA-301 prognostic index (HR 0.13; 95% CI, 0.03-0.57; P = 0.007) had improved OS with AbiRT. Conclusions: cRT before resistance to abiraterone may improve survival in selected mCRPC patients: age ≤65 years old, chemotherapy-naïve, with PSA ≤20 ng/mL at the diagnosis of mCRPC and intermediate prognosis.
Potential hemo-biological identification markers to the left displaced abomasum in dairy cows
Authors: Song Yuxiang , Loor Juan J , Zhao Chenchen , Huang Dan , Du Xiliang , Li Xiaobing , Wang Zhe , Liu Guowen , Li Xinwei 
Published: November 2020

Abstract
Background: Left displaced abomasum (LDA) occurs at high frequency in the early postpartum period and can affect production performance of dairy cows. Clinical diagnosis of LDA is usually done by abdominal auscultation and percussion. The purpose of this study was to explore the potential applicability of blood biomarkers for early warning and diagnosis of LDA in dairy cows. Results: Twenty early postpartum healthy cows and thirty early postpartum LDA cows of similar parity were used. A receiver operating characteristic curve (ROC) method was used to analyze the sensitivity of hematological biomarkers to LDA including energy balance metabolic biomarkers, liver/kidney function biomarkers, and minerals. A cut-off point was defined for each of the selected hematological biomarkers deemed sensitive markers of LDA. Compared with healthy cows, body condition score (BCS), dry matter intake (DMI) and milk production were lower in LDA cows. Among energy metabolism markers, serum non-esterified fatty acid (NEFA), β-hydroxybutyric acid (BHBA), insulin (INS), and revised quantitative insulin sensitivity check index (RQUICKI) levels were lower while serum glucagon (GC) was greater in LDA cows. Among the liver/kidney function biomarkers, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), the ratio of AST/ALT and levels of total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), albumin (ALB), blood urea nitrogen (BUN), creatinine, and total protein (TP) were greater in LDA cows. Among minerals analyzed, serum Cl, Ca, and K were lower in LDA cows. After ROC analysis, it was determined that serum Ca, INS, RQUICKI, ALT, GGT, and creatinine are potential indicators for early warning and diagnosis of LDA for early postpartum dairy cows. Conclusions: Dairy cows with LDA were under severe negative energy balance (NEB), had signs of liver damage and potentially lower insulin sensitivity. A combination of multi-hematological biomarkers including Ca, INS, RQUICKI, ALT, GGT and creatinine has the potential to help identify cows at risk of LDA in the early postpartum period.
Multi-locus sequence analyses reveal a clonal L. borgpetersenii genotype in a heterogeneous invasive Rattus spp. community across the City of Johannesburg, South Africa
Authors: Moseley Mark Hamish , Naidoo Kovashnee , Bastos Armanda , Retief Liezl , Frean John , Telfer Sandra , Rossouw Jennifer 
Published: November 2020

Abstract
Background: Rattus spp. are frequently implicated as key reservoir hosts for leptospirosis, one of the most common, but neglected, bacterial zoonoses in the world. Although leptospirosis is predicted to be a significant public health threat in Africa, studies from the continent are limited. Methods: Rattus spp. (n = 171) were sampled (January-May 2016) across the City of Johannesburg, South Africa’s largest inland metropole. Rattus spp. genetic diversity was evaluated by full length (1140 bp) cyt b sequencing of 42 samples. For comparison, a further 12 Rattus norvegicus samples collected in Cape Town, South Africa’s largest coastal metropole, were also genotyped. Leptospira infections were identified and genotyped using real-time PCR and multi-locus (lfb1, secY and lipL41) DNA sequencing. Results: Five R. norvegicus haplotypes were identified across Johannesburg, four of which have not previously been detected in South Africa, and one in Cape Town. Across Johannesburg we identified a Leptospira spp. infection prevalence of 44% (75/171) and noted significant differences in the prevalence between administrative regions within the metropole. Multi-locus sequence analyses identified a clonal genotype consistent with L. borgpetersenii serogroup Javanica (serovar Ceylonica).Discussion: The prevalence of infection identified in this study is amongst the highest detected in Rattus spp. in similar contexts across Africa. Despite the complex invasion history suggested by the heterogeneity in R. norvegicus haplotypes identified in Johannesburg, a single L. borgpetersenii genotype was identified in all infected rodents. The lack of L. interrogans in a rodent community dominated by R. norvegicus is notable, given the widely recognised host-pathogen association between these species and evidence for L. interrogans infection in R. norvegicus in Cape Town. It is likely that environmental conditions (cold, dry winters) in Johannesburg may limit the transmission of L. interrogans. Spatial heterogeneity in prevalence suggest that local factors, such as land use, influence disease risk in the metropole. Conclusions: In South Africa, as in other African countries, leptospirosis is likely underdiagnosed. The high prevalence of infection in urban rodents in Johannesburg suggest that further work is urgently needed to understand the potential public health risk posed by this neglected zoonotic pathogen.
Using exosomal miRNAs extracted from porcine follicular fluid to investigate their role in oocyte development
Authors: Hu Junhe , Dong Jinyi , Zeng Zhi , Wu Juan , Tan Xiansheng , Tang Tao , Yan Jiao , Jin Chenzhong 
Published: November 2020

Abstract
Background: Follicular development is crucial to normal oocyte maturation, with follicular size closely related to oocyte maturation. To better understand the molecular mechanisms behind porcine oocyte maturation, we obtained exosomal miRNA from porcine follicular fluid (PFF). These miRNA samples were then sequenced and analyzed regarding their different follicular sizes, as described in the methods section. Results：First, these results showed that this process successfully isolated PFF exosomes. Nearly all valid reads from the PFF exosomal sequencing data were successfully mapped to the porcine genome database. Second, we used hierarchical clustering methods to determine that significantly expressed miRNAs were clustered into A, B, C, and D groups in our heatmap according to different follicle sizes. These results allowed for the targeting of potential mRNAs genes related to porcine oocyte development. Third, we chose ten, significantly expressed miRNAs and predicted their target genes for further GO analysis. These results showed that the expression levels of neurotransmitter secretion genes were greatly changed, as were many target genes involved in the regulation of FSH secretion. Notably, these are genes that are very closely related to oocyte maturation in growing follicles. We then used pathway analysis for these targeted genes based on the originally selected ten miRNAs. Results indicated that the pathways were mainly related to the biosynthesis of TGF-beta and its signaling pathway, which are very closely related to reproductive system functions.Conclusions：Finally, these exosomal miRNAs obtained from PFF may provide a valuable addition to our understanding of the mechanism of porcine oocyte maturation. It is also likely that these exosomal miRNAs could function as molecular biomarkers to choose high-quality oocytes and allow for in vitro porcine embryo production.
Roquin1 inhibits the proliferation of breast cancer cells by inducing G1/S cell cycle arrest via selectively destabilizing the mRNAs of cell cycle–promoting genes
Authors: Lu Wenbao , Zhou Meicen , Wang Bing , Liu Xueting , Li Bingwei 
Published: November 2020

Abstract
Background: Dysregulation of cell cycle progression is a common feature of human cancer cells; however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest in breast cancer.Methods: Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and its association with patient survival. Quantitative real-time PCR and Western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assays, flow cytometry, and in vivo analyses were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA sequencing was applied to identify the differentially expressed genes regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1.Results: We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse-free survival of patients with breast cancer. Roquin1 overexpression inhibited cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizes cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2), by targeting the stem–loop structure in the 3' untranslated region (3'UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs.Conclusions: Our findings demonstrated that Roquin1 is a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might be a potential molecular target for breast cancer treatment.
Gene&nbsp;Expression and&nbsp;Regulatory Webwork&nbsp;of POLR2K in Bladder Carcinogenesis by Integrated Bioinformatics Approaches
Authors: Yang Liliang , Wang Kaizhen , Guo Wenjing , Chen Xian , Guo Qinglong , Wei Libin , Zhou Yuxin 
Published: November 2020

Abstract
Background：RNA polymerase II subunit K (POLR2K) belongs to one of the multiple subunits of RNA polymerase II (Pol II), whose biological function is to synthesize mRNA. Aberrant POLR2K expression is related to carcinogenesis. However, POLR2K’s underlying role in bladder cancer has not been explored. In the current study, we intend to analyze the function of POLR2K and its regulatory network within bladder cancer.Methods: Public sequencing data was obtained from GEO and TCGA to investigate POLR2K expression and regulatory network within bladder cancer (BLCA) by using GEPIA and Oncomine as well as cBioPortal online tool. LinkedOmics was employed to identify genes displaying significantly differential expression patterns and to perform GO and KEGG analyses. After differential genes was assigned and ranked, GSEA analysis was performed to obtain target networks for transcription factors, miRNAs, and kinases that could regulate POLR2K–associated gene network. Subsequent functional webwork analyses were used to identify cancer-relevant pathways Moreover, POLR2K gene is verified by ChIP-seq in MCF-7 cell line with transcription factor binding evidence in the ENCODE Transcription Factor Binding Site Profiles dataset. In the end, the biological behavior of POLR2K in BLCA was validated by cell function experiments and tissue micro-assay.Conclusions: The current study implies that POLR2K gene is overexpressed and often amplified in BLCA, providing the first evidence that POLR2K deregulation, especially increased transcription, may promote BLCA. Knocking down POLR2K in BLCA 5637 and T24 cells could decrease cellular viability, reduce metastasis ability and induce G1 arrest, which might be mediated by E2F1. These findings uncover a unique expression pattern of POLR2K and its potential regulatory networks in BLCA, contributing greatly to study of the role of POLR2K in cancer development.
Phylogenetic analysis of variable and conserved genomic regions in severe acute respiratory syndrome coronavirus 2 (COVID-19)
Authors: Nahas Abeer F. El , Elkatatny Nasema M. , Abo-Al-Ela Haitham G. 
Published: November 2020

Abstract
SARS-CoV-2 has rapidly spread around the world. Several mutations have been detected in its genome, but they do not seem to affect the abilities of the virus to spread or infect. We aimed to explore the conserved genomic regions in coronavirus that could contain the key strengths of the virus. SARS-CoV-2 sequence data were retrieved from Genbank from the period of December 2019 to March 2020. Phylogenetic analyses were conducted for 207 sequences using MEGAX compared with the reference sequence (MN908947.3- CHN-Wuhan Dec-2019). The analysis included seven important genomic regions, the ORF1ab gene (21,290 bp), S gene (3,822 bp), Orf3a gene (827 bp), E gene (227 bp), M gene (669 bp), and N gene (1,259 bp), which play critical roles in virus invasion and replication. Furthermore, the variant nucleotides and amino acids were detected by MEGAX and BLAST. Through the phylogenetic analysis and amino acid substitution, the ORF1ab gene showed 11 conserved regions and also several variable sites. The E and M genes were mainly conserved, and all sequences were included in one clade, with one or two amino acid variants. Orf3a and the N gene have four conserved sites distributed along the genes. The S gene has 12 mutations and four main large conserved regionsWe conclude that the favored occurrence of mutations at the ORFab and Orf3a genes during the SARS-CoV epidemic is an important mechanism for virus pathogenesis. The E and M proteins have an almost conserved structure, whereas the S and N genes have many conserved regions, which could serve as possible targets for vaccine design for SARS-CoV.
Low-loss polyacrylate dielectric elastomer with outstanding actuation performance by optimizing crosslinking network
Authors: Yin Li-Juan , Zhao Yu , Zhu Jing , Yang Minhao , Pei Jia-Yao , Zhong Shao-Long , Dang Zhi-Min 
Published: November 2020

Abstract
This work reports the low-loss polyacrylate dielectric elastomer with outstanding actuation performance by employing a molecular engineering route. It is found that the difunctional macromolecular crosslinking agent we choose can not only effectively tune the dimensions of elastomer meshes and avoid uneven distribution of crosslinking points in elastomer matrix, accordingly eliminating the stress concentration and delaying the failure of elastomer, but also as “soft segments” and alleviate the strong dipole-dipole interaction between adjacent side groups of polyacrylate, which makes the dielectric elastomer with low elastic modulus and low mechanical loss. Simultaneously, a certain amount of uncrosslinked chains will remain in the free volume space of elastomer network, which would increase the dielectric constant of as-synthesized elastomers owing to their strong orientation ability. Therefore, the improvements in mechanical and dielectric properties of elastomer will contribute to the amelioration of actuation performance. We also design a home-made non-magnetic motor apparatus to verify the optimized actuation performance. This finding represents the first molecular engineering approach to improve the intrinsic actuation performance of dielectric elastomers, which are key materials of choice for flexible dielectric elastomer actuators.
Alleloscope: Integrative single cell analysis of allele-specific copy number alterations and chromatin accessibility in cancer
Authors: Wu Chi-Yun , Lau Billy , Kim Heonseok , Sathe Anuja , Grimes Susan M , Ji Hanlee , Zhang Nancy 
Published: November 2020

Abstract
Cancer progression is driven by both somatic copy number aberrations (CNAs) and chromatin remodeling, yet little is known about the interplay between these two classes of events in shaping the clonal diversity of cancers. We present Alleloscope, a method for allele-specific copy number estimation that can be applied to single cell DNA and ATAC sequencing data, either separately or in combination. This approach allows for integrative multi-omic analysis of allele-specific copy number and chromatin accessibility on the same cell. On scDNA-seq data from gastric, colorectal, and breast cancer samples, with extensive validation using matched linked-read sequencing, Alleloscope finds pervasive occurrence of highly complex, multi-allelic copy number aberrations, where cells that carry varying allelic configurations adding to the same total copy number co-evolve within a tumor. The contributions of such allele-specific events to intratumor heterogeneity have been under-reported and under-studied due to the lack of methods for their detection. On scATAC-seq from two basal cell carcinoma samples and a gastric cancer cell line, Alleloscope detects multi-allelic copy number events and copy neutral loss-of-heterozygosity, enabling the dissection of the contributions of chromosomal instability and chromatin remodeling in tumor evolution.
WITHDRAWN: Complete Chloroplast Genome of Calligonum Mongolicum: Genome Organization, Codon Usage Pattern, Phylogenetic Relationships, Comparative Structure and Adaptive Evolution Analysis
Authors: Duan Hui-rong , Zhang Qian , Yang Hongshan , Tian Fuping , Hu Yu , Wang Chunmei , Lu Yuan , Yuan Huijun , Cui Guangxin 
Published: November 2020

Abstract
BackgroundThe perennial shrub of Calligonum mongolicum is a dominant native plant in all Calligonum species, which has the largest and most widespread geographic distribution in arid deserts of northern China. Understanding the phylogenetic relationship between C. mongolicum and closely related plant species will offer guidance on the classification and identification of inter-species and their varieties. The chloroplast (cp) genome is an optimal model to decipher phylogenetic relationships and genome evolution in related plant families. In the present study, the complete cp genome of C. mongolicum was sequenced, and the characteristics were described, then the genomic structure was compared to other three Polygonaceae species.ResultsThe cp genome of C. mongolicum was 162,124 bp in length with a quadripartite structure. A total of 131 functional genes were annotated, 14 different genes of which harbored introns and exons, 50 long repeat sequences and 244 simple sequences repeats were identiﬁed. Synonymous codon usage (SCU) analysis exhibited A/T preference, and 7 codons were identified as the optimal codons. Multivariate statistical analysis of parity rule 2, ENC-plot, and neutrality plot were combined conducted to imply natural selection as the crucial constraint in SCU bias in C. mongolicum cp genome.The phylogenetic tree showed that Rumex acetosa was the most related plant to C. mongolicum. From the comparative analysis of genomic structures, the inverted repeat regions (IRa and IRb) were less divergent than other parts and coding regions was relatively conserved than non-coding regions. Compared to other species in the Polygonaceae, the borders of IRb/SSC and SSC/IRa in C. mongolicum changed greatly. Furthermore, adaptive evolution analysis of 75 orthologous protein-coding genes indicated that only the psbK gene was under positive selection, which might be crucial in the adaptive evolution of C. mongolicum.ConclusionsOur results comprehensively depicts the architecture of C. mongolicum cp genome, and will lay a vigorous foundation for further study on molecular marker selection, phylogenetic analysis, and population researches in Calligonum species.
Association of Serum Antibodies Against the Mycobacterium Avium Complex and Hemoptysis: A Cross-Sectional Study
Authors: Ogata Hiroaki , Moriwaki Atsushi , Nakagawa Taisuke , Sakoda Soichiro , Ishimatsu Akiko , Taguchi Kazuhito , Aso Hiroshi , Nogami Hiroko , Kadowaki Masako , Tateshi Yuko , Yoshida Makoto 
Published: November 2020

Abstract
Background: Hemoptysis is very common and can be life threatening in clinical practice for nontuberculous mycobacteria. The serum antibody against the Mycobacterium avium complex (MAC-Ab), the majority of nontuberculous mycobacteria species, is well known to reflect the activity of MAC lung disease; however, there is no study investigating the association between the MAC-Ab and hemoptysis in MAC patients. Therefore, we assessed whether the MAC-Ab is a good biomarker for hemoptysis among subjects with MAC lung disease. Methods: This study was conducted as a five-year retrospective survey at the National Hospital Organization Fukuoka National Hospital. A total of 155 patients aged ≥ 20 years with MAC lung disease were enrolled and separated into seropositive and seronegative groups using the cutoff for MAC-Ab levels of 0.7 U/ml. The prevalence of hemoptysis and odds ratios for the presence of hemoptysis were estimated and compared between the groups. To investigate the linear trends in the relationship between MAC-Ab levels and hemoptysis, the subjects were classified into three groups using the tertile distribution of the MAC-Ab. Results: The prevalence of hemoptysis was twice as high in the seropositive group than in the seronegative group (42.2% and 21.7%, respectively, P = 0.02). The multivariable-adjusted risk of hemoptysis was elevated in the seropositive group as compared with the seronegative group (odds ratio = 2.79 (95% confidence interval 1.15–7.44)). Likewise, when categorizing the subjects into three groups, the risk of hemoptysis increased parallel to higher MAC-Ab levels (P = 0.03 for trend). Conclusions: A positive MAC-Ab level was a significant risk factor for hemoptysis among patients with MAC lung disease. There were also positive trends in the association between the MAC-Ab titer and the likelihood of hemoptysis. MAC patients who tested positive for the MAC-Ab should be carefully followed up for the potential development of hemoptysis.