bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of risk stratification using blood parameters for nivolumab in Japanese patients with metastatic renal-cell carcinoma
Authors: Yamamoto Yoshiaki , Matsuyama Hideyasu , Matsumoto Hiroaki , Sakano Shigeru , Fuji Nakanori , Oba Kazuo , Yamamoto Mitsutaka , Kamiryo Yoriaki , Hiragino Takeshi , Nagao Kazuhiro , Takai Kimio , Aoki Akihiko 
Published: October 2019

Abstract

Background
Nivolumab is a standard treatment for previously treated advanced renal-cell carcinoma. However, nivolumab is effective in only a limited number of patients; therefore, we evaluated the prognostic value of several biomarkers, including inflammation-based prognostic scores and changes in these scores following nivolumab treatment in Japanese patients with metastatic renal-cell carcinoma.

Methods
We retrospectively reviewed the medical records of 65 patients with previously treated metastatic renal-cell carcinoma and who received nivolumab. Inflammation-based prognostic scores, including neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, and Glasgow prognostic score before and 6 weeks after the treatment were recorded. Categorical variables influencing disease-specific survival were compared using Cox proportional-hazards regression models.

Results
Univariate analysis showed that Memorial Sloan-Kettering Cancer Center risk score (P = 0.0052), lactate dehydrogenase (P = 0.0266), lymphocyte/monocyte ratio (P = 0.0113), and platelet/lymphocyte ratio (P = 0.0017) had a significant effect on disease-specific survival. Multivariate analyses showed that platelet/lymphocyte ratio and lactate dehydrogenase were found to be independent prognostic factors for disease-specific survival (P = 0.0008, risk ratio (RR) = 7.95, 95% confidence interval, 2.16–51.64 and P = 0.0123, RR = 3.92, 95% confidence interval, 1.37–10.80, respectively). The combination of platelet/lymphocyte ratio and lactate dehydrogenase was the most significant prognostic biomarker in metastatic renal-cell carcinoma (P &lt; 0.0001). Changes in lymphocyte/monocyte ratio and platelet/lymphocyte ratio in response to nivolumab were significant prognostic factors for disease-specific survival (P &lt; 0.0001 and P = 0.0477, respectively).

Conclusions
The combination of platelet/lymphocyte ratio and lactate dehydrogenase may be a potential biomarker for estimating disease-specific survival in Japanese patients with metastatic renal-cell carcinoma treated by nivolumab.
Prospective observational study on the safety of an original fiducial marker insertion for radiotherapy in gynecological cancer by a simple method
Authors: Sekii Shuhei , Tsujino Kayoko , Kubota Hikaru , Yamaguchi Satoshi , Kosaka Kengo , Miyazaki Shuichiro , Sulaiman Nor Shazrina , Matsumoto Yoko , Ota Yosuke , Soejima Toshinori , Sasaki Ryohei 
Published: October 2019

ABSTRACT
Our observational study aimed to verify the safety of our original titanium fiducial markers in gynecological cancer by using a simple insertion method. We prospectively evaluated the safety in patients with gynecological cancer who had undergone our insertion procedure of the titanium markers. The decision to implant a titanium marker was at the discretion of each radiation oncologist. The fiducial markers were manufactured by severing ligating clips for surgery into 3–6 mm pieces and were sterilized thereafter. We inserted an 18-gauge injection needle containing the marker before the marker was extruded by a 22-gauge Cattelan needle or shape memory alloy wire into the tumor or tissues close to the tumor. Severe complications within 3 months after implantation were scored according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 4.0. Between August 2016 and December 2018, we enrolled 46 patients. Of 46, 44 underwent implantation. The median age was 58.5 years. The most common primary site was the cervix. Two patients experienced detachment of the markers after implantation. No Grade 3 or higher level of complications was observed. Our simple insertion technique for original titanium fiducial markers was well-tolerated.
Bacterial cell cycle and growth phase switch by the essential transcriptional regulator CtrA
Authors: Delaby Marie , Panis Gaël , Viollier Patrick H 
Published: October 2019

Abstract
Many bacteria acquire dissemination and virulence traits in G1-phase. CtrA, an essential and conserved cell cycle transcriptional regulator identified in the dimorphic alpha-proteobacterium Caulobacter crescentus, first activates promoters in late S-phase and then mysteriously switches to different target promoters in G1-phase. We uncovered a highly conserved determinant in the DNA-binding domain (DBD) of CtrA uncoupling this promoter switch. We also show that it reprograms CtrA occupancy in stationary cells inducing a (p)ppGpp alarmone signal perceived by the RNA polymerase beta subunit. A simple side chain modification in a critical residue within the core DBD imposes opposing developmental phenotypes and transcriptional activities of CtrA and a proximal residue can direct CtrA towards activation of the dispersal (G1-phase) program. Hence, we propose that this conserved determinant in the CtrA primary structure dictates promoter reprogramming during the growth transition in other alpha-proteobacteria that differentiate from replicative cells into dispersal cells.
PhaSePro: the database of proteins driving liquid–liquid phase separation
Authors: Mészáros Bálint , Erdős Gábor , Szabó Beáta , Schád Éva , Tantos Ágnes , Abukhairan Rawan , Horváth Tamás , Murvai Nikoletta , Kovács Orsolya P , Kovács Márton , Tosatto Silvio C E , Tompa Péter , Dosztányi Zsuzsanna , Pancsa Rita 
Published: October 2019

Abstract
Membraneless organelles (MOs) are dynamic liquid condensates that host a variety of specific cellular processes, such as ribosome biogenesis or RNA degradation. MOs form through liquid–liquid phase separation (LLPS), a process that relies on multivalent weak interactions of the constituent proteins and other macromolecules. Since the first discoveries of certain proteins being able to drive LLPS, it emerged as a general mechanism for the effective organization of cellular space that is exploited in all kingdoms of life. While numerous experimental studies report novel cases, the computational identification of LLPS drivers is lagging behind, and many open questions remain about the sequence determinants, composition, regulation and biological relevance of the resulting condensates. Our limited ability to overcome these issues is largely due to the lack of a dedicated LLPS database. Therefore, here we introduce PhaSePro (https://phasepro.elte.hu), an openly accessible, comprehensive, manually curated database of experimentally validated LLPS driver proteins/protein regions. It not only provides a wealth of information on such systems, but improves the standardization of data by introducing novel LLPS-specific controlled vocabularies. PhaSePro can be accessed through an appealing, user-friendly interface and thus has definite potential to become the central resource in this dynamically developing field.
VISDB: a manually curated database of viral integration sites in the human genome
Authors: Tang Deyou , Li Bingrui , Xu Tianyi , Hu Ruifeng , Tan Daqiang , Song Xiaofeng , Jia Peilin , Zhao Zhongming 
Published: October 2019

Abstract
Virus integration into the human genome occurs frequently and represents a key driving event in human disease. Many studies have reported viral integration sites (VISs) proximal to structural or functional regions of the human genome. Here, we systematically collected and manually curated all VISs reported in the literature and publicly available data resources to construct the Viral Integration Site DataBase (VISDB, https://bioinfo.uth.edu/VISDB). Genomic information including target genes, nearby genes, nearest transcription start site, chromosome fragile sites, CpG islands, viral sequences and target sequences were integrated to annotate VISs. We further curated VIS-involved oncogenes and tumor suppressor genes, virus–host interactions involved in non-coding RNA (ncRNA), target gene and microRNA expression in five cancers, among others. Moreover, we developed tools to visualize single integration events, VIS clusters, DNA elements proximal to VISs and virus–host interactions involved in ncRNA. The current version of VISDB contains a total of 77 632 integration sites of five DNA viruses and four RNA retroviruses. VISDB is currently the only active comprehensive VIS database, which provides broad usability for the study of disease, virus related pathophysiology, virus biology, host–pathogen interactions, sequence motif discovery and pattern recognition, molecular evolution and adaption, among others.
Understanding the binding specificities of mRNA targets by the mammalian Quaking protein
Authors: Sharma Monika , Sharma Shakshi , Alawada Apoorv 
Published: October 2019

AbstractMammalian Quaking (QKI) protein, a member of STAR family of proteins is a mRNA-binding protein, which post-transcriptionally modulates the target RNA. QKI protein possesses a maxi-KH domain composed of single heterogeneous nuclear ribonucleoprotein K homology (KH) domain and C-terminal QUA2 domain, that binds a sequence-specific QKI RNA recognition element (QRE), CUAAC. To understand the binding specificities for different mRNA sequences of the KH-QUA2 domain of QKI protein, we introduced point mutations at different positions in the QRE resulting in twelve different mRNA sequences with single nucleotide change. We carried out long unbiased molecular dynamics simulations using two different sets of recently updated forcefield parameters: AMBERff14SB+RNAχOL3 and CHARMM36 (with CMAP correction). We analyzed the changes in intermolecular dynamics as a result of mutation. Our results show that AMBER forcefields performed better to model the interactions between mRNA and protein. We also calculated the binding affinities of different mRNA sequences and found that the relative order correlates to the reported experimental studies. Our study shows that the favorable binding with the formation of stable complex will occur when there is an increase of the total intermolecular contacts between mRNA and protein, but without the loss of native contacts within the KH-QUA domain.
WormBase: a modern Model Organism Information Resource
Authors: Harris Todd W , Arnaboldi Valerio , Cain Scott , Chan Juancarlos , Chen Wen J , Cho Jaehyoung , Davis Paul , Gao Sibyl , Grove Christian A , Kishore Ranjana , Lee Raymond Y N , Muller Hans-Michael , Nakamura Cecilia , Nuin Paulo , Paulini Michael , Raciti Daniela , Rodgers Faye H , Russell Matthew , Schindelman Gary , Auken Kimberly V , Wang Qinghua , Williams Gary , Wright Adam J , Yook Karen , Howe Kevin L , Schedl Tim , Stein Lincoln , Sternberg Paul W 
Published: October 2019

Abstract
WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture. In this update, we describe progress in each of these three areas. In particular, we discuss the status of literature curation and recently added data, detail new features of the web interface and options for users wishing to conduct data mining workflows, and discuss our efforts to build a robust and scalable architecture by leveraging commercial cloud offerings. We conclude with a description of WormBase's role as a founding member of the nascent Alliance of Genome Resources.
MBKbase for rice: an integrated omics knowledgebase for molecular breeding in rice
Authors: Peng Hua , Wang Kai , Chen Zhuo , Cao Yinghao , Gao Qiang , Li Yan , Li Xiuxiu , Lu Hongwei , Du Huilong , Lu Min , Yang Xin , Liang Chengzhi 
Published: October 2019

Abstract
To date, large amounts of genomic and phenotypic data have been accumulated in the fields of crop genetics and genomic research, and the data are increasing very quickly. However, the bottleneck to using big data in breeding is integrating the data and developing tools for revealing the relationship between genotypes and phenotypes. Here, we report a rice sub-database of an integrated omics knowledgebase (MBKbase-rice, www.mbkbase.org/rice), which integrates rice germplasm information, multiple reference genomes with a united set of gene loci, population sequencing data, phenotypic data, known alleles and gene expression data. In addition to basic data search functions, MBKbase provides advanced web tools for genotype searches at the population level and for visually displaying the relationship between genotypes and phenotypes. Furthermore, the database also provides online tools for comparing two samples by their genotypes and finding target germplasms by genotype or phenotype information, as well as for analyzing the user submitted SNP or sequence data to find important alleles in the germplasm. A soybean sub-database is planned for release in 3 months and wheat and maize will be added in 1–2 years. The data and tools integrated in MBKbase will facilitate research in crop functional genomics and molecular breeding.
AraPheno and the AraGWAS Catalog 2020: a major database update including RNA-Seq and knockout mutation data for Arabidopsis thaliana
Authors: Togninalli Matteo , Seren Ümit , Freudenthal Jan A , Monroe J Grey , Meng Dazhe , Nordborg Magnus , Weigel Detlef , Borgwardt Karsten , Korte Arthur , Grimm Dominik G 
Published: October 2019

Abstract
Genome-wide association studies (GWAS) are integral for studying genotype-phenotype relationships and gaining a deeper understanding of the genetic architecture underlying trait variation. A plethora of genetic associations between distinct loci and various traits have been successfully discovered and published for the model plant Arabidopsis thaliana. This success and the free availability of full genomes and phenotypic data for more than 1,000 different natural inbred lines led to the development of several data repositories. AraPheno (https://arapheno.1001genomes.org) serves as a central repository of population-scale phenotypes in A. thaliana, while the AraGWAS Catalog (https://aragwas.1001genomes.org) provides a publicly available, manually curated and standardized collection of marker-trait associations for all available phenotypes from AraPheno. In this major update, we introduce the next generation of both platforms, including new data, features and tools. We included novel results on associations between knockout-mutations and all AraPheno traits. Furthermore, AraPheno has been extended to display RNA-Seq data for hundreds of accessions, providing expression information for over 28 000 genes for these accessions. All data, including the imputed genotype matrix used for GWAS, are easily downloadable via the respective databases.
Assembly and annotation of the mitochondrial minicircle genome of a differentiation-competent strain of Trypanosoma brucei
Authors: Cooper Sinclair , Wadsworth Elizabeth S , Ochsenreiter Torsten , Ivens Alasdair , Savill Nicholas J , Schnaufer Achim 
Published: October 2019

AbstractKinetoplastids are protists defined by one of the most complex mitochondrial genomes in nature, the kinetoplast. In the sleeping sickness parasite Trypanosoma brucei, the kinetoplast is a chain mail-like network of two types of interlocked DNA molecules: a few dozen ∼23-kb maxicircles (homologs of the mitochondrial genome of other eukaryotes) and thousands of ∼1-kb minicircles. Maxicircles encode components of respiratory chain complexes and the mitoribosome. Several maxicircle-encoded mRNAs undergo extensive post-transcriptional RNA editing via addition and deletion of uridines. The process is mediated by hundreds of species of minicircle-encoded guide RNAs (gRNAs), but the precise number of minicircle classes and gRNA genes was unknown. Here we present the first essentially complete assembly and annotation of the kinetoplast genome of T. brucei. We have identified 391 minicircles, encoding not only ∼930 predicted ‘canonical’ gRNA genes that cover nearly all known editing events (accessible via the web at http://hank.bio.ed.ac.uk), but also ∼370 ‘non-canonical’ gRNA genes of unknown function. Small RNA transcriptome data confirmed expression of the majority of both categories of gRNAs. Finally, we have used our data set to refine definitions for minicircle structure and to explore dynamics of minicircle copy numbers.
Control of ϕC31 integrase-mediated site-specific recombination by protein trans-splicing
Authors: Olorunniji Femi J , Lawson-Williams Makeba , McPherson Arlene L , Paget Jane E , Stark W Marshall , Rosser Susan J 
Published: October 2019

AbstractSerine integrases are emerging as core tools in synthetic biology and have applications in biotechnology and genome engineering. We have designed a split-intein serine integrase-based system with potential for regulation of site-specific recombination events at the protein level in vivo. The ϕC31 integrase was split into two extein domains, and intein sequences (Npu DnaEN and Ssp DnaEC) were attached to the two termini to be fused. Expression of these two components followed by post-translational protein trans-splicing in Escherichia coli generated a fully functional ϕC31 integrase. We showed that protein splicing is necessary for recombination activity; deletion of intein domains or mutation of key intein residues inactivated recombination. We used an invertible promoter reporter system to demonstrate a potential application of the split intein-regulated site-specific recombination system in building reversible genetic switches. We used the same split inteins to control the reconstitution of a split Integrase-Recombination Directionality Factor fusion (Integrase-RDF) that efficiently catalysed the reverse attR x attL recombination. This demonstrates the potential for split-intein regulation of the forward and reverse reactions using the integrase and the integrase-RDF fusion, respectively. The split-intein integrase is a potentially versatile, regulatable component for building synthetic genetic circuits and devices.
Bovine Genome Database: new annotation tools for a new reference genome
Authors: Shamimuzzaman Md , Le Tourneau Justin J , Unni Deepak R , Diesh Colin M , Triant Deborah A , Walsh Amy T , Tayal Aditi , Conant Gavin C , Hagen Darren E , Elsik Christine G 
Published: October 2019

Abstract
The Bovine Genome Database (BGD) (http://bovinegenome.org) has been the key community bovine genomics database for more than a decade. To accommodate the increasing amount and complexity of bovine genomics data, BGD continues to advance its practices in data acquisition, curation, integration and efficient data retrieval. BGD provides tools for genome browsing (JBrowse), genome annotation (Apollo), data mining (BovineMine) and sequence database searching (BLAST). To augment the BGD genome annotation capabilities, we have developed a new Apollo plug-in, called the Locus-Specific Alternate Assembly (LSAA) tool, which enables users to identify and report potential genome assembly errors and structural variants. BGD now hosts both the newest bovine reference genome assembly, ARS-UCD1.2, as well as the previous reference genome, UMD3.1.1, with cross-genome navigation and queries supported in JBrowse and BovineMine, respectively. Other notable enhancements to BovineMine include the incorporation of genomes and gene annotation datasets for non-bovine ruminant species (goat and sheep), support for multiple assemblies per organism in the Regions Search tool, integration of additional ontologies and development of many new template queries. To better serve the research community, we continue to focus on improving existing tools, developing new tools, adding new datasets and encouraging researchers to use these resources.
Arteriovenous access placement and renal function decline
Authors: Hahn Lundström Ulrika , Hedin Ulf , Gasparini Alessandro , Caskey Fergus J , Carrero Juan-Jesus , Evans Marie 
Published: October 2019

Abstract

Background
There is controversial evidence on whether arteriovenous access (AVA) placement may protect renal function and hence should be considered in the timing of access placement. This study aimed to investigate the association between AVA placement and estimated glomerular filtration rate (eGFR) decline as compared with the placement of a peritoneal dialysis catheter (PDC) at a similar time point.

Methods
We studied a cohort of 744 pre-dialysis patients in Stockholm, Sweden, who underwent surgery for AVA or PDC between 2006 and 2012. Data on comorbidity, medication and laboratory measures were collected 100 days before and after surgery. Patients were followed until dialysis start, death or 100 days, whichever came first. The primary outcome was difference in eGFR decline after AVA surgery compared with PDC. Decline in eGFR was estimated through linear mixed models with random intercept and slope, before and after surgery.

Results
There were 435 AVA and 309 PDC patients. The AVA patients had higher eGFR (8.1 mL/min/1.73 m2 versus 7.0 mL/min/1.73 m2) and less rapid eGFR decline before surgery (−5.6 mL/min/1.73 m2/year compared with −6.7 mL/min/1.73 m2/year for PDC). We found no difference in eGFR decline after surgery in AVA patients compared with PDC patients [AVA progressed 0.26 (95% confidence interval −0.88 to 0.35) mL/min/1.73 m2/year faster after surgery compared with PDC].

Conclusions
There was no significant difference in eGFR decline after placement of an AVA compared with a PDC. Both forms of access were associated with reduced eGFR decline in our population. The need for dialysis remains the main determinant for timing of access surgery.
Central Sensitization and Catastrophism Symptoms Are Associated with Chronic Myofascial Pain in the Gastrocnemius of Athletes
Authors: San-Antolín Marta , Rodríguez-Sanz David , Becerro-de-Bengoa-Vallejo Ricardo , Losa-Iglesias Marta Elena , Casado-Hernández Israel , López-López Daniel , Calvo-Lobo César 
Published: October 2019

AbstractObjectiveTo compare central sensitization symptoms, presence of central sensitivity syndrome (CSS), catastrophism, rumination, magnification, and helplessness symptoms between athletes with gastrocnemius myofascial pain and healthy athletes. Furthermore, to predict central sensitization symptoms based on sociodemographic and descriptive data, catastrophism features, and presence of gastrocnemius myofascial pain in athletes.DesignCase–control study.SettingOutpatient clinic.SubjectsFifty matched paired athletes were recruited and divided into patients with chronic (more than three months) gastrocnemius myofascial pain (N = 25) and healthy subjects (N = 25).MethodsCentral sensitization symptoms and CSS presence (≥40 points) were determined by the Central Sensitization Questionnaire (CSQ). Catastrophism symptoms and rumination, magnification, and helplessness domains were measured by the Pain Catastrophizing Scale (PCS). Statistical significance was set at P &lt; 0.01 for a 99% confidence interval.ResultsStatistically significant differences (P ≤ 0.001) with a large effect size (d = 1.05–1.19) were shown for higher CSQ scores and PCS total and domain scores in athletes with gastrocnemius myofascial pain vs healthy athletes. Nevertheless, CSS presence (CSQ ≥ 40 points) did not show statistically significant differences (P = 0.050) between groups. A linear regression model (R2 = 0.560, P &lt; 0.01) predicted higher CSQ scores based on PCS total score (R2 = 0.390), female sex (R2 = 0.095), and myofascial pain presence (R2 = 0.075).ConclusionsGreater symptoms of central sensitization, catastrophism, rumination, magnification, and helplessness were shown in athletes with gastrocnemius myofascial pain compared with healthy athletes. Nevertheless, there was not a statistically significant presence of CSS comparing both groups. Greater central sensitization symptoms were predicted by catastrophism symptoms, female sex, and presence of gastrocnemius myofascial pain in athletes.