bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subclinical bacteriuria in a mixed population of 179 middle-aged and elderly cats: a prospective cross-sectional study
Authors: Moberg Frida S , Langhorn Rebecca , Bertelsen Pernille V , Pilegaard Louise M , Sørensen Tina M , Bjørnvad Charlotte R , Damborg Peter , Kieler Ida N , Jessen Lisbeth R 
Published: September 2019

Objectives Subclinical bacteriuria (SBU) is the presence of bacteria in urine with no clinical evidence of lower urinary tract disease. The aims of this study were to investigate if being overweight and/or obesity predispose cats to SBU, to investigate previously reported risk factors and to determine the prevalence of SBU in a prospectively sampled cohort of middle-aged and elderly cats. Methods Cats aged ⩾6 years presenting to the University Hospital for Companion Animals in Copenhagen from 2015–2019 for causes unrelated to the lower urinary tract were eligible for enrolment. Body condition scoring was performed on a 9-point scale. Overweight was defined as a body condition score (BCS) ⩾6 and obese as a BCS ⩾8. The correlation between SBU and the variables of sex, healthy/diseased, age, BCS and comorbidities (chronic kidney disease, diabetes mellitus, hyperthyroidism, hepatic disorders and gastrointestinal disease) were analysed by binominal logistic regression. Results In total, 179 cats ranging from 6–20 (median 10) years of age were included. SBU was identified in 11/179 cats (6.1%). Being overweight was not a significant risk factor (overweight/obese odds ratio [OR] 0.3, 95% confidence interval [CI] 0.06–1.6, relative risk [RR] 0.3 [95% CI 0.05–1.3] vs lean; P = 0.2) and neither was obesity compared with lean and overweight cats ( P = 0.99). Female sex (OR 6.2 [95% CI 1.3–30], RR 4.7 [95% CI 1.5–12] vs male; P = 0.02) and the presence of hepatic disease (OR 7.5 [95% CI 1.4–39], RR 5.3 [95% CI 1.3–12]; P = 0.02) were significant risk factors. Conclusions and relevance The prevalence of SBU in cats is low, and being overweight/obese was not identified as a predisposing factor. The increased risk associated with hepatic disease has not been previously reported, and further studies are needed to confirm this finding.
Laser Doppler Flowmetry to Differentiate Arterial From Venous Occlusion in Free Tissue Transfer
Authors: Gazyakan Emre , Kao Huang-Kai , Cheng Ming-Huei , Engel Holger 
Published: September 2019

Purpose: The differentiation of arterial versus venous occlusion in free tissue transfers has rarely been described. This study investigated changes in blood flow caused by arterial and venous occlusion and the potential for laser Doppler flowmetry to distinguish between these 2 conditions for better clinical assessment and management of free tissue transfer. Methods: Six patients with a mean age of 43.5 years underwent microsurgical free tissue transfer. The venous and arterial blood flow of the vessels and skin flap were monitored using laser Doppler flowmetry with high-frequency pulsed Doppler transducers for vessels and skin before, during, and after clamping the vessels for 10 minutes. Results: The average decreases in blood flow in the artery and vein caused by clamping were 94.4% and 93.8%, respectively. On average, arterial occlusion demonstrated a sudden drop of 67.7% and venous occlusion caused a decrease of 26.6% on laser Doppler flowmetry in free tissue skin. Conclusion: Using a vessel-holding probe, laser Doppler flowmetry could be used to differentiate between arterial and venous occlusion in free tissue transfer, thereby aiding decision-making for better clinical management.
Effective editing for lysophosphatidic acid acyltransferase 2/5 in allotetraploid rapeseed (Brassica napus L.) using CRISPR-Cas9 system
Authors: Zhang Kai , Nie Liluo , Cheng Qiqi , Yin Yongtai , Chen Kang , Qi Fuyu , Zou Dashan , Liu Haohao , Zhao Weiguo , Wang Baoshan , Li Maoteng 
Published: September 2019

Abstract

Background
Brassica napus is one of the most important oilseed crops, and can supply considerable amounts of edible oil as well as provide raw materials for the production of biodiesel in the biotechnology industry. Lysophosphatidic acid acyltransferase (LPAT), a key enzyme in the Kennedy pathway, catalyses fatty acid chains into 3-phosphoglycerate and promotes further production of oil in the form of triacylglycerol. However, because B. napus is an allotetraploid with two subgenomes, the precise genes which involved in oil production remain unclear due to the intractability of efficiently knocking out all copies with high genetic redundancy. Therefore, a robust gene editing technology is necessary for gene function analysis.

Results
An efficient gene editing technology was developed for the allotetraploid plant B. napus using the CRISPR-Cas9 system. Previous studies showed poor results in either on-target or off-target activity in B. napus. In the present study, four single-gRNAs and two multi-gRNAs were deliberately designed from the conserved coding regions of BnLPAT2 which has seven homologous genes, and BnLPAT5, which has four homologous genes. The mutation frequency was found to range from 17 to 68%, while no mutation was observed in the putative off-target sites. The seeds of the Bnlpat2/Bnlpat5 mutant were wizened and showed enlarged oil bodies, disrupted distribution of protein bodies and increased accumulation of starch in mature seeds. The oil content decreased, with an average decrease of 32% for Bnlpat2 lines and 29% for Bnlpat5 lines in single-gRNA knockout lines, and a decline of 24% for Bnlpat2 mutant lines (i.e., g123) and 39% for Bnlpat2/Bnlpat5 double mutant lines (i.e., g134) in multi-gRNA knockout lines.

Conclusions
Seven BnLPAT2 homologous genes and four BnLPAT5 homologous genes were cleaved completely using the CRISPR-Cas9 system, which indicated that it is effective for editing all homologous genes in allotetraploid rapeseed, despite the relatively low sequence identities of both gene families. The size of the oil bodies increased significantly while the oil content decreased, confirming that BnLPAT2 and BnLPAT5 play a role in oil biosynthesis. The present study lays a foundation for further oil production improvement in oilseed crop species.
Efficient marker free CRISPR/Cas9 genome editing for functional analysis of gene families in filamentous fungi
Authors: van Leeuwe Tim M. , Arentshorst Mark , Ernst Tim , Alazi Ebru , Punt Peter J. , Ram Arthur F. J. 
Published: September 2019

AbstractBackgroundCRISPR/Cas9 mediated genome editing has expedited the way of constructing multiple gene alterations in filamentous fungi, whereas traditional methods are time-consuming and can be of mutagenic nature. These developments allow the study of large gene families that contain putatively redundant genes, such as the seven-membered family ofcrh-genes encoding putative glucan–chitin crosslinking enzymes involved in cell wall biosynthesis.ResultsHere, we present a CRISPR/Cas9 system forAspergillus nigerusing a non-integrative plasmid, containing a selection marker, a Cas9 and a sgRNA expression cassette. Combined with selection marker free knockout repair DNA fragments, a set of the seven single knockout strains was obtained through homology directed repair (HDR) with an average efficiency of 90%. Cas9–sgRNA plasmids could effectively be cured by removing selection pressure, allowing the use of the same selection marker in successive transformations. Moreover, we show that either two or even three separate Cas9–sgRNA plasmids combined with marker-free knockout repair DNA fragments can be used in a single transformation to obtain double or triple knockouts with 89% and 38% efficiency, respectively. By employing this technique, a seven-memberedcrh-gene family knockout strain was acquired in a few rounds of transformation; three times faster than integrative selection marker (pyrG) recycling transformations. An additional advantage of the use of marker-free gene editing is that negative effects of selection marker gene expression are evaded, as we observed in the case of disrupting virtually silentcrhfamily members.ConclusionsOur findings advocate the use of CRISPR/Cas9 to create multiple gene deletions in both a fast and reliable way, while simultaneously omitting possible locus-dependent-side-effects of poor auxotrophic marker expression.
Risk factors for positive depression screening across a shipboard deployment cycle
Authors: Arcury-Quandt Alice E. , Harbertson Judith , Ziajko Lauretta , Hale Braden R. 
Published: September 2019

Background
Depression is a leading cause of healthcare use and risk for suicide among US military personnel. Depression is not well characterised over the shipboard deployment cycle, and personnel undergo less screening than with land-based deployments, making early identification less likely.

Aims
To determine the demographic and behavioural risk factors associated with screening positive for risk of depression (ROD) across the shipboard deployment cycle.

Method
Active-duty ship assigned personnel completed an anonymous assessment using the Center for Epidemiologic Studies Depression Scale (CES-D) in the year prior to deployment, during deployment and in the months following deployment. Longitudinal models were used to determine risk factors.

Results
In total, 598 people were included in the analysis. Over 50% of the study population screened positive for ROD (CES-D score ≥16) and over 25% screened positive for risk of major depressive disorder (CES-D score ≥22) at all time points. Lower age, female gender, alcohol use, stress and prior mental health diagnoses were all associated with greater odds of screening positive for ROD in multivariable models.

Conclusions
Although the risk factors associated with screening positive for ROD are similar to those in other military and civilian populations, the proportion screening positive exceeds previously reported prevalence. This suggests that shipboard deployment or factors associated with shipboard deployment may present particular stressors or increase the likelihood of depressive symptoms.

Declaration of interest
The authors are military service members (or employees of the US Government). This work was prepared as part of the authors' official duties. Title 17, U.S.C. §105 provides the ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17, USC, §101 defines a US Government work as work prepared by a military service member or employee of the US Government as part of that person's official duties. The views expressed in this research are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of the Army, Department of the Air Force, Department of Veterans Affairs, Department of Defense, or the US Government. Approved for public release; distribution unlimited. Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense.
Prediction of Drug Approval After Phase I Clinical Trials in Oncology: RESOLVED2
Authors: Beinse Guillaume , Tellier Virgile , Charvet Valentin , Deutsch Eric , Borget Isabelle , Massard Christophe , Hollebecque Antoine , Verlingue Loic 
Published: September 2019

PURPOSE Drug development in oncology currently is facing a conjunction of an increasing number of antineoplastic agents (ANAs) candidate for phase I clinical trials (P1CTs) and an important attrition rate for final approval. We aimed to develop a machine learning algorithm (RESOLVED2) to predict drug development outcome, which could support early go/no-go decisions after P1CTs by better selection of drugs suitable for further development. METHODS PubMed abstracts of P1CTs reporting on ANAs were used together with pharmacologic data from the DrugBank5.0 database to model time to US Food and Drug Administration (FDA) approval (FDA approval-free survival) since the first P1CT publication. The RESOLVED2 model was trained with machine learning methods. Its performance was evaluated on an independent test set with weighted concordance index (IPCW). RESULTS We identified 462 ANAs from PubMed that matched with DrugBank5.0 (P1CT publication dates 1972 to 2017). Among 1,411 variables, 28 were used by RESOLVED2 to model the FDA approval-free survival, with an IPCW of 0.89 on the independent test set. RESOLVED2 outperformed a model that was based on efficacy/toxicity (IPCW, 0.69). In the test set at 6 years of follow-up, 73% (95% CI, 49% to 86%) of drugs predicted to be approved were approved, whereas 92% (95% CI, 87% to 98%) of drugs predicted to be nonapproved were still not approved (log-rank P < .001). A predicted approved drug was 16 times more likely to be approved than a predicted nonapproved drug (hazard ratio, 16.4; 95% CI, 8.40 to 32.2). CONCLUSION As soon as P1CT completion, RESOLVED2 can predict accurately the time to FDA approval. We provide the proof of concept that drug development outcome can be predicted by machine learning strategies.
Integrative Molecular Analysis of Patients With Advanced and Metastatic Cancer
Authors: Sailer Verena , Eng Kenneth Wa , Zhang Tuo , Bareja Rohan , Pisapia David J. , Sigaras Alexandros , Bhinder Bhavneet , Romanel Alessandro , Wilkes David , Sticca Evan , Cyrta Joanna , Rao Rema , Sahota Sheena , Pauli Chantal , Beg Shaham , Motanagh Samaneh , Kossai Myriam , Fontugne Jacqueline , Puca Loredana , Rennert Hanna , Xiang Jenny Zhaoying , Greco Noah , Kim Rob , MacDonald Theresa Y. , McNary Terra , Blattner-Johnson Mirjam , Schiffman Marc H. , Faltas Bishoy M. , Greenfield Jeffrey P. , Rickman David , Andreopoulou Eleni , Holcomb Kevin , Vahdat Linda T. , Scherr Douglas S. , van Besien Koen , Barbieri Christopher E. , Robinson Brian D. , Fine Howard Alan , Ocean Allyson J. , Molina Ana , Shah Manish A. , Nanus David M. , Pan Qiulu , Demichelis Francesca , Tagawa Scott T. , Song Wei , Mosquera Juan Miguel , Sboner Andrea , Rubin Mark A. , Elemento Olivier , Beltran Himisha 
Published: September 2019

PURPOSE We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis. PATIENTS AND METHODS Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated. RESULTS Most frequent tumor types were prostate (19.4%), brain (16.5%), bladder (15.4%), and kidney cancer (9.2%). Most frequently altered genes were TP53 (33%), CDKN2A (11%), APC (10%), KTM2D (8%), PTEN (8%), and BRCA2 (8%). Pathogenic germline alterations were present in 10.7% of patients, most frequently CHEK2 (1.9%), BRCA1 (1.5%), BRCA2 (1.5%), and MSH6 (1.4%). Novel gene fusions were identified, including a RBM47-CDK12 fusion in a metastatic prostate cancer sample. The rate of clinically relevant alterations was 39% by whole-exome sequencing, which was improved by 16% by adding RNA sequencing. In patients with more than one sequenced tumor sample (n = 146), 84.62% of actionable mutations were concordant. CONCLUSION Integrative analysis may uncover informative alterations for an advanced pan-cancer patient population. These alterations are consistent in spatially and temporally heterogeneous samples.
Model systems for regeneration: zebrafish
Authors: Marques Ines J. , Lupi Eleonora , Mercader Nadia 
Published: September 2019

ABSTRACT
Tissue damage can resolve completely through healing and regeneration, or can produce permanent scarring and loss of function. The response to tissue damage varies across tissues and between species. Determining the natural mechanisms behind regeneration in model organisms that regenerate well can help us develop strategies for tissue recovery in species with poor regenerative capacity (such as humans). The zebrafish (Danio rerio) is one of the most accessible vertebrate models to study regeneration. In this Primer, we highlight the tools available to study regeneration in the zebrafish, provide an overview of the mechanisms underlying regeneration in this system and discuss future perspectives for the field.
Effects of evidence-based clinical practice guidelines in cardiovascular health care quality improvements: A systematic review
Authors: Ramírez-Morera Anggie , Tristan Mario , Vazquez Juan Carlos 
Published: September 2019

Background: The development of evidence-based clinical practice guidelines (EB-CPGs) has increasing global growth; however, the certainty of impact on patients and health systems, as well as the magnitude of the impact, is not apparent. The objective of this systematic review was to assess the effectiveness of the application of EB-CPGs for the improvement of the quality of health care in three dimensions: structure, process and results in the patient for the management of cardiovascular disease. Methods: We followed the methods described by the Cochrane Handbook and present a descriptive analysis because of the high heterogeneity found across the included studies. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE databases, as well as the grey literature, between 1990 and June 2016. No language restrictions were applied. Only randomised clinical trials (RCTs) were selected. Three authors independently carried out the data extraction, using a modified version of the Cochrane Effective Practice and Organization of Care form. Results: Of the total of 84 interventions included in the nine RCTs evaluated, three (4%) were related to health care structure, 54 (64%) to the health care delivery process and 27 (32%) to patient outcomes. Regarding the impact of using the EB-CPGs, in 55 interventions (65%), there were no significant differences between control and experimental groups. In four interventions (5%), the result favoured the control group, and the result favoured the intervention group on 25 of the interventions (30%). Conclusions: This systematic review showed that EB-CPGs could be useful to improve the process and structure of health care and, to a lesser extent, to improve the patients’ outcomes. After analysing many studies, we could have one more hypothesis for further research, which could shed more light upon those undiscovered variables that might interfere with the use of the EB-CPGs. Registration: PROSPERO CRD42013003589
Punishing the individual or the group for norm violation
Authors: El Zein Marwa , Seikus Chloe , De-Wit Lee , Bahrami Bahador 
Published: September 2019

Background: It has recently been proposed that a key motivation for joining groups is the protection from consequences of negative behaviours, such as norm violations. Here we empirically test this claim by investigating whether cooperative decisions and the punishment of associated fairness-based norm violations are different in individuals vs. collectives in economic games. Methods: In the ultimatum game, participants made or received offers that they could reject at a cost to their outcome, a form of social punishment. In the dictator game with third-party punishment, participants made offers to a receiver while being observed by a punisher, or could themselves punish unfair offers. Results: Participants made lower offers when making a collective rather than an individual decision. This difference correlated with participants’ overall mean offers: those who were generally less generous were even less so in a group, suggesting that the collective structure was compatible with their intention. Participants were slower when punishing vs not punishing an unfair offer. Importantly here, they were slower when deciding whether to punish groups as compared to individuals, only when the offer concerned them directly in second party punishment. Participants thus seem reluctant to punish others, and even more so when facing a group of proposers. Conclusions: Together, these results show that people behave differently in a group, both in their willingness to share with others and in their punishment of norm violations. This could be explained by the fact that being in a collective structure allows to share responsibility with others, thereby protecting from negative consequences of norm violations.
Judgments Based on Stocks and Flows: Different Presentations of the Same Data Can Lead to Opposing Inferences
Authors: Spiller Stephen A. , Reinholtz Nicholas , Maglio Sam J. 
Published: September 2019

Time-series data—measurements of a quantity over time—can be presented as stocks (the quantity at each point in time) or flows (the change in quantity from one point in time to the next). In a series of six experiments, we find that the choice of presenting data as stocks or flows can have a consequential impact on judgments. The same data can lead to positive or negative assessments when presented as stocks versus flows and can engender optimistic or pessimistic forecasts for the future. For example, when employment data from 2007 to 2013 are shown as flows (jobs created or lost), President Obama’s impact on the economy during his first year in office is viewed positively, whereas when the same data are shown as stocks (total jobs), his impact is viewed negatively. The results highlight a challenge that accompanies the growing reliance on data and analytics for decision making within organizations: seemingly benign choices—such as that between two informationally equivalent data presentations—can substantively impact how data are interpreted and used, even though the underlying information is the same. This paper was accepted by Yuval Rottenstreich, decision analysis.
Editorial
Authors: Suppo Hugo , Giaccaglia Clarissa 
Published: September 2019

A Revista Neiba, Cadernos Argentina Brasil, criada em 2012, acaba de ser promovida no ranking da avaliação da CAPES de B3 para B2. Esse reconhecimento é fruto do trabalho de uma equipe abnegada, que foi se renovando ao longo do tempo. A partir deste ano, a revista tem seu Conselho Editorial ampliado e conta com a incorporação da professora Clarisa Giaccaglia (UNR) como co-editora responsável junto ao professor Hugo Suppo (UERJ), reforçando assim o caráter binacional da publicação.Dando continuidade ao processo de aperfeiçoamento da revista, ela continuará a ser publicada anualmente, adotando o método de fluxo contínuo, segundo o qual os artigos são disponibilizados conforme seus processos de análise e editoração forem sendo concluídos. Dessa forma, ao final do ano, todos os artigos são reunidos em um único número. Esse formato garante a circulação do conhecimento de maneira mais fluida acelerando o processo de comunicação das pesquisas.É importante assinalar que nesse tipo de formato já não se utiliza mais a numeração de páginas tradicional, pois todos os artigos tem um identificador eletrônico, denominado elocation-id (electronic location identifier). Trata-se de um identificador único dentro do volume, que permite a correta identificação e citação dos artigos. Ressalte-se que a revista continuará utilizando o identificador de objetos digitais, DOI (Digital Object Identifier), o que que garante a respectiva localização na rede.Além disso, um novo visual da revista foi desenvolvido, tanto no portal como no seu conteúdo, graças à colaboração de Nathalia Avila, do Portal de Publicações Eletrônicas da UERJ/EdUERJ/UERJ e de Talita Ribeiro, nossa assistente de editoração.Nesta nova etapa de renovação da Revista Neiba, Cadernos Argentina Brasil, contamos mais uma vez com a colaboração de nossos prestigiados pareceristas, autores e membros da equipe técnica, sem os quais ela não teria logrado êxito. Hugo SuppoClarisa GiaccagliaEditores chefes