bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimized photo-stimulation of halorhodopsin for long-term neuronal inhibition
Authors: Zhang Chuanqiang , Yang Shang , Flossmann Tom , Gao Shiqiang , Witte Otto W. , Nagel Georg , Holthoff Knut , Kirmse Knut 
Published: November 2019

Abstract
Background
Optogenetic silencing techniques have expanded the causal understanding of the functions of diverse neuronal cell types in both the healthy and diseased brain. A widely used inhibitory optogenetic actuator is eNpHR3.0, an improved version of the light-driven chloride pump halorhodopsin derived from Natronomonas pharaonis. A major drawback of eNpHR3.0 is related to its pronounced inactivation on a time-scale of seconds, which renders it unsuited for applications that require long-lasting silencing.

Results
Using transgenic mice and Xenopus laevis oocytes expressing an eNpHR3.0-EYFP fusion protein, we here report optimized photo-stimulation techniques that profoundly increase the stability of eNpHR3.0-mediated currents during long-term photo-stimulation. We demonstrate that optimized photo-stimulation enables prolonged hyperpolarization and suppression of action potential discharge on a time-scale of minutes.

Conclusions
Collectively, our findings extend the utility of eNpHR3.0 to the long-lasting inhibition of excitable cells, thus facilitating the optogenetic dissection of neural circuits.
Development of a CRISPR/Cas9 system against ruminant animal brucellosis
Authors: Karponi Garyfalia , Kritas Spyridon K. , Papadopoulou Gina , Akrioti Elissavet-Kalliopi , Papanikolaou Eleni , Petridou Evanthia 
Published: November 2019

Abstract
Background
Brucellosis, caused by several Brucella species, such as the bacterium Brucella melitensis, is considered one of the most severe zoonotic diseases worldwide. Not only does it affect ruminant animal populations, leading to a substantial financial burden for stockbreeders, but also poses severe public health issues. For almost four decades in southern Europe and elsewhere, eradication of the disease has been based on ambiguously effective programs, rendering massive sanitation of livestock urgent and indispensable. Gene therapy, which has been proved effective in the clinic, could possibly constitute an alternative option towards a permanent cure for brucellosis, by aiding in the deletion or inactivation of genes associated with the replication of Brucella within the host cells.

Results
We infected ovine macrophages with B.melitensis, to simulate the host cell/microorganism interaction in vitro, and transduced the infected cells with CRISPR/Cas9 lentiviral vectors that target Brucella’s RNA polymerase subunit A (RpolA) or virulence-associated gene virB10 at a multiplicity of infection of 60. We demonstrate a significant decrease in the bacterial load per cell when infected cells are transduced with the RpolA vector and that the number of internalized brucellae per cell remains unaffected when macrophages are transduced with a conventional lentiviral vector expressing the green fluorescence protein, thus underlining the bactericidal effect of our CRISPR/Cas9 system.

Conclusions
Pending in vivo verification of our findings, overall, these results may prove critical not only for the treatment of human brucellosis, but for other infectious diseases in general.
The expression of cytokines in the milk somatic cells, blood leukocytes and serum of goats infected with small ruminant lentivirus
Authors: Jarczak Justyna , Słoniewska Danuta , Kaba Jarosław , Bagnicka Emilia 
Published: November 2019

Abstract
Background
The present study aimed to determine the expression of cytokines, which is associated with the immunological response of dairy goats against small ruminant lentivirus (SRLV). The study was conducted on 26 dairy goats in their second to sixth lactation, which were divided by breed and parity into two groups: SRLV naturally infected (N = 13) and non-infected (N = 13) animals. All goats in the study were asymptomatic. The milk and blood samples, which served as studied material were taken on days 7, 30, 120 and 240 of the lactation. The gene and protein expression of several cytokines was studied using Real-Time PCR and ELISA methods.

Results
INF-β and INF-γ expression was down-regulated in the milk somatic cells (MSC) of SRLV-infected goats. However, an increased concentration of INF-β was observed in the MSC in SRLV-infected goats, while INF-γ expression was not observed in both SRLV-infected and non-infected animals The SRLV-infected goats also displayed decreased expression of IL-1α, IL-1β, IL-6 and INF-γ genes in the blood leukocytes,with IL-1α, IL-1β and IL-6 protein levels also being decreased in the sera. TNF-α was the only gene that demonstrated increased expression in both the MSC and the blood of infected animals; however, no such overexpression was observed at the protein level.

Conclusions
SRLV probably influences the immune system of infected animals by deregulating of the expression of cytokines. Further, epigenetic studies may clarify the mechanisms by which SRLV regulates the gene and protein expression of the host.
Prognostic significance of platelet-to-lymphocyte ratio in urothelial carcinoma patients: a meta-analysis
Authors: Bao Yuhai , Wang Yin , Li Xiaodong , Pan Mingjun , Zhang Hongze , Cheng Zegen , Wang Xueyi 
Published: November 2019

Abstract
Background
The prognostic value of pre-treatment platelet-to-lymphocyte ratio (PLR) in patients with urothelial carcinoma (UC) remains controversial. Therefore, this meta-analysis aimed to identify the prognostic impact of PLR on UC.

Methods
The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to summarize the correlations between PLR and overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and cancer-specific survival (CSS). Odds ratios (ORs) with 95% CIs were used to measure the association between PLR and tumor clinicopathological factors.

Results
The meta-analysis included 15 studies published from 2015 to 2019 with a total of 5354 patients. Overall, a high PLR was correlated to poorer PFS (HR = 1.81, 95% CI 1.28–2.56, p = 0.001) and DFS (HR = 1.09, 95% CI 1.31–2.16, p < 0.001) but not poor OS (HR = 1.23, 95% CI 0.95–1.59, p = 0.124) or CSS (HR = 1.000, 95% CI 0.998–1.002, p = 0.919) in UC. In addition, an elevated PLR was correlated with patient age > 65 years (OR = 1.72, 95% CI 1.25–2.38, p = 0.001) and hypertension (OR = 1.48, 95% CI 1.01–2.18, p = 0.046). However, no significant association was observed between PLR and sex (OR = 0.79, 95% CI 0.56–1.14, p = 0.206) or diabetes (OR = 1.29, 95% CI 0.77–2.15, p = 0.333).

Conclusions
Our results demonstrated a significant correlation between elevated PLR and poor prognosis in UC. The prognostic role of PLR may help guide the management and prognostication of UC patients.
Integrating community health representatives with health care systems: clinical outcomes among individuals with diabetes in Navajo Nation
Authors: Trevisi Letizia , Orav John E. , Atwood Sidney , Brown Christian , Curley Cameron , King Caroline , Muskett Olivia , Sehn Hannah , Nelson Katrina A. , Begay Mae-Gilene , Shin Sonya S. 
Published: November 2019

Abstract
Background
We studied the impact of Community Outreach and Patient Empowerment (COPE) intervention to support Community Health Representatives (CHR) on the clinical outcomes of patients living with diabetes in the Navajo Nation extending into the States of Arizona, Utah, and New Mexico. The COPE intervention integrated CHRs into healthcare teams by providing a structured approach to referrals and home visits.

Methods
We abstracted routine clinical data from the Indian Health Service’s information system on individuals with diabetes mellitus seen at participating clinical sites from 2010 to 2014. We matched 173 COPE participants to 2880 patients with similar demographic and clinical characteristics who had not participated in COPE. We compared the changes in clinical outcomes between the two groups using linear mixed models.

Results
Over the four years of the study, COPE patients had greater improvements in glycosylated hemoglobin (− 0.56%) than non-COPE participants (+ 0.07%) for a difference in differences of 0.63% (95% confidence interval (CI): 0.50, 0.76). Low-density lipoprotein fell more steeply in the COPE group (− 10.58 mg/dl) compared to the non-COPE group (− 3.18 mg/dl) for a difference in differences of 7.40 mg/dl (95%CI: 2.00, 12.80). Systolic blood pressure increased slightly more among COPE (2.06 mmHg) than non-COPE patients (0.61 mmHg). We noted no significant change for body mass index in either group.

Conclusion
Structured outreach by Community Health Representatives as part of an integrated care team was associated with improved glycemic and lipid levels in the target Navajo population.

Trial registration
Trial registration: NCT03326206. Registered 31 October 2017 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT03326206.
Snus: a compelling harm reduction alternative to cigarettes
Authors: Clarke Elizabeth , Thompson Keith , Weaver Sarah , Thompson Joseph , O’Connell Grant 
Published: November 2019

AbstractSnus is an oral smokeless tobacco product which is usually placed behind the upper lip, either in a loose form or in portioned sachets, and is primarily used in Sweden and Norway. The purpose of this review is to examine the reported effects of snus use in relation to specified health effects, namely lung cancer, cardiovascular disease, pancreatic cancer, diabetes, oral cancer and non-neoplastic oral disease. The review also examines the harm reduction potential of snus as an alternative to cigarettes by comparing the prevalence of snus use and cigarette smoking, and the reported incidence of tobacco-related diseases across European Union countries. The scientific literature generally indicates that the use of snus is not a significant risk factor for developing lung cancer, cardiovascular disease, pancreatic cancer or oral cancer. Studies investigating snus use and diabetes have reported that high consumption of snus (estimated as being four or more cans per week) may be associated with a higher risk of developing diabetes or components of metabolic syndrome; however, overall results are not conclusive. Snus use is associated with the presence of non-neoplastic oral mucosal lesions which are reported to heal rapidly once use has stopped. The most recent Eurobarometer data from 2017 reported that Sweden had the lowest prevalence of daily cigarette use in the European Union at 5% whilst daily “oral tobacco” use was reported to be 20%. European data published by the World Health Organisation in 2018 indicated that Sweden had the lowest rate of tobacco-related mortality and the lowest incidence of male lung cancer. Overall, prevalence statistics and epidemiological data indicate that the use of snus confers a significant harm reduction benefit which is reflected in the comparatively low levels of tobacco-related disease in Sweden when compared with the rest of Europe. The available scientific data, including long-term population studies conducted by independent bodies, demonstrates that the health risks associated with snus are considerably lower than those associated with cigarette smoking.
CircRNA expression profile and functional analysis in testicular tissue of patients with non-obstructive azoospermia
Authors: Ge Pan , Zhang Jian , Zhou Liang , Lv Mo-qi , Li Yi-xin , Wang Jin , Zhou Dang-xia 
Published: November 2019

Abstract
Background
Non-obstructive azoospermia (NOA) is a multifactorial disorder whose molecular basis remains largely unknown. Circular RNAs (CircRNAs), a novel class of endogenous RNAs, have been recognized to play important roles in many biological processes. However, little is known about the expression patterns and functions of circRNAs in human testes involved in NOA.

Methods
In this study, the testicular circRNA expression profile were explored in NOA patients and the controls by high-throughput circRNA microarray. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm the microarray data. Bioinformatics analyses including the circRNA/miRNA/mRNA interaction network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict the functions of differentially expressed circRNAs.

Results
A total of 368 differentially down-regulated and 526 up-regulated circRNAs were detected in NOA patients. These findings have been verified by qRT-PCR on 6 selected circRNAs. Among these differentially expressed circRNAs, the hsa_circRNA_0023313 was obviously up-regulated in testicular tissue of NOA patients. The most likely potential target miRNA for hsa_circRNA_0023313 include hsa-miR-520d-3p, hsa-miR-373-3p, hsa-miR-372-3p, hsa-miR-302c-3p and hsa-miR-130b-5p. Function analysis indicated that hsa_circRNA_0023313 was ubiquitin-protein transferase activity and chromatin binding. KEGG analysis revealed that the top five pathways related to hsa_circRNA_0023313 were endocytosis, meiosis, FoxO signaling pathway, ubiquitin mediated proteolysis and AMPK signaling pathway.

Conclusions
This is the first report that the testicular circRNA expression profile is altered in NOA patients indicating circRNAs might play important roles in regulating spermatogenesis and be potential biomarkers for the diagnosis and treatment of NOA.
Out of sync: a Shared Mental Models perspective on policy implementation in healthcare
Authors: Evans Jenna M. , Palmer Karen S. , Brown Adalsteinn D. , Marani Husayn , Russell Kirstie K. , Martin Danielle , Ivers Noah M. 
Published: November 2019

AbstractThe impact of policy ambiguity on implementation is a perennial concern in policy circles. The degree of ambiguity of policy goals and the means to achieve them influences the likelihood that a policy will be uniformly understood and implemented across implementation sites. We argue that the application of institutional and organisational theories to policy implementation must be supplemented by a socio-cognitive lens in which stakeholders’ interpretations of policy are investigated and compared. We borrow the concept of ‘Shared Mental Models’ from the literature on industrial psychology to examine the microprocesses of policy implementation. Drawing from interviews with 45 key informants involved in the implementation of a hospital funding reform, known as Quality-Based Procedures in Ontario, Canada, we identify divergent mental models and explain how these divergences may have affected implementation and change management. We close with considerations for future research and practice.
The relationship between the different low birth weight strata of newborns with infant mortality and the influence of the main health determinants in the extreme south of Brazil
Authors: Vilanova Cássia Simeão , Hirakata Vânia Naomi , de Souza Buriol Viviane Costa , Nunes Marina , Goldani Marcelo Zubaran , da Silva Clécio Homrich 
Published: November 2019

AbstractBackgroundLow birth weight (LBW) newborns present different health outcomes when classified in different birth weight strata. This study evaluated the relationship of birth weight with Infant mortality (IM) through the influence of biological, social, and health care factors in a time series.MethodsRetrospective cohort study with data collected from Information Systems (Live Births and Mortality). The mortality trends were performed for each birth weight stratum: extremely low, < 1000 g; very low, 1000–1499 g; low, 1500–2499 g; insufficient, 2500–2999 g; adequate, 3000–3900 g; and macrosomia, > 4000 g. Chi-square tests analyzed IM rates. Sequential Poisson regression analyzed the impact of the determinant factors.ResultsA total of 277,982 newborns were included in the study and 2088 died before their first year. There was a tendency for a decrease in mortality in all strata of weight. With the exception of macrosomics, all other strata had a higher risk for IM when compared with adequate birth weight. Extremely LBW newborns presented higher risk for mortality when born in a public hospital. A higher percentage of infant deaths were associated with lower maternal age and lower schooling for all strata. Prenatal care with less than three visits demonstrated a risk for IM in low, insufficient, and adequate birth weight strata. The cesarean section was a protective factor for IM in Extremely and Very LBW strata and it was a risk factor in adequate birth weight stratum.ConclusionsLBW had a greater association with IM, especially those children of younger mothers and those born in public hospitals.
Eating behaviors and weight loss outcomes in a 12-month randomized trial of diet and/or exercise intervention in postmenopausal women
Authors: Mason Caitlin , de Dieu Tapsoba Jean , Duggan Catherine , Wang Ching-Yun , Alfano Catherine M. , McTiernan Anne 
Published: November 2019

Abstract
Background
Certain eating behaviors are common among women with obesity. Whether these behaviors influence outcomes in weight loss programs, and whether such programs affect eating behaviors, is unclear.

Methods
Our aim was to examine the effect of baseline eating behaviors on intervention adherence and weight among postmenopausal women with overweight or obesity, and to assess intervention effects on eating behaviors.
Four hundred and 39 women (BMI ≥25 kg/m2) were randomized to 12 months of: i) dietary weight loss with a 10% weight loss goal (‘diet’; n = 118); ii) moderate-to-vigorous intensity aerobic exercise for 225 mins/week (‘exercise’; n = 117); iii) combined dietary weight loss and exercise (‘diet + exercise’; n = 117); or iv) no-lifestyle change control (n = 87). At baseline and 12 months, restrained eating, uncontrolled eating, emotional eating and binge eating were measured by questionnaire; weight and body composition were assessed. The mean change in eating behavior scores and weight between baseline and 12 months in the diet, exercise, and diet + exercise arms were each compared to controls using the generalized estimating equation (GEE) modification of linear regression adjusted for age, baseline BMI, and race/ethnicity.

Results
Baseline restrained eating was positively associated with change in total calories and calories from fat during the dietary intervention but not with other measures of adherence. Higher baseline restrained eating was associated with greater 12-month reductions in weight, waist circumference, body fat and lean mass. Women randomized to dietary intervention had significant reductions in binge eating (− 23.7%, p = 0.005 vs. control), uncontrolled eating (− 24.3%, p < 0.001 vs. control), and emotional eating (− 31.7%, p < 0.001 vs. control) scores, and a significant increase in restrained eating (+ 60.6%, p < 0.001 vs. control); women randomized to diet + exercise reported less uncontrolled eating (− 26.0%, p < 0.001 vs. control) and emotional eating (− 22.0%, p = 0.004 vs. control), and increased restrained eating (+ 41.4%, p < 0.001 vs. control). Women randomized to exercise alone had no significant change in eating behavior scores compared to controls.

Conclusions
A dietary weight loss intervention helped women modify eating behaviors. Future research should investigate optimal behavioral weight loss interventions for women with both disordered eating and obesity.

Trial registration
NCT00470119 (https://clinicaltrials.gov). Retrospectively registered May 7, 2007.
Deltaretroviruses have circulated since at least the Paleogene and infected a broad range of mammalian species
Authors: Hron Tomáš , Elleder Daniel , Gifford Robert J. 
Published: November 2019

AbstractThe Deltaretrovirus genus of retroviruses (family Retroviridae) includes the human T cell leukemia viruses and bovine leukemia virus (BLV). Relatively little is known about the biology and evolution of these viruses, because only a few species have been identified and the genomic ‘fossil record’ is relatively sparse. Here, we report the discovery of multiple novel endogenous retroviruses (ERVs) derived from ancestral deltaretroviruses. These sequences—two of which contain complete or near complete internal coding regions—reside in genomes of several distinct mammalian orders, including bats, carnivores, cetaceans, and insectivores. We demonstrate that two of these ERVs contain unambiguous homologs of the tax gene, indicating that complex gene regulation has ancient origins within the Deltaretrovirus genus. ERVs demonstrate that the host range of the deltaretrovirus genus is much more extensive than suggested by the relatively small number of exogenous deltaretroviruses described so far, and allow the evolutionary timeline of deltaretrovirus-mammal interaction to be more accurately calibrated.
Quality of websites about long-acting reversible contraception: a descriptive cross-sectional study
Authors: Eriksson Catrin , Skinstad Matilda , Georgsson Susanne , Carlsson Tommy 
Published: November 2019

AbstractBackgroundToday, there are various short- and long-acting contraceptive alternatives available for those who wish to prevent unintended pregnancy. Long-acting reversible contraception are considered effective methods with a high user satisfaction. High-quality information about contraception is essential in order to empower individuals to reach informed decisions based on sufficient knowledge. Use of the Web for information about contraception is widespread, and there is a risk that those who use it for this purpose could come in contact with sources of low quality.ObjectiveThe overarching aim was to investigate the quality of websites about long-acting reversible contraception.MethodsSwedish client-oriented websites were identified through searches in Google (n = 46 included websites). Reliability and information about long-acting reversible contraceptive choices were assessed by two assessors with the DISCERN instrument, transparency was analyzed with the Journal of the American Medical Association benchmarks, completeness was assessed with inductive content analysis and readability was analyzed with Readability Index.ResultsThe mean DISCERN was 44.1/80 (SD 7.7) for total score, 19.7/40 (SD 3.7) for reliability, 22.1/35 (SD 4.1) for information about long-acting reversible contraceptive choices, and 2.3/5 (SD 1.1) for overall quality. A majority of the included websites had low quality with regard to what sources were used to compile the information (n = 41/46, 89%), when the information was produced (n = 40/46, 87%), and if it provided additional sources of support and information (n = 30/46, 65%). Less than half of the websites adhered to any of the JAMA benchmarks. We identified 23 categories of comprehensiveness. The most frequent wascontraceptive mechanism(n = 39/46, 85%) and the least frequent waswhen contraception may be initiated following an abortion(n = 3/46, 7%). The mean Readability Index was 42.5 (SD 6.3, Range 29–55) indicating moderate to difficult readability levels, corresponding to a grade level of 9.ConclusionsThe quality of client-oriented websites about long-acting reversible contraception is poor. There is an undeniable need to support and guide laypersons that intend to use web-based sources about contraceptive alternatives, so that they may reach informed decisions based on sufficient knowledge.