bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel DNA Binding and Regulatory Activities for σ
54
(RpoN) in Salmonella enterica Serovar Typhimurium 14028s
Authors: Bono Ashley C. , Hartman Christine E. , Solaimanpour Sina , Tong Hao , Porwollik Steffen , McClelland Michael , Frye Jonathan G. , Mrázek Jan , Karls Anna C. 
Published: April 2017

ABSTRACT

The variable sigma (σ) subunit of the bacterial RNA polymerase (RNAP) holoenzyme, which is responsible for promoter specificity and open complex formation, plays a strategic role in the response to environmental changes.
Salmonella enterica
serovar Typhimurium utilizes the housekeeping σ
70
and five alternative sigma factors, including σ
54
. The σ
54
-RNAP differs from other σ-RNAP holoenzymes in that it forms a stable closed complex with the promoter and requires ATP hydrolysis by an activated cognate bacterial enhancer binding protein (bEBP) to transition to an open complex and initiate transcription. In
S.
Typhimurium, σ
54
-dependent promoters normally respond to one of 13 different bEBPs, each of which is activated under a specific growth condition. Here, we utilized a constitutively active, promiscuous bEBP to perform a genome-wide identification of σ
54
-RNAP DNA binding sites and the transcriptome of the σ
54
regulon of
S.
Typhimurium. The position and context of many of the identified σ
54
RNAP DNA binding sites suggest regulatory roles for σ
54
-RNAP that connect the σ
54
regulon to regulons of other σ factors to provide a dynamic response to rapidly changing environmental conditions.

IMPORTANCE
The alternative sigma factor σ
54
(RpoN) is required for expression of genes involved in processes with significance in agriculture, bioenergy production, bioremediation, and host-microbe interactions. The characterization of the σ
54
regulon of the versatile pathogen
S.
Typhimurium has expanded our understanding of the scope of the σ
54
regulon and how it links to other σ regulons within the complex regulatory network for gene expression in bacteria.
Electronic nicotine delivery system (ENDS) use during smoking cessation: a qualitative study of 40 Oklahoma quitline callers
Authors: Vickerman Katrina A , Beebe Laura A , Schauer Gillian L , Magnusson Brooke , King Brian A 
Published: April 2017

ObjectivesApproximately 10% (40 000) of US quitline enrollees who smoke cigarettes report current use of electronic nicotine delivery systems (ENDS); however, little is known about callers' ENDS use. Our aim was to describe why and how quitline callers use ENDS, their beliefs about ENDS and the impact of ENDS use on callers' quit processes and use of FDA-approved cessation medications.DesignQualitative interviews conducted 1-month postregistration. Interviews were recorded, transcribed, double-coded and analysed to identify themes.SettingOklahoma Tobacco Helpline.Participants40 callers aged ≥18 who were seeking help to quit smoking were using ENDS at registration and completed ≥1 programme calls.ResultsAt 1-month postregistration interview, 80% of callers had smoked cigarettes in the last 7 days, almost two-thirds were using ENDS, and half were using cessation medications. Nearly all believed ENDS helped them quit or cut down on smoking; however, participants were split on whether they would recommend cessation medications, ENDS or both together for quitting. Confusion and misinformation about potential harms of ENDS and cessation medications were reported. Participants reported using ENDS in potentially adaptive ways (eg, using ENDS to cut down and nicotine replacement therapy to quit, and stepping down nicotine in ENDS to wean off ENDS after quitting) and maladaptive ways (eg, frequent automatic ENDS use, using ENDS in situations they did not previously smoke, cutting down on smoking using ENDS without a schedule or plan to quit), which could impact the likelihood of quitting smoking or continuing ENDS use.ConclusionsThese qualitative findings suggest quitline callers who use ENDS experience confusion and misinformation about ENDS and FDA-approved cessation medications. Callers also use ENDS in ways that may not facilitate quitting smoking. Opportunities exist for quitlines to educate ENDS users and help them create a coordinated plan most likely to result in completely quitting combustible tobacco.
Cardiovascular risk factors—using repeated cross-sectional surveys to assess time trends in socioeconomic inequalities in neighbouring countries
Authors: Hughes John , Kabir Zubair , Kee Frank , Bennett Kathleen 
Published: April 2017

ObjectivesThis study compares trends in socioeconomic inequalities related to key cardiovascular risk factors in neighbouring countries Northern Ireland (NI) and the Republic of Ireland (RoI).DesignRepeated cross-sectional studies.SettingPopulation based.Participants3500–4000 in national surveys in NI and 5000–9000 in RoI, aged 20–69 years.MeasuresEducational attainment was used as a socioeconomic indicator by which the magnitude and direction of trends in inequalities for smoking, diabetes, obesity and physical inactivity in NI and RoI were examined between 1997/1998 and 2007/2011. Gender-specific relative and absolute inequalities were calculated using the Relative Index of Inequality (RII) and Slope Index of Inequality (SII) for both countries.ResultsIn both countries, the prevalence of diabetes and obesity increased whereas levels of smoking and physical inactivity decreased over time. In NI relative inequalities increased for obesity (RII 1.1 in males and 2.1 in females in 2010/2011) and smoking (RII 4.5 in males and 4.2 in females in 2010/2011) for both genders and absolute inequalities increased for all risk factors in men and increased for diabetes and obesity in women. In RoI greater inequality was observed in women, particularly for smoking (RII 2.8 in 2007) and obesity (RII 8.2 in 2002) and in men for diabetes (RII 3.2 in 2002).ConclusionsInterventions to reduce inequalities in risk factors, particularly smoking, obesity and diabetes are encouraged across both countries.
Link between healthy lifestyle and psychological well-being in Lithuanian adults aged 45–72: a cross-sectional study
Authors: Sapranaviciute-Zabazlajeva Laura , Luksiene Dalia , Virviciute Dalia , Bobak Martin , Tamosiunas Abdonas 
Published: April 2017

ObjectiveThis study uses a cross-sectional study design to analyse the connection between psychological well-being (PWB) and components of a healthy lifestyle in the Lithuanian population aged 45–72. The purpose of our study is to establish the links between PWB and lifestyle factors such as physical activity, smoking, alcohol consumption and dietary patterns in people above the age of 44.ParticipantsA stratified sample of 10 940 urban citizens aged 45–72 years were randomly selected from the National Population Register. The response rate was 65%.MethodsPWB was evaluated by using a Control Autonomy Self-realization and Pleasure (CASP-12) questionnaire. The standard questionnaire included questions regarding the respondent's sociodemographic, socioeconomic and social status. The lifestyle questionnaire evaluated behavioural factors as smoking status, alcohol consumption, nutrition habits and physical activity. Objective measurements of cardiovascular disease (CVD) risk factors were taken.ResultsAdjusted for sociodemographic, socioeconomic, social and biological CVD risk factors, the probability of higher PWB increased for physically active men and women and male former smokers. Higher PWB was directly associated with consumption of fresh vegetables and fruits. Responders who consumed potatoes, meat, boiled vegetables and eggs less frequently than average were more likely to have higher PWB. A direct association was ascertained between PWB and consumption of chicken and fish, as well as an inverse association between PWB and consumption of sweets in women.ConclusionsHealthy lifestyle education efforts should focus on increasing physical activity, controlling smoking and improving diversity in healthy food consumption including the consumption of fresh vegetables and fruits, particularly among older adults with lower PWB.
Prognostic value of stromal tumour infiltrating lymphocytes and programmed cell death-ligand 1 expression in breast cancer
Authors: Polónia António , Pinto Regina , Cameselle-Teijeiro Jorge F , Schmitt Fernando C , Paredes Joana 
Published: April 2017

AimThe present work aims to evaluate the presence of stromal tumour-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PDL1) expression in breast carcinomas and their correlation with available clinicopathological features.MethodsTwo independent series of invasive breast cancer (IBC), one including ductal carcinoma in situ (DCIS) pair-matched cases, were selected, and quantification of TILs was accomplished in each case. Immunohistochemistry was also performed to evaluate the expression of PDL1.ResultsIn both cohorts evaluated, increased stromal TILs and PDL1 expression were present in about 10% of IBCs, being significantly associated with each other and both with grade 3 and triple-negative subtype. We observed a similar distribution of stromal TILs and PDL1 expression between DCIS and IBC. Finally, we observed that increased stromal TILs and PDL1 expression were significantly associated with cancer stem cell (CSC) markers, basal cell markers and vimentin expression. Interestingly, in IBC cases with vimentin expression, increased stromal TILs, as well as decreased PDL1 expression, disclosed a better clinical outcome, independently of the main classical BC prognostic factors.ConclusionsWe have confirmed the association of stromal TILs and PDL1 expression with aggressive forms of BC and that both are already found in in situ stages. We also showed that stromal TILs and PDL1 expression are associated with clinical outcome in cases enriched for a mesenchymal immunophenotype. We describe for the first time a close relationship between CSC markers and PDL1 expression.
High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial
Authors: Massard Christophe , Michiels Stefan , Ferté Charles , Le Deley Marie-Cécile , Lacroix Ludovic , Hollebecque Antoine , Verlingue Loic , Ileana Ecaterina , Rosellini Silvia , Ammari Samy , Ngo-Camus Maud , Bahleda Rastislav , Gazzah Anas , Varga Andrea , Postel-Vinay Sophie , Loriot Yohann , Even Caroline , Breuskin Ingrid , Auger Nathalie , Job Bastien , De Baere Thierry , Deschamps Frederic , Vielh Philippe , Scoazec Jean-Yves , Lazar Vladimir , Richon Catherine , Ribrag Vincent , Deutsch Eric , Angevin Eric , Vassal Gilles , Eggermont Alexander , André Fabrice , Soria Jean-Charles 
Published: April 2017

Abstract
High-throughput genomic analyses may improve outcomes in patients with advanced cancers. MOSCATO 01 is a prospective clinical trial evaluating the clinical benefit of this approach. Nucleic acids were extracted from fresh-frozen tumor biopsies and analyzed by array comparative genomic hybridization, next-generation sequencing, and RNA sequencing. The primary objective was to evaluate clinical benefit as measured by the percentage of patients presenting progression-free survival (PFS) on matched therapy (PFS2) 1.3-fold longer than the PFS on prior therapy (PFS1). A total of 1,035 adult patients were included, and a biopsy was performed in 948. An actionable molecular alteration was identified in 411 of 843 patients with a molecular portrait. A total of 199 patients were treated with a targeted therapy matched to a genomic alteration. The PFS2/PFS1 ratio was &gt;1.3 in 33% of the patients (63/193). Objective responses were observed in 22 of 194 patients (11%; 95% CI, 7%–17%), and median overall survival was 11.9 months (95% CI, 9.5–14.3 months).
Significance: This study suggests that high-throughput genomics could improve outcomes in a subset of patients with hard-to-treat cancers. Although these results are encouraging, only 7% of the successfully screened patients benefited from this approach. Randomized trials are needed to validate this hypothesis and to quantify the magnitude of benefit. Expanding drug access could increase the percentage of patients who benefit. Cancer Discov; 7(6); 586–95. ©2017 AACR.
See related commentary by Schram and Hyman, p. 552.
This article is highlighted in the In This Issue feature, p. 539
Extinction risk or lack of sampling in a threatened species: Genetic structure and environmental suitability of the neotropical frog Pristimantis penelopus (Anura: Craugastoridae)
Authors: Restrepo Adriana , Velasco Julian A. , Daza Juan M. 
Published: April 2017

IUCN Red Lists have been a valuable tool to prioritize conservation plans in endemic neotropical frogs. However, many areas in this region are poorly known in terms of their diversity and endemism. Based on examined museum specimens of the threatened species Pristimantis penelopus we revised its geographic distribution and determined the habitat suitability using niche modeling techniques. Using a mitochondrial fragment of COI gene, we determine the phylogenetic position and the extent of the genetic variation across its distribution in Colombia. We present the first records of P. penelopus for the Cordillera Oriental, the western versant of Cordillera Occidental and the northern portion of the Cauca river basin. Based on the molecular phylogenetic analysis, Pristimantis penelopus belongs to the P. ridens series sensu Padial et al. (2014). The mean of intraspecific genetic variation is 2.1% and the variation among population ranges between 2.3 and 3.5%. The genetic distance between the western populations and the Magdalena Valley populations suggests a potential phylogeographic break in northwestern Antioquia. We expand the realized distribution by 258 kilometers north, 200 km east and 223 km northwest. Based on our results and according to the IUCN criteria we propose a new category for the species and highlight the need to increase the surveys in poorly known regions to better understand the geographic distribution and conservation status of listed species.
Trap-nesting bees and wasps (Hymenoptera, Aculeata) in a Semidecidual Seasonal Forest fragment, southern Brazil
Authors: Oliveira Priscila Soares , Gonçalves Rodrigo Barbosa 
Published: April 2017

Trap-nesting bee and wasp inventories are common in Brazil but many phytophysiognomies are still poorly studied. The main objective of this study is to survey trap-nesting bees and wasps in a Semidecidual Seasonal Forest fragment. Also, we test the differences on nesting between interior and edge transects. A sum of 1,500 trap nests was made with bamboo cane internodes and two consecutive years were monitored. In the first year 46 nests were occupied by Pachodynerus grandis (19 nests), Pachodynerus guadulpensis (19), Centris analis (two), and Centris tarsata, Megachile fiebrigi, Megachile guaranitica, Megachile susurrans, Trypoxylon sp and Zethus smithii with one nest each. No statistical differences were found between interior and edge transects for richness and occupation rate, but the species composition was different. In the second year 39 nests were occupied by four species, three previously recorded, C. analis (seven nests), P. guadulpensis and P. grandis (six nests each), plus Monobia angulosa with 15 nests. Parasitoids from four families and one cleptoparasite were recorded and the mortality rate was higher in bees than in wasps. These findings reinforce the notion that trap nests assemblages from different studies are not directly comparable for richness and composition.
Personalizing the Intensity of Blood Pressure Control
Authors: Patel Krishna K. , Arnold Suzanne V. , Chan Paul S. , Tang Yuanyuan , Pokharel Yashashwi , Jones Philip G. , Spertus John A. 
Published: April 2017

Background—
In SPRINT (Systolic Blood Pressure Intervention Trial), patients with hypertension and high cardiovascular risk treated with intensive blood pressure (BP) control (<120 mm Hg) had fewer major adverse cardiovascular events (MACE) and deaths but higher rates of treatment-related serious adverse events (SAE) than patients randomized to standard BP control (<140 mm Hg). However, the degree of benefit or harm for an individual patient could vary because of heterogeneity in treatment effect.

Methods and Results—
Using patient-level data from 9361 randomized patients in SPRINT, we developed models to predict risk for MACE or death and treatment-related SAE to allow for individualized BP treatment goals based on each patient’s projected risk and benefit of intensive versus standard BP control. Models were internally validated using bootstrap resampling and externally validated on 4741 patients from the ACCORD-BP (The Action to Control Cardiovascular Risk in Diabetes blood pressure) trial. Among 9361 SPRINT patients, 755 patients (8.1%) had a MACE or death event and 338 patients (3.6%) had a treatment-related SAE during a median follow-up of 3.3 years. The MACE/death and the SAE model had C statistics of 0.72 and 0.70, respectively, in the derivation cohort and 0.69 and 0.65 in ACCORD. The MACE/death model had 10 variables including treatment interactions with age, baseline systolic BP, and diastolic BP, and the SAE model had 8 variables including treatment interaction with number of BP medications. Intensive BP treatment was associated with a mean 2.2±2.6% lower risk of MACE/death compared with standard treatment (range, 20.7% lower risk to 19.6% greater risk among individual patients) and a mean 2.2±1.2% higher risk for SAEs (range, 0.5%–15.8% more harm in individual patients).

Conclusions—
To translate the findings from SPRINT to clinical practice, we developed prediction models to tailor the intensity of BP control based on the projected risk and benefit for each unique patient. This approach should be prospectively tested to better engage patients in shared medical decision making and to improve outcomes.

Clinical Trial Registration—

URL:
https://clinicaltrials.gov
. Unique identifier: NCT01206062.
Statin Treatment and Clinical Outcomes of Heart Failure Among Africans: An Inverse Probability Treatment Weighted Analysis
Authors: Bonsu Kwadwo Osei , Owusu Isaac Kofi , Buabeng Kwame Ohene , Reidpath Daniel D. , Kadirvelu Amudha 
Published: April 2017

Background

Randomized control trials of statins have not demonstrated significant benefits in outcomes of heart failure (
HF
). However, randomized control trials may not always be generalizable. The aim was to determine whether statin and statin type–lipophilic or –hydrophilic improve long‐term outcomes in Africans with
HF
.

Methods and Results

This was a retrospective longitudinal study of
HF
patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for
HF
(index admission) and followed up to time of all‐cause, cardiovascular, and
HF
mortality or end of study. Multivariable time‐dependent Cox model and inverse‐probability‐of‐treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person‐years of observation. Using the time‐dependent Cox model, the 5‐year adjusted hazard ratios with 95%
CI
for statin treatment on all‐cause, cardiovascular, and
HF
mortality were 0.68 (0.55–0.83), 0.67 (0.54–0.82), and 0.63 (0.51–0.79), respectively. Use of inverse‐probability‐of‐treatment weighting resulted in estimates of 0.79 (0.65–0.96), 0.77 (0.63–0.96), and 0.77 (0.61–0.95) for statin treatment on all‐cause, cardiovascular, and
HF
mortality, respectively, compared with no statin use.

Conclusions

Among Africans with
HF
, statin treatment was associated with significant reduction in mortality.
Bilirubin Prevents Atherosclerotic Lesion Formation in Low‐Density Lipoprotein Receptor‐Deficient Mice by Inhibiting Endothelial VCAM‐1 and ICAM‐1 Signaling
Authors: Vogel Megan E. , Idelman Gila , Konaniah Eddy S. , Zucker Stephen D. 
Published: April 2017

Background

Numerous epidemiological studies support an inverse association between serum bilirubin levels and the incidence of cardiovascular disease; however, the mechanism(s) by which bilirubin may protect against atherosclerosis is undefined. The goals of the present investigations were to assess the ability of bilirubin to prevent atherosclerotic plaque formation in low‐density lipoprotein receptor‐deficient (
Ldlr

−/−

) mice and elucidate the molecular processes underlying this effect.

Methods and Results

Bilirubin, at physiological concentrations (≤20 μmol/L), dose‐dependently inhibits
THP
‐1 monocyte migration across tumor necrosis factor α–activated human umbilical vein endothelial cell monolayers without altering leukocyte binding or cytokine production. A potent antioxidant, bilirubin effectively blocks the generation of cellular reactive oxygen species induced by the cross‐linking of endothelial vascular cell adhesion molecule 1 (
VCAM
‐1) or intercellular adhesion molecule 1 (
ICAM
‐1). These findings were validated by treating cells with blocking antibodies or with specific inhibitors of
VCAM
‐1 and
ICAM
‐1 signaling. When administered to
Ldlr

−/−

mice on a Western diet, bilirubin (30 mg/kg intraperitoneally) prevents atherosclerotic plaque formation, but does not alter circulating cholesterol or chemokine levels. Aortic roots from bilirubin‐treated animals exhibit reduced lipid and collagen deposition, decreased infiltration of monocytes and lymphocytes, fewer smooth muscle cells, and diminished levels of chlorotyrosine and nitrotyrosine, without changes in
VCAM
‐1 or
ICAM
‐1 expression.

Conclusions

Bilirubin suppresses atherosclerotic plaque formation in
Ldlr

−/−

mice by disrupting endothelial
VCAM
‐1‐ and
ICAM
‐1‐mediated leukocyte migration through the scavenging of reactive oxygen species signaling intermediaries. These findings suggest a potential mechanism for the apparent cardioprotective effects of bilirubin.
Prognostic Significance of Interleukin‐34 (IL‐34) in Patients With Chronic Heart Failure With or Without Renal Insufficiency
Authors: Tao Rong , Fan Qin , Zhang Hang , Xie Hongyang , Lu Lin , Gu Gang , Wang Fang , Xi Rui , Hu Jian , Chen Qiujing , Niu Wenquan , Shen Weifeng , Zhang Ruiyan , Yan Xiaoxiang 
Published: April 2017

Background

Renal dysfunction, commonly associated with cardiac dysfunction, has predictive value for adverse long‐term outcomes in heart failure (
HF
). We previously identified a novel renal biomarker, interleukin‐34 (
IL
‐34), elevated in
HF
patients and associated with kidney dysfunction and coronary artery disease during
HF
. However, the prognostic value of
IL
‐34 in
HF
remains unclear, so that the present study aimed to determine it.

Methods and Results

This prospective, observational study included 510 consecutive
HF
patients with their serum
IL
‐34 as well as other variables measured at baseline, and they were followed up for 2 years. The primary end point was a composite of cardiovascular death or a first
HF
hospitalization, with cardiovascular death,
HF
hospitalization, and all‐cause mortality as secondary outcomes. There was a significant and gradual increase in risk as
IL
‐34 increased, determined by log‐rank tests with Kaplan–Meier curves. Serum
IL
‐34 was also a significant prognostic predictor of the primary end point (1.301 [1.115–1.518];
P
=0.001), cardiovascular death (1.347 [1.096–1.655];
P
=0.005),
HF
hospitalization (1.234 [1.018–1.494];
P
=0.032), and all‐cause mortality (1.343 [1.115–1.618];
P
=0.002) in
HF
as per
SD
increase in the log
IL
‐34 level after adjusting for age, sex, traditional risk factors, and N‐terminal pro‐brain natriuretic peptide. Especially,
IL
‐34 had a more‐significant prognostic value in
HF
patients with kidney impairment than those without.

Conclusions

IL
‐34 is a significant predictor of cardiovascular death,
HF
hospitalization, and all‐cause mortality in chronic
HF
, especially when concomitant with renal dysfunction. Serum
IL
‐34 measurement may provide new insights linking kidney impairment to poor
HF
outcomes beyond other renal markers.