bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mucoactive agents for chronic, non‐cystic fibrosis lung disease: A systematic review and meta‐analysis
Authors: Tarrant Benjamin J. , Le Maitre Caitlin , Romero Lorena , Steward Ranjana , Button Brenda M. , Thompson Bruce R. , Holland Anne E. 
Published: April 2017

ABSTRACT
Inhaled mucoactive agents are used in respiratory disease to improve mucus properties and enhance secretion clearance. The effect of mannitol, recombinant human deoxyribonuclease/dornase alfa (rhDNase) and hypertonic saline (HS) or normal saline (NS) are not well described in chronic lung conditions other than cystic fibrosis (CF). The aim of this review was to determine the benefit and safety of inhaled mucoactive agents outside of CF. We searched Medline, Embase, CINAHL and CENTRAL for randomized controlled trials investigating the effects of mucoactive agents on lung function, adverse events (AEs), health‐related quality of life (HRQOL), hospitalization, length of stay, exacerbations, sputum clearance and inflammation. There were detrimental effects of rhDNase in bronchiectasis, with average declines of 1.9–4.3% in forced expiratory volume in 1 s (FEV1
) and 3.7–5.4% in forced vital capacity (FVC) (n = 410, two studies), and increased exacerbation risk (relative risk = 1.35, 95% CI = 1.01–1.79 n = 349, one study). Some participants exhibited a reduction in FEV1
(≥10–15%) with mucoactive agents on screening (mannitol = 158 of 1051 participants, rhDNase = 2 of 30, HS = 3 of 80). Most AEs were mild and transient, including bronchospasm, cough and breathlessness. NS eased symptomatic burden in COPD, while NS and HS improved spirometry, HRQOL and sputum burden in non‐CF bronchiectasis. Mannitol improved mucociliary clearance in asthma and bronchiectasis, while the effects of N‐acetylcysteine were unclear. In chronic lung diseases outside CF, there are small benefits of mannitol, NS and HS. Adverse effects of rhDNase suggest this should not be administered in non‐CF bronchiectasis.
Prevalence of obesity hypoventilation syndrome in ambulatory obese patients attending pathology laboratories
Authors: Borel Jean‐Christian , Guerber Fabrice , Jullian‐Desayes Ingrid , Joyeux‐Faure Marie , Arnol Nathalie , Taleux Nellie , Tamisier Renaud , Pépin Jean‐Louis 
Published: April 2017

ABSTRACT
Background and objectiveThe prevalence of obesity hypoventilation syndrome (OHS) in the unselected obese is unknown. Our objectives were: (i) to determine the prevalence of OHS in ambulatory obese patients not previously referred to a pulmonologist for suspicion of sleep breathing disorders and (ii) to assess whether venous bicarbonate concentration [HCO3

−
v] can be used to detect OHS.MethodsIn this prospective multicentric study, we measured [HCO3

−
v] in consenting obese patients attending pathology analysis laboratories. Patients with [HCO3

−
v] ≥ 27 mmol/L were referred to a pulmonologist for comprehensive sleep and respiratory evaluations. Those with [HCO3

−
v] < 27 mmol/L were randomized to either referral to a pulmonologist or ended the study.ResultsFor the 1004 screened patients, the [HCO3

−
v] was ≥27 mmol/L in 24.6% and <27 mmol/L in 45.9%. A total of 29.5% who had previously consulted a pulmonologist were excluded. A population of 241 obese patients underwent sleep and respiratory assessments. The prevalence of OHS in this population was 1.10 (95% CI = 0.51; 2.27). In multivariate analysis, PaCO2
, forced expiratory volume in 1 s (FEV1
), apnoea–hypopnoea index (AHI), BMI, use of ≥3 anti‐hypertensive drugs, anti‐diabetics, proton pump inhibitors and/or paracetamol were related to raised [HCO3

−
v].ConclusionThe prevalence of OHS in our obese population was lower than previous estimations based on hospitalized patients or clinical cohorts with sleep breathing disorders. Apart from hypercapnia, increased [HCO3

−
v] may also reflect multimorbidity and polypharmacy, which should be taken into account when using [HCO3

−
v] to screen for OHS.
Growth in a time of austerity: evidence from the UK
Authors: Amann Juergen , Middleditch Paul 
Published: April 2017

AbstractThis paper uses an empirical approach to test the specific causal relationship between debt and growth in the UK, in the context of the debate surrounding the use of a policy known as austerity measures. This time series perspective makes use of more recent Granger causality and cointegration tests that allow for non‐stationarity in macroeconomic time series data in the presence of structural breaks. Controlling for exogenous shocks associated with the period around the financial crisis, we find no evidence of a causal relationship between economic growth and public debt for the UK.
The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma
Authors: Keller Alexandra , Wingelhofer Bettina , Peter Barbara , Bauer Karin , Berger Daniela , Gamperl Susanne , Reifinger Martin , Cerny‐Reiterer Sabine , Moriggl Richard , Willmann Michael , Valent Peter , Hadzijusufovic Emir 
Published: April 2017

BackgroundMastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non‐resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma.Materials and MethodsWe employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated their effects on 2 mastocytoma cell lines, C2 and NI‐1.ResultsActivated JAK2 and STAT5 were detected in both cell lines. The drugs applied were found to inhibit proliferation and survival in these cells with the following rank‐order of potency: R763 > TG101348 > AZD1480 > pimozide > ruxolitinib > piceatannol. Moreover, synergistic anti‐neoplastic effects were obtained by combining pimozide with KIT‐targeting drugs (toceranib, masitinib, nilotinib, midostaurin) in NI‐1 cells.ConclusionThe JAK2/STAT5 pathway is a novel potential target of therapy in canine mastocytoma.
Correlation of cytologic and histopathologic findings with perinodal echogenicity of abdominal lymph nodes in dogs and cats
Authors: Davé Aditya C. , Zekas Lisa J. , Auld Danelle M. 
Published: April 2017

AbstractAbdominal lymphadenopathy in dogs and cats is routinely investigated with ultrasound. As the determination between benign and neoplastic etiologies of lymphadenopathy affects patient management, specific sonographic characteristics associated with both benign and neoplastic lymph nodes have been suggested. However, a significant overlap between these characteristics exists, necessitating a cytologic or histopathologic diagnosis in most instances. The objectives of this retrospective, cross‐sectional study were to evaluate whether echogenicity of perinodal fat could be a discriminator between benign and neoplastic abdominal lymphadenopathy and to assess if additional sonographic features associated with malignancy could be identified in lymph nodes with hyperechoic perinodal fat. Small animal patients (257 dogs and 117 cats) with sonographic evidence of abdominal lymphadenopathy and a cytological or histopathological diagnosis were evaluated for differences in the proportions of sonographic features between benign and neoplastic groups. Greater maximum long axis diameter (in dogs and cats) and a greater number of abnormal lymph nodes (in cats) were associated with malignancy in lymph nodes with hyperechoic perinodal fat. Canine lymph nodes with round cell neoplasia were significantly more likely to have hyperechoic perinodal fat. Lymph nodes affected with other neoplasia or with lymphadenitis were equally likely to have normal or hyperechoic perinodal fat. Reactive lymph nodes were significantly less likely to have hyperechoic perinodal fat in both species. These results suggest that though echogenicity of perinodal fat is a nonspecific finding, abdominal lymph nodes with hyperechoic perinodal fat are less likely to be reactive and sampling of these lymph nodes may be indicated.
Comorbidity assessment in localized prostate cancer: a systematic review protocol
Authors: Moretti Kim , Coombe Robyn 
Published: April 2017

Review objective/questions:
The objective of this study is to review and summarize the methods and tools used to measure comorbidity in localized prostate cancer (PCa) and in particular to assess whether these tools are adequately validated and reliable for determining the impact of comorbidity on survival and treatment decisions for this disease.
Specifically, the review questions are:What are the methods and tools used to measure comorbidity in localized PCa? (A detailed description and overview of psychometric properties will be provided for those methods and tools identified).Is there an optimal index(ices)/method(s) for use in localized PCa to assess overall survival and non-cancer survival?What is the effect of comorbidity assessment on treatment choice and curative therapy?
Effectiveness of the Manchester Triage System on time to treatment in the emergency department: a systematic review protocol
Authors: Cicolo Emilia A. , Ayache Nishi Fernanda , Ciqueto Peres Heloísa H. , Cruz Diná de Almeida Lopes Monteiro da 
Published: April 2017

Review question/objective:
The review aims to find the best available evidence on the effectiveness of the Manchester Triage System on time to treatment in the emergency department.
Click Chemistry-Facilitated Structural Diversification of Nitrothiazoles, Nitrofurans, and Nitropyrroles Enhances Antimicrobial Activity against Giardia lamblia
Authors: Kim Wan Jung , Korthals Keith A. , Li Suhua , Le Christine , Kalisiak Jarosław , Sharpless K. Barry , Fokin Valery V. , Miyamoto Yukiko , Eckmann Lars 
Published: April 2017

ABSTRACT

Giardia lamblia
is an important and ubiquitous cause of diarrheal disease. The primary agents in the treatment of giardiasis are nitroheterocyclic drugs, particularly the imidazoles metronidazole and tinidazole and the thiazole nitazoxanide. Although these drugs are generally effective, treatment failures occur in up to 20% of cases, and resistance has been demonstrated
in vivo
and
in vitro
. Prior work had suggested that side chain modifications of the imidazole core can lead to new effective 5-nitroimidazole drugs that can combat nitro drug resistance, but the full potential of nitroheterocycles other than imidazole to yield effective new antigiardial agents has not been explored. Here, we generated derivatives of two clinically utilized nitroheterocycles, nitrothiazole and nitrofuran, as well as a third heterocycle, nitropyrrole, which is related to nitroimidazole but has not been systematically investigated as an antimicrobial drug scaffold. Click chemistry was employed to synthesize 442 novel nitroheterocyclic compounds with extensive side chain modifications. Screening of this library against representative
G. lamblia
strains showed a wide spectrum of
in vitro
activities, with many of the compounds exhibiting superior activity relative to reference drugs and several showing >100-fold increase in potency and the ability to overcome existing forms of metronidazole resistance. The majority of new compounds displayed no cytotoxicity against human cells, and several compounds were orally active against murine giardiasis
in vivo
. These findings provide additional impetus for the systematic development of nitroheterocyclic compounds with nonimidazole cores as alternative and improved agents for the treatment of giardiasis and potentially other infectious agents.
Metabolic Genetic Screens Reveal Multidimensional Regulation of Virulence Gene Expression in Listeria monocytogenes and an Aminopeptidase That Is Critical for PrfA Protein Activation
Authors: Friedman Sivan , Linsky Marika , Lobel Lior , Rabinovich Lev , Sigal Nadejda , Herskovits Anat A. 
Published: April 2017

ABSTRACT

Listeria monocytogenes
is an environmental saprophyte and intracellular bacterial pathogen. Upon invading mammalian cells, the bacterium senses abrupt changes in its metabolic environment, which are rapidly transduced to regulation of virulence gene expression. To explore the relationship between
L. monocytogenes
metabolism and virulence, we monitored virulence gene expression dynamics across a library of genetic mutants grown under two metabolic conditions known to activate the virulent state: charcoal-treated rich medium containing glucose-1-phosphate and minimal defined medium containing limiting concentrations of branched-chain amino acids (BCAAs). We identified over 100 distinct mutants that exhibit aberrant virulence gene expression profiles, the majority of which mapped to nonessential metabolic genes. Mutants displayed enhanced, decreased, and early and late virulence gene expression profiles, as well as persistent levels, demonstrating a high plasticity in virulence gene regulation. Among the mutants, one was noteworthy for its particularly low virulence gene expression level and mapped to an X-prolyl aminopeptidase (PepP). We show that this peptidase plays a role in posttranslational activation of the major virulence regulator, PrfA. Specifically, PepP mediates recruitment of PrfA to the cytoplasmic membrane, a step identified as critical for PrfA protein activation. This study establishes a novel step in the complex mechanism of PrfA activation and further highlights the cross regulation of metabolism and virulence.
Identification of Acute HIV-1 Infection by Hologic Aptima HIV-1 RNA Qualitative Assay
Authors: Manak Mark M. , Eller Leigh Anne , Malia Jennifer , Jagodzinski Linda L. , Trichavaroj Rapee , Oundo Joseph , Lueer Cornelia , Cham Fatim , de Souza Mark , Michael Nelson L. , Robb Merlin L. , Peel Sheila A. 
Published: April 2017

ABSTRACT
The Hologic Aptima HIV-1 Qualitative RNA assay was used in a rigorous screening approach designed to identify individuals at the earliest stage of HIV-1 infection for enrollment into subsequent studies of cellular and viral events in early infection (RV 217/Early Capture HIV Cohort [ECHO] study). Volunteers at high risk for HIV-1 infection were recruited from study sites in Thailand, Tanzania, Uganda, and Kenya with high HIV-1 prevalence rates among the populations examined. Small-volume blood samples were collected by finger stick at twice-weekly intervals and tested with the Aptima assay. Participants with reactive Aptima test results were contacted immediately for entry into a more comprehensive follow-up schedule with frequent blood draws. Evaluation of the Aptima test prior to use in this study showed a detection sensitivity of 5.5 copies/ml (50%), with all major HIV-1 subtypes detected. A total of 54,306 specimens from 1,112 volunteers were examined during the initial study period (August 2009 to November 2010); 27 individuals were identified as converting from uninfected to infected status. A sporadic reactive Aptima signal was observed in HIV-1-infected individuals under antiretroviral therapy. Occasional false-reactive Aptima results in uninfected individuals, or nonreactive results in HIV-1-infected individuals not on therapy, were observed and used to calculate assay sensitivity and specificity. The sensitivity and specificity of the Aptima assay were 99.03% and 99.23%, respectively; positive and negative predictive values were 92.01% and 99.91%, respectively. Conversion from HIV-1-uninfected to -infected status was rapid, with no evidence of a prolonged period of intermittent low-level viremia.
Quality of life and psychological and gastrointestinal symptoms after cholecystectomy: a population-based cohort study
Authors: Talseth Arne , Edna Tom-Harald , Hveem Kristian , Lydersen Stian , Ness-Jensen Eivind 
Published: April 2017

ObjectiveThe study aims to examine gastrointestinal symptoms, quality of life and the risk of psychological symptoms after cholecystectomy.DesignThis is a prospective population-based cohort study based on the Nord-Trøndelag Health Study (HUNT) Norway. HUNT is a repeated health survey of the county population and includes a wide range of health-related items. In the present study, all 3 HUNT surveys were included, performed between 1984 and 2008. Selected items were scores on quality of life, the Hospital Anxiety and Depression Scale (HADS) and selected gastrointestinal symptoms. Participants who underwent cholecystectomy for gallstone disease between 1 January 1990 and until 1 year before attending HUNT3 were compared with the remaining non-operated cohort. Associations between cholecystectomy and the postoperative scores and symptoms were assessed by multivariable regression models.ResultsParticipants in HUNT1, HUNT2 and HUNT3 were 77 212 (89.4% of those invited), 65 237 (69.5%) and 50 807 (54.1%), respectively. In the study period, 931 participants were operated with cholecystectomy. Cholecystectomy was associated with an increased risk of diarrhoea and stomach pain postoperatively. In addition, cholecystectomy was associated with an increased risk of nausea postoperatively in men. We found no associations between cholecystectomy and quality of life, symptoms of anxiety and depression, constipation, heartburn, or acid regurgitation following surgery.ConclusionsIn this large population-based cohort study, cholecystectomy was associated with postoperative diarrhoea and stomach pain. Cholecystectomy for gallstone colic was associated with nausea in men. There were no associations between quality of life, symptoms of anxiety and depression, constipation, heartburn, or acid regurgitation.
ONC201 Demonstrates Antitumor Effects in Both Triple-Negative and Non–Triple-Negative Breast Cancers through TRAIL-Dependent and TRAIL-Independent Mechanisms
Authors: Ralff Marie D. , Kline Christina L.B. , Küçükkase Ozan C. , Wagner Jessica , Lim Bora , Dicker David T. , Prabhu Varun V. , Oster Wolfgang , El-Deiry Wafik S. 
Published: April 2017

Abstract
Breast cancer is a major cause of cancer-related death. TNF-related apoptosis-inducing ligand (TRAIL) has been of interest as a cancer therapeutic, but only a subset of triple-negative breast cancers (TNBC) is sensitive to TRAIL. The small-molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here, we show that ONC201 is efficacious against both TNBC and non-TNBC cells (n = 13). A subset of TNBC and non-TNBC cells succumbs to ONC201-induced cell death. In 2 of 8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2. The proapoptotic effect of ONC201 translates to in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested (6/8), ONC201 has an antiproliferative effect but does not induce apoptosis. ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the G1 phase of the cell cycle. pRb expression is associated with sensitivity to the antiproliferative effects of ONC201, and the compound synergizes with taxanes in less sensitive cells. All non-TNBC cells (n = 5) are growth inhibited following ONC201 treatment, and unlike what has been observed with TRAIL, a subset (n = 2) shows PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL independent. Our data demonstrate that ONC201 has potent antiproliferative and proapoptotic effects in a broad range of breast cancer subtypes, through TRAIL-dependent and TRAIL-independent mechanisms. These findings develop a preclinical rationale for developing ONC201 as a single agent and/or in combination with approved therapies in breast cancer. Mol Cancer Ther; 16(7); 1290–8. ©2017 AACR.
Mechanism of Progressive Heart Failure and Significance of Pulmonary Hypertension in Obstructive Hypertrophic Cardiomyopathy
Authors: Covella Michele , Rowin Ethan J. , Hill Nicholas S. , Preston Ioana R. , Milan Alberto , Opotowsky Alexander R. , Maron Barry J. , Maron Martin S. , Maron Bradley A. 
Published: April 2017

Background—
There are limited data on the prevalence, pathophysiology, and management implications of pulmonary hypertension in patients with obstructive hypertrophic cardiomyopathy and advanced heart failure.

Methods and Results—
To assess the clinical significance of measured cardiopulmonary hemodynamics in hypertrophic cardiomyopathy patients with heart failure, we retrospectively assessed right heart catheterization data in 162 consecutive patients with outflow tract gradients (median [interquartile range], 90 mm Hg [70–110 mm Hg]), 59±11 years old, and 49% men, predominately New York Heart Association class III/IV status. Pulmonary hypertension (mean pulmonary artery pressure, ≥25 mm Hg) was present in 82 patients (51%), including 29 (18%) regarded as moderate-severe (mean pulmonary artery pressure, ≥35 mm Hg) and 28 (34%) also had increased pulmonary vascular resistance >3.0 WU. The pulmonary artery wedge pressure was ≤15 mm Hg in 54%, indicating that left atrial hypertension was absent in a majority of patients. Notably, 9 patients (11%) met hemodynamic criteria for precapillary pulmonary hypertension (mean pulmonary artery pressure, ≥25 mm Hg; pulmonary vascular resistance, >3.0 WU; pulmonary artery wedge pressure, ≤15 mm Hg). Over a median follow-up of 327 days (90–743 days) after surgical myectomy (or alcohol septal ablation), 92% and 95% of patients with or without preoperative pulmonary hypertension, respectively, were asymptomatic or mildly symptomatic. One postoperative death occurred in a 59-year-old woman with acute respiratory failure and mean pulmonary artery pressure of 65 mm Hg.

Conclusions—
Pulmonary hypertension was common in obstructive hypertrophic cardiomyopathy patients with advanced heart failure. Although possibly a contributor to preoperative heart failure, pulmonary hypertension did not significantly influence clinical and surgical outcome. Notably, a novel patient subgroup was identified with resting invasive hemodynamics consistent with pulmonary vascular disease.
Optimal Timing of Complete Revascularization in Acute Coronary Syndrome: A Systematic Review and Meta‐Analysis
Authors: Gaffar Rouan , Habib Bettina , Filion Kristian B. , Reynier Pauline , Eisenberg Mark J. 
Published: April 2017

Background
Studies have suggested that complete revascularization is superior to culprit‐only revascularization for the treatment of enzyme‐positive acute coronary syndrome. However, the optimal timing of complete revascularization remains unclear. We conducted a systematic review and meta‐analysis of randomized controlled trials comparing single‐stage complete revascularization with multistage percutaneous coronary intervention in patients with ST‐segment elevation myocardial infarction or non–ST‐segment elevation myocardial infarction with multivessel disease.

Methods and Results
We systematically searched the Cochrane Central Register of Controlled Trials, Embase, PubMed, and MEDLINE for randomized controlled trials comparing single‐stage complete revascularization with multistage revascularization in patients with enzyme‐positive acute coronary syndrome. The primary outcome was the incidence of major adverse cardiovascular events at longest follow‐up. Data were pooled using DerSimonian and Laird random‐effects models. Four randomized controlled trials (n=838) were included in our meta‐analysis. The risk of unplanned repeat revascularization at longest follow‐up was significantly lower in patients randomized to single‐stage complete revascularization (risk ratio, 0.68; 95% CI, 0.47–0.99). Results also suggest a trend towards lower risks of major adverse cardiovascular events for patients randomized to single‐stage revascularization at 6 months (risk ratio, 0.67; 95% CI, 0.40–1.11) and at longest follow‐up (risk ratio, 0.79; 95% CI, 0.52–1.20). Risks of mortality and recurrent myocardial infarction at longest follow‐up were also lower with single‐stage revascularization, but 95% CIs were wide and included unity.

Conclusions
Our results suggest that single‐stage complete revascularization is safe. There also appears to be a trend towards lower long‐term risks of mortality and major adverse cardiovascular events; however, additional randomized controlled trials are required to confirm the potential benefits of single‐stage multivessel percutaneous coronary intervention.