bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hardening or softening? An observational study of changes to the prevalence of hardening indicators in Victoria, Australia, 2001–2016
Authors: Brennan Emily , Greenhalgh Elizabeth M , Durkin Sarah J , Scollo Michelle M , Hayes Linda , Wakefield Melanie A 
Published: May 2019

BackgroundThe hardening hypothesis predicts that as smoking prevalence declines, remaining smokers will be more heavily addicted to nicotine and/or less interested in quitting. We tested this hypothesis in a population exposed to a comprehensive tobacco control programme over a 16-year period.MethodsAnnual cross-sectional surveys randomly sampled adults (aged 26+) in the state of Victoria, Australia, between 2001 and 2016. Until 2010, participants were recruited through random digit dialling to landline telephones; from 2011, sampling frames also included mobile phones. Logistic regressions assessed changes over time in the prevalence of smoking and each hardening indicator; additional models examined interactions by sex, age, education and socioeconomic status.ResultsSmoking prevalence declined significantly between 2001 and 2016 (20.1%–13.0%), as did the prevalence of seven hardening indicators: daily smoking, heavy consumption, no quit attempt in the past 5 years or past 12 months, no intention to quit in the next 6 months or next 30 days, and happiness to keep smoking. In addition, the proportion of smokers defined as ‘hardcore’ decreased from 17.2% to 9.1%. On the whole, hardening indicators decreased to a similar extent among demographic subgroups.ConclusionsThese results are inconsistent with the hardening hypothesis. Rather, they suggest that a comprehensive tobacco control programme that combines provision of cessation support to individual smokers with implementation of population-level interventions to drive all smokers towards quitting, can successfully reduce both smoking prevalence and levels of dependence and desire to keep smoking among the remaining population of smokers.
Disparities in current cigarette smoking among US adults, 2002–2016
Authors: Agaku Israel T , Odani Satomi , Okuyemi Kolawole S , Armour Brian 
Published: May 2019

BackgroundTo assess disparities in current (past 30 days) cigarette smoking among US adults aged ≥ 18 years during 2002–2016.MethodsNine indicators associated with social disadvantage were analysed from the 2002 to 2016 National Survey on Drug Use and Health: education, annual family income, sex, race/ethnicity, urbanicity, serious psychological distress, health insurance, public assistance, and employment status. Using descriptive and multivariable analyses, we measured trends in smoking overall and within the assessed variables. We also evaluated effect of interactions on disparities and estimated the excess number of smokers attributable to disparities.ResultsDuring 2002–2016, current cigarette smoking prevalence declined overall (27.5%–20.7%; p trend < 0.01), and among all subgroups except Medicare insurees and American Indians/Alaska Natives (AI/ANs). Overall inequalities in cigarette smoking grew even wider or remained unchanged for several indicators during the study period. In 2016, comparing groups with the least versus the most social advantage, the single largest disparity in current smoking prevalence was seen by race/ethnicity (prevalence ratio = 5.1, AI/ANs vs Asians). Education differences alone explained 38.0% of the observed racial/ethnic disparity in smoking prevalence. Interactions were also present; compared with the population-averaged prevalence among all AI/AN individuals (34.0%), prevalence was much higher among AI/ANs with <high school diploma (53.0%), unemployed (58.0%), or with serious psychological distress (66.9%). The burden of smoking attributable to race/ethnic disparities in smoking prevalence was an estimated 27.6 million smokers.ConclusionsOverall smoking inequality increased or remained unchanged because of slower declines in smoking prevalence among disadvantaged groups. Targeted interventions among high-risk groups can narrow disparities.
Male smoking reduction behaviour in response to China’s 2015 cigarette tax increase
Authors: Yu Lingwei , Cohen Joanna E , Hoe Connie , Yang Tingzhong , Wu Dan 
Published: May 2019

ObjectiveThis study aims to evaluate Chinese male smokers’ responses to China’s 2015 6% ad valorem and RMB0.1 specific excise tax increase per cigarettes pack.MethodsA male population-based cross-sectional survey with multistaged stratified sampling was employed to collect data in six cities in China. Descriptive methods and logistic models were used to assess responses and associated factors following the cigarette tax increase among male Chinese smokers.ResultsAmong a potential sample of 6500 Chinese males, 6010 individuals were contacted and 5782 participants completed the questionnaires. Of the 2852 current smokers, 60.7% (95% CI: 58.9 to 62.5) did not think cigarettes were expensive, 77.9% (95% CI: 76.4 to 79.5) reported no reduction in smoking in response to the 2015 tax increase and 21.3% (95% CI: 19.8 to 22.8) were not aware of the cigarette tax increase. Smokers who were occasional smokers, intended to quit and thought cigarettes expensive were more likely to report reducing cigarette smoking following the tax increase, while those who had higher household income per capita, smoked more cigarettes, and purchased more expensive cigarettes were less likely to report reducing cigarette consumption.ConclusionsAbout one in five male Chinese smokers reported reduction in smoking following China’s 2015 cigarette tax increase. This is a relatively large impact given the very modest tax increase. Even with the 2015 increase, the excise tax represents only 36.3% of the cigarette price in China. Tax increases are needed to achieve the WHO’s recommended level of 70%.
Strong legacy effect of peat composition on physicochemical properties of reclamation coversoil
Authors: Calver Teri , Yarmuch Marty , Conway Alexandra J. , Stewart Katherine 
Published: May 2019

Incorporation of salvaged peat in soil cover designs for oil sands mine reclamation is a common practice. However, current peat salvage practices do not differentiate between peatland types or the botanical composition of peat. In this study, we characterized the botanical composition of natural peat and coversoil on reclaimed sites and examined the influence of botanical composition on the physicochemical characteristics of reclaimed coversoil. Peat samples were collected from 15 natural peatlands (bog, poor fen, and rich fen) and peat coversoils were sampled from six reclaimed sites in the Athabasca oils sands region. The botanical compositions (Sphagnum, wood Sphagnum, woody, and woody/moss herbaceous) of all samples were determined. We found that natural peatland types had different physicochemical properties, primarily driven by Sphagnum-dominated samples with a high carbon:nitrogen (C:N) ratio and low total exchange capacity (TEC) when compared with samples dominated by more woody/moss herbaceous material. Similarly, we found that coversoil with Sphagnum-dominated peat compared with woody/moss herbaceous peat had lower TEC, pH, and total nitrogen values and higher C:N ratios (∼40 vs. 20 for Sphagnum and woody/moss herbaceous, respectively). Our results indicate that physicochemical properties driven by botanical composition remain in coversoil 5 yr after placement.
Heat therapy improves soleus muscle force in a model of ischemia-induced muscle damage
Authors: Kim Kyoungrae , Reid Blake A. , Ro Bohyun , Casey Caitlin A. , Song Qifan , Kuang Shihuan , Roseguini Bruno T. 
Published: May 2019

Leg muscle ischemia in patients with peripheral artery disease (PAD) leads to alterations in skeletal muscle morphology and reduced leg strength. We tested the hypothesis that exposure to heat therapy (HT) would improve skeletal muscle function in a mouse model of ischemia-induced muscle damage. Male 42-wk-old C57Bl/6 mice underwent ligation of the femoral artery and were randomly assigned to receive HT (immersion in a water bath at 37°C, 39°C, or 41°C for 30 min) or a control intervention for 3 wk. At the end of the treatment, the animals were anesthetized and the soleus and extensor digitorum longus (EDL) muscles were harvested for the assessment of contractile function and examination of muscle morphology. A subset of animals was used to examine the impact of a single HT session on the expression of genes involved in myogenesis and the regulation of muscle mass. Relative soleus muscle mass was significantly higher in animals exposed to HT at 39°C compared with the control group (control: 0.36 ± 0.01 mg/g versus 39°C: 0.40 ± 0.01 mg/g, P = 0.024). Maximal absolute force of the soleus was also significantly higher in animals treated with HT at 37°C and 39°C (control: 274.7 ± 6.6 mN; 37°C: 300.1 ± 7.7 mN; 39°C: 299.5 ± 10 mN, P < 0.05). In the soleus, but not the EDL muscle, a single session of HT enhanced the mRNA expression of myogenic factors as well as of both positive and negative regulators of muscle mass. These findings suggest that the beneficial effects of HT are muscle specific and dependent on the treatment temperature in a model of PAD.NEW & NOTEWORTHY This is the first study to comprehensively examine the impact of temperature and muscle fiber type composition on the adaptations to repeated heat stress in a model of ischemia-induced muscle damage. Exposure to heat therapy (HT) at 37°C and 39°C, but not at 41°C, improved force development of the isolated soleus muscle. These results suggest that HT may be a practical therapeutic tool to restore muscle mass and strength in patients with peripheral artery disease.
IL12 Abrogates Calcineurin-Dependent Immune Evasion during Leukemia Progression
Authors: Rabe Jennifer L. , Gardner Lori , Hunter Rae , Fonseca Jairo A. , Dougan Jodi , Gearheart Christy M. , Leibowitz Michael S. , Lee-Miller Cathy , Baturin Dmitry , Fosmire Susan P. , Zelasko Susan E. , Jones Courtney L. , Slansky Jill E. , Rupji Manali , Dwivedi Bhakti , Henry Curtis J. , Porter Christopher C. 
Published: May 2019

AbstractExploitation of the immune system has emerged as an important therapeutic strategy for acute lymphoblastic leukemia (ALL). However, the mechanisms of immune evasion during leukemia progression remain poorly understood. We sought to understand the role of calcineurin in ALL and observed that depletion of calcineurin B (CnB) in leukemia cells dramatically prolongs survival in immune-competent but not immune-deficient recipients. Immune-competent recipients were protected from challenge with leukemia if they were first immunized with CnB-deficient leukemia, suggesting robust adaptive immunity. In the bone marrow (BM), recipients of CnB-deficient leukemia harbored expanded T-cell populations as compared with controls. Gene expression analyses of leukemia cells extracted from the BM identified Cn-dependent significant changes in the expression of immunoregulatory genes. Increased secretion of IL12 from CnB-deficient leukemia cells was sufficient to induce T-cell activation ex vivo, an effect that was abolished when IL12 was neutralized. Strikingly, recombinant IL12 prolonged survival of mice challenged with highly aggressive B-ALL. Moreover, gene expression analyses from children with ALL showed that patients with higher expression of either IL12A or IL12B exhibited prolonged survival. These data suggest that leukemia cells are dependent upon calcineurin for immune evasion by restricting the regulation of proinflammatory genes, particularly IL12.Significance:This report implicates calcineurin as an intracellular signaling molecule responsible for immune evasion during leukemia progression and raises the prospect of re-examining IL12 as a therapeutic in leukemia.
mTORC2 Suppresses GSK3-Dependent Snail Degradation to Positively Regulate Cancer Cell Invasion and Metastasis
Authors: Zhang Shuo , Qian Guoqing , Zhang Qian-Qian , Yao Yuying , Wang Dongsheng , Chen Zhuo G. , Wang Li-Jing , Chen Mingwei , Sun Shi-Yong 
Published: May 2019

Abstract

mTOR complex 1 (mTORC1) positively regulates cell invasion and metastasis by enhancing translation of Snail. A connection between mTOR complex 2 (mTORC2) and cell invasion and metastasis has also been suggested, yet the underlying biology or mechanism is largely unknown and thus is the focus of this study. Inhibition of mTOR with both mTOR inhibitors and knockdown of key components of mTORC, including rictor, Sin1, and raptor, decreased Snail protein levels. Inhibition of mTOR enhanced the rate of Snail degradation, which could be rescued by inhibition of the proteasome. Critically, inhibition of mTORC2 (by knocking down rictor) but not mTORC1 (by knocking down raptor) enhanced Snail degradation. Therefore, only mTORC2 inhibition induces Snail proteasomal degradation, resulting in eventual Snail reduction. Interestingly, inhibition of GSK3 but not SCF/β-TrCP rescued the Snail reduction induced by mTOR inhibitors, suggesting GSK3-dependent, but SCF/β-TrCP–independent proteasomal degradation of Snail. Accordingly, mTOR inhibitors elevated E-cadherin levels and suppressed cancer cell migration and invasion in vitro and metastasis in vivo. Collectively, this study reveals that mTORC2 positively regulates Snail stability to control cell invasion and metastasis.

Significance:
These findings delineate a new regulation mechanism of Snail, an important master regulator of epithelial–mesenchymal transition and invasion in cancers.
The Highly Recurrent PP2A Aα-Subunit Mutation P179R Alters Protein Structure and Impairs PP2A Enzyme Function to Promote Endometrial Tumorigenesis
Authors: Taylor Sarah E. , O'Connor Caitlin M. , Wang Zhizhi , Shen Guobo , Song Haichi , Leonard Daniel , Sangodkar Jaya , LaVasseur Corinne , Avril Stefanie , Waggoner Steven , Zanotti Kristine , Armstrong Amy J. , Nagel Christa , Resnick Kimberly , Singh Sareena , Jackson Mark W. , Xu Wenqing , Haider Shozeb , DiFeo Analisa , Narla Goutham 
Published: May 2019

Abstract

Somatic mutation of the protein phosphatase 2A (PP2A) Aα-subunit gene PPP2R1A is highly prevalent in high-grade endometrial carcinoma. The structural, molecular, and biological basis by which the most recurrent endometrial carcinoma–specific mutation site P179 facilitates features of endometrial carcinoma malignancy has yet to be fully determined. Here, we used a series of structural, biochemical, and biological approaches to investigate the impact of the P179R missense mutation on PP2A function. Enhanced sampling molecular dynamics simulations showed that arginine-to-proline substitution at the P179 residue changes the protein's stable conformation profile. A crystal structure of the tumor-derived PP2A mutant revealed marked changes in A-subunit conformation. Binding to the PP2A catalytic subunit was significantly impaired, disrupting holoenzyme formation and enzymatic activity. Cancer cells were dependent on PP2A disruption for sustained tumorigenic potential, and restoration of wild-type Aα in a patient-derived P179R-mutant cell line restored enzyme function and significantly attenuated tumorigenesis and metastasis in vivo. Furthermore, small molecule–mediated therapeutic reactivation of PP2A significantly inhibited tumorigenicity in vivo. These outcomes implicate PP2A functional inactivation as a critical component of high-grade endometrial carcinoma disease pathogenesis. Moreover, they highlight PP2A reactivation as a potential therapeutic strategy for patients who harbor P179R PPP2R1A mutations.

Significance:
This study characterizes a highly recurrent, disease-specific PP2A PPP2R1A mutation as a driver of endometrial carcinoma and a target for novel therapeutic development.
See related commentary by Haines and Huang, p. 4009
Integrative Pharmacogenomics Analysis of Patient-Derived Xenografts
Authors: Mer Arvind S. , Ba-Alawi Wail , Smirnov Petr , Wang Yi X. , Brew Ben , Ortmann Janosch , Tsao Ming-Sound , Cescon David W. , Goldenberg Anna , Haibe-Kains Benjamin 
Published: May 2019

Abstract

Identifying robust biomarkers of drug response constitutes a key challenge in precision medicine. Patient-derived tumor xenografts (PDX) have emerged as reliable preclinical models that more accurately recapitulate tumor response to chemo- and targeted therapies. However, the lack of computational tools makes it difficult to analyze high-throughput molecular and pharmacologic profiles of PDX. We have developed Xenograft Visualization & Analysis (Xeva), an open-source software package for in vivo pharmacogenomic datasets that allows for quantification of variability in gene expression and pathway activity across PDX passages. We found that only a few genes and pathways exhibited passage-specific alterations and were therefore not suitable for biomarker discovery. Using the largest PDX pharmacogenomic dataset to date, we identified 87 pathways that are significantly associated with response to 51 drugs (FDR &lt; 0.05). We found novel biomarkers based on gene expressions, copy number aberrations, and mutations predictive of drug response (concordance index &gt; 0.60; FDR &lt; 0.05). Our study demonstrates that Xeva provides a flexible platform for integrative analysis of preclinical in vivo pharmacogenomics data to identify biomarkers predictive of drug response, representing a major step forward in precision oncology.

Significance:
A computational platform for PDX data analysis reveals consistent gene and pathway activity across passages and confirms drug response prediction biomarkers in PDX.
See related commentary by Meehan, p. 4324
CD44 Regulates Formation of Spheroids and Controls Organ-Specific Metastatic Colonization in Epithelial Ovarian Carcinoma
Authors: Sacks Suarez Joelle , Gurler Main Hilal , Muralidhar Goda G. , Elfituri Osama , Xu Hao-Liang , Kajdacsy-Balla Andre A. , Barbolina Maria V. 
Published: May 2019

AbstractDisseminating epithelial ovarian cancer cells often become assembled into spheroids prior to their arrival at metastatic sites within the peritoneal cavity. Although epithelial ovarian carcinoma (EOC) is the deadliest gynecologic malignancy, the mechanisms regulating formation and metastatic potential of spheroids are poorly understood. We show that expression of a cell surface glycoprotein CD44 is an important contributing factor for spheroid formation and spheroid adhesion to mesothelial cells, and its loss impairs mesenteric metastasis. In contrast, loss of CD44 resulted in significant increase of tumor burden at several locoregional sites, including liver, and unleashed distant metastases to the thoracic cavity. Altogether our studies suggest that CD44 regulates metastatic progression of EOC in an organ-specific manner.Implications:Expression of CD44 promotes spheroid formation, mesothelial adhesion, and formation of mesenteric metastasis, but it suppresses development of metastasis to several peritoneal sites, including liver, and the thoracic cavity.
Echocardiographic Abnormalities and Determinants of 1‐Month Outcome of Stroke Among West Africans in the SIREN Study
Authors: Adeoye Abiodun M. , Ovbiagele Bruce , Akinyemi Joshua O. , Ogah Okechukwu S. , Akinyemi Rufus , Gebregziabher Mulugeta , Wahab Kolawole , Fakunle Adekunle G. , Akintunde Adeseye , Adebayo Oladimeji , Aje Akinyemi , Tiwari Hemant K. , Arnett Donna , Agyekum Francis , Appiah Lambert T. , Amusa Ganiyu , Olunuga Taiwo O. , Onoja Akpa , Sarfo Fred S. , Akpalu Albert , Jenkins Carolyn , Lackland Daniel , Owolabi Lukman , Komolafe Morenikeji , Faniyan Moyinoluwalogo M. , Arulogun Oyedunni , Obiako Reginald , Owolabi Mayowa 
Published: May 2019

Background

Little is known about the relationship between echocardiographic abnormalities and outcome among patients with acute stroke. We investigated the pattern and association of baseline echocardiographic variables with 1‐month disability and mortality among patients with stroke in the
SIREN
(Stroke Investigative Research and Education Network) study.

Methods and Results

We enrolled and followed up consecutive 1020 adult patients with acute stroke with baseline transthoracic echocardiography from west Africa. To explore the relationship between echocardiographic variables and 1‐month disability (using modified Rankin scale >3) and fatality, regression models were fitted. Relative risks were computed with 95% CIs. The participants comprised 60% men with a mean age of 59.2±14.6 years. Ischemic stroke was associated with smaller aortic root diameter (30.2 versus 32.5,
P
=0.018) and septal (16.8 versus 19.1,
P
<0.001) and posterior wall thickness at systole (18.9 versus 21.5,
P
=0.004). Over 90% of patients with stroke had abnormal left ventricular (LV) geometry with eccentric hypertrophy predominating (56.1%). Of 13 candidate variables investigated, only baseline abnormal
LV
geometry (concentric hypertrophy) was weakly associated with 1‐month disability (unadjusted relative risk, 1.80; 95%
CI
, 0.97–5.73). Severe
LV
systolic dysfunction was significantly associated with increased 1‐month mortality (unadjusted relative risk, 3.05; 95%
CI
, 1.36–6.83).

Conclusions

Nine of 10 patients with acute stroke had abnormal
LV
geometry and a third had systolic dysfunction. Severe
LV
systolic dysfunction was significantly associated with 1 month mortality. Larger studies are required to establish the independent effect and unravel predictive accuracy of this association.
100 Years of Progress in Understanding the Dynamics of Coupled Atmosphere–Ocean Variability
Authors: Battisti David S. , Vimont Daniel J. , Kirtman Benjamin P. 
Published: May 2019

AbstractIn situ observation networks and reanalyses products of the state of the atmosphere and upper ocean show well-defined, large-scale patterns of coupled climate variability on time scales ranging from seasons to several decades. We summarize these phenomena and their physics, which have been revealed by analysis of observations, by experimentation with uncoupled and coupled atmosphere and ocean models with a hierarchy of complexity, and by theoretical developments. We start with a discussion of the seasonal cycle in the equatorial tropical Pacific and Atlantic Oceans, which are clearly affected by coupling between the atmosphere and the ocean. We then discuss the tropical phenomena that only exist because of the coupling between the atmosphere and the ocean: the Pacific and Atlantic meridional modes, the El Niño–Southern Oscillation (ENSO) in the Pacific, and a phenomenon analogous to ENSO in the Atlantic. For ENSO, we further discuss the sources of irregularity and asymmetry between warm and cold phases of ENSO, and the response of ENSO to forcing. Fundamental to variability on all time scales in the midlatitudes of the Northern Hemisphere are preferred patterns of uncoupled atmospheric variability that exist independent of any changes in the state of the ocean, land, or distribution of sea ice. These patterns include the North Atlantic Oscillation (NAO), the North Pacific Oscillation (NPO), and the Pacific–North American (PNA) pattern; they are most active in wintertime, with a temporal spectrum that is nearly white. Stochastic variability in the NPO, PNA, and NAO force the ocean on days to interannual times scales by way of turbulent heat exchange and Ekman transport, and on decadal and longer time scales by way of wind stress forcing. The PNA is partially responsible for the Pacific decadal oscillation; the NAO is responsible for an analogous phenomenon in the North Atlantic subpolar gyre. In models, stochastic forcing by the NAO also gives rise to variability in the strength of the Atlantic meridional overturning circulation (AMOC) that is partially responsible for multidecadal anomalies in the North Atlantic climate known as the Atlantic multidecadal oscillation (AMO); observations do not yet exist to adequately determine the physics of the AMO. We review the progress that has been made in the past 50 years in understanding each of these phenomena and the implications for short-term (seasonal-to-interannual) climate forecasts. We end with a brief discussion of advances of things that are on the horizon, under the rug, and over the rainbow.