bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoadjusted versus fixed CPAP for obstructive sleep apnoea: a multicentre, randomised equivalence trial
Authors: Bloch Konrad E , Huber Fabienne , Furian Michael , Latshang Tsogyal D , Lo Cascio Christian M , Nussbaumer-Ochsner Yvonne , Senn Oliver , Russi Erich W , Kohler Malcolm , Schoch Otto D , Turk Alexander , Imhof Edelbert , Laube Irène , Matthews Felix , Thurnheer Robert 
Published: October 2017

BackgroundThe obstructive sleep apnoea syndrome (OSAS) is conventionally treated by continuous positive airway pressure set at a fixed level (fCPAP). Automatic mask pressure adjustment (autoCPAP) is increasingly used during home therapy. We investigated whether autoCPAP is equivalent to fCPAP in improving sleepiness in patients with OSAS in the long-term.MethodsIn this multicentre equivalence trial, 208 patients with OSAS, with median Epworth sleepiness score (ESS) 13, apnoea/hypopnoea index 48.4/hour, were randomised to treatment with autoCPAP (5–15 mbar) or fCPAP (pressure set at the 90th percentile applied by autoCPAP during 2–4 weeks adaptation). Coprimary outcomes were changes in subjective and objective sleepiness from baseline to 2 years after treatment. Equivalence ranges were ±2 points in ESS and ±3 min sleep resistance time evaluated by recording responses to light signals.ResultsAt 2 years, in the intention to treat analysis, the reduction in sleepiness versus pretreatment baseline was similar in patients using autoCPAP (n=113, mean ESS-change −6.3, 95% CI −7.1 to −5.5; sleep resistance time +8.3 min, +6.9 to +9.7) and fCPAP (n=95, mean ESS-change −6.2, 95% CI −7.0 to −5.3; sleep resistance time +6.3 min, +4.7 to +7.8). The 95% CI of difference in ESS-reduction between autoCPAP and fCPAP was −0.9 to +1.4 and the 95% CI of difference in increase in sleep resistance time was −2.6 to +1.0 min. Blood pressure reduction and OSAS-related costs were similar between groups.ConclusionsAutoCPAP and fCPAP are equivalent within prespecified ranges in improving subjective and objective sleepiness in patients with OSAS over the course of 2 years. Costs of these treatments are similar.Trial registration numberClinicalTrials.gov NCT00280800.
Relationship between smoking and health and education spending in Chile
Authors: Paraje Guillermo , Araya Daniel 
Published: October 2017

ObjectiveTo estimate the degree to which tobacco consumption is associated with spending on a set of goods and services in Chile, especially health and education, for the total population as well as for specific subgroups.MethodsA seemingly unrelated regression equation system was used to estimate the statistical relationship between having tobacco expenditures and the budget share allocated to other items for the total population and for specific subgroups in Chile (eg, households within the bottom/top 33% by total expenditures). The use of household-level data allows for the control of a number of sociodemographic characteristics. The nationally representative 2012 Chilean Household Expenditure Survey was used for the analysis.ResultsTobacco consumption is associated with lower budget shares allocated to healthcare, education and housing expenses, especially for poorer households. In the case of health, not consuming tobacco is related to higher health expenditures: up to 32% for the total population. Similarly, in the case of education, not consuming tobacco is statistically related to higher education expenditures: up to 16% for the total population. For all groups, tobacco consumption is also related to a significantly higher budget share allocated to alcoholic beverages.ConclusionsThe strong significant statistical relationship found between tobacco consumption and resources allocated to healthcare and education consumption may be indicative of the existence of a crowding out effect of tobacco. This effect, in turn, may increase the burden that the rest of society must bear for the increased healthcare that they require because of tobacco consumption.
Effects of slaughter weight and growth rate on the longissimus muscle metabolic characteristics, and pork sensory quality in pigs of two sexes
Authors: Duan Yan , Faucitano Luigi , Rivest Joël , Graveline Nancy , Cliche Simon , Gariépy Claude 
Published: October 2017

A total of 119 pigs were used to investigate the effect of slaughter weight (107, 115, and 125 kg), growth rate (fast vs. slow), and sex (barrows vs. gilts) on the longissimus muscle biochemical and sensory traits. Increasing slaughter weight to 125 kg resulted in greater postmortem activity of calpastatin (P = 0.01), lactate dehydrogenase (P = 0.01), and citrate synthase (P = 0.02). Pork toughness and juiciness at 6 d were affected by the interaction slaughter weight × growth rate × sex, with pork being tougher (P = 0.04) and juicer (P = 0.03) in slow-growing gilts slaughtered at 125 and 115 kg, respectively. Flavour was scored higher (P = 0.03) in pork from gilts than from barrows. Overall, based on the slight and likely undetectable differences by the average consumer in the meat sensory traits, it can be concluded that slaughter weight can be increased to 125 kg without appreciable effect on the sensory properties.
Interview column
Authors: Riegler Michael Alexander , Engelbrecht Herman , Lux Mathias 
Published: October 2017

The interviews in the SIGMM records aim to provide the community with the insights, visions, and views from outstanding researchers in multimedia. With the interviews we particularly try to find out what makes these researchers outstanding and also to a certain extend what is going on in their mind, what are their visions and what are their thoughts about current topics. Examples from the last issues include interviews with Judith Redi, Klara Nahrstedt, and Wallapak Tavanapong.
The interviewers are conducted via Skype or - even better - in person by meeting them at conferences or other community events. We aim to publish three to four interviews a year. If you have suggestions for who to interview, please feel free to contact one of the column editors, which are:
Pulmonary vasodilation by phosphodiesterase 5 inhibition is enhanced and nitric oxide independent in early pulmonary hypertension after myocardial infarction
Authors: van Duin Richard W. B. , Houweling Birgit , Uitterdijk André , Duncker Dirk J. , Merkus Daphne 
Published: October 2017

Myocardial infarction (MI) may result in pulmonary hypertension (PH). Inhibition of phosphodiesterase 5 (PDE5), the enzyme responsible for the breakdown of cGMP in vascular smooth muscle, has become part of the contemporary therapeutic armamentarium for pulmonary arterial hypertension and may also be beneficial for PH secondary to MI. Nitric oxide (NO) is an important activator of cGMP synthesis and can be enhanced in early PH and decreased in severe PH. In the present study, we investigated if PDE5 inhibition ameliorates pulmonary hemodynamics in swine with PH secondary to MI and whether NO is essential. The PDE5 inhibitor EMD360527 was administered in awake, chronically instrumented swine with or without MI. At rest, PDE5 inhibition produced pulmonary vasodilation as evidenced by a decrease in pulmonary vascular resistance, which was more pronounced in MI ( n = 5) compared with normal swine ( n = 10, P ≤ 0.01) and was accompanied by an increase in stroke volume in MI swine. Both pulmonary vasodilation and increased stroke volume were maintained during exercise, suggesting that this therapy may improve exercise capacity in patients with PH secondary to MI. Interestingly, prior inhibition of NO significantly enhanced ( P ≤ 0.01) pulmonary vasodilation by PDE5 inhibition in both normal ( n = 8) and MI swine ( n = 5, P ≤ 0.05 vs. normal). This suggests that the increased vasodilator responses to PDE5 inhibition after MI were not due to an increase in NO-induced cGMP production. These observations indicate that PDE5 inhibition represents an interesting pharmacotherapeutic approach in early PH after a recent MI to prevent overt PH.NEW & NOTEWORTHY This research article is the first to describe that pulmonary vasodilation to phosphodiesterase 5 inhibition is enhanced and nitric oxide independent in resting and exercising swine with pulmonary hypertension as a result of myocardial infarction. This suggests that phosphodiesterase 5 inhibition can normalize pulmonary hemodynamics in postcapillary pulmonary hypertension after a recent myocardial infarction and may improve exercise capacity.
Dual effects of hyperglycemia on endothelial cells and cardiomyocytes to enhance coronary LPL activity
Authors: Chiu Amy Pei-Ling , Bierende Denise , Lal Nathaniel , Wang Fulong , Wan Andrea , Vlodavsky Israel , Hussein Bahira , Rodrigues Brian 
Published: October 2017

In the diabetic heart, there is excessive dependence on fatty acid (FA) utilization to generate ATP. Lipoprotein lipase (LPL)-mediated hydrolysis of circulating triglycerides is suggested to be the predominant source of FA for cardiac utilization during diabetes. In the heart, the majority of LPL is synthesized in cardiomyocytes and secreted onto cell surface heparan sulfate proteoglycan (HSPG), where an endothelial cell (EC)-releasable β-endoglycosidase, heparanase cleaves the side chains of HSPG to liberate LPL for its onward movement across the EC. EC glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) captures this released enzyme at its basolateral side and shuttles it across to its luminal side. We tested whether the diabetes-induced increase of transforming growth factor-β (TGF-β) can influence the myocyte and EC to help transfer LPL to the vascular lumen to generate triglyceride-FA. In response to high glucose and EC heparanase secretion, this endoglycosidase is taken up by the cardiomyocyte (Wang Y, Chiu AP, Neumaier K, Wang F, Zhang D, Hussein B, Lal N, Wan A, Liu G, Vlodavsky I, Rodrigues B. Diabetes 63: 2643–2655, 2014) to stimulate matrix metalloproteinase-9 expression and the conversion of latent to active TGF-β. In the cardiomyocyte, TGF-β activation of RhoA enhances actin cytoskeleton rearrangement to promote LPL trafficking and secretion onto cell surface HSPG. In the EC, TGF-β signaling promotes mesodermal homeobox 2 translocation to the nucleus, which increases the expression of GPIHBP1, which facilitates movement of LPL to the vascular lumen. Collectively, our data suggest that in the diabetic heart, TGF-β actions on the cardiomyocyte promotes movement of LPL, whereas its action on the EC facilitates LPL shuttling.NEW & NOTEWORTHY Endothelial cells, as first responders to hyperglycemia, release heparanase, whose subsequent uptake by cardiomyocytes amplifies matrix metalloproteinase-9 expression and activation of transforming growth factor-β. Transforming growth factor-β increases lipoprotein lipase secretion from cardiomyocytes and promotes mesodermal homeobox 2 to enhance glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1-dependent transfer of lipoprotein lipase across endothelial cells, mechanisms that accelerate fatty acid utilization by the diabetic heart.
HDL protects against doxorubicin-induced cardiotoxicity in a scavenger receptor class B type 1-, PI3K-, and Akt-dependent manner
Authors: Durham Kristina K. , Chathely Kevin M. , Mak Kei Cheng , Momen Abdul , Thomas Cyrus T. , Zhao Yuan-Yuan , MacDonald Melissa E. , Curtis Jonathan M. , Husain Mansoor , Trigatti Bernardo L. 
Published: October 2017

Doxorubicin is a widely used chemotherapeutic with deleterious cardiotoxic side effects. HDL has been shown to protect cardiomyocytes in vitro against doxorubicin-induced apoptosis. Scavenger receptor class B type 1 (SR-B1), a high-affinity HDL receptor, mediates cytoprotective signaling by HDL through Akt. Here, we assessed whether increased HDL levels protect against doxorubicin-induced cardiotoxicity in vivo and in cardiomyocytes in culture and explored the intracellular signaling mechanisms involved, particularly the role of SR-B1. Transgenic mice with increased HDL levels through overexpression of human apolipoprotein A1 (apoA1Tg/Tg) and wild-type mice (apoA1+/+) with normal HDL levels were treated repeatedly with doxorubicin. After treatment, apoA1+/+mice displayed cardiac dysfunction, as evidenced by reduced left ventricular end-systolic pressure and +dP/d t, and histological analysis revealed cardiomyocyte atrophy and increased cardiomyocyte apoptosis after doxorubicin treatment. In contrast, apoA1Tg/Tgmice were protected against doxorubicin-induced cardiac dysfunction and cardiomyocyte atrophy and apoptosis. When SR-B1 was knocked out, however, overexpression of apoA1 did not protect against doxorubicin-induced cardiotoxicity. Using primary neonatal mouse cardiomyocytes and human immortalized ventricular cardiomyocytes in combination with genetic knockout, inhibitors, or siRNA-mediated knockdown, we demonstrated that SR-B1 is required for HDL-mediated protection of cardiomyocytes against doxorubicin-induced apoptosis in vitro via a pathway involving phosphatidylinositol 3-kinase and Akt1/2. Our findings provide proof of concept that raising apoA1 to supraphysiological levels can dramatically protect against doxorubicin-induced cardiotoxicity via a pathway that is mediated by SR-B1 and involves Akt1/2 activation in cardiomyocytes.NEW & NOTEWORTHY We have identified an important role for the scavenger receptor class B type 1 in facilitating high-density lipoprotein-mediated protection of cardiomyocytes against stress-induced apoptosis and shown that increasing plasma high-density lipoprotein protects against the deleterious side effects of the chemotherapeutic and cardiotoxic drug doxorubicin.
Copper Chelation Inhibits BRAFV600E-Driven Melanomagenesis and Counters Resistance to BRAFV600E and MEK1/2 Inhibitors
Authors: Brady Donita C. , Crowe Matthew S. , Greenberg Danielle N. , Counter Christopher M. 
Published: October 2017

Abstract
MEK1/2 and BRAFV600E inhibitors are used to treat BRAFV600E-positive melanoma, with other cancers under evaluation. Genetic perturbation of copper import or pharmacologic reduction of copper with the clinical copper chelator TTM inhibits MEK1/2 kinase activity and reduces BRAFV600E-driven tumorigenesis. In this study, we report that TTM inhibited transformed growth of melanoma cell lines resistant to BRAF or MEK1/2 inhibitors and enhanced the antineoplastic activity of these inhibitors. TTM also provided a survival advantage in a genetically engineered mouse model of melanoma, and when accounting for putative overdosing, trended toward an increase in the survival benefit afforded by BRAF inhibition. This effect was phenocopied by genetically inhibiting copper import in tumors, which was linked to a reduction in MAPK signaling. Thus, TTM reduces copper levels and MAPK signaling, thereby inhibiting BRAFV600E-driven melanoma tumor growth. These observations inform and support clinical evaluation of TTM in melanoma. Cancer Res; 77(22); 6240–52. ©2017 AACR.
Loss of FOXO1 Cooperates with TMPRSS2–ERG Overexpression to Promote Prostate Tumorigenesis and Cell Invasion
Authors: Yang Yinhui , Blee Alexandra M. , Wang Dejie , An Jian , Pan Yunqian , Yan Yuqian , Ma Tao , He Yundong , Dugdale Joseph , Hou Xiaonan , Zhang Jun , Weroha S. John , Zhu Wei-Guo , Wang Y. Alan , DePinho Ronald A. , Xu Wanhai , Huang Haojie 
Published: October 2017

Abstract
E26 transformation-specific transcription factor ERG is aberrantly overexpressed in approximately 50% of all human prostate cancer due to TMPRSS2-ERG gene rearrangements. However, mice with prostate-specific transgenic expression of prostate cancer–associated ERG alone fail to develop prostate cancer, highlighting that ERG requires other lesions to drive prostate tumorigenesis. Forkhead box (FOXO) transcription factor FOXO1 is a tumor suppressor that is frequently inactivated in human prostate cancer. Here, we demonstrate that FOXO1, but not other FOXO proteins (FOXO3 and FOXO4), binds and inhibits the transcriptional activity of prostate cancer–associated ERG independently of FOXO1 transcriptional activity. Knockdown of endogenous FOXO1 increased invasion of TMPRSS2–ERG fusion–positive VCaP cells, an effect completely abolished by ERG knockdown. Patient specimen analysis demonstrated that FOXO1 and ERG protein expression inversely correlated in a subset of human prostate cancer. Although human ERG transgene expression or homozygous deletion of Foxo1 alone in the mouse prostate failed to promote tumorigenesis, concomitant ERG transgene expression and Foxo1 deletion resulted in upregulation of ERG target genes, increased cell proliferation, and formation of high-grade prostatic intraepithelial neoplasia. Overall, we provide biochemical and genetic evidence that aberrantly activated ERG cooperates with FOXO1 deficiency to promote prostate tumorigenesis and cell invasion. Our findings enhance understanding of prostate cancer etiology and suggest that the FOXO1–ERG signaling axis can be a potential target for treatment of prostate cancer. Cancer Res; 77(23); 6524–37. ©2017 AACR.
Chemotherapeutic Dose Scheduling Based on Tumor Growth Rates Provides a Case for Low-Dose Metronomic High-Entropy Therapies
Authors: West Jeffrey , Newton Paul K. 
Published: October 2017

Abstract
We extended the classical tumor regression models such as Skipper's laws and the Norton–Simon hypothesis from instantaneous regression rates to the cumulative effect over repeated cycles of chemotherapy. To achieve this end, we used a stochastic Moran process model of tumor cell kinetics coupled with a prisoner's dilemma game-theoretic cell–cell interaction model to design chemotherapeutic strategies tailored to different tumor growth characteristics. Using the Shannon entropy as a novel tool to quantify the success of dosing strategies, we contrasted MTD strategies as compared with low-dose, high-density metronomic strategies (LDM) for tumors with different growth rates. Our results show that LDM strategies outperformed MTD strategies in total tumor cell reduction. This advantage was magnified for fast-growing tumors that thrive on long periods of unhindered growth without chemotherapy drugs present and was not evident after a single cycle of chemotherapy but grew after each subsequent cycle of repeated chemotherapy. The evolutionary growth/regression model introduced in this article agrees well with murine models. Overall, this model supports the concept of designing different chemotherapeutic schedules for tumors with different growth rates and develops quantitative tools to optimize these schedules for maintaining low-volume tumors. Cancer Res; 77(23); 6717–28. ©2017 AACR.
Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion
Authors: Liu Yongqiang , Yuelling Larra W. , Wang Yuan , Du Fang , Gordon Renata E. , O'Brien Jenny A. , Ng Jessica M.Y. , Robins Shannon , Lee Eric H. , Liu Hailong , Curran Tom , Yang Zeng-Jie 
Published: October 2017

Abstract
Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. Although astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here, we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor-associated astrocytes (TAA) secrete the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drives expression of Nestin in MB cells through a smoothened-dependent, but Gli1-independent mechanism. Ablation of TAA dramatically suppresses Nestin expression and blocks tumor growth. These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression. Cancer Res; 77(23); 6692–703. ©2017 AACR.
Emerging Trends in Family History of Breast Cancer and Associated Risk
Authors: Shiyanbola Oyewale O. , Arao Robert F. , Miglioretti Diana L. , Sprague Brian L. , Hampton John M. , Stout Natasha K. , Kerlikowske Karla , Braithwaite Dejana , Buist Diana S.M. , Egan Kathleen M. , Newcomb Polly A. , Trentham-Dietz Amy 
Published: October 2017

Abstract
Background: Increase in breast cancer incidence associated with mammography screening diffusion may have attenuated risk associations between family history and breast cancer.
Methods: The proportions of women ages 40 to 74 years reporting a first-degree family history of breast cancer were estimated in the Breast Cancer Surveillance Consortium cohort (BCSC: N = 1,170,900; 1996–2012) and the Collaborative Breast Cancer Study (CBCS: cases N = 23,400; controls N = 26,460; 1987–2007). Breast cancer (ductal carcinoma in situ and invasive) relative risk estimates and 95% confidence intervals (CI) associated with family history were calculated using multivariable Cox proportional hazard and logistic regression models.
Results: The proportion of women reporting a first-degree family history increased from 11% in the 1980s to 16% in 2010 to 2013. Family history was associated with a &gt;60% increased risk of breast cancer in the BCSC (HR, 1.61; 95% CI, 1.55–1.66) and CBCS (OR, 1.64; 95% CI, 1.57–1.72). Relative risks decreased slightly with age. Consistent trends in relative risks were not observed over time or across stage of disease at diagnosis in both studies, except among older women (ages 60–74) where estimates were attenuated from about 1.7 to 1.3 over the last 20 years (P trend = 0.08 for both studies).
Conclusions: Although the proportion of women with a first-degree family history of breast cancer increased over time and by age, breast cancer risk associations with family history were nonetheless fairly constant over time for women under age 60.
Impact: First-degree family history of breast cancer remains an important breast cancer risk factor, especially for younger women, despite its increasing prevalence in the mammography screening era. Cancer Epidemiol Biomarkers Prev; 26(12); 1753–60. ©2017 AACR.
Deep Learning–Based Multi-Omics Integration Robustly Predicts Survival in Liver Cancer
Authors: Chaudhary Kumardeep , Poirion Olivier B. , Lu Liangqun , Garmire Lana X. 
Published: October 2017

AbstractIdentifying robust survival subgroups of hepatocellular carcinoma (HCC) will significantly improve patient care. Currently, endeavor of integrating multi-omics data to explicitly predict HCC survival from multiple patient cohorts is lacking. To fill this gap, we present a deep learning (DL)–based model on HCC that robustly differentiates survival subpopulations of patients in six cohorts. We built the DL-based, survival-sensitive model on 360 HCC patients' data using RNA sequencing (RNA-Seq), miRNA sequencing (miRNA-Seq), and methylation data from The Cancer Genome Atlas (TCGA), which predicts prognosis as good as an alternative model where genomics and clinical data are both considered. This DL-based model provides two optimal subgroups of patients with significant survival differences (P = 7.13e−6) and good model fitness [concordance index (C-index) = 0.68]. More aggressive subtype is associated with frequent TP53 inactivation mutations, higher expression of stemness markers (KRT19 and EPCAM) and tumor marker BIRC5, and activated Wnt and Akt signaling pathways. We validated this multi-omics model on five external datasets of various omics types: LIRI-JP cohort (n = 230, C-index = 0.75), NCI cohort (n = 221, C-index = 0.67), Chinese cohort (n = 166, C-index = 0.69), E-TABM-36 cohort (n = 40, C-index = 0.77), and Hawaiian cohort (n = 27, C-index = 0.82). This is the first study to employ DL to identify multi-omics features linked to the differential survival of patients with HCC. Given its robustness over multiple cohorts, we expect this workflow to be useful at predicting HCC prognosis prediction. Clin Cancer Res; 24(6); 1248–59. ©2017 AACR.