bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late outcomes after the Fontan procedure in patients with single ventricle: a meta-analysis
Authors: Schwartz Ilana , McCracken Courtney E , Petit Christopher J , Sachdeva Ritu 
Published: March 2018

ObjectiveMore patients with Fontan physiology are reaching adulthood. The purpose of this meta-analysis was to evaluate the late outcomes of patients palliated with Fontan procedure and to assess the risk factors for mortality.MethodsPubMed, Embase and Web of Science were queried to retrieve observational studies of survival in patients following the Fontan procedure with ≥5 years of follow-up. A random-effects model was used to determine pooled survival estimates at 5, 10 and 15 years. Meta-regression was used to assess potential moderators for death.ResultsNineteen articles with a total of 5859 patients were included. The weighted mean follow-up time was 8.94±2.64 years with overall 8.3% deaths and 1.5% transplants. Pooled survival estimates at 5, 10 and 15 years were 90.7%, 87.2% and 87.5%, respectively; and 88.4%, 85.7% and 84.1%, respectively, for studies that included all three time intervals (n=4). Earliest surgical year included in the study, proportion of atriopulmonary connections versus extracardiac conduit or lateral tunnel, and older age at Fontan were associated with higher rates of death, but ventricular morphology was not. Protein-losing enteropathy, reoperation and pacemaker insertion were reported in 2.1%, 5.6% and 6.8% patients, respectively.ConclusionsSurvival following the Fontan procedure has improved with time and is influenced by Fontan type and age at the time of Fontan. At a mean follow-up of 8.9 years, there was no significant association between survival and ventricular morphology, not taking into account the mortality prior to Fontan.
Association of ambient pollution with inhaler use among patients with COPD: a panel study
Authors: Magzamen Sheryl , Oron Assaf P , Locke Emily R , Fan Vincent S 
Published: March 2018

BackgroundStudies have linked ambient air pollution to chronic obstructive pulmonary disease (COPD) healthcare encounters. However, the association between air quality and rescue medication use is unknown.ObjectivesWe assessed the role of air pollution exposure for increased short-acting beta-2-agonist (SABA) use in patients with COPD through use of remote monitoring technology.MethodsParticipants received a portable electronic inhaler sensor to record the date, time and location for SABA use over a 3-month period. Ambient air pollution data and meteorological data were collected from a centrally located federal monitoring station. Mixed-effects Poisson regression was used to examine the association of daily inhaler use with pollutant levels. Four criteria pollutants (PM2.5, PM10, O3and NO2), two particulate matter species (elemental carbon (EC) and organic carbon), estimated coarse fraction of PM10(PM10–2.5) and four multipollutant air quality measures were each examined separately, adjusting for covariates that passed a false discovery rate (FDR) screening.ResultsWe enrolled 35 patients with COPD (94.3% male and mean age: 66.5±8.5) with a mean forced expiratory volume in 1 s (FEV1) % predicted of 44.9+17.2. Participants had a median of 92 observation days (range 52–109). Participants’ average SABA inhaler use ranged from 0.4 to 13.1 puffs/day (median 2.8). Controlling for supplemental oxygen use, long-acting anticholinergic use, modified Medical Research Council Dyspnoea Scale and influenza season, an IQR increase in PM10concentration (8.0 µg/m3) was associated with a 6.6% increase in daily puffs (95% CI 3.5% to 9.9%; FDR <0.001). NO2and EC concentration were also significantly associated with inhaler use (3.9% and 2.9% per IQR increase, respectively).ConclusionsExposure to increased ambient air pollution were associated with a significant increase in SABA use for patients with COPD residing in a low-pollution area.
Sol–gel synthesis and optical properties of titanium dioxide thin film
Authors: Ullah Irfan , Khattak Shaukat Ali , Ahmad Tanveer , Saman  , Ludhi Nayab Ali 
Published: March 2018

The titanium dioxide (TiO2) is synthesized by sol–gel method using titanium-tetra-iso-propoxide (TTIP) as a starting material, and deposited on the pre-cleaned glass substrate using spin coating technique at optimized parameters. Energy dispersive X-ray (EDX) spectroscopy confirms successful TiO2 growth. The optical properties concerning the transmission and absorption spectra show 85% transparency and 3.28 eV wide optical band gap for indirect transition, calculated from absorbance. The exponential behavior of absorption edge is observed and attributed to the localized states electronic transitions, curtailed in the indirect band gap of the thin film. The film reveals decreasing refractive index with increasing wavelength. The photoluminescence (PL) study ascertains that luminescent properties are due to the surface defects.
Petrography, mineralogy and geochemistry of jadeite-rich artefacts from the Playa Grande excavation site, northern Hispaniola: evaluation of local provenance from the Río San Juan Complex
Authors: Schertl Hans-Peter , Maresch Walter V. , Knippenberg Sebastiaan , Hertwig Andreas , López Belando Adolfo , Rodríguez Ramos Reniel , Speich Laura , Hofman Corinne L. 
Published: March 2018

Abstract

Many archaeological sites with jadeitite artefacts are known in the Caribbean region, but defining the source of the raw material is a major problem because of great mineralogical heterogeneity both in potential sources and in artefacts. The archaeological settlement site of Playa Grande on the northern coast of the Dominican Republic is particularly significant because it yielded evidence of on-site axe manufacture, and lies only 20–30 km NE of a recently discovered potential source area of serpentinite mélanges in the nearby Río San Juan Complex (RSJC). A suite of nine artefacts was chosen from a collection of over 100 excavated woodworking tools rich in jadeite, as well as two blueschist artefacts. Permission to perform destructive analysis allowed data on petrography, mineral chemistry and bulk-rock chemistry to be obtained. Seven of the nine artefacts are jadeitite
sensu stricto
(>90 vol% jadeite), which are identical to material known from the RSJC. Two artefacts are jadeite–lawsonite rocks. These and the two blueschists show only minor differences from corresponding rocks of the RSJC source. With this direct linking of source and site material, it is now possible to better define source discriminators for the Caribbean and to assess sampling bias.
Folate Receptor Alpha Peptide Vaccine Generates Immunity in Breast and Ovarian Cancer Patients
Authors: Kalli Kimberly R. , Block Matthew S. , Kasi Pashtoon M. , Erskine Courtney L. , Hobday Timothy J. , Dietz Allan , Padley Douglas , Gustafson Michael P. , Shreeder Barath , Puglisi-Knutson Danell , Visscher Dan W. , Mangskau Toni K. , Wilson Glynn , Knutson Keith L. 
Published: March 2018

Abstract
Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity, and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients.
Patients and Methods: We conducted a phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low-dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to 1 year later.
Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in more than 90% of patients examined. Unlike recall immunity to tetanus toxoid (TT), FR T-cell responses developed slowly over the course of vaccination with a median time to maximal immunity in 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months.
Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen, and the developed vaccine is testable for therapeutic activity in most patients whose tumors express FR, regardless of HLA genotype. Clin Cancer Res; 24(13); 3014–25. ©2018 AACR.
TFAP2E Methylation and Expression Status Does Not Predict Response to 5-FU-based Chemotherapy in Colorectal Cancer
Authors: Murcia Oscar , Jover Rodrigo , Egoavil Cecilia , Perez-Carbonell Lucia , Juárez Miriam , Hernández-Illán Eva , Rojas Estefania , Alenda Cristina , Balaguer Francesc , Andreu Montserrat , Llor Xavier , Castells Antoni , Boland C. Richard , Goel Ajay 
Published: March 2018

Abstract
Purpose: A recent study reported that 5-fluorouracil (5-FU)-based chemotherapy is less effective in treating patients with advanced colorectal cancer demonstrating hypermethylation of the TFAP2E gene. The aim of our study was to confirm and validate these findings in large, uniformly treated, well-characterized patient cohorts.
Experimental Design: Two cohorts of 783 patients with colorectal cancer: 532 from a population-based, multicenter cohort (EPICOLON I) and 251 patients from a clinic-based trial were used to study the effectiveness of TFAP2E methylation and expression as a predictor of response of colorectal cancer patients to 5-FU–based chemotherapy. DNA methylation status of the TFAP2E gene in patients with colorectal cancer was assessed by quantitative bisulfite pyrosequencing analysis. IHC analysis of the TFAP2E protein expression was also performed.
Results: Correlation between TFAP2E methylation status and IHC staining was performed in 607 colorectal cancer samples. Among 357 hypermethylated tumors, only 141 (39.6%) exhibited loss of protein expression. Survival was not affected by TFAP2E hypermethylation in stage IV patients [HR, 1.21; 95% confidence interval (CI), 0.79–1.87; log-rank P = 0.6]. In stage II–III cases, disease-free survival was not influenced by TFAP2E hypermethylation status in 5-FU–treated (HR, 0.91; 95% CI, 0.52–1.59; log-rank P = 0.9) as well as in nontreated patients (HR, 0.88; 95% CI, 0.5–1.54; log-rank P = 0.7).
Conclusions: TFAP2E hypermethylation does not correlate with loss of its protein expression. Our large, systematic, and comprehensive study indicates that TFAP2E methylation and expression may not play a major role in predicting response to 5-FU–based chemotherapy in patients with colorectal cancer. Clin Cancer Res; 24(12); 2820–7. ©2018 AACR.
ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment
Authors: Patel Hetal , Periyasamy Manikandan , Sava Georgina P. , Bondke Alexander , Slafer Brian W. , Kroll Sebastian H. B. , Barbazanges Marion , Starkey Richard , Ottaviani Silvia , Harrod Alison , Aboagye Eric O. , Buluwela Laki , Fuchter Matthew J. , Barrett Anthony G. M. , Coombes R. Charles , Ali Simak 
Published: March 2018

AbstractRecent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting that targeting the transcriptional machinery provides new approaches to cancer treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (PolII) to enable transcription initiation. CDK7 additionally regulates the activities of a number of transcription factors, including estrogen receptor (ER)-α. Here we describe a new, orally bioavailable CDK7 inhibitor, ICEC0942. It selectively inhibits CDK7, with an IC50 of 40 nmol/L; IC50 values for CDK1, CDK2, CDK5, and CDK9 were 45-, 15-, 230-, and 30-fold higher. In vitro studies show that a wide range of cancer types are sensitive to CDK7 inhibition with GI50 values ranging between 0.2 and 0.3 μmol/L. In xenografts of both breast and colorectal cancers, the drug has substantial antitumor effects. In addition, combination therapy with tamoxifen showed complete growth arrest of ER-positive tumor xenografts. Our findings reveal that CDK7 inhibition provides a new approach, especially for ER-positive breast cancer and identify ICEC0942 as a prototype drug with potential utility as a single agent or in combination with hormone therapies for breast cancer. ICEC0942 may also be effective in other cancers that display characteristics of transcription factor addiction, such as acute leukaemia and small-cell lung cancer. Mol Cancer Ther; 17(6); 1156–66. ©2018 AACR.
Potent Immune Modulation by MEDI6383, an Engineered Human OX40 Ligand IgG4P Fc Fusion Protein
Authors: Oberst Michael D. , Augé Catherine , Morris Chad , Kentner Stacy , Mulgrew Kathy , McGlinchey Kelly , Hair James , Hanabuchi Shino , Du Qun , Damschroder Melissa , Feng Hui , Eck Steven , Buss Nicholas , de Haan Lolke , Pierce Andrew J. , Park Haesun , Sylwester Andrew , Axthelm Michael K. , Picker Louis , Morris Nicholas P. , Weinberg Andrew , Hammond Scott A. 
Published: March 2018

Abstract
Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a hexameric structure and exerts potent agonist activity following engagement of OX40. MEDI6383 displayed solution-phase agonist activity that was enhanced when the fusion protein was clustered by Fc gamma receptors (FcγRs) on the surface of adjacent cells. The resulting costimulation of OX40 on T cells induced NFκB promoter activity in OX40-expressing T cells and induced Th1-type cytokine production, proliferation, and resistance to regulatory T cell (Treg)-mediated suppression. MEDI6383 enhanced the cytolytic activity of tumor-reactive T cells and reduced tumor growth in the context of an alloreactive human T cell:tumor cell admix model in immunocompromised mice. Consistent with the role of OX40 costimulation in the expansion of memory T cells, MEDI6383 administered to healthy nonhuman primates elicited peripheral blood CD4 and CD8 central and effector memory T-cell proliferation as well as B-cell proliferation. Together, these results suggest that OX40 agonism has the potential to enhance antitumor immunity in human malignancies. Mol Cancer Ther; 17(5); 1024–38. ©2018 AACR.
PI3K Positively Regulates YAP and TAZ in Mammary Tumorigenesis Through Multiple Signaling Pathways
Authors: Zhao Yulei , Montminy Tess , Azad Taha , Lightbody Elizabeth , Hao Yawei , SenGupta Sandip , Asselin Eric , Nicol Christopher , Yang Xiaolong 
Published: March 2018

Abstract
Breast cancer is a leading cause of death in women worldwide. Active mutations of PI3K catalytic subunit PIK3CA (e.g., H1047R) and amplification of its homolog PIK3CB are observed in a large number of breast cancers. In recent years, aberrant activation of Transcriptional coactivator with PDZ binding motif (TAZ) and its paralog Yes-associated protein (YAP) have also been found to be important for breast cancer development and progression. However, whether PI3K interacts with YAP/TAZ during mammary tumorigenesis is unknown. Through a systematic gain-of-function screen for kinases involved in mammary tumorigenesis, we identified PIK3CB as a transformation-inducing kinase in breast cells. We further determined that PIK3CB positively regulates YAP and TAZ to promote transformation and inhibit mammary cell death in vitro. PIK3CB coexpression with TAZ, rather than PIK3CB or TAZ alone, in human MCF10A nontumorigenic mammary cells is sufficient for tumor formation in mice in vivo. Interestingly, we also determined that PIK3CA-H1047R enhances YAP and TAZ activity in mammary tumorigenesis in vitro. Mechanistically, the regulation of YAP/TAZ by both PIK3CA and PIK3CB occurs through multiple signaling pathways including LATS-dependent and LATS-independent pathways. Therefore, in this study, we determine that PI3K and YAP/TAZ interact to promote breast cancer cell transformation.
Implications: This study provides the first evidence that the Hippo pathway effectors TAZ and YAP are critical mediators of PI3K-induced mammary tumorigenesis and synergistically function together with PI3K in transformation of mammary cells. These findings may provide a novel rationale for targeting YAP/TAZ alone or in combination with PI3K inhibitors for breast cancer therapy in the future. Mol Cancer Res; 16(6); 1046–58. ©2018 AACR.
Tissue-Specific Immunoregulation: A Call for Better Understanding of the “Immunostat” in the Context of Cancer
Authors: Pao William , Ooi Chia-Huey , Birzele Fabian , Ruefli-Brasse Astrid , Cannarile Michael A. , Reis Bernhard , Scharf Sebastian H. , Schubert David A. , Hatje Klas , Pelletier Nadege , Spleiss Olivia , Reed John C. 
Published: March 2018

Abstract
Checkpoint inhibitor therapy has been a breakthrough in cancer research, but only some patients with cancer derive substantial benefit. Although mechanisms underlying sensitivity and resistance to checkpoint inhibitors are being elucidated, the importance of organ-specific regulation of immunity is currently underappreciated. Here, we call for a greater understanding of tissue-specific immunoregulation, namely, “tissue-specific immunostats,” to make advances in treatments for cancer. A better understanding of how individual organs at baseline regulate the immune system could enable an improved precision medicine approach to cancer immunotherapy. Cancer Discov; 8(4); 395–402. ©2018 AACR.
ОСОБЛИВОСТІ ПОЄДНАНОГО ПЕРЕБІГУ ХРОНІЧНОГО ОБСТРУКТИВНОГО ЗАХВОРЮВАННЯ ЛЕГЕНЬ ТА ГІПЕРТОНІЧНОЇ ХВОРОБИ
Authors: Maksiv K. Ya. , Pirus I. V. , Osinchuk R. R. , Habor H. H. , Krynytska I. Ya. , Marushchak M. I. 
Published: March 2018

Мета: проаналізувано особливості поєднаного перебігу хронічного обструктивного захворювання легень (ГХ) ІІ стадії та гіпертонічної хвороби ІІ стадії в гендерному аспекті.Матеріали і методи. Ретроспективно проаналізовано 420 історій хвороб пацієнтів, які перебували на стаціонарному лікуванні у пульмонологічному відділенні Тернопільської університетської лікарні з діагнозом «хронічне обструктивне захворювання легень» (ХОЗЛ) протягом 2014 і 2016 рр.Результати. Серед пацієнтів з ХОЗЛ переважали особи чоловічої статі (65,95 %). Розподіл за статтю пацієнтів з ХОЗЛ II стадії виглядає наступним чином: чоловіки – 59,86 %, жінки – 40,14 %.Висновки. Серед пацієнтів з ХОЗЛ II стадії 28, 67 % хворих не мали супутньої патології, 27,27 % - перебіг основного захворювання поєднувався з гіпертонічною хворобою II стадії, 43,36 % - ХОЗЛ поєднувався з іншими захворюваннями. Аналіз отриманих даних за гендерною ознакою вказує на переважання у пацієнтів чоловічої статі коморбідності ХОЗЛ з іншими патологіями, причому найчастіше (у 33 % хворих) з гіпертонічною хворобою. В осіб жіночої статі, хворих на ХОЗЛ, окрім гіпертонічної хвороби, з високою частотою зустрічалась ішемічна хвороба серця й захворювання ендокринної системи.
Association of Obesity With Severity of Heart Failure Exacerbation: A Population‐Based Study
Authors: Hirayama Atsushi , Goto Tadahiro , Shimada Yuichi J. , Faridi Mohammad Kamal , Camargo Carlos A. , Hasegawa Kohei 
Published: March 2018

Background

Obesity and heart failure (
HF
) are important public health problems in the United States. Although studies have reported the association between obesity and higher chronic morbidity of
HF
, little is known about the relations of obesity with severity of
HF
exacerbation and in‐hospital mortality; therefore, we aimed to investigate the associations of obesity with severity of
HF
exacerbation and in‐hospital mortality.

Methods and Results

This retrospective cohort study of adults hospitalized for
HF
exacerbation used population‐based data sets (the State Inpatient Databases) of 7
US
states from 2012 to 2013. The outcomes were acute severity measures—use of positive pressure ventilation and hospital length of stay—and in‐hospital mortality. We determined the associations between obesity and these outcomes, including adjustment for sociodemographic factors and comorbidities. We identified 219 465 patients hospitalized for
HF
exacerbation. Of those, 37 539 (17.1%) were obese. Obese patients had a significantly higher risk of positive pressure ventilation use compared with nonobese patients (13.6% versus 8.8%), with a corresponding adjusted odds ratio of 1.61 (95% confidence interval, 1.55–1.68;
P
<0.001). Likewise, obese patients were more likely to have hospital length of stay of ≥4 days compared with nonobese patients (62.5% versus 56.7%), with an adjusted odds ratio of 1.40 (95% confidence interval, 1.37–1.44;
P
<0.001). In contrast, obese patients had significantly lower in‐hospital mortality compared with nonobese patients (1.7% versus 3.3%), with an adjusted odds ratio of 0.87 (95% confidence interval, 0.80–0.95;
P
=0.002).

Conclusions

Based on large population‐based data sets of patients with
HF
exacerbation, obesity was associated with higher acute severity measures but lower in‐hospital mortality.
Role of Blood Lipids in the Development of Ischemic Stroke and its Subtypes
Authors: Hindy George , Engström Gunnar , Larsson Susanna C. , Traylor Matthew , Markus Hugh S. , Melander Olle , Orho-Melander Marju 
Published: March 2018

Background and Purpose—
Statin therapy is associated with a lower risk of ischemic stroke supporting a causal role of low-density lipoprotein (LDL) cholesterol. However, more evidence is needed to answer the question whether LDL cholesterol plays a causal role in ischemic stroke subtypes. In addition, it is unknown whether high-density lipoprotein cholesterol and triglycerides have a causal relationship to ischemic stroke and its subtypes. Our aim was to investigate the causal role of LDL cholesterol, high-density lipoprotein cholesterol, and triglycerides in ischemic stroke and its subtypes through Mendelian randomization (MR).

Methods—
Summary data on 185 genome-wide lipids-associated single nucleotide polymorphisms were obtained from the Global Lipids Genetics Consortium and the Stroke Genetics Network for their association with ischemic stroke (n=16 851 cases and 32 473 controls) and its subtypes, including large artery atherosclerosis (n=2410), small artery occlusion (n=3186), and cardioembolic (n=3427) stroke. Inverse-variance–weighted MR was used to obtain the causal estimates. Inverse-variance–weighted multivariable MR, MR-Egger, and sensitivity exclusion of pleiotropic single nucleotide polymorphisms after Steiger filtering and MR-Pleiotropy Residual Sum and Outlier test were used to adjust for pleiotropic bias.

Results—
A 1-SD genetically elevated LDL cholesterol was associated with an increased risk of ischemic stroke (odds ratio: 1.12; 95% confidence interval: 1.04–1.20) and large artery atherosclerosis stroke (odds ratio: 1.28; 95% confidence interval: 1.10–1.49) but not with small artery occlusion or cardioembolic stroke in multivariable MR. A 1-SD genetically elevated high-density lipoprotein cholesterol was associated with a decreased risk of small artery occlusion stroke (odds ratio: 0.79; 95% confidence interval: 0.67–0.90) in multivariable MR. MR-Egger indicated no pleiotropic bias, and results did not markedly change after sensitivity exclusion of pleiotropic single nucleotide polymorphisms. Genetically elevated triglycerides did not associate with ischemic stroke or its subtypes.

Conclusions—
LDL cholesterol lowering is likely to prevent large artery atherosclerosis but may not prevent small artery occlusion nor cardioembolic strokes. High-density lipoprotein cholesterol elevation may lead to benefits in small artery disease prevention. Finally, triglyceride lowering may not yield benefits in ischemic stroke and its subtypes.