bluuebunny/crossref_metadata_2025_split huggingface dataset:
FOLFOX plus ziv‐aflibercept or placebo in first‐line metastatic esophagogastric adenocarcinoma: A double‐blind, randomized, multicenter phase 2 trial
Authors: Cleary James M. , Horick Nora K. , McCleary Nadine Jackson , Abrams Thomas A. , Yurgelun Matthew B. , Azzoli Christopher G. , Rubinson Douglas A. , Brooks Gabriel A. , Chan Jennifer A. , Blaszkowsky Lawrence S. , Clark Jeffrey W. , Goyal Lipika , Meyerhardt Jeffrey A. , Ng Kimmie , Schrag Deborah , Savarese Diane M. F. , Graham Christopher , Fitzpatrick Bridget , Gibb Kathryn A. , Boucher Yves , Duda Dan G. , Jain Rakesh K. , Fuchs Charles S. , Enzinger Peter C. 
Published: March 2019

BackgroundAntiangiogenic therapy is a proven therapeutic modality for refractory gastric and gastroesophageal junction adenocarcinoma. This trial assessed whether the addition of a high affinity angiogenesis inhibitor, ziv‐aflibercept, could improve the efficacy of first‐line mFOLFOX6 (oxaliplatin, leucovorin, and bolus plus infusional 5‐ fluorouracil) in metastatic esophagogastric adenocarcinoma.MethodsPatients with treatment‐naive metastatic esophagogastric adenocarcinoma were randomly assigned (in a 2:1 ratio) in a multicenter, placebo‐controlled, double‐blind trial to receive first‐line mFOLFOX6 with or without ziv‐aflibercept (4 mg/kg) every 2 weeks. The primary endpoint was 6‐month progression‐free survival (PFS).ResultsSixty‐four patients were randomized to receive mFOLFOX6 and ziv‐aflibercept (43 patients) or mFOLFOX6 and a placebo (21 patients). There was no difference in the PFS, overall survival, or response rate. Patients treated with mFOLFOX6/ziv‐aflibercept tended to be more likely to discontinue study treatment for reasons other than progressive disease (P = .06). The relative dose intensity of oxaliplatin and 5‐fluorouracil was lower in the mFOLFOX6/ziv‐aflibercept arm during the first 12 and 24 weeks of the trial. There were 2 treatment‐related deaths due to cerebral hemorrhage and bowel perforation in the mFOLFOX6/ziv‐aflibercept cohort.ConclusionsZiv‐aflibercept did not increase the anti‐tumor activity of first‐line mFOLFOX6 in metastatic esophagogastric cancer, potentially because of decreased dose intensity of FOLFOX. Further evaluation of ziv‐aflibercept in unselected, chemotherapy‐naive patients with metastatic esophagogastric adenocarcinoma is not warranted.
High‐intensity end‐of‐life care among children, adolescents, and young adults with cancer who die in the hospital: A population‐based study from the French national hospital database
Authors: Revon‐Rivière Gabriel , Pauly Vanessa , Baumstarck Karine , Bernard Cecile , André Nicolas , Gentet Jean‐Claude , Seyler Catherine , Fond Guillaume , Orleans Veronica , Michel Gérard , Auquier Pascal , Boyer Laurent 
Published: March 2019

BackgroundEfforts to improve the quality of end‐of‐life (EOL) care depend on better knowledge of the care that children, adolescents, and young adults with cancer receive, including high‐intensity EOL (HI‐EOL) care. The objective was to assess the rates of HI‐EOL care in this population and to determine patient‐ and hospital‐related predictors of HI‐EOL from the French national hospital database.MethodsThis was a population‐based, retrospective study of a cohort of patients aged 0 to 25 years at the time of death who died at hospital as a result of cancer in France between 2014 and 2016. The primary outcome was HI‐EOL care, defined as the occurrence of ≥1 chemotherapy session <14 days from death, receiving care in an intensive care unit ≥1 time, >1 emergency room admission, and >1 hospitalization in an acute care unit in the last 30 days of life.ResultsThe study included 1899 individuals from 345 hospitals; 61.4% experienced HI‐EOL care. HI‐EOL was increased with social disadvantage (adjusted odds ratio [AOR], 1.30; 95% confidence interval [CI], 1.03‐1.65; P = .028), hematological malignancies (AOR, 2.09; 95% CI, 1.57‐2.77; P < .001), complex chronic conditions (AOR, 1.60; 95% CI, 1.23‐2.09; P = .001) and care delivered in a specialty center (AOR, 1.70; 95% CI, 1.22‐2.36; P = .001). HI‐EOL was reduced in cases of palliative care (AOR, 0.31; 95% CI, 0.24‐0.41; P < .001).ConclusionA majority of children, adolescents, and young adults experience HI‐EOL care. Several features (eg, social disadvantage, cancer diagnosis, complex chronic conditions, and specialty center care) were associated with HI‐EOL care. These findings should now be discussed with patients, families, and professionals to define the optimal EOL.
Impact of myocardial infarction on intraventricular vortex and flow energetics assessed using computational simulations
Authors: Chan Bee Ting , Ahmad Bakir Azam , Al Abed Amr , Dokos Socrates , Leong Chin Neng , Ooi Ean Hin , Lim Renly , Lim Einly 
Published: March 2019

AbstractFlow energetics have been proposed as early indicators of progressive left ventricular (LV) functional impairment in patients with myocardial infarction (MI), but its correlation with individual MI parameters has not been fully explored. Using electro–fluid‐structure interaction LV models, this study investigated the correlation between four MI parameters: infarct size, infarct multiplicity, regional enhancement of contractility at the viable myocardium area (RECVM), and LV mechanical dyssynchrony (LVMD) with intraventricular vortex and flow energetics. In LV with small infarcts, our results showed that infarct appearance amplified the energy dissipation index (DI), where substantial viscous energy loss was observed in areas with high flow velocity and near the infarct‐vortex interface. The LV with small multiple infarcts and RECVM showed remarkable DI increment during systole and diastole. In correlation analysis, the systolic kinetic energy fluctuation index (E′) was positively related to ejection fraction (EF) (R2 = 0.982) but negatively correlated with diastolic E′ (R2 = 0.970). Diastolic E′ was inversely correlated with vortex kinetic energy (R2 = 0.960) and vortex depth (R2 = 0.876). We showed an excessive systolic DI could differentiate infarcted LV with normal EF from healthy LV. Strong flow acceleration, LVMD, and vortex‐infarct interactions were predominant factors that induced excessive DI in infarcted LVs. Instead of causing undesired flow turbulence, high systolic E′ suggested the existence of energetic flow acceleration, while high diastolic E′ implied an inefficient diastolic filling. Thus, systolic E′ is not a suitable early indicator for progressive LV dysfunction in MI patients, while diastolic E′ may be a useful index to indicate diastolic impairment in these patients.
Visceral adiposity index outperforms common anthropometric indices in predicting 10‐year diabetes risk: Results from the ATTICA study
Authors: Koloverou Efi , Panagiotakos Demosthenes B. , Kyrou Ioannis , Stefanadis Christodoulos , Chrysohoou Christina , Georgousopoulou Ekavi N. , Skoumas Ioannis , Tousoulis Dimitrios , Pitsavos Christos ,   the ATTICA Study group
Published: March 2019

AbstractBackgroundVisceral adiposity index (VAI) is a novel marker of visceral adipose tissue accumulation and dysfunction. The study aim was to explore the association of VAI with the 10‐year type 2 diabetes mellitus (T2DM) incidence in apparently healthy individuals and compare its T2DM predictive ability against common anthropometric indices.MethodsIn 2001 to 2002, the ATTICA study (Greece) recruited a random sample of 1514 and 1528 CVD‐free men (18‐87 years old) and women (18‐89 years old), respectively. Sociodemographic, lifestyle, clinical, and biochemical characteristics of participants were measured at baseline, and the 10‐year follow‐up was performed during 2011 to 2012. After excluding participants with diabetes at baseline and participants without complete follow‐up information regarding diabetes status and/or baseline VAI values, the working sample consisted of 1049 participants. In this sample, the predictive value of baseline VAI value was studied in relation to 10‐year diabetes incidence.ResultsOne hundred thirty‐three incident cases of diabetes were documented (10‐year incidence: 12.7%). In the fully adjusted model, VAI significantly increased diabetes risk by 22% (OR per 1‐unit increase =1.22; 95%CI, 1.09‐1.37). Markers of oxidative stress and inflammation were found to, at least partly, mediate this relationship. Also, a moderating effect of menstruation status was revealed among women. VAI showed the highest predictive ability and contributed the most, along with waist‐to‐height ratio, to the correct classification of participants who developed diabetes.ConclusionsThe present findings suggest that VAI may be a useful index for predicting long‐term diabetes development and may exhibit better predictive ability to commonly used anthropometric indices.
Phylogeography of Potamon ibericum (Brachyura: Potamidae) identifies Quaternary glacial refugia within the Caucasus biodiversity hot spot
Authors: Parvizi Elaheh , Keikhosravi Alireza , Naderloo Reza , Solhjouy‐Fard Samaneh , Sheibak Farahnaz , Schubart Christoph D. 
Published: March 2019

AbstractRefugia are critical for the maintenance of biodiversity during the periods of Quaternary climatic oscillations. The long‐term persistence of refugial populations in a large continuous refugium has resulted in a homogenous pattern of genetic structure among populations, while highly structured evolutionary lineages characterize the restriction of refugial populations to smaller subrefugia. These mechanisms have resulted in the identification of hot spots of biodiversity within putative glacial refugia. We studied phylogeography of Potamon ibericum (Brachyura: Potamidae) in the drainages of the western Caucasus biodiversity hot spot (i.e., Colchis and the Caucasus) to infer spatial genetic structure and potential refugia for a freshwater crab in this region. These areas have traditionally considered as a refugium due to the presence of Tertiary relict species. We integrated population genetic data and historical demographic analysis from cytochrome oxidase subunit I sequences and paleoclimatic data from species distribution modeling (SDM). The results revealed the lack of phylogeographic structure and provided evidence for demographic expansion. The SDM presented a rather homogenous and large refugium that extended from northeast Turkey to Colchis during the last glacial period. In contrast to these findings, previous phylogeographic study on P. ibericum of the eastern Caucasus biodiversity hot spot (i.e., Hyrcania) identified multiple independent refugia. By combining these results, we explain the significance of this important western Palearctic hot spot of biological diversity in shaping the geographic distribution of intraspecific genetic diversity in a freshwater taxon.
Molecular basis underlying the successful invasion of hexaploid cytotypes ofSolidago canadensisL.: Insights from integrated gene and miRNA expression profiling
Authors: Xu Chanchan , Ge Yimeng , Wang Jianbo 
Published: March 2019

AbstractDissecting complex connections between cytogenetic traits (ploidy levels) and plant invasiveness has emerged as a popular research subject in the field of invasion biology. Although recent work suggests that polyploids are more likely to be invasive than their corresponding diploids, the molecular basis underlying the successful invasion of polyploids remains largely unexplored. To this end, we adopted an RNA‐seq and sRNA‐seq approach to describe how polyploids mediate invasiveness differences in two contrasting cytotypes ofSolidago canadensisL., a widespread wild hexaploid invader with localized cultivated diploid populations. Our analysis of the leaf transcriptome revealed 116,801 unigenes, of which 12,897 unigenes displayed significant differences in expression levels. A substantial number of these differentially expressed unigenes (DEUs) were significantly associated with the biosynthesis of secondary metabolites, carbohydrate metabolism, lipid metabolism, and environmental adaptation pathways. Gene Ontology term enrichment‐based categorization of DEU‐functions was consistent with this observation, as terms related to single‐organism, cellular, and metabolic processes including catalytic, binding, transporter, and enzyme regulator activity were over‐represented. Concomitantly, 186 miRNAs belonging to 44 miRNA families were identified in the same leaf tissues, with 59 miRNAs being differentially expressed. Furthermore, we discovered 83 miRNA‐target interacting pairs that were oppositely regulated, and a meticulous study of these targets depicted that several unigenes encoding transcription factors, DNA methyltransferase, and leucine‐rich repeat receptor‐like kinases involved in the stress response were greatly influenced. Collectively, these transcriptional and epigenetic data provide new insights into miRNA‐mediated gene expression regulatory mechanisms that may operate in hexaploid cytotypes to favor successful invasion.
Overcompensation: a 30‐year perspective
Authors: Ramula Satu , Paige Ken N. , Lennartsson Tommy , Tuomi Juha 
Published: March 2019

AbstractBiomass removal by herbivores usually incurs a fitness cost for the attacked plants, with the total cost per unit lost tissue depending on the value of the removed tissue (i.e., how costly it is to be replaced by regrowth). Optimal defense theory, first outlined in the 1960s and 1970s, predicted that these fitness costs result in an arms race between plants and herbivores, in which selection favors resistance strategies that either repel herbivores through morphological and chemical resistance traits in order to reduce their consumption, or result in enemy escape through rapid growth or by timing the growth or flowering to the periods when herbivores are absent. Such resistance against herbivores would most likely evolve when herbivores are abundant, cause extensive damage, and consume valuable plant tissues. The purpose of this Special Feature is to celebrate the 30th anniversary of the phenomenon of overcompensation, specifically, where the finding has brought us and where it is leading us 30 yr later. We first provide a short overview of how the phenomenon of overcompensation has led to broader studies on plant tolerance to herbivory, summarize key findings, and then discuss some promising new directions in light of six featured research papers.
Compositional Changes Among Triglycerides and Phospholipids During FATP4 Sensitization with Palmitate Lead to ER Stress in Cultured Cells
Authors: Seessle Jessica , Liebisch Gerhard , Schmitz Gerd , Stremmel Wolfgang , Chamulitrat Walee 
Published: March 2019

FATP4 expression is upregulated in acquired obesity and polymorphisms in the FATP4 gene are associated with increased blood triglycerides (TG). Since non‐alcoholic fatty liver disease (NAFLD) is a manifestation of obesity, it is of interest to understand how FATP4 upon fat overload mediates alterations of lipids that lead to pathogenesis of fatty liver. A model system with FATP4‐overexpressed (FATP4) and control Huh‐7 cell lines is used to determine FATP4 response to palmitate (Pal). By lipidomics methods, cellular phospholipids (PL), neutral lipids TG, free cholesterol (FC), and cholesterol esters (CE) as well as lipoprotein secretion are determined. Without Pal, FATP4 cells show a significant increase of TG, phosphatidylcholine (PC), and the release of TG‐rich and cholesterol‐rich low density lipoproteins. Pal‐treated FATP4 cells show an increase of all PL subclasses except for phosphatidylserine (PS), TG, FC, and CE. By analyses of ratios among PL subclasses and between PL and neutral lipids, it is determined that FATP4 in response to Pal causes sequentially fatty‐acid channeling with a shift from PC and phosphatidylinositol (PI) to neutral lipids and from neutral lipids to PS and phosphatidylethanolamine (PE). This response is concomitant with an activation of CAAT/enhancer binding homologous protein and MAP Kinase JNK. Thus, FATP4 overexpression in response to Pal leads to enhancement of neutral lipids which play a central role in fatty‐acid distribution from PC and PI to PE and PS that led to an alteration of ER and mitochondrial membranes and subsequent stress signalling.Practical Applications: Activation of fatty acids by fatty acid transport proteins (FATP) plays an important role in development of obesity and NAFLD. This work highlights functional role of FATP4 on fatty‐acid distribution among neutral lipids and phospholipids upon fat overload. These changes may contribute to stress signalling in the pathogenesis of NAFLD.Compositional shift among total PL subclasses and neutral lipids.
Oxidative Stability, Affective and Descriptive Sensory Properties of Roasted Peanut Flavored with Oregano, Laurel, and Rosemary Essential Oils as Natural Preservatives of Food Lipids
Authors: Olmedo Rubén H. , Grosso Nelson R. 
Published: March 2019

The objective of the study is to evaluate lipid oxidation stability in roasted peanuts with essential oils as natural antioxidants. Laurel, oregano, and rosemary essential oil (LEO, OEO, and REO, respectively) provide preliminary antioxidant activity determined by free radical scavenging activity (DPPH test) of 61.1, 58.4, and 47.9% and total phenolic content of 10.3, 10.6, and 8.4 mg g−1 for LEO, OEO, and REO, respectively. Essential oil (EO; 0.02% p/p) is added to roasted peanuts and an affective sensory test (nine‐point hedonic scale) shows that samples with OEO have greater values (6.74) than those of other samples (≈6.20). Chemical (peroxide anisidine diene content and Totox values) volatile (hexanal and 2‐heptenal) and sensory (oxidized and cardboard intensity) indicators change over 84 storage days. Samples with EOs show lower values than those for controls decreasing lipid oxidation. Samples with BHT have the lowest values for deterioration indicators. Principal component analysis of EOs for all indicators and samples with EOs shows that LEO and OEO have better antioxidant properties than REO. Coefficient regression between sensory variables peroxide value and hexanal has a good correlation and can be used as a predictor equation. Essential oils can be used as flavor and natural antioxidant agent in roasted peanut.Practical Applications: The authors believe in the importance of replacing the use of synthetic antioxidants with natural antioxidants in foods. Synthetic antioxidants are being questioned by the perception of safety that these offer by consumers. The essential oils present an antioxidant alternative since their components possess these properties and the application of them is a reason for research to be able to provide more information to the food industry. The sensory properties of essential oils are well received by consumers and the potential for their application as functional flavorings is in its initial stages. That is why this research collaborates with the use of the essential oils of oregano, laurel, and rosemary as possible antioxidants and flavors in peanuts roasted or in other food (which is susceptible to oxidative processes) evidenced its antioxidant properties and the modification of taste and sensory perception by the consumers.Oregano, laurel, and rosemary essential oils can be used as antioxidants in peanut products and foods with high lipid content.
Effect of Water Addition on the Microstructure, Lipid Incorporation, and Lipid Oxidation of Corn Extrudates
Authors: Amft Jonas , Bauer Jonas L. , Rostek Jens , Spielvogel Sandra , Schwarz Karin 
Published: March 2019

Lipid oxidation is a major cause of quality deterioration during the production and storage of fat containing extrudates, which is a result of the high‐specific surface of the matrix with increased oxygen access. During the extrusion process, corn starch gelatinizes and forms an amorphous matrix that incorporates lipids. To estimate the effect of incorporation on oxidative stability of lipids a model extrudate of corn meal, water, and a mixture of sunflower‐ and rapeseed oil is developed. The extrusion process is conducted on a laboratory twin screw extruder with varying moisture contents, affecting in turn process parameters such as the specific mechanical energy. A fractionated extraction protocol serves to obtain surface lipids, inner surface lipids, and lipids incorporated in the starch matrix. Oxidation is analyzed at different points in time during storage at 40 °C in the three lipid fractions. Furthermore, the microstructure of the extrudates is analyzed by computerized microtomography (µCT). The results show that increasing fat inclusion decreases the rate of lipid oxidation. A compact structure with low expansion is achieved by high‐water contents. These extrudates in turn exhibit an increased amount of incorporated lipids less susceptible to oxidation.Practical Applications: The presented work investigates extrusion technology, widely used by industry. Lipid oxidation covers an important topic, as stable products are necessary in order to avoid waste. The stabilization of lipids in extrudates against oxidation is therefore of great interest. With the model extrudate used in this study and a newly developed lipid fraction extraction protocol, it is possible to define the regions in terms of oxidation status. The results of this study provide the basis for products with an enhanced stability against lipid oxidation because of their structural characteristics considering the principles of green chemistry.The aim of the present study is to investigate the relationship between the microstructure and lipid oxidation in corn extrudates. Therefore, a new fractionated lipid extraction protocol is developed. Increasing feed water extrudates expand less and thicker cell walls are formed. Increasing the degree of lipid inclusion results in lower degree of oxidation.
Prediction of platinum‐resistance patients of gastric cancer using bioinformatics
Authors: Pan Jiaomeng , Xiang Zhen , Dai Qingqiang , Wang Zhenqiang , Liu Bingya , Li Chen 
Published: March 2019

AbstractLack of guidelines for personalized chemotherapy treatment after surgery has caused gastric cancer (GC) patients' unnecessary exposure to toxicity and the financial burden of chemotherapy treatments. In our study, we aimed to identify potential biomarkers to predict GC patients' susceptibility to platinum‐based on Gene Expression Omnibus (GEO) data sets. A total of 603 differentially expressed genes (DEGs) were identified between platinum‐resistant cell lines and platinum‐sensitive cell lines based on the Cancer Cell Line Encyclopedia (CCLE) data sets. A total of 253 patients who had accepted radical gastrectomy were recruited, of which 97 received platinum‐based chemotherapy and 156 were untreated. Three biomarkers (BRMS1, ND6, SRXN1) were then selected by univariate and multivariate Cox regression analysis to establish the predictive models using nomogram. Then this model was further validated through the GEO data set (GSE62254) which showed that this model could precisely predict the disease‐free survival and overall survival of patients treated with platinum‐based chemotherapy after surgery compared with untreated GC patients (P < 0.0001). This predictive model might provide helpful messages about the patients' susceptibility to platinum to guide personalized chemotherapy.