bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin Sensitivity and Insulin Clearance Are Heritable and Have Strong Genetic Correlation in Mexican Americans
Authors: Goodarzi Mark O. , Langefeld Carl D. , Xiang Anny H. , Chen Yii‐Der I. , Guo Xiuqing , Hanley Anthony J. G. , Raffel Leslie J. , Kandeel Fouad , Nadler Jerry L. , Buchanan Thomas A. , Norris Jill M. , Fingerlin Tasha E. , Lorenzo Carlos , Rewers Marian J. , Haffner Steven M. , Bowden Donald W. , Rich Stephen S. , Bergman Richard N. , Rotter Jerome I. , Watanabe Richard M. , Wagenknecht Lynne E. 
Published: October 2013

ObjectiveThe GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium is described, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI).MethodsGUARDIAN is comprised of seven cohorts, consisting of 4,336 Mexican‐American individuals in 1,346 pedigrees. Insulin sensitivity (SI), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI were measured by hyperinsulinemic‐euglycemic clamp in three cohorts. Heritability and genetic and environmental correlations were estimated within the family cohorts (totaling 3,925 individuals) using variance components.ResultsAcross studies, age, and gender‐adjusted heritability of insulin sensitivity (SI, M, M/I) ranged from 0.23 to 0.48 and of MCRI from 0.35 to 0.73. The ranges for the genetic correlations were 0.91 to 0.93 between SI and MCRI; and −0.57 to −0.59 for AIRg and MCRI (all P < 0.0001). The ranges for the environmental correlations were 0.54 to 0.74 for SI and MCRI (all P < 0.0001); and −0.16 to −0.36 for AIRg and MCRI (P < 0.0001‐0.06).ConclusionsThese data support a strong familial basis for insulin sensitivity and MCRI in Mexican Americans. The strong genetic correlations between MCRI and SI suggest common genetic determinants.
An Application of Unconditional Quantile Regression to Cigarette Taxes
Authors: Maclean Johanna Catherine , Webber Douglas A. , Marti Joachim 
Published: October 2013

AbstractThis study investigates heterogeneous response to state cigarette tax increases using unconditional quantile regression (UQR). We make two contributions to the empirical policy analysis literature. First, we argue that UQR provides more policy‐relevant information than conventional quantile regression in most empirical state policy analyses. Second, we document cigarette tax elasticity across a sample of adult smokers in the Current Population Survey Tobacco Use Supplements between 1992 and 2011. Our ordinary least squares regression show an imprecise negative relationship between taxes and cigarettes smoked in the past 30 days, while UQR reveals a U‐shaped relationship: Only moderate smokers reduce their smoking following a cigarette tax increase, and the magnitude of the effect is small. A $1.00 (135 percent) increase in the cigarette tax leads to a 3.5 percent reduction in the number of cigarettes smoked in the past 30 days among the most responsive smokers (implied tax elasticity = −0.03).
The evolving genomic classification of lung cancer
Authors: Shames David S , Wistuba Ignacio I 
Published: October 2013

AbstractEGFR gene mutations and ALK gene fusions are well‐characterized molecular targets in NSCLC. Activating alterations in a variety of potential oncogenic driver genes have also been identified in NSCLC, including ROS1, RET, MET, HER2, and BRAF. Together with EGFR and ALK, these mutations account for ∼20% of NSCLCs. The identification of these oncogenic drivers has led to the design of rationally targeted therapies that have produced superior clinical outcomes in tumours harbouring these mutations. Many patients, however, have de novo or acquired resistance to these therapies. In addition, most NSCLCs are genetically complex tumours harbouring multiple potential activating events. For these patients, disease subsets are likely to be defined by combination strategies involving a number of targeted agents. These targets include FGFR1, PTEN, MET, MEK, PD‐1/PD‐L1, and NaPi2b. In light of the myriad new biomarkers and targeted agents, multiplex testing strategies will be invaluable in identifying the appropriate patients for each therapy and enabling targeted agents to be channelled to the patients most likely to gain benefit. The challenge now is how best to interpret the results of these genomic tests, in the context of other clinical data, to optimize treatment choices in NSCLC. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Carcinoma‐associated fibroblasts derive from mesothelial cells via mesothelial‐to‐mesenchymal transition in peritoneal metastasis
Authors: Sandoval Pilar , Jiménez‐Heffernan Jose Antonio , Rynne‐Vidal Ángela , Pérez‐Lozano María Luisa , Gilsanz Álvaro , Ruiz‐Carpio Vicente , Reyes Raquel , García‐Bordas Julio , Stamatakis Konstantinos , Dotor Javier , Majano Pedro L , Fresno Manuel , Cabañas Carlos , López‐Cabrera Manuel 
Published: October 2013

AbstractPeritoneal dissemination is a frequent metastatic route for cancers of the ovary and gastrointestinal tract. Tumour cells metastasize by attaching to and invading through the mesothelial cell (MC) monolayer that lines the peritoneal cavity. Metastases are influenced by carcinoma‐associated fibroblasts (CAFs), a cell population that derives from different sources. Hence, we investigated whether MCs, through mesothelial–mesenchymal transition (MMT), were a source of CAFs during peritoneal carcinomatosis and whether MMT affected the adhesion and invasion of tumour cells. Biopsies from patients with peritoneal dissemination revealed the presence of myofibroblasts expressing mesothelial markers in the proximity of carcinoma implants. Prominent new vessel formation was observed in the peritoneal areas harbouring tumour cells when compared with tumour‐free regions. The use of a mouse model of peritoneal dissemination confirmed the myofibroblast conversion of MCs and the increase in angiogenesis at places of tumour implants. Treatment of omentum MCs with conditioned media from carcinoma cell cultures resulted in phenotype changes reminiscent of MMT. Adhesion experiments demonstrated that MMT enhanced the binding of cancer cells to MCs in a β1‐integrin‐dependent manner. Scanning electron microscopy imaging showed that the enhanced adhesion was mostly due to increased cell–cell interaction and not to a mere matrix exposure. Invasion assays suggested a reciprocal stimulation of the invasive capacity of tumour cells and MCs. Our results demonstrate that CAFs can derive from mesothelial cells during peritoneal metastasis. We suggest that MMT renders the peritoneum more receptive for tumour cell attachment/invasion and contributes to secondary tumour growth by promoting its vascularization. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Amplification and over‐expression of MAP3K3 gene in human breast cancer promotes formation and survival of breast cancer cells
Authors: Fan Yihui , Ge Ningling , Wang Xiaosong , Sun Wenjing , Mao Renfang , Bu Wen , Creighton Chad J , Zheng Pingju , Vasudevan Sanjeev , An Lei , Yang Jinshu , Zhao Yi‐Jue , Zhang Huiyuan , Li Xiao‐Nan , Rao Pulivarthi H , Leung Eastwood , Lu Yong‐Jie , Gray Joe W , Schiff Rachel , Hilsenbeck Susan G , Osborne C Kent , Yang Jianhua , Zhang Hong 
Published: October 2013

AbstractGene amplifications in the 17q chromosomal region are observed frequently in breast cancers. An integrative bioinformatics analysis of this region nominated the MAP3K3 gene as a potential therapeutic target in breast cancer. This gene encodes mitogen‐activated protein kinase kinase kinase 3 (MAP3K3/MEKK3), which has not yet been reported to be associated with cancer‐causing genetic aberrations. We found that MAP3K3 was amplified in approximately 8–20% of breast cancers. Knockdown of MAP3K3 expression significantly inhibited cell proliferation and colony formation in MAP3K3‐amplified breast cancer cell lines MCF‐7 and MDA‐MB‐361 but not in MAP3K3 non‐amplified breast cancer cells. Knockdown of MAP3K3 expression in MAP3K3‐amplified breast cancer cells sensitized breast cancer cells to apoptotic induction by TNFα and TRAIL, as well as doxorubicin, VP‐16 and fluorouracil, three commonly used chemotherapeutic drugs for treating breast cancer. In addition, ectopic expression of MAP3K3, in collaboration with Ras, induced colony formation in both primary mouse embryonic fibroblasts and immortalized human breast epithelial cells (MCF‐10A). Combined, these results suggest that MAP3K3 contributes to breast carcinogenesis and may endow resistance of breast cancer cells to cytotoxic chemotherapy. Therefore, MAP3K3 may be a valuable therapeutic target in patients with MAP3K3‐amplified breast cancers, and blocking MAP3K3 kinase activity with a small molecule inhibitor may sensitize MAP3K3‐amplified breast cancer cells to chemotherapy. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mouse tumour models to guide drug development and identify resistance mechanisms
Authors: Das Thakur Meghna , Pryer Nancy K , Singh Mallika 
Published: October 2013

AbstractWe need improved, translatable and predictive tumour models for the evaluation of response and the evolution of resistance to targeted therapeutics. We provide a review of the use of different types of preclinical tumour models to evaluate novel anticancer agents, and model the rapidly evolving landscape of resistance to targeted therapy. We focus on describing the various preclinical models available for candidate drug development and design considerations for preclinical experiments, depending on the aspect of drug action being interrogated. We discuss selected examples of how experimental findings have translated into clinical outcomes for targeted agents, predicted mechanisms that drive resistance and strategies to overcome the evolution thereof. We discuss challenges in preclinical experimental design and interpretation and possible improvements in animal models of therapeutic response and resistance, with an emphasis on improved translation of experimental research into clinical practice. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours
Authors: Galon Jérôme , Mlecnik Bernhard , Bindea Gabriela , Angell Helen K , Berger Anne , Lagorce Christine , Lugli Alessandro , Zlobec Inti , Hartmann Arndt , Bifulco Carlo , Nagtegaal Iris D , Palmqvist Richard , Masucci Giuseppe V , Botti Gerardo , Tatangelo Fabiana , Delrio Paolo , Maio Michele , Laghi Luigi , Grizzi Fabio , Asslaber Martin , D'Arrigo Corrado , Vidal‐Vanaclocha Fernando , Zavadova Eva , Chouchane Lotfi , Ohashi Pamela S , Hafezi‐Bakhtiari Sara , Wouters Bradly G , Roehrl Michael , Nguyen Linh , Kawakami Yutaka , Hazama Shoichi , Okuno Kiyotaka , Ogino Shuji , Gibbs Peter , Waring Paul , Sato Noriyuki , Torigoe Toshihiko , Itoh Kyogo , Patel Prabhu S , Shukla Shilin N , Wang Yili , Kopetz Scott , Sinicrope Frank A , Scripcariu Viorel , Ascierto Paolo A , Marincola Francesco M , Fox Bernard A , Pagès Franck 
Published: October 2013

AbstractThe American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression‐based stratification. These parameters rely on tumour‐cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named ‘Immunoscore’ has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM‐I (TNM‐Immune). © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
In Brief: Notch signalling in health and disease
Authors: Aster Jon C 
Published: October 2013

AbstractThe Notch pathway controls many aspects of development and is mutated in various human cancers. Remarkably, Notch function changes during the development of cellular hierarchies and can be either oncogenic or tumour‐suppressive, depending on cellular context. Notch dysregulation is also important in cardiovascular disease and disorders of immunity. This mini‐review outlines key features of the Notch signalling pathway and emerging data linking it to human diseases. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Favorable outcome of patients affected by rhabdoid tumors due to rhabdoid tumor predisposition syndrome (RTPS)
Authors: Kordes Uwe , Bartelheim Kerstin , Modena Piergiorgio , Massimino Maura , Biassoni Veronica , Reinhard Harald , Hasselblatt Martin , Schneppenheim Reinhard , Frühwald Michael C. 
Published: October 2013

AbstractRhabdoid tumor predisposition syndrome is usually associated with shorter survival in patients with malignant rhabdoid tumors regardless of anatomical origin. Here we present four children harboring truncating heterozygous SMARCB1/INI1 germline mutations with favorable outcome. All four patients received multi‐modality treatment, three according to therapeutic recommendations by the EU‐RHAB registry, two without radiotherapy, and mean event‐free survival accounts for 7 years. In conclusion, intensive treatment with curative intent is justified for children with rhabdoid tumors even if an underlying rhabdoid predisposition syndrome is demonstrated. Pediatr Blood Cancer 2014;61:919–921. © 2013 Wiley Periodicals, Inc.
Identification of Nuclear Factor‐κB Inhibitors and β2 Adrenergic Receptor Agonists in Chinese Medicinal Preparation Fuzilizhong Pills Using UPLC with Quadrupole Time‐of‐flight MS
Authors: Dong Linyi , Cheng Binfeng , Luo Yi , Zhang Ning , Duan Hongquan , Jiang Min , Wang Yiming , Bai Gang , Luo Guoan 
Published: October 2013

ABSTRACTIntroductionFuzilizhong Pills (FZLZ), a modified form of a famous traditional Chinese medicine (TCM) Lizhong Wan in Treatise on Febrile Diseases and consisting of Panax ginseng C.A.Mey. (Ren Shen), Aconitum carmichaelii Debx. (Fu Zi, Zhi), Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L. (Gan Cao), Atractylodes macrocephala Koidz. (Bai Zhu) and Zingiber offcinale Rosc. (Gan Jiang), show strong clinical therapeutic effects for dyspnea and pulmonary oedema. However, the bioactive compounds are still unclear. In this study, FZLZ was analysed using a rapid detection method to identify its anti‐inflammatory and spasmolytic constituents.ObjectiveTo develop a simple screening method to detect the anti‐inflammatory and spasmolytic constituents of FZLZ.MethodsUltra‐performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry combined with dual‐bioactive (NF‐κB and β2‐adrenergic receptor) luciferase reporter assay systems was employed.ResultsTwo β2‐adrenergic receptor agonists (salsolinol and higeramine) and three terpenoidal analogues of NF‐κB inhibitors such as ginsenosides derivatives, triperpenoids derivatives and diester‐diterpenoid aconitum alkaloid derivatives were characterised. Mesaconitine, flaconitine, ginsenosides Rb2, Rf, Rg2, F1 and Ro were considered to be new NF‐κB inhibitors. Furthermore, IL‐8 detection by enzyme linked immunosorbent assay confirmed the anti‐inflammatory effects of the potential NF‐κB inhibitors.ConclusionCompared with conventional fingerprints, activity‐integrated fingerprints that contain both chemical and bioactive details offer a more comprehensive understanding of the chemical composition of plant materials. This strategy clearly demonstrated that dual bioactivity‐integrated fingerprinting is a powerful tool for the improved screening and identification of potential dual‐target lead compounds in complex herbal medicines. Copyright © 2013 John Wiley & Sons, Ltd.
First trimester maternal serum placental growth factor levels in twin pregnancies
Authors: Cowans Nicholas J. , Spencer Kevin 
Published: October 2013

ABSTRACTBackgroundAn understanding of the normal behavior of biochemical markers in twin pregnancies is necessary in order to offer prenatal screening to this subgroup. This study investigates the levels of first trimester maternal serum placental growth factor (PlGF) in twin and singleton pregnancies.MethodsThe PlGF concentrations were measured by an automated assay in the first trimester maternal serum of 440 dichorionic twin, 116 monochorionic twin, and 607 singleton pregnancy samples thawed from frozen storage.ResultsThe PlGF concentrations in singleton levels were predicted by gestational age, maternal ethnicity, and smoking status. Following the correction for these variables, PlGF levels were, on average, 41% higher in dichorionics, but only 16% higher in monochorionics, compared to singleton pregnancies.ConclusionsFirst trimester maternal serum PlGF levels are increased in twin pregnancies compared with singleton pregnancies, but to less of an extent than is common with other screening markers, especially in monochorionic twins. © 2013 John Wiley & Sons, Ltd.
Prescribing of antipsychotic drugs in patients with dementia: a comparison with age‐matched and sex‐matched non‐demented controls
Authors: Schulze Jana , Glaeske Gerd , van den Bussche Hendrik , Kaduszkiewicz Hanna , Koller Daniela , Wiese Birgitt , Hoffmann Falk 
Published: October 2013

ABSTRACTPurposeSince the beginning of the 21st century, serious adverse events and an increased risk of mortality have been documented in patients with dementia treated with antipsychotics. The aim of this study was to assess antipsychotic prescribing in patients with incident dementia compared with a non‐demented control group.MethodsWe analysed the claims data of a German health insurance company for incident dementia patients and age‐matched and sex‐matched non‐demented controls aged 65 years and older in 2004 to 2006. The data were used to analyse the prescribing patterns of antipsychotics in the year of dementia incidence. We estimated odds ratios stratified by age, sex, care setting and care dependence and in a multivariate logistic regression.ResultsThe 1848 patients with and 7385 persons without dementia were on average 78.8 years old (standard deviation: 7.4), and 47.6% were women. A total of 25.4% of the dementia patients received antipsychotics compared with 4.3% of the controls (ORcrude: 7.61; 95%CI: 6.52–8.87). An increase in care level, age, female gender and living in a nursing home is associated with a considerably higher prevalence of at least one prescription for antipsychotics. After adjusting for all these variables, a significant influence of age could no longer be found.ConclusionsThe results show that antipsychotics play an important role in dementia care—despite the risk of adverse events. Further research is needed with regard to safe pharmacological and non‐pharmacological approaches for the behavioural and psychological symptoms of dementia in this vulnerable group. Copyright © 2013 John Wiley & Sons, Ltd.
The Role of Pharmacogenetics in the Treatment of Chronic Hepatitis C Infection
Authors: Kawaguchi‐Suzuki Marina , Frye Reginald F. 
Published: October 2013

Hepatitis C virus (HCV) chronically infects 170 million people worldwide. Until recently, combination therapy with peginterferon‐α (pegIFN) and ribavirin (RBV) has been the standard of care. However, for many patients, especially those infected with the most common HCV genotype 1 (HCV‐1), this treatment has resulted in unsatisfactory treatment response rates. Many clinical factors, including pharmacogenetics, influence the treatment response rate. Genetic variation in the interleukin 28B (IL28B) gene is the major determinant of treatment response, a finding that has been replicated in multiple independent cohorts. This review focuses on the association between pharmacogenetics and conventional pegIFN/RBV therapy in patients infected with HCV non–genotype 1; patients reinfected with HCV after liver transplantation; and patients coinfected with HCV and human immunodeficiency virus. We also review the pharmacogenetic data for boceprevir and telaprevir triple therapy in patients with HCV‐1 infection, as well as viral genomic polymorphisms and genetic variants that may protect against anemia. Pharmacogenetic information offers a personalized medicine approach to help clinicians and patients make better informed decisions to maximize response and minimize toxicity for the treatment of chronic HCV infection.
All‐screen‐printed back‐contact back‐junction silicon solar cells with aluminum‐alloyed emitter and demonstration of interconnection of point‐shaped metalized contacts
Authors: Woehl Robert , Rüdiger Marc , Biro Daniel , Wilde Jürgen 
Published: October 2013

AbstractIn the following, high‐efficiency back‐contact back‐junction silicon solar cells with aluminum‐alloyed emitter are described. First, the theoretical background for the cell concept is explained. To that purpose, the bulk lifetime and the front surface field characteristics are considered. Three different process sequences for the phosphorus‐diffused profiles on the front and back surfaces are depicted: One exhibits a shallow field, and two sequences have deeper, driven‐in profiles. For realizing high efficiencies, such cell structures must meet several prerequisites, such as firing‐stable front and rear passivations, and functional small screen‐printed Al structures. Furthermore, it must be possible to create contacts on the Si surfaces using the driven‐in P‐profiles. With such a structure, cell efficiencies of 20.0% are reached. An analysis of the series resistance and area‐weighted recombination is performed. The results are compared with the measured cell parameters. Two‐dimensional simulations show the efficiency potential when decreasing the width of the backside field and when a cell structure, which would inhibit a passivated aluminum‐alloyed p+‐emitter, is created. Also, an advanced concept is demonstrated where a point array of both polarities on the cell backside is interconnected externally on module level. To that purpose, the cell is soldered to a printed wiring circuit board by using a reflow soldering process. Copyright © 2013 John Wiley & Sons, Ltd.