bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic selection allowing for marker‐by‐environment interaction
Authors: Schulz‐Streeck Torben , Ogutu Joseph O. , Gordillo Andrés , Karaman Zivan , Knaak Carsten , Piepho Hans‐Peter 
Published: October 2013

AbstractGenomic selection has been routinely implemented in plant breeding in two stages. The first stage usually omits the marker information and estimates adjusted means of genotypes across environments. The second stage uses the adjusted means to predict genomic breeding values. However, if the effects of markers vary substantially between different environments, it may be important to account for this variation for varieties adapted to different environments. Using two maize data sets, we investigated whether modelling the marker‐by‐environment interaction can improve the predictive ability of genomic selection relative to modelling genotype‐by‐environment interaction alone. Modelling the marker‐by‐environment interaction did not substantially increase the predictive ability relative to modelling only the genotype‐by‐environment interaction for the two tested data sets. Thus, genomic selection, carried out in a stagewise fashion, such that the marker information is omitted until the last stage of the process, may suffice for most practical purposes. Moreover, predictive ability did not reduce substantially even when the number of markers with consistent effects across environments used for genomic prediction was reduced to about 50.
CostalBCGosteomyelitis developing 1 year afterBCGvaccination
Authors: Oyachi Noboru , Obana Kazuko , Suzuki Takeyuki , Kimura Shuri , Chino Kozo , Oyama Toshio , Takano Kunio 
Published: October 2013

AbstractReported here is the case of a 15‐month‐old boy with costal osteomyelitis due to the bacillusCalmette–Guérin (BCG) vaccine against tuberculosis. Mild complications of this vaccine, such as localized abscess and regional lymphadenitis, are occasionally recognized, but its association with osteomyelitis is extremely rare.
Thrombolytic therapy in Kawasaki disease: A report of four cases
Authors: Harada Mana , Akimoto Katsumi , Otaka Masao , Sato Keiko , Oda Hisayuki , Otsuki Masahiro , Takahashi Ken , Kishiro Masahiko , Shimizu Toshiaki 
Published: October 2013

AbstractFour patients with a thrombus in a coronary artery aneurysm due to Kawasaki disease (KD) were treated at our hospital between 1994 and 2009. All the cases were treated with intravenous coronary thrombolysis (IVCT) therapy and the cases with acute myocardial infarction were treated with additional intracoronary thrombolysis therapy. Although both thrombolytic therapies were effective, IVCT required more time than intracoronary thrombolysis to resolve the thrombus. We concluded that IVCT can be used as the first‐line thrombolytic therapy for KD, except in cases with acute myocardial infarction.
Post‐streptococcal acute glomerulonephritis associated with pneumococcal infection
Authors: Hibino Satoshi , Hoshino Akihiro , Fujii Takanari , Abe Yoshifusa , Watanabe Shuichiro , Uemura Osamu , Itabashi Kazuo 
Published: October 2013

AbstractStreptococcus pyogenes is the most common cause of post‐infectious glomerulonephritis. Described herein is the case of a 5‐year‐old girl with febrile post‐streptococcal acute glomerulonephritis (PSAGN) associated with pneumococcal bacteremia. The chief complaints were fever and macrohematuria without respiratory symptoms. Urinalysis indicated a protein level of 3+. Serological data showed elevated anti‐streptolysin O (ASO) and hypocomplementemia. Blood culture was positive for S. pneumoniae. Her acute renal failure was mild and improved over several days. Although PSAGN was confirmed by elevated ASO and transient hypocomplementemia, the clinical course was consistent with those of several reported cases of AGN associated with pneumococcal infection. To our knowledge, there have been few reports on the relationship between pneumococcal infection and the incidence of PSAGN. We suggest the hypothesis that pneumococcal infection itself could exaggerate the complement reaction leading to PSAGN. It is important to consider PSAGN associated with a microbial infection such as S. pneumoniae when faced with a febrile patient with AGN.
Anaplastic sarcoma of the kidney: Case report and literature review
Authors: Watanabe Noriko , Omagari Daisuke , Yamada Tsutomu , Nemoto Norimichi , Furuya Takeshi , Sugito Kiminobu , Koshinaga Tsugumichi , Yagasaki Hiroshi , Sugitani Masahiko 
Published: October 2013

AbstractAnaplastic sarcoma of the kidney (ASK) is a relatively newly recognized pediatric renal tumor. The present patient, a 13‐year‐old boy with a large renal mass, underwent surgery. Pathological findings showed proliferation of short spindle‐shaped cells with anaplastic features including multiple foci in hyaline cartilage. Complex chromosomal abnormalities were detected in the tumor cells. Postoperative chemotherapy with the regimen for Ewing's sarcoma achieved complete remission but the tumor recurred and the patient died during re‐induction chemotherapy. Autopsy indicated the cause of death as duodenal hemorrhage. Because there were no viable tumor cells, the recurrent tumor was considered to have been completely cured by chemotherapy. ASK is a very rare tumor, of unknown pathogenesis, and no standard treatment has yet been established, but the tumor cells may be responsive to chemotherapy. Further study is needed to establish the optimal treatment strategy.
Erythrocyte dysplasia in peripheral blood smears from 5 thrombocytopenic dogs treated with vincristine sulfate
Authors: Collicutt Nancy B. , Garner Bridget 
Published: October 2013

AbstractSecondary dyserythropoiesis has been associated with vincristine administration in dogs. Evaluation of bone marrow aspirates for the presence of morphologic abnormalities in the erythroid lineage aids in the diagnosis. However, morphologic features of circulating erythroid precursors in these cases have not been described previously. The purpose of this report was to describe the cytologic features of dyserythropoiesis in peripheral blood and also bone marrow smears in a case series of dogs with immune‐mediated thrombocytopenia (IMT) treated with vincristine sulfate. Nineteen dogs receiving vincristine for treatment ofIMTwere identified by retrospectively searching a computerized medical record system. There were 5 dogs that had dysplastic erythroid precursors in peripheral blood smears within 7 days of vincristine treatment. Two of those 5 dogs also had evidence for erythrodysplasia in modified Wright's‐stained bone marrow smears obtained postvincristine administration. Morphologic changes included bizarre or inappropriate mitotic figures, abnormal nuclear configurations (fragmentation, elongation, indentation, and binucleation), atypical nuclear remnants (Howell‐Jolly bodies), or nuclear and cytoplasmic asynchrony within the erythroid precursors. A brief review of the literature with discussion of the etiologies for dyserythropoiesis is provided. The dyserythropoiesis was clinically insignificant in all 5 cases and resolved. However, pathologists and clinicians should be aware of these potential findings to prevent misdiagnosis of other conditions.
Genes–Environment Interactions in Obesity- and Diabetes-Associated Pancreatic Cancer: A GWAS Data Analysis
Authors: Tang Hongwei , Wei Peng , Duell Eric J. , Risch Harvey A. , Olson Sara H. , Bueno-de-Mesquita H. Bas , Gallinger Steven , Holly Elizabeth A. , Petersen Gloria M. , Bracci Paige M. , McWilliams Robert R. , Jenab Mazda , Riboli Elio , Tjønneland Anne , Boutron-Ruault Marie Christine , Kaaks Rudolf , Trichopoulos Dimitrios , Panico Salvatore , Sund Malin , Peeters Petra H.M. , Khaw Kay-Tee , Amos Christopher I. , Li Donghui 
Published: October 2013

Abstract
Background: Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level.
Methods: Using genome-wide association studies (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study of 2,028 cases and 2,109 controls to examine gene–obesity and gene–diabetes interactions in relation to pancreatic cancer risk by using the likelihood-ratio test nested in logistic regression models and Ingenuity Pathway Analysis (IPA).
Results: After adjusting for multiple comparisons, a significant interaction of the chemokine signaling pathway with obesity (P = 3.29 × 10−6) and a near significant interaction of calcium signaling pathway with diabetes (P = 1.57 × 10−4) in modifying the risk of pancreatic cancer were observed. These findings were supported by results from IPA analysis of the top genes with nominal interactions. The major contributing genes to the two top pathways include GNGT2, RELA, TIAM1, and GNAS. None of the individual genes or single-nucleotide polymorphism (SNP) except one SNP remained significant after adjusting for multiple testing. Notably, SNP rs10818684 of the PTGS1 gene showed an interaction with diabetes (P = 7.91 × 10−7) at a false discovery rate of 6%.
Conclusions: Genetic variations in inflammatory response and insulin resistance may affect the risk of obesity- and diabetes-related pancreatic cancer. These observations should be replicated in additional large datasets.
Impact: A gene–environment interaction analysis may provide new insights into the genetic susceptibility and molecular mechanisms of obesity- and diabetes-related pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 23(1); 98–106. ©2013 AACR.
Trastuzumab Emtansine: A Novel Antibody–Drug Conjugate for HER2-Positive Breast Cancer
Authors: Krop Ian , Winer Eric P. 
Published: October 2013

Abstract
Trastuzumab emtansine (T-DM1) is a novel HER2-directed antibody–drug conjugate. T-DM1 consists of the potent antimicrotubule agent DM1, linked via a noncleavable linker to the HER2-specific monoclonal antibody trastuzumab. Preclinical studies demonstrate that T-DM1 has dual mechanisms of action: selective delivery of DM1 to the HER2-positive (HER2+) tumor cell combined with trastuzumab's activation of antibody-dependent cell-mediated cytotoxicity and inhibition of HER2-mediated signal transduction. In phase II studies, T-DM1 was active in patients with trastuzumab- and lapatinib-refractory metastatic breast cancer and led to improved progression-free survival compared with the combination of trastuzumab and docetaxel in the first-line setting. In a recent phase III trial in patients with metastatic breast cancer who previously received trastuzumab and a taxane, T-DM1 resulted in improved progression-free and overall survival compared with capecitabine and lapatinib. T-DM1 is associated with a favorable toxicity profile; reversible thrombocytopenia and hepatic transaminase elevations are the only grade ≥3 adverse event present in 5% or more of patients. Alopecia, peripheral neuropathy, and neutropenia are distinctly uncommon. On the basis of its improved efficacy and toxicity compared with capecitabine/lapatinib, T-DM1 should be considered the standard for patients with HER2+ metastatic breast cancer who have previously progressed on trastuzumab and a taxane. Results from additional randomized studies in metastatic breast cancer are pending, and trials in the (neo)adjuvant setting are being initiated. Clin Cancer Res; 20(1); 15–20. ©2013 AACR.
ATP Citrate Lyase Mediates Resistance of Colorectal Cancer Cells to SN38
Authors: Zhou Yunfei , Bollu Lakshmi Reddy , Tozzi Federico , Ye Xiangcang , Bhattacharya Rajat , Gao Guang , Dupre Elizabeth , Xia Ling , Lu Jia , Fan Fan , Bellister Seth , Ellis Lee M. , Weihua Zhang 
Published: October 2013

AbstractCombination chemotherapy is standard for metastatic colorectal cancer; however, nearly all patients develop drug resistance. Understanding the mechanisms that lead to resistance to individual chemotherapeutic agents may enable identification of novel targets and more effective therapy. Irinotecan is commonly used in first- and second-line therapy for patients with metastatic colorectal cancer, with the active metabolite being SN38. Emerging evidence suggests that altered metabolism in cancer cells is fundamentally involved in the development of drug resistance. Using Oncomine and unbiased proteomic profiling, we found that ATP citrate lyase (ACLy), the first-step rate-limiting enzyme for de novo lipogenesis, was upregulated in colorectal cancer compared with its levels in normal mucosa and in chemoresistant colorectal cancer cells compared with isogenic chemo-naïve colorectal cancer cells. Overexpression of exogenous ACLy by lentivirus transduction in chemo-naïve colorectal cancer cells led to significant chemoresistance to SN38 but not to 5-fluorouracil or oxaliplatin. Knockdown of ACLy by siRNA or inhibition of its activity by a small-molecule inhibitor sensitized chemo-naïve colorectal cancer cells to SN38. Furthermore, ACLy was significantly increased in cancer cells that had acquired resistance to SN38. In contrast to chemo-naïve cells, targeting ACLy alone was not effective in resensitizing resistant cells to SN38, due to a compensatory activation of the AKT pathway triggered by ACLy suppression. Combined inhibition of AKT signaling and ACLy successfully resensitized SN38-resistant cells to SN38. We conclude that targeting ACLy may improve the therapeutic effects of irinotecan and that simultaneous targeting of ACLy and AKT may be warranted to overcome SN38 resistance. Mol Cancer Ther; 12(12); 2782–91. ©2013 AACR.
The Molecular Balancing Act of p16INK4a in Cancer and Aging
Authors: LaPak Kyle M. , Burd Christin E. 
Published: October 2013

Abstract
p16INK4a, located on chromosome 9p21.3, is lost among a cluster of neighboring tumor suppressor genes. Although it is classically known for its capacity to inhibit cyclin-dependent kinase (CDK) activity, p16INK4a is not just a one-trick pony. Long-term p16INK4a expression pushes cells to enter senescence, an irreversible cell-cycle arrest that precludes the growth of would-be cancer cells but also contributes to cellular aging. Importantly, loss of p16INK4a is one of the most frequent events in human tumors and allows precancerous lesions to bypass senescence. Therefore, precise regulation of p16INK4a is essential to tissue homeostasis, maintaining a coordinated balance between tumor suppression and aging. This review outlines the molecular pathways critical for proper p16INK4a regulation and emphasizes the indispensable functions of p16INK4a in cancer, aging, and human physiology that make this gene special. Mol Cancer Res; 12(2); 167–83. ©2013 AACR.
Crucial Role of ROCK2 in Vascular Smooth Muscle Cells for Hypoxia-Induced Pulmonary Hypertension in Mice
Authors: Shimizu Toru , Fukumoto Yoshihiro , Tanaka Shin-ichi , Satoh Kimio , Ikeda Shohei , Shimokawa Hiroaki 
Published: October 2013

Objective—
Rho/Rho-kinase (ROCK) pathway in vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of cardiovascular diseases, including pulmonary arterial hypertension (PAH). Rho-kinase has 2 isoforms, ROCK1 and ROCK2, with different functions in different cells; ROCK1 for circulating inflammatory cells and ROCK2 for the vasculature. In the present study, we aimed to examine whether ROCK2 in VSMC is involved in the pathogenesis of PAH.

Approach and Results—

In patients with PAH, the expression of ROCK2 was increased in pulmonary arterial media and primary pulmonary arterial smooth muscle cells when compared with controls. To investigate the role of ROCK2 in VSMC, we generated VSMC-specific heterozygous ROCK2-deficient (ROCK2
+/−
) mice and VSMC-specific ROCK2-overexpressing transgenic (ROCK2-Tg) mice. The extent of hypoxia-induced pulmonary hypertension was reduced in ROCK2
+/−
mice and was enhanced in ROCK2-Tg mice compared with respective littermates. The protein expression of ROCK activity and phosphorylated extracellular signal–regulated kinase and the number of Ki67-positive proliferating cells in the lung were reduced in ROCK2
+/−
mice and were increased in ROCK2-Tg mice compared with respective littermates. In cultured mouse aortic VSMC, migration and proliferation activities were reduced in ROCK2
+/−
mice, and migration activity was increased in ROCK2-Tg mice compared with respective littermates. In addition, in primary pulmonary arterial smooth muscle cells from a patient with PAH, ROCK2 was required for migration and proliferation through ROCK and extracellular signal–regulated kinase activation.

Conclusions—
ROCK2 in VSMC contributes to the pathogenesis of PAH.
Pericyte Regulation of Vascular Remodeling Through the CXC Receptor 3
Authors: Bodnar Richard J. , Rodgers Margaret E. , Chen William C.W. , Wells Alan 
Published: October 2013

Objective—
To understand the role, if any, played by pericytes in the regulation of newly formed vessels during angiogenesis. In this study, we investigate whether pericytes regulate the number of nascent endothelial tubes.

Approach and Results—
Using an in vitro angiogenesis assay (Matrigel assay), we demonstrate that pericytes can inhibit vessel formation and induce vessel dissociation via CXCR3-induced involution of the endothelial cells. In a coculture Matrigel assay for cord formation, pericytes prevented endothelial cord formation of human dermal microvascular endothelial cells but not umbilical vein endothelial cells. Blockade of endothelial CXCR3 function or expression inhibited the repressing effect of the pericytes. We further show that pericytes are also able to induce regression of newly formed microvascular cords through CXCR3 activation of calpain. When CXCR3 function was inhibited by a neutralizing antibody or downregulated by siRNA, cord regression mediated by pericytes was abolished.

Conclusions—
We show for the first time that pericytes regulate angiogenic vessel formation, and that this is mediated through CXCR3 expressed on endothelial cells. This suggests a role for pericytes in the pruning of immature vessels overproduced during wound repair.
Assessment of Mitral Valve Area During Percutaneous Mitral Valve Repair Using the MitraClip System
Authors: Biaggi Patric , Felix Christian , Gruner Christiane , Herzog Bernhard A. , Hohlfeld Sabine , Gaemperli Oliver , Stähli Barbara E. , Paul Michaela , Held Leonhard , Tanner Felix C. , Grünenfelder Jürg , Corti Roberto , Bettex Dominique 
Published: October 2013

Background—
Quantification of the mitral valve area (MVA) is important to guide percutaneous mitral valve repair using the MitraClip system. However, little is known about how to best assess MVA in this specific situation.

Methods and Results—

Immediately before and after MitraClip implantation, comprehensive 3-dimensional (3D) transesophageal echocardiography data were acquired for MVA assessment by the pressure half-time method and by two 3D quantification methods (mitral valve quantification software and 3D quantification software). In addition, transmitral gradients by continuous-wave Doppler (dPmean
CW
) were measured to indirectly assess MVA. Data are given as median (interquartile range). Thirty-three patients (39% women) with a median age of 77.1 years (12.4 years) were studied. Before intervention, the median MVAs by the pressure half-time method, mitral valve quantification software, and 3D quantification software were 4.4 cm
2
(2.0 cm
2
), 4.7 cm
2
(2.4 cm
2
), and 6.2 cm
2
(2.4 cm
2
), respectively (
P
<0.001). After intervention, MVA was reduced to 1.9 cm
2
(0.7 cm
2
), 2.1 cm
2
(1.1 cm
2
), and 2.8 cm
2
(1.1 cm
2
), respectively (
P
=0.001). The median values for dPmean
CW
before and after intervention were 1.0 mm Hg (1.0 mm Hg) and 3.0 mm Hg (3.0 mm Hg;
P
<0.001), respectively. At discharge, the median dPmean
CW
was 4.0 mm Hg (3.0 mm Hg). In multivariate regression analyses including body surface area, the 3 different MVA methods, and dPmean
CW
, a post-dPmean
CW
≥5 mm Hg was the best independent predictor of an elevated transmitral gradient at discharge.

Conclusions—
Transmitral gradients by continuous-wave Doppler are quick, feasible in all patients, and superior to direct peri-interventional assessment of MVA. A postinterventional transmitral gradient by continuous-wave Doppler of ≥5 mm Hg best predicted elevated transmitral gradients at discharge.
Placental Vascular Dysfunction, Fetal and Childhood Growth, and Cardiovascular Development
Authors: Gaillard Romy , Steegers Eric A.P. , Tiemeier Henning , Hofman Albert , Jaddoe Vincent W.V. 
Published: October 2013

Background—
Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development.

Methods and Results—

This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (
P
values < 0.05). These differences in length and weight growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (
P
values<0.05). These associations were not explained by birth weight. Stronger associations tended to be present among girls as compared with boys.

Conclusions—
Higher third trimester feto-placental vascular resistance, but not utero-placental vascular resistance, was associated with slower fetal growth rates and cardiovascular adaptations in childhood.