bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Pathogenic Mammalian Orthoreovirus from Diarrheic Pigs and Swine Blood Meal in the United States
Authors: Thimmasandra Narayanappa Athmaram , Sooryanarain Harini , Deventhiran Jagadeeswaran , Cao Dianjun , Ammayappan Venkatachalam Backiyalakshmi , Kambiranda Devaiah , LeRoith Tanya , Heffron Connie Lynn , Lindstrom Nicole , Hall Karen , Jobst Peter , Sexton Cary , Meng Xiang-Jin , Elankumaran Subbiah 
Published: May 2015

ABSTRACT
Since May 2013, outbreaks of porcine epidemic diarrhea have devastated the U.S. swine industry, causing immense economic losses. Two different swine enteric coronaviruses (porcine epidemic diarrhea virus and Delta coronavirus) have been isolated from the affected swine population. The disease has been reported from at least 32 states of the United States and other countries, including Mexico, Peru, Dominican Republic, Canada, Columbia, Ecuador, and Ukraine, with repeated outbreaks in previously infected herds. Here we report the isolation and characterization of a novel mammalian orthoreovirus 3 (MRV3) from diarrheic feces of piglets from these outbreaks in three states and ring-dried swine blood meal from multiple sources. MRV3 could not be isolated from healthy or pigs that had recovered from epidemic diarrhea from four states. Several MRV3 isolates were obtained from chloroform-extracted pig feces or blood meal in cell cultures or developing chicken embryos. Biological characterization of two representative isolates revealed trypsin resistance and thermostability at 90°C. NextGen sequencing of ultrapurified viruses indicated a strong homology of the S1 segment to mammalian and bat MRV3. Neonatal piglets experimentally infected with these viruses or a chloroform extract of swine blood meal developed severe diarrhea and acute gastroenteritis with 100% mortality within 3 days postinfection. Therefore, the novel porcine MRV3 may contribute to enteric disease along with other swine enteric viruses. The role of MRV3 in the current outbreaks of porcine epidemic diarrhea in the United States remains to be determined, but the pathogenic nature of the virus warrants further investigations on its epidemiology and prevalence.

IMPORTANCE
Porcine orthoreoviruses causing diarrhea have been reported in China and Korea but not in the United States. We have isolated and characterized two pathogenic reassortant MRV3 isolates from swine fecal samples from porcine epidemic diarrhea outbreaks and ring-dried swine blood meal in the United States. These fecal and blood meal isolates or a chloroform extract of blood meal induced severe diarrhea and mortality in experimentally infected neonatal pigs. Genetic and phylogenetic analyses of two MRV3 isolates revealed that they are identical but differed significantly from nonpathogenic mammalian orthoreoviruses circulating in the United States. The present study provides a platform for immediate development of suitable vaccines and diagnostics to prevent and control porcine orthoreovirus diarrhea.
Effectiveness of moxibustion for allergic rhinitis: protocol for a systematic review
Authors: Chen Sheng , Guo Shengnan , Wang Jun , Ha Eunhae , Marmori Federico , Wang Yanping , Zhao Jiping 
Published: May 2015

IntroductionThe objective of this review is to systematically evaluate the effectiveness of moxibustion for treating allergic rhinitis (AR).Methods and analysisThe following databases will be searched from their inception to January 2015: MEDLINE, EMBASE, CINAHL, AMED, Web of Science, Ovid Healthstar, PubMed, SciELO, the China National Knowledge Infrastructure Database, the Chongqing VIP Chinese Science and Technology Periodical Database, the Chinese Biomedical Database, the Wanfang Database, the Japanese Medical Research Database, and Korean Medical Databases. The methodological quality will be assessed using the Cochrane risk of bias tool. The primary outcome is total nasal symptoms, which may be evaluated by any appropriate scores or other forms of measurement. Secondary outcome measures will include quality of life, total non-nasal symptoms, use of daily medication and laboratory indicators.Ethics and disseminationBecause this study will not involve patients, institutional review body permission is not required. The systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print to help guide healthcare practice and policy.Trial registration numberPROSPERO CRD42014013275.
Workload and management of childhood fever at general practice out-of-hours care: an observational cohort study
Authors: de Bont Eefje G P M , Lepot Julie M M , Hendrix Dagmar A S , Loonen Nicole , Guldemond-Hecker Yvonne , Dinant Geert-Jan , Cals Jochen W L 
Published: May 2015

ObjectiveEven though childhood fever is mostly self-limiting, children with fever constitute a considerable workload in primary care. Little is known about the number of contacts and management during general practitioners’ (GPs) out-of-hours care. We investigated all fever related telephone contacts, consultations, antibiotic prescriptions and paediatric referrals of children during GP out-of-hours care within 1 year.DesignObservational cohort study.Setting and patientsWe performed an observational cohort study at a large Dutch GP out-of-hours service. Children (<12 years) whose parents contacted the GP out-of-hours service for a fever related illness in 2012 were included.Main outcome measuresNumber of contacts and consultations, antibiotic prescription rates and paediatric referral rates.ResultsWe observed an average of 14.6 fever related contacts for children per day at GP out-of-hours services, with peaks during winter months. Of 17 170 contacts in 2012, 5343 (31.1%) were fever related and 70.0% resulted in a GP consultation. One in four consultations resulted in an antibiotic prescription. Prescriptions increased by age and referrals to secondary care decreased by age (p<0.001). The majority of parents (89.5%) contacted the out-of-hours service only once during a fever episode (89.5%) and 7.6% of children were referred to secondary care.ConclusionsThis study shows that childhood fever does account for a large workload at GP out-of-hours services. One in three contacts is fever related and 70% of those febrile children are called in to be assessed by a GP. One in four consultations for childhood fever results in antibiotic prescribing and most consultations are managed in primary care without referral.
DNA sequence analysis and genotype–phenotype assessment in 71 patients with syndromic hearing loss or auditory neuropathy
Authors: Tang Hsiao-Yuan , Fang Ping , Lin Jerry W , Darilek Sandra , Osborne Brooke T , Haymond Jo Ann , Manolidis Spiros , Roa Benjamin B , Oghalai John S , Alford Raye L 
Published: May 2015

ObjectivesAetiological assessment of 71 probands whose clinical presentation suggested a genetic syndrome or auditory neuropathy.MethodsSanger sequencing was performed on DNA isolated from peripheral blood or lymphoblastoid cell lines. Genes were selected for sequencing based on each patient's clinical presentation and suspected diagnosis. Observed DNA sequence variations were assessed for pathogenicity by review of the scientific literature, and mutation and polymorphism databases, through the use of in silico tools including sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen), and according to the recommendations of the American College of Medical Genetics and Genomics for the interpretation of DNA sequence variations. Novel DNA sequence variations were sought in controls.ResultsDNA sequencing of the coding and near-coding regions of genes relevant to each patient's clinical presentation revealed 37 sequence variations of known or uncertain pathogenicity in 9 genes from 25 patients. 14 novel sequence variations were discovered. Assessment of phenotypes revealed notable findings in 9 patients.ConclusionsDNA sequencing in patients whose clinical presentation suggested a genetic syndrome or auditory neuropathy provided opportunities for aetiological assessment and more precise genetic counselling of patients and families. The failure to identify a genetic aetiology in many patients in this study highlights the extreme heterogeneity of genetic hearing loss, the incompleteness of current knowledge of aetiologies of hearing loss, and the limitations of conventional DNA sequencing strategies that evaluate only coding and near-coding segments of genes.
Immunohistochemical panel to differentiate endometrial stromal sarcoma, uterine leiomyosarcoma and leiomyoma: something old and something new
Authors: Hwang Helena , Matsuo Koji , Duncan Kara , Pakzamir Elham , Pham Huyen Q , Correa Adrian , Fedenko Alexander , Mhawech-Fauceglia Paulette 
Published: May 2015

AimsTo evaluate an immunohistochemical panel differentiating endometrial stromal sarcoma (ESS) from uterine leiomyosarcoma (ULMS) and leiomyoma (LM).Methods94 cases (28 ESS, 41 ULMS, 25 LM) were retrieved and arrayed. 10 immunomarkers (estrogen receptor (ER), progesterone receptor (PR), CD10, smooth muscle actin, desmin, h-caldesmon, transgelin, GEM, ASC1, stathmin1) were used. A predictive model was constructed and examined by receiver operating characteristics curve analysis to determine area under the curve (AUC).ResultsThe combination of ER+/PR+/CD10+/GEM−/h-caldesmon−/transgelin−can predict ESS versus ULMS with AUC predictive value of 0.872 (95% CI 0.784 to 0.961, p<0.0001). The combination of ER+/PR+/CD10+/h-caldesmon−/transgelin−can predict low grade (LG) ESS from ‘LG’ ULMS with AUC predictive value of 0.914 (95% CI 0.832 to 0.995, p<0.0001). Finally, ULMS and ESS, including the LGs, were more likely to be stathmin1+than LM.ConclusionsDue to the different clinical course and management, adding novel antibodies (GEM, transgelin) to the well established immunohistochemistry panel seemed to be useful in distinguishing ESS from ULMS and LG ESS from ‘LG’ ULMS. Finally, stathmin1 expression could be of value in differentiating LM from uterine sarcomas.
Observer variability in the assessment of CT coronary angiography and coronary artery calcium score: substudy of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial
Authors: Williams Michelle C , Golay Saroj K , Hunter Amanda , Weir-McCall Jonathan R , Mlynska Lucja , Dweck Marc R , Uren Neal G , Reid John H , Lewis Steff C , Berry Colin , van Beek Edwin J R , Roditi Giles , Newby David E , Mirsadraee Saeed 
Published: May 2015

IntroductionObserver variability can influence the assessment of CT coronary angiography (CTCA) and the subsequent diagnosis of angina pectoris due to coronary heart disease.MethodsWe assessed 210 CTCAs from the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial for intraobserver and interobserver variability. Calcium score, coronary angiography and image quality were evaluated. Coronary artery disease was defined as none (<10%), mild (10–49%), moderate (50–70%) and severe (>70%) luminal stenosis and classified as no (<10%), non-obstructive (10–70%) or obstructive (>70%) coronary artery disease. Post-CTCA diagnosis of angina pectoris due to coronary heart disease was classified as yes, probable, unlikely or no.ResultsPatients had a mean body mass index of 29 (28, 30) kg/m2, heart rate of 58 (57, 60)/min and 62% were men. Intraobserver and interobserver agreements for the presence or absence of coronary artery disease were excellent (95% agreement, κ 0.884 (0.817 to 0.951) and good (91%, 0.791 (0.703 to 0.879)). Intraobserver and interobserver agreement for the presence or absence of angina pectoris due to coronary heart disease were excellent (93%, 0.842 (0.918 to 0.755) and good (86%, 0.701 (0.799 to 0.603)), respectively. Observer variability of calcium score was excellent for calcium scores below 1000. More segments were categorised as uninterpretable with 64-multidetector compared to 320-multidetector CTCA (10.1% vs 2.6%, p<0.001) but there was no difference in observer variability.ConclusionsMulticentre multidetector CTCA has excellent agreement in patients under investigation for suspected angina due to coronary heart disease.Trial registration numberNCT01149590.
NOS Inhibition Modulates Immune Polarization and Improves Radiation-Induced Tumor Growth Delay
Authors: Ridnour Lisa A. , Cheng Robert Y.S. , Weiss Jonathan M. , Kaur Sukhbir , Soto-Pantoja David R. , Basudhar Debashree , Heinecke Julie L. , Stewart C. Andrew , DeGraff William , Sowers Anastasia L. , Thetford Angela , Kesarwala Aparna H. , Roberts David D. , Young Howard A. , Mitchell James B. , Trinchieri Giorgio , Wiltrout Robert H. , Wink David A. 
Published: May 2015

Abstract
Nitric oxide synthases (NOS) are important mediators of progrowth signaling in tumor cells, as they regulate angiogenesis, immune response, and immune-mediated wound healing. Ionizing radiation (IR) is also an immune modulator and inducer of wound response. We hypothesized that radiation therapeutic efficacy could be improved by targeting NOS following tumor irradiation. Herein, we show enhanced radiation-induced (10 Gy) tumor growth delay in a syngeneic model (C3H) but not immunosuppressed (Nu/Nu) squamous cell carcinoma tumor-bearing mice treated post-IR with the constitutive NOS inhibitor NG-nitro-l-arginine methyl ester (L-NAME). These results suggest a requirement of T cells for improved radiation tumor response. In support of this observation, tumor irradiation induced a rapid increase in the immunosuppressive Th2 cytokine IL10, which was abated by post-IR administration of L-NAME. In vivo suppression of IL10 using an antisense IL10 morpholino also extended the tumor growth delay induced by radiation in a manner similar to L-NAME. Further examination of this mechanism in cultured Jurkat T cells revealed L-NAME suppression of IR-induced IL10 expression, which reaccumulated in the presence of exogenous NO donor. In addition to L-NAME, the guanylyl cyclase inhibitors ODQ and thrombospondin-1 also abated IR-induced IL10 expression in Jurkat T cells and ANA-1 macrophages, which further suggests that the immunosuppressive effects involve eNOS. Moreover, cytotoxic Th1 cytokines, including IL2, IL12p40, and IFNγ, as well as activated CD8+ T cells were elevated in tumors receiving post-IR L-NAME. Together, these results suggest that post-IR NOS inhibition improves radiation tumor response via Th1 immune polarization within the tumor microenvironment. Cancer Res; 75(14); 2788–99. ©2015 AACR.
The Impact of DNA Input Amount and DNA Source on the Performance of Whole-Exome Sequencing in Cancer Epidemiology
Authors: Zhu Qianqian , Hu Qiang , Shepherd Lori , Wang Jianmin , Wei Lei , Morrison Carl D. , Conroy Jeffrey M. , Glenn Sean T. , Davis Warren , Kwan Marilyn L. , Ergas Isaac J. , Roh Janise M. , Kushi Lawrence H. , Ambrosone Christine B. , Liu Song , Yao Song 
Published: May 2015

Abstract
Background: Whole-exome sequencing (WES) has recently emerged as an appealing approach to systematically study coding variants. However, the requirement for a large amount of high-quality DNA poses a barrier that may limit its application in large cancer epidemiologic studies. We evaluated the performance of WES with low input amount and saliva DNA as an alternative source material.
Methods: Five breast cancer patients were randomly selected from the Pathways Study. From each patient, four samples, including 3 μg, 1 μg, and 0.2 μg blood DNA and 1 μg saliva DNA, were aliquoted for library preparation using the Agilent SureSelect Kit and sequencing using Illumina HiSeq2500. Quality metrics of sequencing and variant calling, as well as concordance of variant calls from the whole exome and 21 known breast cancer genes, were assessed by input amount and DNA source.
Results: There was little difference by input amount or DNA source on the quality of sequencing and variant calling. The concordance rate was about 98% for single-nucleotide variant calls and 83% to 86% for short insertion/deletion calls. For the 21 known breast cancer genes, WES based on low input amount and saliva DNA identified the same set variants in samples from a same patient.
Conclusions: Low DNA input amount, as well as saliva DNA, can be used to generate WES data of satisfactory quality.
Impact: Our findings support the expansion of WES applications in cancer epidemiologic studies where only low DNA amount or saliva samples are available. Cancer Epidemiol Biomarkers Prev; 24(8); 1207–13. ©2015 AACR.
Genome-Wide Analysis Uncovers Novel Recurrent Alterations in Primary Central Nervous System Lymphomas
Authors: Braggio Esteban , Van Wier Scott , Ojha Juhi , McPhail Ellen , Asmann Yan W. , Egan Jan , da Silva Jackline Ayres , Schiff David , Lopes M. Beatriz , Decker Paul A. , Valdez Riccardo , Tibes Raoul , Eckloff Bruce , Witzig Thomas E. , Stewart A. Keith , Fonseca Rafael , O'Neill Brian Patrick 
Published: May 2015

Abstract
Purpose: Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma confined to the central nervous system. Whether there is a PCNSL-specific genomic signature and, if so, how it differs from systemic diffuse large B-cell lymphoma (DLBCL) is uncertain.
Experimental Design: We performed a comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL patients. Testing comprised array-comparative genomic hybridization and whole exome sequencing.
Results: Biallelic inactivation of TOX and PRKCD was recurrently found in PCNSL but not in systemic DLBCL, suggesting a specific role in PCNSL pathogenesis. In addition, we found a high prevalence of MYD88 mutations (79%) and CDKN2A biallelic loss (60%). Several genes recurrently affected in PCNSL were common with systemic DLBCL, including loss of TNFAIP3, PRDM1, GNA13, TMEM30A, TBL1XR1, B2M, CD58, activating mutations of CD79B, CARD11, and translocations IgH-BCL6. Overall, B-cell receptor/Toll-like receptor/NF-κB pathways were altered in &gt;90% of PNCSL, highlighting its value for targeted therapeutic approaches. Furthermore, integrated analysis showed enrichment of pathways associated with immune response, proliferation, apoptosis, and lymphocyte differentiation.
Conclusions: In summary, genome-wide analysis uncovered novel recurrent alterations, including TOX and PRKCD, helping to differentiate PCNSL from systemic DLBCL and related lymphomas. Clin Cancer Res; 21(17); 3986–94. ©2015 AACR.
Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine Therapy–Resistant Breast Cancer
Authors: Wardell Suzanne E. , Ellis Matthew J. , Alley Holly M. , Eisele Koleen , VanArsdale Todd , Dann Stephen G. , Arndt Kim T. , Primeau Tina , Griffin Elizabeth , Shao Jieya , Crowder Robert , Lai Jin-Ping , Norris John D. , McDonnell Donald P. , Li Shunqiang 
Published: May 2015

AbstractPurpose: Endocrine therapy, using tamoxifen or an aromatase inhibitor, remains first-line therapy for the management of estrogen receptor (ESR1)–positive breast cancer. However, ESR1 mutations or other ligand-independent ESR1 activation mechanisms limit the duration of response. The clinical efficacy of fulvestrant, a selective estrogen receptor downregulator (SERD) that competitively inhibits agonist binding to ESR1 and triggers receptor downregulation, has confirmed that ESR1 frequently remains engaged in endocrine therapy–resistant cancers. We evaluated the activity of a new class of selective estrogen receptor modulators (SERM)/SERD hybrids (SSH) that downregulate ESR1 in relevant models of endocrine-resistant breast cancer. Building on the observation that concurrent inhibition of ESR1 and the cyclin-dependent kinases 4 and 6 (CDK4/6) significantly increased progression-free survival in advanced patients, we explored the activity of different SERD– or SSH–CDK4/6 inhibitor combinations in models of endocrine therapy–resistant ESR1+ breast cancer.Experimental Design: SERDs, SSHs, and the CDK4/6 inhibitor palbociclib were evaluated as single agents or in combination in established cellular and animal models of endocrine therapy–resistant ESR1+ breast cancer.Results: The combination of palbociclib with a SERD or an SSH was shown to effectively inhibit the growth of MCF7 cell or ESR1-mutant patient-derived tumor xenografts. In tamoxifen-resistant MCF7 xenografts, the palbociclib/SERD or SSH combination resulted in an increased duration of response as compared with either drug alone.Conclusions: A SERD– or SSH–palbociclib combination has therapeutic potential in breast tumors resistant to endocrine therapies or those expressing ESR1 mutations. Clin Cancer Res; 21(22); 5121–30. ©2015 AACR.See related commentary by DeMichele and Chodosh, p. 4999
Prediagnostic Obesity and Physical Inactivity Are Associated with Shorter Telomere Length in Prostate Stromal Cells
Authors: Joshu Corinne E. , Peskoe Sarah B. , Heaphy Christopher M. , Kenfield Stacey A. , Van Blarigan Erin L. , Mucci Lorelei A. , Giovannucci Edward L. , Stampfer Meir J. , Yoon GhilSuk , Lee Thomas K. , Hicks Jessica L. , De Marzo Angelo M. , Meeker Alan K. , Platz Elizabeth A. 
Published: May 2015

Abstract
Obesity and inactivity have been associated with advanced-stage prostate cancer, and poor prostate cancer outcomes, though the underlying mechanism(s) is unknown. To determine whether telomere shortening, which has been associated with lethal prostate cancer, may be a potential underlying mechanism, we prospectively evaluated the association between measures of adiposity, physical activity, and telomere length in 596 participants in the Health Professionals Follow-up Study, who were surgically treated for prostate cancer. Using tissue microarrays, we measured telomere length in cancer and benign cells using a telomere-specific FISH assay. Adiposity and activity were assessed via questionnaire within 2 years of diagnosis. Adjusting for age, pathologic stage, and grade, the median and SD of the per cell telomere signals were determined for each man for stromal cells and cancer cells by adiposity and activity categories. Overweight/obese men (54%) were similar to normal weight men on most factors, but had higher Gleason sum and lower activity levels. Overweight/obese men had 7.4% shorter telomeres in stromal cells than normal weight men (P = 0.06). The least active men had shorter telomeres in stromal cells than more active men (Ptrend = 0.002). Men who were overweight/obese and the least active had the shortest telomeres in stromal cells (20.7% shorter; P = 0.0005) compared with normal weight men who were the most active. Cancer cell telomere length and telomere length variability did not differ by measures of adiposity or activity. Telomere shortening in prostate cells may be one mechanism through which lifestyle influences prostate cancer risk and outcomes. Cancer Prev Res; 8(8); 737–42. ©2015 AACR.
Selective Serotonin Reuptake Inhibitors (SSRIs) and the Risk of Congenital Heart Defects: A Meta‐Analysis of Prospective Cohort Studies
Authors: Wang Shang , Yang Lijuan , Wang Lian , Gao Ling , Xu Biao , Xiong Yunyun 
Published: May 2015

Background

Recent studies have reported conflicting results on the association between selective serotonin reuptake inhibitors (
SSRI
s) and the risk of heart defects. We aimed to assess the association between
SSRI
s in pregnant women during the first trimester and the risk of congenital heart defects.

Methods and Results

PubMed and
EMBASE
up to July 2014 were searched for population‐based cohort studies that reported
SSRI
s in pregnant women during the first trimester and live infants’ heart defects at follow‐up. A meta‐analysis of published data was undertaken primarily by means of fixed‐effects models. Four cohort studies including 1 996 519 participants were included with a mean follow‐up period ranging from discharge to 72 months.
SSRI
s were not associated with increased risks of heart defects 1.06 (95% confidence interval: 0.94 to 1.18).

Conclusions

SSRI
s during the first trimester in pregnant women were not associated with increased risks for newborn heart defects.