bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastro‐esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease
Authors: Ingebrigtsen Truls S. , Marott Jacob L. , Vestbo Jørgen , Nordestgaard Børge G. , Hallas Jesper , Lange Peter 
Published: October 2014

AbstractBackground and objectiveWe tested the hypothesis that gastro‐esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD).MethodsAmong 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD and information on gastro‐esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We applied a multivariable Cox regression analysis with adjustment for well‐established risk factors associated with COPD exacerbations or gastro‐esophageal reflux disease, including COPD severity, and symptoms.ResultsIndividuals with COPD and gastro‐esophageal reflux disease had more chronic bronchitis (31 vs 21%, P = 0.004), more breathlessness (39 vs 22%, P < 0.001), and more of them had a history of respiratory infections (6.8 vs 1.4%, P < 0.001) than individuals with COPD but without gastro‐esophageal reflux disease. Among individuals with COPD and gastro‐esophageal reflux disease, those who did not use acid inhibitory treatment regularly had an increased risk of COPD exacerbations during follow‐up, hazards ratio (HR): HR = 2.7 (1.3–5.4, P = 0.006). Individuals with gastro‐esophageal reflux disease, using acid inhibitory treatment regularly did not have an increased risk of exacerbations, HR = 1.2 (0.6–2.7, P = 0.63).ConclusionsGastro‐esophageal reflux disease was associated with an increased risk of medically treated exacerbations of COPD, but only in those individuals who did not use acid inhibitory treatment regularly.
Twenty Years of Rural Entrepreneurship: A Bibliometric Survey
Authors: Pato Maria Lúcia , Teixeira Aurora A.C. 
Published: October 2014

AbstractEntrepreneurship has become a dynamic field of research in the last two decades. However, ‘rural entrepreneurship’ has been largely overlooked. It seems therefore timely to present a quantitative survey of the literature in this particular area. Based on 181 articles on rural entrepreneurship published in journals indexed inScopus, we found that rural entrepreneurship is an essentiallyEuropean concern, whose most prolific authors are affiliated with institutions in theUKandSpain. Organisational characteristics, policy measures and institutional frameworks and governance have attracted considerable attention in recent years, being considered emergent topics of research. In contrast, theory building has not attracted much research over the period in analysis, which suggests that the theoretical body of rural entrepreneurship is still incipient, hindering the establishment of its boundaries and of a suitable research agenda. Empirical literature on rural entrepreneurship has focused mainly on developed countries, most notably, theUK, theUSA,Spain,Finland andGreece. Given the potential rural entrepreneurship represents for less developed and underdeveloped countries, more research on the topic targeting these countries is an imperative.
Endorheic or exorheic: differential isostatic effects of Cenozoic sediments on the elevations of the cratonic basins around the Tibetan Plateau
Authors: Yu Xiangjiang , Guo Zhaojie , Fu Suotang 
Published: October 2014

AbstractBased on isostasy, this paper elegantly explains the differential modern elevations of the large‐scale cratonic basins around the Tibetan Plateau. The Qaidam and Tarim basins are endorheic regions with thick Cenozoic deposits, and they uplifted dramatically during the Cenozoic. In contrast, the Sichuan basin is exorheic and most Cenozoic sediments flowed out of the basin; no visible Cenozoic uplift is observed. We suggest that whether a basin is endorheic or exorheic significantly influences its modern elevation, illustrating how exogenic geological processes impact endogenic geological processes. In addition, a new method of estimating paleoelevation is proposed, which predicts successively accelerating uplift of the Qaidam basin during the Cenozoic and provides good constraints on the geological evolution of the northern Tibetan Plateau.
Bacteremia due to Campylobacter in renal transplantation: a case report and review of literature
Authors: Pereira L. , Sampaio S. , Tavares I. , Bustorff M. , Pestana M. 
Published: October 2014

AbstractCampylobacter species are the leading cause of acute bacterial diarrhea in industrialized countries. However, bacteremia is detected in <1% of patients with Campylobacter enteritis and is most likely to occur in patients who are immunocompromised or of older age. To our knowledge, only 2 cases of Campylobacter jejuni bacteremia have been reported in renal transplant recipients (RTRs). We present a case of an RTR with C. jejuni bacteremia presenting as self‐limiting diarrhea followed by fever and cellulitis. The patient was successfully treated with a 2‐week course of imipenem and developed no other complications. We review all cases of Campylobacter bacteremia in RTRs, and discuss clinical presentation and treatment of this potentially fatal disease.
Development and application of the incident command tool for drinking water protection
Authors: Samuels William B. , Bahadur Rakesh , Ziemniak Christopher , Amstutz David E. 
Published: October 2014

AbstractThe Incident Command Tool for Drinking Water Protection (ICWater) provides real‐time assessments of the travel and dispersion of contaminants in streams and rivers. It is structured around the RiverSpill model which has been enhanced to make use of the 1:100 000 scale National Hydrography Dataset Plus, Version 1.0 (NHDPlusV1). NHDPlusV1 is a hydrologically connected river network that contains over 3 million reach segments in the United States. This allows for both downstream and upstream tracing (which serves in forensic analysis). Mean flow and velocity have been calculated by the US Geological Survey (USGS) and Environmental Protection Agency (EPA) for each reach. These mean values are updated by flow from web accessible real‐time gauging stations. Example databases available within ICWater include: dams, reservoirs, water supplies, gauges, municipal and industrial dischargers and transportation networks. A contaminant database is also included which identifies biological, chemical and radiological contaminants and their toxicities. Navigating the river network upstream coupled with mass‐balance calculations from breakthrough curves allows for backtracking of the contamination to determine the origin and source strength.
Spatiospectral denoising framework for multispectral optoacoustic imaging based on sparse signal representation
Authors: Tzoumas Stratis , Rosenthal Amir , Lutzweiler Christian , Razansky Daniel , Ntziachristos Vasilis 
Published: October 2014

Purpose:One of the major challenges in dynamic multispectral optoacoustic imaging is its relatively low signal‐to‐noise ratio which often requires repetitive signal acquisition and averaging, thus limiting imaging rate. The development of denoising methods which prevent the need for signal averaging in time presents an important goal for advancing the dynamic capabilities of the technology.Methods:In this paper, a denoising method is developed for multispectral optoacoustic imaging which exploits the implicit sparsity of multispectral optoacoustic signals both in space and in spectrum. Noise suppression is achieved by applying thresholding on a combined wavelet‐Karhunen–Loève representation in which multispectral optoacoustic signals appear particularly sparse. The method is based on inherent characteristics of multispectral optoacoustic signals of tissues, offering promise for general application in different incarnations of multispectral optoacoustic systems.Results:The performance of the proposed method is demonstrated on mouse images acquired in vivo for two common additive noise sources: time‐varying parasitic signals and white noise. In both cases, the proposed method shows considerable improvement in image quality in comparison to previously published denoising strategies that do not consider multispectral information.Conclusions:The suggested denoising methodology can achieve noise suppression with minimal signal loss and considerably outperforms previously proposed denoising strategies, holding promise for advancing the dynamic capabilities of multispectral optoacoustic imaging while retaining image quality.
Breast tumor segmentation in high resolution x‐ray phase contrast analyzer based computed tomography
Authors: Brun E. , Grandl S. , Sztrókay‐Gaul A. , Barbone G. , Mittone A. , Gasilov S. , Bravin A. , Coan P. 
Published: October 2014

Purpose:Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human‐guided breast tumor segmentation. This method has been applied to high‐resolution images of excised human organs, each of several gigabytes.Methods:The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure's possible applications.Results:A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists.Conclusions:The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high‐resolution x‐ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.
Evaluation of the Xpert
vanA
/
vanB
Assay Using Enriched Inoculated Broths for Direct Detection of
vanB
Vancomycin-Resistant Enterococci
Authors: Zhou X. , Arends J. P. , Kampinga G. A. , Ahmad H. M. , Dijkhuizen B. , van Barneveld P. , Rossen J. W. A. , Friedrich A. W. 
Published: October 2014

ABSTRACT

Rapid and accurate detection of VRE (vancomycin-resistant enterococci) is required for adequate antimicrobial treatment and infection prevention measures. Previous studies using PCR for the detection of VRE, including Cepheid's Xpert
vanA
/
vanB
assay, reported accurate detection of
vanA
VRE; however, many false-positive results were found for
vanB
VRE. This is mainly due to nonenterococcal
vanB
genes, which can be found in the gut flora. Our goal was to optimize the rapid and accurate detection of
vanB
VRE and to improve the positive predictive value (PPV) by limiting false-positive results. We evaluated the use of the Xpert
vanA
/
vanB
assay on rectal swabs and on enriched inoculated broths for the detection of
vanB
VRE. By adjusting the cycle threshold (

C
T

) cutoff value to ≤25 for positivity by PCR on enriched broths, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 96.9%, 100%, 100%, and 99.5% for
vanB
VRE, respectively. As shown in this study,

C
T

values of ≤25 acquired from enriched broths can be considered true positive. For broths with

C
T

values between 25 and 30, we recommend confirming the results by culture.

C
T

values of >30 appeared to be true negative. In conclusion, this study shows that the Cepheid's Xpert
vanA
/
vanB
assay performed on enriched inoculated broths with an adjusted cutoff

C
T

value is a useful and rapid tool for the detection of
vanB
VRE.
Matrix-Assisted Laser Desorption Ionization–Time of Flight (MALDI-TOF) Mass Spectrometry Using the Vitek MS System for Rapid and Accurate Identification of Dermatophytes on Solid Cultures
Authors: De Respinis Sophie , Monnin Valérie , Girard Victoria , Welker Martin , Arsac Maud , Cellière Béatrice , Durand Géraldine , Bosshard Philipp P. , Farina Claudio , Passera Marco , Van Belkum Alex , Petrini Orlando , Tonolla Mauro 
Published: October 2014

ABSTRACT

The objective of this research was to extend the Vitek MS fungal knowledge base version 2.0.0 to allow the robust identification of clinically relevant dermatophytes, using a variety of strains, incubation times, and growth conditions. First, we established a quick and reliable method for sample preparation to obtain a reliable and reproducible identification independently of the growth conditions. The Vitek MS V2.0.0 fungal knowledge base was then expanded using 134 well-characterized strains belonging to 17 species in the genera
Epidermophyton
,
Microsporum
, and
Trichophyton
. Cluster analysis based on mass spectrum similarity indicated good species discrimination independently of the culture conditions. We achieved a good separation of the subpopulations of the
Trichophyton
anamorph of
Arthroderma benhamiae
and of anthropophilic and zoophilic strains of
Trichophyton interdigitale
. Overall, the 1,130 mass spectra obtained for dermatophytes gave an estimated identification performance of 98.4%. The expanded fungal knowledge base was then validated using 131 clinical isolates of dermatophytes belonging to 13 taxa. For 8 taxa all strains were correctly identified, and for 3 the rate of successful identification was >90%; 75% (6/8) of the
M. gypseum
strains were correctly identified, whereas only 47% (18/38) of the African
T. rubrum
population (also called
T. soudanense
) were recognized accurately, with a large quantity of strains misidentified as
T. violaceum
, demonstrating the close relationship of these two taxa. The method of sample preparation was fast and efficient and the expanded Vitek MS fungal knowledge base reliable and robust, allowing reproducible dermatophyte identifications in the routine laboratory.
A Highly Sensitive Europium Nanoparticle-Based Immunoassay for Detection of Influenza A/B Virus Antigen in Clinical Specimens
Authors: Zhang Panhe , Vemula Sai Vikram , Zhao Jiangqin , Du Bingchen , Mohan Haleyurgirisetty , Liu Jikun , El Mubarak Haja Sittana , Landry Marie L. , Hewlett Indira 
Published: October 2014

ABSTRACT
We report the development of a novel europium nanoparticle-based immunoassay (ENIA) for rapid detection of influenza A and influenza B viruses. The ENIA demonstrated sensitivities of 90.7% (147/162) for influenza A viruses and 81.80% (9/11) for influenza B viruses compared to those for an in-house reverse transcription (RT)-PCR assay in testing of influenza-positive clinical samples.
Unabated Adenovirus Replication following Activation of the cGAS/STING-Dependent Antiviral Response in Human Cells
Authors: Lam Eric , Falck-Pedersen Erik 
Published: October 2014

ABSTRACTThe cGAS/STING DNA sensing complex has recently been established as a predominant pathogen recognition receptor (PRR) for DNA-directed type I interferon (IFN) innate immune activation. Using replication-defective adenovirus vectors and replication-competent wild-type adenovirus, we have modeled the influence of the cGAS/STING cascade in permissive human cell lines (A549, HeLa, ARPE19, and THP1). Wild-type adenovirus induced efficient early activation of the cGAS/STING cascade in a cell-specific manner. In all responsive cell lines, cGAS/STING short hairpin RNA (shRNA) knockdown resulted in a loss of TBK1 and interferon response factor 3 (IRF3) activation, a lack of beta interferon transcript induction, loss of interferon-dependent STAT1 activation, and diminished induction of interferon-stimulated genes (ISGs). Adenoviruses that infect through the coxsackievirus-adenovirus receptor (CAR) (Ad2 and Ad5) and the CD46 (Ad35) and desmoglein-2 (Ad7) viral receptors all induce the cGAS/STING/TBK1/IRF3 cascade. The magnitude of the IRF3/IFN/ISG antiviral response was strongly influenced by serotype, with Ad35>Ad7>Ad2. For each serotype, no enhancement of viral DNA replication or virus production occurred in cGAS or STING shRNA-targeted cell line pools. We found no replication advantage in permissive cell lines that do not trigger the cGAS/STING cascade following infection. The cGAS/STING/TBK1/IRF3 cascade was not a direct target of viral antihost strategies, and we found no evidence that Ad stimulation of the cGAS/STING DNA response had an impact on viral replication efficiency.IMPORTANCEThis study shows for the first time that the cGAS DNA sensor directs a dominant IRF3/IFN/ISG antiviral response to adenovirus in human cell lines. Activation of cGAS occurs with viruses that infect through different high-affinity receptors (CAR, CD46, and desmoglein-2), and the magnitude of the cGAS/STING DNA response cascade is influenced by serotype-specific functions. Furthermore, activation of the cGAS cascade occurred in a cell-specific manner. Activation of the cGAS/STING response did not impact viral replication, and viral immune evasion strategies did not target the cGAS/STING/TBK1/IRF3 cascade. These studies provide novel insight into the early innate recognition response to adenovirus.
MHC-Restricted Phosphopeptides from Insulin Receptor Substrate-2 and CDC25b Offer Broad-Based Immunotherapeutic Agents for Cancer
Authors: Zarling Angela L. , Obeng Rebecca C. , Desch A. Nicole , Pinczewski Joel , Cummings Kara L. , Deacon Donna H. , Conaway Mark , Slingluff Craig L. , Engelhard Victor H. 
Published: October 2014

Abstract
Cancer cells display novel phosphopeptides in association with MHC class I and II molecules. In this study, we evaluated two HLA-A2–restricted phosphopeptides derived from the insulin receptor substrate (IRS)-2 and the cell-cycle regulator CDC25b. These proteins are both broadly expressed in multiple malignancies and linked to cancer cell survival. Two phosphopeptides, termed pIRS-21097–1105 and pCDC25b38–46, served as targets of strong and specific CD8 T-cell memory responses in normal human donors. We cloned T-cell receptor (TCR) cDNAs from murine CD8 T-cell lines specific for either pIRS-21097–1105 or pCDC25b38–46. Expression of these TCRs in human CD8 T cells imparted high-avidity phosphopeptide-specific recognition and cytotoxic and cytokine-secreting effector activities. Using these cells, we found that endogenously processed pIRS-21097–1105 was presented on HLA-A2+ melanomas and breast, ovarian, and colorectal carcinomas. Presentation was correlated with the level of the Ser1100-phosphorylated IRS-2 protein in metastatic melanoma tissues. The highest expression of this protein was evident on dividing malignant cells. Presentation of endogenously processed pCDC25b38–46 was narrower, but still evident on HLA-A2+ melanoma, breast carcinoma, and lymphoblastoid cells. Notably, pIRS-21097–1105–specific and pCDC25b38–46–specific TCR-expressing human CD8 T cells markedly slowed tumor outgrowth in vivo. Our results define two new antigens that may be developed as immunotherapeutic agents for a broad range of HLA-A2+ cancers. Cancer Res; 74(23); 6784–95. ©2014 AACR.
Inhibition of Adaptive Immunity by IL9 Can Be Disrupted to Achieve Rapid T-cell Sensitization and Rejection of Progressive Tumor Challenges
Authors: Hoelzinger Dominique B. , Dominguez Ana Lucia , Cohen Peter A. , Gendler Sandra J. 
Published: October 2014

Abstract
The tolerogenic cytokine IL9 promotes T regulatory cell function and allergic airway inflammation, but it has not been extensively studied in cancer. In this report, we used IL9-deficient mice to investigate the effects of IL9 in multiple models of breast and colon cancer development. Eliminating endogenous IL9 enabled sensitization of host T cells to tumors, leading to their early rejection without the requirement of vaccines or immunomodulatory therapies. Notably, IL9-deficient mice acquired immunologic memory, which actively protected from residual disease and tumor rechallenge, an effect linked to activation of CD8+ T cells. Depletion of either CD8+ or CD4+ T cells abolished the benefits of IL9 loss to tumor control. Adoptive transfer experiments showed that T cells from tumor-rejecting IL9-deficient mice retained their effector competency in wild-type animals. Moreover, neutralizing IL9 antibody phenocopied the effects of IL9 gene deletion by slowing tumor progression in wild-type animals. Our results show the ability of IL9 to function as an inhibitor of adaptive immunity that prevents the formation of immunologic memory to a growing tumor, highlighting the potential for IL9 neutralization as a unique tool for cancer immunotherapy. Cancer Res; 74(23); 6845–55. ©2014 AACR.
HSP90 Supports Tumor Growth and Angiogenesis through PRKD2 Protein Stabilization
Authors: Azoitei Ninel , Diepold Kristina , Brunner Cornelia , Rouhi Arefeh , Genze Felicitas , Becher Alexander , Kestler Hans , van Lint Johan , Chiosis Gabriela , Koren John , Fröhling Stefan , Scholl Claudia , Seufferlein Thomas 
Published: October 2014

Abstract
The kinase PRKD2 (protein kinase D) is a crucial regulator of tumor cell-endothelial cell communication in gastrointestinal tumors and glioblastomas, but its mechanistic contributions to malignant development are not understood. Here, we report that the oncogenic chaperone HSP90 binds to and stabilizes PRKD2 in human cancer cells. Pharmacologic inhibition of HSP90 with structurally divergent small molecules currently in clinical development triggered proteasome-dependent degradation of PRKD2, augmenting apoptosis in human cancer cells of various tissue origins. Conversely, ectopic expression of PRKD2 protected cancer cells from the apoptotic effects of HSP90 abrogation, restoring blood vessel formation in two preclinical models of solid tumors. Mechanistic studies revealed that PRKD2 is essential for hypoxia-induced accumulation of hypoxia-inducible factor-1α (HIF1α) and activation of NF-κB in tumor cells. Notably, ectopic expression of PRKD2 was able to partially restore HIF1α and secreted VEGF-A levels in hypoxic cancer cells treated with HSP90 inhibitors. Taken together, our findings indicate that signals from hypoxia and HSP90 pathways are interconnected and funneled by PRKD2 into the NF-κB/VEGF-A signaling axis to promote tumor angiogenesis and tumor growth. Cancer Res; 74(23); 7125–36. ©2014 AACR.
Hedgehog Signaling Drives Radioresistance and Stroma-Driven Tumor Repopulation in Head and Neck Squamous Cancers
Authors: Gan Gregory N. , Eagles Justin , Keysar Stephen B. , Wang Guoliang , Glogowska Magdalena J. , Altunbas Cem , Anderson Ryan T. , Le Phuong N. , Morton J. Jason , Frederick Barbara , Raben David , Wang Xiao-Jing , Jimeno Antonio 
Published: October 2014

Abstract
Local control and overall survival in patients with advanced head and neck squamous cell cancer (HNSCC) remains dismal. Signaling through the Hedgehog (Hh) pathway is associated with epithelial-to-mesenchymal transition, and activation of the Hh effector transcription factor Gli1 is a poor prognostic factor in this disease setting. Here, we report that increased GLI1 expression in the leading edge of HNSCC tumors is further increased by irradiation, where it contributes to therapeutic inhibition. Hh pathway blockade with cyclopamine suppressed GLI1 activation and enhanced tumor sensitivity to radiotherapy. Furthermore, radiotherapy-induced GLI1 expression was mediated in part by the mTOR/S6K1 pathway. Stroma exposed to radiotherapy promoted rapid tumor repopulation, and this effect was suppressed by Hh inhibition. Our results demonstrate that Gli1 that is upregulated at the tumor–stroma intersection in HNSCC is elevated by radiotherapy, where it contributes to stromal-mediated resistance, and that Hh inhibitors offer a rational strategy to reverse this process to sensitize HNSCC to radiotherapy. Cancer Res; 74(23); 7024–36. ©2014 AACR.