bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering Dynamics of Epidemic Spread: The Case of Influenza Virus
Authors: Upadhyay Ranjit Kumar , Roy Parimita , Rai Vikas 
Published: May 2014

In this paper, we have proposed and analyzed a simple model of Influenza spread with an asymptotic transmission rate. Existence and uniqueness of solutions are established and shown to be uniformly bounded for all non-negative initial values. We have also found a sufficient condition which ensures the persistence of the model system. This implies that both susceptible and infected will always coexist at any location of the inhabited domain. This coexistence is independent of values of the diffusivity constants for two subpopulations. The global stability of the endemic equilibrium is established by constructing a Lyapunov function. By linearizing the system at the positive constant steady-state solution and analyzing the associated characteristic equation, conditions for Hopf and Turing bifurcations are obtained. We have also studied the criteria for diffusion-driven instability caused by local random movements of both susceptible and infective subpopulations. Turing patterns selected by the reaction–diffusion system under zero flux boundary conditions have been explored.Numerical simulations show that contact rate, β which is related to the reproduction number [Formula: see text], plays an important role in spatial pattern formation. It was found that diffusion has appreciable influence on spatial spread of epidemics. The wave of chaos appears to be a dominant mode of disease dispersal. This suggests a bidirectional spread for influenza epidemics. The epidemic propagates in the form of nonchaotic and chaotic waves as observed in H1N1 incidence data of positive tests in 2009 in the United States. We have conducted numerical simulations to confirm the analytic work and observed interesting behaviors. This suggests that influenza has a complex dynamics of spatial spread which evolves with time.
C-Reactive Protein and Colorectal Cancer Mortality in U.S. Adults
Authors: Goyal Abhishek , Terry Mary Beth , Jin Zhezhen , Siegel Abby B. 
Published: May 2014

AbstractBackground: Chronic inflammation has been associated with colorectal cancer. Prediagnostic levels of C-reactive protein (CRP), a highly sensitive marker of inflammation, have been weakly associated with increased colorectal cancer incidence, but few data are available examining its relationship with colorectal cancer mortality.Methods: In the Third National Health and Nutrition Examination Survey (NHANES III), 65% of the 15,924 adult participants had CRP levels ≤0.21 mg/dL. Using this as the reference group, we calculated hazard ratios (HR) for higher CRP categories and colorectal cancer mortality, and compared them with HRs for other mortality causes.Results: Over a median follow-up period of 14.2 years, there were 92 deaths from colorectal cancer. Compared with the reference group, multivariable adjusted HRs for colorectal cancer mortality were 2.66 [95% confidence interval (CI), 1.36–5.20] for CRP levels 0.22–0.50 mg/dL; 3.40 (95% CI, 1.48–7.77) for levels 0.51–1.00 mg/dL; and 3.96 (95% CI, 1.64–9.52) for levels &gt;1.00 mg/dL. Estimates for colorectal cancer mortality did not change appreciably after excluding deaths within the first 3 years or by limiting follow-up to 5 or 10 years.Conclusions: In a large representative study of U.S. adults, we observed strong dose–response associations between CRP levels and colorectal cancer mortality.Impact: Further evaluation of CRP may help identify high-risk groups for colorectal cancer screening and those who might benefit most from prophylactic anti-inflammatory therapy. Cancer Epidemiol Biomarkers Prev; 23(8); 1609–18. ©2014 AACR.
PLCE1 mRNA and Protein Expression and Survival of Patients with Esophageal Squamous Cell Carcinoma and Gastric Adenocarcinoma
Authors: Li Wen-Qing , Hu Nan , Burton Victoria H. , Yang Howard H. , Su Hua , Conway Catherine M. , Wang Lemin , Wang Chaoyu , Ding Ti , Xu Yi , Giffen Carol , Abnet Christian C. , Goldstein Alisa M. , Hewitt Stephen M. , Taylor Philip R. 
Published: May 2014

Abstract
Background: Germline genetic variants in PLCE1 (10q23) have demonstrated consistent associations with risk of esophageal squamous cell carcinoma (ESCC) and gastric cancer among Chinese. We evaluated PLCE1 mRNA and protein expression in paired tumor-normal tissues, and their relationship with survival.
Methods: PLCE1 mRNA was profiled using three probes in the Affymetrix GeneChip U133 for paired tumor-normal tissues of ESCC (n = 132), gastric cardia adenocarcinoma (GCA, n = 62), and gastric noncardia adenocarcinoma (GNCA, n = 72). We used immunohistochemistry to detect PLCE1 protein on slides from tissue microarrays in paired tumor-normal tissues of ESCC (n = 303), and tumors of GCA (n = 298) and GNCA (n = 124).
Results: Compared with normal tissues, PLCE1 mRNA expression was significantly reduced in ESCC tumors (P = 0.03, probe_205112_at), as well as in GCA and GNCA tumors (P &lt; 0.0001, each probe). Protein expression was nonsignificantly reduced in ESCC tumors (P = 0.51). Increased tumor-normal mRNA fold change (probe_205112_at) was associated with longer survival in ESCC (9.6 months for highest vs. lowest quartile; Ptrend = 0.02). Increased mRNA tumor-normal fold change (probe_205111_at) was associated with longer survival for GCA (10.7 months for highest quartile; Ptrend = 0.04), but not for GNCA cases (P = 0.72). Similar to mRNA, elevated tumor-normal fold change for protein in ESCC was also associated with improved survival (8.1 months for highest quartile; Ptrend = 0.04).
Conclusions: Dysregulated PLCE1 mRNA expression was observed for both ESCC (one probe only) and GCA tumors, and the altered PLCE1 expression seems to be associated with cancer prognosis.
Impact: A potential role for PLCE1 in the early detection and/or therapy of ESCC and GCA warrants further investigation. Cancer Epidemiol Biomarkers Prev; 23(8); 1579–88. ©2014 AACR.
Inhibition of Protein Phosphatase 2A Enhances Cytotoxicity and Accessibility of Chemotherapeutic Drugs to Hepatocellular Carcinomas
Authors: Bai Xue-Li , Zhang Qi , Ye Long-Yun , Hu Qi-Da , Fu Qi-Han , Zhi Xiao , Su Wei , Su Ri-Ga , Ma Tao , Chen Wei , Xie Shang-Zhi , Chen Cong-Lin , Liang Ting-Bo 
Published: May 2014

Abstract
Hepatocellular carcinoma (HCC) is one of the most common and therapeutically challenging malignancies worldwide. For patients ineligible for “curative resection” or liver transplantation, chemotherapy is an important minimally effective option. Strategies for chemosensitization are urgently needed. Here, we report that LB-100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor, enhances the cytotoxicity of chemotherapy for HCC in vitro and in vivo. We found that LB-100 significantly enhanced inhibition of HCC by doxorubicin and cisplatin in vitro and in vivo in a PP2A-dependent way, while having little inhibitory activity when used alone. LB-100 promoted vascular endothelial growth factor secretion and vasculogenic mimicry, associated with increased microvessel density and blood perfusion of tumor cell xenografts. LB-100 also enhanced paracellular endothelial permeability to Evans Blue dye and doxorubicin in vivo and in vitro, presumably by altering vascular endothelial–cadherin contact between cells. Changes in permeability and perfusion were accompanied by increased accumulation of doxorubicin in HCC xenografts but not in normal liver tissue. In conclusion, LB-100 enhances chemotherapy by interfering with DNA damage–induced defense mechanisms and by increasing angiogenesis and drug penetration into tumor cells. The induction of angiogenesis and vascular permeability of tumor xenografts by inhibition of PP2A may be a novel approach for enhancing the cytotoxic treatment of HCC and potentially other cancers. Mol Cancer Ther; 13(8); 2062–72. ©2014 AACR.
SIRT2 Interacts with β-Catenin to Inhibit Wnt Signaling Output in Response to Radiation-Induced Stress
Authors: Nguyen Phuongmai , Lee Sunmin , Lorang-Leins Dominique , Trepel Jane , Smart DeeDee K. 
Published: May 2014

Abstract
Wnt signaling is critical to maintaining cellular homeostasis via regulation of cell division, mitigation of cell stress, and degradation. Aberrations in Wnt signaling contribute to carcinogenesis and metastasis, whereas sirtuins have purported roles in carcinogenesis, aging, and neurodegeneration. Therefore, the hypothesis that sirtuin 2 (SIRT2) directly interacts with β-catenin and whether this interaction alters the expression of Wnt target genes to produce an altered cellular phenotype was tested. Coimmunoprecipitation studies, using mouse embryonic fibroblasts (MEF) from Sirt2 wild-type and genomic knockout mice, demonstrate that β-catenin directly binds SIRT2. Moreover, this interaction increases in response to oxidative stress induced by ionizing radiation. In addition, this association inhibits the expression of important Wnt target genes such as survivin (BIRC5), cyclin D1 (CCND1), and c-myc (MYC). In Sirt2 null MEFs, an upregulation of matrix metalloproteinase 9 (MMP9) and decreased E-cadherin (CDH1) expression is observed that produces increased cellular migration and invasion. Together, these data demonstrate that SIRT2, a tumor suppressor lost in multiple cancers, inhibits the Wnt signaling pathway in nonmalignant cells by binding to β-catenin and that SIRT2 plays a critical role in the response to oxidative stress from radiation.
Implications: Disruption of the SIRT2–β-catenin interaction represents an endogenous therapeutic target to prevent transformation and preserve the integrity of aging cells against exogenous stressors such as reactive oxygen species. Mol Cancer Res; 12(9); 1244–53. ©2014 AACR.
Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition
Authors: González-Billalabeitia Enrique , Seitzer Nina , Song Su Jung , Song Min Sup , Patnaik Akash , Liu Xue-Song , Epping Mirjam T. , Papa Antonella , Hobbs Robin M. , Chen Ming , Lunardi Andrea , Ng Christopher , Webster Kaitlyn A. , Signoretti Sabina , Loda Massimo , Asara John M. , Nardella Caterina , Clohessy John G. , Cantley Lewis C. , Pandolfi Pier Paolo 
Published: May 2014

Abstract
Prostate cancer is the most prevalent cancer in males, and treatment options are limited for advanced forms of the disease. Loss of the PTEN and TP53 tumor suppressor genes is commonly observed in prostate cancer, whereas their compound loss is often observed in advanced prostate cancer. Here, we show that PARP inhibition triggers a p53-dependent cellular senescence in a PTEN-deficient setting in the prostate. Surprisingly, we also find that PARP-induced cellular senescence is morphed into an apoptotic response upon compound loss of PTEN and p53. We further show that superactivation of the prosurvival PI3K–AKT signaling pathway limits the efficacy of a PARP single-agent treatment, and that PARP and PI3K inhibitors effectively synergize to suppress tumorigenesis in human prostate cancer cell lines and in a Pten/Trp53–deficient mouse model of advanced prostate cancer. Our findings, therefore, identify a combinatorial treatment with PARP and PI3K inhibitors as an effective option for PTEN-deficient prostate cancer.
Significance: The paucity of therapeutic options in advanced prostate cancer displays an urgent need for the preclinical assessment of novel therapeutic strategies. We identified differential therapeutic vulnerabilities that emerge upon the loss of both PTEN and p53, and observed that combined inhibition of PARP and PI3K provides increased efficacy in hormone-insensitive advanced prostate cancer. Cancer Discov; 4(8); 896–904. ©2014 AACR.
This article is highlighted in the In This Issue feature, p. 855
Retrospective studies of end-of-life resource utilization and costs in cancer care using health administrative data: A systematic review
Authors: Langton Julia M , Blanch Bianca , Drew Anna K , Haas Marion , Ingham Jane M , Pearson Sallie-Anne 
Published: May 2014

Background: There has been an increase in observational studies using health administrative data to examine the nature, quality, and costs of care at life’s end, particularly in cancer care. Aim: To synthesize retrospective observational studies on resource utilization and/or costs at the end of life in cancer patients. We also examine the methods and outcomes of studies assessing the quality of end-of-life care. Design: A systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (A Measurement Tool to Assess Systematic Reviews) methodology. Data sources: We searched MEDLINE, Embase, CINAHL, and York Centre for Research and Dissemination (1990–2011). Independent reviewers screened abstracts of 14,424 articles, and 835 full-text manuscripts were further reviewed. Inclusion criteria were English-language; at least one resource utilization or cost outcome in adult cancer decedents with solid tumors; outcomes derived from health administrative data; and an exclusive end-of-life focus. Results: We reviewed 78 studies examining end-of-life care in over 3.7 million cancer decedents; 33 were published since 2008. We observed exponential increases in service use and costs as death approached; hospital services being the main cost driver. Palliative services were relatively underutilized and associated with lower expenditures than hospital-based care. The 15 studies using quality indicators demonstrated that up to 38% of patients receive chemotherapy or life-sustaining treatments in the last month of life and up to 66% do not receive hospice/palliative services. Conclusion: Observational studies using health administrative data have the potential to drive evidence-based palliative care practice and policy. Further development of quality care markers will enhance benchmarking activities across health care jurisdictions, providers, and patient populations.
Age-dependent effects on the treatment response of natalizumab in MS patients
Authors: Matell Henrik , Lycke Jan , Svenningsson Anders , Holmén Carolina , Khademi Mohsen , Hillert Jan , Olsson Tomas , Piehl Fredrik 
Published: May 2014

Background: Natalizumab is approved for treatment of active forms of relapsing–remitting multiple sclerosis (MS) based on a pivotal phase III study comprising patients aged 18–50 years. The effect of natalizumab has not been specifically studied in older patients. Objective: We analyzed age-dependent effects on treatment-related outcome measures in 1872 patients, 189 of whom were aged 50 or more, included in the Swedish post-marketing natalizumab surveillance program. Methods: In three MS centers registry data for patients aged >50 years were validated. Results: At baseline older patients had longer disease duration, higher Expanded Disability Status Scale (EDSS) and lower Symbol Digit Modality Test (SDMT) scores than younger patients. The influence from natalizumab on outcome measures was significantly reduced and 18.7% of patients >50 years stopped treatment for lack of effect compared to 7.7% in the younger age group. At baseline, the cerebrospinal fluid levels of the chemokine CXCL13 and the leukocyte cell count were negatively correlated with age in a smaller subgroup of patients. Conclusion: These results were in agreement with previous findings suggesting that inflammation is more pronounced in younger patients and therefore the beneficial effects of potent anti-inflammatory treatments are subsiding with older ages.
Phosphorylation of mTOR and S6RP predicts the efficacy of everolimus in patients with metastatic renal cell carcinoma
Authors: Li Siming , Kong Yan , Si Lu , Chi Zhihong , Cui Chuanliang , Sheng Xinan , Guo Jun 
Published: May 2014

Abstract

Background
The incidence of renal cell cancer (RCC) has been increasing for the past decade, and the 5-year survival for patients with metastatic RCC (mRCC) is rather low. Everolimus (RAD001), a new inhibitor for mammalian target of rapamycin (mTOR), is generally well tolerated, and demonstrates clinical benefit to patients with anti-VEGF-refractory mRCC. However, factors for selection of patients who may benefit from everolimus remain largely unknown. Here we aimed to explore potential molecular indicators for mRCC patients who may benefit from everolimus treatment.

Methods
Paraffin-embedded tumor tissue specimens derived from 18 mRCC patients before everolimus treatment, who participated the phase 1b trial of everolimus in VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI)-refractory Chinese patients with mRCC (clinicaltrials.gov, NCT01152801), were examined for the expression levels of phosphorylated AKT, mTOR, eukaryotic initiation factor 4E (eIF4E) binding protein-1 (4EBP1) and 40S ribosomal protein S6 (S6RP) by immunohistochemistry. Clinical benefit rate (complete response [CR], partial response [PR], plus stable disease [SD] ≥ 6 months) and progression-free survival time (PFS) were correlated with expression levels of these mTOR-associated molecules.

Results
In these 18 patients, there were 1 PR, 15 SDs (including 9 SDs ≥ 6 months), and 2 progressive diseases (PD). The clinical benefit rate (CBR) was 55.6% (10/18), and the median PFS time was 8.4 months. Patients with positive expression of phospho-mTOR showed a better CBR (71.4% versus 0%, P = 0.023) and PFS time (11.3 versus 3.7 months, P = 0.001) than those patients with negative expression. The median PFS of patients with positive phospho-S6RP expression was longer (11.3 versus 3.7 months, P = 0.002) than that of patients negative for phospho-S6RP expression. However, expression levels of phospho-4EBP1 and phospho-AKT were unassociated to efficacy of everolimus treatment with respect to CBR and PFS. Co-expression of phosphorylated mTOR, S6RP and/or 4EBP1 may improve the predictive value of the biomarkers for patients treated with everolimus.

Conclusions
The expression levels of phospho-mTOR and phospho-S6RP may be potential predictive biomarkers for efficacy of everolimus in patients with mRCC. Combining examinations of phosphorylated mTOR, S6RP and/or 4EBP1 may be a potential strategy to select mRCC patients sensitive to mTOR inhibitor treatment.
Metastatic squamous cell carcinoma from hand skin causing small bowel obstruction: an unusual case presentation
Authors: Li Ruixin , Chen Zihua , Wen Qiaocheng , Chen Zhikang 
Published: May 2014

Abstract
The small bowel rarely suffers from metastatic tumors from outside the abdomen. Small bowel obstructions caused by the metastatic spread of squamous cell carcinoma (SCC) of the hand to the intestines are even rarer. A 71-year-old man with intermittent abdominal distension and pain for 4 months was diagnosed with partial bowel obstruction. The patient underwent a video capsule endoscopic examination; however, the patient was unable to pass the capsule, which worsened the abdominal distension. He was transferred to our department for acute intestinal obstruction, and an emergency exploratory laparotomy was performed. Intraoperatively, a tumoral stricture of the intestine at a distance of 150 cm from the ileo-cecum and dilation of the proximal bowel was found. The involved segment was resected, and ileo-ileal anastomosis was performed. The pathological sections confirmed the lesion to be a moderately differentiated SCC with whole bowel layer infiltration. Immunohistochemical staining showed positive expression of cytokeratin 5/6 and p63. The patient had an uneventful recovery. However, 6 months later, he was hospitalized again with intestinal obstruction. Reoperation was performed and revealed multiple metastases in the small bowel. He died 4 months later. In this unusual case, metastasizing SCC of the hand skin led to intestinal obstruction and poor prognosis. Therefore, follow-up procedures regarding intestinal spread should be performed in patients with SCC who present with abdominal symptoms.
Estimation of diffusion coefficients from voltammetric signals by support vector and gaussian process regression
Authors: Bogdan Martin , Brugger Dominik , Rosenstiel Wolfgang , Speiser Bernd 
Published: May 2014

Abstract

Background
Support vector regression (SVR) and Gaussian process regression (GPR) were used for the analysis of electroanalytical experimental data to estimate diffusion coefficients.

Results
For simulated cyclic voltammograms based on the EC, Eqr, and EqrC mechanisms these regression algorithms in combination with nonlinear kernel/covariance functions yielded diffusion coefficients with higher accuracy as compared to the standard approach of calculating diffusion coefficients relying on the Nicholson-Shain equation. The level of accuracy achieved by SVR and GPR is virtually independent of the rate constants governing the respective reaction steps. Further, the reduction of high-dimensional voltammetric signals by manual selection of typical voltammetric peak features decreased the performance of both regression algorithms compared to a reduction by downsampling or principal component analysis. After training on simulated data sets, diffusion coefficients were estimated by the regression algorithms for experimental data comprising voltammetric signals for three organometallic complexes.

Conclusions
Estimated diffusion coefficients closely matched the values determined by the parameter fitting method, but reduced the required computational time considerably for one of the reaction mechanisms. The automated processing of voltammograms according to the regression algorithms yields better results than the conventional analysis of peak-related data.
Overeducation among immigrants in Sweden: incidence, wage effects and state dependence
Authors: Joona Pernilla Andersson , Gupta Nabanita Datta , Wadensjö Eskil 
Published: May 2014

Abstract
The utilization and reward of the human capital of immigrants in the labor market of the host country has been studied extensively. Using Swedish register data from 2001–2008, we extend the immigrant educational mismatch literature by analyzing incidence, wage effects and state dependence in overeducation among natives and immigrants. In line with previous research we find a higher incidence and a lower return to overeducation among immigrants indicating that immigrants lose more from being overeducated. We find a high degree of state dependence in overeducation both among natives and immigrants, but considerably higher among immigrants.

JEL codes

J61, I21, J24, J31, F22