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Dengue virus (DENV) is the most prevalent human arthropod-borne virus and causes severe problems worldwide, mainly in tropical and sub-tropical regions. However, there is no specific antiviral drug against DENV infection. We and others recently reported that stearoyl-CoA desaturase-1 (SCD1) inhibitor showed potent suppression of hepatitis C virus replication. In this study, we examined the impact of SCD1 on DENV replication. We found that SCD1 inhibitors (MK8245 and #1716) dramatically suppressed DENV replication in a dose-dependent manner without cytotoxicity. This anti-DENV efficacy was observed against all four DENV serotypes and other flaviviruses, including Zika virus and Japanese encephalitis virus. A subgenomic replicon system of DENV was used to confirm that SCD1 inhibitor suppressed viral RNA replication. Interestingly, exogenous supplementation of unsaturated fatty acids resulted in recovery of the DENV titer even in the presence of SCD1 inhibitor, suggesting that fatty acid biosynthesis contributes to DENV genome replication. These findings indicate that SCD1 is a novel host factor required for DENV replication, and SCD1 inhibitor is a potential candidate for treating dengue fever.

A simple aqueous-phase synthesis of PbSe nanocubes with tunable sizes has been developed by first preparing a Na2 SeSO3 stock solution through dissolution of selenium powder in a solution of Na2 SO3 at 90-100 °C for 30 min, and adding part of this solution to a mixture of lead acetate and acetic acid at room temperature with stirring for only 5-8 min to complete the nanocrystal growth. Adjusting the volume of acetic acid and Na2 SeSO3 solution added enabled the size of the nanocrystals to be tuned, with average edge lengths of 13 to 121 nm attained. Changes in solution color revealed very different crystal growth rates for the 13 and 121 nm nanocubes. The PbSe cubes exhibit size-dependent absorption bands in the ultraviolet and visible-light region; the band positions show progressive redshifts with increasing particle size. Slight photocatalytic activity upon 532 nm laser irradiation of the nanocubes suggests the presence of higher energy levels in the band structure of PbSe. The synthetic conditions can be easily scaled up to obtain a large quantity of PbSe nanocubes for applications.

Purpose To examine associations by gender between cancer history and major health insurance transitions (gains and losses), and relationships between insurance transitions and access to care. Methodology Longitudinal 2008–2013 Medical Expenditure Panel Survey data were pooled yielding 2,223 cancer survivors and 50,692 individuals with no cancer history ages 18–63 years upon survey entry, with gender-specific sub-analyses. Access-to-care implications of insurance loss or gain were compared by cancer history and gender. Findings Initially uninsured cancer survivors were significantly more likely to gain insurance coverage than individuals with no cancer history (RR: 1.25; 95% CI: 1.08–1.44). Females in particular were significantly more likely to gain insurance (unmarried RR: 1.16; 95% CI: 1.06–1.28; married RR: 1.09; 95% CI: 1.02–1.16). Significantly higher rates of difficulty accessing needed medical care and prescription medications were reported by those remaining uninsured, those who lost insurance, and women in general. Remaining uninsured, losing insurance, and male gender were associated with lack of a usual source of care. Research implications Additional outreach to disadvantaged populations is needed to improve access to affordable insurance and medical care. Future longitudinal studies should assess whether major Affordable Care Act (ACA) provisions enacted after the 2008–2013 study period (or those of ACA’s replacement) are addressing these important issues. Originality Loss of health insurance coverage can reduce health care access resulting in poor health outcomes. Cancer survivors may be particularly at risk of insurance coverage gaps due to the long-term chronic disease trajectory. This study is novel in exploring associations between cancer history by gender and health insurance transitions, both gains and losses, in a national non-elderly adult sample.

Fibrolamellar carcinoma is a rare primary hepatocellular malignancy arising in noncirrhotic livers of young individuals. Patients commonly present with a large solitary liver mass and nonspecific symptoms. Characteristic histologic features include large polygonal cells with oncocytic cytoplasm and prominent nucleoli separated into trabeculae and cords by dense parallel bands of collagen. Important differential diagnoses include classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma, which may be distinguished by a judicious panel of immunohistochemical studies, including cytokeratin 7, CD68, and hepatocyte paraffin 1 (HepPar-1). In addition, fibrolamellar carcinomas are characterized by activation of protein kinase A. Prognosis of fibrolamellar carcinoma is similar to classical hepatocellular carcinoma occurring in the absence of liver cirrhosis and is strongly correlated with tumor resectability. Other treatment options include liver transplant, chemotherapy, and hepatic artery embolization. In this article, we review the clinical features, gross and microscopic pathology, molecular genetics, differential diagnosis, treatment, and prognosis of this rare and interesting tumor.

Background: High-grade primary gliomas are aggressively growing and have an unfavorable prognosis. The utility of prognostic biomarkers of outcome in glioma patients is important for medical practice. Cell division cycle-associated 7-like (CDCA7L) protein modifies cancer progression and metastasis. Nevertheless, its character in defining the clinical prognosis of human gliomas has not been illuminated. Subjects and Methods: The hypothesis of this study was that CDCA7L is upregulated in human gliomas. We studied two de-linked data from Gene Expression Omnibus (GEO) profile. The first dataset (GDS1816/225081_s_at/CDCA7L) in primary high-grade glioma included age, gender, and survival time. Another dataset (GDS1962/225081_s_at/CDCA7L) was also encompassed to estimate CDCA7L gene expression in each pathological grading. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to survey the protein-protein interaction (PPI) network of CDCA7L-regulated oncogenesis. Results: Statistical analysis of the GEO profile revealed that the World Health Organization (WHO) Grade IV (n = 81) gliomas had higher CDCA7L mRNA expression level than in Grade II (n = 7, P = 2.15 × 10 −14) gliomas and nontumor controls (n = 23, P = 2.87 × 10 − 18). Kaplan-Meier analysis reported that patients with high CDCA7L mRNA levels (n = 49) had adverse survival than those with low CDCA7L expression (n = 28). The PPI analysis of CDCA7L-regulated oncogenesis showed CDCA7L as a potential hub protein. Conclusions: The expression of CDCA7L has a positive correlation with the WHO pathological grading and shorter survival. This finding suggests that CDCA7L may be a potential biomarker of prognosis in human gliomas.

An estimated 60,290 new cases of breast carcinoma in situ are expected to be diagnosed in 2015, and approximately 1 in 33 women is likely to receive an in situ breast cancer diagnosis in her lifetime. Although in situ breast cancers are relatively common, their clinical significance and optimal treatment are topics of uncertainty and concern for both patients and clinicians. In this article, the American Cancer Society provides information about occurrence and treatment patterns for the 2 major subtypes of in situ breast cancer in the United States-ductal carcinoma in situ and lobular carcinoma in situ-using data from the North American Association of Central Cancer Registries and the 13 oldest Surveillance, Epidemiology, and End Results registries. The authors also present an overview of in situ breast cancer detection, treatment, risk factors, and prevention and discuss research needs and initiatives.

OBJECTIVE To assess whether there is an association of patient sociodemographic factors with stage at diagnosis, treatment, and overall survival in patients with vulvar cancer in the National Cancer Database. METHODS This was a retrospective cohort study of patients with primary squamous vulvar carcinoma identified from the National Cancer Database (1998-2004). Multivariate logistic regression was conducted to examine risk factors associated with advanced-stage (stage III or IV) disease at diagnosis. Multivariable Cox regression models were performed to explore risk factors associated with 5-year all-cause mortality. RESULTS Of 11,153 patients, 42.3% (n=4,713) were diagnosed with stage I disease, 24.6% (n=2,745) stage II, 22.9% (n=2,556) stage III, and 10.2% (n=1,139) stage IV. Advanced stage was significantly associated with older age, nonprivate insurance, and treatment at a lower case volume center (P

Purpose Geographic access to care may be associated with receipt of chemotherapy but has not been fully examined. This study sought to evaluate the association between density of oncologists and travel distance and receipt of adjuvant chemotherapy for colon cancer within 90 days of colectomy. Patients and Methods Patients in the National Cancer Data Base with stage III colon cancer, diagnosed between 2007 and 2010, and age 18 to 80 years were selected. Generalized estimating equation clustering by hospital service area was conducted to examine the association between geographic access and receipt of oncology services, controlling for patient sociodemographic and clinical characteristics. Results Of 34,694 patients in the study cohort, 75.7% received adjuvant chemotherapy within 90 days of colectomy. Compared with travel distance less than 12.5 miles, patients who traveled 50 to 249 miles (odds ratio [OR], 0.87; P = .009) or ≥ 250 miles (OR, 0.36; P < .001) had decreased likelihood of receiving adjuvant chemotherapy. Density level of oncologists was not statistically associated with receipt of adjuvant chemotherapy (low v high density: OR, 0.98; P = .77). When stratifying analyses by insurance status, non–privately insured patients who resided in areas with low density of oncologists were less likely to receive adjuvant chemotherapy (OR, 0.85; P = .03). Conclusion Increased travel burden was associated with a decreased likelihood of receiving adjuvant chemotherapy, regardless of insurance status. Patients with nonprivate insurance who resided in low-density oncologist areas were less likely to receive adjuvant chemotherapy. If these findings are validated prospectively, interventions to decrease geographic barriers may improve the timeliness and quality of colon cancer treatment.

Surgical procedures require general anesthesia using combinations of drugs including fentanyl and/or lidocaine. Because many of these drugs have bimodal anticonvulsant/proconvulsant effects, they must be administered carefully. We herein report a case of seizure attack during anesthesia induction with low-dose fentanyl and lidocaine in a young child with no history of seizures. A 10-year-old girl was scheduled to receive an elective tenectomy. After a few seconds of fentanyl and lidocaine administration for anesthesia induction, she developed generalized tonic-clonic seizures. Seizures subsided spontaneously after 3 minutes. The patient's blood sugar, serum electrolytes, and arterial blood gas analysis were normal immediately after the event. She remained hemodynamically stable; however, the surgery was postponed after communication and discussion with the surgeon. Postoperatively, there was no evidence of postictal phase, and serum electrolytes and magnetic resonance imaging of the brain were normal. The patient had an uneventful recovery. However, electroencephalogram showed that hyperventilation stimulation test induced isolated epileptiform spikes over O1, suggesting a potential paroxysmal disorder over the left occipital area. This report is on a rare complication likely caused by fentanyl or lidocaine, which suggests that these drugs should be used cautiously in children whose clinical epileptic activities have been verified or are strongly suspected.

BACKGROUND Cytology is an accurate, safe, cost-effective, and guideline-recommended method for the diagnosis of small cell lung carcinoma (SCLC), but little is known about whether its use varies by treatment facility and patient characteristics. METHODS Methods of diagnosis (cytology vs histology) for 86,830 patients with SCLC from 1314 facilities that contributed data to a nationwide registry and associations of diagnostic methods with patient and facility characteristics were studied in bivariate and multivariate analyses. RESULTS The percentages of SCLC cases diagnosed by cytology in community cancer programs, comprehensive community cancer programs, academic cancer programs, and National Cancer Institute-designated cancer centers were 13.2%, 15.4%, 23.3%, and 31.3%, respectively (P

This paper focuses on the aspect of sport, finding out the problem in Taipei's urban planning. Especially, in the view of people's sporting lifestyle from 1895 to now to open up a new way. The following will divide the Taipei's urban planning into three parts, the Japanese occupation (1895-1945), retrocession of Taiwan (1945-1980), localization of Taiwan (1980-). Each period has its own planning values and characteristics in sporting space. Appeal the urban governance to change its way from developmental model to human model and rewrite our life into Taipei.

Recently, resistive switching memory attracts much attention because of its simple structure, easy operation, and non-volatility. In addition, transparent and flexible electronic equipment also attracts much attention. Therefore, ITO/GO/ITO/PES flexible and transparent resistive switching memory devices are proposed. The resistive switching characteristics of the flexible devices are almost unchanged after performing a bending test. So the flexibility of the devices is demonstrated. The retention time of the flexible devices reaches to 10 5 s. The transmittance of the flexible devices is over 80% for the visible light region. Generally speaking, the proposed ITO/GO/ITO/PES device shows great performance. It possibly can be used in the next-generation flexible and transparent electronic equipment.

Background Physicians managing patients with prostate cancer play a critical role in subsequent specialist consultations and initial treatment choice, especially in cases for which no consensus exists regarding optimal treatment strategy. The NCCN Guidelines for Prostate Cancer recommend radiation as a therapy option for patients with locoregional prostate cancer. Purpose The authors examined the association of urologist characteristics with the likelihood that patients would consult radiation oncologists. Methods A retrospective cohort of 39,934 patients aged 66 years or older who were diagnosed with locoregional prostate cancer between 2004 and 2007, and the 2405 urologists who performed the patient diagnostic biopsies were constructed using the SEER-Medicare linked database and the American Medical Association Physician Masterfile. Logistic multilevel regression analysis was used to evaluate the influence of urologists' characteristics on radiation oncologist consultation within 9 months of locoregional prostate cancer diagnosis. Results Overall, 24,549 (61.5%) patients consulted a radiation oncologist. After adjusting for patient and urologist characteristics, patients diagnosed by urologists in noninstitutional settings (eg, physician office) were significantly more likely to consult a radiation oncologist (odds ratio [OR], 1.40; 95% CI, 1.17-1.67; P=.0002) compared with those diagnosed by urologists in institutional settings with a major medical school affiliation. In addition, patients diagnosed by urologists older than 57 years were significantly more likely to consult a radiation oncologist (OR, 1.21; 95% CI, 1.07-1.38, P=.003).

INTRODUCTION Breast cancer in young women tends to be more aggressive, but timely treatment may not be always available, particularly to those without health insurance. We aim to examine whether the dependent coverage expansion under the Affordable Care Act (ACA-DCE) implemented in 2010 was associated with changes in time to treatment among women diagnosed with early stage breast cancer. METHODS A total of 7,176 patients diagnosed with early stage breast cancer in 2007-2009 (pre-ACA) and 2011-2013 (post-ACA) were identified from the National Cancer Database. A quasi-experimental design difference-in-differences (DD) approach was used, with patients aged 19-25 (targeted by the policy) considered as the intervention group, and patients aged 26-34 years (not affected by the policy) as the control group. Changes in the following treatment outcomes were examined: time from diagnosis to surgery, time from surgery to adjuvant chemotherapy, and time from adjuvant chemotherapy to radiation. RESULTS Compared with the control group of patients aged 26-34, young patients aged 19-25 experienced a statistically nonsignificant decrease of 2.7 percentage points (95% CI [-1.2, 6.5]) in the uninsured rate. This did not translate into more reduction in delays to surgery (DD = 2.7 days, 95% CI [-3.2, 8.3]), chemotherapy (DD = -1.0 days, 95% CI [-7.2, 5.2]) or radiation (DD = 5.3 days, 95% CI [-15.6, 26.3]) in the younger cohort than the older cohort. CONCLUSIONS AND RELEVANCE No significant changes in time to treatment were found among young women diagnosed with early stage breast cancer after the implementation of the ACA-DCE. Future studies examining impacts of health care policy reform on breast cancer care are warranted to include patients from low-income families and to consider effects from Medicaid expansion.

Histological classification of renal cell carcinoma (RCC) has become increasingly important for clinical management. We identified 295483 RCC diagnosed from 1998-2014 in the National Cancer Database (NCDB) to examine temporal trends in proportions of RCC with unspecified histology and several specific histologies from the 1998 and 2004 World Health Organization classifications of RCC. Further, multivariable log binomial analysis of 101062 RCC diagnosed from 2010 to 2014 was used to determine whether the association of diagnosing/treating facility type and the proportion of unspecified RCC is independent of patient demographic and clinical factors. Between 1998 and 2014, the proportion of histologically unspecified RCC decreased substantially in all facility types, with the decrease smallest in community programs (from 86.0% to 28.1%) and largest in National Cancer Institute-designated centers (from 85.1% to 9.8%). These decreases were offset by increases in percentages of papillary, clear cell, and chromophobe RCC cases. During 2010 to 2014, relative to community programs, RCCs were 21% less likely to be reported as unspecified histology (adjusted prevalence ratio [aPR] = 0.79; 95% CI, 0.68-0.92) in comprehensive community programs, 32% less likely in integrated network programs (aPR = 0.68; 95% CI, 0.57-0.92) and academic programs (aPR = 0.68; 95% CI, 0.54-0.87), and 63% less likely (aPR = 0.37; 95% CI, 0.26-0.52) in National Cancer Institute -designated programs. These results have implications for the optimal selection of targeted systemic therapies for patients with advanced disease, and for the potential value of cancer registry data in pathology quality improvement programs to promote more rapid and consistent adoption of new classifications of RCC and other neoplasms.

Nonrepresentative biopsy sampling of prostate cancers with a biopsy Gleason score of 8 can adversely influence decisions regarding androgen deprivation in men receiving primary radiation therapy. The frequency of and factors associated with downgrading Gleason 8 biopsies at prostatectomy are not well known.We used records from NCDB (National Cancer Database), a hospital based registry in the United States, of 72,556 men with prostate cancer diagnosed from 2010 to 2013, including 5,474 with Gleason 8 biopsies and no other high progression risk criteria according to NCCN (National Comprehensive Cancer Network®) Guidelines®. The prevalence of Gleason 8 downgrading was calculated. Generalized estimating equation multivariable regression models were used to estimate the prevalence ratios and 95% CIs of downgrading by demographic and clinical factors, and evaluate the association of Gleason 8 downgrading with cT (clinical T) to pathological T category up staging.Of 5,474 Gleason 8 biopsies in men lacking other high progression risk criteria 3,263 (60%) were downgraded, changing the progression risk category from high to intermediate. A higher prevalence of Gleason 8 downgrading was significantly and independently associated with decreasing age, African American race, lower cT category, lower prostate specific antigen quartile and certain combinations of primary and secondary Gleason grades (3 + 5 greater than 4 + 4 greater than 5 + 3). Gleason 8 downgrading in cases of cT less than 3 was independently and significantly associated with a lower prevalence of up staging (prevalence ratio = 0.65, 95% CI 0.61-0.69).Downgrading Gleason 8 biopsies is common. Patient evaluation based on Gleason 8 biopsies often results in overestimating progression risk and disease extent, which may lead to overtreatment.

ObjectivesNeurodegenerative disorders are reportedly characterised by decreased regional cerebral blood flow. However, the association between vertebrobasilar insufficiency (VBI) and dementia remains unclear. In this nationwide, population-based, retrospective cohort study, we explored the potential association between VBI and dementia.DesignNationwide population-based cohort study.SettingPatients with VBI were newly diagnosed between 2000 and 2005 from the Taiwan National Health Insurance Research Database.ParticipantsWe included 3642 subjects as the VBI group. The control cohort included 14 568 randomly selected age-matched and sex-matched VBI-free individuals.Outcome measuresAll subjects were followed until the diagnosis of dementia, death or the end of 2010. Patients with VBI, dementia (viz, vascular and non-vascular, including Alzheimer’s) subtypes and other confounding factors were identified according to the International Classification of Diseases Clinical Modification Codes. Cox proportional hazards regression analysis was employed to examine adjusted HRs after adjusting for confounding factors.ResultsPatients with VBI had a 1.807-fold (95% CI 1.643 to 1.988, pConclusionPatients with VBI appear to have an increased risk of developing dementia. Further research is needed to investigate the underlying pathophysiology.

We explore the use of cubic-zinc peroxide (ZnO2) as a switching material for electrochemical metallization memory (ECM) cell. The ZnO2 was synthesized with a simple peroxide surface treatment. Devices made without surface treatment exhibits a high leakage current due to the self-doped nature of the hexagonal-ZnO material. Thus, its switching behavior can only be observed when a very high current compliance is employed. The synthetic ZnO2 layer provides a sufficient resistivity to the Cu/ZnO2/ZnO/ITO devices. The high resistivity of ZnO2 encourages the formation of a conducting bridge to activate the switching behavior at a lower operation current. Volatile and non-volatile switching behaviors with sufficient endurance and an adequate memory window are observed in the surface-treated devices. The room temperature retention of more than 104 s confirms the non-volatility behavior of the devices. In addition, our proposed device structure is able to work at a lower operation current among other reported ZnO-based ECM cells.

Background Interval colorectal cancer (CRC) accounts for 3% to 8% of all cases of CRC in the United States. Data on interval CRC by race/ethnicity are scant. Objective To examine whether risk for interval CRC among Medicare patients differs by race/ethnicity and whether this potential variation is accounted for by differences in the quality of colonoscopy, as measured by physicians' polyp detection rate (PDR). Design Population-based cohort study. Setting Medicare program. Participants Patients aged 66 to 75 years who received colonoscopy between 2002 and 2011 and were followed through 2013. Measurements Kaplan-Meier curves and adjusted Cox models were used to estimate cumulative probabilities and hazard ratios (HRs) of interval CRC, defined as a CRC diagnosis 6 to 59 months after colonoscopy. Results There were 2735 cases of interval CRC identified over 235 146 person-years of follow-up. A higher proportion of black persons (52.8%) than white persons (46.2%) received colonoscopy from physicians with a lower PDR. This rate was significantly associated with interval CRC risk. The probability of interval CRC by the end of follow-up was 7.1% in black persons and 5.8% in white persons. Compared with white persons, black persons had significantly higher risk for interval CRC (HR, 1.31 [95% CI, 1.13 to 1.51]); the disparity was more pronounced for cancer of the rectum (HR, 1.70 [CI, 1.25 to 2.31]) and distal colon (HR, 1.45 [CI, 1.00 to 2.11]) than for cancer of the proximal colon (HR, 1.17 [CI, 0.96 to 1.42]). Adjustment for PDR did not alter HRs by race/ethnicity, but differences between black persons and white persons were greater among physicians with higher PDRs. Limitation Colonoscopy and polypectomy were identified by using billing codes. Conclusion Among elderly Medicare enrollees, the risk for interval CRC was higher in black persons than in white persons; the difference was more pronounced for cancer of the distal colon and rectum and for physicians with higher PDRs. Primary funding source American Cancer Society.

Importance The use of contralateral prophylactic mastectomies (CPMs) among patients with invasive unilateral breast cancer has increased substantially during the past decade in the United States despite the lack of evidence for survival benefit. However, whether this trend varies by state or whether it is correlated with changes in proportions of reconstructive surgery among these patients is unclear. Objective To determine state variation in the temporal trend and in the proportion of CPMs among women with early-stage unilateral breast cancer treated with surgery. Design, Setting, and Participants A retrospective cohort study of 1.2 million women 20 years of age or older diagnosed with invasive unilateral early-stage breast cancer and treated with surgery from January 1, 2004, through December 31, 2012, in 45 states and the District of Columbia as compiled by the North American Association of Central Cancer Registries. Data analysis was performed from August 1, 2015, to August 31, 2016. Exposure Contralateral prophylactic mastectomy. Main Outcomes and Measures Temporal changes in the proportion of CPMs among women with early-stage unilateral breast cancer treated with surgery by age and state, overall and in relation to changes in the proportions of those who underwent reconstructive surgery. Results Among the 1 224 947 women with early-stage breast cancer treated with surgery, the proportion who underwent a CPM nationally increased between 2004 and 2012 from 3.6% (4013 of 113 001) to 10.4% (12 890 of 124 231) for those 45 years or older and from 10.5% (1879 of 17 862) to 33.3% (5237 of 15 745) for those aged 20 to 44 years. The increase was evident in all states, although the magnitude of the increase varied substantially across states. For example, among women 20 to 44 years of age, the proportion who underwent a CPM from 2004-2006 to 2010-2012 increased from 14.9% (317 of 2121) to 24.8% (436 of 1755) (prevalence ratio [PR], 1.66; 95% CI, 1.46-1.89) in New Jersey compared with an increase from 9.8% (162 of 1657) to 32.2% (495 of 1538) (PR, 3.29; 95% CI, 2.80-3.88) in Virginia. In this age group, CPM proportions for the period from 2010 to 2012 were over 42% in the contiguous states of Nebraska, Missouri, Colorado, Iowa, and South Dakota. From 2004 to 2012, the proportion of reconstructive surgical procedures among women aged 20 to 44 years who were diagnosed with early-stage breast cancer and received a CPM increased in many states; however, it did not correlate with the proportion of women who received a CPM. Conclusions and Relevance The increase in the proportion of CPMs among women with early-stage unilateral breast cancer treated with surgery varied substantially across states. Notably, in 5 contiguous Midwest states, nearly half of young women with invasive early-stage breast cancer underwent a CPM from 2010 to 2012. Future studies should examine the reasons for the geographic variation and increasing trend in the use of CPMs.

BACKGROUND Version 2 of the Collaborative Stage Data Collection System (CSv2) became effective with cases diagnosed in 2010. This report focuses on the CSv2 components required to derive the American Joint Committee on Cancer (AJCC) stage for prostate cancer and on the site-specific factors for prostate cancer captured in CSv2. The report also highlights differences between the AJCC 6th and 7th editions for classifying prostate cancer stage. METHODS Data from 18 Surveillance, Epidemiology, and End Results (SEER) Program population-based registries (SEER-18) were analyzed for the years 2004-2010, which included 400,591 prostate cancer cases. RESULTS CSv2 provides specificity with regard to the Gleason grading system by distinguishing between clinical and pathologic patterns and scores. The AJCC 7th edition incorporates prostate-specific antigen values into staging, subdivides stage II into IIA and IIB, and reclassifies extraprostatic invasion with microscopic bladder neck invasion from T4 in the 6th edition to T3a; this latter change affected the AJCC stage of 283 cases in 2010. Of the 44,578 prostate cancer cases diagnosed in 2010 that would have been classified as stage II in the AJCC 6th edition, 32.7%, 27.5%, and 39.8% are classified as stages I, IIA, and IIB, respectively, in the 7th edition. CONCLUSIONS CSv2 provides more information than was previously available to researchers using SEER prostate data. The absence of a clearly defined clinical stage for each prostate case is the overriding limitation that researchers face in relying on Collaborative Stage information to analyze prostate cancer data. Cancer 2014;120(23 suppl):3758-70. © 2014 American Cancer Society.

Background & Aims Hepatitis C virus (HCV) infection leads to glucose abnormality. HCV depends on lipid droplets (LDs) and very-low density lipoproteins for assembly/releasing; however, the components and locations for this process remain unidentified. Apolipoprotein J (ApoJ), upregulated by glucose, functions as Golgi chaperone of secreted proteins and resides abundantly in very-low density lipoproteins. This study investigates the interplay between glucose, ApoJ and HCV virion production. Methods The effects of high glucose on ApoJ expression and HCV production were evaluated with cultivated HuH7.5, primary human hepatocytes, and in treatment naive chronic hepatitis C patients. How ApoJ affects HCV lifecycle was assessed using siRNA knockdown strategy in JFH1 infected and subgenomic replicon cells. The interactions and locations of ApoJ with viral and host components were examined by immunoprecipitation, immunofluorescence and subcellular fractionation experiments. Results HCV infection increased ApoJ expression, which in parallel with HCV infectivity was additionally elevated with high glucose treatment. Serum ApoJ correlated positively with fasting blood glucose concentration and HCV-RNA titre in patients. ApoJ silencing reduced intracellular and extracellular HCV infectivity and extracellular HCV-RNA, but accumulated intracellular HCV-RNA in HCV-infected cells. ApoJ interacted with HCV core and NS5A and stabilized the dual protein complex. HCV infection dispersed cytoplasmic ApoJ from the compact zones of the Golgi to encircle LDs, where co-localization of the core, NS5A, HCV-RNA, subcellular markers for LDs, endoplasmic reticulum (ER), Golgi, and membrane contact sites occurred. Conclusions ApoJ facilitates infectious HCV particle production via stabilization of core/NS5A, which might surround LDs at the ER-Golgi membrane contact site.

BACKGROUND The management of stage I testicular seminoma is evolving rapidly. This study examined modern trends in the management of stage I testicular seminoma and the effects of sociodemographic factors on therapy choice. METHODS Data from the National Cancer Data Base on 34,067 patients with stage I testicular seminoma who were treated between 1998 and 2011 were analyzed. Multivariate logistic regression models were used to assess factors associated with adjuvant management strategies. RESULTS For patients with stage IA/B testicular seminoma, rates of observation after orchiectomy increased from 23.7% to 54.0%, the receipt of adjuvant chemotherapy increased from 1.5% to 16.0%, and the receipt of radiotherapy decreased from 70.8% to 28.8%. A similar pattern was seen in stage IS testicular seminoma, although these patients were more likely to receive adjuvant radiotherapy/chemotherapy (60.7% vs 44.8% for stage IA/B in 2011, P

BACKGROUND Serious psychological distress (SPD) is associated with adverse health outcomes such as poor quality of life and shorter survival in cancer survivors, but to the authors’ knowledge, the relationship between SPD and health care use and medical expenditures is not clear.

Objectives Physician characteristics and changes in drug reimbursement rates have been shown to influence practice patterns regardless of clinical guidelines, patient, clinical, or sociodemographic factors. We concurrently examined the association between urologists׳ characteristics and non–evidence-based use of primary medical androgen deprivation therapy (ADT) for clinically localized patients with prostate cancer, before and after the 2003 Medicare Modernization Act׳s reductions in ADT reimbursement rates. Methods and materials The Surveillance, Epidemiology, and End Results-Medicare–linked database and the American Medical Association Physician Masterfile are used in a retrospective analysis of 12,255 patients diagnosed between 2001 and 2007 with clinical stage T1-T2, low- to intermediate-grade prostate cancer, and the 1,863 urologists who treated them. Logistic multilevel regression analyses are used to evaluate the association of urologists׳ characteristics on ADT use among patients within 6 months of diagnosis. Results Overall, 3,866 (32%) patients received non–evidence-based ADT. After adjusting for patient and urologist characteristics, patients treated by urologists with no medical school affiliations, compared with those treated by urologists with major medical school affiliations, are significantly more likely to receive non–evidence-based medical ADT (odds ratio = 2.35; 95% CI: 1.71–3.23; P P Conclusions Patients treated by non–medical school–affiliated or non–US-trained urologists or both are significantly more likely to receive non–evidence-based ADT before and after the passage of the Medicare Modernization Act. Better strategies to encourage evidence-based ADT use on clinically localized patients with prostate cancer may be of benefit especially among non–medical school–affiliated or non–US-trained urologists or both.

Resistive switching memory with good performance can be possibly used in next-generation nonvolatile memory and flexible electronics. In the previous studies, some of the flexible resistive switching layers were organic materials. In this paper, an inorganic Al/Al 2 O 3 /ZrO 2 /Al flexible resistive switching memory fabricated at room temperature is proposed for the first time. The resistive switching can be reproduced for over 100 times with stable resistive switching characteristics. In addition, a possible resistive switching filamentary model of the flexible device is demonstrated in this paper. The flexibility and nonvolatility of the flexible device are also demonstrated. Based on the experimental results, the proposed Al/Al 2 O 3 /ZrO 2 /Al flexible device is possibly used in next-generation flexible electronics.

The number of cancer survivors continues to increase due to the aging and growth of the population and improvements in early detection and treatment. In order for the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborated to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results (SEER) program registries. In addition, current treatment patterns for the most common cancer types are described based on information in the National Cancer Data Base and the SEER and SEER-Medicare linked databases; treatment-related side effects are also briefly described. Nearly 14.5 million Americans with a history of cancer were alive on January 1, 2014; by January 1, 2024, that number will increase to nearly 19 million. The 3 most common prevalent cancers among males are prostate cancer (43%), colorectal cancer (9%), and melanoma (8%), and those among females are cancers of the breast (41%), uterine corpus (8%), and colon and rectum (8%). The age distribution of survivors varies substantially by cancer type. For example, the majority of prostate cancer survivors (62%) are aged 70 years or older, whereas less than one-third (32%) of melanoma survivors are in this older age group. It is important for clinicians to understand the unique medical and psychosocial needs of cancer survivors and to proactively assess and manage these issues. There are a growing number of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship.

Ce 0.8 Sm 0.15 R 0.05 O 2− δ (R = Sm, Mg, Ca, Sr, and Ba) specimens were successfully prepared using a solid-state reaction, and they were used in an intermediate temperate solid oxide fuel cell (IT-SOFC) electrolyte. This study focused on the effects of co-doping and an aging treatment for the conductivities and microstructures of CeO 2 -based ceramics and also analyzed the variation of the conductivity in the reducing atmosphere. The study showed that the conductivities of the CeO 2 -based materials have a higher conductivity at 500–800 °C by the co-doping aliovalent cations Sm and R. The conductivity increased with the increasing oxygen vacancies that were induced from charge compensation. The XRD and EDS analyses showed that the MgO and BaCeO 3 phases appeared in the Ce 0.8 Sm 0.15 Mg 0.05 O 2− δ and Ce 0.8 Sm 0.15 Ba 0.05 O 2− δ specimens, respectively. The conductivity of the Ce 0.8 Sm 0.15 Ca 0.05 O 2− δ specimens was higher, approximately 0.0837 S/cm at 800 °C in the air. The thermal expansion coefficient (TEC) in all samples was ca. 11–15 × 10 −6 /°C at 200–800 °C. After an aging treatment at 700 °C for a holding time of 1000 h, the conductivities of all samples showed almost no change. However, the conductivity in Ce 0.8 Sm 0.15 Ca 0.05 O 2− δ decreased from 0.0837 to 0.0581 S/cm, and the grain size increased. The conductivities of the CeO 2 -based specimens were also measured under a 5%H 2 –95%N 2 atmosphere, and the conductivity greatly increased in the reducing atmosphere because the Ce 4+ ions reduced to Ce 3+ ions.

To examine the accuracy of clinical staging and its effects on outcome in bladder cancer (BC) patients treated with radical cystectomy (RC), using a large national database.A total of 16,953 patients with BC without distant metastases treated with RC from 1998 to 2009 were analyzed. Factors associated with clinical-pathologic stage discrepancy were assessed by multivariate generalized estimating equation models. Survival analysis was conducted for patients treated between 1998 and 2004 (n=7270) using the Kaplan-Meier method and Cox proportional hazards models.At RC 41.9% of patients were upstaged, whereas 5.9% were downstaged. Upstaging was more common in females, the elderly, and in patients who underwent a more extensive lymphadenectomy. Downstaging was less common in patients treated at community centers, in the elderly, and in Hispanics. Receipt of preoperative chemotherapy was highly associated with downstaging. Five-year overall survival rates for patients with clinical stages 0, I, II, III, and IV were 67.2%, 62.9%, 50.4%, 36.9%, and 27.2%, respectively, whereas those for the same pathologic stages were 70.8%, 75.8%, 63.7%, 41.5%, and 24.7%, respectively. On multivariate analysis, upstaging was associated with increased 5-year mortality (hazard ratio [HR] 1.80, P.001), but downstaging was not associated with survival (HR 0.88, P=.160). In contrast, more extensive lymphadenectomy was associated with decreased 5-year mortality (HR 0.76 for ≥10 lymph nodes examined, P.001), as was treatment at an National Cancer Institute-designated cancer center (HR 0.90, P=.042).Clinical-pathologic stage discrepancy in BC patients is remarkably common across the United States. These findings should be considered when selecting patients for preoperative or nonoperative management strategies and when comparing the outcomes of bladder sparing approaches to RC.

Up to now, different metals have been adopted as the electrode materials for MoOx/Si photodetectors and solar cells, but the influence of these different metals has not been investigated. We have systematically studied and proved that the choice of metal has great impact on optoelectronic performance. Ag and Al with similar low work functions display similar current-voltage behavior before and after introduction of MoOx; whereas Au and Ni which own similar high work functions lead to another type of current-voltage behavior. MoOx in the metal/MoOx/Si samples brings the superior diode behavior with an enhanced responsivity and decreased dark current as compared with the metal/Si samples. The choice of Ag as the top electrode on MoOx/Si has low alloying or defect formation with the MoOx/Si structure preventing the deterioration of the diode behavior, and the large downward band bending in MoOx at the Ag/MoOx junction facilitates the multitunnelling capture emission. This leads to high responsivity while maintaining the low dark current.

Hydrogen peroxide treatment induces the phase transformation of hexagonal ZnO to cubic ZnO2 on the surface of the ZnO switching memory film; this oxidation process effectively reduces the concentration of n-type donor defects (oxygen vacancies and zinc interstitials) in the switching film. The chemically oxidized ZnO2 layer not only lowers the operation current of the device but also can serve as an oxygen “bank” to improve the endurance of the memristor. The oxidation reaction of peroxide treatment can be easily controlled to achieve an analog behavior with good switching uniformity. The analog memristor device is able to perform two-bit per cell and synaptic operations. Based on the experimental synaptic data, an image processing of 7 × 9 pixels using a simulated artificial neural network comprises 63 synapses is evaluated to mimic the visual cortex function of the brain.

BACKGROUND A prior assessment of concordance between the diagnosis month in SEER records and Medicare claims found reasonable agreement; however, no assessment of the impact of discordance on cancer treatment ascertainment was conducted. OBJECTIVES The aim of this study was to assess the concordance between the SEER diagnosis date (Sdx) and Medicare claim-derived diagnosis date and the impact of discordance on identification of treatment received. METHODS The first Medicare claim date with a cancer diagnosis (Mdx) was compared with the Sdx among patients diagnosed with breast, colorectal, or lung cancer. The Mdx was considered concordant with the Sdx if the Mdx was within 16 days. Claims within 4 months after both the Mdx and Sdx were examined to collect treatment information. Treatment rate agreement was measured by κ-statistics. RESULTS Among 50,731 breast, 51,025 colorectal, and 61,384 lung cancer patients, the Sdx and Mdx were concordant in 79%, 86%, and 73% of cases, respectively. Most discordant Mdx cases were identified in the month after the SEER diagnosis month. A small proportion of cases (7%-12%) preceded the SEER diagnosis month. Agreement for receipt of surgery was very good across all 3 cancer sites (κ>0.88) and was excellent for radiation therapy (κ>0.96). CONCLUSIONS Although most cases were concordant for both diagnosis date and treatment ascertainment, there was still a small proportion of cases discordant for both diagnosis date and treatment identification. This study underscores the importance of examining claims in the months preceding diagnosis in the SEER-Medicare dataset to ensure patients are appropriately selected for analysis.

Homocysteine (Hcy) levels may rise after a stroke, but the mechanism of Hcy-induced cerebral endothelial cell (CEC) dysfunction has not been explored. In this study we examined the role of the acid sphingomyelinase (Asm)–ceramide pathway in the molecular mechanism of Hcy-induced CEC dysfunction. Murine CECs were prepared from fresh mouse brains. CECs were treated with 50–500 μM Hcy and 30–100 μM C2-ceramide for 48 h. Sphingomyelinase assays were performed to determine Asm activity. Quantitative assessments of cell survival and death by the MTT reduction and LDH release were conducted. Treatment of murine CECs with Hcy and ceramide caused cell death in a dose-dependent manner as determined by LDH and MTT assays. 250 μM Hcy and 50 μM C2-ceramide caused 50% cell death. Hcy induced murine CEC death also occurred in a time-dependant manner with substantial cell death noted as early as 24 h after Hcy exposure. C2-ceramide-induced murine CEC death occurred earlier than Hcy-induced cell death by about 18 h. Hcy treatment increased Asm activity and intracellular ceramide accumulation. This study demonstrated that Hcy and C2-ceramide can cause murine CEC death. Hcy induces CEC death possibly by activating the Asm–ceramide pathway.

BACKGROUND Prostate cancer treatment choices have been shown to vary by physician and patient characteristics. For patients with low-risk, clinically localized prostate cancer, the authors examined the impact of their clinical, sociodemographic, and radiation oncologists' (RO) characteristics on the likelihood that the patients would receive combined external beam radiotherapy and brachytherapy, a treatment regimen that is at variance with clinical guidelines. METHODS The Surveillance, Epidemiology and End Results (SEER)-Medicare linked database and the American Medical Association Physician Masterfile were used in a retrospective analysis of 5531 patients with low-risk, clinically localized prostate cancer who were diagnosed between 2004 and 2007, and the 708 ROs who treated them. Hierarchical logistic regression analyses were used to evaluate the relationship between patient and RO characteristics and the use of combined therapy within 6 months of diagnosis. RESULTS Overall, 356 patients (6.4%) received combined therapy. Nonclinical factors were found to be associated with combined therapy. After adjusting for patient and RO characteristics, the odds of receiving combined therapy for patients residing in Georgia were found to be significantly greater than for all other SEER regions. Black patients were significantly less likely to receive combined therapy (odds ratio, 0.62; 95% confidence interval, 0.40-0.96 [P = .03]) compared with white patients. In addition, ROs accounted for 36.6% of the variation in patients receiving combined therapy. CONCLUSIONS Geographic and sociodemographic factors were found to be significantly associated with guideline-discordant combined therapy for patients diagnosed with low-risk, clinically localized prostate cancer. Which RO a patient consults is important in determining whether they receive combined therapy. Cancer 2013;119:3619–3628. © 2013 American Cancer Society.

Herein we report the first total synthesis of the natural product Urkuthaplestatin A (Ustat A) utilizing a convergent synthetic strategy. The characterization and biological activity match those of the previously published natural product. Interestingly, several intermediates, including the linear and serine cyclized precursors, show a 100-fold decrease in cytotoxicity, with IC50's in the low micromolar range. These data indicate that the rigidity and the consecutive aromatic heterocyclic system are responsible for the biological activity.

A polymeric material consisting of self-terminated oligomers with hyper branched architecture, also known as STOBA, is used as surface coating of Li(Ni0.4Co0.2Mn0.4)O2 cathode particles, and it is shown to effectively suppress thermal runaway and slow down voltage drop of graphite/Li(Ni0.4Co0.2Mn0.4)O2 18650-battery during nail-penetration test. In situ synchrotron X-ray diffraction study indicates that the STOBA coating does not affect the layer-to-spinel phase transformation, suggesting that the suppressing mechanism is operative below the temperature of oxygen release from the oxide particles. Data of electrochemical and differential scanning calorimetry (DSC) analyses suggest that STOBA coating passivates the surface activity of charged cathode particles so that formation of solid-electrolyte-interphase (SEI) under high potential is suppressed and that heat-generation rate arising from SEI break-down and electrolyte decomposition by the charged cathode surface upon heating is significantly reduced. The combination of the reduced joule-heating and diminished heat generation by the electrolyte-oxide interfacial reaction may contribute to the suppression of thermal runaway as a result of the STOBA coating.

Flexible electronics attracts much attention due to its advantages of flexibility and light weight. The resistive switching memory fabricated at low temperature with good performance is possibly used in the flexible electronics. In this work, an Al/TiO2/Al structural device is successfully fabricated on a flexible substrate at room temperature for the first time. The resistive switching properties of the flexible device are investigated. A possible resistive switching mechanism is proposed. The non-volatility of the flexible device is also demonstrated. Based on the experimental results, the proposed flexible device is possibly used in flexible non-volatile memory.

In this work, the effects of crystallization and non-lattice oxygen atoms on the Cu(x)O-based memory device are investigated. The 150 degrees C-deposited Cu(x)O film possesses a larger amount of non-lattice oxygen atoms than those deposited at the higher temperatures, leading to the formation of AIOy interface layer during the sputtering deposition of Al top electrode. Resistive switching occurring within the interface layer is easily controlled, so the set and reset voltages are decreased. In addition, it is demonstrated that the set and reset processes agree with the formation and rupture of a conductive filament in the Cu(x)O film. The 150 degrees C-deposited Cu(x)O-based memory device with good non-volatility is possibly used in the next-generation non-volatile memory.

We report the synthesis, cytotoxicity, and phenotypic analysis of oxazole and thiazole containing fragments. Evaluating the optimal size and heterocycle for growth inhibition and apoptosis showed that activity required at least two thiazoles sequentially connected. This is the first detailed comparison of biological activity between multi-heterocyclic containing fragments.

Background Headache such as migraine is associated with stroke. Studies focused on primary headache disorders (PHDs) as a risk factor for stroke are limited. The purpose of this population-based cohort study was to explore whether patients with PHDs were at a high risk for developing stroke. Methods A total of 1346 patients with PHDs were enrolled and compared with 5384 age-, gender- and co-morbidity-matched control cohorts. International Classification of Diseases, Clinical Modification codes were administered for the definition of PHDs, stroke, and stroke risk factors. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR). Results PHDs patients exhibited a 1.49 times (95% CI :1.15–1.98, p < 0.01) higher risk for developing ischaemic stroke compared with that of control cohorts. Both migraine (HR = 1.22, 95% CI :1.13–1.97, p < 0.05) and tension-type headache (HR = 2.29, 95% CI :1.22–2.80, p < 0.01) were associated with an increased risk of ischemic stroke. Females with PHDs were at greater risk of developing ischaemic stroke (HR = 1.49, 95% CI :1.13–1.90, p < 0.01) than those without PHDs. PHDs patient aged 45 to 64 years displayed significantly higher risk to develop ischaemic stroke (HR = 1.50, 95% CI: 1.11–2.10, p < 0.05) than the matched controls. The impact of PHDs on ischaemic stroke risk became gradually apparent by different following time intervals beyond 2 years after first diagnosis. Conclusion PHDs is suggestive of an incremental risk for ischaemic stroke with gender-dependent, age-specific and time-dependent characteristics. Electronic supplementary material The online version of this article (doi:10.1186/s10194-016-0701-2) contains supplementary material, which is available to authorized users.

Although the comorbidity of migraine and restless legs syndrome (RLS) has been well-documented, the association between RLS and migraine frequency has yet to be elucidated. The present study aims to evaluate the prevalence of RLS among individuals who experience low-frequency, high-frequency, or chronic migraine presenting with and without aura. We conducted a cross-sectional, case-controlled study involving 505 participants receiving outpatient headache treatment. Standardized questionnaires were administered to collect information on experiences of migraine, RLS, sleep quality, anxiety, depression, and demographics. Participants were categorized into low-frequency (1–8/month), high-frequency (9–14/month), and chronic (≥15/month) headache groups. RLS was diagnosed according to the criteria outlined by the International RLS Study Group (IRLSSG). The Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) were used to assess sleep quality and identify symptoms of anxiety and depression. Associations between migraine frequency and RLS prevalence were investigated using multivariate linear and logistic regression. Univariate analysis revealed an effect of migraine frequency on RLS prevalence (p = 0.026), though this effect did not persist following adjustment for baseline characteristics (p = 0.256). The trend was robust in patients whose migraines presented with auras (p univariate = 0.002; p multivariate = 0.043) but not in those without auras (p univariate and p multivariate > 0.05). Higher anxiety [odds ratio (OR) = 1.18, p = 0.019] and sleep disturbance (OR = 1.17, p = 0.023) scores were associated with higher RLS prevalence. Higher migraine frequency correlates with a higher prevalence of RLS, particularly among patients with auras.

A key challenge in neurobiology is to understand how neural circuits function to guide appropriate animal behaviors. Drosophila melanogaster is an excellent model system for such investigations due to its complex behaviors, powerful genetic techniques, and compact nervous system. Laboratory behavioral assays have long been used with Drosophila to simulate properties of the natural environment and study the neural mechanisms underlying the corresponding behaviors (e.g. phototaxis, chemotaxis, sensory learning and memory)(1-3). With the recent availability of large collections of transgenic Drosophila lines that label specific neural subsets, behavioral assays have taken on a prominent role to link neurons with behaviors(4-11). Versatile and reproducible paradigms, together with the underlying computational routines for data analysis, are indispensable for rapid tests of candidate fly lines with various genotypes. Particularly useful are setups that are flexible in the number of animals tested, duration of experiments and nature of presented stimuli. The assay of choice should also generate reproducible data that is easy to acquire and analyze. Here, we present a detailed description of a system and protocol for assaying behavioral responses of Drosophila flies in a large four-field arena. The setup is used here to assay responses of flies to a single olfactory stimulus; however, the same setup may be modified to test multiple olfactory, visual or optogenetic stimuli, or a combination of these. The olfactometer setup records the activity of fly populations responding to odors, and computational analytical methods are applied to quantify fly behaviors. The collected data are analyzed to get a quick read-out of an experimental run, which is essential for efficient data collection and the optimization of experimental conditions.