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| 1 | Predictive biomarkers in precision medicine and drug development against lung cancer显示文摘The molecular characterization of various cancers has shown that cancers with the same origins,histopathologic diagnoses,and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis.A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been identified.Therapeutic agents targeting some of these cancer drivers have been successfully developed,resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer patients.However,because such therapeutic drugs often benefit only a limited number of patients,the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted therapies.Thus,biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug development.This review discusses the molecular heterogeneity of lung cancer pathogenesis;predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),c-ros oncogene 1 receptor tyrosine kinase[ROSl),and immune checkpoints;biomarkers associated with resistance to these therapeutics;and approaches to identify predictive biomarkers in anticancer drug development.The identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition rate.Additionally,such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits. | Bingliang Fang Reza J Mehran John V Heymach Stephen G Swisher | 2015 | Chinese Journal of Cancer2015，34，7： | 5 |
| 2 | Hepatitis B infection among adults in the philippines:A national seroprevalence study显示文摘AIM:To determine the prevalence of hepatitis B surface antigen(HBsAg)seropositivity among adult Filipinos.METHODS:Testing for HBsAg was performed on serum samples from persons aged ≥ 20 years old who participated in the National Nutrition and Health Survey(NNHeS)conducted in 2003.Information on age,sex,marital status,educational attainment,employment status,and income were collected.For this study,marital status was classified as never married or otherwise(i.e.,married,divorced,separated,widowed);educational attainment was classified as high school graduate or below or at least some tertiary education;and employment status was classified as currently employed or currently unemployed.Annual income was divided into 4 quartiles in Philippine pesos(PhP):Q1,≤ PhP 53064;Q2,PhP 53065-92192;Q3,PhP 92193-173387;and Q4,≥ PhP 173388.Prevalence estimates were weighted so that they represented the general population.Social and demographic factors were correlated with HBsAg seropositivity.Multivariate analysis was used to determine independent predictors of HBsAg seropositivity.RESULTS:A total of 2150 randomly selected adults,20 years and over,out of the 4753 adult participants of NNHeS were tested for HBsAg.The HBsAg seroprevalence was 16.7%(95%CI:14.3%-19.1%),which corresponded to an estimated 7278968 persons infected with hepatitis B.There was no significant difference between males and females(17.5% vs 16.0%;P = 0.555).This corresponded to an estimated 3721775 men and 3557193 women infected with hepatitis B.The HBsAg seroprevalence peaked at age 20-39 years old,with declining prevalence in the older age groups.The only independent predictor of HBsAg seropositivity was the annual income,with persons in the highest income quartile being less likely to be HBsAg positive(age-adjusted OR = 0.51;95%CI:0.30-0.86)compared to subjects in the lowest income quartile.Sex,marital status,educational attainment,and employment status were not found to be independent predictors of HBsAg seropositivity.CONCLUSION:The high HBsAg seroprevalence among adults in the Philippines classifies the country as hyperendemic for HBV infection and appears unchanged over the last few decades. | Stephen N Wong Janus P Ong Madalinee Eternity D Labio Oscar T Cabahug Maria Lourdes O Daez Erlinda V Valdellon Jose D Sollano Jr Marilyn O Arguillas | 2013 | World Journal of Hepatology2013，5，4： | 3 |
| 3 | Hepatocellular carcinoma with child Pugh-A Cirrhosis treated with stereotactic body radiotherapy显示文摘AIM To evaluate the control, survival, and hepatic function for Child Pugh(CP)-A patients after Stereotactic body radiotherapy(SBRT) in hepatocellular carcinoma(HCC).METHODS From 2009 to 2016, 40 patients with Barcelona Liver Clinic(BCLC) stages 0-B HCC and CP-A cirrhosis completed liver SBRT. The mean prescription dose was 45 Gy(40 to 50 Gy in 4-5 fractions). Local relapse, defined as recurrence within the planning target volume was assessed with intravenous multiphase contrast computed tomography or magnetic resonance imaging every 4-6 mo after completion of SBRT. Progression of cirrhosis was evaluated by CP and Model for End Stage Liver Disease scores every 3-4 mo. Toxicities were graded per the Common Terminology Criteria for Adverse Events(v4.03). Median follow-up was 24 mo.RESULTS Forty-nine HCC lesions among 40 patients were analyzed in this IRB approved retrospective study. Median tumor diameter was 3.5 cm(1.5-8.9 cm). Six patients with tumors ≥ 5 cm completed planned selected transarterial chemoembolization(TACE) in combination with SBRT. Eight patients underwent orthotropic live transplant(OLT) with SBRT as a bridging treatment(median time to transplant was 12 mo, range 5 to 23 mo). The Pathologic complete response(PCR) rate in this group was 62.5%. The 2-year in-field local control was 98%(1 failure). Intrahepatic control was 82% and 62% at 1 and 2 years, respectively. Overall survival(OS) was 92% and 60% at 1 and 2 years, with a median survival of 41 mo per Kaplan Meier analysis. At 1 and 2 years, 71% and 61% of patients retained CPA status. Of the patients with intrahepatic failures, 58% developed progressive cirrhosis, compared to 27% with controlled disease(P = 0.06). Survival specific to hepatic failure was 92%, 81%, and 69% at 12, 18, and 24 mo. There was no grade 3 or higher toxicity. On univariate analysis, gross tumor volume(GTV) < 23 cc was associated with freedom from CP progression(P = 0.05), hepatic failure-specific survival(P = 0.02), and trended with OS(P = 0.10).CONCLUSION SBRT is safe and effective in HCC with early cirrhosis and may extend waiting time for transplant in patients who may not otherwise be immediate candidates. | Shaakir Hasan Ngoc Thai Tadahiro Uemura Vijay Kudithipudi Paul Renz Stephen Abel Alexander V Kirichenko | 2017 | World Journal of Gastrointestinal Surgery2017，9，12： | 2 |
| 4 | Landscape features and weather influence nest survival of a ground-nesting bird of conservation concern,the greater sage-grouse,in humanaltered environments显示文摘Introduction:Ground-nesting birds experience high levels of nest predation.However,birds can make selection decisions related to nest site location and characteristics that may result in physical,visual,and olfactory impediments to predators.Methods:We studied daily survival rate[DSR]of greater sage-grouse(Centrocercus urophasianus)from 2008 to 2010 in an area in Wyoming experiencing large-scale alterations to the landscape.We used generalized linear mixed models to model fixed and random effects,and a correlation within nesting attempts,individual birds,and years.Results:Predation of the nest was the most common source of nest failure(84.7%)followed by direct predation of the female(13.6%).Generally,landscape variables at the nest site(≤30 m)were more influential on DSR of nests than features at larger spatial scales.Percentage of shrub canopy cover at the nest site(15-m scale)and distances to natural gas wells and mesic areas had a positive relationship with DSR of nests,whereas distance to roads had a negative relationship with DSR of nests.When added to the vegetation model,maximum wind speed on the day of nest failure and a 1-day lag in precipitation(i.e.,precipitation the day before failure)improved model fit whereby both variables negatively influenced DSR of nests.Conclusions:Nest site characteristics that reduce visibility(i.e.,shrub canopy cover)have the potential to reduce depredation,whereas anthropogenic(i.e.,distance to wells)and mesic landscape features appear to facilitate depredation.Last,predators may be more efficient at locating nests under certain weather conditions(i.e.,high winds and moisture). | Stephen L Webb Chad V Olson Matthew R Dzialak Seth M Harju Jeffrey B Winstead Dusty Lockman | 2012 | Ecological Processes2012，1，1： | 2 |
| 5 | Labeling of influenza viruses with synthetic fluorescent and biotin-labeled lipids显示文摘Direct labeling of virus particles is a powerful tool for the visualization of virus–cell interaction events. However, this technique involves the chemical modification of viral proteins that affects viral biological properties. Here we describe an alternative approach of influenza virus labeling that utilizes Function-Spacer-Lipid(FSL) constructs that can be gently inserted into the virus membrane. We assessed whether labeling with fluorescent(fluo-Ad-DOPE) or biotin-labeled(biot-CMG2-DOPE) probes has any deleterious effect on influenza virus hemagglutinin(HA) receptor specificity, neuraminidase(NA) activity, or replicative ability in vitro. Our data clearly show that neither construct significantly affected influenza virus infectivity or viral affinity to sialyl receptors. Neither construct influenced the NA activities of the influenza viruses tested, except the A/Puerto Rico/8/34(H1N1) strain. Our data indicate that lipid labeling provides a powerful tool to analyze influenza virus infection in vitro. | Natalia A Ilyushina Evgeny S Chernyy Elena Y Korchagina Aleksra S Gambaryan Stephen M Henry Nicolai V Bovin | 2014 | Virologica Sinica2014，29，4： | 2 |
| 6 | IL 28 B genotype is not useful for predicting treatment outcome in A sian chronic hepatitis B patients treated with pegylated interferon‐α显示文摘 | Jacinta A Holmes Tin Nguyen Dilip Ratnam Neel M Heerasing Jane V Tehan Sara Bonanzinga Anouk Dev Sally Bell Stephen Pianko Robert Chen Kumar Visvanathan Rachel Hammond David Iser Ferry Rusli William Sievert Paul V Desmond D Scott Bowden Alexander J Thomps | 2013 | J Gastroenterol Hepatol2013，，5： | 2 |
| 7 | Computer simulations of electrokinetic injection techniques in microfluidic devices 显示文摘 | Sergey V E Stephen C J Ramsey J M | 2000 | Anal Chem2000，72，15： | 1 |
| 8 | Resistance spot welding of aluminum alloy to steel with transition material显示文摘 | Sun X Stephens E V Khaleel M A | 2004 | Welding Journal2004，83，6： | 1 |
| 9 | Analysis of the efficacy and safety of excimer laser PTK in the treatment of corneal disease显示文摘 | Stephen J Zuckerman James V Aquavella Steve B Park | 1996 | Cornea1996，15，1： | 1 |
| 10 | Analysis of bacterial function by multi - colour fluorescence flow cytometry and single cell sorting 显示文摘 | Nebe V Caron G Stephens P J | 2000 | J Microbiol Methods2000，42，1： | 1 |
| 11 | Transgenic pigs as bioreactors: a comparison ofgamma-carboxylation of glutamic acid in recombinant humanprotein C and factor Ⅸ by the mammary gland显示文摘 | KEVIN E V C STEPHEN P B CHRISTOPHER G R | 1999 | Genetic Analysis: Biomolecular Engineering1999，15，： | 1 |
| 12 | Linear multiuser receivers:effective interference effective bandwidth and user capacity 显示文摘 | Stephen V Hanly | 1999 | IEEE Transactions on information the ory1999，45，2： | 1 |
| 13 | Hydrology and the Ec-ological Quality of Scottish River Ecosystems显示文摘 | D J Gilvear K V Heal A Stephen | 2002 | TheScience of the Total Environment2002，294，6： | 1 |
| 14 | Promoting ecosystem and human health in urban areas using Green Infrastructurc: A literature review显示文摘 | Konstanrinos T Kalevi K Stephen V | 2007 | Lndscape and Urban Planning2007，81，3： | 1 |
| 15 | Effects of fusion zone size and failure mode on peak load and energy absorption of advanced high strength steel spot welds under lap shear loading conditions显示文摘 | Sun X Stephens E V Khaleel M A | 2008 | Engineering Failure Analysis2008，15，4： | 1 |
| 16 | Determination of polysorbate 80 in parenteral formulations by highperformance liquid chromatography and evaporative light scattering detection显示文摘 | NAIR L M STEPHENS N V VINCENT S V | 2003 | J Chromatogr A2003，1012，1： | 1 |
| 17 | Light Microscopy Techniques for Live Cell Imaging显示文摘 | STEPHENS D J ALLAN V J | 2003 | Science2003，300，5616： | 1 |
| 18 | Emergence of resistant Acinetobacter baumannii in critically ill patients within an acute care teaching hospital and a long-term acute care hospital显示文摘 | Stephens C Francis SJ Abell V | 2007 | Am J Infect Control2007，35，4： | 1 |
| 19 | Magnetization behaviour of electrodeposited Ni Mn alloys显示文摘 | Stephen A Nagarajan T Ananth M V | 1998 | Materials Science and Engineering1998，55，： | 1 |
| 20 | Genome-wide comparative diversity uncovers multiple targets of selection for improvement in hexaploid wheat landraces and cultivars 显示文摘 | Cavanagh CS Chao S Wang BE Huang BE Stephen S Kiani S Forrest K Saintenac C Brown-Guedira GL Akhunova A See D Bai G Pumphrey M Tomar L Wong D Kong S Reynolds M da Silva ML Bockelman H Talbert L Anderson JA Dreisigacker S Baenziger S Carter A Korzun V Morrell PL Dubcovsky J Morell MK Sorrells ME Hayden MJ Akhunov E | 2013 | PNAS2013，110，： | 1 |
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