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Advances in immuno-oncology biomarkers for gastroesophageal cancer:programmed death ligand 1,microsatellite instability,and beyond

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World journal of Gastroenterology 2018年第25期24卷 2686-2697页

作者： Emily M Lin jun Gong samuel j klempner joseph Chao Department of Internal Medicine Harbor-UCLA Medical CenterTorranceCA 90509United States Department of Medical Oncology and Developmental Therapeutics City of Hope Comprehensive Cancer CenterDuarteCA 91010United States The Angeles Clinic and Research Institute Los AngelesCA 90404United States samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical CenterLos AngelesCA 90048United States

Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEj) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEj cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEj cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEj cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEj cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEj cancer.

关键词： Immunotherapy programmed cell death 1 programmed death ligand 1 microsatellite instablility Gastric cancer

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Chemotherapy predictors and a time-dependent chemotherapy effect in metastatic esophageal cancer

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World journal of Gastrointestinal Oncology 2022年第2期14卷 511-524页

作者： Lauren Midthun Sungjin Kim Andrew Hendifar Arsen Osipov samuel j klempner joseph Chao May Cho Michelle Guan Veronica R Placencio-Hickok Alexandra Gangi Miguel Burch De-Chen Lin Kevin Waters Katelyn Atkins Mitchell Kamrava jun Gong Department of Medicine Division of Hematology and OncologyCedars-Sinai Medical CenterLos AngelesCA 90048United States Biostatistics and Bioinformatics Research Center Cedars Sinai Medical CenterLos AngelesCA 90048United States samuel Oschin Cancer Center Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Beth Israel Deaconess Medical Center/Harvard Medical SchoolBrigham and Women's Hospital/Harvard Medical SchoolBostonMA 02114United States Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaIrvineCA 92697United States Department of Medicine Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Pathology and Laboratory Medicine Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Chemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal ***,not all patients with metastatic disease receive *** To evaluate a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and *** We interrogated the National Cancer Database(NCDB)between 2004-2015 and included patients with M1 disease who had received or did not receive chemotherapy.A logistic regression model was used to examine the associations between chemotherapy and potential confounders and a Cox proportional hazards model was employed to examine the effect of chemotherapy on overall survival(OS).Propensity score analyses were further performed to balance measurable confounders between patients treated with and without *** A total of 29182 patients met criteria for inclusion in this analysis,with 21911(75%)receiving chemotherapy and 7271(25%)not receiving *** median follow-up was 69.45 *** median OS for patients receiving chemotherapy was 9.53 mo(9.33-9.72)vs 2.43 mo(2.27-2.60)with no *** of diagnosis 2010-2014[odds ratio(OR):1.29,95%confidence interval(CI):1.17-1.43,P value$46000(OR:1.49,95%CI:1.27-1.75,P value<0.001),and node-positivity(OR:1.35,95%CI:1.20-1.52,P<0.001)were independent predictors of receiving chemotherapy,while female gender(OR:0.86,95%CI:0.76-0.98,P=0.019),black race(OR:0.76,95%CI:0.67-0.93,P=0.005),uninsured status(OR:0.41,95%CI:0.33-0.52,P<0.001),and high Charlson Comorbidity Index(CCI)(OR for CCI≥2:0.61,95%CI:0.50-0.74,P<0.001)predicted for lower odds of receiving *** the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo,after which there is no significant effect on ***,uninsured status[hazard ratio(HR):1.20,95%CI:1.09-1.31,P<0.001],being from the geographic

关键词： Esophageal cancer Metastatic Chemotherapy Predictors Survival

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Impact of palliative therapies in metastatic esophageal cancer patients not receiving chemotherapy

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World journal of Gastrointestinal Surgery 2020年第9期12卷 377-389页

作者： Sungjin Kim Timothy P DiPeri Michelle Guan Veronica R Placencio-Hickok Haesoo Kim jar-Yee Liu Andrew Hendifar samuel j klempner Ryan Nipp Alexandra Gangi Miguel Burch Kevin Waters May Cho joseph Chao Katelyn Atkins Mitchell Kamrava Richard Tuli jun Gong Biostatistics and Bioinformatics Research Center Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Surgical Oncology Department of SurgerySamuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Division of Hematology and OncologySamuel Oschin Comprehensive Cancer InstituteCedars Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Massachusetts General Hospital Cancer CenterHarvard Medical SchoolBostonMA 02114United States Department of Pathology and Laboratory Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaDavisSacramentoCA 95817United States Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Department of Radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Memorial Sloan Kettering Cancer CenterNew YorkNY 10065United States

BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor *** all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are *** To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving *** The National Cancer Database was used to identify patients between *** with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(RT),pain management,or any combination thereof]were *** with unknown chemotherapy,RT,or nonprimary surgery status were ***-Meier estimates of OS were *** proportional hazards regression models were employed to examine factors influencing *** Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete *** age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic *** majority(72.7%)did not receive other palliative *** both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(HR)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(HR 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(HR 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(HR 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(HR 1.17,95%CI:1.03-1.32)were associated with increased *** histologic grade and T-stage were also as

关键词： Esophageal cancer Metastatic Palliative Chemotherapy Radiotherapy Survival

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Power Factor Estimation of Distributed Energy Resources Using Voltage Magnitude Measurements

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journal of Modern Power Systems and Clean Energy 2021年第4期9卷 859-869页

作者： samuel Talkington Santiago Grijalva Matthew j.Reno School of Electrical and Computer Engineering Georgia Institute of TechnologyAtlantaGA 30318USA Electric Power Systems Research Department Sandia National LaboratoriesAlbuquerqueNM 87123USA

This paper presents a new method for the estimation of the injection state and power factor of distributed energy resources (DERs) using voltage magnitude measurements only. A physics-based linear model is used to develop estimation heuristics for net injections of real and reactive power at a set of buses under study, allowing a distribution engineer to form a robust estimate for the operating state and the power factor of the DER at those buses. The method demonstrates and exploits a mathematical distinction between the voltage sensitivity signatures of real and reactive power injections for a fixed power system model. Case studies on various test feeders for a model of the distribution circuit and statistical analyses are presented to demonstrate the validity of the estimation method. The results of this paper can be used to improve the limited information about inverter parameters and operating state during renewable planning, which helps mitigate the uncertainty inherent in their integration.

关键词： Decentralized power system control detection and estimation power factor sparse approximation

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Distance assessment of detours by jum ping spiders

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Current Zoology 2020年第3期66卷 263-273页

作者： samuel AGUILAR-ARGUELLO Daniel GERHARD Ximena j.NELSON School of Biological Sciences University of CanterburyPrivate Bag 4800Christchurch 8140New Zealand School of Mathem atics and Statistics University of CanterburyPrivate Bag 4800Christchurch 8140New Zealand

To take an indirect route(detour)in order to reach a specific target requires complex cognitive *** more demanding,from the cognitive point of view,is when the goal is only visible at the beginning of the *** spiders from the family Sa lticidae,vision is a key sensory modal-ity mediating navigation and prey *** acute vision allows them to perform complicated detours,possibly as a consequence of the multitude of potential routes in their typically complex 3-dimensional *** used a 4-route choice test,in which routes differed in being either short or long and in the presence or absence of a lure of a prey item,to investigate route assessment in 2 salticid species,Trite planiceps and Marpissa *** both species showed evidence of motivation to follow lured-routes,judging by the number of times they re-oriented toward them while detouring,we found that Trite chose short routes in preference to long routes,but did not prefer the *** contrast,Marpissa exhibited random route choice,although it ori-ented toward lured-routes more often than control routes(lure absent).Our results suggest that decision-making processes about which route to take occurs before embarking on a route,but this is cognitively *** exhibited cognitive limitations in which the lack of visibility of the goal affected ***,the severity of cognitive limitations depended on *** suggest that variability in spatial ability across the Salticidae may be related to the habitat complexity inhabited by each species.

关键词： cognition cognitive limitations decision-making detour behavior Salticidae spatial task

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Sulfurized-polyacrylonitrile in lithium-sulfur batteries:Interactions between undercoordinated carbons and polymer structure under low lithiation

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journal of Energy Chemistry 2022年第3期31卷 587-596,I0016页

作者： samuel Bertolini Timo jacob Institute of Electrochemistry Ulm UniversityAlbert-Einstein-Allee 4789081 UlmGermany Helmholtz-Institute Ulm(HIU) Electrochemical Energy StorageHelmholtzstr.1189081 UlmGermany Karlsruhe Institute of Technology(KIT) P.O.Box 364076021 KarlsruheGermany

Lithium-sulfur battery(LSB)represents an important candidate to be used in energy storage applications,due to its high specific ***-polyacrylonitrile(SPAN)is a candidate as a host material in LSB to replace graphite,due to its ability to chemisorb polysulfides(PSs).The sulfur chains attached to the polymer can reversibly form Li2S,and SPAN indicates to have a good cyclability and better performance than graphite,thus,SPAN acts partially as an active and also as a host *** this study,we investigated the capacity of the solvent or the SPAN to lose a hydrogen atom from the backbone,to predict possible anodic reactions between solvent and host *** simulation suggests that the photophilic salts may preferentially react with the solvent,and possibly building a cathode electrolyte interphase(CEI).We observed that an undercoordinated carbon(C_(uc))can be thermodynamically created,due to *** Cuccan react with the solvent on the polymer backbone through different mechanisms,however,the simulations indicated that the reaction should be affected by the interaction between the solvent and C_(uc),according to SPAN’s ***,C_(uc)reacts with long sulfur chains attached to SPAN,capturing sulfur and forming a C-S bond.A sulfur chain from one SPAN can connect to another polymer backbone,however,this process is affected by lithiation and ***,this work also investigates the formation of interconnected SPAN structures and the multiple C_(uc)effects.

关键词： Density functional theory Ab initio molecular dynamics Lithium-sulfur batteries Sulfurized-polyacrylonitrile

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Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease

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World journal of Gastrointestinal Oncology 2021年第8期13卷 772-798页

作者： Alexa R Weingarden samuel j S Rubin john Gubatan Division of Gastroenterology and Hepatology Department of MedicineStanford UniversityRedwood CityCA 94063United States Stanford University School of Medicine Stanford UniversityRedwood CityCA 94063United States

Immune checkpoint inhibitors(ICI)have markedly changed the landscape of cancer *** re-invigorating the immune system against tumors,ICI provide novel therapeutic options for a broad variety of malignancies,including many gastrointestinal(GI)***,these therapies can also induce autoimmune-like side effects in healthy tissue across the *** of the most common of these side effects is ICI-mediated colitis and diarrhea(IMC).Here,we review the incidence and risk of IMC in ICI therapy,with a focus on what is known regarding IMC in patients with GI *** also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease,as these patients may have increased risk of IMC due to their underlying intestinal pathology.

关键词： Immune checkpoint inhibitors Cytotoxic T-lymphocyte antigen 4 Programmed cell death protein-1 Inflammatory bowel disease Gastrointestinal cancer

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Rituximab as a treatment for human immunodeficiency virusassociated nemaline myopathy:What does the literature have to tell us?

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World journal of Clinical Cases 2022年第4期10卷 1454-1456页

作者： jucier Gonçalves júnior samuel Katsuyuki Shinjo Division of Rheumatology São Paulo UniversitySão Paulo 01246-903Brazil

We presented a letter about a case of a 37-year-old Black female with a history of human immunodeficiency virus and an undetectable viral *** was evaluated with weakness in the scapular(grade III)and pelvic girdles(grade II),elevation of creatine phosphokinase levels and muscle biopsy compatible with nemaline *** was treated with rituximab showing improvement of the condition.

关键词： Case report Human immunodeficiency virus Nemaline myopathy Rituximab Rheumatology Therapy

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Impulse force reductions and their effects on WBV exposures in high impact shovel loading operations

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International journal of Mining Science and Technology 2018年第3期28卷 423-435页

作者： Danish Ali samuel Frimpong Mining & Nuclear Engineering Department Missouri University of Science and Technology

When shovels load the dump trucks with over 100-ton passes under gravity dumping conditions, they will create a large impact force on the dump truck body which generates high frequency shock waves which expose the operators to whole body vibrations （WBV）. The main cause of such truck vibrations is the large impact force due to the gravity dumping of large tonnage passes. Therefore a rigorous mathematical model has been developed for the impact force containing all the necessary factors upon which it depends. Latter, a thorough analysis shows that percentage reduction of 7.19%, 9.40%, 13.27%, 14.8%, 17.30% and 18.13% can he achieved by reducing the dumping distance to 6.33 m, 6.0 m, 5.5 m, 5.33 m, 5.0 m and 4.9 m, respectively, as compared to when the dumping distance was 7.33 m. Even more reduction in the magnitude of impact force can he observed if the shovel pass gets divided into more than two sub-passes. Therefore, these models can he used to figure out the number of sub-passes into which a single ore pass can he divided and/or the extent to which the dumping distance can he reduced which would reduce the impact force significantly enough to obtain safer yet economic operations.

关键词： Impact force HISLO Mathematical modeling Dumping distance Shovel ore sub-passes

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Single-atom Pt on carbon nanotubes for selective electrocatalysis

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Carbon Energy 2024年第1期6卷 63-71页

作者： samuel S.Hardisty Xiaoqian Lin Anthony R.j.Kucernak David Zitoun Department of Chemistry Bar Ilan Institute of Nanotechnology and Advanced Materials(BINA)Bar Ilan UniversityRamat GanIsrael Department of Chemistry Molecular Science Research HubImperial College LondonLondonUK

Utilizing supported single atoms as catalysts presents an opportunity to reduce the usage of critical raw materials such as platinum,which are essential for electrochemical reactions such as hydrogen oxidation reaction(HOR).Herein,we describe the synthesis of a Pt single electrocatalyst inside single-walled carbon nanotubes(SWCNTs)via a redox *** via electron microscopy,X-ray photoelectron microscopy,and X-ray absorption spectroscopy show the single-atom nature of the *** electrochemical behavior of the sample to hydrogen and oxygen was investigated using the advanced floating electrode technique,which minimizes mass transport limitations and gives a thorough insight into the activity of the *** single-atom samples showed higher HOR activity than state-of-the-art 30%Pt/C while almost no oxygen reduction reaction activity in the proton exchange membrane fuel cell operating *** selective activity toward HOR arose as the main fingerprint of the catalyst confinement in the SWCNTs.

关键词： confinement electrocatalysis hydrogen platinum single atom catalysts

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