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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 j.urnal of Gastroenterology 2018年第25期24卷 2686-2697页

作者： Emily M Lin j.n 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 j.nction(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

Mental health status in veterans residing in rural versus non-rural areas: results from the veterans’ health study

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Military Medical Research 2021年第1期8卷 79-89页

作者： joseph j.Boscarino Charles R.Figley Richard E.Adams Thomas G.Urosevich H.Lester Kirchner joseph A.Boscarino Clinical Psychology Department William James CollegeNewtonMA 02459USA School of Social Work Tulane UniversityNew OrleansLA 70112USA Department of Sociology Kent State UniversityKentOH 44242USA Ophthalmology Service Geisinger ClinicMount PoconoPA 18344USA Department of Population Health Sciences Geisinger Clinic100 N.Academy Avenue44-00DanvillePA 17822USA

Background: The maj.rity of Veterans Affair(VA) hospitals are in urban areas. We examined whether veterans residing in rural areas have lower mental health service use and poorer mental health ***: Veterans with at least 1 warzone deployment in central and northeastern Pennsylvania were randomly selected for an interview. Mental health status, including posttraumatic stress disorder(PTSD), maj.r depression, alcohol abuse and mental health global severity, were assessed using structured interviews. Psychiatric service use was based on self-reported utilization in the past 12 months. Results were compared between veterans residing in rural and non-rural areas. Data were also analyzed using multivariate logistic regression to minimize the influence by confounding ***: A total of 1730 subj.cts(55% of the eligible veterans) responded to the survey and 1692 of them had complete geocode information. Those that did not have this information(n=38), were excluded from some analyses. Veterans residing in rural areas were older, more often of the white race, married, and experienced fewer stressful events. In comparison to those residing in non-rural areas, veterans residing in rural areas had lower global mental health severity scores;they also had fewer mental health visits. In multivariate logistic regression, rural residence was associated with lower service use, but not with PTSD, maj.r depression, alcohol abuse, and global mental health severity score after adj.sting confounding factors(e.g., age, gender, marital status and education).Conclusions: Rural residence is associated with lower mental health service use, but not with poor mental health in veterans with former warzone deployment, suggesting rural residence is possibly protective.

关键词： Veterans Rural Risk factors PTSD Alcohol abuse Depression Service use Census data

Connexin 43 hemichannels protect bone loss during estrogen deficiency

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Bone Research 2019年第2期7卷 183-194页

作者： Liang Ma Rui Hua Yi Tian Hongyun Cheng Roberto j.se Faj.rdo joseph j. Pearson Tej. Guda Daniel Brian Shropshire Sumin Gu j.an X. j.ang Department of Orthopaedics Jinan Central Hospital Affiliated to Shandong UniversityJinanShandongChina Department of Biochemistry and Structural Biology UT Health San AntonioSan AntonioTX 78229USA Department of Orthopedics UT Health San AntonioSan AntonioTX 78229USA Department of Biomechanical Engineering University of Texas at San AntonioSan AntonioTX 78249USA

Estrogen deficiency in postmenopausal women is a maj.r cause of bone loss,resulting in osteopenia,osteoporosis,and a high risk for bone *** 43 (Cx43) hemichannels (HCs) in osteocytes play an important role in osteocyte viability,bone formation,and *** showed here that estrogen deficiency reduced Cx43 expression and HC *** determine if functional HCs protect osteocytes and bone loss during estrogen deficiency,we adopted an ovariectomy model in wild-type (WT) and two transgenic Cx43 mice:R76W (dominant-negative mutant inhibiting only gap j.nction channels) and Cx43 Δ130–136 (dominant-negative mutant compromising both gap j.nction channels and HCs).The bone mineral density (BMD),bone structure,and histomorphometric changes of cortical and trabecular bones after ovariectomy were *** results showed that the Δ130–136 transgenic cohort had greatly decreased vertebral trabecular bone mass compared to WT and R76W mice,associated with a significant increase in the number of apoptotic osteocyte and empty ***,osteoclast surfaces in trabecular and cortical bones were increased after ovariectomy in the R76W and WT mice,respectively,but not in Δ130–136 *** data demonstrate that impairment of Cx43 HCs in osteocytes accelerates vertebral trabecular bone loss and increase in osteocyte apoptosis,and further suggest that Cx43 HCs in osteocytes protect trabecular bone against catabolic effects due to estrogen deficiency.

关键词： hemichannels protect estrogen deficiency

Analysis of Land-Cover Changes and Anthropogenic Activities in Itigi Thicket, Tanzania

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Advances in Remote Sensing 2016年第4期5卷 269-283页

作者： joseph S. Makero j.phet j. Kashaigili Forestry Training Institute Arusha Tanzania Department of Forest Resources Assessment and Management Sokoine University of Agriculture Morogoro Tanzania

Assessing land cover changes from the 1991 to 2011 for Itigi thicket is imperative for determining changes between land cover types and understanding anthropogenic impact during this period. Remote sensing (RS) data, Geographic Information System (GIS) techniques and forest inventory data were used. ILWIS 3.3 Academic software was used to analyze the satellite imageries to determine the land use, land cover change;while data on anthropogenic activities were analysed in MS Excel software. The results showed that between 1991/2000 and 2000/2011, the areas of thicket declined by 6.23% while non-thicket areas increased by 3.92%. The decline in thicket areas was attributed to increase in anthropogenic activities such as wood extraction, clearing for agriculture, livestock grazing and fires. The study highlights the importance of integrating remote sensing and forest inventory in understanding the thicket resources dynamics and generating information that could be used to overcome the Itigi thicket problems for the sustainability of this unique vegetation.

关键词： Itigi Thicket Land Cover Change Remote Sensing GIS

High-enthalpy hypersonic flows

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Advances in Aerodynamics 2020年第1期2卷 373-411页

作者： joseph j.S.Shang Hong Yan Wright State University 3640 Colonel Glenn HighwayDaytonOH 45435USA School of Power and Energy Northwestern Polytechnical University127West Youyi RoadXi’an 710072China

Nearly all illuminating classic hypersonic flow theories address aerodynamic phenomena as a perfect gas in the high-speed range and at the upper limit of continuum gas *** hypersonic flow is quantitatively defined by the Mach number independent principle,which is derived from the asymptotes of the Rankine-Hugoniot ***,most hypersonic flows encounter strong shock-wave compressions resulting in a high enthalpy gas environment that always associates with nonequilibrium thermodynamic and quantum chemical-physics *** this circumstance,the theoretic linkage between the microscopic particle dynamics and macroscopic thermodynamics properties of gas is *** the air mixture is ionized to become an electrically conducting medium,the governing physics now ventures into the regimes of quantum physics and ***,the hypersonic flows are no longer a pure aerodynamics subj.ct but a multidisciplinary *** order to better understand the realistic hypersonic flows,all pertaining disciplines such as the nonequilibrium chemical kinetics,quantum physics,radiative heat transfer,and electromagnetics need to bring forth.

关键词： Hypersonic flow Nonequilibrium chemical kinetics Ionization Quantum mechanics Electromagnetics Radiation

A Comparative Investigation of Dye-Sensitized Titanium Dioxide(TiO_2) Nanorods Grown on Indium Tin Oxide(ITO) Substrates by Direct and Seed-Mediated Hydrothermal Methods

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Acta Metallurgica Sinica(English Letters) 2016年第5期29卷 457-463页

作者： V.Chandrakala j.Annai joseph Steffy Neena Bachan W.j.thi j.yarani Tenzin Tenkyong j.Merline Shyla Department of Physics Energy Nanotechnology Centre (ENTeC) Loyola Institute of Frontier Energy (LIFE)Loyola College

We report a comparative investigation of the characteristics of modified TiO2 nanorods grown on conducting indium tin oxide glass （/TO） substrates by two different hydrothermal methods： the direct method by which rutile TiOa nanorods were grown directly on plain ITO substrates and the seed-mediated one using which a thin film of anatase TiO2 seed layer was laid down by spin coating and annealing prior to the growth of TiO2 nanorods on it. Microstructural analysis of the samples using X-ray diffraction confirmed their rutile nature. The average crystallite size estimated using Scherrer＇s formula was found to fall in the range of 11-17 nm in both cases. Field emission scanning electron microscopy revealed the nanorod morphologies of a dandelion arrangement in the case of directly grown ones and a proper vertical orientation in the case of the seed-mediated method. UV-Vis spectroscopy analysis of both the samples exhibited redshifts with intense absorption of visible radiation, and the seed-mediated one was found to possess an increased bandgap. The transport nature of the samples was characterized by significant increase in both dark and photocurrents. The results show that the dark and photocurrent values of the directly grown TiO2 nanorods were greater than those of the seed-mediated ones by - seven and five folds, respectively, and therefore, it could serve as efficient photoelectrodes in dye-sensitized solar cells.

关键词： Dye-sensitized solar cells Hydrothermal Seed-mediated Photoconductivity Spin coating Safranine 0 dye Ti02 nanorods

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j.urnal of Sport and Health Science 2023年第3期12卷 414-422页

作者： joseph M.Bano Rebecca j.McAdams Kristin j.Roberts j.ngzhen Yang Lara B.McKenzie Center for Inj.ry Research and Policy Abigail Wexner Research Institute at Nationwide Children's HospitalColumbusOH 43205USA Department of Pediatrics The Ohio State UniversityCollege of MedicineColumbusOH 43205USA Division of Epidemiology The Ohio State UniversityCollege of Public HealthColumbusOH 43210USA

Background:Lacrosse is one of the fastest-growing sports in the United *** rules regarding permitted contact differ by sex and *** are no known studies using a nationally representative data set to analyze lacrosse inj.ry patterns over several years by sex and age in the youth ***:A retrospective analysis was performed using data from the National Electronic Inj.ry Surveillance System for youth aged 11-18 years who were treated for lacrosse-related inj.ries in *** departments from 2000 to *** on our review of the case narratives,we created and coded a new inj.ry-mechanism *** generated national estimates from 6406 ***:An estimated 206,274 lacrosse-related inj.ries to youths aged 11-18 years were treated in *** departments from 2000 to *** rate of inj.ries per 10,000 significantly increased from 1.9 in 2000 to a peak of 5.3 in 2012(pj.ry mechanism,body part inj.red,and diagnosis differed by *** were 1.62 times(95%confidence interval(95%CI):1.25-2.09)more likely than girls to be inj.red by player-to-player *** were 2.21 times(95%CI:1.96-2.49)more likely than boys to have non-contact ***,as age increased,the percentage of inj.ries from lacrosse sticks decreased and player-toplayer contact ***:Despite additional protective regulations in the sport,lacrosse is an important source of inj.ry where we continue to see differences by sex and *** study supports the continuation,modification,and addition of rules aimed at reducing lacrosse inj.ry risk.

关键词： Lacrosse National Electronic Inj.ry Surveillance System Sex differences Youth inj.ries

Pyramid-Textured Antireflective Silicon Surface In Graphene Oxide/Single-Wall Carbon Nanotube–Silicon Heteroj.nction Solar Cells

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Energy & Environmental Materials 2018年第4期1卷 232-240页

作者： LePing Yu Munkhbayar Batmunkh Mahnaz Dadkhah Cameron j.Shearer joseph G.Shapter Flinders Institute for Nanoscale Science and Technology College of Science and EngineeringFlinders UniversityBedford ParkSA 5042Australia School of Chemistry and Chemical EngineeringShanghai University of Engineering ScienceShanghai201620PR China Flinders Institute for Nanoscale Science and Technology College of Science and EngineeringFlinders UniversityBedford ParkSA 5042Australia Australian Institute for Bioengineering and Nanotechnology University of QueenslandSt.Lucia Qld 4072Australia Department of Chemistry The University of AdelaideAdelaideSA 5005Australia

Antireflection layers are commonly used in photovoltaics to increase light absorption and therefore increase maximum ***,pyramid structures are created on Si surfaces with alkaline solution *** extent of pyramid cover... 详细信息

关键词： antireflection treatment carbon nanotubes solar cells

ER stress-induced aggresome trafficking of HtrA1 protects against proteotoxicity

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j.urnal of Molecular Cell Biology 2017年第6期9卷 516-532页

作者： Maximilian j. Gerhardt joseph A. Marsh Margaux Morrison Andrius Kazlauskas Arogya Khadka Stephan Rosenkranz Margaret M. DeAngelis Magali Saint-Geniez Sarah Melissa P. j.cobo Department of Ophthalmology Harvard Medical School The Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary Boston MA 02114 USA Department III of Internal Medicine Cologne University Heart Center Center for Molecular Medicine University of Cologne 50931 Cologne Germany MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh EH4 2XU UK Department of Ophthalmology and Visual Sciences University of Utah and John A. Moran Eye Center Salt Lake City UT 84132 USA

High temperature requirement A1 （HtrA1） belongs to an ancient protein family that is linked to various human disorders. The pre- cise role of exon 1-encoded N-terminal domains and how these influence the biological functions of human HtrAZ remain elusive. In this study, we traced the evolutionary origins of these N-terminal domains to a single gene fusion event in the most recent common ancestor of vertebrates. We hypothesized that human HtrA1 is impticated in unfotded protein response. ｜n highly secre- tory cells of the retinal pigmented epithelia, endoplasmic reticulum （ER） stress upregulated HtrA1. HtrA1 co-localized with vimen- tin intermediate filaments in highly arborized fashion. Upon ER stress, HtrA1 tracked along intermediate filaments, which collapsed and bundled in an aggresome at the microtubule organizing center. Gene silencing of HtrA1 altered the schedule and amplitude of adaptive signaling and concomitantly resulted in apoptosis. Restoration of wild-type HtrA1, but not its protease inactive mutant, was necessary and sufficient to protect from apoptosis. A variant of HtrA1 that harbored exon 1 substitutions dis- played reduced efficacy in rescuing cells from proteotoxicity. Our results illuminate the integration of HtrA1 in the toolkit of mam- malian cells against protein misfolding and the implications of defects in HtrA1 in proteostasis.

关键词： ER stress unfolded protein response RPE HtrA1 multi-domain protein evolution proteostasis