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Targeting KRAS in pancreatic adenocarcinoma:Progress in demystifying the holy grail

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世界临床肿瘤学杂志:英文版 2023年第8期14卷 285-296页

作者： Ahmed Elhariri Ahmed Alhaj Daniel Ahn Mohamad Bassam Sonbol Tanios Bekaii-Saab Christina Wu Michael scott Rutenberg john Stauffer Jason Starr Umair Majeed Jeremy Jones Mitesh Borad Hani Babiker Division of Hematology-Oncology Department of MedicineMayo Clinic FloridaMayo Clinic Cancer CenterJacksonvilleFL 32224United States Division of Hematology-Oncology Department of MedicineMayo Clinic ArizonaMayo Clinic Cancer CenterPhoenixAZ 85054United States Department of Radiation-Oncology Mayo Clinic FloridaMayo Clinic Cancer CenterJacksonvilleFL 32224United States Department of Surgical Oncology Hepatopancreatobiliary SurgeryMayo Clinic FloridaJacksonvilleFL 32224United States

Pancreatic cancer(PC)remains one of the most challenging diseases,with a very poor 5-year overall survival of around 11.5%.Kirsten rat sarcoma virus(KRAS)mutation is seen in 90%-95%of PC patients and plays an important role in cancer cell proliferation,differentiation,metabolism,and survival,making it an essential mutation for targeted *** extensive efforts in studying this oncogene,there has been little success in finding a drug to target this pathway,labelling it for decades as“undruggable”.In this article we summarize some of the efforts made to target the KRAS pathway in PC,discuss the challenges,and shed light on promising clinical trials.

关键词： Kirsten rat sarcoma virus Targeted therapy Pancreatic cancer Drug resistance Next generation sequencing Clustered regularly interspaced short palindromic repeats

The 10th Antarctic Meteorological Observation,Modeling,and Forecasting Workshop

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Advances in Atmospheric Sciences 2016年第5期33卷 I0001-I0003页

作者： Steve R.COLWELL Arthur M.CAYETTE Matthew A.LAZZARA Jordan G.POWERS David H.BROMWICH john J.CASSANO scott CARPENTIER British Antarctic Survey CambridgeUnited Kingdom Space and Naval Warfare System Center Office of Polar Programs North Charleston SCUSA Antarctic Meteorological Research Center Space Science and Engineering Center University of Wisconsin-Madisonand Department of Physical SciencesSchool of Arts and SciencesMadison Area Technical CollegeMadison WIUSA National Center for Atmospheric Research Boulder COUSA Polar Meteorology Group Byrd Polar&Climate Research CenterThe Ohio State UniversityColumbus OHUSA Cooperative Institute for Research in Environmental Sciences and Department of Atmospheric and Oceanic Sciences University of Colorado-BoulderBoulder COUSA Bureau of Meteorology HobartTasmaniaAustralia

1. Overview The 10th Antarctic Meteorological Observation, Modeling, and Forecasting Workshop （hereinafter AMOMFW） took place June 17-19, 2015 in the historic city of Cambridge, United Kingdom. The meeting followed its purpose of connecting Antarctic atmospheric science to weatherrelated operational issues and advances in observing, modeling, forecasting, and understanding the Antarctic environment.

关键词： AMRC Modeling

Mesalamine induced symptom exacerbation of ulcerative colitis: Case report and brief discussion

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2010年第6期1卷 132-134页

作者： Maneesh Kumar Gupta scott Pollack john J Hutchings Department of Internal Medicine LSU Health Sciences Center Department of Medicine Section of Gastroen-terology and Hepatology Tulane University Health Sciences Center Department of Medicine Section of Gas-troenterology and Hepatology LSU Health Sciences Center

This paper describes a rare case in which the oral ad-ministration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-ami-nosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, di-arrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the impor-tance of ruling out mesalamine as the causative agent in cases of UC exacerbations.

关键词： Mesalamine Exacerbation Ulcerative coli-tis Inflammation Adverse drug reaction

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心理创伤的治疗指南

The Benefits and Barriers Related to Regular Participation in Physical Activity by African-American Women: Implications for Intervention Development

作者： (美)john Briere (美)Catherine scott

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Open Journal of Preventive Medicine 2015年第4期5卷 169-176页

作者： Meredith S. scott Roy F. Oman Robert john Department of Health Promotion Sciences University of Oklahoma Health Sciences Center Oklahoma City USA

A common strategy for improving health behaviors is to emphasize the benefits and reduce the barriers to behavior change. This study investigated potential differences in perceived benefits and barriers related to participation in physical activity (PA) between women in pre-maintenance versus the maintenance phase of PA behavior to determine if perceived benefits were greater and perceived barriers lower in women with more extensive and successful PA participation experience. Data were collected from a community-based sample (N = 113) of middle-aged African-American women. The sample was stratified into two groups according to how long they had been regularly engaging in PA (6 months or longer versus less than 6 months). Chi-square analyses were conducted to investigate possible differences between the two groups of women in regard to perceived benefits and barriers associated with PA. Descriptive data showed that nearly all of the benefits and barriers to PA were perceived as being important for a majority of the participants and chi-square and t-test results indicated few significant between-group differences (p < .05) in regard to these perceptions. Additional analyses indicated there was no significant between-group difference (p < .05) for Body Mass Index. The results suggest the benefits and barriers related to PA behavior are already valued and understood by many African-American women. Further, the results do not support the commonly held belief that effective health behavior improvement programming should emphasize the benefits and reduce the barriers related to the behavior. Practitioners should consider focusing on other evidenced based factors proven to promote PA behavior such as counseling regarding social support (e.g., buddy system) and increasing self-efficacy (e.g., goal setting) to initiate and sustain a physically active lifestyle.

关键词： Physical Activity Behavior African American Women Benefits and Barriers Maintenance of Physical Activity Behavior Initiation of Physical Activity Behavior Transtheoretical Model

The 13th and 14th Workshops on Antarctic Meteorology and Climate

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Advances in Atmospheric Sciences 2020年第5期37卷 423-430页

作者： Matthew A.LAZZARA Sophie A.ORENDORF Taylor P.NORTON Jordan G.POWERS David H.BROMWICH scott CARPENTIER john J.CASSANO Steven R.COLWELL Arthur M.CAYETTE Kirstin WERNER Antarctic Meteorological Research Center Space Science and Engineering CenterUniversity of Wisconsin-MadisonMadisonWI 53706USA Department of Physical Sciences School of Arts and SciencesMadison Area Technical CollegeMadison WI 53704USA Department of Atmospheric Sciences University of Wisconsin-MadisonMadisonWI 53706USA National Center for Atmospheric Research Boulder CO 53706USA Polar Meteorology Group Byrd Polar&Climate Research CenterThe Ohio State UniversityColumbus OH 43210USA Bureau of Meteorology HobartTasmania 7001Australia Cooperative Institute for Research in Environmental Sciences and Department of Atmospheric and Oceanic Sciences University of ColoradoBoulderCO 80309USA British Antarctic Survey Cambridge CB30ETUnited Kingdom Naval Information Warfare Center CharlestonSC 29406USA Year of Polar Prediction(YOPP)International Coordination Office Alfred Wegener InstituteHelmholtz Centre for Polar and Marine ResearchBremerhaven 27570Germany

*** In July 2018,the Antarctic community came together to meet at the 13th Workshop on Antarctic Meteorology and Climate(WAMC)in Madison,Wisconsin,USA(Fig.1);and in the following year in June 2019,the 14th WAMC was held in Charleston,South Carolina,USA(Fig.2).With a growing history,the WAMC addresses the topics of Antarctic meteorology and climate(Kameda et al.,2008;Colwell et al.,2016;Lazzara et al.,2018)as well as weather-related issues of scientific and operational *** workshops bring together researchers,operational forecasters,numerical modelers,observational specialists,and *** themes of both workshops included Antarctic meteorological observations,Antarctic atmospheric numerical modeling,Antarctic meteorological and climate research,and Antarctic weather forecasting and operational *** 2018 and 2019 WAMC were both followed by a one-day focus on the Year of Polar Prediction-Southern Hemisphere(YOPP-SH),when preparations and follow-up discussions were made with regard to the YOPP Special Observing Period from 16 November 2018 to 15 February 2019.

关键词： Antarctic weather meteorological

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对海平面上升和可变性的理解

国外科技新书评介 2011年第10期 8-9页

作者： john A．church（等）孙方敏不详中国科学院电子学研究所

近年来，全球海平面的上升和可变引起了广泛的关注。海平面的上升不仅威胁到地势低洼的沿海城市的生存，而且对整个生态系统的平衡有着严重的影响。要了解海平面的可变性，我们必须知道导致海平面变化的因素，如地面蓄水、冰冻圈等对海... 详细信息

近年来，全球海平面的上升和可变引起了广泛的关注。海平面的上升不仅威胁到地势低洼的沿海城市的生存，而且对整个生态系统的平衡有着严重的影响。要了解海平面的可变性，我们必须知道导致海平面变化的因素，如地面蓄水、冰冻圈等对海平面变化的影响。

关键词：海平面上升可变性海平面变化沿海城市生态系统地面蓄水冰冻圈

Impact of 1,7-malaria reactive community-based testing and response(1,7-mRCTR)approach on malaria prevalence inTanzania

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Infectious Diseases of Poverty 2023年第6期12卷 103-104页

作者： Wei Chang Jessica Cohen Duo‑Quan Wang Salim Abdulla Muhidin Kassim Mahende Tegemeo Gavana Valerie scott Hajirani M.Msuya Mary Mwanyika‑Sando Ritha john ANjau Shen‑Ning Lu Silas Temu Honorati Masanja Wilbald Anthony Maru Aregawi W Naveen Sunder Tang Kun Katia Bruxvoort Jovin Kitau Fadhila Kihwele Godlove Chila Mihayo Michael Marcia Castro Nicolas AMenzies Sein Kim Xiao Ning Xiao‑Nong Zhou Prosper Chaki Yeromin P.Mlacha Department of Global Health and Population Harvard T.H. Chan School of Public Health Boston USA Chinese Center for Disease Control and Prevention National Institute of Parasitic Diseases Shanghai People’s Republic of China School of Global Health Chinese Center for Tropical Diseases Research Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of China Chinese Center for Tropical Diseases Research Shanghai People’s Republic of China WHO Collaborating Centre for Tropical Diseases Shanghai People’s Republic of China Ifakara Health Institute Dar es Salaam United Republic of Tanzania Africa Academy for Public Health Dar es Salaam Tanzania Muhimbili University of Health and Allied Sciences Dar es Salaam Tanzania National Center for International Research on Tropical Diseases Ministry of Science and Technology Shanghai People’s Republic of China Global Malaria Programme World Health Organization Geneva Switzerland Bentley University Waltham USA Vanke School of Public Health Tsinghua University Beijing People’s Republic of China School of Public Health University of Alabama at Birmingham Birmingham USA The Pan-African Mosquito Control Association (PAMCA) KEMRI Headquarters Nairobi Kenya

Background Progress in malaria control has stalled in recent years and innovative surveillance and response approaches are needed to accelerate malaria control and elimination eforts in endemic areas of ***‑ing on a previous China-UK-Tanzania pilot study on malaria control,this study aimed to assess the impact of the 1,7-malaria Reactive Community-Based Testing and Response(1,7-mRCTR)approach implemented over two years in three districts of *** The 1,7-mRCTR approach provides community-based malaria testing via rapid diagnostic tests and treat‑ment in villages with the highest burden of malaria incidence based on surveillance data from health *** used a diference-in-diferences quasi-experimental design with linear probability models and two waves of crosssectional household surveys to assess the impact of 1,7-mRCTR on malaria *** conducted sensitivity analyses to assess the robustness of our results,examined how intervention efects varied in subgroups,and explored alternative explanations for the observed *** Between October 2019 and September 2021,244,771 community-based malaria rapid tests were com‑pleted in intervention areas,and each intervention village received an average of 3.85 rounds of *** prevalence declined from 27.4%at baseline to 11.7%at endline in the intervention areas and from 26.0%to 16.0%in the control areas.1,7-mRCTR was associated with a 4.5-percentage-point decrease in malaria prevalence(95%confdence interval:−0.067,−0.023),equivalent to a 17%reduction from the *** Rufji,a district characterized by lower prevalence and where larviciding was additionally provided,1,7-mRCTR was associated with a 63.9%decline in malaria *** The 1,7-mRCTR approach reduced malaria *** implementation interruptions due to the COVID-19 pandemic and supply chain challenges,the study provided novel evidence on the efectiveness of community-based reactive approache

关键词： Malaria Surveillance and response Incidence rate Community-health worker Health facility Communitybased testing and treatment 1,7-mRCTR Tanzania

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World Journal of Gastroenterology 2014年第14期20卷 3986-4000页

作者： Bjarte Fosby Sigrid Nss Johannes R Hov James Traherne Kirsten M Boberg john Trowsdale Aksel Foss Pl-Dag Line Andre Franke Espen Melum Helge scott Tom H Karlsen Norwegian PSC Research Center Division of CancerSurgery and TransplantationOslo University Hospital Institute of Clinical Medicine Faculty of MedicineUniversity of Oslo KG Jebsen Inflammation Research Centre Research Institute of Internal MedicineOslo University Hospital Department of Transplantation Medicine Division of CancerSurgery and TransplantationOslo University Hospital Division of Immunology Department of PathologyUniversity of Cambridge and Cambridge Institute for Medical ResearchUniversity of Cambridge Institute of Clinical Molecular Biology Christian-Albrechts-University Department of Pathology Divisoin of Diagnostics and InterventionInstitute of PathologyOslo University Hospital

AIM:To investigate influence of human leukocyte antigen(HLA)and killer immunoglobuline-like receptor(KIR)genotypes on risks of acute rejection(AR)after liver transplantation(LTX).METHODS:In this retrospective study we included143 adult donor-recipient pairs with a minimum of 6mo follow-up after LTX for whom DNA was available from both donor and *** data,all early complications including episodes and severity of AR and graft/patient survival were *** diagnosis of AR was based on clinical,biochemical and histological *** suspected episodes of AR were biopsy *** classical HLA loci(HLA-A,HLA-B,HLA-C and HLA-DRB1)were genotyped using Sanger sequencing.16 KIR genes were genotyped using a novel real time PCR approach which allows for determination of the diploid copy number of each KIR *** staining for T(CD3),B(CD20)and natural killer(NK)cells(CD56 and CD57)were performed on liver biopsies from 3 different patient groups[primary sclerosing cholangitis(PSC),primary biliary cirrhosis and non-autoimmune liver disease],10 in each group,with similar grade of ***:Fourty-four(31%)patients were transplanted on the basis of PSC,40%of them had AR vs 24%in the non-PSC group(P=0.04).No significant impact of donor-recipient matching for HLA and KIR genotypes was *** the overall recipient population an increased risk of AR was detected for HLA-B*08(P=0.002,OR=2.5;95%CI:1.4-4.6),HLA-C*07(P=0.001,OR=2.4;95%CI:1.4-4.0)and HLA-DRB1*03(P=0.03,OR=1.9;95%CI:1.0-3.3)and a decreased risk for HLA-DRB1*04(P=0.001,OR=0.2;95%CI:0.1-0.5).For HLA-B*08,HLA-C*07 and DRB1*04 the associations remained evident in a subgroup analysis of non-PSC recipients(P=0.04,P=0.003 and P=0.02,respectively).In PSC recipients corresponding P values were 0.002,0.17 and 0.01 for HLA-B*08,HLA-C*07and DRB1*04,respectively.A dosage effect of AR prevalence according to the PSC associated HLA alleles was also notable in the total recipient populat

关键词： Liver transplantation Primary sclerosing cholangit