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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der burg Jannie borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS b.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

Antibiotic use in early childhood and risk of obesity: longitudinal analysis of a national cohort

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World Journal of Pediatrics 2019年第4期15卷 390-397页

作者： Dervla Kelly Alan Kelly tom O'Dowd Catherine b.Hayes Department of Public Health and Primary Care Trinity College DublinRussell CenterTallaght CrossDublin 24Ireland

background Taking oral antibiotics during childhood has been linked with an increased risk of childhood *** study assessed any potential association in number of courses of antibiotics taken between 2-3 and 4-5 years of age and body mass trajectory up to age *** The study was a secondary analysis of 8186 children and their parents from the infant cohort of the Irish National Longitudinal Study of *** use was measured by parental recall between ages 2-3 and *** models described the relationship between antibiotic exposure and body mass index (bMI) standard deviation scores andbinary outcomes,and examined interactions between covariates,which included socioeconomic status,diet assessed by food frequency questionnaires and maternal *** Any antibiotic usage between 2 and 3 years did not predict risk of overweight or obesity at age *** or more courses of antibiotics between 2 and 3 years were independently associated with obesity at age 5 (odds ratio 1.6,95% confidence interval 1.11-2.31).Effect size was modest (coefficient + 0.09 body mass SD units,standard error 0.04,P =0.037).Maternal bMI modified the relationship:≥ 4 courses of antibiotics between 2 and 3 years were associated with a + 0.12 body mass SD units increase in weight at age 5 among children of normal-weight mothers (P=0.035),but not in children of overweight *** Number of antibiotic courses,rather than antibiotic use,may be an important factor in any link between early antibiotic exposure and subsequent childhood *** is needed to confirm differential effects on babies of normal versus overweight/obese mothers independent of socioeconomic factors.

关键词： Antibiotics body mass index Early childhood Infants Obesity

Rock joint coefficients and their computerized classification

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International Journal of Mining Science and Technology 2019年第5期29卷 701-709页

作者： tomás Ficker Faculty of Civil Engineering Brno University of Technology60200 BrnoCzech Republic

A computerized method for determining rock joint coefficients is *** relative similarity indicators are introduced to classify surface morphology of rock *** classification enables to compare investigated and database rock *** a comparison aims at finding the couple of surfaces that are distinguished by the highest dynamical *** first absolute indicator results from the Fourier matrix and evaluates wavy shapes of *** second absolute indicator quantifies the heights of surface reliefs and is defined as the root mean square height of the surface *** reliability of these indicators is tested within the surface analysis of a series of limestone *** the computerized assessment,25 people have performed visual assessment of these limestone *** results of visual assessments have been statistically processed and compared to the results received from the computerized *** newly introduced absolute indicators have proved to be prospective numerical tools for evaluating joint rock coefficients.

关键词： Rock joints Shear strength Joint rock coefficients Numerical indicators Computerized assessment

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韩国前首富被捕身家大缩水

商业周刊（中文版） 2024年第12期 17-19页

作者： Yoolim Lee Sohee Kim tom Maloney Shinhye Kang 逸思(译) 不详

Kakao创始人金范洙突然被捕,引发了市场对这家互联网公司前景的质疑三年前,金范洙(brian Kim)站到了韩国互联网行业的顶峰_成为知名企业家,为韩国5000万人口创建了主流的信息平台。如今已被拘捕的他,正准备在法庭上为自己的自由和企业... 详细信息

Kakao创始人金范洙突然被捕,引发了市场对这家互联网公司前景的质疑三年前,金范洙(brian Kim)站到了韩国互联网行业的顶峰_成为知名企业家,为韩国5000万人口创建了主流的信息平台。如今已被拘捕的他,正准备在法庭上为自己的自由和企业帝国而战。7月23日凌晨1点刚过,这位Kakao Corp.的创始人因涉嫌在对K-pop经纪公司SM Entertainment Co.备受瞩目的收购战中操纵价格而被捕。

关键词：互联网行业信息平台金范经纪公司操纵价格韩国收购战

Abnormal Umbilical Doppler: Incidence and Neonatal Outcomes among Hypertensive Disorders in Pregnancy at KCMC: A Hospital-based Prospective Cohort Study

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Open Journal of Obstetrics and Gynecology 2024年第8期14卷 1253-1266页

作者： Yusuph Mwidibo Pendo Mlay Adnan Sadiq Gosbert George bariki Mchome Nasra batchu Glory Mangi Raziya Gaffur Rafiki Mjema Eusebius Maro tom Kakumbi Doris Rwenyagila Gileard Masenga Patricia Swai Department of Obstetrics and Gynecology Kilimanjaro Christian Medical Center (KCMC) Moshi Tanzania Department of Obstetrics and Gynecology Kilimanjaro Christian Medical University College (KCMUCo) Moshi Tanzania Department of Radiology Kilimanjaro Christian Medical Center (KCMC) Moshi Tanzania

Hypertensive disorders of pregnancy (HDP) are the most common maternal and perinatal health challenges. Globally, the incidence of HDP increased from 16.30 million to 18.08 million, with a total increase of about 10.9% from 1990 to 2019. Umbilical Doppler study in hypertensive disorders of pregnancy helps to predict neonatal outcomes and prevent neonatal and maternal morbidity and mortality. Objective: This study aims to determine the incidence of abnormal umbilical Doppler among hypertensive pregnant women, to identify the adverse neonatal outcomes associated with abnormal umbilical Doppler, and also to detect the diagnostic predictive values of umbilical Doppler to neonatal outcomes at KCMC. Material and methods: A hospital-based prospective cohort study included women with hypertensive disorders of pregnancy from the gestational age of 28 weeks and above, followed up to delivery during the study period from August 2022 to March 2023. Multivariate logistic regression analysis was used to determine the association between AUD and neonatal outcomes. Results: Out of 112 women with HDP, the incidence of abnormal umbilical Doppler was 38 (33.93%). Abnormal umbilical Doppler was associated with neonates with low birth weight aOR (95% of CI) of 4.52 (1.59 - 12.83) p = 0.005 and neonatal ICU admission 9.71 (2.90 - 32.43) p Conclusion: The incidence of abnormal umbilical Doppler is high in hypertensive disorders of pregnancy which is associated with an increase in neonatal low birth weight and neonatal ICU admissions, the sensitivity of abnormal umbilical Doppler in prediction of low birth weight and neonatal ICU admission is significant hence the routine use of umbilical Doppler assessment among hypertensive pregnant women is crucial.

关键词： Hypertensive Disorders in Pregnancy Umbilical Doppler Neonatal Outcomes KCMC

Competing-risks model for predicting the prognosis of patients with regressive melanoma based on the SEER database

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Malignancy Spectrum 2024年第2期1卷 123-135页

作者： Chaodi Huang Liying Huang Jianguo Huang Xinkai Zheng Congjun Jiang Kong Ching tom UTim Wu WenHsien Ethan Huang Yunfei Gao Fangmin Situ Hai Yu Liehua Deng Jun Lyu Department of Dermatology The First Affiliated Hospital of Jinan University and Jinan University Institute of DermatologyGuangzhouGuangdongChina Department of Clinical Research The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdongChina Department of Dermatology Huadu District People's Hospital of GuangzhouGuangzhouGuangdongChina Department of Dermatology The First Affiliated Hospital of Bengbu Medical CollegeBengbuAnhuiChina Primax biotech Company Hong KongChina Meng Yi Centre Limited MacaoChina GeneHope Clinic TaipeiTaiwanChina Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment Zhuhai Institute of Translational MedicineZhuhai People's Hospital Affiliated with Jinan UniversityZhuhaiGuangdongChina The biomedical Translational Research Institute Faculty of Medical ScienceJinan UniversityGuangzhouGuangdongChina Department of Dermatology The Fifth Affiliated Hospital of Jinan UniversityHeyuanGuangdongChina Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization GuangzhouGuangdongChina

background:The relationship between the regression and prognosis of melanoma has been debated for *** competing-risk events are present,using traditional survival analysis methods may induce bias in the identified prognostic factors that affect patients with regressive ***:Data on patients diagnosed with regressive melanoma were extracted from the Surveillance,Epidemiology,and End Results(SEER)database during *** incidence function and Gray's test were used for the univariate analysis,and the Cox proportional-hazards model and the Fine-Gray model were used for the multivariate ***:A total of 1442 eligible patients were diagnosed with regressive melanoma,including 529 patients who died:109 from regressive melanoma and 420 from other *** multivariate analysis using the Fine-Gray model revealed that SEER stage,surgery status,and marital status were important factors that affected the prognosis of regressive *** to the existence of competing-risk events,the Cox model may have induced biases in estimating the effect values,and the competing-risks model was more advantageous in the analysis of multipleendpoint clinical survival ***:The findings of this study may help clinicians to better understand regressive melanoma and provide reference data for clinical decisions.

关键词： competing-risks model prognosis regressive melanoma SEER Cox model

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Shape design of arch dams under load uncertainties with robust optimization

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Frontiers of Structural and Civil Engineering 2019年第4期13卷 852-862页

作者： Fengjie TAN tom LAHMER Institute of Structural Mechanics Bauhaus-UniversitatWeimar D-99423Germany

Due to an increased need in hydro-electricity, water storage, and flood protection, it is assumed that a series of new dams will be build throughout the world. The focus of this paper is on the non-probabilistic-based design of new arch-type dams by applying means of robust design optimization (RDO). This type of optimization takes into account uncertainties in the loads and in the material properties of the structure. As classical procedures of probabilistic-based optimization under uncertainties, such as RDO and reliability-based design optimization (RbDO), are in general computationally expensive and rely on estimates of the system’s response variance, we will not follow a full-probabilistic approach but work with predefined confidence levels. This leads to a bi-level optimization program where the volume of the dam is optimized under the worst combination of the uncertain parameters. As a result, robust and reliable designs are obtained and the result is independent from any assumptions on stochastic properties of the random variables in the model. The optimization of an arch-type dam is realized here by a robust optimization method under load uncertainty, where hydraulic and thermal loads are considered. The load uncertainty is modeled as an ellipsoidal expression. Comparing with any traditional deterministic optimization method, which only concerns the minimum objective value and offers a solution candidate close to limit-states, the RDO method provides a robust solution against uncertainty. To reduce the computational cost, a ranking strategy and an approximation model are further involved to do a preliminary screening. by this means, the robust design can generate an improved arch dam structure that ensures both safety and serviceability during its lifetime.

关键词： arch dam shape optimization robust optimization load uncertainty approximation model

Survival trends of patients with non-metastatic gastric adenocarcinoma in the US and European countries:the impact of decreasing resection rates

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Cancer Communications 2022年第7期42卷 648-662页

作者： Lei Huang Lina Jansen Rob H.A.Verhoeven Jelle P.Ruurda Liesbet Van Eycken Harlinde De Schutter Jan Johansson Mats Lindblad tom.b.johannesen Vesna Zadnik Tina Zagar Sjoerd M.Lagarde Cornelis J.Hvan de Velde Petra Schrotz-King Hermann brenner Division of Clinical Epidemiology and Aging Research German Cancer Research Center(DKFZ)Heidelberg 69120Germany Medical Faculty Heidelberg of Heidelberg University Heidelberg 69120Germany German Cancer Consortium German Cancer Research CenterHeidelberg 69120Germany Department of Research&Development Netherlands Comprehensive Cancer OrganizationUtrecht 3501 DBThe Netherlands Department of Medical Oncology Amsterdam University Medical CentersAmsterdam 1105 AZThe Netherlands Department of Surgery University Medical Center UtrechtUtrecht 3508 GAThe Netherlands belgian Cancer Registry Brussels B-1210Belgium Department of Esophageal and Gastric Surgery Lund University HospitalLund 22185Sweden Department of Clinical Science Interventionand TechnologyDivision of SurgeryKarolinska University HospitalStockholm 17176Sweden Registry Department The Cancer Registry of NorwayOslo 0379Norway Epidemiology and Cancer Registry Institute of Oncology LjubljanaLjubljana 1000Slovenia Department of Surgery Erasmus Medical Centre-University Medical Centre RotterdamRotterdam 3015 CEThe Netherlands Department of Surgical Oncology Leiden University Medical CenterLeiden 2300 RCThe Netherlands Division of Preventive Oncology German Cancer Research Center and National Center for Tumor DiseasesHeidelberg 69120Germany

background:We previously observed decreasing resection rates of nonmetastatic gastric adenocarcinoma(GaC)in the US and some European *** and to what extent these trends affect the trends in overall survival(OS)of patients with non-metastatic GaC at the population level remain *** large international population-based cohort study aimed to assess the impact of the previously observed decreasing resection rates on multivariable-adjusted trends in the long-term OS of patients with non-metastatic ***:Individual-level data of patients with non-metastatic GaC were obtained from the national cancer registries of the Netherlands,belgium,Sweden,Norway,and Slovenia,and the US Surveillance,Epidemiology,and End Results *** analyzed data for each country *** between year of diagnosis and OS were assessed using Cox proportional hazards regression model with adjustment for multiple prognostic variables,with and without including resection and chemotherapy as potential explanatory ***:A total of 66,398 non-metastatic GaC patients diagnosed in 2003-2016 were analyzed,with an accumulated follow-up of 172,357 *** adjustment for resection,OS was improved only slightly in the US[hazard ratio(HR)_(per year)=0.99;HR_(≥vs.bserved in the investigated European countries,with OS even worsening in Sweden(HR_(per year)=1.03;HR_(≥vs.became stronger in the US(HR_(per year)=0.98;HR_(≥vs.became insignificant in *** Slovenia(HR_(per year)=0.99;HR_(≥vs.bserved in the US,the Netherlands,and *** for chemotherapy did not alter the observed *** analyses by tumor location showedm

关键词： gastric adenocarcinoma resection rate adjusted overall survival temporal trend prognostic factors international population-based cohort study

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巴勒收藏博物馆英国格拉斯哥

世界建筑导报 2024年第4期39卷 75-79页

作者： Chris Ravenscroft Heather Macey Katherine Watts tom Roberts Paddy Pugh Hannah Lawson 约翰•麦卡兰建筑事务所

巴勒珍藏馆是欧洲最好的博物馆之一,也是为数不多的A类苏格兰战后建筑之一。珍藏馆拥有约9000件精美和装饰性的艺术作品,极其丰富的藏品来自的年代横跨6 000年。1983年,巴勒珍藏馆被置于由三位年轻剑桥建筑师学者巴里·加松、布力特·... 详细信息

巴勒珍藏馆是欧洲最好的博物馆之一,也是为数不多的A类苏格兰战后建筑之一。珍藏馆拥有约9000件精美和装饰性的艺术作品,极其丰富的藏品来自的年代横跨6 000年。1983年,巴勒珍藏馆被置于由三位年轻剑桥建筑师学者巴里·加松、布力特·安德烈森和约翰·梅乌涅尔设计的、广受好评的博物馆建筑中。这座20世纪开创性的建筑由红色邓弗里斯郡砂岩、抛光混凝土、不锈钢、木材和玻璃建成,位于距格拉斯哥市中心4英里的波洛克郊野公园的环境中。2016年,代表格拉斯哥市议会提供文化、体育和学习活动的慈善机构格拉斯哥慈善组织指定约翰·麦卡兰建筑事务所为建筑师和景观设计师,负责博物馆的五年翻新和提升项目。

关键词：建筑事务所博物馆建筑郊野公园格拉斯哥安德烈波洛克慈善机构市议会

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