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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

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance

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World journal of Radiology 2016年第4期8卷 410-418页

作者： larissa j vos Michele janoski Keith Wachowicz Atiyah Yahya Oleksandr Boychak john Amanie Nadeem Pervez Matthew B Parliament Edith Pituskin B Gino Fallone Nawaid Usmani Department of Oncology Cross Cancer InstituteUniversity of Alberta Department of Radiology and Diagnostic Imaging Cross Cancer InstituteUniversity of Alberta

AIM:To examine whether addition of 3T multiparametric magnetic resonance imaging(mp MRI)to an active surveillance protocol could detect aggressive or progressive prostate ***:Twenty-three patients with low risk disease were enrolled on this active surveillance study,all of which had Gleason score 6 or less *** patients had clinical assessments,including digital rectal examination and prostate specific antigen(PSA)testing,every 6 mo with annual 3T mp MRI scans with gadolinium contrast and minimum sextant prostate *** MRI images were anonymized of patient identifiers and clinical information and each scan underwentradiological review without the other results *** statistics for demographics and follow-up as well as the sensitivity and specificity of mp MRI to identify prostate cancer and progressive disease were ***:During follow-up(median 24.8 mo)11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive *** progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 *** 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mp MRI scans at baseline(43.5% sensitivity).Aggressive disease prediction from baseline mpM RI scans had satisfactory specificity(81.8%)but low sensitivity(58.3%).Twentytwo patients had serial mp MRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy(30% specificity and 100% sensitivity).CONCLUSION:Addition of mp MRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods.

关键词： Active surveillance Treatment triaging Magnetic resonance imaging Indolent disease Prostate cancer

Resilience, the 6th Vital Sign: Conceptualizing, Contextualizing, and Operationalizing All Six Vital Signs

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Health 2024年第7期16卷 657-673页

作者： Rose E. Constantino Betty j. Braxter Chi Ching Vivian Hui larissa C. Allen Lillian j. Wolfe Katherine H. Endres jezyl Cempron Cutamora Laurence L. Garcia Daisy R. Palompon Kathleen Thimsen Brayden N. Kameg Margarete L. Zalon Department of Health and Community Systems School of Nursing University of Pittsburgh Pittsburgh PA USA Undergraduate Affairs School of Nursing University of Pittsburgh Pittsburgh PA USA The Hong Kong Polytechnic University Hong Kong China School of Nursing Adjunct Faculty at the University of Pittsburgh Pittsburgh PA USA School of Nursing University of Pittsburgh Pittsburgh PA USA Department of Health Promotion and Development School of Nursing University of Pittsburgh Pittsburgh PA USA College of Nursing Cebu Normal University Cebu City Philippines School of Nursing University of Nevada Las Vegas USA Department of Health and Community Systems University of Pittsburgh PA USA Department of Nursing University of Scranton Scranton PA USA

There are five vital signs that healthcare providers assess: temperature, pulse, respiration, blood pressure, and pain. Normal levels for the five vital signs are published by the American Heart Association, and other specialty organizations, however, the sixth vital sign (resilience) which adopts the measure of immune resilience is suggested in this paper. Resilience is the ability of the immune system to respond to attacks and defend effectively against infections and inflammatory stressors, and psychological resilience is the capacity to resist, adapt, recover, thrive, and grow from a challenge or a stressor. Individuals with better optimal immune resilience had better health outcomes than those with minimal immune resilience. The purpose of this paper is to conceptualize, contextualize, and operationalize all six vital signs. We suggest measuring resilience subjectively and objectively. Subjectively, use a 5-item guided interview revised from the Connor-Davidson Resilience Scale (CDRC), a scale of 10 items. The revised CDRC scale is a 5-item scale. The scale is rated on a 5-point Likert scale from 0 (not true) to 4 (true all the time). The total score ranges from 0 to 20, with higher total scores indicating greater resilience. The scale demonstrated good construct validity and internal consistency (α = 0.85) during the development of the scale. The CD-RISC had a good Cronbach’s alpha level of 0.85. The Revised CD-RISC can be completed in 2 - 4 minutes. To measure resilience objectively, we suggest using Immune Resilience (IR) levels, the level of resilience to preserve and/or rapidly restore immune resilience functions that promote disease resistance and control inflammation and other inflammatory stress. IR levels are gauged with two peripheral blood metrics that quantify the balance between CD8 and CD4 T-cell levels and gene expression signatures tracking longevity-associated immunocompetence and mortality- or entropy-associated inflammation. IR deregulation i

关键词： Conceptualization Contextualization Operationalization Body Temperature Pulse Respiration Blood Pressure Pain Resilience

Cholangiocarcinoma:A 7-year experience at a single center in Greece

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World journal of Gastroenterology 2008年第40期14卷 6213-6217页

作者： Alexandra Alexopoulou Aspasia Soultati Spyros P Dourakis larissa Vasilieva Athanasios j Archimandritis 2nd Department of Medicine University of Athens Medical SchoolHippokration General Hospital

AIM： To evaluate survival rate and clinical outcome of cholangiocarcinoma. METHODS： The medical records of 34 patients with cholangiocarcinoma, seen at a single hospital between the years 1999-2006, were retrospectively reviewed. RESULTS： Thirty-four patients with a median age of 75 years were included. Seventeen （50%） had painless jaundice at presentation. Sixteen （47.1%） were perihilar, 15 （44.1%） extrahepatic and three （8.8%） intrahepatic. Endoscopic retrograde cholangiography （ERCP） and/or magnetic resonance cholangiography （MRCP） were used for the diagnosis. Pathologic confirmation was obtained in seven and positive cytological examination in three. Thirteen patients had co-morbidities （38.2%）. Four cases were managed with complete surgical resection. All the rest of the cases （30） were characterized as non-resectable due to advanced stage of the disease. Palliative biliary drainage was performed in 26/30 （86.6%）. The mean follow-up was 32 mo （95% CI, 20-43 too）. Overall median survival was 8.7 mo （95% CI, 2-16 mo）. The probability of 1-year, 2-year and 3-year survival was 46%, 20% and 7%, respectively. The survival was slightly longer in patients who underwent resection compared to those who did not, but this difference failed to reach statistical significance. Patients who underwent biliary drainage had an advantage in survival compared to those who did not （probability of survival 53% vs 0% at 1 year, respectively, P = 0.038）. CONCLUSION： Patients with cholangiocarcinoma were usually elderly with co-morbidities and/oradvanced disease at presentation. Even though a slight amelioration in survival with palliative biliary drainage was observed, patients had dismal outcome without resection of the tumor.

关键词： Cholangiocarcinoma Surgical resection Palliative biliary drainage Survival

Predicting utility of a model for end stage liver disease in alcoholic liver disease

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World journal of Gastroenterology 2006年第25期12卷 4020-4025页

作者： Aspasia S Soultati Spyridon P Dourakis Alexandra Alexopoulou Melanie Deutsch larissa Vasilieva Athanasios j Archimandritis 2nd Department of Internal Medicine University of Athens Medical School Hippokration General Hospital114 Vas Sofias AvenuesAthens 11527Greece

AIM： To validate the statistic utility of both the Maddrey Discriminant Function score and the Model for End-Stage Liver Disease as predictors of short term （30 d and 90 d） mortality in patients with alcoholic hepatitis and to assess prognostic factors among clinical characteristics and laboratory variables of patients with alcoholic hepatitis. METHODS： Thirty-four patients with the diagnosis of alcoholic hepatitis admitted to Hippokration University Hospital of Athens from 2000 to 2005 were assessed in the current retrospective study and a statistical analysis was conducted. RESULTS： 30- and 90-d mortality rates were reported at 5.9% （2/34） and 14.7% （5/34）, respectively. Significant correlation was demonstrated for the Model for End- Stage Liver Disease （P30 = 0.094, P90 = 0.046） and the Maddrey Discriminant Function score （P30 = 0.033, P90 = 0.038） with 30- and 90-d mortality whereas a significant association was also established for alanine aminotrans- ferase （P = 0.057）, fibrin degradation products （P = 0.048） and C-reactive protein （P = 0.067） with 90-d mortality. For 30-d mortality the Area Under the Curve was 0.969 （95%CI： 0.902-1.036, P = 0.028） for the Model for End-Stage Liver Disease score and 0.984 （95%CI： 0.942-1.027, P = 0.023） for the Maddrey Discriminant Function score with the optimal cut off point of 30.5 （sensitivity 1, specificity 0.937） and 108.68 （sensitivity 1, specificity 0.969）, respectively. Accordingly, for 90-d mortality the Area Under the Curve was 0.762 （95%CI： 0.559-0.965, P = 0.065） for the Model for End-Stage Liver Disease score and 0.752 （95%CI： 0.465-1.038, P = 0.076） for the Maddrey Discriminant Function score with the optimal cut off point of 19 （sensitivity 0.6, specificity 0.6） and 92 （sensitivity 0.6, specificity 0.946）, respectively. The observed Kaplan Meier survival rates for different score-categories were compared with logrank tests and higher score values were correlated with a lower survival. CONCLUSION： Equivale

关键词： Alcoholic liver disease Alcoholic hepatitis Maddrey discriminant function score Model for end-stage liver disease score

Good accuracy of the alpha-defensin lateral flow test for hip periprosthetic joint infection: A pilot study in a retrospective cohort of 52 patients

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World journal of Orthopedics 2020年第1期11卷 36-46页

作者： jesse WP Kuiper Pieter Pander Stan j vos Department of Orthopedic Surgery Noordwest ZiekenhuisgroepAlkmaar 1815 JDNetherlands Centre for Orthopedic Research Alkmaar Noordwest ZiekenhuisgroepAlkmaar 1815 JDNetherlands

BACKGROUND The alpha-defensin lateral flow(ADLF)test is a new diagnostic tool for periprosthetic joint infection(PjI).Test accuracy for combined cohorts of hip and knee PjI has been reported to be *** To assess the accuracy of the ADLF test for hip PjI,and to compare three different diagnostic criteria for *** A cohort of 52 patients was identified,with a painful or poor-functioning total hip-or hemi-arthroplasty,that underwent aspiration and a subsequent ADLF *** was diagnosed with Musculoskeletal Infection Society(MSIS)criteria,and sensitivity,specificity,overall accuracy,positive predictive value and negative predictive value were ***,test specifics were compared with the European Bone and joint Infection Society(EBjIS)and 2018 International Consensus Meeting(ICM)criteria for *** Using MSIS criteria,sensitivity was 100%(CI:54%-100%)and specificity was 89%(CI:76%-96%).Six true positives and 5 false positives were found,including one case of *** EBjIS criteria,more PjIs were found(11 vs 6),sensitivity was lower(71%,CI:42%-92%)and specificity was higher(97%,CI:86%-100%),with 4 false negatives and one false positive *** 2018 ICM criteria,sensitivity was 91%(62%-100%)and specificity 100%(91%-100%).The results in this cohort are comparable to previous *** Overall test accuracy of the ADLF test was good in this cohort,with a sensitivity of 100%and specificity of 89%.Using different PjI definition criteria,sensitivity and specificity changed slightly but overall accuracy remained around 90%.Using the ADLF test in metallosis cases can result in false positive results and should be performed with caution.

关键词： Periprosthetic Arthroplasty Replacement Hip Infection Periprosthetic joint infection Alpha-defensin Synovasure

Three-dimensional perfused human in vitro model of nonalcoholic fatty liver disease

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World journal of Gastroenterology 2017年第2期23卷 204-215页

作者： Tomasz Kostrzewski Terri Cornforth Sophie A Snow larissa Ouro-Gnao Cliff Rowe Emma M Large David j Hughes CN Bio Innovations Limited Welwyn Garden City AL7 3AXUnited Kingdom

AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture *** The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds.

关键词： Non-alcoholic fatty liver disease Liver disease Three-dimensional cell culture Organ-on-chip Primary cell culture Fatty liver Hepatocytes

Broadband Optical Active Waveguides Written by Femtosecond Laser Pulses in Lithium Fluoride

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Chinese Physics Letters 2014年第1期31卷 72-75页

作者： Ismael Chiamenti Francesca Bonfigli Anderson S. L. Gomes Rosa Maria Montereali larissa N. da Costa Hypolito j. Kalinowski Federal University of Technology- Parang 80230-901 Curitiba Brazil ENEA C. R. Frascati Photonics Micro and Nanostructures Laboratory UTAPRAD-MNF V. E. Fermi 45 00044 Frascati (Rome) Italy Department of Physics Universidade Federai de Pernambuco necife Brazil

Broadband waveguiding through light-emitting strips directly written in a blank lithium fluoride crystal with a femtosecond laser is reported. Light guiding was observed at several optical wavelengths, from blue, 458 nm, to near-infrared, at 155nm. Visible photoluminescence spectra of the optically active F2 and F33 color centers produced by the fs laser writing process were measured. The wavelength-dependent refractive index increase was estimated to be in the order of 10-3-10-4 in the visible and near-infrared spectral intervals, which is consistent with the stable formation of point defects in LiF.

关键词： Fluorine compounds

Large-diameter trees, snags, and deadwood in southern Utah, USA

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Ecological Processes 2021年第1期10卷 130-141页

作者： james A.Lutz Soren Struckman Tucker j.Furniss joseph D.Birch larissa *** Darren j.McAvoy Department of Wildland Resources S.J.and Jessie E.Quinney College of Natural ResourcesUtah State University5230 Old Main HillLoganUT 84322-5230USA. Department of Renewable Resources University of AlbertaEdmontonAlbertaCanada.

Background:The epidemic Dendroctonus rufipennis(spruce beetle)outbreak in the subalpine forests of the Colorado Plateau in the 1990s killed most larger Picea engelmannii(Engelmann spruce)*** quarter century later,the larger snags are beginning to fall,transitioning to deadwood(down woody debris)where they may influence fire behavior,regeneration,and habitat ***:We tracked all fallen trees≥1 cm in diameter at breast height(1.37-m high)and mapped all pieces of deadwood≥10-cm diameter and≥1 m in length within 13.64 ha of a high-elevation mixed-species forest in the Picea–Abies zone annually for 5 years from 2015 through *** examined the relative contribution of Picea engelmannii to snag and deadwood pools relative to other species and the relative contributions of large-diameter trees(≥33.2 cm at this subalpine site).We compared spatially explicit mapping of deadwood to traditional measures of surface fuels and introduce a new method for approximating vertical distribution of ***:In this mixed-species forest,there was relatively high density and basal area of live Picea engelmannii 20 years after the beetle outbreak(36 trees ha^(−1) and 1.94 m^(2) ha^(−1)≥10-cm diameter)contrasting with the near total mortality of mature Picea in forests *** from tree boles≥10-cm diameter on the ground had biomass of 42 Mg ha^(−1),7 Mg ha^(−1) of Picea engelmannii,and 35 Mg ha^(−1) of other *** live aboveground biomass was 119 Mg ha^(−1),while snag biomass was 36 Mg ha^(−1).Mean total fuel loading measured with planar transects was 63 Mg ha^(−1) but varied more than three orders of magnitude(0.1 to 257 Mg ha^(−1)).Planar transects recorded 32 Mg ha^(−1) of wood≥7.62-cm diameter compared to the 42 Mg ha^(−1) of wood≥10-cm diameter recorded by explicit *** pieces of deadwood were often stacked,forming a vertical structure likely to contribute to active fire ***:Bark beetle mortality in the 1990s has made

关键词： Cedar Breaks National Monument Dendroctonus rufipennis Utah Forest Dynamics Plot Vertical fuel structure