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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

Implementation of an international medical student pen-pal club:survey outcomes of perceptions in cultural competency and global health

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Global Health journal 2024年第1期8卷 11-15页

作者： Max j.Goodman jennifer livschitz ji Won Kim Megan l.Schultz Medical College of Wisconsin MilwaukeeWI 53226USA Department of Pediatrics Division of Emergency MedicineMedical College of WisconsinMilwaukeeWI53226USA

Background:Pen-pal clubs(PPC)are used worldwide for students to learn about different cultures and other skillsets without the need for *** medical students are interested in global health opportunities abroad but costs,scheduling,and other barriers allow few to participate in such *** is important that medical students have nuanced global medical perspectives and can contribute to the global medical ***:The purpose of this study is to demonstrate that an international medical student PPC improves medical students'perspectives of cultural competency and global health ***:In 2021,a novel medical student PPC was established that began between an American and japanese medical *** a shareholders meeting,it was decided that the number of medical schools involved globally be expanded through previous institutional affiliations and online *** total,the club connected 50 American medical students and 52 medical students from 17 high-and middle-income *** primary form of communication was online;pen-pals were encouraged to communicate monthly using provided topics,although frequency and way of communication was their *** February 2022,American PPC members were emailed a qualitative survey to assess the PPC's ***:The survey was completed by 42%of American PPC members,95%of which were 22-26 *** were preclinical medical students,60%whom were female and the majority either white(47%)or Asian(43%).Overall,the PPC positively influenced American medical students'perception of global medicine,medical education,and their cultural competency after joining the PPC compared to prior(P=0.004).Conclusion:PPCs encourage medical students to think from a global perspective and foster open-mindedness within varying social and cultural *** a global communication platform for students during medical school education may be an additional way to train aspiring global l

关键词： Pen-pals Medical student Global health Cultural competency

Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma

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Oncology Research 2024年第7期32卷 1163-1172页

作者： lISANNE K.A.NEIjENHUIS lEUTA l.NAUMANN SONIA A.M.FERKEl SAMUEl j.S.RUBIN STEPHAN ROGAllA Division of Gastroenterology and Hepatology Department of MedicineSchool of MedicineStanford UniversityStanford94305USA Department of Surgery Leiden University Medical CenterLeiden2333 ZAThe Netherlands Centre for Human Drug Research Leiden2333 CLThe Netherlands Department of General VisceralVascular and Thoracic SurgeryCharite University Medicine BerlinBerlin10117Germany

Background:Osteosarcoma is the most common malignant primary bone *** prognosis for patients with disseminated disease remains very poor despite recent advancements in ***,current treatment regimens bear a signiﬁcant risk of serious side ***,there is an unmet clinical need for effective therapies with improved safety proﬁ*** is an antibacterial agent that has been shown to induce cell death in different types of cancer cell ***:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BAlB/c mice on day *** were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal ***:After 35 days,mice were euthanized,and the tumors were harvested for *** mice were excluded from the analysis due to *** weight was signiﬁcantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this *** tumor weight was signiﬁcantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the *** antineoplastic effects were observed on intramuscular tumors or for intravenous administration of *** were no signiﬁcant differences in microvessel density or mitotic rate between treatment *** body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is ***:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are ***,its toxic proﬁle grants further *** these observations,further research is necessary to

关键词： Osteosarcoma Taurolidine Cancer treatment Chemotherapy Murine models

Serum ferritin and the risk of early-onset colorectal cancer

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World journal of Gastrointestinal Oncology 2024年第8期16卷 3496-3506页

作者： Adam l Urback Kylee Martens Hannah Stowe McMurry Emerson Y Chen Caitlin Citti Anil Sharma Adel Kardosh joseph j Shatzel Division of Internal Medicine Oregon Health&Science UniversityPortlandOR 97239United States Division of Hematology and Medical Oncology Knight Cancer InstituteOregon Health&Science UniversityPortlandOR 97239United States Division of Gastroenterology&Hepatology Oregon Health&Science UniversityPortlandOR 97239United States

BACKGROUND The incidence of early-onset colorectal cancer(EO-CRC)is rising in the United States,and is often diagnosed at advanced *** serum ferritin is often incidentally discovered in young adults,however,the indication for endoscopy in EO-CRC is *** To compare serum ferritin between patients with EO-CRC and healthy controls(HCs),and examine the association of serum ferritin in EO-CRC with patient-and disease-specific *** A retrospective study of patientsly-diagnosed EO-CRC was conducted from 1/2013-12/*** were included if serum ferritin was measured within 2 years prior to 1 year following CRC histologic *** supplement the analysis,a cohort of HCs meeting similar inclusion and exclusion criteria were identified for comparison.A sensitivity analysis including only patients with serum ferritin obtained at or before diagnosis was separately performed to minimize risk of *** Among 85 patients identified with EO-CRC(48 females),the median serum ferritin level was 26 ng/ml(rangel).Compared to HCs(n=80211),there were a higher proportion of individuals with EO-CRC with serum ferritinl(female 65%,male 40%)versus HCs(female 32.1%,male 7.2%)age 29-39 years(P=0.002 and Ply).Stage IV disease was associated with significantly higher serum ferritin compared to less advanced stages(Plower than levels obtained after *** findings were confirmed in the sensitivity *** Severe iron deficiency may indicate an increased risk of EO-CRC,particularly at earlier *** studies defining the optimal serum ferritin threshold and routine incorporation of serum ferritin in screening algorithms is essential to develop more effective screening strategies for EO-CRC.

关键词： Early-onset Young-onset Colorectal cancer Age Ferritin Iron deficiency

Effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness:A multi-country cluster randomized controlled trial

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journal of Sport and Health Science 2024年第1期13卷 90-98页

作者： Tania Pinto-Escalona Erica Gobbi Pedro l.Valenzuela Simon j.Bennett Pierluigi Aschieri Manuel Martin-loeches Antonio Paoli Oscar Martinez-de-Quel Faculty of Education Complutense University of MadridMadrid 28040Spain Department of Biomolecular Sciences University of Urbino“Carlo Bo”Urbino 61029Italy Department of Systems Biology University of AlcaláMadrid 28805Spain Research Institute for Sport and Exercise Sciences Faculty of ScienceLiverpool John Moores UniversityLiverpoolL33AFUK Italian judo WrestlingKarate and Martial Arts FederationRome 00122Italy Psychobiology&Methods for the Behavioural Sciences Department Complutense University of MadridMadrid 28040Spain Department of Biomedical Sciences University of PaduaPadua 35122Italy

Purpose:To examine the effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness in children aged 7-8 ***:Twenty schools in 5 different European countries(2 second-grade classrooms per school)participated in a cluster randomized controlled trial(Sport at School trial).Participants were assigned to either a control group,which continued with their habitual physical education lessons,or to an intervention group,which replaced these lessons with a 1-year karate intervention(Karate Mind and Movement program).A total of 721 children(344 girls and 377 boys,7.4±0.5 years old,mean±SD)completed the study,of which 333 and 388 were assigned to the control group and intervention group,*** included academic performance(average grade),psychosocial functioning(Strengths and Difficulties Questionnaire for parents),and different markers of physical fitness(cardiorespiratory fitness,balance,and flexibility).Results:The intervention provided small but significant benefits compared to the control group for academic achievement(d=0.16;p=0.003),conduct problems(d=-0.28;p=0.003),cardiorespiratory fitness(d=0.36;plance(d=0.24;p=0.015).There was a trend towards significant benefits for flexibility(d=0.24;p=0.056).No significant benefits were observed for other variables,including psychosocial difficulties,emotional symptoms,hyperactivity/inattention,peer problems,or prosocial behaviour(all p>0.05).Conclusion:A 1-year school-based karate intervention was effective in improving academic achievement,conduct problems,and physical fitness in primary school *** results support the inclusion of karate during physical education lessons.

关键词： Academic performance Cardiorespiratory fitness Conduct problems Karate Physical fitness

Degradation and resynthesis of chlorophyll during increased oxidative stress and prolonged darkness differ between annual and perennial flax(linum l.)

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Oil Crop Science 2024年第2期9卷 121-130页

作者： Kenyon j. Nisbett Abida Alokozai Su Hyun Elizabeth Ko G. Adam Mott jason C.l. Browna Department of Biological Sciences University of Toronto ScarboroughTorontoONCanada Department of Cell&Systems Biology University of TorontoTorontoONCanada Centre for the Analysis of Genome Evolution&Function University of TorontoTorontoONCanada

Among plants,there is considerable variation in lifespan:annuals live less than one year,whereas perennials live for several years,with the longest-living perennial having survived 43,600 *** proposed by the Disposable Soma Theory,this lifespan variation among plants likely reflects differential investment of limited energy and nutrient resources,with perennials investing more energy and nutrients into biomolecular maintenance compared to annuals in order to ensure persistence over multiple *** differential investment may be particularly important during periods of exogenous stress,which are known to accelerate biomolecular *** present study evaluated this hypothesis using annual and perennial flax(linum l.)subjected to two exogenous stressors—increased oxidative stress(i.e.,foliar H2O2spraying)and complete prolonged *** chlorophyll has been shown to exhibit degradation in response to changes in environmental conditions,we utilized changes in chlorophyll levels during and after periods of exogenous stress to evaluate our *** predicted that i)perennials would exhibit a slower rate of chlorophyll degradation during exposure to exogenous stressors compared to annuals,and ii)perennials would exhibit a faster rate of chlorophyll resynthesis following such exposure compared to *** levels before,during,and after exposure to both exogenous stressors were measured in two separate trails,once using image colour analysis and once using *** chlorophyll degradation rates in response to oxidative stress did not differ between annuals and perennials,contrary to our predictions,chlorophyll resynthesis rates following such exposure were significantly higher in perennials,as *** plants were subjected to complete prolonged darkness,chlorophyll degradation rates were significantly lower in perennials than annuals,as predicted;however,when plants were subsequently reintroduced to natural photoperiod,ch

关键词： Ageing life history Maximum lifespan Oxidative stress Somatic maintenance

Harnessing the power of complex light propagation in multimode fibers for spatially resolved sensing

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Photonics Research 2024年第3期12卷 411-422页

作者： DARCY l.SMITH lINH V.NGUYEN MOHAMMAD I.REjA ERIK P.SCHARTNER HEIKE EBENDORFF-HEIDEPRIEM DAVID j.OTTAWAY STEPHEN C.WARREN-SMITH Institute for Photonics and Advanced Sensing and School of Physics Chemistry and Earth SciencesThe University of AdelaideAdelaideSA 5005Australia Australian Research Council Centre of Excellence for Gravitational Wave Discovery(OzGrav) AdelaideSAAustralia Future Industries Institute University of South AustraliaMawson LakesSA 5095Australia laser Physics and Photonics Devices laboratory University of South AustraliaMawson LakesSA 5095Australia

The propagation of coherent light in multimode optical fibers results in a speckled output that is both complex and sensitive to environmental *** properties can be a powerful tool for sensing,as small perturbations lead to significant changes in the output of the ***,the mechanism to encode spatially resolved sensing information into the speckle pattern and the ability to extract this information are thus far *** this paper,we demonstrate that spatially dependent mode coupling is crucial to achieving spatially resolved *** leverage machine learning to quantitatively extract the spatially resolved sensing information from three fiber types with dramatically different characteristics and demonstrate that the fiber with the highest degree of spatially dependent mode coupling provides the greatest accuracy.

关键词： fiber spatially resolved

Obstructive sleep apnea:Overlooked comorbidity in patients with diabetes

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World journal of Diabetes 2024年第7期15卷 1448-1460页

作者： Eric D Tenda joshua Henrina jin H Cha Muhammad R Triono Ersananda A Putri Dahliana j Aristy Dicky l Tahapary Division of Respirology and Critical Care Department of Internal MedicineFaculty of Medicine Universitas Indonesia-Cipto Mangunkusumo HospitalDKI JakartaJakarta Pusat 10430Indonesia Head of Research Group Artificial Intelligence and Digital Health Indonesian Medical Education and Research InstituteFaculty of Medicine University of IndonesiaDKI JakartaJakarta Pusat 10430Indonesia Division of Endocrinology Metabolism and DiabetesDepartment of Internal MedicineFaculty of Medicine Universitas Indonesia-Cipto Mangunkusumo HospitalDKI JakartaJakarta Pusat 10430Indonesia

In this review article,we explore the interplay between obstructive sleep apnea(OSA)and type 2 diabetes mellitus(T2DM),highlighting a significant yet often overlooked *** delve into the pathophysiological links between OSA and diabetes,specifically how OSA exacerbates insulin resistance and disrupts glucose *** research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related *** the importance of comprehensive management,including weight control and positive airway pressure therapy,the study advocates integrated approaches to improve outcomes for patients with T2DM and *** review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.

关键词： Obstructive sleep apnea Type 2 diabetes mellitus Macrovascular Microvascular Weight loss Positive airway pressure

Conservative management of spinal pathology with autologous conditioned serum: A systematic review of the literature

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World journal of Orthopedics 2024年第9期15卷 870-881页

作者： Christian j Rajkovic Matthew l Merckling Alyssa W lee Galadu Subah Aryan Malhotra Zachary D Thomas Sabrina l Zeller john V Wainwright Merritt D Kinon Department of Neurosurgery Westchester Medical CenterValhallaNY 10595United States

BACKGROUND Chronic inflammatory pain is associated with increased expression of interleukin(Il)-1,an inflammatory cytokine,and activity on its receptor(Il-1R).In response,the body produces Il-1R antagonist(Il-1Ra)to reduce this *** conditioned serum(ACS)is the only biologic therapy for spinal pathologies that enhances the action of endogenous Il-1Ra reserves to improve *** systematic review investigates the effectiveness of ACS in treating pain and dis-ability caused by spinal *** To evaluate the use of ACS as a conservative management option for spinal *** A systematic review of PubMed/Medline was performed to identify studies inve-stigating administration of ACS for treatment of any spinal *** Six articles were included,comprising 684 patients treated with epidural(n=133)or transforaminal(n=551)ACS *** had an average age of 54.0 years with slight female predominance(53.2%).The lumbar spine was most com-monly treated,with 567 patients(82.9%)receiving injections for lumbar radicu-lopathy(n=67),degenerative disc disease(DDD)(n=372),or spinal stenosis(n=128);cervical injections were performed in 109 patients(15.9%).Mean(SD)follow-up was 21.7(4.8)weeks from first ACS *** studies investigating mecha-nical lumbar and lumbar or cervical radicular pain reported significant pain re-duction at final follow-up compared to *** achieved comparable or su-perior results to lumbar epidural steroid *** events were reported in 21 patients(3.1%),with no serious adverse *** ACS injection is a safe and effective intervention for pain reduction in many spinal pathologies,including cervical and lumbar radiculopathies.

关键词： Spine Autologous conditioned serum Orthokine Regenokine Epidural steroid injection Interleukin-1 Inter-leukin-1 receptor antagonist