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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKm supports antitumor immunity

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Cellular & molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda mackenzie m.Lieberman Caitlin m.James Shivana m.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou andrew m.Intlekofer Richard m.Higashi Teresa W.m.Fan andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber Cancer Institute BostonMA 02215USA Present address:massachusetts Institute of Technology BostonMA 02139USA Present address:melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the m1 isoform of pyruvate kinase in favor of PKm2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKm alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKm2

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Customized scaffolds for large bone defects using 3D‑printed modular blocks from 2D‑medical images

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Bio-Design and manufacturing 2024年第1期7卷 74-87页

作者： Anil AAcar Evangelos Daskalakis Paulo Bartolo andrew Weightman Glen Cooper Gordon Blunn Bahattin Koc Faculty of Engineering and Natural Sciences Sabanci UniversityIstanbul 34956Türkiye D Bioprinting Laboratory Sabanci University Nanotechnology Research and Application CenterIstanbul 34956Türkiye School of mechanical Aerospace and Civil EngineeringManchester Institute of BiotechnologyUniversity of ManchesterManchester M139PLUK Singapore Centre for 3D Printing School of Mechanical and Aerospace EngineeringNanyang Technological UniversitySingapore 639798Singapore School of Pharmacy and Biomedical Sciences University of PortsmouthPortsmouth PO12UPUK

Additive manufacturing(Am)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering *** use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and ***,these sophisticated techniques can be timeconsuming,labor-intensive,and ***,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma *** this study,a novel design and Am methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a *** modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during *** proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or *** algorithm can generate both patient-specific and average bone ***,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or *** algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based Am *** and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.

关键词： Additive manufacturing modular scaffolds Large bone defect Customized scaffold design Patient-specific scaffolds

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Evaluating implicit gender bias at Canadian otolaryngology meetings through use of professional title

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 12-17页

作者： Kylen Van Osch Agnieszka Dzioba Khadija Ahmed andrew macDonald Jamila Skinner Harley Williams Julie E.Strychowsky m.Elise Graham Department of Otolaryngology-Head&Neck Surgery Schulich School of Medicine&DentistryWestern UniversityLondonOntarioCanada Department of Otolaryngology London Health Sciences Centre Children's HospitalLondonOntarioCanada Faculty of medicine Schulich School of Medicine&DentistryWestern UniversityLondonOntarioCanada

Objectives:Increasing numbers of women enter medical school *** number of female physicians in leadership positions has been much slower to *** are also well‐documented differences in the treatment of women as compared to men in professional *** presenters are less likely to be introduced by their professional title(“Doctor”)for grand rounds and conferences,especially with a man performing the *** study reviewed the Canadian Society of Otolaryngology–Head and Neck Surgery(CSOHNS)meetings from 2017 to 2020 to determine the proportion of presenters introduced by their professional title and whether this varied by ***:Recordings from CSOHNS meetings were reviewed and coded for introducer and presenter demographics,including leadership positions and ***‐squared tests of proportion and multivariate logistic regression was used to compare genders and identify factors associated with professional versus unprofessional forms of ***:No significant association was found between professional title use and introducer or presenter *** presenters were introduced with professional title 69.6%of the time,while male presenters were introduced with professional title 67.6%of the time(P=0.69).Residents were introduced with a professional title with the most frequency(75.8%),while attending staff were introduced with a professional title with the least frequency(63.0%)(P=0.02).Conclusions:The lack of gender bias in speaker introductions at recent CSOHNS meetings demonstrates progress in achieving gender equity in *** efforts should continue to define additional forms of unconscious bias that may be contributing to gender inequity in leadership positions.

关键词： attitude of health personnel gender identity Otolaryngology women

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Network analyses:Inhibition of androgen receptor signaling reduces inflammation in the lung through AR-mAF-IL6 signaling axes

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Genes & Diseases 2024年第3期11卷 140-143页

作者： Albert R.Wang andrew m.Baschnagel Zijian Ni Sean R.Brennan Hypatia K.Newton Darya Buehler Christina Kendziorski Randall J.Kimple Gopal lyer Department of Human Oncology University of Wisconsin School of Medicine and Public HealthUniversity of WisconsinMadisonWI 53705USA Department of Biomedical Engineering University of Wisconsin-MadisonMadisonWI 53705USA University of Wisconsin Carbone Cancer Center MadisonWI 53705USA Department of Biostatistics and medical Informatics University of Wisconsin-MadisonMadisonWI 53706USA Department of Biology Tufts UniversityMedfordMA 02155USA Department of Pathology and Laboratory medicine University of Wisconsin School of Medicine and Public HealthUniversity of WisconsinMadisonWI 53705USA

Androgen receptor(AR)is a major transcription factor that plays a role in inflammatory response including interleukin-6(IL6)signaling.1 While AR regulation through paracrine loop signaling in prostate tissue is well-studied,its impact through an IL6 autocrine loop in the lung has not been wellstudied despite the organ's response to respiratory viral *** inhibition and RNA knockdown of AR identified a bZIP transcription factor mAF to be a common target of inflammation using these perturbations in lung cells.

关键词： inflammation lung respiratory

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A state-of-the-art review on delayed expansion of cemented paste backfill materials

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Rare metals 2024年第8期43卷 3475-3500页

作者： meng-Yuan Li Li-Jie Guo Yue Zhao Lei Zhang Kai Yang Xiao-Peng Peng andrew Pan BGRImm Technology Group Beijing 100160China National Centre for International Research On Green metal mining Beijing102628China Department of Civil and mineral Engineering University of TorontoTorontoON M5S 1A4Canada

Utilizing delayed expansion cemented paste backfill materials(DECPB) in mine backfill operations offers an effective solution to the challenge of achieving proper contact between the in-situ cemented backfill mass and the roof in mined-out areas(backfill-roof contact).This article presents recent progress in both theoretical and experimental research concerning *** types and mechanisms of expansive additives,including expansive agents,foaming agents,and expansive mineral materials relevant to DECPB,are explained,along with their impact on the expansive properties and mechanical characteristics of *** composition,material characteristics,preparation methods,and controlled release mechanisms of microcapsules are *** methods for measuring the volume change rate of paste backfill slurries are *** indicates that an appropriate content of expansive additives not only enhances the expansive properties of cemented paste backfill materials but also contributes to improving their mechanical *** foaming agents and bentonite are found to be more suitable for preparing DECPB compared to expansive *** delayed expansion of cemented paste backfill material is influenced by microcapsules,with their wall materials,preparation parameters,and the alkaline slurry environment affecting their controlled release *** and optimizing precise measurement devices and methods forfor the volume change rate of cemented paste backfill materials is essential requirement for studying the performance of *** delayed expansion technology with retarding techniques in cemented paste backfill materials can provide a reliable solution for achieving proper backfill-roof contact in the future.

关键词： Paste backfill Delayed expansion mining with backfill Expansive additives Tailings

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Panel Discussion on“Development Trends of Computer Science in the New Era”

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计算机教育 2024年第3期 26-29页

作者： andrew Yao Nancy m.Amato Ann Copestake Sukyoung Ryu Yike Guo Yaqin Zhang Institute for Interdisciplinary Information Sciences Tsinghua UniversityBeijing100084China Department of Computing University of IllinoisUrbana61801U.S Department of Computer Science and Technology University of CambridgeCambridgeCB30FDUK Korea Advanced Institute of Science and Technology(KAIST) Yuseong-gu Daejeon34141Korea Hong Kong University of Science and Technology Hong Kong999077China Institute for AI Industry Research(AIR) Tsinghua UniversityBeijing100084China

At the panel session of the 3rd Global Forum on the Development of Computer Science,attendees had an opportunity to deliberate recent issues affecting computer science departments as a result of the recent growth in the field.6 heads of university computer science departments participated in the discussions,including the moderator,Professor andrew *** first issue was how universities are managing the growing number of applicants in addition to swelling class *** approaches were suggested,including increasing faculty hiring,implementing scalable teaching tools,and working closer with other departments through degree programs that integrate computer science with other *** second issue was about the position and role of computer science within broader *** generally agreed that all fields are increasingly relying on computer science techniques,and that effectively disseminating these techniques to others is a key to unlocking broader scientific progress.

关键词： Development trends Computer science

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Organoid intelligence:Integration of organoid technology and artificial intelligence in the new era of in vitro models

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medicine in Novel Technology and Devices 2024年第1期21卷 39-44页

作者： Huaiyu Shi andrew Kowalczewski Danny Vu Xiyuan Liu Asif Salekin Huaxiao Yang Zhen ma Department of Biomedical&Chemical Engineering Syracuse UniversitySyracuseNYUSA BioInspired Institute for material and Living Systems Syracuse UniversitySyracuseNYUSA Department of mechanical&Aerospace Engineering Syracuse UniversitySyracuseNYUSA Department of Electrical Engineering&Computer Science Syracuse UniversitySyracuseNYUSA Department of Biomedical Engineering University of North TexasDentonTXUSA

Organoid Intelligence ushers in a new era by seamlessly integrating cutting-edge organoid technology with the power of artificial ***,three-dimensional miniature organ-like structures cultivated from stem cells,offer an unparalleled opportunity to simulate complex human organ systems in *** the convergence of organoid technology and AI,researchers gain the means to accelerate discoveries and insights across various *** intelligence algorithms enable the comprehensive analysis of intricate organoid behaviors,intricate cellular interactions,and dynamic responses to *** synergy empowers the development of predictive models,precise disease simulations,and personalized medicine approaches,revolutionizing our understanding of human development,disease mechanisms,and therapeutic *** Intelligence holds the promise of reshaping how we perceive in vitro modeling,propelling us toward a future where these advanced systems play a pivotal role in biomedical research and drug development.

关键词： Organoids machinelearning Deep learning Artificial intelligence Stem cells

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Climate-influenced vector-borne diseases in Africa: a call to empower the next generation of African researchers for sustainable solutions

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贫困所致传染病(英文) 2024年第2期13卷 1-10页

作者： Obame-Nkoghe Judica?l Agossou Adjoavi Esse mboowa Gerald Kamgang Basile Caminade Cyril Duke Dawn C. Githeko andrew Karanja Ogega Obed m. Elloué Nestor Engone Sarr Fatou Bintou Nkoghe Dieudonné Kengne Pierre Ndam Nicaise T. Paupy Christophe Bockarie moses Otomo Patricks Voua molecular and Cellular Biology Laboratory (LabmC) Biology Department University of Science and Technology of Masuku BP Franceville Gabon Ecology and Health Research Unit Interdisciplinary Center for Medical Research of Franceville BP Franceville Gabon Department of Zoology and Entomology Faculty of Natural and Agricultural Sciences University of the Free State Private Bag x13 Phuthaditjhaba Republic of South Africa Laboratory of Pharmacology and Improved Traditional medicines Department of Animal Physiology Faculty of Science and Technology University of Abomey-Calavi BP Cotonou Benin The African Center of Excellence in Bioinformatics and Data-Intensive Sciences Infectious Diseases Institute College of Health Sciences Makerere University P. O Box Kampala Uganda Africa Centers for Disease Control and Prevention African Union Commission Roosevelt Street P.O. Box WKAddis Ababa Ethiopia Centre for Research in Infectious Diseases P.O. Box Yaoundé Cameroon Earth System Physics Department The Abdus Salam International Centre for Theoretical Physics Trieste Italy Africa Research Excellence Fund Charterhouse Street London EC1MHR UK Community Health Support Program P.O. Box Kisumu Kenya The African Academy of Sciences Nairobi Kenya Center for Phylosophical Studies and Research (CERP) Omar Bongo University (UOB) BP Libreville Gabon UmRED Health Training and Research Unit University of Iba Der Thiam of Thiès BP Thiès Senegal National Parasitic Diseases Control Program Ministry of Health Libreville Gabon mIVEGEC Univ. Montpellier CNRS IRD Montpellier France mERIT IRD Paris Cité University Paris France Department of Parasitology Noguchi Memorial Institute for Medical Research University of Ghana LG Accra Ghana School of Community Health Sciences Njala University Bo Sierra Leone

We look at the link between climate change and vector-borne diseases in low- and middle-income countries in Africa. The large endemicity and escalating threat of diseases such as malaria and arboviral diseases, intensified by climate change, disproportionately affects vulnerable communities globally. We highlight the urgency of prioritizing research and development, advocating for robust scientific inquiry to promote adaptation strategies, and the vital role that the next generation of African research leaders will play in addressing these challenges. Despite significant challenges such as funding shortages within countries, various pan-African-oriented funding bodies such as the African Academy of Sciences, the Africa Research Excellence Fund, the Wellcome Trust, the U.S. National Institutes of Health, and the Bill and melinda Gates Foundation as well as initiatives such as the African Research Initiative for Scientific Excellence and the Pan-African mosquito Control Association, have empowered (or are empowering) these researchers by supporting capacity building activities, including continental and global networking, skill development, mentoring, and African-led research. This article underscores the urgency of increased national investment in research, proposing the establishment of research government agencies to drive evidence-based interventions. Collaboration between governments and scientific communities, sustained by pan-African funding bodies, is crucial. Through these efforts, African nations are likely to enhance the resilience and adaptive capacity of their systems and communities by navigating these challenges effectively, fostering scientific excellence and implementing transformative solutions against climate-sensitive vector-borne diseases.

关键词： Climate change Vector-borne diseases Africa Environmental justice Research and development Pan-African funding initiatives

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The efficacy of vitamin E in preventing arthrofibrosis after joint replacement

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Animal models and Experimental medicine 2024年第2期7卷 145-155页

作者： Yingfang Fan Jean Yuh Sashank Lekkala mehmet D.Asik andrew Thomson madeline mcCanne mark A.Randolph Antonia F.Chen Ebru Oral Harris Orthopaedic Laboratory Department of Orthopaedic SurgeryMassachusetts General HospitalBostonMassachusettsUSA Department of Orthopaedic Surgery Harvard Medical SchoolBostonMassachusettsUSA Department of Surgery Harvard Medical SchoolBostonMassachusettsUSA Department of Orthopaedic Surgery Brigham and Women's HospitalBostonMassachusettsUSA

Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint *** E is an antioxidant with potential anti-fibroblastic *** aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint ***:We simulated knee replacement in 16 male Sprague–Dawley *** immobilized the surgical leg with a suture in full *** control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of *** staining andα2-macroglobulin(α2m)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic *** weight bearing(total internal reflection)and range of motion(ROm)were collected for functional ***:The ROm and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both *** analysis confirmed fibrosis in both lateral and posterior periarticular *** E supplementation showed a moderate anti-inflammatory effect on the local and systemic *** vitamin E group exhibited significant improvement in ROm and weight-bearing symmetry at day 84 compared to the control ***:This model is viable for simulating arthrofibrosis after joint *** E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.

关键词： arthrofibrosis range of motion total knee arthroplasty vitamin E

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C19mC miRNA-520G induces SP100 antiviral gene transcription and inhibits melanin production in skin cutaneous melanoma

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Genes & Diseases 2024年第1期11卷 60-63页

作者： Goodwin G.Jinesh marian T.Smallin Nino mtchedlidze Isha Godwin marco Napoli Nicole Hackel manali S.Phadke Avani A.Deshpande Xiaobo Li John H.Lockhart Jaden R.Baldwin Suehelay Acevedo-Acevedo Yifeng Gao michelle A.Reiser Keiran S.m.Smalley Elsa R.Flores andrew S.Brohl Department of molecular Oncology H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA molecular medicine Program H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Saveetha medical College ChennaiTamil Nadu 602105India Tumor Biology Department H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Sarcoma Department H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA

SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(HPV)and multiple other viruses,and viruses in turn block sUmO-1-mediated stabilization of SP100 and promotes its degradation(Table S1).Interferon(IFN)signaling could still produce more SP100 through transcription to counteract viruses.1 Viruses also disable the transcriptional up-regulation of SP100 to achieve persistent infection in hosts.

关键词： SP100 melanoma stabilization

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