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  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Immunology Research Vol. 10, No. 1_Supplement ( 2022-01-01), p. P019-P019
    In: Cancer Immunology Research, American Association for Cancer Research (AACR), Vol. 10, No. 1_Supplement ( 2022-01-01), p. P019-P019
    Abstract: Patients with highly innervated tumors have a worse prognosis than those with less innervated disease. However, the process by which intra-tumoral nerves contribute to poor outcomes remains unclear. Previously, we identified that head and neck squamous cell carcinomas (HNSCCs) are infiltrated by sensory (TRPV1+) nerves. To map the source of these tumor infiltrating nerves, we intra-tumorally injected the fluorescently tagged nerve tracer lectin, wheat germ agglutinin (WGA), in our hind limb placed HNSCC tumors. Similar to other nerve tracers, WGA is taken up at nerve terminals and retrogradely transported to the neural somas. WGA labeled the somas of dorsal root ganglia (DRG), identifying them as the source of intra-tumoral nerves. Traced nerves were further characterized by immunostaining and identified as TRPV1+ (sensory), consistent with our initial findings. To test the contributions of tumor innervation to tumor growth and survival, wildtype and TRPV1-DTA (genetically deleted of TRPV1+ neurons) mice were implanted with a mouse model of human papillomavirus-induced (HPV+) HNSCC, mEERL cells. The absence of TRPV1 nerves results in slower tumor growth and improves survival. To mechanistically define how depletion of intra-tumoral nerves reduce tumor growth, we first collected tumors 25 days after injection in the hind limb and stained with a 12-color antibody panel. Stained tumors were then analyzed with flow cytometry to identify differences in the infiltrative immune cell populations between tumors grown in C57Bl/6 control mice and our TRPV1-DTA mouse model. Flow cytometry analysis indicated a decrease in the infiltrative myeloid derived suppressor cell (MDSC) population following ablation of TRPV1+ nerves. To understand how loss of TRPV1+ nerves mediate changes in the infiltrative immune cell population we conducted cytokine array analysis of condition media from cancer cells alone and in co-culture with DRG. Results indicate a shift in secreted cytokines following co-culture with DRG. These data indicate that intra-tumoral sensory nerves are recruited from loco-regional DRG to tumors injected in the hind limb. Our data also suggest that ablation of TRPV1+ nerves alter the intra-tumoral MDSC population and, in this way, potentially contributes to tumor growth. Finally, co-culture of mEERL cells with DRG in vitro results in changes in secreted cytokines, potentially explaining the change in the infiltrative immune cell populations. Together, these data indicate a potential role for sensory nerves to regulate the local immune response in developing tumors. Citation Format: Anthony C. Restaino, Christopher T. Lucido, Jeffrey Barr, Paola D. Vermeer. Intra-tumoral nerves regulate the local immune response at the tumor bed [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P019.
    Type of Medium: Online Resource
    ISSN: 2326-6066 , 2326-6074
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2732517-9
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  • 2
    Online Resource
    Online Resource
    Charter Services New York d/b/a Journal of Orthopaedic Experience and Innovation ; 2023
    In:  Journal of Orthopaedic Experience & Innovation
    In: Journal of Orthopaedic Experience & Innovation, Charter Services New York d/b/a Journal of Orthopaedic Experience and Innovation
    Abstract: There is a paucity of information regarding the demographic characteristics of faculty at Accreditation Council for Graduate Medical Education (ACGME) orthopaedic surgery residency programs. The purpose of this study was to determine the demographics and education training of all current orthopaedic surgery residency program faculty members. We hypothesized that there would be a sex discrepancy among orthopaedic surgery faculty, and that there would be fewer DO (Doctor of Osteopathic Medicine) than MD (Medical Doctor) orthopaedic surgeons in academic medicine. Methods The Fellowship and Residency Electronic Interactive Database was used to identify all orthopaedic surgery residency programs in the United States. The following information was collected from each program website: faculty sex, degree, academic role, administrative title, and subspecialty. Faculty roles, titles, and subspecialties were compared across type of institution, degree earned, and sex using Chi squared and Analysis of Variance (ANOVA). Results Of the 4,325 faculty members identified, 3,893 were male (90%) and 4,033 were MDs (93%). The most common subspecialty was sports medicine (789, 18%). While traditional ACGME programs still had more MD faculty (3,728, 97.5%) (p 〈 0.001), the majority of faculty at traditional American Osteopathic Association (AOA) programs were also MDs (305, 61%). There were more male DOs than male MDs (95.6% vs. 89.3%, p 〈 0.001). More DOs practiced general orthopaedics (14.8% vs. 4.1%), whereas more MDs practiced upper extremity and orthopaedic oncology (p 〈 0.001). More male faculty practiced adult reconstruction (616, 15.8%), trauma (489, 12.6%), spine (471, 12.1%), and sports medicine (719, 18.5%), whereas more female faculty practiced pediatrics (135, 31.3%), upper extremity (100, 23.1%), and oncology (33, 7.6%). More male faculty held titles as chair of orthopaedic surgery (145, 3.7%) and fellowship director (111, 2.9%) than females (5, 1.2% and 5, 1.2%). Males were also listed as assistant professor (1057, 27.2% vs 188, 43.5%), associate professor (636, 16.3% vs 86, 19.9%), and professor (618, 15.9% vs 41, 9.5%) more commonly than females. Conclusion The current faculty of orthopaedic surgery residency programs is heavily male dominated, holding higher academic roles and administrative titles than women. There is also a high prevalence of MDs with higher academic roles and administrative titles than DOs.
    Type of Medium: Online Resource
    ISSN: 2691-6541
    Language: English
    Publisher: Charter Services New York d/b/a Journal of Orthopaedic Experience and Innovation
    Publication Date: 2023
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  • 3
    In: Science Advances, American Association for the Advancement of Science (AAAS), Vol. 9, No. 19 ( 2023-05-10)
    Abstract: Electro-physiologically active intratumoral nerves contribute to cancer progression through the release of substance P.
    Type of Medium: Online Resource
    ISSN: 2375-2548
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
    detail.hit.zdb_id: 2810933-8
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  • 4
    Online Resource
    Online Resource
    Association for Computing Machinery (ACM) ; 1970
    In:  ACM SIGOPS Operating Systems Review Vol. 4, No. 3 ( 1970-12), p. 21-23
    In: ACM SIGOPS Operating Systems Review, Association for Computing Machinery (ACM), Vol. 4, No. 3 ( 1970-12), p. 21-23
    Abstract: The routine I will describe was started as a PL/I routine written by Mr. Gib Scranton, at ISU, for a graduate course. The routine used much core (70-80k), and that is a commodity that is quite scarce in any installation. A second iteration was performed in Assembler F by Mr. Dana Zimmerli, an instructor and systems analyst.
    Type of Medium: Online Resource
    ISSN: 0163-5980
    RVK:
    Language: English
    Publisher: Association for Computing Machinery (ACM)
    Publication Date: 1970
    detail.hit.zdb_id: 2082220-0
    detail.hit.zdb_id: 243805-7
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  • 5
    In: Acta Neuropathologica, Springer Science and Business Media LLC, Vol. 134, No. 2 ( 2017-8), p. 255-269
    Type of Medium: Online Resource
    ISSN: 0001-6322 , 1432-0533
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 1458410-4
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  • 6
    Online Resource
    Online Resource
    Association for Computing Machinery (ACM) ; 1972
    In:  ACM SIGGRAPH Computer Graphics Vol. 6, No. 4 ( 1972-12-02), p. 165-168
    In: ACM SIGGRAPH Computer Graphics, Association for Computing Machinery (ACM), Vol. 6, No. 4 ( 1972-12-02), p. 165-168
    Abstract: Comments from the editors To determine the current status of some of the work being done by our readers I have put together a questionnaire. The questionnaire itself will be found following this short note. I would appreciate hearing from all persons currently doing some work in the area of computer graphics, or from anyone wishing to contribute information on a system in use. I will try to put all responses together (assuming someone out there responds) and summarize what is being done, as indicated by the returned questionnaires.
    Type of Medium: Online Resource
    ISSN: 0097-8930
    Language: English
    Publisher: Association for Computing Machinery (ACM)
    Publication Date: 1972
    detail.hit.zdb_id: 2088979-3
    detail.hit.zdb_id: 282142-4
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  Open Forum Infectious Diseases Vol. 7, No. Supplement_1 ( 2020-12-31), p. S128-S128
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 7, No. Supplement_1 ( 2020-12-31), p. S128-S128
    Abstract: Beta lactams and fluoroquinolones (FQ) have been evaluated as step-down therapy options for Gram-negative bacteremia (GNB), but the preferred oral step-down antibiotic remains unclear. Methods This retrospective, non-inferiority, cohort study included adult patients who received oral step-down therapy with cefprozil or FQ (ciprofloxacin, levofloxacin) for GNB caused by Proteus spp, Klebsiella spp, or E. coli at SSM Health St. Louis between 1/1/2016 and 2/28/2020. The primary outcome was treatment failure, defined as all-cause mortality or recurrent infection within 30 days of initial bacteremia episode. Assuming an 85% success rate, to achieve 80% power with a noninferiority margin of 15%, 71 patients were required in each arm. Multivariate logistic regression was used to evaluate factors for treatment failure. Factors evaluated for inclusion in the multivariate model were oral antibiotic, age & gt;65 years, urinary source, Pitt bacteremia score & gt;2, ICU admission, and IV antibiotics for & gt;5 days prior to step-down. Results A total of 174 patients were included— 103 received cefprozil and 71 received FQ. Most baseline characteristics were similar between groups. Patients in the cefprozil group had more ICU admissions (21.3% vs. 7%; p=0.01), had a higher mean Pitt bacteremia score (1.6 vs 0.7; p & lt; 0.001), and received a longer duration (days) of IV antibiotics prior to step-down therapy (5.2 vs 4.1; p & lt; 0.001). Mean total treatment duration (days) was similar between groups (13.1 vs 13.2; p=0.75). Cefprozil 500 mg PO BID was administered in 84.5% of cefprozil patients. Treatment failure occurred in 3.88% (4/103) of cefprozil patients compared to 1.41% (1/71) of FQ patients (mean difference -2.47%; 95% CI -7.52% to 2.58%). The rate of adverse drug reactions was significantly higher in the FQ arm (2.9% vs 12.6%; p=0.016). In the univariate model, E. coli bacteremia, Pitt bacteremia score & gt;2, and IV antibiotic duration & gt;5 days met pre-defined criteria (p & lt; 0.2) for inclusion in the multivariate model. In the multivariate analysis, these factors were not found to be significant. Conclusion Cefprozil was non-inferior to FQ in regard to treatment failure. Cefprozil is an efficacious alternative to FQ for oral step-down treatment of GNB and was associated with significantly fewer adverse effects. Disclosures All Authors: No reported disclosures
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2757767-3
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  • 8
    In: Nature, Springer Science and Business Media LLC, Vol. 611, No. 7935 ( 2022-11-10), p. 405-412
    Abstract: Solid tumours are innervated by nerve fibres that arise from the autonomic and sensory peripheral nervous systems 1–5 . Whether the neo-innervation of tumours by pain-initiating sensory neurons affects cancer immunosurveillance remains unclear. Here we show that melanoma cells interact with nociceptor neurons, leading to increases in their neurite outgrowth, responsiveness to noxious ligands and neuropeptide release. Calcitonin gene-related peptide (CGRP)—one such nociceptor-produced neuropeptide—directly increases the exhaustion of cytotoxic CD8 + T cells, which limits their capacity to eliminate melanoma. Genetic ablation of the TRPV1 lineage, local pharmacological silencing of nociceptors and antagonism of the CGRP receptor RAMP1 all reduced the exhaustion of tumour-infiltrating leukocytes and decreased the growth of tumours, nearly tripling the survival rate of mice that were inoculated with B16F10 melanoma cells. Conversely, CD8 + T cell exhaustion was rescued in sensory-neuron-depleted mice that were treated with local recombinant CGRP. As compared with wild-type CD8 + T cells, Ramp1 −/ − CD8 + T cells were protected against exhaustion when co-transplanted into tumour-bearing Rag1 -deficient mice. Single-cell RNA sequencing of biopsies from patients with melanoma revealed that intratumoral RAMP1 -expressing CD8 + T cells were more exhausted than their RAMP1 -negative counterparts, whereas overexpression of RAMP1 correlated with a poorer clinical prognosis. Overall, our results suggest that reducing the release of CGRP from tumour-innervating nociceptors could be a strategy to improve anti-tumour immunity by eliminating the immunomodulatory effects of CGRP on cytotoxic CD8 + T cells.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    RVK:
    RVK:
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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