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The number of clinical trials is rapidly growing, and automation of literature processing is becoming desirable but unresolved. Our purpose was to assess and increase the readiness of clinical trial reports for supporting automated retrieval and implementation in public health practice. We searched the Medline database for a random sample of clinical trials of HIV/AIDS management with likely relevance to public health in Africa. Five authors assessed trial reports for inclusion, extracted data, and assessed quality based on the FAIR principles of scientific data management (findable, accessible, interoperable, and reusable). Subsequently, we categorized reported results in terms of outcomes and essentials of implementation. A sample of 96 trial reports was selected. Information about the tested intervention that is essential for practical implementation was largely missing, including personnel resources needed 32·3% (.95 CI: 22·9-41·6); material/supplies needed 33·3% (.95 CI: 23·9-42·8); major equipment/building investment 42·8% (CI: 33·8-53·7); methods of educating providers 53·1% (CI: 43·1-63·4); and methods of educating the community 27·1% (CI: 18·2-36·0). Overall, 65% of studies measured health/biologic outcomes, among them, only a fraction showed any positive effects. Several specific design elements were identified that frequently make clinical trials unreal and their results unusable. To sort and interpret clinical trial results easier and faster, a new reporting structure, a practice- and retrieval-oriented trial outline with numeric outcomes (PROTON) table was developed and illustrated. Many clinical trials are either inconsequential by design or report incomprehensible results. According to the latest expectations of FAIR scientific data management, all clinical trial reports should include a consistent and practical impact-oriented table of clinical trial results.
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The Medical College of Georgia (MCG) responded to the COVID-19 pandemic's challenges to medical education with a novel, comprehensive curriculum. The Pandemic Medicine Elective was an effective solution with a safe, virtual alternative to traditional clinical experiences. As the elective evolved to include pre-clinical students and service initiatives across Georgia, students and faculty navigated online platforms to execute critical community-based projects. This curricular development utilized an interdisciplinary approach by faculty across each of MCG's regional campuses. We describe the curriculum of the electives, the student initiatives, and lessons learned while quickly adapting curriculum during the COVID-19 pandemic.
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PURPOSE: Poor prognosis of patients with muscle-invasive bladder cancer that often metastasizes drives the need for discovery of molecular determinants of bladder cancer progression. Chondroitin sulfate proteoglycans, including CD44, regulate cancer progression; however, the identity of a chondroitinase (Chase) that cleaves chondroitin sulfate from proteoglycans is unknown. HYAL-4 is an understudied gene suspected to encode a Chase, with no known biological function. We evaluated HYAL-4 expression and its role in bladder cancer. EXPERIMENTAL DESIGN: In clinical specimens, HYAL-4 wild-type (Wt) and V1 expression was evaluated by RT-qPCR, IHC, and/or immunoblotting; a novel assay measured Chase activity. Wt and V1 were stably expressed or silenced in normal urothelial and three bladder cancer cell lines. Transfectants were analyzed for stem cell phenotype, invasive signature and tumorigenesis, and metastasis in four xenograft models, including orthotopic bladder. RESULTS: HYAL-4 expression, specifically a novel splice variant (V1), was elevated in bladder tumors; Wt expression was barely detectable. V1 encoded a truncated 349 amino acid protein that was secreted. In bladder cancer tissues, V1 levels associated with metastasis and cancer-specific survival with high efficacy and encoded Chase activity. V1 cleaved chondroitin-6-sulfate from CD44, increasing CD44 secretion. V1 induced stem cell phenotype, motility/invasion, and an invasive signature. CD44 knockdown abrogated these phenotypes. V1-expressing urothelial cells developed angiogenic, muscle-invasive tumors. V1-expressing bladder cancer cells formed tumors at low density and formed metastatic bladder tumors when implanted orthotopically. CONCLUSIONS: Our study discovered the first naturally-occurring eukaryotic/human Chase and connected it to disease pathology, specifically cancer. V1-Chase is a driver of malignant bladder cancer and potential predictor of outcome in patients with bladder cancer.
Assuntos
Processamento Alternativo , Biomarcadores Tumorais , Transformação Celular Neoplásica/genética , Hialuronoglucosaminidase/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Animais , Apoptose/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Hialuronoglucosaminidase/química , Hialuronoglucosaminidase/metabolismo , Imuno-Histoquímica , Camundongos , Invasividade Neoplásica , Prognóstico , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Differential expression of chemokines/chemokine receptors in colorectal cancer (CRC) may enable molecular characterization of patients' tumors for predicting clinical outcome. OBJECTIVE: To evaluate the prognostic ability of these molecules in a CRC cohort and the CRC TCGA-dataset. METHODS: Chemokine (CXCL-12α, CXCL-12ß, IL-17A, CXCL-8, GM-CSF) and chemokine receptor (CXCR-4, CXCR-7) transcripts were analyzed by RT-qPCR in 76 CRC specimens (normal: 27, tumor: 49; clinical cohort). RNA-Seq data was analyzed from the TCGA-dataset (n= 375). Transcript levels were correlated with outcome; analyses: univariate, multivariable, Kaplan-Meier. RESULTS: In the clinical cohort, chemokine/chemokine receptor levels were elevated 3-10-fold in CRC specimens (P⩽ 0.004) and were higher in patients who developed metastasis (P= 0.03 - < 0.0001). CXCR-4, CXCR-7, CXCL-12α, CXCL-8, IL-17 and GM-CSF levels predicted metastasis (P⩽ 0.0421) and/or overall survival (OS; P⩽ 0.0373). The CXCR-4+CXCR-7+CXCL-12 marker (CXCR-4/7+CXCL-12 (α/b) signature) stratified patients into risk for metastasis (P= 0.0014; OR, 2.72) and OS (P= 0.0442; OR, 2.7); sensitivity: 86.67%, specificity: 97.06%. In the TCGA-dataset, the CXCR-4/7+CXCL-12 signature predicted metastasis (P= 0.011; OR, 2.72) and OS (P= 0.0006; OR: 4.04). In both datasets, the signature was an independent predictor of clinical outcome. CONCLUSIONS: Results of 451 specimens from both cohorts reveal that the CXCR-4/7+CXCL-12 signature potentially predicts outcome in CRC patients and may allow earlier intervention.