14 results on '"Vandenbussche C"'
Search Results
2. Chapter 17: Practical experiences of IoT applications for pig, broiler and cattle beef production: IoF2020 meat trial
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Maselyne, J., Vandenbussche, C., Fernández, I., García, E., Kassahun, A., Bugueiro, A., Gómez-Maqueda, I., and Gelada, J.
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Life Science ,Toegepaste Informatiekunde ,WASS ,Information Technology - Abstract
Internet of Things (IoT) technology offers a significant potential for livestock farming, as animals and their living environments can be monitored and relevant insights can be extracted from the data gathered. As part of the IoF2020 project (Internet of Food & Farm 2020, 2017-2021, EU H2020 programme) IoT devices were tested and demonstrated in six use cases for livestock farming for meat production. The results and lessons learned give insights in how IoT devices can technically and practically be used in livestock farming and how companies can create businesses from the technologies. The use cases are part of the meat trial of the IoF2020 project and each developed IoTbased products to solve one or more specific challenges that the livestock sector faces. The products were developed in close collaboration with the end-users, who are mainly livestock farmers and meat processors, who helped to formulate requirements, provided their facilities as a testbed and gave feedback to improve the products. The use cases cover three livestock species: pigs, broilers and beef cattle. Diverse IoT solutions and products were developed, including sensors for health and welfare monitoring, environmental monitoring, location tracking and feed silo monitoring. In addition, business intelligence dashboards, transparency/traceability systems and auditing services were also developed. The use cases had installations in 64 sites (farms, slaughterhouses) in 10 different EU countries. In this chapter, we present the objectives, results, challenges and lessons learned from the use cases. We also discuss the stakeholders involved and the business models that have been developed. Feedback from end-users proved to be crucial for steering the developments in the right direction.
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- 2022
3. Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the molecule
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VandenBussche, C J, Mulrooney, T J, Frazier, W R, Dakshanamurthy, S, and Hurley, C K
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- 2009
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4. Analytical validity of a microRNA-based assay for diagnosing indeterminate thyroid FNA smears from routinely prepared cytology slides
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Benjamin, H, Schnitzer Perlman, T, Shtabsky, A, Vandenbussche, C, Ali, S, Kolar, Z, Pagni, F, Bar, D, Meiri, E, Meiri, E., Benjamin, H, Schnitzer Perlman, T, Shtabsky, A, Vandenbussche, C, Ali, S, Kolar, Z, Pagni, F, Bar, D, Meiri, E, and Meiri, E.
- Abstract
BACKGROUND: The majority of thyroid nodules are diagnosed using fine-needle aspiration (FNA) biopsies. The authors recently described the clinical validation of a molecular microRNA-based assay, RosettaGX Reveal, which can diagnose thyroid nodules as benign or suspicious using a single stained FNA smear. This paper describes the analytical validation of the assay. METHODS: More than 800 FNA slides were tested, including slides stained with Romanowsky-type and Papanicolaou stains. The assay was examined for the following features: intranodule concordance, effect of stain type, minimal acceptable RNA amounts, performance on low numbers of thyroid cells, effect of time since sampling, and analytical sensitivity, specificity, and reproducibility. RESULTS: The assay can be run on FNA slides for which as little as 1% of the cells are thyroid epithelial cells or from which only 5 ng of RNA have been extracted. Samples composed entirely of blood failed quality control and were not classified. Stain type did not affect performance. All slides were stored at room temperature. However, the length of time between FNA sampling and processing did not affect assay performance. There was a high level of concordance between laboratories (96%), and the concordance for slides created from the same FNA pass was 93%. CONCLUSIONS: The microRNA-based assay was robust to various physical processing conditions and to differing sample characteristics. Given the assay's performance, robustness, and use of routinely prepared FNA slides, it has the potential to provide valuable aid for physicians in the diagnosis of thyroid nodules. Cancer Cytopathol 2016;124:711–21.
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- 2016
5. Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the molecule
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VandenBussche, C J, primary, Mulrooney, T J, additional, Frazier, W R, additional, Dakshanamurthy, S, additional, and Hurley, C K, additional
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- 2008
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6. Analytical validity of a microRNA-based assay for diagnosing indeterminate thyroid FNA smears from routinely prepared cytology slides
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Zdenek Kolar, Hila Benjamin, Eti Meiri, Fabio Pagni, Alexander Shtabsky, Syed Z. Ali, Temima Schnitzer-Perlman, Dganit Bar, Christopher J. VandenBussche, Benjamin, H, Schnitzer Perlman, T, Shtabsky, A, Vandenbussche, C, Ali, S, Kolar, Z, Pagni, F, Bar, D, and Meiri, E
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0301 basic medicine ,Thyroid nodules ,Cancer Research ,medicine.medical_specialty ,Pathology ,nodule ,smears ,Cytodiagnosis ,Concordance ,Biopsy, Fine-Needle ,fine‐needle aspiration (FNA) ,Papanicolaou stain ,Carcinoma, Papillary, Follicular ,Validation Studies as Topic ,Stain ,Specimen Handling ,thyroid ,03 medical and health sciences ,0302 clinical medicine ,Biomarkers, Tumor ,Humans ,Medicine ,Sampling (medicine) ,Thyroid Neoplasms ,Thyroid Nodule ,fine-needle aspiration (FNA) ,Thyroid Epithelial Cells ,microRNA ,business.industry ,Thyroid ,smear ,Reproducibility of Results ,indeterminate ,Original Articles ,Prognosis ,medicine.disease ,molecular test ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Molecular Diagnostic Techniques ,Oncology ,Cytopathology ,030220 oncology & carcinogenesis ,Original Article ,Radiology ,business ,nodules - Abstract
BACKGROUND The majority of thyroid nodules are diagnosed using fine‐needle aspiration (FNA) biopsies. The authors recently described the clinical validation of a molecular microRNA‐based assay, RosettaGX Reveal, which can diagnose thyroid nodules as benign or suspicious using a single stained FNA smear. This paper describes the analytical validation of the assay. METHODS More than 800 FNA slides were tested, including slides stained with Romanowsky‐type and Papanicolaou stains. The assay was examined for the following features: intranodule concordance, effect of stain type, minimal acceptable RNA amounts, performance on low numbers of thyroid cells, effect of time since sampling, and analytical sensitivity, specificity, and reproducibility. RESULTS The assay can be run on FNA slides for which as little as 1% of the cells are thyroid epithelial cells or from which only 5 ng of RNA have been extracted. Samples composed entirely of blood failed quality control and were not classified. Stain type did not affect performance. All slides were stored at room temperature. However, the length of time between FNA sampling and processing did not affect assay performance. There was a high level of concordance between laboratories (96%), and the concordance for slides created from the same FNA pass was 93%. CONCLUSIONS The microRNA‐based assay was robust to various physical processing conditions and to differing sample characteristics. Given the assay's performance, robustness, and use of routinely prepared FNA slides, it has the potential to provide valuable aid for physicians in the diagnosis of thyroid nodules. Cancer Cytopathol 2016;124:711–21. © 2016 Rosetta Genomics. Cancer Cytopathology published by Wiley Periodicals, Inc. on behalf of American Cancer Society., Analytical validation of a novel molecular assay for the diagnosis of thyroid nodules with indeterminate cytology using stained fine‐needle aspiration smears is described. The results demonstrate the assay's robustness to various physical processing conditions.
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- 2016
7. Pancreaticobiliary Cytology Practice in 2021: Results of a College of American Pathologists Survey.
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Li Z, Tabbara SO, Nwosu A, Souers RJ, Goyal A, Kurian EM, Lin X, VandenBussche C, and Nguyen LN
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- Humans, Biliary Tract pathology, Biliary Tract cytology, Biopsy, Fine-Needle methods, Pancreas pathology, Pancreatic Neoplasms pathology, Pancreatic Neoplasms diagnosis, Pathology, Clinical methods, Practice Patterns, Physicians' statistics & numerical data, Societies, Medical, Surveys and Questionnaires, United States, Cytodiagnosis methods, Pathologists
- Abstract
Context.—: The College of American Pathologists (CAP) surveys provide national benchmarks of pathology practice., Objective.—: To investigate pancreaticobiliary cytology practice in domestic and international laboratories in 2021., Design.—: We analyzed data from the CAP Pancreaticobiliary Cytology Practice Supplemental Questionnaire that was distributed to laboratories participating in the 2021 CAP Nongynecologic Cytopathology Education Program., Results.—: Ninety-three percent (567 of 612) of respondent laboratories routinely evaluated pancreaticobiliary cytology specimens. Biliary brushing (85%) was the most common pancreaticobiliary cytology specimen evaluated, followed by pancreatic fine-needle aspiration (79%). The most used sampling methods reported by 235 laboratories were 22-gauge needle for fine-needle aspiration (62%) and SharkCore needle for fine-needle biopsy (27%). Cell block was the most used slide preparation method (76%), followed by liquid-based cytology (59%) for pancreatic cystic lesions. Up to 95% (303 of 320) of laboratories performed rapid on-site evaluation (ROSE) on pancreatic solid lesions, while 56% (180 of 320) performed ROSE for cystic lesions. Thirty-six percent (193 of 530) of laboratories used the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology in 2021. Among all institution types, significant differences in specimen volume, specimen type, ROSE practice, and case sign-out were identified. Additionally, significant differences in specimen type, slide preparation, and ROSE practice were found., Conclusions.—: This is the first survey from the CAP to investigate pancreaticobiliary cytology practice. The findings reveal significant differences among institution types and between domestic and international laboratories. These data provide a baseline for future studies in a variety of practice settings., Competing Interests: The authors are or were members of the College of American Pathologists Cytopathology Committee. Nwosu and Souers are employees of the College of American Pathologists., (© 2024 College of American Pathologists.)
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- 2024
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8. Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.
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Paniccia A, Polanco PM, Boone BA, Wald AI, McGrath K, Brand RE, Khalid A, Kubiliun N, O'Broin-Lennon AM, Park WG, Klapman J, Tharian B, Inamdar S, Fasanella K, Nasr J, Chennat J, Das R, DeWitt J, Easler JJ, Bick B, Singh H, Fairley KJ, Sarkaria S, Sawas T, Skef W, Slivka A, Tavakkoli A, Thakkar S, Kim V, Vanderveldt HD, Richardson A, Wallace MB, Brahmbhatt B, Engels M, Gabbert C, Dugum M, El-Dika S, Bhat Y, Ramrakhiani S, Bakis G, Rolshud D, Millspaugh G, Tielleman T, Schmidt C, Mansour J, Marsh W, Ongchin M, Centeno B, Monaco SE, Ohori NP, Lajara S, Thompson ED, Hruban RH, Bell PD, Smith K, Permuth JB, Vandenbussche C, Ernst W, Grupillo M, Kaya C, Hogg M, He J, Wolfgang CL, Lee KK, Zeh H, Zureikat A, Nikiforova MN, and Singhi AD
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- Humans, Retrospective Studies, Prospective Studies, High-Throughput Nucleotide Sequencing, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Genomics, Mitogen-Activated Protein Kinases genetics, Cystadenoma, Serous diagnosis, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms genetics, Pancreatic Neoplasms surgery, Pancreatic Cyst diagnosis, Pancreatic Cyst genetics, Pancreatic Cyst therapy
- Abstract
Background & Aims: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time., Methods: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens., Results: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations., Conclusions: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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9. Reappraisal of Renal Arteritis in ANCA-associated Vasculitis: Clinical Characteristics, Pathology, and Outcome.
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Boudhabhay I, Delestre F, Coutance G, Gnemmi V, Quemeneur T, Vandenbussche C, Lazareth H, Canaud G, Tricot L, Gosset C, Hummel A, Terrier B, Rabant M, van Daalen EE, Wester Trejo MAC, Bajema IM, Karras A, and Duong Van Huyen JP
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- Aged, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis mortality, Arteritis mortality, Disease-Free Survival, Female, France, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis complications, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis diagnosis, Arteritis complications, Arteritis diagnosis, Kidney Failure, Chronic epidemiology, Renal Artery
- Abstract
Background: Renal involvement in ANCA-associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail., Methods: In a multicenter cohort of patients with AAV and renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis, and to retrospectively analyze their prognostic value., Results: We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older, and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival ( P =0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with ESKD. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone, versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status ( P =0.008); ESKD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk, according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype., Conclusions: Our findings suggest AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed., (Copyright © 2021 by the American Society of Nephrology.)
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- 2021
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10. Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer.
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Li J, Downs BM, Cope LM, Fackler MJ, Zhang X, Song CG, VandenBussche C, Zhang K, Han Y, Liu Y, Tulac S, Venkatesan N, de Guzman T, Chen C, Lai EW, Yuan J, and Sukumar S
- Abstract
Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the cytologist's experience. We proposed that the 5-h automated GeneXpert system-based prototype breast cancer detection assay (BCDA) that quantitatively measures DNA methylation in ten tumor-specific gene markers could provide a facile, accurate test for detecting cancer in FNA of enlarged lymph nodes. We validated the assay in ALN-FNA samples from a prospective study of patients (N = 230) undergoing SLNB. In a blinded analysis of 218 evaluable LN-FNAs from 108 malignant and 110 benign LNs by histology, BCDA displayed a sensitivity of 90.7% and specificity of 99.1%, achieving an area under the ROC curve, AUC of 0.958 (95% CI: 0.928-0.989; P < 0.0001). Next, we conducted a study of archival FNAs of ipsilateral palpable LNs (malignant, N = 72, benign, N = 53 by cytology) collected in the outpatient setting prior to neoadjuvant chemotherapy (NAC). Using the ROC-threshold determined in the prospective study, compared to cytology, BCDA achieved a sensitivity of 94.4% and a specificity of 92.5% with a ROC-AUC = 0.977 (95% CI: 0.953-1.000; P < 0.0001). Our study shows that the automated assay detects cancer in suspicious lymph nodes with a high level of accuracy within 5 h. This cancer detection assay, scalable for analysis to scores of LN FNAs, could assist in determining eligibility of patients to different treatment regimens.
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- 2021
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11. Correction: Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy.
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Springer SU, Chen CH, Rodriguez Pena MDC, Li L, Douville C, Wang Y, Cohen JD, Taheri D, Silliman N, Schaefer J, Ptak J, Dobbyn L, Papoli M, Kinde I, Afsari B, Tregnago AC, Bezerra SM, VandenBussche C, Fujita K, Ertoy D, Cunha IW, Yu L, Bivalacqua TJ, Grollman AP, Diaz LA, Karchin R, Danilova L, Huang CY, Shun CT, Turesky RJ, Yun BH, Rosenquist TA, Pu YS, Hruban RH, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Dickman KG, and Netto GJ
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- 2018
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12. Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy.
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Springer SU, Chen CH, Rodriguez Pena MDC, Li L, Douville C, Wang Y, Cohen JD, Taheri D, Silliman N, Schaefer J, Ptak J, Dobbyn L, Papoli M, Kinde I, Afsari B, Tregnago AC, Bezerra SM, VandenBussche C, Fujita K, Ertoy D, Cunha IW, Yu L, Bivalacqua TJ, Grollman AP, Diaz LA, Karchin R, Danilova L, Huang CY, Shun CT, Turesky RJ, Yun BH, Rosenquist TA, Pu YS, Hruban RH, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Dickman KG, and Netto GJ
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- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Transitional Cell genetics, Carcinoma, Transitional Cell urine, Child, Child, Preschool, Female, Genetic Testing methods, Humans, Male, Middle Aged, Sensitivity and Specificity, Telomerase genetics, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms urine, Young Adult, Aneuploidy, Carcinoma, Transitional Cell diagnosis, Early Detection of Cancer methods, Mutation, Urinary Bladder Neoplasms diagnosis
- Abstract
Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer., Competing Interests: SS, CC, MR, LL, CD, YW, JC, DT, NS, JS, JP, LD, MP, IK, BA, AT, SB, CV, KF, DE, IC, LY, TB, AG, LD, RK, LD, CH, CS, RT, BY, TR, YP, RH, CT, KD, GN No competing interests declared, NP Founder of Personal Genome Diagnostics and PapGene and advises Sysmex-Inostics. These companies and others have licensed technologies from Johns Hopkins, of which BV, KK, and NP are inventors on a patent (U.S. 20140227705 A1) and receive royalties. The terms of these arrangements are managed by the university in accordance with its conflict of interest policies. Luis A Diaz: Member of the board of directors of Personal Genome Diagnostics (PGDx) and Jounce Therapeutics. LAD holds equity in PapGene, Personal Genome Diagnostics (PGDx) and Phoremost. He is a paid consultant for Merck, PGDx and Phoremost. LAD is an inventor of licensed intellectual property related to technology for ctDNA analyses and mismatch repair deficiency for diagnosis and therapy from Johns Hopkins University. These licenses and relationships are associated with equity or royalty payments to LAD. The terms of all these arrangements are being managed by Johns Hopkins and Memorial Sloan Kettering in accordance with their conflict of interest policies. In addition, in the past 5 years, LAD has participated as a paid consultant for one-time engagements with Caris, Lyndra, Genocea Biosciences, Illumina and Cell Design Labs. KK Ken W Kinzler: Founder of Personal Genome Diagnostics and PapGene and advises Sysmex-Inostics. These companies and others have licensed technologies from Johns Hopkins, of which BV, KK, and NP are inventors on a patent (U.S. 20140227705 A1) and receive royalties. The terms of these arrangements are managed by the university in accordance with its conflict of interest policies. BV Bert Vogelstein: Founder of Personal Genome Diagnostics and PapGene and advises Sysmex-Inostics. These companies and others have licensed technologies from Johns Hopkins, of which BV, KK, and NP are inventors on a patent (U.S. 20140227705 A1) and receive royalties. The terms of these arrangements are managed by the university in accordance with its conflict of interest policies., (© 2018, Springer et al.)
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- 2018
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13. Involvement of epigenetics and EMT-related miRNA in arsenic-induced neoplastic transformation and their potential clinical use.
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Michailidi C, Hayashi M, Datta S, Sen T, Zenner K, Oladeru O, Brait M, Izumchenko E, Baras A, VandenBussche C, Argos M, Bivalacqua TJ, Ahsan H, Hahn NM, Netto GJ, Sidransky D, and Hoque MO
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- Adult, Aged, Aged, 80 and over, Apoptosis, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Blotting, Western, Case-Control Studies, Cell Movement, Cell Proliferation, Cell Transformation, Neoplastic chemically induced, Cell Transformation, Neoplastic genetics, Cells, Cultured, Cohort Studies, DNA Methylation, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Immunoenzyme Techniques, Male, MicroRNAs genetics, Middle Aged, Neoplasm Invasiveness, PTEN Phosphohydrolase genetics, PTEN Phosphohydrolase metabolism, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, TOR Serine-Threonine Kinases genetics, TOR Serine-Threonine Kinases metabolism, Urinary Bladder drug effects, Urinary Bladder metabolism, Urinary Bladder Neoplasms drug therapy, Urinary Bladder Neoplasms genetics, Young Adult, Arsenic adverse effects, Cell Transformation, Neoplastic pathology, Epigenesis, Genetic genetics, Epithelial-Mesenchymal Transition, MicroRNAs analysis, Urinary Bladder pathology, Urinary Bladder Neoplasms pathology
- Abstract
Exposure to toxicants leads to cumulative molecular changes that overtime increase a subject's risk of developing urothelial carcinoma. To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic-exposed subjects, urothelial carcinoma patients, and controls. To prepare an in vitro model, we chronically exposed an immortalized normal human bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a time-dependent manner after arsenic treatment and cellular morphology was changed. In a soft agar assay, colonies were observed only in arsenic-treated cells, and the number of colonies gradually increased with longer periods of treatment. Similarly, invaded cells in an invasion assay were observed only in arsenic-treated cells. Withdrawal of arsenic treatment for 2.5 months did not reverse the tumorigenic properties of arsenic-treated cells. Western blot analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic-treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were downregulated in arsenic-exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P = 0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases from controls with high sensitivity and specificity (AUC = 0.845). Our study suggests that exposure to arsenic rapidly induces a multifaceted dedifferentiation program and miR-205 has potential to be used as a marker of arsenic exposure as well as a maker of early urothelial carcinoma detection., (©2015 American Association for Cancer Research.)
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- 2015
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14. Community-acquired aspiration pneumonia in intensive care units. Epidemiological and prognosis data.
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Leroy O, Vandenbussche C, Coffinier C, Bosquet C, Georges H, Guery B, Thevenin D, and Beaucaire G
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- Adult, Aged, Cross Infection complications, Female, France epidemiology, Humans, Intensive Care Units, Male, Middle Aged, Multivariate Analysis, Prognosis, Prospective Studies, Respiration, Artificial, Retrospective Studies, Risk Factors, Superinfection complications, Survival Rate, Treatment Outcome, Hospitalization, Pneumonia, Aspiration epidemiology, Pneumonia, Aspiration etiology, Pneumonia, Aspiration mortality, Pneumonia, Aspiration therapy
- Abstract
Over a 9-yr period, among 505 patients exhibiting severe community-acquired pneumonia and admitted into a total of six medical ICUs in the north of France, we collected 116 patients (23%) meeting the usual criteria for aspiration pneumonia. Main medical grounds of ICU admission were respiratory distress in 54 patients and neurological disturbances in 62 patients. The main underlying risk factor for aspiration pneumonia was drug overdose (39%). Mechanical ventilation was required for 73 patients. Initial shock was present in 15 patients. Pulmonary involvement was bilateral in 27 patients. There were 94 aerobic organisms isolated from 70 patients (60%), the most frequent being gram-negative bacilli (n = 38), Staphyloccus spp. (n = 27) and Streptococcus pneumoniae (n = 22). Overall mortality was 22%, but only 11 (11%) deaths were directly or indirectly related to aspiration pneumonia. Stepwise multivariate analysis identified four independent predictors of mortality: ineffective initial antimicrobial therapy (p = 0.0001), positive initial blood culture (p = 0.0001), hospital-acquired lower respiratory tract superinfections (p = 0.0054), and use of inotropic support (p = 0.0078). The importance of prevention of hospital-acquired superinfections and permanent optimization of our antimicrobial strategies warranting efficacy of the initial antimicrobial therapy is underlined.
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- 1997
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