tbuckley/cabot-search huggingface dataset:
Multiparametric magnetic resonance imaging of multifocal prostate cancer to reveal intra-prostatic genomic heterogeneity and novel radio-genomic correlates: Results of the Smarter Prostate Interventions and Therapeutics (SPIRIT) study.
Authors: Glenn Bauman, Rohann Correa, Erfan Aref-Eshghi, Ryan Alfano, Bekim Sadikovic, John Bartlett, Paul Christopher Boutros, Stephen E. Pautler, Joseph Chin, Mena Gaed, Zahra Kassam, Jose Gomez Lemus, Madeleine Moussa, Aaron Ward
Journal: Journal of Clinical Oncology (2020)

20 Background: Multi-focality and heterogeneity in prostate cancer can confound the selection of appropriate clinical management. Our study aimed to explore radio-genomic correlations using multiparametric magnetic resonance imaging (mpMRI) against a histopathologic reference standard. Methods: Eight men with prostate cancer who underwent mpMRI followed by prostatectomy were selected for this pilot. Whole-mount histopathology was digitized and co-registered to corresponding MRI slices using a validated high-fidelity methodology.(1) Foci, including central/transitional and peripheral zone lesions were identified by a pathologist, and contoured on digitized histopathology specimens and these digitized maps were used to guide macrodissection of the individual foci for genomic copy-number aberration (CNA) analysis. Correlation of radiomics signatures with the histologic findings and genomic analysis was performed. Results: We found a broad range of CNAs revealing inter-patient and intra-prostatic heterogeneity. Recurrently-altered loci ( e.g., 8p21) containing genes of known significance ( e.g., NKX3-1) were observed. Only radiomic features derived from apparent diffusion coefficient (ADC) independently correlated with both Gleason grade (Rho=-0.62, p=0.003) and median CNA burden (Rho=-0.68, p&lt;0.001). While greater CNA burden expectedly correlated with higher grade, intermediate-grade (Gleason score 3+4 or 4+3) lesions appeared more like either high-grade (Gleason scores ≥4+4) or low-grade (Gleason score 3+3) disease when clustered based on CNA and ADC metrics. Conclusions: These findings suggest ADC derived radiomic metrics may be a useful imaging biomarker across both central and peripheral zone lesion and could aid in further characterization of intra-prostatic biologic heterogeneity. These proof-of-principle data reveal novel radio-genomic correlations that could supplement histologic grading and conventional imaging, thus warranting expanded study and validation. 1) Int J Rad Oncol Biol Phys. 2016; 96(1):188-96.
Tumor cell intrinsic androgen biosynthesis by 3β-hydroxy steroid dehydrogenase (HSD3B1) to modulate radiosensitivity in prostate cancer cells.
Authors: Shinjini Ganguly, Aysegul Balyimez, Zaeem Lone, Aimalie Hardaway, Mona Patel, Elai Davicioni, Moshe Chaim Ornstein, Jorge A. Garcia, Kevin L. Stephans, Jay P. Ciezki, Rahul D. Tendulkar, Eric A. Klein, Nima Sharifi, Omar Y. Mian
Journal: Journal of Clinical Oncology (2020)

349 Background: Resistance to ADT is associated with a gain of function mutation in the 3β-HSD enzyme, which catalyzes extragonadal/intratumoral DHT synthesis. As androgen signaling is known to upregulate the DNA damage response (DDR), we investigated whether HSD3B1 genotype modulates DDR and radiosensitivity in PCa. Methods: We stably knocked down HSD3B1 in LNCaP, C42 and VCaP cell lines (which carry the protein stabilizing variant allele) and overexpressed the variant HSD3B1 allele in LAPC4 (harbors a WT allele which readily undergoes degradation). We examined the proliferative and clonogenic capacity of these cells in presence and absence of substrate, DHEA, followed by treatment with IR (400-800 cGy, single fraction). We studied DNA DSB formation and resolution kinetics using γH2AX foci formation in response to radiation. We also measured changes in mRNA expression of DDR response genes pre- and post-radiation. Results: Control shRNA transduced cell lines had increased cell proliferation (p&lt;0.001) and clonogenic survival (2 logs at 800cGy single fraction radiation, p&lt;0.001) in the presence of DHEA compared to HSD3B1 knockdown cells. Variant HSD3B1 cell lines were more radioresistant and exhibited more efficient γH2AX foci resolution at 24 hrs (p &lt;0.05) in a DHEA dependent manner. We observe increased mRNA expression of DDR genes from specific repair networks including non-homologous end joining (PRKDC, XRCC4, XRCC5) and homologous recombination (RAD51, RAD54) in variant HSD3B1 cells. Transcriptional induction of DDR genes following radiation in presence of DHEA was significantly more pronounced in HSD3B1 variant cells, suggesting a more permissive chromatin context. Conclusions: Increased intracellular 3β-HSD drives transcription of NHEJ and HR genes, more rapid resolution of γH2AX foci, and radioresistance in prostate cancer. This work has therapeutic implications related to strategies for combined radiation and androgen directed therapy in localized and metastatic prostate cancer. Prospective validation of treatment strategies combining blockade of adrenal steroid precursor synthesis, ADT, and XRT in high risk disease is warranted.
Characterization of PSMA and 18F-fluciclovine transporter gene expression in localized prostate cancer.
Authors: Carissa Chu, Mohammed Alshalalfa, Martin Sjöström, Shuang Zhao, Annika Herlemann, Jonathan Chou, Brandon Arvin Virgil Mahal, Amar Upadhyaya Kishan, Daniel Eidelberg Spratt, Jeffrey Karnes, Eric Jay Small, Anthony C. Wong, Sima P. Porten, Thomas Hope, Elai Davicioni, Paul L. Nguyen, Peter Carroll, Edward M. Schaeffer, Felix Y Feng, Matthew R. Cooperberg
Journal: Journal of Clinical Oncology (2020)

295 Background: While 18 F-fluciclovine PET/CT is approved in the US and recommended by the NCCN, prostate-specific membrane antigen (PSMA) PET/CT is more common in Europe/Australia and recommended by the EAU. Less is known about the biology of lesions detected by either modality. 18 F-fluciclovine PET relies on radiotracer uptake by amino acid transporters LAT1-4 and ASCT1-2. PSMA PET is dependent on surface expression of PSMA. We compared relative expression of PSMA and fluciclovine transporter genes in radical prostatectomy (RP) samples to determine their distribution across subtypes and correlation with outcomes. Methods: Gene expression data of 19,102 RP samples were analyzed using the Affymetrix Human Exon 1.0 ST microarray. 1,135 patients had long term follow up. Associations between expression of PSMA and fluciclovine transporter genes (LAT1-4 and ASCT1-2) and pathologic variables, molecular subtypes, and clinical outcomes were conducted. Results: All fluciclovine transporter genes (LAT 1-4, ASCT1-2) were expressed at lower levels than PSMA (p &lt;0.0001). PSMA expression was positively correlated with genomic risk score and pathologic Gleason score (p&lt;0.0001), but LAT2-3 and ASCT2 were inversely correlated with genomic risk in primary tumors (p&lt;0.0001) and less expressed in GS 9-10 tumors (p&lt;0.0001). PSMA expression was associated with worse metastasis-free survival (MFS) (HR 1.45, p=0.001) and lymph node involvement (HR 2.14, p&lt;0.0001). Expression of LAT2, LAT3, ASCT2 expression was associated with better MFS (HR 0.85, 0.63, 0.74, p&lt;0.0001-0.04). After multivariable adjustment, PSMA expression remained independently prognostic of poorer MFS (HR 1.3, p=0.028). Luminal B subtype was notable for PSMA overexpression; Luminal A was enriched in ASCT2 and LAT2 (p&lt;0.0001). PSMA expression did not correlate with ERG fusion prostate cancers, but LAT2, ASCT1, and ASCT2 were overexpressed in ERG fusion negative tumors (p&lt;0.0001). Conclusions: PSMA expression is associated with more aggressive disease and poorer clinical outcomes than fluciclovine transporter genes in localized prostate cancer. Molecular subtypes of prostate cancer vary in PSMA and fluciclovine transporter gene expression.
Erythematous Patch With Central Papules on the Forehead of a Middle-aged Woman
Authors: Danielle L. Perna, Robert T. Spaulding, Janine C. Malone
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
The Association Between Patient-Reported Asthma Morbidity and Electronic Health Record (EHR)-Identified Data Among Pediatric Asthma Patients Njeze O, Lee A, Singh A, Cosar E, Hsia B, Lin I, Jariwala SP. Division of Allergy/Immunology, Albert Einstein College of Medicine, Bronx, NY.
Authors: Obumneme Njeze, Audrey Lee, Anjani Singh, Emine Cosar, Brian Hsia, Iris Lin, Sunit Jariwala
Journal: Journal of Allergy and Clinical Immunology (2020)
Using natural language processing (NLP) tools to identify veterans with metastatic prostate cancer (mPCa).
Authors: Patrick R. Alba, Julie Ann Lynch, Anthony Gao, Kyung Min Lee, Tori Anglin-Foote, Brian Robison, Jeremy B. Shelton, Olga Efimova, Olga V Patterson, Scott L. DuVall
Journal: Journal of Clinical Oncology (2020)

60 Background: Veterans may benefit from promising innovations in treatments for mPCa. The Veterans Affairs (VA) and Prostate Cancer Foundation (PCF) leadership issued a challenge to identify, in real time, the national census of Veterans receiving care for mPCa. Administrative diagnostic and procedural coding do not accurately identify the risk status or disease state of prostate cancer (PCa). This study reports the development and validation of NLP tools deployed on clinical notes to identify risk status or disease state. Methods: Using diagnosis and histology codes, we queried the VA Corporate Data Warehouse to identify Veterans with prostate cancer. We included structured laboratory tests, medications, procedures, and surgeries related to prostate cancer diagnosis or treatment in the analysis. Using structured data, we identified 1000 likely mPCa cases and controls. Medical records were reviewed to confirm status and to extract term dictionaries related to cancer, anatomy, metastasis, and other diagnostic concepts. We went through several iterations of testing to refine and validate the NLP tool on a limited set of known cases and controls. We deployed the tool on all cancer, urology, pathology, and radiation oncology notes. Results: The NLP system was able to identify the patients' history of metastatic disease with 0.975 precision and 0.828 recall. Among the 1,081,137 Veterans with prostate cancer, NLP identified 63,222 (5.8%) with mPCa. There are 16,282 Veterans alive with mPCa. Mean age of diagnosis was 67 and 8,847 (54.3%) were diagnosed in the VA. Demographics were: White 9,756 (60%), Black 4,466 (27%), and other 2,060 (13%). Conclusions: NLP is a reliable tool for identifying Veterans who may benefit from novel innovations in mPCa diagnosis and treatment.[Table: see text]
Do nursing interventions targeting concurrent symptoms hold promise for managing fatigue in patients with advanced cancer? [Letter to the Editor]
Authors: Ray Chan
Journal: Journal of Clinical Oncology (2014)

TO THE EDITOR: It was with great interest that I read two recent articles by de Raaf et al1, and Bruera et al2. These authors are to be congratulated for completing two of the very few high quality randomized trials that evaluate complex interventions for managing fatigue in patients with advanced cancer. de Raaf et al conducted a non-blinded RCT with 152 patients with advanced cancer and reported significant reduction of fatigue in patients who received a nurse-led monitoring and protocol-guided treatment of physical symptoms compared with those who received usual care1. Patients who received this intervention experienced a significant improvement over time in general fatigue, at one-month follow-up and two-month follow-up. Another recent RCT conducted with 141 patients with advanced cancer by Bruera et al2 did not find any benefits of a nursing telephone intervention that involved systematic symptom assessment/management, medication review, psychosocial support and patient education in fatigue reduction, compared to those who received a control telephone intervention conducted by a non-professional...
A phase 1/2 study of ruxolitinib and decitabine in patients with post-myeloproliferative neoplasm acute myeloid leukemia
Authors: Prithviraj Bose, Srdan Verstovsek, Jorge E. Cortes, Susan Tse, Yvonne Gasior, Nitin Jain, Elias J. Jabbour, Zeev Estrov, Yesid Alvarado, Courtney D. DiNardo, Naveen Pemmaraju, Steven M. Kornblau, Tapan M. Kadia, Naval G. Daver, Kiran Naqvi, Nicholas J. Short, Lucia Masarova, John Villareal, Sherry A. Pierce, Graciela Nogueras-Gonzalez, Xuelin Huang, Guillermo Garcia-Manero, Hagop M. Kantarjian, Farhad Ravandi
Journal: Leukemia (2020)
Interferon-gamma ELISpot assay facilitates safe drug rechallenge in severe cutaneous adverse reactions caused by anti-tuberculosis drugs
Authors: Amornrat Prasertcharoensuk, Yuda Chongpison, Pattarawat Thantiworasit, Supranee Buranapraditkun, Pawinee Rerknimitr, Hiroshi Chantaphakul, Jettanong Klaewsongkram
Journal: Journal of Allergy and Clinical Immunology (2020)
Screening for Cognitive Impairment in Older Adults
Authors: Douglas K. Owens, Karina W. Davidson, Alex H. Krist, Michael J. Barry, Michael Cabana, Aaron B. Caughey, Chyke A. Doubeni, John W. Epling, Martha Kubik, C. Seth Landefeld, Carol M. Mangione, Lori Pbert, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2020)

<h3>Importance</h3> Dementia (also known as major neurocognitive disorder) is defined by a significant decline in 1 or more cognitive domains that interferes with a person’s independence in daily activities. Dementia affects an estimated 2.4 to 5.5 million individuals in the United States, and its prevalence increases with age. <h3>Objective</h3> To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on screening for cognitive impairment, including mild cognitive impairment and mild to moderate dementia, in community-dwelling adults, including those 65 years or older residing in independent living facilities. <h3>Population</h3> This recommendation applies to community-dwelling older adults 65 years or older, without recognized signs or symptoms of cognitive impairment. <h3>Evidence Assessment</h3> The USPSTF concludes that the evidence is lacking, and the balance of benefits and harms of screening for cognitive impairment cannot be determined. <h3>Recommendation</h3> The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for cognitive impairment in older adults. (I statement)
Abstract 12513: Machine Learning Significantly Improves Accuracy to Predict Survival Over the Seattle Heart Failure Model
Authors: Manar D Samad, Linyuan Jing, Alvaro E Ulloa Cerna, Dustin N Hartzel, Brent A Williams, Christopher W Good, Sanjay Doddamani, Christopher M Haggerty, Brandon K Fornwalt
Journal: Circulation (2018)

Introduction: The Seattle Heart Failure Model (SHFM) is a validated, widely-used risk model to predict survival in patients with heart failure (HF). The SHFM was developed with a multivariate Cox m...
Replacing TURBT with mpMRI for staging MIBC: Pilot data from the BladderPath study.
Authors: Nicholas D. James, Sarah Pirrie, Wenyu Liu, Rashid Amir, Jean Gallagher, Ana Hughes, Kieran Jefferson, Allen Knight, Veronica Nanton, Harriet Paige Mintz, Ann Pope, James WF Catto, Prashant Patel, Richard T. Bryan
Journal: Journal of Clinical Oncology (2020)

446 Background: The diagnostic pathways for bladder cancer are largely unchanged for 30 years. The BladderPath trial objectives are to: improve staging, accelerate treatment, and reduce iatrogenic tumour spread by avoiding TURBT. We hypothesise that substituting TURBT with mpMRI will avoid unnecessary surgery, accelerate correct MIBC treatment and improve outcomes. Methods: A randomised phase 2/3 trial of standard of care (Pathway 1) versus risk-stratified mpMRI-directed care (Pathway 2) in visually-diagnosed incident bladder cancer. Patients with bladder lesions suspicious for malignancy at flexible cystoscopy are stratified by a 5-point Likert scale: strongly agree (1) or agree (2) that the lesion is NMIBC, equivocal (3) NMIBC or MIBC, and agree (4) or strongly agree (5) the lesion is MIBC. All patients are randomised; those with probable NMIBC (Likert 1 &amp; 2) undergo TURBT in both pathways, and those with possible MIBC (Likert 3-5) undergo TURBT (Pathway 1) or mpMRI (Pathway 2). Endpoints: feasibility, time to correct MIBC therapy and clinical progression-free survival. We report preliminary feasibility data. Results: To date, 218 potentially eligible patients have been registered; on cystoscopy, 151 patients had no bladder lesions and 5 were excluded for other reasons. Of 62 patients randomised, we report results from 45 with preliminary data. Of the 21 patients in Pathway 1, 11 patients classified as probable NMIBC underwent TURBT (pathology: 11/11 NMIBC); 9/10 patients classified as possible MIBC underwent TURBT (pathology: 4/9 NMIBC &amp; 5/9 MIBC) and 1 patient incorrectly underwent mpMRI (staging: MIBC). Of the 24 patients in Pathway 2, 11/12 patients classified as probable NMIBC underwent TURBT (pathology: 9/11 NMIBC &amp; 2/11 MIBC) and one patient incorrectly underwent mpMRI (staging: NMIBC); 12 patients classified as possible MIBC underwent mpMRI (staging: 6/12 NMIBC &amp; 6/12 MIBC). Conclusions: A 5-point Likert scale accurately identifies patients with a low risk of MIBC (Likert 1 &amp; 2). It is feasible to randomise possible MIBC patients to TURBT or mpMRI for staging. The study is ongoing to investigate the intermediate outcome of time to correct therapy for MIBC and NMIBC and the final outcome of clinical progression-free survival. Clinical trial information: 35296862.
A modification of the clip-flap technique: the clip-band-flap technique
Authors: Adolfo Parra-Blanco, Miguel Fraile-López
Journal: Endoscopy (2020)

The clip-flap technique was described to facilitate creating a mucosal flap at the beginning of colorectal endoscopic submucosal dissection (ESD) [1] [2] [3] [4]. The creation of the mucosal flap is a critical step in colorectal ESD, with a high risk of perforation especially for beginners. The clip-band technique has been used in gastric and colorectal ESD. The second clip is used to clamp the band, and it is attached to the normal mucosa distal or opposite to the resection site after the circumferential incision is complete [5] ([Fig. 1]).
Polycaprolactone/polysaccharide functional composites for low-temperature fused deposition modelling
Authors: Yu-Qing Zhao, Ji-Hao Yang, Xiaokang Ding, Xuejia Ding, Shun Duan, Fu-Jian Xu
Journal: Bioactive Materials (2020)

Fused deposition modelling (FDM) is a commonly used 3D printing technology. The development of FDM materials was essential for the product quality of FDM. In this work, a series of polycaprolactone (PCL)-based composites for low-temperature FDM were developed. By melt blending technique, different ratios of starch were added into PCL to improve the performances of FDM, and the printability, tensile strength, rheological properties, crystallization behaviors and biological performances of the composites were studied. The PCL/starch composite had the best performance in FDM process with the starch ratio of 9 ph at 80–90 °C. The melting strength and solidification rate of PCL/starch composites were improved. The starch also increased the crystallization temperature, degree of crystallinity and crystallization rate of PCL/starch composites, while had no negative effects on the tensile strength of PCL. Due to the low printing temperature, various kinds of bioactive components were added into PCL/starch composites for preparation of antibacterial and biocompatible materials for FDM. The present work provides a new method to develop novel low-temperature FDM materials with various functions.
Utility of a general molecular screening program in patients with GU malignancies: The ProfiLER trial experience.
Authors: Armelle Vinceneux, Guillaume Moriceau, Marianne Lorcet, Mélodie Carbonnaux, Philippe Alexandre Cassier, Catherine Terret, Christian Baudet, Valéry Attignon, Daniel Pissaloux, Sylvie Chabaud, Qing Wang, David Pérol, Olivier Tredan, Jean-Yves Blay, Sylvie Negrier, Helen Jane Boyle, Aude Flechon
Journal: Journal of Clinical Oncology (2020)

528 Background: Advances in comprehensive tumor molecular pathology in genito-urinary (GU) tumors have driven development of targeted agents since ten years and changed the landscape of GU tumors treatment. We describe our experience with the institutional molecular trial ProfiLER. Methods: Retrospective review of patients with advanced genitourinary malignancies included in the prospective molecular profiling trial ProfiLER (NCT01774409) Tumor samples were analyzed by sequencing a 69 gene panel by next generation sequencing (NGS, Ion torrent PGM system) and whole genome array comparative genomic hybridization (Agilent platform). Clinical data were collected retrospectively. Cases were presented in a molecular board to drive prescription of molecular targeted therapy (MTT) according to the molecular abnormalities observed. Results: Between February 2013 and December 2018 156 adult patients were included, 42 had kidney cancer (including 32 clear cell carcinoma, 5 papillary type 2); 38 prostate cancer, 52 urothelial carcinoma including (16 upper tract), 12 cisplatin-refractory testicular germ cell tumor, 4 penile cancer, 3 adenocarcinoma of the urachus, 2 urethral carcinoma and 3 Leydig cell tumor. Median age at inclusion was 62 years (range 19, 80). Overall NGS and CGH failed in 11.5% of cases, and in 24% of prostate cancer cases.28.8% patients had at least one actionable target (n=45) with a recommended MTT. Only 17.8 % (n=8) patients actually received MTT corresponding to 5.1% of the total screened population. Only one patient had a clinical benefit from MTT. The most frequently initiated MTT were PIK3/AKT/mTOR pathway inhibitors (44,4%), FGRF/EGFR pathway inhibitors (13.3%) PARP inhibitors (8.7%) or cyclin kinase inhibitors (8.7%). The most frequent reasons for lack of MTT initiation were early death, ineligibility for clinical trials due to general condition. Conclusions: Non tumor-specific molecular profiling is feasible in GU cancers. However the use of targeted sequencing with a tumor type specific panel and at an earlier clinical stage may improve the proportion of MTT recommendations.
Clinical Correlates and Outcomes of Bone Marrow Failure and Myeloid Clonal Evolution in Patients with Germline GATA2 Haploinsufficiency
Authors: Candace Haddox, Juliana Perez Botero, Thanh Ho, Roshini Abraham, Shakila Khan, Vilmarie Rodriguez, Animesh Pardanani, Naseema Gangat, William J. Hogan, Mark R. Litzow, Matthew T Howard, Mrinal M. Patnaik
Journal: Blood (2017)