tbuckley/cabot-search huggingface dataset:
Long non-coding RNA SOX2OT promotes the stemness phenotype of bladder cancer cells by modulating SOX2
Authors: Yonghao Zhan, Zhicong Chen, Shiming He, Yanqing Gong, Anbang He, Yifan Li, Lianghao Zhang, Xuepei Zhang, Dong Fang, Xuesong Li, Liqun Zhou
Journal: Molecular Cancer (2020)

Abstract Background Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. However, the clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown. Methods The expression level of SOX2OT was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell (BCC) lines. Bladder cancer stem cells (BCSCs) were isolated from BCCs using flow cytometry based on the stem cell markers CD44 and ALDH1. Loss-of-function experiments were performed to investigate the biological roles of SOX2OT in the stemness phenotype of BCSCs. Comprehensive transcriptional analysis, RNA FISH, dual-luciferase reporter assays and western blots were performed to explore the molecular mechanisms underlying the functions of SOX2OT. Results SOX2OT was highly expressed in bladder cancer, and increased SOX2OT expression was positively correlated with a high histological grade, advanced TNM stage and poor prognosis. Further experiments demonstrated that knockdown of SOX2OT inhibited the stemness phenotype of BCSCs. Moreover, inhibition of SOX2OT delayed xenograft tumour growth and decreased metastases in vivo. Mechanistically, we found that SOX2OT was mainly distributed in the cytoplasm and positively regulated SOX2 expression by sponging miR-200c. Furthermore, SOX2 overexpression reversed the SOX2OT silencing-induced inhibition of the BCSC stemness phenotype. Conclusion This study is the first to demonstrate that SOX2OT plays an important regulatory role in BCSCs and that SOX2OT may serve as a potential diagnostic biomarker and therapeutic target in bladder cancer.
In-between the ears: how concussion reshaped my life
Authors: Christopher Luff
Journal: British Journal of Sports Medicine (2020)

Life was good, playing football, going out with friends and working as a boilermaker! Even after my first two concussions this pattern continued; I had no idea what was ahead.

My first concussion was in 2012 playing football. I took a big hit, was disorientated and confused, but recovered quickly. I went out drinking with friends the next day and played, symptom free, the following week. A year later I was involved in a scuffle while intoxicated outside a club. I received a blow to the back of the head, vomited for the next 48 hours and had headaches for a week. My symptoms then resolved and I thought no more of them.

Four years later, I was sling-tackled during a game. Unable to brace, my head slapped the ground. I played on, but postgame felt confused, unsteady and like an outsider watching in on what was happening around me. On this occasion my symptoms persisted. One week later, I still did not feel ‘quite right’ and I sat out for 6 weeks due to visual disturbance, light hypersensitivity, headaches and disturbed mood.

After 6 weeks on the bench I was desperate to return to football. I convinced myself that I was well and reported to the medical team that I was asymptomatic; …
The impact of marital status on the survival of transitional cell carcinoma of the bladder.
Authors: Anas M. Saad, Firas Baidoun, Mohamed M. Gad, Inas A. Ruhban, Khalid Jazieh, Muneer J. Al-Husseini, Moshe Chaim Ornstein, Brian I. Rini, Shilpa Gupta
Journal: Journal of Clinical Oncology (2020)

578 Background: Marital status is one of the multiple lifestyle factors that affect the survival of several malignancies. Prior literature has demonstrated that married individuals have better survival in cases of transitional cell carcinoma (TCC). In this study, we aim to demonstrate the association in a large cohort of patients. Methods: Data of TCC patients with known marital status who were diagnosed between 1973 and 2015 in the US was obtained using the Surveillance Epidemiology and End Results (SEER) database. We compared the overall and cancer-specific survival of patients according to their marital status using Kaplan-Meier test and multivariable covariate-adjusted Cox models. Results: We reviewed 204,862 TCC patients, of which 64.26%, 10.64%, 1.01%, 7.31%, and 16.78% were married, single, separated, divorced, and widowed, respectively. Married patients had the highest overall survival (median 123 months), followed by single patients (median 111 months), divorced (median 102 months), separated (median 60 months), and widowed (median 43 months). Bladder cancer-specific survival followed relatively similar trends with married patients having significantly better survival when compared to other groups. When we adjusted for age, sex, race, stage, grade, and undergoing cancer-targeted surgery, married patients had better survival outcomes when compared to single patients (HR = 1.322, p-value &lt; 0.001), separated patients (HR = 1.409, p-value &lt; 0.001), divorced patients (HR = 1.358, p-value &lt; 0.001), and widowed patients (HR = 1.242, p-value &lt; 0.001). Conclusions: Our results demonstrate a clear survival advantage in cases of transitional cell carcinoma of the bladder with married individuals having the highest overall and cancer-specific median survival. These results shed the light on the lifestyle and the psychosocial factors, including the social support that married patients may have comparing to unmarried patients, and their effect on the disease prognosis and survival. Understanding the social and psychological factors associated with the observed disparity may help enhance management plans for affected patients.
FDA Assesses Potential Cancer Risk Associated With Weight Loss Drug
Authors: Rebecca Voelker
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Is there a role for conventional-dose chemotherapy in relapsed germ cell tumors?
Authors: Luana Toledo Manhaes, Daniel Musse Gomes, Isabele Small, Luiz H. Araujo, Pedro Masson Domingues
Journal: Journal of Clinical Oncology (2020)

404 Background: Patients with germ cell tumors (GCT) that relapse after first-line platinum-based chemotherapy can still be successfully rescued with second-line regimens. High-dose chemotherapy has shown favorable outcomes, and is a preferred option in most instances. Herein, we argued if conventional-dose chemotherapy (CDCT) could also be an alternative in selected patients. Methods: We performed a retrospective observational study, analyzing medical data of 57 GCT male patients treated with salvage chemotherapy after relapse to first-line platinum-based treatment from 2000 to 2015 at the Brazilian National Cancer Institute. Results: The median age was 28 years (range 15 to 49). 26 patients (46%) were Afro-Brazilian, 45 (79%) were non-seminoma, and 53 (93%) had primary testis tumors. 14 patients (25%) had bone, liver or brain metastasis at relapse, and in 35 (61%) the progression-free interval (PFI) after first-line was &lt; 3months. The International Prognostic Factors Study Group (IPFSG) risk classification at relapse for very-low/low, intermediate and high/very-high risk were 8 (14%), 25 (44%), 24 (42%), respectively. After a median follow-up of 8 years, the 2-year PFS was 30% (95% IC, 20 % to 45 %) and the 2-year overall survival (OS) was 34% (95% IC, 23% to 49%). PFI &lt; 3m after first-line (HR 2,38; p&lt;0,005) and AFP &gt; 1000 at relapse (HR 2,38, p&lt;0,023) were negative prognostic factors for PFS and OS. The 2-year PFS and OS for IPFSG risk classification very-low/low, intermediate and high/very-high risk were 75% and 73%, 28% and 32%, 18% and 24%, respectively. Conclusions: In patients with relapsed GCT and very-low/low risk disease by the IPFSG classification, CDCT may be a reasonable option, achieving long-term survival rates. However, CDCT was associated with poor outcome in intermediate and high/very-high risk groups. Further studies should be conducted to assess the best treatment in this subset, since even in second-line, many of patients are still potentially curable.
Overall survival results for durvalumab and savolitinib in metastatic papillary renal cancer.
Authors: Cristina Suarez Rodriguez, James M. G. Larkin, Poulam Patel, Begona Pérez Valderrama, Alejo Rodriguez-Vida, Hilary Glen, Fiona Thistlethwaite, Christy Ralph, Gopalakrishnan Srinivasan, Maria Jose José Mendez Vidal, Abigail Carter, Charlotte Tyson, Aaron Prendergast, Kelly Mousa, Thomas Powles
Journal: Journal of Clinical Oncology (2020)

619 Background: There is a strong rationale for investigating MET and PD-L1 inhibition in metastatic papillary renal cancer (PRC). We previously reported response rates (RR) and progression free survival (PFS) for savolitinib (MET inhibitor) and durvalumab (PD-L1 inhibitor) together. Here we report overall survival (OS) data available 12 months after the last patient was enrolled. Methods: This single arm phase I/II trial explores durvalumab (1500mg Q4W) and savolitinib (600mg OD) together in PRC, with a 4wk savolitinib run in. Treatment naïve or previously treated patients with metastatic PRC were included. Confirmed RR (RECIST v1.1), PFS, tolerability (CTCAE v4.03) and overall survival (OS) were analysed. MET and PD-L1 biomarkers were explored (NCT02819596). Results: 42 patients were enrolled with 41 receiving at least one dose of study treatment. Safety and efficacy analyses were performed on these 41 patients. The median follow up was 14.3 months. IMDC good, intermediate and poor risk disease occurred in 29%, 63%, and 7% of patients respectively. Overall confirmed RR was 27% while median PFS was 4.9 months (95% CI: 2.5 – 12.0 months). Median OS was 12.3 months (95% CI: 5.8 – 21.3 months). Confirmed RR and median OS in the previously untreated cohort (N=27) were 33% and 12.3 months (95% CI: 4.7 – not reached (NR) months) respectively. Treatment related Grade 3/4 toxicity occurred in 34% of patients. No new safety signals were seen. PD-L1 and MET expression were not associated with higher RR (25% and 40% respectively) or longer OS. Conclusions: The combination of savolitinib and durvalumab has clinical activity in PRC and outcomes were not enhanced in biomarker positive cancers. Clinical trial information: NCT02819596.
Soluble PD-L1 as a marker of progressive disease on nivolumab in kidney cancer.
Authors: Kathleen Margaret Mahoney, Petra B. Ross-Macdonald, Sachet A. Shukla, David A. Braun, Linan Song, Eliseo Veras, Megan Wind-Rotolo, Eliezer Mendel Van Allen, David F. McDermott, F. Stephen Hodi, Toni K. Choueiri, Gordon J. Freeman
Journal: Journal of Clinical Oncology (2020)

746 Background: Higher levels of soluble PD-L1 (sPD-L1) are associated with poor prognosis in patients with solid tumors including in renal cell carcinoma (RCC). Here we have tested whether in patients with advanced RCC, sPD-L1 levels are associated with PD-L1 expression on tumor tissue or with clinical outcomes on PD-1 blockade. Methods: Serum from 91 patients with advanced clear-cell RCC on a biomarker study of nivolumab (NCT01358721) obtained at baseline (Day 1), Day 29 and Day 63, was tested by SiMoa™ for sPD-L1 (capture mAb 298.12B1, detection mAb 339.4C10; Freeman laboratory and Quanterix). Tumor PD-L1 (tPD-L1) was assessed on pretreatment biopsies (Dako). Association of sPDL1 and tPD-L1 with clinical outcomes was analyzed, including best overall response by RECIST (BOR), objective response of &gt;20% (OR), progression free survival (PFS), and overall survival (OS). Results quote Wilcoxon Rank Sum test or paired t-test with significance at P &lt; 0.05. Results: Median sPD-L1 was highest in patients with progressive disease (PD) at all timepoints (Table). Compared to baseline, sPD-L1 levels significantly increased in patients with PD on Day 29 and Day 63, while sPD-L1 levels significantly decreased in patients with CR/PR on Day 63. In addition, we found significantly higher baseline sPD-L1 in patients with prior therapy compared to those who were treatment-naïve. High tPD-L1 was weakly associated with favorable OR, but also weakly associated with high baseline sPD-L1. Conclusions: Unlike tPD-L1, sPD-L1 levels may show promise for association with clinical response to nivolumab in RCC. In this exploratory study, sPD-L1 increase on-treatment was significantly associated with lack of OR, and may be of utility as an early marker for PD worthy of future validation. Analysis of RNASeq from patients’ tumor specimen is underway to assess whether high sPD-L1 with PD is associated with immune suppressive signatures.[Table: see text]
Real-world management of advanced prostate cancer: A Canadian comparison of academic specialists and community-based prostate cancer physicians.
Authors: Sebastien J. Hotte, Antonio Finelli, Kim N. Chi, Christina M. Canil, Neil Fleshner, Anil Kapoor, Michael Paul Kolinsky, Shawn Malone, Chris Morash, Tamim Niazi, Krista Noonan, Michael Ong, Frederic Pouliot, Bobby Shayegan, Alan So, Delna Sorabji, Huong Hew, Laura Park-Wyllie, Fred Saad
Journal: Journal of Clinical Oncology (2020)

29 Background: The Canadian GU Research Consortium recently conducted a consensus development conference with 27 academic prostate cancer (PC) specialists leading to 31 consensus recommendations. We conducted a survey to compare community-based practice with the consensus recommendations on the management of metastatic castration sensitive prostate cancer (mCSPC), metastatic castration resistant prostate cancer (mCRPC) and non-metastatic castration resistant prostate cancer (nmCRPC). Methods: An 87-item online questionnaire was sent to 600 Canadian community urologists, medical oncologists, radiation oncologists, and general practitioner oncologists involved in the treatment of PC. Results: Seventy-two physicians responded to the questionnaire (12% response). A discordance of &gt;25% was observed in 15 of 31 recommendations (48%). Among the areas of discordance were treatment approach for patients with nmCRPC and PSADT &lt; 10 months who are negative for metastases on conventional imaging but metastatic on PET-based imaging. Of the academic physicians, 89% indicated treating with agents approved for nmCRPC compared to 50% of community physicians (p=0.0005). Important discrepancies were also observed across academic and community physicians for radiation to the prostate for low-volume mCSPC which was 74% vs 27%, (p&lt;0.0001) respectively; criteria for stopping therapy in mCRPC in which 78% of academic physicians favored continuation of therapy in the event of PSA progression only, compared to 24% of community physicians. Sequencing of therapy after prior apalutamide for nmCRPC using subsequent docetaxel treatment was observed in 81% of academic physicians vs 35% of community physicians, (p&lt;0.0001), and use of genetic testing was favored by 74% of academics vs 36% of community physicians, (p&lt;0.0001) for newly diagnosed metastatic prostate cancer. Conclusions: The areas of discordance between a national sample of community-based PC physicians and academic consensus recommendations represent potential areas for education, practice tools and future research.
An Appraisal of the Association of Clinical Outcomes With the Severity of Regurgitant Volume Relative to End-Diastolic Volume in Patients With Secondary Mitral Regurgitation
Authors: William H. Gaasch, Gerard P. Aurigemma, Theo E. Meyer
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Two randomized clinical trials of transcatheter edge-to-edge mitral valve repair in patients with secondary mitral regurgitation (the Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation [MITRA-FR] and the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]) report clinical outcome disparities that are largely unexplained. This appraisal sought to provide insight and an explanation for the differences in clinical outcomes (survival and hospitalization rates) in the 2 clinical trials. The mean echocardiogram Doppler results (and derived volume parameters) from each of the 2 clinical trials were compared and examined relative to the clinical outcomes. Special emphasis was placed on the assessment of mitral regurgitation proportionality coefficients that were determined as the ratio of effective regurgitant orifice area (EROA) to end-diastolic volume and the ratio of mitral regurgitant volume to end-diastolic volume. <h3>Observations</h3> In this analysis of the differences in the clinical outcomes of the MITRA-FR and COAPT clinical trials, the ratio of the EROA to the end-diastolic volume in the COAPT study was found to be twice that of the MITRA-FR study (0.002 cm<b>-</b><sup>1</sup>vs 0.001 cm<b>-</b><sup>1</sup>, respectively). The finding of a larger proportional EROA in the COAPT study suggests more severe mitral regurgitation compared with the MITRA-FR study, thereby providing a potential explanation for the different outcomes in the 2 clinical trials. In contrast, the ratio of the mitral regurgitant volume to the end-diastolic volume in the COAPT study was similar to (but slightly lower than) that of the MITRA-FR study (0.15 vs 0.18, respectively), indicating that the proportional mitral regurgitant volume was comparable in the 2 clinical trials. This finding contradicts the conclusions of the EROA analysis. <h3>Conclusions and Relevance</h3> The results of proportionality analyses based on EROA differ from those based on a volume analysis. This disparity casts doubt on the notion that an EROA analysis alone can explain the different results of the 2 randomized clinical trials.
Premature Mortality in Epilepsy—A Reminder for the Untreated Millions—Reply
Authors: Colin B. Josephson, Samuel Wiebe
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
From reads to insight: a hitchhiker’s guide to ATAC-seq data analysis
Authors: Feng Yan, David R. Powell, David J. Curtis, Nicholas C. Wong
Journal: Genome biology (2020)

Abstract Assay of Transposase Accessible Chromatin sequencing (ATAC-seq) is widely used in studying chromatin biology, but a comprehensive review of the analysis tools has not been completed yet. Here, we discuss the major steps in ATAC-seq data analysis, including pre-analysis (quality check and alignment), core analysis (peak calling), and advanced analysis (peak differential analysis and annotation, motif enrichment, footprinting, and nucleosome position analysis). We also review the reconstruction of transcriptional regulatory networks with multiomics data and highlight the current challenges of each step. Finally, we describe the potential of single-cell ATAC-seq and highlight the necessity of developing ATAC-seq specific analysis tools to obtain biologically meaningful insights.
Akiko Iwasaki: Women in STEM
Authors: Stephanie Houston
Journal: The Journal of Experimental Medicine (2020)

Akiko Iwasaki is a Waldemar Von Zedtwitz Professor of Immunobiology, a Professor of Molecular and Cellular and Developmental Biology at Yale, and an Investigator at the Howard Hughes Medical Institute. Her laboratory works on a wide variety of topics, from mucosal immunology to viruses, and recently she published a pioneering paper showing how the meningeal lymphatic vasculature can be manipulated with VEGF-C to promote an immune response to glioblastoma. She is the future president of the American Association of Immunologists, a JEM Advisory Editor, has been awarded numerous prizes, and is a true Twitter celebrity. I chatted with Akiko to find out about her career so far and about being a woman in STEM.
Large concomitant outbreaks of acute gastroenteritis emergency visits in adults and food-borne events suspected to be linked to raw shellfish, France, December 2019 to January 2020
Authors: Anne Fouillet, Nelly Fournet, Cécile Forgeot, Gabrielle Jones, Alexandra Septfons, Léa Franconeri, Katia Ambert-Balay, Jeannot Schmidt, Patrick Guérin, Henriette de Valk, Céline Caserio-Schönemann
Journal: Eurosurveillance (2020)

On 27 December 2019, the French Public Health Agency identified a large increase in the number of acute gastroenteritis and vomiting visits, both in emergency departments and in emergency general practitioners' associations providing house-calls. In parallel, on 26 and 27 December, an unusual number of food-borne events suspected to be linked to the consumption of raw shellfish were reported through the mandatory reporting surveillance system. This paper describes these concomitant outbreaks and the investigations' results.
Aberrant RAG-mediated recombination contributes to multiple structural rearrangements in lymphoid blast crisis of chronic myeloid leukemia
Authors: Daniel W. Thomson, Nur Hezrin Shahrin, Paul P. S. Wang, Carol Wadham, Naranie Shanmuganathan, Hamish S. Scott, Marcel E. Dinger, Timothy P. Hughes, Andreas W. Schreiber, Susan Branford
Journal: Leukemia (2020)