tbuckley/cabot-search huggingface dataset:
Analysis of plasma KIM-1 as a biomarker for recurrence risk after resection for localized renal cell carcinoma.
Authors: Wenxin Xu, Maneka Puligandla, Brian Halbert, Naomi B. Haas, Keith Flaherty, Robert Guy Uzzo, Janice P. Dutcher, Robert S. DiPaola, Venkata Sabbisetti, Rupal Satish Bhatt
Journal: Journal of Clinical Oncology (2021)

342 Background: Recurrence is common after nephrectomy for renal cell carcinoma (RCC), but no circulating biomarkers are available to identify patients at highest risk of recurrence who may benefit from adjuvant therapy. Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy. Methods: Banked plasma samples were analyzed from the ECOG-ACRIN 2805 (ASSURE) trial evaluating adjuvant sunitinib, sorafenib, and placebo in resected high-risk RCC. KIM-1 levels were measured at trial enrollment 4-12 weeks post-nephrectomy (baseline) and on cycle 2 day 1 (C2D1) using a previously validated microbead assay. A lognormal accelerated failure time model was used to test for association between circulating KIM-1 and disease-free survival (DFS). Results: Plasma samples from 418 patients were analyzed. In univariable and multivariable analyses, higher post-nephrectomy KIM-1 was associated with worse DFS across all study arms. This association remained independently significant after adjustment for Fuhrman grade, T-stage, N-stage, and tumor histology (survival time ratio 0.56 for 75 th vs 25 th percentile of KIM-1, 95% CI 0.42-0.73, p &lt; 0.001). The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement. The addition of baseline KIM-1 improved the concordance of both the SSIGN and UISS prognostic models (SSIGN concordance 0.57 vs 0.43, p = 0.05; UISS concordance 0.60 vs 0.40, p = 0.0005). C2D1 KIM-1 was not an independent predictor for DFS after adjusting for baseline KIM-1. Conclusions: Elevated plasma KIM-1 level at post-nephrectomy baseline is associated with worse DFS in RCC. This is consistent with the hypothesis that post-nephrectomy plasma KIM-1 may be a biomarker for microscopic residual disease. The model was additionally adjusted for papillary and chromophobe histology, sex, and ECOG performance status. [Table: see text]
Treatment of Fibromyalgia in the 21st Century
Authors: Maria J. Silveira, Kevin F. Boehnke, Dan Clauw
Journal: JAMA Internal Medicine (2021)

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 Internal Medicine 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 Internal Medicine journal
Blue rubber bleb nevus syndrome: an unusual cause of intestinal bleeding in the elderly
Authors: Jérôme Winkler, Marion Bonnet, Aurélie Haffner, Géraldine Gascou-Tessonnier, Laurent Heyries, Philippe Grandval, Diane Mege
Journal: Endoscopy (2021)

Blue rubber bleb nevus syndrome (or Bean syndrome) is a rare cause of gastrointestinal bleeding. Only three cases have been reported in the elderly [1] [2] [3].
RETRACTED: Changes in soft drinks purchased by British households associated with the UK soft drinks industry levy: controlled interrupted time series analysis
Authors: David Pell, Oliver Mytton, Tarra L Penney, Adam Briggs, Steven Cummins, Catrin Penn-Jones, Mike Rayner, Harry Rutter, Peter Scarborough, Stephen J Sharp, Richard D Smith, Martin White, Jean Adams
Journal: BMJ (2021)

To determine changes in household purchases of drinks and confectionery one year after implementation of the UK soft drinks industry levy (SDIL).
Association Between Cardiovascular Risk Factors and Cognitive Impairment in People With Schizophrenia
Authors: Katsuhiko Hagi, Tadashi Nosaka, Dwight Dickinson, Jean Pierre Lindenmayer, Jimmy Lee, Joseph Friedman, Laurent Boyer, Mei Han, Nur Amirah Abdul-Rashid, Christoph U. Correll
Journal: JAMA Psychiatry (2021)

Schizophrenia is associated with cognitive dysfunction and cardiovascular risk factors, including metabolic syndrome (MetS) and its constituent criteria. Cognitive dysfunction and cardiovascular risk factors can worsen cognition in the general population and may contribute to cognitive impairment in schizophrenia.To study the association between cognitive dysfunction and cardiovascular risk factors and cognitive impairment in individuals with schizophrenia.A search was conducted of Embase, Scopus, MEDLINE, PubMed, and Cochrane databases from inception to February 25, 2020, using terms that included synonyms of schizophrenia AND metabolic adversities AND cognitive function. Conference proceedings, clinical trial registries, and reference lists of relevant publications were also searched.Studies were included that (1) examined cognitive functioning in patients with schizophrenia or schizoaffective disorder; (2) investigated the association of cardiovascular disease risk factors, including MetS, diabetes, obesity, overweight, obesity or overweight, hypertension, dyslipidemia, and insulin resistance with outcomes; and (3) compared cognitive performance of patients with schizophrenia/schizoaffective disorder between those with vs without cardiovascular disease risk factors.Extraction of data was conducted by 2 to 3 independent reviewers per article. Data were meta-analyzed using a random-effects model.The primary outcome was global cognition, defined as a test score using clinically validated measures of overall cognitive functioning.Twenty-seven studies involving 10 174 individuals with schizophrenia were included. Significantly greater global cognitive deficits were present in patients with schizophrenia who had MetS (13 studies; n = 2800; effect size [ES] = 0.31; 95% CI, 0.13-0.50; P = .001), diabetes (8 studies; n = 2976; ES = 0.32; 95% CI, 0.23-0.42; P < .001), or hypertension (5 studies; n = 1899; ES = 0.21; 95% CI, 0.11-0.31; P < .001); nonsignificantly greater deficits were present in patients with obesity (8 studies; n = 2779; P = .20), overweight (8 studies; n = 2825; P = .41), and insulin resistance (1 study; n = 193; P = .18). Worse performance in specific cognitive domains was associated with cognitive dysfunction and cardiovascular risk factors regarding 5 domains in patients with diabetes (ES range, 0.23 [95% CI, 0.12-0.33] to 0.40 [95% CI, 0.20-0.61]) and 4 domains with MetS (ES range, 0.15 [95% CI, 0.03-0.28] to 0.40 [95% CI, 0.20-0.61]) and hypertension (ES range, 0.15 [95% CI, 0.04-0.26] to 0.27 [95% CI, 0.15-0.39]).In this systematic review and meta-analysis, MetS, diabetes, and hypertension were significantly associated with global cognitive impairment in people with schizophrenia.
Cardiac risk factors and events in patients with prostate cancer commencing androgen deprivation therapy: Analysis from a tertiary care center in the Middle East.
Authors: Mona Hassan, Talar Telvizian, Mostafa Abohelwa, Hadi Skouri, Deborah Mukherji
Journal: Journal of Clinical Oncology (2021)

73 Background: Androgen deprivation therapy (ADT) is the mainstay of treatment for advanced prostate cancer, improving symptoms and prolonging survival. There is an association between ADT use and cardiovascular events, particularly in men with pre-existing risk factors. There are no definite guidelines to stratify patients based on cardiovascular risk prior to ADT initiation. This is the first study on cardiac risks and events in patients on ADT from Lebanon and the Middle East region, a population known to have a high prevalence of cardiovascular risk factors. Methods: A retrospective chart review of 236 patients with prostate cancer who received ADT therapy at a tertiary care center in Lebanon was performed. 167 had a full set of data and were included in analysis. Cardiovascular risk factors at baseline and cardiovascular events on ADT were reviewed. Results: The median age of our cohort was 68, range 48-92 years. The majority of patients had stage 4 diseases at diagnosis (49.8%) with a median duration of 12 months on ADT. In our cohort 24.4% had body mass index &gt; 30, 52.1% had smoking history, 27.4% were diabetic, 28.8 % had history of coronary artery disease, 10.6% had heart failure history and 54.6% had hypertension. Less than half of the patients had a documented lipid profile at baseline. Twenty two patients (9.5%) had documented cardiac events following ADT initiation. Conclusions: In this cohort of patients from the Middle East we found that one third of the population had established coronary artery disease at baseline and 9.5% had documented cardiac events on ADT initiation. Our study highlights the gaps in cardiovascular risk assessment for this high risk group of patients with prostate cancer. Risk and resource-stratified algorithms are needed before starting ADT therapy for optimal cardiovascular health. Increased awareness, collaboration and referral mechanisms between oncologists, urologist and cardiologists are also needed.
Cancer-Specific Targeting of Taurine-Upregulated Gene 1 Enhances the Effects of Chemotherapy in Pancreatic Cancer
Authors: Yoshihiko Tasaki, Miho Suzuki, Keisuke Katsushima, Keiko Shinjo, Kenta Iijima, Yoshiteru Murofushi, Aya Naiki-Ito, Kazuki Hayashi, Chenjie Qiu, Akiko Takahashi, Yoko Tanaka, Tokuichi Kawaguchi, Minoru Sugawara, Tomoya Kataoka, Mitsuru Naito, Kanjiro Miyata, Kazunori Kataoka, Tetsuo Noda, Wentao Gao, Hiromi Kataoka, Satoru Takahashi, Kazunori Kimura, Yutaka Kondo
Journal: Cancer Research (2021)

Abstract Overcoming drug resistance is one of the biggest challenges in cancer chemotherapy. In this study, we examine whether targeting the long noncoding RNA taurine upregulated gene 1 (TUG1) could be an effective therapeutic approach to overcome drug resistance in pancreatic ductal adenocarcinoma (PDAC). TUG1 was expressed at significantly higher levels across 197 PDAC tissues compared with normal pancreatic tissues. Overall survival of patients with PDAC who had undergone 5-FU–based chemotherapy was shorter in high TUG1 group than in low TUG1 group. Mechanistically, TUG1 antagonized miR-376b-3p and upregulated dihydropyrimidine dehydrogenase (DPD). TUG1 depletion induced susceptibility to 5-FU in BxPC-3 and PK-9 pancreatic cell lines. Consistently, the cellular concentration of 5-FU was significantly higher under TUG1-depleted conditions. In PDAC xenograft models, intravenous treatment with a cancer-specific drug delivery system (TUG1-DDS) and 5-FU significantly suppressed PDAC tumor growth compared with 5-FU treatment alone. This novel approach using TUG1-DDS in combination with 5-FU may serve as an effective therapeutic option to attenuate DPD activity and meet appropriate 5-FU dosage requirements in targeted PDAC cells, which can reduce the systemic adverse effects of chemotherapy. Significance: Targeting TUG1 coupled with a cancer-specific drug delivery system effectively modulates 5-FU catabolism in TUG1-overexpressing PDAC cells, thus contributing to a new combinatorial strategy for cancer treatment.
Prognostic significance of concurrent gene mutations in intensively treated patients with<i>IDH</i>-mutated AML: an ALFA study
Authors: Matthieu Duchmann, Jean-Baptiste Micol, Nicolas Duployez, Emmanuel Raffoux, Xavier Thomas, Jean-Pierre Marolleau, Thorsten Braun, Lionel Adès, Sylvain P Chantepie, Emilie Lemasle, Celine Berthon, Jean-Valère Malfuson, Cecile Pautas, Juliette Lambert, Nicolas Boissel, Karine Celli-Lebras, Denis Caillot, Pascal Turlure, Norbert Vey, Arnaud Pigneux, Christian Récher, Christine Terré, Claude j Gardin, Raphaël A. Itzykson, Claude Preudhomme, Hervé Dombret, Stéphane de Botton
Journal: Blood (2021)
Australia and New Zealand (ANZ) outcomes of high-dose chemotherapy and stem cell transplantation for relapsed or refractory germ cell tumors (GCT) from 1999 to 2019: Multicenter registry-based study with ABMTRR.
Authors: Elizabeth Anne Connolly, Andrew James Weickhardt, Peter S. Grimison, Gillian Heller, Jeremy Howard Lewin, Elizabeth Chien Hern Liow, Iris Tung, Ben Tran, Sean Hill, Euan Thomas Walpole, Jane McKenzie, Anna Kuchel, Garry Forgeson, Alvin Boon Tee Tan, Abhishek Joshi, Alistair Wickham, Thean Hsiang Tan, Yang Wang, Nada Hamad, Vanessa Wong
Journal: Journal of Clinical Oncology (2021)

382 Background: High dose chemotherapy (HDCT) with autologous stem-cell transplant (ASCT) is effective in advanced germ cell tumours (GCT) that are refractory to, or progress after, first-line therapies. Five-year overall survival in North American and European series range from 48-60%1,2,3. This study aimed to assess ANZ outcomes for quality assurance. Methods: Retrospective multi-centre audit of all male patients with GCT who underwent HDCT and ASCT from 1999-2019. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. Primary outcomes included overall and progression- free survival (OS, PFS). Results: 111 patients were identified at 13 centres, each treating a median (range) of 7 (1-27) patients. Median (range) age was 30 (14-68) years. 88 (79%) had testicular primary. 16% were pure seminoma. Median time from first diagnosis to first stem cell cycle was 11 months (range 3 months-38 years). Prior to ASCT, 35% had primary refractory disease and 65% had relapsed. IPFSG risk score was very low in 5%, low in 13%, intermediate in 36%, high in 25%, and very high in 21%. HDCT regimen was CE in 78% (as part of TI-CE regimen in 38%), Carbop-EC-T in 6%, ICE in 6%, CEC in 5% and other in 4%. 89% completed all planned HDCT and ASCT cycles. Five treatment related deaths occurred. Progressive disease on treatment occurred in 14%. At median follow-up time 4.4 years (95% CI: 2.9 to 6.0), 51% were disease-free, 13% alive with disease, 34% deceased. 3 patients displayed late progression over 2 years after ASCT. The estimated 1, 2 and 5-year PFS rates were 62%, 57% and 52% respectively and OS rates were 73%, 65% and 61%. Survival by IPFSG and IGCCG risk categories are displayed in the table below. Conclusions: This is the first registry-based audit of HDCT for metastatic GCT from ANZ, which has demonstrated our outcomes are comparable with best international practice. References: Gossi Bone Marrow Transplant 2018;53:820-825. Adra J Clin Onc 2017; 35(10):1096-1102. Feldman J Clin Onc 2010; 28(10):1706-13. [Table: see text]
8MO CC-90010, a reversible, potent oral bromodomain and extraterminal inhibitor (BETi) in patients (pts) with advanced solid tumours (aSTs) and relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Longer follow-up from parts A &amp; B and first reporting of part C of a phase I study
Authors: V. Moreno, M. Vieito Villar, J.M. Sepulveda Sanchez, V. Galvao, T. Hernández Guerrero, B. Doger, O. Saavedra, C. Carlo Stella, J-M. Michot, A. Italiano, M. Magagnoli, C. Carpio, R. Sarmiento, B. Amoroso, I. Aronchik, E. Filvaroff, B. Hanna, A. Pinto, Z. Nikolova, I. Braña
Journal: Annals of Oncology (2021)
SSRE: Cell Type Detection Based on Sparse Subspace Representation and Similarity Enhancement
Authors: Zhenlan Liang, Min Li, Ruiqing Zheng, Yu Tian, Xuhua Yan, Jin Chen, Fang-Xiang Wu, Jianxin Wang
Journal: Genomics Proteomics & Bioinformatics (2021)

Accurate identification of cell types from single-cell RNA sequencing (scRNA-seq) data plays a critical role in a variety of scRNA-seq analysis studies. This task corresponds to solving an unsupervised clustering problem, in which the similarity measurement between cells affects the result significantly. Although many approaches for cell type identification have been proposed, the accuracy still needs to be improved. In this study, we proposed a novel single-cell clustering framework based on similarity learning, called SSRE. SSRE models the relationships between cells based on subspace assumption, and generates a sparse representation of the cell-to-cell similarity. The sparse representation retains the most similar neighbors for each cell. Besides, three classical pairwise similarities are incorporated with a gene selection and enhancement strategy to further improve the effectiveness of SSRE. Tested on ten real scRNA-seq datasets and five simulated datasets, SSRE achieved the superior performance in most cases compared to several state-of-the-art single-cell clustering methods. In addition, SSRE can be extended to visualization of scRNA-seq data and identification of differentially expressed genes. The matlab and python implementations of SSRE are available at https://github.com/CSUBioGroup/SSRE.
Corrigendum to ‘Conditioned medium-electrospun fiber biomaterials for skin regeneration’ [Bioact. Mater. 6 (2021) 361–374]
Authors: Lu Chen, Liying Cheng, Zhen Wang, Jianming Zhang, Xiyuan Mao, Zhimo Liu, Yuguang Zhang, Wenguo Cui, Xiaoming Sun
Journal: Bioactive Materials (2021)
Tumor-derived ILT4 induces T cell senescence and suppresses tumor immunity
Authors: Aiqin Gao, Xia Liu, Wenli Lin, Jingnan Wang, Shuyun Wang, Fusheng Si, Lan Huang, Yangjing Zhao, Yuping Sun, Guangyong Peng
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Current immunotherapies including checkpoint blockade therapy have limited success rates in certain types of cancers. Identification of alternative checkpoint molecules for the development of effective strategies for tumor immunotherapy is urgently needed. Immunoglobulin-like transcript 4 (ILT4) is an immunosuppressive molecule expressed in both myeloid innate cells and malignant tumor cells. However, the role of tumor-derived ILT4 in regulating cancer biology and tumor immunity remains unclear. Methods ILT4 expression in tumor cells and patient samples was determined by real-time PCR, flow cytometry, and immunohistochemistry. T cell senescence induced by tumor was evaluated using multiple markers and assays. Moreover, metabolic enzyme and signaling molecule expression and lipid droplets in tumor cells were determined using real-time PCR, western blot and oil red O staining, respectively. Loss-of-function and gain-of-function strategies were used to identify the causative role of ILT4 in tumor-induced T cell senescence. In addition, breast cancer and melanoma mouse tumor models were performed to demonstrate the role of ILT4 as a checkpoint molecule for tumor immunotherapy. Results We reported that ILT4 is highly expressed in human tumor cells and tissues, which is negatively associated with clinical outcomes. Furthermore, tumor-derived ILT4/PIR-B (ILT4 ortholog in mouse) is directly involved in induction of cell senescence in naïve/effector T cells mediated by tumor cells in vitro and in vivo. Mechanistically, ILT4/PIR-B increases fatty acid synthesis and lipid accumulation in tumor cells via activation of MAPK ERK1/2 signaling, resulting in promotion of tumor growth and progression, and induction of effector T cell senescence. In addition, blocking tumor-derived PIR-B can reprogram tumor metabolism, prevent senescence development in tumor-specific T cells, and enhance antitumor immunity in both breast cancer and melanoma mouse models. Conclusions These studies identify a novel mechanism responsible for ILT4-mediated immune suppression in the tumor microenvironment, and prove a novel concept of ILT4 as a critical checkpoint molecule for tumor immunotherapy.
Prognostic impact of serum cytokeratin 19 fragments in patient with metastatic urothelial cancer (mUC) treated with first-line chemotherapy.
Authors: Yuki Endo, Go Kimura, Jun Akatsuka, Masato Yanagi, Hikaru Mikami, Hayato Takeda, Hiroya Hasegawa, Yuka Toyama, Shunsuke Ikuma, Yoshihiro Nishikawa, Suisen Takasaki, Tatsuro Hayashi, Yukihiro Kondo
Journal: Journal of Clinical Oncology (2021)

473 Background: Even today, when several immune checkpoint Inhibitors have been approved for the treatment of metastatic urothelial cancer (mUC), cytotoxic chemotherapy (CTC) still remains the mainstay for first-line treatment. We believe that the prognostic factors for the first-line CTC have become more important again and need to be re-analyzed. Current guidelines do not yet provide recommendations for any serum tumor markers in patients with mUC. Previous studies have shown that serum cytokeratin 19 fragments levels (sCK) were correlated with depth of tumor invasion and metastatic burden in patients with bladder cancer. In this study we evaluated whether sCK, and other clinical parameters could predict overall survival (OS) in patients with mUC treated with CTC. Methods: Two hundreds fifty two patients with mUC received CTC from December 2006 to 2016 at our institution. sCK had been measured in 128 patients at diagnosis of mUC. OS rate were analyzed by Kaplan–Meier curves and log–rank test. Multivariate analysis was carried out using the Cox hazards model. Tumor burden (TB) was measured based on Response Evaluation Criteria In Solid Tumor (version 1.1). Results: Of 128 patients, with median age of 72 (44-93), 36 (28%) had lung metastasis, 11 (9%) had bone metastasis, 10 (8%) had liver metastasis (LM). Ninety five (74%) patients received platinum based chemotherapy as a first-line treatment. During the median follow-up period of 19 (1-89) months, 72 patients (70%) had died. A 1-year (1y) OS was 51% and a 2y-OS was 36%. On univariate analysis, performance status (PS) (HR2.0, p&lt;0.005), sCK (HR3.9, p&lt;0.001), CRP (HR4.0, p&lt;0.001), neutrophil-lymphocyte ratio (HR1.9, p&lt;0.049), LM (HR2.0, p=0.042) and TB (HR2.4, p&lt;0.001) were the significant prognostic factors for OS. On multivariate analysis, PS (HR2.0, 95%CI (1.05-3.85) p=0.036 ), sCK (HR3.1, 95%CI (1.3-8.3), p=0.011), and LM (HR3.0, 95%CI (1.06-6.98), p=0.022) were the independent prognostic factors for OS. Based on these 3 factors we divided patients into three groups, good risk (G, 0 factor), intermediate risk (I, 1 factor) and poor risk (P, 2-3 factors). There was a significant difference between the three groups. (G vs I: p&lt;0.001, I vs P: p=0.001). Conclusions: PS, sCK, and LM were the independent prognostic factors for OS in patients with mUC receiving CTC. For the patients in good or intermediate risk with this score, early exposure of ICIs should be performed after CTCs. Treatment strategy should be changed in patients with poor risk since CTC is primary refractory in such population.