tbuckley/cabot-search huggingface dataset:
Smoking status and PD-L1 mRNA-expression as a predictor of response to neoadjuvant chemotherapy in patients diagnosed with muscle invasive bladder cancer.
Authors: Moritz Reike, Hendrik Juette, Ralph Wirtz, Philipp Erben, Karl Tully, Markus Eckstein, Veronika Weyerer, Arndt Hartmann, Maximilian Kriegmair, Felix Wezel, Christian Bolenz, Andrea Tannapfel, Joachim Noldus, Florian Roghmann
Journal: Journal of Clinical Oncology (2020)

530 Background: Patients with muscle-invasive bladder cancer (MIBC) that underwent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) show improved overall survival. Patients with a pathological complete response (pCR) usually have the best prognosis. In the literature, impaired response to immune checkpoint therapy has been reported in active smokers. The aim of our study was to examine the association of smoking status with pCR at RC after NAC. Moreover, we investigated the interaction of smoking status and Programmed Death Ligand 1 (PD-L1) mRNA expression at transurethral resection (TUR) and pCR prediction at RC after NAC. Methods: Clinical Data and formalin fixed paraffin embedded tumor tissue samples from TUR and RC of 49 patients with MIBC were retrospectively analyzed. Using RT-PCR PD-L1 mRNA expression was measured in 40-∆C t values and normalized against the control gene CALM2. Smoking status was defined as never, former and active. After NAC, RC was performed and the specimens were evaluated for pCR, defined as ypT0N0M0. Statistical analyses comprised nonparametric and chi 2 testing, partition models and spearman correlation analyses. Results: The study cohort had a median age of 63 years and consisted of 38/49 (78%) males. Regarding smoking status 11/49 (22%) were never, 17/49 (35%) were former and 21/49 (43%) were active smokers. After NAC, 17/49 patients (35%) had a pCR. Never/former smokers did not show a higher rate of pCR compared to active smokers (43%vs.24%, p=0.16). Comparing smoking status (never/former vs. active smokers) within the subgroup showing high PD-L1 expression (≥32.1∆C t ), a higher rate of pCR was found in never/former smokers (58% vs. 25%, p=0.047). Conclusions: Never and former smokers with MIBC that show high PD-L1 mRNA expression patterns are more likely to show pCR at RC after NAC. Smoking cessation is important for the management of MIBC patients undergoing NAC and RC.
Prognostic value of epithelial-mesenchymal transition markers in clear cell renal cell carcinoma.
Authors: Yuan-Yuan Qu, Xi Tian, Wenhao Xu, Aihemutaijiang Anwaier, Dingwei Ye, Hailiang Zhang
Journal: Journal of Clinical Oncology (2020)

739 Background: Epithelial-to-mesenchymal transition (EMT) in important in tumor invasiveness and metastasis. We aimed to determine prognostic value of six key EMT markers (CDH1, CDH2, SNAI1, SNAI2, VIM, TWIST1) in clear cell renal cell carcinoma (ccRCC). Methods: A total of 533 ccRCC patients with RNASeq data from The Cancer Genome Atlas (TCGA) cohort were included for analysis. Gene expression of these EMT markers was compared between tumor and normal tissues based on Oncomine database and TCGA cohort. Their correlations with progression-free survival (PFS) and overall survival (OS) were also examined in both TCGA cohort and FUSCC (Fudan University Shanghai Cancer Center) cohort. Cox proportional hazards regression model and Kaplan-Meier plot were used to assess the relative factors. Functional enrichment analyses were utilized to describe biologic function annotations and significantly involved hallmarks pathways of each gene. Results: We found that Epithelial marker, CDH1 expression was lower, while mesenchymal markers (CDH2, SNAI1, VIM, TWIST1) expression was higher in ccRCC primary tumors. In the TCGA cohort, we found that patients with higher expression of VIM, TWIST1 or lower expression of CDH1 had worse prognosis. Further, in the FUSCC cohort, we confirmed the predictive ability of mesenchymal markers and epithelial marker expression in PFS and OS of ccRCC patients. After generating Cox regression models, EMT markers (CDH1, SNAI1, VIM, and TWIST1) were independent prognostic factors of both PFS and OS in ccRCC patients. Conclusions: Our preliminary EMT prediction model can facilitate further screening of EMT biomarkers and cast a better understanding of EMT gene function in ccRCC.
Role of miR-449 family on doxorubicin-based chemotherapy response in triple-negative breast cancer
Authors: E. Tormo Martin, A. Adam-Artigues, I. Garrido-Cano, B. Pineda Merlo, B. Pattanayak, P. Cabello, J. Albanell, F. Rojo, A. Lluch, P. Eroles
Journal: Annals of Oncology (2018)

Background: microRNAs (miRNAs) emerge as a new step in the modulation of breast cancer response to treatment. The family of microRNAs 449 has been described as strong inducers of cell cycle arrest (including senescence) and apoptosis in distinct tumor types. The aim of this work is to analyse the miR-449 role in doxorubicin chemotherapy-based treatment of triple-negative breast cancer (TNBC). Methods: Experiments were made on MDA-MB-231 and MDA-MB-231R (doxorubicin resistant) triple-negative breast cancer cells. Signature of miRs-449 and their target expression was measured by real time PCR and western blot. Functional and molecular studies of loss/gain of function and response to treatment were carried out trough transient transfection of miRNAs mimics/inhibitors. Functional studies included Cell Proliferation Studies (MTT/Colony Formation Assay), Viability, Apoptosis and Cell cycle (Flow Cytometry), Invasion and Metastasis (Wound healing/Migration-Invasion Chambers). Results: Through bioinformatic tools, we obtained the promoter sequence of the miR-449/CDC20B gene, emerging as a "hot spot", since it presented mutations, copy number variation (CVN), simple nucleotide polymorphisms (SNPs), and methylation. We also identified targets of this miRNAs family related to cancer pathways. Through in vitro studies, we obtained results of differential expression of miRs-449 between MDA-MB-231 and MDA-MB-231R treated with doxorubicin. In loss/gain of miR-449 function studies, we verified the modulation of some of their targets, and their impact on viability and on the cell cycle. Ex vivo studies have confirmed the positive correlation of the expression of the inducer factor of miRs-449, E2F1, with the sensitivity to doxorubicin treatment in triple-negative breast cancer patients. Using the KM Plotter-miRPower software, we have been able to correlate the overexpression of the CDC20B gene and the miR-449 with a higher probability of survival in breast cancer patients. Conclusions: Results reveal for the first time the involvement of the miRNA-449 family in TNBC doxorubicin resistance, and suggest that regulation of its target genes, may be the mechanism behind their involvement. Legal entity responsible for the study: INCLIVA Biomedical Research Institute. Funding: CIBERONC / INCLIVA. Disclosure: All authors have declared no conflicts of interest.
High-dose vitamin C enhances cancer immunotherapy
Authors: Alessandro Magrì, Giovanni Germano, Annalisa Lorenzato, Simona Lamba, Rosaria Chilà, Monica Montone, Vito Amodio, Tommaso Ceruti, Francesco Sassi, Sabrina Arena, Sergio Abrignani, Maurizio D’Incalci, Massimo Zucchetti, Federica Di Nicolantonio, Alberto Bardelli
Journal: Science Translational Medicine (2020)

Vitamin C promotes anticancer adaptive immunity and enhances efficacy of immune checkpoint therapy.
Peak Concentrations of Ustekinumab After Intravenous Induction Therapy Identify Patients With Crohn’s Disease Likely to Achieve Endoscopic and Biochemical Remission
Authors: Jurij Hanžel, Jurij Zdovc, Tina Kurent, Nejc Sever, Katarina Javornik, Katja Tuta, Matic Koželj, Nataša Smrekar, Gregor Novak, Borut Štabuc, Erwin Dreesen, Debby Thomas, Tomaž Vovk, Iztok Grabnar, David Drobne
Journal: Clinical Gastroenterology and Hepatology (2020)
Abstract 15804: Feasibility of Magnetic Resonance Imaging in Patients With Cardiac Implantable Electronic Devices With Epicardial or Abandoned Leads
Authors: Lindsey Gakenheimer-Smith, Susan Etheridge, Zhining Ou, Angela Presson, Patricia Whitaker, Jason Su, Michael Puchalski, Sarah Y Asaki, Mary Niu, Thomas Pilcher
Journal: Circulation (2018)

Introduction: Recent guidelines approved MRI scans in adult patients with a cardiovascular implantable electronic device (CIED). However, guidelines excluded pediatric patients or patients with epi...
A deep learning algorithm to predict coexisting metastatic disease using intraprostatic [F18]DCFPYL PSMA image alone in veterans with prostate cancer.
Authors: Nicholas George Nickols, Aseem Anand, Karl Sjöstrand, Lida Jafari, John Ceccoli, Tess Lin, Jens Richter, Matthew Rettig
Journal: Journal of Clinical Oncology (2020)

25 Background: [F18]DCFPyL (PyL) is a PSMA targeted imaging agent for prostate cancer. Independent of manual feature selection, a deep learning algorithm might offer additional insight into the disease biology. We explored the performance of a deep learning algorithm on PyL images of the primary tumor to predict co-existing distant metastases. Methods: 74 veterans with high risk primary prostate cancer tumors were imaged with both PyL PSMA PET/CT and conventional imaging (bone scan and CT or MRI of the abdomen/pelvis). 26% were confirmed with metastatic disease (M1) by conventional imaging. The PyL images of the primary tumor were analyzed with EXINI’s PyL-AI algorithm. Location of the prostate was defined on low dose CT via automatic segmentation using a deep convolutional network. The segmentations were used to map the PyL PET image of the prostate. The image based PyL-AI model was made up of a Conv3D layer of 4 kernels, a Conv3D layer of 8 kernels, a dense layer of 64 nodes followed by a final dense layer with 2 nodes. The model training was performed on the images using 5-fold cross validation with non-overlapping validation sets. The test predictions were compared with ground truth (M1); the area under ROC curve (AUC) was computed to determine the performance of the model in predicting the presence of distant metastases. A logistical regression model from baseline clinicopathologic features of the primary tumor (baseline PSA, biopsy gleason score, percent cores positive, T stage) was created as a comparator. Results: The logistical regression model using clinicopathologic features had an AUC of 0.71, while the PyL-AI model based on intra-prostatic PyL Images alone had an AUC of 0.81 for prediction of metastatic disease as defined by conventional imaging. Adding clinical parameters in the image based PyL-AI model incrementally increased the AUC to 0.82. Conclusions: The image based PyL-AI deep learning model demonstrates a higher predictive accuracy over the logistic model using classical clinicopathologic features. The study is hypothesis generating observation that needs prospective validation in an independent data set.
Role of Forced oscillation technique for asthma diagnosis in preschool wheeze
Authors: Pailin Yooma, Wiparat Manuyakorn, Suwat Benjaponpitak, Wasu Kamchaisatian, Watcharoot Kanchongkittiphon, Wanlapa Jotikasthira, Cherapat Sasisakulporn, Potjanee Kiewngam
Journal: Journal of Allergy and Clinical Immunology (2020)
A Novel Splice Variant of HYAL-4 Drives Malignant Transformation and Predicts Outcome in Patients with Bladder Cancer
Authors: Vinata B. Lokeshwar, Daley S. Morera, Sarrah L. Hasanali, Travis J. Yates, Marie C. Hupe, Judith Knapp, Soum D. Lokeshwar, Jiaojiao Wang, Martin J.P. Hennig, Rohitha Baskar, Diogo O. Escudero, Ronny R. Racine, Neetika Dhir, Andre R. Jordan, Kelly Hoye, Ijeoma Azih, Murugesan Manoharan, Zachary Klaassen, Sravan Kavuri, Luis E. Lopez, Santu Ghosh, Bal L. Lokeshwar
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Poor prognosis of patients with muscle-invasive bladder cancer that often metastasizes drives the need for discovery of molecular determinants of bladder cancer progression. Chondroitin sulfate proteoglycans, including CD44, regulate cancer progression; however, the identity of a chondroitinase (Chase) that cleaves chondroitin sulfate from proteoglycans is unknown. HYAL-4 is an understudied gene suspected to encode a Chase, with no known biological function. We evaluated HYAL-4 expression and its role in bladder cancer. Experimental Design: In clinical specimens, HYAL-4 wild-type (Wt) and V1 expression was evaluated by RT-qPCR, IHC, and/or immunoblotting; a novel assay measured Chase activity. Wt and V1 were stably expressed or silenced in normal urothelial and three bladder cancer cell lines. Transfectants were analyzed for stem cell phenotype, invasive signature and tumorigenesis, and metastasis in four xenograft models, including orthotopic bladder. Results: HYAL-4 expression, specifically a novel splice variant (V1), was elevated in bladder tumors; Wt expression was barely detectable. V1 encoded a truncated 349 amino acid protein that was secreted. In bladder cancer tissues, V1 levels associated with metastasis and cancer-specific survival with high efficacy and encoded Chase activity. V1 cleaved chondroitin-6-sulfate from CD44, increasing CD44 secretion. V1 induced stem cell phenotype, motility/invasion, and an invasive signature. CD44 knockdown abrogated these phenotypes. V1-expressing urothelial cells developed angiogenic, muscle-invasive tumors. V1-expressing bladder cancer cells formed tumors at low density and formed metastatic bladder tumors when implanted orthotopically. Conclusions: Our study discovered the first naturally-occurring eukaryotic/human Chase and connected it to disease pathology, specifically cancer. V1-Chase is a driver of malignant bladder cancer and potential predictor of outcome in patients with bladder cancer.
Sequential Targeted Therapy Following Pazopanib (PZ) in Patients (PTS) with Metastatic Renal Cell Cancer (MRCC): Efficacy and Toxicity
Authors: F. Pons Valladares, T.K. Choueiri, T.E. Hutson, T.B. Powles, C. Porta, S. Bracarda, M.E. Lampron, L. Cerbone, C.N. Sternberg, J. Bellmunt
Journal: Annals of Oncology (2012)
Urological malignancy incidence rates over time by county rurality.
Authors: Adam John Gadzinski, John L. Gore, Anobel Y. Odisho, Sima P. Porten, Peter Carroll, Matthew R. Cooperberg
Journal: Journal of Clinical Oncology (2020)

750 Background: Approximately 20% of the U.S. population resides in non-metropolitan (rural) areas. We aimed to evaluate urological cancer incidence among populations residing in metropolitan (metro) and rural counties, categorized by adjacency to a metro area. Methods: Using data from CDC’s National Program of Cancer Registries and NCI’s Surveillance, Epidemiology, and End Results Program, we compared incidence rates of prostate (PCa), kidney (KCa), and bladder (BCa) cancers diagnosed during 2007–2011 and 2012–2016 among adults age ≥ 20 years residing in metro and rural counties, as designated by rural-urban continuum codes. Rural counties were divided into those adjacent to a metro area (Rural-A) and those not adjacent to a metro area (Rural-NA). For the time period studied, these data cover approximately 97% of the US population. Rates were age-adjusted to the 2000 U.S. standard population. Results: We identified 1,980,168 PCa, 541,225 KCa, and 688,562 BCa cases newly diagnosed during 2007–2016. Patients from rural-A counties comprised 11% of all cases, rural-NA counties 6%, and metro counties 83%. Table shows the age-adjusted incidence per 100,000 with 95% confidence intervals. Overall, PCa and BCa incidence decreased over time; KCa incidence increased. PCa exhibited higher incidence rates in metro areas; KCa and BCa had higher incidence rates in rural counties (Table). Conclusions: Rural counties have higher BCa and KCa incidence relative to metro counties, but lower PCa incidence. Changes in PCa screening practices may have contributed to decreases in PCa incidence. Further investigation is needed to understand how rurality influences KCa and BCa epidemiology. Disclaimer: The findings and conclusion of this report are those of the authors and do not represent the official position of the CDC.[Table: see text]
Endoscopic extraction of a special foreign body impacted in the colon
Authors: Yilong Feng, Nianhong Wu, Liansong Ye, Xianglei Yuan, Bing Hu
Journal: Endoscopy (2020)

A 22-year-old man was admitted to the emergency department reporting insertion of a long foreign body into his anus 6 hours previously. Physical examination showed no signs of peritonitis. An abdominal computed tomography (CT) scan showed the foreign body in the descending colon and proximal rectum, with no signs of perforation ([Fig. 1]). Emergent endoscopy was performed and showed that the foreign body was 35 cm from the anus and completely obstructing the bowel lumen ([Fig. 2]).
The Diagnostic Utility of IgE to Ses i 1 Singly, and In Combination with Basophil Activation and Skin Prick Testing For the Diagnosis Of Sesame Food Allergy.
Authors: Michael Goldberg, Michael Appel, Liat Nachshon, Po Hsuan Huang, Naama Epstein-Rigbi, Michael Levy, Jonas Lidholm, Arnon Elizur
Journal: Journal of Allergy and Clinical Immunology (2020)
Hierarchical Bayesian modeling to evaluate the impacts of intelligent speed adaptation considering individuals’ usual speeding tendencies: A correlated random parameters approach
Authors: Kojiro Matsuo, Mitsuru Sugihara, Motohiro Yamazaki, Yasuhiro Mimura, Jia Yang, Komei Kanno, Nao Sugiki
Journal: Analytic Methods in Accident Research (2020)

Although there have been a large number of short- and long-term field trials and driving simulator-based studies on intelligent speed adaptation (ISA), there are a limited number of methods for evaluating the impact of ISA. In particular, appropriately evaluating the impacts of ISA through field trials requires the consideration of a number of factors related to detailed road characteristics. In addition, because of the "target speed" features of ISA itself, it is necessary to consider the usual speeding tendencies of individual drivers to avoid underestimating the impact of the ISA. In this study, a hierarchical Bayesian model with correlated random effects was developed to examine the impact of ISA on driver speed based on the driver's typical speeding tendency and road characteristic conditions as confounding factors. The model was applied to clarify and compare the impacts of informative and incentive ISAs on community streets with a 30 km/h speed limit ("Zone 30") based on data collected in a field trial. The modeled effects of many road characteristics were found to match intuitive expectations, suggesting that they were well-controlled in our assessment of the ISAs' impacts. It was also confirmed that the incentive ISA had a large speed reduction effect on the behavior of drivers who tended to speed, while the informative ISA did not. In particular, although the impact of the incentive ISA on all drivers was only 2 km/h greater on average than that of the informative ISA, the impact of the incentive ISA on drivers who tended to speed was 7 km/h greater than that of the informative ISA when correlated random effects were considered.
Lung Fibrosis is induced in Adarb1 transgenic mice via HuR induced CTGF signaling
Authors: Ramani Soundararajan, Sai Manasa Varanasi, Sahebgowda Patil, Helena Hernandez-Cuervo, Alexander Czachor, Adeeb Bulkhi, Sriraja Srinivas, Jutaro Fukumoto, Matthew Alleyn, Lakshmi Galam, Richard Lockey, Narasaiah Kolliputi
Journal: Journal of Allergy and Clinical Immunology (2020)
Chromosome 21 gain is dispensable for transient myeloproliferative disorder driven by a novel GATA1 mutation
Authors: Julius Lukes, Petr Danek, Oriol Alejo-Valle, Eliska Potuckova, Ondrej Gahura, Dirk Heckl, Julia Starkova, Jan Stary, Ester Mejstrikova, Meritxell Alberich-Jorda, Jan Zuna, Jan Trka, Jan-Henning Klusmann, Marketa Zaliova
Journal: Leukemia (2020)
Transcriptomic profiling as proof of concept for investigation of collecting duct carcinoma (CDC).
Authors: Giuseppe Procopio, Elena Verzoni, Pierangela Sepe, Alessia Mennitto, Melanie Claps, Valentina Guadalupi, Marco Stellato, Emma Zattarin, Filippo G. De Braud, Marialuisa Sensi, Chiara Gargiuli, Matteo Dugo
Journal: Journal of Clinical Oncology (2020)

714 Background: Collecting duct carcinoma is a rare, highly aggressive and molecularly uncharacterized kidney disease with poor outcome. To date, no standard therapies are available and treatment choice is based on retrospective data. Identifying molecular features of this tumor could provide a biologic rationale for novel targeted systemic therapies. Methods: Total RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissues of 6 CDCs, 5 clear cell renal carcinomas (ccRCCs) and 4 adjacent normal tissues. Samples were profiled by GeneChip Human Transcriptome Array 2.0 (Affymetrix) and constituted the Istituto Nazionale dei Tumori (INT) dataset. Data were pre-processed using the robust multi-array average method and differentially expressed genes were identified according to the limma pipeline. Genes with a false discovery rate &lt; 0.25 were selected. Pathway analysis was performed by gene set enrichment analysis (GSEA), single sample (ss) GSEA, DAVID Bioinformatics Resources 6.8 and Pathfinder Bioconductor package. Moreover, a list of genes representing angiogenesis and immune biology, previously used in the IMmotion150 study, was chosen to explore further functional subcategories of CDC. Available RNA-Seq data of 7 CDCs and 5 matched normal tissue from GSE89122 dataset were used for validation. Results: Comparison of transcriptome profiles of CDCs and ccRCCs versus normal tissue led to the identification of a core of 14 genes specifically up-regulated in CDC, 5 of which (SFN, S100A11, CKAP5, CDH1 and CD44) were significantly involved in extracellular matrix organization. Other deregulated genes were related to immune system, cell cycle progression, glucose and pentose phosphate metabolism and EGFR-signaling. In addition, ssGSEA permitted to identify two major distinct biological subgroups in CDC of both INT and GSE89122 datasets, based on relative expression levels of angiogenesis and immune genes. Conclusions: Our study reveals novel insights into the biology and heterogeneity of CDCs. Although further validation using larger samples is needed, the current findings suggest that this heterogeneity could have clinical implications for the treatment of patients with this rare kidney cancer.
Publisher Correction: Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma
Authors: Richard P. Koche, Elias Rodriguez-Fos, Konstantin Helmsauer, Martin Burkert, Ian C. MacArthur, Jesper Maag, Rocio Chamorro, Natalia Munoz-Perez, Montserrat Puiggròs, Heathcliff Dorado Garcia, Yi Bei, Claudia Röefzaad, Victor Bardinet, Annabell Szymansky, Annika Winkler, Theresa Thole, Natalie Timme, Katharina Kasack, Steffen Fuchs, Filippos Klironomos, Nina Thiessen, Eric Blanc, Karin Schmelz, Annette Künkele, Patrick Hundsdörfer, Carolina Rosswog, Jessica Theissen, Dieter Beule, Hedwig Deubzer, Sascha Sauer, Joern Toedling, Matthias Fischer, Falk Hertwig, Roland F. Schwarz, Angelika Eggert, David Torrents, Johannes H. Schulte, Anton G. Henssen
Journal: Nature Genetics (2020)
Covid-19: Italy confirms 11 deaths as cases spread from north
Authors: Michael Day
Journal: BMJ (2020)

Covid-19: Italy confirms 11 deaths as cases spread from northMichael Day London Confirmed cases of covid-19 in Italy leapt by 45% to reach 322 on 25 February, and four more deaths were confirmed amid signs that the infection was spreading around the country and across borders.New cases in Italy were reported in central Tuscany, the coastal region of Liguria, and Sicily in the south.Officials confirmed that the national death toll was now 11.Authorities in Austria and Croatia also reported their first cases of covid-19 and said that the patients affected had recently travelled from Italy's Lombardy region, confirming fears that travellers were starting to carry the infection from its European epicentre.An Italian couple from the north of Italy tested positive on the Spanish island of Tenerife, forcing the quarantine of their hotel.Despite these developments health ministers from France, Germany, Italy, and the EU Commission said that borders with Italy would remain open for now.