tbuckley/cabot-search huggingface dataset:
Targeted Metabolic Reprogramming to Improve the Efficacy of Oncolytic Virus Therapy
Authors: Barry E. Kennedy, Maryanne Sadek, Shashi A. Gujar
Journal: Molecular Therapy (2020)

Oncolytic viruses (OVs) represent a promising new class of cancer therapeutics and cause antitumor effects by two major mechanisms: (1) directly killing cancer cells in a process known as oncolysis, or (2) initiating a powerful antitumor immune response. Interestingly, energy metabolism, within either cancer cells or immune cells, plays a pivotal role in defining the outcome of OV-mediated antitumor effects. Following therapeutic administration, OVs must hijack host cell metabolic pathways to acquire building blocks such as nucleotides, lipids, and amino acids for the process of replication that is necessary for oncolysis. Additionally, OV-stimulated antitumor immune responses are highly dependent on the metabolic state within the tumor microenvironment. Thus, metabolic reprogramming strategies bear the potential to enhance the efficacy of both OV-mediated oncolysis and antitumor immune responses.
PERIPHERAL VERSUS CENTRAL ACCESS FOR ALTERNATIVE ACCESS TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR): RESULTS FROM THE TVT REGISTRY
Authors: Tsuyoshi Kaneko, Farhang Yazdchi, Sameer Hirji, Marc Pelletier, Piotr Sobieszczyk, Charles B. Nyman, Douglas Shook, Yee-Ping Sun, Alice Kim, David J. Cohen, Amanda Stebbins, Michel Zeitouni, Sreekanth Vemulapalli, Vinod H. Thourani, Pinak Shah, Patrick T. O'Gara
Journal: Journal of the American College of Cardiology (2020)
Alternative therapies in academic medical centers compromise evidence-based patient care
Authors: Donald M. Marcus
Journal: Journal of Clinical Investigation (2020)

During the past 20 years, integrative medicine centers that promote the use of alternative therapies were established in more than 70 medical and nursing schools.A survey of hospital websites and interviews with physicians, hospital administrators, and staff revealed that 15 research-intensive medical schools in the United States provide alternative therapies in their integrative medicine centers and affiliated hospitals (1).The treatments are claimed to provide benefits for a broad spectrum of diseases, including heart disease, cancer, digestive disorders, pain, autism, and autoimmune disorders.Duke Integrative Medicine offers acupuncture for treatment of 21 conditions, including rheumatoid arthritis, stroke, and essential hypertension.Johns Hopkins offers reiki therapy in which "the practitioner seeks to transmit Universal Life Energy to the client" (1).Hospital administrators state that they provide alternative therapies in response to consumer interest and that, even if those services don't generate profits, they build the hospitals' market share (1).A recent article addressed the challenges of medical education in the era of alternative facts and the increasing use of social media to obtain information (2).It noted that medical educators should be "guiding our students past the barrage of misleading signals."Unfortunately, some of those misleading signals about the safety and efficacy of alternative therapies are coming from medical educators in integrative medicine centers.
AORTIC PLAQUE PROGRESSION IN PATIENTS TREATED WITH IMMUNE CHECKPOINT INHIBITORS
Authors: Lili Zhang, Jana Taron, Zsofia Drobni, Raza Alvi, Amna Zafar, Adam Rokicki, Thomas Mayrhofer, Tomas G. Neilan, Udo Hoffmann
Journal: Journal of the American College of Cardiology (2020)
Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (PET-Plan): a multicentre, open-label, randomised, controlled trial
Authors: Ursula Nestle, Tanja Schimek-Jasch, Stephanie Kremp, Andrea Schaefer-Schuler, Michael Mix, Andreas Küsters, Marco Tosch, Thomas Hehr, Susanne Martina Eschmann, Yves-Pierre Bultel, Peter Hass, Jochen Fleckenstein, Alexander Thieme, Marcus Stockinger, Karin Dieckmann, Matthias Miederer, Gabriele Holl, H Christian Rischke, Eleni Gkika, Sonja Adebahr, Jochem König, Anca-Ligia Grosu, A L Grosu, W Weber, P Meyer, H Hoffmanns, U Nestle, R Aurisch, W Schäfer, T Hehr, S M Eschmann, W Dornoff, B Siekmeyer, L Trampert, G Gademann, T Brunner, A Amthauer, J Ricke, M Pech, C Rübe, C M Kirsch, S Ezzidin, H Schmidberger, M Schreckenberger, M Bamberg, D Zips, R Bares, C La Fougere, V Budach, W Brenner, M Beck, R Freiherr von Gumppenberg, D Aebersold, T Krause, H J Feldmann, A Hertel, G Stüben, J Sciuk, H Annweiler, G Holl, W Oehler, I Schlöcker, R Baum, B Kimmig, J Dunst, E Henze, U Lützen, M Schwaiger, K Strehle, W Alberti, M Piroth, M Tosch, R Pötter, J Widder, C Herold, U Freund, F Momm, W Weber, M L Sautter-Bihl, K Tatsch, G Hildebrandt, B Krause
Journal: The Lancet Oncology (2020)
Correction to ‘Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF’ [J Hepatol 2020 (72) 688–701]
Authors: Richard Moreau, Joan Clària, Ferran Aguilar, François Fenaille, Juan José Lozano, Christophe Junot, Benoit Colsch, Paolo Caraceni, Jonel Trebicka, Marco Pavesi, Carlo Alessandria, Frederik Nevens, Faouzi Saliba, Tania M. Welzel, Agustin Albillos, Thierry Gustot, Javier Fernández, Christophe Moreno, Maurizio Baldassarre, Giacomo Zaccherini, Salvatore Piano, Sara Montagnese, Victor Vargas, Joan Genescà, Elsa Solà, William Bernal, Noémie Butin, Thaïs Hautbergue, Sophie Cholet, Florence Castelli, Christian Jansen, Christian Steib, Daniela Campion, Raj Mookerjee, Miguel Rodríguez-Gandía, German Soriano, François Durand, Daniel Benten, Rafael Bañares, Rudolf E. Stauber, Henning Gronbaek, Minneke J. Coenraad, Pere Ginès, Alexander Gerbes, Rajiv Jalan, Mauro Bernardi, Vicente Arroyo, Paolo Angeli
Journal: Journal of Hepatology (2020)
Correlation between marital status and adequate pap test screening among Canadian women: An analysis of sociodemographic factors from the Canadian community health survey, 2007–2008.
Authors: Patricia Moretto, Christina M. Canil, Johanne Ingrid Weberpals
Journal: Journal of Clinical Oncology (2012)

e15537 Background: Medical literature shows that marital status serves as an important factor which influences the likelihood of women undergoing cervical cancer screening. In Canada, women have universal access to health care as well as cancer screening facilities. This study was conducted to determine the association between adequate Pap test screening (APT) and marital status, stratified by age, and the prevalence of APT among the Canadian women. Methods: Data for the analysis were obtained from the Canadian Community Health Survey (CCHS), a national cross-sectional study, conducted during 2007 and 2008. The analysis included 22,530 women who were 18 to 69 years of age. The regression model used accounted for potential effect modification and confounders to assess the association between marital status (being married), and adequate cervical cancer screening (APT). Results: The weighted prevalence of APT was 75%, and was higher among married women (79%). The group with APT had a higher weighted prevalence of presence of a regular doctor, were white, had higher educational level and were non-obese, in comparison to the group with inadequate pap test (IPT). After adjusting for covariates, stratifying by age and weighting for the general population, married women, in the age groups 18-29 (RR 1.32, 95% CI 1.27;1.37), 40-49 (RR 1.07, 95% CI 1.03;1.12) and 60-69 years (RR 1.10, 95% CI 1.02;1.2) had a statistically significant increase in the risk of APT compared to non-married women. Conclusions: Marital status is associated with an increase in adequate Pap test screening in almost all age groups of the Canadian female population. This finding reinforces that providers of cancer screening services should target their efforts to improve the results among non-married women.
Use of gene expression signature to discriminate oropharyngeal cancers according to HPV16 status.
Authors: Haitham Mirghani, Catherine Ory, Nicolas Ugolin, Furrat Amen, Joel Guigay, Jean Lacau Saint Guily, Sylvie Chevillard, Roger Lacave
Journal: Journal of Clinical Oncology (2013)

6055 Background: Strong evidence supports the hypothesis that high-risk human papillomavirus (HPV), particularly HPV16, is a causative agent for an increasing subset of oropharyngeal squamous cell carcinomas (OPSCC). These tumors have distinct oncogenic mechanisms and a more favorable prognosis than tobacco induced OPSCC. Although these differences emphasize the need for a specific therapeutic approach, HPV status is still not used to guide treatment. A better understanding of the molecular profile related to HPV16 induced OPSCC may help to develop personalized treatments. Methods: To identify an HPV16-related molecular signature, we compared the gene expression profile of 15 transcriptionally active HPV16-positive and 15 HPV16-negative OPSCC. The study was conducted in two steps. First, a learning set of 16 OPSCC comprising 8 HPV16-positives and 8 HPV16-negatives OPSCC was analyzed in order to identify the signature. Potentially confounding factors of stage, sex and tobacco consumption were equally distributed in both groups. Secondarily, the robustness of this signature was further confirmed by blind case-by-case classification of an independent set of 14 OPSCC. Results: We identified a signature composed of 224 genes which discriminates HPV16-induced OPSCC from their tobacco induced counterparts. After the viral status was revealed, 13 out of 14 tumors were correctly classified according to tumor etiology, 1/14 was undetermined and none were misclassified. Interestingly, deregulated genes in HPV16-positive tumors are principally involved in innate immunity, in cell cycle regulation through the TP53/RB/E2F pathway, and autophagy through mTOR regulation. Well known targets of E6 and E7 proteins are also found to be deregulated. Conclusions: Our results demonstrate that a set of selected genes can distinguish OPSCC according to etiology. These genes shed light on HPV16 induced carcinogenesis since specific molecular pathways are deregulated. Further investigations are required for a better understanding of the differing natural histories and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HPV-related OPSCC.
LIMITED PROGNOSTIC ABILITY OF SPECT IN THE HEART TRANSPLANT POPULATION: ANALYSIS FROM A SINGLE LARGE-VOLUME CENTER
Authors: Jack Aguilar, Robert Miller, Balaji Tamarappoo, Sean W. Hayes, John Friedman, Piotr Slomka, Louise Thomson, Jignesh Patel, Jon A. Kobashigawa, Daniel S. Berman
Journal: Journal of the American College of Cardiology (2020)
CLINICAL IMPACT OF BLOOD UREA NITROGEN-BODY MASS INDEX RATIO IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE
Authors: Taichi Kato, Daisuke Abe, Hitoshi Hirano, Koichi Ohashi, Akira Takayama, Yoshiaki Yui, Norihiro Kuroki, Takao Yuba, Kou Suzuki
Journal: Journal of the American College of Cardiology (2020)
SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR COMPARED TO HIGH-SENSITIVITY TROPONIN, C-REACTIVE PROTEIN AND B-TYPE NATRIURETIC PEPTIDE IN PREDICTING OUTCOMES
Authors: Salim Hayek, Ayman Samman Tahhan, Anurag Mehta, Yi-An Ko, Ayman Alkhoder, Ravila Bhimani, Joy Hartsfield, Jonathan Kim, Leslee J. Shaw, Changli Wei, Jochen Reiser, Arshed A. Quyyumi
Journal: Journal of the American College of Cardiology (2020)
Topotecan (T) and carboplatin (C) in the treatment of platinum sensitive relapsed ovarian cancer (ROC): Results of a multicenter phase I/II study
Authors: D. Koensgen, A. Belau, P. Klare, T. Steck, O. Camara, H. Sommer, G. Oskay-Oezcelik, A. Coumbos, W. Lichtenegger, J. Sehouli
Journal: Journal of Clinical Oncology (2006)

5089 Background: Despite of the effectiveness of radical surgery and first-line chemotherapy, most patients (pts) with advanced ovarian cancer will relapse. Paclitaxel (P) in combination with C as second-line treatment improves the outcome of pts with platinum-sensitive ROC in comparison to C monotherapy. Due to polyneuropathy and alopecia this regimen can not be offered to all pts. Therefore, other platinum-combinations are required. We conducted a phase I/II study to define the dose limiting toxicities (DLT) and the tolerability of combination therapy with T and C. Methods: Pts with platinum-sensitive ROC and primary standard therapy were stratified according to treatment-free interval (TFI): 6–12 months (A) and ≥12 months (B). Following dose regimens were analysed: T 1mg/m 2 /d1–3 + C AUC5/d3 and T 0.75 mg/m 2 /d1–3 + C AUC5/d3, q21d. DLT was based on the first 4 courses and defined as: CTC grade 3/4 hematological and grade 2 non-hematological toxicity (excepted alopecia, vomiting), treatment delay &gt;7d. Primary endpoints were DLT and tolerability. Secondary endpoints were remission rate (RR) and progression-free survival (PFS). Results: From 06/04 to 08/05, 28 pts were enrolled, 26 pts (A:13 pts, B:13 pts) were eligible. Median age was 61.5 years. A total of 141 cycles were analysed, median number of cycles was 6 (range A:2–8, B:1–10). DLTs were: leucopenia (n = 5) and thrombocytopenia (n = 1). MTD was reached at dose: T: 0.75mg/m 2 and C: AUC5. Overall, grade 3/4 hematologic toxicities (in% of all cycles), for (A) and (B) respectively, were: anemia 4% vs. 4%, leucopenia 34% vs. 13%, neutropenia 30% vs. 31%, thrombocytopenia 7% vs. 6%. Febrile neutropenia 4.3% vs. 0%. Darbepoetin alfa was given in 13.5% of all cycles. Overall, grade 3/4 non-hematologic toxicities were infrequent (&lt; 5%). Overall RR (95% CI) was 50% (29.7–70.1) [A: 30.8% (0.1–61.1), B: 69.3% (38.7–90.9)]. Median follow-up was 5.8 mo, median PFS (95% CI) was 7.7 mo (1.3–9.4) [A: 6.2 (1.3–7.2), B: 8.0 (7.3–9.4)]. Median overall survival was not reached. Conclusions: TC is a feasible and effective chemotherapy regimen for platinum sensitive ROC. Tolerability is not associated to TFI. The recommended dose for subsequent studies is T:0.75 and C:AUC5. No significant financial relationships to disclose.
Antibacterial, Cytocompatible, Sustainably Sourced: Cellulose Membranes with Bifunctional Peptides for Advanced Wound Dressings
Authors: Ramon Weishaupt, Janina N. Zünd, Lukas Heuberger, Flavia Zuber, Greta Faccio, Francesco Robotti, Aldo Ferrari, Giuseppino Fortunato, Qun Ren, Katharina Maniura‐Weber, Anne Géraldine Guex
Journal: Advanced Healthcare Materials (2020)

Abstract Progressive antibiotic resistance is a serious condition adding to the challenges associated with skin wound treatment, and antibacterial wound dressings with alternatives to antibiotics are urgently needed. Cellulose‐based membranes are increasingly considered as wound dressings, necessitating further functionalization steps. A bifunctional peptide, combining an antimicrobial peptide (AMP) and a cellulose binding peptide (CBP), is designed. AMPs affect bacteria via multiple modes of action, thereby reducing the evolutionary pressure selecting for antibiotic resistance. The bifunctional peptide is successfully immobilized on cellulose membranes of bacterial origin or electrospun fibers of plant‐derived cellulose, with tight control over peptide concentrations (0.2 ± 0.1 to 4.6 ± 1.6 µg mm −2 ). With this approach, new materials with antibacterial activity against Staphylococcus aureus (log4 reduction) and Pseudomonas aeruginosa (log1 reduction) are developed. Furthermore, membranes are cytocompatible in cultures of human fibroblasts. Additionally, a cell adhesive CBP‐RGD peptide is designed and immobilized on membranes, inducing a 2.2‐fold increased cell spreading compared to pristine cellulose. The versatile concept provides a toolbox for the functionalization of cellulose membranes of different origins and architectures with a broad choice in peptides. Functionalization in tris‐buffered saline avoids further purification steps, allowing for translational research and multiple applications outside the field of wound dressings.
Hepatitis B Virus–Telomerase Reverse Transcriptase Promoter Integration Harnesses Host ELF4, Resulting in Telomerase Reverse Transcriptase Gene Transcription in Hepatocellular Carcinoma
Authors: Karen Man‐Fong Sze, Daniel Wai‐Hung Ho, Yung‐Tuen Chiu, Yu‐Man Tsui, Lo‐Kong Chan, Joyce Man‐Fong Lee, Kenneth Siu‐Ho Chok, Albert Chi‐Yan Chan, Chung‐Ngai Tang, Victor Wai‐Lun Tang, Irene Lai‐Oi Lo, Derek Tsz‐Wai Yau, Tan‐To Cheung, Irene Oi‐Lin Ng
Journal: Hepatology (2020)

Background and Aims Hepatitis B virus (HBV) integrations are common in hepatocellular carcinoma (HCC). In particular, alterations of the telomerase reverse transcriptase ( TERT ) gene by HBV integrations are frequent; however, the molecular mechanism and functional consequence underlying TERT HBV integration are unclear. Approach and Results We adopted a targeted sequencing strategy to survey HBV integrations in human HBV‐associated HCCs (n = 95). HBV integration at the TERT promoter was frequent (35.8%, n = 34/95) in HCC tumors and was associated with increased TERT mRNA expression and more aggressive tumor behavior. To investigate the functional importance of various integrated HBV components, we employed different luciferase reporter constructs and found that HBV enhancer I (EnhI) was the key viral component leading to TERT activation on integration at the TERT promoter. In addition, the orientation of the HBV integration at the TERT promoter further modulated the degree of TERT transcription activation in HCC cell lines and patients’ HCCs. Furthermore, we performed array‐based small interfering RNA library functional screening to interrogate the potential major transcription factors that physically interacted with HBV and investigated the cis‐activation of host TERT gene transcription on viral integration. We identified a molecular mechanism of TERT activation through the E74 like ETS transcription factor 4 (ELF4), which normally could drive HBV gene transcription. ELF4 bound to the chimeric HBV EnhI at the TERT promoter, resulting in telomerase activation. Stable knockdown of ELF4 significantly reduced the TERT expression and sphere‐forming ability in HCC cells. Conclusions Our results reveal a cis‐activating mechanism harnessing host ELF4 and HBV integrated at the TERT promoter and uncover how TERT HBV‐integrated HCCs may achieve TERT activation in hepatocarcinogenesis.
TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH SEVERE AORTIC STENOSIS IS ASSOCIATED WITH IMPROVED RIGHT VENTRICULAR SYSTOLIC FUNCTION AND PULMONARY ARTERY PRESSURES
Authors: Andreas Kyvernitakis, Mahmoud Elsayed, Garima Dahiya, Andrew Begg, Robert Biederman, Amresh Raina, Mark Doyle, Stephen Bailey, David Lasorda, Raymond Benza
Journal: Journal of the American College of Cardiology (2020)
VERTEBRAL ARTERY TORTUOSITY IS A BIOMARKER FOR ARTERIAL EVENTS IN CHILDREN AND YOUNG ADULTS WITH VASCULAR EHLERS-DANLOS SYNDROME
Authors: Sara Stephens, Sherene Shalhub, Nicholas Dodd, Seitaro Oda, Kalyan Kancheria, Tam Doan, Justin Weigand, Justin P. Zachariah, Federico M. Asch, Taylor Beecroft, Alana Cecchi, Teniola Shittu, Liliana Preiss, Scott A. Lemaire, Richard B. Devereux, Reed E. Pyeritz, Kathryn W. Holmes, Mary J. Roman, Ronald V. Lacro, Ralph Shohet, Rajesh Krishnamurthy, Kim Eagle, Peter H. Byers, Dianna M. Milewicz, Shaine A. Morris
Journal: Journal of the American College of Cardiology (2020)
EVIDENCE OF FIXED ISTHMUS BOUNDARIES FOR HUMAN REENTRY DURING SINUS RHYTHM:VALUE OF DIFFERENTIAL PACING WITH IMPLICATIONS FOR CATHETER ABLATION OF VENTRICULAR TACHYCARDIA
Authors: Takuro Nishimura, Michael Raiman, Dalise Shatz, Gaurav Upadhyay, Zaid Aziz, Andrew D. Beaser, Hemal M. Nayak, Roderick Tung
Journal: Journal of the American College of Cardiology (2020)
The utility of PET scanning in colorectal cancer liver metastases being considered for surgery.
Authors: Jeffri R. M. Ismail, Ciara Marie Kelly, Marian Hanrick, Cara Regan Downey, Lauragh McCarthy, Aine O'Reilly, Peter MacEneaney, Michael William Bennett, Kevin N. O'Regan, Erica Mulvihill, Adrian O'Sullivan, Criostoir O Suilleabhain, John McCaffrey, Seamus O'Reilly, Derek Gerard Power
Journal: Journal of Clinical Oncology (2013)

e14519 Background: Liver resection remains the only potentially curative option for a subset of patients with colorectal cancer liver metastases (CRCLM). Preoperative imaging used to determine resectability includes computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). The objective of this study was to determine the utility of PET scanning for potentially resectable CRCLM. Methods: We retrospectively reviewed a prospectively maintained database for all patients considered for resection of CRCLM from July 2010 to July 2012 in two specialist colorectal/hepatobiliary cancer centres. We extracted and analyzed data with respect to preoperative staging imaging and definitive treatment performed on completion of staging. Results: We identified 100 patients who underwent preoperative staging investigations for potentially resectable CRCLM. The imaging techniques performed included: CT (n=99, 99%), MRI liver (n=75, 75%), PET (n= 96, 96%). In 22 (22/96, 23%) patients PET scanning added to the preoperative staging information, identifying local recurrence (n=3, 3.1%), confirming liver metastases following an inconclusive CT/MRI (n=2, 2.1%), outruling liver metastases (n=1, 1%) and identifying extrahepatic sites (EHS) suspicious for disease (n=16, 16.7%). The EHS included either lung (n=6), bone (n=2), peritoneum (n=1) or lymph nodes (n=7). There were 2 false positive results. One patient with FDG-avid mediastinal lymph nodes had no cancer on endobronchial biopsy. One patient with FDG avidity at the primary anastomosis had no evidence of disease at colonoscopy. PET definitively changed the therapeutic strategy in 16 patients (16/96, 16.6%): precluding liver resection in 10 patients (10/96, 10.4%), leading to resection of extrahepatic disease in 4 patients (4/96, 4.1%), resection of local recurrence in 1 patient (1/96, 1%) and resection of hepatic metastases in one patient (1/96, 1%). Conclusions: In this small retrospective cohort the addition of metabolic imaging altered management in 16.6% of patients with potentially resectable CRCLM. There is a need for randomized evidence to support the routine use of PET in addition to cross-sectional imaging in this setting.
LONG TERM MORTALITY AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATINTS WITH CHRONIC KIDNEY DISEASE NOT ON HEMODIALYSIS
Authors: Justyna Rzucidlo, Vita Jaspan, Binita Shah, Darien Paone, Illya Pushkar, Anna Kapitman, Homam Ibrahim, Kazuhiro Hisamoto, Peter Neuburger, Muhamed Saric, Cezar Staniloae, Alan Vainrib, Daniel Bamira, Hasan Jilaihawi, Michael Querijero, Mathew Williams
Journal: Journal of the American College of Cardiology (2020)