tbuckley/cabot-search huggingface dataset:
Biology and Clinical Application of Regulatory RNAs in Hepatocellular Carcinoma
Authors: Antonio Pea, Nigel B. Jamieson, Chiara Braconi
Journal: Hepatology (2020)

Most of the human genome consists of DNA genes that are translated into RNAs but not into proteins. These RNA molecules are named noncoding RNAs (ncRNA). While in the past it was thought that ncRNAs would be redundant without relevant functions, it is now well established that ncRNAs identify a class of regulatory molecules that finely tune cell homeostasis and are deregulated in disease states, including hepatocellular carcinoma (HCC). Of note, the number of ncRNAs within a cell increases progressively, with the complexity of the species indicating their essential role in the maintenance of regulatory networks that affect the intricacy of the organism. ncRNAs have been demonstrated to mediate HCC development and progression by affecting intrinsic cancer cell signaling and crosstalk between malignant cells and the microenvironment. Moreover, ncRNAs hold promise as clinical biomarkers, but further evidence is warranted before their translation and integration within clinical practice.
AN ELECTRONIC HEALTH RECORD-BASED ALGORITHM TO ALERT CLINICIANS TO THE PRESENCE OF POSSIBLE FAMILIAL HYPERCHOLESTEROLEMIA
Authors: Hana Bangash, Joseph Sutton, Omar Elsekaily, Ozan Dikilitas, Justin H. Gundelach, Stephen Kopecky, Robert Freimuth, Pedro Caraballo, Iftikhar J. Kullo
Journal: Journal of the American College of Cardiology (2020)
The efficacy of axillary ultrasound in the detection of nodal metastasis in breast cancer.
Authors: Belinda Lee, Adrian K. Lim, Jonathan Krell, Keshthra Satchithananda, Jacqueline S Lewis, R. Charles Coombes, Justin Stebbing
Journal: Journal of Clinical Oncology (2012)

e21137 Background: Recent reports indicate a lack of survival benefit for axillary node dissection (ALND) versus sentinel lymph node biopsy in early breast cancer. To study this further we assessed the accuracy and effectiveness of ultrasound in detecting axillary nodal involvement in breast cancer patients, aimed at refining and evaluating our current clinical pathways as newly diagnosed invasive breast cancer patients routinely undergo pre-surgical axillary ultrasound. Methods: Ultrasound data were collected from consecutive breast cancer cases over 3 years. Images were reviewed by experienced radiologists and made the following assessments on size, morphology, fatty hilum and cortical thickness of the ipsilateral axillary nodes. The findings were correlated with histology outcomes following ALND. Results: 260 cases were included in the analysis, 113 (43.5%) had evidence of metastatic nodal involvement at final histology. Of these, 59/113 (52.2%) reported positive findings on ultrasonography. The overall positive predictive value of ultrasound for detecting metastatic nodal involvement measured 0.70. The negative predictive value was 0.61. The sensitivity was 52%, specificity measured 78% and the accuracy was 65%. The ultrasound morphological lymph node features with the greatest correlation with malignancy were absence of a fatty hilum (p=0.003) and increased cortical thickness (p=0.03). Cases with a metastatic nodal burden density of a least 20% were more likely to report an abnormal axillary ultrasound. (p=0.009). Conclusions: Axillary ultrasound has a low NPV and negative sonographic results do not exclude axillary node metastases with sufficient sensitivity, to justify its routine clinical use. Clinical pathways need to consider an evidence-based approach, focusing on the criteria by which we select breast cancer patients for axillary nodal dissection.
American Heart Association Goals Through a 20/20 Lens
Authors: Erica S. Spatz
Journal: JAMA Cardiology (2020)

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DIASTOLIC FUNCTION ASSESSED WITH SPECKLE TRACKING OVER A DECADE AND ITS PROGNOSTIC VALUE: THE COPENHAGEN CITY HEART STUDY
Authors: Kristoffer Skaarup, Mats Højbjerg Lassen, Niklas Dyrby Johansen, Sofie Reumert Biering-Sørensen, Daniel Modin, Peter Godsk Jørgensen, Gorm Jensen, Peter Schnohr, Eva Prescott, Peter Sogaard, Gunnar Gislason, Rasmus Møgelvang, Tor Biering-Sorensen
Journal: Journal of the American College of Cardiology (2020)
Identification of potential molecular biomarkers for response of soft tissue sarcoma to eribulin: Translational results of EORTC trial 62052.
Authors: Agnieszka Wozniak, Erik A.C. Wiemer, Herman Burger, Joke Allemeersch, Rudy van Eijsden, Ron H.J. Mathijssen, Stefan Sleijfer, Marcel Smid, Giuseppe Floris, Sandrine Marreaud, Axelle Nzokirantevye, Raf Sciot, Patrick Schoffski
Journal: Journal of Clinical Oncology (2013)

10573 Background: The phase II study EORTC 62052 demonstrated potential antitumor activity of eribulin, a tubulin-interacting cytotoxic agent, which is a synthetic analogue of the natural compound halichondrin B, in patients with various subtypes of metastatic soft tissue sarcoma (STS) including leiomyo- (LMS) and adipocytic (ADI) sarcomas, but not synovial sarcomas (SYN) and other sarcoma histotypes (OTH) (Schöffski P et al. Lancet Oncol. 2011;12:1045) . In addition to histotypes, we aimed to identify potential biomarkers responsible for eribulin sensitivity or resistance to eribulin using gene expression and miRNA profiling. Methods: From 68 consenting patients archived tumor tissue was collected, including 22 LMS, 15 ADI, 10 SYN and 21 OTH sarcoma histotypes. Total RNA was isolated from 65 samples and analyzed using GeneChip Human Exon ST Array (for mRNA expression) and Taqman Low Density Array (for miRNA). Progression free survival (PFS) at week 12 (RECIST 1.0) was the primary endpoint of the clinical trial and used for correlative studies. Eighteen out of 56 (32.1%) evaluable patients in this analyzed subset had non progressive disease at week 12 (“responders”). Results: Overall expression of 62 transcripts including ALS2CR11 (uncorrected p&lt;0.001) and 26 miRNAs (p&lt;0.05) differed significantly between non-responders and responders. Additional transcripts and miRNAs were identified when considering the different histological groups (Table). Conclusions: The level of (mi)RNA expression in soft tissue sarcoma samples may predict response of soft tissue sarcoma to eribulin. Further validation studies are required. [Table: see text]
COMPLETE VS CULPRIT-ONLY REVASCULARIZATION IN ST ELEVATION MYOCARDIAL INFARCTION, A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Ahmad Al-Abdouh, Nazir Savji, Rani K. Hasan, Anas Bizanti, Ibrahim Abudaya, Hadi Elias, Sireesha Upadhrasta, Di Zhao, Erin Michos
Journal: Journal of the American College of Cardiology (2020)
FSENC-A NOVEL APPROACH TO ANALYZING MYOCARDIAL DEFORMATION IN PATIENTS WITH ACUTE CHEST PAIN
Authors: Deborah Siry, Janek Salatzki, Florian André, Marco Ochs, Evangelos Giannitsis, Hugo A. Katus, Matthias G. Friedrich, Johannes Riffel
Journal: Journal of the American College of Cardiology (2020)
CHANGE IN GLOBAL LONGITUDINAL STRAIN AND RISK OF HEART FAILURE FOLLOWING ACUTE CORONARY SYNDROME
Authors: Kirstine Ravnkilde, Kristoffer Skaarup, Daniel Modin, Anne Nielsen, Mathilde Musoni Falsing, Allan Iversen, Sune Pedersen, Thomas Hansen, Soren Galatius, Thomas Jespersen, Amil M. Shah, Gunnar Gislason, Tor Biering-Sorensen
Journal: Journal of the American College of Cardiology (2020)
IMPAIRED SOD2 ACTIVITY LINKED WITH EXCESSIVE MITOCHONDRIAL SUPEROXIDE IS RESPONSIBLE FOR DIMINISHED RE-ENDOTHELIALIZATION OF ENDOTHELIAL PROGENITOR CELLS IN HYPERTENSION
Authors: Jiang He, Gaoxing Zhang, Xing Liu, Bingbo Yu, Xinzhu Tong, Yijia Shao, Jiapan Sun, Jun Tao
Journal: Journal of the American College of Cardiology (2020)
Leukemia-induced dysfunctional TIM-3+CD4+ bone marrow T cells increase risk of relapse in pediatric B-precursor ALL patients
Authors: Franziska Blaeschke, Semjon Willier, Dana Stenger, Mareike Lepenies, Martin A. Horstmann, Gabriele Escherich, Martin Zimmermann, Francisca Rojas Ringeling, Stefan Canzar, Theresa Kaeuferle, Meino Rohlfs, Vera Binder, Christoph Klein, Tobias Feuchtinger
Journal: Leukemia (2020)
KLK6 expression in skin induces PAR1-mediated psoriasiform dermatitis and inflammatory joint disease
Authors: Allison C. Billi, Jessica E. Ludwig, Yi Fritz, Richard Rozic, William R. Swindell, Lam C. Tsoi, Dennis Gruzska, Shahla Abdollahi-Roodsaz, Xianying Xing, Doina Diaconu, Ranjitha Uppala, Maya I. Camhi, Philip A. Klenotic, Mrinal K. Sarkar, M. Elaine Husni, Jose U. Scher, Christine McDonald, J. Michelle Kahlenberg, Ronald J. Midura, Johann E. Gudjonsson, Nicole L. Ward
Journal: Journal of Clinical Investigation (2020)

Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease hypothesized to promote inflammation via cleavage of protease-activated receptor 1 (PAR1) and PAR2. KLK6 levels are elevated in multiple inflammatory and autoimmune conditions, but no definitive role in pathogenesis has been established. Here, we show that skin-targeted overexpression of KLK6 causes generalized, severe psoriasiform dermatitis with spontaneous development of debilitating psoriatic arthritis-like joint disease. The psoriatic skin and joint phenotypes are reversed by normalization of skin KLK6 levels and attenuated following genetic elimination of PAR1 but not PAR2. Conservation of this regulatory pathway was confirmed in human psoriasis using vorapaxar, an FDA-approved PAR1 antagonist, on explanted lesional skin from patients with psoriasis. Beyond defining a critical role for KLK6/PAR1 signaling in promoting psoriasis, our results demonstrate that KLK6/PAR1-mediated inflammation in the skin alone is sufficient to drive inflammatory joint disease. Further, we identify PAR1 as a promising cytokine-independent target in therapy of psoriasis and psoriatic arthritis.
EMPAGLIFLOZIN REDUCES ENDOGENOUS GLYCEROL-DEPENDENT HEPATIC GLUCONEOGENESIS IN VISCERALLY OBESE ADULTS WITHOUT TYPE 2 DIABETES MELLITUS
Authors: Natalia de Albuquerque Rocha, Ian J. Neeland, Connor Hughes, Colby Ayers, Craig Malloy, Eunsook S. Jin
Journal: Journal of the American College of Cardiology (2020)
The burnout syndrome among Brazilian medical oncologists
Authors: J. Glasberg, L. Horiuti, M. Novais, A. Canavezzi, V. Miranda, F. Chicoli, M. Gonçalves, C. Bensi, A. Del Giglio
Journal: Journal of Clinical Oncology (2006)

16038 Background: The burnout syndrome (BNS) is prevalent among oncologists and is characterized by three components: emotional exhaustion, depersonalization and low personal accomplishment. BNS is associated with depression anxiety and impaired job performance. We aimed at evaluating the prevalence of BNS among brazilian medical oncologists and the variables that correlate with its presence. Methods: We sent three questionnaires (general, Maslach burnout questionnaire and an opinion survey) to the 458 members of the Brazilian Society of Medical Oncology (SBOC) and we attempted to increase the amount of answers by an email recall to all members. In order to evaluate correlations between variables we used Fisher, Chisquare and ANOVA tests, and considered significant only p values lower than 0.05. We used logistical regression to conduct multivariate analysis, having the presence of BNS as a dependent variable. Results: The response rate was 22.3%. When asked if they would choose oncology as a career again, 90 (88.25%) answered affirmatively. According with the criteria proposed by Grunfeld, that considers BNS present when at least one dominion is severely abnormal, the incidence of this syndrome was 68.6% (95% CI: 58,68% to 77.45%). By univariate analysis, we observed a negative significant correlation of BNS with having regular physical activity and/or a hobby, reporting to have a religious affiliation and with willingness to choose oncology as a career again. We found a positive significant correlation of BNS with living together with someone and reporting vacation time as insufficient. By multivariate analysis having a hobby/physical activity, a religious affiliation, living with a companion and rating vacation’s time as sufficient were all correlated significantly and independently with BNS. Conclusions: BNS is prevalent among brazilian medical oncologists, nevertheless most of them would choose medical oncology as a career again. To have a hobby and/or a regular physical activity, enough time of vacations and a religious affiliation correlate negatively with the presence of BNS and are potentially modifiable preventive measures to decrease the frequency of this syndrome. No significant financial relationships to disclose.
A phase II study of low-dose prolonged infusional gemcitabine combined with oral treosulfan in patients with platinum- and taxane-resistant ovarian cancer or other Mullerian tract carcinomas
Authors: C. M. Kurbacher, J. A. Kurbacher, E. Cramer, U. Reinhold, W. J. Nagel, R. Reichelt, I. A. Cree
Journal: Journal of Clinical Oncology (2006)

15004 The prognosis of patients (pts) with epthelial ovarian cancer (EOC) and other Mullerian tract carcinomas such as papillary-serous peritoneal carcinoma (PSPC), fallopian tube cancer (FTC), and uterine papillary-serous carcinoma (UPSC) resistant to both platinum and taxanes is particularly poor. Recently, we have reported preliminary results of modified GeT - gemcitabine (dFdC) and treosulfan (TREO) (Kurbacher et al, Proc ASCO 2005). Now, mature results of this phase II trial are available. A total of 35 patients (pts) were included (EOC, 29; FTC, 4; PSPC, 1; UPSC, 1). Patients had failed a median of 2 prior chemotherapies (1, n = 10; 2, n = 11; 3, n = 7; 4, n = 3; 5, n = 3; 7, n = 1) including platinum and paclitaxel in all, anthracyclines in 16, dFdC in either 6, and topotecan in 5 pts. GeT was administered at a q2w schedule with dFdC at 450 mg/m 2 (3 h infusion), day 1, and oral TREO at 1,000 mg/m 2 /d, day 1–4. A total of 192 cycles were given with a median of 6 (range: 2–10). All pts had measurable or evaluable disease according to RECIST and Rustin criteria, repectively. All treatments were evaluable for both toxicity and response. Myelosuppression was frequent but exceeded NCI-CTC grade 2 in only 17/192 cycles (9%). G 3–4 neutropenia was observed during 5/192 cycles (3%), G 3–4 thrombocytopenia did not occur. Interval prolongation due to febrile urinary tract infection or subileus was necessary in two pts. In another patient, treatment was terminated due to non-fatal pulmonary embolism. Other toxicities did not exceed NCI-CTC grade 2 nor did any other patient require hospitalization due to therapy-related complications. A total of 11 CR, 7 PR, 9 SD, and 8 PD were recorded accounting for an objective response rate of 51% with 27 pts (77%) benefiting from GeT. The median progression-free survival was 27 weeks. Until now, 15 pts are still alive, the median overall survival is 76.5 weeks. Regarding the intensive pre-treatment of the pts, the modified GeT treatment was easy to tolerate and produced a promising clinical efficacy in EOC and other Mullerian tract carcinomas resistant to both platinum and taxanes. Large-scaled clinical trials are now warrented to confirm these encouraging results. No significant financial relationships to disclose.
Tobacco Use in High-Risk Populations
Authors: Wilson M. Compton, Emily B. Einstein
Journal: JAMA Network Open (2020)

Wajiha Z. Akhtar, PhD, MPH; Marlon P. Mundt, PhD; Ruth Koepke, MPH; Sarah Krechel, MPH; Michael C. Fiore, MD, MPH, MBA; David W. Seal, PhD; Ryan P. Westergaard, MD, PhD, MPH
EFFICACY OF REMOTE PULMONARY ARTERY HEMODYNAMIC MONITORING SYSTEM IN REDUCING HOSPITAL ENCOUNTERS IN HEART FAILURE PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Smitha Narayana Gowda, Udit Bhatnagar, Mason Blue, Jon Orvarsson, Roman Pham, Hafez Abdullah, Adam T. Stys, Tomasz Stys, Marian Petrasko, Naveen Rajpurohit, Valerie Bares, Aarabhi Gurumoorthy, Orvar Jonsson
Journal: Journal of the American College of Cardiology (2020)
Modernizing and designing evaluation frameworks for connected sensor technologies in medicine
Authors: Andrea Coravos, Megan Doerr, Jennifer Goldsack, Christine Manta, Mark Shervey, Beau Woods, William A. Wood
Journal: npj Digital Medicine (2020)

Abstract This manuscript is focused on the use of connected sensor technologies, including wearables and other biosensors, for a wide range of health services, such as collecting digital endpoints in clinical trials and remotely monitoring patients in clinical care. The adoption of these technologies poses five risks that currently exceed our abilities to evaluate and secure these products: (1) validation, (2) security practices, (3) data rights and governance, (4) utility and usability; and (5) economic feasibility. In this manuscript we conduct a landscape analysis of emerging evaluation frameworks developed to better manage these risks, broadly in digital health. We then propose a framework specifically for connected sensor technologies. We provide a pragmatic guide for how to put this evaluation framework into practice, taking lessons from concepts in drug and nutrition labels to craft a connected sensor technology label.
Addition of algenpantucel-L immunotherapy to standard of care (SOC) adjuvant therapy for pancreatic cancer.
Authors: Jeffrey M Hardacre, Mary Frances Mulcahy, William Small, Mark S. Talamonti, Jennifer Carrie Obel, Caio Max S. Rocha Lima, Howard Safran, Heinz-Josef Lenz, E. Gabriela Chiorean, Nicholas N. Vahanian, Charles J. Link
Journal: Journal of Clinical Oncology (2012)

4049 Background: Resected pancreatic cancer carries a one year survival rate of ~65%. Algenpantucel (HyperAcute-Pancreas, HAPa) exploits the hyperacute rejection mechanism of xenotransplantation by administering genetically modified, irradiated, allogeneic tumor cells expressing aGal moieties on their surface. We propose that addition of algenpantucel-L to SOC adjuvant therapy may improve survival for patients with resected pancreatic cancer. Methods: Open-label, dose-finding, Phase 2 study (16 sites) evaluating HAPa (100/300 M cells / dose) + SOC (RTOG-9704: Gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Primary endpoint: 1-year disease-free survival (DFS). Secondary Endpoints: overall survival (OS), toxicity and immunologic analysis. Results: : 70 patients, median age 62 years, 47% female, 81% lymph node positive, median tumor size 3.2 cm, and 17% post-operative CA 19-9 ≥ 180 received SOC + HAPa. 1-year DFS of 63% and OS of 86% compares favorably to historical controls (~45%% and 65%, respectively) for this high risk population. Subgroup analysis of patients receiving 300M cells /dose shows a higher 12-month DFS compared to 100M cells/dose, 81% vs. 52% (p = 0.02). Likewise, patients receiving 300M cells/dose tended to better 1-year survival compared to a 100M cells/dose, 96% vs. 80% (p = 0.053). Forty-four (63%) developed strong (G1-G3) skin reactions at the injection sites including many long term survival patients with periodic skin flares at injection sites far beyond their last vaccination. In 13/45 (29%) tested patients, an increase of &gt;30% in anti-mesothelin Ab titer was seen after immunization. Thirty-nine (56%) presented with eosinophilia (range: 5- 45%), including one patient with persistent eosinophilia and stable lung metastasis for over 2 years. Conclusions: Addition of HAPa to standard adjuvant therapy for resected pancreatic cancer shows promising immunological activation and may improve survival. A multi-institutional, phase 3 study is currently underway.
Investigating an orally available small-molecule inhibitor (vemurafenib) of BRAF<sup>V600E</sup> in a novel preclinical model of human papillary thyroid cancer.
Authors: Mark Duquette, Peter M. Sadow, Carmen Priolo, Andrew Fischer, Richard Hodin, Sareh Parangi, Jack Lawler, Carmelo Nucera
Journal: Journal of Clinical Oncology (2013)

e17014 Background: Patients with BRAF V600E -positive human papillary thyroid cancer (PTC) have poorer prognosis, higher rates of metastases and mortality, and resistance to radioiodine treatment. The goal of this study was to assess the therapeutic efficacy of vemurafenib (a new orally available BRAF V600E selective inhibitor) in a translational therapeutic model of BRAF V600E human nonmetastatic or metastatic PTC. Methods: We have established in vitro cultures of human primary PTC cells with or without heterozygous BRAF WT/V600E , primary normal thyroid (NT) cells, and used previously established human PTC cell lines with BRAF V600E . Immunocytochemistry was used to characterize markers of differentiation. Genotyping (over 500 genes analyzed) by mass spectrometry was performed to determine genetic alterations. Cell viability assays were performed upon different concentrations of vemurafenib: 0.01, 0.1, 1, 5, and 10 µM. Phosphorylation (p) of ERK1/2 (downstream BRAF V600E ) was used to measure BRAF V600E activity. Results: We have isolated 8 independent batches of primary human non-metastatic or metastatic PTC cells from total thyroidectomy patients with PTC &gt;1.1 cm, and 4 independent batches of primary NT cells from normal matched thyroid tissue specimens. 62.5% of the isolated batches of PTC cells were heterozygous BRAF WT/V600E and expressed epithelial markers and thyroid differentiation markers (e.g. PAX8, TSH-receptor). The NT cells showed no mutations. BRAF WT/V600E nonmetastatic PTC cells showed decreased viability (IC 50 : 5 µM) and pERK1/2 levels (IC 90 : 10 µM) when exposed to vemarufenib, with no toxic effects. PTC cells with BRAF WT , or NT cells showed no change in viability and pERK1/2 levels when exposed to vemarufenib. Importantly, BRAF WT/V600E metastatic PTC cells showed a partial suppression of viability and inhibition of pERK1/2 but only at a higher dose (10 µM) of vemurafenib. Conclusions: We have established the first translational therapeutic model of heterozygous BRAF WT/V600E- PTC. Testing of PTC samples for BRAF WT/V600E and testing in vitro will help predict therapeutic efficacy of Vemurafenib in patients with BRAF WT/V600E- PTC.