tbuckley/cabot-search huggingface dataset:
A phase 1 dose escalation study of the oncolytic adenovirus enadenotucirev, administered intravenously to patients with epithelial solid tumors (EVOLVE)
Authors: Jean-Pascal Machiels, Ramon Salazar, Sylvie Rottey, Ignacio Duran, Luc Dirix, Karen Geboes, Christine Wilkinson-Blanc, Gillian Pover, Simon Alvis, Brian Champion, Kerry Fisher, Hilary McElwaine-Johnn, John Beadle, Emiliano Calvo
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Enadenotucirev is a chimeric adenovirus with demonstrated preclinical tumor-selective cytotoxicity and a short half-life. Further clinical mechanism of action data showed that enadenotucirev can gain access to and replicate within different types of epithelial tumors. This phase 1 dose escalation study assessed intravenous (IV) dose escalation with enadenotucirev to establish the maximum tolerated dose (MTD) and subsequently identify a suitable schedule for repeated cycles. <h3>Methods</h3> Sixty-one patients with advanced epithelial tumors unresponsive to conventional therapy were enrolled and received enadenotucirev monotherapy as part of this study. During the phase 1a dose escalation (<i>n</i>&nbsp;= 22) and expansion (<i>n</i>&nbsp;= 9), delivery of enadenotucirev between 1 × 10<sup>10</sup> and 1 × 10<sup>13</sup> viral particles (vp) on days 1, 3, and 5 (single cycle) was used to determine an appropriate MTD. Subsequent treatment cohorts (phase 1a, <i>n</i>&nbsp;= 6 and phase 1b, <i>n</i>&nbsp;= 24) examined the feasibility of repeated dosing cycles in either 3-weekly or weekly dosing regimens. <h3>Results</h3> Enadenotucirev displayed a predictable and manageable safety profile at doses up to the MTD of 3 × 10<sup>12</sup> vp, irrespective of infusion time or dosing schedule. The most commonly reported treatment-emergent adverse events (TEAEs) of grade 3 or higher were hypoxia, lymphopenia, and neutropenia. The frequency of all TEAEs (notably pyrexia and chills) was highest within 24 h of the first enadenotucirev infusion and decreased upon subsequent dosing. Additionally, delivery of three doses of enadenotucirev over 5 days optimized pharmacokinetic and chemokine profiles in the circulation over time. <h3>Conclusions</h3> This study provides key clinical data in patients with solid epithelial tumors following treatment with IV enadenotucirev monotherapy and supports further investigation of enadenotucirev in combination with other therapeutic agents at doses up to the MTD of 3 × 10<sup>12</sup> vp. <h3>Trial registration</h3> (ClinicalTrials.gov Identifier: NCT02028442). Trial registration date: 07 January 2014 – Retrospectively registered.
Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): a multicentre, randomised, placebo-controlled, double-blind phase 2 trial
Authors: Magdy Selim, Lydia D Foster, Claudia S Moy, Guohua Xi, Michael D Hill, Lewis B Morgenstern, Steven M Greenberg, Michael L James, Vineeta Singh, Wayne M Clark, Casey Norton, Yuko Y Palesch, Sharon D Yeatts, Monica Dolan, Erlinda Yeh, Kevin Sheth, Kimberly Kunze, Susanne Muehlschlegel, Iryna Nieto, Jan Claassen, Cristina Falo, David Huang, Anne Beckwith, Steven Messe, Melissa Yates, Kristine O'Phelan, Andrea Escobar, Kyra Becker, Patricia Tanzi, Nicole Gonzales, Chad Tremont, Chitra Venkatasubramanian, Rosita Thiessen, Supriya Save, Steven Verrault, Karin Collard, Michael DeGeorgia, Valerie Cwiklinski, Bradford Thompson, Lesley Wasilewski, Charles Andrews, Robert Burfeind, Michel Torbey, Mohammad Hamed, Kenneth Butcher, Leka Sivakumar, Nicolaou Varelas, Kathleen Mays-Wilson, Enrique Leira, Heena Olalde, Scott Silliman, Rhonda Calhoun, Neha Dangayach, Ricardo Renvill, Rishi Malhotra, Kristina Kordesch, Aaron Lord, Thomas Calahan, Romergryko Geocadin, Michelle Parish, James Frey, Mary Harrigan, Dana Leifer, Ryna Mathias, Michael Schneck, Tara Bernier, Sergio Gonzales-Arias, Josette Elysee, George Lopez, Josephine Volgi, Robert Brown, Sara Jasak, Stephen Phillips, Judith Jarrett, Joao Gomes, Moneen McBride, Francois Aldrich, Charlene Aldrich, Joshua Kornbluth, Michelle Bettle, Joshua Goldstein, Gregory Tirrell, Qaisar Shaw, Karin Jonczak
Journal: The Lancet Neurology (2019)
Abstract P089: Predictors of a Southern Diet Pattern in the REGARDS Study
Authors: Catherine Couch, George Howard, Virginia J Howard, Leann Long, James Shikany, Orlando Gutierrez, Neil Zakai, Mary Cushman, Emily Levitan, Jennifer Manly, Suzanne E Judd
Journal: Circulation (2019)

Background: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study identified a dietary pattern from factor analysis associated with multiple diseases. This Southern dietary pattern, includes fried food, organ meats, processed meats, and sugar-sweetened beverages and is associated with increased risk of hypertension, cardiovascular disease stroke, sepsis, kidney disease, and cognitive impairment. Further, this dietary pattern mediates much of the black-white difference in incidence of both stroke and hypertension. Factors related to adherence to this dietary pattern have been less commonly studied. In this cross-sectional study, we examined predictors of the Southern diet in REGARDS, including 17212 black and white participants aged 45 and older. Studied predictors were race, sex, residence in the Southeast, education, income, neighborhood advantage, smoking status, living in an urban area, age, dietary factors, physical activity, medication adherence, general self-rated health, report of depressive symptoms, and living in a food desert. We used linear regression to obtain beta coefficients and modeled a one standard deviation difference in the Southern diet score. Of REGARDS participants with dietary data, 34% were black, 44% were male, 72% lived in an urban setting, and 37% had graduated from college. Among the possible predictors of adherence to a Southern diet pattern, black participants, males, residents of the Southeast, and current smokers were strongly adherent to the dietary pattern, even after adjustment for the other factors (table). Markers of socioeconomic status were strong predictors in unadjusted models but after adjustment for race, they were attenuated. Black race was the most potent predictor of a higher adherence to a Southern dietary pattern in REGARDS. As this diet is strongly associated with risk of several incident diseases, further work should focus on the contribution of this diet to broad racial disparities in chronic disease and life expectancy.
Allogeneic Hematopoietic Stem-Cell Transplantation for Patients with Richter's Syndrome:the SFGM-TC Experience
Authors: Laura Bounaix, Stephanie Nguyen, Didier Blaise, David Michonneau, Jean-Henri Bourhis, Johan Maertens, Xavier Poire, Patrice Chevallier, Natacha Maillard, Ibrahim Yakoub-Agha, Lionel Mannone, Marc Bernard, Thierry de Revel, Helene Labussiere-Wallet, Patrice Ceballos, Richard Lemal, Eric Hermet, Aurélie Ravinet, Olivier Tournilhac, Jacques-Olivier Bay, Romain Guieze
Journal: Blood (2018)
Hospital and patient factors associated with resection of the primary tumor at first presentation of metastatic colorectal cancer in the New Jersey State Cancer Registry.
Authors: Rebecca Anne Moss, Dirk Moore, Melissa Y Chan, Chunxia Chen, Xiaoling Niu, Lisa M. Roche, Lisa E. Paddock
Journal: Journal of Clinical Oncology (2015)

e14689 Background: Upfront resection of the primary tumor (ROP) for patients with metastatic colorectal cancer (mCRC) is of uncertain benefit absent curable disease or life-threatening symptoms. Few studies have assessed use of ROP for first presentation of mCRC outside of the SEER-Medicare population. The purpose of this study was to identify patient (pt) and hospital characteristics associated with ROP. Laterality was studied as obstruction is more common with left-sided tumors. Methods: New Jersey (NJ) residents older than 20, diagnosed with histologically confirmed mCRC between 2000 and 2010, and treated at a NJ facility with complete treatment information were identified using high-quality data from the NJ State Cancer Registry. Data for 80 facilities were obtained from the American Hospital Association and a telephone survey. ROP within 60 days of diagnosis and before other therapy was the primary endpoint. Univariate logistic regression analysis was conducted. A descriptive analysis was performed. All statistical tests were 2-sided. Results: 8500 cases of mCRC were eligible for analysis (median age 70).ROP was less likely at larger and at academic hospitals (see Table). ROP was more common prior to 2004 (p < 0.0001). Pts who underwent ROP (n = 3644, 45%) were more likely to have private insurance (p = 0.0187), be female (p = 0.0011), and be age ≤ 70 (p = 0.0003). Left-sided tumors were associated with less ROP (p < 0.0001). Conclusions: ROP in patients with mCRC was common in NJ.With available clinical information, left-sided tumors had fewer ROPs. The decision to undergo ROP may have been influenced by non-clinical factors such as insurance or gender, and was less likely at hospitals with an academic or oncologic focus as assessed by American College of Surgeons (ACOS) approval, tumor boards, and teaching affiliation. Hospital characteristics Lower ROP Higher ROP P-value # of admissions Middle & Upper tertile Lower tertile 0.0012 # of Tumor Boards/month* More Tumor Boards, lower ROP < 0.0001 Teaching affiliation Major Minor 0.0492 Nonteaching < 0.0001 ACOS approved Yes No < 0.0001 ACGME affiliated Yes No < 0.0001 * as of September, 2013
Synergistic Dual Inhibition of BCR-ABL1 and the Unfolded Protein Response Causes p38 MAPK-Mediated Cell Death and Sensitizes BCR-ABL1+ Acute Lymphoblastic Leukemia to Dexamethasone
Authors: Margherita Vieri, Christian Preisinger, Mirle Schemionek, Azam Salimi, John B. Patterson, Afshin Samali, Tim H Brümmendorf, Iris Appelmann, Behzad Kharabi Masouleh
Journal: Blood (2018)
Identifying predictive biomarkers for metastatic progression in stage I and II clear cell renal cell carcinoma.
Authors: Neal J Murphy, Andrew Shih, Zachary Kozel, Paras Shah, Oksana Yaskiv, Houman Khalili, Anthony Liew, Louis R Kavoussi, Simon Hall, Manish Arvind Vira, Annette Lee, Xinhua Zhu
Journal: Journal of Clinical Oncology (2019)

631 Background: For most clear cell renal cell carcinoma (ccRCC) patients with early stage disease, surgical resection offers definitive cure. However, for the small percentage of tumors that metastasize, analyzing gene expression profiles from the primary site at the time of nephrectomy can serve as a model to understand the molecular aberrations behind a metastatic phenotype. Differences in gene expression profiles between patients with Stage I and II ccRCC who experience metastasis versus patients who maintain cure after surgery may help elucidate significant molecular targets and stratify patients at higher risk for metastasis. Methods: Nineteen Stage I and twenty Stage II ccRCC tumors preserved in FFPE blocks after nephrectomy were included in this study. Patients were matched for age, gender, tumor size and grade. In both stages, approximately half the patients that experienced metastasis within 5 years of surgery were part of the experimental group, whereas the control group had &gt; 5 years of follow-up without evidence of disease. Extracted RNA for Stage I patients was sequenced using Illumina TruSeq RNA Access Library. Gene counts were assessed by ht-seq counts and differential expression using DESeq2. Significant genes found were validated in the Stage II group using RT-qPCR. Results: In the Stage I experimental group, statistically significant upregulation of several genes associated with unfavorable prognosis in RCC were found: COL1A1, NUMBL, and STEAP3. Random forest classification accurately separated Stage I control versus experimental patients based on expression of COL1A1. Affected genes were consistent with molecular changes seen in TCGA analysis. In the Stage II group, a double-blinded analysis correctly identified the clinical outcome for the majority of the patients using qPCR expression of COL1A1, NUMBL, and STEAP3. Conclusions: Differences in gene expression profiles harbored in the primary site of early stage ccRCC may be employed to predict patients at high risk for developing metastasis. Validating these findings in a larger study carries the potential to better understand mechanisms of metastasis and identify an at risk cohort of patients with early stage disease.
Characterization of dominant T-cell clones by T-cell receptor (TCR) deep sequencing as a potential predictive biomarker to neoadjuvant trastuzumab (tras) in HER2-positive (HER2+) breast cancer.
Authors: David B. Page, Yong Hannah Wen, Edi Brogi, Jianda Yuan, Ryan O Emerson, Sujata Patil, Chau T. Dang, Larry Norton, Clifford A. Hudis, Heather L. McArthur
Journal: Journal of Clinical Oncology (2015)

609 Background: Because TIL quantity by H&E predicts pathologic complete response (pCR) to neoadjuvant tras in HER2+ disease, and because clinical responses to tras could be mediated by dominant T-cell clones reactive to the HER2-protein, we hypothesize that the quantity of dominant clones by TCR deep sequencing may predict tras-induced pCRs. Here, we evaluate the influence of specimen age on feasibility of TCR sequencing on breast cancer FFPE-preserved diagnostic core biopsies (bxs), and explore potential associations with pCR in a HER2+ subset. Methods: Two groups with pre-treatment bx’s were selected and sequenced using the ImmunoSEQ platform: 12 neoadjuvant tras-treated women with “archival” HER2+ bxs (median 35mo from procurement, 12-54mo; 6 with pCRs) and 14 women treated on an immunotherapy protocol with “contemporary” bxs (median 10mo from procurement, 4-18mo). Viability was assessed by calculating the proportion of nucleotide sequences yielding productive, in-frame amino acid sequences. T-cell quantity (the proportion of T-cell to total DNA) and dominant T-cell clone quantity (# clones in top decile of reads) were measured by TCR sequencing and evaluated for associations with pCR (Wilcoxon rank sum). Accuracy of T-cell quantity was assessed by comparing with H&E TIL count. Results: TCR sequencing viability was lower in archival compared to contemporary bxs (median .67 v .81; p < .0001), and was inversely correlated with sample age (Spearman r = -0.62, p = .0008) but not input DNA amount (r = -.05, NS). T-cell quantity by TCR sequencing correlated with TIL quantity by H&E in contemporary (r = 0.66, p = 0.03) but not archival bxs (r = .21, NS). In the HER2+ group, dominant T-cell clone quantity (median # clones: pCR, 15; no-pCR, 6, p = 0.05) but not TIL nor T-cell quantity were associated with pCR to tras. Conclusions: Despite the potential influence of specimen age on accuracy of T-cell quantity by TCR sequencing, the # of dominant clones predicted for pCR in this small dataset, highlighting the possibility that dominant clones may mediate response to tras. These findings warrant further study in a larger dataset.
The cost of prostate cancer care to society and to patients in the United States.
Authors: Nicholas George Zaorsky, John Lin, Djibril Ba, Joel E Segel, Heath B. Mackley, Joseph Drabick, Guodong Liu, Doug Leslie
Journal: Journal of Clinical Oncology (2019)

116 Background: Our objectives are to characterize prostate cancer patient resource consumption and cost (I) to society, in 1 calendar year; and (II) to the patient, 1 year after his diagnosis. Methods: The MarketScan database was used to summarize cost, including gross payment to provider for service, copayment, and deductibles. We identified the top 20 Current Procedural Terminology (CPT) codes to characterize which procedures drove costs for both objectives. For Objective I, diagnoses were identified in 1 calendar year (2014); codes and their costs for all patients were calculated. For Objective II, diagnoses were set at time = 0, and all CPT and International Classification of Diseases codes were characterized 1 year after diagnosis (2012-2013). Results: For objective I, there were 95,642 procedures totalling $38,696,423. The plurality of procedures were hospital consultations, level 2 (i.e. history + physical + straightforward decision-making; 17,103 performed, average $80 each, total $1,418,954) and level 3 (+ low complexity decision-making; 9,726 performed; average $127 each, total $1,232,928). The most costly procedure to society was a radical prostatectomy (8,883 performed, average $2,003 each, total $17,694,508) with accompanying anesthesia (7,960 performed, average $1262 each, total $10,048,653). For objective II (characterized in Table), the mean payment per month was $2,794, including mean gross cost $2,673, mean copayment $32, and mean deductible $46. Conclusions: The typical cost of therapy to a prostate cancer patient is $2,800/month after diagnosis, primarily from surgery (constituting the majority of cost to society) and subsequently from office visits (constituting the plurality of procedures). Societal measures to reduce cost should be aimed at the operating room and consultations.[Table: see text]
Excision repair cross-complementation group 1 (ERCC1) protein expression and clinical outcome in resectable cholangiocarcinoma.
Authors: Kosin Wirasorn, Mongkhon Sompornrattanaphan, Sakkarn Sangkhamannon, Sakda Waraasawapati, Aumkhae Sookprasert, Narong Khuntikao, Ake Pakkhem
Journal: Journal of Clinical Oncology (2015)

e15128 Background: Excision repair cross-complementation group 1 gene (ERCC1) encodes an enzyme, which is essential for the effective repair of DNA damage induced by alkylating agents. Mitomycin-based chemotherapy is the common regimen for adjuvant cholangiocarcinoma treatment. Our study investigated a relationship between ERCC1 expression and benefits from adjuvant chemotherapy. Methods: A retrospective study included newly-diagnosed 109 cholangiocarcinoma patients, who were undergone curative resection in Srinagarind Hospital (a 1000-bed university hospital), during January 2009 - December 2011. These patients had pathological reports with clear margins (R0) or microscopic margins (R1). ERCC1 expression was detected by immunohistochemical staining in paraffin-embedded tumor samples. Results: There were only 28 patients, who had ERCC1 positive staining. This group had significantly higher levels of serum CEA above 2.5 ng/dL and CA 19-9 above 35 U/L compared to ERCC-1 negative group (CEA, 68.2% vs. 31.8%, P = 0.02; CA 19-9, 72.7% vs. 27.3%, P = 0.04). For cholangiocarcinoma patients without adjuvant chemotherapy, patients with ERCC1 negative had longer overall median survival time compared to positive group (22 vs.13 months, P = 0.74). Conversely, ERCC1 positive patients also had longer overall median survival time compared to negative group in patients, who received adjuvant chemotherapy (30 vs. 24 months, P = 0.75). Interestingly, patients with ERCC1 negative, who were treated with a combination of mitomycin and 5-FU regimen, had significantly longer overall median survival time compared to positive group (18 vs.13 months, P= 0.009). Conclusions: ERCC1 is a significant predictive factor for cholangiocarcinoma patients who undergone mitomycin-based chemotherapy. In addition, negative ERCC1 might indicate no benefit of adjuvant chemotherapy in cholangiocarcinoma patients. However, non mitomycin-based chemotherapy might still provide benefit for positive ERCC1 patients.
FITNESS AND 10-YEAR RISK OF MORTALITY AMONG ADULTS ≥70 YEARS OLD AT THE EXTREMES OF CARDIOVASCULAR DISEASE RISK FACTOR BURDEN: THE FIT PROJECT
Authors: Seamus P. Whelton, Paul McAuley, Olusola Orimoloye, Erin Michos, Clinton Brawner, Jonathan Ehrman, Steven Keteyian, Mouaz Al-Mallah, Michael Blaha
Journal: Journal of the American College of Cardiology (2019)
A genome-wide algal mutant library and functional screen identifies genes required for eukaryotic photosynthesis
Authors: Xiaobo Li, Weronika Patena, Friedrich Fauser, Robert E. Jinkerson, Shai Saroussi, Moritz T. Meyer, Nina Ivanova, Jacob M. Robertson, Rebecca Yue, Ru Zhang, Josep Vilarrasa-Blasi, Tyler M. Wittkopp, Silvia Ramundo, Sean R. Blum, Audrey Goh, Matthew Laudon, Tharan Srikumar, Paul A. Lefebvre, Arthur R. Grossman, Martin C. Jonikas
Journal: Nature Genetics (2019)
Abstract MP38: Association of Changes in Plant-Based Diet Indices with Total and Cause-Specific Mortality
Authors: Megu Y Baden, Gang Liu, Ambika Satija, Yanping Li, Qi Sun, Teresa T Fung, Eric B Rimm, Walter C Willett, Frank B Hu, Shilpa N Bhupathiraju
Journal: Circulation (2019)

Introduction: Plant-based diets have been associated with health benefits, including lower risk of type 2 diabetes (T2D) and coronary heart disease (CHD). However, the association between plant-based diets and mortality remains unclear as previous studies did not take into account the quality of plant-based foods. To overcome this limitation, we recently developed three plant-based diet indices—an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI, emphasizing processed carbohydrates and fats)—and reported that hPDI and uPDI were differentially associated with T2D and CHD. In this study, we investigate associations between long-term changes in plant-based diet indices and subsequent total and cause-specific mortality in the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). Hypothesis: We hypothesized that improved plant-based diet quality is associated with lower total and cardiovascular disease (CVD) mortality. Method: We included 47,983 women, aged 63±7y (mean±SD) in the NHS and 25,737 men, aged 63±9y in the HPFS who had no history of CVD or cancer on or before 1998 (baseline). We used multivariable Cox proportional-hazards regression to assess the association between 12-y pre-baseline changes (1986-1998) in three plant-based diet indices and subsequent total and cause-specific mortality (1998-2014). We adjusted for age, race, initial corresponding plant-based diet index score, BMI, family history of diabetes, myocardial infarction, or cancer, history of hypertension, hypercholesterolemia, or T2D, medications, postmenopausal status and postmenopausal hormone use in women, initial and 12-y pre-baseline changes in weight and other lifestyle-related factors. Results: Compared with those participants whose diets remained relatively stable during the pre-baseline 12-year period, among participants with the greatest increase in plant-based diet indices, the pooled hazard ratio (95% confidence interval [CI]) for total mortality was 0.92 (95% CI, 0.87 to 0.97) for PDI, 0.90 (95% CI, 0.86 to 0.95) for hPDI, and 1.11 (95% CI, 1.05 to 1.16) for uPDI. For CVD-specific mortality, a 10-point increase in hPDI was associated with a 10% lower risk (95% CI, 5 to 15), while a 10-point increase in uPDI was associated with a 6% higher risk (95% CI, 0 to 12). We found no evidence for changes in plant-based diet indices and subsequent risk of cancer mortality. Conclusions: Improved plant-based diet quality over a 12-year period was associated with a lower risk of total and CVD mortality, whereas increased consumption of an unhealthful plant-based diet was associated with a higher risk of total and CVD mortality.