tbuckley/cabot-search huggingface dataset:
Clinical Validity of HPV Circulating Tumor DNA in Advanced Anal Carcinoma: An Ancillary Study to the Epitopes-HPV02 Trial
Authors: Alice Bernard-Tessier, Emmanuelle Jeannot, David Guenat, Alice Debernardi, Marc Michel, Charlotte Proudhon, Anne Vincent-Salomon, Ivan Bièche, Jean-Yves Pierga, Bruno Buecher, Aurélia Meurisse, Éric François, Romain Cohen, Marine Jary, Véronique Vendrely, Emmanuelle Samalin, Farid El Hajbi, Nabil Baba-Hamed, Christophe Borg, François-Clément Bidard, Stefano Kim
Journal: Clinical Cancer Research (2018)

Human papillomavirus (HPV) is found in 90% of squamous cell carcinomas of the anal canal (SCCA). We investigated the clinical validity of HPV circulating tumor DNA (ctDNA) detection in patients enrolled in the Epitopes-HPV02 trial that demonstrated the efficacy of docetaxel, cisplatin, and 5-FU as first-line chemotherapy in advanced SCCA.According to the protocol, serum samples were collected before chemotherapy and on completion of chemotherapy. HPV16 ctDNA was quantified by droplet digital PCR (ddPCR) and correlated with prospectively registered patient characteristics and outcomes. A landmark was set at the time of chemotherapy completion for postchemotherapy progression-free survival (PFS) analyses.Among 57 patients with HPV16-related advanced SCCA, HPV ctDNA was detected in 91.1% (95% confidence interval, 81.1-96.2) of baseline samples. Baseline HPV ctDNA levels were not associated with any patient characteristics; baseline ctDNA level below the cutoff obtained by AUC (area under the curve) was associated with a longer PFS (HR = 2.1; P = 0.04). Among the 36 patients who completed 5 months of chemotherapy, residual HPV ctDNA was detected after chemotherapy in 38.9% of patients. Residual HPV ctDNA detected at chemotherapy completion was associated with shorter postchemotherapy PFS (median PFS 3.4 months vs. not reached; HR = 5.5; P < 0.001) and a reduction of 1-year overall survival rate (OR = 7.0; P = 0.02).This prospective study in advanced SCCA demonstrated a significant prognostic impact of HPV ctDNA level before first-line chemotherapy and HPV ctDNA negativity after chemotherapy completion. With a limited cost and short turnaround, this assay is a promising tool to optimize the therapeutic management of SCCA.See related commentary by Morris, p. 2030.
#18 Treatment of Hidradenitis Suppurativa Evaluation Study (THESEUS) (poster presentation)
Authors: J. Ingram, K. Thomas, T. Burton, J. Rodrigues, R. Howes, K. Hood, E. Thomas-Jones, R. Cannings-John, F. Collier, P. Tappenden, P. Leighton
Journal: International Journal of Surgery (2018)
Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial
Authors: Deepak Cyril D'Souza, Jose Cortes-Briones, Gina Creatura, Grai Bluez, Halle Thurnauer, Emma Deaso, Kim Bielen, Toral Surti, Rajiv Radhakrishnan, Aarti Gupta, Swapnil Gupta, John Cahill, Mohamed A Sherif, Alexandros Makriyannis, Peter T Morgan, Mohini Ranganathan, Patrick D Skosnik
Journal: The Lancet Psychiatry (2018)
Abstract 23075: Machine Learning Outperformed ACC/AHA Pooled Cohort Equations Risk Calculator for Detection of High-Risk Asymptomatic Individuals and Recommending Treatment for Prevention of Cardiovascular Events in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Ioannis Kakadiaris, Michalis Vrigkas, Matthew Budoff, Albert Yen, Morteza Naghavi
Journal: Circulation (2017)

Background: Studies have shown that the status quo for atherosclerotic cardiovascular disease (ASCVD) prediction in the U.S. - using ACC/AHA Pooled Cohort Equations Risk Calculator - is inaccurate and results in overtreatment of low-risk and undertreatment of high-risk individuals. Machine Learning (ML) is poised to revolutionize healthcare. We used ML to develop a new ASCVD risk calculator and tackled the problem. Methods: We developed a ML Risk Calculator using the latest 13-year follow up dataset from MESA (Multi-Ethnic Study of Atherosclerosis) of 6,814 participants who were free of clinical CVD at baseline. We gave identical input to both calculators and compared their accuracy for recommending statin to 5,415 subjects (age 60.6 ± 9.7 years; 47.3% males) who were not on lipid lowering treatment at baseline. Results: Over 13 years, 775 (14.3%) “All CVD” and 381 (7.0%) “Hard CVD” events occurred. According to ACC/AHA Risk Calculator and a 7.5% 10-year risk threshold for treatment, 42.9% would be recommended to take statin. Despite the high proportion recommended for statin treatment, 25.7% of “Hard CVD” and 26.3% of “All CVD” events occurred in those not recommended statin, resulting in sensitivity (Sn) 0.74, specificity (Sp) 0.60, and AUC 0.72 for “Hard CVD” and Sn 0.73, Sp 0.62, and AUC 0.73 for “All CVD”. In sharp contrast, the ML Risk Calculator recommended only 10.6% to take statin, and only 15.0% of “Hard CVD” and 4.9% of “All CVD” events occurred in those not recommended statin, resulting in Sn 0.84, Sp 0.95, and AUC 0.92 for “Hard CVD” and Sn 0.95, Sp 0.88, and AUC 0.95 for “All CVD”. Conclusions: ML clearly outperformed the ACC/AHA Risk Calculator by recommending less drug therapy and missing fewer events. Further studies are underway to validate these findings in other cohorts. As we introduce our ML model to more data particularly to cases in which events occurred weeks or months following data collection instead of years, short-term risk prediction may be possible.
AB0058 Il2 decrease and increase of il10 and inf1a are associated to clinical activity in systemic lupus erythematouspatients
Authors: E. Grau, C. Feced, E. Labrador, F.M. Ortiz, C. Alcañiz, K. Arevalo, I. Chalmeta, M. De la Rubia, J. Fragio, R. Gonzalez, L. Gonzalez, J. Ivorra, I. Martinez, R. Negueroles, J. Oller, E. Vicens, C. Najera, I. Canovas, D. Hervas, M. Fernandez, N. Fernandez-Llanio, J.A. Castellano, F. Mayo, J.A. Roman
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematous (SLE) is an autoimmune disease characterised by deregulation of cytokine production. INF1A is a proinflamatory cytokine considered as a key molecule in the SLE etiopathogenesis, being responsible indirectly of IL10 upregulation. BLyS is involved in autoantibodies production and clinical activity in SLE, and its expression is regulated by other cytokines as IL10 and INF1A. IL2 is an anti-inflammatory cytokine in SLE, but its loss leads to the production of Th2 proinflammatory cytokines as IL4, IL5 and IL13. <h3>Objectives</h3> To analyse the association among inflammatory cytokine levels and clinical activity, as well as to identify a cytokine profile related to disease activity in SLE. <h3>Methods</h3> A cross-sectional, observational study of 142 patients diagnosed of SLE<sup>SLICC 2012</sup> criteria), and 35 healthy controls, was performed. A complete blood-test and an interview were carried out to collect their clinical data. We analysed inflammatory cytokines serum levels by colorimetric methods. Biostatistical analysis with R was performed. <h3>Results</h3> Mean cytokine levels for the SLE patients and healthy controls are shown in the table 1. The mean clinical activity measured by SLEDAI was 5.91±5.06, and we observed a statistically significant association between high levels of IL10 and high clinical activity (p=0.001). Statistical analysis indicates that complement consumption is associated with increased levels of IL10 (p=0.029), INF1A (p&lt;0.001), IL4 (p=0.004), IL5 (p=0.009) and decreased levels of IL2 (p=0.045),; or anti-DNA positivity is associated with increased levels of INF1A (p=0.002) and decreased levels of IL2 (p=0.045), IL4 (p=0.034) and IL5 (p=0.007). Moreover, BLyS seems to have increased in patients with positive antiphospholipid antibodies and anti-DNA. IL10 is associated with ENAs positivity (p=0.022). In patients with other autoimmune disease associated with SLE, an increase of INF1A (p=0.008) and IL5 (p=0.044) is observed. SLE patients were categorised by normal, low or high level of the eight citokines. Despite the fact that no specific cytokine profile associated with clinical activity was observed, those patients with high SLEDAI score had increased levels of IL10 and INF1A and decreased levels of IL2 and IL21. <h3>Conclusions</h3> Our SLE patients displayed mainly IL10, INF1A and BLyS increased, and IL2 decreased. Although IL10 seems to be the cytokine which best fits to clinical activity in SLE, altered levels of INF1A, IL2, IL4, and IL5 are associated with complement consumption or anti-DNA positivity. <h3>Disclosure of Interest</h3> None declared
Abstract 14070: Significant Correlation Between Coronary Fractional Flow Reserve and Dobutamine Stress Echocardiography in Patients With Moderate Coronary Artery Disease
Authors: Abdelkrim Ahres, Balázs Jablonkai, Gábor Rubóczky, Ágnes Oze, Zsolt Szigeti, Béla Nagybaczoni, Zsuzsanna D Balogh, Astrid Apor, Karola Wohlfart, Peter Andrássy
Journal: Circulation (2016)

Introduction: Both the fractional flow reserve (FFR) measurement and the dobutamine stress echo (DSE) are accepted diagnostic methods to indicate revascularisation of a moderate coronary stenosis (...
Attention Deficit–Hyperactivity Disorder and Month of School Enrollment
Authors: Timothy J. Layton, Michael L. Barnett, Tanner R. Hicks, Anupam B. Jena
Journal: New England Journal of Medicine (2018)

Younger children in a school grade cohort may be more likely to receive a diagnosis of attention deficit-hyperactivity disorder (ADHD) than their older peers because of age-based variation in behavior that may be attributed to ADHD rather than to the younger age of the children. Most U.S. states have arbitrary age cutoffs for entry into public school. Therefore, within the same grade, children with birthdays close to the cutoff date can differ in age by nearly 1 year.We used data from 2007 through 2015 from a large insurance database to compare the rate of ADHD diagnosis among children born in August with that among children born in September in states with and states without the requirement that children be 5 years old by September 1 for enrollment in kindergarten. ADHD diagnosis was determined on the basis of diagnosis codes from the International Classification of Diseases, 9th Revision. We also used prescription records to compare ADHD treatment between children born in August and children born in September in states with and states without the cutoff date of September 1.The study population included 407,846 children in all U.S. states who were born in the period from 2007 through 2009 and were followed through December 2015. The rate of claims-based ADHD diagnosis among children in states with a September 1 cutoff was 85.1 per 10,000 children (309 cases among 36,319 children; 95% confidence interval [CI], 75.6 to 94.2) among those born in August and 63.6 per 10,000 children (225 cases among 35,353 children; 95% CI, 55.4 to 71.9) among those born in September, an absolute difference of 21.5 per 10,000 children (95% CI, 8.8 to 34.0); the corresponding difference in states without the September 1 cutoff was 8.9 per 10,000 children (95% CI, -14.9 to 20.8). The rate of ADHD treatment was 52.9 per 10,000 children (192 of 36,319 children; 95% CI, 45.4 to 60.3) among those born in August and 40.4 per 10,000 children (143 of 35,353 children; 95% CI, 33.8 to 47.1) among those born in September, an absolute difference of 12.5 per 10,000 children (95% CI, 2.43 to 22.4). These differences were not observed for other month-to-month comparisons, nor were they observed in states with non-September cutoff dates for starting kindergarten. In addition, in states with a September 1 cutoff, no significant differences between August-born and September-born children were observed in rates of asthma, diabetes, or obesity.Rates of diagnosis and treatment of ADHD are higher among children born in August than among children born in September in states with a September 1 cutoff for kindergarten entry. (Funded by the National Institutes of Health.).
Super-Enhancer–Associated Long Noncoding RNA HCCL5 Is Activated by ZEB1 and Promotes the Malignancy of Hepatocellular Carcinoma
Authors: Li Peng, Binyuan Jiang, Xiaoqing Yuan, Yuntan Qiu, Jiangyun Peng, Yongsheng Huang, Chaoyang Zhang, Yin Zhang, Zhaoyu Lin, Jinsong Li, Weicheng Yao, Weixi Deng, Yaqin Zhang, Meng Meng, Xi Pan, Chunquan Li, Dong Yin, Xinyu Bi, Guancheng Li, De-Chen Lin
Journal: Cancer Research (2018)

Abstract Hepatocellular carcinoma (HCC) is one of the most dominant causes of neoplasm-related deaths worldwide. In this study, we identify and characterize HCCL5, a novel cytoplasmic long noncoding RNA (lncRNA), as a crucial oncogene in HCC. HCCL5 promoted cell growth, G1–S transition, invasion, and metastasis while inhibiting apoptosis of HCC cells both in vitro and in vivo. Moreover, HCCL5 was upregulated in TGF-β1-induced classical epithelial-to-mesenchymal transition (EMT) models, and this lncRNA in turn accelerated the EMT phenotype by upregulating the expression of transcription factors Snail, Slug, ZEB1, and Twist1. HCCL5 was transcriptionally driven by ZEB1 via a super-enhancer and was significantly and frequently overexpressed in human HCC tissues, correlating with worse overall survival of patients with HCC. Together, this study characterizes HCCL5 as a super-enhancer–driven lncRNA promoting HCC cell viability, migration, and EMT. Our data also suggest that HCCL5 may serve as a novel prognostic biomarker and therapeutic target in HCC. Significance: These findings identify the lncRNA HCCL5 as a super-enhancer–driven oncogenic factor that promotes the malignancy of hepatocellular carcinoma.
Newly Proposed ALBI Grade and ALBI-T Score as Tools for Assessment of Hepatic Function and Prognosis in Hepatocellular Carcinoma Patients
Authors: Atsushi Hiraoka, Takashi Kumada, Kojiro Michitaka, Masatoshi Kudo
Journal: Liver Cancer (2018)

Background: Because of the rapid progression of antiviral treatment options and the increasing frequency of nonviral-related hepatocellular carcinoma (HCC) due to the aging of society, the number of HCC patients with good hepatic function has been increasing and a more detailed method of assessment of hepatic function is needed. The Child-Pugh classification (CP) is used worldwide as an assessment tool for hepatic reserve function, even though it has some weaknesses. Recently, the albumin-bilirubin (ALBI) grade, calculated based on only albumin and total bilirubin, was proposed, and recent investigations have suggested that ALBI grade instead of CP can be used as an assessment tool for hepatic function as part of therapeutic strategies such as Barcelona Clinic Liver Cancer staging and a practical guideline presented by the Japan Society of Hepatology as well for total staging scoring systems. There has been an increasing number of reports showing that it has better capability than CP for HCC patients who undergo not only curative but also palliative treatments. Transcatheter arterial chemoembolization (TACE) is a major palliative treatment used for unresectable HCC, and the idea of TACE-refractory status has been proposed to indicate the possibility of switching to a tyrosine kinase inhibitor (TKI). However, TKI administration requires a maintained hepatic reserve function, thus the importance of assessment of hepatic function in patients undergoing TACE treatments has increased. We consider that ALBI grade might also play a significant role as part of a detailed assessment of relative changes in hepatic function during treatment. In this review, we evaluate the practical usefulness of ALBI grade for assessing hepatic function and HCC prognosis. Key Message: A detailed assessment of hepatic function is required for recent HCC therapeutic strategies. ALBI grade may be a powerful tool to improve treatment options for affected patients.
Left Ventricular Dyssynchrony Predicts the Cardiomyopathy Associated With Premature Ventricular Contractions
Authors: Tomos E. Walters, Dolkun Rahmutula, Judit Szilagyi, Christina Alhede, Richard Sievers, Qizhi Fang, Jeffrey Olgin, Edward P. Gerstenfeld
Journal: Journal of the American College of Cardiology (2018)
Oral co-administration of a bacterial protease inhibitor in the vaccine formulation increases antigen delivery at the intestinal epithelial barrier
Authors: Lorena M. Coria, Gabriela S. Risso, Francisco F. Guaimas, Mariana C. Ferrero, Laura Bruno, Karina A. Pasquevich, Juliana Cassataro
Journal: Journal of Controlled Release (2018)

The study of capture and processing of antigens (Ags) by intestinal epithelial cells is very important for development of new oral administration systems. Efficient oral Ag delivery systems must resist enzymatic degradation by gastric and intestinal proteases and deliver the Ag across biological barriers. The recombinant unlipidated outer membrane protein from Brucella spp. (U-Omp19) is a protease inhibitor with immunostimulatory properties used as adjuvant in oral vaccine formulations. In the present work we further characterized its mechanism of action and studied the interaction and effect of U-Omp19 on the intestinal epithelium. We found that U-Omp19 inhibited protease activity from murine intestinal brush-border membranes and cysteine proteases from human intestinal epithelial cells (IECs) promoting co-administered Ag accumulation within lysosomal compartments of IECs. In addition, we have shown that co-administration of U-Omp19 facilitated the transcellular passage of Ag through epithelial cell monolayers in vitro and in vivo while did not affect epithelial cell barrier permeability. Finally, oral co-delivery of U-Omp19 in mice induced the production of Ag-specific IgA in feces and the increment of CD103+ CD11b− CD8α+ dendritic cells subset at Peyer's patches. Taken together, these data describe a new mechanism of action of a mucosal adjuvant and support the use of this rationale/strategy in new oral delivery systems for vaccines.
Abstract 14472: Left Ventricular and Atrial Function Indexes Derived From New Echocardiographic Techniques Are Independent Prognostic Predictors in Chagas Disease
Authors: Roberto M Saraiva, Nicole P Pacheco, Gabriel F Alves, Fabiana S Madeira, Maria Eduarda S Bouret, Iane M Pereira, Mauro Felippe F Mediano, Andrea S Sousa, Marcelo T Holanda, Andréa R Costa, Luiz Henrique C Sangenis, Fernanda S Mendes, Sérgio S Xavier, Alejandro Marcel H Moreno
Journal: Circulation (2017)

Introduction: Chagas disease affects around 8 million people worldwide. Chagas disease hallmarks include sudden death and heart failure (HF). Indexes derived from new echocardiographic techniques c...
Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: long-term follow-up of a single-centre, phase 2 study
Authors: Elias Jabbour, Nicholas J Short, Farhad Ravandi, Xuelin Huang, Naval Daver, Courtney D DiNardo, Marina Konopleva, Naveen Pemmaraju, William Wierda, Guillermo Garcia-Manero, Koji Sasaki, Jorge Cortes, Rebecca Garris, Joseph D Khoury, Jeffrey Jorgensen, Nitin Jain, Joie Alvarez, Susan O'Brien, Hagop Kantarjian
Journal: The Lancet Haematology (2018)
Health after cancer: Early patient experience in a pilot survivorship clinic embedded in primary care.
Authors: Lidia Schapira, Marcy Winget, Siqi WU, Jennifer Kim, Cati Brown-Johnson
Journal: Journal of Clinical Oncology (2018)

180 Background: Prior research has identified barriers to provision of quality survivorship care in primary care settings such as lack of expert knowledge and training, primary care burden and insufficient communication with oncologists. We implemented a survivorship clinic at an academic medical center in the primary care division with the goal of defining the elements required for a seamless transition and co-management. Methods: The primary care physician received training in cancer survivorship based on the ASCO Curriculum, shadowing of 3 breast medical oncologists and 1 gynecologic oncologist, attendance at the 2018 Cancer Survivorship Symposium and NCCN’s Cancer Survivorship Advocacy Meeting. Patients with breast and gynecologic cancers were referred by their oncologists or APP (PA or NP) at various points in their cancer trajectory. Clinical characteristics of patients were abstracted from the electronic medical record and in-depth interviews were conducted with 2 patients. Results: 41 patients attended the survivorship clinic. The majority (88%) were breast (63%) or gynecologic (24%) cancer survivors. Patient age was evenly distributed with 8 age &lt; 46, 11 age 46-59, and 7 age &gt; = 60. 23 (56%) patients had stage &lt; 3 at diagnosis. 21 (51%) had been cancer-free for five years + and 4 were referred by their oncologist to help with patient co-management during cancer treatment. Of the 8 breast cancer patients &lt; 46 years old, 6 had a genetic mutation and 7 were interested in fertility. 15/26 breast cancer patients are currently on endocrine therapy. Interviewed patients expressed appreciation for receiving whole-person care and knowing there is bidirectional communication between clinicians. Conclusions: Cancer survivors are open to and interested in a survivorship visit based in a primary care clinic; this includes both patients who have been cancer-free &gt; 5 years as well as those recently treated with curative intent. Greater efforts are needed to train primary care physicians to deliver survivorship visits that are customized to meet the needs of cancer survivors.
Efficacy and Tolerability of Ixazomib, Daratumumab and Low Dose Dexamethasone (IDd) in Unfit and Frail Newly Diagnosed Multiple Myeloma (NDMM) Patients; First Interim Safety Analysis of the Phase II HOVON 143 Study
Authors: Claudia A.M. Stege, Kazem Nasserinejad, Mark-David Levin, Noortje Thielen, Saskia K. Klein, Inge Ludwig, Matthijs Westerman, Paula F Ypma, Yavuz Bilgin, Maaike Sohne, Esther de Waal, Niels WCJ van de Donk, Pieter Sonneveld, Sonja Zweegman
Journal: Blood (2018)