tbuckley/cabot-search huggingface dataset:
Abstract P006: A Comparative Case Study of the American Heart Association ANCHOR Partnerships Program
Authors: Whitney R Garney, Kristen Garcia, Kenneth McLeroy, Laura King Hahn, Victoria Taffe
Journal: Circulation (2017)

Purpose: In 2014, the American Heart Association (AHA) started a new initiative called the Accelerating National Community Health Outcomes through Reinforcing (ANCHOR) Partnerships Program. The ANCHOR Program works to improve cardiovascular health using population-based strategies targeting policy, systems and environmental (PSE) level changes. From March 2015-April 2016, the ANCHOR program supported 15 markets within AHA Affiliates as they implemented community-based interventions using PSE strategies to increase access to healthy food and beverages, physical activity, and smoke-free environments. This community-based approach is relatively new for the organization therefore, a comparative case study was conducted to understanding how the ANCHOR Program worked within the AHA and its Affiliates, as well as what community-based strategies were most successful. Methods: Using a systematic selection procedure that assessed level of readiness, the 15 sites were categorized as either “implementation ready (IR)” or “capacity building (CB)”. After stratifying the sites by intervention focus three markets from each category (n=6) were selected as the units of analysis. Evaluators conducted site visits in each market from February-April 2016. During site visits, a total of 24 interviews were conducted with Affiliate staff, program managers, implementation partners, and community partners. Each interview assessed expected outcomes, planning processes, community support, and success. Interviews were audio recorded, transcribed, and synthesized using a thematic analysis. Results: Significant differences were found in expected outcomes. IR sites wanted to increase community engagement, while CB focused on policy change. Both sites were supported by their Affiliates and partners. Action plans were developed by program managers with Affiliate input, and were used to plan in both sites. IR sites identified barriers at the beginning of planning, while CB sites made revisions frequently as barriers were encountered. Both sites engaged partners in planning. Program managers at IR sites worked closely with partners on implementation, whereas those at CB sites led implementation and partners provided support and connections. Differences were also found in how sites engaged partners. CB sites built broad community engagement and IR sites focused on implementation partner buy-in. Overall, the IR sites felt most successful, while CB sites laid groundwork but were not able to create tangible outcomes. Discussion: This comparative case study provides important information about how the AHA can embed community-based work within their ongoing efforts using existing Affiliate structures. The multiple viewpoints captured provides insight into implementation processes and how this type of work is best accomplished, as well as how level of readiness can impact progress.
A systematic approach to smoking cessation in Ontario’s Regional Cancer Programs.
Authors: William K. Evans, Roseanna Presutti, Mohammad Haque, Rebecca Truscott, Marcia Bassier-Paltoo, Alice Peter, Linda Rabeneck
Journal: Journal of Clinical Oncology (2015)

6544 Background: Smoking cessation (SC) is rarely undertaken in busy cancer centres but potential health benefits in cancer patients include improved general health, improved all-cause and cancer-specific mortality, reduced toxicity, greater response to treatment, decreased risk of disease recurrence and of second primaries. Based on this evidence, Cancer Care Ontario (CCO) undertook a SC initiative for new ambulatory cancer patients in its Regional Cancer Programs (RCPs). Methods: A steering committee recommended a framework for SC in RCPs in 2012, based on the Ottawa Model for Smoking Cessation. The initiative was piloted in all 14 provincial health regions in 2014. Regional SC “champions” participated in monthly web meetings, data calls and in-person meetings led by a secretariat at CCO. Presentations on the health benefits of SC were made to physicians and other health care providers in the RCPs. New ambulatory cancer patients are screened, advised and referred to internal or external SC services dependent on regional resources. CCO’s data collection processes capture performance metrics. Patient data are aggregated at the RCP-level and provincial performance indicators reported quarterly. A standardized cancer patient resource on SC will be available in both French and English in a print-ready format and adapted for the Aboriginal population by March 2015. Results: During Q1 and Q2 of the 2014/15 fiscal year, 56.0% (Q1) and 51.5% (Q2) of new ambulatory cancer cases were screened for their smoking status: 25% of those screened were current or recent smokers (within last 6 months); 75% of these were advised of the benefits of cessation; nearly 50% were recommended a referral for cessation services, and about 67% of those referred accepted a referral. Conclusions: CCO’s approach has led to province-wide implementation of a standardized intervention in a relatively short timeframe despite limited financial resources. Despite oncologist resistance and limited regional resources, there has been substantial progress. Framing SC as a quality of care issue has been critical to the success to date. Sustainability of the initiative will be dependent on funding for dedicated SC counselors and evidence of program cost-effectiveness.
A Learning Health System Approach to the Opioid Crisis
Authors: Elizabeth C. Wick, Niraj L. Sehgal
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Novel fluorescent probes of 10-hydroxyevodiamine: autophagy and apoptosis-inducing anticancer mechanisms
Authors: Shuqiang Chen, Guoqiang Dong, Shanchao Wu, Na Liu, Wannian Zhang, Chunquan Sheng
Journal: Acta Pharmaceutica Sinica B (2018)

Natural product evodiamine and its derivatives represent a promising class of multi-target antitumor agents. However, the clinical development of these compounds has been hampered by a poor understanding of their antitumor mechanisms. To tackle this obstacle, herein, novel fluorescent probes were designed to elucidate the antitumor mode of action of 10-hydroxyevodiamine. This compound was proven to be distributed in the mitochondria and lysosomes and to act by autophagy and apoptosis mechanisms.
Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small-cell lung cancer: results from the exploratory, controlled, randomized, international phase II IMPULSE study
Authors: M. Thomas, S. Ponce-Aix, A. Navarro, J. Riera-Knorrenschild, M. Schmidt, E. Wiegert, K. Kapp, B. Wittig, C. Mauri, M. Dómine Gómez, J. Kollmeier, P. Sadjadian, K -P Fröhling, R.M. Huber, M. Wolf, Georg Pall, Veerle Surmont, Léon Bosquee, Paul Germonpré, Wolfgang Brückl, Christina Grah, Christian Herzmann, Rumo Leistner, Andreas Meyer, Lothar Müller, Oliver Schmalz, Christian Scholz, Michael Schröder, Monika Serke, Claas Wesseler, Christian Brandts, Hans-Georg Kopp, Wolfgang Blau, Frank Griesinger, Maria Rosario Garcia Campelo, Yolanda Garcia Garcia, José Manuel Trigo Perez
Journal: Annals of Oncology (2018)

The immune surveillance reactivator lefitolimod (MGN1703), a DNA-based TLR9 agonist, might foster innate and adaptive immune response and thus improve immune-mediated control of residual cancer disease. The IMPULSE phase II study evaluated the efficacy and safety of lefitolimod as maintenance treatment in extensive-stage small-cell lung cancer (ES-SCLC) after objective response to first-line chemotherapy, an indication with a high unmet medical need and stagnant treatment improvement in the last decades.103 patients with ES-SCLC and objective tumor response (as per RECIST 1.1) following four cycles of platinum-based first-line induction therapy were randomized to receive either lefitolimod maintenance therapy or local standard of care at a ratio of 3 : 2 until progression or unacceptable toxicity.From 103 patients enrolled, 62 were randomized to lefitolimod, 41 to the control arm. Patient demographics and response patterns to first-line therapy were balanced. Lefitolimod exhibited a favorable safety profile and pharmacodynamic assessment confirmed the mode-of-action showing a clear activation of monocytes and production of interferon-gamma-induced protein 10 (IP-10). While in the intent-to-treat (ITT) population no relevant effect of lefitolimod on progression-free and overall survival (OS) could be observed, two predefined patient subgroups indicated promising results, favoring lefitolimod with respect to OS: in patients with a low frequency of activated CD86+ B cells (hazard ratio, HR 0.53, 95% CI: 0.26-1.08; n = 38 of 88 analyzed) and in patients with reported chronic obstructive pulmonary disease (COPD) (HR 0.48, 95% CI: 0.20-1.17, n = 25 of 103).The IMPULSE study showed no relevant effect of lefitolimod on the main efficacy end point OS in the ITT, but (1) the expected pharmacodynamic response to lefitolimod, (2) positive OS efficacy signals in two predefined subgroups and (3) a favorable safety profile. These data support further exploration of lefitolimod in SCLC.
Prostate Cancer Radiotherapy: An Evolving Paradigm
Authors: Charles N. Catton, Himu Lukka, Jarad Martin
Journal: Journal of Clinical Oncology (2018)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A urologist referred a 69-year-old man for a radiotherapy opinion regarding a recently diagnosed adenocarcinoma of the prostate. Annual serum prostate-specific antigen (PSA) testing over 7 years demonstrated a rise in PSA from 1.36 ng/mL to 5.8 ng/mL, prompting a transrectal ultrasound that revealed a heterogeneous 37-mL gland containing no visualized hypoechoic nodules. Biopsy disclosed a Gleason score 3+4 (grade group 2) adenocarcinoma of the prostate. The synoptic report stated that six of 14 cores and 17% of the tissue were involved, with the greatest core involvement being 80% at the right apex. Perineural invasion was present without lymphovascular invasion. Disease was present bilaterally at the base, midgland, and apex.His medical history was significant only for treated peptic ulcer disease and he was taking no medication. His International Prostate Symptom Score was six of 35, and he reported being sexually active with good erectile function. There was no family history of prostate cancer. He is retired. Digital rectal examination revealed moderate benign prostatic hypertrophy with no suspicious nodules. A staging computerized tomography (CT) scan of the abdomen and pelvis and a whole-body bone scan ordered by his referring urologist reported no evidence of metastatic disease. The patient had discussed surgical options with his urologist and now wished to consider radiotherapy approaches.
Gasdermin D plays a vital role in the generation of neutrophil extracellular traps
Authors: Gabriel Sollberger, Axel Choidas, Garth Lawrence Burn, Peter Habenberger, Raffaella Di Lucrezia, Susanne Kordes, Sascha Menninger, Jan Eickhoff, Peter Nussbaumer, Bert Klebl, Renate Krüger, Alf Herzig, Arturo Zychlinsky
Journal: Science Immunology (2018)

The death of a cell is an inevitable part of its biology. During homeostasis, most cells die through apoptosis. If homeostasis is disturbed, cell death can switch to proinflammatory forms of death, such as necroptosis, pyroptosis, or NETosis. We demonstrate that the formation of neutrophil extracellular traps (NETs), a special form of neutrophil cell death that releases chromatin structures to the extracellular space, is dependent on gasdermin D (GSDMD). GSDMD is a pore-forming protein and an executor of pyroptosis. We screened a chemical library and found a small molecule based on the pyrazolo-oxazepine scaffold that efficiently blocks NET formation and GSDMD-mediated pyroptotic cell death in human cells. During NETosis, GSDMD is proteolytically activated by neutrophil proteases and, in turn, affects protease activation and nuclear expansion in a feed-forward loop. In addition to the central role of GSDMD in pyroptosis, we propose that GSDMD also plays an essential function in NETosis.
Comparison of Therapies for Primary Prevention of Esophageal Variceal Bleeding: A Systematic Review and Network Meta‐analysis
Authors: Mayank Sharma, Siddharth Singh, Vivek Desai, Vijay H. Shah, Patrick S. Kamath, Mohammad Hassan Murad, Douglas A. Simonetto
Journal: Hepatology (2018)

We performed a systematic review with network meta‐analysis (NMA) to compare the efficacy of different approaches in primary prevention of esophageal variceal bleeding and overall survival in patients with cirrhosis with large varices. Thirty‐two randomized clinical trials (RCTs) with 3,362 adults with cirrhosis with large esophageal varices and no prior history of bleeding, with a minimum of 12 months of follow‐up, were included. Nonselective beta‐blockers (NSBB), isosorbide‐mononitrate (ISMN), carvedilol, and variceal band ligation (VBL), alone or in combination, were compared with each other or placebo. Primary outcomes were reduction of all‐cause mortality and prevention of esophageal variceal bleeding. Random‐effects NMA was performed and summary estimates were expressed as odds ratio and 95% confidence intervals (OR; CI). Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. Moderate quality evidence supports NSBB monotherapy (0.70; 0.49‐1.00) or in combination with VBL (0.49; 0.23‐1.02) or ISMN (0.44; 0.21‐0.93) for decreasing mortality in patients with cirrhosis with large esophageal varices and no prior history of bleeding. Moderate‐quality evidence supports carvedilol (0.21; 0.08‐0.56) and VBL monotherapy (0.33; 0.19‐0.55) or in combination with NSBB (0.34; 0.14‐0.86), and low‐quality evidence supports NSBB monotherapy (0.64; 0.38‐1.07) for primary prevention of variceal bleeding. VBL carries a higher risk of serious adverse events compared with NSBB. Conclusion: NSBB monotherapy may decrease all‐cause mortality and the risk of first variceal bleeding in patients with cirrhosis with large esophageal varices. Additionally, NSBB carries a lower risk of serious complications compared with VBL. Therefore, NSBB may be the preferred initial approach for primary prophylaxis of esophageal variceal bleeding.
Nuclear Folate Metabolism
Authors: Martha S. Field, Elena Kamynina, James Chon, Patrick J. Stover
Journal: Annual Review of Nutrition (2018)

Despite unequivocal evidence that folate deficiency increases risk for human pathologies, and that folic acid intake among women of childbearing age markedly decreases risk for birth defects, definitive evidence for a causal biochemical pathway linking folate to disease and birth defect etiology remains elusive. The de novo and salvage pathways for thymidylate synthesis translocate to the nucleus of mammalian cells during S- and G2/M-phases of the cell cycle and associate with the DNA replication and repair machinery, which limits uracil misincorporation into DNA and genome instability. There is increasing evidence that impairments in nuclear de novo thymidylate synthesis occur in many pathologies resulting from impairments in one-carbon metabolism. Understanding the roles and regulation of nuclear de novo thymidylate synthesis and its relationship to genome stability will increase our understanding of the fundamental mechanisms underlying folate- and vitamin B12-associated pathologies.
Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract
Authors: Amelie T. van der Ven, Dervla M. Connaughton, Hadas Ityel, Nina Mann, Makiko Nakayama, Jing Chen, Asaf Vivante, Daw-yang Hwang, Julian Schulz, Daniela A. Braun, Johanna Magdalena Schmidt, David Schapiro, Ronen Schneider, Jillian K. Warejko, Ankana Daga, Amar J. Majmundar, Weizhen Tan, Tilman Jobst-Schwan, Tobias Hermle, Eugen Widmeier, Shazia Ashraf, Ali Amar, Charlotte A. Hoogstraaten, Hannah Hugo, Thomas M. Kitzler, Franziska Kause, Caroline M. Kolvenbach, Rufeng Dai, Leslie Spaneas, Kassaundra Amann, Deborah R. Stein, Michelle A. Baum, Michael J.G. Somers, Nancy M. Rodig, Michael A. Ferguson, Avram Z. Traum, Ghaleb H. Daouk, Radovan Bogdanović, Natasa Stajić, Neveen A. Soliman, Jameela A. Kari, Sherif El Desoky, Hanan M. Fathy, Danko Milosevic, Muna Al-Saffar, Hazem S. Awad, Loai A. Eid, Aravind Selvin, Prabha Senguttuvan, Simone Sanna-Cherchi, Heidi L. Rehm, Daniel G. MacArthur, Monkol Lek, Kristen M. Laricchia, Michael W. Wilson, Shrikant M. Mane, Richard P. Lifton, Richard S. Lee, Stuart B. Bauer, Weining Lu, Heiko M. Reutter, Velibor Tasic, Shirlee Shril, Friedhelm Hildebrandt
Journal: Journal of the American Society of Nephrology (2018)

Background Congenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent cause of kidney disease in the first three decades of life. Previous gene panel studies showed monogenic causation in up to 12% of patients with CAKUT. Methods We applied whole-exome sequencing to analyze the genotypes of individuals from 232 families with CAKUT, evaluating for mutations in single genes known to cause human CAKUT and genes known to cause CAKUT in mice. In consanguineous or multiplex families, we additionally performed a search for novel monogenic causes of CAKUT. Results In 29 families (13%), we detected a causative mutation in a known gene for isolated or syndromic CAKUT that sufficiently explained the patient’s CAKUT phenotype. In three families (1%), we detected a mutation in a gene reported to cause a phenocopy of CAKUT. In 15 of 155 families with isolated CAKUT, we detected deleterious mutations in syndromic CAKUT genes. Our additional search for novel monogenic causes of CAKUT in consanguineous and multiplex families revealed a potential single, novel monogenic CAKUT gene in 19 of 232 families (8%). Conclusions We identified monogenic mutations in a known human CAKUT gene or CAKUT phenocopy gene as the cause of disease in 14% of the CAKUT families in this study. Whole-exome sequencing provides an etiologic diagnosis in a high fraction of patients with CAKUT and will provide a new basis for the mechanistic understanding of CAKUT.
Abstract B48: Proteomic analysis of extracellular vesicles from resistant gastric cancer cell line
Authors: Edson Kuatelela Cassinela, Grabriela Pintar Oliveira, Michele Christine Landemberger, Vilma Regina Martins
Journal: Clinical Cancer Research (2018)

Abstract Background: Gastric cancer is the fourth most common cause of cancer death worldwide and one of the tumors with higher mortality rates in Brazil. Chemotherapy is one of the major treatments for gastric cancer, but drug resistance limits the effectiveness, resulting in treatment failure. The mechanisms of gastric cancer pathogenesis are largely unknown, as is what causes limitations in the personalized treatment. Neoadjuvant therapy has been largely applied in these tumors because it can improve tumor resectability and survival of patients. However, tumors can develop resistance during chemotherapy, or this resistance can be present intrinsically before chemotherapy. Indeed, mechanisms associated to chemotherapy resistance in gastric cancer are complex and multifactorial; understanding the variety of these factors that are involved in chemoresistance is of great relevance. Materials and Methods: Gastric adenocarcinoma cell line (AGS) was treated with increased concentration of 5-fluorouracil to generate a resistant cell (rAGS_FU). Extracellular vesicles (EVs) secreted from AGS and rAGS_FU cell lines were isolated by ultracentrifugation, quantified, and evaluated regarding their aggressiveness through invasion and colony assays. Proteomics analysis of EVs and secreting cells were performed to identify potential markers for chemotherapy resistance in gastric cancer cell lines. Results: We found proteins involved in resistance to chemotherapy upregulated in EVs derived from resistant cells; parental cells treated with EVs derived from resistant cells were able to promote high colony formation and increased invasion potential. Thus, cells resistant to chemotherapy have a more aggressive phenotype and are able to transfer these acquired characteristics to the nonresistant ones using EVs. We compared the proteomes of EVs derived from the two cell lines and revealed important pathways that can be associated with chemoresistance in gastric cancers. Conclusion: It is crucial to understand these chemoresistance mechanisms and develop efficient treatment strategies to overcome them. A deep investigation of these data is needed to understand and create new opportunities for the discovery of new biomarkers of response to chemotherapy in gastric cancers and contribute to the better understanding of the biologic role of molecules shuttled by EVs. Citation Format: Edson Kuatelela Cassinela, Grabriela Pintar Oliveira, Michele Christine Landemberger, Vilma Regina Martins. Proteomic analysis of extracellular vesicles from resistant gastric cancer cell line [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B48.
Abstract 20619: Feasibility of Ultrasound Guided Vascular Access for Implantable Cardiac Devices
Authors: Jeffrey Lin, Graham Adsit, Anne Barnett, Mathew Tattersall, Jennifer Wright
Journal: Circulation (2016)

Introduction: Ultrasound (US) guided access for venous catheter placement has previously been shown to improve success rates and decrease access-related complications. Little is known about the fea...