tbuckley/cabot-search huggingface dataset:
Genetic Advances in Chronic Obstructive Pulmonary Disease. Insights from COPDGene
Authors: Margaret F. Ragland, Christopher J. Benway, Sharon M. Lutz, Russell P. Bowler, Julian Hecker, John E. Hokanson, James D. Crapo, Peter J. Castaldi, Dawn L. DeMeo, Craig P. Hersh, Brian D. Hobbs, Christoph Lange, Terri H. Beaty, Michael H. Cho, Edwin K. Silverman
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Chronic obstructive pulmonary disease (COPD) is a common and progressive disease that is influenced by both genetic and environmental factors. For many years, knowledge of the genetic basis of COPD was limited to Mendelian syndromes, such as alpha-1 antitrypsin deficiency and cutis laxa, caused by rare genetic variants. Over the past decade, the proliferation of genome-wide association studies, the accessibility of whole-genome sequencing, and the development of novel methods for analyzing genetic variation data have led to a substantial increase in the understanding of genetic variants that play a role in COPD susceptibility and COPD-related phenotypes. COPDGene (Genetic Epidemiology of COPD), a multicenter, longitudinal study of over 10,000 current and former cigarette smokers, has been pivotal to these breakthroughs in understanding the genetic basis of COPD. To date, over 20 genetic loci have been convincingly associated with COPD affection status, with additional loci demonstrating association with COPD-related phenotypes such as emphysema, chronic bronchitis, and hypoxemia. In this review, we discuss the contributions of the COPDGene study to the discovery of these genetic associations as well as the ongoing genetic investigations of COPD subtypes, protein biomarkers, and post-genome-wide association study analysis.
Abstract P3-14-06: Concordance assessment of IBM Watson for Oncology with MDT in patients with breast cancer
Authors: J Xu, T Sun, S Hua
Journal: Cancer Research (2019)

Abstract Objective: IBM Watson for Oncology (WFO) is an artificial intelligence cognitive clinical decision support system which provides evidence-based treatment recommendations in cancer. This study aimed to examine the level of agreement (concordance) between treatment recommendations made by WFO and a multidisciplinary tumor (MDT) board for adjuvant therapy in early stage breast cancer and first-line therapy in metastatic breast cancer. Methods: Treatment recommendations were provided by WFO and MDT board for 92 early stage and 40 metastatic breast cancer cases between Jan 2017 and Jan 2018. WFO treatment recommendations were provided in 3 categories: “Recommended”, “For Consideration” and “Not Recommended.” It was considered concordant if the tumor board recommendations were designated 'recommended' or 'for consideration' by WFO Version 17.10. Results: Overall treatment concordance between WFO and MDT was 76.51%, 73 cases with early stage breast cancer (79.35%) and 28 cases with metastatic breast cancer (70.00%) we concordant. Among all the 132 cases, 49 cases were in 'Recommended' category, 52 cases were in 'for consideration' category, and 26 cases were disconcordant. Subgroup analysis found that patients with stageIIIdisease or triple-negative breast cancer were the most likely to be concordant. Luminal A type and HER2-positive cases were less likely to be concordant than other types. In early stage breast cancer, based on the low recurrence risk, 11 cases and 2 cases were treated with TC and EC regimen instead of AC-T or CMF regimen recommended by WFO. 4 patients with HER2-positive were disconcordance by using TCbH or AC-TH regimen instead of AC-TH or CMFH regimen recommended by WFO. The main reason of disconcordance in metastatic cancer was that CDK4/6 inhibitors had not been approved in China. Conclusion: Treatment recommendations made by WFO and the tumor board showed highly concordant in breast cancer. Cancer stage and subtype had significant influence on concordance, and Watson for Oncology need to be optimized in localization. Citation Format: Xu J, Sun T, Hua S. Concordance assessment of IBM Watson for Oncology with MDT in patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-14-06.
Targeting the tumor stroma with an oncolytic adenovirus secreting a fibroblast activation protein-targeted bispecific T-cell engager
Authors: Jana de Sostoa, Carlos Alberto Fajardo, Rafael Moreno, Maria D. Ramos, Martí Farrera-Sal, Ramon Alemany
Journal: Journal for ImmunoTherapy of Cancer (2019)

Oncolytic virus (OV)-based therapies have an emerging role in the treatment of solid tumors, involving both direct cell lysis and immunogenic cell death. Nonetheless, tumor-associated stroma limits the efficacy of oncolytic viruses by forming a barrier that blocks efficient viral penetration and spread. The stroma also plays a critical role in progression, immunosuppression and invasiveness of cancer. Fibroblast activation protein-α (FAP) is highly overexpressed in cancer-associated fibroblasts (CAFs), the main cellular component of tumor stroma, and in this study we assessed whether arming oncolytic adenovirus (OAd) with a FAP-targeting Bispecific T-cell Engager (FBiTE) could retarget infiltrated lymphocytes towards CAFs, enhancing viral spread and T cell-mediated cytotoxicity against the tumor stroma to improve therapeutic activity.The bispecific T-cell Engager against FAP was constructed using an anti-human CD3 single-chain variable fragment (scFv) linked to an anti-murine and human FAP scFv. This FBiTE was inserted in the oncolytic adenovirus ICOVIR15K under the control of the major late promoter, generating the ICO15K-FBiTE. ICO15K-FBiTE replication and potency were assessed in HT1080 and A549 tumor cell lines. The expression of the FBiTE and the activation and proliferation of T cells that induced along with the T cell-mediated cytotoxicity of CAFs were evaluated by flow cytometry in vitro. In vivo, T-cell biodistribution and antitumor efficacy studies were conducted in NOD/scid/IL2rg-/- (NSG) mice.FBiTE expression did not decrease the infectivity and replication potency of the armed virus. FBiTE-mediated binding of CD3+ effector T cells and FAP+ target cells led to T-cell activation, proliferation, and cytotoxicity of FAP-positive cells in vitro. In vivo, FBiTE expression increased intratumoral accumulation of T cells and decreased the level of FAP, a marker of CAFs, in tumors. The antitumor activity of the FBiTE-armed adenovirus was superior to the parental virus.Combination of viral oncolysis of cancer cells and FBiTE-mediated cytotoxicity of FAP-expressing CAFs might be an effective strategy to overcome a key limitation of oncolytic virotherapy, encouraging its further clinical development.
Prophylactic pancreatic duct stenting in severe acute necrotizing pancreatitis: a prospective randomized study
Authors: Heikki Karjula, Palle Nordblad Schmidt, Jyrki Mäkelä, Janne H. Liisanantti, Pasi Ohtonen, Arto Saarela
Journal: Endoscopy (2019)

Abstract Background Pancreatic duct disruption is common and is associated with high morbidity in cases of acute necrotizing pancreatitis (ANP). In this study, we tested the feasibility and safety of prophylactic pancreatic duct stenting (PPDS) in ANP and compared PPDS with conservative treatment. Methods We prospectively enrolled patients (aged 18 – 75 years) diagnosed with ANP between February 2011 and July 2015. These patients were prospectively randomized to receive PPDS or conservative treatment at two tertiary centers. PPDS was performed as soon as possible after randomization. Results Concern regarding iatrogenic infections with pancreatic necrosis in the PPDS group prompted interim analysis, which confirmed a highly elevated risk. Thus, the trial was terminated prematurely for ethical reasons. Of the 11 patients in the PPDS group, all patients with successful pancreatic duct placement (5/5, 100 %) presented with infection, compared with only 3 of the 13 patients (23.1 %) in the conservative treatment group (P = 0.01). Analysis revealed success rates of 63.6 % for pancreatic duct cannulation, 45.5 % for pancreatic duct stenting, and 18.2 % for placement of a stent bridging the necrosis. Cannulation and stenting failures were due to duodenal edema and pancreatic duct stenosis. Conclusions PPDS in ANP is associated with an unacceptably high risk of pancreatic necrosis infection. In addition, the procedure is technically challenging due to duodenal edema and ductal stenosis.
Trends in Medicaid Prices, Market Share, and Spending on Long-Acting Insulins, 2006-2018
Authors: Inmaculada Hernandez, Chester B. Good, William H. Shrank, Walid F. Gellad
Journal: JAMA (2019)

This study uses Medicaid drug utilization data to describe reimbursement and market share of long-acting insulins before and after approval of new insulin products and to estimate savings associated with a "biosimilar" for insulin glargine approved in 2015.
Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis
Authors: Sjoerd van der Post, Karolina S Jabbar, George Birchenough, Liisa Arike, Noreen Akhtar, Henrik Sjovall, Malin E V Johansson, Gunnar C Hansson
Journal: Gut (2019)

Objective The colonic inner mucus layer protects us from pathogens and commensal-induced inflammation, and has been shown to be defective in active UC. The aim of this study was to determine the underlying compositional alterations, their molecular background and potential contribution to UC pathogenesis. Design In this single-centre case–control study, sigmoid colon biopsies were obtained from patients with UC with ongoing inflammation (n=36) or in remission (n=28), and from 47 patients without colonic disease. Mucus samples were collected from biopsies ex vivo, and their protein composition analysed by nanoliquid chromatography-tandem mass spectrometry. Mucus penetrability and goblet cell responses to microbial stimulus were assessed in a subset of patients. Results The core mucus proteome was found to consist of a small set of 29 secreted/transmembrane proteins. In active UC, major structural mucus components including the mucin MUC2 (p&lt;0.0001) were reduced, also in non-inflamed segments. Active UC was associated with decreased numbers of sentinel goblet cells and attenuation of the goblet cell secretory response to microbial challenge. Abnormal penetrability of the inner mucus layer was observed in a subset of patients with UC (12/40; 30%). Proteomic alterations in penetrable mucus samples included a reduction of the SLC26A3 apical membrane anion exchanger, which supplies bicarbonate required for colonic mucin barrier formation. Conclusion Core mucus structural components were reduced in active UC. These alterations were associated with attenuation of the goblet cell secretory response to microbial challenge, but occurred independent of local inflammation. Thus, mucus abnormalities are likely to contribute to UC pathogenesis.
CLO19-031: Immune Checkpoint Inhibitors: Optimization of Pharmacy Services in Toxicity Management
Authors: Olivia G. Fahey, Elizabeth N. Dow, Jennifer K. Piccolo, Ticiana A. Leal
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Use of immune checkpoint inhibitors (ICPi) in oncology continues to rapidly expand. ICPis have a unique toxicity profile and can lead to immune related adverse events (irAEs), some serious and potentially life-threatening. Early detection and appropriate treatment may limit the morbidity and mortality of irAEs and allow patients who are deriving benefit from ICPi to continue treatment. Pharmacists practicing in UW Health Carbone Cancer Center clinics are uniquely positioned to educate patients about common ICPi toxicities and ensure appropriate, early recognition and management of irAEs in collaboration with the multidisciplinary team. Methods: Within lung, melanoma, and gastrointestinal medical oncology clinics, a program was implemented involving pharmacists educating patients and families prior to the start of treatment as well as contacting patients at regular intervals to assess for any signs or symptoms of irAEs. The primary outcome is the number of patients experiencing Common Terminology Criteria for Adverse Events version 5.0 (CTCAE) grade 1 or 2 irAEs identified by a pharmacist enrolled in the program. Secondary outcomes include grade ≥ 3 irAEs identified by a pharmacist, the total number of patients enrolled in the program with any irAE, reason for discontinuation of ICPi, emergency department visits, and hospital admissions during the study period. Results: Between November 14, 2017 and October 15, 2018, a total of 81 patients were enrolled in the program with 49 of those patients still enrolled at the end of the study period. These patients experienced a total of 39 grade 1 and 13 grade 2 irAEs, of which 53.8% (n=28) were identified by pharmacists. The most common grade 1 or 2 toxicities identified by pharmacists were gastrointestinal (n=15) and dermatologic (n=6). Endocrine (n=7) and dermatologic (n=7) were the most common grade 1 or 2 irAEs identified by other providers. There were 4 grade 3 irAEs (endocrine, fatigue, liver, and pneumonitis) identified by other providers, and there were no grade 4 irAEs. Conclusion: Proactive pharmacist contact at regular intervals during ICPi treatment resulted in the early discovery of grade 1 or 2 irAEs experienced by patients. This pharmacist-driven approach may allow for earlier treatment of any toxicities experienced after ICPi treatment and reduce the rates of serious irAEs. Current efforts are focused on expanding these services to all UW Health Carbone Cancer Center clinics.
Balance of Anti-CD123 Chimeric Antigen Receptor (CAR) Binding Affinity and Density for the Treatment of Acute Myeloid Leukemia
Authors: Silvia Arcangeli, Marco Bardelli, Maria Caterina Rotiroti, Luca Simonelli, Chiara F. Magnani, Luca Varani, Andrea Biondi, Ettore Biagi, Sarah Tettamanti
Journal: Blood (2016)
Structure and quality assurance of Fellowship Training in General Surgery: Consensus recommendations from the Association of Surgeons in Training
Authors: Christina Fleming, Philip Pucher, Elizabeth Elsey, James Glasbey, John Conneely, Aisling Hogan, Robert Adair, Jonathan Lund, Natalie Blencowe, Andrew Smith, Christos Athanasiou, Kelvin Wong, Ofuchi Egbuji, Aysha Latif, Saira Bibi, Emer O'Connell, Michael Flanagan, Umasankar Thiyagarajan, Elizabeth Kane, Yangi Baeiv, Renol Koshy, Abhilash Sudarsanam, Struvan Gray, Mark Johnstone, Ahmed El Muntasar, Adetunji Adeyanzu, Mavis Orizu, Nisha Mallya, Sita Kotecha, Prita Daliya, Ben E. Byrne, Pippa Leighton, Zoe Oliphant, Kieran Clement, Duncan Scrimgeour, David Holroyd, Matthew Doe, Shelly Griffiths, Alice Chambers, Ji Tham, Priya Arunachalam, John O'Callaghan, Maria Irene Bellini, Jelizaveta Pereca, Oram Hoq, Peter Sagar, Ardit Begaj, Gemma Humm, Adam Williams, Anthony Thaventhiran, Joshua Michael Clements, Henry Ferguson, Siobhan C. McKay, Helen Mohan, Christina Fleming, Elizabeth Elsey, James Glasbey, Natalie Blencowe, Helen Mohan, Elizabeth Elsey, James Glasbey, Helen Mohan, Christina Fleming, Elizabeth Kane, Jonathan Lund, Joshua Clements, James Glasbey, Henry Ferguson, Siobhan C McKay, Natalie Blencowe, Adam Peckham-Cooper, Philip Pucher, Gemma Humm, Helen Mohan
Journal: International Journal of Surgery (2019)
An Elderly Woman With Violaceous Swelling With Telangiectasia and Necrosis on the Face
Authors: Qian-Nan Jia, Hong-Zhong Jin, Yue-Ping Zeng
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
CLO19-055: Implementing Scalp Cooling: Considerations and Best Practice
Authors: Brittany Unthank, Lynne Laurence Brophy, Lindsey Radcliff, Heidi Basinger, Sabrenna Bourque
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Scalp cooling is a useful technique for decreasing hair loss and reducing the stigma patients feel when they experience alopecia. It was used for a period of time in the U.S. more than 20 years ago and then was removed from the market while use continued in Europe. Recently, better equipment has been developed and approved by the FDA for use with patients who have solid tumors. Current evidence supports this technology and will be summarized in this presentation. Discussion: Setting up scalp cooling as an offered service at any setting presents many challenges and changes in workflow affecting physicians and nursing staff. The purpose of this presentation is to prepare oncology providers who wish to implement scalp cooling using a machine based system at their setting. Our implementation process will be used as a teaching case study. Product support, logistics, patient satisfaction, equipment, and education needs will be discussed. This project description will highlight the steps taken to implement scalp cooling at a comprehensive cancer center for breast and gynecology oncology patients. Initial efforts to review the literature, investigate equipment choices, and compare use with other centers will be reviewed. The management aspects of setting up a new service, eg, business plan, physical plan considerations, informed consent, costs, staffing, workflow, clinic schedules, safety, and staff education will be shared. Important tips for keeping patients safe and comfortable while achieving maximum therapeutic benefit will be discussed. Evaluation will be presented in the form of lessons learned during implementation resulting in more efficient work flow and greater patient comfort during scalp cooling. Patient satisfaction data will be disseminated. Conclusion: The oncology community is eager to provide patients with scalp cooling, but no literature to date has described the management aspects of implementation. This presentation will offer comprehensive information to assist in addressing anticipated needs when initiating scalp cooling.
Failed immune responses across multiple pathologies share pan-tumor and circulating lymphocytic targets
Authors: Anne Monette, Antigoni Morou, Nadia A. Al-Banna, Louise Rousseau, Jean-Baptiste Lattouf, Sara Rahmati, Tomas Tokar, Jean-Pierre Routy, Jean-François Cailhier, Daniel E. Kaufmann, Igor Jurisica, Réjean Lapointe
Journal: Journal of Clinical Investigation (2019)

Tumor-infiltrating lymphocytes (TILs) are widely associated with positive outcomes, yet carry key indicators of a systemic failed immune response against unresolved cancer. Cancer immunotherapies can reverse their tolerance phenotypes while preserving tumor reactivity and neoantigen specificity shared with circulating immune cells. We performed comprehensive transcriptomic analyses to identify gene signatures common to circulating and TILs in the context of clear cell renal cell carcinoma. Modulated genes also associated with disease outcome were validated in other cancer types. Through comprehensive bioinformatics analyses, we identified practical diagnostic markers and actionable targets of the failed immune response. On circulating lymphocytes, 3 genes (LEF1, FASLG, and MMP9) could efficiently stratify patients from healthy control donors. From their associations with resistance to cancer immunotherapies and microbial infections, we uncovered not only pan-cancer, but pan-pathology, failed immune response profiles. A prominent lymphocytic matrix metallopeptidase cell migration pathway is central to a panoply of diseases and tumor immunogenicity, correlates with multi-cancer recurrence, and identifies a feasible noninvasive approach to pan-pathology diagnoses. The differentially expressed genes we have identified warrant future investigation into the development of their potential in noninvasive precision diagnostics and precision pan-disease immunotherapeutics.
Tuberculosis research questions identified through the WHO policy guideline development process
Authors: Nebiat Gebreselassie, Dennis Falzon, Matteo Zignol, Tereza Kasaeva
Journal: European Respiratory Journal (2019)

<b>WHO guideline development groups identify research questions using systematic reviews, economic analyses and stakeholder consultations during policy guidance development to identify urgent research gaps in the policy/implementation interface</b>http://ow.ly/lUUw30nQZRO
Identification of Cysteine‐Rich Angiogenic Inducer 61 as a Potential Antifibrotic and Proangiogenic Mediator in Scleroderma
Authors: Pei‐Suen Tsou, Dinesh Khanna, Amr H. Sawalha
Journal: Arthritis & Rheumatology (2019)

We previously identified CYR61 as a histone deacetylase 5 (HDAC-5)-repressed gene in systemic sclerosis (SSc; scleroderma) endothelial cells (ECs). When overexpressed, cysteine-rich angiogenic inducer 61 (CYR-61) promoted angiogenesis in SSc ECs. This study was undertaken to examine the role of CYR-61 in fibrosis and determine the mechanisms involved in CYR-61-mediated angiogenesis in SSc.Dermal ECs and fibroblasts were isolated from biopsy specimens from healthy subjects and patients with SSc. CYR-61 level was determined by quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. CYR-61 was overexpressed using a CYR61 vector or knocked down using small interfering RNA, and functional and mechanistic studies were then conducted in fibroblasts and ECs.Lower CYR61 messenger RNA levels were observed in dermal fibroblasts and ECs from SSc patients than in those from healthy controls. In SSc fibroblasts, overexpression of CYR-61 led to significant reduction in the expression of profibrotic genes, including COL1A1 (P = 0.002) and ACTA2 (P = 0.04), and an increase in the expression of matrix-degrading genes, including MMP1 (P = 0.002) and MMP3 (P =0.004), and proangiogenic VEGF (P = 0.03). The antifibrotic effect of CYR-61 was further demonstrated by delay in wound healing, inhibition of gel contraction, inactivation of the transforming growth factor β pathway, and early superoxide production associated with senescence in SSc fibroblasts. In SSc ECs, overexpression of CYR-61 led to increased production of vascular endothelial cell growth factor. The proangiogenic effects of CYR-61 were mediated by signaling through αvβ3 receptors and downstream activation of AMP-activated protein kinase, AKT, and the endothelial cell nitric oxide synthase/nitric oxide pathway system.CYR-61, which is epigenetically regulated by HDAC-5, is a potent antifibrotic and proangiogenic mediator in SSc. Therapeutic intervention to promote CYR-61 activity or increase CYR-61 levels might be of benefit in SSc.
Liver macrophages regulate systemic metabolism through non-inflammatory factors
Authors: Cecilia Morgantini, Jennifer Jager, Xidan Li, Laura Levi, Valerio Azzimato, André Sulen, Emelie Barreby, Connie Xu, Michaela Tencerova, Erik Näslund, Chanchal Kumar, Francisco Verdeguer, Sara Straniero, Kjell Hultenby, Niklas K. Björkström, Ewa Ellis, Mikael Rydén, Claudia Kutter, Tracey Hurrell, Volker M. Lauschke, Jeremie Boucher, Aleš Tomčala, Gabriela Krejčová, Adam Bajgar, Myriam Aouadi
Journal: Nature Metabolism (2019)