tbuckley/cabot-search huggingface dataset:
Abstract P412: Toward A Biomarker Kit Suitable For Clinical Practice; A Novel Metabolomic Biomarker Risk Score Improves The Prognostic Value Of Cardiovascular Mortality In Elderly Congestive Heart Failure Patients
Authors: Peter McGranaghan, Anshul Saxena, Muni Rubens, Jasmin Radenkovic, Doris Bach, Leonhard Schleußner, Burkert Pieske, Frank Edelmann, Tobias Trippel
Journal: Circulation (2020)

Aims: The Cardiac Lipid Panel (CLP) is a newly discovered panel of metabolite-based biomarkers that has previously shown to improve the diagnostic value of NT-proBNP. Little is known about its usefulness in predicting outcomes. In this study, the aim was to develop a risk score for 4-year cardiovascular death in elderly CHF patients. Methods and Results: We included 280 patients &gt;65 years of age with CHF randomly selected from the CIBIS-ELD trial. A targeted metabolomic analysis of the three CLP biomarkers was performed on baseline serum samples. Cox proportional hazards regression was used to determine the relationship of the biomarkers with the outcome and adjusted for established risk factors (age, sex, BMI, creatinine, LDL, triglycerides, and LVEF). The CLP risk score was calculated by counting the number of biomarkers above a cut-off determined using the Youden’s indexes. During the follow-up period, mean 50 months [±8 months], 35 (18%) subjects met the primary endpoint of cardiovascular death. The area under the receiver operating curve (AUROC) for the model based on only clinical variables was 0.72, the second model with clinical variables plus NT-proBNP was 0.79, and the final model with clinical variables, NT-proBNP, plus the CLP was 0.83. Conclusions: A risk score based on a panel of 3 metabolite-based biomarkers was found to improve the prognostic value of traditional risk factors and NT-proBNP in a cohort of CHF subjects. Our next steps include validating the prognostic value of the CLP biomarker kit in order to provide a better clinical risk assessment of CHF patients.
Melanoma-Secreted Lysosomes Trigger Monocyte-Derived Dendritic Cell Apoptosis and Limit Cancer Immunotherapy
Authors: Nadine Santana-Magal, Leen Farhat-Younis, Amit Gutwillig, Annette Gleiberman, Diana Rasoulouniriana, Lior Tal, Dvir Netanely, Ron Shamir, Rachel Blau, Meora Feinmesser, Oran Zlotnik, Haim Gutman, Ian L. Linde, Nathan E. Reticker-Flynn, Peleg Rider, Yaron Carmi
Journal: Cancer Research (2020)

The recent success of checkpoint blockade therapies has established immunotherapy as one of the most promising treatments for melanoma. Nonetheless, a complete curative response following immunotherapy is observed only in a fraction of patients. To identify what factors limit the efficacy of immunotherapies, we established mouse models that cease to respond to immunotherapies once their tumors exceed a certain stage. Analysis of the immune systems of the organisms revealed that the numbers of tumor-infiltrating dendritic cells (TIDC) drastically decreased with time. Further, in contrast to the current paradigm, once melanoma was established, TIDC did not migrate into sentinel lymph nodes. Instead, they underwent local cell death due to excessive phagocytosis of lysosomes. Importantly, TIDC were required to license the cytotoxic activity of tumor CD8+ T cells, and in their absence, T cells did not lyse melanoma cells. Our results offer a paradigm shift regarding the role of TIDC and a framework to increase the efficacy of immunotherapies. SIGNIFICANCE: This work redefines the role of monocyte-derived dendritic cells in melanoma and provides a novel strategy to increase the efficacy of T-cell-based immunotherapies in nonresponding individuals. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/10/1942/F1.large.jpg.
TCR-mimic antibody-drug conjugates targeting intracellular tumor-specific mutant antigen KRAS G12V mutation
Authors: Ying Shen, Xiaoyue Wei, Shijie Jin, Yue Wu, Wenbin Zhao, Yingchun Xu, Liqiang Pan, Zhan Zhou, Shuqing Chen
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Limited clinical application of antibody-drug conjugates (ADCs) targeting tumor associated antigens (TAAs) is usually caused by on-target off-tumor side effect. Tumor-specific mutant antigens (TSMAs) only expressed in tumor cells which are ideal targets for ADCs. In addition, intracellular somatic mutant proteins can be presented on the cell surface by human leukocyte antigen class I (HLA I)molecules forming tumor-specific peptide/HLA I complexes. KRAS G12V mutation frequently occurred in varied cancer and was verified as a promising target for cancer therapy. In this study, we generated two TCR-mimic antibody-drug conjugates (TCRm-ADCs), 2E8-MMAE and 2A5-MMAE, targeting KRAS G12V/HLA-A*0201 complex, which mediated specific antitumor activity in vitro and in vivo without obvious toxicity. Our findings are the first time validate the strategy of TCRm-ADCs targeting intracellular TSMAs, which improves the safety of antibody-based drugs and provides novel strategy for precision medicine in cancer therapy.
左室真性りゅうから仮性心室りゅうへ進展をきたしたと考えられる前壁心筋梗塞の一例 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 松久誠司, 畑田憲吾, 中村誠志, 菊池早苗, 西上尚志, 木村穣, 神畠宏, 岩坂寿二
Journal: Circulation (2002)
Impact of a Telephonic Intervention to Improve Diabetes Control on Health Care Utilization and Cost for Adults in South Bronx, New York
Authors: Bahman P. Tabaei, Renata E. Howland, Jeffrey S. Gonzalez, Shadi Chamany, Elizabeth A. Walker, Clyde B. Schechter, Winfred Y. Wu
Journal: Diabetes Care (2020)

Self-management education and support are essential for improved diabetes control. A 1-year randomized telephonic diabetes self-management intervention (Bronx A1C) among a predominantly Latino and African American population in New York City was found effective in improving blood glucose control. To further those findings, this current study assessed the intervention's impact in reducing health care utilization and costs over 4 years.We measured inpatient (n = 816) health care utilization for Bronx A1C participants using an administrative data set containing all hospital discharges for New York State from 2006 to 2014. Multilevel mixed modeling was used to assess changes in health care utilization and costs between the telephonic diabetes intervention (Tele/Pr) arm and print-only (PrO) control arm.During follow-up, excess relative reductions in all-cause hospitalizations for the Tele/Pr arm compared with PrO arm were statistically significant for odds of hospital use (odds ratio [OR] 0.89; 95% CI 0.82, 0.97; P < 0.01), number of hospital stays (rate ratio [RR] 0.90; 95% CI 0.81, 0.99; P = 0.04), and hospital costs (RR 0.90; 95% CI 0.84, 0.98; P = 0.01). Reductions in hospital use and costs were even stronger for diabetes-related hospitalizations. These outcomes were not significantly related to changes observed in hemoglobin A1c during individuals' participation in the 1-year intervention.These results indicate that the impact of the Bronx A1C intervention was not just on short-term improvements in glycemic control but also on long-term health care utilization. This finding is important because it suggests the benefits of the intervention were long-lasting with the potential to not only reduce hospitalizations but also to lower hospital-associated costs.
Abstract P259: Using Natural Language Processing and Machine Learning to Identify Incident Stroke From Electronic Health Records
Authors: Yiqing Zhao, Sunyang Fu, Suzette J Bielinski, Paul Decker, Alanna M Chamberlain, Veronique L Roger, Hongfang Liu, Nicolas B Larson
Journal: Circulation (2020)

Background: The focus of most existing phenotyping algorithms based on electronic health record (EHR) data has been to accurately identify cases and non-cases of specific diseases. However, a more challenging task is to accurately identify disease incidence, as identifying the first occurrence of disease is more important for efficient and valid clinical and epidemiological research. Moreover, stroke is a challenging phenotype due to diagnosis difficulty and common miscoding. This task generally requires utilization of multiple types of EHR data (e.g., diagnoses and procedure codes, unstructured clinical notes) and a more robust algorithm integrating both natural language processing and machine learning. In this study, we developed and validated an EHR-based classifier to accurately identify stroke incidence among a cohort of atrial fibrillation (AF) patients Methods: We developed a stroke phenotyping algorithm using International Classification of Diseases, Ninth Revision (ICD-9) codes, Current Procedural Terminology (CPT) codes, and expert-provided keywords as model features. Structured data was extracted from Rochester Epidemiology Project (REP) database. Natural Language Processing (NLP) was used to extract and validate keyword occurrence in clinical notes. A window of ±30 days was considered when including/excluding keywords/codes into the input vector. Frequencies of keywords/codes were used as input feature sets for model training. Multiple competing models were trained using various combinations of feature sets and two machine learning algorithms: logistic regression and random forest. Training data were provided by two nurse abstractors and included validated stroke incidences from a previously established atrial fibrillation cohort. Precision, recall, and F-score of the algorithm were calculated to assess and compare model performances. Results: Among 4,914 patients with atrial fibrillation, 1,773 patients were screened. 3,141 patients had no stroke-related codes or keywords and were presumed to be free of stroke during follow-up. Among the screened patients, 740 had validated strokes and 1,033 did not have a stroke based on review of the EHR by trained nurse abstractors. The best performing stroke incidence phenotyping classifier utilized Keywords+ICD-9+CPT features using a random forest classifier, achieving a precision of 0.942, recall of 0.943, and F-score of 0.943. Conclusion: In conclusion, we developed and validated a stroke algorithm that performed well for identifying stroke incidence in an enriched population (AF cohort), which extends beyond the typical binary case/non-case stroke identification problem. Future work will involve testing the generalizability of this algorithm in a general population.
Considerations in Analysis of Medicare Graduate Medical Education Payment Policies
Authors: Susan Xu, Janis M. Orlowski
Journal: JAMA Internal Medicine (2020)

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 Internal Medicine 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 Internal Medicine journal
Beware of the isolated intermediate quality measure: A lesson in choosing an ovarian cancer surgeon
Authors: J. H. Silber, P. R. Rosenbaum, D. Polsky, A. M. Millman, R. N. Ross, O. Even-Shoshan, J. S. Schwartz, K. Armstrong, T. Randall
Journal: Journal of Clinical Oncology (2007)

6546 Background: Measuring surgical quality has recently focused on isolated processes (such as P4P measures) and intermediate outcomes (such as infection rates). Some have argued that such isolated measures are inherently flawed since they may have only minor influence on more important primary outcomes such as survival. Hence, referral decisions based on such isolated processes or intermediate outcomes may lead to less than optimal care. We asked whether surgeon type influenced isolated process measures (longer operative time, thought to be a function of increased node sampling), intermediate outcomes (deep wound infection, often found to be a function of operative time) and the primary outcome of survival. Methods: We obtained SEER-Medicare claims for the years 1991–2001 for ovarian cancer. We identified the first definitive cancer surgery and the surgical provider type for that procedure: General Surgeon (GS) N=545 and GYN Oncologist (GO) N=1,554. We determined operative time from the anesthesia claims, number of nodes sampled from the SEER record, deep wound infection from the ICD9CM secondary diagnoses and survival from Medicare vital status files. Models were adjusted for 30 patient characteristics and comorbidities. To account for potential reclassification bias due to variations in the pattern of node dissection across GO and GS surgical types, which can potentially influence stage identification, we report survival results both with and without stage adjustments. Results: Definitive surgery by GOs was associated with more extensive node dissection and longer operative time. GO patients also displayed a trend for increased deep wound infection as compared to cases operated on by GS. However, 5-year survival was significantly longer in the GO group, with or without stage adjustment. Conclusions: GO cases took longer, tended to have higher infection rates, yet had better overall 5-year survival. Isolated intermediate outcome measures, such as deep wound infection, may not be good quality indicators. No significant financial relationships to disclose. [Table: see text]
US Supreme Court hears pivotal abortion case as pro-lifers seek to undermine Roe <i>v</i> Wade
Authors: Owen Dyer
Journal: BMJ (2020)

The matter of abortion was before the US Supreme Court on 4 March for the first time since President Trump’s judicial appointments gave the country’s highest bench a 5-4 conservative majority.

Many in the “pro-life” movement hope that the ideological shift will bring a ruling that overturns Roe v Wade, the landmark 1973 case that legalised abortion in the US.

Some states have recently passed laws that are deliberately incompatible with Roe v Wade, in the hope that challenges to those laws will allow the conservative majority to revisit that precedent.

But this week the court tackled …
Survivin expression in esophageal cancer: Association with histomorphological response to neoadjuvant therapy and prognosis
Authors: D. Vallboehmer, E. Kuhn, J. Brabender, R. Metzger, U. Warnecke-Eberz, S. E. Baldus, U. Drebber, A. H. Hölscher, P. M. Schneider
Journal: Journal of Clinical Oncology (2007)

4536 Background: The poor prognosis associated with locally advanced esophageal cancer prompted an evaluation of combined modality treatments including neoadjuvant radiochemotherapy in combination with surgery. However, it has been well established that only patients with a complete pathological response to neoadjuvant therapy will have a significant survival benefit. Therefore, predictive markers to allow a tailored radiochemotherapy are needed. The aim of this study was to examine the association of the protein expression of survivin, an inhibitor of apoptosis, with histopathologic response to neoadjuvant radiochemotherapy and prognosis of patients with locally-advanced esophageal cancer. Methods: 59 patients with esophageal cancer (cT2–4, N x , M 0 ) received neoadjuvant radiochemotherapy (cisplatin, 5-FU, 36 Gy) followed by esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10 % and as minor response when resected specimens contained more than 10 % of residual vital tumor cells. Pre- and post-therapeutic intratumoral protein expression of survivin was determined and correlated with clinicopathologic parameters. Results: The pre-therapeutic intratumoral survivin protein expression was not associated with any clinicopathologic factor, including histopathologic response and prognosis. Survivin protein expression was significantly reduced during neoadjuvant therapy, showing lower levels in post-therapeutic tumor samples (p&lt;0.01). Higher postoperative survivin levels were significantly associated with a higher ypT-stage (p&lt;0.009), a poorer histopathologic response (p&lt;0.01) and a shorter overall survival (p&lt;0.028). Conclusions: The intratumoral protein expression of survivin was significantly down-regulated during neoadjuvant therapy, whereas a higher survivin level after pre-operative therapy was significantly associated with a worse histopathologic response and prognosis. Therapeutic strategies which are able to reduce survivin expression or to block survivin mediated pathways might increase the histopathologic response rate and prognosis in the multimodal therapy of patients with locally-advanced esophageal cancer. No significant financial relationships to disclose.
Abstract MP12: Lay- vs Professional-led Weight Loss Interventions for Overweight and Obese Youth: A Systematic Review and Network Meta-analysis
Authors: Jonathan M McGavock, Sara Boissoneault, Nika Klaprat, Rasheda Rabbani, Ahmed Abou-Setta
Journal: Circulation (2020)

Context: In this network meta analysis, we examine the short and long-term effects of professional and lay-led behavioural interventions for obese youth. Objective: The appropriate approach for weight loss among overweight and obese youth remains unclear. We evaluated the comparative effectiveness of behavioural pediatric weight loss interventions led by lay persons and professionals. Data Sources: MEDLINE, Embase, the Cochrane Library, and CINAHL between January 1996 and June 2019. Study Selection: Randomized controlled trials of behavioural lifestyle interventions that enrolled overweight and obese children and adolescents (5-18 years old) administered for at least 12 weeks. Data Extraction: A network meta-analyses using a Bayesian framework and Markov-chain Monte-Carlo simulation methods were used to combine direct and indirect evidence. The immediate and sustained change from baseline in weight (kg) and body mass index (BMI; kg/m2) were primary outcomes. Results: Of 34,384 citations retrieved, we included 78 RCTs (4,556 participants), delivered for 12 to 104 weeks. Compared to standard care, professional-led weight loss interventions were associated with a significant reduction in body weight [-1.6 kg, 95% credible interval (CrI) -2.3, -0.99, 64 trials] that was not sustained long-term [-1.02 kg, 95% CrI -2.2, +0.34, 21 trials]. There was no evidence of a meaningful weight loss for lay-led interventions in the short-term [-1.4 kg; 95% CrI -3.0, +0.26; 5 trials], or long-term [-0.98 kg, 95% CrI -3.6, +1.8, 1 trial] compared to standard care. Direct comparisons revealed expert and lay-led interventions yield similar effects (-0.25 kg, 95%CrI -1.9, +1.3, 5 trials). Conclusions: Professional-led weight loss interventions are the most effective for achieving and sustaining weight reduction among overweight and obese youth. There is a need for high quality trials of lay-led weight loss interventions for obese youth.
The role of transporters in cancer redox homeostasis and cross-talk with nanomedicines
Authors: Longfa Kou, Xinyu Jiang, Huirong Huang, Xinlu Lin, Youting Zhang, Qing Yao, Ruijie Chen
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Tumor cell usually exhibits high levels of reactive oxygen species and adaptive antioxidant system due to the metabolic, genetic, and microenvironment-associated alterations. The altered redox homeostasis can promote tumor progression, development, and treatment resistance. Several membrane transporters are involved in the resetting redox homeostasis and play important roles in tumor progression. Therefore, targeting the involved transporters to disrupt the altered redox balance emerges as a viable strategy for cancer therapy. In addition, nanomedicines have drawn much attention in the past decades. Using nanomedicines to target or reset the redox homeostasis alone or combined with other therapies has brought convincing data in cancer treatment. In this review, we will introduce the altered redox balance in cancer metabolism and involved transporters, and highlight the recent advancements of redox-modulating nanomedicines for cancer treatment.
Clinical trials, case reports, and observational databases as sources of information on serious cancer-related adverse drug reactions (sADRs): Lessons learned from the Research on Adverse Drug Events and Reports (RADAR) project
Authors: C. Bennett, K. Gleason, B. Djulbegovic, D. Raisch
Journal: Journal of Clinical Oncology (2007)

19591 Background: Serious adverse drug reactions (sADRs) such as venous thromboembolism resulting from cancer pharmaceutical use are underappreciated and often misattributed to the cancer diagnosis, rather than the therapy. The Research on Adverse Drug events And Reports (RADAR) group evaluated factors associated with identification of serious cancer-related sADRs (i.e. an adverse drug reaction that results in death or severe organ failure). Methods: Information on sources of clinical information, incidence, setting, and time from FDA approval to initial identification was obtained for sADRs that resulted in death or severe organ failure. Most of the ADRs are described as Black Box warnings or in “Dear Doctor” letters. Results: Summarized in table . Conclusion: Clinical trial safety reports from off-label settings facilitate identification of common (&gt;3% rate) cancer associated sADRs. Case reports and observational databases from on-label settings facilitate detection of rare cancer-associated sADRs (&lt;1%) often at lengthy time intervals from initial FDA approval. No significant financial relationships to disclose. [Table: see text]
Epigenetic basis for monocyte dysfunction in patients with severe alcoholic hepatitis
Authors: Laura Weichselbaum, Abdulkader Azouz, Kinga K. Smolen, Jishnu Das, Marion Splittgerber, Antonia Lepida, Christophe Moreno, Jonas Schreiber, Thomas Sersté, Eric Trepo, Frederick Libert, Thierry Gustot, Stanislas Goriely
Journal: Journal of Hepatology (2020)