tbuckley/cabot-search huggingface dataset:
Tissue factor pathway inhibitor primes monocytes for antiphospholipid antibody-induced thrombosis
Authors: Nadine Müller-Calleja, Anne Hollerbach, Svenja Ritter, Denise G. Pedrosa, Dennis Strand, Claudine Graf, Christoph Reinhardt, Susanne Strand, Philippe Poncelet, John H. Griffin, Karl J. Lackner, Wolfram Ruf
Journal: Blood (2019)
Planned Parenthood rejects restrictive US government funding and “gag rule”
Authors: Janice Hopkins Tanne
Journal: BMJ (2019)

Planned Parenthood, the largest provider of reproductive healthcare to low income women in the US, pulled out of the government funded Title X program on 19 August because new rules from the Trump administration prohibited it from referring for abortions or providing them—the so called “gag rule.”

Alexis McGill Johnson, acting president of Planned Parenthood, said, “We believe that the Trump administration is doing this as an attack on reproductive healthcare and to keep providers like Planned Parenthood from serving our patients.” She said that the organization would continue to serve patients.

“Our patients come to us because they expect the best information and healthcare available. And we have a commitment to provide that to them. But the gag rule would make it impossible for us to provide that,” she said.

Planned Parenthood executives would not say how much the organization was rejecting, …
Distinct Clinical Phenotypes of Patients with Myeloid Neoplasms Carrying SF3B1 Hotspot Mutations
Authors: Jack Khouri, Vera Adema, Ying Ni, Heesun J. Rogers, Bartlomiej P. Przychodzen, Cassandra M. Hirsch, Elise Lemelle, Teodora Kuzmanovic, Anjali S. Advani, Aaron T. Gerds, Sudipto Mukherjee, Aziz Nazha, Yogenthiran Saunthararajah, Yazan F. Madanat, Bhumika J. Patel, Francesc Sole, Steffan T. Nawrocki, Jennifer Carew, Matt Kalaycio, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Valeria Visconte, Hetty E. Carraway
Journal: Blood (2017)
Head and neck cancer in Fanconi anemia and dyskeratosis congenita.
Authors: Blanche P Alter, Neelam Giri, Sharon H Savage
Journal: Journal of Clinical Oncology (2012)

5563 Background: Fanconi Anemia (FA) and dyskeratosis congenita (DC) are inherited bone marrow failure syndromes (IBMFS) with extraordinarily high risks of cancer, particularly head and neck squamous cell carcinoma (HNSCC). The standardized incidence ratios (SIR) for solid tumors are 40 in FA and 10 in DC, and for HNSCC 700 and 900 respectively. In the general population, cancers of the oropharynx may be associated with human papilloma virus (HPV) more than the oral cavity. The specific locations of HNSCC in FA and DC have not been reviewed, and thus the hypothetical role of HPV in these cancers is unknown. Methods: Literature cases were reviewed through PubMed searches using the terms “Fanconi anemia” and “dyskeratosis congenita”. All papers were reviewed, and details of the specific cancers recorded. FA literature included reports from 1927 through 2011, and DC literature from 1910 through 2011. Participants in the National Cancer Institute (NCI) IBMFS retrospective/prospective protocol (NCI 02-C-0052, opened in 2002) were also analyzed for cancer. The HPV vaccine was not available during most of the time frame of this study. Results: There were 411 cases of cancer among 2190 (19%) cases of FA described individually in the literature, and 21 cancer cases out of 116 (18%) FA patients in the NCI cohort. HNSCC were reported in 112 FA literature cases (5%), and 9 (8%) in the cohort. The oropharynx was the initial site for HNSCC in 31/112 literature cases (28%) and 3/9 NCI cases (33%). With regard to DC, 51/647 (8%) cases in the literature had cancer, as did 9 of 94 (10%) NCI participants. HNSCC were reported in 21/647 (3%) DC literature cases, and in 5/94 (5%) from the NCI cohort. Four of the 21 HNSCC (19%) in the literature were oropharyngeal, and 2/5 (40%) in the NCI cohort. The cumulative incidences of any HNSCC in the NCI FA and DC cohorts were 50% and 21% by 40 years of age (censored at death from other causes). Conclusions: Patients with FA and DC have extremely high risks of HNSCC at substantially younger ages than the general population. Approximately 30% of these cancers occur in the oropharynx. The HPV vaccine could be important in prevention of these cancers. Future studies of the HPV status of oral cavity and oropharynx HNSCC tumors from patients with FA and DC will be informative.
Belgian Superior Health Council advises against the use of the DSM categories
Authors: Stijn Vanheule, Pieter Adriaens, Ariane Bazan, Piet Bracke, Ignaas Devisch, Jean-Louis Feys, Brenda Froyen, Sylvie Gerard, Dorien H. Nieman, Jim Van Os, Marc Calmeyn
Journal: The Lancet Psychiatry (2019)
Development of Exercise as Interception Therapy for Cancer
Authors: Neil M. Iyengar, Lee W. Jones
Journal: JAMA Oncology (2019)

Observational data linking physical activity and exercise exposure with reduced risk of either development or progression of cancer have fueled interest in the initiation of large-scale definitive trials to test the association of exercise therapy with disease outcomes. However, several major knowledge gaps impede the rational and optimal design of such trials.Critical requirements underpinning the success of several recent contemporary anticancer agents have included adequate demonstration of antitumor activity (in phase 1/2 trials) as well as identification of essential prerequisites (eg, biologically effective dose and predictors of response) permitting optimal design of definitive trials. The existing evidence base investigating exercise as a candidate anticancer preventive or treatment strategy is predominantly confined to observational data, which have several inherent limitations. Consequently, the antitumor activity of exercise remains unclear and, perhaps more important, such data are not sufficient to accurately derive the exercise dose, prescription regimen, or patients most likely to benefit from exercise. In adherence with translational frameworks for lifestyle therapy development, the need for early phase 1/2-equivalent trials to fill current knowledge gaps to optimize the development and potential efficacy of exercise therapy is highlighted.Exercise therapy has significant promise to be an efficacious and cost-effective therapy to improve cancer outcomes, with few toxic effects. Although most nontraditional therapies in cancer prevention and prognosis fail in definitive trials, these failures provide critical lessons for the continued development of exercise as a candidate anticancer therapy.
Tolerogenic Dendritic Cells Attenuate Experimental Autoimmune Antimyeloperoxidase Glomerulonephritis
Authors: Dragana Odobasic, Virginie Oudin, Kenji Ito, Poh-Yi Gan, A. Richard Kitching, Stephen R. Holdsworth
Journal: Journal of the American Society of Nephrology (2019)

Background Because of their capacity to induce antigen-specific immunosuppression, tolerogenic dendritic cells are a promising tool for treatment of autoimmune conditions, such as GN caused by autoimmunity against myeloperoxidase (MPO).We sought to generate tolerogenic dendritic cells to suppress anti-MPO GN by culturing bone marrow cells with an NFκB inhibitor (BAY 11-7082) and exposing them to a pulse of MPO. After administering these MPO/BAY dendritic cells or saline to mice with established anti-MPO or anti-methylated BSA (mBSA) immunity, we assessed immune responses and GN. We also examined mechanisms of action of MPO/BAY dendritic cells.MPO/BAY dendritic cells decreased anti-MPO immunity and GN without inhibiting immune responses against mBSA; they also induced IL-10-producing regulatory T cells in MPO-immunized mice without affecting IL-10+ CD4+Foxp3- type 1 regulatory T cells or regulatory B cells. MPO/BAY dendritic cells did not inhibit anti-MPO immunity when CD4+Foxp3+ cells were depleted in vivo, showing that regulatory T cells are required for their effects. Coculture experiments with dendritic cells and CD4+Foxp3- or CD4+Foxp3+ cells showed that MPO/BAY dendritic cells generate Foxp3+ regulatory T cells from CD4+Foxp3- cells through several pathways, and induce IL-10+ regulatory T cells via inducible costimulator (ICOS), which was confirmed in vivo. Transfer of MPO/BAY dendritic cell-induced regulatory T cells in vivo, with or without anti-IL-10 receptor antibody, demonstrated that they suppress anti-MPO immunity and GN via IL-10.MPO/BAY dendritic cells attenuate established anti-MPO autoimmunity and GN in an antigen-specific manner through ICOS-dependent induction of IL-10-expressing regulatory T cells. This suggests that autoantigen-loaded tolerogenic dendritic cells may represent a novel antigen-specific therapeutic option for anti-MPO GN.
Influenza Nanovaccines: A Universal Influenza Nanovaccine for “Mixing Vessel” Hosts Confers Potential Ability to Block Cross‐Species Transmission (Adv. Healthcare Mater. 16/2019)
Authors: Peiyang Ding, Qianyue Jin, Wen Zhou, Yongxiao Chai, Xiao Liu, Yao Wang, Xinxin Chen, Junqing Guo, Ruiguang Deng, George F. Gao, Gaiping Zhang
Journal: Advanced Healthcare Materials (2019)

In article number 1900456 by Gaiping Zhang and co-workers, an influenza nanovaccine for “mixing vessel” hosts is developed. The nanovaccine is constructed by displaying conserved ectodomain of influenza matrix protein 2 (M2e) on self-assembling capsid protein (Cap) of porcine circovirus type 2 (PCV2). The nanovaccine provides dual protection against different subtypes of influenza and PCV2 in mouse and pig models, and confers potential ability to block cross-species transmission.
Assessment of Prognostic Value of Left Ventricular Global Longitudinal Strain for Early Prediction of Chemotherapy-Induced Cardiotoxicity
Authors: Evangelos K. Oikonomou, Damianos G. Kokkinidis, Polydoros N. Kampaktsis, Eitan A. Amir, Thomas H. Marwick, Dipti Gupta, Paaladinesh Thavendiranathan
Journal: JAMA Cardiology (2019)

Echocardiographic left ventricular global longitudinal strain (GLS) detects early subclinical ventricular dysfunction and can be used in patients receiving potentially cardiotoxic chemotherapy. A meta-analysis of the prognostic value of GLS for cancer therapy-related cardiac dysfunction (CTRCD) has not been performed, to our knowledge.To explore the prognostic value of GLS for the prediction of CTRCD.Systematic search of the MEDLINE, Embase, Scopus, and the Cochrane Library databases from database inception to June 1, 2018.Cohort studies assessing the prognostic or discriminatory performance of GLS before or during chemotherapy for subsequent CTRCD.Random-effects meta-analysis and hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the prognostic and discriminatory performance of different GLS indices. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity.The primary outcome was CTRCD, defined as a clinically significant change in left ventricular ejection fraction with or without new-onset heart failure symptoms.Analysis included 21 studies comprising 1782 patients with cancer, including breast cancer, hematologic malignancies, or sarcomas, treated with anthracyclines with or without trastuzumab. The incidence of CTRCD ranged from 9.3% to 43.8% over a mean follow-up of 4.2 to 23.0 months (pooled incidence, 21.0%). For active treatment absolute GLS (9 studies), the high-risk cutoff values ranged from -21.0% to -13.8%, with worse GLS associated with a higher CTRCD risk (odds ratio, 12.27; 95% CI, 7.73-19.47; area under the HSROC, 0.86; 95% CI, 0.83-0.89). For relative changes vs a baseline value (9 studies), cutoff values ranged from 2.3% to 15.9%, with a greater decrease linked to a 16-fold higher risk of CTRCD (odds ratio, 15.82; 95% CI, 5.84-42.85; area under the HSROC, 0.86; 95% CI, 0.83-0.89). Both indices showed significant publication bias. Meta-regression identified differences in sample size and CTRCD definition but not GLS cutoff value as significant sources of interstudy heterogeneity.In this meta-analysis, measurement of GLS after initiation of potentially cardiotoxic chemotherapy with anthracyclines with or without trastuzumab had good prognostic performance for subsequent CTRCD. However, risk of bias in the original studies, publication bias, and limited data on the incremental value of GLS and its optimal cutoff values highlight the need for larger prospective multicenter studies.
A review of chromosome 3q abnormalities in lung cancer.
Authors: Subramony Subramonia-Iyer, Borys Hrinczenko
Journal: Journal of Clinical Oncology (2012)

e21154 Background: With the refinement of genetic analytic techniques more detailed and precise information about 3q abnormalities has become available. The aim of this study was to review and summarize the literature about chromosome 3q in the pathogenesis, classification, treatment and prognosis of lung cancer. Methods: A MEDLINE search was conducted with the terms “lung cancer” and “3q”. Papers that described 3q abnormalities in the context of lung cancer were included in this review. Results: From 1990-2011, 61 papers were identified that described chromosome 3q changes in lung cancer. Initial studies showed 3q amplification in premalignant lesions, bronchial dysplasia, NSCLC and SCLC tumor tissue. Similar 3q amplifications were found in lung cancer cell lines at the 3q26-q28 region, including the gene for telomerase (hTR). Amplification of 3q segments were more prevalent in squamous (40 -100%) than in adenocarcinoma (6 - 25%) and in smokers than in non-smokers. However, malignant cells from pleural effusions of adenocarcinoma showed 3q gains in nearly 40% of cases. Genes located on 3q such as RAP2B, CLDN1 and TBL1XR1 were overexpressed in squamous carcinoma. High gain levels were also found at PIK3CA, EVI1 (3q26.2), LPP (3q27-28) and FHF-1 (3q28) gene loci. Also, 3q gains were associated with EGFR mutations in squamous carcinoma and TP53 mutations in adenocarcinoma. Prognostic importance of several chromosomal changes in lung cancer has also been examined. In one study, overexpression of eIF5A-2, located on 3q, was found to correlate with gene amplification, increased cell proliferation, local invasion, advanced T stage, and poor prognosis in stage I NSCLC [He, Int J Cancer, 2011]. Conclusions: Genetic abnormalities and changes in chromosome 3q have been increasingly well characterized with specific genes identified. Differential expression in various histological types of NSCLC indicates that these genes may contribute to the pathogenetic pathway in squamous carcinoma, and also in locally advanced adenocarcinoma with pleural effusions. These genes have also been shown to be prognostically important. With these promising results, further identification of specific 3q gene products may lead to the development of novel therapeutic targets in lung cancer.
Meeting the Unique Dermatologic Needs of Black Patients
Authors: Susan C. Taylor
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
Longitudinal health-related quality of life assessment: Implications for prognosis in ovarian cancer.
Authors: Donald Peter Braun, Digant Gupta, Edgar Donald Staren, Maurie Markman
Journal: Journal of Clinical Oncology (2012)

5049 Background: Several studies in the oncology literature have demonstrated the prognostic value of baseline quality of life (QoL). However, there is little to no information on the prognostic effects of changes in QoL during treatment. We investigated whether changes in QoL could predict survival in ovarian cancer patients treated with an integrative model of care. Methods: We evaluated 137 ovarian cancer patients treated at our institution between Jan 2001 and Dec 2009 who were available for a minimum follow-up of 3 months. QoL was evaluated at baseline and after 3 months of treatment using EORTC-QLQ-C30. The QLQ-C30 incorporates a global scale, 5 function scales and 8 symptom scales. Patient survival was defined as the time between date of first patient visit and date of death from any cause/date of last contact. Cox regression was performed to evaluate the prognostic significance of baseline and changes in QoL scores after adjusting for age, treatment history and stage at diagnosis. Results: Mean age at diagnosis was 51.1 years. 28 patients were newly diagnosed while 109 were previously treated. Stage at diagnosis was I, 16; II, 15; III, 72; IV, 28; and 6 indeterminate. Median overall survival was 33.5 months (95% CI: 11.5-55.6 months). Baseline QoL scale predictive of survival upon multivariate analysis was nausea/vomiting (p=0.04). Associations between changes in QoL and survival were observed for global function, appetite loss and constipation. Every 10-point increase (improvement) in global function from baseline to 3 months was associated with a 10% decreased risk of death (HR=0.90; 95% CI=0.81 to 0.99, p=0.03). The corresponding HRs for 10-point increase (deterioration) in appetite loss and constipation scales were 1.20 (1.06 to 1.35; p=0.005) and 1.13 (1.02, 1.24; p=0.02) respectively. Conclusions: This exploratory study provides some preliminary evidence to indicate that ovarian cancer patients whose QoL improves within 3 months of treatment have a significantly increased survival time compared to those who fail to demonstrate improvement. These findings might be used in clinical practice to systematically address QoL-related problems of ovarian cancer patients throughout their treatment course.
Phase I study of samalizumab in chronic lymphocytic leukemia and multiple myeloma: blockade of the immune checkpoint CD200
Authors: Daruka Mahadevan, Mark C. Lanasa, Charles Farber, Manjari Pandey, Maria Whelden, Susan J. Faas, Terrie Ulery, Anjli Kukreja, Lan Li, Camille L. Bedrosian, Xiaoping Zhang, Leonard T. Heffner
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Purpose</h3> Samalizumab is a novel recombinant humanized monoclonal antibody that targets CD200, an immunoregulatory cell surface member of the immunoglobulin superfamily that dampens excessive immune responses and maintains self-tolerance. This first-in-human study investigated the therapeutic use of samalizumab as a CD200 immune checkpoint inhibitor in chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). <h3>Experimental design</h3> Twenty-three patients with advanced CLL and 3 patients with MM were enrolled in an open-label phase 1 study (NCT00648739). Patients were assigned sequentially to one of 7 dose level cohorts (50 to 600 mg/m<sup>2</sup>) in a 3 + 3 study design, receiving a single dose of samalizumab intravenously once every 28 days. Primary endpoints were safety, identification of the maximum tolerated dose (MTD), and pharmacokinetics. Secondary endpoints were samalizumab binding to CD200, pharmacodynamic effects on circulating tumor cells and leukocyte subsets, and clinical responses. <h3>Results</h3> Twenty-one patients received &gt; 1 treatment cycle. Adverse events (AEs) were generally mild to moderate in severity. Samalizumab produced dose-dependent decreases in CD200 expression on CLL cells and decreased frequencies of circulating CD200 + CD4+ T cells that were sustained at higher doses. The MTD was not reached. Decreased tumor burden was observed in 14 CLL patients. One CLL patient achieved a durable partial response and 16 patients had stable disease. All MM patients had disease progression. <h3>Conclusions</h3> Samalizumab had a good safety profile and treatment was associated with reduced tumor burden in a majority of patients with advanced CLL. These preliminary positive results support further development of samalizumab as an immune checkpoint inhibitor. <h3>Trial registration</h3> ClinicalTrials.gov, NCT00648739 registered April 1, 2008.
Chemotherapy of Systemic Mycoses
Authors: John E. Bennett
Journal: New England Journal of Medicine (1974)

5-Fluorocytosine5-Fluorocytosine (Flucytosine; 5-FC) is a commercially available, synthetic antifungal agent. The drug has been of value in treatment of certain cases of visceral candidiasis, cryptococcal meningitis, chromomycosis and torulopsosis. Although current indications for 5-fluorocytosine used alone appear to be limited, the drug is of interest because of its relatively low toxicity, its excellent absorption from the gastrointestinal tract and its potential use in combination chemotherapy.SusceptibilityDifferent laboratories have disagreed substantially about how often one can expect a pretreatment isolate of candida or Torulopsis glabrata to be sensitive to 5-FC.30 31 32 33 34 35 36 This discrepancy appears to reflect the fact that drug-sensitive . . .
Abstract 2150: A European and Canadian Multicenter Randomized, Double-Blind Trial of the Sirolimus-Eluting Stent (SES) in Patients with De Novo Native Coronary Artery Lesions (NEW-SIRIUS): 5-Year Clinical Outcomes
Authors: Eric Schampaert, Joachim Schofer, Guenther Breithardt, Eric A. Cohen, Michael Schlüter, Thomas Wichter, Kristel Wittebols, Hans-Peter Stoll
Journal: Circulation (2007)

Background : NEW-SIRIUS is the pooled analysis of the E-SIRIUS (n=352) and C-SIRIUS (n=100) studies, respectively, performed in Europe and Canada. Identical in design, these are multicenter randomized, double-blind trials examining the safety and efficacy of the sirolimus-eluting stent (SES) vs. an identical bare-metal stent (BMS) in 452 patients to treat de novo native long lesions in small coronary arteries, with adjunctive clopidogrel for only 2 months. Methods : The primary endpoint was in-stent minimum lumen diameter (MLD) at 8-month follow-up. Among the secondary endpoints were major adverse cardiac events(MACE) at 1, 6, 9 and 12 months, and annually up to 5 years post-procedure, as well as target lesion revascularization (TLR), target vessel revascularization (TVR) and protocol-defined stent thrombosis. Results : At 8 months, the MLD was 2.27±0.47mm in the SES vs. 1.36±0.66 mm in the BMS (p &lt; 0.001). The binary in-lesion restenosis rate was 5.1% in the SES vs. 44.2% in the BMS (p &lt; 0.001). At 4 years, there was a significantly lower incidence of MACE (SES: 15.1% vs BMS: 33.9%, p &lt; 0.001), primarily driven by a significant difference in clinically-driven TLR rates (SES: 7.1% vs. BMS: 26.0%, p &lt; 0.001). A subgroup analysis in diabetic patients (45 SES, 60 BMS) demonstrated that the in-stent MLD was larger in SES than in BMS (2.20±0.47 vs 1.14±0.64 mm, p &lt; 0.001) and the binary in-lesion restenosis rate was reduced from 56.1% (BMS) to 10.0% (RRR: 82.2%, p &lt; 0.001) at 8 months. At 4 years, the freedom from MACE in diabetic patients was 80.0% in the SES vs. 61.7% in the BMS (p = 0.031), again mainly driven by an improved freedom from clinically driven-TLR (SES: 90.8% vs. BMS: 66.9%, p=0.005), with no evidence of a late catch-up effect. Conclusion : Up to 4 years, SES were superior to BMS in the total cohort as well as in the diabetic subgroup without evidence of a late catch-up. Five-year follow-up data, including antiplatelet therapies utilization and a diabetic subgroup analyses will be available by July 2007 and presented.