tbuckley/cabot-search huggingface dataset:
Abstract 12181: Pulmonary Embolism Outcomes After Discharge From the Emergency Department: The CVRN VTE Study
Authors: Margaret C Fang, Dongjie Fan, Daniel M Witt, John R Schmelzer, Steven H Yale, Steven R Steinhubl, Sue Hee Sung, Alan S Go
Journal: Circulation (2013)

Background:  Patients with acute pulmonary embolism (PE) have conventionally been hospitalized for initial management and initiation of anticoagulants. However, recently developed risk scores have been able to identify patients at low risk for poor PE outcomes. We compared short-term outcomes of patients with acute PE discharged from the emergency department (ED) compared to hospitalized patients with PE.   METHODS:  We used electronic databases from Kaiser Permanente Northern California, an integrated healthcare delivery system, from January 1, 2004 to December 31, 2010. We identified patients aged ≥ 21 years discharged with an incident primary diagnosis code of PE during an ED visit or inpatient hospitalization, and who were prescribed anticoagulants within 7 days of discharge. We excluded patients with prior venous thromboembolism diagnoses or prior anticoagulant prescriptions. Clinical, utilization, and mortality data were obtained from automated clinical databases. We compared 30-day mortality and readmission rates between ED and hospitalized patients with PE using multivariable logistic regression   RESULTS:  We identified 4598 patients with a primary diagnosis of PE who were discharged on anticoagulants. The majority, 4325 (94%), were hospitalized and 292 (6.3%) were discharged from the ED. Hospitalized patients with PE were on average older (age 63.7 vs. 61.5, p=0.05) and more likely to have at least one risk factor for worse outcome after PE (age > 80, history of cancer, or cardiopulmonary disease): 62.6% vs. 55.8%, p=0.02. ED patients had somewhat lower 30-day mortality compared to hospitalized patients (0.7% vs. 2.4%, p=0.06), and significantly lower 30-day readmission rates (11% vs. 23%, p≤0.01). After adjusting for age, sex, and comorbid conditions, there was no significant difference in 30-day mortality between ED and hospitalized patients (adjusted odds ratio = 1.0 [0.9-1.0]), while 30-day readmission was significantly lower in ED patients (adjusted odds ratio = 0.9 [0.8-0.9]).   Conclusions:  Approximately 1 in 16 patients with acute PE were safely discharged directly from the ED. This suggests that a subgroup of patients identified as lower risk with PE may be managed as outpatients.
Interactions Between Axons and their Sheath Cells
Authors: G M Bray, M Rasminsky, A J Aguayo
Journal: Annual Review of Neuroscience (1981)

The demonstration in the early 1950s that myelin is formed by the surface membranes of sheath cells was a turning point in the understanding of axon-sheath cell relationships. The subsequent development of ultrastructu­ ral, electrophysiologic, biochemical, and immunologic techniques has made possible the identification of many facets of the complex interdependencies in fibers of both the central and peripheral nervous systems. Furthermore, it is now recognized that nerve fibers both influence and are influenced by cellular and extracellular components of their immediate environment. In this selective review, we discuss structural and functional relationships of axons and sheath cells in normal and abnormal nerves. Our concern is primarily with axons and Schwann cells in the peripheral nervous system but we also touch on the more complicated relationships involving axons, oligodendrocytes, and other neuroglia in the central nervous system.
Cellular and Molecular Mechanisms of Allograft Rejection
Authors: R B Colvin
Journal: Annual Review of Medicine (1990)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Taselisib (GDC-0032), a Potent β-Sparing Small Molecule Inhibitor of PI3K, Radiosensitizes Head and Neck Squamous Carcinomas Containing Activating<i>PIK3CA</i>Alterations
Authors: Zachary S. Zumsteg, Natasha Morse, Gabriel Krigsfeld, Gaorav Gupta, Daniel S. Higginson, Nancy Y. Lee, Luc Morris, Ian Ganly, Stephan L. Shiao, Simon N. Powell, Christine H. Chung, Maurizio Scaltriti, José Baselga
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Activating PIK3CA genomic alterations are frequent in head and neck squamous cell carcinoma (HNSCC), and there is an association between phosphoinositide 3-kinase (PI3K) signaling and radioresistance. Hence, we investigated the therapeutic efficacy of inhibiting PI3K with GDC-0032, a PI3K inhibitor with potent activity against p110α, in combination with radiation in HNSCC. Experimental Design: The efficacy of GDC-0032 was assessed in vitro in 26 HNSCC cell lines with crystal violet proliferation assays, and changes in PI3K signaling were measured by Western blot analysis. Cytotoxicity and radiosensitization were assessed with Annexin V staining via flow cytometry and clonogenic survival assays, respectively. DNA damage repair was assessed with immunofluorescence for γH2AX foci, and cell cycle analysis was performed with flow cytometry. In vivo efficacy of GDC-0032 and radiation was assessed in xenografts implanted into nude mice. Results: GDC-0032 inhibited potently PI3K signaling and displayed greater antiproliferative activity in HNSCC cell lines with PIK3CA mutations or amplification, whereas cell lines with PTEN alterations were relatively resistant to its effects. Pretreatment with GDC-0032 radiosensitized PIK3CA-mutant HNSCC cells, enhanced radiation-induced apoptosis, impaired DNA damage repair, and prolonged G2–M arrest following irradiation. Furthermore, combined GDC-0032 and radiation was more effective than either treatment alone in vivo in subcutaneous xenograft models. Conclusions: GDC-0032 has increased potency in HNSCC cell lines harboring PIK3CA-activating aberrations. Further, combined GDC-0032 and radiotherapy was more efficacious than either treatment alone in PIK3CA-altered HNSCC in vitro and in vivo. This strategy warrants further clinical investigation. Clin Cancer Res; 22(8); 2009–19. ©2015 AACR.
Response to Comment on Weber et al. Type 1 Diabetes Is Associated With an Increased Risk of Fracture Across the Life Span: A Population-Based Cohort Study Using The Health Improvement Network (THIN). Diabetes Care 2015;38:1913–1920
Authors: David R. Weber, Kevin Haynes, Mary B. Leonard, Steven M. Willi, Michelle R. Denburg
Journal: Diabetes Care (2015)

A key finding of our study is that children with type 1 diabetes were at increased risk of fracture compared with age-, sex-, and practice-matched participants without diabetes (1). In his commentary (2), Dr. Shah questions the clinical significance of childhood fractures and the contribution of type 1 diabetes to fracture risk in children. To clarify, in participants with type 1 diabetes and participants without diabetes, we found that fracture incidence was highest in the 10–20-year age-group for males only; the highest incidence in females occurred in those aged 80–90 years.

From a statistical standpoint, the large sample size of our data set would be expected …
Subtype-Specific Metagene-Based Prediction of Outcome after Neoadjuvant and Adjuvant Treatment in Breast Cancer
Authors: Maurizio Callari, Vera Cappelletti, Francesca D'Aiuto, Valeria Musella, Antonio Lembo, Fabien Petel, Thomas Karn, Takayuki Iwamoto, Paolo Provero, Maria Grazia Daidone, Luca Gianni, Giampaolo Bianchini
Journal: Clinical Cancer Research (2015)

Abstract Purpose: In spite of improvements of average benefit from adjuvant/neoadjuvant treatments, there are still individual patients with early breast cancer at high risk of relapse. We explored the association with outcome of robust gene cluster–based metagenes linked to proliferation, ER-related genes, and immune response to identify those high-risk patients. Experimental Design: A total of 3,847 publicly available gene-expression profiles were analyzed (untreated, N = 826; tamoxifen-treated, N = 685; chemotherapy-treated, N = 1,150). Genes poorly performing in formalin-fixed samples were removed. Outcomes of interest were pathologic-complete response (pCR) and distant metastasis-free survival (DMFS). In ER+HER2−, the proliferation and ER-related metagenes were combined to define three risk groups. In HER2+ and ER−HER2− risk groups were defined by tertiles of an immune-related metagene. Results: The high-proliferation/low-ER group of ER+HER2− breast cancer had significantly higher pCR rate [OR, 5.01 (1.76–17.99), P = 0.005], but poorer outcome [HR = 3.73 (1.63–8.51), P = 0.0018] than the low-proliferation/high-ER. A similar association with outcome applied to patients with residual disease (RD) after neoadjuvant chemotherapy (P = 0.01). In ER−HER2− and HER2+ breast cancer, immune metagene in the high tertile was linked to higher pCR [33.7% vs. 11.6% in high and low tertile, respectively; OR, 3.87 (1.79–8.95); P = 0.0009]. In ER−HER2−, after adjuvant/neoadjuvant chemotherapy, 5-year DMFS was 85.4% for high-tertile immune metagene, and 43.9% for low tertile. The outcome association was similar in patients with RD (P = 0.0055). In HER2+ breast cancer treated with chemotherapy the association with risk of relapse was not significant. Conclusions: We developed metagene-based predictors able to define low and high risk of relapse after adjuvant/neoadjuvant therapy. High-risk patients so defined should be preferably considered for trials with investigational agents. Clin Cancer Res; 22(2); 337–45. ©2015 AACR.
Folic Acid and the Prevention of Birth Defects
Authors: C. E. Butterworth, Adrianne Bendich
Journal: Annual Review of Nutrition (1996)

Thirty years ago, it was suggested that maternal intake of certain vitamins during pregnancy affected the incidence of serious fetal malformations. Subsequent research has revealed that folate (folic acid), a B vitamin, plays a crucial role in the development of the central nervous system during the early weeks of gestation, which is generally before the pregnancy is confirmed. In a significant number of embryos, an inadequate supply of folate at this time leads to a failure of the primitive neural tube to close and differentiate normally and results in neural tube birth defects (NTD). Numerous studies have confirmed the importance of an adequate intake of folate during the weeks just before and after conception. Overall, the data predict that if women consume multivitamin supplements containing folic acid during the periconceptional period, the number of children born with serious malformations (such as spina bifida and anencephaly) could be reduced by half. Although programs to increase dietary folate intake of potential mothers may be effective in reducing NTD, the only proven and practical preventive measure currently available is to take oral multivitamin supplements containing folic acid. Multivitamin supplementation has also been associated with reduced incidence of other congenital malformations. Current research is focusing on the role of micronutrients in embryogenesis, and on methods to identify prospective mothers at increased risk for bearing a child with NTD or with other major malformations shown to occur at reduced frequency with multivitamin supplementation. Of equal importance is the development of methods to communicate current knowledge as a public health measure.
The problem is obvious, the solution is not: numbers do matter in cardiac cell therapy!: EXPERT'S PERSPECTIVE
Authors: J. Muller-Ehmsen
Journal: Cardiovascular Research (2012)

This editorial refers to an article by Z. Pasha et al. [7][1] published in Cardiovascular Research in 2008. It is accompanied by a retrospective editorial by two of the authors of that original article, Z. Pasha and M. Ashraf (doi:10.1093/cvr/cvs209), as part of this Spotlight on Landmark Papers in Cardiovascular Research . 

Cardiac cell therapy was first proposed in 1992 to be a valuable treatment option for myocardial infarction and heart failure.1 Meanwhile, many cell types and many routes of application have been studied, and many clinical studies have also been performed. The original approach of cardiac cell therapy was aimed at replacing lost cells by newly seeded cardiomyocytes or precursors thereof, which ideally actively contribute to cardiac contractility.2 This approach is hampered by the lack of sufficient cardiomyocyte resources and by the inability of bone marrow cells to transdifferentiate into heart muscle cells, by environmental influence only. A second approach of cardiac cell therapy appears easier to conduct, in which progenitor cells (e.g. bone marrow cells) are used as carriers of cytokines or other anti-scar formation agents that beneficially influence cardiac structure and function after myocardial infarction. This latter approach has already been studied extensively in …

 [1]: #ref-7
Summary of Notifiable Noninfectious Conditions and Disease Outbreaks: Foodborne and Waterborne Disease Outbreaks — United States, 1971–2012
Authors: Daniel Dewey-Mattia, Virginia Roberts, Jonathan Yoder, L. Hannah Gould
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

20 minutes per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information.
Angiostatin inhibits tumor growth via the regulation of fibrinolytic system through binding its receptor annexin II
Authors: Mahesh C. Sharma, Vicki Rothman, Meena Sharma, George Tuszynski
Journal: Cancer Research (2004)

4783   Angiostatin, an internal fragment of plasminogen, was discovered based on its potent and selective endothelial cytostatic activity in vitro. Angiostatin was shown to posses’ potent anti-angiogenic and anti-tumor activity without any visible toxicity in animal studies. Promising preclinical studies showed that AS inhibits the growth of solid tumors and prevents their metastasis, this anti-angiogenic compound was one of the earliest to enter anti-tumor clinical trials. Despite many pharmacological studies, the current knowledge of AS’s molecular mode of action is limited. Various mechanism(s) of AS’s mode of action have been suggested including from our laboratory. We reported that AS binds to fibrinolytic receptor annexin II on EC surface and may be blocking plasmin generation, strong serine protease, which facilitate angiogenic process via degradation of extra cellular matrix (ECM) ( Microvascular Research 64, 448-462, 2002 ). Our results further provide evidence that fibrinolytic and clotting system directly involved in the angiogenic process.In the present report we demonstrate that annexin II is up regulated by potent angiogenic cytokine bFGF. Interestingly, annexin II expression was found specifically in endothelial cells but not in fibroblast cells (NIH3T3) suggesting its possible role in angiogenesis. We further showed that AS competes for plasminogen (PLG) binding on EC surface annexin II and interfering with plasmin generation, which is crucial for angiogenesis. We further tested whether blocking annexin II in EC will inhibit proliferation, angiogenesis in vitro and tumor growth in vivo. Surprisingly, anti-annexin II antibody treatment induces EC death and inhibits proliferation in a dose dependent manner. Antibody treatment also disrupted microvessels formation on collagen gel. We further explored the feasibility of treating solid Lewis lung carcinoma in mice model using monoclonal anti-annexin II antibody. Intravenous injection of single dose of antibody (200mg/kg of body weight) inhibited tumor growth almost 75%. Serum analysis of these animals showed complete inhibition of plasmin generation after antibody treatment but in contrast very high levels of plasmin was detected in IgG treated animals. These data suggest that annexin II facilitate angiogenic process by fostering cell surface proteolytic activity of plasmin and promote new vessel remodeling. To the best of my knowledge this is the first report showing that targeted blocking of angiostatin’s receptor annexin II may be used as a therapy for cancer. These observations provide great deal of hope that functional blocking of AS’s receptor annexin II may be used to inhibit pathological angiogenesis and tumor growth.
Dose-related immunologic effects of levamisole in patients with cancer.
Authors: J Janik, W C Kopp, J W Smith, D L Longo, W G Alvord, W H Sharfman, R G Fenton, M Sznol, R G Steis, S P Creekmore
Journal: Journal of Clinical Oncology (1993)

This phase I study was conducted to determine the maximum-tolerated dose (MTD) and the immunologic properties of levamisole in cancer patients when administered alone and in combination with interferon gamma (IFN-gamma).Twenty patients with advanced cancer and 36 patients with completely resected melanoma (n = 33) or renal cell cancer (n = 3) received levamisole orally every other day for six doses at 1.0, 2.5, 5.0, or 10.0 mg/kg. Ten days later, patients restarted levamisole and began IFN-gamma 0.1 mg/m2 by subcutaneous injection every other day. Blood samples were collected for measurement of neopterin and soluble interleukin-2 receptor (sIL-2R), and for flow-cytometric analysis.The MTD of levamisole was 5 mg/kg, and this was not changed by the addition of IFN-gamma. Dose-related increases in serum levels of neopterin and sIL-2R were noted. Multiple doses of > or = 5 mg/kg of levamisole were required to elicit immune changes, which were more prominent in patients with minimal tumor burdens. Increased expression of CD64 and class I and class II major histocompatibility antigens on monocytes was also observed. The combination of IFN-gamma and levamisole did not result in greater immunologic effects than those observed in previous trials of IFN-gamma alone.Levamisole induces dose-related immunologic changes in patients with large or minimal tumor burdens. These changes may be involved in the beneficial effects noted in recent adjuvant trials of levamisole. Ongoing clinical trials should correlate immune changes with response, and trials exploring different schedules of administration using higher, more immunologically active, doses of levamisole should be performed.
Time to Definitive Failure to the First Tyrosine Kinase Inhibitor in Localized GI Stromal Tumors Treated With Imatinib As an Adjuvant: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup Randomized Trial in Collaboration With the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas
Authors: Paolo G. Casali, Axel Le Cesne, Andres Poveda Velasco, Dusan Kotasek, Piotr Rutkowski, Peter Hohenberger, Elena Fumagalli, Ian R. Judson, Antoine Italiano, Hans Gelderblom, Antoine Adenis, Jörg T. Hartmann, Florence Duffaud, David Goldstein, Javier M. Broto, Alessandro Gronchi, Angelo P. Dei Tos, Sandrine Marréaud, Winette T.A. van der Graaf, John R. Zalcberg, Saskia Litière, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2015)

In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery patients with localized, high- or intermediate-risk GI stromal tumor (GIST).Patients were randomly assigned to 2 years of imatinib 400 mg daily or no further therapy after surgery. The primary end point was overall survival; relapse-free survival (RFS), relapse-free interval, and toxicity were secondary end points. In 2009, given the concurrent improvement in prognosis of patients with advanced GIST, we changed the primary end point to imatinib failure-free survival (IFFS), with agreement of the independent data monitoring committee. We report on a planned interim analysis.A total of 908 patients were randomly assigned between December 2004 and October 2008: 454 to imatinib and 454 to observation. Of these, 835 patients were eligible. With a median follow-up of 4.7 years, 5-year IFFS was 87% in the imatinib arm versus 84% in the control arm (hazard ratio, 0.79; 98.5% CI, 0.50 to 1.25; P = .21); RFS was 84% versus 66% at 3 years and 69% versus 63% at 5 years (log-rank P < .001); and 5-year overall survival was 100% versus 99%, respectively. Among 528 patients with high-risk GIST by local pathologist, 5-year IFFS was 79% versus 73%; among 336 centrally reviewed high-risk patients, it was 77% versus 73%, respectively.This study confirms that adjuvant imatinib has an overt impact on RFS. No significant difference in IFFS was observed, although in the high-risk subgroup there was a trend in favor of the adjuvant arm. IFFS was conceived as a potential end point in the adjuvant setting because it is sensitive to secondary resistance, which is the main adverse prognostic factor in patients with advanced GIST.
Randomized phase III study of adjuvant chemotherapy with S-1 versus capecitabine (cape) in patients with stage III colon cancer (CC): Results of Japan Clinical Oncology Group study (JCOG0910).
Authors: Tetsuya Hamaguchi, Yasuhiro Shimada, Junki Mizusawa, Yusuke Kinugasa, Yukihide Kanemitsu, Masayuki Ohue, Shoichi Fujii, Nobuhiro Takiguchi, Toshimasa Yatsuoka, Yasumasa Takii, Hitoshi Ojima, Hiroyuki Masuko, Yoshiro Kubo, Hideyuki Mishima, Takashi Yamaguchi, HIroyuki Bandou, Toshihiko Sato, Takeshi Kato, Kenichi Nakamura, Haruhiko Fukuda
Journal: Journal of Clinical Oncology (2015)

3512 Background: We previously reported the results of the JCOG0205 study, which indicated that D2/D3 lymph node dissection followed by adjuvant fluoropyrimidine (F) monotherapy resulted in better disease-free survival (DFS) and overall survival (OS) in Japan than in Western countries (EJC 2014). Cape is one of standard adjuvant chemotherapy for stage III CC (NEJM 2005). Recently, S-1 was demonstrated to be non-inferior to uracil and tegafur plus leucovorin in DFS (Ann Oncol 2014). This is the first report of JCOG0910, which compared S-1 with cape. Methods: Key eligibility criteria were: stage III, colorectal adenocarcinoma except for lower rectal cancer, R0 with D2/3 lymph node dissection, 20-80 years old. Patients were randomized to 8 courses of cape (2,500 mg/m2/day, days 1–14, q3w) or 4 courses of S-1 (80 mg/m2/day, days 1–28, q6w). Primary endpoint was DFS. Planned sample size was 1,550 to provide 80% power with a non-inferiority margin of hazard ratio (HR) of 1.24 and 1-sided α = 0.05; with interim analyses after 50% of the planned accrual and 1 year after completion of accrual. Results: Between Mar 2010 and Aug 2013, 1,564 pts were randomized to cape (n = 782) or S-1 (n = 782). Median age was 66; male/female: 52%/48%, colon/rectum: 68%/32%, number of positive nodes ≤ 3/4 ≤ : 84%/16%. At the second interim analysis on Sep 2014, 48% of required events (258/535) were observed, and JCOG Data and Safety Monitoring Committee recommended early publication because S-1 was apparently inferior to cape in DFS. With median follow-up of 23.7 months for all randomized pts, 3-year DFS was 82.0% in cape and 77.9% in S-1. The HR of DFS was 1.23 (99.05% CI, 0.887–1.70) and the non-inferiority of S-1 was not demonstrated (P = 0.111). The incidence of grade 3/4 adverse events was 21.2% in cape and 12.1% in S-1. Hand-foot syndrome was common in cape, whereas diarrhea and anorexia were common in S-1. Conclusions: This study failed to demonstrate the non-inferior of adjuvant S-1 to cape in DFS. Adjuvant cape remains the standard treatment and S-1 should not be used for stage III CC. Clinical trial information: UMIN000003272.
A Review of: “George Annas. 2004, American Bioethics: Crossing Human Rights and Health Law Boundaries”
Authors: Albert R. Jonsen
Journal: The American Journal of Bioethics (2005)

"A Review of: “George Annas. 2004, American Bioethics: Crossing Human Rights and Health Law Boundaries”." The American Journal of Bioethics, 5(3), pp. 71–72