tbuckley/cabot-search huggingface dataset:
Advanced Ovarian Cancer: Phase III Randomized Study of Sequential Cisplatin–Topotecan and Carboplatin–Paclitaxel vs Carboplatin–Paclitaxel
Authors: P. Hoskins, I. Vergote, A. Cervantes, D. Tu, G. Stuart, P. Zola, A. Poveda, D. Provencher, D. Katsaros, B. Ojeda, P. Ghatage, R. Grimshaw, A. Casado, L. Elit, C. Mendiola, A. Sugimoto, V. D'Hondt, A. Oza, J. R. Germa, M. Roy, L. Brotto, D. Chen, E. A. Eisenhauer
Journal: JNCI Journal of the National Cancer Institute (2010)

Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy.Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided.A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007)Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and paclitaxel alone, but without improved efficacy. Carboplatin plus paclitaxel remains the standard of care for advanced epithelial ovarian cancer.
Toward automatic constructive learning
Authors: Thomas R. Shultz
Journal: Behavioral and Brain Sciences (2008)

Abstract Neuroconstructivist modeling can be usefully extended with algorithms that build their own topology and recruit existing knowledge, effectively constructing a hierarchy of network modules. Possible benefits include allowing abilities to emerge naturally, in a way that affords objective study, deeper insights, and more rapid progress, and provides more serious consideration of the implications of constructivism.
High altitude and asthma: beyond house dust mites
Authors: Denis Charpin
Journal: European Respiratory Journal (2012)

In this issue of the European Respiratory Journal , Rijssenbeek-Nouwens et al . [1] demonstrated that the benefit of a stay at high altitude was comparable in allergic and nonallergic adult asthmatic patients (allergy was defined on the basis of specific immunoglobulin (Ig)E to a panel of common aero-allergens). This benefit was substantial, exemplified by a discontinuation in oral steroids intake over the course of the stay in about 40% of both groups of asthmatic patients and an average reduction of 50% in the other patients.

The causality of the relationship between decreased exposure to house dust mites (HDM) allergens and asthma control in HDM-allergic patients is indicated through the following evidence: HDM allergen level decreases as altitude increases, apart from in humid climates; asthma control improves [2]; and specific HDM-IgE level [2] and local airway inflammation is reduced during a stay at high altitude [3]. Airway specific as well as nonspecific airway reactivity decreases and goes back to baseline values when the patient returns home [4]. Apart from HDM allergens, exposure to pollen is shorter and lower at high altitude, which, in pollen-allergic patients, …
Systematic Review of Bariatric Surgery—Reply
Authors: Jonathan R. Treadwell, Charles M. Turkelson, C. David Sjöström, Henry Buchwald, Yoav Avidor, Eugene Braunwald, Michael D. Jensen, Walter Pories, Kyle Fahrbach, Karen Schoelles
Journal: JAMA (2005)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Sodium cromoglycate in childhood asthma
Authors: Edwards A, Holgate S, Howell J, Warner J, Stevens M, Aberg N, Callaghan B, Ikura Y, König P, Reinhardt D, Stenius-Aarniala B, Weinberg E
Journal: Thorax (2001)

The review of placebo controlled trials of sodium cromoglycate (SCG) in childhood asthma by Tasche et al 1 concludes that “there is insufficient evidence that SCG has a beneficial effect as maintenance treatment in children with asthma”.

We do not believe this conclusion is justified. The principal criteria for assessing the efficacy of inhaled SCG are the mean differences in the effect on the symptoms of cough and wheeze between SCG and placebo across all trials included in the review. The 95% confidence intervals for these differences are 0.12 to 0.27 for cough and 0.11 to 0.26 for wheeze. As the differences are in favour of SCG and the confidence intervals do not include zero, the only conclusion that can be drawn is that there is strong statistical evidence for a beneficial effect of SCG in children with asthma—the reverse conclusion to that presented.

The review identified 24 randomised controlled trials and is claimed to include “all published randomised, placebo controlled trials”. Two published trials are not included (those by Berman et al 2 and Mikawa et al 3) and the trial by Silverman et al ,4 which is included, does not meet the author's criteria. Both excluded trials, which involved 472 children, reported statistically significant differences in favour of SCG compared with placebo. The study by Silverman et al compared the combination of inhaled SCG and isoprenaline with isoprenaline alone and did not include a placebo comparison.

The authors have calculated a tolerance distribution for study effects and we believe it is this distribution which has been fundamentally misinterpreted. They provide a tolerance interval for the results of future studies based on the between study variation seen. The fact that this interval contains zero does not mean that there is no evidence of a difference between treatments, as …
Recombinant Immunoproapoptotic Proteins with Furin Site Can Translocate and Kill HER2-Positive Cancer Cells
Authors: Tao Wang, Jing Zhao, Jun-Lin Ren, Li Zhang, Wei-Hong Wen, Rui Zhang, Wei-Wei Qin, Lin-Tao Jia, Li-Bo Yao, Ying-Qi Zhang, Si-Yi Chen, An-Gang Yang
Journal: Cancer Research (2007)

Abstract We previously reported the selective killing of HER2-positive tumor cells by a class of immunoproapoptotic proteins containing single-chain antibody, translocation domain of Pseudomonas exotoxin A (domain II; PEA II), and constitutively active human apoptotic molecules. In this study, a novel class of antitumor immunoproapoptotic proteins was explored to mediate tumor-specific apoptosis both in vitro and in vivo. Three furin cleavage sequences, including a synthetic polyarginine tract, and two furin cleavable sequences from PEA and diphtheria toxin were respectively used to replace PEA II in the previously constructed immunoproapoptotic protein. When produced and secreted by the genetically modified Jurkat cells, the novel targeted proapoptotic proteins selectively bound to HER2, which is often overexpressed on tumor cell surface. Followed by receptor-mediated endocytosis and furin cleavage in the endosome, the recombinant proteins could translocate into the cytosol, leading to irreversible cell death. Moreover, delivery of these proteins by either i.m. plasmid injection or i.v. injection of plasmid-expressing Jurkat cells led to tumor regression and prolonged animal survival in a nude mouse xenograft tumor model, indicating in vivo antitumor activity of the recombinant proteins. We conclude that the new class of immunoproapoptotic proteins show comparable activity with PEA II–containing counterpart and provide an attractive therapeutic alternative as they contain much less exogenous fragments. [Cancer Res 2007;67(24):11830–39]
New Gene-Immunotherapy Combining TRAIL-Lymphocytes and EpCAMxCD3 Bispecific Antibody for Tumor Targeting
Authors: Ariane Groth, Alexei V. Salnikov, Sabine Ottinger, Jury Gladkich, Li Liu, Georgios Kallifatidis, Olga Salnikova, Eduard Ryschich, Nathalia Giese, Thomas Giese, Frank Momburg, Markus W. Büchler, Gerhard Moldenhauer, Ingrid Herr
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To enhance T-cell responsiveness toward cancer cells, we overexpressed TRAIL in lymphocytes, as this death ligand induces tumor-specific apoptosis. To increase contact time of lymphocytes with tumor cells and thereby of TRAIL with its death receptors, lymphocytes were linked to the CD3 arm of bispecific antibody EpCAMxCD3, to guide the lymphocytes to tumor cells positive for the cancer stem cell marker EpCAM/ESA. Experimental Design: Lymphocytes were transduced with TRAIL lentivirus and the antitumor effect in presence and absence of EpCAMxCD3 was evaluated in vitro and in xenograft studies using epithelial cell adhesion molecule (EpCAM)–positive pancreatic and prostate cancer cells. Results: Compared with control lymphocytes, TRAIL-lymphocytes increased cytotoxicity and further induced expression of several apoptosis-related molecules. Cotransplantation of TRAIL-lymphocytes and tumor cells in mice or peritumoral injection of TRAIL-lymphocytes in larger xenografts retarded growth and induced apoptosis. Combination of TRAIL-lymphocytes with EpCAMxCD3 potentiated tumor eradication by enhancing antiapoptotic and antiproliferative signaling and by decreasing tumor vasculature. Intratumoral cyst formation was involved and associated with enhanced chemokine secretion and infiltration of mouse macrophages, suggesting contribution of an inflammatory host response. Most importantly, tumorigenicity of pancreatic cancer cells with cancer stem cell features resistant to conventional chemotherapy was strongly reduced. Conclusions: This gene-immunotherapeutic approach may be a new tool to support endogenous immune responses toward cancer even in its advanced stages. Clin Cancer Res; 18(4); 1028–38. ©2012 AACR.
PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice
Authors: Jingying Zhou, Allen K.L. Cheung, Zhiwu Tan, Haibo Wang, Wenbo Yu, Yanhua Du, Yuanxi Kang, Xiaofan Lu, Li Liu, Kwok-Yung Yuen, Zhiwei Chen
Journal: Journal of Clinical Investigation (2013)

Viral vector-based vaccines that induce protective CD8+ T cell immunity can prevent or control pathogenic SIV infections, but issues of preexisting immunity and safety have impeded their implementation in HIV-1. Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells (DCs) by fusing soluble PD1 with HIV-1 GAG p24 antigen. As compared with non-DC-targeting vaccines, intramuscular immunization via electroporation (EP) of the fusion DNA in mice elicited consistently high frequencies of GAG-specific, broadly reactive, polyfunctional, long-lived, and cytotoxic CD8+ T cells and robust anti-GAG antibody titers. Vaccination conferred remarkable protection against mucosal challenge with vaccinia GAG viruses. Soluble PD1-based vaccination potentiated CD8+ T cell responses by enhancing antigen binding and uptake in DCs and activation in the draining lymph node. It also increased IL-12-producing DCs and engaged antigen cross-presentation when compared with anti-DEC205 antibody-mediated DC targeting. The high frequency of durable and protective GAG-specific CD8+ T cell immunity induced by soluble PD1-based vaccination suggests that PD1-based DNA vaccines could potentially be used against HIV-1 and other pathogens.
Spontaneous Transformation of Cultured Mouse Bone Marrow–Derived Stromal Cells
Authors: Yi Fu Zhou, Marta Bosch-Marce, Hiroaki Okuyama, Balaji Krishnamachary, Hideo Kimura, Li Zhang, David L. Huso, Gregg L. Semenza
Journal: Cancer Research (2006)

Abstract Bone marrow–derived stromal cells have engendered interest because of their therapeutic potential for promoting tissue vascularization and repair. When mononuclear cells isolated from mouse bone marrow were cultured in DMEM supplemented with 10% fetal bovine serum, cell populations arose that showed rapid proliferation and loss of contact inhibition. These cells formed invasive soft tissue sarcomas after i.m. injection into nude or scid mice. I.v. injection resulted in the formation of tumor foci in the lungs. The tumors were transplantable into syngeneic immunocompetent mice. Direct injection of cultured cells into immunocompetent mice also resulted in tumor formation. Karyotype analysis showed that increased chromosome number and multiple Robertsonian translocations occurred at passage 3 coincident with the loss of contact inhibition. The remarkably rapid malignant transformation of cultured mouse bone marrow cells may have important implications for ongoing clinical trials of cell therapy and for models of oncogenesis. (Cancer Res 2006; 66(22): 10849-54)
Linkage Disequilibrium of the Brain-Derived Neurotrophic Factor <i>Val66Met</i> Polymorphism in Children With a Prepubertal and Early Adolescent Bipolar Disorder Phenotype
Authors: Barbara Geller, Judith A. Badner, Rebecca Tillman, Susan L. Christian, Kristine Bolhofner, Edwin H. Cook
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Transmission of the brain-derived neurotrophic factor (BDNF) Val66 allele in children with a prepubertal and early adolescent bipolar disorder phenotype was examined. METHOD: The prepubertal and early adolescent bipolar disorder phenotype was defined as current DSM-IV bipolar I disorder (manic or mixed phase) with at least one cardinal mania criterion (i.e., euphoria and/or grandiosity) to ensure differentiation from attention deficit hyperactivity disorder. Probands (mean age=10.7 years, SD=2.7) were obtained by consecutive new case ascertainment from designated pediatric and psychiatric venues. Parents and probands were interviewed separately by research nurses who were blind to the probands' diagnoses. Genotyping was done with TaqMan Assay-on-Demand. Analysis was done with the Family Based Association Test program. RESULTS: There were 53 complete, independent trios. The BDNF Val66 allele was preferentially transmitted (Family Based Association Test: χ2=6.0, df=1, p=0.014). CONCLUSIONS: This finding in child bipolar disorder is consistent with data for adults with bipolar disorder that show preferential transmission of the Val66 allele.
Re: Promoting Healthy Skepticism in the News: Helping Journalists Get It Right
Authors: T. L. Lash, M. P. Fox, S. Greenland, A. M. Jurek, K. J. Hoggatt, S. R. Cole, G. Maldonado, D. Brooks, K. J. Rothman, C. Poole
Journal: JNCI Journal of the National Cancer Institute (2010)
Clinical correlates of angiographically diagnosed idiopathic pulmonary hypertension.
Authors: H H Gray, J M Morgan, I H Kerr, G A Miller
Journal: Thorax (1990)

During 1970-87 43 patients with unexplained pulmonary hypertension (mean pulmonary arterial pressure greater than 25 mm Hg) were admitted to the Brompton Hospital and classified by angiographic criteria as having either symmetrical peripheral pulmonary artery pruning (thought to represent primary plexogenic pulmonary arteriopathy), n = 21, or asymmetrical pulmonary arterial occlusions (thought to represent chronic thromboembolic disease), n = 22. Patients with symmetrical pulmonary arteriopathy had significantly higher mean pulmonary arterial pressures (67 mm Hg) at the time of presentation than those with asymmetrical pulmonary arteriopathy (49 mm Hg). Clinical distinction between these two groups was impossible. Survival from the time of diagnosis was similarly poor in the two groups (26 weeks and 38 weeks) and did not correlate with any of the haemodynamic measurements. The difficulties in making distinctions between these conditions are discussed.
Febrile respiratory illnesses in infancy and atopy are risk factors for persistent asthma and wheeze
Authors: M.M.H. Kusel, T. Kebadze, S.L. Johnston, P.G. Holt, P.D. Sly
Journal: European Respiratory Journal (2011)

Severe viral respiratory illnesses and atopy are risk factors for childhood wheezing and asthma. The aim of this study was to explore associations between severe respiratory infections and atopy in early childhood with wheeze and asthma persisting into later childhood. 147 children at high atopic risk were followed from birth to age 10 yrs. Data on all respiratory infections occurring in infancy were collected prospectively and viral aetiology ascertained. Atopy was measured by skin prick tests at 6 months, and 2 and 5 yrs. History of wheeze and doctor-diagnosed eczema and asthma was collected regularly until 10 yrs of age. At 10 yrs, 60% of the cohort was atopic, 25.9% had current eczema, 18.4% current asthma and 20.4% persistent wheeze. 35.8% experienced at least one lower respiratory infection (LRI) associated with fever and/or wheeze in first year of life. Children who had wheezy or, in particular, febrile LRI in infancy and were atopic by 2 yrs, were significantly more likely to have persistent wheeze (RR 3.51, 95% CI 1.83–6.70; p&lt;0.001) and current asthma (RR 4.92, 95% CI 2.59–9.36; p&lt;0.001) at 10 yrs. Severe viral respiratory infections in infancy and early atopy are risk factors for persistent wheeze and asthma. The strongest marker of the asthmatogenic potential of early life infections was concurrent fever. The occurrence of fever during respiratory illnesses is an important marker of risk for wheeze and asthma later in childhood, suggesting it should be measured in prospective studies of asthma aetiology.
HFE Mutation and Dietary Iron Content Interact to Increase Ischemia/Reperfusion Injury of the Heart in Mice
Authors: Tibor Turoczi, Li Jun, Gerald Cordis, James E. Morris, Nilanjana Maulik, Richard G. Stevens, Dipak K. Das
Journal: Circulation Research (2003)

Hereditary hemochromatosis is an inherited pathological condition characterized by iron overload in several vital organs including heart. To increase our understanding of the underlying pathogenic mechanisms of hereditary hemochromatosis, we used a HFE gene knockout mouse model that replicates hereditary hemochromatosis. A group of mice with no copies of HFE gene and corresponding wild-type mice were maintained either on low-iron (30 ppm) or high-iron (300 ppm) diet since birth. The results of our study revealed that HFE gene knockout mouse hearts were susceptible to ischemia-reperfusion injury as evidenced by increased postischemic ventricular dysfunction, increased myocardial infarct size and cardiomyocyte apoptosis compared with wild-type control hearts. The degree of injury increased in the hearts of the mice fed high-iron diet. The hearts of the HFE knockout mice showed increased iron deposition, increased content of reactive oxygen species (ROS) as evidenced by the increased formation of malondialdehyde, and reduced antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase. The results suggest that increased amount of ROS and reduced antioxidant reserve secondary to iron overloading may be instrumental for the susceptibility of the HFE gene knockout mice to cardiac injury.
Dexamethasone reverses monocrotaline-induced pulmonary arterial hypertension in rats
Authors: L.C. Price, D. Montani, C. Tcherakian, P. Dorfmüller, R. Souza, N. Gambaryan, M-C. Chaumais, D.M. Shao, G. Simonneau, L.S. Howard, I.M. Adcock, S.J. Wort, M. Humbert, F. Perros
Journal: European Respiratory Journal (2010)

Pulmonary arterial hypertension (PAH) is associated with dysregulated bone morphogenetic protein receptor (BMPR)-II signaling and pulmonary vascular inflammation. We evaluated the effects of dexamethasone on monocrotaline (MCT)-induced PAH in rats for potential reversal of PAH at late time-points. Saline-treated control, MCT-exposed, MCT-exposed and dexamethasone-treated rats (5 mg·kg −1 ·day −1 , 1.25 mg·kg −1 and 2.5 mg·kg −1 ·48 h −1 ) were evaluated at day 28 and day 35 following MCT for haemodynamic parameters, right ventricular hypertrophy, morphometry, immunohistochemistry, and IL6 and BMPR2 expression. Dexamethasone improved haemodynamics and pulmonary vascular remodelling, preventing PAH development at early (day 1–14 and 1–28) and reversing PAH at late (day 14–28 and 21–35) time-points following MCT, as well as improving survival in MCT-exposed rats compared with controls. Both MCT-induced pulmonary IL6 overexpression and interleukin (IL)-6-expressing adventitial inflammatory cell infiltration were reduced with dexamethasone. This was associated with pulmonary BMPR2 downregulation following MCT, which was increased with dexamethasone, in whole lung and control pulmonary artery smooth muscle cells. Dexamethasone also reduced proliferation of rat pulmonary artery smooth muscle cells in vitro . Experimental PAH can be prevented and reversed by dexamethasone, and survival is improved. In this model, mechanisms may involve reduction of IL-6-expressing inflammatory cells, restoration of pulmonary BMPR2 expression and reduced proliferation of vascular smooth muscle cells.