tbuckley/cabot-search huggingface dataset:
SKI-606, an Src Inhibitor, Reduces Tumor Growth, Invasion, and Distant Metastasis in a Mouse Model of Thyroid Cancer
Authors: Won Gu Kim, Celine J. Guigon, Laura Fozzatti, Jeong Won Park, Changxue Lu, Mark C. Willingham, Sheue-yann Cheng
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Src is overexpressed or hyperactivated in a variety of human cancers, including thyroid carcinoma. Src is a central mediator in multiple signaling pathways that are important in oncogenesis and cancer progression. In this study, we evaluated the effects of an Src inhibitor, SKI-606 (bosutinib), in a spontaneous metastatic thyroid cancer model with constitutively activated Src (ThrbPV/PVPten+/− mice). Experimental Design: ThrbPV/PVPten+/− mice were treated with SKI-606 or vehicle controls, beginning at 6 weeks of age until the mice succumbed to thyroid cancer. We assessed the effects of SKI-606 on thyroid cancer progression and analyzed the impact of SKI-606 on aberrant Src-mediated signaling. Results: SKI-606 effectively inhibited aberrant activation of Src and its downstream targets to markedly inhibit the growth of thyroid tumor, thereby prolonging the survival of treated mice. While Src inhibition did not induce cell apoptosis, it decreased cell proliferation by affecting the expression of key regulators of cell-cycle progression. Importantly, SKI-606 dramatically prevented dedifferentiation, vascular invasion, and lung metastasis of thyroid cancer cells. These responses were meditated by downregulation of mitogen-activated protein kinase pathways and inhibition of the epithelial–mesenchymal transition. Conclusions: Our findings suggest that Src is critical in the progression of thyroid cancer, making oral SKI-606 a promising treatment strategy for refractory thyroid cancer. Clin Cancer Res; 18(5); 1281–90. ©2012 AACR.
Interleukin 27 negatively regulates the development of interleukin 17–producing T helper cells during chronic inflammation of the central nervous system
Authors: Jason S Stumhofer, Arian Laurence, Emma H Wilson, Elaine Huang, Cristina M Tato, Leanne M Johnson, Alejandro V Villarino, Qiulong Huang, Akihiko Yoshimura, David Sehy, Christiaan J M Saris, John J O'Shea, Lothar Hennighausen, Matthias Ernst, Christopher A Hunter
Journal: Nature Immunology (2006)
A NOVEL PREHOSPITAL ECG SCORING SYSTEM OUTPERFORMS REPERFUSION DELAY FOR PREDICTION OF LEFT VENTRICULAR FUNCTION IN PATIENTS WITH STEMI
Authors: Said Yama Fakhri, Mads Ersboll, Lars Kober, Christian Hassager, Rasmus Hesselfeldt, Jacob Steinmetz, Peter Clemmensen, Mikkel Schoos
Journal: Journal of the American College of Cardiology (2013)
Gaucher's Disease
Authors: David Yi-Yung Hsia, Jean Naylor, John A. Bigler
Journal: New England Journal of Medicine (1959)

GAUCHER'S disease is an uncommon hereditary metabolic disorder characterized by the accumulation of cerebrosides in the reticuloendothelial system. Some 300 cases have been reported in the literature since the condition was first described by Gaucher in 1882.In the "adult" form, the clinical picture is that of enlargement of the spleen and liver accompanied later by pigmentation of the skin, mainly of the exposed parts, and wedge-shaped, brown thickening of the sclera. A mild anemia, leukopenia and thrombocytopenia with a bleeding diathesis may develop. The infiltration of Gaucher cells may cause pulmonary1 2 3 4 5 6 7 8 and bone involvement,9 , 10 giving characteristic x-ray findings. Gaucher's . . .
Blood Pressure, Fitness, and Fatness in 5- and 6-Year-Old Children
Authors: Bernard Gutin
Journal: JAMA (1990)

Cross-sectional relations among blood pressure (BP), aerobic fitness, body fatness, and fat patterning were studied in 216 primarily Hispanic inner-city 5- and 6-year-olds. Fitness was measured with a submaximal treadmill test, and fatness was measured with five skin folds. Diastolic BP was inversely related to fitness in the boys and girls, and positively related to fatness for the boys. Systolic BP was positively related to fatness for the boys and girls. Using multiple regression and including parental BPs, fatness explained significant proportions of the variance in systolic BP for both the boys and girls and in diastolic BP for the boys. There were tendencies for central skin folds to explain more of the variation in BP than peripheral skin folds only for the boys. Fitness and fatness were inversely related for the boys and girls. Thus, at 5 and 6 years of age children exhibit some of the same risk factors for cardiovascular disease seen in adults.
Myopathy Associated With Primary Biliary Cirrhosis Demonstrating Muscle Involvement on Bone Scanning
Authors: Hulya Ortapamuk
Journal: Clinical Nuclear Medicine (2004)

A 58-year-old woman with primary biliary cirrhosis (PBC) was admitted to the hospital because of muscle weakness, increasing fatigability, loss of weight, abnormal serum liver and alkaline phosphatase enzyme levels. She was referred to the nuclear medicine department for a bone scan to investigate possible metabolic bone disease.
Appeal court judges say scientific controversies must be settled by science not law
Authors: C. Dyer
Journal: BMJ (2010)

The science writer Simon Singh has won a landmark victory at the Court of Appeal in London giving stronger free speech protection to writers facing libel threats for raising issues of scientific controversy.

Three of the most senior judges in England and Wales have allowed his appeal against a high court preliminary ruling that when he accused the British Chiropractic Association (BCA) of “happily promoting bogus treatments” he could not claim the defence of “fair comment” ( BMJ 2009;338:b2127, doi:10.1136/bmj.b2127).

Lord Judge, the lord chief justice, said he and his fellow judges adopted a statement by Judge Easterbrook, now chief judge of the US Seventh Circuit Court of Appeals: “[Plaintiffs] cannot, by simply filing suit and crying ‘character assassination,’ silence those who hold divergent views, no matter how adverse those views …
Compendia and Anticancer Therapy Under Medicare
Authors: Katherine Tillman, Brijet Burton, Louis B. Jacques, Steve E. Phurrough
Journal: Annals of Internal Medicine (2009)

In 1993, Congress directed the Medicare program to refer to 3 existing published compendia, American Medical Association Drug Evaluations (AMA-DE), United States Pharmacopoeia Drug Information for the Health Professional (USP-DI), and American Hospital Formulary Service Drug Information (AHFS-DI), to identify unlabeled but medically accepted uses of drugs and biologicals in anticancer chemotherapy regimens. Public discussion during the preceding years had centered on whether to designate unlabeled uses of anticancer treatments as experimental and thus outside the scope of Medicare benefits. American Medical Association Drug Evaluations and USP-DI subsequently ceased publication, and the Medicare program faced increasing calls to revise the list of acceptable compendia, as authorized in the statute. In 2007, the Centers for Medicare & Medicaid Services used its regulatory authority to establish a publicly transparent process to revise the list. The Centers for Medicare & Medicaid Services considered 5 requests in 2008 and added National Comprehensive Cancer Network Drugs and Biologics Compendium, DRUGDEX, and Clinical Pharmacology to the list of compendia. DrugPoints was not added, and AMA-DE was removed. Because of the potential for conflicts of interest to lead to biased judgments, the 2008 Medicare Improvements for Patients and Providers Act has a provision that explicitly prohibits inclusion of compendia that do not have a publicly transparent process for evaluating therapies and identifying potential conflicts of interest.
Isotretinoin for Acne
Authors: Peter E. Pochi
Journal: New England Journal of Medicine (1985)

The report in 1979 by Peck et al. that treatment of severe, therapy-resistant acne with oral isotretinoin (13-cis-retinoic acid) effected complete remission of the disease evoked much excitement and eager expectation.1 A particularly striking observation was that patients given this synthetic vitamin A derivative remained free of disease for prolonged periods after the completion of a course of treatment lasting four to five months. This was in contradistinction to the effect of traditional acne therapies that ordinarily require long-term use for suppression.Since September 1982, when oral isotretinoin was first marketed for use in the United States, more . . .
Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammation
Authors: George T. De Sanctis, James A. MacLean, Shixin Qin, Walter W. Wolyniec, Hartmut Grasemann, Chandri N. Yandava, Aiping Jiao, Thomas Noonan, Joan Stein-Streilein, Francis H.Y. Green, Jeffrey M. Drazen
Journal: Journal of Clinical Investigation (1999)

We examined the role of the interleukin-8 (IL-8) receptor in a murine model of allergen-induced pulmonary inflammation using mice with a targeted deletion of the murine IL-8 receptor homologue (IL-8r–/–). Wild-type (Wt) and IL-8r–/– mice were systemically immunized to ovalbumin (OVA) and were exposed with either single or multiple challenge of aerosolized phosphate-buffered saline (OVA/PBS) or OVA (OVA/OVA). Analysis of cells recovered from bronchoalveolar lavage (BAL) revealed a diminished recruitment of neutrophils to the airway lumen after single challenge in IL-8r–/– mice compared with Wt mice, whereas multiply challenged IL-8r–/– mice had increased B cells and fewer neutrophils compared with Wt mice. Both Wt and IL-8r–/– OVA/OVA mice recruited similar numbers of eosinophils to the BAL fluid and exhibited comparable degrees of pulmonary inflammation histologically. Both total and OVA-specific IgE levels were greater in multiply challenged IL-8r–/– OVA/OVA mice than in Wt mice. Both the IL-8r–/– OVA/OVA and OVA/PBS mice were significantly less responsive to methacholine than their respective Wt groups, but both Wt and IL-8r mice showed similar degrees of enhancement after multiple allergen challenge. The data demonstrate that the IL-8r modulates IgE production, airway responsiveness, and the composition of the cells (B cells and neutrophils) recruited to the airway lumen in response to antigen.
Antithymocyte globulin therapy for steroid‐resistant acute graft versus host disease
Authors: Mónica Ballesteros, Christelle Ferrá, David Serrano, Montserrat Batlle, Josep María Ribera, José Luis Díez‐Martín
Journal: American Journal of Hematology (2008)

RAD51 and XRCC3 polymorphism frequency and risk of myelodysplastic syndromes P value for w 2 or Fisher's exact test for allele frequency where appropriate.
Abstract 4914: Integrated molecular profiles of primary breast tumors reveal differential interleukin signaling and improved prognostic power
Authors: Vessela N. Kristensen
Journal: Cancer Research (2012)

Abstract The accumulation of high throughput molecular profiles of tumors at various levels has been a long and costly process worldwide. Combined analysis of gene regulation at various levels may point to specific biological functions and molecular pathways that are deregulated in multiple epithelial cancers and reveal novel subgroups of patients for tailored therapy and monitoring. We have collected high throughput data at several molecular levels derived from fresh frozen samples from primary tumors and matched blood from approximately 110 breast cancer patients (the MicMa dataset) with information about presence of disseminated tumor cells (DTC) and long term follow-up. The MicMa set has been used in parallel pilot studies of whole-genome mRNA expression (1), arrayCGH (2), DNA-methylation (3), whole genome SNP-CGH array (4), whole-genome miRNA expression analyses (5), TP53 mutation status dependent pathways (6) and high throughput paired-end sequencing (7). We have explored the extent to which these new profiles, acquired by molecular analyses at various levels recapitulate the initially discovered expression subclasses and their prognostic potential. Further, we attempted to integrate these by modeling mRNA, CNAs, miRNAs, and methylation in a pathway context using Paradigm (Pathway Recognition Algorithm using Data integration on Genomic Models) (8). We were able to show that combining mRNA expression and DNA copy-number leads to better discrimination of patients with respect to prognosis than any of the molecular levels studied separately. The pathways whose perturbations most strongly contributed to this classification were ERBB4, also previously found deregulated in breast and ovarian cancers, FoxM1 transcription, deregulated also in the ovarian and glioblastoma TCGA datasets, Angiopoientin receptor Tie2-mediated signaling and most notably the immune response (TCR) and interleukin signaling, IL4, IL6, IL12 and IL23 signaling. Massive interleukin signaling and similar sub-classification was observed also in DCIS (ductal carcinoma in situ) together with extracellular matrix and cell-cell adhesion regulating pathways. 1. Naume B et al. (2007) Mol. Oncol. 1, 160-171. 2. Russnes HG and Vollan HK et al. (2010) Sci. Transl. Med. 2, 38ra47. 3. Ronneberg J A et al. (2011) Mol. Oncol. 5, 61-76. 4. Van LP et al. (2010) Proc. Natl. Acad. Sci. U. S. A. 107, 16910-16915. 5. Enerly E and Steinfeld I et al. (2011) PLoS. One. 6, e16915. 6. Joshi H et al. submitted (2011). 7. Stephens P et al. (2009) Nature. 462, 1005-1010. 8. Kristensen V et al (2011)PNAS, 2001, Epub ahead Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4914. doi:1538-7445.AM2012-4914
An Ethical Evaluation of the 2006 Centers for Disease Control and Prevention Recommendations for HIV Testing in Health Care Settings
Authors: M. Teresa Celada, Roland C. Merchant, Michael J. Waxman, Angela M. Sherwin
Journal: The American Journal of Bioethics (2011)

When in 2006 the Centers for Disease Control and Prevention issued revised recommendations for HIV testing in health care settings, vocal opponents charged that use of an "opt-out" approach to presenting HIV testing to patients; the implementation of nontargeted, widespread HIV screening; the elimination of a separate signed consent; and the decoupling of required HIV prevention counseling from HIV testing are unethical. Here we undertake the first systematic ethical examination of the arguments both for and against the recommendations. Our examination reveals that the ethical concerns raised by the critics predominately pertain not to ethically suspect elements of the recommendations themselves, but to suspicions that they will be implemented improperly. It has not been shown that the recommendations cannot be implemented properly. Here we show that in the United States the recommendations are morally justifiable and that safeguards or regulatory oversight may serve to ensure that the recommendations are properly implemented.
Nocturnal deaths among patients with chronic bronchitis and emphysema.
Authors: W T McNicholas, M X Fitzgerald
Journal: BMJ (1984)

BRITISH MEDICAL JOuRNAL VOLUmE 289 6 ocrom 1984 not seen in club scramblers.In this small series the incidence of injuries around the right knee was high, and further work is being done to define injury patterns, mechanisms, and possible preventive measures in scrambling accidents in all ages.Our purpose is to highlight these injuries to children, which do not appear in official road accident statistics.We have shown that they may be of a substantial nature and warrant further study.We thank the orthopaedic consultant staff for permission to report on their patients.
Chronic Atrial Dilation, Electrical Remodeling, and Atrial Fibrillation in the Goat
Authors: Hans-Ruprecht Neuberger, Ulrich Schotten, Yuri Blaauw, Dirk Vollmann, Sabine Eijsbouts, Arne van Hunnik, Maurits Allessie
Journal: Journal of the American College of Cardiology (2006)
Distribution and determinants of mouse allergen exposure in low-income New York City apartments.
Authors: Ginger L Chew, Matthew S Perzanowski, Rachel L Miller, Juan C Correa, Lori A Hoepner, Carlos M Jusino, Mark G Becker, Patrick L Kinney
Journal: Environmental Health Perspectives (2003)

Previous studies of mouse allergens and laboratory-animal-worker-related allergy and asthma suggest that quantifying mouse allergen levels in homes could augment our understanding of inner-city asthma. We hypothesized that levels of mouse allergen in inner-city homes would be related to certain household characteristics. Dust samples were collected from the kitchens and beds of 221 mothers enrolled in a prospective birth cohort study, 92 of African American and 129 of Dominican ethnicity. Samples were analyzed for mouse urinary protein. The geometric mean for kitchen samples was 4.6 micro g/g [95% confidence interval (95% CI), 3.2-6.5] and for bed samples was 0.9 micro g/g (95% CI, 0.8-1.1). The variables associated with mouse allergen levels in the home were frequency of mouse sightings, use of traps or pesticides for mice, presence of holes in ceilings or walls, absence of a cat, and living in a building with fewer than eight floors. Statistically significant neighborhood differences in levels of mouse allergen and report of rodents in the home were also observed. In conclusion, mouse allergen was prevalent among inner-city apartments, and the positive predictive value of self-reported frequent mouse sightings was high (90% for kitchens). However, high levels of mouse allergen were also found in many homes where mothers reported never seeing mice.
The in vitro effects of vincristine on peripheral blood leukocyte progenitor cells (CFU-C) in patients in blast crisis of chronic granulocytic leukemia: Correlation with clinical response
Authors: Jack Goldberg, Kenneth W. Zamkoff, Douglas A. Nelson, Frederick R. Davey, Arlan J. Gottlieb
Journal: American Journal of Hematology (1983)

The in vitro sensitivity of circulating progenitor cells (CFU-C) of 20 patients in blast crisis of chronic granulocytic leukemia (CGL) to vincristine was correlated with the clinical response to vincristine in vivo. Eleven patients who achieved either a good or partial clinical response displayed a reduction in the number of colonies or clusters formed by their peripheral blood leukocytes in a double layer agar culture assay following incubation with vincristine. The CFU-C of five of six patients who failed to respond clinically to vincristine and prednisone were not suppressed following incubation with up to 12 microM vincristine. Three additional patients were not evaluable due to early post-treatment deaths. In vitro assay of the effects of vincristine on CFU-C appears to have predictive value for in vivo response in blast crisis of CGL.
13C-Pyruvate Imaging Reveals Alterations in Glycolysis that Precede c-Myc-Induced Tumor Formation and Regression
Authors: Simon Hu, Asha Balakrishnan, Robert A. Bok, Brittany Anderton, Peder E.Z. Larson, Sarah J. Nelson, John Kurhanewicz, Daniel B. Vigneron, Andrei Goga
Journal: Cell Metabolism (2011)
Present Position of the Chemotherapy of Bacterial Infections
Authors: L. P. Garrod
Journal: BMJ (1955)

HYPOPHYSECTOMY IN MANMJouRNrL diet containing 1,400-1,700 calories daily, and men one of 1,600-2,000 calories, together with a daily mainten- ance dose of 8-24 units of a long-acting insulin.In the surviving casesjthe operation was followed by a fall in blood pressure and a decrease in heart volume.Where calcification of peripheral vessels existed before operation this was not affected, but no calcification occurred in other cases.Capillary fragility was normal.A definite decrease in albuminuria and in glomerular filtration rate was achieved, but the effective renal plasma flow remained unchanged.This can be con- sidered to indicate a favourable effect on the renal circu- lation.No signs of progression of the renal disease were observed, though no conclusions are drawn as to improvement in the condition of the kidneys.The visual capacity improved in some cases, and the retinal changes did not progress further.The limited period of observation and the small num- ber of cases do not permit conclusions as to the thera- peutic value of hypophysectomy for the vascular complications of diabetes, but results so far obtained are encouraging.The work described above was aided
CQC warns more providers over poor care standards
Authors: M. Limb
Journal: BMJ (2013)

The Care Quality Commission has reported a big increase in the number of warning notices it has served to care providers over “unacceptable” standards. 

In 2012-13, the CQC issued 910 warning notices compared with 638 in 2011-12, according to its latest annual report.1 More than 90% (818) of those notices were issued to providers in adult social care, which covers care homes and domiciliary care. NHS trusts received 20 warning notices, and 41 were issued to independent healthcare facilities. …
Abstract 5574: mTOR is a target for omega-3 fatty acid modulation of prostate cancer progression
Authors: Shruti A. Apte, David Cavazos, Stephan Hursting, Leticia Nogueira, Linda A. deGraffenried
Journal: Cancer Research (2011)

Abstract Prostate cancer is the second leading cause of cancer related deaths in men. The primary obstacle in effective treatment of prostate cancer is the progression of the disease from a hormone-dependent to a hormone-independent state. Previous studies indicate that activation of the mammalian Target of Rapamycin (mTOR) signaling pathway may be involved in progression of prostate cancer to androgen independence. Recent data indicate that the combination of androgen deprivation with mTOR inhibition provides an additive anti-tumor effect in vivo. mTOR activity is regulated by both growth factors and nutrients, suggesting that certain dietary interventions may have anti-cancer effects through regulation of mTOR. Epidemiological studies indicate an inverse relation between dietary intake of omega-3 fatty acids and prostate cancer risk. Omega-3 fatty acids have been shown to inhibit prostate cell growth both in vitro and in vivo. Preliminary data from our laboratory demonstrated that treatment of LNCaP prostate cancer cells with omega-3 fatty acids, specifically docosahexaonoic acid (DHA), delayed development of androgen independence in vitro. This delay correlated with a decrease in protein expression of downstream targets of mTOR regulation, including phosphorylated S6, Bcl-2, and cyclin D. We hypothesize that omega-3 fatty acids may prevent prostate cancer progression to a hormone independent phenotype in part through modulation of mTOR. To test this hypothesis, we established stable transfectant LNCaP cell lines that express a constitutively active mTOR. These clones displayed less sensitivity to hormone deprivation, resembling the response observed in our previously generated hormone refractory LNCaP cell line. Importantly, these clones with constitutively active mTOR also showed resistance to the inhibitory effects of DHA. Ongoing studies are using these clones to determine if omega-3 fatty acids mediate their effect on mTOR in an Akt-independent manner to delay progression of prostate cancer to a hormone refractory phenotype. We will investigate alternative pathways through which mTOR activity is modulated in prostate cancer signaling, These studies indicate that mTOR is critical for cellular response to hormone ablation, and that mTOR may be a viable target for delaying progression to a hormone refractory disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5574. doi:10.1158/1538-7445.AM2011-5574