tbuckley/cabot-search huggingface dataset:
Protease-activated receptors 1 and 4 do not stimulate Gi signaling pathways in the absence of secreted ADP and cause human platelet aggregation independently of Gisignaling
Authors: Soochong Kim, Carolyn Foster, Anna Lecchi, Todd M. Quinton, Dina M. Prosser, Jianguo Jin, Marco Cattaneo, Satya P. Kunapuli
Journal: Blood (2002)
Disruption of Existing Mental Health Treatments and Failure to Initiate New Treatment After Hurricane Katrina
Authors: Philip S. Wang, Michael J. Gruber, Richard E. Powers, Michael Schoenbaum, Anthony H. Speier, Kenneth B. Wells, Ronald C. Kessler
Journal: American Journal of Psychiatry (2007)

The authors examined the disruption of ongoing treatments among individuals with preexisting mental disorders and the failure to initiate treatment among individuals with new-onset mental disorders in the aftermath of Hurricane Katrina.English-speaking adult Katrina survivors (N=1,043) responded to a telephone survey administered between January and March of 2006. The survey assessed posthurricane treatment of emotional problems and barriers to treatment among respondents with preexisting mental disorders as well as those with new-onset disorders posthurricane.Among respondents with preexisting mental disorders who reported using mental health services in the year before the hurricane, 22.9% experienced reduction in or termination of treatment after Katrina. Among those respondents without preexisting mental disorders who developed new-onset disorders after the hurricane, 18.5% received some form of treatment for emotional problems. Reasons for failing to continue treatment among preexisting cases primarily involved structural barriers to treatment, while reasons for failing to seek treatment among new-onset cases primarily involved low perceived need for treatment. The majority (64.5%) of respondents receiving treatment post-Katrina were treated by general medical providers and received medication but no psychotherapy. Treatment of new-onset cases was positively related to age and income, while continued treatment of preexisting cases was positively related to race/ethnicity (non-Hispanic whites) and having health insurance.Many Hurricane Katrina survivors with mental disorders experienced unmet treatment needs, including frequent disruptions of existing care and widespread failure to initiate treatment for new-onset disorders. Future disaster management plans should anticipate both types of treatment needs.
Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia.
Authors: S S Hull, E Vanoli, P B Adamson, R L Verrier, R D Foreman, P J Schwartz
Journal: Circulation (1994)

Seven conscious dogs documented to be at high risk by the occurrence of ventricular fibrillation (VF) during acute myocardial ischemia were randomly assigned to 6 weeks of either daily exercise training or cage rest followed by exercise training. After 6 weeks of daily treadmill training, heart rate variability, a marker of vagal tone, increased by 74% (P &lt; .001); baroreflex sensitivity, a marker of the capability to reflexly augment vagal activity, increased by 69% (P &lt; .01); the repetitive extrasystole threshold, a marker of ventricular electrical stability, increased by 44% (P &lt; .05). After exercise training, the incidence of ventricular fibrillation during acute myocardial ischemia decreased by 100%, as all animals survived. Neither passage of time nor heart rate level during ischemia contributed to the outcome. The most likely mechanism to explain the striking change in risk status is the shift in autonomic balance characterized by increased cardiac vagal activity, which was previously shown to have an antifibrillatory effect. These results suggest that exercise training in healthy individuals may decrease their likelihood of developing lethal arrhythmias during acute myocardial ischemia.
A Bayesian Hierarchical Approach for Relating PM <sub>2.5</sub> Exposure to Cardiovascular Mortality in North Carolina
Authors: Christopher H. Holloman, Steven M. Bortnick, Michele Morara, Warren J. Strauss, Catherine A. Calder
Journal: Environmental Health Perspectives (2004)

Considerable attention has been given to the relationship between levels of fine particulate matter (particulate matter < or = 2.5 microm in aerodynamic diameter; PM(2.5) in the atmosphere and health effects in human populations. Since the U.S. Environmental Protection Agency began widespread monitoring of PM(2.5) levels in 1999, the epidemiologic community has performed numerous observational studies modeling mortality and morbidity responses to PM(2.5) levels using Poisson generalized additive models (GAMs). Although these models are useful for relating ambient PM(2.5) levels to mortality, they cannot directly measure the strength of the effect of exposure to PM(2.5) on mortality. In order to assess this effect, we propose a three-stage Bayesian hierarchical model as an alternative to the classical Poisson GAM. Fitting our model to data collected in seven North Carolina counties from 1999 through 2001, we found that an increase in PM(2.5) exposure is linked to increased risk of cardiovascular mortality in the same day and next 2 days. Specifically, a 10- microg/m3 increase in average PM(2.5) exposure is associated with a 2.5% increase in the relative risk of current-day cardiovascular mortality, a 4.0% increase in the relative risk of cardiovascular mortality the next day, and an 11.4% increase in the relative risk of cardiovascular mortality 2 days later. Because of the small sample size of our study, only the third effect was found to have > 95% posterior probability of being > 0. In addition, we compared the results obtained from our model to those obtained by applying frequentist (or classical, repeated sampling-based) and Bayesian versions of the classical Poisson GAM to our study population.
Abstract 1072: Activation of the Ras signaling pathway promotes the over-expression of anti-apoptotic heme oxygenase-1 in human renal cancer
Authors: Pallavi Banerjee, Aninda Basu, Soumitro Pal
Journal: Cancer Research (2011)

Abstract Activation of the proto-oncogene ras may play a critical role in the development and rapid progression of different types of human cancers, including renal cancer. It has been shown that the Ras pathway can mediate pro-survival signals in cancer cells by inhibiting cellular apoptosis. It is established that the cytoprotective enzyme heme oxygenase-1 (HO-1) is over-expressed in several cancers, and may play a significant role in the growth and metastasis of tumors by inducing cell survival pathways. However, it is not known if there is an association between Ras activation and HO-1 over-expression in cancer. We have recently demonstrated that the treatment of human renal cancer cells with the immunosuppressive agent cyclosporine may activate the H-Ras pathway, and promote a rapid progression of the disease. We have also shown that HO-1 is over-expressed in human renal cancer, and plays a key role in the survival of renal cancer cells by inhibiting cellular apoptosis. Here, we wished to analyze if the activation of H-Ras pathway can regulate the expression of HO-1 in two different human renal cancer cell lines 786-0 and Caki-1. In co-transfection assays, using a full-length HO-1 promoter-luciferase construct, we found that the activated form of H-Ras (H-Ras12V) promoted HO-1 transcriptional activation as observed by increased luciferase activity. We also found that the activation of H-Ras increased the mRNA expression of HO-1 as observed by real-time PCR. By using a dominant-inhibitory mutant construct H-Ras17N, we confirmed that the inhibition of H-Ras expression significantly decreased HO-1 promoter activity. We next wanted to determine which effector molecule(s) (Raf, Rho and PI-3K) is functional for H-Ras-mediated HO-1 over-expression. We made use of three different effector domain mutant constructs of H-Ras; Ras(12V,35S) retains full-length Raf-1 binding activity, Ras(12V,37G) retains Rho binding activity, and Ras(12V,40C) retains PI-3K binding activity. In co-transfection assays using these effector domain mutant constructs, we observed that the Ras-induced HO-1 transcriptional activation is mediated primarily through the Raf-1 signaling pathway. Together, our findings suggest that the Ras-Raf signaling pathway might play an important role in the survival of human renal cancer cells through the induction of HO-1 over-expression. Thus, targeting this H-Ras pathway for HO-1 over-expression might act as novel therapeutics to inhibit human renal tumors through the induction of cellular apoptosis. 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 1072. doi:10.1158/1538-7445.AM2011-1072
Bristol-Myers Squibb to pay $0.5bn to settle US lawsuits
Authors: Janice Hopkins Tanne
Journal: BMJ (2007)

Bristol-Myers Squibb and its subsidiary Apothecon have agreed to pay more than $515m (£255m; €365m) in a settlement with the US Department of Justice and the Office of the United States Attorney for Massachusetts to resolve allegations involving their drug marketing and pricing practices.

The Department of Justice said in a press release that the “settlement covers a wide assortment of illegal marketing and pricing practices.”

The department said that from about 2000 to mid-2003 Bristol-Myers Squibb made illegal payments to doctors and other healthcare providers to induce them …
Dietary Exposures to Selected Metals and Pesticides
Authors: David L. MacIntosh, John D. Spengler, Haluk Ozkaynak, Ling-hui Tsai, P. Barry Ryan
Journal: Environmental Health Perspectives (1996)

Average daily dietary exposures to 11 contaminants were estimated for approximately 120,000 U.S. adults by combining data on annual diet, as measured by a food frequency questionnaire, with contaminant residue data for table-ready foods that were collected as part of the annual U.S. Food and Drug Administration Total Diet Study. The contaminants included in the analysis were four heavy metals (arsenic, cadmium, lead, mercury), three organophosphate pesticides (chlorpyrifos, diazinon, malathion), and four organochlorine pesticides (dieldrin, p,p'-DDE, lindane, heptachlor epoxide). Dietary exposures to these contaminants were highly variable among individuals, spanning two to three orders of magnitude. Intraindividual exposures to the metals, organophosphates, and organochlorines were estimated to be strongly correlated; Pearson's correlation coefficients ranged from 0.28 for lindane:dieldrin to 0.84 for lead:mercury. For some of the compounds (e.g., arsenic and dieldrin), a substantial fraction of the population was estimated to have dietary intakes in excess of health-based standards established by the EPA. Before use for risk assessment or epidemiologic purposes, however, the validity of the exposure estimates must be evaluated by comparison with biological indicators of chronic exposure. Because of their low detection rate in table-ready foods, the estimated distributions of exposures for dieldrin, p,p'-DDE, heptachlor epoxide, lindane, diazinon, and chlorpyrifos were found to be sensitive to assumed values for nondetect samples. Reliable estimates of the population distribution of dietary exposures to most other contaminants cannot be made currently, due to their low rate of detection in table-ready foods. Monitoring programs that use more sensitive study designs and population-based assessments for other subpopulations should be a priority for future research.
Observations on EXOPHTHALMIC GOITRE
Authors: W. H. C. Romanis
Journal: BMJ (1933)

Exophthalmic goitre is a mysterious disease, and of its pathology we are very ignorant.We know many isolated facts about its causes and onset, but it is difficult to correlate these and to give each fact its proper position in the aetiology of the disease.Thus there is little doubt of the correctness of the Lollowing facts, though they advance us very little in assigning a true pathological cause:The disease is far more common in women than in men, in blondes than in brunettes, and in single women than in married ones.It almost always causes more enlargement of the right side of the )hyroid than of the left.It exhibits a slight tendency to frequency in certain parts of the world, but these localities are not usually those whete ordinary parenchymatous goitres abound.It is rarely seen at the extremes of life, being uncommon under the age of 15 and over the age of 55.
Impact of Replacing Smear Microscopy with Xpert MTB/RIF for Diagnosing Tuberculosis in Brazil: A Stepped-Wedge Cluster-Randomized Trial
Authors: Betina Durovni, Valeria Saraceni, Susan van den Hof, Anete Trajman, Marcelo Cordeiro-Santos, Solange Cavalcante, Alexandre Menezes, Frank Cobelens
Journal: PLoS Medicine (2014)

Betina Durovni and colleagues evaluated whether implementation of Xpert MTB/RIF increased the notification rate of laboratory-confirmed pulmonary tuberculosis and reduced the time to tuberculosis treatment initiation in 14 Brazilian primary care laboratories. Please see later in the article for the Editors' Summary
Abstract P2-10-02: PD-L1 protein expression is a prognostic biomarker in breast cancer
Authors: H Wimberly, K Schalper, L Chen, V Velcheti, L Pusztai, D Rimm
Journal: Cancer Research (2013)

Abstract BACKGROUND: Programmed death ligand 1 (PD-L1) and its receptor, PD1, are involved in limiting immune response. In the context of cancer, tumor cells expressing PD-L1 can suppress the immune response of PD1-expressing tumor infiltrating lymphocytes (TILs). Disruption of this pathway with antibodies to either the ligand or the receptor has shown promise in the treatment of non small cell lung cancer, melanoma and renal cell cancer. Here we investigate the pathway in breast cancer. METHODS: PD-L1 protein expression was assessed on two Yale TMA breast cancer cohorts with two-fold redundancy by quantitative immunofluorescence (QIF) using AQUA technology. Cohort 1 (YTMA201) consists of 400 patients with has extensive follow-up and adjuvant treatment information. Cohort 2 (YTMA128) consists of 245 patients with limited follow-up and no treatment information. The PD-L1 antibody (Lieping Chen, clone 5H1) has been previously validated for specificity and reproducibility using transfected cell models. TILs were assessed by a pathologist for each cohort using a score from 0-3 based on the amount of TILs within the spot. AQUA scores for PD-L1 were used as a continuous variable and also cut at the median for outcome analysis. RESULTS: PD-L1 protein is positively correlated with TILs (p&amp;lt;0.0001 on cohort 1 and p = 0.0072 on cohort 2) and inversely correlated with estrogen receptor status (p&amp;lt;0.0001 on cohort 1 and p = 0.0188 on cohort 2) on both breast cancer cohorts examined (total n = 594). On cohort 1, PD-L1 protein expression is a marker of good prognosis as a continuous variable (p = 0.0271) as well as when cut at the median (p = 0.0151), particularly in the estrogen receptor positive subset of patients. CONCLUSIONS: PD-L1 expression in breast cancer is positively associated with TILs and inversely associated with estrogen receptor status on two independent breast cancer cohorts. PD-L1 protein expression shows prognostic value in breast cancer patients, particularly the ER positive subset of patients. Further assessment of PD-1 axis marker expression may be valuable as the associated therapeutics are being tested in breast cancer patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-10-02.
Isolation and immunologic characterization of a human. B-lymphocyte-specific, cell surface antigen.
Authors: R E Humphreys, J M McCune, L Chess, H C Herrman, D J Malenka, D L Mann, P Parham, S F Schlossman, J L Strominger
Journal: The Journal of Experimental Medicine (1976)

In addition to HL-A antigens, another cell surface protein complex has been obtained from membranes of the human B-lymphoblast cell line IM-1. This complex which was solubilized with papain, consisted of polypeptides of 23,000 and 30,000 daltons (p23, 30). Rabbit antisera to this material precipitated from [35S]methionine-labeled detergent-solubilized cells, three proteins of 39,000, 34,000, and 29,000 daltons. These antisera were specifically cytotoxic for B lymphocytes of peripheral blood, for B-lymphoblast cell lines, and for EAC rosette receptor-positive surface Ig-negative (Null) lymphocytes. The p23,30 complex was not present on T lymphocytes, EAC rosette receptor-negative Null lymphocytes, or platelets. In addition, the p23,30 complex from several cell lines inhibited alloantisera from multiparous Amish women which had been shown to recognize non-HL-A, B-lymphocyte antigens. Some other properties of the anti-p23,30 sera antisera were described.
Identification and management of inherited cancer susceptibility.
Authors: F P Li
Journal: Environmental Health Perspectives (1995)

Identification of inherited cancer-predisposing genes offers opportunities for cancer prevention. Inherited susceptibility genes have been identified, primarily through studies of unusual cancer cases and families but also through general population studies. Examples include the RB1 gene for retinoblastoma; the WT1 gene for Wilms' tumor; germline p53 mutations in families with the Li-Fraumeni syndrome; the NF1 and NF2 genes for neuroblastomatosis, types 1 and 2; the VHL gene for renal cancer and other tumors associated with Von Hippel-Lindau disease; the APC gene for adenomatous polyposis coli; the BRCA1 gene for hereditary breast and ovarian cancer; and the mismatch repair genes for colon and other common cancers. For some cancers, identification of gene carriers might be beneficial for targeting screening and chemopreventive interventions. On the other hand, predisposition testing for cancer has the potential for harm from loss of insurability and employability, psychological distress, social stigmatization and other adverse effects. Research is needed to identify predisposition testing procedures that maximize benefits while minimizing harm to subjects. Chemoprevention trials in genetically susceptible populations offer the prospect of finding effective methods of reducing future cancer risk.
Chemotherapy with cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone (CHOEP) is not effective in patients with enteropathy-type intestinal T-cell lymphoma
Authors: S. Wöhrer, A. Chott, J. Drach, A. Püspök, M. Hejna, M. Hoffmann, M. Raderer
Journal: Annals of Oncology (2004)
Why I'm needled by thrombolysis target
Authors: D. Geggie
Journal: BMJ (2002)

Up and down the United Kingdom emergency departments are in crisis (again!) with senior managers and medical staff burning the midnight oil. The reason for this increased activity is the government's national service framework (NSF) for coronary heart disease (www.doh.gov.uk/nsf/coronary.htm). At present, the guidelines on thrombolysis in acute myocardial infarction are that 75% of patients should receive thrombolysis (“door to needle time”) within 30 minutes. Many emergency departments currently struggle to reach these targets. However, these guidelines are due to change to 75% of patients receiving thrombolysis within 20 minutes by April 2003. This is not going to be easy to achieve and there are increased funds available from the Department of Health (as well as the potential for penalties for failure) in order that these targets are met. Many departments are looking at employing extra staff and using more expensive “bolus thrombolytics” in order to meet these targets. …
TREATMENT OF HOOKWORM INFECTION
Authors: H. W. Brown
Journal: JAMA (1942)

<h3>To the Editor:—</h3> On page 679 of the February 21 issue ofThe Journalthe question of therapy of hookworm infection is discussed. The answer to the question begins as follows: "The drug of choice in hookworm disease is hexylresorcinol," and a little further down the following statement: "Hexylresorcinol in a single dose will remove 80 to 100 per cent of the parasites...." I believe that both of these statements are rather misleading and not strictly in accord with the scientific data available. Hexylresorcinol seldom removes more than 70 to 75 per cent of the hookworms present. Occasionally it removes more and often it removes less. It is rather expensive, particularly in view of the fact that hookworm infection occurs in the lower economic groups. Tetrachlorethylene, in general, is much more effective in the removal of hookworms. This drug will remove from 80 to 97 per cent of all the
Protection From Colorectal Cancer After Colonoscopy
Authors: Hermann Brenner, Jenny Chang-Claude, Christoph M. Seiler, Alexander Rickert, Michael Hoffmeister
Journal: Annals of Internal Medicine (2011)

Background: Colonoscopy with detection and removal of adenomas is considered a powerful tool to reduce colorectal cancer (CRC) incidence. However, the degree of protection achievable in a population setting with high-quality colonoscopy resources remains to be quantified. Objective: To assess the association between previous colonoscopy and risk for CRC. Design: Population-based case–control study. Setting: Rhine-Neckar region of Germany. Patients: A total of 1688 case patients with colorectal cancer and 1932 control participants aged 50 years or older. Measurements: A detailed lifetime history of CRC risk factors and preventive factors, including history and results of previous colonoscopies, and of medical data obtained by self-reports and medical records. Odds ratios of CRC associated with colonoscopy in the preceding 10 years were estimated, after adjustment for sex, age, education level, participation in a general health screening examination, family history of CRC, smoking status, body mass index, and use of nonsteroidal anti-inflammatory drugs or hormone replacement therapy. Results: Overall, colonoscopy in the preceding 10 years was associated with 77% lower risk for CRC. Adjusted odds ratios for any CRC, right-sided CRC, and left-sided CRC were 0.23 (95% CI, 0.19 to 0.27), 0.44 (CI, 0.35 to 0.55), and 0.16 (CI, 0.12 to 0.20), respectively. Strong risk reduction was observed for all cancer stages and all ages, except for right-sided cancer in persons aged 50 to 59 years. Risk reduction increased over the years in both the right and the left colon. Limitation: The study was observational, with potential for residual confounding and selection bias. Conclusion: Colonoscopy with polypectomy can be associated with strongly reduced risk for CRC in the population setting. Aside from strong risk reduction with respect to left-sided CRC, risk reduction of more than 50% was also seen for right-sided colon cancer. Primary Funding Source: German Research Council and German Federal Ministry of Education and Research.
Dental Surgery During Anticoagulant Therapy
Authors: John M. Askey
Journal: JAMA (1961)

To the Editor:—  The article by Behrman and Wright inThe Journal, Feb. 11, 1961, p. 483, pleased me and supported the conclusions of my study, that dental surgery can be performed safely while patients are on anticoagulant therapy. Without this timely evidence, the adverse reports from Boston in 1957 might have continued to deter physicians from permitting such treatment. Since the first report, many more patients have undergone dental surgery while under antithrombotic drug treatment. With observance of ordinary precaution and proper selection of patients, the physician and the dentist will have little trouble.  The four steps advocated by Behrman and Wright during dental surgery and the follow-up precautions are excellent. It is to be hoped that this report will receive wide distribution among dentists, so that there need be less insistence on the part of the referring physician that the dental surgery is a safe procedure within the