tbuckley/cabot-search huggingface dataset:
Role of Urokinase Receptor in Tumor Progression and Development
Authors: Hyangsoon Noh, Sungguan Hong, Shuang Huang
Journal: Theranostics (2013)

Elevated level of urokinase receptor (uPAR) is detected in various aggressive cancer types and is closely associated with poor prognosis of cancers.Binding of uPA to uPAR triggers the conversion of plasminogen to plasmin and the subsequent activation of metalloproteinases.These events confer tumor cells with the capability to degrade the components of the surrounding extracellular matrix, thus contributing to tumor cell invasion and metastasis.uPA-uPAR interaction also elicits signals that stimulate cell proliferation/survival and the expression of tumor-promoting genes, thus assisting tumor development.In addition to its interaction with uPA, uPAR also interacts with vitronectin and this interaction promotes cancer metastasis by activating Rac and stimulating cell migration.Although underlying mechanisms are yet to be fully elucidated, uPAR has been shown to facilitate epithelial-mesenchymal transition (EMT) and induce cancer stem cell-like properties in breast cancer cells.The fact that uPAR lacks intracellular domain suggests that its signaling must be mediated through its co-receptors.Indeed, uPAR interacts with diverse transmembrane proteins including integrins, ENDO180, G protein-coupled receptors and growth factor receptors in cancer cells and these interactions are proven to be critical for the role of uPAR in tumorigenesis.Inhibitory peptide that prevents uPA-uPAR interaction has shown the promise to prolong patients' survival in the early stage of clinical trial.The importance of uPAR's co-receptor in uPAR's tumor-promoting effects implicate that anti-cancer therapeutic agents may also be developed by disrupting the interactions between uPAR and its functional partners.
Waterborne outbreak control: which disinfectant?
Authors: E W Akin, J C Hoff, E C Lippy
Journal: Environmental Health Perspectives (1982)

Drinking water disinfection was shown to be an important public health measure around the turn of the century. In the United States, it was perhaps the single most important factor in controlling typhoid fever, a waterborne disease that was rampant throughout the world during the last century. It may also be assumed that disinfection was important in limiting the number of cases of other diseases known to be capable of waterborne transmission, i.e., cholera, amebiasis, shigellosis, salmonellosis, and hepatitis A. Even though modern treatment has eliminated water as a major vehicle of infectious disease transmission, outbreaks still occur. In fact, the annual number has been increasing since 1966. Interruption in chlorination or failure to achieve adequate levels of chlorine residual is the most often identified deficiency of the involved water supplies. This finding indicates that waterborne microbial pathogens remain as a potential health threat and underscores the importance of disinfection. From the outset, chlorination has been the drinking water disinfectant of choice in the country. Numerous studies have demonstrated its ability to inactivate bacterial, viral, and protozoal pathogens when applied under proper conditions. However, the finding that chlorinated organics that are potentially carcinogenic are formed has prompted an evaluation of alternative disinfectants. The viable alternatives to chlorine currently under consideration for widespread use are ozone, chlorine dioxide, and chloramines. In terms of biocidal efficiency, ozone is the most potent of the three. Chlorine dioxide is about the equivalent of free chlorine in the hypochlorous acid form but much more efficient than the hypochlorite form of free chlorine. The chloramines are weaker biocides than hypochlorite. Although this general order of ranking of efficiency holds for diverse types of microorganisms, quantitative comparisons vary with different microorganisms and experimental conditions.
Physician Decision Making and Trends in the Use of Cardiac Stress Testing in the United States
Authors: Joseph A. Ladapo, Saul Blecker, Pamela S. Douglas
Journal: Annals of Internal Medicine (2014)

Cardiac stress testing, particularly with imaging, has been the focus of debates about rising health care costs, inappropriate use, and patient safety in the context of radiation exposure.To determine whether U.S. trends in cardiac stress test use may be attributable to population shifts in demographics, risk factors, and provider characteristics and evaluate whether racial/ethnic disparities exist in physician decision making.Analyses of repeated cross-sectional data.National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (1993 to 2010).Adults without coronary heart disease.Cardiac stress test referrals and inappropriate use.Between 1993 to 1995 and 2008 to 2010, the annual number of U.S. ambulatory visits in which a cardiac stress test was ordered or performed increased from 28 per 10,000 visits to 45 per 10,000 visits. No trend was found toward more frequent testing after adjustment for patient characteristics, risk factors, and provider characteristics (P = 0.134). Cardiac stress tests with imaging comprised a growing portion of all tests, increasing from 59% in 1993 to 1995 to 87% in 2008 to 2010. At least 34.6% were probably inappropriate, with associated annual costs and harms of $501 million and 491 future cases of cancer. Authors found no evidence of a lower likelihood of black patients receiving a cardiac stress test (odds ratio, 0.91 [95% CI, 0.69 to 1.21]) than white patients, although some evidence of disparity in Hispanic patients was found (odds ratio, 0.75 [CI, 0.55 to 1.02]).Cross-sectional design with limited clinical data.National growth in cardiac stress test use can largely be explained by population and provider characteristics, but use of imaging cannot. Physician decision making about cardiac stress test use does not seem to contribute to racial/ethnic disparities in cardiovascular disease.National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences.
Phenotypic characteristics of joint fluid cells from patients with continuous joint effusion after total knee arthroplasty
Authors: Yasuo Niki, Hideo Matsumoto, Toshiro Otani, Taku Yatabe, Atsushi Funayama, Shinichi Maeno, Taisuke Tomatsu, Yoshiaki Toyama
Journal: Biomaterials (2005)
The Utility of Fractional Exhaled Nitric Oxide Suppression in the Identification of Nonadherence in Difficult Asthma
Authors: Diarmuid M. McNicholl, Michael Stevenson, Lorcan P. McGarvey, Liam G. Heaney
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Nonadherence to inhaled corticosteroid therapy (ICS) is a major contributor to poor control in difficult asthma, yet it is challenging to ascertain.Identify a test for nonadherence using fractional exhaled nitric oxide (Fe(NO)) suppression after directly observed inhaled corticosteroid (DOICS) treatment.Difficult asthma patients with an elevated Fe(NO) (>45 ppb) were recruited as adherent (ICS prescription filling >80%) or nonadherent (filling <50%). They received 7 days of DOICS (budesonide 1,600 μg) and a test for nonadherence based on changes in Fe(NO) was developed. Using this test, clinic patients were prospectively classified as adherent or nonadherent and this was then validated against prescription filling records, prednisolone assay, and concordance interview.After 7 days of DOICS nonadherent (n = 9) compared with adherent subjects (n = 13) had a greater reduction in Fe(NO) to 47 ± 21% versus 79 ± 26% of baseline measurement (P = 0.003), which was also evident after 5 days (P = 0.02) and a Fe(NO) test for nonadherence (area under the curve = 0.86; 95% confidence interval, 0.68-1.00) was defined. Prospective validation in 40 subjects found the test identified 13 as nonadherent; eight confirmed nonadherence during interview (three of whom had excellent prescription filling but did not take medication), five denied nonadherence, two had poor inhaler technique (unintentional nonadherence), and one also denied nonadherence to prednisolone despite nonadherent blood level. Twenty-seven participants were adherent on testing, which was confirmed in 21. Five admitted poor ICS adherence but of these, four were adherent with oral steroids and one with omalizumab.Fe(NO) suppression after DOICS provides an objective test to distinguish adherent from nonadherent patients with difficult asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 01219036).
Hand injuries in competition climbers.
Authors: S R Bollen, C K Gunson
Journal: British Journal of Sports Medicine (1990)

All 67 of the competitors at the first British Open climbing competition were examined for signs of previous or present hand injury. The most important clinical findings were that 26 per cent of the climbers had signs of previous injury to the A2 pulley of the ring finger, and that fixed flexion deformity of the proximal interphalangeal joints of the fingers was present in 24 per cent.
Abstract 2062: Peptidylprolyl cis/trans isomerase A1 (Pin1) is modified by lipid electrophiles generated during oxidative stress
Authors: Christopher D. Aluise, Lawrence J. Marnett
Journal: Cancer Research (2012)

Abstract Oxidation of membrane phospholipids is associated with inflammation and cancer. Phospholipid peroxidation results in the production of reactive electrophiles that adduct proteins and modulate their function. 4-Hydroxynonenal (HNE), a common product of oxidative damage to lipids, adducts proteins at exposed Cys, His, or Lys residues. Here, we provide evidence that peptidyl-prolyl cis/trans isomerase A1 (Pin1), an enzyme that catalyzes the conversion of pSer/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE-modification. Incubation of purified Pin1 with HNE followed by MALDI-TOF/TOF mass spectrometry revealed that the most reactive amino acids are His-157 and Cys-113, both of which are active site residues. Pin1 was adducted in MDA-MB-231 breast cancer cells treated with 8-alkynyl-HNE as judged by click chemistry conjugation with biotin followed by streptavidin-based pulldown and western blotting with anti-Pin1 antibody. siRNA knockdown of Pin1 in MDA-MB-231 cells partially protected the cells from HNE-induced toxicity. Recent studies indicate that Pin1 is an important molecular target for the chemopreventive effects of green tea polyphenols. The present study establishes that it is also a target for electrophilic modification by products of lipid peroxidation. 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 2062. doi:1538-7445.AM2012-2062
Superstition in Teratology.
Authors: Emile Aronson
Journal: JAMA (1907)

Dallas, Tex., Jan. 30, 1907. <h3>To the Editor:</h3> —The article of Dr. E. T. Shelly, published inThe Journal, January 26, contained many convincing arguments and the author's views will undoubtedly be endorsed by every progressive physician. I do not wish to take issue with him, on the views expressed by him, in regard to the subject of contiguity and continuity of mother and fetus, although he seems to have overlooked the unquestioned factor of heredity, but I wish to relate one interesting case in connection with this subject. A man had one child born by his first wife, with a pes equino varus. He married again, his second wife became pregnant, and although there was no other case of malformation in her husband's or her own family, she was constantly worried about the possibility of having a deformed baby. She gave birth to an otherwise perfectly healthy child, but
Housing and house‐dust mites
Authors: A. Dornelas de Andrade, J. Birnbaum, A. Lanteaume, J. L. Izard, P. Corget, M. F. Artillan, M. Toumi, D. Vervloet, D. Charpin
Journal: Allergy (1995)

Because the mite-allergen content in homes is highly variable even in the same geographic area, we tried to determine which variables influence mite infestation. We evaluated mite-allergen content in bedding relative to housing conditions and living habits. This cross-sectional study included 108 homes. Housing conditions were assessed by an architect and living habits by a researcher specialized in social and family economics. Group I allergen level was measured on the mattress dust with monoclonal antibodies, and relative humidity (RH) was monitored in the bedroom during a 2-week period. Homes with low RH did have low mite-allergen content. In contrast, homes with intermediate RH levels had very variable mite-allergen content. Using analysis of variance and a logistic regression analysis, we were unable to identify any variable predictive of mite-allergen content. Thus, factors other than relative humidity seem to influence mite infestation. Moreover, the absence of association between mite infestation and ventilation rate might be accounted for by the gentle climate in our area with notable outdoor RH.
ERBB-2 overexpression and cyclooxygenase-2 up-regulation in human cholangiocarcinoma and risk conditions
Authors: Kanenori Endo, Byung-IL Yoon, Chawalit Pairojkul, Anthony J. Demetris, Alphonse E. Sirica
Journal: Hepatology (2002)

Quantitative immunohistochemistry of ERBB-2 and MET receptor proteins and of cyclooxygenase 2 (COX-2) was undertaken to determine if there is a positive correlation between overexpression of either ERBB-2 or MET and up-regulation of COX-2 in human cholangiocarcinogenesis. ERBB-2, MET, and COX-2 immunoreactivities were measured in cancerous parenchyma of 71 archival cases of human cholangiocarcinoma (ChC) compared with hyperplastic small biliary ducts in surrounding nonneoplastic liver and with bile ducts of normal adult human liver. ERBB-2, MET, and COX-2 immunoreactivities were also assessed in both large and small hyperplastic biliary ducts (HBDs) in 27 archival cases of hepatolithiasis and 20 archival cases of primary sclerosing cholangitis (PSC), both of which are risk conditions for human cholangiocarcinogenesis. There was a strong positive correlation between increased ERBB-2, but not MET, and COX-2 immunoreactivity measured in the tumors and risk conditions. Enhanced immunoreactivity for ERBB-2 and COX-2 also correlated directly with tumor differentiation and was highest in well-differentiated tumors. Interestingly, some but not all cases of hepatolithiasis and most cases of PSC showed increased ERBB-2 and COX-2 immunostaining in the large but not small HBDs, whereas strong MET immunostaining was detected in both the large and small ducts. In conclusion, overexpression of ERBB-2 and COX-2 may herald an early carcinogenic event in the human hepatic biliary tract and one that is consistent with a frequent anatomic site of origin of the tumors. The results also suggest ERBB-2 and COX-2 as potentially important targets relevant to chemoprevention or adjunct therapy of ChC.
Varieties of Healing. 2: A Taxonomy of Unconventional Healing Practices
Authors: Ted J. Kaptchuk, David M. Eisenberg
Journal: Annals of Internal Medicine (2001)

The first of two essays in this issue demonstrated that the United States has had a rich history of medical pluralism. This essay seeks to present an overview of contemporary unconventional medical practices in the United States. No clear definition of "alternative medicine" is offered because it is a residual category composed of heterogeneous healing methods. A descriptive taxonomy of contemporary unconventional healing could be more helpful. Two broad categories of unconventional medicine are described here: a more prominent, "mainstream" complementary and alternative medicine (CAM) and a more culture-bound, "parochial" unconventional medicine. The CAM component can be divided into professional groups, layperson-initiated popular health reform movements, New Age healing, alternative psychological therapies, and non-normative scientific enterprises. The parochial category can be divided into ethno-medicine, religious healing, and folk medicine. A topologic examination of U.S. health care can provide an important conceptual framework through which health care providers can understand the current situation in U.S. medical pluralism.
Abstract 1312: Buformin, an anti-diabetic biguanide, inhibits proliferation, invasion and adhesion, and acts synergistically with paclitaxel in endometrial cancer cell lines
Authors: Joshua Kilgore, Amanda Jackson, Haifeng Qiu, Chunxiao Zhou, Paola Gehrig, Victoria Bae-Jump
Journal: Cancer Research (2014)

Abstract Objectives: Epidemiologic and pre-clinical studies suggest that anti-diabetic biguanide drugs, such as metformin and buformin, may have anti-tumorigenic effects and behave as chemosensitizers. Thus, we evaluated the effects of buformin alone and in combination with paclitaxel on proliferation in human endometrial cancer (EC) cell lines as well as the impact of buformin on apoptosis and adhesion/invasion. Methods: The ECC-1 and Ishikawa EC cell lines were treated with varying doses of buformin alone and in combination with paclitaxel. Cell growth was determined by MTT assay. Cell cycle progression was assessed by Cellometer. Apoptosis was evaluated by Annexin V-FITC assay. Invasion was demonstrated by transwell invasion assay. Adhesion was assessed by ELISA. Effects on AMPK and S6 expression were documented by Western blotting. Results: Buformin inhibited proliferation in a dose-dependent manner in the EC cell lines (IC50 1000 μM for ECC-1, 10μM for Ishikawa, p=0.00001-0.0010). Treatment with buformin resulted in G1 arrest in the ECC-1 cell line and G2 arrest in the Ishikawa cell line. Buformin induced apoptosis in the Ishikawa cell line, but not in the ECC-1 cell line. Treatment with buformin resulted in inhibition of adhesion (p=0.42-0.0009) and invasion (p=0.00001-0.227) in both EC cell lines. Western blotting analysis demonstrated that buformin increased phosphorylation of AMPK and decreased phosphorylation of S6. Paclitaxel inhibited proliferation in a dose-dependent manner in both cell lines with IC50 values of 0.1-0.5 nM and 1-5 nM for Ishikawa and ECC-1 cells, respectively. To assess synergy of paclitaxel and buformin, the combination index (CI) was calculated by the method of Chou and Talalay. Simultaneous exposure of cells to various doses of paclitaxel in combination with buformin (0.1-1 μM) resulted in a significant synergistic anti-proliferative effect (CI &amp;lt;1, range 0.009-0.85). Conclusions: Buformin inhibited proliferation in EC cell lines, via AMPK activation and mTOR pathway inhibition. Inhibition of adhesion/invasion was also seen with buformin. Buformin acted synergistically with paclitaxel to inhibit cell proliferation. More work is needed to determine if buformin and other biguanides alone or in combination with cytotoxic agents will be beneficial in the treatment of women with EC. Citation Format: Joshua Kilgore, Amanda Jackson, Haifeng Qiu, Chunxiao Zhou, Paola Gehrig, Victoria Bae-Jump. Buformin, an anti-diabetic biguanide, inhibits proliferation, invasion and adhesion, and acts synergistically with paclitaxel in endometrial cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1312. doi:10.1158/1538-7445.AM2014-1312
A Tale of Two Islands
Authors: George Dunea
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Once upon a time all was well on the islands of the common language, and the medical schools taught everything. A few students tarried in hospitals for a while, but most became ordinary doctors. Some had a hard time at first, but most were happy because they were not poor and they were loved. It was easy to get a doctor for ordinary sick people because there was one with a black bag at every corner. Some wanted to become learned. So they worked in the outpatient clinic at the hospital for many years for free. But they were still ordinary doctors They read heavy books and clever journals and tried for hard examinations. Some became little chiefs and were allowed to take care of patients in two beds at the hospital for free. A few became big chiefs and took care of many patients at the
Florida ophthalmologist received almost $21m from Medicare in one year
Authors: M. McCarthy
Journal: BMJ (2014)

The US government revealed on Wednesday 9 April what Medicare paid to more than 880 000 healthcare providers for outpatient care in 2012. The data include payments for over 6000 services, ranging from brief office visits and laboratory tests to surgery and chemotherapy.

The database shows that one Florida ophthalmologist took in nearly $21m (£12.5m; €15m) from Medicare that year, making him the highest paid doctor listed. Another top earner was also from Florida: a cardiologist who was reimbursed for more than $18m. Ophthalmologists, oncologists, and pathologists were among the highest paid physicians.

An analysis by the Wall Street Journal , which along with other news organizations was given early access to …
Outcomes and Complications Associated With Off-Label and Untested Use of Drug-Eluting Stents
Authors: Nirat Beohar, Charles J. Davidson, Kevin E. Kip, Lynne Goodreau, Helen Aslanidou Vlachos, Sheridan N. Meyers, Keith H. Benzuly, James D. Flaherty, Mark J. Ricciardi, Charles L. Bennett, David O. Williams
Journal: JAMA (2007)

Limited data exist regarding use of drug-eluting stents outside of approved indications in real-world settings.To determine the frequency, safety, and effectiveness of drug-eluting stents for off-label (restenosis, bypass graft lesion, long lesions, vessel size outside of information for use recommendation) and untested (left main, ostial, bifurcation, or total occlusion lesions) indications in percutaneous coronary intervention (PCI).Observational, prospective, multicenter registry to evaluate in-hospital, 30-day, and 1-year outcomes among patients undergoing PCI between January and June 2005 in 140 US academic and community medical centers. Of 7752 PCI-treated patients, 6993 (90%) received drug-eluting stents; of these, 5851 (84%) received no other devices. Standard, off-label, and untested use was determined in 5541 (95%) of these 5851 patients, constituting the study cohort.Frequency of off-label and untested use, 1-year repeat target vessel revascularization, and composite of death, myocardial infarction (MI), or stent thrombosis at in-hospital follow-up and during 1 year of follow-up.Of 5541 patients receiving drug-eluting stents, 2588 (47%) received stents for off-label or untested indications. Adjusted in-hospital risk of death, MI, or stent thrombosis was not statistically different with off-label or untested vs standard use. At 30 days, the risk of this composite end point was significantly higher with off-label use (adjusted hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.24-3.48; P = .005) but not untested use (adjusted HR, 1.45; 95% CI, 0.79-2.67; P = .23). Excluding early events, this end point was not different at 1 year with off-label use (adjusted HR, 1.10; 95% CI, 0.79-1.54; P = .57) or untested use (adjusted HR, 0.91; 95% CI, 0.60-1.38; P = .66). At 1 year, compared with standard use, significantly higher rates of target vessel revascularization were associated with off-label use (adjusted HR, 1.49; 95% CI, 1.13-1.98; P = .005) and untested use (adjusted HR, 1.49; 95% CI, 1.10-2.02; P = .01), although absolute rates were low (standard, 4.4% [n = 113]; off-label, 7.6% [n = 95]; untested, 6.7% [n = 72]).In contemporary US practice, off-label and untested use of drug-eluting stents is common. Compared with standard use, relative early safety is lower with off-label use, and the long-term effectiveness is lower with both off-label and untested use. However, the absolute event rates remain low.