tbuckley/cabot-search huggingface dataset:
A retrospective 30-year follow-up study of former Swedish-elite male athletes in power sports with a past anabolic androgenic steroids use: a focus on mental health
Authors: A S Lindqvist, T Moberg, B O Eriksson, C Ehrnborg, T Rosén, C Fahlke
Journal: British Journal of Sports Medicine (2013)

The knowledge concerning the long-term effect of former anabolic androgenic steroids (AAS)-use on mental health is sparse.This study aims to investigate whether previous AAS-use affects mental health, present sociodemographic data, sport activity and substance abuse in a retrospective 30-year follow-up study of former elite athletes.Swedish male-elite power sport athletes (n=683) on the top 10 national ranking lists during any of the years 1960-1979 in wrestling, Olympic lifting, powerlifting and the throwing events in track and field answered a questionnaire.At least 20% of the former athletes admitted previous AAS-use. They had more often sought professional expertise for mental problems and had used illicit drugs compared to those not having used AAS. The AAS-users also differed in former sport activity pattern compared to non AAS-users.It is clear that a relationship exists between use of AAS and mental-health problems. Further studies need to be done in order to clarify this relationship.
The molecular basis of asbestos induced lung injury
Authors: D. W Kamp, S. A Weitzman
Journal: Thorax (1999)

Asbestos causes progressive pulmonary fibrosis (asbestosis), pleural disease (effusion and pleural plaques), and malignancies such as bronchogenic carcinoma and malignant mesothelioma.1-3 Asbestos is a generic term for a group of naturally occurring hydrated silicate fibres whose tensile strength and resilient structural and chemical properties are ideally suited for various construction and insulating purposes. The toxic effects of asbestos depend upon the cumulative dose and the time since the first exposure. Asbestos related diseases typically occur after a 15–40 year latency period following initial fibre exposure. The two classes of asbestos fibres, serpentine and amphibole fibres, can each cause pulmonary disease. Serpentine fibres, of which chrysotile is the principal commercial variety, are curly-stranded structures whereas amphiboles (crocidolite, amosite, tremolite and others) are straight, rod-like fibres. Chrysotile accounts for over 95% of world asbestos consumption.4 Asbestos induced pulmonary diseases remain a significant health concern. In the United States over 30 million tons of asbestos have been mined, processed and applied since the early 1900s.1 Moreover, non-occupational asbestos exposure may originate from existing buildings that contain enormous amounts of the fibres.5 Finally, it is estimated that the cumulative total number of asbestos associated deaths in the United States may exceed 200 000 by the year 2030.6 

Extensive investigations over the last two decades have revealed some of the pathogenic mechanisms of asbestos pulmonary diseases. A further benefit of these studies is that asbestos induced pulmonary toxicity is an excellent paradigm to explore the mechanisms underlying other common causes of pulmonary fibrosis and malignancy. Asbestos is an established genotoxic agent that can induce DNA damage, gene transcription, and protein expression important in modulating cell proliferation, cell death, and inflammation.1 2 7-9 Recent comprehensive reviews have described in detail the histopathological and clinical features of asbestos related diseases1-3 9 …
Insurance Status and the Use of Guideline Therapy in the Treatment of Selected Cancers
Authors: Linda C. Harlan, Amanda L. Greene, Limin X. Clegg, Margaret Mooney, Jennifer L. Stevens, Martin L. Brown
Journal: Journal of Clinical Oncology (2005)

This study estimates the impact of type of insurance coverage on the receipt of guideline therapy in a population-based sample of cancer patients treated in the community.Patients (n = 7,134) from the National Cancer Institute's Patterns of Care studies who were newly diagnosed with 11 different types of cancer were analyzed. The definition of guideline therapy was based on the National Comprehensive Cancer Network treatment recommendations. Insurance status was categorized as a mutually exclusive hierarchical variable (no insurance, any private insurance, any Medicaid, Medicare only, and all other). Multivariate analyses were used to examine the association between insurance and receipt of guideline therapy.Adjusting for clinical and nonclinical variables, insurance status was a modest, although statistically significant, determinant of receipt of guideline therapy, with 65% of the privately insured patients receiving recommended therapy compared with 60% of patients with Medicaid. Seventy percent of the uninsured patients received guideline therapy, which was nonsignificantly different compared with private insurance. When stratified by race, insurance was a statistically significant predictor of the receipt of guideline therapy only for non-Hispanic blacks.Overall, levels of guideline treatment were lower than expected and particularly low for patients with Medicaid or Medicare only. The use of guideline therapy for ovarian and cervical cancer patients and for patients with rectal cancers was unrelated to type of insurance. Of particular concern is the significantly lower use of guideline therapy for non-Hispanic black patients with Medicaid. After adjusting for other factors, only half of these patients received guideline therapy.
C-Raf Is Associated with Disease Progression and Cell Proliferation in a Subset of Melanomas
Authors: Lucia B. Jilaveanu, Christopher R. Zito, Saadia A. Aziz, Patricia J. Conrad, John C. Schmitz, Mario Sznol, Robert L. Camp, David L. Rimm, Harriet M. Kluger
Journal: Clinical Cancer Research (2009)

Raf-kinases include three major isoforms. Although the role of B-Raf in melanoma is well established, little is known about C-Raf. We studied effects of C-Raf knockdown in vitro and assessed expression of C-Raf in a large cohort of melanomas and nevi.Using specific siRNAs, we knocked down C-Raf expression, and determined the effect on viability, MAP extracellular signal-regulated kinase (ERK)/ERK kinase signaling, and apoptosis in seven melanoma cell lines. We determined the IC(50) of the C-Raf inhibitors sorafenib and GW5074, and studied the effects of GW5074 on cell signaling. Using an automated method to measure in situ protein expression, we quantified C-Raf expression in 263 nevi and 523 melanomas.C-Raf was knocked down in three cell lines with detectable phospho-C-Raf, resulting in decreased viability in two of the three (YULAC and YUROB). This resulted in decreased Bcl-2 expression and phospho-Bad cleavage, without affecting phospho-MEK and phospho-ERK. Sensitivity to sorafenib and GW5074 varied. GW5074 inhibited mitogen-activated protein kinase signaling without Bcl-2 and phospho-Bad down-regulation. C-Raf was highly expressed in melanomas compared with nevi (P < 0.0001), and no nevi had high C-Raf expression. C-Raf expression was higher in metastatic than primary specimens (P = 0.0225).C-Raf siRNA knock-down results in decreased viability of YULAC (B-Raf(V600K)) and YUROB (B-Raf(WT)) melanoma cells, likely mediated by Bcl-2 inhibition rather than mitogen-activated protein kinase inhibition. Cotargeting C-Raf and parallel pathways might be an effective therapeutic approach for melanoma. C-Raf expression is up-regulated in a subset of melanomas but not in nevi, suggesting that it might be a valuable diagnostic marker and therapeutic target.
The evolution of rational demons
Authors: Colin Allen
Journal: Behavioral and Brain Sciences (2000)

If fast and frugal heuristics are as good as they seem to be, who needs logic and probability theory? Fast and frugal heuristics depend for their success on reliable structure in the environment. In passive environments, there is relatively little change in structure as a consequence of individual choices. But in social interactions with competing agents, the environment may be structured by agents capable of exploiting logical and probabilistic weaknesses in competitors' heuristics. Aspirations toward the ideal of a demon reasoner may consequently be adaptive for direct competition with such agents.
Phase I Study of Bortezomib in Refractory or Relapsed Acute Leukemias
Authors: Jorge Cortes, Deborah Thomas, Charles Koller, Francis Giles, Elihu Estey, Stefan Faderl, Guillermo Garcia-Manero, David McConkey, Gira Patel, Roberto Guerciolini, John Wright, Hagop Kantarjian
Journal: Clinical Cancer Research (2004)

Abstract Bortezomib (Velcade, formerly PS-341) is proteasome inhibitor with documented antitumor activity in multiple myeloma and other lymphoid malignancies. We performed a Phase I study to investigate the maximum tolerated dose and dose-limiting toxicity of bortezomib in patients with acute leukemias refractory to or relapsing after prior therapy. Fifteen patients were treated with 0.75 (n = 3), 1.25 (n = 7), or 1.5 (n = 5) mg/m2 bortezomib administered twice weekly for 4 weeks every 6 weeks. Dose-limiting toxicity included orthostatic hypotension (n = 2), nausea (n = 2), diarrhea (n = 1), and fluid retention (n = 1), all at 1.5 mg/m2 bortezomib. Proteasome inhibition was dose dependent and reached 68% at 1.5 mg/m2 bortezomib. Peak inhibition was observed 1 h after treatment and returned to near baseline levels by 72 h after treatment. Incubation of blast cells with bortezomib in vitro showed induction of apoptosis in three of five patients investigated. We conclude that the maximum tolerated dose of bortezomib in patients with acute leukemia is 1.25 mg/m2, using a twice-weekly for 4 weeks every 6 weeks schedule. The in vitro evidence of antileukemia and transient hematological improvements observed in some patients warrants further investigation of bortezomib in acute leukemias, probably in combination with other agents.
Repeaters count: a sentinel method for asthma outbreaks. Barcelona Soybean-Asthma Group.
Authors: J B Soriano, J M Anto, A Plasencia
Journal: Thorax (1995)

BACKGROUND--Asthma outbreaks have not been detected in Barcelona, Spain since the epidemic of 1981-7. On 29 October 1994 several subjects attended a Barcelona hospital because of acute attacks of asthma and were identified as former soybean epidemic asthma patients (repeaters), raising the possibility of an asthma soybean-related episode. The usefulness of counting repeaters to evaluate small increases of acute asthma in a non-epidemic period is illustrated. METHODS--A retrospective identification of asthma admissions was performed, pollution filters collected before and after the index day were analysed for contents of low molecular weight soybean allergen, and soybean unloading activities were investigated. RESULTS--There was no epidemic increase of asthma patients during this day in the whole of Barcelona, but an unusually high number were repeaters (seven observed v 0.483 expected). A relationship with increased levels of low molecular weight soybean allergen (U/m3) was detected in the available pollution filters collected the day before and after the index day. Two ships were unloading soybean in the city harbour on the index day. CONCLUSION--Soybean unloading at the harbour of Barcelona released soybean dust and produced a small cluster of emergency room visits for asthma in patients formerly affected by soybean asthma epidemics. It is suggested that counting repeaters could provide the basis for a systematic epidemiological surveillance of sensitised populations.
Scalable signaling mediated by T cell antigen receptor–CD3 ITAMs ensures effective negative selection and prevents autoimmunity
Authors: Jeff Holst, Haopeng Wang, Kelly Durick Eder, Creg J Workman, Kelli L Boyd, Zachary Baquet, Harvir Singh, Karen Forbes, Andrzej Chruscinski, Richard Smeyne, Nicolai S C van Oers, Paul J Utz, Dario A A Vignali
Journal: Nature Immunology (2008)
INFLAMMATORY MECHANISMS INVOLVED IN TENDON OVERUSE: RECENT INSIGHTS
Authors: Alex Scott, Hayedeh Behzad
Journal: British Journal of Sports Medicine (2013)

This presentation will synthesise and review recent findings from our laboratory and others' on inflammatory mechanisms involved in tendon overuse injuries. Tendinopathy is a state of chronic tendon thickening and pain, usually as a result of overuse. Recent work has shown that repetitive loading of human tendon-derived cells leads to upregulation of TAC1, the mRNA encoding for Substance P1—a pro-inflammatory neuropeptide which is known to contribute to tendon pain.2 In addition, previous work has found that mast cells are present in greater numbers in chronically overused tendon,3 and that they degranulate in response to SP, releasing substances that directly influence human tenocyte collagen remodelling. Thus, both SP and one of its main targets—the mast cell—are over-represented in tendinopathic tissue. Mast cells have a high affinity for human tenocytes, forming elaborate inter-cellular junctions, and releasing substances which substantially influence tenocyte behaviour that could have relevance for improving outcomes following injury or overuse. For example, inhibiting mast cells results in a reduction of TGF-beta-related genes (related to scarring) and reduces the amount of tendon thickening following injury.4 Additionally, mast cells induce a large increase in COX-2 expression by human tenocytes. It is possible that a clinical strategy which incorporates inhibitors of mast cells could improve on outcomes with standard treatment.5
Oxidative Stress and AP-1 Activity in Tamoxifen-Resistant Breast Tumors In Vivo
Authors: Rachel Schiff, Praveen Reddy, Markku Ahotupa, Ester Coronado-Heinsohn, Matt Grim, Susan G. Hilsenbeck, Richard Lawrence, Susan Deneke, Rafael Herrera, Gary C. Chamness, Suzanne A. W. Fuqua, Powel H. Brown, C. Kent Osborne
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Most breast cancers, even those that are initially responsive to tamoxifen, ultimately become resistant. The molecular basis for this resistance, which in some patients is thought to involve stimulation of tumor growth by tamoxifen, is unclear. Tamoxifen induces cellular oxidative stress, and because changes in cell redox state can activate signaling pathways leading to the activation of activating protein-1 (AP-1), we investigated whether tamoxifen-resistant growth in vivo is associated with oxidative stress and/or activation of AP-1 in a xenograft model system where resistance is caused by tamoxifen-stimulated growth. Methods: Control estrogen-treated, tamoxifen-sensitive, and tamoxifen-resistant MCF-7 xenograft tumors were assessed for oxidative stress by measuring levels of antioxidant enzyme (e.g., superoxide dismutase [SOD], glutathione S-transferase [GST], and hexose monophosphate shunt [HMS]) activity, glutathione, and lipid peroxidation. AP-1 protein levels, phosphorylated c-jun levels, and phosphorylated Jun NH2-terminal kinase (JNK) levels were examined by western blot analyses, and AP-1 DNA-binding and transcriptional activities were assessed by electrophoretic mobility shift assays and a reporter gene system. All statistical tests are two-sided. Results: Compared with control estrogen-treated tumors, tamoxifen resistant tumors had statistically significantly increased SOD (more than threefold; P = .004) and GST (twofold; P = .004) activity and statistically significantly reduced glutathione levels (greater than twofold; P<.001) and HMS activity (10-fold; P<.001). Lipid peroxides were not significantly different between control and tamoxifen-resistant tumors. We observed no differences in AP-1 protein components or DNA-binding activity. However, AP-1-dependent transcription (P = .04) and phosphorylated c-Jun and JNK levels (P<.001) were statistically significantly increased in the tamoxifen-resistant tumors. Conclusion: Our results suggest that the conversion of breast tumors to a tamoxifen-resistant phenotype is associated with oxidative stress and the subsequent antioxidant response and with increased phosphorylated JNK and c-Jun levels and AP-1 activity, which together could contribute to tumor growth.
Dental evaluation of scuba diving mouthpieces using a subject assessment index and radiological analysis of jaw position
Authors: R S Hobson, J P Newton
Journal: British Journal of Sports Medicine (2001)

Objective —To compare two experimental scuba mouthpieces with a commercially available design. Methods —A laboratory study using six men to assess effort, muscle pain, muscle fatigue, facial discomfort, tooth discomfort, and loss of lip sensation using a visual analogue scale. Cephalometric radiographs and analysis of jaw position with each mouth piece were also used. Results —Fully customised mouthpieces caused the least discomfort, muscle pain, fatigue, and effort. They also resulted in the least mandibular displacement from the resting position. Radiographic analysis of jaw position showed that the fully customised design resulted in the least displacement from normal jaw position. Conclusions —A fully customised design gives the greatest comfort, least effort, and least mandibular displacement. This design is recommended, particularly for divers who experience temporomandibular dysfunction associated with diving.
Practical issues around putting the patient at the centre of care
Authors: N. Dunn
Journal: Journal of the Royal Society of Medicine (2003)

Patient-centred care is the concept of 'informing and involving patients, responding quickly and effectively to patients' needs and wishes, and ensuring that patients are treated in a dignified and supportive manner'.1 It is a popular talking-point at present, having been brought into the limelight by the Bristol inquiry,2 but it is not new. Balint in the 1950s was proposing that doctors put more emphasis on listening to what the patient was trying to say behind the simple presenting complaint.3 Pendleton and colleagues in the 1980s were strong proponents of the notion that communication skills are the basis of fruitful consultations4—another way of saying that the patient's perspective is important. Indeed most medical readers of this article, if they became 'patients', would wish to be actively involved in the management of their illness. Patients are increasingly coming to be seen as consumers of healthcare, with rights like those of any other consumer. As Richard Smith, editor of the BMJ, has put it:'There is no ”truth” defined by experts. Rather there are many opinions.... Doctors might hanker after a world where their view is dominant. But that world is disappearing fast'.5 Persuasive evidence that patient-centred care helps patients has been published—for instance, reduction in blood pressure was greater in patients who, during visits to the doctor, had been allowed to express their health concerns without interruptions;6 and, in patients with headache, improvement was most likely in those enabled to discuss their condition in full.7 There is also, admittedly, some evidence to the contrary: patients randomized to receive diabetes care from workers trained in patient-centred care did worse than the comparison group in some clinical measures (though they were more satisfied with their treatment).8
Antisense Oligonucleotides Delivered to the Mouse CNS Ameliorate Symptoms of Severe Spinal Muscular Atrophy
Authors: Marco A. Passini, Jie Bu, Amy M. Richards, Cathrine Kinnecom, S. Pablo Sardi, Lisa M. Stanek, Yimin Hua, Frank Rigo, John Matson, Gene Hung, Edward M. Kaye, Lamya S. Shihabuddin, Adrian R. Krainer, C. Frank Bennett, Seng H. Cheng
Journal: Science Translational Medicine (2011)

Central nervous system–directed antisense therapy ameliorates symptoms in a severe neuromuscular disorder in mice.
Noninvasive estimation of left ventricular filling pressure by e/e′ is a powerful predictor of survival after acute myocardial infarction
Authors: Graham S Hillis, Jacob E Møller, Patricia A Pellikka, Bernard J Gersh, R.Scott Wright, Steve R Ommen, Guy S Reeder, Jae K Oh
Journal: Journal of the American College of Cardiology (2004)
Effects of propranolol on gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy
Authors: Julián Panés, Josep M. Bordas, Josep M. Piqué, Juan C. García-pagán, Faust Feu, Josep Terés, Jaime Bosch, Joan Rodés
Journal: Hepatology (1993)

This study investigated the effects of the short-term administration of propranolol on gastric blood perfusion in cirrhotic patients with portal hypertensive gastropathy. Portal hypertensive gastropathy is a common cause of nonvariceal bleeding in cirrhosis, which is associated with increased gastric mucosal perfusion and is favorably influenced by propranolol therapy. Gastric mucosal perfusion was evaluated with laser-Doppler flowmetry and reflectance spectrophotometry. Measurements were performed under basal conditions and after the double-blind administration of propranolol (0.15 mg/kg intravenously) or placebo. Propranolol administration significantly reduced (p < 0.001) the laser-Doppler signal (2.93 +/- 0.23 vs. 2.25 +/- 0.22 V) and the hemoglobin content of the gastric mucosa (99.2 +/- 3.8 vs. 89.3 +/- 3.1 arbitrary units), whereas the oxygen content remained unchanged (37.4 +/- 1.2 vs. 36.9 +/- 1.0 arbitrary units). Placebo administration had no effect in any of these parameters. Changes in gastric perfusion after propranolol administration were associated with a significant decrease in hepatic venous pressure gradient and azygos blood flow. We conclude that short-term propranolol administration, in addition to lowering portal pressure, reduces the increased gastric blood perfusion in cirrhotic patients with portal hypertensive gastropathy, an effect that may contribute to prevention of bleeding from these lesions.
Drug-Induced and Other Orofacial-Cervical Dyskinesias
Authors: JOSEPH JANKOVIC
Journal: Annals of Internal Medicine (1981)

Tardive dyskinesia is one of the most prevalent and disabling of the iatrogenic disorders. Characterized by involuntary movements of the orofacial-cervical musculature that develop after prolonged use of neuroleptic drugs, it is sometimes confused with other involuntary movements involving predominantly the head and neck region. In this review the differential diagnosis of the orofacial-cervical dyskinesias is discussed. A therapeutic approach is presented in view of our recent understanding of the possible biochemical mechanisms of tardive dyskinesia.
Colchicine responsive periodic fever syndrome associated with pyrin I591T
Authors: B A C Fisher
Journal: Annals of the Rheumatic Diseases (2005)

This case illustrates the usefulness of a therapeutic trial of colchicine monitored objectively by frequent acute phase protein measurements in patients with undiagnosed periodic fever syndromes.It also raises the possibility that a low threshold for analysing the FMF gene might disclose a wider spectrum of associated disease.
Molecular markers in melanoma
Authors: M. Kashani-Sabet
Journal: British Journal of Dermatology (2013)

The last few years have witnessed the dawn of the molecular era in melanoma treatment. With the advent of successful therapy targeting mutant BRAF, melanoma is leading the field of cancer research in the molecular approach to therapy of advanced disease. Attempting to keep pace with advances in therapy are advances in the molecular assessment of melanoma progression, facilitated by the availability of genome-wide approaches to interrogate the malignant phenotype. At the DNA level, this has included approaches such as comparative genomic hybridization. At the RNA level, this has consisted of gene expression profiling using various assay methodologies. In certain instances, markers identified using these platforms have been further examined and developed using fluorescence in situ hybridization and immunohistochemical analysis. In this article, we will review recent progress in the development of novel molecular markers for melanoma that are nearing clinical application. We will review developments in the molecular classification of melanoma, in the molecular diagnosis of melanoma, and in the molecular assessment of melanoma prognosis.