tbuckley/cabot-search huggingface dataset:
Impact of Diabetes Mellitus on Regression of Electrocardiographic Left Ventricular Hypertrophy and the Prediction of Outcome During Antihypertensive Therapy
Authors: Peter M. Okin, Richard B. Devereux, Eva Gerdts, Steven M. Snapinn, Katherine E. Harris, Sverker Jern, Sverre E. Kjeldsen, Stevo Julius, Jonathan M. Edelman, Lars H. Lindholm, Björn Dahlöf
Journal: Circulation (2006)

Background— Diabetes mellitus is associated with increased cardiovascular (CV) morbidity and mortality and with greater ECG left ventricular hypertrophy (LVH); however, it is unclear whether diabetes attenuates regression of hypertensive LVH and whether regression of ECG LVH has similar prognostic value in diabetic and nondiabetic hypertensive individuals. Methods and Results— A total of 9193 hypertensive patients (1195 with diabetes) in the Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study were treated with losartan- or atenolol-based regimens and followed up with serial ECG and blood pressure determinations at baseline and 6 months and then yearly until death or study end. ECG LVH was defined with gender-adjusted Cornell voltage-duration product (CP) criteria &gt;2440 mm · ms. After a mean follow-up of 4.8±0.9 years, patients with diabetes had less regression of CP LVH (−138±866 versus −204±854 mm · ms, P &lt;0.001), remained more likely to have LVH by CP (56.0% versus 48.1%, P &lt;0.001), and had higher rates of CV death, myocardial infarction, stroke, and all-cause mortality and of the LIFE composite end point of CV death, myocardial infarction, or stroke. In multivariable Cox proportional hazards models, in-treatment regression or absence of ECG LVH by CP was associated with between 17% and 35% reductions in event rates in patients without diabetes but did not significantly predict outcome in patients with diabetes. Conclusions— Hypertensive patients with diabetes have less regression of CP LVH in response to antihypertensive therapy than patients without diabetes, and regression of ECG LVH is less useful as a surrogate marker of outcomes in hypertensive patients with diabetes. These findings may in part explain the higher CV morbidity and mortality in hypertensive patients with diabetes, and the absence of a demonstrable improvement in prognosis in diabetic patients in response to regression of ECG LVH suggests a more complex interrelation between underlying LV structural and functional abnormalities and outcome in these patients.
Diagnosing emphysema from the lung scan
Authors: V. Y. Muir
Journal: Thorax (1971)

Lung scan appearances thought to be characteristic of emphysema are described. Three criteria are stated and 44 scans showing all these criteria were selected from 154 lung scans done during a 10-month period: in fact the scans of all the patients (seen in the Clinical Physiology Department during the 10 months) who were thought on clinical grounds to have emphysema had been selected. Three scans were of patients with fibrosing alveolitis with no evidence of airways obstruction and they were easily identified from the chest radiograph. In six patients the diagnosis of emphysema is reasonable but unproved. Three patients show no real evidence of emphysema. Firstly, all the 154 lung scans were done using technetium-99m as the source of γ-radiation, whereas most authors have used iodine-131; secondly, the scanner setting was the same for all the scans, with a minimum γ-radiation intensity of 30,000 counts/min being necessary to produce an adequate scan. The results of this investigation suggest that there is a scan appearance characteristic of emphysema as long as the patient shows other evidence of airways obstruction.
The cannabinoid WIN55, 212-2 abrogates dermal fibrosis in scleroderma bleomycin model
Authors: Epifania Balistreri, Estrella Garcia-Gonzalez, Enrico Selvi, Alfiya Akhmetshina, Katrin Palumbo, Sauro Lorenzini, Roberta Maggio, Monica Lucattelli, Mauro Galeazzi, Jörg W H Distler
Journal: Annals of the Rheumatic Diseases (2010)

There is increasing evidence that the endocannabinoid system may be involved in pathological fibrosis, and that its modulation might limit fibrotic responses. The aim of this study was to examine the capacity of a synthetic cannabinoid receptor agonist to modify skin fibrosis in the bleomycin mouse model of scleroderma. Skin fibrosis was induced by local injections of bleomycin in two groups of DBA/2J mice. One group was cotreated with the synthetic cannabinoid WIN55,212-2 at 1 mg/kg/day. Skin fibrosis was evaluated by histology and skin thickness and hydroxyproline content were quantified. Markers of fibroblast activation, including α smooth muscle actin and the profibrotic cytokines transforming growth factor (TGF)β, connective tissue growth factor (CTGF) and platelet-derived growth factor (PDGF)-BB, were examined. Levels of PSMAD2/3, which are crucial in extracellular matrix overproduction, were analysed. Bleomycin treatment induced typical skin fibrosis. Upon WIN55,212-2 treatment dermal fibrosis was completely prevented. Subcutaneous inflammatory cell infiltration, dermal thickness and collagen content resulted similar to those of the control group. The synthetic cannabinoid prevented fibroblasts activation induced by bleomycin, paralleled by a strong inhibition of TGFβ, CTGF and PDGF-BB expression. Phosphorylation of SMAD2/3 was significantly downregulated after WIN55,212-2 exposure. Taken together, the results indicate that the synthetic cannabinoid WIN55,212-2 is capable of preventing skin fibrosis in a mouse model of scleroderma.
Medical schools: are we paying for education or for technical training?
Authors: S. Leinster
Journal: Journal of the Royal Society of Medicine (2003)

Not the least of the challenges facing medical schools in the UK is an increasing pressure on funding. The first major challenge came from the Research Assessment Exercise in 2001. Research units within higher education in the UK were categorized on a 5-point scale according to the national or international profile of the research that they conducted. The grade awarded determines the research support funding that the institution receives until the next assessment exercise. There was widespread expectation within the sector that units with grades of 3a (research of national significance) through to 5 (research of international importance) would receive funding; the level of funding being adjusted according to the grade obtained. In the event, funding went only to units with grade 5 or 5*. Many medical schools’ research units received grade 4 (research of national importance with some of international importance). These units lost the research support funding and in some cases this led to redundancies among academic staff.

The medical schools have been further hit by the Government’s Widening Participation programme. The medical schools, many of which have already established programmes to facilitate the entry of educationally disadvantaged students, support the concept of widening participation in higher education. However, the way the programme is funded has resulted in loss of income of some 5.5% to the medical schools since it is focused on students at the lower end of the ability range rather than targeting students of all abilities who have been prevented from reaching their full potential.

It has been suggested that the financial difficulties could be ameliorated if the responsibility for funding of medical education was transferred from the Department for Education and Skills (DfES) to the Department of Health (DoH).
Prognostic Value of Lung Sestamibi Uptake in Myocardial Perfusion Imaging of Patients With Known or Suspected Coronary Artery Disease
Authors: William D. Leslie, Shawn A. Tully, Marina S. Yogendran, Linda M. Ward, Khaled A. Nour, Colleen J. Metge
Journal: Journal of the American College of Cardiology (2005)
Validated questionnaires should not be modified
Authors: E. F. Juniper
Journal: European Respiratory Journal (2009)

The reformatting and changes that were made to the Asthma Control Questionnaire (ACQ) 1 for the Post-cold Asthma Control and Exacerbation (PAX) study 2 raise some important concerns about modifying validated questionnaires.

Just like mechanical and electrical measurement instruments, validated questionnaires are precision measurement instruments. The only difference being that they measure subjective rather than objective health status. Like any mechanical or electrical instrument, a great deal of care and expertise goes into the development of these questionnaires. Many studies have provided developers with the knowledge of how to: specify what the questionnaire is intended to measure (its construct); structure and select the right questions; formulate the responses; select the time specifications; optimise the page formulation for accurate completion; conduct validation studies (measurement properties and whether the instrument is measuring what it is meant to measure) and provide users the wherewithal to place a clinical interpretation on the data. For the same reason that one would never think of changing the numbers on the dial of a mechanical spirometer, one should never change a validated questionnaire. Even very small changes can destroy its validity.

Questions are selected by well-established methods (usually either “importance” or “factor analysis”) 3 and their position in the questionnaire carefully ordered. Wording is checked for ease and accuracy of understanding (cognitive debriefing). For the analysis, each question has a weighting. For some questionnaires, this means that an algorithm must be used ( e.g. The Short Form (SF)-36 Health Survey) 4, in others ( e.g. the ACQ) questions are selected in such a way that they have equal weighting and the overall score is the mean of all the responses. The wording of questions should never be changed. Shortened versions should only be used when they have been …
Statistical Alignment of Retropseudogenes and Their Functional Paralogs
Authors: Miklós Csűrös, István Miklós
Journal: Molecular Biology and Evolution (2005)

We describe a model for the sequence evolution of a processed pseudogene and its paralog from a common protein-coding ancestor. The model accounts for substitutions, insertions, and deletions and combines nucleotide- and codon-level mutation models. We give a dynamic programming method for calculating the likelihood of homology between two sequences in the model and describe the accompanying alignment algorithm. We also describe how ancestral codons can be computed when the same gene produced multiple pseudogene homologs. We apply our methods to the evolution of human cytochrome c.
Epidemiology and morbidity of scabies and pediculosis capitis in resource-poor communities in Brazil
Authors: J. Heukelbach, T. Wilcke, B. Winter, H. Feldmeier
Journal: British Journal of Dermatology (2005)

Journal Article Epidemiology and morbidity of scabies and pediculosis capitis in resource‐poor communities in Brazil Get access J. Heukelbach, J. Heukelbach Departamento de Saúde Comunitária, Faculdade de Medicina, Universidade Federal do Ceará, Rua Prof. Costa Mendes 1608–5° andar, Fortaleza, CE 60430–140, Brazil *Department of Medical Microbiology and Immunology of Infection, Institute for Infection Medicine, Charité Medical School, Campus Benjamin Franklin, Berlin, Germany Jörg Heukelbach. E‐mail: samsa@mcanet.com.br Search for other works by this author on: Oxford Academic Google Scholar T. Wilcke, T. Wilcke Departamento de Saúde Comunitária, Faculdade de Medicina, Universidade Federal do Ceará, Rua Prof. Costa Mendes 1608–5° andar, Fortaleza, CE 60430–140, Brazil *Department of Medical Microbiology and Immunology of Infection, Institute for Infection Medicine, Charité Medical School, Campus Benjamin Franklin, Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar B. Winter, B. Winter Departamento de Saúde Comunitária, Faculdade de Medicina, Universidade Federal do Ceará, Rua Prof. Costa Mendes 1608–5° andar, Fortaleza, CE 60430–140, Brazil *Department of Medical Microbiology and Immunology of Infection, Institute for Infection Medicine, Charité Medical School, Campus Benjamin Franklin, Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar H. Feldmeier H. Feldmeier Departamento de Saúde Comunitária, Faculdade de Medicina, Universidade Federal do Ceará, Rua Prof. Costa Mendes 1608–5° andar, Fortaleza, CE 60430–140, Brazil *Department of Medical Microbiology and Immunology of Infection, Institute for Infection Medicine, Charité Medical School, Campus Benjamin Franklin, Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 1, 1 July 2005, Pages 150–156, https://doi.org/10.1111/j.1365-2133.2005.06591.x Published: 01 July 2005 Article history Accepted: 07 January 2005 Published: 01 July 2005
Clinical Significance of Nonpalpable Prostate Cancer with Favorable Biopsy Features in Japanese Men
Authors: Yoshiyuki Kakehi, Toshiyuki Kamoto, Osamu Ogawa, Tetsuro Kato, Ken-ichi Tobisu, Koichiro Akakura, Shin Egawa, Michiyuki Usami, Osamu Maeda, Yoichi Arai, Yoshiteru Sumiyoshi, Yoriaki Kamiryo, Osamu Yoshida
Journal: European Urology (2000)
Identification of the molecular target for the suppression of contact hypersensitivity by ultraviolet radiation.
Authors: L A Applegate, R D Ley, J Alcalay, M L Kripke
Journal: The Journal of Experimental Medicine (1989)

This study was conducted to explore the involvement of DNA damage in the suppression of contact hypersensitivity (CHS) by UV irradiation. The opossum, Monodelphis domestica, was used because cells of these marsupials have an enzyme that is activated by visible light (photoreactivating enzyme) and repairs ultraviolet radiation (UVR)-induced pyrimidine dimers in DNA. A single dose of 1,500 J/m2 of UVB (280-320 nm) radiation, representing 2 minimal erythema doses, was administered to the dorsal skin of opossums. This treatment prevented the opossums from developing a CHS response to dinitrofluorobenze (DNFB) applied either at the site of irradiation or an unirradiated site. In addition, this dose of UVR decreased the number of ATPase+ epidermal Langerhans cells in the dorsal epidermis to approximately 3% of that in unirradiated skin at the time of DNFB application. Treatment of the animals with wavelengths that activate the repair enzyme (320-500 nm, photoreactivating light, PRL) for 120 min immediately after UV irradiation inhibited the UVR-induced suppression of CHS almost completely. Exposure to PRL before UVR did not prevent UVR-induced suppression of CHS. PRL treatment after UV irradiation also prevented the decrease in the number of ATPase+ Langerhans cells. Measurements of lesions in DNA indicated that PRL treatment removed around 85% of the UVR-induced pyrimidine dimers. These data provide direct evidence that DNA, and most likely, the pyrimidine dimer, is the primary molecular target for the UVB-induced suppression of contact hypersensitivity to haptens applied to irradiated or unexposed skin.
The dynamical hypothesis: The role of biological constraints on cognition
Authors: Keith Davids, Simon Bennett
Journal: Behavioral and Brain Sciences (1998)

For the dynamical hypothesis to be defended as a viable alternative to a computational perspective on natural cognition, the role of biological constraints needs to be considered. This task requires a detailed understanding of the structural organization and function of the dynamic nervous system, as well as a theoretical approach that grounds cognitive activity within the constraints of organism and ecological context.
Temozolomide as Monotherapy Is Effective in Treatment of Advanced Malignant Neuroendocrine Tumors
Authors: Sara Ekeblad, Anders Sundin, Eva Tiensuu Janson, Staffan Welin, Dan Granberg, Henrik Kindmark, Kristina Dunder, Gordana Kozlovacki, Håkan Örlefors, Mattias Sigurd, Kjell Öberg, Barbro Eriksson, Britt Skogseid
Journal: Clinical Cancer Research (2007)

Abstract Purpose: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. Experimental Design: Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m2) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of O6-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n = 23) and compared with response to temozolomide. Results: Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with O6-methylguanine DNA methyltransferase immunoreactivity in &amp;lt;10% of nuclei, whereas four patients showed radiologic responses. Conclusions: Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.
Increased absorption of polyethylene glycol 600 deposited in the colon in active ulcerative colitis.
Authors: S Almer, L Franzen, G Olaison, K Smedh, M Strom
Journal: Gut (1993)

A defect in the barrier function of the intestinal mucosa has been proposed as important in both the pathogenesis and systemic manifestations of inflammatory bowel disease. After colonoscopy, polymers of polyethylene glycol (PEG) with molecular weights of 414-810 (mean 600), were instilled in the descending colon of patients with ulcerative colitis (n = 17) and in controls without intestinal inflammation (n = 8). The patients with active ulcerative colitis (n = 6) had a significantly increased uptake of PEGs in the molecular weight range 458-810, measured as urinary excretion over the first 6 hours after instillation. The median values for their excretion were 2.85-3.80% of PEGs instilled compared with 0.32-0.94% for patients in remission (n = 11) (p &lt; 0.05-0.01) and 0.17-0.60% for the controls (p &lt; 0.05-0.01). The differences in absorption of PEG 414 did not reach the present level of statistical significance. There was a positive correlation between PEG absorption and the endoscopic and histological grading of inflammatory activity in the sigmoid colon (p &lt; 0.01-0.001). These findings support a correlation between the presence of active inflammation and PEG absorption. There was little evidence to support the presence of a primary defect in the colonic barrier in patients with ulcerative colitis.
Blood and lymphatic vasculature in the ovary: development, function and disease
Authors: H.M. Brown, D.L. Russell
Journal: Human Reproduction Update (2013)

The remodelling of the blood vasculature has been the subject of much research while rapid progress in the understanding of the factors controlling lymphangiogenesis in the ovary has only been reported more recently. The ovary undergoes cyclic remodelling throughout each menstrual/estrous cycle. This process requires significant vascular remodelling to supply each new cohort of growing follicles. Literature searches were performed to review studies on the ovarian lymphatic vasculature that described spatial, temporal and functional data in human or animal species. The role of ovarian blood and lymphatic vasculature in the pathogenesis of ovarian disease and dysfunction was also explored. Research in a number of species including zebrafish, rodents and primates has described the lymphatic vasculature within the remodelling ovary, while recent research in mouse has confirmed hormonal regulation of lymphangiogenic growth factors, their receptors and also a role for the protease, ADAMTS1 in the development of the lymphatic vasculature. With a critical role in the maintenence of fluid homeostasis, the ovarian lymphatic vasculature is important for normal ovarian function and has been linked to syndromes involving ovarian fluid imbalance, including ovarian hyperstimulation syndrome and massive ovarian edema. The lymphatic vasculature has also been heavily implicated in the metastatic cancer process. The spatial and temporal regulation of the ovarian lymphatic vasculature has now been reported in a number of species and the data also implicate the ovarian lymphatic vasculature in ovarian pathologies, including cancer and those linked with use of artificial reproduction technologies.
A long-term follow-up study on hepatitis B surface antigen–positive patients undergoing allogeneic hematopoietic stem cell transplantation
Authors: Chee-kin Hui, Albert Lie, Wing-yan Au, Yu-hung Leung, Shing-yan Ma, Winnie W. W. Cheung, Hai-ying Zhang, Chor-sum Chim, Yok-lam Kwong, Raymond Liang, George K. K. Lau
Journal: Blood (2005)
TMPRSS2–ERG-Mediated Feed-Forward Regulation of Wild-Type ERG in Human Prostate Cancers
Authors: Ram-Shankar Mani, Matthew K. Iyer, Qi Cao, J. Chad Brenner, Lei Wang, Aparna Ghosh, Xuhong Cao, Robert J. Lonigro, Scott A. Tomlins, Sooryanarayana Varambally, Arul M. Chinnaiyan
Journal: Cancer Research (2011)

Recurrent gene fusions involving ETS family genes are a distinguishing feature of human prostate cancers, with TMPRSS2-ERG fusions representing the most common subtype. The TMPRSS2-ERG fusion transcript and its splice variants are well characterized in prostate cancers; however, not much is known about the levels and regulation of wild-type ERG. By employing an integrative approach, we show that the TMPRSS2-ERG gene fusion product binds to the ERG locus and drives the overexpression of wild-type ERG in prostate cancers. Knockdown of TMPRSS2-ERG in VCaP cells resulted in the downregulation of wild-type ERG transcription, whereas stable overexpression of TMPRSS2-ERG in the gene fusion-negative PC3 cells was associated with the upregulation of wild-type ERG transcript. Further, androgen signaling-mediated upregulation of TMPRSS2-ERG resulted in the concomitant upregulation of wild-type ERG transcription in VCaP cells. The loss of wild-type ERG expression was associated with a decrease in the invasive potential of VCaP cells. Importantly, 38% of clinically localized prostate cancers and 27% of metastatic prostate cancers harboring the TMPRSS2-ERG gene fusions exhibited overexpression of wild-type ERG. Taken together, these results provide novel insights into the regulation of ERG in human prostate cancers.
Cell Mechanics: Mechanical Response, Cell Adhesion, and Molecular Deformation
Authors: Cheng Zhu, Gang Bao, Ning Wang
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract As the basic unit of life, the cell is a biologically complex system, the understanding of which requires a combination of various approaches including biomechanics. With recent progress in cell and molecular biology, the field of cell mechanics has grown rapidly over the last few years. This review synthesizes some of these recent developments to foster new concepts and approaches, and it emphasizes molecular-level understanding. The focuses are on the common themes and interconnections in three related areas: (a) the responses of cells to mechanical forces, (b) the mechanics and kinetics of cell adhesion, and (c) the deformation of biomolecules. Specific examples are also given to illustrate the quantitative modeling used in analyzing biological processes and physiological functions.