tbuckley/cabot-search huggingface dataset:
Has mortality from malignant melanoma stopped rising in Spain? Analysis of trends between 1975 and 2001
Authors: A. Cayuela, S. Rodriguez-Dominguez, J. Lapetra-Peralta, J.S. Conejo-Mir
Journal: British Journal of Dermatology (2005)

There have been suggestions that mortality from cutaneous malignant melanoma (CMM) is starting to level off in the European Union.To analyse changes in CMM mortality trends in Spain during 1975-2001 using joinpoint regression models.Mortality data were obtained from the National Statistics Institute. For each gender, age group-specific and standardized (overall and truncated) rates were calculated by the direct method (using the world standard population). The joinpoint analysis was used to identify the best-fitting points where a statistically significant change in the trend occurred.In women, there was a marked increase from 1975 to 1994 in age-adjusted (overall and truncated) CMM mortality rates [estimated annual percentage change (EAPC) 6.6% and 7.0%, respectively; P < 0.05], followed by a levelling off (EAPC - 0.3% and - 1.3%, respectively; not significant). In men, age-adjusted (35-64 years) mortality rates increased steadily from 1975 to 1991 (EAPC 9.1%, P < 0.05) and then levelled off.We confirmed that CMM mortality rates in Spain rose dramatically from the mid-1970s to the beginning of the 1990s, but we also found that mortality rates are now levelling off in middle-aged adults (35-64 years), following a similar tendency to that observed in other countries.
In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography
Authors: D L Francis
Journal: Gut (2003)

and aims: Positron emission tomography (PET) using (18)F labelled 2-fluoro-2-deoxy-D-glucose ((18)FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3-fluorothymidine ((18)FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of (18)FLT and (18)FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC).Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54-87), were evaluated. Patients underwent (18)FDG and (18)FLT PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells).Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both (18)FLT and (18)FDG. Three of the five resected liver metastases were also avid for (18)FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of (18)FLT had correspondingly very low proliferation. There was a statistically significant positive correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with (18)FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with (18)FDG avid lesions (r =0.4).(18)FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy.
Amoxapine and imipramine in the treatment of depressed outpatients: a controlled study
Authors: K Rickels, W G Case, J Werblowsky, I Csanalosi, A Schless, C C Weise
Journal: American Journal of Psychiatry (1981)

In a double-blind, controlled study 158 outpatients with unipolar depression were treated for six weeks with amoxapine, imipramine, or placebo to assess the antidepressant effects of the new dibenzooxazepine compound, amoxapine. Forty-five amoxapine, 43 imipramine, and 27 placebo patients completed at least four weeks of treatment. Active drugs produced significantly more improvement at treatment endpoint, according to several physician-rated measures, but patient-rated measures failed to differentiate among treatments. Both active drugs at daily doses up to 200 mg produced an equal amount of moderate and marked global improvement, and both produced significantly more side effects than did placebo.
Pulmonary Embolism and Deep Venous Thrombosis.
Journal: Annals of Internal Medicine (1985)

The heart pumps oxygenated blood through the aorta to smaller arteries. After the blood supplies nutrients to vital organs, it returns through veins for reoxygenation in the lungs (Figures 1 and 2⇓). Blood clots called deep vein thrombi (DVT) often develop in the deep leg veins. Pulmonary embolism (PE) occurs when clots break off from vein walls and travel through the heart to the pulmonary arteries. The broader term venous thromboembolism (VTE) refers to DVT, PE, or to a combination of both. 



Figure 1. The arterial (red) and venous systems (blue) are depicted. The left ventricle (LV) ejects oxygenated blood into the aorta, which circulates blood to vital organs. Deoxygenated blood travels through the venous system to the right atrium, right ventricle, and pulmonary artery. Adapted with permission from MediClip, Clinical Cardiopulmonary Images 1997, CCP01026.TIF, Williams & Wilkins, Baltimore, Md.





Figure 2. Deoxygenated blood returns to the heart and lungs for reoxygenation. SVC indicates superior vena cava; IVC, inferior vena cava; RA, right atrium; RV, right ventricle; and PA, pulmonary artery. Adapted with permission from MediClip, Clinical Cardiopulmonary Images 1997, CATHRHT.TIF, Williams & Wilkins, Baltimore, Md.



VTE poses a public health threat with an estimated incidence in the United States of 250 000 to 2 million cases per year. Predisposition to VTE arises from acquired conditions, inherited disorders, or both. Many of the acquired risk factors can be modified, thus lessening the likelihood of PE or DVT.

Long-haul air travel is the most talked-about risk factor for PE. Other acquired risk factors include obesity, …
Increased Hippocampal Glutamate and Volumetric Deficits in Unmedicated Patients With Schizophrenia
Authors: Nina V. Kraguljac, David M. White, Meredith A. Reid, Adrienne C. Lahti
Journal: JAMA Psychiatry (2013)

Alterations in glutamatergic neurotransmission have been postulated to be a key pathophysiologic mechanism in schizophrenia.To evaluate hippocampal volumetric measures and neurometabolites in unmedicated patients with schizophrenia and the correlations between these markers. Our a priori hypothesis was that glutamate levels would negatively correlate with hippocampal volume in schizophrenia.Combined 3-T structural magnetic resonance imaging and single-voxel proton magnetic resonance spectroscopy study at the Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, of 27 unmedicated patients with schizophrenia and 27 healthy controls.Hippocampal volumetric measures and neurometabolites, and the correlations between volumetric measurements and neurometabolites.Hippocampal volumetric deficits, increased ratios of hippocampal glutamate and glutamine to creatine (Glx/Cr), and a loss of correlation between hippocampal N-acetylaspartate (NAA)/Cr and Glx/Cr in patients with schizophrenia were found. Significant correlations between hippocampal volumetric measures and Glx/Cr were also found in patients with schizophrenia but not healthy controls.Our findings support the theory that alterations in hippocampal glutamate levels potentially account for structural deficits in the hippocampus observed in schizophrenia neuroimaging studies.
T-Cell Costimulation and Coinhibition in Atherosclerosis
Authors: Israel Gotsman, Arlene H. Sharpe, Andrew H. Lichtman
Journal: Circulation Research (2008)

Evidence from many human and rodent studies has established that T lymphocytes enhance inflammation in atherosclerotic plaques and contribute to lesion progression and remodeling. Recent work also indicates that regulatory T cells are important in limiting proatherogenic T-cell responses. Given the important role of T cells in atherosclerosis, there is a need to fully understand how proatherogenic T cells are activated and regulated. Antigen-dependent activation of naïve T cells, leading to clonal expansion and effector T-cell differentiation, and effector and memory T cells, is enhanced by signals provided by costimulatory molecules expressed by antigen presenting cells, which bind to receptors on the T cells. In addition, T-cell responses to antigen are negatively regulated by coinhibitory molecules expressed by antigen-presenting cells, which bind to receptors on T cells. Two major families of costimulatory molecules include the B7 and the tumor necrosis factor (TNF) families. These molecules bind to receptors on T cells belonging to the CD28 or TNF receptor families, respectively. The best-defined coinhibitors and their receptors belong to the B7 and CD28 families. Recent work has begun to define how these T-cell costimulatory and coinhibitory pathways influence atherosclerosis, largely in mouse models of the disease. Profound effects are attributable to molecules in both the B7/CD28 (B7-1/2, ICOS, and PDL-1/2) and the TNF/TNF receptor (CD40, OX40, and CD137) families. One emerging theme is that both pathogenic effector T-cell responses and regulatory T cells are influenced by overlapping sets of costimulators and coinhibitors. These complexities must be considered as immunotherapeutic approaches for atherosclerotic disease are developed.
Allergen avoidance in the treatment of asthma and atopic disorders
Authors: A Custovic, A Simpson, M D Chapman, A Woodcock
Journal: Thorax (1998)

All the studies reviewed in table 1 suggestUniversity of Virginia, gen levels were attempted in patients' homes.that asthmatic subjects allergic to mites im-Charlottesville, prove when moved from their homes into a Virginia, USA low allergen environment.They also provide M D Chapman      information on the duration of avoidance The levels of mite allergen are dramatically
NOTCH3 Expression Is Induced in Mural Cells Through an Autoregulatory Loop That Requires Endothelial-Expressed JAGGED1
Authors: Hua Liu, Simone Kennard, Brenda Lilly
Journal: Circulation Research (2009)

Endothelial cells and mural cells (smooth muscle cells, pericytes, or fibroblasts) are known to communicate with one another. Their interactions not only serve to support fully functional blood vessels but also can regulate vessel assembly and differentiation or maturation. In an effort to better understand the molecular components of this heterotypic interaction, we used a 3D model of angiogenesis and screened for genes, which were modulated by coculturing of these 2 different cell types. In doing so, we discovered that NOTCH3 is one gene whose expression is robustly induced in mural cells by coculturing with endothelial cells. Knockdown by small interfering RNA revealed that NOTCH3 is necessary for endothelial-dependent mural cell differentiation, whereas overexpression of NOTCH3 is sufficient to promote smooth muscle gene expression. Moreover, NOTCH3 contributes to the proangiogenic abilities of mural cells cocultured with endothelial cells. Interestingly, we found that the expression of NOTCH3 is dependent on Notch signaling, because the γ-secretase inhibitor DAPT blocked its upregulation. Furthermore, in mural cells, a dominant-negative Mastermind-like1 construct inhibited NOTCH3 expression, and endothelial-expressed JAGGED1 was required for its induction. Additionally, we demonstrated that NOTCH3 could promote its own expression and that of JAGGED1 in mural cells. Taken together, these data provide a mechanism by which endothelial cells induce the differentiation of mural cells through activation and induction of NOTCH3. These findings also suggest that NOTCH3 has the capacity to maintain a differentiated phenotype through a positive-feedback loop that includes both autoregulation and JAGGED1 expression.
Inherited Determinants of Ovarian Cancer Survival
Authors: E. L. Goode, M. J. Maurer, T. A. Sellers, C. M. Phelan, K. R. Kalli, B. L. Fridley, R. A. Vierkant, S. M. Armasu, K. L. White, G. L. Keeney, W. A. Cliby, D. N. Rider, L. E. Kelemen, M. B. Jones, P. P. Peethambaram, J. M. Lancaster, J. E. Olson, J. M. Schildkraut, J. M. Cunningham, L. C. Hartmann
Journal: Clinical Cancer Research (2010)

Due to variation of outcome among cases, we sought to examine whether overall survival in ovarian cancer was associated with common inherited variants in 227 candidate genes from ovarian cancer-related pathways including angiogenesis, inflammation, detoxification, glycosylation, one-carbon transfer, apoptosis, cell cycle regulation, and cellular senescence.Blood samples were obtained from 325 women with invasive epithelial ovarian cancer diagnosed at the Mayo Clinic from 1999 to 2006. During a median follow-up of 3.8 years (range, 0.1-8.6 years), 157 deaths were observed. Germline DNA was analyzed at 1,416 single nucleotide polymorphisms (SNP). For all patients, and for 203 with serous subtype, we assessed the overall significance of each gene and pathway, and estimated risk of death via hazard ratios (HR) and 95% confidence intervals (CI), adjusting for known prognostic factors.Variation within angiogenesis was most strongly associated with survival time overall (P = 0.03) and among patients with serous cancer (P = 0.05), particularly for EIF2B5 rs4912474 (all patients HR, 0.69; 95% CI, 0.54-0.89; P = 0.004), VEGFC rs17697305 (serous subtype HR, 2.29; 95% CI, 1.34-3.92; P = 0.003), and four SNPs in VHL. Variation within the inflammation pathway was borderline significant (all patients, P = 0.09), and SNPs in CCR3, IL1B, IL18, CCL2, and ALOX5 which correlated with survival time are worthy of follow-up.An extensive multiple-pathway assessment found evidence that inherited differences may play a role in outcome of ovarian cancer patients, particularly in genes within the angiogenesis and inflammation pathways. Our work supports efforts to target such mediators for therapeutic gain.
Resistance of quiescent and proliferating airway epithelial cells to H2O2 challenge
Authors: M. P. Smit-de Vries, M. van der Toorn, R. Bischoff, H. F. Kauffman
Journal: European Respiratory Journal (2007)

Alveolar epithelial cell injury and recovery are important in the pathogenesis of oxidant-induced lung damage. The alveolar cell line A549 was used to study responses of proliferating and quiescent cells in culture to time- and dose-dependent hydrogen peroxide (H 2 O 2 ) challenges. Recovery was monitored after 24 h of incubation in fresh medium with 10% serum. The adherent cells were counted and the resistance and recovery of the attached cells was assessed by appearance, by measuring the number of viable, apoptotic and necrotic cells using fluorescent-activated cell sorting, and by determining the intracellular free thiol content. A549 cells recovered from a 1-h challenge with up to 1 mM H 2 O 2 but could not sustain a more prolonged challenge (6 or 24 h) with 0.5 mM or 1.0 mM H 2 O 2 . These more severe conditions resulted in: loss of cells by detachment from the plate surface; reduced numbers of viable cells primarily due to necrosis; and a strong reduction of the intracellular free thiol content. Quiescent cells proved to be more sensitive to oxidative stress than proliferating cells. Intracellular free thiol levels apparently play a decisive role in cell survival, preferentially protecting proliferating cells.
Getting sports injury prevention on to public health agendas – addressing the shortfalls in current information sources
Authors: Caroline F Finch
Journal: British Journal of Sports Medicine (2011)

Public health policy is a successful population-level strategy for injury prevention but it is yet to be widely applied to the sports sector. Such policy is generally coordinated by government health departments concerned with the allocation of limited resources to health service delivery and preventive programs for addressing large community health issues. Prioritisation of sports injury prevention (SIP) requires high-quality evidence about the size of the problem and its public health burden; identification of at-risk vulnerable groups; confirmed effective prevention solutions; evidence of intervention cost-effectiveness; and quantification of both financial and policy implications of inaction. This paper argues that the major reason for a lack of sports injury policy by government departments for health or sport to date is a lack of relevant information available for policy makers to make their decisions. Key information gaps evident in Australia are used to highlight this problem. SIP policy does not yet rank highly because, relative to other health/injury issues, there is very little hard evidence to support: claims for its priority ranking, the existence of solutions that can be implemented and which will work, and potential cost-savings to government agencies. Moreover, policy action needs to be integrated across government portfolios, including sport, health and others. Until sports medicine research generates high-quality population-level information of direct relevance and importance to policy makers, especially intervention costing and implementation cost-benefit estimates, and fully engage in policy-informing partnerships, SIP will continue to be left off the public health agenda.
Reproducibility of cardiorespiratory measurements during submaximal and maximal running in children.
Authors: V B Unnithan, L A Murray, J A Timmons, D Buchanan, J Y Paton
Journal: British Journal of Sports Medicine (1995)

With the increased use of oxygen consumption measurements in clinical and sporting studies, measurement variability has become more important to both the paediatric clinician and the sports scientist. In this study we assessed the reproducibility of cardiorespiratory measurements during submaximal and maximal running in children. Ten healthy, physically active boys (mean(s.d.) age 10.7(0.71) years) performed two submaximal and two maximal running tests within a 4 week period. The submaximal protocol consisted of three 6 minute runs at 7.2, 8.0 and 8.8 km/h. Every attempt was made to minimize the sources of non-biological variability at each testing session. During submaximal exercise, oxygen consumption (VO2), heart rate (HR) and fractional utilization appeared to be the most reliable measures accounting for over two-thirds of the total variation (coefficients of reliability (CR) of 68%, 94% and 82% respectively). Ventilation (Ve) and respiratory exchange ratio (RER) proved to be only moderately reliable accounting for less than half of the total variation (CR 50% and 45% respectively). At maximal exercise, VO2, Ve and time to exhaustion were most reliable, accounting for approximately two-thirds of the total variation (CR 65%, 63% and 63% respectively). Within this test environment, a two visit submaximal assessment was capable of estimating VO2 with a standard error of +/- 1.25 ml/kg/min. Similarly, for maximal testing a two visit assessment estimated peak VO2 with a standard error of +/- 2.28 ml/kg/min. On the evidence of these results a two visit assessment for submaximal and maximal exercise testing seems adequate to estimate the stability of submaximal cardiorespiratory measures and peak VO2 in healthy, normally active boys.
Is childhood immunisation associated with atopic disease from age 7 to 32 years?
Authors: K. Nakajima, S. C Dharmage, J. B Carlin, C. L Wharton, M. A Jenkins, G. G Giles, M. J Abramson, E Haydn Walters, J. L Hopper
Journal: Thorax (2006)

There is ongoing conjecture over whether childhood immunisation leads to an increased risk of developing atopic diseases.To examine associations between childhood immunisation and the risk of atopic disease.Immunisation histories of 8443 Tasmanian children born in 1961 obtained from school medical records were linked to the Tasmanian Asthma Study. Associations between immunisation status and atopic diseases were examined while adjusting for possible confounders using multiple logistic regression.Diphtheria immunisation was weakly associated with an increased risk of asthma by age 7 years (odds ratio (OR) 1.3, 95% confidence interval (CI) 1.1 to 1.7), but there was no evidence of any association for four other vaccinations studied. An increased risk of eczema by age 7 years was associated with immunisation against diphtheria (OR 1.5, 95% CI 1.1 to 2.1), tetanus (OR 1.5, 95% CI, 1.1 to 2.0), pertussis (OR 1.5, 95% CI 1.1 to 1.9) and polio (OR 1.4, 95% CI 1.0 to 1.9) but not small pox. Similar but slightly weaker patterns of association were observed between the risk of food allergies and immunisation against diphtheria (OR 1.5, 95% CI 1.0 to 2.1), pertussis (OR 1.4, 95% CI 1.1 to 1.9), polio (OR 1.4, 95% CI 1.00 to 2.1) and tetanus (OR 1.30 95% CI 0.99 to 1.70), but not with small pox. There was no evidence of associations between immunisation history and hay fever, or incidence of later-onset atopic outcomes.The few effects seen in this study are small and age-dependent, and nearly all our findings support numerous previous studies of no effect of vaccines on asthma. Based on these findings, the fear of their child developing atopic disease should not deter parents from immunising their children, especially when weighed against the benefits.
Crizotinib Treatment in Patients (PTS) with Advanced ROS1-Rearranged Non-Small Cell Lung Cancer (NSCLC)
Authors: S.-H. I. Ou, D.-W. Kim, R. Camidge, G.J. Riely, R. Salgia, G. Shapiro, J.W. Clark, L. Tye, A.J. Iafrate, A. Shaw
Journal: Annals of Oncology (2013)
Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: a study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression
Authors: Frank Dicker, Susanne Schnittger, Torsten Haferlach, Wolfgang Kern, Claudia Schoch
Journal: Blood (2006)
An Evaluation of the Efficacy of Methods Used in Screening for Lower-Limb Arterial Disease in Diabetes
Authors: Dean T. Williams, Keith G. Harding, Patricia Price
Journal: Diabetes Care (2005)

OBJECTIVE—Foot-related disease is the most common cause for hospital admission among the diabetic population. Lower-limb peripheral arterial occlusive disease (PAOD) is a major risk factor in diabetic foot disease. Screening for PAOD commonly includes foot pulses and the ankle-brachial pressure index (ABPI) and/or the toe-brachial pressure index (TBI), but concerns persist regarding their accuracy. We evaluated the efficacy of several commonly used screening methods in different subject populations. RESEARCH DESIGN AND METHODS—We studied 130 limbs in 68 individuals with no critical ischemia over 8 months. Limbs were grouped on the basis of the presence or absence of diabetes, clinically detectable peripheral neuropathy, and PAOD identified on color duplex imaging. Comparative analyses of foot pulses, the ABPI, the TBI, and distal Doppler waveform analysis were performed. RESULTS—Foot pulses, the TBI, and qualitative waveform analyses were highly sensitive screening methods in individuals with and without diabetes. However, detectable peripheral neuropathy was associated with a reduced sensitivity and poor specificity of foot pulses, a reduction in sensitivity of the ABPI (71 to 38%), and a reduction in specificity of the TBI (81 to 61%) and qualitative waveform analysis (96 to 66%). Quantitative analysis failed to detect disease with severely damped and low-intensity signals. CONCLUSIONS—Screening tools that are effective in screening for lower-limb PAOD in the nondiabetic population are less efficacious in diabetes, particularly in the presence of detectable peripheral neuropathy. Qualitative waveform analysis and the TBI were demonstrated to be more effective screening methods than the ABPI and foot pulses particularly in high-risk limbs with detectable peripheral neuropathy.