tbuckley/cabot-search huggingface dataset:
Risk of Diabetes Among Young Adults Born Preterm in Sweden
Authors: Casey Crump, Marilyn A. Winkleby, Kristina Sundquist, Jan Sundquist
Journal: Diabetes Care (2011)

OBJECTIVE Previous studies have suggested that preterm birth is associated with diabetes later in life. These studies have shown inconsistent results for late preterm births and have had various limitations, including the inability to evaluate diabetic outpatients or to estimate risk across the full range of gestational ages. Our objective was to determine whether preterm birth is associated with diabetes medication prescription in a national cohort of young adults. RESEARCH DESIGN AND METHODS This was a national cohort study of 630,090 infants born in Sweden from 1973 through 1979 (including 27,953 born preterm, gestational age &amp;lt;37 weeks), followed for diabetes medication prescription in 2005–2009 (ages 25.5–37.0 years). Medication data were obtained from all outpatient and inpatient pharmacies throughout Sweden. RESULTS Individuals born preterm, including those born late preterm (gestational age 35–36 weeks), had modestly increased odds ratios (ORs) for diabetes medication prescription relative to those born full term, after adjusting for fetal growth and other potential confounders. Insulin and/or oral diabetes medications were prescribed to 1.5% of individuals born preterm compared with 1.2% of those born full term (adjusted OR 1.13 [95% CI 1.02–1.26]). Insulin without oral diabetes medications was prescribed to 1.0% of individuals born preterm compared with 0.8% of those born full term (1.22 [1.08–1.39]). CONCLUSIONS Preterm birth, including late preterm birth, is associated with a modestly increased risk of diabetes in young Swedish adults. These findings have important public health implications given the increasing number of preterm births and the large disease burden of diabetes, particularly when diagnosed in young adulthood.
The Need for National Registries in Rare Diseases
Authors: Rogério Souza, Carlos Jardim, Carlos Carvalho
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Humbert and colleagues, in their recent article, have published results from the national registry of pulmonary arterial hypertension (PAH) in France (1). Beyond the interesting data regarding the demographics and functional characteristics of the patients enrolled in the study, allowing the comparison with the national registry from the United States, which was published in the early 1990s by D’Alonzo and coworkers (2), the proportion of the different disease subtypes (i.e., idiopathic, associated with connective tissue diseases, or related to portal hypertension) indicates a key feature of national registries in rare diseases: the data raise the possibility of better allocation of medical and research resources. One clear example of this is the prevalence of pulmonary hypertension in association with schistosomiasis in developing countries. For example, a recent study from two reference centers in Brazil (3, 4), which included schistosomiasisrelated pulmonary hypertension together with other causes of PAH, found that about 30% of the cases of PAH could be associated with schistosomiasis. This astonishing proportion, besides being a clear consequence of social conditions inmany parts of the country, should, more importantly, draw the attention of researchers and clinicians to a regional characteristic that needs to be addressed and also that needs to be considered when extrapolating diagnostic and treatment algorithms to particular populations (5, 6). This merit of Humbert and coworkers’ article could be extrapolated to many other rare or orphan diseases whose regional distribution or characteristics should be considered at the time of the implementation of health policies.
The Dynamics of QuantiFERON-TB Gold In-Tube Conversion and Reversion in a Cohort of South African Adolescents
Authors: Jason R. Andrews, Mark Hatherill, Hassan Mahomed, Willem A. Hanekom, Monica Campo, Thomas R. Hawn, Robin Wood, Thomas J. Scriba
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Interferon-γ release assays are used to diagnose tuberculosis infection. In developed countries, high rates of reversion following conversion have been described.To assess QuantiFERON TB Gold In-Tube test (QFT) conversion and reversion dynamics in a tuberculosis-endemic setting.Adolescents aged 12-18 years residing near Cape Town were recruited. Tuberculin skin tests (TSTs) and QFTs were performed at baseline and after 2 years of follow up. Half of the participants had TST and QFT performed at additional time points. Participants were observed for incident tuberculosis disease for up to 5 years.Among 5,357 participants, 2,751 (51.4%) and 2,987 (55.8%) had positive QFT and TST results, respectively, at baseline. Annualized QFT and TST conversion risks were 14.0 and 13.0%, respectively, and reversion risks were 5.1 and 4.1%, respectively. Concordance was excellent for conversions (κ = 0.74), but poor for reversions (κ = 0.12). Among recent QFT converters, the magnitude of the QFT value was strongly inversely associated with risk of reversion (P < 0.0001). When longitudinal QFT data were analyzed in a cross-sectional manner, the annual risk of infection was 7.3%, whereas inclusion of reversions in the analysis showed that the actual risk of infection was 14.0%. Incident tuberculosis was 8-fold higher among QFT reverters than in participants with all negative QFT results (1.47 vs. 0.18 cases/100 person-years, P = 0.011).In this tuberculosis-endemic setting, annual risk of infection was extremely high, whereas QFT and TST conversion concordance was higher and QFT reversion rates were lower than reported in low-burden settings.
Genetic Risk Prediction: Individualized Variability in Susceptibility to Toxicants
Authors: Daniel W. Nebert, Ge Zhang, Elliot S. Vesell
Journal: The Annual Review of Pharmacology and Toxicology (2013)

Genetic risk prediction uses genetic data to individualize prediction of outcome or effect from a known harmful toxicant. Several examples of toxicogenetics (usually binary traits) are discussed, reflecting largely Mendelian traits before the Human Genome Project began in 1990. Numerous complexities of the genome and what constitutes “a gene” have emerged during these past two decades. Examples of toxicogenomics (continuous outcomes, gradients) are examined. Most xenobiotic-induced environmental diseases resemble human complex diseases or other multifactorial traits such as height; these traits result from hundreds of low-effect genes. Consequently, uncovering an association between a trait and a genetic variant in a large cohort can provide important information about underlying biology; however, screening for a specific variant in an individual worker or patient has poor predictive value and little clinical utility. Individualized risk assessment for toxicants that cause environmental diseases, although a lofty goal, remains to be achieved.
Transluminal endoscopic necrosectomy: revisited from the surgeon's perspective
Authors: Werner Hartwig, Jens Werner, Markus W Büchler
Journal: Gut (2010)

In a retrospective analysis of 93 patients, Seifert et al 1 investigated the role of transluminal endoscopic necrosectomy after acute pancreatitis. From the authors' point of view, the mortality rate of only 7.5% and a good long-term outcome appear to make this relatively new approach look favourable when compared with the results of published studies on surgical debridement in necrotising pancreatitis. However, a detailed look at the characteristics of the patients in the GEPARD study shows that this is like comparing apples and oranges. Surgical series on acute pancreatitis predominantly investigate the subset of patients with infected necrosis and severe organ dysfunction. Data on the severity of …
Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor–induced chemotaxis: contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration
Authors: Shuji Ueda, Masao Mizuki, Hirokazu Ikeda, Tohru Tsujimura, Itaru Matsumura, Kazushi Nakano, Hanako Daino, Zen-ichiro Honda, Junko Sonoyama, Hirohiko Shibayama, Hiroyuki Sugahara, Takashi Machii, Yuzuru Kanakura
Journal: Blood (2002)
Greater risk of wheeze in young female compared to male smokers - Results from the Swedish GA2LEN survey
Authors: Anders Bjerg, Linda Ekerljung, Jonas Eriksson, Inga Sif Olafsdottir, Roelinde Middelveld, Karl Franklin, Bertil Forsberg, Kjell Larsson, Jan Lötvall, Kjell Torén, Sven-Erik Dahlén, Bo Lundbäck, Christer Janson
Journal: European Respiratory Journal (2012)

Smoking has greater negative impacts on lung function and COPD risk in females. However, sex-related differences in smoking burden, body composition and exposures confound this association. We studied wheeze in relation to smoking and sex in a large well-characterised population.  In 2008 the GA2LEN questionnaire was mailed to 45.000 Swedish adults (16-75 yrs), and 60% participated. Respiratory symptoms, smoking and other exposures were analysed by multivariate regression. Asthmatic wheeze: wheeze with breathlessness and without a cold.  Females reported more wheeze and asthmatic wheeze, 17.3% vs. 15.8% and 7.1% vs. 6.1%, all p 52 yrs.  In this large, population-based study female compared to male smokers had higher risk of wheeze after adjustment for important confounders. This increased susceptibility was greater in pre-menopausal ages, and was not explained by differences in body composition or smoking habits. This points toward biological, possibly hormonal, underlying mechanisms.
Assessment of asthma control and its impact on optimal treatment strategy
Authors: B. Lundback, R. Dahl
Journal: Allergy (2007)

Achieving and maintaining optimal asthma control is a major asthma management goal advocated by the Global Initiative for Asthma (GINA). Recent evidence suggests that while asthma control is clearly achievable in most asthmatics, not all asthmatics attain optimal asthma control. The difficulty is compounded further because patients, physicians and regulatory bodies have different perceptions of what is meant by asthma control. The challenge therefore remains as to how best to assess asthma control and define management strategies to ensure that this control is achieved and maintained. Despite the availability of several patient-based tools for assessing asthma control, these are mostly employed in a research setting or in selected specialist clinics. A symptom-based treatment approach also may have its limitations because patients can be poor judges of disease symptoms and severity and under-estimation may lead to inadequate treatment of airway inflammation and airway hyperresponsiveness (AHR) when treatment is administered as on-demand reliever therapy, since the effect of treatment on these underlying features occurs over a longer time course. The clinical benefits of sustained maintenance treatment for at least 3 months has been documented in recent studies of salmeterol/fluticasone propionate combination, which have demonstrated correlations between reduction in airway inflammation/AHR and reduction in exacerbation rates. In view of the putative limitations of a purely symptom-based asthma management plan, we suggest that treatment should be focussed on management of all aspects of the disease rather than management of symptoms alone, with a practical approach being treatment for a minimum of 3 months with an optimal dose to ensure maximal effects are seen on asthma control, airway inflammation, lung function, and remodelling.
Dietary Lycopene, Angiogenesis, and Prostate Cancer: A Prospective Study in the Prostate-Specific Antigen Era
Authors: K. Zu, L. Mucci, B. A. Rosner, S. K. Clinton, M. Loda, M. J. Stampfer, E. Giovannucci
Journal: JNCI Journal of the National Cancer Institute (2014)

The role of lycopene in prostate cancer prevention remains controversial. We examined the associations between dietary lycopene intake and prostate cancer, paying particular attention to the influence of prostate-specific antigen screening, and evaluated tissue biomarkers in prostate cancers in relation to lycopene intake. Among 49898 male health professionals, we obtained dietary information through questionnaires and ascertained total and lethal prostate cancer cases from 1986 through January 31, 2010. Cox regression was used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). Tissue microarrays and immunohistochemistry were used to assess tumor biomarker expression in a subset of men. Two-sided χ 2 tests were used to calculate the P values. Higher lycopene intake was inversely associated with total prostate cancer and more strongly with lethal prostate cancer (top vs bottom quintile: HR = 0.72; 95% CI = 0.56 to 0.94; Ptrend = .04). In a restricted population of screened participants, the inverse associations became markedly stronger (for lethal prostate cancer: HR = 0.47; 95% CI = 0.29 to 0.75; Ptrend = .009). Comparing different measures of dietary lycopene, early intake, but not recent intake, was inversely associated with prostate cancer. Higher lycopene intake was associated with biomarkers in the cancer indicative of less angiogenic potential. Dietary intake of lycopene was associated with reduced risk of lethal prostate cancer and with a lesser degree of angiogenesis in the tumor. Because angiogenesis is a strong progression factor, an endpoint of lethal prostate cancer may be more relevant than an endpoint of indolent prostate cancer for lycopene in the era of highly prevalent prostate-specific antigen screening.
Effect of Noncompetitive Proteasome Inhibition on Bortezomib Resistance
Authors: Xiaoming Li, Tabitha E. Wood, Remco Sprangers, Gerrit Jansen, Niels E. Franke, Xinliang Mao, Xiaoming Wang, Yi Zhang, Sue Ellen Verbrugge, Hans Adomat, Zhi Hua Li, Suzanne Trudel, Christine Chen, Tomasz L. Religa, Nazir Jamal, Hans Messner, Jacqueline Cloos, David R. Rose, Ami Navon, Emma Guns, Robert A. Batey, Lewis E. Kay, Aaron D. Schimmer
Journal: JNCI Journal of the National Cancer Institute (2010)

Bortezomib and the other proteasome inhibitors that are currently under clinical investigation bind to the catalytic sites of proteasomes and are competitive inhibitors. We hypothesized that proteasome inhibitors that act through a noncompetitive mechanism might overcome some forms of bortezomib resistance.5-amino-8-hydroxyquinoline (5AHQ) was identified through a screen of a 27-compound chemical library based on the quinoline pharmacophore to identify proteasome inhibitors. Inhibition of proteasome activity by 5AHQ was tested by measuring 7-amino-4-methylcoumarin (AMC) release from the proteasome substrate Suc-LLVY-AMC in intact human and mouse leukemia and myeloma cells and in tumor cell protein extracts. Cytotoxicity was assessed in 5AHQ-treated cell lines and primary cells from myeloma and leukemia patients using AlamarBlue fluorescence and MTS assays, trypan blue staining, and annexin V staining. 5AHQ-proteasome interaction was assessed by nuclear magnetic resonance. 5AHQ efficacy was evaluated in three leukemia xenograft mouse models (9-10 mice per group per model). All statistical tests were two-sided.5AHQ inhibited the proteasome when added to cell extracts and intact cells (the mean concentration inhibiting 50% [IC(50)] of AMC release in intact cells ranged from 0.57 to 5.03 microM), induced cell death in intact cells from leukemia and myeloma cell lines (mean IC(50) values for cell growth ranged from 0.94 to 3.85 microM), and preferentially induced cell death in primary myeloma and leukemia cells compared with normal hematopoietic cells. 5AHQ was equally cytotoxic to human myelomonocytic THP1 cells and to THP1/BTZ500 cells, which are 237-fold more resistant to bortezomib than wild-type THP1 cells because of their overexpression and mutation of the bortezomib-binding beta5 proteasome subunit (mean IC(50) for cell death in the absence of bortezomib, wild-type THP1: 3.7 microM, 95% confidence interval = 3.4 to 4.0 microM; THP1/BTZ500: 6.6 microM, 95% confidence interval = 5.9 to 7.5 microM). 5AHQ interacted with the alpha subunits of the 20S proteasome at noncatalytic sites. Orally administered 5AHQ inhibited tumor growth in all three mouse models of leukemia without overt toxicity (eg, OCI-AML2 model, median tumor weight [interquartile range], 5AHQ vs control: 95.7 mg [61.4-163.5 mg] vs 247.2 mg [189.4-296.2 mg], P = .002).5AHQ is a noncompetitive proteasome inhibitor that is cytotoxic to myeloma and leukemia cells in vitro and inhibits xenograft tumor growth in vivo. 5AHQ can overcome some forms of bortezomib resistance in vitro.
Low-level expression of HER2 and CK19 in normal peripheral blood mononuclear cells: relevance for detection of circulating tumor cells
Authors: Fanglei You, Lisa A Roberts, S Peter Kang, Raquel A Nunes, Cinara Dias, J Dirk Iglehart, Natalie A Solomon, Paula N Friedman, Lyndsay N Harris
Journal: Journal of Hematology & Oncology (2008)

Abstract Background Detection of circulating tumor cells (CTC) in the blood of cancer patients may have prognostic and predictive significance. However, background expression of 'tumor specific markers' in peripheral blood mononuclear cells (PBMC) may confound these studies. The goal of this study was to identify the origin of Cytokeratin 19 (CK19) and HER-2 signal in PBMC and suggest an approach to enhance techniques involved in detection of CTC in breast cancer patients. Methods PBMC from healthy donors were isolated and fractionated into monocytes, lymphocytes, natural killer cells/granulocytes and epithelial populations using immunomagnetic selection and fluorescent cell-sorting for each cell type. RNA isolated from each fraction was analyzed for CK19, HER2 and Beta 2 microglobulin (B2M) using real-time qRT-PCR. Positive selection for epithelial cells and negative selection for NK/granulocytes were used in an attempt to reduce background expression of CK19 and HER2 markers. Results In normal PBMC, CK19 was expressed in the lymphocyte population while HER-2 expression was highest in the NK/granulocyte population. Immunomagnetic selection for epithelial cells reduced background CK19 signal to a frequency of &lt;5% in normal donors. Using negative selection, the majority (74–98%) of HER2 signal could be removed from PBMC. Positive selection methods are variably effective at reducing these background signals. Conclusion We present a novel method to improve the specificity of the traditional method of detecting CTC by identifying the source of the background signals and reducing them by negative immunoselection. Further studies are warranted to improve sensitivity and specificity of methods of detecting CTC will prove to be useful tools for clinicians in determining prognosis and monitoring treatment responses of breast cancer patients.
The Biotic-Abiotic Interface
Authors: Patrick A. Tresco, Greg A. Gerhardt
Journal: Brain-Computer Interfaces (2008)

Brain-computer interfaces (BCI), or brain-machine interfaces (BMI), are systems designed to aid humans with central nervous system disabilities, including disabilities in movement, communication, and independent control of one's environment (Donoghue, 2002; Friehs et al., 2004; Lebedev and Nicolelis, 2006; Schwartz et al., 2006). Although these same approaches have the potential to augment normal function, as currently envisioned this new class of biomedical devices is being developed to help those with disabilities. As such, these devices may be useful for patients suffering from a variety of conditions including spinal cord injury, musculodegenerative diseases, stroke, amyotrophic lateral sclerosis, or other neurological or neuromuscular diseases. The intent of these devices and their associated components is to provide or supplement motor or sensory function that has been lost. The theoretical basis for such devices lies in our ability to detect neural signals and translate volitional commands into control signals for external devices including computers, robotics, or other machines. The acquisition of neural signals has traditionally occurred in the cerebral cortex, and the recording of these signals from implanted electrodes has a fairly extensive history.
Knee alignment differences between Chinese and Caucasian subjects without osteoarthritis
Authors: W F Harvey, J Niu, Y Zhang, P I McCree, D T Felson, M Nevitt, L Xu, P Aliabadi, D J Hunter
Journal: Annals of the Rheumatic Diseases (2008)

Despite the lower prevalence of obesity (a known risk factor for osteoarthritis (OA)), the prevalence of lateral tibiofemoral OA is higher in Chinese communities compared with Caucasian communities. One potential explanation is the difference in knee alignment between the two populations. We measured various knee alignment indices among Chinese and Caucasians and assessed whether these indices were different between the two racial groups.We selected participants from the Framingham Osteoarthritis Study (FOA) and the Beijing Osteoarthritis Study (BOA), all without knee OA (Kellgren & Lawrence grade <2). Bilateral, fully extended anteroposterior knee radiographs were measured for the following angles in both knees: the anatomic axis (AA), the condylar angle (CA), the tibial plateau angle and the condylar-plateau angle (CP). We compared the mean of each measurement between the two racial groups adjusting for age and body mass index using linear regression and stratified by sex.The mean AA, CA and CP were significantly different in the BOA compared with the FOA. For women, the mean AA and CA were significantly more valgus in BOA subjects, while in men, the mean AA and CP were more valgus in BOA subjects.There are significant differences in knee morphology between Chinese and Caucasian cohorts, which result in a more valgus alignment of the distal femur in Chinese. This would serve to shift the mechanical loading towards the lateral compartment, and provide a possible explanation why Chinese have a higher prevalence of lateral tibiofemoral OA.
Relative Potency in SPT of Solution and Tablet SLIT Allergen Extracts of Timothy Grass Pollen from 2 European Manufacturers Compared to a US Reference Extract
Authors: Désirée E.S. Larenas Linnemann, Robert E. Esch, Jaswinder Singh, Juan Jose Matta, Nelson A. Rosario, Jorge F. Maspero, Alexandra Michels, Ralph Mosges
Journal: Journal of Allergy and Clinical Immunology (2015)
SETBP1 overexpression is a novel leukemogenic mechanism that predicts adverse outcome in elderly patients with acute myeloid leukemia
Authors: Ion Cristóbal, Francisco J. Blanco, Laura Garcia-Orti, Nerea Marcotegui, Carmen Vicente, José Rifon, Francisco J. Novo, Eva Bandres, María J. Calasanz, Carmelo Bernabeu, María D. Odero
Journal: Blood (2009)