tbuckley/cabot-search huggingface dataset:
A Simple Screening Score for Diabetes for the Korean Population
Authors: Yong-ho Lee, Heejung Bang, Hyeon Chang Kim, Hee Man Kim, Seok Won Park, Dae Jung Kim
Journal: Diabetes Care (2012)

We developed and validated a self-assessment score for diabetes risk in Korean adults and compared it with other established screening models.The Korea National Health and Nutrition Examination Survey (KNHANES) 2001 and 2005 data were used to develop a diabetes screening score. After excluding patients with known diabetes, 9,602 participants aged ≥ 20 years were selected. Undiagnosed diabetes was defined as a fasting plasma glucose ≥ 126 mg/dL and/or nonfasting plasma glucose ≥ 200 mg/dL. The SAS Survey Logistic Regression analysis was used to determine predictors of undiagnosed diabetes (n = 341). We validated our model and compared it with other existing methods using the KNHANES 2007-2008 data (n = 8,391).Age, family history of diabetes, hypertension, waist circumference, smoking, and alcohol intake were independently associated with undiagnosed diabetes. We calculated a diabetes screening score (range 0-11), and a cut point of ≥ 5 defined 47% of adults as being at high risk for diabetes and yielded a sensitivity of 81%, specificity of 54%, positive predictive value of 6%, and positive likelihood ratio of 1.8 (area under the curve [AUC] = 0.73). Comparable results were obtained in validation datasets (sensitivity 80%, specificity 53%, and AUC = 0.73), showing better performance than other non-Asian models from the U.S. or European population.This self-assessment score may be useful for identifying Korean adults at high risk for diabetes. Additional studies are needed to evaluate the utility and feasibility of this score in various settings.
CD44 Binds to Macrophage Mannose Receptor on Lymphatic Endothelium and Supports Lymphocyte Migration via Afferent Lymphatics
Authors: Marko Salmi, Marika Karikoski, Kati Elima, Pia Rantakari, Sirpa Jalkanen
Journal: Circulation Research (2013)

Macrophage mannose receptor (MRC) is one of the few molecules known to be involved in lymphocyte trafficking via the lymphatic vessels. In endothelial cells of efferent lymphatics, it binds L-selectin on lymphocytes. In afferent lymphatics, MRC mediates trafficking of both normal and malignant L-selectin-negative cells to the draining lymph nodes.This work was designed to search for additional lymphocyte ligands of MRC to elucidate how lymphocytes migrate into the draining lymph nodes.Using immunoprecipitation and binding studies with natural and recombinant proteins, we show that MRC and CD44 can interact with each other. Fine mapping revealed that the cysteine-rich domain of MRC binds to the chondroitin sulfate side chains of CD44. In vivo homing experiments with MRC- and CD44-deficient mice verified that MRC and CD44 function as a receptor-ligand pair in supporting lymphocyte migration via the afferent lymphatics into the draining lymph nodes.These data identify a new counter-receptor for MRC and reveal CD44 as a new molecule involved in the poorly understood process of lymphocyte transit via the lymphatic vasculature.
Monthly Antibiotic Chemoprophylaxis and Incidence of Sexually Transmitted Infections and HIV-1 Infection in Kenyan Sex Workers
Authors: Rupert Kaul, Joshua Kimani, Nico J. Nagelkerke, Karoline Fonck, Elizabeth N. Ngugi, Florence Keli, Kelly S. MacDonald, Ian W. Maclean, Job J. Bwayo, Marleen Temmerman, Allan R. Ronald, Stephen Moses, None for the Kibera HIV Study Group
Journal: JAMA (2004)

ContextSexually transmitted infections (STIs) are common in female sex workers (FSWs) and may enhance susceptibility to infection with human immunodeficiency virus type 1 (HIV-1).ObjectiveTo examine regular antibiotic prophylaxis in FSWs as a strategy for reducing the incidence of bacterial STIs and HIV-1.Design, Setting, and ParticipantsRandomized, double-blind, placebo-controlled trial conducted between 1998-2002 among FSWs in an urban slum area of Nairobi, Kenya. Of 890 FSWs screened, 466 who were seronegative for HIV-1 infection were enrolled and randomly assigned to receive azithromycin (n = 230) or placebo (n = 236). Groups were well matched at baseline for sexual risk taking and STI rates.InterventionMonthly oral administration of 1 g of azithromycin or identical placebo, as directly observed therapy. All participants were provided with free condoms, risk-reduction counseling, and STI case management.Main Outcome MeasuresThe primary study end point was incidence of HIV-1 infection. Secondary end points were the incidence of STIs due to Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, and Haemophilus ducreyi, as well as bacterial vaginosis. Analysis of herpes simplex virus type 2 (HSV-2) infection was performed post hoc.ResultsSeventy-three percent of participants (n = 341) were followed up for 2 or more years or until they reached an administrative trial end point. Incidence of HIV-1 did not differ between treatment and placebo groups (4% [19 cases per 473 person-years of follow-up] vs 3.2% [16 cases per 495 person-years of follow-up] rate ratio [RR], 1.2; 95% CI, 0.6-2.5). Incident HIV-1 infection was associated with preceding infection with N gonorrhoeae (rate ratio [RR], 4.9; 95% CI, 1.7-14.3) or C trachomatis (RR, 3.0; 95% CI, 1.1-8.9). There was a reduced incidence in the treatment group of infection with N gonorrhoeae (RR, 0.46; 95% CI, 0.31-0.68), C trachomatis (RR, 0.38; 95% CI, 0.26-0.57), and T vaginalis (RR, 0.56; 95% CI, 0.40-0.78). The seroprevalence of HSV-2 infection at enrollment was 72.7%, and HSV-2 infection at baseline was independently associated with HIV-1 acquisition (RR, 6.3; 95% CI, 1.5-27.1).ConclusionsDespite an association between bacterial STIs and acquisition of HIV-1 infection, the addition of monthly azithromycin prophylaxis to established HIV-1 risk reduction strategies substantially reduced the incidence of STIs but did not reduce the incidence of HIV-1. Prevalent HSV-2 infection may have been an important cofactor in acquisition of HIV-1.
MicroRNAs Micromanage Themselves
Authors: Alan Jiao, Frank J. Slack
Journal: Circulation Research (2012)

Since their discovery not long ago, microRNAs (miRNAs) have been extensively studied in hundreds of laboratories around the world. Initially thought of as merely cytoplasmic repressors of mRNA expression, it has since become more apparent that they also play regulatory roles in the nucleus. A recent study published in Nature introduces novel concepts in both miRNA regulation and function by showing that the let-7 miRNA regulates its own expression.
Prevalence and Predictors of Depression Treatment in an International Primary Care Study
Authors: Gregory E. Simon, Marcelo Fleck, Ramona Lucas, Donald M. Bushnell
Journal: American Journal of Psychiatry (2004)

The purpose of the study was to evaluate the prevalence and predictors of depression treatment in a diverse cross-national sample of primary care patients.At primary care facilities in six countries (Spain, Israel, Australia, Brazil, Russia, and the United States), a two-stage screening process was used to identify 1,117 patients with current depressive disorder. At baseline, all patients completed a structured diagnostic interview as well as measures of anxiety symptoms, alcohol use, chronic comorbid physical conditions, and perceived barriers to treatment. Primary care physicians were advised if the research interview indicated a probable depressive disorder in their patients. Three and 9 months later, participants reported all health services (including specialty mental health care and antidepressant medication) used in the preceding 3 months.Across the six sites, the proportion of patients receiving any antidepressant pharmacotherapy ranged from a high of 38% in Seattle to a low of 0% in St. Petersburg; the proportion receiving any specialty mental health care varied from a high of 29% in Melbourne to a low of 3% in St. Petersburg. Patient characteristics were not consistently associated with receipt of either pharmacotherapy or specialty mental health care. Out-of-pocket cost was the most commonly reported barrier to treatment for depression; the percentage of patients who reported this barrier ranged from 24% in Barcelona to 75% in St. Petersburg.Depression screening and physician notification are not sufficient to prompt adequate treatment for depression. The probability of treatment may be more influenced by characteristics of health care systems than by the clinical characteristics of individual patients. Financial barriers may be more important than stigma as impediments to appropriate care.
Influences of antigen processing on the expression of the T cell repertoire. Evidence for MHC-specific hindering structures on the products of processing.
Authors: S J Brett, K B Cease, J A Berzofsky
Journal: The Journal of Experimental Medicine (1988)

Two lines of evidence in the current study indicate that antigen processing is a major factor, in addition to MHC binding and T cell repertoire, that determines Ir gene responsiveness and epitope immunodominance. First, immunization with synthetic peptides of myoglobin sequences revealed new reactivities that had not appeared after priming with native myoglobin. For example, B10.S mice (H-2S) immune to equine myoglobin predominantly responded to peptide 102-118, whereas there was little, if any, response to this peptide in B10.BR (H-2k) mice immunized with native equine myoglobin. However, after immunization with the 102-118 peptide, both strains responded to the peptide. After in vitro restimulation, B10.BR T cells responded as well as B10.S T cells. Similarly, some individual 102-118-specific T cell clones from mice of both haplotypes showed similar dose responses and fine specificity patterns. Thus, low responsiveness to this site is due neither to a hole in the repertoire nor to a failure to bind to the appropriate MHC molecule. An alternative explanation was suggested by the observation that, whereas B10.S T cells from peptide 102-118-immune mice responded almost as well to whole myoglobin as to the peptide, the B10.BR T cells from peptide immune mice, while responding well to peptide, were poorly stimulated by whole myoglobin. Thus, the product of natural processing of equine myoglobin probably has hindering structures in the regions flanking the core epitope 102-118 that interfere with presentation by I-Ak but not I-AS. The second line of evidence that processing of native myoglobin may influence the apparent specificity of the T cell response was obtained using the I-Ad-restricted sperm whale myoglobin 102-118-specific clone 9.27. This clone discriminated readily between whole sperm whale myoglobin and equine myoglobin, but it did not distinguish between peptides corresponding to 102-118 of the sperm whale and equine sequences. This distinction between equine peptide and native equine myoglobin could be overcome by artificial "processing" of equine myoglobin with cyanogen bromide. In both sets of experiments, F1 APCs that present the same epitope well to T cells of another haplotype failed to overcome the defect, which was therefore not due to the availability of different processed cleavage fragments in APC of different haplotypes, as would be expected if there were MHC-linked processing. Thus, the differential responses to peptides versus native molecule for both I-Ad- and I-Ak-restricted clones appeared to depend on the restricting molecule used.(ABSTRACT TRUNCATED AT 400 WORDS)
Flat Dosing of Carboplatin Is Justified in Adult Patients with Normal Renal Function
Authors: Corine Ekhart, Milly E. de Jonge, Alwin D.R. Huitema, Jan H.M. Schellens, Sjoerd Rodenhuis, Jos H. Beijnen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The Calvert formula is a widely applied algorithm for the a priori dosing of carboplatin based on patients glomerular filtration rate (GFR) as accurately measured using the 51Cr-EDTA clearance. Substitution of the GFR in this formula by an estimate of creatinine clearance or GFR as calculated by formulae using serum creatinine (SCR; Cockcroft-Gault, Jelliffe, and Wright) is, however, routine clinical practice in many hospitals. The goal of this study was to validate this practice retrospectively in a large heterogeneous adult patient population. Experimental Design: Concentration-time data of ultrafilterable platinum of 178 patients (280 courses, 3,119 samples) with different types of cancer receiving carboplatin-based chemotherapy in conventional and high doses were available. Data were described with a linear two-compartment population pharmacokinetic model. Relations between SCR-based formulae for estimating renal function and carboplatin clearance were investigated. Results: None of the tested SCR-based estimates of renal function were relevantly related to the pharmacokinetic variables of carboplatin. Neither SCR (median, 51; range, 18-124 μmol/L) nor the estimated GFR using the three different formulae was related to carboplatin clearance. Conclusions: Our data do not support the application of modifications of the Calvert formula by estimating GFR from SCR in the a priori dosing of carboplatin in patients with relatively normal renal function (creatinine clearance, &amp;gt;50 mL/min). For targeted carboplatin exposures, the original Calvert formula, measuring GFR using the 51Cr-EDTA clearance, remains the method of choice. Alternatively, in patients with normal renal function, a flat dose based on the mean population carboplatin clearance should be administered.
Melanoma Cells Present a MAGE-3 Epitope to CD4+ Cytotoxic T Cells in Association with Histocompatibility Leukocyte Antigen DR11
Authors: Simona Manici, Tiziana Sturniolo, Maria Adele Imro, Juergen Hammer, Francesco Sinigaglia, Christoph Noppen, Giulio Spagnoli, Benedetta Mazzi, Matteo Bellone, Paolo Dellabona, Maria Pia Protti
Journal: The Journal of Experimental Medicine (1999)

In this study we used TEPITOPE, a new epitope prediction software, to identify sequence segments on the MAGE-3 protein with promiscuous binding to histocompatibility leukocyte antigen (HLA)-DR molecules. Synthetic peptides corresponding to the identified sequences were synthesized and used to propagate CD4+ T cells from the blood of a healthy donor. CD4+ T cells strongly recognized MAGE-3281–295 and, to a lesser extent, MAGE-3141–155 and MAGE-3146–160. Moreover, CD4+ T cells proliferated in the presence of recombinant MAGE-3 after processing and presentation by autologous antigen presenting cells, demonstrating that the MAGE-3 epitopes recognized are naturally processed. CD4+ T cells, mostly of the T helper 1 type, showed specific lytic activity against HLA-DR11/MAGE-3–positive melanoma cells. Cold target inhibition experiments demonstrated indeed that the CD4+ T cells recognized MAGE-3281–295 in association with HLA-DR11 on melanoma cells. This is the first evidence that a tumor-specific shared antigen forms CD4+ T cell epitopes. Furthermore, we validated the use of algorithms for the prediction of promiscuous CD4+ T cell epitopes, thus opening the possibility of wide application to other tumor-associated antigens. These results have direct implications for cancer immunotherapy in the design of peptide-based vaccines with tumor-specific CD4+ T cell epitopes.
Obesity, adipokines and asthma
Authors: T. Jartti, L. Saarikoski, L. Jartti, I. Lisinen, A. Jula, R. Huupponen, J. Viikari, O. T. Raitakari
Journal: Allergy (2009)

The prevalence of asthma and obesity is increasing concomitantly, but many aspects of this link are unclear. Our objective was to examine whether obesity is associated with asthma in three time points of life, and whether immunomodulatory adipokines, leptin and adiponectin are linked to overweight-associated asthma.We studied the association between obesity and asthma at ages 3-18 years [mean (SD), 10 years (5), n = 3582, year 1980], 9-24 years [16 years (5), n = 2764, 1986] and 24-39 years [32 years (5), n = 2620, 2001] in a prospective cohort study and further tested for associations with serum leptin and adiponectin concentrations. Data on allergy status, smoking and other laboratory values (serum insulin, plasma C-reactive protein and serum lipid values) were also analyzed.Allergy and parental asthma were significantly associated with asthma at all ages. At ages 24-39 years, but not earlier, body mass index (BMI) (odds ratio, OR 1.05; P = 0.019) and female gender (OR 1.56; P = 0.031) were independently associated with asthma. Increase in BMI was also associated with incident asthma during adulthood (OR 1.08; P = 0.030). Levels of leptin, adiponectin or any other obesity-related biomarker were not independently associated with asthma.Asthma is linked with obesity in adults, but our results do not support a significant role for leptin, adiponectin or any other obesity-related biomarker studied in this association. Other factors should be sought for better understanding the connection between obesity and asthma.
Insulin Resistance and Progression to Type 1 Diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)
Authors: Polly J. Bingley, Jeffrey L Mahon, Edwin A.M. Gale
Journal: Diabetes Care (2007)

Insulin resistance can modulate progression to type 1 diabetes in individuals with ongoing islet autoimmunity. We wanted to see whether measures of insulin resistance improved risk assessment in islet cell antibody (ICA)-positive relatives when added to other immune and metabolic markers.The retrospective cohort analysis included 213 family members participating in the European Nicotinamide Diabetes Intervention Trial. All were aged <25 years, with at least one islet antibody in addition to ICA >or=20 Juvenile Diabetes Foundation units. Median length of follow-up was 4.21 years, and 105 individuals developed diabetes. Oral and intravenous glucose tolerance tests were performed at baseline; antibodies to GAD, IA-2, and insulin were determined by radioimmunoassay; and insulin resistance was estimated by homeostasis model assessment. Risk was assessed by Cox regression analysisThe overall cumulative risk of diabetes within 5 years was 54.1% (95% CI 46.0-62.3). Multivariate analysis confirmed that baseline first-phase insulin response (FPIR) quartile (P < 0.0001), number of additional antibody markers (P < 0.0001), and 120-min glucose in the oral glucose tolerance test (P < 0.0001) were independent determinants of risk of progression, whereas addition of homeostasis model assessment of insulin resistance (HOMA2-IR) achieved only borderline significance (P = 0.06). HOMA2-IR was an independent determinant in participants with loss of FPIR (P = 0.025) but not in those with preserved FPIR (P = 0.3).These data suggest that insulin resistance accelerates progression to type 1 diabetes in antibody-positive relatives in whom insulin secretion is markedly reduced but does not affect progression when insulin secretion is relatively well preserved.
The Body Image and Relationships Scale: Development and Validation of a Measure of Body Image in Female Breast Cancer Survivors
Authors: Julia M. Hormes, Leslie A. Lytle, Cynthia R. Gross, Rehana L. Ahmed, Andrea B. Troxel, Kathryn H. Schmitz
Journal: Journal of Clinical Oncology (2008)

Purpose A self-report measure of body image in female breast cancer survivors, the Body Image and Relationships Scale (BIRS), was developed to address attitudes about appearance, health, physical strength, sexuality, relationships, and social functioning following treatment. Methods The 32-item measure, generated by expert consensus and revised based on focus group feedback, was administered to 95 female breast cancer participants twice within 1 to 2 weeks. Test-retest reliability, internal consistency, and validity of the measure were assessed using standard-scale construction techniques. The structure of the proposed measure was evaluated using exploratory factor analysis. Associations of the resulting factors and other variables were assessed using extreme groups analyses. Results The BIRS had satisfactory test-retest reliability and internal consistency. Principal axis factoring revealed three factors: (1) health and strength, (2) social barriers, and (3) appearance and sexuality. Correlations of the subscales with standardized measures of related constructs were significant and in the anticipated directions. Extreme groups analyses suggested associations between less physical activity and more impairment on factors 1 and 3, premenopausal status at first diagnosis and more impairment on factor 2, and younger age at the time of survey administration and more impairment on factor 3. Conclusion The proposed scale demonstrated satisfactory reliability and internal consistency. Factor analysis revealed three subscales with coherent item content and differential associations with measures of activity level, menopause status, and age. Observed relationships with other measures support convergent and divergent validity. Results suggest that the proposed scale is useful for clinical and research applications.
Interstitial lung disease in patients with scleroderma: treatment with rituximab
Authors: A. Munoz, R. Martinez, M. Leon, F. Gallo, M. L. Velloso, S. Rodriguez, L. Mayordomo, E. Rejon, J. L. Marenco
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Introduction</h3> Interstitial lung disease (ILD) is a severe complication of systemic sclerosis, more common among patients with diffuse scleroderma. Cyclophosphamide (CYC) is the treatment normally used in those patients, with irregular response. The authors have successfully treated three patients refractory to CYC with rituximab (RTX). <h3>Patients and methods</h3> <i>Patient 1</i>: A 43-year-old woman developed progressive cough and dyspnea, with radiological changes of ILD. She began treatment with oral glucocorticoids and monthly boluses of CYC (1 g intravenously). <i>Patient 2</i>: A 53-year-old woman with a diagnosis of diffuse scleroderma 3 years earlier, started with dyspnea during low strain at the beginning. ILD was diagnosed with characteristic ground glass pattern on thoracic CT. She was given six boluses of CYC and oral glucocorticoids. <i>Patient 3</i>: A 48-year-old women, with skin lesions suggestive of dermatomyositis (DM). In 2007 she was diagnosed of amyopathic DM with scleroderma overlap. Three 3 months after the diagnosis, she began with cough and dry expectoration, together with dyspnea. ILD was diagnosed with characteristic ground glass pattern on thoracic CT. She was initially treated monthly with CYC for 7 months. All patients, the authors started a treatment with RTX (2×1 g) plus CYC. <h3>Results</h3> Respiratory function tests showed improvements (see table 1). <h3>Conclusions</h3> Overexpression of B lymphocytes in Scleroderma pathogenesis, and the bad evolution of ILD in those patients aimed them to try RTX (anti-CD-20) after CYC failure. The authors have observed clinical improvement with respiratory test (table 1) without progression in lung CT changes. Further studies would be necessary to establish this therapeutic approach.