tbuckley/cabot-search huggingface dataset:
A comprehensive time-course–based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set
Authors: Timothy E. Sweeney, Aaditya Shidham, Hector R. Wong, Purvesh Khatri
Journal: Science Translational Medicine (2015)

Five publicly available gene expression cohorts comparing SIRS/trauma to sepsis were split into time-matched subcohorts and summarized via multicohort analysis, which yielded an 11-gene set that was validated for discriminating patients with sepsis or infection in 15 independent cohorts.
The treatment of malignant brain tumors in infants and very young children: An update of the Pediatric Oncology Group experience
Authors: Patricia K. Duffner, Marc E. Horowitz, Jeffrey P. Krischer, Peter C. Burger, Michael E. Cohen, Robert A. Sanford, Henry S. Friedman, Larry E. Kun
Journal: Neuro-Oncology (1999)

The State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY 14222, and the Roswell Park Cancer Institute, Buffalo, NY 14263 [P.K.D., M.E.C.]; Baylor College of Medicine, Houston, TX 77030 [M.E.H.]; H. Lee Moftt Cancer Center, Tampa, FL 33612 [J.P.K.]; The Johns Hopkins Hospital, Baltimore, MD 21287 [P.C.B.]; St. Jude Children’s Research Hospital, Memphis, TN 38101 [R.A.S., L.E.K.]; Duke University Medical Center, Durham, NC 27710 [H.S.F.]; and the Pediatric Oncology Group, Chicago, IL 60611
Case Number 26: Systemic idiopathic fibrosis associated with aortitis
Authors: O Schultz
Journal: Annals of the Rheumatic Diseases (2003)

Background: The progression of rheumatoid arthritis (RA) can be retarded or halted by disease modifying antirheumatic drugs (DMARDs).Next to inefficacy, toxicity limits their use.Objective: To explore the toxicity profiles of DMARDs in daily life.Patients and methods: Five hundred and ninety three patients with RA charts (>2300 patient years of treatment) were reviewed at two rheumatology outpatient clinics.All recorded data on toxicity and reasons for stopping treatment were collected.Results: Adverse events were common reasons for treatment discontinuation (42% of treatments).In 70% they were subjectively reported at the clinical visit, while substantial laboratory abnormalities were seen relatively rarely (9% of treatments: abnormal liver function tests in 5%; haematological abnormalities in 3%; impaired renal function in 1%).No single case of retinopathy from antimalarial drugs (that is, an incidence of <0.3 events/1000 patient years) was found, although eye examinations by the specialists were abnormal 30 times per 1000 patient years, mostly revealing keratopathy.Most commonly reported symptoms per 1000 patient years were nausea (54 events), abdominal pain (37 events), and rashes (34 events).Adverse events were more likely to occur with increasing number of consecutive DMARD courses. Conclusion:The first DMARD course in a patient seems to be safer than the consecutive ones.In addition, the incidence of adverse events (AEs) seems to be similar for high and low dose treatment.Data are also provided on types and incidence of AEs that are consistent with previous studies in other countries and different settings.. . . . . . .
Genetic and environmental influence on asthma: a population-based study of 11,688 Danish twin pairs
Authors: LR Skadhauge, K Christensen, KO Kyvik, T Sigsgaard
Journal: European Respiratory Journal (1999)

The aim of this study was to estimate the relative influence of genetic and environmental factors on the aetiology of asthma. The classic twin study design was used to analyse data on self-reported asthma obtained by a questionnaire mailed to 34,076 individuals, aged 12-41 yrs and originating from the Danish Twin Register. The cumulative incidence of asthma was 6.2% in the pooled sample. The data showed a decreasing cumulative incidence with age for males, but no sex or zygosity difference was observed. Substantially higher concordance rates, odds ratios and correlations for asthma were estimated in the monozygotic than in the dizygotic twins. Using biometric modelling, a model including additive genetic and nonshared environmental effects provided the best overall fit to the data. According to this model, 73% of the variation in liability to asthma was explained by genetic factors. No sex difference or age-dependency in the magnitude of genetic effects was observed. The biometric analysis emphasized a major influence of genetic factors in the aetiology of asthma. However, a substantial part of the variation in liability to asthma is due to the impact of environmental factors specific to the individual. There is no evidence for a substantial impact of genetic dominance or the shared environment.
PTH-189 Double Balloon Enteroscopy in the Elderly with Obscure GI Bleeding- is it Worth the Push and Pull?
Authors: R Sidhu, S Hardcastle, D S Sanders
Journal: Gut (2013)

<h3>Introduction</h3> Double Balloon enteroscopy (DBE) is an increasingly important procedure particularly in the context of obscure GI bleeding (OGB) with a high reported diagnostic yield. There is however paucity of data on its use in the elderly. The aim of this study was to assess the utility of DBE in the elderly and risk of complications compared to a younger cohort. <h3>Methods</h3> A prospective review of consecutive patients who underwent DBE over the last six years for the indication of OGB was conducted. The majority of patients underwent a capsule endoscopy prior to DBE, either locally or at our centre. Data was collected on demographics, procedure duration, dose of sedation/analgesia, diagnostic yield and subsequent change in management and complications encountered. Patients were divided into group 1: age≥ 70 years, group 2: age &lt; 70 years. <h3>Results</h3> One hundred and forty eight DBE procedures were carried out for the indications of OGB. The majority were for the indication of iron deficiency anaemia (IDA, n = 109.74%), 53% were males and the oral route was carried out in 69% of patients. Group 1 (age≥ 70 years) consisted of 27% (n = 40) of the cohort with a mean age of 77 years (range 70–83 years). There were 38% of patients with the presence of significant co-morbidity and four patients were on warfarin. The diagnostic yield in Group 1 was 53%. There was no significant difference in the yield between those with IDA and overt bleeding (p = 0.7). The commonest diagnosis in the elderly was angioectasia (45%, n = 18). The other findings included a small bowel tumour and mantle cell lymphoma (n = 2) and a Meckels diverticulum (n = 1). Therapeutics was performed in 45%. There was one respiratory arrest in a patient with known chronic airways disease (COPD). This patient was subsequently discharged home after a short stay on intensive care. The mean age in group 2 (n = 108) was 54 years, 44% females and the diagnostic yield was 35%. Comparison of the two groups demonstrated a trend towards a higher diagnostic yield in the elderly (p = 0.06). On logistic regression, previous transfusion requirement was associated with a higher yield with DBE in all patients (p = 0.04).Subsequent management was altered in a significant greater proportion of the elderly (28% versus 50%, p = 0.01, OR 2.6, 95% CI 1.2–5.5). There was no difference in the duration of the procedure between the two groups (p = 0.4), whilst the median dose of midazolam and fentanyl was significantly greater in group 2 (4.5 mg versus 6 mg, p &lt; 0.001, 50mcg versus 75mcg, p &lt; 0.001 respectively).There were no complications in group 2. <h3>Conclusion</h3> DBE has a high diagnostic yield with a positive impact on patient management in the elderly. Albeit low rate of complications, careful selection of patients would help reduce risks in this age group. <h3>Disclosure of Interest</h3> None Declared.
Cost-Effectiveness of 6 and 12 Months of Interferon-α Therapy for Chronic Hepatitis C
Authors: W. Ray Kim
Journal: Annals of Internal Medicine (1997)

Background: Interferon-α is effective in only a small number of patients with chronic hepatitis C, although prolonged treatment may increase the response rate. There is concern that the expense of interferon-α therapy may not be justified by the low response rates and uncertain long-term benefit. Objective: To compare clinical and economic outcomes after 6 months and 12 months of interferon-α therapy for chronic hepatitis C. Design: A Markov model depicting the natural progression of chronic hepatitis C. On the basis of this model, a simulated trial compared no therapy with 6 and 12 months of interferon-α therapy at standard doses (3 million U three times weekly). Patients: Four age-specific cohorts (30, 40, 50, and 60 years of age) with chronic hepatitis C. Measurements: Number of deaths from liver disease, total costs, and cumulative quality-adjusted life-years (QALYs). Results: Six and 12 months of interferon-α treatment gained 0.25 QALYs at an incremental cost of $1000 and 0.37 QALYs at an incremental cost of $1900, respectively. Thus, although 6 months of interferon-α therapy was less efficacious than 12 months of therapy, it was more cost-effective ($4000 per QALY gained compared with $5000 per QALY gained). Nonetheless, in patients younger than 60 years of age, both 6 and 12 months of therapy compared favorably with other established medical interventions, such as screening mammography and cholesterol reduction programs. Important variables affecting the cost-effectiveness of interferon-α treatment included the cost and efficacy of interferon-α, the cost of treatment for decompensated cirrhosis, and quality of life in patients with chronic hepatitis C. Conclusion: From the standpoint of cost-effectiveness, interferon-α therapy for 6 or 12 months may be justified in patients with chronic hepatitis C. The possible exception is patients older than 60 years of age.
Glutathione<i>S</i>-Transferase P1: Gene Sequence Variation and Functional Genomic Studies
Authors: Ann M. Moyer, Oreste E. Salavaggione, Tse-Yu Wu, Irene Moon, Bruce W. Eckloff, Michelle A.T. Hildebrandt, Daniel J. Schaid, Eric D. Wieben, Richard M. Weinshilboum
Journal: Cancer Research (2008)

Glutathione S-transferase P1 (GSTP1) is of importance for cancer research because of its role in detoxifying carcinogens, activating antineoplastic prodrugs, metabolizing chemotherapeutic agents, and its involvement in cell cycle and apoptosis regulation. Two common GSTP1 genetic polymorphisms have been studied extensively. However, the full range of GSTP1 genetic variation has not been systematically characterized in the absence of disease pathology. We set out to identify common GSTP1 polymorphisms in four ethnic groups, followed by functional genomic studies. All exons, splice junctions, and the 5'-flanking region of GSTP1 were resequenced using 60 DNA samples each from four ethnic groups. The 35 single-nucleotide polymorphisms (SNP) identified included six nonsynonymous SNPs and 17 previously unreported polymorphisms. GSTP1 variant allozymes were then expressed in COS-1 cells, and five displayed significantly altered levels of enzyme activity. One decreased to 22% of the wild-type (WT) activity. Four variant allozymes had K(m) values that differed significantly from that of the WT, and five showed altered levels of immunoreactive protein compared with WT, with a significant correlation (r = 0.79, P < 0.007) between levels of immunoreactive protein and enzyme activity in these samples. In the Mexican American population, five linked SNPs were significantly associated with GSTP1 mRNA expression, one of which was found by electrophoretic mobility shift assay to alter protein binding. These studies have identified functionally significant genetic variation, in addition to the two frequently studied GSTP1 nonsynonymous SNPs, that may influence GSTP1's contribution to carcinogen and drug metabolism, and possibly disease pathogenesis and/or drug response.
Effect of nitrazepam and flurazepam on the ventilatory response to carbon dioxide.
Authors: D M Geddes, M Rudolf, K B Saunders
Journal: Thorax (1976)

Ventilatory response to CO2 was measured before and after two different benzodiazepine hypnotics in both chronic bronchitics and patients without chest disease. Flurazepam, but not nitrazepam, produced a significant decrease in CO2 sensitivity, although there was no significant change in FEV1 or mixed venous PCO2. This is the first unequivocal evidence of central depression of respiration by a benzodiazepine and may be the mechanism by which benzodiazepines cause deterioration in patients with respiratory failure.
Environmental Cardiology
Authors: Aruni Bhatnagar
Journal: Circulation Research (2006)

Environmental factors are considered key determinants of cardiovascular disease. Although lifestyle choices such as smoking, diet, and exercise are viewed as major environmental influences, the contribution of pollutants and environmental chemicals is less clear. Accumulating evidence suggests that exposure to pollutants and chemicals could elevate the risk of cardiovascular disease. Many epidemiological studies report that exposure to fine particles present in ambient air is associated with an increase in cardiovascular mortality. Statistically significant relationships between particulate air pollution and ischemic heart disease, arrhythmias, and heart failure have been reported. Animal studies show that exposure to ambient air particles increases peripheral thrombosis and atherosclerotic lesion formation. Exposures to arsenic, lead, cadmium, pollutant gases, solvents, and pesticides have also been linked to increased incidence of cardiovascular disease. Mechanistically, these effects have been attributed to changes in the synthesis or reactivity of nitric oxide that may be caused by environmental oxidants or increased endogenous production of reactive oxygen species. Additional studies are urgently needed to: identify the contribution of individual pollutants to specific aspects of cardiovascular disease; establish causality; elucidate the underlying physiological and molecular mechanisms; estimate the relative susceptibility of diseased and healthy individuals and that of specific population groups; and determine whether pollutant exposure are risk correlates, that is, whether they influence major risk factors, such as hypertension, cholesterol, or diabetes, or whether they contribute to the absolute risk of heart disease. Collectively, these investigations could contribute to the emergent field of environmental cardiology.
Different Effects of Oral Conjugated Equine Estrogen and Transdermal Estrogen Replacement Therapy on Size and Oxidative Susceptibility of Low-Density Lipoprotein Particles in Postmenopausal Women
Authors: Akihiko Wakatsuki, Yuji Okatani, Nobuo Ikenoue, Takao Fukaya
Journal: Circulation (2002)

Background— Postmenopausal estrogen replacement therapy (ERT) has an antioxidant effect that opposes the oxidation of LDL particles. Oral ERT-induced increases in plasma triglyceride, however, decrease LDL particle size, which may counteract this antioxidant effect. Because transdermal ERT decreases plasma triglyceride, it may not decrease LDL particle size and may preserve estrogen’s antioxidant effect. The present study investigates whether transdermal ERT can eliminate the adverse effects of oral ERT on the size and oxidative susceptibility of LDL in postmenopausal women. Methods and Results— Postmenopausal women received no treatment (n=12) or were treated with either 0.625 mg oral conjugated equine estrogen daily (n=16) or with transdermal estradiol (50 μg/d, n=16) for 3 months. Plasma lipids and the diameter of LDL particles were determined. Susceptibility of LDL to oxidation was analyzed by incubation with CuSO 4 and subsequent measurement of thiobarbituric acid reactive substance (TBARS) concentrations. Oral ERT significantly increased plasma triglyceride and decreased LDL diameter but did not affect LDL-derived TBARS concentrations. In contrast, transdermal ERT significantly decreased the concentrations of plasma triglyceride and LDL-derived TBARS and significantly increased LDL diameter. Estrogen-induced changes in LDL diameter correlated negatively with changes in plasma triglyceride ( r =−0.51, P &lt;0.001) and LDL-derived TBARS ( r =−0.50, P &lt;0.001). Conclusions— Because transdermal, but not oral ERT, decreases plasma triglyceride and produces larger LDL particles that are resistant to oxidation, the antioxidant effect of estrogen can be preserved.
CTLA-4: a negative regulator of autoimmune disease.
Authors: N J Karandikar, C L Vanderlugt, T L Walunas, S D Miller, J A Bluestone
Journal: The Journal of Experimental Medicine (1996)

CTLA-4, a CD28 homologue expressed on activated T cells, binds with high affinity to the CD28 ligands, B7-1 (CD80) and B7-2 (CD86). This study was designed to examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating disease mediated by PLP139-151-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4 mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro-inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition of either reagent to in vitro activation cultures potentiated the ability of T cells to adoptively transfer disease to naive recipients. In vivo administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific T cells resulted in accelerated and exacerbated disease. Finally, anti-CTLA-4 treatment of mice during disease remission resulted in the exacerbation of relapses. Collectively, these results suggest that CTLA-4 mediates the downregulation of ongoing immune responses and plays a major role in regulating autoimmunity.
Role of I-region gene products in macrophage induction of an antibody response. II. Restriction at the level of T cell in recognition of I-J-subregion macrophage determinants.
Authors: J E Niederhuber, P Allen
Journal: The Journal of Experimental Medicine (1980)

The effect of specific anti-I-J reagents on macrophage-T cell interactions was studied in an in vitro antibody response to burro erythrocytes. Macrophages were prepared from the spleens of F1 hybrid mice whose parental strains differed at the I-J subregion. Two F1 hybrids were used for these experiments, [B10.A(3R) X B10.A(5R)]F1 and [B10.S(9R) X B10.HTT]F1. F1 macrophages responded equally well with F1 T-B cells or with T-B cells of either parental strain. When F1 macrophages were pretreated with anti-I-J serum (without complement) specific for one parental haplotype, they were only able to cooperate with T helper (TH) cells of the unblocked haplotype and with F1 TH cells. Identical results were obtained with (Jb X Jk)F1 and (Js X Jk)F1 mice. The results indicate that TH cells possess genetically restricted receptors for macrophage I-J-subregion gene products and that the interaction between this receptor and the macrophage I-J-subregion determinants is essential for the initiation of a primary in vitro antibody response to an erythrocyte antigen.
The Circadian Study:
Authors: Guido Freckmann, Lois Jovanovic, Annette Baumstark, Cornelia Haug, Wim van der Helm
Journal: Diabetes Care (2008)

Continuous subcutaneous insulin infusion (CSII) is the most advanced form of insulin administration in patients with type 1 diabetes. CSII can be initiated by one basal rate, providing the same amount of insulin every hour for the whole day, or by multiple basal rates providing a circadian variation of basal insulin with an increased infusion rate in the morning and evening hours (1). A circadian basal rate is considered to be closer to physiology and therefore to result in better glycemic control. Improved glycemia is thought to result mainly from an increase in insulin delivery in the early morning hours to antagonize the dawn phenomenon (2–4).

Individual adaptation of basal rates is time-consuming and frequently …
Changes in mechanical loading lead to tendonspecific alterations in MMP and TIMP expression: influence of stress deprivation and intermittent cyclic hydrostatic compression on rat supraspinatus and Achilles tendons
Authors: G M Thornton, X Shao, M Chung, P Sciore, R S Boorman, D A Hart, I K Y Lo
Journal: British Journal of Sports Medicine (2008)

Background Tendinopathy commonly occurs in tendons with large in vivo loading demands like the Achilles tendon (AT) and supraspinatus tendon (SST). In addition to differences in their local anatomic environment, these tendons are designed for different loading requirements because of the muscles to which they attach, with the AT experiencing higher loads than the SST. One possible factor in the progression of tendinopathy is the interplay between mechanical loading and the regulation of enzymes that degrade the extracellular matrix (matrix metalloproteinases (MMPs)) and their inhibitors (tissue inhibitor of metalloprotienases (TIMPs)). Thus, overuse injuries may have different biological consequences in tendons designed for different in vivo loading demands. Aim In this study, the tendon-specific regulation of MMP-13, MMP-3 and TIMP-2 expression in rat AT and SST exposed to two different mechanical environments was investigated. Methods Rat AT and SST were exposed to stress deprivation (ie, detached from attachments) and intermittent cyclic hydrostatic compression (with attachments intact). Levels of MMP-13, MMP-3 and TIMP-2 mRNA were evaluated in time-zero control, attached, stressdeprived and “compressed” tendons. Results Stress deprivation led to elevated expression of MMP-13, MMP-3 and TIMP-2 in both tendons, although the magnitude of the increase was greater for the SST than the AT. Intermittent cyclic hydrostatic compression of attached tendons increased expression of MMP-13 in the SST, but not the AT. Conclusions The results of this study suggest that stress deprivation may be one contributor to the progression of tendinopathy in AT and SST, where the tendon designed for the lower in vivo loading demand (SST) was the most affected by a change in mechanical loading. The unique upregulation of MMP-13 with hydrostatic compression supports the impingement injury theory for rotator cuff tears.
Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice
Authors: Gerold Bongers, Michelle E. Pacer, Thais H. Geraldino, Lili Chen, Zhengxiang He, Daigo Hashimoto, Glaucia C. Furtado, Jordi Ochando, Kevin A. Kelley, Jose C. Clemente, Miriam Merad, Harm van Bakel, Sergio A. Lira
Journal: The Journal of Experimental Medicine (2014)

The preferential localization of some neoplasms, such as serrated polyps (SPs), in specific areas of the intestine suggests that nongenetic factors may be important for their development. To test this hypothesis, we took advantage of transgenic mice that expressed HB-EGF throughout the intestine but developed SPs only in the cecum. Here we show that a host-specific microbiome was associated with SPs and that alterations of the microbiota induced by antibiotic treatment or by embryo transfer rederivation markedly inhibited the formation of SPs in the cecum. Mechanistically, development of SPs was associated with a local decrease in epithelial barrier function, bacterial invasion, production of antimicrobials, and increased expression of several inflammatory factors such as IL-17, Cxcl2, Tnf-α, and IL-1. Increased numbers of neutrophils were found within the SPs, and their depletion significantly reduced polyp growth. Together these results indicate that nongenetic factors contribute to the development of SPs and suggest that the development of these intestinal neoplasms in the cecum is driven by the interplay between genetic changes in the host, an inflammatory response, and a host-specific microbiota.