tbuckley/cabot-search huggingface dataset:
Stress-impaired transcription factor expression and insulin secretion in transplanted human islets
Authors: Chunhua Dai, Nora S. Kayton, Alena Shostak, Greg Poffenberger, Holly A. Cyphert, Radhika Aramandla, Courtney Thompson, Ioannis G. Papagiannis, Christopher Emfinger, Masakazu Shiota, John M. Stafford, Dale L. Greiner, Pedro L. Herrera, Leonard D. Shultz, Roland Stein, Alvin C. Powers
Journal: Journal of Clinical Investigation (2016)

Type 2 diabetes is characterized by insulin resistance, hyperglycemia, and progressive β cell dysfunction. Excess glucose and lipid impair β cell function in islet cell lines, cultured rodent and human islets, and in vivo rodent models. Here, we examined the mechanistic consequences of glucotoxic and lipotoxic conditions on human islets in vivo and developed and/or used 3 complementary models that allowed comparison of the effects of hyperglycemic and/or insulin-resistant metabolic stress conditions on human and mouse islets, which responded quite differently to these challenges. Hyperglycemia and/or insulin resistance impaired insulin secretion only from human islets in vivo. In human grafts, chronic insulin resistance decreased antioxidant enzyme expression and increased superoxide and amyloid formation. In human islet grafts, expression of transcription factors NKX6.1 and MAFB was decreased by chronic insulin resistance, but only MAFB decreased under chronic hyperglycemia. Knockdown of NKX6.1 or MAFB expression in a human β cell line recapitulated the insulin secretion defect seen in vivo. Contrary to rodent islet studies, neither insulin resistance nor hyperglycemia led to human β cell proliferation or apoptosis. These results demonstrate profound differences in how excess glucose or lipid influence mouse and human insulin secretion and β cell activity and show that reduced expression of key islet-enriched transcription factors is an important mediator of glucotoxicity and lipotoxicity.
AB0357 Hypothyroidism in Patients with Rheumatoid Arthritis and Its Relation to Disease Activity
Authors: E.A. Elattar, T.B. Younes, S.A. Mobasher
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The relationship between thyroid disease and rheumatic disorders has been the subject of considerable debate. Thyroid abnormal function and/or autoimmune thyroid disease (AITD) were observed in patients with rheumatoid arthritis (RA), what could be explained by the natural feature of autoimmune diseases and their tendency to overlap (1,2). <h3>Objectives</h3> To investigate the association of hypothyroidism and thyroid autoantibodies with RA and study their correlation with RA disease activity. <h3>Methods</h3> One hundred and fifty RA patients &amp; fifty control subjects were included in this study. RA patients were subjected to full medical &amp; rheumatological history and examination as well as routine lab tests. Patients and controls underwent thyroid function testing including thyroid antibodies. Patients9 disease activity was determined using the Modified Disease Activity Score (MDAS28), while their functional status was assessed with the Modified Health Assessment Questionnaire (MHAQ). <h3>Results</h3> The commonest thyroid dysfunction was hypothyroidism which was found in 36 RA patients (24%), followed by subclinical hypothyroidism in 6 patients (4%) while, subclinical hyperthyroidism was present in 2 patients (1.3%). AITD was present in 10 patients (6.6%) and absent in the controls. There was a significant positive correlation between TSH levels and RA disease activity parameters. <h3>Conclusions</h3> Hypothyroidism was the commonest thyroid disorder associated with RA, present in (24%) with a significant association with RA disease activity parameters. <h3>References</h3> Tunbridge WM, Vanderpump MP. (2000): Population screening for autoimmune thyroid disease. Endocrinol Metab Clin North Am.; 29(2): 239-253. Porkodi R, Ramesh S, Mahesh A, Kanakarani P, Rukmangathrajan S, Panchapakesa C. (2004).: Thyroid dysfunction in Sysytemic Lupus Erythematosus and Rheumatoid Arthritis. J Indian Rheumatol Assoc.; 12: 88 – 90. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4521
PTU-088 Non-coeliac Gluten Sensitivity Can Be Present In Inflammatory Bowel Disease, Not Just Irritable Bowel Syndrome
Authors: I Aziz, SN Winfield, A Kelsall, N Rugg, K Pearson, J Priest, DS Sanders
Journal: Gut (2014)

<h3>Introduction</h3> Self-reported gluten sensitivity (GS) commonly occurs in the absence of coeliac disease, and is termed non-coeliac gluten sensitivity (NCGS); a controversial, heterogeneous, clinical entity perceived by some to belong to the spectrum of irritable bowel syndrome (IBS) due its lack of putative biomarkers. <h3>Aims</h3> We evaluated whether NCGS may be reported in organic gastrointestinal pathologies. <h3>Methods</h3> A validated questionnaire screened for self-reported GS in four patient groups (cohort A); i) IBS, ii) crohns disease (CrD), iii) ulcerative colitis (UC) and iv) gastro-oesophageal reflux disease (GORD). In addition, the prevalence of organic pathology in a seperate group presenting and diagnosed with NCGS was also determined (cohort B). <h3>Results</h3> Cohort A: 59 cases of IBS (mean-age 32.7 yrs, 80% female), 75 CrD (mean-age 47.1 yrs, 59% female), 71 UC (mean-age 43.2 yrs, 68% female) and 109 GORD (mean-age 51.7 years, 61% female); <i>p</i> value for age &lt; 0.001 and gender 0.05. The presence of GS was 42.4% for IBS, 29% CrD, 25.3% UC and 18.3% for GORD. Adjusting for age and sex, IBS individuals were significantly more likely to self-report GS compared to individuals with GORD (p 0.02, OR 2.56, C. I 1.15–5.73). However, there was no difference in self-reported GS between IBS, CrD or UC. In CrD the presence of strictures (p 0.04, OR 3.12, C. I 1.03–9.45) and CrD-activity index &gt; 220 (p.0001, OR 8, C. I 2.45–2.62) were predictors of self-reporting GS. In contrast, a CrDAI score &lt; 150 was supportive of not being GS (p 0.002, OR 5.35, C. I 1.8–15.9). The simple colitis activity score did not influence the presence or absence of GS in UC. Cohort B: Analysis of 200 NCGS patients (mean-age 39.1 yrs, 83% female) shows that 3% were subsequently found to have organic pathology (two cases of UC, one case each of CrD and pyloric stricture). <h3>Conclusion</h3> NCGS is not exclusive to IBS and can also be seen in established organic gastrointestinal pathologies, such as inflammatory bowel disease. Its presence may be reflecting severe and stenotic disease. Occasionally, NCGS may be the first presentation of organic pathology. <h3>Disclosure of Interest</h3> None Declared.
FRI0477 Outcome of Large-Vessel Involvement in GIANT Cell Arteritis after 1-Year of Glucocorticoid Treatment: Prospective Study Using Computed Tompography Angiography
Authors: S. Prieto-González, A. García-Martínez, J. Hernández-Rodríguez, M.A. Alba, I. Tavera-Bahillo, M. Corbera-Bellalta, E. Planas-Rigol, G. Espígol-Frigolé, P. Arguis, M.C. Cid
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In a previous study, computed tomography angiography (CTA) disclosed signs of large-vessel vasculitis (LVV) in 67.5% of giant cell arteritis (GCA) patients at the time of diagnosis. Moreover, 15% of patients already had aortic dilation at that assessment. <h3>Objectives</h3> To prospectively evaluate the outcome of large-vessel involvement in GCA patients by comparing CTA findings at the time of diagnosis and those obtained after 1 year of GC treatment. <h3>Methods</h3> The 40 GCA-patients evaluated by CTA at diagnosis, were prospectively treated and followed, and scheduled a new CTA after approximately 1 year of treatment GC with homogeneous tapering schedule. Vessel wall thickening, contrast enhancement and vessel diameter at aorta and its tributaries were evaluated. Results were compared to those obtained at the time of GCA diagnosis. <h3>Results</h3> Follow-up CTA could be performed in 35 patients after a mean of 13.8 months (range from 12,5 to 24 months) of follow-up. Wall thickening suggesting LVV was still present in 17 patients (68% of the patients who initially had LVV). The number of affected segments and mean wall thickening significantly decreased with no patients developing new inflammatory lesions, new aortic dilation or increase in previous dilations. Moreover, contrast enhancement disappeared in almost all the patients (93.75% of 16 patients where this finding could be assessed). <h3>Conclusions</h3> After 1 year of GC treatment, CTA signs of LVV persisted in two thirds of patients who initially presented abnormal findings. However, wall thickening significantly decreased as well as the number of affected segments. Contrast enhancement practically disappeared and there were no changes in lumen diameters during this period of time. Longer follow-up would be necessary to determine clinical significance of these findings and their relationship with the development of aortic dilatation. Supported by SAF 11/30073. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5203
P4-11-19: Healthcare Resource Utilization among Breast Cancer Patients with Bone Metastases and Skeletal-Related Events: A Population-Based Cohort Study in Denmark (1997 - 2009).
Authors: M Yong, CF Christiansen, H Gammelager, C Sværke, V Chia, C Atchison, J Fryzek
Journal: Cancer Research (2011)

Abstract Background The healthcare resource utilization (HRU) of breast cancer patients who develop bone metastases and skeletal-related events (SREs) has not been well-characterized. Our objective was to describe the HRU associated with SREs in a large population-based cohort of Danish breast cancer patients with bone metastases and one or more SRE. Methods: We identified women diagnosed with incident breast cancer from January 1, 1997 through December 31, 2006 using the Danish Cancer Registry. We followed this cohort of patients for development of subsequent bone metastases and SREs identified through the Danish National Registry of Patients through December 31, 2009. SREs were defined as pathologic fracture, spinal cord compression, and radiation or surgery to bone. Among patients with only one SRE, the HRU period, composed of all HRU occurring within a 90-day period after the SRE and within a two-week diagnostic period prior to the SRE, was assessed. For patients with multiple SREs (each one separated by less than 90 days), the HRU period, composed of all HRU occurring within a two-week diagnostic period prior to the first SRE up until 90 days after the last SRE, was described. Patients may have had multiple HRU periods if SREs were separated by more than 90 days. The HRU summarized included number of inpatient hospitalizations, length of hospitalization stay, outpatient physician visits, emergency room visits, and procedures. Results: We identified 1,148 patients with bone metastases and SREs among 38,485 breast cancer patients. The mean age at breast cancer diagnosis for those who developed bone metastases and SREs was 59 years (SD, 13 years) and the majority (72%) of patients had multiple SREs during the first HRU period. Approximately 20% to 30% of patients with single and multiple SREs, respectively, died within the first HRU period. Overall, length of hospitalization was longest for patients with spinal cord compression followed by patients with pathologic fracture. In general, patients with multiple SREs had higher HRU compared to those with a single SRE in the first HRU period, particularly in length of hospitalization stay. Conclusion: SREs secondary to bone metastases are serious events. In Denmark, high HRU was observed in all patients with SREs, but especially in those with multiple SREs, where increased lengths of hospitalization were observed. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-19.
THE IMPACT OF BODY WEIGHT ON ADVERSE OUTCOMES WITH NOVEL ORAL ANTICOAGULANTS AND WARFARIN: PRELIMINARY RESULTS FROM THE INTEGRATE STUDY
Authors: Yining Xu, Teresa Kus, Isabelle Greiss, Martine Montigny, Jean-Francois Sarrazin, Danielle Dion, Robert Breton, Vidal Essebag, Vartan Mardigyan, Lawrence Rudski, Miguel Barrero Garcia, Mladen Palaic, Franco Sandrin, Francois Philippon, Gilles O’Hara, Thao Huynh
Journal: Journal of the American College of Cardiology (2016)
Microvascular Deposition of Complement Membrane Attack Complex in Dermatomyositis
Authors: John T. Kissel, Jerry R. Mendell, Kottil W. Rammohan
Journal: New England Journal of Medicine (1986)

We examined the role of the complement system in the pathogenesis of dermatomyositis. Using an antibody against the neoantigens of the terminal C5b-9 membrane attack complex, we performed immunocytochemical studies that localized this complex to the intramuscular microvasculature (arterioles and capillaries) of muscle biopsy specimens from 10 of 12 patients (83 percent) with childhood dermatomyositis and 5 of 19 patients (26 percent) with adult dermatomyositis. Fifty-two control specimens, including 14 from patients with polymyositis and 12 from patients with denervation atrophy (a condition known to be associated with necrotic capillaries), showed no deposition of membrane attack complex in the microvasculature. These findings indicate that the complement system is deposited, bound, and activated to completion within the intramuscular microvasculature of patients with dermatomyositis. In addition to providing further evidence for the presence of vasculopathy in dermatomyositis, these findings suggest a primary role for complement in mediating vessel injury in the disease, particularly in its childhood form.
A Comparison of Dietary Trends among Racial and Socioeconomic Groups in the United States
Authors: Barry M. Popkin, Anna Maria Siega-Riz, Pamela S. Haines
Journal: New England Journal of Medicine (1996)

Using data from a representative sample of adults, we compared dietary trends among blacks and whites of varying socioeconomic status. We developed comparable measures of diet and of the consumption of macronutrients and food groups for 6061 participants in the 1965 Nationwide Food Consumption Surveys, 16,425 in the 1977–1978 Nationwide Food Consumption Surveys, and 9920 in the 1989–1991 Continuing Survey of Food Intake by In-dividuals (all conducted by the U.S. Department of Agriculture). The primary outcome was the score (range, 0 to 16) on the Diet Quality Index, a composite of eight food-and-nutrient–based recommendations from the National Academy of Sciences. A score of 4 or less was considered to indicate a relatively more healthful diet, and a value of 10 or more a relatively less healthful diet.
The Association of Changes in Physical-Activity Level and Other Lifestyle Characteristics with Mortality among Men
Authors: Ralph S. Paffenbarger, Robert T. Hyde, Alvin L. Wing, I-Min Lee, Dexter L. Jung, James B. Kampert
Journal: New England Journal of Medicine (1993)

Recent trends toward increasing physical exercise, stopping cigarette smoking, and avoiding obesity may increase longevity. We analyzed changes in the lifestyles of Harvard College alumni and the associations of these changes with mortality.Men who were 45 to 84 years of age in 1977 and who had reported no life-threatening disease on questionnaires completed in 1962 or 1966 and again in 1977 were classified according to changes in lifestyle characteristics between the first and second questionnaires. We analyzed changes in their level of physical activity, cigarette smoking, blood pressure, and body weight, and the relation of these factors to mortality between 1977 and 1985.Of the 10,269 men, 476 died during this period (which totaled 90,650 man-years of observation). Beginning moderately vigorous sports activity (at an intensity of 4.5 or more metabolic equivalents) was associated with a 23 percent lower risk of death (95 percent confidence interval, 4 to 42 percent; P = 0.015) than not taking up moderately vigorous sports. Quitting cigarette smoking was associated with a 41 percent lower risk (95 percent confidence interval, 20 to 57 percent; P = 0.001) than continuing smoking, but with a 23 percent higher risk than constant nonsmoking. Men with recently diagnosed hypertension had a lower risk of death than those with long-term hypertension (relative risk, 0.75; 95 percent confidence interval, 0.55 to 1.02; P = 0.057), as did men with consistently normal blood pressure (relative risk, 0.52; 95 percent confidence interval, 0.40 to 0.68; P < 0.001). Maintenance of lean body mass was associated with a lower mortality rate than long-term, recent, or previous obesity. The associations between changes in lifestyle and mortality were independent and were largely undiminished by age. Our findings on death from coronary heart disease mirrored those on death from all causes.Beginning moderately vigorous sports activity, quitting cigarette smoking, maintaining normal blood pressure, and avoiding obesity were separately associated with lower rates of death from all causes and from coronary heart disease among middle-aged and older men.
Case 15-2013
Authors: Jatin M. Vyas, R. Gilberto González, Virginia M. Pierce
Journal: New England Journal of Medicine (2013)

A 76-year-old man with chronic renal disease was admitted to this hospital because of fever, worsening renal function, and confusion. Brain imaging revealed a small amount of material with restricted diffusion layering in the occipital horns of the lateral ventricles.
Prognostic value of interferon-γ release assays, a population-based study from a TB low-incidence country
Authors: Thomas Stig Hermansen, Troels Lillebaek, Kristina Langholz Kristensen, Peter H Andersen, Pernille Ravn
Journal: Thorax (2016)

The ability of interferon-γ release assays to predict the development of TB has been investigated in many studies, but few cases develop TB during follow-up limiting the generalisation of results.We assessed QuantiFERON-TB Gold In-Tube test (QFT) results from 15 980 Danish individuals and data on all TB cases in Denmark from 2005 to 2012 and determined the predictive value of the QFT for coprevalent TB (0-90 days after testing) and incident TB (>90 days).Coprevalent TB was diagnosed in 10.7% (183/1703) and 0.3% (38/13 463) cases with a positive and negative QFT, respectively. For the QFT-positive cases, coprevalent TB was more frequent among persons <35 years compared with those >35 years (19.3% vs 7.2%, p<0.001). The cohort was followed-up for 52 807 person-years, median follow-up time was 3.36 years. For incident TB, the positive and negative predictive values (PPV and NPV) were 1.32% and 99.85%, respectively. Incidence rates (IR) for incident TB among QFT-positives and QFT-negatives were 383 per 10(5) and 45 per 10(5) person-years, respectively. Among cases with a positive QFT, IR for incident TB was associated with time interval since QFT (<2 years, p<0.001), but not with age (<35 years, p=0.087).We confirmed a high NPV of the QFT and found positive QFT associated with a higher risk of subsequent incident TB. Overall, the PPV for incident cases was 1.32%, and development of incident TB was associated with time interval after the QFT, but not with age.
Effect of an improved biomass stove on acute lower respiratory infections in young children in rural Nepal: a cluster-randomised, step-wedge trial
Authors: James M Tielsch, Joanne Katz, Subarna K Khatry, Laxman Shrestha, Patrick Breysse, Scott Zeger, William Checkley, Luke C Mullany, Naoko Kozuki, Steven C LeClerq, Ramesh Adhikari
Journal: The Lancet Global Health (2016)

Background Acute lower respiratory infections (ALRI) are an important cause of death in young children in low-income countries. High concentrations of fine particulate matter (PM2.5) indoors caused by open burning of biomass are associated with risk of ALRI. However, improved biomass stoves reduce emissions and might reduce the incidence of lower respiratory illness. A cluster-randomised, step-wedge, community-based trial was conducted to estimate the effect that a change from open burning of biomass to improved biomass stoves could have on rates of ALRI in children younger than 36 months in a rural area of southern Nepal.
Abstract 3513: MK-2206 combined with ridaforolimus or topoisomerase inhibitors synergistically impede the growth of sarcoma cells
Authors: Christopher L. Cubitt, Jillaina L. Menth, Jana L. Dawson, Damon R. Reed, Daniel M. Sullivan
Journal: Cancer Research (2011)

Abstract The number of effective drugs available for the treatment of soft tissue and bone sarcomas is limited to a small group of antineoplastic agents. The goal of this study was to determine the effectiveness of MK-2206 (Akt inhibitor) when used in combination with Ridaforolimus (mTor inhibitor), Cisplatin, Topotecan or Etoposide in a panel of ten cell lines. Six different types of sarcomas are represented in the panel, including rhabdo-, osteo-, Ewing, leiomyo-, lipo- and fibrosarcomas. Cell Titer-Blue cell viability experiments were performed to test dilutions of MK-2206 alone and in combination at various molar ratios over a 72 hour time period. The observed IC50s for MK-2206 or Ridaforolimus alone ranged from 4.2 to 12.9 µM or 23.7 to 62.3 µM, respectively. The observed IC50 range for Etoposide was 0.5 to 7.5 µM. To determine the relative potentiation of drug combinations, Excess over Highest Single Agent (HSA) analysis was performed (Table). The average Excess HSA score for MK-2206 combinations with Ridaforolimus or Etoposide were 0.17 and 0.15 respectively with levels of significance (p value) &amp;lt; 0.032. This was in contrast to MK-2206 combinations containing Cisplatin or Topotecan with average HSA scores of 0.084 and 0.085, respectively, indicating less potentiation. Using Chou and Talalay combination index (CI) analyses (effective dose levels of 0.7, 0.9 and 0.95), a synergistic to strongly synergistic reduction in cell viability was observed in 5 cell lines for MK-2206 plus Ridaforolimus and MK-2206 plus Etoposide combinations. Ongoing experiments are underway to identify the effects of MK-2206 combinations on apoptosis and the effect of drug sequencing on growth inhibition. The results of this study indicate that a MK-2206 plus Ridaforolimus or a MK-2206 plus Etoposide combination may be an effective treatment regimen for sarcoma patients. This work was funded by the Pediatric Cancer Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3513. doi:10.1158/1538-7445.AM2011-3513
A Comparison of the Effect of Vitamin B<sub>12</sub>with That of Liver Extract in the Treatment of Pernicious Anemia during Relapse and for Maintenance
Authors: William P. Murphy, Isabel Howard
Journal: New England Journal of Medicine (1952)

SINCE the isolation of vitamin B12 from liver and its extracts by Rickes and his associates1 and by Smith,2 sufficient evidence of its effectiveness for the control of pernicious anemia has been presented so that a detailed discussion of this question need not be included here. The early studies of West,3 Spies,4 West and Reisner5 and others have demonstrated that vitamin B12 when administered parenterally will initiate a remission of the anemia and control the other manifestations of the disease as liver does when ingested or given parenterally in extract form. Few direct comparisons of these effects and . . .