tbuckley/cabot-search huggingface dataset:
How to develop a more accurate risk prediction model when there are few events
Authors: Menelaos Pavlou, Gareth Ambler, Shaun R Seaman, Oliver Guttmann, Perry Elliott, Michael King, Rumana Z Omar
Journal: BMJ (2015)

When the number of events is low relative to the number of predictors, standard regression could produce overﬁtted risk models that make inaccurate predictions. Use of penalised regression may improve the accuracy of risk prediction
Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis
Authors: Ulrich Specks, Peter A. Merkel, Philip Seo, Robert Spiera, Carol A. Langford, Gary S. Hoffman, Cees G.M. Kallenberg, E. William St. Clair, Barri J. Fessler, Linna Ding, Lisa Viviano, Nadia K. Tchao, Deborah J. Phippard, Adam L. Asare, Noha Lim, David Ikle, Brett Jepson, Paul Brunetta, Nancy B. Allen, Fernando C. Fervenza, Duvuru Geetha, Karina Keogh, Eugene Y. Kissin, Paul A. Monach, Tobias Peikert, Coen Stegeman, Steven R. Ytterberg, Mark Mueller, Lourdes P. Sejismundo, Kathleen Mieras, John H. Stone
Journal: New England Journal of Medicine (2013)

The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is unknown.
Impact of intelligent volume assured pressure support on sleep quality, compliance and gas exchange in patients with stable hypercapnic COPD
Authors: Emelie Ekkernkamp, David Walker, Jan Hendrik Storre, Wolfram Windisch, Michael Dreher
Journal: European Respiratory Journal (2012)

Introduction: Noninvasive positive pressure ventilation (NPPV) using the technique of high-intensity-NPPV (HI-NPPV) has been shown to treat hypoventilation in stable hypercapnic COPD patients with an overall good sleep quality (SQ). iVAPS (intelligent volume assured pressure support) using target alveolar ventilation is a hybrid mode of NPPV. Its impact on SQ still needs to be addressed. The aim of the study was to compare SQ and gas exchange using iVAPS and HI-NPPV in hospital and at home.  Methods: In a randomized crossover design patients used iVAPS and HI-NPPV. Objective and subjective SQ as well as comfort with NPPV were assessed by polysomnography and questionnaires. Blood gas measurements were performed in hospital and at home. (Figure 1)  Results: 14 patients were included. Beside applied pressure being rated more disturbing with iVAPS, there was no further difference with regard to SQ in hospital. At home, patients reported more restful sleep using iVAPS. There was no difference in daily usage (6.2±1.6 vs. 6.5±1.3h, p=0.27). PaCO2 in hospital was lower during iVAPS (41±8mmHg vs. 44±7 mmHg; p=0.04), whereas no difference was found at home (43±7 vs. 44±10mmHg; p=0.37).  Conclusion: NPPV using iVAPS and HI-NPPV revealed no differences in SQ in hospital. At home, patients reported more restful sleep during iVAPS without differences in comfort with NPPV and daily usage.
Erosive oesophagitis: outcome of repeated long term maintenance treatment with low dose omeprazole 10 mg or placebo
Authors: K D Bardhan, P Cherian, A Vaishnavi, R B Jones, M Thompson, P Morris, A Brooks, J D’Silva, K R W Gillon, C Wason, J Patterson, J Polak, A Bishop
Journal: Gut (1998)

Aims —To investigate the efficacy of daily maintenance treatment with omeprazole 10 mg in reducing the relapse rate of healed erosive oesophagitis. Methods —Three hundred patients with erosive oesophagitis (grade 2 or greater) received omeprazole 20 mg daily for 12 weeks, followed by 40 mg daily for a further 12 weeks if required. After healing, patients were randomised to double blind treatment with omeprazole 10 mg daily or placebo for up to 18 months. On relapse the treatment cycle was repeated. Results —The cumulative healing rate at 12 weeks in the initial healing period was 95%, and 96% and 98% on rehealing courses after relapse in the first and second maintenance periods respectively. After 12 weeks of treatment, 98% of patients were free from heartburn and 97% were free of all reflux related symptoms. Relapse in the subgroup of patients who relapsed in both maintenance periods was infrequent on omeprazole 20 mg daily: only 9% at two years. Gastrin concentrations rose above normal in one third of patients. One patient had linear hyperplasia of endocrine cells and another had micronodular hyperplasia. There were no side effects definitely attributable to omeprazole. Conclusion —Maintenance treatment with omeprazole 10 mg daily keeps about 60% of patients with erosive oesophagitis in prolonged remission. Patients relapsing once are likely to do so again; they can subsequently be treated effectively with omeprazole 20 mg daily.
Positive association of genetic variants in the upstream region of NKX2-3 with Crohn's disease in Japanese patients
Authors: K Yamazaki, A Takahashi, M Takazoe, M Kubo, Y Onouchi, A Fujino, N Kamatani, Y Nakamura, A Hata
Journal: Gut (2008)

<h3>Background and aims:</h3> A number of genome-wide association studies have been performed as a robust means of identifying susceptibility loci for Crohn's disease (CD). The loci detected after the completion of the HapMap project are quite concordant among these studies, suggesting that the results are reliable. Recently, the Wellcome Trust Case Control Consortium (WTCCC) reported the primary scanning of 17 000 individuals for seven diseases, including CD, and a subsequent study has validated these susceptible genetic variants in independent UK sample sets. The purpose of this study was to study the possible association of the variants reported by the WTCCC with CD in a Japanese population. <h3>Patients and methods:</h3> A total of 484 patients with CD and 470 healthy controls were examined. Seventeen genetic variants at eight newly identified loci, including <i>IRGM</i>, <i>NKX2-3</i> and <i>PTPN2</i>, were genotyped using the TaqMan assay or the invader assay. <h3>Results:</h3> A positive association signal presumably common to different ethnic groups for rs10883365 was detected in the upstream region of <i>NKX2-3</i> (p = 0.019 under the genotypic model, p = 0.0065 under the allelic model, p = 0.019 under the recessive model, p = 0.036 under the dominant model). In addition to rs10883365, marginal associations for two single nucleotide polymorphisms (SNPs) were detected in the Japanese population; rs6887695 near <i>IL12B</i> and rs10761659 on 10q21. Further genotype–phenotype analysis found a significant association between rs6887695 and patients with pure ileal CD. <h3>Conclusions:</h3> The results indicate that the three loci are possible candidates for conferring susceptibility to CD in people of different ethnicities.
The B Cell Antigen Receptor Controls Integrin Activity through Btk and PLCγ2
Authors: Marcel Spaargaren, Esther A. Beuling, Mette L. Rurup, Helen P. Meijer, Melanie D. Klok, Sabine Middendorp, Rudolf W. Hendriks, Steven T. Pals
Journal: The Journal of Experimental Medicine (2003)

Integrin-mediated adhesion and B cell antigen receptor (BCR) signaling play a critical role in B cell development and function, including antigen-specific B cell differentiation. Here we show that the BCR controls integrin alpha4beta1 (VLA-4)-mediated adhesion of B cells to vascular cell adhesion molecule-1 and fibronectin. Molecular dissection of the underlying signaling mechanism by a combined biochemical, pharmacological, and genetic approach demonstrates that this BCR-controlled integrin-mediated adhesion requires the (consecutive) activation of Lyn, Syk, phosphatidylinositol 3-kinase, Bruton's tyrosine kinase (Btk), phospholipase C (PLC)gamma2, IP3R-mediated Ca2+ release, and PKC. In contrast, activation of mitogen-activated protein kinase kinase (MEK) or extracellular signal-regulated kinase (ERK) is not required, and simultaneous activation of MEK, ERK, and PKB is not sufficient either. Furthermore, Btk is also involved in the control of integrin-mediated adhesion of preB cells. The control of integrin alpha4beta1-mediated B cell adhesion by the BCR involves cytoskeletal reorganization and integrin clustering. These results reveal a novel function for the BCR and Btk, i.e., regulation of integrin alpha4beta1 activity, thereby providing new insights into the control of B cell development and differentiation, as well as into the pathogenesis of the immunodeficiency disease X-linked agammaglobulineamia (XLA).
An analysis of β‐lactam‐derived antigens on spleen cell and serum proteins by ELISA and Western blotting
Authors: E. V. Wairbrick, A. L. Thomas, V. Stejskal, J. W. Coleman
Journal: Allergy (1995)

Penicillins and related β‐lactam antibiotics are known to conjugate to proteins to generate potentially antigenic (haptenic) determinants. In the present study, we used a rabbit polyclonal antibody raised against benzylpenicillin (BP) to investigate the capacity of six penicillins and one cephalosporin to generate haptenic groups in vitro on cultured mouse spleen cells and on serum proteins in the culture medium. All of the drugs tested, namely, BP, amoxicillin (AMX), ampicillin (AMP), cephalothin (CEP), cloxacillin (CLX), flucloxacillin (FLX), and phenoxymethylpenicillin (PMP) generated antigens in a concentration‐dependent manner on cell and serum proteins, which could be detected by ELISA, although antigens generated by BP, CEP, FLX, or PMP in either cell‐ or serum‐conjugated form were more readily detected than those generated by AMX, AMP, or CLX. Western blot analysis revealed that BP‐derived antigens were generated relatively slowly on cell proteins (maximum binding was not yet reached after 8 h), compared to serum proteins (maximum binding within 1 h). BP, CEP, and PMP all generated similar distinctive patterns of immunostaining of electrophoresed cell or serum proteins which did not reflect the relative abundance of different proteins as revealed by Coomassie brilliant blue staining. FLX, CLX, AMP, and AMX did not generate antigens that could be detected on Western blots. In conclusion, we have shown that various β‐lactam antibiotics generate antigens on cell and serum proteins that can be detected and characterized immunochemically with polyclonal antiserum. Further application of these methods may offer potential for further identification of immunologically relevant cellular and serum antigens generated by these drugs.
Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051)
Authors: A.C. Lockhart, C.E. Reed, P.A. Decker, B.F. Meyers, M.K. Ferguson, A.R. Oeltjen, J.B. Putnam, S.D. Cassivi, A.J. Montero, T.E. Schefter
Journal: Annals of Oncology (2014)
SUPPRESSION OF EXPERIMENTAL "ALLERGIC" ENCEPHALOMYELITIS IN GUINEA PIGS BY ENCEPHALITOGENIC PROTEINS EXTRACTED FROM HOMOLOGOUS BRAIN
Authors: Cheng-Mei Shaw, Willson J. Fahlberg, Marian W. Kies, Ellsworth C. Alvord
Journal: The Journal of Experimental Medicine (1960)

The intradermal injection of aqueous solutions of certain homologous neural proteins will suppress the encephalomyelitis which is induced in guinea pigs by the previous injection of whole homologous brain with Freund's adjuvants. These neural proteins extracted by dilute acid from defatted guinea pig brain are themselves highly encephalitogenic when injected with adjuvants, but the specificity of this suppression for encephalitogenic as compared to non-encephalitogenic extracts remains to be proven. Suppression is probably not due to a non-specific stress reaction, as indicated by the absence of suppression by intradermal injections of alcohol and by statistically insignificant and inconstant effects of similar injections of tuberculin.
Myocardial Mechanics and Collagen Structure in the Osteogenesis Imperfecta Murine ( <i>oim</i> )
Authors: Sara M. Weis, Jeffrey L. Emery, K. David Becker, Daniel J. McBride, Jeffrey H. Omens, Andrew D. McCulloch
Journal: Circulation Research (2000)

Abstract —Because the amount and structure of type I collagen are thought to affect the mechanics of ventricular myocardium, we investigated myocardial collagen structure and passive mechanical function in the osteogenesis imperfecta murine ( oim ) model of pro-α2(I) collagen deficiency, previously shown to have less collagen and impaired biomechanics in tendon and bone. Compared with wild-type littermates, homozygous oim hearts exhibited 35% lower collagen area fraction ( P &lt;0.05), 38% lower collagen fiber number density ( P &lt;0.05), and 42% smaller collagen fiber diameter ( P &lt;0.05). Compared with wild-type, oim left ventricular (LV) collagen concentration was 45% lower ( P &lt;0.0001) and nonreducible pyridinoline cross-link concentration was 22% higher ( P &lt;0.03). Mean LV volume during passive inflation from 0 to 30 mm Hg in isolated hearts was 1.4-fold larger for oim than wild-type ( P =NS). Uniaxial stress-strain relations in resting right ventricular papillary muscles exhibited 60% greater strains ( P &lt;0.01), 90% higher compliance ( P =0.05), and 64% higher nonlinearity ( P &lt;0.05) in oim . Mean opening angle, after relief of residual stresses in resting LV myocardium, was 121±9 degrees in oim compared with 45±4 degrees in wild-type ( P &lt;0.0001). Mean myofiber angle in oim was 23±8 degrees greater than wild-type ( P &lt;0.02). Decreased myocardial collagen diameter and amount in oim is associated with significantly decreased fiber and chamber stiffness despite modestly increased collagen cross-linking. Altered myofiber angles and residual stress may be beneficial adaptations to these mechanical alterations to maintain uniformity of transmural fiber strain. In addition to supporting and organizing myocytes, myocardial collagen contributes directly to ventricular stiffness at high and low loads and can influence stress-free state and myofiber architecture.
Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database
Authors: I. Tzoulaki, M. Molokhia, V. Curcin, M. P Little, C. J Millett, A. Ng, R. I Hughes, K. Khunti, M. R Wilkins, A. Majeed, P. Elliott
Journal: BMJ (2009)

<b>Objective</b> To investigate the risk of incident myocardial infarction, congestive heart failure, and all cause mortality associated with prescription of oral antidiabetes drugs. <b>Design</b> Retrospective cohort study. <b>Setting</b> UK general practice research database, 1990-2005. <b>Participants</b> 91 521 people with diabetes. <b>Main outcome measures</b> Incident myocardial infarction, congestive heart failure, and all cause mortality. Person time intervals for drug treatment were categorised by drug class, excluding non-drug intervals and intervals for insulin. <b>Results</b> 3588 incident cases of myocardial infarction, 6900 of congestive heart failure, and 18 548 deaths occurred. Compared with metformin, monotherapy with first or second generation sulphonylureas was associated with a significant 24% to 61% excess risk for all cause mortality (P&lt;0.001) and second generation sulphonylureas with an 18% to 30% excess risk for congestive heart failure (P=0.01 and P&lt;0.001). The thiazolidinediones were not associated with risk of myocardial infarction; pioglitazone was associated with a significant 31% to 39% lower risk of all cause mortality (P=0.02 to P&lt;0.001) compared with metformin. Among the thiazolidinediones, rosiglitazone was associated with a 34% to 41% higher risk of all cause mortality (P=0.14 to P=0.01) compared with pioglitazone. A large number of potential confounders were accounted for in the study; however, the possibility of residual confounding or confounding by indication (differences in prognostic factors between drug groups) cannot be excluded. <b>Conclusions</b> Our findings suggest a relatively unfavourable risk profile of sulphonylureas compared with metformin for all outcomes examined. Pioglitazone was associated with reduced all cause mortality compared with metformin. Pioglitazone also had a favourable risk profile compared with rosiglitazone; although this requires replication in other studies, it may have implications for prescribing within this class of drugs.
Calcium Concentration of Individual Coronary Calcified Plaques as Measured by Multidetector Row Computed Tomography
Authors: Fabian Moselewski, Christopher J. O’Donnell, Stephan Achenbach, Maros Ferencik, Joe Massaro, Ann Nguyen, Ricardo C. Cury, Suhny Abbara, Ik-Kyung Jang, Thomas J. Brady, Udo Hoffmann
Journal: Circulation (2005)

Characteristics of individual calcified plaques, especially calcium concentration (CC), may provide incremental value to global calcium scores in the assessment of plaque burden and risk of coronary events and evaluation of therapeutic intervention. In this study, therefore, we assessed the characteristics of individual calcified plaques and their relationship to other parameters derived from CT analysis of coronary calcium in a community-based cross-sectional cohort.Coronary artery calcium (CAC) was analyzed in 612 participants of the Framingham Heart Study (third-generation and offspring cohorts) using prospectively ECG-triggered multidetector CT. We determined the CC, Agatston score, calcified volume, and mineral mass of individual calcified plaques in each subject. Heterogeneity of CC was defined as the standard deviation of CC of all individual calcified plaques in a subject. CAC was detected in 274 of 605 subjects. After excluding 57 subjects (21%) because of motion artifacts, we identified a total of 956 calcified coronary plaques in 217 subjects (74 women, 143 men; mean age, 57.1+/-10.8 years) with detectable CAC and no image artifacts. CC of individual calcified plaques was independent of subject age (P=0.76) and sex (197.8+/-74.8 versus 183.6+/-52.8 mg/cm3 for men versus women; P=0.21). Among a subgroup of 125 subjects with multiple (> or =3) individual calcified plaques, CC was heterogeneous within individual subjects (mean SD of CC, 43.6+/-23.1 mg/cm3). The degree of heterogeneity of CC in these subjects was independent of age (P=0.60), sex (P=0.99), and number of plaques (P=0.06).The CC of individual calcified plaques is independent of age and sex but heterogeneous within a subject, which may reflect that the pathological process of calcified plaque formation and progression is the same in men and women regardless of age. CC may have incremental value to global calcium scores in the assessment of plaque burden and risk of coronary events and the evaluation of therapeutic intervention. Further studies are warranted to confirm that individual plaque analysis is preferable to global CAC scores to evaluate progression of atherosclerosis and to assess whether individual plaque analysis may be complementary to global CAC measures to assess coronary event risk.
Abnormal Tryptophan Metabolism in Patients with Adult Celiac Disease, with Evidence for Deficiency of Vitamin B6*
Authors: O. Dhodanand Kowlessar, Lorraine J. Haeffner, Gordon D. Benson
Journal: Journal of Clinical Investigation (1964)

Increased urinary excretion of certain aromatic metabolites of tryptophan has been described in a wide variety of pathologic conditions: pyridox- ine deficiency either primary or secondary to isoniazid or deoxypyridoxine (1); metabolic dis- eases such as in phenylketonuria (2), porphyria (3, 4), and Hartnup's disease (5); a variety of malignancies-metastatic malignant carcinoid (6), bladder carcinoma (4, 7), leukemia (8), and lymphoma (8); mental disorders (4); pregnancy (9, 10) ; and collagen vascular diseases (4, 11).Recently, elevated urinary levels of 5-hydroxyindoleacetic acid and indole-3-acetic acid have been found in symptomatic, untreated adult celiac disease with subsequent fall to normal during clini- cal and biochemical remission (12, 13).To study this abnormality further, we measured six urinary metabolites of tryptophan simultaneously in patients with adult celiac disease in various stages of their illness both before and after tryp- tophan loading.Also assessed was the role of vitamin B6 deficiency in the abnormal tryptophan metabolism of this disease.
Computed Tomographic Measurements of Airway Dimensions and Emphysema in Smokers
Authors: YASUTAKA NAKANO, SHIGEO MURO, HIROAKI SAKAI, TOYOHIRO HIRAI, KAZUO CHIN, MITSUHIRO TSUKINO, KOICHI NISHIMURA, HARUMI ITOH, PETER D. PARÉ, JAMES C. HOGG, MICHIAKI MISHIMA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow obstruction caused by emphysema or airway narrowing, or both. Low attenuation areas (LAA) on computed tomography (CT) have been shown to represent macroscopic or microscopic emphysema, or both. However CT has not been used to quantify the airway abnormalities in smokers with or without airflow obstruction. In this study, we used CT to evaluate both emphysema and airway wall thickening in 114 smokers. The CT measurements revealed that a decreased FEV1 (%predicted) is associated with an increase of airway wall area and an increase of emphysema. Although both airway wall thickening and emphysema (LAA) correlated with measurements of lung function, stepwise multiple regression analysis showed that the combination of airway and emphysema measurements improved the estimate of pulmonary function test abnormalities. We conclude that both CT measurements of airway dimensions and emphysema are useful and complementary in the evaluation of the lung of smokers.
Smoking and asthma.
Authors: F E Cayley
Journal: BMJ (1978)

perimentally it is well established that once the endothelial barrier is breeched the stage is set for atherosclerosis and even a mild rise in plasma cholesterol concentration above 5 5 mmol/l (220 mg/100 ml) is sufficient to induce atherosclerotic change.However, changes may develop before there is any detectable rise in blood lipids.4It is hardly to be expected that dietary cholesterol as calculated from tables and on a single occasion would be representative of the usual amount consumed from day to day and over the many years of developing athero- sclerosis.However, it is known that dietary cholesterol contributes about one-quarter to one-third to plasma cholesterol,> which is a very substantial amount since the body synthesises all its requirements.Plasma concentrations are also greatly influenced by the amount and composition of fat in the diet.Professor Yudkin makes no reference to these important aspects, an appreciation of which puts the situation into better prospective.
Retroviruses in rheumatoid arthritis.
Authors: G S Panayi, A G Dalgleish
Journal: Annals of the Rheumatic Diseases (1986)

seen, but for the majority of patients the slight reduction in longevity is in no way equivalent to that in the lymphomas.While we may anguish over the ravaging and debilitating aspects of this disease, I do not think this justifies, at the