tbuckley/cabot-search huggingface dataset:
Development and validation of risk prediction equations to estimate future risk of blindness and lower limb amputation in patients with diabetes: cohort study
Authors: J. Hippisley-Cox, C. Coupland
Journal: BMJ (2015)

<b>Study question</b> Is it possible to develop and externally validate risk prediction equations to estimate the 10 year risk of blindness and lower limb amputation in patients with diabetes aged 25-84 years? <b>Methods</b> This was a prospective cohort study using routinely collected data from general practices in England contributing to the QResearch and Clinical Practice Research Datalink (CPRD) databases during the study period 1998-2014. The equations were developed using 763 QResearch practices (n=454 575 patients with diabetes) and validated in 254 different QResearch practices (n=142 419) and 357 CPRD practices (n=206 050). Cox proportional hazards models were used to derive separate risk equations for blindness and amputation in men and women that could be evaluated at 10 years. Measures of calibration and discrimination were calculated in the two validation cohorts. <b>Study answer and limitations</b> Risk prediction equations to quantify absolute risk of blindness and amputation in men and women with diabetes have been developed and externally validated. In the QResearch derivation cohort, 4822 new cases of lower limb amputation and 8063 new cases of blindness occurred during follow-up. The risk equations were well calibrated in both validation cohorts. Discrimination was good in men in the external CPRD cohort for amputation (D statistic 1.69, Harrell’s C statistic 0.77) and blindness (D statistic 1.40, Harrell’s C statistic 0.73), with similar results in women and in the QResearch validation cohort. The algorithms are based on variables that patients are likely to know or that are routinely recorded in general practice computer systems. They can be used to identify patients at high risk for prevention or further assessment. Limitations include lack of formally adjudicated outcomes, information bias, and missing data. <b>What this study adds</b> Patients with type 1 or type 2 diabetes are at increased risk of blindness and amputation but generally do not have accurate assessments of the magnitude of their individual risks. The new algorithms calculate the absolute risk of developing these complications over a 10 year period in patients with diabetes, taking account of their individual risk factors. <b>Funding, competing interests, data sharing</b> JH-C is co-director of QResearch, a not for profit organisation which is a joint partnership between the University of Nottingham and Egton Medical Information Systems, and is also a paid director of ClinRisk Ltd. CC is a paid consultant statistician for ClinRisk Ltd.
Cardiometabolic Risk Profiles and Carotid Atherosclerosis in Individuals With Prediabetes Identified by Fasting Glucose, Postchallenge Glucose, and Hemoglobin A1c Criteria
Authors: Maria A. Marini, Elena Succurro, Ersilia Castaldo, Sabrina Cufone, Franco Arturi, Angela Sciacqua, Renato Lauro, Marta L. Hribal, Francesco Perticone, Giorgio Sesti
Journal: Diabetes Care (2012)

We evaluated whether cardiometabolic risk profiles differ for subjects identified as having prediabetes by A1C, fasting glucose (FPG), or 2-h postchallenge glucose (2-PG) criteria.Atherosclerosis risk factors, oral glucose tolerance test, and ultrasound measurement of carotid intima-media thickness (IMT) were analyzed in 780 nondiabetic individuals.Poor agreement existed for A1C and FPG criteria for identification of subjects with prediabetes (κ coefficient = 0.332). No differences in cardiometabolic risk profiles were observed among the three groups of individuals with prediabetes by A1C only, FPG only, and both A1C and FPG. Poor agreement also existed for A1C and 2-PG criteria for identification of individuals with prediabetes (κ coefficient = 0.299). No significant differences in cardiometabolic risk factors were observed between IGT-only and individuals with prediabetes by A1C and 2-PG. Compared with subjects with prediabetes identified by A1C only, IGT-only individuals exhibited a worse cardiometabolic risk profile, with significantly higher systolic blood pressure, pulse pressure, 2-h postchallenge insulin, triglycerides, high-sensitivity C-reactive protein, and carotid IMT, and lower HDL cholesterol levels and insulin sensitivity.These results suggest that considerable discordance between A1C, FPG, and 2-PG exists for the identification of individuals with prediabetes and that the cardiometabolic risk profile of these individuals varies by metabolic parameter, with 2-PG showing the stronger association with cardiometabolic risk factors and subclinical atherosclerosis than FPG or A1C.
IgG4 associated autoimmune hepatitis: a differential diagnosis for classical autoimmune hepatitis
Authors: T Umemura, Y Zen, H Hamano, T Ichijo, S Kawa, Y Nakanuma, K Kiyosawa
Journal: Gut (2007)

Autoimmune pancreatitis is characterised by raised serum levels of IgG4 and IgG4-bearing plasma cells in the inflammatory tissue.1 Similar pathology can also occur in the larger bile ducts, resembling sclerosing cholangitis.2 We report a patient with hepatitis and chronic cholecystitis, raised IgG4 level, and IgG4-bearing plasma cells in the liver and gall bladder wall, but no evident pancreatic disease.

In January 2003, a cholecystectomy was undertaken on a 54 year old woman for chronic cholecystitis. The extracted gall bladder showed lymphoplasmacytic infiltration and subserosal fibrosis. A liver biopsy was done because of abnormal liver function tests and showed severe lobular hepatitis with mild portal inflammation. Plasma cell infiltration was observed in the portal tracts and parenchyma, though fibrosis was not significant. IgG4 bearing plasma cell infiltration was found both in the liver and the gall bladder wall. After six months, liver function was still abnormal: aspartate …
Codon-optimized Human Sodium Iodide Symporter (opt-hNIS) as a Sensitive Reporter and Efficient Therapeutic Gene
Authors: Young-Hwa Kim, Hyewon Youn, Juri Na, Kee-Jong Hong, Keon Wook Kang, Dong Soo Lee, June-Key Chung
Journal: Theranostics (2014)

To generate a more efficient in vivo reporter and therapeutic gene, we optimized the coding sequence of the human sodium/iodide symporter (NIS) gene by replacing NIS DNA codons from wild type to new codons having the highest usage in human gene translation. The Codon Adaptation Index (CAI), representing the number of codons effective for human expression, was much improved (0.79 for hNIS, 0.97 for opt-hNIS). Both wild-type (hNIS) and optimized human NIS (opt-hNIS) were cloned into pcDNA3.1 and pMSCV vectors for transfection. Various cancer cell lines such as thyroid (TPC-1, FRO, B-CPAP), breast (MDA-MB-231), liver (Hep3B), cervical (HeLa), and glioma (U87MG) were transfected with pcDNA3.1/hNIS or pcDNA3.1/opt-hNIS. 125I uptake by opt-hNIS-expressing cells was 1.6~2.1 times higher than uptake by wild-type hNIS-expressing cells. Stable cell lines were also established by retroviral transduction using pMSCV/hNIS or pMSCV/opt-hNIS, revealing higher NIS protein levels and 125I uptake in opt-hNIS-expressing cells than in hNIS-expressing cells. Moreover, scintigraphic images from cell plates and mouse xenografts showed stronger signals from opt-hNIS-expressing cells than hNIS-expressing cells, and radioactivity uptake by opt-hNIS-expressing tumors was 2.3-fold greater than that by hNIS-expressing tumors. To test the efficacy of radioiodine therapy, mouse xenograft models were established with cancer cells expressing hNIS or opt-hNIS. 131I treatment reduced tumor sizes of hNIS- and opt-hNIS-expressing tumors to 0.57- and 0.27- fold, respectively, compared to their sizes before therapy, suggesting an improved therapeutic effect of opt-hNIS. In summary, this study shows that codon optimization strongly increases hNIS protein levels and radioiodine uptake, thus supporting opt-hNIS as a more sensitive reporter and efficient therapeutic gene.
Hydrogen‐Bonded Multilayers of Tannic Acid as Mediators of T‐Cell Immunity
Authors: Veronika Kozlovskaya, Bing Xue, Weiqi Lei, Lindsey E. Padgett, Hubert M. Tse, Eugenia Kharlampieva
Journal: Advanced Healthcare Materials (2014)

Type 1 diabetes is an autoimmune‐mediated disease resulting in the destruction of insulin‐secreting pancreatic β ‐cells. Transplantation of insulin‐producing islets is a viable treatment to restore euglycemia in Type 1 diabetics; however, the clinical application remains limited due to the use of toxic immunosuppressive therapies to prevent immune‐mediated rejection. A nanothin polymer material with dual antioxidant and immunosuppressive properties capable of modulating both innate and adaptive immune responses crucial for transplantation outcome is presented. Through the use of hollow microparticles (capsules) composed of hydrogen‐bonded multilayers of natural polyphenol (tannic acid) with poly( N ‐vinylpyrrolidone) (TA/PVPON) and with poly( N ‐vinylcaprolactam) (TA/PVCL), proinflammatory reactive oxygen and nitrogen species are efficiently dissipated and the production of interferon (IFN)‐ γ and tumor necrosis factor (TNF)‐ α proinflammatory cytokines is attenuated by cognate antigen‐stimulated autoreactive CD4+ T cells. These results provide evidence that TA‐containing capsules are efficacious in immunomodulation and may provide physical transplant protection and prevent diabetogenic autoreactive T‐cell responses. Future studies will determine if xeno‐ and allotransplantation with (TA/PVPON)‐ or (TA/PVCL)‐coated pancreatic islets will decrease the risk of graft rejection due to attenuation of oxidative stress and IFN‐ γ , and restore euglycemia in Type 1 diabetics.
PRAGMA-CF. A Quantitative Structural Lung Disease Computed Tomography Outcome in Young Children with Cystic Fibrosis
Authors: Tim Rosenow, Merel C. J. Oudraad, Conor P. Murray, Lidija Turkovic, Wieying Kuo, Marleen de Bruijne, Sarath C. Ranganathan, Harm A. W. M. Tiddens, Stephen M. Stick
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Chest computed tomography (CT) is the gold standard for demonstrating cystic fibrosis (CF) airway disease. However, there are no standardized outcome measures appropriate for children younger than 6 years.We developed the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF), a quantitative measure of airway disease, and compared it with the commonly used CF-CT scoring method.CT scans from the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort in Western Australia were included. PRAGMA-CF was performed by annotating a grid overlaid on 10 axial slices for the presence of bronchiectasis, mucous plugging, or other airway abnormalities (inspiratory scans) and trapped air (expiratory scans). The separate proportions of total disease (%Dis), bronchiectasis (%Bx), and trapped air (%TA) were determined. Thirty scans were used for observer reliability, and 30 paired scans obtained at 1 and 3 years old were used for comparison with a validated standard and biologic plausibility.Intraobserver, intraclass correlation coefficients (95% confidence interval) for %Dis, %Bx, and %TA were 0.93 (0.86-0.97), 0.93 (0.85-0.96), and 0.96 (0.91-0.98), respectively. The change in %Dis (P = 0.004) and %Bx (P = 0.001) with PRAGMA-CF was related to neutrophil elastase presence at age 3, whereas only the change in bronchiectasis score was related to neutrophil elastase (P < 0.001) with CF-CT. Sample-size calculations for various effect sizes are presented.PRAGMA-CF is a sensitive and reproducible outcome measure for assessing the extent of lung disease in very young children with CF.
SC erythrocytes have an abnormally high intracellular hemoglobin concentration. Pathophysiological consequences.
Authors: M E Fabry, D K Kaul, C Raventos-Suarez, H Chang, R L Nagel
Journal: Journal of Clinical Investigation (1982)

We have examined 20 SC patients on Percoll-Stractan continuous density gradients and find that they have an elevated mean corpuscular hemoglobin concentration (MCHC). Reduction of the MCHC to normal values results in amelioration of four physiologically important blood abnormalities: decreased oxygen affinity, viscosity of deoxygenated erythrocyte suspensions, rate of sickling, and deoxygenation induced K+ efflux. These observations suggest that the rehydration of SC cells to normal values should be considered a potential approach in the therapeutic manipulation of this disease.
Estrogen Receptor (ER) mRNA and ER-Related Gene Expression in Breast Cancers That Are 1% to 10% ER-Positive by Immunohistochemistry
Authors: Takayuki Iwamoto, Daniel Booser, Vicente Valero, James L. Murray, Kimberly Koenig, Francisco J. Esteva, Naoto T. Ueno, Jie Zhang, Weiwei Shi, Yuan Qi, Junji Matsuoka, Elliana J. Yang, Gabriel N. Hortobagyi, Christos Hatzis, W. Fraser Symmans, Lajos Pusztai
Journal: Journal of Clinical Oncology (2012)

We examined borderline estrogen receptor (ER) -positive cancers, defined as having 1% to 10% positivity by immunohistochemistry (IHC), to determine whether they show the same global gene-expression pattern and high ESR1 mRNA expression as ER-positive cancers or if they are more similar to ER-negative cancers.ER status was determined by IHC in 465 primary breast cancers and with the Affymetrix U133A gene chip. We compared expressions of ESR1 mRNA and a 106 probe set ER-associated gene signature score between ER-negative (n = 183), 1% to 9% (n = 25), 10% (n = 6), and more than 10% (n = 251) ER-positive cancers. We also assessed the molecular class by using the PAM50 classifier and plotted survival by ER status.Among the 1% to 9%, 10%, and more than 10% ER IHC-positive patients, 24%, 67%, and 92% were also positive by ESR1 mRNA expression. The average ESR1 expression was significantly higher in the ≥ 10% ER-positive cohorts compared with the 1% to 9% or ER-negative cohort. The average ER gene signature scores were similar for the ER-negative and 1% to 9% IHC-positive patients and were significantly lower than in ≥ 10% ER-positive patients. Among the 1% to 9% ER-positive patients, 8% were luminal B and 48% were basal-like; among the 10% ER-positive patients, 50% were luminal. The overall survival rate of 1% to 9% ER-positive patients with cancer was between those of patients in the ≥ 10% ER-positive and ER-negative groups.A minority of the 1% to 9% IHC ER-positive tumors show molecular features similar to those of ER-positive, potentially endocrine-sensitive tumors, whereas most show ER-negative, basal-like molecular characteristics. The safest clinical approach may be to use both adjuvant endocrine therapy and chemotherapy in this rare subset of patients.
Phospholipase-A2-dependent signalling in the heart
Authors: M. Van Bilsen, G.J. Van der Vusse
Journal: Cardiovascular Research (1995)

Journal Article Phospholipase-A2-dependent signalling in the heart Get access M. Van Bilsen, M. Van Bilsen * Department of Physiology, Cardiovascular Research Institute Maastricht, University of Limburg, P.O. Box 616, 6200 MD Maastricht, Netherlands *Corresponding author. Tel.: (+43) 3 881204; Fax: (+43) 3 671028. Search for other works by this author on: Oxford Academic PubMed Google Scholar G.J. Van der Vusse G.J. Van der Vusse Department of Physiology, Cardiovascular Research Institute Maastricht, University of Limburg, P.O. Box 616, 6200 MD Maastricht, Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 4, October 1995, Pages 518–529, https://doi.org/10.1016/S0008-6363(95)00098-4 Published: 01 October 1995 Article history Received: 13 January 1995 Accepted: 24 April 1995 Published: 01 October 1995
Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses' Health Study cohorts
Authors: H. Khalili, A. N. Ananthakrishnan, G. G. Konijeti, X. Liao, L. M. Higuchi, C. S. Fuchs, D. Spiegelman, J. M. Richter, J. R. Korzenik, A. T. Chan
Journal: BMJ (2013)

<b>Objective</b> To examine the association between physical activity and risk of ulcerative colitis and Crohn's disease. <b>Design</b> Prospective cohort study. <b>Setting</b> Nurses' Health Study and Nurses' Health Study II. <b>Participants</b> 194 711 women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided data on physical activity and other risk factors every two to four years since 1984 in the Nurses' Health Study and 1989 in the Nurses' Health Study II and followed up through 2010. <b>Main outcome measure</b> Incident ulcerative colitis and Crohn's disease. <b>Results</b> During 3 421 972 person years of follow-up, we documented 284 cases of Crohn's disease and 363 cases of ulcerative colitis. The risk of Crohn's disease was inversely associated with physical activity (P for trend 0.02). Compared with women in the lowest fifth of physical activity, the multivariate adjusted hazard ratio of Crohn's disease among women in the highest fifth of physical activity was 0.64 (95% confidence interval 0.44 to 0.94). Active women with at least 27 metabolic equivalent task (MET) hours per week of physical activity had a 44% reduction (hazard ratio 0.56, 95% confidence interval 0.37 to 0.84) in risk of developing Crohn's disease compared with sedentary women with &lt;3 MET h/wk. Physical activity was not associated with risk of ulcerative colitis (P for trend 0.46). The absolute risk of ulcerative colitis and Crohn's disease among women in the highest fifth of physical activity was 8 and 6 events per 100 000 person years compared with 11 and 16 events per 100 000 person years among women in the lowest fifth of physical activity, respectively. Age, smoking, body mass index, and cohort did not significantly modify the association between physical activity and risk of ulcerative colitis or Crohn's disease (all P for interaction &gt;0.35). <b>Conclusion</b> In two large prospective cohorts of US women, physical activity was inversely associated with risk of Crohn's disease but not of ulcerative colitis.
Intravenous Gene Therapy With PIM-1 Via a Cardiotropic Viral Vector Halts the Progression of Diabetic Cardiomyopathy Through Promotion of Prosurvival Signaling
Authors: Rajesh Katare, Andrea Caporali, Lorena Zentilin, Elisa Avolio, Graciela Sala-Newby, Atsuhiko Oikawa, Daniela Cesselli, Antonio Paolo Beltrami, Mauro Giacca, Costanza Emanueli, Paolo Madeddu
Journal: Circulation Research (2011)

Studies in transgenic mice showed the key role of (Pim-1) (proviral integration site for Moloney murine leukemia virus-1) in the control of cardiomyocyte function and viability.We investigated whether Pim-1 represents a novel mechanistic target for the cure of diabetic cardiomyopathy, a steadily increasing cause of nonischemic heart failure.In streptozotocin-induced type 1 diabetic mice, Pim-1 protein levels declined during progression of cardiomyopathy, along with upregulation of Pim-1 inhibitors, protein phosphatase 2A, and microRNA-1. Moreover, diabetic hearts showed low levels of antiapoptotic B-cell lymphoma-2 (Bcl-2) protein and increased proapoptotic caspase-3 activity. Studies on adult rat cardiomyocytes and murine cardiac progenitor cells challenged with high glucose confirmed the in vivo expressional changes. In rescue studies, anti-microRNA-1 boosted Pim-1 and Bcl-2 expression and promoted cardiomyocyte and cardiac progenitor cell survival under high glucose conditions. Similarly, transfection with Pim-1 plasmid prevented high glucose-induced cardiomyocyte and cardiac progenitor cell apoptosis. Finally, a single intravenous injection of human PIM-1 via cardiotropic serotype-9 adeno-associated virus (1 × 10(10) or 5 × 10(10) plaque-forming units per animal) at 4 weeks after diabetes induction led to sustained cardiac overexpression of Pim-1 and improved diastolic function and prevented left ventricular dilation and failure. Histological examination showed reduced cardiomyocyte apoptosis and fibrosis in association with increased c-kit(+) cells and cardiomyocyte proliferation, whereas molecular analysis confirmed activation of the prosurvival pathway and conservation of sarcoendoplasmic reticulum Ca(2+)-ATPase and α-myosin heavy chain in Pim-1-treated hearts.Pim-1 downregulation contributes in the pathogenesis of diabetic cardiomyopathy. Systemic delivery of human PIM-1 via cardiotropic adeno-associated virus serotype-9 represents a novel and effective approach to treat diabetic cardiomyopathy.
SUPERIMPOSITION OF A RETROGRADE UPON A DIRECT INTUSSUSCEPTION
Authors: J. P. Buckley
Journal: BMJ (1919)

On account of the prolonged stay. in ho.lspital and the enforced recumbency, a stern but kind discipline has..to be maintained to ensure the lhapp'iness of the children, and in this the three and a' balf hours per day school tuition wlichl is given lias.been of great help.In giving exercise to their minds and an occupation to their lhands it proves a powerful aid to cure.The details anid technique of the local treatment are beyond the scope of this paper.It is carried out on con- servative lines, and its aims are the preservation and restorationi of the diseased.parts.All gases of tuber- culosis otlher than, pulmonary are admitted, the.majority being those with bony, articular, or glandular foci.With the exception of peritoneal cases no experience of visceral lesions lhas been gained.c.'Eighty per cent.of.the.cases,adritted, are discharged under the heading of "'Disoase arrestel," but the degvee ;of cure of necessity varies with the type of case.In the bony and articular types the.a`onvalescent stage.oftlle treatment is prolonaed as long as possible in order tlhat tle 'disability may be overwome.In cases wlher the de- formities are severe corrective operations are performed.It must be recorded that the type of case admitted has improved during the five years that the lhospital has been opened, and that cases with marked deformity and longstanding sinus formation are not so common as formerly.The result of this is that the averagge duration of stay has been.slhortened, and the degree of cure lhas improved.With the spread of knowledge of surgical tuberculosis a still furtlher improvement is hoped for.The following statistics are deduced from the cases -disceharged during 1918i: *DIscharged, disease having been arrested- Tuberculous spine Average stay, 617 days 19
Effect of Ischemia on Adenine Nucleotides in Cardiac and Skeletal Muscle
Authors: SHOICHI IMAI, ARTHUR L. RILEY, ROBERT M. BERNE
Journal: Circulation Research (1964)

Rabbit skeletal muscle contains 56% more ATP and 225% more creatine phosphate than rabbit cardiac muscle. With ischemia the per cent reduction in ATP and creatine phosphate is less in skeletal than cardiac muscle and ADP and AMP decrease in skeletal and increase in cardiac muscle, IMP is present in skeletal muscle and increases with ischemia, whereas it is absent in cardiac muscle but appears with ischemia. Adenosine, inosine, and hypoxanthine are absent in skeletal and cardiac muscle. Ischemia results in the appearance of adenosine, inosine, and hypoxanthine in cardiac muscle but only the latter two compounds appear in ischemic skeletal muscle. Although complete ischemia is required to demonstrate the presence of adenosine in cardiac muscle, the appearance of this nucleoside is nevertheless consistent with the hypothesis that under physiological conditions quantities of adenosine, undetectable by present methods, may play a role in the regulation of coronary blood flow.
Anthony John (Tony) McMichael
Authors: S. Tong
Journal: BMJ (2014)

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