tbuckley/cabot-search huggingface dataset:
Sociodemographic Correlates of the Increasing Trend in Prevalence of Gestational Diabetes Mellitus in a Large Population of Women Between 1995 and 2005
Authors: Vibeke Anna, Hidde P. van der Ploeg, N. Wah Cheung, Rachel R. Huxley, Adrian E. Bauman
Journal: Diabetes Care (2008)

Gestational diabetes mellitus (GDM) is an increasingly prevalent risk factor for the development of type 2 diabetes in the mother and is responsible for morbidity in the child. To better identify women at risk of developing GDM we examined sociodemographic correlates and changes in the prevalence of GDM among all births between 1995 and 2005 in Australia's largest state.A computerized database of all births (n = 956,738) between 1995 and 2005 in New South Wales, Australia, was used in a multivariate logistic regression that examined the association between sociodemographic characteristics and the occurrence of GDM.Between 1995 and 2005, the prevalence of GDM increased by 45%, from 3.0 to 4.4%. Women born in South Asia had the highest adjusted odds ratio (OR) of any region (4.33 [95% CI 4.12-4.55]) relative to women born in Australia. Women living in the three lowest socioeconomic quartiles had higher adjusted ORs for GDM relative to women in the highest quartile (1.54 [1.50-1.59], 1.74 [1.69-1.8], and 1.65 [1.60-1.70] for decreasing socioeconomic status quartiles). Increasing age was strongly associated with GDM, with women aged >40 years having an adjusted OR of 6.13 (95% CI 5.79-6.49) relative to women in their early 20s. Parity was associated with a small reduced risk. There was no association between smoking and GDM.Maternal age, socioeconomic position, and ethnicity are important correlates of GDM. Future culturally specific interventions should target prevention of GDM in these high-risk groups.
Chemopreventive Effects of Deguelin, a Novel Akt Inhibitor, on Tobacco-Induced Lung Tumorigenesis
Authors: Ho-Young Lee, Seung-Hyun Oh, Jong K. Woo, Woo-Young Kim, Carolyn S. Van Pelt, Roger E. Price, Dianna Cody, Hai Tran, John M. Pezzuto, Robert M. Moriarty, Waun Ki Hong
Journal: JNCI Journal of the National Cancer Institute (2005)

Tobacco carcinogens induce Akt activation and lung carcinogenesis. We previously demonstrated that deguelin, a natural plant product, specifically inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by blocking Akt activation. To evaluate the ability of deguelin to block tobacco carcinogen-induced lung tumorigenesis, we evaluated the in vivo effects of deguelin on Akt activation and lung tumorigenesis in transgenic mice in which Akt expression was induced by tamoxifen and in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)/benzo(a)pyrene (BaP)-treated A/J mice. Deguelin suppressed Akt activation in vivo, as measured by immunohistochemistry and immunoblotting, and statistically significantly reduced NNK/BaP-induced lung tumor multiplicity, volume, and load in A/J mice, as monitored by microcomputed tomography image analysis, with no detectable toxicity. These results indicate that deguelin warrants consideration as a chemopreventive agent for early-stage lung carcinogenesis in a clinical lung cancer chemoprevention trial.
Notch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis
Authors: Yoshiharu Miyamoto, Anirban Maitra, Bidyut Ghosh, Ulrich Zechner, Pedram Argani, Christine A. Iacobuzio-Donahue, Virote Sriuranpong, Tatsuya Iso, Ingrid M. Meszoely, Michael S. Wolfe, Ralph H. Hruban, Douglas W. Ball, Roland M. Schmid, Steven D. Leach
Journal: Cancer Cell (2003)
Platelet transfusion therapy. One-hour posttransfusion increments are valuable in predicting the need for HLA-matched preparations
Authors: P. A. Daly
Journal: JAMA (1980)

Seventy-nine platelet transfusions to 73 thrombocytopenic patients with cancer were analyzed to determine whether a platelet count obtained one hour after transfusion could help differentiate between alloimmunization and other clinical factors that result in rapid platelet destruction. These transfusions were selected because 18- to 24-hour increments were inadequate in response to fresh, random donor platelets. A corrected count increment (Cl) (Cl=[posttransfusion count-pretransfusion count]Xbody surface area [sq m]/platelets transfusedX10'') at one hour of 10X103/microliter or greater was associated with absence of lymphocytotoxic antibody, whereas increments of less than 10X103/microliter were generally associated with high levels of strongly cytotoxic antibody. HLA-matched transfusions produced no improvement in increments when the previous one-hour Cl had been 10X103/microliter or greater, whereas in the other group significantly better increments were obtained. A one-hour posttransfusion count is a simple test that correlates well with the presence of antibody against HLA antigens, is valuable in predicting the need for HLA-matched platelets, and helps avoid wasteful, empirical use of such transfusions.
The treatment of psoriatic nail dystrophy with intradermal steroid injections
Authors: R.D.G. PEACHEY, R.J. PYE, R.R.M. HARMAN
Journal: British Journal of Dermatology (1976)

Thirty-seven patients with psoriatic nail dystrophy were treated with intradermal nail-fold injections of either triamcinolone acetonide or triamcinolone hexacetonide, using the Port-O-Jet needleless injector. Mild nail-matrix changes showed a very good response to treatment, whilst nail-bed and/or hyponychial changes causing onycholysis and the more severe types of dystrophy usually showed little improvement. Although in occasional cases this may be a useful form of treatment, we would not recommend its general use in patients with psoriatic nail dystrophy.
Variation in Surgical-Readmission Rates and Quality of Hospital Care
Authors: Thomas C. Tsai, Karen E. Joynt, E. John Orav, Atul A. Gawande, Ashish K. Jha
Journal: New England Journal of Medicine (2013)

Reducing hospital-readmission rates is a clinical and policy priority, but little is known about variation in rates of readmission after major surgery and whether these rates at a given hospital are related to other markers of the quality of surgical care.Using national Medicare data, we calculated 30-day readmission rates after hospitalization for coronary-artery bypass grafting, pulmonary lobectomy, endovascular repair of abdominal aortic aneurysm, open repair of abdominal aortic aneurysm, colectomy, and hip replacement. We used bivariate and multivariate techniques to assess the relationships between readmission rates and other measures of surgical quality, including adherence to surgical process measures, procedure volume, and mortality.For the six index procedures, there were 479,471 discharges from 3004 hospitals. The median risk-adjusted composite readmission rate at 30 days was 13.1% (interquartile range, 9.9 to 17.1). In a multivariate model adjusting for hospital characteristics, we found that hospitals in the highest quartile for surgical volume had a significantly lower composite readmission rate than hospitals in the lowest quartile (12.7% vs. 16.8%, P<0.001), and hospitals with the lowest surgical mortality rates had a significantly lower readmission rate than hospitals with the highest mortality rates (13.3% vs. 14.2%, P<0.001). High adherence to reported surgical process measures was only marginally associated with reduced readmission rates (highest quartile vs. lowest quartile, 13.1% vs. 13.6%; P=0.02). Patterns were similar when each of the six major surgical procedures was examined individually.Nearly one in seven patients hospitalized for a major surgical procedure is readmitted to the hospital within 30 days after discharge. Hospitals with high surgical volume and low surgical mortality have lower rates of surgical readmission than other hospitals.
Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm
Authors: Stephen P. Methot, Ludivine C. Litzler, Felipe Trajtenberg, Astrid Zahn, Francis Robert, Jerry Pelletier, Alejandro Buschiazzo, Brad G. Magor, Javier M. Di Noia
Journal: The Journal of Experimental Medicine (2015)

Activation-induced deaminase (AID) initiates mutagenic pathways to diversify the antibody genes during immune responses. The access of AID to the nucleus is limited by CRM1-mediated nuclear export and by an uncharacterized mechanism of cytoplasmic retention. Here, we define a conformational motif in AID that dictates its cytoplasmic retention and demonstrate that the translation elongation factor eukaryotic elongation factor 1 α (eEF1A) is necessary for AID cytoplasmic sequestering. The mechanism is independent of protein synthesis but dependent on a tRNA-free form of eEF1A. Inhibiting eEF1A prevents the interaction with AID, which accumulates in the nucleus and increases class switch recombination as well as chromosomal translocation byproducts. Most AID is associated to unspecified cytoplasmic complexes. We find that the interactions of AID with eEF1A and heat-shock protein 90 kD (HSP90) are inversely correlated. Despite both interactions stabilizing AID, the nature of the AID fractions associated with HSP90 or eEF1A are different, defining two complexes that sequentially produce and store functional AID in the cytoplasm. In addition, nuclear export and cytoplasmic retention cooperate to exclude AID from the nucleus but might not be functionally equivalent. Our results elucidate the molecular basis of AID cytoplasmic retention, define its functional relevance and distinguish it from other mechanisms regulating AID.
Lung Dysfunction in Diabetes
Authors: Michael David Goldman
Journal: Diabetes Care (2003)

Clear decrements in lung function have been reported in patients with diabetes over the past 2 decades, and many reports have suggested plausible pathophysiological mechanisms. However, at the present time, there are no reports of functional limitations of activities of daily living ascribable to pulmonary disease in patients with diabetes. Accordingly, this review is directed toward a description of the nature of reported lung dysfunction in diabetes, with an emphasis on the emerging potential clinical implications of such dysfunction.

More than a quarter-century ago, Schuyler et al. (1) investigated lung function in 11 young (21–28 years old) patients with type 1 diabetes and age-matched normal control subjects. This classic study was the first to report measurements of nearly all the available tests of lung function, including lung elasticity, capacity to transfer carbon monoxide (CO, a surrogate for oxygen transfer capacity), absolute thoracic gas volumes, airflow resistance, and maximal forced spirometric pulmonary function tests (PFTs). As their subjects were lifelong nonsmokers without allergies or lung disease, their finding that lung elastic recoil was decreased in these young patients with diabetes was interpreted to reflect effects of diabetes on lung elastic proteins. This was the first suggestion in the literature that the lung may be a target organ of diabetes. Because the elastic structure of the lung supports the intrathoracic airways and helps to maintain their patency, the authors suggested that patients with diabetes were at risk for developing chronic airflow obstruction. While small changes in lung elastic recoil do not have direct clinical implications, subsequent development of chronic airflow obstruction could incur significant disability due to mechanical dysfunction of the lungs and airways.

Schernthaner et al. (2) could not confirm the findings of Schuyler et al. in patients with type 1 diabetes. However Sandler et al. (3) did find decreased lung …
Acute Budd-Chiari syndrome with hepatic failure and obstruction of the inferior vena cava as presenting manifestations of hereditary protein C deficiency.
Authors: M Bourliere, Y P Le Treut, D Arnoux, P Castellani, L Bordigoni, A Maillot, M Antoni, D Botta, B Pol, A P Gauthier
Journal: Gut (1990)

The protein C system is essential in limiting the activation of coagulation in vivo. We report on a 29 year old woman with Budd-Chiari syndrome and occlusion of the inferior vena cava who presented with acute liver failure. She was successfully treated with an emergency mesoatrial shunt. Eight months after surgery, she has no ascites and normal liver function. She had a low concentration of plasma protein C on admission to hospital and during the follow up. Protein C deficiency subsequently was found in her father and two sisters, who were asymptomatic. Hereditary protein C deficiency should be considered in patients with Budd-Chiari syndrome.
Lobular endocervical glandular hyperplasia and peritoneal pigmentation associated with Peutz–Jeghers syndrome due to a germline mutation of STK11
Authors: A. Hirasawa, T. Akahane, T. Tsuruta, Y. Kobayashi, K. Masuda, K. Banno, T. Fujii, N. Susumu, T. Itsubo, K. Kameyama, K. Sugano, D. Aoki
Journal: Annals of Oncology (2012)
Hirschsprung’s disease: genetic mutations in mice and men
Authors: K ROBERTSON, I MASON, S HALL
Journal: Gut (1997)

Hirschsprung's disease is a neuronal dysplasia of the hindgut, characterised by a loss of neurones, which affects about 1 in 5000 live births. Genetic factors have been implicated in the aetiology of this disease in about 20% of cases and a dominant pattern of inheritance has been revealed in several families. The pathogenesis of the aganglionosis is often attributed to a failure of migration of neural crest cells, although this has not been proven. Recently, mutations in a developmentally regulated receptor tyrosine kinase gene, ret, and mutations in the endothelin receptor-B gene (ENDR-B) have both been linked to familial Hirschsprung's disease in humans. Moreover, certain mutant mouse strains--namely piebald lethal and lethal spotted--exhibit striking similarities to the human condition. The mutation which gives rise to piebald lethal has now been found to be in the ENDR-B gene, and the mutation associated with lethal spotted occurs in the gene for endothelin-3 (ET-3), a ligand for ENDR-B. Two transgenic mouse lines have been developed which also reflect the human disease: ret-k-, which has a loss of function mutation of the ret gene, and ENDR-B null. In addition, the introduction of a Lac-Z reporter gene into neural crest cells of aganglionic mice has made it possible to study directly the fate of enteric neuroblasts which are affected by "Hirschsprung's-like" mutations. Here, we review the possible roles of RET and endothelin in the normal development of the enteric nervous system, and the significance of their mutated forms in the pathogenesis of familial aganglionosis. This review focuses on recent advances in our understanding of the genetic basis of the lesions which have been implicated in congenital forms of Hirschsprung's disease. Disruption of these genes in the mouse, either by transgenic "knockout" approaches or in mutant mouse lines, offers the prospect of greater understanding of both the cellular and developmental bases of the human disease.
Baseline Factors Associated With Glycemic Control and Weight Loss When Exenatide Twice Daily Is Added to Optimized Insulin Glargine in Patients With Type 2 Diabetes
Authors: Julio Rosenstock, Sylvia K. Shenouda, Richard M. Bergenstal, John B. Buse, Leonard C. Glass, Cory R. Heilmann, Anita Y.M. Kwan, Leigh A. MacConell, Byron James Hoogwerf
Journal: Diabetes Care (2012)

To determine variables associated with glycemic and body weight responses when adding exenatide to basal insulin-treated type 2 diabetes.Exploratory subgroup analyses based on baseline A1C, disease duration, and BMI of a 30-week study comparing exenatide twice daily to placebo, added to optimized insulin glargine (intent-to-treat analysis: 137 exenatide; 122 placebo).Exenatide participants had greater A1C reductions compared with optimized insulin glargine alone, irrespective of baseline A1C (P < 0.001). Exenatide participants with longer diabetes duration and those with lower BMI had greater A1C reductions (P < 0.01). Exenatide participants lost more weight, regardless of baseline A1C or BMI (P < 0.05). Exenatide participants with longer diabetes duration lost the most weight (P < 0.001).Exenatide added to optimized basal insulin was associated with improved glycemic control and weight loss, irrespective of baseline A1C, diabetes duration, and BMI. Changes were evident in modestly obese patients and in those with longer diabetes duration.
Calprotectin (a major S100 leucocyte protein) predicts 10-year radiographic progression in patients with rheumatoid arthritis
Authors: H Berner Hammer, S Ødegård, S W Syversen, R Landewé, D van der Heijde, T Uhlig, P Mowinckel, T K Kvien
Journal: Annals of the Rheumatic Diseases (2008)

Background: Plasma levels of calprotectin, a major S100 leucocyte protein, are cross-sectionally associated with clinical and laboratory markers of inflammation and with radiographic damage in rheumatoid arthritis (RA). High amounts of calprotectin are found in synovial fluid from patients with RA. Objective: To examine whether calprotectin might be an independent predictor of joint destruction over time. Methods: 124 patients with RA were assessed at baseline and after 10 years with inflammatory markers (calprotectin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)), serological variables (antibodies to cyclic citrullinated peptide (anti-CCP), IgA rheumatoid factor (RF) and IgM RF) and radiographic and clinical assessments of joint damage (hand radiographs and Rheumatoid Arthritis Articular Damage (RAAD) score). Progression of radiographic damage was assessed according to the van der Heijde modified Sharp score. Results: At both examinations the highest calprotectin levels were found in patients positive for anti-CCP, IgA and IgM RF. Calprotectin had moderate to good correlations with inflammatory and serological markers (r = 0.41–0.67). Patients with normal baseline calprotectin levels had a lower degree of joint damage. High univariate associations were found between baseline calprotectin levels and progression in the Sharp score as well as the RAAD score. Baseline calprotectin was independently associated with progression in the Sharp score and with the RAAD score in multiple linear regression analyses, including baseline levels of CRP, ESR, anti-CCP in addition to demographic variables. Conclusion: Calprotectin was an independent predictor of clinical and radiographic joint damage after 10 years. These findings support the proposal that calprotectin may be a prognostic biomarker for erosive disease in patients with RA.
Long Noncoding RNAs in Cardiac Development and Pathophysiology
Authors: Nicole Schonrock, Richard P. Harvey, John S. Mattick
Journal: Circulation Research (2012)

Heart function requires sophisticated regulatory networks to orchestrate organ development, physiological responses, and environmental adaptation. Until recently, it was thought that these regulatory networks are composed solely of protein-mediated transcriptional control and signaling systems; consequently, it was thought that cardiac disease involves perturbation of these systems. However, it is becoming evident that RNA, long considered to function primarily as the platform for protein production, may in fact play a major role in most, if not all, aspects of gene regulation, especially the epigenetic processes that underpin organogenesis. These include not only well-validated classes of regulatory RNAs, such as microRNAs, but also tens of thousands of long noncoding RNAs that are differentially expressed across the entire genome of humans and other animals. Here, we review this emerging landscape, summarizing what is known about their functions and their role in cardiac biology, and provide a toolkit to assist in exploring this previously hidden layer of gene regulation that may underpin heart adaptation and complex heart diseases.
A Spontaneous Lower Motor Neuron Disease Apparently Caused by Indigenous Type-C RNA Virus in Wild Mice2
Authors: Murray B. Gardner, Brian E. Henderson, J. Earle Officer, Robert W. Rongey, John C. Parker, Cynthia Oliver, John D. Estes, Robert J. Huebner
Journal: JNCI Journal of the National Cancer Institute (1973)

Abstract A high incidence of spontaneous lower-limb paralysis occurred in a population of wild mice (Mus musculus) which had a high incidence of naturally occurring lymphoma and elevated indigenous type-C virus activity. Experimental transmission evidence indicated that both the neurologic and lymphomatous disorders almost certainly were caused by the indigenous type-C virus. The virus appeared to have a direct neurotropic effect on anterior horn neurons in the lower spinal cord.
Rilotumumab Exposure–Response Relationship in Patients with Advanced or Metastatic Gastric Cancer
Authors: Sameer Doshi, Per Olsson Gisleskog, Yilong Zhang, Min Zhu, Kelly S. Oliner, Elwyn Loh, Juan Jose Perez Ruixo
Journal: Clinical Cancer Research (2015)

Rilotumumab is an investigational, fully human monoclonal antibody to hepatocyte growth factor. In a randomized phase II study, trends toward improved survival were observed with rilotumumab (7.5 or 15 mg/kg) plus epirubicin, cisplatin, and capecitabine (ECX) versus placebo plus ECX in gastric/gastroesophageal junction (GEJ) cancer patients, especially in MET-positive patients. Here, we quantitatively characterized the longitudinal exposure-response [tumor growth (TG) and overall survival (OS)] relationship for rilotumumab.Rilotumumab concentrations, tumor sizes, and survival time from the phase II study were pooled to develop a longitudinal exposure versus TG model and parametric OS model that explored predictive/prognostic/treatment effects (MET expression, rilotumumab exposure, relative tumor size). Model evaluation included visual predictive checks, nonparametric bootstrap, and normalized prediction distribution errors. Simulations were undertaken to predict the relationship between rilotumumab dose and OS.Rilotumumab exhibited linear time-independent pharmacokinetics not affected by MET expression. The TG model adequately described tumor size across arms. A Weibull distribution best described OS. Rilotumumab exposure and change in tumor size from baseline at week 24 were predictive of OS. MET-positive patients showed shorter survival and responded better to rilotumumab than MET-negative patients. Simulations predicted a median (95% confidence interval) HR of 0.38 (0.18-0.60) in MET-positive patients treated with 15 mg/kg rilotumumab Q3W.Rilotumumab plus ECX demonstrated concentration-dependent effects on OS, influenced by MET expression, and tumor size in gastric/GEJ cancer patients. These findings support the phase II testing of rilotumumab 15 mg/kg every 3 weeks in MET-positive gastric/GEJ cancer (RILOMET-1; NCT01697072).
Renal FcRn Reclaims Albumin but Facilitates Elimination of IgG
Authors: Menaka Sarav, Ying Wang, Bradley K. Hack, Anthony Chang, Mark Jensen, Lihua Bao, Richard J. Quigg
Journal: Journal of the American Society of Nephrology (2009)

The widely distributed neonatal Fc receptor (FcRn) contributes to maintaining serum levels of albumin and IgG in adults. In the kidney, FcRn is expressed on the podocytes and the brush border of the proximal tubular epithelium. Here, we evaluated the role of renal FcRn in albumin and IgG metabolism. Compared with wild-type controls, FcRn −/− mice had a lower t ½ for albumin (28.7 versus 39.9 h) and IgG (29.5 versus 66.1 h). Renal loss of albumin could account for the former, suggested by the progressive development of hypoalbuminemia in wild-type mice transplanted with FcRn-deficient kidneys. Furthermore, serum albumin levels returned to normal in FcRn−/− recipients of wild-type kidneys after removing the native FcRn-deficient kidneys. In contrast, renal loss could not account for the enhanced elimination of IgG in FcRn −/− mice. These mice had minimal urinary excretion of native and labeled IgG, which increased to wild-type levels in FcRn −/− recipients of a single FcRn-sufficient kidney ( t ½ of IgG was 21.7 h). Taken together, these data suggest that renal FcRn reclaims albumin, thereby maintaining the serum concentration of albumin, but facilitates the loss of IgG from plasma protein pools.