tbuckley/cabot-search huggingface dataset:
Continuous Subcutaneous Insulin Infusion (CSII) of Insulin Aspart Versus Multiple Daily Injection of Insulin Aspart/Insulin Glargine in Type 1 Diabetic Patients Previously Treated With CSII
Authors: Irl B. Hirsch, Bruce W. Bode, Satish Garg, Wendy S. Lane, Allen Sussman, Peter Hu, Olga M. Santiago, Jerzy W. Kolaczynski
Journal: Diabetes Care (2005)

Multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion (CSII) with aspart in type 1 diabetic patients previously treated with CSII.One hundred patients were enrolled in a randomized, multicenter, open-label, crossover study. After a 1-week run-in period with aspart by CSII, 50 subjects were randomly assigned to MDI therapy (aspart immediately before each meal and glargine at bedtime) and 50 subjects continued CSII. After 5 weeks of the first treatment, subjects crossed over to the alternate treatment for 5 weeks. During the last week of each treatment period, subjects wore a continuous glucose monitoring system for 48-72 h.Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy (343 +/- 47 vs. 355 +/- 50 micromol/l, respectively; P = 0.0001). Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40% lower for CSII than MDI as measured by area under the curve (AUC) glucose >/=80 mg/dl (1,270 +/- 742 vs. 1,664 +/- 1,039 mg . h . dl(-1); P < 0.001) and AUC glucose >/=140 mg/dl (464 +/- 452 vs. 777 +/- 746 mg . h . dl(-1), CSII vs. MDI, respectively; P < 0.001). Similar percentages of subjects reported hypoglycemic episodes (CSII: 92%, MDI: 94%) and nocturnal (12:00 a.m. to 8:00 a.m.) hypoglycemic episodes (CSII: 73%, MDI: 72%). Major hypoglycemia was infrequent (CSII: two episodes, MDI: five episodes).In a trial of short duration, CSII therapy with insulin aspart resulted in lower glycemic exposure without increased risk of hypoglycemia, as compared with MDI with insulin aspart and glargine.
Risk of Incident Diabetes in Relation to Long-term Exposure to Fine Particulate Matter in Ontario, Canada
Authors: Hong Chen, Richard T. Burnett, Jeffrey C. Kwong, Paul J. Villeneuve, Mark S. Goldberg, Robert D. Brook, Aaron van Donkelaar, Michael Jerrett, Randall V. Martin, Jeffrey R. Brook, Ray Copes
Journal: Environmental Health Perspectives (2013)

Laboratory studies suggest that fine particulate matter (≤ 2.5 µm in diameter; PM(2.5)) can activate pathophysiological responses that may induce insulin resistance and type 2 diabetes. However, epidemiological evidence relating PM2.5 and diabetes is sparse, particularly for incident diabetes.
Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients.
Authors: U Eppenberger, W Kueng, J M Schlaeppi, J L Roesel, C Benz, H Mueller, A Matter, M Zuber, K Luescher, M Litschgi, M Schmitt, J A Foekens, S Eppenberger-Castori
Journal: Journal of Clinical Oncology (1998)

To compare the prognostic impact of tumor angiogenesis factors (vascular endothelial growth factor [VEGF], angiogenin, and basic fibroblast growth factor [bFGF]), tumor proteolysis factors (urokinase-type plasminogen activator [uPA] and plasminogen activator inhibitor-1 [PAI-1]), and conventional tumor markers (stage, grade, and steroid receptors) in early breast cancer.In the primary clinical study, tumor angiogenesis and other factors were detected in frozen biopsies from 305 primary breast tumors. VEGF expression was assessed by chemiluminescence immunosorbent assay (ICMA); angiogenin, bFGF, uPA, and PAI-1 by enzyme-linked immunosorbent assay (ELISA); and steroid receptors (estrogen receptor [ER] and progesterone receptor [PgR]) by enzyme immunoassay (EIA). In the validating clinical study, another set of 190 node-negative primary breast tumor samples were collected at a separate institution.Univariate analysis of the primary study showed that VEGF levels were positively correlated with recurrence (P < .001). Angiogenin levels were positively correlated with disease relapse (P < .005) for the overall collective group, but not within the node-negative subset. No significant correlations were found between tumor bFGF levels and patient survival. In multivariate regression analysis, the only independent predictors of relapse-free survival (RFS) were VEGF, uPA, and lymph node status. In the validation set, the distribution of VEGF and uPA values were similar to those in the primary study; low expression of both VEGF and uPA identified patients with a < or = 20% likelihood of recurrence within 7 years.Separate primary and validating clinical studies concur that tumor VEGF level is the most important prognostic parameter among several markers of tumor angiogenesis and proteolysis.
Cost of Lost Productive Work Time Among US Workers With Depression
Authors: Walter F. Stewart
Journal: JAMA (2003)

From Health Conditions in the US: Results From the American Productivity Audit, is available from W.F.S. on request).Evidence consistently indicates that common conditions including migraine, 1-8 low back pain, 9,10 diabetes, 1 1 , 1 2 allergic rhinitis, 5 , 1 3 -1 8 gastroesophageal reflux, [19][20][21] and depression 5,10,[22][23][24][25] dominate healthrelated lost labor time costs.Among these, depression is among the most costly because it is highly prevalent and comorbid with other conditions.Furthermore, although workers with depression are usually present at work, their performance can be substantially reduced.Model-based estimates indicate that depression costs US employers $24 billion annually in lost productive work time. 23However, some notable limitations challenge the relevance of this and other estimates.Using a human capital approach, this model makes important assumptions regarding the prevalence of depression in the workforce, the duration of depressive episodes, their imputed impact on productive time at work, and the cost to employers.Furthermore, although stated in 1990 terms, the cost estimate is based on data collected in the early to mid-1980s.The management and treatment of depression has changed substantially since the 1980s; use of pharmaceutical care and, more generally, access to care have increased 26 and may have influenced disability status and how work time is lost.
Cdc42 Deficiency Causes Ciliary Abnormalities and Cystic Kidneys
Authors: Soo Young Choi, Maria F. Chacon-Heszele, Liwei Huang, Sarah McKenna, F. Perry Wilson, Xiaofeng Zuo, Joshua H. Lipschutz
Journal: Journal of the American Society of Nephrology (2013)

Ciliogenesis and cystogenesis require the exocyst, a conserved eight-protein trafficking complex that traffics ciliary proteins. In culture, the small GTPase Cdc42 co-localizes with the exocyst at primary cilia and interacts with the exocyst component Sec10. The role of Cdc42 in vivo, however, is not well understood. Here, knockdown of cdc42 in zebrafish produced a phenotype similar to sec10 knockdown, including tail curvature, glomerular expansion, and mitogen-activated protein kinase (MAPK) activation, suggesting that cdc42 and sec10 cooperate in ciliogenesis. In addition, cdc42 knockdown led to hydrocephalus and loss of photoreceptor cilia. Furthermore, there was a synergistic genetic interaction between zebrafish cdc42 and sec10, suggesting that cdc42 and sec10 function in the same pathway. Mice lacking Cdc42 specifically in kidney tubular epithelial cells died of renal failure within weeks of birth. Histology revealed cystogenesis in distal tubules and collecting ducts, decreased ciliogenesis in cyst cells, increased tubular cell proliferation, increased apoptosis, increased fibrosis, and led to MAPK activation, all of which are features of polycystic kidney disease, especially nephronophthisis. Taken together, these results suggest that Cdc42 localizes the exocyst to primary cilia, whereupon the exocyst targets and docks vesicles carrying ciliary proteins. Abnormalities in this pathway result in deranged ciliogenesis and polycystic kidney disease.
ECONOMETRICS IN OUTCOMES RESEARCH: The Use of Instrumental Variables
Authors: Joseph P. Newhouse, Mark McClellan
Journal: Annual Review of Public Health (1998)

▪ Abstract We describe an econometric technique, instrumental variables, that can be useful in estimating the effectiveness of clinical treatments in situations when a controlled trial has not or cannot be done. This technique relies upon the existence of one or more variables that induce substantial variation in the treatment variable but have no direct effect on the outcome variable of interest. We illustrate the use of the technique with an application to aggressive treatment of acute myocardial infarction in the elderly.
Novel antitumor agents from higher plants
Authors: Kuo-Hsiung Lee
Journal: Medicinal Research Reviews (1999)

This review article describes research on cytotoxic natural products isolated from plant sources, primarily preclinical lead identification and structural modification studies performed in the Natural Products Laboratory of Dr. K. H. Lee. As a result of this work, more than 100 new cytotoxic antitumor compounds and their synthetic analogs have shown confirmed activity in NCI's in vitro human tumor cell lines bioassay and are of current interest to NCI for further in vivo evaluation. A significant and ongoing project involves novel antitumor analogs related to podophyllotoxin and etoposide, and has led to a potent derivative designated GL331 (17). This compound is currently in Phase IIa clinical trials and shows promise as an anticancer drug, especially for drug-resistant cancers. Bioactivity-directed fractionation and isolation of medicinal herbs (primarily herbs of Chinese origin) have also led to many classes of cytotoxic compounds including polyphenolic compounds, sesquiterpene lactones, lignans, quassinoids, triterpene glucosides, flavonoids, colchicine derivatives, and quinone derivatives.
<i>IDH1</i> Mutations as Molecular Signature and Predictive Factor of Secondary Glioblastomas
Authors: Sumihito Nobusawa, Takuya Watanabe, Paul Kleihues, Hiroko Ohgaki
Journal: Clinical Cancer Research (2009)

To establish the frequency of IDH1 mutations in glioblastomas at a population level, and to assess whether they allow reliable discrimination between primary (de novo) glioblastomas and secondary glioblastomas that progressed from low-grade or anaplastic astrocytoma.We screened glioblastomas from a population-based study for IDH1 mutations and correlated them with clinical data and other genetic alterations.IDH1 mutations were detected in 36 of 407 glioblastomas (8.8%). Glioblastoma patients with IDH1 mutations were younger (mean, 47.9 years) than those with EGFR amplification (60.9 years) and were associated with significantly longer survival (mean, 27.1 versus 11.3 months; P < 0.0001). IDH1 mutations were frequent in glioblastomas diagnosed as secondary (22 of 30; 73%), but rare in primary glioblastomas (14 of 377; 3.7%: P < 0.0001). IDH1 mutations as genetic marker of secondary glioblastoma corresponded to the respective clinical diagnosis in 95% of cases. Glioblastomas with IDH1 mutation diagnosed as primary had clinical and genetic profiles similar to those of secondary glioblastomas, suggesting that they may have rapidly progressed from a less malignant precursor lesion that escaped clinical diagnosis and were thus misclassified as primary. Conversely, glioblastomas without IDH1 mutations clinically diagnosed as secondary typically developed from anaplastic rather than low-grade gliomas, suggesting that at least some were actually primary glioblastomas, that may have been misclassified, possibly due to histologic sampling error.IDH1 mutations are a strong predictor of a more favorable prognosis and a highly selective molecular marker of secondary glioblastomas that complements clinical criteria for distinguishing them from primary glioblastomas.
Increase in age at onset of giant cell arteritis: a population-based study
Authors: T. A. Kermani, V. S. Schafer, C. S. Crowson, G. G. Hunder, S. E. Gabriel, E. L. Matteson, K. J. Warrington
Journal: Annals of the Rheumatic Diseases (2009)

Giant cell arteritis (GCA) is a granulomatous vasculitis of large and medium-sized arteries that occurs in individuals aged ≥50 years.1 A recent study suggested that the age at incidence of GCA may be increasing.2 To address this issue, we studied the trends in mean age at onset of GCA over a 55-year period.

A population-based incident cohort of 173 patients with GCA diagnosed between 1 January 1950 and 31 December 1999 has been established using the resources of the Rochester Epidemiology Project.3 4 We extended the cohort to include 34 new cases of GCA diagnosed between 1 January 2000 and 31 December 2004. Patients were included in the study if they fulfilled the 1990 American College of Rheumatology criteria.5 Age- and sex-specific incidence rates were calculated based …
Circulating Tumor Cells: Will They Be Clinically Useful?
Authors: N. J. Nelson
Journal: JNCI Journal of the National Cancer Institute (2010)

N E W Sversus 10.1 months) and progression-free survival (7.0 versus 2.7 months) than those with fi ve or more CTCs per 7.5 mL of blood.Three to 4 weeks later, after therapy, the difference between the groups remained statistically signifi cant.And after therapy, the number of women in the lower-level CTC group increased, presumably because of a positive response.In a follow-up study with the same patients, published in Clinical Cancer Research in 2006, G. Thomas Budd, M.D. , professor of medicine at the Cleveland Clinic in Ohio, reported that the number of CTCs in this population was a better indicator of disease progression than traditional imaging techniques such as computed tomography and magnetic resonance imaging; CTCs were more reproducible, were better predictors of survival, and estimated disease progression earlier.A 2009 Annals of Oncology article reported that CTC levels were a good predictor of overall survival in metastatic breast cancer patients.Colon cancer patients have shown similar results.Neal Meropol, M.D., from University Hospitals Case Medical Center in Cleveland, was part of a team that tested whether CTCs were associated with prognosis in patients with metastatic colorectal cancer.Among the 430 patients who took part in this study, there was a statistically signifi cant difference associated with CTC levels.
Treatment of severe nosocomial pneumonia: a prospective randomised comparison of intravenous ciprofloxacin with imipenem/cilastatin
Authors: A Torres
Journal: Thorax (2000)

<h3>Background</h3> A renewed interest for activity and chronicity indices as predictors of lupus nephritis (LN) outcome has emerged. Revised National Institutes of Health activity and chronicity indices have been proposed to classify LN lesions, but they should be validated by future studies. The aims of this study were (<i>1</i>) to detect the histologic features associated with the development of kidney function impairment (KFI), and (<i>2</i>) to identify the best clinical-histologic model to predict KFI at time of kidney biopsy. <h3>Methods</h3> Patients with LN who had more than ten glomeruli per kidney biopsy specimen were admitted to the study. Univariate and multivariate logistic regression and Cox proportional hazards models were used to investigate whether activity and chronicity indices could predict KFI development. <h3>Results</h3> Among 203 participants with LN followed for 14 years, correlations were found between the activity index, and its components, and clinical-laboratory signs of active LN at baseline. The chronicity index was correlated with serum creatinine. Thus, serum creatinine was significantly and directly correlated with both activity and chronicity indices. In the multivariate analysis, glomerulosclerosis (OR, 3.05; 95% CI, 1.17 to 7.91; <i>P</i>=0.02) and fibrous crescents (OR, 6.84; 95% CI, 3.22 to 14.52; <i>P</i>&lt;0.001) associated with either moderate/severe tubular atrophy (OR, 3.17; 95% CI, 1.04 to 9.64; <i>P</i>=0.04), or with interstitial fibrosis (OR, 2.36; 95% CI, 1.05 to 5.32; <i>P</i>=0.04), predicted KFI. Considering both clinical and histologic features, serum creatinine (OR, 1.68; 95% CI, 1.31 to 2.15; <i>P</i>&lt;0.001), arterial hypertension (OR, 4.64; 95% CI, 1.90 to 11.32; <i>P</i>&lt;0.001), glomerulosclerosis (OR, 2.12; 95% CI, 1.00 to 4.50; <i>P</i>=0.05), and fibrous crescents (OR, 5.18; 95% CI, 2.43 to 11.04; <i>P</i>&lt;0.001) independently predicted KFI. Older age (<i>P</i>&lt;0.001) and longer delay between clinical onset of LN and kidney biopsy (<i>P</i>&lt;0.001) were significantly correlated with baseline chronicity index. <h3>Conclusions</h3> The chronicity index and its components, but not the activity index, were significantly associated with an impairment of kidney function. The Cox model showed that serum creatinine, arterial hypertension, chronic glomerular lesions, and delay in kidney biopsy predicted KFI. These data reinforce the importance of timely kidney biopsy in LN.
Survival in Patients with Glioblastoma Receiving Valganciclovir
Authors: Cecilia Söderberg-Nauclér, Afsar Rahbar, Giuseppe Stragliotto
Journal: New England Journal of Medicine (2013)

A retrospective analysis of selected patients with glioblastoma who received treatment for cytomegalovirus with their anticancer treatment showed surprisingly good 2-year survival. A randomized trial is needed.
Nilotinib versus imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours (ENESTg1): a randomised phase 3 trial
Authors: Jean-Yves Blay, Lin Shen, Yoon-Koo Kang, Piotr Rutkowski, Shukui Qin, Dmitry Nosov, Desen Wan, Jonathan Trent, Vichien Srimuninnimit, Zsuzsanna Pápai, Axel Le Cesne, Steven Novick, Lilia Taningco, Shuyuan Mo, Steven Green, Peter Reichardt, George D Demetri
Journal: The Lancet Oncology (2015)
Randomized trial comparing albumin and saline in the prevention of paracentesis-induced circulatory dysfunction in cirrhotic patients with ascites
Authors: Javier Sola-Vera, Josep Miñana, Elena Ricart, Montserrat Planella, Begoña González, Xavier Torras, Jose Rodríguez, José Such, Sonia Pascual, Germán Soriano, Miguel Pérez-Mateo, Carlos Guarner
Journal: Hepatology (2003)

Paracentesis–induced circulatory dysfunction (PICD) is a recently described complication that can be prevented with the administration of plasma expanders. The aim of this study was to compare the efficacy of saline versus albumin in the prevention of PICD. Patients were randomized to receive albumin or saline after total paracentesis. Patients readmitted as a consequence of a second episode of tense ascites were treated with total paracentesis and the alternative plasma expander. After randomization, 35 patients received saline and 37 received albumin. Twenty–one patients were readmitted for tense ascites and treated with the alternative expander. Significant increases in plasma renin activity (PRA) were found 24 hours and 6 days after paracentesis when saline was used (baseline, 5.6 ± 5.7; 24 hours, 7.6 ± 6.9; 6 days, 8.5 ± 8.0 ng · mL -1 · hr -1 ; P &lt; .05 and P &lt; .01 vs. baseline, respectively), whereas no significant changes were observed with albumin. The incidence of PICD was significantly higher in the saline group versus the albumin group (33.3% vs. 11.4%, respectively; P = .03). However, no significant differences were found when less than 6 L of ascitic fluid was evacuated (6.7% vs. 5.6% in the saline and albumin groups, respectively; P = .9). Similar results were observed when analyzing patients who received 2 consecutive paracentesis ( i.e. , a significant increase in PRA after saline [ P &lt; .01] without significant variations after albumin). In conclusion, albumin is more effective than saline in the prevention of PICD. Saline is a valid alternative to albumin when less than 6 L of ascitic fluid is evacuated.
Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling
Authors: Jian Huang, Da-Li Zheng, Feng-Song Qin, Na Cheng, Hui Chen, Bing-Bing Wan, Yu-Ping Wang, Hua-Sheng Xiao, Ze-Guang Han
Journal: Journal of Clinical Investigation (2009)

The epigenetic silencing of tumor suppressor genes is a crucial event during carcinogenesis and metastasis. Here, in a human genome-wide survey, we identified scavenger receptor class A, member 5 (SCARA5) as a candidate tumor suppressor gene located on chromosome 8p. We found that SCARA5 expression was frequently downregulated as a result of promoter hypermethylation and allelic imbalance and was associated with vascular invasion in human hepatocellular carcinoma (HCC). Furthermore, SCARA5 knockdown via RNAi markedly enhanced HCC cell growth in vitro, colony formation in soft agar, and invasiveness, tumorigenicity, and lung metastasis in vivo. By contrast, SCARA5 overexpression suppressed these malignant behaviors. Interestingly, SCARA5 was found to physically associate with focal adhesion kinase (FAK) and inhibit the tyrosine phosphorylation cascade of the FAK-Src-Cas signaling pathway. Conversely, silencing SCARA5 stimulated the signaling pathway via increased phosphorylation of certain tyrosine residues of FAK, Src, and p130Cas; it was also associated with activation of MMP9, a tumor metastasis-associated enzyme. Taken together, these data suggest that the plasma membrane protein SCARA5 can contribute to HCC tumorigenesis and metastasis via activation of the FAK signaling pathway.
Activity and Thermosensitivity of Canine Cutaneous Veins after Inhibition of Monoamine Oxidase and Catechol-O-Methyl Transferase
Authors: PAUL M. VANHOUTTE, JOHN T. SHEPHERD
Journal: Circulation Research (1969)

The lateral saphenous vein of the dog was perfused with homologous blood at constant flow. Changes in driving pressure were used to measure active changes in venous tone. Administration of tranylcypromine greatly reduced the activity of monoamine oxidase in the vein and increased its response to electric stimulation of the lumbar sympathetic chain and to norepinephrine infusions. Administration of pyrogallol (a catechol-O-methyl transferase inhibitor) also increased the response of the vein to adrenergic stimulation. These chemicals did not alter the increase in the sensitivity of the venous smooth muscle to sympathetic nerve impulses and infused norepinephrine produced by cooling the perfusate. Thus, the potentiating effect of local cooling on the response of the cutaneous veins to adrenergic stimulation cannot be explained by interference with the local enzymatic inactivation of catecholamines.
Maintenance rituximab following induction chemoimmunotherapy may prolong progression-free survival in mantle cell lymphoma: a pilot study from the Wisconsin Oncology Network
Authors: B.S. Kahl, W.L. Longo, J.C. Eickhoff, J. Zehnder, C. Jones, J. Blank, T. McFarland, W. Bottner, H. Rezazedeh, J. Werndli, H.H. Bailey
Journal: Annals of Oncology (2006)
Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children
Authors: Supinda Bunyavanich, Sheryl L. Rifas-Shiman, Thomas A. Platts-Mills, Lisa Workman, Joanne E. Sordillo, Carlos A. Camargo, Matthew W. Gillman, Diane R. Gold, Augusto A. Litonjua
Journal: Journal of Allergy and Clinical Immunology (2014)