tbuckley/cabot-search huggingface dataset:
A Risk Score for Type 1 Diabetes Derived From Autoantibody-Positive Participants in the Diabetes Prevention Trial–Type 1
Authors: Jay M. Sosenko, Jeffrey P. Krischer, Jerry P. Palmer, Jeffrey Mahon, Catherine Cowie, Carla J. Greenbaum, David Cuthbertson, John M. Lachin, Jay S. Skyler
Journal: Diabetes Care (2008)

OBJECTIVE—The accurate prediction of type 1 diabetes is essential for appropriately identifying prevention trial participants. Thus, we have developed a risk score for the prediction of type 1 diabetes. RESEARCH DESIGN AND METHODS—Diabetes Prevention Trial–Type 1 (DPT-1) participants, islet cell autoantibody (ICA)-positive relatives of type 1 diabetic patients (n = 670), were randomly divided into development and validation samples. Risk score values were calculated for the validation sample from development sample model coefficients obtained through forward stepwise proportional hazards regression. RESULTS—A risk score based on a model including log-BMI, age, log-fasting C-peptide, and postchallenge glucose and C-peptide sums from 2-h oral glucose tolerance tests (OGTTs) was derived from the development sample. The baseline risk score strongly predicted type 1 diabetes in the validation sample (χ2 = 82.3, P &amp;lt; 0.001). Its strength of prediction was almost the same (χ2 = 83.3) as a risk score additionally dependent on a decreased first-phase insulin response variable from intravenous glucose tolerance tests (IVGTTs). Biochemical autoantibodies did not contribute significantly to the risk score model. A final type 1 diabetes risk score was then derived from all participants with the same variables as those in the development sample model. The change in the type 1 diabetes risk score from baseline to 1 year was in itself also highly predictive of type 1 diabetes (P &amp;lt; 0.001). CONCLUSIONS—A risk score based on age, BMI, and OGTT indexes, without dependence on IVGTTs or additional autoantibodies, appears to accurately predict type 1 diabetes in ICA-positive relatives.
Pegylated Interferon Alfa-2b vs Standard Interferon Alfa-2b, Plus Ribavirin, for Chronic Hepatitis C in HIV-Infected Patients&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Fabrice Carrat
Journal: JAMA (2004)

ContextTreatment of chronic hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)–infected patients is a growing concern. Most data on the virologic efficacy and safety of the combination of peginterferon alfa-2b and ribavirin in coinfected patients come from uncontrolled studies.ObjectiveTo study the safety and efficacy of peginterferon alfa-2b plus ribavirin vs standard interferon alfa-2b plus ribavirin in HIV-HCV coinfected patients.Design and SettingsA multicenter, randomized, parallel-group, open-label trial. Patients were enrolled from February 2000 to February 2002 and followed up for 72 weeks.PatientsFour hundred twelve HIV-HCV coinfected patients with detectable serum HCV-RNA, abnormal liver histology, a CD4 cell count of at least 200 × 106/L, and stable plasma HIV-RNA.InterventionTreatment with ribavirin 400 mg twice a day, orally, plus either peginterferon alfa-2b (1.5 μg/kg subcutaneous injection once a week) or standard interferon alfa-2b (3 million units of subcutaneous injection 3 times a week) for 48 weeks.Main Outcome MeasuresSustained virologic response, defined by undetectable serum HCV-RNA at week 72.ResultsMore patients had sustained virologic responses in the peginterferon group than in the standard interferon group (27% vs 20%, P = .047). This difference between the treatments was found in patients with HCV genotype 1 or 4 infection (17% for peginterferon vs 6% for standard interferon, P = .006) but was not found in patients with HCV genotype 2, 3, or 5 (44% for peginterferon vs 43% for standard interferon, P = .88). Together, a decline in HCV-RNA of less than 2 log10 from baseline and detectable serum HCV-RNA at week 12 predicted 99% of treatment failures. Histologic activity diminished and fibrosis stabilized in virologic responders. The 2 regimens showed similar tolerability although dose modifications for clinical and biological events were more frequent with peginterferon. Eleven cases of pancreatitis or symptomatic hyperlactatemia were observed, all in patients receiving didanosine-containing antiretroviral regimens.ConclusionIn combination with ribavirin, treatment with peginterferon alfa-2b is more effective than standard interferon alfa-2b for HCV infection in HIV-infected patients.
Albendazole in the treatment of pulmonary echinococcosis.
Authors: P Aggarwal, J P Wali
Journal: Thorax (1991)

Ten patients with pulmonary hydatid disease diagnosed on the basis of a chest radiograph and a positive response to the indirect haemagglutination test for hydatid disease were treated with albendazole 10 mg/kg/day for eight weeks. None of the 10 patients showed any radiological or serological improvement with this treatment regimen. Albendazole in these doses appears to have little role in the treatment of pulmonary hydatid disease.
PD-1 Inhibits Antiviral Immunity at the Effector Phase in the Liver
Authors: Yoshiko Iwai, Seigo Terawaki, Masaya Ikegawa, Taku Okazaki, Tasuku Honjo
Journal: The Journal of Experimental Medicine (2003)

Unlike naive T cells, effector T cells can be activated by either T cell receptor signal or costimulatory signal alone and therefore the absence of costimulatory molecules on tissue cells cannot explain the tolerance mechanism at the effector phase. Here we report that PD-L1, the ligand for the immunoinhibitory receptor PD-1, was expressed on vascular endothelium in peripheral tissues. Liver nonparenchymal cells including sinusoidal endothelial cells and Kupffer cells constitutively expressed PD-L1 and inhibited proliferation and cell division of activated T cells expressing PD-1. The absence of PD-1 induced proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus. These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity.
Proteinuria and Hyperglycemia Induce Endoplasmic Reticulum Stress
Authors: Maja T. Lindenmeyer, Maria P. Rastaldi, Masami Ikehata, Matthias A. Neusser, Matthias Kretzler, Clemens D. Cohen, Detlef Schlo[Combining Diaeresis]ndorff
Journal: Journal of the American Society of Nephrology (2008)

The endoplasmic reticulum (ER) is an important site for protein folding and becomes "stressed" when its capacity to fold proteins is overwhelmed. In response, "unfolded protein response" (UPR) genes are induced, increasing the capacity to fold proteins; if the response is insufficient, then apoptosis ensues. For investigation of whether proteinuria and hyperglycemia induce ER stress in renal epithelial cells, microarray data from biopsies of established diabetic nephropathy (DN) were analyzed. Expression of UPR genes was significantly different in these biopsies than in control kidneys or biopsies of patients with mild DN, suggesting an association between the degree of DN and UPR gene expression. Expression of the transcription factor XBP1 and the ER chaperones HSPA5 and HYOU1 were increased, but the proapoptotic gene DDIT3 was unchanged. These findings were replicated in an independent cohort of patients with established DN by real-time reverse transcriptase-PCR. Immunofluorescence of renal biopsies from patients with DN confirmed the upregulation for HSPA5 and HYOU1 proteins in tubular epithelia. In biopsies of minimal-change disease, the mRNA levels of some ER stress molecules were also induced, but protein expression of HSPA5 and HYOU1 remained significantly lower than that observed in DN. Exposure of renal tubular epithelial cells to albumin and high glucose in vitro enhanced expression of genes involved in ER stress. These observations suggest that in proteinuric diseases, tubular epithelial cells undergo ER stress, which induces an adaptive, protective UPR. Although this may protect the cells from ER stress, persistence of hyperglycemia and proteinuria may eventually lead to apoptosis.
Ventricular receptors activated following myocardial prostaglandin synthesis initiate reflex hypotension, reduction in heart rate, and redistribution of cardiac output in the dog.
Authors: T H Hintze, G Kaley
Journal: Circulation Research (1984)

Arachidonic acid (250 micrograms) injected into the left circumflex coronary artery of anesthetized dogs, with carotid arteries tied to reduce baroreflex-induced changes, caused a reduction in heart rate (-15 +/- 1.6 beats/min), mean arterial pressure (-27 +/- 3.4 mm Hg), and left ventricular dP/dt (-939 +/- 138 mm Hg/sec). In contrast, injection of arachidonic acid into the left anterior descending coronary artery caused smaller changes in heart rate (-4.6 +/- 1.6 beats/min), arterial pressure (-14 +/- 2.8 mm Hg), and left ventricular dP/dt (-118 +/- 131 mm Hg/sec). The hypotension following the injection of arachidonic acid results from an increase in perfusion of the kidney and skeletal muscle (as measured by radioactive microspheres), and is entirely reflex, since the changes in renal blood flow, as well as the reduction in heart rate and the hypotension, are eliminated by bilateral vagal section. Increasing the dose of arachidonic acid results in dose-related changes in heart rate, arterial pressure, and left ventricular dP/dt. Prostacyclin and prostaglandin E2, the two principle coronary vasodilator metabolites of arachidonic acid, but not nitroprusside, cause a fall in blood pressure and heart rate, establishing that coronary vasodilation per se is not responsible for initiating the reflex fall in arterial pressure and heart rate. In two dogs with sinoaortic denervation, circumflex injection of arachidonic acid caused larger reductions in heart rate (-21 +/- 1.5 beats/min) and mean arterial pressure (-51 +/- 3.5 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
Cochrane Reviews: new blocks on the kids
Authors: I Shrier
Journal: British Journal of Sports Medicine (2003)

The Cochrane Collaboration should be congratulated for its dedication to documenting continuing clinical trials, teaching critical appraisal, and supporting research into new methods of reviewing the literature. However, Cochrane Reviews can be created by untrained people who simply follow an algorithmic approach and are unaware of important methodological issues. Therefore, the objective of this article is to highlight important limitations of Cochrane Reviews, including the Review Manager software1 that is required,2 the inappropriate use of a summary statistic, and finally the restriction to only randomised controlled trial (RCT) data. To illustrate these points, I have used a 1% random sample of Cochrane Reviews—that is, 16 studies numbered 1, 101, 201…1501 of 1596 of the Cochrane Database on 3 April 2003.3–18

There are important limitations to the software required by the Cochrane Collaboration (Review Manager). Most important is that Review Manager cannot include ( a ) results based on survival analyses—for example, most appropriate analysis for time to next injury—and instead calculates relative risks based on simple proportions (this leads to inappropriate estimates when patients have different lengths of follow up19) and ( b ) analyses adjusted for confounding—that is, multiple regression analysis. Software is available, but requires statistical expertise that would preclude the algorithmic approach.

Whereas the Cochrane Collaboration could improve its software, the other two major problems are process oriented. The Cochrane Collaboration promotes wide participation, and this leads to inexperienced authors and peer reviewers. For example, it is not always appropriate to pool data into one overall summary statistic,20 and, even when it is, there are different methods—that is, fixed and random effects models—to be used depending on the structure of the data.20,21 In the …
SURVIVAL ANALYSIS IN PUBLIC HEALTH RESEARCH
Authors: Elisa T. Lee, Oscar T. Go
Journal: Annual Review of Public Health (1997)

▪ Abstract This paper reviews the common statistical techniques employed to analyze survival data in public health research. Due to the presence of censoring, the data are not amenable to the usual method of analysis. The improvement in statistical computing and wide accessibility of personal computers led to the rapid development and popularity of nonparametric over parametric procedures. The former required less stringent conditions. But, if the assumptions for parametric methods hold, the resulting estimates have smaller standard errors and are easier to interpret. Nonparametric techniques include the Kaplan-Meier method for estimating the survival function and the Cox proportional hazards model to identify risk factors and to obtain adjusted risk ratios. In cases where the assumption of proportional hazards is not tenable, the data can be stratified and a model fitted with different baseline functions in each stratum. Parametric modeling such as the accelerated failure time model also may be used. Hazard functions for the exponential, Weibull, gamma, Gompertz, lognormal, and log-logistic distributions are described. Examples from published literature are given to illustrate the various methods. The paper is intended for public health professionals who are interested in survival data analysis.
RBMY, a novel inhibitor of glycogen synthase kinase 3β, increases tumor stemness and predicts poor prognosis of hepatocellular carcinoma
Authors: Huey‐Huey Chua, Daw‐Jen Tsuei, Po‐Huang Lee, Yung‐Ming Jeng, Jean Lu, Jia‐Feng Wu, De‐Shiuan Su, Ya‐Hui Chen, Chin‐Sung Chien, Pei‐Chi Kao, Chien‐Nan Lee, Rey‐Heng Hu, Yen‐Hsuan Ni, Mei‐Hwei Chang
Journal: Hepatology (2015)

Male predominance of hepatocellular carcinoma (HCC) occurs particularly among young children aged 6‐9 years, indicative of a possible role of the Y chromosome–encoded oncogene in addition to an androgenic effect. The discovery of oncogenic activation of RBMY (RNA‐binding motif on Y chromosome), which is absent in normal hepatocytes but present in male HCC tissues, sheds light on this issue. Herein, we report on a critical hepatocarcinogenic role of RBMY and its ontogenic origin. During liver development, the Ser/Thr phosphorylated RBMY is expressed in the cytoplasm of human and rodent fetal livers. It is then silenced in mature hepatocytes and restricted to scarce expression in the bile ductular cells. Upon hepatocarcinogenesis, a noteworthy increase of cytoplasmic and nuclear RBMY is observed in HCC tissues; however, only the former is expressed dominantly in hepatic cancer stem cells and correlates significantly to a poor prognosis and decreased survival rate in HCC patients. Cytoplasmic expression of RBMY, which is mediated by binding to nuclear exporter chromosome region maintenance 1 and further enriched upon Wnt‐3a stimulation, confers upon tumor cells the traits of cancer stem cell by augmenting self‐renewal, chemoresistance, cell‐cycle progression, proliferation, and xenograft tumor growth. This is achieved mechanistically through increasing Ser9 phosphorylation‐inactivation of glycogen synthase kinase 3β by RBMY, thereby impeding the glycogen synthase kinase 3β–dependent degradation of β‐catenin and eventually inducing the nuclear entry of β‐catenin for the transcription of downstream oncogenes. Conclusion : RBMY is a novel oncofetal protein that plays a key role in attenuating glycogen synthase kinase 3β activity, leading to aberrant activation of Wnt/β‐catenin signaling, which facilitates malignant hepatic stemness; because of its absence from normal human tissues except the testis, RBMY represents a feasible therapeutic target for the selective eradication of HCC cells in male patients. (H epatology 2015;62:1480–1496)
Risk Factors and Other Epidemiologic Considerations for Cervical Cancer Screening: A Narrative Review for the U.S. Preventive Services Task Force
Authors: Kimberly K. Vesco, Evelyn P. Whitlock, Michelle Eder, Brittany U. Burda, Caitlyn A. Senger, Kevin Lutz
Journal: Annals of Internal Medicine (2011)

Despite the success of cervical cancer screening programs, questions remain about the appropriate time to begin and end screening. This review explores epidemiologic and contextual data on cervical cancer screening to inform decisions about when screening should begin and end. Cervical cancer is rare among women younger than 20 years. Screening for cervical cancer in this age group is complicated by lower rates of detection and higher rates of false-positive results than in older women. Methods used to diagnose and treat cervical intraepithelial neoplasia have important potential adverse effects. High-risk human papillomavirus infections and abnormalities on cytologic and histologic examination have relatively high rates of regression. Accordingly, cervical cancer screening in women younger than 20 years may be harmful. The incidence of, and mortality rates from, cervical cancer and the proportion of U.S. women aged 65 years or older who have had a Papanicolaou smear within 3 years have decreased since 2000. Available evidence supports discontinuation of cervical cancer screening among women aged 65 years or older who have had adequate screening and are not otherwise at high risk. Further reductions in the burden of cervical cancer in older women are probably best achieved by focusing on screening those who have not been adequately screened.
The Mechanism of Phosphorus as a Cardiovascular Risk Factor in CKD
Authors: Suresh Mathew, Kimberly S. Tustison, Toshifumi Sugatani, Lala R. Chaudhary, Leonard Rifas, Keith A. Hruska
Journal: Journal of the American Society of Nephrology (2008)

Hyperphosphatemia and vascular calcification have emerged as cardiovascular risk factors among those with chronic kidney disease. This study examined the mechanism by which phosphorous stimulates vascular calcification, as well as how controlling hyperphosphatemia affects established calcification. In primary cultures of vascular smooth muscle cells derived from atherosclerotic human aortas, activation of osteoblastic events, including increased expression of bone morphogenetic protein 2 (BMP-2) and the transcription factor RUNX2, which normally play roles in skeletal morphogenesis, was observed. These changes, however, did not lead to matrix mineralization until the phosphorus concentration of the media was increased; phosphorus stimulated expression of osterix, a second critical osteoblast transcription factor. Knockdown of osterix with small interference RNA (siRNA) or antagonism of BMP-2 with noggin prevented matrix mineralization in vitro. Similarly, vascular BMP-2 and RUNX2 were upregulated in atherosclerotic mice, but significant mineralization occurred only after the induction of renal dysfunction, which led to hyperphosphatemia and increased aortic expression of osterix. Administration of oral phosphate binders or intraperitoneal BMP-7 decreased expression of osterix and aortic mineralization. It is concluded that, in chronic kidney disease, hyperphosphatemia stimulates an osteoblastic transcriptional program in the vasculature, which is mediated by osterix activation in cells of the vascular tunica media and neointima.
Identification and localization of polycystin, the PKD1 gene product.
Authors: L Geng, Y Segal, B Peissel, N Deng, Y Pei, F Carone, H G Rennke, A M Glücksmann-Kuis, M C Schneider, M Ericsson, S T Reeders, J Zhou
Journal: Journal of Clinical Investigation (1996)

Polycystin, the product of autosomal dominant polycystic kidney disease (ADPKD) 1 gene (PKD1) is the cardinal member of a novel class of proteins. As a first step towards elucidating the function of polycystin and the pathogenesis of ADPKD, three types of information were collected in the current study: the subcellular localization of polycystin, the spatial and temporal distribution of the protein within normal tissues and the effects of ADPKD mutations on the pattern of expression in affected tissues. Antisera directed against a synthetic peptide and two recombinant proteins of different domains of polycystin revealed the presence of an approximately 400-kD protein (polycystin) in the membrane fractions of normal fetal, adult, and ADPKD kidneys. Immunohistological studies localized polycystin to renal tubular epithelia, hepatic bile ductules, and pancreatic ducts, all sites of cystic changes in ADPKD, as well as in tissues such as skin that are not known to be affected in ADPKD. By electron microscopy, polycystin was predominantly associated with plasma membranes. Polycystin was significantly less abundant in adult than in fetal epithelia. In contrast, polycystin was overexpressed in most, but not all, cysts in ADPKD kidneys.
Inhibition of Angiogenesis and Tumor Metastasis by Targeting a Matrix Immobilized Cryptic Extracellular Matrix Epitope in Laminin
Authors: Abebe Akalu, Jennifer M. Roth, Maresa Caunt, Desiree Policarpio, Leonard Liebes, Peter C. Brooks
Journal: Cancer Research (2007)

Abstract Angiogenesis and tumor metastasis depend on extracellular matrix (ECM) remodeling and subsequent cellular interactions with these modified proteins. An in-depth understanding of how both endothelial and tumor cells use matrix-immobilized cryptic ECM epitopes to regulate invasive cell behavior may lead to the development of novel strategies for the treatment of human tumors. However, little is known concerning the existence and the functional significance of cryptic laminin epitopes in regulating angiogenesis and tumor cell metastasis. Here, we report the isolation and characterization of a synthetic peptide that binds to a cryptic epitope in laminin. The STQ peptide selectively bound denatured and proteolyzed laminin but showed little interaction with native laminin. The cryptic laminin epitope recognized by this peptide was selectively exposed within malignant melanoma in vivo, whereas little if any was detected in normal mouse skin. Moreover, the STQ peptide selectively inhibited endothelial and tumor cell adhesion, migration, and proliferation in vitro and inhibited angiogenesis, tumor growth, and experimental metastasis in vivo. This inhibitory activity was associated with a selective up-regulation of the cyclin-dependent kinase inhibitor P27KIP1 and induction of cellular senescence. These novel findings suggest the existence of functionally relevant cryptic laminin epitopes in vivo and that selective targeting of these laminin epitopes may represent an effective new strategy for the treatment of malignant tumors by affecting both the endothelial and tumor cell compartments. [Cancer Res 2007;67(9):4353–63]
Induced Sputum, Eosinophilic Bronchitis, and Chronic Obstructive Pulmonary Disease
Authors: FREDERICK E. HARGREAVE, RICHARD LEIGH
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Section:ChooseTop of pageAbstract <<SPUTUM INDUCTION AND EXAM...EOSINOPHILIC BRONCHITIS W...EOSINOPHILIC BRONCHITIS I...TREATMENT OF EOSINOPHILIC...ReferencesCITING ARTICLES
Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG)
Authors: A. Josting, C. Rudolph, M. Mapara, J.-P. Glossmann, M. Sieber, H.H. Kirchner, B. Dörken, D.K. Hossfeld, J. Kisro, B. Metzner, W.E. Berdel, V. Diehl, A. Engert, M. Sienawski
Journal: Annals of Oncology (2004)