tbuckley/cabot-search huggingface dataset:
Evidence of a Strong Association Between Frequency of Self-Monitoring of Blood Glucose and Hemoglobin A1c Levels in T1D Exchange Clinic Registry Participants
Authors: Kellee M. Miller, Roy W. Beck, Richard M. Bergenstal, Robin S. Goland, Michael J. Haller, Janet B. McGill, Henry Rodriguez, Jill H. Simmons, Irl B. Hirsch
Journal: Diabetes Care (2013)

Despite substantial evidence of the benefit of frequent self-monitoring of blood glucose (SMBG) in type 1 diabetes, certain insurers limit the number of test strips that they will provide. The large database of the T1D Exchange clinic registry provided an opportunity to evaluate the relationship between the number of SMBG measurements per day and HbA1c levels across a wide age range of children and adults.The analysis included 20,555 participants in the T1D Exchange clinic registry with type 1 diabetes ≥1 year and not using a continuous glucose monitor (11,641 younger than age 18 years and 8,914 18 years old or older). General linear models were used to assess the association between the number of SMBG measurements and HbA1c levels after adjusting for potential confounding variables.A higher number of SMBG measurements per day were associated with non-Hispanic white race, insurance coverage, higher household income, and use of an insulin pump for insulin delivery (P < 0.001 for each factor). After adjusting for these factors, a higher number of SMBG measurements per day was strongly associated with a lower HbA1c level (adjusted P < 0.001), with the association being present in all age-groups and in both insulin pump and injection users.There is a strong association between higher SMBG frequency and lower HbA1c levels. It is important for insurers to consider that reducing restrictions on the number of test strips provided per month may lead to improved glycemic control for some patients with type 1 diabetes.
Evaluation of the Self-Administered Indicator Plaster Neuropad for the Diagnosis of Neuropathy in Diabetes
Authors: Nicholas Tentolouris, Vasilis Achtsidis, Kyriaki Marinou, Nicholas Katsilambros
Journal: Diabetes Care (2008)

To evaluate the inter-rater reliability between patient and health care provider of the indicator plaster neuropad (IPN) in the diagnosis of peripheral neuropathy and the feasibility of the IPN.A total of 156 patients with diabetes were examined. At the same visit, the IPN was evaluated by the health care provider. Afterward, the IPN with written instructions for its use and evaluation for self-testing at home were provided together with a questionnaire asking for the easiness of the IPN.Neuropathy was diagnosed in 56.9% of the participants by the health care provider. The k statistic to measure overall agreement between patient and health care provider of the IPN was very good: 0.88 (95% CI 0.85-0.91). The indicated instructions and the IPN were evaluated as easy by the patients.The high degree of reliability and the easiness of the IPN suggest that it is proper for self-testing for the identification of peripheral neuropathy.
Elevated levels of Wnt3a and low levels of Dickkopf-1 in serum are associated with syndesmophyte formation in ankylosing spondylitis
Authors: Eva Klingberg, Merja Nurkkala, Hans Carlsten, Helena Forsblad-d'Elia
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Ankylosing spondylitis (AS) is associated with both pathologic formation of new bone and enhanced bone resorption. The objectives of this study were to assess a panel of biomarkers reflecting bone turnover and to determine their relationship with syndesmophyte formation, bone mineral density (BMD) and disease activity in AS. <h3>Materials and methods</h3> Inclusion criterion was AS fulfilling modified New York criteria. Exclusion criteria were psoriasis and inflammatory bowel disease. The patients answered questionnaires. BASDAI, ASDAS and CRP were chosen as disease activity parameters. Spinal mobility was assessed for calculation of BASMI. Lateral spine radiographs were scored for syndesmophyte formation (mSASSS). BMD was measured with dual energy x-ray absorptiometry (DXA). Levels of biomarkers were measured with sandwich ELISA in patient sera and compared with levels of healthy blood donor controls. The biomarkers studied were: Wingless proteins (Wnt3a, Wnt5a), Dickkopf-1 (Dkk-1), sclerostin, soluble receptor activator of nuclear factors-κΒ ligand (sRANKL) and osteoprotegerin (OPG). <h3>Results</h3> 204 patients (57% men) with a mean age of 50±13 years and disease duration 15±11 years and 80 age and sex matched controls were included. The AS patients demonstrated significantly higher levels of Wnt3a (3.72±0.99 vs 2.88±0.84 ng/ml; p&lt;0.001) and Dkk-1 (3.05±1.05 vs 2.79±8.70 ng/ml; p=0.048) as compared with the controls, whereas the level of sclerostin (35.33±21.54 vs 38.33±13.96 pmol/l; p=0.014) was lower in AS. No difference in serum levels between AS patients and controls were detected for Wnt5a, sRANKL or OPG. None of the studied biomarkers showed any significant correlation with BASDAI or ASDAS. High CRP was significantly correlated with lower levels of sclerostin (r<sub>S</sub>=−0.208, p=0.003) and Dkk-1(r<sub>S</sub>=−0.140, p=0.045). Age and male sex were highly significantly correlated with increasing mSASSS (p&lt;0.001). After adjusting for age and sex in multivariate analysis high Wnt3a (Stand.Β=0.140; p=0.017) and low Dkk-1 (Stand.Β=−0.132; p=0.025) remained independently associated with increasing mSASSS (R<sup>2</sup>=0.333). Low sclerostin (Stand.Β=0.262; p&lt;0.001) and high mSASSS (Stand.Β=−0.215; p=0.003) were independently associated with low Z-score for BMD femoral neck (R<sup>2</sup>=0.103). <h3>Conclusions</h3> The understanding of bone biomarkers in AS is challenged by the two enhanced opposite bone remodelling processes of the disease. The findings that high Wnt3a and low Dkk-1 is associated with syndesmophyte formation and low sclerostin with low BMD, merit further investigation.
COPD: problems in diagnosis and measurement
Authors: S.T. Weiss, D.L. DeMeo, D.S. Postma
Journal: European Respiratory Journal (2003)

Chronic obstructive pulmonary disease (COPD) is the most rapidly rising cause of death in individuals &gt;65 yrs of age, the most rapidly growing segment of the USA population. Advancing the clinical research agenda for COPD entails careful consideration of several issues and problems: defining COPD, reliance on physiological testing, outcome measurements and comorbidities. In addition, issues pertaining to the recent dramatic increase in chronic obstructive pulmonary disease mortality in females, smoking susceptibility and the relationship of respiratory symptoms with hyperresponsiveness, as well as chronic obstructive pulmonary disease heterogeneity, are discussed.
Detecting and Locating Whole Genome Duplications on a Phylogeny: A Probabilistic Approach
Authors: Charles-Elie Rabier, Tram Ta, Cécile Ané
Journal: Molecular Biology and Evolution (2013)

Whole genome duplications (WGDs) followed by massive gene loss occurred in the evolutionary history of many groups. WGDs are usually inferred from the age distribution of paralogs (Ks-based methods) or from gene collinearity data (synteny). However, Ks-based methods are restricted to detect the recent WGDs due to saturation effects and the difficulty to date old duplicates, and synteny is difficult to reconstruct for distantly related species. Recently, Jiao et al. (Jiao Y, Wickett N, Ayyampalayam S, Chanderbali AS, Landherr L, Ralph PE, Tomsho LP, Hu Y, Liang H, Soltis PS, et al. 2011. Ancestral polyploidy in seed plants and angiosperms. Nature 473:97-100) introduced an empirical method that aims to detect a peak in duplication ages among nodes selected from a previous phylogenetic analysis. In this context, we present here two rigorous methods based on data from multiple gene families and on a new probabilistic model. Our model assumes that all gene lineages are instantaneously duplicated at the WGD event with a possible almost-immediate loss of some extra copies. Our reconciliation method relies on aligned molecular sequences, whereas our gene count method relies only on gene count data across species. We show, using extensive simulations, that both methods have a good detection power. Surprisingly, the gene count method enjoys no loss of power compared with the reconciliation method, despite the fact that sequence information is not used. We finally illustrate the performance of our methods on a benchmark yeast data set. Both methods are able to detect the well-known WGD in the Saccharomyces cerevisiae clade and agree on a small retention rate at the WGD, as established by synteny-based methods.
Sequence analysis and expression of an X-linked, lymphocyte-regulated gene family (XLR).
Authors: J N Siegel, C A Turner, D M Klinman, M Wilkinson, A D Steinberg, C L MacLeod, W E Paul, M M Davis, D I Cohen
Journal: The Journal of Experimental Medicine (1987)

The XLR gene family consists of approximately 10 X-linked genes, the expression of which is regulated in lymphocyte development. Certain members of the gene family are closely linked to the murine xid immune deficiency mutation. Sequence analysis of a cDNA clone pM1 derived from the plasmacytoma MOPC167 showed an open reading frame capable of coding for a protein of 208 amino acids and mol wt 24,000. The lack of a signal peptide or transmembrane region indicates a probable cytoplasmic or nuclear localization for the predicted pM1 protein. The predicted protein shares significant homology with lamins A and C and other members of the intermediate filament family of proteins, and shares features important for the coiled-coil structure proposed for these proteins. Analysis of cDNA clones derived from a presecretory lymphoma and from adult thymus indicates that B and T lymphocytes transcribe a common major mRNA identical to pM1, while other rare transcripts were also identified by these studies. A series of clonal T lymphoma lines representing distinct stages of thymic differentiation showed that, as with B lymphoid tumors, XLR expression is correlated with the maturation of the thymomas.
14-3-3ε is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller–Dieker syndrome
Authors: Kazuhito Toyo-oka, Aki Shionoya, Michael J Gambello, Carlos Cardoso, Richard Leventer, Heather L Ward, Ramses Ayala, Li-Huei Tsai, William Dobyns, David Ledbetter, Shinji Hirotsune, Anthony Wynshaw-Boris
Journal: Nature Genetics (2003)
DEVELOPMENT OF THE VERTEBRATE NEUROMUSCULAR JUNCTION
Authors: Joshua R. Sanes, Jeff W. Lichtman
Journal: Annual Review of Neuroscience (1999)

▪ Abstract We describe the formation, maturation, elimination, maintenance, and regeneration of vertebrate neuromuscular junctions (NMJs), the best studied of all synapses. The NMJ forms in a series of steps that involve the exchange of signals among its three cellular components—nerve terminal, muscle fiber, and Schwann cell. Although essentially any motor axon can form NMJs with any muscle fiber, an additional set of cues biases synapse formation in favor of appropriate partners. The NMJ is functional at birth but undergoes numerous alterations postnatally. One step in maturation is the elimination of excess inputs, a competitive process in which the muscle is an intermediary. Once elimination is complete, the NMJ is maintained stably in a dynamic equilibrium that can be perturbed to initiate remodeling. NMJs regenerate following damage to nerve or muscle, but this process differs in fundamental ways from embryonic synaptogenesis. Finally, we consider the extent to which the NMJ is a suitable model for development of neuron-neuron synapses.
INITIATION AND PROCESSING OF SIGNALS FROM THE B CELL ANTIGEN RECEPTOR
Authors: Michael Reth, J. Wienands
Journal: Annual Review of Immunology (1997)

Current models of signal transduction from the antigen receptors on B and T cells still resemble equations with several unknown elements. Data from recent knockout experiments in cell lines and mice contradict the assumption that Src-family kinase and tyrosine kinases of the Syk/Zap-70 family are the transducer elements that set signaling from these receptors in motion. Using a functional definition of signaling elements, we discuss the current knowledge of signaling events from the BCR and suggest the existence of an as-yet-unknown BCR transducer complex.
GENETIC ANALYSIS OF HOST RESISTANCE: Toll-Like Receptor Signaling and Immunity at Large
Authors: Bruce Beutler, Zhengfan Jiang, Philippe Georgel, Karine Crozat, Ben Croker, Sophie Rutschmann, Xin Du, Kasper Hoebe
Journal: Annual Review of Immunology (2006)

Classical genetic methods, driven by phenotype rather than hypotheses, generally permit the identification of all proteins that serve nonredundant functions in a defined biological process. Long before this goal is achieved, and sometimes at the very outset, genetics may cut to the heart of a biological puzzle. So it was in the field of mammalian innate immunity. The positional cloning of a spontaneous mutation that caused lipopolysaccharide resistance and susceptibility to Gram-negative infection led directly to the understanding that Toll-like receptors (TLRs) are essential sensors of microbial infection. Other mutations, induced by the random germ line mutagen ENU (N-ethyl-N-nitrosourea), have disclosed key molecules in the TLR signaling pathways and helped us to construct a reasonably sophisticated portrait of the afferent innate immune response. A still broader genetic screen—one that detects all mutations that compromise survival during infection—is permitting fresh insight into the number and types of proteins that mammals use to defend themselves against microbes.
Penetration of VP 16-213 into cerebrospinal fluid after high-dose intravenous administration.
Authors: P E Postmus, J J Holthuis, H Haaxma-Reiche, N H Mulder, L M Vencken, W J van Oort, D T Sleijfer, H J Sluiter
Journal: Journal of Clinical Oncology (1984)

VP 16-213 in standard doses is active against a number of solid tumors. Its penetration into the cerebrospinal fluid (CSF) is very limited at these dose levels. In 10 patients treated with high-dose VP 16-213 (0.9-2.5 g/m2), CSF levels of up to 0.54 microgram/mL were detected. In two patients with central nervous system (CNS) metastases of small cell lung cancer (SCLC) a response was seen after 1.0 and 1.5 g/m2 intravenously. High-dose VP 16-213 can possibly play a role in the treatment of CNS metastases of SCLC. Its application in late intensification regimens as a form of prophylaxis of CNS metastases should be investigated.
CYTOCHEMICAL AND ELECTRON MICROSCOPIC STUDIES OF RAT LIVER WITH REDUCED CAPACITY TO TRANSPORT CONJUGATED BILIRUBIN
Authors: Sidney Goldfischer, Irwin M. Arias, Edward Essner, Alex B. Novikoff
Journal: The Journal of Experimental Medicine (1962)

ALTHOUGH THE LIVERS OF RATS TREATED WITH AGENTS KNOWN TO SUPPRESS BILIRUBIN TRANSPORT APPEARED RELATIVELY NORMAL ON ROUTINE HISTOLOGICAL SECTIONS, CYTOCHEMICAL AND ELECTRON MICROSCOPIC PREPARATIONS REVEALED MARKED CHANGES IN: (a) levels of alkaline phosphatase and apparent ATPase activities of the cell membrane at the sinusoids, bile canaliculi, and between adjacent cells; (b) morphology of the bile canaliculi such as dilatation, fragmentation, vesiculation and reduced numbers of microvilli; (c) the number of lysosomes and their distribution within the cell. Similar changes in the cytochemistry of the liver cell were induced by extrahepatic obstruction.
SUCCESSFUL RENAL TRANSPLANTATION IN 3 CHILDREN WITH CONGENITAL NEPHROTIC SYNDROME
Authors: J.R. Hoyer, C.M. Kjellstrand, R.L. Simmons, J.S. Najarian, S.M. Mauer, T.J. Buselmeier, A.F. Michael, R.L. Vernier
Journal: The Lancet (1973)
Mechanisms of Function and Disease of Natural and Replacement Heart Valves
Authors: Frederick J. Schoen
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Over the past several decades, there has been substantial progress toward understanding the mechanisms of heart valve function and dysfunction. This review summarizes an evolving conceptual framework of heart valve functional structure, developmental biology, and pathobiology and explores the implications of key insights. I emphasize: (a) valve cell and extracellular matrix biology and the impact of biomechanical factors on function, homeostasis, environmental adaptation, and key pathological processes; (b) the role of developmental processes, valvular cell behavior, and extracellular matrix remodeling in congenital and acquired valve abnormalities; and (c) the cell/matrix biology of degeneration in replacement tissue valves. I also summarize how these considerations may ultimately inform the potential for prevention and treatment of major diseases and potentially therapeutic regeneration of the cardiac valves. Recent advances and opportunities for research and clinical translation are highlighted.
Abstract 1381: The vascular targeted and antitumor effects of gene electrotransfer of plasmid silencing endoglin with tissue specific and constitutive promoter
Authors: Monika Stimac, Tanja Dolinsek, Ursa Lampreht, Maja Cemazar, Gregor Sersa
Journal: Cancer Research (2015)

Abstract Endoglin, the transforming growth factor-β (TGF-β) co-receptor, mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. It is promising target for vascular targeted therapies for the treatment of cancer, although its specific, safe and long-lasting targeting remains the challenge. One of the options for targeted and prolonged silencing is gene electrotransfer (GET) of plasmid DNA encoding shRNA against endoglin. In our study we used two plasmid DNAs; one with tissue specific promoter for endothelial cells (TS plasmid) and the other with constitutive promoter (CON promoter). In vitro, we evaluated the transfection efficacy using flow cytometry measurement of transfected cells and determined the vascular targeted effects by tube formation assay. The therapeutic potential of the GET of plasmids and comparison of theirs efficacies in vitro was obtained by measuring tumor growth and by analyzing histological sections for determining area of necrosis and a number of activated blood vessels. In vitro, we demonstrated the tissue specificity of TS plasmid on several cell lines, and the antiangiogenic efficacy of GET of either of both plasmids, as reduced tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of GET of either of both plasmids in treatment of smaller tumors in avascular phase of growth, as well as on bigger tumors, already well vascularized, possibly due to both, the antiangiogenic and vascular disrupting effect. In order to support that, the histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. Therefore, using GET of TS plasmid we were able to demonstrate that it is specific, safe and has quite the same efficacy as the GET of CON plasmid. Therefore, our approach can represent a novel alternative to other therapeutic approaches that aim at silencing endoglin, which represents also an alternative target in VEGF resistant (unresponsive) tumors. Citation Format: Monika Stimac, Tanja Dolinsek, Ursa Lampreht, Maja Cemazar, Gregor Sersa. The vascular targeted and antitumor effects of gene electrotransfer of plasmid silencing endoglin with tissue specific and constitutive promoter. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1381. doi:10.1158/1538-7445.AM2015-1381
Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial
Authors: Taha E Taha, Newton I Kumwenda, Amanda Gibbons, Robin L Broadhead, Susan Fiscus, Valentino Lema, George Liomba, Chiwawa Nkhoma, Paolo G Miotti, Donald R Hoover
Journal: The Lancet (2003)
The Molecular Basis for the Pharmacokinetics and Pharmacodynamics of Curcumin and Its Metabolites in Relation to Cancer
Authors: Michal Heger, Rowan F. van Golen, Mans Broekgaarden, Martin C. Michel
Journal: Pharmacological Reviews (2013)

This review addresses the oncopharmacological properties of curcumin at the molecular level. First, the interactions between curcumin and its molecular targets are addressed on the basis of curcumin's distinct chemical properties, which include H-bond donating and accepting capacity of the <i>β</i>-dicarbonyl moiety and the phenylic hydroxyl groups, H-bond accepting capacity of the methoxy ethers, multivalent metal and nonmetal cation binding properties, high partition coefficient, rotamerization around multiple C–C bonds, and the ability to act as a Michael acceptor. Next, the in vitro chemical stability of curcumin is elaborated in the context of its susceptibility to photochemical and chemical modification and degradation (e.g., alkaline hydrolysis). Specific modification and degradatory pathways are provided, which mainly entail radical-based intermediates, and the in vitro catabolites are identified. The implications of curcumin's (photo)chemical instability are addressed in light of pharmaceutical curcumin preparations, the use of curcumin analogues, and implementation of nanoparticulate drug delivery systems. Furthermore, the pharmacokinetics of curcumin and its most important degradation products are detailed in light of curcumin's poor bioavailability. Particular emphasis is placed on xenobiotic phase I and II metabolism as well as excretion of curcumin in the intestines (first pass), the liver (second pass), and other organs in addition to the pharmacokinetics of curcumin metabolites and their systemic clearance. Lastly, a summary is provided of the clinical pharmacodynamics of curcumin followed by a detailed account of curcumin's direct molecular targets, whereby the phenotypical/biological changes induced in cancer cells upon completion of the curcumin-triggered signaling cascade(s) are addressed in the framework of the hallmarks of cancer. The direct molecular targets include the ErbB family of receptors, protein kinase C, enzymes involved in prostaglandin synthesis, vitamin D receptor, and DNA.
Identifying driver mutations in sequenced cancer genomes: computational approaches to enable precision medicine
Authors: Benjamin J Raphael, Jason R Dobson, Layla Oesper, Fabio Vandin
Journal: Genome Medicine (2014)

High-throughput DNA sequencing is revolutionizing the study of cancer and enabling the measurement of the somatic mutations that drive cancer development. However, the resulting sequencing datasets are large and complex, obscuring the clinically important mutations in a background of errors, noise, and random mutations. Here, we review computational approaches to identify somatic mutations in cancer genome sequences and to distinguish the driver mutations that are responsible for cancer from random, passenger mutations. First, we describe approaches to detect somatic mutations from high-throughput DNA sequencing data, particularly for tumor samples that comprise heterogeneous populations of cells. Next, we review computational approaches that aim to predict driver mutations according to their frequency of occurrence in a cohort of samples, or according to their predicted functional impact on protein sequence or structure. Finally, we review techniques to identify recurrent combinations of somatic mutations, including approaches that examine mutations in known pathways or protein-interaction networks, as well as de novo approaches that identify combinations of mutations according to statistical patterns of mutual exclusivity. These techniques, coupled with advances in high-throughput DNA sequencing, are enabling precision medicine approaches to the diagnosis and treatment of cancer.