tbuckley/cabot-search huggingface dataset:
The MATRICS Consensus Cognitive Battery, Part 1: Test Selection, Reliability, and Validity
Authors: Keith H. Nuechterlein, Michael F. Green, Robert S. Kern, Lyle E. Baade, Deanna M. Barch, Jonathan D. Cohen, Susan Essock, Wayne S. Fenton, Frederick J. Frese, James M. Gold, Terry Goldberg, Robert K. Heaton, Richard S.E. Keefe, Helena Kraemer, Raquelle Mesholam-Gately, Larry J. Seidman, Ellen Stover, Daniel R. Weinberger, Alexander S. Young, Steven Zalcman, Stephen R. Marder
Journal: American Journal of Psychiatry (2008)

Objective: The lack of an accepted standard for measuring cognitive change in schizophrenia has been a major obstacle to regulatory approval of cognition-enhancing treatments. A primary mandate of the National Institute of Mental Health’s Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was to develop a consensus cognitive battery for clinical trials of cognition-enhancing treatments for schizophrenia through a broadly based scientific evaluation of measures. Method: The MATRICS Neurocognition Committee evaluated more than 90 tests in seven cognitive domains to identify the 36 most promising measures. A separate expert panel evaluated the degree to which each test met specific selection criteria. Twenty tests were selected as a beta battery. The beta battery was administered to 176 individuals with schizophrenia and readministered to 167 of them 4 weeks later so that the 20 tests could be compared directly. Results: The expert panel ratings are presented for the initially selected 36 tests. For the beta battery tests, data on test-retest reliability, practice effects, relationships to functional status, practicality, and tolerability are presented. Based on these data, 10 tests were selected to represent seven cognitive domains in the MATRICS Consensus Cognitive Battery. Conclusions: The structured consensus method was a feasible and fair mechanism for choosing candidate tests, and direct comparison of beta battery tests in a common sample allowed selection of a final consensus battery. The MATRICS Consensus Cognitive Battery is expected to be the standard tool for assessing cognitive change in clinical trials of cognition-enhancing drugs for schizophrenia. It may also aid evaluation of cognitive remediation strategies.
Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: Results of Dutch Childhood Leukemia Study Group Protocol ALL-7 (1988-1991)
Authors: W.A. Kamps, J.P.M. Bökkerink, K. Hählen, J. Hermans, H. Riehm, H. Gadner, M. Schrappe, R. Slater, E. van den Berg-de Ruiter, L.A. Smets, G.A.M. de Vaan, R.S. Weening, J.F. van Weerden, E.R. van Wering, A. van der Does-van den Berg
Journal: Blood (1999)
Strategies to Prevent Suicide—Reply
Authors: J. John Mann
Journal: JAMA (2006)

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Biglycan Is Required for Adaptive Remodeling After Myocardial Infarction
Authors: D. Westermann, J. Mersmann, A. Melchior, T. Freudenberger, C. Petrik, L. Schaefer, R. Lüllmann-Rauch, O. Lettau, C. Jacoby, J. Schrader, S.-M. Brand-Herrmann, M.F. Young, H.P. Schultheiss, B. Levkau, H.A. Baba, T. Unger, K. Zacharowski, C. Tschöpe, J.W. Fischer
Journal: Circulation (2008)

After myocardial infarction (MI), extensive remodeling of extracellular matrix contributes to scar formation and preservation of hemodynamic function. On the other hand, adverse and excessive extracellular matrix remodeling leads to fibrosis and impaired function. The present study investigates the role of the small leucine-rich proteoglycan biglycan during cardiac extracellular matrix remodeling and cardiac hemodynamics after MI.Experimental MI was induced in wild-type (WT) and bgn(-/0) mice by permanent ligation of the left anterior descending coronary artery. Biglycan expression was strongly increased at 3, 7, and 14 days after MI in WT mice. bgn(-/0) mice showed increased mortality rates after MI as a result of frequent left ventricular (LV) ruptures. Furthermore, tensile strength of the LV derived from bgn(-/0) mice 21 days after MI was reduced as measured ex vivo. Collagen matrix organization was severely impaired in bgn(-/0) mice, as shown by birefringence analysis of Sirius red staining and electron microscopy of collagen fibrils. At 21 days after MI, LV hemodynamic parameters were assessed by pressure-volume measurements in vivo to obtain LV end-diastolic pressure, end-diastolic volume, and end-systolic volume. bgn(-/0) mice were characterized by aggravated LV dilation evidenced by increased LV end-diastolic volume (bgn(-/0), 111+/-4.2 microL versus WT, 96+/-4.4 microL; P<0.05) and LV end-diastolic pressure (bgn(-/0), 24+/-2.7 versus WT, 18+/-1.8 mm Hg; P<0.05) and severely impaired LV function (EF, bgn(-/0), 12+/-2% versus WT, 21+/-4%; P<0.05) 21 days after MI.Biglycan is required for stable collagen matrix formation of infarct scars and for preservation of cardiac hemodynamic function.
Kidney-Specific Inactivation of the Megalin Gene Impairs Trafficking of Renal Inorganic Sodium Phosphate Cotransporter (NaPi-IIa)
Authors: Sebastian Bachmann, Uwe Schlichting, Beate Geist, Kerim Mutig, Thomas Petsch, Desa Bacic, Carsten A. Wagner, Brigitte Kaissling, Jürg Biber, Heini Murer, Thomas E. Willnow
Journal: Journal of the American Society of Nephrology (2004)

Renal reabsorption of inorganic phosphate is mediated by the type IIa sodium phosphate cotransporter (NaPi-IIa) of the proximal tubule. Changes in renal phosphate handling are mainly attributable to altered NaPi-IIa brush border membrane (BBM) expression. Parathyroid hormone (PTH) induces inactivation of NaPi-IIa by endocytic membrane retrieval and degradation. The key elements triggering this process are not clear to date. Megalin serves as a receptor for the endocytosis of multiple ligands and is coexpressed with NaPi-IIa in the proximal tubule. Investigated was the role of megalin in the regulation of NaPi-IIa in steady state and during inactivation. Kidneys and tubular BBM fractions from mice with a renal-specific megalin gene defect and from controls were analyzed by light and electron microscopic histochemical techniques and Western blot test. Steady-state levels of NaPi-IIa in BBM were significantly enhanced, mRNA levels preserved, and phosphaturia reduced in the absence of megalin. Fluid-phase endocytosis was prevented and the apical endocytic apparatus markedly reduced. Systemic administration of PTH resulted in a defective retrieval and impaired degradation of NaPi-IIa. In vitro, the application of various stimuli of the PTH-induced signaling cascade had no effect either. Adequate steady-state expression of NaPi-IIa and the capacity of the proximal tubule cell to react on PTH-driven inactivation of NaPi-IIa by endocytosis and intracellular translocation require the presence of megalin.
Targeting Nrf2 Signaling Improves Bacterial Clearance by Alveolar Macrophages in Patients with COPD and in a Mouse Model
Authors: Christopher J. Harvey, Rajesh K. Thimmulappa, Sanjay Sethi, Xiaoni Kong, Lonny Yarmus, Robert H. Brown, David Feller-Kopman, Robert Wise, Shyam Biswal
Journal: Science Translational Medicine (2011)

Bacterial clearance in macrophages from lungs with chronic obstructive pulmonary disease is improved by stimulating the Nrf2 antioxidant signaling pathway.
The Matthew effect in health development.
Authors: G. W. Evans
Journal: BMJ (1989)

and leaves the choice of drugs to those who know local needs.To people in developing countries struggling to develop and use an essential drug list, I can also give moral support by developing my own rafional prescribing policy in my practice here.This exercise has failed to convince me that the effort needed to collect, sort, and dispatch the drugs I can obtain in the course of my practice is worth while.
<i>In vitro</i> and <i>In vivo</i> Pharmacokinetic-Pharmacodynamic Relationships for the Trisubstituted Aminopurine Cyclin-Dependent Kinase Inhibitors Olomoucine, Bohemine and CYC202
Authors: Florence I. Raynaud, Steven R. Whittaker, Peter M. Fischer, Steven McClue, Michael I. Walton, S. Elaine Barrie, Michelle D. Garrett, Paul Rogers, Simon J. Clarke, Lloyd R. Kelland, Melanie Valenti, Lisa Brunton, Suzanne Eccles, David P. Lane, Paul Workman
Journal: Clinical Cancer Research (2005)

To investigate pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine, and CYC202 (R-roscovitine; seliciclib) in the HCT116 human colon carcinoma model.The in vitro activity of the agents was determined in a human tumor panel using the sulforhodamine B assay. The concentration and time dependence was established in HCT116 cells. Molecular biomarkers, including RB phosphorylation and cyclin expression, were assessed by Western blotting. Pharmacokinetic properties were characterized in mice following analysis by liquid chromatography-tandem mass spectrometry. Based on these studies, a dosing regimen was developed for CYC202 that allowed therapeutic exposures in the HCT116 tumor xenograft.The antitumor potency of the agents in vitro was in the order olomoucine (IC50, 56 micromol/L) < bohemine (IC50, 27 micromol/L) < CYC202 (IC50, 15 micromol/L), corresponding to their activities as cyclin-dependent kinase inhibitors. Antitumor activity increased with exposure time up to 16 hours. The agents caused inhibition of RB and RNA polymerase II phosphorylation and depletion of cyclins. They exhibited relatively rapid clearance following administration to mice. CYC202 displayed the slowest clearance from plasma and the highest tumor uptake, with oral bioavailability of 86%. Oral dosing of CYC202 gave active concentrations in the tumor, modulation of pharmacodynamic markers, and inhibition of tumor growth.CYC202 showed therapeutic activity on human cancer cell lines in vitro and on xenografts. Pharmacodynamic markers are altered in vitro and in vivo, consistent with the inhibition of cyclin-dependent kinases. Such markers may be potentially useful in the clinical development of CYC202 and other cyclin-dependent kinase inhibitors.
A ZFN/piggyBac step closer to autologous liver cell therapy
Authors: Aras N. Mattis, Holger Willenbring
Journal: Hepatology (2012)

Abstract Human induced pluripotent stem cells (iPSCs) represent a unique opportunity for regenerative medicine because they offer the prospect of generating unlimited quantities of cells for autologous transplantation, with potential application in treatments for a broad range of disorders. However, the use of human iPSCs in the context of genetically inherited human disease will require the correction of disease-causing mutations in a manner that is fully compatible with clinical applications. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome. Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of human iPSCs. Here we show that a combination of zinc finger nucleases (ZFNs) and piggyBac technology in human iPSCs can achieve biallelic correction of a point mutation (Glu342Lys) in the α1-antitrypsin ( A1AT , also known as SERPINA1 ) gene that is responsible for α1-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo . This approach is significantly more efficient than any other gene-targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle, to our knowledge, for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies.
Effects of Intracavitary Blood Flow and Electrode–Target Distance on Radiofrequency Power Required for Transient Conduction Block in a Langendorff-Perfused Canine Model
Authors: Timothy A Simmers, Jacques M.T de Bakker, Ruben Coronel, Fred H.M Wittkampf, Frans J van Capelle, Michiel J Janse, Richard N.W Hauer
Journal: Journal of the American College of Cardiology (1998)
Psychosocial Aspects of Chronic Disease
Authors: Daniel Cukor, Scott D Cohen, Rolf A Peterson, Paul L Kimmel
Journal: Journal of the American Society of Nephrology (2007)

Psychosocial issues are an understudied yet important concern in the overall health of hemodialysis (HD) patients. Stress is a concomitant of chronic illness and its treatment, and may have meaningful influences on psychological and medical outcomes. This article reviews the influences of psychopathology, social support, family issues, dialysis unit culture, and socioeconomic status on patients treated with center HD. Depressive affect and decreased perception of social support have been linked with mortality in several studies of ESRD patients. Decreased marital satisfaction, disturbances in family dynamics, and lower socioeconomic status (SES) have been associated with poorer health outcomes and can affect patients' perception of social support and depressive affect. Chronically ill ESRD patients who undergo treatment with constant interaction and observation by medical staff are potentially an ideal group for evaluation of the effects of stress and psychosocial factors on outcomes in those with chronic disease, as well as an excellent patient population for intervention to reduce morbidity and mortality. These interactions between potentially modifiable psychosocial risk factors for disease and medical aspects of illness form a paradigm for the study of interventions related to adjustment to chronic illness in the ESRD population.
A double-blind placebo controlled trial of etanercept in patients with giant cell arteritis and corticosteroid side effects
Authors: V M Martinez-Taboada, V Rodriguez-Valverde, L Carreno, J Lopez-Longo, M Figueroa, J Belzunegui, E M Mola, G Bonilla
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> Open label studies have suggested that tumour necrosis factor (TNF) antagonists led to sustained improvement and corticosteroid sparing effect in patients with giant cell arteritis (GCA). To confirm these observations, we conducted a randomised, double-blind, placebo controlled trial with etanercept in patients with biopsy-proven GCA with side effects secondary to corticosteroids. <h3>Methods:</h3> We randomly assigned patients with GCA to receive etanercept (n = 8) or placebo (n = 9) over 1 year together with corticosteroids that were reduced according to a predefined schedule. The primary outcome was the ability to withdraw the corticosteroid therapy and control the disease activity at 12 months. <h3>Results:</h3> Baseline characteristics were similar in the two groups, although patients in the etanercept group showed higher levels of basal glycaemia (p = 0.02) and a higher erythrocyte sedimentation rate (ESR) (p = 0.01). After 12 months, 50% of the patients in the etanercept group and 22.2% in the placebo group were able to control the disease without corticosteroid therapy (p value not significant). Patients in the etanercept group had a significant lower dose of accumulated prednisone during the first year of treatment (p = 0.03). There were no differences in the number and type of adverse events. <h3>Conclusion:</h3> The limited number of patients included in this study does not allow us to draw definitive conclusions. Etanercept therapy was well tolerated in this aged population. The therapeutic role of etanercept in patients with GCA should be evaluated in studies with a larger number of patients.
Characteristics of mycobacterial infection in patients with immunodeficiency and nuclear factor–κB essential modulator mutation, with or without ectodermal dysplasia
Authors: Yang-Shia Dai, Marilyn G. Liang, Stephen E. Gellis, Francisco A. Bonilla, Lynda C. Schneider, Raif S. Geha, Jordan S. Orange
Journal: Journal of the American Academy of Dermatology (2004)
Patchy enteropathy in childhood.
Authors: P D Manuel, J A Walker-Smith, N E France
Journal: Gut (1979)

Two hundred and seventy-eight duodenal biopsy specimens taken consecutively from children using either a single port paediatric Crosby capsule or a double port modification were examined both histologically and by dissecting microscopy, in order to determine the incidence of patchy mucosal lesions. One hundred and six specimens were abnormal and 49 of these were patchy. Patchy lesions occurred most commonly in cow9s milk sensitive enteropathy where 66% of 33 specimens were patchy; in comparison all children with undiagnosed coeliac disease taking a normal diet showed a uniformly flat mucosa. Twenty-two per cent of specimens taken using the double port and 10% using the single port capsule were patchy, a statistically significant difference (P = 0.01) using standard errors. Where lesions were uniform, grading by dissecting microscopy correlated well with histological grading; 18 (37%) of specimens were, however, recognised as patchy only on gross appearance. The high incidence of patchy lesions of the proximal small intestine reflected the prevalence of cow9s milk protein intolerance and the postenteritis syndrome in these children. The use of the double port capsule and of dissecting microscopy also contributed to the high incidence found.
Superparamagnetic Iron Oxide Nanoparticles: Amplifying ROS Stress to Improve Anticancer Drug Efficacy
Authors: Gang Huang, Huabing Chen, Ying Dong, Xiuquan Luo, Haijun Yu, Zachary Moore, Erik A. Bey, David A. Boothman, Jinming Gao
Journal: Theranostics (2013)

Superparamagnetic iron oxide nanoparticles (SPION) are an important and versatile nano-platform with broad biological applications.Despite extensive studies, the biological and pharmacological activities of SPION have not been exploited in therapeutic applications.Recently, β-lapachone (β-lap), a novel anticancer drug, has shown considerable cancer specificity by selectively increasing reactive oxygen species (ROS) stress in cancer cells.In this study, we report that pH-responsive SPION-micelles can synergize with β-lap for improved cancer therapy.These SPION-micelles selectively release iron ions inside cancer cells, which interact with hydrogen peroxide (H 2 O 2 ) generated from β-lap in a tumor-specific, NQO1-dependent manner.Through Fenton reactions, these iron ions escalate the ROS stress in β-lap-exposed cancer cells, thereby greatly enhancing the therapeutic index of β-lap.More specifically, a 10-fold increase in ROS stress was detected in β-lap-exposed cells pretreated with SPION-micelles over those treated with β-lap alone, which also correlates with significantly increased cell death.Catalase treatment of cells or administration of an iron chelator can block the therapeutic synergy.Our data suggest that incorporation of SPION-micelles with ROS-generating drugs can potentially improve drug efficacy during cancer treatment, thereby provides a synergistic strategy to integrate imaging and therapeutic functions in the development of theranostic nanomedicine.
ILLUMINATE Sheds More Light
Authors: Stephen D. Wiviott
Journal: Circulation (2011)

I f one could design a metabolic intervention to prevent incident or recurrent cardiovascular events, it might look a lot like torcetrapib.Torcetrapib is the first cholesteryl ester transfer protein (CETP) inhibitor extensively studied in humans.Torcetrapib, in addition to statin therapy, raised high-density lipoprotein (HDL) by Ͼ70%, lowered low-density lipoprotein by 25%, and lowered triglycerides by Ϸ10%. 1 This is an impressive profile for a pharmaceutical agent.What if someone told you that this therapy also improves glycemic control?
Incidence, progression and sequence of development of radiographic knee osteoarthritis in a symptomatic population
Authors: R. Duncan, G. Peat, E. Thomas, E. M. Hay, P. Croft
Journal: Annals of the Rheumatic Diseases (2011)

Symptomatic knee osteoarthritis (OA) is a common disabling condition. Attention has tended to focus on the tibiofemoral joint (TFJ). However, there is evidence that the patellofemoral joint (PFJ) is involved in many cases, but its place in the sequence of development and progression of knee OA is unclear. This study estimates the cumulative incidence, progression and inter-relationship of radiographic changes of OA in the TFJ and the PFJ in symptomatic adults.A population-based observational cohort of 414 adults aged ≥ 50 years with knee pain who had knee x-rays (weight-bearing posteroanterior semiflexed, skyline and lateral views) in 2002-3 and again in 2005-6 (mean interval 36.7 months) was studied. The outcome measure was the development of incident or progressive radiographic OA.The 3-year cumulative incidences of patellofemoral joint osteoarthritis (PFJOA) and tibiofemoral joint osteoarthritis (TFJOA) were 28.8% and 21.7%, respectively. Corresponding estimates of 3-year cumulative progression were 18.9% and 25.3%. PFJOA at baseline was common and increased the risk of incident TFJOA (adjusted OR 2.2, 95% CI 1.1 to 4.1) but less clearly progression of TFJOA (adjusted OR 1.7, 95% CI 0.3 to 9.0). TFJOA at baseline increased the risk of PFJOA incidence and progression (adjusted OR 3.1, 95% CI 1.2 to 8.4 and OR 4.5, 95% CI 1.8 to 11.2, respectively).These results suggest a common sequence in the development of radiographic knee OA in symptomatic adults beginning in the PFJ, with subsequent addition and progression of TFJOA. It is proposed that isolated symptomatic PFJOA may be one marker for the future development of TFJOA and a target for the early management of knee OA.