tbuckley/cabot-search huggingface dataset:
Anemia as a Risk Factor for Cardiovascular Disease and All-Cause Mortality in Diabetes
Authors: Panagiotis T. Vlagopoulos, Hocine Tighiouart, Daniel E. Weiner, John Griffith, Dan Pettitt, Deeb N. Salem, Andrew S. Levey, Mark J. Sarnak
Journal: Journal of the American Society of Nephrology (2005)

Anemia is a potential nontraditional risk factor for cardiovascular disease (CVD). This study evaluated whether anemia is a risk factor for adverse outcomes in people with diabetes and whether the risk is modified by the presence of chronic kidney disease (CKD). Persons with diabetes from four community-based studies were pooled: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Anemia was defined as a hematocrit <36% in women and <39% in men. CKD was defined as an estimated GFR of 15 to 60 ml/min per 1.73 m(2). Study outcomes included a composite of myocardial infarction (MI)/fatal coronary heart disease (CHD)/stroke/death and each outcome separately. Cox regression analysis was used to study the effect of anemia on the risk for outcomes after adjustment for potential confounders. The study population included 3015 individuals: 30.4% were black, 51.6% were women, 8.1% had anemia, and 13.8% had CKD. Median follow-up was 8.6 yr. There were 1215 composite events, 600 MI/fatal CHD outcomes, 300 strokes, and 857 deaths. In a model with a CKD-anemia interaction term, anemia was associated with the following hazard ratios (95% confidence intervals) in patients with CKD: 1.70 (1.24 to 2.34) for the composite outcome, 1.64 (1.03 to 2.61) for MI/fatal CHD, 1.81 (0.99 to 3.29) for stroke, and 1.88 (1.33 to 2.66) for all-cause mortality. Anemia was not a risk factor for any outcome in those without CKD (P > 0.2 for all outcomes). In persons with diabetes, anemia is primarily a risk factor for adverse outcomes in those who also have CKD.
American Society of Clinical Oncology Recommendations on Adjuvant Chemotherapy for Stage II Colon Cancer
Authors: Al B. Benson, Deborah Schrag, Mark R. Somerfield, Alfred M. Cohen, Alvaro T. Figueredo, Patrick J. Flynn, Monika K. Krzyzanowska, Jean Maroun, Pamela McAllister, Eric Van Cutsem, Melissa Brouwers, Manya Charette, Daniel G. Haller
Journal: Journal of Clinical Oncology (2004)

Purpose To address whether all medically fit patients with curatively resected stage II colon cancer should be offered adjuvant chemotherapy as part of routine clinical practice, to identify patients with poor prognosis characteristics, and to describe strategies for oncologists to use to discuss adjuvant chemotherapy in practice. Methods An American Society of Clinical Oncology Panel, in collaboration with the Cancer Care Ontario Practice Guideline Initiative, reviewed pertinent information from the literature through May 2003. Results A literature-based meta-analysis found no evidence of a statistically significant survival benefit of adjuvant chemotherapy for stage II patients. Recommendations The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. However, there are populations of patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology. Conclusion Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.
Staff morale is dropping as NHS money pressures grow, says King's Fund report
Authors: A. O'Dowd
Journal: BMJ (2014)

Worries over deteriorating staff morale and worsening performance are growing among managers as a result of financial pressure on the NHS.

The view has emerged from results of the latest quarterly monitoring report by the health think tank the King’s Fund, published on 30 October.1

Views were sought from 248 NHS trust finance directors, 90 of whom responded, for the three months of July to September and from 202 clinical commissioning group (CCG) finance leads, of whom 43 responded.

Almost half (47%) of the trust finance directors who responded listed staff morale as highest of their top three concerns, twice the proportion in the previous quarter. The report’s …
GWAS in lung disease
Authors: R. P. Young, R. J. Hopkins
Journal: Thorax (2011)

We read with interest the recent article ‘Genome-wide association studies in lung disease’ by Artigas et al. 1 While we agree that a greater understanding of the biological pathways underlying disease development and progression (susceptibility) will be a major outcome from these genetic epidemiological studies, we suggest other benefits may also stem from this research.

The genetics of chronic obstructive pulmonary disease (COPD) and lung cancer represent unique models for the genetics of lung disease because they result in the main from a ‘single’ measurable …
Animal assays for anti-psoriatic., retinoid and sunprotective agents
Authors: N. J. LOWE, M. J. CONNOR, R. ASHTON, M. WORTZMAN
Journal: British Journal of Dermatology (1984)

Journal Article Animal assays for anti‐psoriatic., retinoid and sunprotective agents Get access N. J. LOWE, N. J. LOWE Dermatology Programme, UCLA School of Medicine, Los Angeles, California 90024, U. S. A. Search for other works by this author on: Oxford Academic Google Scholar M. J. CONNOR, M. J. CONNOR Dermatology Programme, UCLA School of Medicine, Los Angeles, California 90024, U. S. A. Search for other works by this author on: Oxford Academic Google Scholar R. ASHTON, R. ASHTON Dermatology Programme, UCLA School of Medicine, Los Angeles, California 90024, U. S. A. Search for other works by this author on: Oxford Academic Google Scholar M. WORTZMAN M. WORTZMAN Dermatology Programme, UCLA School of Medicine, Los Angeles, California 90024, U. S. A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s27, 1 July 1984, Pages 98–108, https://doi.org/10.1111/j.1365-2133.1984.tb15587.x Published: 01 July 1984
Downregulation of Hepatic Cytochrome P450 in Chronic Renal Failure
Authors: FRANCOIS LEBLOND, CARL GUÉVIN, CHRISTIAN DEMERS, ISABELLE PELLERIN, MARIELLE GASCON-BARRÉ, VINCENT PICHETTE
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Chronic renal failure (CRF) is associated with a decrease in drug metabolism. The mechanism remains poorly understood. The present study investigated the repercussions of CRF on liver cytochrome P450 (CYP450). Three groups of rats were defined: control, control paired-fed, and CRF. Total CYP450 activity, protein expression of several CYP450 isoforms as well as their mRNA, and the in vitro N-demethylation of erythromycin were assessed in liver microsomes. The regulation of liver CYP450 by dexamethasone and phenobarbital was assessed in CRF rats. Compared with control and control paired-fed rats, creatinine clearance was reduced by 60% ( P &lt; 0.01) in CRF rats. Weight was reduced by 30% ( P &lt; 0.01) in control paired-fed and CRF rats, compared with control animals. There was no difference in the CYP450 parameters between control and control paired-fed. Compared with control paired-fed rats, total CYP450 was reduced by 47% ( P &lt; 0.001) in CRF rats. Protein expression of CYP2C11, CYP3A1, and CYP3A2 were considerably reduced (&gt;40%, P &lt; 0.001) in rats with CRF. The levels of CYP1A2, CYP2C6, CYP2D, and CYP2E1 were the same in the three groups. Northern blot analysis revealed a marked downregulation in gene expression of CYP2C11, 3A1, and 3A2 in CRF rats. Although liver CYP450 was reduced in CRF, its induction by dexamethasone and phenobarbital was present. N-demethylation of erythromycin was decreased by 50% in CRF rats compared with control ( P &lt; 0.001). In conclusion, CRF in rats is associated with a decrease in liver cytochrome P450 activity (mainly in CYP2C11, CYP3A1, and 3A2), secondary to reduced gene expression.
Letter: Heart block and autoimmunity.
Authors: A J Fairfax, A Leatham
Journal: BMJ (1976)

frequently be avoided if the subjects show the fixity of purpose described here; their determination to minimise the wind-chill factor (by digging a substantial snow cave) and to overcome the urge to sleep undoubtedly prevented a serious outcome for this party, which carried no specific equip- ment to spend a night out near the summit of Everest.
Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics
Authors: Anuoluwapo Osinusi, Eric G. Meissner, Yu-Jin Lee, Dimitra Bon, Laura Heytens, Amy Nelson, Michael Sneller, Anita Kohli, Lisa Barrett, Michael Proschan, Eva Herrmann, Bhavana Shivakumar, Wenjuan Gu, Richard Kwan, Geb Teferi, Rohit Talwani, Rachel Silk, Colleen Kotb, Susan Wroblewski, Dawn Fishbein, Robin Dewar, Helene Highbarger, Xiao Zhang, David Kleiner, Brad J. Wood, Jose Chavez, William T. Symonds, Mani Subramanian, John McHutchison, Michael A. Polis, Anthony S. Fauci, Henry Masur, Shyamasundaran Kottilil
Journal: JAMA (2013)

IMPORTANCEThe efficacy of directly acting antiviral agents in interferon-free regimens for the treatment of chronic hepatitis C infections needs to be evaluated in different populations.OBJECTIVE To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics.Single-center, randomized, 2-part, open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus (HCV) genotype 1 enrolled at the National Institutes of Health (October 2011-April 2012). DESIGN, SETTING, AND PATIENTS INTERVENTIONSIn the study's first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks.In the second part, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks. MAIN OUTCOMES AND MEASURESThe primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR 24 ]). RESULTSIn the first part of the study, 9 participants (90%; 95% CI, 55%-100%) achieved SVR 24.In the second part, 7 participants (28%) in the weight-based group and 10 (40%) in the low-dose group relapsed after treatment completion leading to SVR 24 rates of 68% (95% CI, 46%-85%) in the weight-based group and 48% (95% CI, 28%-69%; P = .20)in the low-dose group.Twenty individuals participated in a pharmacokinetic-viral kinetic substudy, which demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved SVR (clearance, 3.57/d vs 5.60/d; P = .009).The most frequent adverse events were headache, anemia, fatigue, and nausea.There were 7 grade 3 events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis.No one discontinued treatment due to adverse events. CONCLUSION AND RELEVANCEIn a population of patients with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin resulted in SVR 24 rates of 68% and 48%, respectively.
The role of cGMP/cGKI signalling and Trpc channels in regulation of vascular tone
Authors: Florian Loga, Katrin Domes, Marc Freichel, Veit Flockerzi, Alexander Dietrich, Lutz Birnbaumer, Franz Hofmann, Jörg W. Wegener
Journal: Cardiovascular Research (2013)

AimsSignalling via cGMP-dependent protein kinase I (cGKI) is the major pathway in vascular smooth muscle (SM), by which endothelial NO regulates vascular tone. Recent evidence suggests that canonical transient receptor potential (Trpc) channels are targets of cGKI in SM and mediate the relaxant effects of cGMP signalling. We tested this concept by investigating the role of cGMP/cGKI signalling on vascular tone and peripheral resistance using Trpc6−/−, Trpc3−/−, Trpc3−/−/6−/−, Trpc1−/−/3−/−/6−/−, and SM-specific cGKI−/− (sm-cGKI−/−) mice.
Diabodies Targeting Epithelial Membrane Protein 2 Reduce Tumorigenicity of Human Endometrial Cancer Cell Lines
Authors: Kaori Shimazaki, Eric J. Lepin, Bo Wei, Agnes K. Nagy, Catherine P. Coulam, Sergey Mareninov, Maoyong Fu, Anna M. Wu, James D. Marks, Jonathan Braun, Lynn K. Gordon, Madhuri Wadehra
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Endometrial cancer is the most common gynecologic malignancy. One promising biomarker is epithelial membrane protein 2 (EMP2), and its expression is an independent prognostic indicator for tumors with poor clinical outcome expression. The present study assesses the suitability of EMP2 as a therapeutic target. Experimental Design: Human monovalent anti-EMP2 antibody fragments were isolated from a human phage display library and engineered as bivalent antibody fragments (diabodies) with specificity and avidity to both EMP2 peptides and native cell-surface EMP2 protein. Diabodies were assessed using cell death and apoptosis assays. In addition, the efficacy of EMP2 diabodies on endometrial cancer tumors was determined using mouse xenograft models. Results: Treatment of human endometrial adenocarcinoma cell lines with anti-EMP2 diabodies induced significant cell death and caspase-3 cleavage in vitro. These responses correlated with cellular EMP2 expression and were augmented by progesterone, which physiologically induces EMP2 expression. In vivo, treatment of subcutaneous human xenografts of HEC-1A cell lines with anti-EMP2 diabodies suppressed tumor growth and induced cell death in the xenograft. Conclusions: These findings suggest that EMP2 may be a potential pharmacologic target for human endometrial cancer.
In Vitro Expansion of Murine Multipotential Hematopoietic Progenitors from the Embryonic Aorta–Gonad–Mesonephros Region
Authors: Yoh-suke Mukouyama, Takahiko Hara, Ming-jiang Xu, Kazuhiro Tamura, Peter J Donovan, Hee-jung Kim, Hiroshi Kogo, Kohichiro Tsuji, Tatsutoshi Nakahata, Atsushi Miyajima
Journal: Immunity (1998)
Male-Biased Mutation Rate and Divergence in Autosomal, Z-Linked and W-Linked Introns of Chicken and Turkey
Authors: Erik Axelsson, Nick G.C. Smith, Hannah Sundström, Sofia Berlin, Hans Ellegren
Journal: Molecular Biology and Evolution (2004)

To investigate mutation-rate variation between autosomes and sex chromosomes in the avian genome, we have analyzed divergence between chicken (Gallus gallus) and turkey (Meleagris galopavo) sequences from 33 autosomal, 28 Z-linked, and 14 W-linked introns with a total ungapped alignment length of approximately 43,000 bp. There are pronounced differences in the mean divergence among autosomes and sex chromosomes (autosomes [A] = 10.08%, Z chromosome = 10.99%, and W chromosome = 5.74%), and we use these data to estimate the male-to-female mutation-rate ratio (αm) from Z/A, Z/W, and A/W comparisons at 1.71, 2.37, and 2.52, respectively. Because the αm estimates of the three comparisons do not differ significantly, we find no statistical support for a specific reduction in the Z chromosome mutation rate (Z reduction estimated at 4.89%, P = 0.286). The idea of mutation-rate reduction in the sex chromosome hemizygous in one sex (i.e., X in mammals, Z in birds) has been suggested on the basis of theory on adaptive mutation-rate evolution. If it exists in birds, the effect would, thus, seem to be weak; a preliminary power analysis suggests that it is significantly less than 18%. Because divergence may vary within chromosomal classes as a result of variation in mutation and/or selection, we developed a novel double-bootstrapping method, bootstrapping both by introns and sites from concatenated alignments, to estimate confidence intervals for chromosomal class rates and for αm. The narrowest interval for the αm estimate is 1.88 to 2.97 from the Z/W comparison. We also estimated αm using maximum likelihood on data from all three chromosome classes; this method yielded αm = 2.47 and approximate 95% confidence intervals of 2.27 to 2.68. Our data are broadly consistent with the idea that mutation-rate differences between chromosomal classes can be explained by the male mutation bias alone.
Impact of low-density lipoprotein particle size on carotid intima-media thickness in patients with type 2 diabetes mellitus
Authors: Yuzo Hayashi, Kenji Okumura, Hideo Matsui, Akiko Imamura, Manabu Miura, Ryotaro Takahashi, Ryuichiro Murakami, Yasuhiro Ogawa, Yasushi Numaguchi, Toyoaki Murohara
Journal: Metabolism (2007)
Evaluation and Optimization of Therapeutic Footwear for Neuropathic Diabetic Foot Patients Using In-Shoe Plantar Pressure Analysis
Authors: Sicco A. Bus, Rob Haspels, Tessa E. Busch-Westbroek
Journal: Diabetes Care (2011)

Therapeutic footwear for diabetic foot patients aims to reduce the risk of ulceration by relieving mechanical pressure on the foot. However, footwear efficacy is generally not assessed in clinical practice. The purpose of this study was to assess the value of in-shoe plantar pressure analysis to evaluate and optimize the pressure-reducing effects of diabetic therapeutic footwear.Dynamic in-shoe plantar pressure distribution was measured in 23 neuropathic diabetic foot patients wearing fully customized footwear. Regions of interest (with peak pressure>200 kPa) were selected and targeted for pressure optimization by modifying the shoe or insole. After each of a maximum of three rounds of modifications, the effect on in-shoe plantar pressure was measured. Successful optimization was achieved with a peak pressure reduction of >25% (criterion A) or below an absolute level of 200 kPa (criterion B).In 35 defined regions, mean peak pressure was significantly reduced from 303 (SD 77) to 208 (46) kPa after an average 1.6 rounds of footwear modifications (P<0.001). This result constitutes a 30.2% pressure relief (range 18-50% across regions). All regions were successfully optimized: 16 according to criterion A, 7 to criterion B, and 12 to criterion A and B. Footwear optimization lasted on average 53 min.These findings suggest that in-shoe plantar pressure analysis is an effective and efficient tool to evaluate and guide footwear modifications that significantly reduce pressure in the neuropathic diabetic foot. This result provides an objective approach to instantly improve footwear quality, which should reduce the risk for pressure-related plantar foot ulcers.
The NF-κB negative regulator TNFAIP3 (A20) is inactivated by somatic mutations and genomic deletions in marginal zone lymphomas
Authors: Urban Novak, Andrea Rinaldi, Ivo Kwee, Subhadra V. Nandula, Paola M. V. Rancoita, Mara Compagno, Michaela Cerri, Davide Rossi, Vundavalli V. Murty, Emanuele Zucca, Gianluca Gaidano, Riccardo Dalla-Favera, Laura Pasqualucci, Govind Bhagat, Francesco Bertoni
Journal: Blood (2009)
STUDIES IN EDEMA
Authors: Moyer S. Fleisher, Leo Loeb
Journal: The Journal of Experimental Medicine (1909)

1. As a result of the intravenous infusion of a solution of sodium chloride a characteristic curve indicating the fluid retained in the vascular system is obtained. In the first period of the infusion the maximum of retention of fluid is noted. Then more fluid is removed from the blood vessels, so that for a short time a fall in the curve of dilution takes place, after which the dilution again slowly increases. 2. This curve is not materially changed by the addition of calcium chloride or of adrenalin to the infused solution, and under such conditions adrenalin does not lead to an increased pressing out of fluid from the vascular system, although is causes a constant and decided rise in blood pressure. Myocarditic lesions lead to an increased intravascular retention of fluid. Nephrectomy does not lead to an increased intravascular retention of fluid, but probably causes a diminution of the amount of fluid retained in the blood vessels.
Interaction synchrony and neural circuits contribute to shared intentionality
Authors: Ruth Feldman, Linda C. Mayes, James E. Swain
Journal: Behavioral and Brain Sciences (2005)

In the dyadic and triadic sharing of emotions, intentions, and behaviors in families, interactive synchrony is important to the early life experiences that contribute to the development of cultural cognition. This synchrony likely depends on neurobiological circuits, currently under study with brain imaging, that involve attention, stress response, and memory.
Chemical Mutagens. Principles and Methods for Their Detection.
Authors: Alexander Hollaender, Frederick J. De Serres
Journal: Annals of Internal Medicine (1974)

This book discusses the development and validation of short-term assays designed to detect the mutagenic effects of environmental chemicals. Topics considered include the grasshopper neuroblast short-term assay for evaluating the effects of environmental chemicals on chromosomes and cell kinetics, a comparison of the mutagenic responses of lung-derived and skin-derived human diploid fibroblast populations, the L-arabinose resistance test with Salmonella typhimurium, the Bacillus subtilis multigene sporulation test for the detection of environmental mutagens, the L5178Y/TK gene mutation assay system, the induction of bacteriophage lambda by DNA-interacting chemicals, the granuloma pouch assay, the use of multiply marked Escherichia coli K12 strains in the host-mediated assay, and the detection of mutagens in human feces as an approach to the discovery of causes of colon cancer.