tbuckley/cabot-search huggingface dataset:
Cytosolic Phosphoenolpyruvate Carboxykinase Does Not Solely Control the Rate of Hepatic Gluconeogenesis in the Intact Mouse Liver
Authors: Shawn C. Burgess, TianTeng He, Zheng Yan, Jill Lindner, A. Dean Sherry, Craig R. Malloy, Jeffrey D. Browning, Mark A. Magnuson
Journal: Cell Metabolism (2007)
Medication Initiation Burden Required to Comply With Heart Failure Guideline Recommendations and Hospital Quality Measures
Authors: Larry A. Allen, Gregg C. Fonarow, Li Liang, Phillip J. Schulte, Frederick A. Masoudi, John S. Rumsfeld, P. Michael Ho, Zubin J. Eapen, Adrian F. Hernandez, Paul A. Heidenreich, Deepak L. Bhatt, Eric D. Peterson, Harlan M. Krumholz
Journal: Circulation (2015)

Background— Guidelines for heart failure (HF) recommend prescription of guideline-directed medical therapy before hospital discharge; some of these therapies are included in publicly reported performance measures. The burden of new medications for individual patients has not been described. Methods and Results— We used Get With The Guidelines–HF registry data from 2008 to 2013 to characterize prescribing, indications, and contraindications for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers, aldosterone antagonists, hydralazine/isosorbide dinitrate, and anticoagulants. The difference between a patient’s medication regimen at hospital admission and that recommended by HF quality measures at discharge was calculated. Among 158 922 patients from 271 hospitals with a primary discharge diagnosis of HF, initiation of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was indicated in 18.1% of all patients (55.5% of those eligible at discharge were not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at admission), β-blockers in 20.3% (50.5% of eligible), aldosterone antagonists in 24.1% (87.4% of eligible), hydralazine/isosorbide dinitrate in 8.6% (93.1% of eligible), and anticoagulants in 18.0% (58.0% of eligible). Cumulatively, 0.4% of patients were eligible for 5 new medication groups, 4.1% for 4 new medication groups, 9.4% for 3 new medication groups, 10.1% for 2 new medication groups, and 22.7% for 1 new medication group; 15.0% were not eligible for new medications because of adequate prescribing at admission; and 38.4% were not eligible for any medications recommended by HF quality measures. Compared with newly indicated medications (mean, 1.45±1.23), actual new prescriptions were lower (mean, 1.16±1.00). Conclusions— A quarter of patients hospitalized with HF need to start &gt;1 medication to meet HF quality measures. Systems for addressing medication initiation and managing polypharmacy are central to HF transitional care.
Scatter Spectroscopic Imaging Distinguishes between Breast Pathologies in Tissues Relevant to Surgical Margin Assessment
Authors: Ashley M. Laughney, Venkataramanan Krishnaswamy, Elizabeth J. Rizzo, Mary C. Schwab, Richard J. Barth, Brian W. Pogue, Keith D. Paulsen, Wendy A. Wells
Journal: Clinical Cancer Research (2012)

Abstract Purpose: A new approach to spectroscopic imaging was developed to detect and discriminate microscopic pathologies in resected breast tissues; diagnostic performance of the prototype system was tested in 27 tissues procured during breast conservative surgery. Experimental Design: A custom-built, scanning in situ spectroscopy platform sampled broadband reflectance from a 150-μm-diameter spot over a 1 × 1 cm2 field using a dark field geometry and telecentric lens; the system was designed to balance sensitivity to cellular morphology and imaging the inherent diversity within tissue subtypes. Nearly 300,000 broadband spectra were parameterized using light scattering models and spatially dependent spectral signatures were interpreted using a cooccurrence matrix representation of image texture. Results: Local scattering changes distinguished benign from malignant pathologies with 94% accuracy, 93% sensitivity, 95% specificity, and 93% positive and 95% negative predictive values using a threshold-based classifier. Texture and shape features were important to optimally discriminate benign from malignant tissues, including pixel-to-pixel correlation, contrast and homogeneity, and the shape features of fractal dimension and Euler number. Analysis of the region-based diagnostic performance showed that spectroscopic image features from 1 × 1 mm2 areas were diagnostically discriminant and enabled quantification of within-class tissue heterogeneities. Conclusions: Localized scatter-imaging signatures detected by the scanning spectroscopy platform readily distinguished benign from malignant pathologies in surgical tissues and showed new spectral-spatial signatures of clinical breast pathologies. Clin Cancer Res; 18(22); 6315–25. ©2012 AACR.
Pulmonary immune cells in health and disease: dendritic cells and Langerhans' cells
Authors: AJ Hance
Journal: European Respiratory Journal (1993)

The activation of T-lymphocytes recognizing specific antigens is a crucial and early event in the development of an immune response, but T-lymphocytes cannot respond to antigens without help of a second cell type called accessory cells or antigen-presenting cells. Studies from several groups have indicated that pulmonary dendritic cells and Langerhans' cells, like their counterparts in other tissues, are potent accessory cells, and suggest that these cells may play an extremely important role in initiating lung immune responses. The purpose of this review is to summarize current information concerning pulmonary dendritic cells and Langerhans' cells, including their origin, distribution in the lung and functional capabilities. The possible role of these cells in certain lung diseases of immune origin will also be discussed.
Gestational Diabetes Mellitus: Implications of an Increased Frequency With IADPSG Criteria
Authors: Robert G. Moses
Journal: Diabetes Care (2012)

My sermon on the meaning of the manna in the wilderness can be adapted to almost any occasion, joyful, or, as in the present case, distressing. I have preached it at harvest celebrations, christenings, confirmations, on days of humiliation and festal days.Dr. Chasuble from The Importance of Being Earnest . Oscar Wilde, 1895

And so, to a greater or lesser extent, gestational diabetes mellitus (GDM) continues to provide something for everyone. The implications of recent publications can be interpreted, argued, and adapted in many ways.

The observational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study (1) and the consensus agreement about new diagnostic criteria by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) (2) have made a significant step toward international consensus but in some respects have opened a Pandora’s box (3).

In a recent publication, Ryan (4) calculated that the number of adverse perinatal events that could be hypothetically preventable with the new criteria would be relatively small and implied that a cost-benefit analysis may not be supportive. He also cogently argued that a raised maternal BMI could in most cases be the major predictive factor for large-for-gestational-age babies and that our approach has become too glucocentric. Using an OR of 2.0 rather than 1.75 for the diagnostic criteria would diagnose the same approximate number of women with gestational …
Integrated Analysis of Molecular and Clinical Prognostic Factors in Stage II/III Colon Cancer
Authors: A. D. Roth, M. Delorenzi, S. Tejpar, P. Yan, D. Klingbiel, R. Fiocca, G. d'Ario, L. Cisar, R. Labianca, D. Cunningham, B. Nordlinger, F. Bosman, E. Van Cutsem
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundThe prognostic potential of individual clinical and molecular parameters in stage II/III colon cancer has been investigated, but a thorough multivariable assessment of their relative impact is missing.
Local pH elevation mediated by the intrabacterial urease of Helicobacter pylori cocultured with gastric cells
Authors: Christoph Athmann, Ningxin Zeng, Tao Kang, Elizabeth A. Marcus, David R. Scott, Marina Rektorschek, Anita Buhmann, Klaus Melchers, George Sachs
Journal: Journal of Clinical Investigation (2000)

Helicobacter pylori resists gastric acidity by modulating the proton-gated urea channel UreI, allowing for pHout-dependent regulation of urea access to intrabacterial urease. We employed pH- and Ca2+-sensitive fluorescent dyes and confocal microscopy to determine the location, rate, and magnitude of pH changes in an H. pylori-AGS cell coculture model, comparing wild-type bacteria with nonpolar ureI-deletion strains (ureI-ve). Addition of urea at pH 5.5 to the coculture resulted first in elevation of bacterial periplasmic pH, followed by an increase of medium pH and then pH in AGS cells. No change in periplasmic pH occurred in ureI-deletion mutants, which also induced a slower increase in the pH of the medium. Pretreatment of the mutant bacteria with the detergent C12E8 before adding urea resulted in rapid elevation of bacterial cytoplasmic pH and medium pH. UreI-dependent NH3 generation by intrabacterial urease buffers the bacterial periplasm, enabling acid resistance at the low urea concentrations found in gastric juice. Perfusion of AGS cells with urea-containing medium from coculture at pH 5.5 did not elevate pHin or [Ca2+]in, unless the conditioned medium was first neutralized to elevate the NH3/NH4+ ratio. Therefore, cellular effects of intrabacterial ammonia generation under acidic conditions are indirect and not through a type IV secretory complex. The pHin and [Ca2+]in elevation that causes the NH3/NH4+ ratio to increase after neutralization of infected gastric juice may contribute to the gastritis seen with H. pylori infection.
Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience
Authors: A Al-toma, W H M Verbeek, M Hadithi, B M E von Blomberg, C J J Mulder
Journal: Gut (2007)

Coeliac disease may be regarded as refractory disease (RCD) when symptoms persist or recur despite strict adherence to a gluten-free diet. RCD may be subdivided into types I and II with a phenotypically normal and aberrant intraepithelial T-cell population, respectively. RCD I seems to respond well to azathioprine/prednisone therapy. RCD II is usually resistant to any known therapy and transition into enteropathy-associated T-cell lymphoma (EATL) is common.To provide further insight into RCD and the development of EATL, by reporting on long-term survival and risk of transition of RCD into EATL in a large cohort of patients with complicated coeliac disease.Retrospective comparison of responses to therapy in four groups of patients with complicated coeliac disease: 43, RCD I; 50, RCD II (total), of whom 26 with RCD II developed EATL after a period of refractoriness to a gluten-free diet (secondary EATL) and 13 were EATL patients without preceding history of complicated coeliac disease (de novo EATL).No coeliac-disease-related mortality was recognised in the RCD I group. The overall 5-year survival in the RCD I group it was 96%; in the RCD II (total) group was 58%; and in the RCD II group after developing EATL it was only 8%. The 2-year survival in the de novo EATL group was 20% versus 15% in secondary EATL group (p = 0.63). Twenty-eight (56%) of the 50 patients with RCD II died, 23 (46%) due to EATL, 4 due to a progressive refractory state with emaciation and 1 from neurocoeliac disease.Remarkably, no patient with RCD I developed RCD II or EATL within the mean follow-up period of 5 years (range 2-15 years). A total of 52% of the RCD II patients developed EATL within 4-6 years after the diagnosis of RCD II. More aggressive and targeted therapies seem necessary in RCD II and EATL.
The Effect of Raltegravir Intensification on Low-level Residual Viremia in HIV-Infected Patients on Antiretroviral Therapy: A Randomized Controlled Trial
Authors: Rajesh T. Gandhi, Lu Zheng, Ronald J. Bosch, Ellen S. Chan, David M. Margolis, Sarah Read, Beatrice Kallungal, Sarah Palmer, Kathy Medvik, Michael M. Lederman, Nadia Alatrakchi, Jeffrey M. Jacobson, Ann Wiegand, Mary Kearney, John M. Coffin, John W. Mellors, Joseph J. Eron
Journal: PLoS Medicine (2010)

Background Most HIV-1-infected patients on effective antiretroviral therapy (ART) with plasma HIV-1 RNA levels below the detection limits of commercial assays have residual viremia measurable by more sensitive methods. We assessed whether adding raltegravir lowered the level of residual viremia in such patients. Methods and Findings Patients receiving ART who had plasma HIV-1 RNA levels below 50 copies/mL but detectable viremia by single copy assay (SCA) were randomized to add either raltegravir or placebo to their ART regimen for 12 weeks; patients then crossed-over to the other therapy for an additional 12 weeks while continuing pre-study ART. The primary endpoint was the plasma HIV-1 RNA by SCA averaged between weeks 10 and 12 (10/12) compared between treatment groups. Fifty-three patients were enrolled. The median screening HIV-1 RNA was 1.7 copies/mL. The HIV-1 RNA level at weeks 10/12 did not differ significantly between the raltegravir-intensified (n = 25) and the placebo (n = 24) groups (median 1.2 versus 1.7 copies/mL, p = 0.55, Wilcoxon rank sum test), nor did the change in HIV-1 RNA level from baseline to week 10/12 (median −0.2 and −0.1 copies/mL, p = 0.71, Wilcoxon rank sum test). There was also no significant change in HIV-1 RNA level from weeks 10/12 to weeks 22/24 after patients crossed-over. There was a greater CD4 cell count increase from baseline to week 12 in the raltegravir-intensified group compared with the placebo group (+42 versus −44 cells/mm3, p = 0.082, Wilcoxon rank sum test), which reversed after the cross-over. This CD4 cell count change was not associated with an effect of raltegravir intensification on markers of CD4 or CD8 cell activation in blood. Conclusion In this randomized, double-blind cross-over study, 12 weeks of raltegravir intensification did not demonstrably reduce low-level plasma viremia in patients on currently recommended ART. This finding suggests that residual viremia does not arise from ongoing cycles of HIV-1 replication and infection of new cells. New therapeutic strategies to eliminate reservoirs that produce residual viremia will be required to eradicate HIV-1 infection. Trial Registration ClinicalTrials.gov NCT00515827 Please see later in the article for the Editors' Summary
Immunoglobulin kappa deleting element rearrangements in precursor-B acute lymphoblastic leukemia are stable targets for detection of minimal residual disease by real-time quantitative PCR
Authors: VHJ van der Velden, MJ Willemse, CE van der Schoot, K Hählen, ER van Wering, JJM van Dongen
Journal: Leukemia (2002)
Phase II Study of Capecitabine Plus Trastuzumab in Human Epidermal Growth Factor Receptor 2–Overexpressing Metastatic Breast Cancer Pretreated With Anthracyclines or Taxanes
Authors: Gerhard Schaller, Ilka Fuchs, Thomas Gonsch, Jan Weber, Anke Kleine-Tebbe, Peter Klare, Hans-Joachim Hindenburg, Volker Lakner, Axel Hinke, Nikola Bangemann
Journal: Journal of Clinical Oncology (2007)

The oral fluoropyrimidine carbamate, capecitabine, is a highly active and well-tolerated treatment for metastatic breast cancer. In patients treated previously with anthracyclines and taxanes, capecitabine is an approved single-agent therapy. Trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER-2), is also highly active in HER-2-overexpressing breast cancer. We have conducted a phase II study to confirm activity and feasibility of capecitabine and trastuzumab in combination in HER-2-overexpressing advanced/metastatic breast cancer.Twenty-seven patients with HER-2-overexpressing metastatic breast cancer previously treated with anthracyclines and/or taxanes received oral capecitabine 1,250 mg/m(2) bid for 14 days followed by a 7-day rest period combined with intravenous trastuzumab 4 mg/kg body weight on day 1 (loading dose) followed by 2 mg/kg weekly.Capecitabine/trastuzumab treatment achieved objective responses in 12 patients (45%), including complete response in four patients (15%) and partial response in eight patients (30%). Disease was stabilized in an additional nine patients (33%). The median overall survival time was 28 months, and the median progression-free survival time was 6.7 months. The safety profile of the combination was favorable and predictable, with a low incidence of grade 3/4 adverse events. The most common adverse events were pain, hand-foot syndrome, and GI toxicities. Severe myelosuppression was rare and severe alopecia did not occur.These data confirm that the combination of capecitabine and trastuzumab is highly active in patients with HER-2-overexpressing anthracycline- and/or taxane-pretreated breast cancer, with only slight restrictions regarding quality of life.
Part 10: Acute Coronary Syndromes
Authors: Robert E. O'Connor, William Brady, Steven C. Brooks, Deborah Diercks, Jonathan Egan, Chris Ghaemmaghami, Venu Menon, Brian J. O'Neil, Andrew H. Travers, Demetris Yannopoulos
Journal: Circulation (2010)

There has been tremendous progress in reducing disability and death from ACS. But many patients still die before reaching the hospital because patients and family members fail to recognize the signs of ACS and fail to activate the EMS system. Once the patient with ACS contacts the healthcare system, providers must focus on support of cardiorespiratory function, rapid transport, and early classification of the patient based on ECG characteristics. Patients with STEMI require prompt reperfusion; the shorter the interval from symptom onset to reperfusion, the greater the benefit. In the STEMI population, mechanical reperfusion with percutaenous coronary intervention improves survival and decreases major cardiovascular events compared to fibrinolysis. Patients with UA/NSTEMI (non-STEMI ACS) or nonspecific or normal ECGs require risk stratification and appropriate monitoring and therapy. Healthcare providers can improve survival rates and myocardial function of patients with ACS by providing skilled, efficient, and coordinated out-of-hospital and in-hospital care.
AN EFFICIENT TREATMENT FOR ACNE VULGARIS.
Authors: K. A. Baird
Journal: British Journal of Dermatology (1957)

Journal Article AN EFFICIENT TREATMENT FOR ACNE VULGARIS. Get access K. A. Baird, M.A., M.D., F.A.C.A. K. A. Baird, M.A., M.D., F.A.C.A. Lancaster, New Brunswick, Canada Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 69, Issue 3, 1 March 1957, Pages 86–91, https://doi.org/10.1111/j.1365-2133.1957.tb13234.x Published: 01 March 1957
Phenethyl Isothiocyanate Triggers Apoptosis in Jurkat Cells Made Resistant by the Overexpression of Bcl-2
Authors: Susan J. Thomson, Kristin K. Brown, Juliet M. Pullar, Mark B. Hampton
Journal: Cancer Research (2006)

Abstract Isothiocyanates are a class of naturally occuring chemopreventive agents known to be effective at triggering apoptosis. In this study, we show that whereas overexpression of the oncoprotein Bcl-2 renders Jurkat T-lymphoma cells resistant to a range of cytotoxic agents, phenethyl isothiocyanate is able to overcome the inhibitory action of Bcl-2 and trigger apoptosis. A 50-fold increase in Bcl-2 expression shifted the dose-response curve, with an increase in the phenethyl isothiocyanate LD50 from 7 to 15 μmol/L, but there was still a complete loss in cell viability at doses in excess of 20 μmol/L. At these concentrations, cytotoxicity was strongly associated with caspase activation, phosphatidylserine exposure, and morphologic changes characteristic of apoptosis. Cytotoxicity was inhibited by treatment of the cells with a broad-spectrum caspase inhibitor. A structure-activity analysis showed that the phenethyl and benzyl isothiocyanates were most effective at triggering apoptosis in cells overexpressing Bcl-2 whereas phenyl isothiocyanate and benzyl thiocyanate had no proapoptotic activity. Allyl isothiocyanate also had limited efficacy despite its ability to trigger apoptosis in the parental Jurkat cell line. From this information, we propose that isothiocyanates modify a key cysteine residue in an apoptosis regulatory protein and that the aromatic side chain facilitates access to the target site. An in-depth investigation of the cellular targets of the aromatic isothiocyanates is warranted.(Cancer Res 2006; 66(13): 6772-7)
Current Aspects of the Structure, Function, and Genetics of the Immunoglobulins
Authors: D Gitlin
Journal: Annual Review of Medicine (1966)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Topiramate Treatment for Heavy Drinkers: Moderation by a <i>GRIK1</i> Polymorphism
Authors: Henry R. Kranzler, Jonathan Covault, Richard Feinn, Stephen Armeli, Howard Tennen, Albert J. Arias, Joel Gelernter, Timothy Pond, Cheryl Oncken, Kyle M. Kampman
Journal: American Journal of Psychiatry (2014)

Heavy drinkers trying to cut back but not completely eliminate their alcohol intake were treated with topiramate as an adjunct to counseling and reduced their drinking more rapidly than patients given placebo. The effect of topiramate was significant only in patients with a specific gene variation, the CC genotype of the GRIK1 polymorphism, offering a way to identify heavy drinkers who are likely to respond well to this treatment.
Bifidobacterium pseudocatenulatum is associated with atopic eczema: A nested case-control study investigating the fecal microbiota of infants
Authors: Claudia Gore, Karen Munro, Christophe Lay, Rodrigo Bibiloni, Julie Morris, Ashley Woodcock, Adnan Custovic, Gerald W. Tannock
Journal: Journal of Allergy and Clinical Immunology (2007)