tbuckley/cabot-search huggingface dataset:
The relationship between echodensitometric parameters of respiratory muscles (RM) and indices of body composition (IBC) in men with chronic obstructive pulmonary disease (COPD)
Authors: Sviatlana Lemiasheuskaya, Alexander Makarevich, Alexander Pochtavcev
Journal: European Respiratory Journal (2011)

Introduction:  RM undergo an adaptive reductive remodeling.   Aim:  To investigate changes of active expiration RM in COPD pts.   Methods:  The peak histograms of muscles (external and internal oblique (extOAM and intOAM), transverses and rectus abdominal and internal intercostals) were detected by ultrasonic scanner. We investigated the indices: homogeneity (H), structural density (SD) and echogenicity (E). Fat mass (FM) and Lean mass (FFM) were determined by DXA. FM, FFM were expressed as ratios to height squared to get FMI, FFMI. The COPD pts were subdivided into groups: the 1st was made of 14 men; I stage (GOLD); mean age 55 yrs; BMI 27 kg/m 2 ; the 2nd - 43 pts; II stage; mean age 57; BMI 28 kg/m 2 ; the 3d -20 pts; III stage; mean age 60 yrs; BMI 24,5 kg/m 2 .   Results:  Indices H, SD decrease, while E increases in COPD pts v. control and in process of severity growth of COPD. We have established the positive significant correlations of E with FMI (r=0,61), and negative one between SD and FMI (r=-0,7) of extOAM in the 1st group. The positive significant correlation was detected between E and FMI (r=0,52) and negative one between H and SD of extOAM and FMI (r=-0,42 and r=-0,52) in the 2nd group. The 3d group characterized by the positive significant correlations between E and FFMI (r=0,69) and negative one between H and SD of extOAM and FMI (r=-0,7 and r=-0,75). The index E of intOAM correlated with FMI and FFMI (r=0,62 and r=0,63). Similar results were characteristic of other muscles.   Conclusions:  The possible mechanism of the changes in COPD patients could be protein replacement with fat in muscles.
Abstract 13106: Exercise Tests Cannot Be Used as a Diagnostic Tool for Detection of Coronary Microvessel Dysfunction
Authors: Nynne Dose, Marie M Michelsen, Naja D Mygind, Adam A Pena, Eva Prescott
Journal: Circulation (2014)

Introduction: Current guidelines indicate that patients with angina, a positive exercise test and no obstructive coronary artery disease (CAD) should be suspected of coronary microvessel dysfunction (CMD). The aim of this study was to investigate if exercise tests can identify patients with CMD. Methods: Women with angina pectoris and no obstructive CAD (&lt;50% stenosis on CAG) were consecutively included in the study (n=763). Coronary flow reserve (CFR) was assessed by TTE during dipyridamole infusion (0.84 mg/kg) and information regarding results from exercise test ≤6 months prior to CAG and risk factors were obtained. Results were categorised as 1) positive based on occurrence of ECG changes or typical angina pectoris symptoms 2) negative or 3) inconclusive. Results: Exercise test had been performed prior to CAG in 283 of 642 patients (44 %). Patients lacking information were excluded (n=121). Patients with or without exercise test did not differ in CFR, age, smoking status, years of smoking, type-2 diabetes, BMI, hypertension, hypercholesterolemia or CAG result (all p&gt;0.05).There were no significant differences in mean CFR between patients with a positive, inconclusive or negative test and the proportion with CMD (cut off 2.0 and 2.5, respectively) did not differ. Age, smoking status, type-2 diabetes, hypercholesterolemia or CAG results was similar (table). There was a tendency towards less hypertension in the group of patients with a negative test (p=0.051). Furthermore patients with a negative test had been smoking significantly less than patients with an inconclusive or positive test (p=0.04) Conclusions: No difference in CFR for patients with a positive, inconclusive or negative exercise test was observed. This lack of difference did not seem to be explained by an uneven distribution of risk factors between groups due to selection bias. Exercise tests cannot be used as diagnostic method for CMD, which supports the need for developing novel methods for diagnosing CMD.
Intrathecal Analgesia for Chronic Refractory Pain: Current and Future Prospects
Authors: Catherine Smyth, Nadera Ahmadzai, Jason Wentzell, Ashley Pardoe, Andrew Tse, Tiffany Nguyen, Yvette Goddard, Shona Nair, Patricia A. Poulin, Becky Skidmore, Mohammed T. Ansari
Journal: Drugs (2015)
Carcinoembryonic Antigen in Colon Cancer: Absence in Perchloric Acid Precipitates of Plasma2
Authors: Jeffrey J. Sorokin, Herbert Z. Kupchik, Norman Zamcheck
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Carcinoembryonic Antigen in Colon Cancer: Absence in Perchloric Acid Precipitates of Plasma Get access Jeffrey J. Sorokin, M.D., Jeffrey J. Sorokin, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert Z. Kupchik, Ph.D., Herbert Z. Kupchik, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Norman Zamcheck, M.D. Norman Zamcheck, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 3, September 1973, Pages 1081–1083, https://doi.org/10.1093/jnci/51.3.1081 Published: 01 September 1973 Article history Received: 25 May 1973 Accepted: 06 June 1973 Published: 01 September 1973
Divergent<i>MLS1</i>Promoters Lie on a Fitness Plateau for Gene Expression
Authors: Andrew C. Bergen, Gerilyn M. Olsen, Justin C. Fay
Journal: Molecular Biology and Evolution (2016)

Qualitative patterns of gene activation and repression are often conserved despite an abundance of quantitative variation in expression levels within and between species. A major challenge to interpreting patterns of expression divergence is knowing which changes in gene expression affect fitness. To characterize the fitness effects of gene expression divergence, we placed orthologous promoters from eight yeast species upstream of malate synthase (MLS1) in Saccharomyces cerevisiae. As expected, we found these promoters varied in their expression level under activated and repressed conditions as well as in their dynamic response following loss of glucose repression. Despite these differences, only a single promoter driving near basal levels of expression caused a detectable loss of fitness. We conclude that the MLS1 promoter lies on a fitness plateau whereby even large changes in gene expression can be tolerated without a substantial loss of fitness.
Pregabalin is only partially effective for neuropathic pain
Authors: J. Gwynn
Journal: BMJ (2015)

As a patient with knowledge about research and development (R&D), and marketing, receipt of a prescription for generic pregabalin for neuropathic pain prompted a call to my GP about a possible error. Initially she blamed the pharmacist but the prescription did not specify indication. Subsequent prescriptions have been for Lyrica.

Professionally I am fully aware of escalating R&D costs and maximising patent life. …
Phosphorylation of estrogen receptor α at serine 118 in human breast tumours
Authors: N. Sarwar, J.-S. Kim, J. Jiang, D. Peston, S. Shousha, R. C. Coombes, S. Ali
Journal: Journal of Clinical Oncology (2005)

9576 Background: The purpose of this study was to determine whether estrogen receptor α (ERα) phosphorylated at serine 118 (PS118) could be detected in breast cancer tissues and if successful, to determine its relationship with prognostic factors, survival and outcome of endocrine therapies. To determine an association between resistance to hormonal therapy and phosphorylation, we also looked at the levels of PS118 from patients who had become resistant to endocrine therapy. Methods: Phosphorylation of serine 118 was investigated in human breast tumours in vivo using immunohistochemistry (IHC). Tissue blocks from 112 patients were sectioned and underwent IHC for the detection of PS118. PS118 levels from 21 breast tumour cases who had become resistant to endocrine therapy were also determined. Results: Ninety five (85%) of the tumours were ERα positive and seventeen (15%) were ERα negative. Of the 95 ERα positive patients, 79 (83%) had detectable nuclear staining for PS118. PS118 staining was scored according to McCarthy’s H scoring system. Statistical analysis revealed that there was no significant association with age, size, nodal status and c-erb2 expression. There was however a significant association between PS118 staining and ERα expression (p=0.001), and an association between PS118 and active mitogen-activated protein kinase (MAPK) expression (p=0.001). Progesterone receptor expression, a known estrogen regulated gene, was also found to correlate significantly with PS118 levels (p= 0.02). However there was an inverse relationship with grade and levels of PS118. No association was found between levels of PS118 in tumours and survival. There was however a statistically significant difference in PS118 levels in the pre- and post hormonal therapy biopsies (p=0.05). Of the 21 cases examined, nine (43%) showed an increase in levels of PS118 on recurrence when compared to their pre-treatment IHC scores. Conclusions: Our present study confirms the observation that ERα specifically phosphorylated at serine 118 is expressed by human breast cancers. Our findings also demonstrate that emergence of resistance to tamoxifen is associated with increased phospho-serine 118 levels, both in vitro and in breast cancer biopsies from patients. No significant financial relationships to disclose.
Sixty seconds on . . . the consultant contract
Authors: Abi Rimmer
Journal: BMJ (2016)

Where have you been? The BMA has been holding road show events across England and Northern Ireland over the past couple of weeks to explain the proposed changes.1 These involve scrapping the current clinical excellence awards system and removing the clause that allows consultants to opt out of non-emergency out-of-hours work.2

Negotiations on the contract …
A Phase I Clinical, Pharmacokinetic, and Pharmacodynamic Study of Weekly or Every Three Week Ixabepilone and Daily Sunitinib in Patients with Advanced Solid Tumors
Authors: Alberto J. Montero, Deukwoo Kwon, Aurea Flores, Krisztina Kovacs, Jonathan C. Trent, Pasquale Benedetto, Caio Rocha-Lima, Jaime R. Merchan
Journal: Clinical Cancer Research (2016)

To evaluate the safety, MTD, pharmacokinetics/pharmacodynamics, and early clinical activity of ixabepilone given either weekly or every 3 weeks in combination with daily sunitinib in patients with advanced solid tumors.Eligible patients received either weekly (schedule A) or every 3 weeks (schedule B) ixabepilone at escalating doses (schedule A: 7.5, 15, or 20 mg/m(2); schedule B: 20, 30, or 40 mg/m(2)), and oral sunitinib (37.5 mg daily), starting on day 8 of cycle 1. Dose-limiting toxicities (DLT) were assessed during cycle 1.The ixabepilone and sunitinib combination was fairly well tolerated. DLTs were observed in 3 subjects (1 in schedule 3A and 2 in schedule 3B). The most common grade 3-4 hematologic and nonhematologic adverse events were leukopenia and fatigue, respectively. Four patients (3 in schedule A) achieved a partial response, while 13 patients had stable disease. Nine of 17 heavily pretreated colorectal cancer patients had clinical benefit. Coadministration of sunitinib with ixabepilone on a weekly (but not every 3 week) schedule was associated with a significant increase in the half-life and a significant decrease in the clearance of ixabepilone. Correlative studies demonstrated a significant association between higher baseline plasma angiogenic activity (PAA) and clinical benefit in schedule A patients. Weekly, but not every 3 weeks, ixabepilone led to a significant decrease in PAA postbaseline.Coadministration of ixabepilone with sunitinib has acceptable toxicity and encouraging clinical activity in heavily pretreated patients, particularly in patients with metastatic colorectal cancer. Clin Cancer Res; 22(13); 3209-17. ©2016 AACR.
Effective but costly: How to tackle difficult trade‐offs in evaluating health improving technologies in liver diseases
Authors: Lorenzo Giovanni Mantovani, Paolo Angelo Cortesi, Mario Strazzabosco
Journal: Hepatology (2016)

In the current context of rising health care costs and decreasing sustainability, it is becoming increasingly common to resort to decision analytical modeling and health economics evaluations. Decision analytic models are analytical tools that help decision makers to select the best choice between alternative health care interventions, taking into consideration the complexity of the disease, the socioeconomic context, and the relevant differences in outcomes. We present a brief overview of the use of decision analytical models in health economic evaluations and their applications in the area of liver diseases. The aim is to provide the reader with the basic elements to evaluate health economic analysis reports and to discuss some limitations of the current approaches, as highlighted by the case of the therapy of chronic hepatitis C. To serve its purpose, health economics evaluations must be able to do justice to medical innovation and the market while protecting patients and society and promoting fair access to treatment and its economic sustainability.New approaches and methods able to include variables such as prevalence of the disease, budget impact, and sustainability into the cost-effectiveness analysis are needed to reach this goal. (Hepatology 2016;64:1331-1342).
Effect of Generous Funding for AIDS Research on General Biomedical Research
Authors: S C Dilsaver, J A Coffman
Journal: New England Journal of Medicine (1988)

The direct cost of psychiatric care in the US was US $20 billion in 1983.  Direct and indirect costs related to psychiatric illness came to an estimated US $185 billion.  The total budget of the Alcohol Drug Abuse and Mental Health Administration for the fiscal year 1988 is estimated to come to US $457 million.  22% of this budget has been designated for research projects related to the acquired immunodeficiency syndrome (AIDS).  While 50000 Americans have AIDS more people than that commit suicide annually.  Therefore expenditures for AIDS research appear unreasonable given the relatively small number of patients afflicted with the disease.  These priorities put pressure on investigators to include protocols involving patients with AIDS in grant proposals solely to make the proposals appealing to funding sources.  AIDS is a terrible disease with high mortality and morbidity but allowing its dramatic nature and the public outcry it generates to dictate public policy in health care funding to the extent that it has is questionable.  In the long run such policies could have a detrimental effect on biomedical research as young scientists are channeled into highly fundable areas of study to the neglect of other important areas.
Predicting outcome of antipsychotic drug treatment from early response
Authors: P R May, T Van Putten, C Yale
Journal: American Journal of Psychiatry (1980)

The authors gave 48 newly admitted schizophrenic patients an initial test dose (2.2 mg/kg) of chlorpromazine hydrochloride and additional doses at 24 and 36 hours. Clinical response was measured at 48 hours and at the end of subsequent treatment with a fixed dose (6.6 mg/kg) of chlorpromazine. There was a consistent correlation between 48-hour change and the eventual amount of improvement by the end of drug treatment for all 10 outcome criteria. The authors conclude that change early on in drug treatment is a useful predictor of outcome.
Molecular imaging correlates of tryptophan metabolism via the kynurenine pathway in human meningiomas
Authors: E. Bosnyak, D. O. Kamson, A. R. Guastella, K. Varadarajan, N. L. Robinette, W. J. Kupsky, O. Muzik, S. K. Michelhaugh, S. Mittal, C. Juhasz
Journal: Neuro-Oncology (2015)

Increased tryptophan metabolism via the kynurenine pathway (KP) is a key mechanism of tumoral immune suppression in gliomas. However, details of tryptophan metabolism in meningiomas have not been elucidated. In this study, we evaluated in vivo tryptophan metabolism in meningiomas and compared it with gliomas using α-[(11)C]-methyl-L-tryptophan (AMT)-PET. We also explored expression patterns of KP enzymes in resected meningiomas.Forty-seven patients with MRI-detected meningioma (n = 16) and glioma (n = 31) underwent presurgical AMT-PET scanning. Tumoral AMT uptake and tracer kinetic parameters (including K and k3' evaluating unidirectional uptake and trapping, respectively) were measured, correlated with meningioma grade, and compared between meningiomas and gliomas. Patterns of KP enzyme expression were assessed by immunohistochemistry in all meningiomas.Meningioma grade showed a positive correlation with AMT k3' tumor/cortex ratio (r = 0.75, P = .003), and this PET parameter distinguished grade I from grade II/III meningiomas with 92% accuracy. Kinetic AMT parameters could differentiate meningiomas from both low-grade gliomas (97% accuracy by k3' ratios) and high-grade gliomas (83% accuracy by K ratios). Among 3 initial KP enzymes (indoleamine 2,3-dioxygenase 1/2, and tryptophan 2,3-dioxygenase 2 [TDO2]), TDO2 showed the strongest immunostaining, particularly in grade I meningiomas. TDO2 also showed a strong negative correlation with AMT k3' ratios (P = .001).PET imaging of tryptophan metabolism can provide quantitative imaging markers for differentiating grade I from grade II/III meningiomas. TDO2 may be an important driver of in vivo tryptophan metabolism in these tumors. These results can have implications for pharmacological targeting of the KP in meningiomas.
Virological surveillance of influenza and other respiratory viruses during six consecutive seasons from 2006 to 2012 in Catalonia, Spain
Authors: A. Antón, M.A. Marcos, N. Torner, R. Isanta, M. Camps, A. Martínez, A. Domínguez, M. Jané, M.T. Jiménez de Anta, T. Pumarola
Journal: Clinical Microbiology and Infection (2016)
IL-23 prevents IL-13-dependent tissue repair associated with Ly6C lo monocytes in Entamoeba histolytica -induced liver damage
Authors: Jill Noll, Elena Helk, Helena Fehling, Hannah Bernin, Claudia Marggraff, Thomas Jacobs, Samuel Huber, Penelope Pelczar, Thomas Ernst, Harald Ittrich, Benjamin Otto, Hans-Willi Mittrücker, Christoph Hölscher, Frank Tacke, Iris Bruchhaus, Egbert Tannich, Hannelore Lotter
Journal: Journal of Hepatology (2016)

<h3>Background & Aims</h3> The IL-23/IL-17 axis plays an important role in the pathogenesis of autoimmune diseases and the pathological consequences of infection. We previously showed that immunopathologic mechanisms mediated by inflammatory monocytes underlie the severe focal liver damage induced by the protozoan parasite, <i>Entamoeba histolytica</i>. Here, we analyze the contribution of the IL-23/IL-17 axis to the induction and subsequent recovery from parasite-induced liver damage. <h3>Methods</h3> <i>IL-23p19<sup>−/−</sup></i>, <i>IL-17A/F<sup>−/−</sup></i>, <i>CCR2<sup>−/−</sup></i>, and wild-type (WT) mice were intra-hepatically infected with <i>E. histolytica</i> trophozoites and disease onset and recovery were analyzed by magnetic resonance imaging. Liver-specific gene and protein expression during infection was examined by qPCR, microarray, FACS analysis and immunohistochemistry. Immuno-depletion and substitution experiments were performed in <i>IL-23p19<sup>−/−</sup></i> and WT mice to investigate the role of IL-13 in disease outcome. <h3>Results</h3> Liver damage in infected <i>IL-23p19<sup>−/−</sup></i>, <i>IL-17A/F<sup>−/−</sup></i>, and <i>CCR2<sup>−/−</sup></i> mice was strongly attenuated compared with that in WT mice. <i>IL-23p19<sup>−/−</sup></i> mice showed reduced accumulation of <i>IL-17</i> and <i>CCL2</i> mRNA and proteins. Increased numbers of IL-13-producing CD11b<sup>+</sup>Ly6C<sup>lo</sup> monocytes were associated with disease attenuation in <i>IL-23p19<sup>−/−</sup></i> mice. Immuno-depletion of IL-13 in <i>IL-23p19<sup>−/−</sup></i> mice reversed this attenuation and treatment of infected WT mice with an IL-13/anti-IL-13-mAb complex supported liver recovery. <h3>Conclusions</h3> The IL-23/IL-17 axis plays a critical role in the immunopathology of hepatic amebiasis. IL-13 secreted by CD11b<sup>+</sup>Ly6C<sup>lo</sup> monocytes may be associated with recovery from liver damage. An IL-13/anti-IL13-mAb complex mimics this function, suggesting a novel therapeutic option to support tissue healing after liver damage.
MET:GRB2 complexes define a subset of lung cancer with potential vulnerability to MET inhibition
Authors: Matthew A. Smith, Thomas Licata, Aliya Lakhani, Mariella Varella-Garcia, Hans-Ulrich Schildhaus, Vincent Vuaroqueaux, Heinz-Herbert Fiebig, Eric B. Haura
Journal: Journal of Thoracic Oncology (2016)
Effect of Polyriboinosinic-Polyribocytidylic Acid on the Metabolism and Viability of Cells &lt;italic&gt;In Vitro&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Alison M. Badger, Sidney R. Cooperband, Jon A. Green
Journal: JNCI Journal of the National Cancer Institute (1972)

Addition of polyriboinosinic-polyribocytidylic acid (poly I:C) to a variety of cell lines carried in continuous culture resulted in incorporation of large amounts of 3H-labeled thymidine (3H-TDR) into DNA and 3H-labeled uridine into RNA in the presence of a normal or decreased protein synthesis and in the absence of a change in total cell population. The increased incorporation of label was not an artifact resulting from infectious agents in the culture medium or from an increased uptake of 3H-TDR into the intracellular pool. The label was concentrated in the nucleus of the cell as opposed to the cytoplasm. Virus-inhibiting doses of Rifampicin did not inhibit the increased uptake of labeled precursor into the cells. Microscopically the cultures showed no endoreduplication of nuclei or increased ploidy to account for this new DNA. Primary cell isolates responded quite differently in that DNA and RNA synthesis was suppressed whereas protein synthesis remained normal. Examination of the cytotoxic potential of the poly I:C showed that in murine L cells, increasing cell death correlated with increasing incorporation of 3H-TDR into DNA. However, poly I:C was visibly toxic to only the L cells and WISH amnion as demonstrated by permeability to trypan blue; all the other cells showed no such permeability. However, cytotoxicity might be more subtle, since poly I:C inhibited amoeboid activity of human lymphocytes without increasing permeability to trypan blue.
Gland segmentation in colon histology images: The glas challenge contest
Authors: Korsuk Sirinukunwattana, Josien P.W. Pluim, Hao Chen, Xiaojuan Qi, Pheng-Ann Heng, Yun Bo Guo, Li Yang Wang, Bogdan J. Matuszewski, Elia Bruni, Urko Sanchez, Anton Böhm, Olaf Ronneberger, Bassem Ben Cheikh, Daniel Racoceanu, Philipp Kainz, Michael Pfeiffer, Martin Urschler, David R.J. Snead, Nasir M. Rajpoot
Journal: Medical Image Analysis (2016)