tbuckley/cabot-search huggingface dataset:
Ranibizumab 0.5 mg for Diabetic Macular Edema with Bimonthly Monitoring after a Phase of Initial Treatment
Authors: Ian Pearce, Sanjiv Banerjee, Ben J.L. Burton, Usha Chakravarthy, Louise Downey, Richard P. Gale, Jonathan Gibson, Sergio Pagliarini, Jignesh Patel, Sobha Sivaprasad, Chris Andrews, Christopher Brittain, James Warburton
Journal: Ophthalmology (2015)
Abstract 269: Asymmetric laterality of breast tumors is correlated with place of birth, but not race
Authors: Trevor Sughue, James P. Brody
Journal: Cancer Research (2014)

Abstract More breast cancers are diagnosed in the left breast than the right breast. The ratio of the number of tumors diagnosed in the left breast to the number diagnosed in the right in a population is called the laterality ratio. Previous studies showed that the breast cancer laterality ratio is significantly larger than 1 and significantly different in different quadrants of the breast. We analyzed 1.2 million cases of breast cancer diagnosed in the US between 1973 and 2010 and recorded by the Surveillance, Epidemiology, and End Results (SEER) program data, November 2012 submission. We found that the laterality ratio depends upon the country of birth, but not race of the patient. We identified five countries of birth that had p-values larger than 0.995, while we expected to see less than 1. Those born in Japan (l/r=1.14, p=0.997), the Ryuukyu Islands (l/r= 2.6, p=0.998), Laos (l/r=1.62, p=0.9999) and Algeria (l/r=2.1 p=0.9959) had significantly larger laterality ratios compared to the overall SEER population (l/r=1.04). Those born in Poland (l/r=0.92, p=0.997) had a laterality ratio significantly less than expected. The SEER data classified patients into 30 different race categories. We expect about six of these categories to exceed the two tailed 90% confidence interval based upon chance. We found seven, three of which had p-values exceeding 0.95, but none of which exceeded 0.99. This finding suggests no correlation exists between race and laterality. Next we sought to establish whether the difference in birthplace laterality ratios arose from (1) different distributions of the quadrant in which the tumor occurs or (2) a shift in the laterality ratio of each quadrant where the tumor occurs. First, we compared the distribution of quadrants in which a breast tumor occurs in those born in Poland with those born in Japan. We found that the relative distributions of tumor quadrants were identical. Next, we compared the laterality ratio by quadrant for the two populations. We found the only significant difference was in the laterality ratio of the upper outer quadrant. Thus, the birthplace effect appears to only occur in the upper outer quadrant of the breast. Finally, we found a small, but statistically significant, increase in the breast cancer laterality ratio with age, and decrease with birth year and year of diagnosis. Citation Format: Trevor Sughue, James P. Brody. Asymmetric laterality of breast tumors is correlated with place of birth, but not race. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 269. doi:10.1158/1538-7445.AM2014-269
Abstract 18978: Lysine Acetylation of Pyruvate Dehydrogenase Reduces Enzymatic Activity and Contributes to Impaired Substrate Metabolism in the Failing Myocardium
Authors: Xiaokan Zhang, Ruiping Ji, Xianghai Liao, Lily Y Deng, Estibaliz Castillero, Raymond Givens, Isaac George, P. Christian Schulze
Journal: Circulation (2014)

Introduction: Many heart failure (HF) associated non-histone proteins are modified by post-translational lysine acetylation which regulates protein activity and affects cardiac function. Hypothesis: We hypothesized that acetylation of mitochondrial proteins involved in cardiac metabolism mediate metabolic changes in the failing myocardium. We focused on pyruvate dehydrogenase (PDH) which converts pyruvate, the end-product of glycolysis, to acetyl-CoA, a substrate of the citric acid cycle. Methods: Human myocardial tissue from HF patients, failing rodent myocardium after transverse aortic constriction (TAC) induced pressure-overload HF and human cardiomyocyte-like AC16 cells were used. Western Blot, immunoprecipitation assays and mass spectrometry were performed to analyze protein expression and acetylation levels. Results: In our studies, we observed a significant increase in overall cardiac protein acetylation in both HF patients (5.8-fold, p&lt;0.05) and in TAC mice (1.8-fold) versus controls. Interestingly, these changes are correlated with a 72% decrease in mitochondrial deacetylase SirT3 expression. The sirtuin inhibitor nicotinamide (NAM) was used to induce mitochondrial protein acetylation. In AC16 cells, NAM treatment leads to a 1.4-fold increase in PDH acetylation level and a 26% decrease in PDH activity was observed (p&lt;0.01). Interestingly, immunoprecipitation assays showed that several PDH associated proteins are also acetylated in response to NAM treatment. Human proteomic mass spectrometry screening confirmed increased PDH acetylation in failing human myocardium compared to control samples. Furthermore, PDH expression is reduced by 47% in failing human myocardium compared to controls (p&lt;0.01). Finally, PDH activity was found to be decreased by 56% (p&lt;0.01) in human failing myocardium compared to controls. Conclusions: Together, our data suggest that increased acetylation of PDH due to reduced SirT3 expression in HF contributes to altered mitochondrial substrate metabolism and is associated with cardiac dysfunction. These findings suggest a novel role for acetylation of PDH in the failing myocardium.
Randomized, Double-Blind Trial of Triple Therapy With Saxagliptin Add-on to Dapagliflozin Plus Metformin in Patients With Type 2 Diabetes
Authors: Stephan Matthaei, Doina Catrinoiu, Aleksander Celiński, Ella Ekholm, William Cook, Boaz Hirshberg, Hungta Chen, Nayyar Iqbal, Lars Hansen
Journal: Diabetes Care (2015)

OBJECTIVE The objective of this study was to assess the efficacy and safety of triple therapy with saxagliptin add-on versus placebo add-on to dapagliflozin plus metformin in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients on stable metformin (≥1,500 mg/day) for ≥8 weeks with glycated hemoglobin (HbA1c) 8.0–11.5% (64–102 mmol/mol) at screening received open-label dapagliflozin (10 mg/day) plus metformin immediate release (IR) for 16 weeks. Patients with inadequate glycemic control (HbA1c 7–10.5% [53–91 mmol/mol]) were then randomized to receive placebo (n = 153) or saxagliptin 5 mg/day (n = 162) in addition to background dapagliflozin plus metformin IR. The primary efficacy end point was change in HbA1c from baseline to week 24. RESULTS There was a significantly greater reduction in HbA1c at 24 weeks with saxagliptin add-on (–0.51% [–5.6 mmol/mol]) versus placebo (–0.16% [–1.7 mmol/mol]) add-on to dapagliflozin plus metformin (difference, –0.35% [95% CI –0.52% to –0.18%] and –3.8 [–5.7 to –2.0 mmol/mol], respectively; P &amp;lt; 0.0001). Reductions in fasting plasma glucose and 2-h postprandial glucose were similar between treatment arms. A larger proportion of patients achieved HbA1c &amp;lt;7% (53 mmol/mol) with saxagliptin add-on (35.3%) versus placebo add-on (23.1%) to dapagliflozin plus metformin. Adverse events were similar between treatment groups. Episodes of hypoglycemia were infrequent in both treatment arms, and there were no episodes of major hypoglycemia. CONCLUSIONS Triple therapy with the addition of saxagliptin to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with type 2 diabetes inadequately controlled with dapagliflozin plus metformin.
extended treatment with an acid ceramidase inhibitor modulates the metabolism of ceramide and selects for a radiation-resistant population of human lymphoma cells
Authors: Kazuya Omoto, Michael Epperly, Oriana Hunter, Joel Greenberger, Andrew Amoscato
Journal: Cancer Research (2006)

4401  Sphingolipids and their metabolites participate in cellular signaling and proliferation, and modify several other cellular functions. Of these, ceramide has ability to coordinate a cell’s response to various forms of stress, including cell cycle arrest, cell senescence and apoptosis. In ceramide metabolism, ceramidases catalyze the breakdown of ceramide to sphingosine and the inhibition of ceramidase activity results in the intracellular accumulation of ceramide leading to apoptosis. Herein, we report that modulation of ceramide metabolism by extended treatment with a ceramidase inhibitor allows cells to acquire resistance to radiation-induced apoptosis in a radiosensitive human T cell lymphoma cell line. H9 cells, a human T cell lymphoma cell line, were cultured in medium with the acid ceramidase inhibitor N-oleoyl-ethanolamine (NOE), starting at a concentration level of 10 μM, with gradual increases to an NOE concentration of 100 μM. The cells were maintained in culture at a final NOE concentration of 100 μM. The period for treatment of NOE in medium was 2 days, every 2 weeks. For these experiments, H9 cells were cultured with NOE for more than 6 months. Both untreated and NOE-treated H9 (NOE-H9) cells were irradiated with doses of 0 to 8 Gy. Lipid analysis in these cells was investigated by mass spectrometry. Intracellular accumulation of ceramide was observed in untreated H9 cells after 48hr culture with 100 μM NOE, and greater than 50% of the cells died by apoptosis. Interestingly, there was no intracellular accumulation of ceramide in NOE-treated H9 cells, even after exposure to 100μM NOE. The viability of NOE-treated H9 cells at 48hr post-irradiation with a dose of 8 Gy was significantly higher than that in untreated H9 cells (74.0 ± 3.9% vs. 42.5 ± 1.1%, p=0.0002). Moreover, the intracellular accumulation of ceramide in NOE-H9 cells at 48hr after irradiation with a dose of 8 Gy was significantly less than that in untreated H9 cells (p=0.003). These results suggest that the absence of intracellular accumulation of ceramide following irradiation, through the modulation of ceramide metabolism using an acid ceramidase inhibitor for extended periods of time in culture, represents one potential mechanism for the development of radioresistance.
A member of Forkhead family transcription factor, FKHRL1, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction
Authors: Yoshifumi Kashii, Mie Uchida, Keita Kirito, Masaru Tanaka, Kousuke Nishijima, Masaki Toshima, Tomoko Ando, Kazuki Koizumi, Tomoyuki Endoh, Ken-ichi Sawada, Mariko Momoi, Yasusada Miura, Keiya Ozawa, Norio Komatsu
Journal: Blood (2000)
Abstract 38: HDL Cholesterol, Inflammation and Peripheral Arterial Disease in U.S. Adults
Authors: Lei Kuang, Nathan.D Wong
Journal: Circulation (2014)

Introduction: The protective relation of high density lipoprotein-cholesterol (HDL-C) with coronary heart disease may be weakened in the presence of inflammation; however, whether inflammation may attenuate any association of HDL-C with peripheral arterial disease (PAD) is unknown. Hypothesis: We hypothesized that inflammation measured by high-sensitivity C-reactive protein (hs-CRP) will attenuate any inverse association of HDL-C with PAD. Methods: We studied 6512 men and women aged ≥ 40 years who participated in the National Health and Nutrition Examination Survey (NHANES ) from 1999-2004 who had measures of ankle brachial index (positive for PAD defined as &lt;0.9 or ≥1.5), lipids, high-sensitivity CRP (hs-CRP) and other risk factors. Groups were categorized by low (&lt;40 mg/dL for men or &lt;50 mg/dl or women), intermediate (40 or 50-59 mg/dL), and high (≥60 mg/dL) HDL-C, and low (&lt;1 mg/L), normal (1-3), and high (3 mg/L) hs-CRP levels. We evaluated the odds ratio (ORs) for PAD by logistic regression adjusted for age, race, gender, low density lipoprotein-cholesterol, smoking, diabetes, body mass index, systolic blood pressure waist circumference and triglycerides. Results: Those with the highest hs-CRP levels had the highest prevalence of PAD (8.5-10.8%), regardless of level of HDL-C (figure 1). Using high HDL-C/low hs-CRP as the reference, the likelihood of PAD was significantly increased among those with normal and high hs-CRP within the intermediate HDL-C group: OR 4.7 (95%CI 1.6, 14.1) and OR 4.5 (95% CI 1.4,14.2) , respectively. Among those with normal and high hs-CRP within the low HDL-C group, the likelihood of PAD was also increased:OR 5.0 (95% CI 2.1,12,1) and OR 6.4 (95% CI 2.2,18.1), respectively. Conclusion: High hs-CRP is associated with higher likelihood of PAD across all ranges of HDL-C, but especially when HDL-C is normal or low. These results support the value of combined hs-CRP and HDL-C in risk stratification for PAD which should be validated by prospective studies.
Stroke and its Rehabilitation.
Authors: Sidney Herman Licht
Journal: Annals of Internal Medicine (1975)

This book, the 12th in the Physical Medicine Library series, is a collection of essays dealing with stroke from the physical medicine and rehabilitation viewpoint. Sixteen authors from the fields of physical medicine, neurology, neuropathology, nursing, and social work have contributed 18 chapters and an appendix on stroke. The basic points of the epidemiology, pathology, diagnosis, and acute care of strokes are reviewed in several chapters before the more chronic aspects of stroke care and rehabilitation are discussed. The avowed purpose of this volume is to provide a textbook and reference source on stroke for the resident in rehabilitation medicine; in my opinion, it falls short of its goal. The essays vary in their merit; several are balanced, well-referenced reviews of a topic. Others are personal and anecdotal with few, and in one case no, references. The editor appears to have exercised little control
Methodological Errors in Medical Research. An Incomplete Catalogue
Authors: Bjorn Andersen
Journal: Annals of Internal Medicine (1991)

The problem miscellaneous examples cohort or case-control design a priori hypotheses or fishing expeditions a question of control bias 1 bias 2 regression towards the mean before-after comparsions cross-sectional design diagnostic methods screening the sampling unit mathematical problems ordinal measurement scales variation SD or SE or ? basic biometry statistical problems quis custodiet postscript.
Expert group on meningitis is set up
Authors: Roger Dobson
Journal: BMJ (1999)

An expert group set up to investigate a meningitis outbreak in south Wales in which three people have died is about to meet for the first time. The full terms of reference for the group, to be chaired by Professor Ian Cameron, provost and vice chancellor of the University of Wales, were still being finalised this week.

It is understood that the team may look at possible ways to reduce public anxiety and to increase understanding of preventive measures. “The terms of reference will be very wide, and we will look at what happened …
Myocardial infarction in a patient with β‐thalassemia major: First report
Authors: Zvi G. Fridlender, Deborah Rund
Journal: American Journal of Hematology (2003)

Abstract Thalassemia is the most common hereditary anemia throughout the world. Survival in its most severe long‐term form, β‐thalassemia major, has significantly risen in the last decades. Cardiac morbidity—heart failure and dysrhythmias—is still the most common cause of mortality in these patients. We describe herein a case of myocardial infarction with normal coronary arteries in a 48‐year‐old patient with β‐thalassemia and no other recognized risk factors for coronary artery disease. Thromboembolic phenomena, a known situation in these patients, occur at a frequency of 4–5%. However, as far as we know, this is the first report in the literature of myocardial infarction in association with β‐thalassemia. With the notable improvement in the life expectancy of thalassemia patients, ischemic heart disease may become an important complication encountered in these patients. Am. J. Hematol. 75:52–55, 2004. © 2003 Wiley‐Liss, Inc.
Enhancing quality of care for acute myocardial infarction: shifting the focus of improvement from key indicators to process of care and tool use
Authors: Rajendra H Mehta, Cecelia K Montoye, Jessica Faul, Dorothy J Nagle, James Kure, Ethiraj Raj, Peter Fattal, Shiraz Sharrif, Mohamadali Amlani, Hameem U Changezi, Stephen Skorcz, Nancy Bailey, Theresa Bourque, Mary LaTarte, Donna McLean, Suzanne Savoy, Paul Werner, Patricia L Baker, Anthony DeFranco, Kim A Eagle
Journal: Journal of the American College of Cardiology (2004)

This project evaluated if by focusing on process changes and tool use rather than key indicator rates, the use of evidence-based therapies in patients with acute myocardial infarction (AMI) would increase. The use of tools designed to improve quality of care in the American College of Cardiology AMI Guidelines Applied in Practice Pilot Project resulted in improved adherence to evidence-based therapies for patients, but overall, tool use was modest. The current project, implemented in five hospitals, was modeled after the previous project, but with greater emphasis on tool use. This allowed early identification of barriers to tool use and strategies to overcome barriers. Main outcome measures were AMI quality indicators in pre-measurement (January 1, 2001 to June 30, 2001) and post-measurement (December 15, 2001 to March 31, 2002) samples. One or more tools were used in 93% of patients (standard orders = 82%, and discharge document = 47%). Tool use was associated with significantly higher adherence to most discharge quality indicator rates with increases in aspirin, angiotensin-converting enzyme inhibitors, and smoking cessation and dietary counseling. Patients undergoing coronary artery bypass grafting (CABG) had low rates of discharge indicators. Patients undergoing percutaneous coronary revascularization were more likely to receive evidence-based therapies. These data validate the results of the pilot project that quality of AMI care can be improved through the use of guideline-based tools. Identifying and overcoming barriers to tool use led to substantially higher rates of tool use. The low rates of adherence to quality indicators in patients undergoing CABG suggest that these patients should be particularly targeted for quality improvement efforts.
Abstract 17771: High-Response to Antiplatelet Therapy and the Increasing Risk of Bleeding
Authors: Kengo Tsukahara, Kazuo Kimura, Toshiaki Ebina, Masami Kosuge, Kiyoshi Hibi, Noriaki Iwahashi, Nobuhiko Maejima, Mitsuaki Endo, Satoshi Umemura
Journal: Circulation (2010)

Background: There are few reports demonstrating that high-response to antiplatelet therapy is associated with the increasing risk of bleeding in Caucasian patients receiving dual antiplatelet therapy. As it has been reported that Asian patients have higher bleeding risk, bleeding complication may frequently occur in Asian patients with high-response to antiplatelet therapy. Methods and results: Elective drug-eluting stent implantation was performed in 184 Japanese patients treated with aspirin and thienopyridine. The adenosine diphosphate-induced platelet aggregation was assessed with screen filtration pressure method before stenting. The upper quartile group of platelet inhibition was defined as high-responders. We evaluated the incidence of major bleeding according to REPLACE2 and TIMI definitions during an average of 15 months follow-up between high-responders and the remainder. There were no significant differences in baseline characteristics including duration of antiplatelet therapy among 2 groups. ...
Abstract 19792: Prediction of Right Ventricular Failure After Cardiac Transplantation : A Recipient Transcriptomic Study
Authors: Damien Guijarro, Jean-Pierre Gueffet, Marja Steenman, Jean-Christian Roussel, Jean-Noel Trochu, Guillaume Lamirault
Journal: Circulation (2014)

Introduction: Right ventricle failure (RVF) is a frequent and severe complication after cardiac transplantation. However, risk stratification for RVF is poorly achieved. Development of transcriptomic biomarkers for outcome prediction in cardio-vascular diseases is promising. Hypothesis: Our aim was to identify right ventricular gene expression signature associated to RVF and to define a transcriptomic biomarker that could predict post-transplantation RVF. Methods: Recipient RV myocardial samples of 44 patients transplanted from February 1998 to November 2002 in our center were collected. We retrospectively identified patients with (RVF group) and without (CTL group) post-transplantation RVF. A 4035-gene expression profile was obtained for all patients. Differentially expressed genes between RVF and CTL groups were identified and a molecular RVF predictor was used to determine for each patient a RVF prediction score (RVFs). Results: 9 (20%) and 18 (41%) patients were classified in RVF and CTL groups respectively. As compared to CTL group, RVF patients showed higher pre-operative bilirubin level and higher post-operative death rate. Molecular RVF predictor included 75 differentially expressed genes. Using this predictor, risk for post-transplantation RVF was 2.8-fold greater if RVFs was &gt;0.5 (CI 95%: 1.243-6.305). Sensitivity and specificity of RVFs were 0.778 and 0.889, respectively. Using receiver operating characteristic analysis, RVFs area under curve (AUC) was significantly greater than AUC of commonly used RVF predictors (pulmonary vascular resistance, trans-pulmonary gradient). Conclusions: Gene expression profiling of recipient right ventricle could be used to predict post-transplantation RVF. Transcriptomic biomarkers should be further investigated as a new tool for selection of cardiac transplant candidates.
Abstract 4353: microRNA-196b induces epithelial-to-mesenchymal transition through targeting HOXA9 in non-small cell lung cancer cells
Authors: Ji Woong Son, Seong-Lan Yu, Dong Chul Lee, Shin Yup Lee, Chang Gyo Park, Hoi Young Lee, Jaeku Kang
Journal: Cancer Research (2014)

Abstract MicroRNAs (miRNAs) play important roles as oncogenes or tumor suppressor through modulation of expression of target genes as posttranscriptional regulators. miR-196b has been previously reported dysregulation in multiple tumor types including gastric cancer, colorectal cancer, glioblastoma and breast cancer. However, there is unknown about the role of miR-196b in lung cancer. There has been reported reduction of invasiveness via Homeobox A9 (HOXA9) overexpression in non-small cell lung cancer (NSCLC) cells. We identified an inverse expression between miR-196b and HOXA9 in clinical samples compared to their corresponding normal counterparts. We demonstrated that HOXA9 expression was significantly regulated through alteration of miR-196b expression and miR-196b overexpression or knockdown of HOXA9 induced invasion in NSCLC cells. Moreover, the expression levels of matrix metalloproteinase (MMP) 9 and plasminogen activator, urokinase (uPA) associated with epithelial-mesenchymal transition (EMT) was induced by miR-196b overexpression or knockdown of HOXA9. In addition, the expression level of N-cadherin (Cdh2) was increased by upregulation of miR-196b and knockdown of HOXA9 decreased E-cadherin (Cdh1) expression. Therefore, our findings suggest that miR-196b may be potential therapeutic target in lung cancer. Citation Format: Ji Woong Son, Seong-Lan Yu, Dong Chul Lee, Shin Yup Lee, Chang Gyo Park, Hoi Young Lee, Jaeku Kang. microRNA-196b induces epithelial-to-mesenchymal transition through targeting HOXA9 in non-small cell lung cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4353. doi:10.1158/1538-7445.AM2014-4353