tbuckley/cabot-search huggingface dataset:
RhoE Fine-Tunes Inflammatory Response in Myocardial Infarction
Authors: Yuan Dai, Jiangping Song, Wenjiao Li, Tingli Yang, Xiaojing Yue, Xi Lin, Xiangsheng Yang, Weijia Luo, Junli Guo, Xin Wang, Songqing Lai, Kelsey C. Andrade, Jiang Chang
Journal: Circulation (2019)

Background: Inflammatory response after myocardial infarction (MI) is essential for cardiac healing, whereas excessive and prolonged inflammation extends the infarction and promotes adverse cardiac remodeling. Understanding the mechanistic insight of these tightly controlled inflammatory processes has a significant impact on post-MI recovery and therapy. Here, we uncover the critical role of small GTPase RhoE in post-MI recovery and its clinical implication. Methods: Three genetic mouse lines are used: global RhoE knockout, cardiomyocyte-specific RhoE heterozygous, and cardiomyocyte-specific RhoE overexpression mice. A set of molecular signaling experiments, including bimolecular fluorescence complementation, immunoprecipitation, electrophoretic mobility shift assay, and mRNA microarray analysis, were conducted. Permanent ligation of the left anterior descending artery was performed, followed by the assessments of cardiac function, inflammation, and survival in the first week after MI. Finally, we examined the correlation of the expression levels of RhoE in MI patient heart and patient prognosis. Results: RhoE deficiency turns on a group of proinflammatory gene expressions in mouse heart. Mice with cardiomyocyte-specific haploinsufficiency exhibit excessive inflammatory response with deleterious cardiac function after MI. A profound increase in nuclear factor-κB activity is detected in the mutant heart and the isolated cardiomyocytes. We further find that the expression of RhoE is upregulated in response to MI. Mechanistically, RhoE interacts with p65 and p50 individually in cytosol and blocks their nuclear translocation. RhoE also occupies the dimerization domain of p65 and subsequently disrupts the heterodimerization between p65 and p50. Cardiac RhoE overexpression inhibits nuclear factor-κB activity, restrains post-MI inflammation, and improves cardiac function and survival. Consistently, we find that the expression level of RhoE is elevated in the heart of patients with MI and that the patients with a higher expression level of RhoE exhibit a better prognosis in cardiac function recovery. Conclusions: The study uncovers RhoE as a new fine-tuning factor modulating MI-induced inflammation and promoting injured heart recovery. RhoE may serve as a new potential biomarker for the assessment of MI patient prognosis. Manipulation of RhoE could be as a potential therapeutic approach for MI and other inflammatory diseases.
Abstract 16106: Impact of Visit-to-Visit Systolic Blood Pressure Variability on Coronary Artery Atherosclerosis in Hypertensive Patients Without Known Coronary Artery Disiease
Authors: Kenichiro Otsuka, Shota Fukuda, Atsushi Tanaka, Koki Nakanishi, Haruyuki Taguchi, Kenei Shimada, Minoru Yoshiyama
Journal: Circulation (2014)

Introduction: Visit-to-visit variability in systolic blood pressure (SBP) has been reported as a risk of long-term cardiovascular events in hypertensive patients. However, a little has been known t...
Regulation of podosomes by acetyl-CoA carboxylase
Authors: Kristen Norman, Frances Wheeler, Darren Seals, Steven Kridel
Journal: Cancer Research (2008)

2898  Fatty acid synthesis is the process by which cells generate palmitate, a saturated 16 carbon fatty acid, from the carbohydrate derived precursors acetyl-CoA and malonyl-CoA. Apart from embryogenesis, fatty acid synthesis remains quiescent in normal tissue with the exception of liver and adipose. Conversely, tumor tissue relies on de novo fatty acid synthesis as its sole source of fatty acids, and is consequently upregulated in virtually all types of cancer. Because the fatty acid synthesis pathway is correlated with poor prognosis, aggressive disease, and metastasis, we hypothesize that this pathway is involved, at least in part, in the regulation of invasion and migration in tumor cells and in particular, in the regulation of podosomes, a dynamic membrane structure that is rich in F-actin and functions in adhesion and matrix degradation facilitating invasion and migration. NIH 3T3 fibroblasts transformed with c-src generate podosomes and, interestingly, also have increased levels of fatty acid synthesis compared to their non-transfected counterparts. Because of this, we reasoned that the fatty acid synthesis pathway may be involved in the formation of podosomes. Two nodes of the fatty acid synthesis pathway were targeted; the acetyl-CoA carboxylase (ACC) node and the fatty acid synthase (FASN) node. Pharmacologic inhibition of ACC (by 5-(tetradecyloxy)-2-furoic acid (TOFA)), but not FASN (by Cerulenin and C75) reduces podosome formation. This reduction also correlates with a decrease in cellular invasion and migration as well as a decrease in matrix metalloproteinases (MMP) 2 and 9 activities. Interestingly, treatment of transformed 3T3 cells with TOFA does not result in decreased clonogenic survival. Taken together, these data indicate a possible functional distinction between these two fatty acid synthesis enzymes and, more importantly, links the fatty acid synthesis pathway, at least in some part, to the regulation of podosomes and thus the process of invasion and migration.
Reconstruction of avian ancestral karyotypes reveals differences in the evolutionary history of macro- and microchromosomes
Authors: Joana Damas, Jaebum Kim, Marta Farré, Darren K Griffin, Denis M Larkin
Journal: Genome biology (2018)

Reconstruction of ancestral karyotypes is critical for our understanding of genome evolution, allowing for the identification of the gross changes that shaped extant genomes. The identification of such changes and their time of occurrence can shed light on the biology of each species, clade and their evolutionary history. However, this is impeded by both the fragmented nature of the majority of genome assemblies and the limitations of the available software to work with them. These limitations are particularly apparent in birds, with only 10 chromosome-level assemblies reported thus far. Algorithmic approaches applied to fragmented genome assemblies can nonetheless help define patterns of chromosomal change in defined taxonomic groups. Here, we make use of the DESCHRAMBLER algorithm to perform the first large-scale study of ancestral chromosome structure and evolution in birds. This algorithm allows us to reconstruct the overall genome structure of 14 key nodes of avian evolution from the Avian ancestor to the ancestor of the Estrildidae, Thraupidae and Fringillidae families. Analysis of these reconstructions provides important insights into the variability of rearrangement rates during avian evolution and allows the detection of patterns related to the chromosome distribution of evolutionary breakpoint regions. Moreover, the inclusion of microchromosomes in our reconstructions allows us to provide novel insights into the evolution of these avian chromosomes, specifically.
Phase I and pharmacokinetic study of weekly docetaxel (DOC) plus irinotecan (IRN) in patients with advanced solid tumors
Authors: Kenji Kawada, Yasutsuna Sasaki, Makoto Tahara, Kaori Matsuzawa, Hiromichi Ebi, Kuniaki Ito, Hironobu Minami
Journal: Cancer Research (2005)

3984  Both DOC and IRN are active as single agents against various solid tumors. As preclinical data indicated synergism between taxanes and topoisomerase I inhibitors, we conducted a phase I study of DOC plus IRN to determine the recommended dose (RD) and to investigate the effect of sequence of drug administration on pharmacokinetics and toxicities. Both drugs were infused over 1 hour with a 1-hour interval. Three weekly administrations were repeated with a 1-week rest. First, two doses of DOC (30 or 35 mg/m2) followed by IRN at 50 mg/m2 were tested. Second, to investigate the effect of the sequence of drug administration on toxicities and pharmacokinetics, 8 patients were randomized to this or the reverse sequence for the first cycle at 30 mg/m2 of DOC (optimal in the 1st step) and 50 mg/m2 of IRN. The sequence was reversed for the second cycle. Because toxicities in the sequence of IRN/DOC seemed milder than for DOC/IRN, further dose escalations were performed for the former to determine the RD in the 3rd step. In total, 31 patients (21 men) with a median age of 58, range 32-72, were entered into this study. Two patients failed to complete the 1st cycle for reasons unrelated to dose-dependent drug toxicities (allergic reaction to DOC and consent withdrawal) and were excluded from the analysis. In the 1st step, dose-limiting toxicities (DLTs) were observed in 1 of 6 and 3 of 6 patients treated at 30/50 and 35/50 (DOC/IRN) mg/m2, respectively. Therefore, 30 mg/m2 DOC was used in the 2nd step, in which the sequence of drug administration was randomized in 8 patients. One patient on DOC/IRN experienced DLT. Thus, 2 of 10 patients suffered DLTs in the DOC/IRN sequence at this dose level, while no DLTs were observed for IRN/DOC. In the 3rd step, dose escalations were performed in the IRN/DOC sequence, and 1 of 5 and 3 of 4 patients experienced DLTs at 50 and 60 mg/m2 of IRN, respectively, in combination with 35 mg/m2 of DOC. The dose intensity of DOC (21 mg/m2/week) and IRN (30 mg/m2/week) for IRN 50 mg/m2 followed by DOC 35 mg/m2 was not increased compared with IRN 50 mg/m2 and DOC 30 mg/m2. DLTs observed in the first cycle included grade 4 neutropenia for 5 days or longer (3 patients), dose omission on day 8 because of grade 2 diarrhea (2 patients), grade 3 hyponatremia, and neutropenic fever (1 patient). Response was evaluated (n=26), with PRs in 6 patients (3 head and neck, 1 each NSCLC, ovarian and endometrial cancer). Pharmacokinetics of DOC and IRN were not changed when the sequence of administration was reversed in the 8 randomized patients. Based on these results, DOC 30 mg/m2 and IRN 50 mg/m2 are recommended for both sequences. Considering that synergistic in vitro anti-tumor activity was observed for DOC followed by IRN, DOC 30 mg/m2 followed by IRN 50 mg/m2 is recommended for further investigation.
Electroencephalographic Biomarkers for Treatment Response Prediction in Major Depressive Illness: A Meta-Analysis
Authors: Alik S. Widge, M. Taha Bilge, Rebecca Montana, Weilynn Chang, Carolyn I. Rodriguez, Thilo Deckersbach, Linda L. Carpenter, Ned H. Kalin, Charles B. Nemeroff
Journal: American Journal of Psychiatry (2018)

Reducing unsuccessful treatment trials could improve depression treatment. Quantitative EEG (QEEG) may predict treatment response and is being commercially marketed for this purpose. The authors sought to quantify the reliability of QEEG for response prediction in depressive illness and to identify methodological limitations of the available evidence.
Home Monitoring for Fetal Heart Rhythm During Anti-Ro Pregnancies
Authors: Bettina F. Cuneo, Sven-Erik Sonesson, Stephanie Levasseur, Anita J. Moon-Grady, Anita Krishnan, Mary T. Donofrio, Marie-Josee Raboisson, Lisa K. Hornberger, Peter Van Eerden, Elena Sinkovskaya, Alfred Abuhamad, Bhawna Arya, Anita Szwast, Helena Gardiner, Katherine Jacobs, Grace Freire, Lisa Howley, Aimee Lam, Alexander M. Kaizer, D. Woodrow Benson, Edgar Jaeggi
Journal: Journal of the American College of Cardiology (2018)
Pretreatment Primary Tumor and Nodal SUVmax Values on 18F-FDG PET/CT Images Predict Prognosis in Patients With Salivary Gland Carcinoma
Authors: Cheng-En Hsieh, Nai-Ming Cheng, Wen-Chi Chou, Bhanu Prasad Venkatesulu, Yung-Chih Chou, Chun-Ta Liao, Tzu-Chen Yen, Chien-Yu Lin
Journal: Clinical Nuclear Medicine (2018)

To assess whether primary tumor and nodal F-FDG uptake may predict prognosis in patients with salivary gland carcinoma.We conducted a 2-center, retrospective study on 117 patients with salivary gland carcinoma who underwent F-FDG PET/CT before treatment and were subsequently treated with curative intent between 2004 and 2014. Pretreatment SUVmax of the primary tumor (SUVmax-T) and that of positive nodes (SUVmax-N) were analyzed in relation to clinical outcomes.Patients were followed up for a median of 61 months. The following 5-year rates were observed: locoregional control (LRC), 78%; distant metastasis-free survival (DMFS), 67%; progression-free survival (PFS), 62%; and overall survival (OS), 68%. A cutoff value of 7.0 maximized the prognostic impact of both SUVmax-T and SUVmax-N for PFS. Compared with patients with SUVmax-T and SUVmax-N values below the optimal cutoff, those with SUVmax-T and SUVmax-N of 7 or greater showed less favorable 5-year LRC (P < 0.001 and P < 0.001), DMFS (P < 0.001 and P < 0.001), PFS (P < 0.001 and P < 0.001), and OS (P < 0.001 and P < 0.001) rates. Both SUVmax-T of 7 or greater and SUVmax-N of 7 or greater were identified as independent predictors of LRC (P = 0.010 and 0.022), DMFS (P = 0.001 and P = 0.001), PFS (P < 0.001 and P = 0.007), and OS (P = 0.007 and P = 0.002) in multivariable analysis. We therefore devised a prognostic scoring system based on these 2 variables, which was found to be strongly associated with 5-year LRC (P < 0.001), DMFS (P < 0.001), PFS (P < 0.001), and OS (P < 0.001) rates.SUVmax of the primary tumor and SUVmax-N on pretreatment F-FDG PET/CT images may be a useful guide in predicting treatment outcomes, especially when combined in a prognostic scoring system.
Investigation of the endocrine and haemodynamic changes in resistant hypertension, and its response to spironolactone or amiloride: the PATHWAY-2 mechanisms study
Authors: Bryan Williams, Thomas M MacDonald, Steve V. Morant, David J Webb, Peter Sever, Gordon T. McInnes, Ian Ford, J Kennedy Cruickshank, Mark J Caulfield, Sandosh Padmanabhan, Isla S Mackenzie, Jackie Salsbury, Morris J. Brown
Journal: The Lancet Diabetes & Endocrinology (2018)
A nurse led clinic improves care for patients with Glioblastoma and tumour treating fields
Authors: Antonia Thorpe, Mr Andrew R Brodbelt, Ms Anna Crofton
Journal: Neuro-Oncology (2018)

Poor prognosis and limited access to clinical trials can result in a poor hospital experience for patients diagnosed with Glioblastoma. The role of the clinical nurse specialist (CNS) is pivotal to improving patient experience. TTF (Tumour treating fields) is a novel, non-invasive technique using electrical fields to disrupt cell division, and requires monthly review. Utilisation of a nurse led clinic co-ordinating the TTF patient pathway was examined. All patients in the North West of England on TTF required monthly compliance data collection and assessment by an Optune team member, and three monthly clinical and radiological review as well as ongoing oncological review. A nurse led clinic for patients meeting the criteria for the study was developed, providing co-ordination, holistic needs assessment, support, advice and signposting for patients and carers. Data collection includes EORTC quality of life measures, patient and carer satisfaction surveys and device compliance data. 4 patients have been having treatment for up to 8 months. Clinical visits occur monthly, with imaging and clinical review when required, occurring at the same time as Optune team member review. Device compliance is >80%. There has been a 0% DNA rate, and patients report a positive experience in the clinic setting. The clinic has allowed a buddy system to be developed for patients and carers. Novo TTF remains prohibitively expensive and is a labour intensive device for both patient and healthcare professional. Using a nurse led clinic for clinical review and to coordinate appointments and investigations has reduced patient outpatient attendance, and improved patient experience. Further reduction in cost may be possible by compliance data being collected by the specialist nurse obviating the need for direct on site company support.
Epidemiology and risk factors of asthma-chronic obstructive pulmonary disease overlap in low- and middle-income countries
Authors: Brooks W. Morgan, Matthew R. Grigsby, Trishul Siddharthan, Muhammad Chowdhury, Adolfo Rubinstein, Laura Gutierrez, Vilma Irazola, J. Jaime Miranda, Antonio Bernabe-Ortiz, Dewan Alam, Robert A. Wise, William Checkley
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 18181: Left Ventricular Myocardial Mechanics at Rest and During Exercise in Children After Arterial Switch Operation
Authors: Barbara Cifra, Andreea Dragulescu, Heynric Grotenhuis, Cedric Manlhiot, Mark K Friedberg, Luc Mertens
Journal: Circulation (2015)

Introduction: Arterial switch operation (ASO) is the standard surgical procedure for transposition of the great arteries allowing a complete anatomical and physiological repair. In these patients the functional impact of myocardial perfusion on global and regional myocardial function has not been investigated. Stress echocardiography with visual myocardial assessment has been used to detect regional myocardial dysfunction. Studying LV mechanics using speckle-tracking echocardiography during exercise could provide more quantitative information. The aim of the study was to study the myocardial response to exercise in children after ASO using semi-supine cycle ergometry stress echocardiography (SSCE). Materials and Methods: Forty children after ASO and 29 age and gender matched controls were included. Median age was 14 years. A stepwise SSCE protocol was used. LV global longitudinal strain and circumferential strain was measured in all subjects at rest and at incremental heart rate. Results: Resting HR was similar between groups, peak HR was lower in the ASO group compared with controls (142 ±11 vs 157±14 bpm, p=0.0007). LV global longitudinal strain was lower at rest (19±2.3% vs. 21±2.5%, p=0.004) but not at peak exercise (22.7±5.6 % vs. 24±4.5 % p=0.2) in the ASO group compared to controls. No significant difference was found in LV global circumferential strain at rest (23.7±2.3% vs. 24±3.2 %, p=0.6) and peak exercise (28±2.6% vs. 27.9±4.1 %, p=0.9). Also when plotted versus heart rates the increase in longitudinal and circumferential strain values were not significantly different. Conclusions: These data show that circumferential and longitudinal myocardial deformation during exercise is preserved in children after ASO compared to controls. Earlier data obtained using Tissue Doppler in the same study cohort, showed a normal increase in systolic tissue Doppler velocities. These data suggest a preserved LV reserve during exercise in this patient cohort.
Abstract 12756: Mc4r Genotype and 2-Year Change in Appetite in Response to Weight-loss Diets: The Pounds Lost Trial
Authors: Tao Huang, Yiru Shen, Yan Zheng, Yanping Li, George A Bray, Donald A Williamson, Frank M Sacks, Lu Qi
Journal: Circulation (2014)

Hypothesis:  Obesity associated melanocortin 4 receptor gene (MC4R) plays a pivotal role in the regulation of appetite, eating behavior and energy expenditure, as well as body weight. We examined whether GWAS-identified, obesity related MC4R genotype modified the long-term changes in appetite, food craving and hunger in response to weight loss diet interventions in a randomized controlled trial.   Methods:  We genotyped MC4R rs7227255 in 737 overweight adults in the 2-year Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) trial and assessed four appetite related traits including cravings, fullness, hunger, and prospective consumption.   Results:  We found that dietary protein significantly modified genetic effects on changes in appetite, food cravings, and hunger at 24 m after adjustment for age, sex, ethnicity, baseline body mass index, weight change, baseline value for perspective phenotype (P for interaction=0.02, 0.008, and 0.03). The A allele was associated with a greater increase in appetite (β=0.10, P=0.05) and food cravings (β =0.13, P=0.008) among the participants with high protein diet intake. MC4R rs7227255 did not modify effects of fat and carbohydrate intakes on the appetite measures.   Conclusions:  Our data suggest that individuals with the MC4R rs7227255 A allele might obtain more increases in appetite and food cravings by choosing a higher protein weight-loss diet.
Abstract 20230: Prognostic Value of Low Spot Urine Creatinine is Independent of Lean Body Mass in Patients With Heart Failure
Authors: Piotr Rozentryt, Jacek T Niedziela, Jolanta U Nowak, Bartosz Hudzik, Przemyslaw Leszek, Tomasz Rywik, Ewa A Jankowska, Wolfram Doehner, Stephan von Haehling, Stefan D Anker, Mariusz Gasior
Journal: Circulation (2017)

Introduction: Low urinary excretion of creatinine in heart failure (HF) reflects reduction of muscle mass and worsens prognosis. Spot urinary creatinine (SUCR) has been suggested as a useful prognostic factor. This more practical approach was not tested in unselected HF population. The prognostic role of SUCR was also not adjusted for differences in body composition. Hypothesis: Low SUCR in unselected HF patients is linked to worse outcome after accounting for body composition. Methods: In 719 HF patients (age: 52±10 years, female: 14%, NYHA: 2.9±0.9, LVEF: 25±11%), morning SUCR along with whole body dual-energy X-ray absorptiometry (DEXA) scanning were performed. Patients were divided according to cut-point of 13.1 g/L of SUCR identified on ROC curve for 3-year all-cause mortality. Optimal treatment was applied to all, and patients had no volume overload. Beyond Kaplan-Meier curves, we used Cox method to estimate relative risk of death for low as compared to high SUCR, after adjusting for total fat mass,...
“Fit notes” could become part of GP training, says deputy chief medical officer
Authors: Abi Rimmer
Journal: BMJ (2018)

Modules on understanding “fit notes” may be incorporated into undergraduate and postgraduate GP training, the deputy chief medical officer for England has said.

The fit note, which replaced the “sick note” in 2010, enables GPs to include advice on how a person “may be fit” to work with reasonable workplace adjustments.1

Speaking at the Royal College of General Practitioners annual conference, Gina Radford said, “We are looking to build more training, knowledge, and awareness …
Creating the dream team: introducing participatory sports and exercise medicine via ‘Patient Voices’
Authors: Osman Hassan Ahmed, Jermain Defoe, Liam Richard West, Tracy Blake
Journal: British Journal of Sports Medicine (2018)

There is an accelerating movement calling for decision-making processes that centre the patient as the key driver of their own healthcare process. This concept of ‘Participatory Medicine’ is a world far removed from conventional, patriarchal or top-down healthcare approaches where the clinician ‘expert’ drove all decision-making processes, and the patient was merely a passive passenger along the journey. Organisations such as the Society for Participatory Medicine1 have empowered patients and helped change the archaic healthcare dynamic. Active patient engagement and participation is also growing steadily in research.

Patient and public involvement (PPI) is a pathway to improve the quality and the translation of research; patients participate as collaborators on research grants and authors on research outputs.2 Patients have also been embedded in research conferences, including Stanford University’s ‘Medicine X’ series of conferences where the patient is placed ‘at the centre of the academic medicine’.3 By actively contributing in these ways, patients are able to help clinicians and researchers understand the problems …
Nonmalignant and malignant meningioma incidence and survival in the elderly, 2005–2015, using the Central Brain Tumor Registry of the United States
Authors: Rebecca L Achey, Haley Gittleman, Julia Schroer, Vishesh Khanna, Carol Kruchko, Jill S Barnholtz-Sloan
Journal: Neuro-Oncology (2018)

Meningioma incidence increases significantly with age. In the expanding elderly population, we lack complete understanding of population-based trends in meningioma incidence/survival. We provide an updated, comprehensive analysis of meningioma incidence and survival for individuals aged over 65.