tbuckley/cabot-search huggingface dataset:
Abstract P192: Improving LDL Documentation and Control in Coronary Artery Disease Patients
Authors: Mazen Omar, Abimbola Shofu, Bassam A Omar, Christopher Malozzi, G. Mustafa Awan
Journal: Circulation (2018)

Background: Obtaining a fasting lipid profile prior to a scheduled clinic visit can facilitate decision making at the time of the visit. However, this places extra burden on patients and can decrease compliance. Purpose: To assess the frequency of lipid measurement in patients asked to have blood draw a week before clinic visit versus on the same day of clinic visit, and assess how this will affect achieving lipid targets. Methods: A University-based cardiology clinic notes were examined. Patients were scheduled for a fasting lipid profile a week prior to the clinic visit in year 1. Poor compliance was noted and prompted a same day as clinic visit measurement of lipids if a patient could not comply with laboratory appointment (fasting or non-fasting) in year 2, with further lipid management conducted by phone. Patients with documented coronary artery disease were included. A total of 200 encounters (100 in each year) were analyzed. Results: Only 64 (64%) of patients in year 1 had lipid measurements, compared to 84 (84%) of patients in year 2. LDL level in year 1 was 116 ± 36 mg/dL compared with 97 ± 32 mg/dL in year 2 (P &lt; 0.01). Only 34% (22/64) of the patients in year 1 achieved LDL of &lt; 100 mg/dL, compared with 56% (47/84) in year 2. No differences were observed in HDL, triglycerides or blood pressures during the concurrent visits. Conclusion: Improving documentation and control of LDL is achievable if lipid levels are done on clinic visit day, with less burden on patients who cannot comply with a separate laboratory appointment. Although there were many non-fasting levels as a result, the triglyceride levels where not significantly different among the two groups, probably reflecting an overall more intensive lipid management in year 2. Therefore, as has been shown by others, a lipid profile in most cases does not necessarily have to be fasting, especially in patients being treated for stricter targets such as our cohort, which may decrease the burden on patients unable to comply with a fasting state or added clinic visits.
Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08)
Authors: T. Ruhstaller, P. Thuss-Patience, S. Hayoz, S. Schacher, J.R. Knorrenschild, A. Schnider, L. Plasswilm, W. Budach, W. Eisterer, H. Hawle, C. Mariette, V. Hess, W. Mingrone, M. Montemurro, M. Girschikofsky, S.C. Schmidt, M. Bitzer, L. Bedenne, P. Brauchli, M. Stahl
Journal: Annals of Oncology (2018)

BackgroundThis open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma.Patients and methodsPatients were randomly assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS).ResultsIn total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5–2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58–1.07; P = 0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2–4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52–1.01; P = 0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31–0.90; P = 0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64–1.59, P = 0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings.ConclusionAdding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma.Clinical trial informationNCT01107639
Everolimus and transarterial embolization (TAE) for hepatic metastasis in neuroendocrine tumors (NET).
Authors: Aman Chauhan, Gray Magee, Millicent Horn, Riham Khouli, Heidi Weiss, Steven J Krohmer, Lowell Brian Anthony
Journal: Journal of Clinical Oncology (2018)

485 Background: TAE of hepatic metastases is effective loco-regional therapy for neuroendocrine tumor (NET) patients. Transarterial chemotherapy (TACE) and transarterial radiotherapy (TARE) are other options in controlling hepatic metastases but deliver cytotoxic agents only at the time of the procedure. Systemic therapies such as everolimus or sunitinib are often held 2-4 weeks prior to and after the procedure. We hypothesize that concurrent oral treatment with everolimus and transarterial hepatic embolization is safe. Methods: Medical records of all NET patients (pts) treated at the Markey Cancer Center between July 2016 to July 2017 with concurrent transarterial embolization and everolimus were reviewed. Results: Total number of pts eligible for analysis was 15. Mean age of study cohort was 57.5 years (31-77). Seven pts were small bowel, 4 were pancreatic and remaining 4 were unknown NET primaries. Nine patients had grade 1 (Ki 67 &lt; 2%) and 6 patients had grade 2 NETs (Ki-67 between 2-20%). Mean duration of treatment with everolimus prior to embolization was 3.8 months and mean dose was 10 mg orally every other day. Mean days of hospitalization were 1.46. Eleven (73%) pts were discharged the day after procedure. Ten (67%) pts reported nausea, 9 (60%) reported abdominal pain, 5 (30%) reported emesis. One patient had hematemesis immediately post procedure. Thirteen (87%) pts had no significant change in hemoglobin pre and post procedure (within one numerical point). No patient developed infectious complications. Conclusions: Combining everolimus with TAE is safe and does not result in longer hospitalizations or toxicities greater than that expected from TAE alone.
Vicarious breathlessness: an inferential perceptual learned transposition process that may not be inconsequential to either patient or caregiver
Authors: Miriam J. Johnson, David Gozal
Journal: European Respiratory Journal (2018)

People with common chronic cardiorespiratory conditions can live with chronic breathlessness for years [1]. Disabling chronic breathlessness, persisting despite optimum treatment of the underlying cause [2], is experienced by almost all patients with advanced lung disease, such as chronic obstructive pulmonary disease (COPD) [3], and carries a significant emotional, social, health and economic load. Intimately related to physical activity, chronic breathlessness reduces the ability to carry out activities of daily living [4] and restricts the role in the family, workplace or wider society [5]. These consequences, with additional frightening severe episodes of breathless crises, lead not only to acute emotional responses that not only widely activate a multitude of brain regions [6], but also promote the insidious development of depression, anxiety and panic, and a reduction in physical and mental quality of life proportionate with the severity of breathlessness [7]. Education and training for caregivers of breathless patients is crucially important <http://ow.ly/U52C30iTCpW>
Assessing Pharmaceutical Research and Development Costs
Authors: Toon van der Gronde, Toine Pieters
Journal: JAMA Internal Medicine (2018)

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Abstract 15279: The Response to Valsalva Maneuver Predicts Left Ventricular Filling Pressures in Patients With Heart Failure, Pulmonary Hypertension, and Cardiac Transplant Recipients
Authors: Jagdesh Kandala, Franz Rischard, Mark J Friedman, Frank I Marcus
Journal: Circulation (2016)

Introduction: The blood pressure response to Valsalva maneuver (VM) can reliably assess volume status and filling pressures (FPs) in heart failure patients with reduced ejection fraction (HFrEF). H...
Control of chaos and memory dynamics
Authors: Richard A. Heath
Journal: Behavioral and Brain Sciences (2001)

Neurally inspired models of human cognition exude explanatory power without necessarily making predictions that can be verified behaviorally. This is the case for Tsuda's dynamic model. It is suggested that a simpler principle based on the nonlinear dynamic interaction between modules based on control of chaos, can achieve a similar theoretical goal in a cognitively verifiable way.
William Ronald Murdoch
Authors: Carol Murdoch
Journal: BMJ (2018)

The formative years of William Ronald Murdoch (“Ronald”) were shaped by the second world war. As a child of 12, he saw first hand the devastation of the Clydebank blitz, when on the following morning he and his uncle searched for his father, an engineer with the Singer Corporation. It was an experience he never forgot, and, having been inspired by a local general practitioner, he was driven to study medicine at Glasgow University.

After his residencies he served in the Royal Army Medical Corps in Port Said, in the Middle East, and on return from national service he embarked on his training in medicine. During his senior registrar time at Dumfries Royal Infirmary, he met his wife …
The role of transcriptional factor D-site-binding protein in circadian CCL2 gene expression in anti-Thy1 nephritis
Authors: Yang Lu, Yan Mei, Lei Chen, Lingling Wu, Xu Wang, Yingjie Zhang, Bo Fu, Xizhao Chen, Yuansheng Xie, Guangyan Cai, Xueyuan Bai, Qinggang Li, Xiangmei Chen
Journal: Cellular and Molecular Immunology (2018)
Abstract P171: The “Hub and Spoke” Model of Heart Function Care Achieves Quality Index Markers
Authors: Stephanie Hinton, Karen Geukers, George Heckman, Neville Suskin, Tim Hartley, Karen Harkness, Eva Lonn, Robert McKelvie
Journal: Circulation (2018)

Introduction: Heart failure (HF) affects approximately 2% of the population with major effects on morbidity and mortality. Over 80% of existing Heart Function Clinics (HFC) are located within a hospital setting. The CoHealth (Ontario) “hub-and-spoke” model encourages community-based HFCs for patients who are less complex or relatively stable while more complex/unstable patients receive care in a hospital-based HFC. The purpose of this project was to explore patient populations and achievement of established quality indicators (QIs) within a specialist-supported community-based HFC in a Family Health Team (FHT-HFC) and a HFC in a tertiary hospital (H-HFC) over 12 months. Methods: Retrospective standardized chart reviews were conducted from all 60 patients enrolled in the FHT-HFC since its inception in 2010 to 2015, and 100 patients followed in the H-HFC in 2013. QIs were measured and compared at enrollment, 6 months and 12 months. Results: Patients attending the H-HFC vs FHT-HFC had no difference in age, sex or etiology of HF. However, patients at the H-HFC were significantly more likely to have reduced LV function, have marked HF symptoms, and more likely to have a recent hospital admission. Both cohorts had multiple comorbidities, with greater frequencies of MI, ICD/CRT/pacemaker, smoking and respiratory disease in the H-HFC group. By 6 months’ post enrollment, the number of patients with a HF with a reduced ejection fraction (HFrEF) in the H-HFC (n=65) who were on an ACEi/ARB, beta-blocker, and MRA increased from 75% to 82%, 86% to 88%, and 29% to 34% (vs 99% to 99%, 77% to 89% and 33% to 39%, respectively in the FHT-HFC (n=28)). Over the 12 months following enrollment in a HFC the proportion of patients with NYHA class III symptoms decreased from 67% to 38% (H-HFC) vs 47% to 14% (FHT-HFC) (p &lt; 0.05) and HF hospital admissions were reduced by 31% (H-HFC) vs 68% (FHT-HFC) (p &lt; 0.05). At 12 months 34% (H-HFC) vs 20% (FHT-HFC) (p=0.07) of patients were enrolled in a cardiac rehabilitation program. Conclusion: While the H-HFC and FHT-HFC patients had similar demographics and comorbidities, H-HFC patients tended to more frequently have HFrEF, were more symptomatic and more likely to have been recently hospitalized. Participation in either the H-HFC or FHT-HFC was associated with medication optimization, decreased symptoms and fewer hospitalizations compared to the previous year. In conclusion, this retrospective study shows that the “hub and spoke” HFC model may have merit but needs further evaluation on a wider, more formal scale.
Bile acid oxidation by<i>Eggerthella lenta</i>strains C592 and DSM 2243<sup>T</sup>
Authors: Spencer C. Harris, Saravanan Devendran, Celia Méndez- García, Sean M. Mythen, Chris L. Wright, Christopher J. Fields, Alvaro G. Hernandez, Isaac Cann, Phillip B. Hylemon, Jason M. Ridlon
Journal: Gut Microbes (2018)

Strains of Eggerthella lenta are capable of oxidation-reduction reactions capable of oxidizing and epimerizing bile acid hydroxyl groups. Several genes encoding these enzymes, known as hydroxysteroid dehydrogenases (HSDH) have yet to be identified. It is also uncertain whether the products of E. lenta bile acid metabolism are further metabolized by other members of the gut microbiota. We characterized a novel human fecal isolate identified as E. lenta strain C592. The complete genome of E. lenta strain C592 was sequenced and comparative genomics with the type strain (DSM 2243) revealed high conservation, but some notable differences. E. lenta strain C592 falls into group III, possessing 3α, 3β, 7α, and 12α-hydroxysteroid dehydrogenase (HSDH) activity, as determined by mass spectrometry of thin layer chromatography (TLC) separated metabolites of primary and secondary bile acids. Incubation of E. lenta oxo-bile acid and iso-bile acid metabolites with whole-cells of the high-activity bile acid 7α-dehydroxylating bacterium, Clostridium scindens VPI 12708, resulted in minimal conversion of oxo-derivatives to lithocholic acid (LCA). Further, Iso-chenodeoxycholic acid (iso-CDCA; 3β,7α-dihydroxy-5β-cholan-24-oic acid) was not metabolized by C. scindens. We then located a gene encoding a novel 12α-HSDH in E. lenta DSM 2243, also encoded by strain C592, and the recombinant purified enzyme was characterized and substrate-specificity determined. Genomic analysis revealed genes encoding an Rnf complex (rnfABCDEG), an energy conserving hydrogenase (echABCDEF) complex, as well as what appears to be a complete Wood-Ljungdahl pathway. Our prediction that by changing the gas atmosphere from nitrogen to hydrogen, bile acid oxidation would be inhibited, was confirmed. These results suggest that E. lenta is an important bile acid metabolizing gut microbe and that the gas atmosphere may be an important and overlooked regulator of bile acid metabolism in the gut.
Publisher Correction: Dysregulation of the epigenetic landscape of normal aging in Alzheimer’s disease
Authors: Raffaella Nativio, Greg Donahue, Amit Berson, Yemin Lan, Alexandre Amlie-Wolf, Ferit Tuzer, Jon B. Toledo, Sager J. Gosai, Brian D. Gregory, Claudio Torres, John Q. Trojanowski, Li-San Wang, F. Brad Johnson, Nancy M. Bonini, Shelley L. Berger
Journal: Nature Neuroscience (2018)
Abstract P001: LGB Health Disparities: Examining the Status of Ideal Cardiovascular Health From the 2011-2012 NHANES Survey
Authors: Anshul Saxena, Muni Rubens, Sankalp Das, Tanuja Rajan, Gowtham Grandhi, Lara Arias, Khurram Nasir, Emir Veledar
Journal: Circulation (2018)

Objectives: Extensive data suggests that lesbian, gay and bisexual (LGB) adults are more likely to experience adverse cardiovascular outcomes relative to heterosexuals. However, evidence regarding cardiovascular health (CVH) disparities and sexual orientation is scarce. The aim of this study was to examine the distribution of CVH metrics in a US nationally representative population of heterosexual (HT), and LGB adults. Methods: This cross-sectional study analyzed 2445 participants (representing 115 million) adults aged 18 or over years in the 2011-2012 NHANES survey. The CVH factors of smoking, body mass index (BMI), physical activity (PA), diet, blood pressure (BP), total cholesterol (TC) and glucose (GLU) were measured. Each CVH factor was then classified as ideal; intermediate; or poor. Ideal CVH was defined as presence of &gt;=5 ideal CVH metrics. Results: 95.1% of the weighted sample self-identified as HT (95% CI: 93.5%, 96.6%) compared to 4.9% (95%: 3.3%, 6.5%) LGB. The figure illustrates the distribution of each of the 7 CVH categories according to sexual orientation. In age, gender, and race adjusted analysis, LGB individuals were 36% (AOR: 0.64; 95%: 0.29, 1.4; p &gt; 0.05) less likely to have ideal CVH compared to HT. These proportions go higher after adjusting for age. Conclusions: The results suggest that LGB individuals face a higher risk of being in the category for poor cardiovascular health compared to heterosexuals. Evidence suggests that there are sexual orientation disparities among adults. If confirmed in other studies, results point towards disproportionately higher risk for cardiovascular disease among sexual-minority populations. Figure
Agency enhancement and social psychology
Authors: Matthew Taylor
Journal: Behavioral and Brain Sciences (2018)

This commentary has two aims. First, I raise a practical challenge for accounts of responsible agency: Provide empirically informed strategies for enhancing responsible agency so that actors can become more resistant to the influence of defeaters. Second, I offer an initial sketch of a solution to this practical challenge. My solution is supported by empirical evidence suggesting that responsible agency can be enhanced via self-regulatory strategies (expertise and implementation intentions).
Abstract 15120: Heart Failure Triggers Mitochondrial Dysfunction and ER Stress in Pancreatic Beta Cells
Authors: Jessica Gambardella, Maria J Sanchez Quintero, Alain Lacampagne, Michio Hirano, Guido Iaccarino, Andrew Marks, Gaetano Santulli
Journal: Circulation (2016)

Introduction:  Diabetes and cardiovascular disease are important health concerns in United States and worldwide. However, while the increased risk of cardiovascular disease and  heart failure (HF)  in diabetic patients has been established, the reciprocal relationship,  i.e.  the augmented risk of glucose intolerance and  type 2 diabetes mellitus (TD2M)  in patients with cardiovascular disorders, has been evidenced in the clinical scenario but the underlying mechanisms remain essentially unclear.   Hypothesis:  HF causes pancreatic beta cell dysfunction via endoplasmic reticulum (ER) stress and impairment of mitochondrial dynamics.   Methods/Results:  In this study we focused on the beta cell function in a murine model of post-ischemic HF, obtained via ligation of the coronary artery. The HF group exhibited glucose intolerance and impaired glucose-stimulated insulin release, with no major differences in islet architecture when comparing HF and SHAM. Islets isolated from HF mice displayed upregulation of common markers of ER stress, including BiP and spliced XBP. Ultrastructural analysis revealed significant mitochondrial dysmorphology (fragmented cristae, swelling, and outer membrane disruption) in HF beta cells. We also found significantly altered mitochondrial dynamics in  ex vivo  experiments in HF  vs  SHAM, including reduced glucose-stimulated and glutamine/leucine-stimulated ATP production, impaired oxygen consumption rate (measured at  Seahorse ), decreased mtDNA/nDNA, aconitase activity, and NADPH following glucose stimulation, alongside with augmented generation of reactive oxygen species. Strikingly, we demonstrate that during HF beta cells display decreased intracellular calcium stores, and mitochondria exhibit a significantly reduced glucose-stimulated uptake of calcium, known activator of three matrix dehydrogenases in the tricarboxylic acid (aka Krebs) cycle. Moreover, the expression of mitochondrial calcium uniporter (MCU) was decreased in HF islets.   Conclusions:  Taken together, our  in vivo  and  ex vivo  findings establish that HF induces beta cell failure, characterized by mitochondrial dysfunction, ER stress, and overall impaired fuel-stimulated insulin release.
Involving Pregnant Women in Research: What Should We Recommend When the Regulations Seem Ethically Problematic?
Authors: Holly A. Taylor, Christian Morales
Journal: The American Journal of Bioethics (2018)

"Involving Pregnant Women in Research: What Should We Recommend When the Regulations Seem Ethically Problematic?." The American Journal of Bioethics, 18(4), pp. 91–92