tbuckley/cabot-search huggingface dataset:
A Clinician’s Guide for Trending Cardiovascular Nutrition Controversies
Authors: Andrew M. Freeman, Pamela B. Morris, Karen Aspry, Neil F. Gordon, Neal D. Barnard, Caldwell B. Esselstyn, Emilio Ros, Stephen Devries, James O’Keefe, Michael Miller, Dean Ornish, Kim A. Williams, Travis Batts, Robert J. Ostfeld, Sheldon Litwin, Monica Aggarwal, Andrea Werner, Kathleen Allen, Beth White, Penny Kris-Etherton
Journal: Journal of the American College of Cardiology (2018)
SUMO-defective c-Maf preferentially transactivates Il21 to exacerbate autoimmune diabetes
Authors: Chao-Yuan Hsu, Li-Tzu Yeh, Shin-Huei Fu, Ming-Wei Chien, Yu-Wen Liu, Shi-Chuen Miaw, Deh-Ming Chang, Huey-Kang Sytwu
Journal: Journal of Clinical Investigation (2018)

SUMOylation is involved in the development of several inflammatory diseases, but the physiological significance of SUMO-modulated c-Maf in autoimmune diabetes is not completely understood. Here, we report that an age-dependent attenuation of c-Maf SUMOylation in CD4+ T cells is positively correlated with the IL-21-mediated diabetogenesis in NOD mice. Using 2 strains of T cell-specific transgenic NOD mice overexpressing wild-type c-Maf (Tg-WTc) or SUMOylation site-mutated c-Maf (Tg-KRc), we demonstrated that Tg-KRc mice developed diabetes more rapidly than Tg-WTc mice in a CD4+ T cell-autonomous manner. Moreover, SUMO-defective c-Maf preferentially transactivated Il21 to promote the development of CD4+ T cells with an extrafollicular helper T cell phenotype and expand the numbers of granzyme B-producing effector/memory CD8+ T cells. Furthermore, SUMO-defective c-Maf selectively inhibited recruitment of Daxx/HDAC2 to the Il21 promoter and enhanced histone acetylation mediated by CREB-binding protein (CBP) and p300. Using pharmacological interference with CBP/p300, we illustrated that CBP30 treatment ameliorated c-Maf-mediated/IL-21-based diabetogenesis. Taken together, our results show that the SUMOylation status of c-Maf has a stronger regulatory effect on IL-21 than the level of c-Maf expression, through an epigenetic mechanism. These findings provide new insights into how SUMOylation modulates the pathogenesis of autoimmune diabetes in a T cell-restricted manner and on the basis of a single transcription factor.
Radiofrequency Ablation of Atrial Fibrillation
Authors: ClaudioPratola, ElisaBaldo, PasqualeNotarstefano, TizianoToselli, RobertoFerrari
Journal: Circulation (2008)

Background— Several approaches have been developed for radiofrequency catheter ablation of atrial fibrillation, but the correct intraprocedural end point is still under debate, and few data exist about the destiny of ablation lesions over time. The aim of the present study was to evaluate the long-term maintenance of intraprocedural end points of ablation procedures. Methods and Results— Inclusion criteria were (1) a previous ablation procedure of pulmonary vein (PV) encircling performed for drug-refractory persistent atrial fibrillation; (2) a “complete” intraprocedural end point, which consisted of voltage abatement inside the lesions, PV disconnection, and exit-block pacing from inside the lesions, attained in all PVs; and (3) stable sinus rhythm documented during a minimum follow-up of 2.5 years after the procedure. Twenty volunteers were selected (12 males, mean age 59±7 years) and underwent a repeat electrophysiological study. After a follow-up of 36.4±4.7 months, complete voltage abatement was main...
Hypercoagulable Workup in Thrombotic Cardiovascular Diseases
Authors: Yu-Min Shen, Srikanth Nagalla
Journal: Circulation (2018)

eart disease was the leading cause of death, whereas stroke was the fifth leading cause of death, in the United States in 2015.Arterial obstruction underpins myocardial infarction (MI) and stroke in patients.However, a minority of patients have no obstructive arterial disease found on angiography (termed myocardial infarction with nonobstructive coronary arteries [MINOCA], 6%), 1 or source of embolus determined after extensive evaluation (termed cryptogenic stroke and embolic stroke of undetermined source, 30%). 2 In MINOCA, potential causes include occult plaque rupture, coronary dissection, coronary embolism, vasospasm, microvascular disease, and thrombophilia. 1 In cryptogenic stroke and embolic stroke of undetermined source, potential causes include occult atrial fibrillation, atrial cardiomyopathy, paradoxical embolism/patent foramen ovale, malignancy, and thrombophilia. 2 Thrombophilia, inherited or acquired, results in increased risk of venous or arterial thrombosis.Hematologists are often asked to look for thrombophilia in patients with MINOCA, cryptogenic stroke, or embolic stroke of undetermined source, but the clinical utility of a thrombophilia workup in these scenarios is questionable.
Violaceous Patches in the Axilla
Authors: Brayden Forbes, Marta J. Petersen
Journal: JAMA Dermatology (2018)

A man in his 40s presented with dark red, circular lesions in his right axilla without pain, blisters, or other symptoms; after resolution with a topical cream, similar lesions appeared in his left axilla and inguinal folds 5 months later. What is your diagnosis?
Massive fall in teenage pregnancy down to sensible drinking and more time spent online
Authors: Jacqui Wise
Journal: BMJ (2018)

Teenage pregnancy rates have fallen by 55% in the past decade partly because young people drink considerably less alcohol and spend more time online than previous generations, a report by the British Pregnancy Advisory Service has found.1

Teenagers today spend more time either in the family home or with family members, which may limit their opportunities for sexual relationships, it said. Social, romantic, and sexual relationships are increasingly experienced online and sexting is seen as an alternative, as well as a precursor, to intercourse.

Figures from the Office for National Statistics show that the under 18 conception rate was 41.6 per 1000 women in England and Wales in 2007, and this dropped to 18.9 …
Combination treatment with aromatase inhibitor and capecitabine as first- or second-line treatment in metastatic breast cancer.
Authors: Alberto Alvarado Miranda, Jesus Limon, Fernando Lara Medina, Claudia Arce, Juan Wolfgang Zinser, Enrique Bargallo Rocha, Cynthia Mayte Villarreal-Garza
Journal: Journal of Clinical Oncology (2012)

e11016 Background: Preclinical studies have shown that the combination of an aromatase inhibitor (AI) and oral fluoropyrimidines in estrogen receptor (ER)-positive cell lines enhance antitumor efficacy. This might be explained by reduction of ER-induced growth signaling in addition to decrease in estrogen production. This retrospective analysis of a cohort of patients with metastatic breast cancer (MBC) evaluates the efficacy and safety of combined AI with capecitabine. Methods: Patients with hormone receptor-positive MBC treated with this combination were evaluated and outcomes were compared to women treated with capecitabine (conventional dose) or AI as monotherapy. The administered total dose of capecitabine was 2000 mg. per day in combination with AI. Results: Of 93 patients evaluated, 37 received the combination treatment, 27 capecitabine and 29 an AI. Combination was used in 26 patients as first-line treatment and 11 as second-line. At the time of progression, 92% had a performance status of ≤2 and 58% of patients had visceral disease. No significant difference was observed between the three groups according to clinical and pathological features. Mean follow-up was 23 months (m). The median PFS of first-line treatment was significantly better for the combination (PFS not-reached vs.3.0 m for capecitabine and 13.0 m for AI, p&lt;0.0001). For second-line treatment, the PFS was longer in the combination compared to capecitabine and AI (PFS not reached vs. 6.0 m vs.13.0 m, respectively, p=0-041). For the entire cohort, OS was not reached. The most common adverse events for the combination group were grade 1 and 2 hand-foot syndrome (65%), grade 1 fatigue (52%) and grade 1 diarrhea (5%). Only one grade 3 hand-foot syndrome event was reported. Conclusions: Combination treatment with capecitabine and AI used as first-line treatment or second-line improved PFS compared to treatment with either single agent. The combination was safe and rendered dismal toxicity. Prospective randomized clinical trials should evaluate the use of the combination of capecitabine and an AI in advanced breast cancer in order to confirm our findings.
Is Hypothermia After Cardiac Arrest Effective in Both Shockable and Nonshockable Patients
Authors: FlorenceDumas, DavidGrimaldi, BenjaminZuber, JérômeFichet, JulienCharpentier, FrédéricPène, BenoîtVivien, OlivierVarenne, PierreCarli, XavierJouven, Jean-PhilippeEmpana, AlainCariou
Journal: Circulation (2011)

Background—Although the level of evidence of improvement is significant in cardiac arrest patients resuscitated from a shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia [VF/Vt]), the use of therapeutic mild hypothermia (TMH) is more controversial in nonshockable patients (pulseless electric activity or asystole [PEA/asystole]). We therefore assessed the prognostic value of hypothermia for neurological outcome at hospital discharge according to first-recorded cardiac rhythm in a large cohort. Methods and Results—Between January 2000 and December 2009, data from 1145 consecutive out-of-hospital cardiac arrest patients in whom a successful resuscitation had been achieved were prospectively collected. The association of TMH with a good neurological outcome at hospital discharge (cerebral performance categories level 1 or 2) was quantified by logistic regression analysis. TMH was induced in 457/708 patients (65%) in VF/Vt and in 261/437 patients (60%) in PEA/asystole. Overall, 342...
Anomalous Origin of the Right Coronary Artery From the Left Sinus of Valsalva in an Elderly Man
Authors: YoshihisaNaruse, AkiraSato, YukiKakefuda, TomoyaHoshi, AkitoImai, ChihoTokunaga, YuzuruSakakibara, KazutakaAonuma
Journal: Circulation (2012)
Management of organ transplant recipients attending a high‐throughput skin cancer surgery and surveillance clinic in Queensland
Authors: K. Papier, L.G. Gordon, K. Khosrotehrani, N. Isbel, S. Campbell, A. Griffin, A.C. Green
Journal: British Journal of Dermatology (2018)

The incidence of skin cancer in organ transplant recipients (OTRs) is very high, due mainly to long‐term immunosuppressive therapy. The problem is particularly severe for OTRs living in Queensland, Australia, and results in significant mortality. To describe the experience of the first dedicated outpatient high‐throughput transplant skin clinic in Queensland. This prospective evaluation study was conducted at a newly established, outpatient transplant skin cancer surgery and surveillance clinic. Participants (89 OTRs and 12 non‐OTRs) were referred to the Princess Alexandra Hospital Transplant Skin Clinic during December 2016 to May 2017, and were each followed for 3 months. Self‐completed questionnaires were administered at baseline and the end of follow‐up (n = 94), and details of any skin cancers occurring in that period were extracted from hospital records. In the 3‐month follow‐up of 101 participants, a total of 615 skin lesions were detected in the 3‐month follow‐up of 101 participants, of which 478 (78%) were treated in the clinic and 55 (9%) were referred to another specialist. Of the 478 treated lesions, 268 were histopathologically confirmed skin cancers, equivalent to 2·7 (95% confidence interval 2·5–2·8) skin cancers per participant per 3 months. The overall number needed to treat for any skin cancer was 1·4 (95% confidence interval 1·3–1·5). Three‐quarters (374) of in‐clinic treatments were surgical, and most (90%) were complete excisions. The median time from detection of skin cancer to excision was 7 days. This high‐volume surgical outpatient transplant skin clinic enables efficient treatment of skin cancers in very‐high‐risk OTRs.
A sodium-glucose cotransporter 2 inhibitor attenuates renal capillary injury and fibrosis by a vascular endothelial growth factor–dependent pathway after renal injury in mice
Authors: Yifan Zhang, Daisuke Nakano, Yu Guan, Hirofumi Hitomi, Akiyoshi Uemura, Tsutomu Masaki, Hideki Kobara, Takeshi Sugaya, Akira Nishiyama
Journal: Kidney International (2018)
Bone Scintigraphy in Poststreptococcal Periostitis With Dysproteinemia
Authors: Sophie Bourgeois, Willy Peetermans, Nathalie Noppe, Karolien Goffin, Olivier Gheysens
Journal: Clinical Nuclear Medicine (2018)

Abstract A 39-year-old man presented with severe bone pain in the tibiae and forearms in the wake of a poststreptococcal sepsis complicated with pneumonia and erysipelas 4 months earlier. Bone scintigraphy was indicative of periostitis of the tibia, ulna, and radius bilaterally, and in combination with the increased inflammatory parameters and dysproteinemia, the diagnosis of Goldbloom syndrome was made. Goldbloom syndrome is an idiopathic periosteal hyperostosis associated with dysproteinemia and elevated inflammatory parameters. Although it has only been described in children/adolescents, this case illustrates that, in the specific clinical and biochemical setting, it should also be considered in adults.
Clonal heterogeneity of acute myeloid leukemia treated with the IDH2 inhibitor enasidenib
Authors: Lynn Quek, Muriel D. David, Alison Kennedy, Marlen Metzner, Michael Amatangelo, Alan Shih, Bilyana Stoilova, Cyril Quivoron, Maël Heiblig, Christophe Willekens, Véronique Saada, Samar Alsafadi, M. S. Vijayabaskar, Andy Peniket, Oliver A. Bernard, Sam Agresta, Katharine Yen, Kyle MacBeth, Eytan Stein, George S. Vassiliou, Ross Levine, Stephane De Botton, Anjan Thakurta, Virginie Penard-Lacronique, Paresh Vyas
Journal: Nature Medicine (2018)
Critical role of FOXO3a in carcinogenesis
Authors: Ying Liu, Xiang Ao, Wei Ding, Murugavel Ponnusamy, Wei Wu, Xiaodan Hao, Wanpeng Yu, Yifei Wang, Peifeng Li, Jianxun Wang
Journal: Molecular Cancer (2018)

FOXO3a is a member of the FOXO subfamily of forkhead transcription factors that mediate a variety of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage and tumorigenesis. It also responds to several cellular stresses such as UV irradiation and oxidative stress. The function of FOXO3a is regulated by a complex network of processes, including post-transcriptional suppression by microRNAs (miRNAs), post-translational modifications (PTMs) and protein–protein interactions. FOXO3a is widely implicated in a variety of diseases, particularly in malignancy of breast, liver, colon, prostate, bladder, and nasopharyngeal cancers. Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. In experimental studies, overexpression of FOXO3a inhibits the proliferation, tumorigenic potential, and invasiveness of cancer cells, while silencing of FOXO3a results in marked attenuation in protection against tumorigenesis. The role of FOXO3a in both normal physiology as well as in cancer development have presented a great challenge to formulating an effective therapeutic strategy for cancer. In this review, we summarize the recent findings and overview of the current understanding of the influence of FOXO3a in cancer development and progression.
Longitudinal Effects of Developmental Bisphenol A Exposure on Epigenome-Wide DNA Hydroxymethylation at Imprinted Loci in Mouse Blood
Authors: Joseph J. Kochmanski, Elizabeth H. Marchlewicz, Raymond G. Cavalcante, Bambarendage P. U. Perera, Maureen A. Sartor, Dana C. Dolinoy
Journal: Environmental Health Perspectives (2018)

Epigenetic machinery plays an important role in genomic imprinting, a developmental process that establishes parent-of-origin-specific monoallelic gene expression. Although a number of studies have investigated the role of 5-methylcytosine in imprinting control, the contribution of 5-hydroxymethylcytosine (5-hmC) to this epigenetic phenomenon remains unclear.Using matched mouse blood samples (from mice at 2, 4, and 10 months of age), our objective was to examine the effects of perinatal bisphenol A (BPA) exposure (50 μg/kg diet) on longitudinal 5-hmC patterns at imprinted regions. We also aimed to test the hypothesis that 5-hmC would show defined patterns at imprinted genes that persist across the life course.Genome-wide 5-hmC levels were measured using hydroxymethylated DNA immunoprecipitation sequencing (HMeDIP-seq). Modeling of differential hydroxymethylation by BPA exposure was performed using a pipeline of bioinformatics tools, including the csaw R package.Based on BPA exposure, we identified 5,950 differentially hydroxymethylated regions (DHMRs), including 12 DHMRs that were annotated to murine imprinted genes—Gnas, Grb10, Plagl1, Klf14, Pde10a, Snrpn, Airn, Cmah, Ppp1r9a, Kcnq1, Phactr2, and Pde4d. When visualized, these imprinted gene DHMRs showed clear, consistent patterns of differential 5-hmC by developmental BPA exposure that persisted throughout adulthood.These data show long-term establishment of 5-hmC marks at imprinted loci during development. Further, the effect of perinatal BPA exposure on 5-hmC at specific imprinted loci indicates that developmental exposure to environmental toxicants may alter long-term imprinted gene regulation via an epigenetic mechanism. https://doi.org/10.1289/EHP3441.
Megakaryocytic Leukemia 1 Bridges Epigenetic Activation of NADPH Oxidase in Macrophages to Cardiac Ischemia-Reperfusion Injury
Authors: Liming Yu, Guang Yang, Xinjian Zhang, Peng Wang, Xinyu Weng, Yuyu Yang, Zilong Li, Mingming Fang, Yong Xu, Aijun Sun, Junbo Ge
Journal: Circulation (2018)

Background: Excessive accumulation of reactive oxygen species (ROS), catalyzed by the NADPH oxidases (NOX), is involved in the pathogenesis of ischemia-reperfusion (IR) injury. The underlying epigenetic mechanism remains elusive. Methods: We evaluated the potential role of megakaryocytic leukemia 1 (MKL1), as a bridge linking epigenetic activation of NOX to ROS production and cardiac ischemia-reperfusion injury. Results: Following IR injury, MKL1-deficient (knockout) mice exhibited smaller myocardial infarction along with improved heart function compared with wild-type littermates. Similarly, pharmaceutical inhibition of MKL1 with CCG-1423 also attenuated myocardial infarction and improved heart function in mice. Amelioration of IR injury as a result of MKL1 deletion or inhibition was accompanied by reduced ROS in vivo and in vitro. In response to IR, MKL1 levels were specifically elevated in macrophages, but not in cardiomyocytes, in the heart. Of note, macrophage-specific deletion (MϕcKO), instead of cardiomyocyte-restricted ablation (CMcKO), of MKL1 in mice led to similar improvements of infarct size, heart function, and myocardial ROS generation. Reporter assay and chromatin immunoprecipitation assay revealed that MKL1 directly bound to the promoters of NOX genes to activate NOX transcription. Mechanistically, MKL1 recruited the histone acetyltransferase MOF (male absent on the first) to modify the chromatin structure surrounding the NOX promoters. Knockdown of MOF in macrophages blocked hypoxia/reoxygenation-induced NOX transactivation and ROS accumulation. Of importance, pharmaceutical inhibition of MOF with MG149 significantly downregulated NOX1/NOX4 expression, dampened ROS production, and normalized myocardial function in mice exposed to IR injury. Finally, administration of a specific NOX1/4 inhibitor GKT137831 dampened ROS generation and rescued heart function after IR in mice. Conclusions: Our data delineate an MKL1-MOF-NOX axis in macrophages that contributes to IR injury, and as such we have provided novel therapeutic targets in the treatment of ischemic heart disease.
Abstract XXXXX: Duration of resuscitation eff orts and survival after in-hospital cardiac arrest: an observational study
Authors: Zachary D. Goldberger, Paul S. Chan, Robert A. Berg, Steven L. Kronick, Colin R. Cooke, Mingrui Lu, Mousumi Banerjee, Rodney A. Hayward, Harlan M. Krumholz, Brahmajee K. Nallamothu
Journal: Circulation (2013)

Zachary D. Goldberger, 2013 Finalist and Presenting Author
Pressure Overload Induces Cardiac Dysfunction and Dilation in Signal Transducer and Activator of Transcription 6–Deficient Mice
Authors: ShungoHikoso, OsamuYamaguchi, YoshiharuHiguchi, ShinichiHirotani, ToshihiroTakeda, KazunoriKashiwase, TetsuyaWatanabe, MasayukiTaniike, IkukoTsujimoto, MichioAsahi, YasushiMatsumura, KazuhikoNishida, HiroshiNakajima, ShizuoAkira, MasatsuguHori, KinyaOtsu
Journal: Circulation (2004)

Background— Signal transducer and activator of transcription (STAT) proteins constitute a family of transcription factors that mediate many cytokine-induced responses. STAT6 is activated by angiotensin II and in rat hypertrophied hearts and in human hearts with dilated cardiomyopathy. This suggests that STAT6 may be involved in the pathogenesis of cardiac hypertrophy and heart failure. For this study we used STAT6-deficient (STAT6−/−) mice to examine the in vivo role of STAT6. Methods and Results— STAT6−/− hearts showed no morphological, histological, or functional defects. We examined left ventricular structural and functional remodeling 1 week after thoracic transverse aortic constriction (TAC). Western blot and immunohistochemical analyses showed increased STAT6 activity after TAC in the heart of wild-type mice. STAT6−/− mice showed a significant increase in end-diastolic left ventricular internal dimension accompanied by impaired contractility compared with wild-type mice but no differences in hypertr...
Latest guidance on the management of gout
Journal: BMJ (2018)

### What you need to know

Gout is the most common inflammatory arthritis and its incidence in the UK has steadily increased from 1.5% in 1997 to 2.5% in 2012.12 It is characterised by deposition of monosodium urate crystals in joints and tissues and usually presents with intermittent painful attacks followed by long periods of remission.3 Here, we review the latest guidance on the management of gout and consider the role of long term urate lowering therapy.

The single most important risk factor is sustained hyperuricaemia, which can be caused by overproduction or underexcretion of urate.23 Pathological hyperuricaemia has been defined as the serum uric acid concentration (408 μmol/L) above which monosodium urate crystals form in vitro at physiological pH and temperature. For most people with gout, underexcretion is the main cause of hyperuricaemia. Other factors associated with the development of gout include drugs (such as diuretics, ciclosporin, and low dose aspirin), renal impairment, excessive consumption of red meat or seafood, fructose-sweetened …