tbuckley/cabot-search huggingface dataset:
DNMT3A and TET1 cooperate to regulate promoter epigenetic landscapes in mouse embryonic stem cells
Authors: Tianpeng Gu, Xueqiu Lin, Sean M. Cullen, Min Luo, Mira Jeong, Marcos Estecio, Jianjun Shen, Swanand Hardikar, Deqiang Sun, Jianzhong Su, Danielle Rux, Anna Guzman, Minjung Lee, Lei Stanley Qi, Jia-Jia Chen, Michael Kyba, Yun Huang, Taiping Chen, Wei Li, Margaret A. Goodell
Journal: Genome biology (2018)

DNA methylation is a heritable epigenetic mark, enabling stable but reversible gene repression. In mammalian cells, DNA methyltransferases (DNMTs) are responsible for modifying cytosine to 5-methylcytosine (5mC), which can be further oxidized by the TET dioxygenases to ultimately cause DNA demethylation. However, the genome-wide cooperation and functions of these two families of proteins, especially at large under-methylated regions, called canyons, remain largely unknown. Here we demonstrate that DNMT3A and TET1 function in a complementary and competitive manner in mouse embryonic stem cells to mediate proper epigenetic landscapes and gene expression. The longer isoform of DNMT3A, DNMT3A1, exhibits significant enrichment at distal promoters and canyon edges, but is excluded from proximal promoters and canyons where TET1 shows prominent binding. Deletion of Tet1 increases DNMT3A1 binding capacity at and around genes with wild-type TET1 binding. However, deletion of Dnmt3a has a minor effect on TET1 binding on chromatin, indicating that TET1 may limit DNA methylation partially by protecting its targets from DNMT3A and establishing boundaries for DNA methylation. Local CpG density may determine their complementary binding patterns and therefore that the methylation landscape is encoded in the DNA sequence. Furthermore, DNMT3A and TET1 impact histone modifications which in turn regulate gene expression. In particular, they regulate Polycomb Repressive Complex 2 (PRC2)-mediated H3K27me3 enrichment to constrain gene expression from bivalent promoters. We conclude that DNMT3A and TET1 regulate the epigenome and gene expression at specific targets via their functional interplay.
Abstract 15607: Impact of Left Atrial Enlargement on Incident Cardioembolic Stroke in Patients With Atrial Fibrillation With Low CHADS2 Score
Authors: Masahiro Wanezaki, Tetsu Watanabe, Harutoshi Tamura, Naoto Hashimoto, Gensai Yamaura, Satoshi Nishiyama, Takanori Arimoto, Hiroki Takahashi, Tetsuro Shishido, Takuya Miyamoto, Isao Kubota
Journal: Circulation (2016)

It was reported that there are 2-3% per year of thromboembolic events in patients with atrial fibrillation (AF) despite low CHADS2 score (0-1). Left atrial volume index (LAVI) has been shown to be ...
Esophageal Cancer Clinical Practice Guidelines in Oncology
Authors: Jaffer Ajani, Thomas A D'Amico, James A Hayman, Neal J Meropol, Bruce Minsky
Journal: Journal of the National Comprehensive Cancer Network (2003)

This article summarizes the NCCN clinical practice guidelines for managing esophageal cancer. The guidelines begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, adjuvant treatment, management of recurrent and metastatic disease, and patient surveillance. For the most recent version of the guidelines, please visit NCCN.org
Abstract 10327: Automated Quantitative Modeling of the Aortic Root by Real-Time 3D TEE Predicts Optimal Valve Size for TAVR Planning When Contrast CT is Contraindicated
Authors: Shizhen Liu, Christopher Meduri, Vivek Rajagopal, James R Kauten, Sarah J Rinehart, Venkateshwar Polsani, Xiao Zhou, Zhen Qian, Randolph Martin, Tommaso Mansi, Helene Houle, Mani A Vannan
Journal: Circulation (2015)

Background: While CT is the modality of choice for TAVR planning, contrast CT may be not be possible in those with renal dysfunction. We tested whether automated quantitative modeling of the aortic root by real-time 3D TEE (RT3D-TEE) was a useful alternative in these patients. Methods: 44 patients (76 ± 10 years old) with severe AS who could not have contrast CT for TAVR planning had RT3D TEE during TAVR procedure. The aortic root was modeled automatically using the previously validated eSie valves (Siemens, CA). From the dynamic model maximum, minimum and mean aortic annulus diameters, aortic annulus perimeter, and aortic annulus area were measured in mid/peak systole, whichever was larger. The predicted valve size based on these parameters was compared to the actual valve size used during TAVR (balloon and self-expanding valves). Results: The valve size predicted by automated quantitative RT3D-TEE had excellent correlation with the actual valve size (indexed by body surface area, r=0.96 for mean diameter, 0.94 for perimeter and area derived diameters, p &lt; 0.0001, Figure-upper panel graph). The agreement (Kappa statistic) between actual valve size used and that predicted by RT3D-TEE was 0.82, 0.64 and 0.58, p &lt; 0.0001 for mean diameter, and perimeter and area derived diameters (lower left table). The red dots in the graph in the upper panel show cases where there was discrepancy between 3-D TEE predicted and actual valve size used. Mean diameter had the fewest "underestimation" of the valve size vs. perimeter and area derived prediction. An example of quantitative aortic root modeling in a patient who had TAVR with a 31 mm self-expanding valve, with no PVL (lower right panel). Conclusion: Automated quantitative modeling of the aortic root by real-time 3-D TEE in severe AS is feasible, rapid and an excellent alternative to contrast CT when the latter is contraindicated, for TAVR planning. Mean annulus diameter measured by 3D-TEE seems to be the best predictor of the optimal valve size.
Impact of Tumor Necrosis Factor Inhibitor Versus Nonsteroidal Antiinflammatory Drug Treatment on Radiographic Progression in Early Ankylosing Spondylitis: Its Relationship to Inflammation Control During Treatment
Authors: Jun Won Park, Min Jung Kim, Jeong Seok Lee, You‐Jung Ha, Jin Kyun Park, Eun Ha Kang, Yun Jong Lee, Yeong Wook Song, Eun Young Lee
Journal: Arthritis & Rheumatology (2018)

To investigate the impact of tumor necrosis factor inhibitor (TNFi) treatment and inflammation control on radiographic progression in early ankylosing spondylitis (AS) over 4 years.We included a total of 215 patients with early AS (symptom duration <10 years) treated with TNFi (the TNFi group; n = 135) or with nonsteroidal antiinflammatory drugs (NSAIDs) (the control group; n = 80). Two blinded readers assessed radiographic progression using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Inflammation control was inferred from C-reactive protein (CRP) levels time-averaged between 2 radiologic assessments. Linear mixed modeling was used to estimate mSASSS changes over radiographic intervals as well as the impact of clinical factors on outcomes.The TNFi group had longer disease duration, a higher baseline CRP level, and a higher Bath Ankylosing Spondylitis Disease Activity Index than did controls. The time-averaged CRP level over radiographic intervals was lower with TNFi treatment than with NSAID treatment (mean ± SD 0.27 ± 0.30 mg/dl versus 0.61 ± 0.68 mg/dl; P < 0.001). Overall, mean ± SD mSASSS change over the 2-year interval was 1.30 ± 2.97 units. In the multivariable model adjusted for age, smoking status, baseline CRP level, and the presence of syndesmophytes at baseline, the TNFi group showed less mSASSS change over the 2-year interval (β = -0.90 [95% confidence interval {95% CI} -1.51, -0.29]). However, when a time-averaged CRP level was additionally included, it significantly influenced the mSASSS change (β = 1.02 [95% CI 0.32, 1.71]), decreasing the estimated group difference (β = -0.52 [95% CI -1.17, 0.14]). NSAID indices of both groups were not associated with either time-averaged CRP levels or mSASSS changes.Effective suppression of inflammation by TNFi treatment decreases radiographic progression in early AS.
Update on infection control practices in cancer hospitals
Authors: Ella J. Ariza‐Heredia, Roy F. Chemaly
Journal: CA A Cancer Journal for Clinicians (2018)

ABSTRACT Therapies in oncology have evolved rapidly over the last years. At the same pace, supportive care for patients receiving cancer therapy has also evolved, allowing patients to safely receive the newest advances in treatment in both an inpatient and outpatient basis. The recognition of the role of infection control and prevention (ICP) in the outcomes of patients living with cancer has been such that it is now a requirement for hospitals and involves multidisciplinary groups. Some unique aspects of ICP for patients with cancer that have gained momentum over the past few decades include catheter‐related infections, multidrug‐resistant organisms, community‐acquired viral infections, and the impact of the health care environment on the horizontal transmission of organisms. Furthermore, as the potential for infections to cross international borders has increased, alertness for outbreaks or new infections that occur outside the area have become constant. As the future approaches, ICP in immunocompromised hosts will continue to integrate emerging disciplines, such as antibiotic stewardship and the microbiome, and new techniques for environmental cleaning and for controlling the spread of infections, such as whole‐genome sequencing. CA Cancer J Clin 2018;000:000‐000 . © 2018 American Cancer Society .
Abstract 17867: Prognostic Implications of Two Dimensional, M-mode and Doppler Echo Indices of Right Ventricular Function in Children with Pulmonary Arterial Hypertension
Authors: Eias A Kassem, Mark K Friedberg
Journal: Circulation (2012)

Background Right ventricular (RV) function may be a key determinant of mortality in pediatric idiopathic pulmonary artery hypertension, (iPAH) and that associated with congenital heart disease (cPA...
Resultados del tratamiento con polvo hemostático en hemorragia digestiva
Authors: M Avilés Recio, T Romero García, R Llorca Fernández, A Marqués Ruiz, I Márquez De La Rosa, A Garrido Serrano, L Grande Santamaría
Journal: Endoscopy (2017)

el tratamiento de la hemorragia digestiva de difícil control sigue siendo uno de los retos en la terapéutica endoscópica. La aparición del polvo hemostático supone un avance al ofrecer una nueva opción de tratamiento.
AN EXPERIENCE OF REPEAT ERCPS IN PREVIOUSLY FAILED ERCP IN OTHER CENTRES
Authors: SZ Farrukh, A Taj, A Siddiqui, SA Haqqi, SK Niaz
Journal: Endoscopy (2018)

Data was analyzed and processed on Statistical Package for Social Sciences (SPSS) version 17. Descriptive statistics only are computed: mean median, standard deviation (SD), range and frequencies.
Abstract 108: Exercise Promotes a Cardioprotective Gene Program in Resident Cardiac Fibroblasts
Authors: Janet K Lighthouse, Ryan Burke, Lissette S Velasquez, Ronald A Dirkx, Christine S Moravec, Jeffrey D Alexis, Alex Rosenberg, Eric M Small
Journal: Circulation Research (2017)

Exercise and disease both induce hypertrophic cardiac growth, but only disease results in fibrosis and compromised heart function. Transcriptional profiling of resident cardiac fibroblasts (CFs), the primary cellular source of fibrosis, was used to define the gene expression programs (GEP) underlying this divergent functional outcome. Bioinformatic analyses revealed distinct transcriptional responses to exercise and disease, including induction of Rho- and SRF-dependent remodeling genes in disease and NRF2-dependent antioxidant genes in exercise. The expression of a number of antioxidant genes, including metallothioneins (Mt1 and Mt2), are specifically maintained in CFs after exercise and lost in disease. Mice lacking Mt1/2 show signs of cardiac dysfunction after exercise, including cardiac fibrosis, vascular rarefaction, and reduced heart function. Importantly, Mt levels are also reduced in human heart failure (HF) patients, suggesting a potentially conserved cardioprotective role in humans. Non-canonical TGF-β1-mediated p38-MAPK signaling has previously been implicated in HF, therefore we tested the role of p38 signaling in Mt regulation. Pharmacological inhibition of p38 in human HF fibroblasts restores Mt1 and Mt2 expression and blunts the pathological fibroblast phenotype. Taken together, our study defines the transcriptional response of CFs to exercise and disease and reveals a cardioprotective mechanism that is lost in disease.
High-Titer Retroviral Vectors Containing the Enhanced Green Fluorescent Protein Gene for Efficient Expression in Hematopoietic Cells
Authors: Ana Limón, Javier Briones, Teresa Puig, Mercé Carmona, Oscar Fornas, José Antonio Cancelas, Margarita Nadal, Joan Garcı́a, Félix Rueda, Jordi Barquinero
Journal: Blood (1997)
Abstract 11320: Reduction of Na/k-atpase Regulates Cardiac Remodeling and Regeneration in Partial Nephrectomized Mice
Authors: Christopher Drummond, Kaleigh L Evans, Xiaoliang Wang, Joseph I Shapiro, Jiang Tian
Journal: Circulation (2013)

Reduction of Na/K-ATPase attenuates survival signaling in cardiac cells and potentiates cardiotonic steroid-induced myocyte apoptosis. This study examined the role of Na/K-ATPase in partial nephrectomized (PNx) animals using Na/K-ATPase α1 heterozygous mice (α1+/-) and their wild-type (WT) littermates. PNx was established by ligation of one branch of the left renal artery which was followed by removal of the entire decapsulated right kidney one week later. Our results indicate that PNx induces hypertension and cardiac hypertrophic growth in both α1+/- and WT mice. In point of fact, in α1+/- mice, the heart/body weight ratio was 5.0 for PNx vs 3.8 for sham, whereas in WT animals the ratio was 4.8 vs 3.8. However, immunohistological analyses indicate that PNx causes more cardiac cell apoptosis, as illustrated by the increase in active caspase 3 in the α1+/- mice. To examine if regeneration contributes to the above stated changes, cardiac tissues were probed for the progenitor cell marker c-kit and the proli...
Author Correction: Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear
Authors: Roger Marek, Jingji Jin, Travis D. Goode, Thomas F. Giustino, Qian Wang, Gillian M. Acca, Roopashri Holehonnur, Jonathan E. Ploski, Paul J. Fitzgerald, Timothy Lynagh, Joseph W. Lynch, Stephen Maren, Pankaj Sah
Journal: Nature Neuroscience (2018)
THE CLINICAL SIGNIFICANCE OF COLONOSCOPY IN THE PATIENTS WITH CT-DIAGNOSED ACUTE DIVERTICULITIS
Authors: MC Kim, SB Kim, KO Kim, KH Kim, SH Lee, BI Jang, TN Kim
Journal: Endoscopy (2018)

International guideline recommends performing a colonoscopy after an episode of acute diverticulitis. The aim of this study was to assess the colonoscopy results and its clinical significance in patients with acute diverticulitis on CT scan.
Abstract 4337: Best Outcome Predictor Post Myocardial Infarction: Can Blood Glucose Defeat Left Ventricular Ejection Fraction?
Authors: Silvia Monteiro, Natalia Antonio, Carolina Lourenço, Rogério Teixeira, Rui Batista, Elisabete Jorge, Fátima Saraiva, Pedro Monteiro, Lino Gonçalves, Mário Freitas, Luís Providência
Journal: Circulation (2008)

Introduction: Ventricular dysfunction in acute myocardial infarction (AMI) is a recognized predictor of in-hospital and post-discharge morbidity and mortality. Recently, admission hyperglycaemia has also been considered an important marker of poor prognosis in this patient population. Aim: To compare the predictive value of left ventricular dysfunction with admission glycaemia (GLY) on prognosis of AMI patients and to identify independent predictors of 1-year major acute cardiac events (MACE) and mortality. Population and methods: Retrospective analysis of 583 consecutive patients admitted to a single coronary care unit for AMI. Patients were followed during twelve months after AMI. Re-hospitalization by worsening heart failure, non programmed revascularization, new ACS and death were considered as MACE. Results: After multivariate analysis, age, previous diabetes, necrosis markers, and low ejection fraction (EF) were independent predictors of 1-year mortality, while PCI performance and admission GLY, in addition to parameters listed before were independent predictors of MACE at 1-year of follow-up. We then compared, by multivariate regression analysis, the predictive value of admission GLY and EF in this population. The receiver-operator curves showed that both parameters were equally predictive of both short and long-term MACE and mortality. Conclusion: In this population, admission GLY was as predictive of outcome as EF, a well recognized and strong prognosis determinant post-AMI. This fact, never before described, underlies the importance of metabolic abnormalities and its control in the prognosis of AMI patients.
A RETROSPECTIVE AUDIT OF RECTAL STRICTURES IN PATIENTS WITH LOW RECTAL CANCER WHO HAVE UNDERGONE AN INTER-SPHINCTERIC RESECTION (ISR)
Authors: S Mazumdar, P Patil, S Mehta, A Saklani, A Desouza
Journal: Endoscopy (2018)

Inter-sphincteric resection (ISR) is currently the surgery of choice for patients with low rectal cancer for sphincter preservation. Following ISR, many patients develop anastomotic strictures which need dilatation before stoma closure (SC) can be performed. We present a retrospective analysis of dilatation of anastomotic strictures in post ISR patients.
ENDOSCOPIC TREATMENT OF GIANT COLONIC ADENOMAS. EXPERIENCE OF A THIRD LEVEL HOSPITAL
Authors: M Sánchez Alonso, M Úbeda Muñoz, P Olivencia Palomar, E de la Santa Belda, J Olmedo Camacho, J Rodríguez Sánchez
Journal: Endoscopy (2018)

The size of the lesions has traditionally been considered a crucial factor to indicate an endoscopic treatment. However, there is evidence that this factor is not a limitation when practicing an endoscopic resection, with guarantees of cure comparable to surgical treatment. The aim of this work is to evaluate the efficacy of endoscopic mucosal resection as treatment of colorectal lesions ≥4 cm.
Microparticles Locally Deliver Active Interleukin‐1 Receptor Antagonist In Vivo
Authors: Anna E. B. Clements, Emily R. Groves, Connie S. Chamberlain, Ray Vanderby, William L. Murphy
Journal: Advanced Healthcare Materials (2018)

Abstract Despite significant research in therapeutic protein delivery, localized and sustained delivery of active therapeutic proteins remains a challenge. Delivery is a particular challenge for therapeutic proteins with a short half‐life. Herein, localized delivery of interleukin‐1 receptor antagonist (IL‐1Ra) by mineral coated microparticles (MPs) is assessed in a healing rat medial collateral ligament (MCL). The local tissue concentration and systemic serum concentration of IL‐1Ra, the anti‐inflammatory activity of IL‐1Ra delivered with MPs, and whether IL‐1Ra loaded MPs (IL‐1Ra MPs) are immunogenic in a healing ligament are also examined. IL‐1Ra MPs significantly increase the local concentration of IL‐1Ra compared to soluble IL‐1Ra at 7 and 14 days after treatment but do not elevate the systemic concentration of IL‐1Ra at these time points, indicating localized delivery of IL‐1Ra. IL‐1Ra MPs significantly reduce inflammation caused by the MPs themselves, indicating the IL‐1Ra is active. Finally, IL‐1Ra MPs do not induce a foreign body response and decrease the immunogenicity of human IL‐1Ra in a healing rat MCL. Overall, mineral coated microparticles have the ability to locally deliver active therapeutic proteins for an extended period of time.
Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study
Authors: Kathryn Schnippel, Norbert Ndjeka, Gary Maartens, Graeme Meintjes, Iqbal Master, Nazir Ismail, Jennifer Hughes, Hannetjie Ferreira, Xavier Padanilam, Rodolfo Romero, Julian te Riele, Francesca Conradie
Journal: The Lancet Respiratory Medicine (2018)
Dyspnoea in patients receiving noninvasive ventilation for acute respiratory failure: prevalence, risk factors and prognostic impact
Authors: Laurence Dangers, Claire Montlahuc, Achille Kouatchet, Samir Jaber, Ferhat Meziani, Sébastien Perbet, Thomas Similowski, Matthieu Resche-Rigon, Elie Azoulay, Alexandre Demoule
Journal: European Respiratory Journal (2018)

Dyspnoea is a frequent and intense symptom in intubated patients, but little attention has been paid to dyspnoea during noninvasive mechanical ventilation in the intensive care unit (ICU).The objectives of this study were to quantify the prevalence, intensity and prognostic impact of dyspnoea in patients receiving noninvasive ventilation (NIV) for acute respiratory failure (ARF) based on secondary analysis of a prospective observational cohort study in patients who received ventilatory support for ARF in 54 ICUs in France and Belgium. Dyspnoea was measured by a modified Borg scale.Among the 426 patients included, the median (interquartile range) dyspnoea score was 4 (3-5) on admission and 3 (2-4) after the first NIV session (p=0.001). Dyspnoea intensity ≥4 after the first NIV session was associated with the Sequential Organ Failure Assessment Score (odds ratio (OR) 1.12, p=0.001), respiratory rate (OR 1.03, p=0.032), anxiety (OR 1.92, p=0.006), leaks (OR 2.5, p=0.002) and arterial carbon dioxide tension (OR 0.98, p=0.025). Dyspnoea intensity ≥4 was independently associated with NIV failure (OR 2.41, p=0.001) and mortality (OR 2.11, p=0.009), but not with higher post-ICU burden and altered quality of life.Dyspnoea is frequent and intense in patients receiving NIV for ARF and is associated with a higher risk of NIV failure and poorer outcome.
Who is Matt Hancock, England’s new health secretary?
Authors: Tom Moberly
Journal: BMJ (2018)

Matt Hancock, the new secretary of state for health and social care for England, believes that political progress depends on focusing on “the big questions” and not being “drawn down rabbit holes.”

Hancock, 39, has no history of working in health policy or with the NHS and has not previously worked in the Department of Health and Social Care. He was elected MP for West Suffolk in the 2010 general election and currently has a majority of 17 063. Before becoming an MP, he worked for the family IT business, at the Bank of England, …
A systematic review of advanced endoscopy-assisted lithotripsy for retained biliary tract stones: laser, electrohydraulic or extracorporeal shock wave
Authors: Joyce Veld, Nadine van Huijgevoort, Marja Boermeester, Marc Besselink, Otto van Delden, Paul Fockens, Jeanin van Hooft
Journal: Endoscopy (2018)

When conventional endoscopic treatment of bile duct stones is impossible or fails, advanced endoscopy-assisted lithotripsy can be performed by electrohydraulic lithotripsy (EHL), laser lithotripsy, or extracorporeal shock wave lithotripsy (ESWL). No systematic review has compared efficacy and safety between these techniques.A systematic search was performed in PubMed, the Cochrane Library, and EMBASE for studies investigating EHL, laser lithotripsy, and ESWL in patients with retained biliary tract stones.After screening 795 studies, 32 studies with 1969 patients undergoing EHL (n = 277), laser lithotripsy (n = 426) or ESWL (n = 1266) were included. No randomized studies were available. Although each advanced lithotripsy technique appeared to be highly effective, laser lithotripsy had a higher complete ductal clearance rate (95.1 %) than EHL (88.4 %) and ESWL (84.5 %; P < 0.001). In addition, a higher stone fragmentation rate was reported for laser lithotripsy (92.5 %) than for EHL (75.5 %) and ESWL (89.3 %; P < 0.001). The post-procedural complication rate was significantly higher for patients treated with EHL (13.8 %) than for patients treated with ESWL (8.4 %) or laser lithotripsy (9.6 %; P = 0.04). Data on the recurrence rate of the biliary tract stones were lacking.This systematic review revealed that laser lithotripsy appeared to be the most successful advanced endoscopy-assisted lithotripsy technique for retained biliary tract stones, although randomized studies are lacking.