tbuckley/cabot-search huggingface dataset:
Abstract 17434: National Variation in Post-tavr Antithrombotic Therapy Utilization in Patients With Atrial Fibrillation: Insights From the Sts/acc Tvt Registry®
Authors: Matthew W Sherwood, Sreekanth Vemulapalli, Amit N Vora, David D Dai, Sharif Halim, Todd L Kiefer, G. Charles Hughes, J. Kevin Harrison, Eric D Peterson
Journal: Circulation (2015)

Background: Oral anticoagulant and antiplatelet medications are routinely prescribed for patients with pre-operative atrial fibrillation (AF) after TAVR, however, there are no data on the optimal treatment strategy, or the patterns of medication use for these patients in the United States. Methods: Using the STS/ACC TVT Registry we evaluated patients with atrial fibrillation undergoing TAVR from 2011-2014. Clinical outcomes included death, bleeding, and stroke at 1 year of follow up. Results: Of the 10,514 patients in the TVT registry during this time period, 4540 patients (43%) had pre-existing AF. Of these, 52% (n=2348) of patients were discharged with an OAC (2226 on warfarin, 122 on dabigatran) and 48% (n=2192) of patients were discharged without an OAC, with substantial unadjusted hospital level variation (Figure). Patients discharged on OAC had concomitant ASA monotherapy most frequently (1461; 62%), but dual antiplatelet therapy (DAPT)(405; 17%), clopidogrel monotherapy (224; 9.5%), and no additional therapy (258; 11%) were also used. Patients discharged without OAC were most frequently discharged on DAPT (1401; 64%), though monotherapy (680; 31%), and no antiplatelet therapy (111; 5%) were also prescribed. Patients discharged on OAC compared with those not prescribed OAC were similar with respect to age (84 vs. 85 years), gender (50 vs. 49% female), and most comorbid illnesses, but had lower STS PROM risk scores (7.8 vs. 8.7), and were less likely to have renal failure (6.1 vs. 7.0%). Patients with AF undergoing TAVR had 1-year unadjusted rates of death (23.7%; 95% CI 22.3- 25.1%), bleeding (20.2%; 95% CI 18.8-21.6%), and stroke (3.8%; 95% CI 3.2-4.4%). Conclusions: Given the substantial variation in the patterns of antithrombotic therapy prescribed for US patients with AF post-TAVR and the 1-year rates of death, stroke, and bleeding observed, sustained effort is needed to determine the optimal antithrombotic medical therapy for these patients.
Antimicrobial resistance and antibiotic stewardship programs in the ICU: insistence and persistence in the fight against resistance. A position statement from ESICM/ESCMID/WAAAR round table on multi-drug resistance
Authors: Jan J. De Waele, Murat Akova, Massimo Antonelli, Rafael Canton, Jean Carlet, Daniel De Backer, George Dimopoulos, José Garnacho-Montero, Jozef Kesecioglu, Jeffrey Lipman, Mervyn Mer, José-Artur Paiva, Mario Poljak, Jason A. Roberts, Jesus Rodriguez Bano, Jean-François Timsit, Jean-Ralph Zahar, Matteo Bassetti
Journal: Intensive Care Medicine (2017)
Recognising contributions to work in research collaboratives: Guidelines for standardising reporting of authorship in collaborative research
Authors: Natalie Blencowe, James Glasbey, Nick Heywood, Veeru Kasivisvanathan, Matthew Lee, Dmitri Nepogodiev, Richard Wilkin, Sophie Allen, Aditya Borakati, David Bosanquet, Stephen Chapman, Aswin Chari, Matt Dunstan, Edward Dyson, Ellie Edlmann, Matthew D. Gardner, Rhiannon Harries, James Hunter, Angelos G. Kolias, Aimun Jamjoom, John McGrath, Helen Mohan, Rory Morrison, Gael Nana, Ana-Catarina Pinho-Gomes, Scott McCain, Ana-Catarina Pinho-Gomes, Rhianon Reynolds, Shafaque Sheikh, Joseph Shalhoub, Amy Stimpson, Nicholas Symons Gijs van Boxel, Malcolm West, Jonathan Wild, Daniel Baker, Behrad Barmayehvar, Michael Bath, Andrew J. Beamish, Aneel Bhangu, Richard Canter, Joshua Clements, Arthur Cotton, Nedal Dabab, Daniel Doherty, J. Edward Fitzgerald, Emily Heywood, Maximilian Johnston, Patrick Hickland, Sivesh Kamarajah, Chris Hoo, Jack Marshall, Kenneth McClean, Rachael Morley, Nisaharan Srikandarajah, Simon Fleming, Nathan Stephens, Alex Ward, Ibrahim Yasin, Tariq Yasin, Dion Morton, Jane Blazeby, Tom Pinkney, Amar Rangan, Simon Bach, Adam Williams
Journal: International Journal of Surgery (2017)
Abstract 9315: Regional Heterogeneity of Systolic Dysfunction Leads to Ventricular Dyssynchrony in Patients with Idiopathic Dilated Cardiomyopathy and Narrow QRS Complex; 3-Dimensional Speckle-Tracking Strain Analysis
Authors: kensuke matsumoto, Hidekazu Tanaka, Tatsuya Miyoshi, Mana Hiraishi, Akihiro Kaneko, Takayuki Tsuji, Kohei Yamawaki, Keiko Ryo, Yuko Fukuda, Kazuko Norisada, Kazuhiro Tatsumi, Tetsuari Ohnishi, Hiroya Kawai, Ken-ichi Hirata
Journal: Circulation (2011)

Background: Although left ventricular (LV) mechanical dyssynchrony is commonly observed in patients with wide QRS complex, some patients with a relatively narrow QRS complex also present with significant mechanical dyssynchrony. Moreover, regional heterogeneity of LV contraction, known as dyssynergy, in idiopathic dilated cardiomyopathy (IDC) patients has been previously reported, but no comprehensive analysis of this abnormality has been made nor is its association with LV dyssynchrony fully understood. The objective was to test, by means of novel 3-dimensional (3-D) speckle-tracking strain, the hypothesis that regional heterogeneity of myocardial systolic dysfunction is associated with LV dyssynchrony. Methods: We studied 54 consecutive IDC patients with ejection fraction (EF) of 34±12% and QRS duration of 102±13ms (all&lt;120ms), and 30 age-matched normal controls. The 3-D speckle-tracking LV dyssynchrony (LV dyssynchrony index) was quantified from all 16 LV sites to determine the standard deviation of time-to-peak strain. Similarly, regional heterogeneity of LV systolic function (LV dyssynergy index) was quantified from all 16 LV sites to establish the standard deviation of peak 3-D speckle-tracking strain. Results: The LV dyssynergy and dyssynchrony indices of IDC patients were significantly larger than those of normal controls (10.8±2.2 vs. 8.3±1.5%, and 81±39 vs. 24±8 ms, respectively, p&lt;0.001). Furthermore, IDC patients showed significantly higher Z-scores for septum and inferior regions than for the free wall (3.34±1.21 vs. 1.69±1.06, and 2.79±1.30 vs. 1.69±1.06, respectively, p&lt;0.001). An important findings of multivariable analysis was that the LV dyssynergy index (β=0.70, p&lt;0.001) and LVEF (β=-0.34, p=0.001) were independent determinants of the LV dyssynchrony index. Conclusions: 3-D speckle-tracking strain revealed that the myocardial systolic dysfunction of IDC patients with a narrow QRS complex has a consistent and marked heterogeneous regional distribution. This regional heterogeneity as well as systolic dysfunction is thought to lead to LV dyssynchrony. The study presented here offers new insights into LV dyssynergy and dyssynchrony.
Dynamic Prognostic Score to Predict Kidney Allograft Survival in Patients with Antibody-Mediated Rejection
Authors: Denis Viglietti, Alexandre Loupy, Olivier Aubert, Oriol Bestard, Jean-Paul Duong Van Huyen, Jean-Luc Taupin, Denis Glotz, Christophe Legendre, Xavier Jouven, Michel Delahousse, Nassim Kamar, Carmen Lefaucheur
Journal: Journal of the American Society of Nephrology (2017)

No tool is available for the early assessment of response to antibody-mediated rejection (ABMR) therapies in kidney allograft recipients. This study was designed to define a dynamic composite prognostic ABMR score to predict kidney allograft survival, integrating the disease characteristics at diagnosis and the response to treatment. Among 1978 kidney recipients who underwent transplant between 2008 and 2014, we included 278 patients diagnosed with active ABMR and receiving standard treatment, including plasma exchange, intravenous Ig, and rituximab. Patients were prospectively assessed at diagnosis and after treatment for clinical data, histologic characteristics (allograft biopsy specimen), and donor-specific anti-HLA antibodies (DSA). The dynamic ABMR prediction model included GFR (
The Hajj: communicable and non-communicable health hazards and current guidance for pilgrims
Authors: Z A Memish
Journal: Eurosurveillance (2010)

The Hajj has become the epicenter of mass migration of millions of Muslims of enormous ethnic diversity. No other mass gathering can compare, either in scale or in regularity. Communicable disease outbreaks of various infectious diseases have been reported repeatedly, during and following the Hajj. The Hajj 2010 starts in the first week of November 2010 and this report is a timely reminder that many infectious diseases can be avoided or averted by adopting appropriate prophylactic measures.
Inositol Polyphosphate Multikinase Inhibits Angiogenesis via Inositol Pentakisphosphate-Induced HIF-1α Degradation
Authors: Chenglai Fu, Richa Tyagi, Alfred C. Chin, Tomas Rojas, Ruo-Jing Li, Prasun Guha, Isaac A. Bernstein, Feng Rao, Risheng Xu, Jiyoung Y. Cha, Jing Xu, Adele M. Snowman, Gregg L. Semenza, Solomon H. Snyder
Journal: Circulation Research (2017)

Inositol polyphosphate multikinase (IPMK) and its major product inositol pentakisphosphate (IP5) regulate a variety of cellular functions, but their role in vascular biology remains unexplored.We have investigated the role of IPMK in regulating angiogenesis.Deletion of IPMK in fibroblasts induces angiogenesis in both in vitro and in vivo models. IPMK deletion elicits a substantial increase of VEGF (vascular endothelial growth factor), which mediates the regulation of angiogenesis by IPMK. The regulation of VEGF by IPMK requires its catalytic activity. IPMK is predominantly nuclear and regulates gene transcription. However, IPMK does not apparently serve as a transcription factor for VEGF. HIF (hypoxia-inducible factor)-1α is a major determinant of angiogenesis and induces VEGF transcription. IPMK deletion elicits a major enrichment of HIF-1α protein and thus VEGF. HIF-1α is constitutively ubiquitinated by pVHL (von Hippel-Lindau protein) followed by proteasomal degradation under normal conditions. However, HIF-1α is not recognized and ubiquitinated by pVHL in IPMK KO (knockout) cells. IP5 reinstates the interaction of HIF-1α and pVHL. HIF-1α prolyl hydroxylation, which is prerequisite for pVHL recognition, is interrupted in IPMK-deleted cells. IP5 promotes HIF-1α prolyl hydroxylation and thus pVHL-dependent degradation of HIF-1α. Deletion of IPMK in mouse brain increases HIF-1α/VEGF levels and vascularization. The increased VEGF in IPMK KO disrupts blood-brain barrier and enhances brain blood vessel permeability.IPMK, via its product IP5, negatively regulates angiogenesis by inhibiting VEGF expression. IP5 acts by enhancing HIF-1α hydroxylation and thus pVHL-dependent degradation of HIF-1α.
Integrated Bayesian analysis of rare exonic variants to identify risk genes for schizophrenia and neurodevelopmental disorders
Authors: Hoang T. Nguyen, Julien Bryois, April Kim, Amanda Dobbyn, Laura M. Huckins, Ana B. Munoz-Manchado, Douglas M. Ruderfer, Giulio Genovese, Menachem Fromer, Xinyi Xu, Dalila Pinto, Sten Linnarsson, Matthijs Verhage, August B. Smit, Jens Hjerling-Leffler, Joseph D. Buxbaum, Christina Hultman, Pamela Sklar, Shaun M. Purcell, Kasper Lage, Xin He, Patrick F. Sullivan, Eli A. Stahl
Journal: Genome Medicine (2017)

Integrating rare variation from trio family and case-control studies has successfully implicated specific genes contributing to risk of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASD), intellectual disability (ID), developmental disorders (DDs), and epilepsy (EPI). For schizophrenia (SCZ), however, while sets of genes have been implicated through the study of rare variation, only two risk genes have been identified.We used hierarchical Bayesian modeling of rare-variant genetic architecture to estimate mean effect sizes and risk-gene proportions, analyzing the largest available collection of whole exome sequence data for SCZ (1,077 trios, 6,699 cases, and 13,028 controls), and data for four NDDs (ASD, ID, DD, and EPI; total 10,792 trios, and 4,058 cases and controls).For SCZ, we estimate there are 1,551 risk genes. There are more risk genes and they have weaker effects than for NDDs. We provide power analyses to predict the number of risk-gene discoveries as more data become available. We confirm and augment prior risk gene and gene set enrichment results for SCZ and NDDs. In particular, we detected 98 new DD risk genes at FDR < 0.05. Correlations of risk-gene posterior probabilities are high across four NDDs (ρ>0.55), but low between SCZ and the NDDs (ρ<0.3). An in-depth analysis of 288 NDD genes shows there is highly significant protein-protein interaction (PPI) network connectivity, and functionally distinct PPI subnetworks based on pathway enrichment, single-cell RNA-seq cell types, and multi-region developmental brain RNA-seq.We have extended a pipeline used in ASD studies and applied it to infer rare genetic parameters for SCZ and four NDDs ( https://github.com/hoangtn/extTADA ). We find many new DD risk genes, supported by gene set enrichment and PPI network connectivity analyses. We find greater similarity among NDDs than between NDDs and SCZ. NDD gene subnetworks are implicated in postnatally expressed presynaptic and postsynaptic genes, and for transcriptional and post-transcriptional gene regulation in prenatal neural progenitor and stem cells.
Ataluren‐driven restoration of Shwachman‐Bodian‐Diamond syndrome protein function in Shwachman‐Diamond syndrome bone marrow cells
Authors: Valentino Bezzerri, Donatella Bardelli, Jacopo Morini, Antonio Vella, Simone Cesaro, Claudio Sorio, Andrea Biondi, Cesare Danesino, Piero Farruggia, Baroukh Maurice Assael, Giovanna D'amico, Marco Cipolli
Journal: American Journal of Hematology (2017)

Abstract Shwachman‐Diamond syndrome (SDS) is a rare inherited recessive disease mainly caused by mutations in the Shwachman‐Bodian‐Diamond syndrome ( SBDS ) gene, which encodes for the homonymous protein SBDS, whose function still remains to be fully established. SDS affects several organs causing bone marrow failure, exocrine pancreatic insufficiency, skeletal malformations, and cognitive disorders. About 15% of SDS patients develop myelodysplastic syndrome (MDS) and are at higher risk of developing acute myeloid leukemia (AML). Deficiency in SBDS expression has been associated with increased apoptosis and lack of myeloid differentiation in bone marrow hematopoietic progenitors. Importantly, most SDS patients carry nonsense mutations in SBDS . Since ataluren is a well‐characterized small molecule inhibitor that can suppress nonsense mutations, here, we have assessed the efficacy of this drug in restoring SBDS expression in hematopoietic cells obtained from a cohort of SDS patients. Remarkably, we show that ataluren treatment readily restores SBDS protein expression in different cell types, particularly bone marrow stem cells. Furthermore, ataluren promotes myeloid differentiation in hematopoietic progenitors, reduces apoptotic rate in primary PBMCs, and brings mammalian target of rapamycin phosphorylation levels back to normal in both lymphoblasts and bone marrow mesenchymal stromal cells (BM‐MSCs). Since a specific therapy against SDS is currently lacking, these results provide the rationale for ataluren repurposing clinical trials.
Urinary infections are complex and hard to treat
Authors: James Malone-Lee
Journal: BMJ (2017)

Kronenberg and colleagues find that a quinolone beats a non-steroidal anti-inflammatory drug at treating dipstick positive urinary tract infections (UTIs).1 Why are we testing this? We have vastly more serious problems.

Culture of 103-106 colony forming units per µl of a pathogen is insensitive,2 and dipsticks are even worse.3 Dismissing UTI on dipstick or culture data confuses “no …
Efficacy of anti-programmed cell death-1 immunotherapy for skin carcinomas and melanoma metastases in a patient with xeroderma pigmentosum
Authors: G. Salomon, A. Maza, S. Boulinguez, C. Paul, L. Lamant, E. Tournier, J. Mazereeuw-Hautier, N. Meyer
Journal: British Journal of Dermatology (2017)

Xeroderma pigmentosum (XP) is an orphan disease of poor prognosis. We report one case of parallel efficacy with anti-programmed cell death-1 (PD-1) antibody on both melanoma and skin carcinoma in a patient with XP. A 17-year-old patient presented with metastatic melanoma and multiple nonmelanoma skin cancers. He was treated with pembrolizumab, a monoclonal anti-PD-1 antibody, at a dose of 2 mg kg-1 , every 3 weeks. Parallel therapeutic efficacy of anti-PD-1 was observed in metastatic melanoma and skin carcinomas, and maintained at week 24. This observation suggests anti-PD-1 may be considered in patients with XP and metastatic melanoma in addition to advanced nonmelanoma skin cancer.
Economic Impact Associated with a Reduction in Surgical Eligibility among Adult Patients with Chronic Rhinosinusitis - A Population Cost Offset Model
Authors: Nate J. Smith, Fulton F. Velez, Emmanuel M. Mahlis, Joseph J. Medicis, John C. Messina, Rachel A. Beckerman, Joseph Gricar, Ramy A. Mahmoud
Journal: Journal of Allergy and Clinical Immunology (2018)
Prediction of cardiovascular events in statin-treated patients by lipid and non-lipid biomarkers (Retraction of vol 57, pg 63, 2011)
Authors: Benoit J. Arsenault, Philip Barter, David A. Demicco, Weihang Bao, Gregory M. Preston, John C. LaRosa, Scott M. Grundy, Prakash Deedwania, Heiner Greten, Nanette K. Wenger, James Shepherd, David D. Waters, John J. P. Kastelein
Journal: Journal of the American College of Cardiology (2013)
Abstract 13592: Contribution of Peripheral versus Central a7-Nicotinic Acetylcholine Receptors to Cardio-protective Effects of Donepezil in Chronic Heart Failure Rats
Authors: Meihua Li, Can Zheng, Toru Kawada, Masashi Inagaki, Uemura Kazunori, Masaru Sugimachi
Journal: Circulation (2012)

Introduction:  Parasympathetic activation by donepezil, a cholinesterase inhibitor, improves prognosis in chronic heart failure (CHF) rats, but its mechanisms remain unclear. a7-nicotinic acetylcholine receptors (a7-nAChR) reportedly play an important role in inflammation and angiogenesis. This study examined if blockade of a7-nAChR either centrally or peripherally cancels the beneficial effect of donepezil on CHF rats.   Methods:  One week after extensive (48±4%) myocardial infarction (MI), survived rats were implanted with an ECG transmitter for monitoring heart rate. Seven days after surgery, these MI rats (n=57) were all treated with donepezil (5 mg/kg/day) and were randomly assigned to the following 4 groups: central (a7BDT) or peripheral (a7PDT) infusion of a7-nAChR blocker (methyllcaconitine), and central (SBDT) or peripheral (SPDT) infusion of vehicle. After 4 weeks treatment, the role of a7-nACR was evaluated by means of hemodynamic parameters, neurohumoral states, and histological examination.   Results:  In central infusion groups, a7BDT (vs. SBDT) showed no changes in either cardiac remodeling (2.90±0.19 vs. 2.87±0.18 g/kg) or hemodynamics (cardiac index 111±28 vs. 111±31 ml/min/kg; LVEDP 25±13 vs. 28±7 mmHg; dp/dtmax 3811±579 vs. 3981±647 mmHg/s). In contrast, in peripheral infusion groups, a7PDT (vs. SPDT) had significantly higher heart weight and cardiac fibrosis (3.02±0.28 vs. 2.74±0.24 g/kg, p   Conclusions:  Peripheral blockade of a7-nAChR significantly erases the cardio-protective effects of donepezil in CHF rats, while central blockade does not; suggesting peripheral activation of a7-nAChR plays an important role in cholinergic pharmacotherapy for severe CHF with extensive MI.
Correction to: 2017 American Heart Association Focused Update on Adult Basic Life Support and Cardiopulmonary Resuscitation Quality: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Journal: Circulation (2017)

several corrections were needed.1. On page e9, right column, under the heading "2017 Recommendations-Updated," in recommendation 1, the following items have been updated:• The beginning of the first sentence read, "We recommend...." It has been updated to, "It is reasonable...." The sentence now reads, "It is reasonable that before placement of an advanced airway (supraglottic airway or tracheal tube), EMS providers perform CPR with cycles of 30 compressions and 2 breaths (Class IIa; Level of Evidence B-R)." • The second sentence has been deleted.It read, "As an alternative, it is reasonable for EMS providers to perform CPR in cycles of 30 compressions with 2 breaths without interrupting chest compressions to give breaths (Class IIa; Level of Evidence B-R)." 2. On page e10, top of the left column, second line, in the continuation of recommendation 1, "Level of Evidence C-LD" was updated to "Level of Evidence B-R." 3. On page e10, right column, in the table titled "2017 Focused Update: Adult BLS Recommendations," the following have been updated:• In row 5, in the "Recommendation" column, "We recommend" has been changed to "It is reasonable."• Row 6 has been deleted.It appeared as:• In updated row 6, in the "Recommendation" column, the Level of Evidence has been changed from "C-LD" to "B-R."It now reads, "(Class IIb; Level of Evidence B-R).
Hyperphosphorylation of Cdc25C may lead to radiation-induced mitotic catastrophe in the human non-small cell lung cancer cell line HCC2279.
Authors: Elisabeth Kodym, Reinhard Kodym, Aktar Ali, Michael D. Story, Hak Choy, Debabrata Saha
Journal: Cancer Research (2006)

5174   Purpose: The human non-small cell lung cancer cell line HCC2279 derived from a primary adeno-squamous tumor exclusively undergoes radiation-induced mitotic catastrophe. The purpose of the study is to elucidate the underlying mechanism of the observed phenomenon. Methods: Mitotic catastrophe was scored morphologically after staining the nuclear DNA with Hoechst 33342. Immunoblot analyses were performed to analyze the cell cycle checkpoint functions in this cell line at different time-points after exposure to 10Gy ionizing radiation. Subcellular localization of Cdc25A and Cdc25C were analyzed by immunofluorescence. Results: (i) In HCC2279 cells, radiation caused measurable mitotic catastrophe at doses as low as 4Gy. About 30% of the cells were found to undergo mitotic catastrophe 48h after exposure to a dose of 10Gy. We observed mitotic catastrophe as early as 24h after 10Gy.(ii) Cdc25A was found to be transiently phosphorylated in this cell line in response to radiation. This phosphorylation was detected at 1h, reached maximum at 2h and disappeared at 8h after radiation. (iii) In contrast, Cdc25C was found to be constitutively phosphorylated (Ser216) and localized in the cytoplasm. Conclusion: (i) Our results suggest that the transient phosphorylation of Cdc25A indicates a functional radiation-induced G2/M checkpoint in this cell line. (ii) Our results also demonstrated that the observed mitotic catastrophe is possibly due to the functional inactivation of Cdc25C leading to a lack of maintenance of radiation-induced G2/M arrest. We are currently investigating the potential kinases that are responsible for the constitutive phosphorylation of Cdc25C in this cell line.