bluuebunny/crossref_metadata_2025_split huggingface dataset:
KAP1 Is a Host Restriction Factor That Promotes Human Adenovirus E1B-55K SUMO Modification
Authors: Bürck Carolin , Mund Andreas , Berscheminski Julia , Kieweg Lisa , Müncheberg Sarah , Dobner Thomas , Schreiner Sabrina 
Published: November 2015

ABSTRACT
Once transported to the replication sites, human adenoviruses (HAdVs) need to ensure decondensation and transcriptional activation of their viral genomes to synthesize viral proteins and initiate steps to reprogram the host cell for viral replication. These early stages during adenoviral infection are poorly characterized but represent a decisive moment in the establishment of a productive infection. Here, we identify a novel host viral restriction factor, KAP1. This heterochromatin-associated transcription factor regulates the dynamic organization of the host chromatin structure via its ability to influence epigenetic marks and chromatin compaction. In response to DNA damage, KAP1 is phosphorylated and functionally inactive, resulting in chromatin relaxation. We discovered that KAP1 posttranslational modification is dramatically altered during HAdV infection to limit the antiviral capacity of this host restriction factor, which represents an essential step required for efficient viral replication. Conversely, we also observed during infection an HAdV-mediated decrease of KAP1 SUMO moieties, known to promote chromatin decondensation events. Based on our findings, we provide evidence that HAdV induces KAP1 deSUMOylation to minimize epigenetic gene silencing and to promote SUMO modification of E1B-55K by a so far unknown mechanism.

IMPORTANCE
Here we describe a novel cellular restriction factor for human adenovirus (HAdV) that sheds light on very early modulation processes in viral infection. We reported that chromatin formation and cellular SWI/SNF chromatin remodeling play key roles in HAdV transcriptional regulation. We observed that the cellular chromatin-associated factor and epigenetic reader SPOC1 represses HAdV infection and gene expression. Here, we illustrate the role of the SPOC1-interacting factor KAP1 during productive HAdV growth. KAP1 binds to the viral E1B-55K protein, promoting its SUMO modification, therefore illustrating a crucial step for efficient viral replication. Simultaneously, KAP1 posttranslational modification is dramatically altered during infection. We observed an HAdV-mediated decrease in KAP1 SUMOylation, known to promote chromatin decondensation events. These findings indicate that HAdV induces the loss of KAP1 SUMOylation to minimize epigenetic gene silencing and to promote the SUMO modification of E1B-55K by a so far unknown mechanism.
Identifying Novel Biomarkers for Cardiovascular Events or Death in People With Dysglycemia
Authors: Gerstein Hertzel C. , Paré Guillaume , McQueen Matthew J. , Haenel Heinz , Lee Shun Fu , Pogue Janice , Maggioni Aldo P. , Yusuf Salim , Hess Sibylle 
Published: October 2015

Background—
Serum biomarkers may identify people at risk for cardiovascular (CV) outcomes. Biobanked serum samples from 8494 participants with dysglycemia in the completed Outcome Reduction With Initial Glargine Intervention trial were assayed for 284 biomarkers to identify those that could identify people at risk for a CV outcome or death when added to clinical measurements.

Methods and Results—

A multiplex analysis measured a panel of cardiometabolic biomarkers in 1 mL of stored frozen serum from every participant who provided biobanked blood. After eliminating undetectable or unanalyzable biomarkers, 8401 participants who each had a set of 237 biomarkers were analyzed. Forward-selection Cox regression models were used to identify biomarkers that were each independent determinants of 3 different incident outcomes: (1) the composite of myocardial infarction, stroke, or CV death; (2) these plus heart failure hospitalization or revascularization; and (3) all-cause death. When added to clinical variables, 10 biomarkers were independent determinants of the 1405 CV composite outcomes observed during follow-up; 9 biomarkers (including 8 of these 10) were independent determinants of the 2435 expanded composite outcomes; and 15 (including the 10 CV composite biomarkers) were independent determinants of the 1340 deaths. Adjusted C statistics increased from 0.64 for the clinical variables to 0.71 and 0.68 for the 2 CV composite outcomes, respectively, with the greatest increase to 0.75 for death (
P
<0.001 for the change).

Conclusions—
A systematic hypothesis-free approach identified combinations of up to 15 cardiometabolic biomarkers as independent determinants of CV outcomes or death in people with dysglycemia.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00069784.
Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood–Brain Barrier Integrity and Central Nervous System Homeostasis
Authors: Tran Khiem A. , Zhang Xianming , Predescu Dan , Huang Xiaojia , Machado Roberto F. , Göthert Joachim R. , Malik Asrar B. , Valyi-Nagy Tibor , Zhao You-Yang 
Published: November 2015

Background—
The blood–brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB.

Methods and Results—

Using a mouse model with tamoxifen-inducible endothelial cell–restricted disruption of
ctnnb1
(
iCKO
), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The
iCKO
mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients.

Conclusions—
These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation.
Study of Cardiovascular Health Outcomes in the Era of Claims Data
Authors: Psaty Bruce M. , Delaney Joseph A. , Arnold Alice M. , Curtis Lesley H. , Fitzpatrick Annette L. , Heckbert Susan R. , McKnight Barbara , Ives Diane , Gottdiener John S. , Kuller Lewis H. , Longstreth W.T. 
Published: November 2015

Background—
Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes.

Methods and Results—

Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure were defined in 3 ways: the CHS adjudicated event (CHS[adj]), selected
International Classification of Diseases, Ninth Edition
diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare & Medicaid Services (CMS[1st]), and the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values but low sensitivities. For instance, the positive predictive value of
International Classification of Diseases, Ninth Edition
code 410.x1 for a new acute MI in the first position was 90.6%, but this code identified only 53.8% of incident MIs. The observed event rates for CMS[1st] were low. For MI, the incidence was 14.9 events per 1000 person-years for CHS[adj] MI, 8.6 for CMS[1st] MI, and 12.2 for CMS[any] MI. In general, cardiovascular disease risk factor associations were similar across the 3 methods of defining events. Indeed, traditional cardiovascular disease risk factors were also associated with all first hospitalizations not resulting from an MI.

Conclusions—
The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite end point that includes the outcome of interest and selected (misclassified) nonevent hospitalizations.
Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures in Patients With Congenital Heart Disease
Authors: Beauséjour Ladouceur Virginie , Lawler Patrick R. , Gurvitz Michelle , Pilote Louise , Eisenberg Mark J. , Ionescu-Ittu Raluca , Guo Liming , Marelli Ariane J. 
Published: November 2015

Background—
The burden of low-dose ionizing radiation (LDIR) exposure from medical procedures among individuals with congenital heart disease (CHD) is unknown. In this longitudinal population-based study, we sought to determine exposure to LDIR-related cardiac imaging and therapeutic procedures in children and adults with CHD.

Methods and Results—

In an analysis of the Quebec CHD database, exposure to the following LDIR-related cardiac procedures was recorded: catheter-based diagnostic procedures, structural heart interventions, coronary interventions, computed tomography scans of the chest, nuclear procedures, and pacemaker/implantable cardioverter-defibrillator insertion and repair. From 1990 to 2005, there were 16 253 LDIR-exposed patients with CHD with 317 988 patient-years of available follow-up. The total number of LDIR-related procedures increased from 18.5 to 51.9 per 1000 CHD patients per year (
P
<0.0001). This increase was attributable to increases in rates per 1000 CHD patients in diagnostic cardiac catheterizations (11.7 to 13.7 per 1000), structural heart interventions (1.0 to 5.2 per 1000), coronary interventions (1.0 to 2.4 per 1000), pacemaker/implantable cardioverter-defibrillator insertions (1.6 to 4.4 per 1000), nuclear procedures (4.2 to 13.8 per 1000), and computed tomography scans of the chest (2.5 to 12.3 per 1000). Over time, among children with CHD, the median age at first LDIR procedure decreased from 5.0 years to 9.6 months. Severity of CHD significantly predicted extent of exposure.

Conclusions—
From 1990 to 2005, patients with CHD were exposed to increasing numbers of LDIR-emitting cardiac procedures. This exposure occurred at progressively younger ages. These findings provide an important perspective on longitudinal LDIR exposure in this at-risk population.
Slow chlorine releasing compounds: A viable sterilisation method for bioabsorbable nanocomposite biomaterials
Authors: Naderi Naghmeh , Griffin Michelle , Malins Edward , Becer Remzi , Mosahebi Afshin , Whitaker Iain S , Seifalian Alexander M 
Published: November 2015

Objective Selection of the appropriate sterilisation method for biodegradable materials has been a challenging task. Many conventional sterilisation methods are not suitable for the next generation of biomaterials, mainly due to their complex composition, based on nanomaterials, often incorporating bioactive moieties. In this study, we investigate sterilisation efficacy of slow chlorine releasing compound sodium dichloroisocyanurate dihydrate (SDIC) for polyhedral oligomeric silsesquioxane (POSS)-poly(caprolactone urea-urethane) (PCL) scaffolds in comparison with conventional sterilisation methods. Methods POSS-PCL scaffolds were subjected to 70% ethanol, UV, and SDIC sterilisation methods. Samples were immersed in tryptone soya broth (TSB) and thioglycollate medium (THY) and after seven days visually inspected for signs of microbial growth. Bulk and surface properties and molecular weight distribution profiles of the scaffolds after sterilization were investigated using FTIR analysis, surface hydrophilicity, scanning electron microscopy analysis, tensile strength testing, and gel-permeation chromatography (GPC). Adipose-derived stem cells (ADSC) were seeded on the scaffolds and AlamarBlue® viability assay was performed to investigate cell metabolic activity. Confocal imaging of rhodamine phalloidin and Dapi stained ADSC on scaffolds was used to demonstrate cell morphology. Results GPC results showed that autoclaving led to a significant decrease in the molecular weight of POSS-PCL, whereas ethanol caused visible deformation of the polymer 3D structure and UV radiation did not effectively sterilise the scaffolds. AlamarBlue® analysis showed metabolic activity close to that of tissue culture plastic for ethanol and SDIC. Conclusion SDIC sterilisation can be safely applied to biodegradable scaffolds unsuitable for the more common sterilisation methods.
Perceived Benefit of Teaching Patient Safety to Pharmacy Students by Integrating Classroom Teaching With Introductory (IPPE) Visits
Authors: Trinkley Katy E. , Van Matre Edward T. , Mueller Scott W. , Page Robert L. , Nair Kavita 
Published: October 2015

Introduction: Ensuring a culture that prioritizes and implements patient safety requires educating all future health care professionals to prepare them for their active role in reducing medical errors. There is limited literature describing integration of patient safety education into the curriculum of health care professionals, including pharmacists. The purpose of this study was to evaluate the perceived benefit of integrating patient safety education into a pharmacy curriculum. Methods: Second-year pharmacy students (P2s) completed a patient safety self-study, followed by in-class and experiential application of a root cause analysis (RCA). An electronic, anonymous postsurvey was administered to P2s and third-year pharmacy students (P3s) who had not had formal patient safety education. Results: Of the 310 students, 53% responded to the survey. Significantly more P2s reported more confidence to describe patient safety and its purpose ( P = .0092), describe factors that influence patient safety ( P = .0055), and conduct an RCA ( P < .001). P2s also reported significantly better ability to conduct a RCA compared to P3s (88.9% positive vs 58.7%, respectively; P ≤ .001). Conclusions: Both classes perceived patient safety education to be valuable; however, formal education resulted in some significant improvements in perceived confidence and understanding, including ability to conduct an RCA.
Parents with Borderline Personality Disorder – approaches to early intervention
Authors: Newman Louise 
Published: November 2015

Objective: This paper aims to describe the issues confronting parents with a history of attachment-related trauma and Borderline Personality Disorder (BPD) and outline contemporary approaches to intervention. Method: The paper discusses recent reviews of parenting and BPD and outlines recent clinical developments. Result: BPD raises significant challenges for parents, with potential adverse impact on infant attachment and development. Conclusion: Approaches to early intervention should focus on improving the parental capacity as an attachment figure and their sensitivity to infant emotional communication.
Long-Term Intrathecal Analgesia With a Wireless Analgesia Pump System in the Home Care of Patients With Advanced Cancer
Authors: Liu Hong-jun , Li Wei-yan , Chen Hao-fei , Cheng Zhu-qiang , Jin Yi 
Published: November 2015

Background: Intrathecal analgesia is more effective than conservative delivery methods such as drugs administered orally or intravenously. Programmable devices such as Medtronic’s SynchroMed systems have often been applied for long-term intrathecal analgesia. However, the totally implanted systems are very expensive in China. Considering cost-effectiveness, a reliable transmission protocol for a ZigBee-Based wireless analgesia pump system was used for long-term intrathecal analgesia in the home care of patients. Methods: We retrospectively investigated the efficacy, side effects, and complications of long-term intrathecal analgesia in the home care of patients via the wireless analgesia pump system. Follow-up visits occurred monthly for the initial 3 months after implantation and then every 3 months until patient death, withdrawal from the study, or removal of the device by a designated staff. At each follow-up visit, daily average pain score, pain frequency, satisfaction level, Spitzer Quality of Life Index, and side effects for every patient were recorded. Results: Pain intensity and frequency were significantly decreased by intrathecal analgesia via a wireless analgesia pump system. There were no significant differences in the satisfaction levels between hospitalization and each follow-up visit. The Spitzer Quality of Life Indexes were improved compared with patients who were hospitalized. No serious side effects were observed in this study. Conclusion: Intrathecal analgesia is an effective and safe method for control of refractory cancer pain, and wireless analgesia pump systems can be safely and effectively used for long-term intrathecal analgesia management in the home care of patients with advanced cancer.
Association between apolipoprotein B gene polymorphisms and the risk of coronary heart disease (CHD): an update meta-analysis
Authors: Zhang Jing-Zhan , Zheng Ying-Ying , Yang Yi-Ning , Li Xiao-Mei , Fu Zhen-Yan , Dai Chuan-Fang , Liu Fen , Chen Bang-Dang , Gai Min-Tao , Ma Yi-Tong , Xie Xiang 
Published: November 2015

Objective: Polymorphisms in the apolipoprotein B ( apoB) gene have been reported to be associated with coronary heart disease (CHD). However, the results on this topic are conflicting. The present study aims to derive a more precise estimation of the relationship between CHD and apoB genetic polymorphisms by meta-analysis. Methods: We identified a total of 54 studies involving 7236, 10,912, and 14,102 individuals, respectively, for EcoRI, XbaI, and SpIns/Del polymorphisms by searching in PubMed, Web of Science, Google Scholar, the Cochrane Library, Wanfang Data, SinoMed, and CNKI. We utilized RevMan 5.0 software to perform the meta-analyses. Results: A significant statistical association between apoB EcoRI polymorphism and CHD was observed under an allelic ( p = 0.001, odds ratio (OR) = 1.33, 95% confidence interval (CI) = 1.12–1.57), dominant ( p = 0.005, OR = 1.22, 95% CI = 1.06–1.40), and recessive ( p = 0.04, OR = 1.33, 95% CI = 1.01–1.74) model. We also found similar association of apoB SpIns/Del polymorphism with CHD. However, we did not find association between apoB XbaI polymorphism and CHD. Conclusion: The current meta-analysis found an association of EcoRI polymorphism and SpIns/Del polymorphism with an increased risk of CHD. No significant association between apoB XbaI polymorphism and CHD we observed in the present study.
Predictors of thrombotic complications and mass effect exacerbation after pipeline embolization: The significance of adenosine diphosphate inhibition, fluoroscopy time, and aneurysm size
Authors: Raychev Radoslav , Tateshima Satoshi , Vinuela Fernando , Sayre Jim , Jahan Reza , Gonzalez Nestor , Szeder Viktor , Duckwiler Gary 
Published: November 2015

Background The mechanisms leading to delayed rupture, distal emboli and intraparenchymal hemorrhage in relation to pipeline embolization device (PED) placement remain debatable and poorly understood. The aim of this study was to identify clinical and procedural predictors of these perioperative complications. Methods We conducted a retrospective review of consecutive patients who underwent PED placement. We utilized a non-commercial platelet aggregation method measuring adenosine diphosphate (ADP)% inhibition for evaluation of clopidogrel response. To our knowledge, this is the first study to test ADP in neurovascular procedures. Multivariable regression analysis was used to identify the strongest predictor of three separate outcomes: (1) thrombotic complications, (2) hemorrhagic complications, and (3) aneurysm mass effect exacerbation Results Permanent complication-related morbidity and mortality at 3 months was 6% (3/48). No specific predictors of hemorrhagic complications were identified. In the univariate analysis, the strongest predictors of thrombotic complications were: ADP % inhibition <49 ( p = 0.01), aneurysm size ( p = 0.04) and fluoroscopy time ( p = 0.002). In the final multivariate analysis, among all baseline variables, fluoroscopy time exceeding 52 min was the only factor associated with thrombotic complications ( p = 0.007). Aneurysm size ≥18 mm was the single predictor of mass effect exacerbation ( p = 0.039). Conclusions Procedural complexity, reflected by fluoroscopy time, is the strongest predictor of thrombotic complications in this study. ADP% inhibition is a reliable method of testing clopidogrel response in neurovascular procedures and values of <50% may predict thrombotic complications. Interval mass effect exacerbation after PED placement may be anticipated in large aneurysms exceeding 18 mm.
Successful embolization and long-term follow-up of a rare neonatal diaphragmatic hemangioma
Authors: Wu Lin , Wang Ji Mei , Qiao Zhong Wei , Yan Ying Liu , Wang Lai Shuan 
Published: November 2015

Background: Congenital hemangioma of the diaphragm is an extremely rare disease in childhood. Methods: We report a newborn presenting with progressive respiratory distress and massive right hydrothorax due to congenital diaphragmatic hemangioma, requiring sustained ventilation support and chest drainage. The angiography revealed that the giant diaphragmatic hemangioma was supplied by the right internal thoracic, inferior diaphragmatic, and intercostal arteries. The selective embolization of the main feeding vessels was successfully achieved using the Embosphere particulates. Results: The clinical long-term follow-up demonstrated the resolution of the symptoms, pleural effusion, and nearly complete regression of the hemangioma at 18 months of age. Conclusion: Transcatheter embolization can provide an efficient therapy for symptomatic diaphramatic hemangioma.
Does vaginal estrogen treatment with support pessaries in vaginal prolapse reduce complications?
Authors: Bulchandani Supriya , Toozs-Hobson Philip , Verghese Tina , Latthe Pallavi 
Published: November 2015

Objective Pelvic organ prolapse is often co-existant with atrophy of the genital tract in older women who tend to prefer vaginal pessaries for prolapse. Vaginal estrogen therapy is used by some along with a support pessary for prolapse with no robust evidence to back this practice. We aimed to evaluate differences in complications of support pessaries for vaginal prolapse in postmenopausal women, with and without vaginal estrogen use. Study design We prospectively assessed postmenopausal women attending the urogynaecology clinic for a pessary change. We asked them about the level of discomfort during pessary change (visual analogue scale for pain), discharge, bleeding and infection. Ethics approval was not required as this was a service evaluation project. Statistical analysis for relative risk was performed, including sub-group analysis for ‘ring pessary’ and ‘non-ring group’ (Shelf, Gellhorn, Shaatz). Results Between July 2013 and December 2014, we assessed 120 postmenopausal women using support pessaries for prolapse. The mean age was 70 years; 45% of the patients used vaginal estrogen. There were no statistically significant differences in complications with or without vaginal estrogen use, although the trend was higher amongst non-users. The ‘non-ring’ sub-group not using vaginal estrogen had a higher risk of vaginal ulceration, bleeding and discharge. Conclusion Postmenopausal women may have lesser complications when using vaginal estrogen with a support pessary for prolapse, particularly with pessaries other than the ring. An adequately powered randomised controlled trial is needed to assess conclusively whether vaginal estrogen enhances comfort and reduces complications of support pessaries for prolapse.