bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of renal replacement therapy for diabetic nephropathy in the Netherlands: Dutch diabetes estimates (DUDE)-3
Authors: van Dijk Peter R , Kramer Anneke , Logtenberg Susan J J , Hoitsma Andries J , Kleefstra Nanne , Jager Kitty J , Bilo Henk J G 
Published: January 2015

ObjectivesDescribe the incidence, prevalence and survival of patients needing renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetes mellitus (DM)-related glomerulosclerosis or nephropathy (diabetic nephropathy, DN) in the Netherlands.DesignUsing the national registry for RRT (RENINE-registry), data of all Dutch individuals initiating RRT for ESRD and having DN as primary diagnosis in the period 2000–2012 were obtained.SettingObservational study in the Netherlands.PatientsPatients with ESRD needing RRT for DN.Outcome measurementsAge and gender adjusted incidence and prevalence of RRT for DN in the period 2000–2012. In addition, trends in time and patient's survival were examined.ResultsThe prevalence of DM in the general population increased from approximately 466 000 in 2000 to 815 000 in 2011. The number of individuals who started RRT with DN as primary diagnosis was 17.4 per million population (pmp) in 2000 and 19.1 pmp in 2012, with an annual percentage change (APC) of 0.8% (95% CI −0.4 to 2.0). For RRT due to type 1 DN, the incidence decreased from 7.3 to 3.5 pmp (APC −4.8%, 95% CI −6.5 to −3.1) while it increased for type 2 DN from 10.1 to 15.6 pmp (APC 3.1%, 95% CI 1.3 to 4.8). After 2009, the prevalence of RRT for DN remained stable (APC 1.0%, 95% CI −0.4 to 2.5). Compared to the period 2000–2004, patients initiating RRT and dialysis in 2005–2009 had better survival, HRs 0.8 (95% CI 0.7 to 0.8) and 0.8 (95% CI 0.7 to 0.9), respectively, while survival after kidney transplantation remained stable, HR 0.8, 95% CI 0.5 to 1.1).ConclusionsOver the last decade, the incidence of RRT for DN was stable, with a decrease in RRT due to type 1 DN and an increase due to type 2 DN, while survival increased.
The Dotter method revisited: early experience with a novel method of rapid internal carotid artery revascularization in the setting of acute ischemic stroke
Authors: Woodward Keith , Wegryn Scott , Staruk Carla , Nyberg Eric M 
Published: January 2015

BackgroundTandem occlusive disease in the setting of acute ischemic stroke involving cervical and cerebral arteries has been associated with poor neurological outcome and poses significant challenges to neurointerventionists. Previously described endovascular methods typically involve carotid revascularization with stent placement prior to or following intracranial thrombectomy. Stent-based approaches, however, require the use of antiplatelet therapy which may increase the risk of hemorrhagic transformation. We describe a novel modified Dotter technique which may be used for carotid revascularization in lieu of stenting. This technique can eliminate the need for antiplatelet therapy, reduce procedure times, and possibly reduce hemorrhagic conversion rates.MethodsSeven patients presenting between April 2013 and January 2014 were treated with this technique. All patients had carotid stenosis of 65–100% and tandem middle cerebral artery occlusions. National Institutes of Health (NIH) Stroke Scale scores as well as clinical and procedural times were recorded. Pre- and post-Dotter stenosis was measured using the NASCET criteria. Follow-up imaging and clinical data were reviewed.ResultsThe mean age was 64 years and mean initial NIH Stroke Scale score was 11.7. Mean groin to recanalization time was 26 min. Thrombolysis In Cerebral Infarction grade 2b–3 was achieved in all patients. The mean stenosis was 88% preoperatively and 61% postoperatively. There were no intracranial hemorrhages. The modified Rankin Scale score was 0 in six patients (86%) and 6 in one patient (14%).ConclusionsThe Dotter stroke technique is a feasible and safe alternative to carotid stenting in the setting of acute ischemic stroke and may reduce the risk of hemorrhagic conversion. No re-occlusion occurred during follow-up in patients with post-Dotter stenosis ≤65%.
Rates of local procedural-related structural injury following clipping or coiling of anterior communicating artery aneurysms
Authors: Mortimer Alex M , Steinfort Brendan , Faulder Ken , Erho Tian , Scherman Daniel B , Rao Prashanth J , Harrington Timothy 
Published: February 2015

BackgroundSurgical clipping and endovascular coiling yield similar functional outcomes for the treatment of saccular aneurysms of the anterior communicating (ACOM) artery. However, surgical treatment may be associated with greater rates of cognitive impairment due to injury of adjacent structures. We aimed to quantify the rates of injury (infarction/hemorrhage) for both clipping and coiling of ACOM aneurysms.MethodsThis was a retrospective dual-center radiological investigation of a consecutive series of patients with ruptured and unruptured ACOM aneurysms treated between January 2011 and October 2014. Post-treatment CT or MRI was assessed for new ischemic or hemorrhagic injury. Injury relating to the primary hemorrhage or vasospasm was differentiated. Univariate analysis using χ2tests and multivariate analysis using binary logistic regression was used.Results66 patients treated with clipping were compared with 93 patients treated with coiling. 32/66 (48.5%) patients in the clipping group suffered treatment-related injury (31 ischemic, 1 hemorrhagic) compared with 4/93 (4.4%) patients in the coiling group (3 ischemic, 1 hemorrhagic) (p<0.0001). For patients with subarachnoid hemorrhage, the multivariate OR for infarction for clipping over coiling was 24.42 (95% CI 5.84 to 102.14), p<0.0001. The most common site of infarction was the basal forebrain (28/66 patients, 42.4%), with bilateral infarction in 4. There was injury of the septal/subcallosal region in 12/66 patients (18%).ConclusionsClipping of ACOM aneurysms is associated with significantly higher rates of structural injury than coiling, and this may be a reason for superior cognitive outcomes in patients treated with coiling in previously published studies.
RB and Prognosis in Resected Lung Adenocarcinoma
Authors: Collisson Eric A. 
Published: February 2015

Abstract
The treatment of resected lung adenocarcinoma has ample room for improvement. Can genomic characterization aid us in deciding how and when to apply adjuvant therapy in the smallest resected tumors? Clin Cancer Res; 21(11); 2418–20. ©2015 AACR.
See related article by Choi et al., p. 2613
IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment
Authors: Kinose Yasuto , Sawada Kenjiro , Makino Hiroshi , Ogura Tomonori , Mizuno Tomoko , Suzuki Noriko , Fujikawa Tomoyuki , Morii Eiichi , Nakamura Koji , Sawada Ikuko , Toda Aska , Hashimoto Kae , Isobe Aki , Mabuchi Seiji , Ohta Tsuyoshi , Itai Akiko , Morishige Ken-ichirou , Kurachi Hirohisa , Kimura Tadashi 
Published: January 2015

Abstract
The prolongation of progression-free survival (PFS) in patients with advanced ovarian cancer by antiangiogenic therapy has been shown in several clinical trials. However, although an anti-VEGF antibody (bevacizumab) is the only option currently available, its efficacy is limited and it is not cost effective for use in all patients. Therefore, the development of a novel antiangiogenic drug, especially composed of small-molecule compounds, could be a powerful armament for ovarian cancer treatment. As NF-κB signaling has the potential to regulate VEGF expression, we determined to identify whether VEGF expression is associated with NF-κB activation and to investigate the possibility of a novel IKKβ inhibitor, IMD-0354 (IMMD Inc.), as an antiangiogenic drug. Tissue microarrays from 94 ovarian cancer tissues were constructed and immunohistochemical analyses performed. We revealed that IKK phosphorylation is an independent prognostic factor (PFS: 26.1 vs. 49.8 months, P = 0.011), and is positively correlated with high VEGF expression. In in vitro analyses, IMD-0354 robustly inhibited adhesive and invasive activities of ovarian cancer cells without impairing cell viabilities. IMD-0354 significantly suppressed VEGF production from cancer cells, which led to the inhibition of angiogenesis. In a xenograft model, the treatment of IMD-0354 significantly inhibited peritoneal dissemination with a marked reduction of intratumoral blood vessel formation followed by the inhibition of VEGF expression from cancer cells. IMD-0354 is a stable small-molecule drug and has already been administered safely to humans in other trials. Antiangiogenic therapy targeting IKKβ is a potential future option to treat ovarian cancer. Mol Cancer Ther; 14(4); 909–19. ©2015 AACR.
Variants of Osteoprotegerin Lacking TRAIL Binding for Therapeutic Bone Remodeling in Osteolytic Malignancies
Authors: Higgs Jerome T. , Jarboe John S. , Lee Joo Hyoung , Chanda Diptiman , Lee Carnellia M. , Deivanayagam Champion , Ponnazhagan Selvarangan 
Published: January 2015

Abstract
Osteolytic bone damage is a major cause of morbidity in several metastatic pathologies. Current therapies using bisphosphonates provide modest improvement, but cytotoxic side effects still occur prompting the need to develop more effective therapies to target aggressive osteoclastogenesis. Increased levels of receptor activator of NF–κB ligand (TNFSF11/RANKL), leading to RANKL-RANK signaling, remain the key axis for osteoclast activation and bone resorption. Osteoprotegerin (TNFRSF11B/OPG), a decoy receptor for RANKL, is significantly decreased in patients who present with bone lesions. Despite its potential in inhibiting osteoclast activation, OPG also binds to TNF-related apoptosis-inducing ligand (TNFSF10/TRAIL), making tumor cells resistant to apoptosis. Toward uncoupling the events of TRAIL binding of OPG and to improve its utility for bone remodeling without inducing tumor resistance to apoptosis, OPG mutants were developed by structural homology modeling based on interactive domain identification and by superimposing models of OPG, TRAIL, and its receptor DR5 (TNFRSF10B) to identify regions of OPG for rational design. The OPG mutants were purified and extensively characterized for their ability to decrease osteoclast damage without affecting tumor apoptosis pathway both in vitro and in vivo, confirming their potential in bone remodeling following cancer-induced osteolytic damage.
Implications: OPG variants were developed that lack TRAIL binding, yet retain RANKL binding and suggest new possibilities for therapeutic targeting in osteolytic malignancies. Mol Cancer Res; 13(5); 819–27. ©2015 AACR.
mTOR/MYC Axis Regulates O-GlcNAc Transferase Expression and O-GlcNAcylation in Breast Cancer
Authors: Sodi Valerie L. , Khaku Sakina , Krutilina Raisa , Schwab Luciana P. , Vocadlo David J. , Seagroves Tiffany N. , Reginato Mauricio J. 
Published: January 2015

Abstract
Cancers exhibit altered metabolism characterized by increased glucose and glutamine uptake. The hexosamine biosynthetic pathway (HBP) uses glucose and glutamine, and directly contributes to O-linked-β-N-acetylglucosamine (O-GlcNAc) modifications on intracellular proteins. Multiple tumor types contain elevated total O-GlcNAcylation, in part, by increasing O-GlcNAc transferase (OGT) levels, the enzyme that catalyzes this modification. Although cancer cells require OGT for oncogenesis, it is not clear how tumor cells regulate OGT expression and O-GlcNAcylation. Here, it is shown that the PI3K–mTOR–MYC signaling pathway is required for elevation of OGT and O-GlcNAcylation in breast cancer cells. Treatment with PI3K and mTOR inhibitors reduced OGT protein expression and decreased levels of overall O-GlcNAcylation. In addition, both AKT and mTOR activation is sufficient to elevate OGT/O-GlcNAcylation. Downstream of mTOR, the oncogenic transcription factor c-MYC is required and sufficient for increased OGT protein expression in an RNA-independent manner and c-MYC regulation of OGT mechanistically requires the expression of c-MYC transcriptional target HSP90A. Finally, mammary tumor epithelial cells derived from MMTV-c-myc transgenic mice contain elevated OGT and O-GlcNAcylation and OGT inhibition in this model induces apoptosis. Thus, OGT and O-GlcNAcylation levels are elevated via activation of an mTOR/MYC cascade.
Implications: Evidence indicates OGT as a therapeutic target in c-MYC–amplified cancers. Mol Cancer Res; 13(5); 923–33. ©2015 AACR.
Radiofrequency Catheter Ablation of Idiopathic Ventricular Arrhythmias Originating From Intramural Foci in the Left Ventricular Outflow Tract
Authors: Yamada Takumi , Maddox William R. , McElderry H. Thomas , Doppalapudi Harish , Plumb Vance J. , Kay G. Neal 
Published: January 2015

Backgrounds—
Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the efficacy of sequential and simultaneous unipolar radiofrequency catheter ablation from the endocardial and epicardial sides in treating intramural LVOT VAs.

Methods and Results—
Fourteen consecutive LVOT VAs, which required sequential or simultaneous irrigated unipolar radiofrequency ablation from the endocardial and epicardial sides for their elimination, were studied. The first ablation was performed at the site with the earliest local ventricular activation and best pace map on the endocardial or epicardial side. When the first ablation was unsuccessful, the second ablation was delivered on the other surface. If this sequential unipolar ablation failed, simultaneous unipolar ablation from both sides was performed. The first ablation was performed on the epicardial side in 9 VAs and endocardial side in 5 VAs. The intramural LVOT VAs were successfully eliminated by the sequential (n=9) or simultaneous (n=5) unipolar catheter ablation. Simultaneous ablation was most likely to be required for the elimination of the VAs when the distance between the endocardial and epicardial ablation sites was >8 mm and the earliest local ventricular activation time relative to the QRS onset during the VAs of <–30 ms was recorded at those ablation sites.

Conclusions—
LVOT VAs originating from intramural foci could usually be eliminated by sequential unipolar radiofrequency ablation and sometimes required simultaneous ablation from both the endocardial and epicardial sides.
Percutaneous Epicardial Ablation of Ventricular Arrhythmias Arising From the Left Ventricular Summit
Authors: Santangeli Pasquale , Marchlinski Francis E. , Zado Erica S. , Benhayon Daniel , Hutchinson Mathew D. , Lin David , Frankel David S. , Riley Michael P. , Supple Gregory E. , Garcia Fermin C. , Bala Rupa , Desjardins Benoit , Callans David J. , Dixit Sanjay 
Published: January 2015

Background—
Percutaneous epicardial ablation of ventricular arrhythmias arising from the left ventricular summit is limited by the presence of major coronary vessels and epicardial fat. We report the outcomes of percutaneous epicardial mapping and ablation of ventricular arrhythmias arising from the left ventricular summit and the ECG features associated with successful ablation.

Methods and Results—

Between January 2003 and December 2012, a total of 23 consecutive patients (49±14 years; 39% men) with ventricular arrhythmias arising from the left ventricular summit underwent percutaneous epicardial instrumentation for mapping and ablation because of unsuccessful ablation from the coronary venous system and multiple endocardial LV/right ventricular sites. Successful epicardial ablation was achieved in 5 (22%) patients. In the remaining 18 (78%) cases, ablation was aborted for either close proximity to major coronary arteries or poor energy delivery over epicardial fat. The Q-wave amplitude ratio in aVL/aVR was higher in the successful group, with a ratio of >1.85 present in 4 (80%) patients in the successful group versus 2 (11%) in the unsuccessful group (
P
=0.008). The ratio of R/S wave in V1 was greater in the successful group, with 4 (80%) patients in the successful group having a R/S ratio of >2 in V1 versus 5 (28%) in the unsuccessful group (
P
=0.056). None of the patients in the successful group had an initial q wave in lead V1, as opposed to 6 (33%) in the unsuccessful group. The presence of at least 2 of the 3 ECG criteria above predicted successful ablation with 100% sensitivity and 72% specificity.

Conclusions—
Epicardial instrumentation for mapping and ablation of ventricular arrhythmias arising from the left ventricular summit is successful only in a minority of patients because of close proximity to major coronary arteries and epicardial fat. A Q-wave ratio of >1.85 in aVL/aVR, a R/S ratio of >2 in V1, and absence of q waves in lead V1 help identify appropriate candidates for epicardial ablation.
Upregulation of MG53 Induces Diabetic Cardiomyopathy Through Transcriptional Activation of Peroxisome Proliferation-Activated Receptor α
Authors: Liu Fenghua , Song Ruisheng , Feng Yuanqing , Guo Jiaojiao , Chen Yanmin , Zhang Yong , Chen Tao , Wang Yanru , Huang Yanyi , Li Chuan-Yun , Cao Chunmei , Zhang Yan , Hu Xinli , Xiao Rui-ping 
Published: January 2015

Background—
Diabetic cardiomyopathy, which contributes to >50% diabetic death, is featured by myocardial lipid accumulation, hypertrophy, fibrosis, and cardiac dysfunction. The mechanism underlying diabetic cardiomyopathy is poorly understood. Recent studies have shown that a striated muscle-specific E3 ligase Mitsugumin 53 (MG53, or TRIM72) constitutes a primary causal factor of systemic insulin resistance and metabolic disorders. Although it is most abundantly expressed in myocardium, the biological and pathological roles of MG53 in triggering cardiac metabolic disorders remain elusive.

Methods and Results—
Here we show that cardiac-specific transgenic expression of MG53 induces diabetic cardiomyopathy in mice. Specifically, MG53 transgenic mouse develops severe diabetic cardiomyopathy at 20 weeks of age, as manifested by insulin resistance, compromised glucose uptake, increased lipid accumulation, myocardial hypertrophy, fibrosis, and cardiac dysfunction. Overexpression of MG53 leads to insulin resistant via destabilizing insulin receptor and insulin receptor substrate 1. More importantly, we identified a novel role of MG53 in transcriptional upregulation of peroxisome proliferation-activated receptor alpha and its target genes, resulting in lipid accumulation and lipid toxicity, thereby contributing to diabetic cardiomyopathy.

Conclusions—
Our results suggest that overexpression of myocardial MG53 is sufficient to induce diabetic cardiomyopathy via dual mechanisms involving upregulation of peroxisome proliferation-activated receptor alpha and impairment of insulin signaling. These findings not only reveal a novel function of MG53 in regulating cardiac peroxisome proliferation-activated receptor alpha gene expression and lipid metabolism, but also underscore MG53 as an important therapeutic target for diabetes mellitus and associated cardiomyopathy.
Myocardial Stiffness in Patients With Heart Failure and a Preserved Ejection Fraction
Authors: Zile Michael R. , Baicu Catalin F. , S. Ikonomidis John , Stroud Robert E. , Nietert Paul J. , Bradshaw Amy D. , Slater Rebecca , Palmer Bradley M. , Van Buren Peter , Meyer Markus , M. Redfield Margaret , A. Bull David , L. Granzier Henk , LeWinter Martin M. 
Published: January 2015

Background—
The purpose of this study was to determine whether patients with heart failure and a preserved ejection fraction (HFpEF) have an increase in passive myocardial stiffness and the extent to which discovered changes depend on changes in extracellular matrix fibrillar collagen and cardiomyocyte titin.

Methods and Results—
Seventy patients undergoing coronary artery bypass grafting underwent an echocardiogram, plasma biomarker determination, and intraoperative left ventricular epicardial anterior wall biopsy. Patients were divided into 3 groups: referent control (n=17, no hypertension or diabetes mellitus), hypertension (HTN) without (–) HFpEF (n=31), and HTN with (+) HFpEF (n=22). One or more of the following studies were performed on the biopsies: passive stiffness measurements to determine total, collagen-dependent and titin-dependent stiffness (differential extraction assay), collagen assays (biochemistry or histology), or titin isoform and phosphorylation assays. In comparison with controls, patients with HTN(–)HFpEF had no change in left ventricular end-diastolic pressure, myocardial passive stiffness, collagen, or titin phosphorylation but had an increase in biomarkers of inflammation (C-reactive protein, soluble ST2, tissue inhibitor of metalloproteinase 1). In comparison with both control and HTN(–)HFpEF, patients with HTN(+)HFpEF had increased left ventricular end-diastolic pressure, left atrial volume, N-terminal propeptide of brain natriuretic peptide, total, collagen-dependent, and titin-dependent stiffness, insoluble collagen, increased titin phosphorylation on PEVK S11878(S26), reduced phosphorylation on N2B S4185(S469), and increased biomarkers of inflammation.

Conclusions—
Hypertension in the absence of HFpEF did not alter passive myocardial stiffness. Patients with HTN(+)HFpEF had a significant increase in passive myocardial stiffness; collagen-dependent and titin-dependent stiffness were increased. These data suggest that the development of HFpEF depends on changes in both collagen and titin homeostasis.
Transcatheter Aortic Valve Implantation in the United Kingdom
Authors: Ludman Peter F. , Moat Neil , de Belder Mark A. , Blackman Daniel J. , Duncan Alison , Banya Winston , MacCarthy Philip A. , Cunningham David , Wendler Olaf , Marlee Damian , Hildick-Smith David , Young Christopher P. , Kovac Jan , Uren Neal G. , Spyt Tomasz , Trivedi Uday , Howell Jonathan , Gray Huon 
Published: January 2015

Background—
We assessed trends in the performance of transcatheter aortic valve implantation in the United Kingdom from the first case in 2007 to the end of 2012. We analyzed changes in case mix, complications, outcomes to 6 years, and predictors of mortality.

Methods and Results—

Annual cohorts were examined. Mortality outcomes were analyzed in the 92% of patients from England and Wales for whom independent mortality tracking was available. A total of 3980 transcatheter aortic valve implantation procedures were performed. In successive years, there was an increase in frequency of impaired left ventricular function, but there was no change in Logistic EuroSCORE. Overall 30-day mortality was 6.3%; it was highest in the first cohort (2007–2008), after which there were no further significant changes. One-year survival was 81.7%, falling to 37.3% at 6 years. Discharge by day 5 rose from 16.7% in 2007 and 2008 to 28% in 2012. The only multivariate preprocedural predictor of 30-day mortality was Logistic EuroSCORE ≥40. During long-term follow-up, multivariate predictors of mortality were preprocedural atrial fibrillation, chronic obstructive pulmonary disease, creatinine >200 μmol/L, diabetes mellitus, and coronary artery disease. The strongest independent procedural predictor of long-term mortality was periprocedural stroke (hazard ratio=3.00;
P
<0.0001). Nonfemoral access and postprocedural aortic regurgitation were also significant predictors of adverse outcome.

Conclusions—
We analyzed transcatheter aortic valve implantation in an entire country, with follow-up over 6 years. Although clinical profiles of enrolled patients remained unchanged, longer-term outcomes improved, and patients were discharged earlier. Periprocedural stroke, nonfemoral access, and postprocedural aortic regurgitation are predictors of adverse outcome, along with intrinsic patient risk factors.