bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implication of Inflammation and Epigenetic Readers in Coronary Artery Remodeling in Patients With Pulmonary Arterial Hypertension
Authors: Meloche Jolyane , Lampron Marie-Claude , Nadeau Valérie , Maltais Mélanie , Potus François , Lambert Caroline , Tremblay Eve , Vitry Géraldine , Breuils-Bonnet Sandra , Boucherat Olivier , Charbonneau Eric , Provencher Steeve , Paulin Roxane , Bonnet Sébastien 
Published: May 2017

Objective—
Pulmonary arterial hypertension (PAH) is a vascular disease not restricted to the lungs. Many signaling pathways described in PAH are also of importance in other vascular remodeling diseases, such as coronary artery disease (CAD). Intriguingly, CAD is 4× more prevalent in PAH compared with the global population, suggesting a link between these 2 diseases. Both PAH and CAD are associated with sustained inflammation and smooth muscle cell proliferation/apoptosis imbalance and we demonstrated in PAH that this phenotype is, in part, because of the miR-223/DNA damage/Poly[ADP-ribose] polymerase 1/miR-204 axis activation and subsequent bromodomain protein 4 (BRD4) overexpression. Interestingly, BRD4 is also a trigger for calcification and remodeling processes, both of which are important in CAD. Thus, we hypothesize that BRD4 activation in PAH influences the development of CAD.

Approach and Results—
PAH was associated with significant remodeling of the coronary arteries in both human and experimental models of the disease. As observed in PAH distal pulmonary arteries, coronary arteries of patients with PAH also exhibited increased DNA damage, inflammation, and BRD4 overexpression. In vitro, using human coronary artery smooth muscle cells from PAH, CAD and non-PAH–non-CAD patients, we showed that both PAH and CAD smooth muscle cells exhibited increased proliferation and suppressed apoptosis in a BRD4-dependent manner. In vivo, improvement of PAH by BRD4 inhibitor was associated with a reduction in coronary remodeling and interleukin-6 expression.

Conclusions—
Overall, this study demonstrates that increased BRD4 expression in coronary arteries of patient with PAH contributes to vascular remodeling and comorbidity development.
The Role of Rough Topography in Mediating Impacts of Bottom Drag in Eddying Ocean Circulation Models
Authors: Trossman David S. , Arbic Brian K. , Straub David N. , Richman James G. , Chassignet Eric P. , Wallcraft Alan J. , Xu Xiaobiao 
Published: May 2017

AbstractMotivated by the substantial sensitivity of eddies in two-layer quasigeostrophic (QG) turbulence models to the strength of bottom drag, this study explores the sensitivity of eddies in more realistic ocean general circulation model (OGCM) simulations to bottom drag strength. The OGCM results are interpreted using previous results from horizontally homogeneous, two-layer, flat-bottom, f-plane, doubly periodic QG turbulence simulations and new results from two-layer, β-plane QG turbulence simulations run in a basin geometry with both flat and rough bottoms. Baroclinicity in all of the simulations varies greatly with drag strength, with weak drag corresponding to more barotropic flow and strong drag corresponding to more baroclinic flow. The sensitivity of the baroclinicity in the QG basin simulations to bottom drag is considerably reduced, however, when rough topography is used in lieu of a flat bottom. Rough topography reduces the sensitivity of the eddy kinetic energy amplitude and horizontal length scales in the QG basin simulations to bottom drag to an even greater degree. The OGCM simulation behavior is qualitatively similar to that in the QG rough-bottom basin simulations, in that baroclinicity is more sensitive to bottom drag strength than are eddy amplitudes or horizontal length scales. Rough topography therefore appears to mediate the sensitivity of eddies in models to the strength of bottom drag. The sensitivity of eddies to parameterized topographic internal lee wave drag, which has recently been introduced into some OGCMs, is also briefly discussed. Wave drag acts like a strong bottom drag in that it increases the baroclinicity of the flow, without strongly affecting eddy horizontal length scales.
Correlations of 18F-FDG and 18F-FLT uptake on PET with Ki-67 expression in patients with lung cancer: a meta-analysis
Authors: Shen Guohua , Ma Huan , Pang Fuwen , Ren Pengwei , Kuang Anren 
Published: May 2017

Background Positron emission tomography (PET) imaging using the radiotracers 18F-fluorodeoxyglucose (FDG) or 18F-fluorothymidine (FLT) has been proposed as imaging biomarkers of cell proliferation. Purpose To explore the correlations of FDG and FLT uptake with the Ki-67 labeling index in patients with lung cancer. Material and Methods Major databases were systematically searched for all relevant literature published in English. The correlation coefficient (rho) and its 95% confidence interval (CI) of individual studies were meta-analyzed using a random-effects model. The sources of heterogeneity were explored by subgroup analyses. Results Twenty-seven articles involving 1213 patients were included in this meta-analysis, comprising 22 studies for FDG uptake/Ki-67 expression correlation and eight for FLT uptake/Ki-67 expression correlation. The pooled rho values for 18F-FDG/Ki-67 correlation and 18F-FLT/Ki-67 correlation were 0.45 (95% CI, 0.41–0.50) and 0.65 (95% CI, 0.56–0.73), respectively, which indicated a moderate correlation for the former and a significant one for the latter. Although the subgroup analyses based on study design, scanner, sample method, and Ki-67 labeling method did not significantly explain the heterogeneity, these factors were potential sources of heterogeneity. In lung cancer, the pooled SUVmax of FDG uptake was significantly higher than that of FLT uptake (7.59 versus 3.86, P < 0.05). In addition, compared to FDG, FLT showed higher specificity yet lower sensitivity for the diagnosis of pulmonary lesions. Conclusion Both 18F-FDG and 18F-FLT correlate significantly with the Ki-67 labeling index in pulmonary lesions, and the latter, with a stronger correlation, may be more reliable for assessing tumor cell proliferation in lung cancer.
Acoustic radiation force impulse imaging for detection of liver fibrosis in overweight and obese children
Authors: Berná-Serna Juan D , Sánchez-Jiménez Regina , Velázquez-Marín Francisca , Sainz de Baranda Pilar , Guzmán-Aroca Florentina , Fernández-Hernández Carmen , Doménech-Abellán Ernesto , Abellán-Rivero Dolores , Ruiz-Merino Guadalupe , Madrid-Conesa Juan , Canteras-Jordana Manuel 
Published: May 2017

Background Acoustic radiation force impulse (ARFI) is a non-invasive alternative to a liver biopsy for the evaluation of liver fibrosis (LF). Purpose To investigate the potential usefulness of acoustic radiation force impulse ARFI for detecting LF in overweight and obese children Material and Methods A cross-sectional study was conducted in 148 schoolchildren. A diagnosis of non-alcoholic fatty liver disease (NAFLD) and LF was based on ultrasound (US) and ARFI shear wave velocity (SWV). Results The laboratory parameters were normal in all the children. NAFLD was observed in 50 children (33.8%). The median SWV was 1.18 ± 0.28 m/s. Differences between ARFI categories and hepatic steatosis grades were observed (χ2 = 43.38, P = 0.0005). No fibrosis or insignificant fibrosis (SWV ≤ 1.60 m/s) was detected in 137 children (92.5%), and significant fibrosis (SWV > 1.60 m/s) in 11 children (7.5%), nine of whom had normal US or mild steatosis. Conclusion The present study is the first to evaluate the utility of the ARFI technique for detecting LF in overweight and obese children. The results of the study suggest that children with normal laboratory parameters such as normal liver ultrasound or mild steatosis may present with significant LF.
Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: An observational cohort study
Authors: Martin Vincent T , Allen Janelle R , Houle Timothy T , Powers Scott W , Kabbouche Marielle A , O’Brien Hope L , Kacperski Joanne , LeCates Susan L , White Shannon , Vaughan Polly , Mandell Karen , Hershey Andrew D 
Published: May 2017

Background Fifty-three percent of adolescent girls report headaches at the onset of menses, suggesting fluctuations of ovarian hormones trigger migraine during puberty. Aims To determine if urinary metabolites of estrogen and progesterone are associated with days of headache onset (HO) or severity in girls with migraine. Methods This was a pilot study and included 34 girls with migraine balanced across three age strata (pre-pubertal (8–11), pubertal (12–15), and post-pubertal (16–17) years of age). They collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide (E1G) and pregnandiol glucuronide (PdG) and the daily change was calculated (ΔE1G, ΔPdG). Pubertal development was assessed by age, pubertal development score (PDS), and menstrual cycle variance. The primary outcome measures were HO days and headache severity. Generalized linear mixed models were used, and included the hormonal variables and three different representations of pubertal development as covariates. Results Models of HO days demonstrate a significant age*PdG interaction (OR 0.85 [95% CI 0.75, 0.97]) for a 1 standard deviation increase in PdG and three-year increase in age. A separate model showed a significant PDS*PdG interaction (OR −0.85 [95% CI; 0.76, 0.95]). ΔPDG was associated with headache severity in unadjusted models ( p < 0.017). Conclusion Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine.
Idiopathic hypertrophic pachymeningitis mimicking hemicrania continua: An unusual clinical case
Authors: Russo Antonio , Silvestro Marcello , Cirillo Mario , Tessitore Alessandro , Tedeschi Gioacchino 
Published: May 2017

Background Hemicrania continua (HC) is a primary headache syndrome characterized by a unilateral, moderate, continuous headache with exacerbations marked by migrainous and cranial autonomic symptoms. However, clinical phenotypes similar to primary HC may be subtended by several disorders. Case report We report the case of a 62-year-old man experiencing, over the previous year, a headache completely consistent with HC and its absolute responsiveness to indomethacin therapy. Later, the patient developed diplopia caused by sixth cranial nerve palsy ipsilateral to headache. In this frame, clinical, laboratory and neuroimaging characteristics supported the diagnosis of idiopathic hypertrophic pachymeningitis (IHP). Conclusions IHP is a rare fibrosing inflammatory disorder leading to a localized or diffuse dura mater thickening. IHP clinical manifestations are a progressively worsening headache and signs related to cranial nerves involvement and venous sinus thrombosis. Here, we report, for the first time, a HC phenotype subtended by IHP.
Urine peptidomic biomarkers for diagnosis of patients with systematic lupus erythematosus
Authors: Pejchinovski M , Siwy J , Mullen W , Mischak H , Petri M A , Burkly L C , Wei R 
Published: May 2017

Background Systematic lupus erythematosus (SLE) is characterized with various complications which can cause serious organ damage in the human body. Despite the significant improvements in disease management of SLE patients, the non-invasive diagnosis is entirely missing. In this study, we used urinary peptidomic biomarkers for early diagnosis of disease onset to improve patient risk stratification, vital for effective drug treatment. Methods Urine samples from patients with SLE, lupus nephritis (LN) and healthy controls (HCs) were analyzed using capillary electrophoresis coupled to mass spectrometry (CE-MS) for state-of-the-art biomarker discovery. Results A biomarker panel made up of 65 urinary peptides was developed that accurately discriminated SLE without renal involvement from HC patients. The performance of the SLE-specific panel was validated in a multicentric independent cohort consisting of patients without SLE but with different renal disease and LN. This resulted in an area under the receiver operating characteristic (ROC) curve (AUC) of 0.80 ( p < 0.0001, 95% confidence interval (CI) 0.65–0.90) corresponding to a sensitivity and a specificity of 83% and 73%, respectively. Based on the end terminal amino acid sequences of the biomarker peptides, an in silico methodology was used to identify the proteases that were up or down-regulated. This identified matrix metalloproteinases (MMPs) as being mainly responsible for the peptides fragmentation. Conclusions A laboratory-based urine test was successfully established for early diagnosis of SLE patients. Our approach determined the activity of several proteases and provided novel molecular information that could potentially influence treatment efficacy.
Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis
Authors: Zeydan Burcu , Lowe Val J , Schwarz Christopher G , Przybelski Scott A , Tosakulwong Nirubol , Zuk Samantha M , Senjem Matthew L , Gunter Jeffrey L , Roberts Rosebud O , Mielke Michelle M , Benarroch Eduardo E , Rodriguez Moses , Machulda Mary M , Lesnick Timothy G , Knopman David S , Petersen Ronald C , Jack Clifford R , Kantarci Kejal , Kantarci Orhun H 
Published: May 2017

Background: There is growing interest in white matter (WM) imaging with positron emission tomography (PET). Objectives: We studied the association of cognitive function in late multiple sclerosis (MS) with cortical and WM Pittsburgh compound-B PET (PiB-PET) binding. Methods: In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS (12 underwent PiB-PET). Controls were age and sex matched (5:1). We used automated or semi-automated processing for quantitative image analyses and conditional logistic regression for group differences. Results: MS patients had lower memory ( p = 0.03) and language ( p = 0.02) performance; smaller thalamic volumes ( p = 0.003); and thinner temporal ( p = 0.001) and frontal ( p = 0.045) cortices on magnetic resonance imaging (MRI) than controls. There was no difference in global cortical PiB standardized uptake value ratios between MS and controls ( p = 0.35). PiB uptake was lower in areas of WM hyperintensities compared to normal-appearing white matter (NAWM) in MS ( p = 0.0002). Reduced PiB uptake in both the areas of WM hyperintensities ( r = 0.65; p = 0.02) and NAWM ( r = 0.69; p = 0.01) was associated with decreased visuospatial performance in MS. Conclusion: PiB uptake in the cortex in late MS is not different from normal age-matched controls. PiB uptake in the WM in late MS may be a marker of the large network structures’ integrity such as those involved in visuospatial performance.
Phase 1 multicenter trial of brentuximab vedotin for steroid-refractory acute graft-versus-host disease
Authors: Chen Yi-Bin , Perales Miguel-Angel , Li Shuli , Kempner Maria , Reynolds Carol , Brown Jami , Efebera Yvonne A. , Devine Steven M. , El-Jawahri Areej , McAfee Steven L. , Spitzer Thomas R. , Soiffer Robert J. , Ritz Jerome , Cutler Corey 
Published: May 2017

Key PointsBV has activity for SR-aGVHD. The MTD of BV was 0.8 mg/kg every 2 weeks for 4 doses.
Clinical utility of magnetic resonance imaging in first-episode psychosis
Authors: Falkenberg Irina , Benetti Stefania , Raffin Marie , Wuyts Phillipe , Pettersson-Yeo William , Dazzan Paola , Morgan Kevin D. , Murray Robin M. , Marques Tiago Reis , David Anthony S. , Jarosz Jozef , Simmons Andrew , Williams Steve , McGuire Philip 
Published: May 2017

BackgroundThere is no consensus as to whether magnetic resonance imaging (MRI) should be used as part of the initial clinical evaluation of patients with first-episode psychosis (FEP).Aims(a) To assess the logistical feasibility of routine MRI; (b) to define the clinical significance of radiological abnormalities in patients with FEP.MethodRadiological reports from MRI scans of two FEP samples were reviewed; one comprised 108 patients and 98 healthy controls recruited to a research study and the other comprised 241 patients scanned at initial clinical presentation plus 66 healthy controls.ResultsIn the great majority of patients, MRI was logistically feasible. Radiological abnormalities were reported in 6% of the research sample and in 15% of the clinical sample (odds ratio (OR) = 3.1, 95% CI 1.26–7.57, χ2(1) = 6.63,P= 0.01). None of the findings necessitated a change in clinical management.ConclusionsRates of neuroradiological abnormalities in FEP are likely to be underestimated in research samples that often exclude patients with organic abnormalities. However, the majority of findings do not require intervention.
The recovery of factors associated with decision-making capacity in individuals with psychosis
Authors: Fernandez Colin , Kennedy Harry G. , Kennedy Miriam 
Published: May 2017

BackgroundThere is limited data on the recovery of factors associated with decisional capacity in patients with psychosis.AimsTo study the relationship between changes in mental capacity, symptoms and global functioning using structured measures during treatment for psychosis.MethodFifty-six patients with psychosis were assessed for capacity to consent to treatment on admission and at 6 and 12 weeks following treatment. The MacArthur Competence Assessment Tool – Treatment, the Positive and Negative Symptom Scale and the Global Assessment of Functioning Scale were used to measure mental capacities, symptom severity and global functioning respectively. Treating consultants rated capacity to consent, masked to these measures.ResultsGreater impairments on all measures were found in patients assessed as lacking capacity. These improved with treatment over 12 weeks with significant effect sizes (0.5 to 0.6). Stronger correlations between mental capacities, positive symptoms (-0.47) and global functioning (0.56) were noted in the first 6 weeks.ConclusionsImpairments in capacity in acute stages of psychosis are related to symptom severity and functional impairment. They improve during treatment, particularly in the first 6 weeks.
Outcomes of Patients With Double-Hit Lymphoma Who Achieve First Complete Remission
Authors: Landsburg Daniel J. , Falkiewicz Marissa K. , Maly Joseph , Blum Kristie A. , Howlett Christina , Feldman Tatyana , Mato Anthony R. , Hill Brian T. , Li Shaoying , Medeiros L. Jeffrey , Torka Pallawi , Hernandez-Ilizaliturri Francisco , Reddy Nishitha M. , Singavi Arun , Fenske Timothy S. , Chavez Julio C. , Kaplan Jason B. , Behdad Amir , Petrich Adam M. , Bast Martin A. , Vose Julie M. , Olszewski Adam J. , Costa Cristiana , Lansigan Frederick , Gerson James N. , Barta Stefan K. , Calzada Oscar , Cohen Jonathon B. , Lue Jennifer K. , Amengual Jennifer E. , Rivera Xavier , Persky Daniel O. , Peace David J. , Nathan Sunita , Cassaday Ryan D. 
Published: May 2017

Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.
Outcomes after foot surgery in people with a diabetic foot ulcer and a 12-month follow-up
Authors: Lenselink E. , Holloway S. , Eefting D. 
Published: May 2017

Objective: The aim of this study was to retrospectively measure the outcomes of foot-sparing surgery at one year follow-up for patients with diabetic foot ulcers (DFUs). We assessed wound healing and the need for further surgery in relation to the variables that influence healing. Method: Data were retrospectively collected by reviewing the electronic files of patients attending the Wound Expert Clinic (WEC). Outcomes of surgical debridement, toe, ray and transmetatarsal amputations were assessed. Results: A total of 129 cases in 121 patients were identified for inclusion. The results demonstrated that complete wound healing was reached in 52% (61/117) of the patients within 12 months. The need for additional surgery or for major amputation was 56% (n=72/129) and 30% (n=39/129) respectively. The need for an additional procedure was particularly high after surgical debridement (75%, 33/44) and transmetatarsal amputation (64%, 7/11). Risk factors for non-healing or for a major amputation were: infection (p=0.01), ischaemia (p=0.01), a history of peripheral arterial occlusive disease (p<0.01) and smoking (p=0.01). Additional findings were that not all patients underwent vascular assessment and in half of the patients there was a delay in undergoing revascularisation. Conclusion: The results of the study reveal some areas for improvement including timely revascularisation and performance of multiple debridement procedures if needed in order to save a limb