bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Safety and Effectiveness of Collagenase Clostridium Histolyticum Injection in Patients with Peyronie’s Disease: A Phase 3 Open-Label Study
Authors: Levine Laurence A. , Cuzin Beatrice , Mark Stephen , Gelbard Martin K. , Jones Nigel A. , Liu Genzhou , Kaufman Gregory J. , Tursi James P. , Ralph David J. 
Published: November 2014

ABSTRACT

Introduction
Collagenase clostridium histolyticum (CCH; Xiaflex, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA, USA) is a Food and Drug Administration-approved, intralesional treatment for Peyronie’s disease (PD).

Aim
The aim of this study was to assess the safety and effectiveness of CCH in the treatment of PD.

Methods
This phase 3, open-label study enrolled subjects who were CCH-naïve, were enrolled in a previous pharmacokinetic study, or had received placebo in an earlier phase 2 CCH study. Each treatment cycle included two intralesional injections of CCH 0.58 mg, approximately 24–72 hours apart, and plaque modeling 24–72 hours after the second injection of each cycle. The treatment cycle was repeated after 6 weeks for ≤4 treatment cycles.

Main Outcome Measures
The co-primary end points were the mean percent change in penile curvature deformity and the mean improvement in PD bother score (range 0–16) from baseline to week 36.

Results
Of the 347 subjects treated with ≥1 injection, 238 had both a penile curvature measurement and a Peyronie’s Disease Questionnaire response at baseline and ≥1 subsequent time point. Mean baseline penile curvature deformity was 53.0° and mean PD symptom bother was 7.3. Statistically significant mean improvements from baseline to week 36 were observed in both penile curvature deformity (34.4% [95% confidence interval {CI}, 31.2%, 37.6%]) and PD symptom bother score (3.3 [95% CI, 2.8, 3.7]). Most adverse events (AEs) were mild or moderate in severity and local to the penis. There were three serious treatment-related AEs, two penile hematomas and one corporal rupture; all resolved with treatment.

Conclusions
Potentially clinically meaningful and statistically significant improvements in penile curvature deformity and PD symptom bother scores were observed with intralesional injection of CCH compared with baseline in men with PD. CCH was generally well tolerated, with AEs primarily transient and local to injection site. In conjunction with previous studies, the results of this open-label study support the use of CCH in the treatment of PD.
Prospective evaluation of PBC‐specific health‐related quality of life questionnaires in patients with primary sclerosing cholangitis
Authors: Raszeja‐Wyszomirska Joanna , Wunsch Ewa , Krawczyk Marek , Rigopoulou Eirini I , Bogdanos Dimitrios , Milkiewicz Piotr 
Published: November 2014

AbstractBackground & AimsPrimary biliary cirrhosis and Primary sclerosing cholangitis are autoimmune cholestatic liver diseases sharing a lot in common, including a significant impairment of patients’ health‐related quality of life HRQoL HRQoL in PBC is assessed with disease‐specific PBC‐40 and PBC‐27 questionnaires. A PSC‐specific questionnaire has not been developed. Neither PBC‐40 nor PBC‐27s applicability for PSC has been evaluated. We applied these three questionnaires for HRQoL assessment in a large homogenous cohort of PSC patients.Patients and MethodsThis cross‐sectional study enrolled 102 Caucasian PSCs and 53 matched healthy controls and measured HRQoL using generic SF‐36, and disease‐specific (PBC‐40/PBC‐27) questionnaires.Results(i) SF‐36. Most SF‐36 domains were significantly lower in PSCs than controls. Physical Functioning and Mental Component Summary scores were significantly lower in female patients and correlated negatively with age but not with concurrent inflammatory bowel disease. Cirrhosis was associated with lower Physical Functioning, Role Physical, General Health, Vitality and Physical Component Summary. (ii) PBC‐40 and PBC‐27. Both tools showed similar HRQoL impairment scoring. Fatigue and Cognitive were impaired in female patients. Several correlations existed between HRQoL and laboratory parameters, including cholestatic tests and Itch. Cirrhosis correlated with Other symptoms and Fatigue PBC‐40. (iii) PBC‐40 vs PBC‐27. Strong correlations among most domains of both questionnaires were seen, as well as between (iv) SF‐36 vs PBC‐40 or SF‐36 vs PBC‐27.ConclusionThis is the first study directly comparing PBC‐40, PBC‐27 and SF‐36 in PSC. PSC patients, especially females, show HRQoL impairment. PBC‐40 and PBC‐27 questionnaires could be of potential use for HRQoL assessment in PSC.
Transcutaneous measurement of glomerular filtration rate in small rodents: Through the skin for the win?
Authors: Ellery Stacey J , Cai Xiaochu , Walker David D , Dickinson Hayley , Kett Michelle M 
Published: November 2014

AbstractRodent models of renal physiology and pathology are crucial to our understanding of the molecular, histological and functional sequelae that contribute to kidney diseases. One of the most important measures of renal function is glomerular filtration rate (GFR). While the accurate determination of GFR is pivotal to understanding the progression of disease and/or the benefits of treatment strategies, in rodents the conventional methods for assessment of GFR are inconvenient and cumbersome, not the least because they involve stress and often anaesthesia. The legitimacy of assay‐based assessment of plasma and urine markers of GFR in mice has also been heavily scrutinized for their insensitivity to minor declines in GFR and inaccurate detection of renal biomarkers. While infusion‐based clearance methods of GFR assessment are thus the gold standard in terms of accuracy, they are limited by the fact that they are primarily non‐recovery procedures. This presents a dilemma when trying to document the progression of renal disease, as these measures cannot be taken in the same experimental subject. Here we review a technique of transcutaneous measurement of fluorescein isothiocyanate‐labelled sinistrin to calculate GFR in small rodents, using a non‐invasive clearance device (NIC‐Kidney Device). This is a recently validated non‐invasive technique for measuring GFR in small rodents that allows for the real‐time measurement of GFR in conscious animals, without the need for plasma and urine assays.
Effects of 1‐week sacral nerve stimulation on the rectal intestinal epithelial barrier and neuromuscular transmission in a porcine model
Authors: Provost M. , Brégeon J. , Aubert P. , Duchalais‐Dassonneville E. , D'Aldebert E. , Vergnolle N. , Neunlist M. , Meurette G. 
Published: November 2014

AbstractBackgroundSacral nerve stimulation (SNS) is a validated treatment for fecal incontinence, although the mechanism of action remains unknown. Short‐term effects of SNS on the intestinal epithelial barrier (IEB) have been reported previously. The aim of our study was to assess the impact of a 1‐week SNS on the IEB in a preclinical model.MethodsFourteen pigs were implanted for bilateral SNS. Seven pigs received 7‐day stimulation, whereas the remaining animals received no stimulation. Rectal biopsies were performed before and after SNS. We assessed IEB permeability, mucosal tight junction and cytokine mRNA expression, IL‐6 production in an organotypic culture model, and neuromuscular transmission in muscle strips.Key ResultsIEB permeability was not modified after stimulation, as compared with baseline. The PAR‐induced increase in IEB permeability and the mucosal ZO‐1 mRNA decrease observed in the controls were not observed into the stimulated group. Cytokine overexpression was not observed in the mucosa in either group. SNS decreased IL‐6 production in the organotypic culture model. In the stimulated group, the area‐under‐the‐curve of the EFS‐induced contractile response was significantly increased.Conclusions & InferencesThe main conclusions of our work are (i) the successful development of a preclinical model of bilateral SNS and (ii) in physiological conditions, 1‐week SNS did not lead to functional changes in the mucosa. While under stress‐induced conditions, SNS modified the properties of the IEB, leading to a decrease in its permeability. Neuromuscular transmission was modified by SNS, leading to neuronal hyperexcitability. These results add evidence to the reinforcement of the IEB by SNS.
Preserving whole blood in formalin extends the specimen stability period for manual cell counts for fish
Authors: Arnold Jill E. , Matsche Mark A. , Rosemary Kevin 
Published: November 2014

BackgroundTotal blood cell counts for fish are challenging, especially due to cell fragility. Thrombocyte aggregation, cell distortion, and lysis can occur within hours of collection; therefore, hemocytometer counts may not be possible for large sample numbers. Preserving whole blood in formalin offers a simple way to extend the specimen stability period for cell counts.ObjectivesThe objectives of this study were to characterize and compare the analytical performance of the Natt–Herrick method for fish blood cell counts using freshly collected and formalin‐fixed specimens.MethodsSpecimens from 11 elasmobranch species (n = 36) were compared for WBC counts. WBC, RBC, and thrombocyte counts from 50 striped bass, Morone saxatilis, were compared including 2 time points for the formalin‐preserved cells (appr. 1‐week and 1‐month storage). Coefficient of variation (CV), bias, and total error (TEcalc) were calculated. TEcalc was compared with allowable total error (TEa) defined by the Clinical Laboratory Improvements Amendment (CLIA) for human blood cell counts.ResultsThe CV and TEcalc for fresh and fixed WBC and thrombocyte counts met CLIA limits. In both the fresh and preserved cells, the RBC CV and TEcalc were nearly 3 times higher than the TEa.ConclusionsPreserving freshly collected blood in 10% formalin is a reliable method to maintain cell morphology for manual counts for up to 1 month post collection. This is especially useful for field studies, where laboratory access is limited. Further evaluation is needed to determine the clinical usefulness of the manual RBC count in fish.
Relationship between aneurysm occlusion and flow diverting device oversizing in a rabbit model
Authors: Hodis Simona , Ding Yong-Hong , Dai Daying , Lingineni Ravi , Mut Fernando , Cebral Juan , Kallmes David , Kadirvel Ramanathan 
Published: November 2014

Background and purposeImplanted, actual flow diverter pore density is thought to be strongly influenced by proper matching between the device size and parent artery diameter. The objective of this study was to characterize the correlation between device sizing, metal coverage, and the resultant occlusion of aneurysms following flow diverter treatment in a rabbit model.MethodsRabbit saccular aneurysms were treated with flow diverters (iso-sized to proximal parent artery, 0.5 mm oversized, or 1.0 mm oversized, respectively, n=6 for each group). Eight weeks after implantation, the angiographic degree of aneurysm occlusion was graded (complete, near-complete, or incomplete). The ostium of the explanted aneurysm covered with the flow diverter struts was photographed. Based on gross anatomic findings, the metal coverage and pore density at the ostium of the aneurysm were calculated and correlated with the degree of aneurysm occlusion.ResultsAngiographic results showed there were no statistically significant differences in aneurysm geometry and occlusion among groups. The mean parent artery diameter to flow diverter diameter ratio was higher in the 1.0 mm oversized group than in the other groups. Neither the percentage metal coverage nor the pore density showed statistically significant differences among groups. Aneurysm occlusion was inversely correlated with the ostium diameter, irrespective of the size of the device implanted.ConclusionsDevice sizing alone does not predict resultant pore density or metal coverage following flow diverter implantation in the rabbit aneurysm model. Aneurysm occlusion was not impacted by either metal coverage or pore density, but was inversely correlated with the diameter of the ostium.
Paradoxical Decrease in the Capture and Lymph Node Delivery of Cancer Vaccine Antigen Induced by a TLR4 Agonist as Visualized by Dual-Mode Imaging
Authors: Kadayakkara Deepak K. , Korrer Michael J. , Bulte Jeff W.M. , Levitsky Hyam I. 
Published: November 2014

Abstract
Traditionally, cell-mediated immune responses to vaccination in animal models are evaluated by invasive techniques such as biopsy and organ extraction. We show here that by combining two noninvasive imaging technologies, MRI and bioluminescence imaging (BLI), we can visualize both the afferent and efferent arms of cellular events following vaccination longitudinally. To this end, we evaluated the immune response elicited by a novel Toll-like receptor 4 agonist vaccine adjuvant, glucopyranosyl lipid A (GLA), using a whole-cell tumor vaccine. After magnetovaccination, MRI was used to visualize antigen-presenting cell-mediated antigen capture and subsequent migration to draining lymph nodes (DLN). Paradoxically, we observed that the incorporation of GLA in the vaccine reduced these critical parameters of the afferent immune response. For the efferent arm, the magnitude of the ensuing antigen-specific T-cell response in DLN visualized using BLI correlated with antigen delivery to the DLN as measured by MRI. These findings were confirmed using flow cytometry. In spite of the GLA-associated reduction in antigen delivery to the DLN, however, the use of GLA as a vaccine adjuvant led to a massive proliferation of vaccine primed antigen-specific T cells in the spleen. This was accompanied by an enhanced tumor therapeutic effect of the vaccine. These findings suggest that GLA adjuvant changes the temporal and anatomical features of both the afferent and efferent arms of the vaccine response and illustrates the utility of quantitative noninvasive imaging as a tool for evaluating these parameters during vaccine optimization. Cancer Res; 75(1); 51–61. ©2014 AACR.
Increased Risk for Intracranial Arterial Stenosis in Subjects With Coronary Artery Calcification
Authors: Oh Hyung-Geun , Chung Pil-Wook , Rhee Eun-Jung 
Published: November 2014

Background and Purpose—
Intracranial arterial stenosis (ICAS) is considered an important cause of stroke in Asians. Coronary artery calcification (CAC) is a surrogate marker for subclinical atherosclerosis. We aimed to analyze the association of ICAS assessed by transcranial Doppler ultrasonography and CAC in middle-aged Korean population.

Methods—
This study included 10 550 participants (81.3% men, mean age 43 years) from a health screening program, in whom transcranial Doppler ultrasonography was used to detect >50% intracranial stenosis based on criteria modified from the stroke outcomes and neuroimaging of intracranial atherosclerosis trial. Multidetector computed tomography was used to assess coronary artery calcium score (CACS). CAC grade (0, 1−100, and >100) was defined by CACS.

Results—

The subjects with CAC showed significantly higher proportion of subjects with ICAS compared with those without CAC (4.4% versus 2.8%;
P
<0.01). Conversely, the subjects with ICAS showed significantly higher proportion of subjects with CAC (24.8% versus 17.1%;
P
<0.01). When logistic regression analysis was performed with ICAS as the dependent variable, the presence of CAC showed significantly increased risk for ICAS after adjustment for confounding variables (odds ratio, 1.439; 95% confidence interval, 1.095–1.891). When CACS grade was included in the model, the odds ratio for ICAS was the highest in subjects with CACS >400 compared with those with CACS=0 (odds ratio, 2.754; 95% confidence interval, 1.205–2.936).

Conclusions—
The risk for ICAS was significantly increased in middle-aged Korean subjects with CAC compared with that in those without CAC. These findings suggest the possibility of a separate undetected atherosclerotic focus in subjects with 1 atherosclerotic event.
Patterns of Modulation in the Activity and Connectivity of Motor Cortex during the Repeated Generation of Movement Sequences
Authors: Gabitov Ella , Manor David , Karni Avi 
Published: November 2014

Abstract
It is not clear how the engagement of motor mnemonic processes is expressed in online brain activity. We scanned participants, using fMRI, during the paced performance of a finger-to-thumb opposition sequence (FOS), intensively trained a day earlier (T-FOS), and a similarly constructed, but novel, untrained FOS (U-FOS). Both movement sequences were performed in pairs of blocks separated by a brief rest interval (30 sec). We have recently shown that in the primary motor cortex (M1) motor memory was not expressed in the average signal intensity but rather in the across-block signal modulations, that is, when comparing the first to the second performance block across the brief rest interval. Here, using an M1 seed, we show that for the T-FOS, the M1–striatum functional connectivity decreased across blocks; however, for the U-FOS, connectivity within the M1 and between M1 and striatum increased. In addition, in M1, the pattern of within-block signal change, but not signal variability per se, reliably differentiated the two sequences. Only for the U-FOS and only within the first blocks in each pair, the signal significantly decreased. No such modulation was found within the second corresponding blocks following the brief rest interval in either FOS. We propose that a network including M1 and striatum underlies online motor working memory. This network may promote a transient integrated representation of a new movement sequence and readily retrieves a previously established movement sequence representation. Averaging over single events or blocks may not capture the dynamics of motor representations that occur over multiple timescales.
Recollection and Familiarity Exhibit Dissociable Similarity Gradients: A Test of the Complementary Learning Systems Model
Authors: Elfman Kane W. , Yonelinas Andrew P. 
Published: November 2014

Abstract
Memory can often be triggered by retrieval cues that are quite different from the originally encoded events, but how different memory processes respond to variations in cue–target similarity is poorly understood. We begin by presenting simulations using a neurocomputational model of recognition memory (i.e., the complementary learning systems model), which proposes that the hippocampus supports recollection of associative information whereas the surrounding cortex supports assessments of item familiarity. The simulations showed that increases in the similarity between retrieval cues and learned items led to relatively linear increases in a cortex-based memory signal but led to steeper and more thresholded increases in the hippocampal signal. We then tested the predictions of the model by examining the effects of varying cue–target similarity in two recognition memory experiments in which participants studied a list of computer-generated faces and then, at test, gave confidence and remember/know responses to morphed faces. In both experiments, as cue–target similarity was increased, familiarity-based recognition increased in a gradual and relatively linear fashion, whereas recollection showed significantly steeper gradients. The results show that recollection and familiarity exhibit distinct similarity functions in recognition memory that correspond with predicted retrieval dynamics of the hippocampus and cortex, respectively.
Epithelial‐Mesenchymal Transition: Clinical Implications for Nodal Metastasis and Prognosis of Tongue Cancer
Authors: Han Myung Woul , Lee Jong Cheol , Kim Young Min , Cha Hee Jeong , Roh Jong‐Lyel , Choi Seung‐Ho , Nam Soon Yuhl , Cho Kyung‐Ja , Kim Seong Who , Kim Sang Yoon 
Published: November 2014

ObjectiveThe development of biomarkers for the prediction of lymph node metastasis and prognosis is critical for deciding the treatment modality of tongue cancer. The purpose of our study is to investigate the clinical implications of epithelial‐mesenchymal transition (EMT) expression in tongue cancer.Study DesignHistorical cohort studySettingTertiary‐care hospital.Subjects and MethodsThe study included 95 subjects with tongue cancer who underwent wide excision and neck dissection. According to characteristics of immunohistochemical staining for E‐cadherin and vimentin, we classified the tumors as complete EMT phenotype, incomplete EMT phenotype, or epithelial phenotype. The correlation between risk factors and nodal metastasis was assessed, and disease‐free survival (DFS) was analyzed.ResultsPositive lymph nodes were detected in 46 (48.4%) patients and was found to correlate significantly with depth of invasion ≥4 mm and EMT expression on multivariate analysis (P =. 030, P =. 022, respectively). The mean follow‐up period of all patients was 96.3 months (range, 6‐149 months). Overall 5‐year DFS was 61.7%. On multivariate analysis, the only factors affecting DFS were nodal stage and EMT expression (P =. 033, P =. 021, respectively).ConclusionsOur study reveals that EMT expression is a significant biomarker for predicting lymph node metastasis and tumor recurrence in tongue cancer. Evaluation of EMT expression in tongue cancer can allow therapy to be offered accordingly.
Voice Assessment and Voice‐related Quality of Life in Patients with Benign Thyroid Disease
Authors: Pernambuco Leandro de Araújo , Almeida Marluce Nascimento de , Matias Keliane Gomes , Costa Erika Beatriz de Morais 
Published: November 2014

ObjectiveTo identify the relationship between vocal self‐assessment, the assessment of voice by a speech‐language pathologist (SLP), and the effect of voice on the quality of life of patients with benign thyroid diseases.Study DesignCross‐sectional study.SettingUniversity hospital.Subjects and MethodA total of 67 women with a mean age of 44.7 ± 14.8 years and a diagnosis of benign thyroid disease were included in the study. Vocal self‐assessment and SLP assessment were performed using a visual analogue scale (VAS). The Voice‐related Quality of Life Questionnaire (V‐RQOL) was used to identify the effect of voice on quality of life. The Mann‐Whitney and Kruskal‐Wallis nonparametric tests were used. Correlations between assessments were verified by the Spearman correlation test. The significance level was 5%.ResultsPatients with vocal complaints had lower scores in all assessments. Patients with thyroid nodules performed worse on the SLP assessment and on the physical functioning domain of V‐RQOL. A moderate correlation was found between the self‐assessment and quality of life and between the physical functioning domain of V‐RQOL and the SLP assessment. A weak correlation existed between the self‐assessment and the SLP assessment.ConclusionPatients with benign thyroid diseases had lower scores in vocal self‐assessment, the clinical evaluation of voice, and the V‐RQOL. These dimensions of voice assessment showed correlations ranging from mild to moderate and should complement the clinical routine.