bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of diabetes mellitus and biochemical knee cartilage composition assessed by T2 relaxation time measurements: Data from the osteoarthritis initiative
Authors: Chanchek Nattagan , Gersing Alexandra S. , Schwaiger Benedikt J. , Nevitt Michael C. , Neumann Jan , Joseph Gabby B. , Lane Nancy E. , Zarnowski Julia , Hofmann Felix C. , Heilmeier Ursula , McCulloch Charles E. , Link Thomas M.
Published: May 2017

Purpose

To investigate the association of the presence and severity of diabetes mellitus (DM) with articular cartilage composition, using magnetic resonance imaging (MRI)‐based T2 relaxation time measurements, and structural knee abnormalities.

Materials and Methods

In the Osteoarthritis Initiative 208, participants with DM (age 63.0 ± 8.9 years; 111 females) and risk factors for osteoarthritis (OA) or mild radiographic tibiofemoral OA (Kellgren–Lawrence [KL] grade ≤2) were identified and group‐matched with 208 controls without DM (age 63.3 ± 9.1 years; 111 females). Subjects with diabetes‐related renal or ophthalmological complications or insulin treatment at baseline (n = 50) were defined as severe DM. 3T MR images of the right knee were assessed for articular cartilage T2, including texture and laminar analyses derived from the patella, medial, and lateral femur and tibia and for structural abnormalities using the modified whole‐organ magnetic resonance imaging score (WORMS). Clustered linear regression analyses were used to assess associations of DM with MRI findings.

Results

DM subjects had significantly higher cartilage T2 in the patella (mean difference 0.92 msec [95% confidence interval (CI) 0.79, 1.06]; P = 0.001) and medial femur (mean difference 0.36 msec [95% CI 0.27, 0.81]; P = 0.006) compared to controls. Averaged over all compartments, DM subjects showed significantly higher texture parameters (variance, P = 0.001; contrast, P = 0.002; entropy, P < 0.001). Subjects with severe DM additionally showed higher T2 in the medial tibial deep and superficial layers (P = 0.011 and P = 0.041) compared to controls. No significant differences in cartilage, meniscus, and overall WORMS were found between the groups (P > 0.05).

Conclusion

In comparison to nondiabetic controls, cartilage in DM subjects showed higher and more heterogeneous cartilage T2 values, indicating increased articular cartilage degeneration. This affected even more compartments in subjects with severe DM.

Level of Evidence: 2

Technical Efficacy: 5

J. Magn. Reson. Imaging 2018;47:380–390.
Computer‐aided diagnosis program for classifying the risk of hepatocellular carcinoma on MR images following liver imaging reporting and data system (LI‐RADS)
Authors: Kim Youngwoo , Furlan Alessandro , Borhani Amir A. , Bae Kyongtae T.
Published: May 2017

Purpose

To develop and evaluate a computer‐aided diagnosis (CAD) program for liver lesions on magnetic resonance (MR) images for classification of the risk of hepatocellular carcinoma (HCC) following the liver imaging reporting and data system (LI‐RADS).

Materials and Methods

Liver MR images from 41 patients with hyperenhancing liver lesions categorized as LR 3, 4, and 5 were evaluated by two radiologists. The major LI‐RADS features of each index liver lesion were recorded, including size (maximum transverse diameter), presence of hyperenhancement, washout appearance, and capsule appearance. A CAD program was implemented to register MR images at different contrast‐enhancement phases, segment liver lesions, extract lesion features, and classify lesions according to LI‐RADS. The LI‐RADS features quantified by CAD were compared with those assessed by radiologists using the intraclass correlation coefficient (ICC) and receiver operator curve (ROC) analyses. The LI‐RADS categorization between CAD and radiologists was evaluated using the weighted Cohen's kappa coefficient.

Results

The mean and standard deviation of the lesion diameters were 21 ± 11 mm (range, 7–70 mm) by radiologists and 22 ± 11 mm (range, 8–72 mm) by CAD (ICC, 0.96–0.97). The area under the curve (AUC) for the washout assessment by CAD was 0.79–0.93 with sensitivity 0.69–0.82 and specificity 0.79–1. The AUC for the capsule assessment by CAD was 0.79–0.9 with sensitivity 0.75–0.9 and specificity 0.82–0.96. The classifications by the radiologists and CAD coincided in 76–83% lesions (k = 0.57–0.71), while the agreements between radiologists were in 78% lesions (k = 0.59).

Conclusion

We developed a CAD program for liver lesions on MR images and showed a substantial agreement in the LI‐RADS‐based classification of the risk of HCCs between the CAD and radiologists.

Level of Evidence: 1

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2018;47:710–722.
Distribution of blood flow velocity in the normal aorta: Effect of age and gender
Authors: Garcia Julio , van der Palen Roel L.F. , Bollache Emilie , Jarvis Kelly , Rose Michael J. , Barker Alex J. , Collins Jeremy D. , Carr James C. , Robinson Joshua , Rigsby Cynthia K. , Markl Michael
Published: May 2017

Purpose

To apply flow distribution analysis in the entire aorta across a wide age range from pediatric to adult subjects.

Material and Methods

In all, 98 healthy subjects (age 9–78 years, 41 women) underwent 4D flow MRI at 1.5T and 3T for the assessment of 3D blood flow in the thoracic aorta. Subjects were categorized into age groups: group 1 (n = 9, 5 women): 9–15 years; group 2 (n = 13, 8 women): 16–20 years; group 3 (n = 27, 14 women): 21–39 years; group 4 (n = 40, 11 women): 40–59 years; group 5 (n = 9, 3 women): >60 years. Data analysis included the 3D segmentation of the aorta, aortic valve peak velocity, mid‐ascending aortic diameter, and calculation of flow velocity distribution descriptors (mean, median, standard deviation, incidence of velocities >1 m/s, skewness, and kurtosis of aortic velocity magnitude). Ascending aortic diameter was normalized by body surface area.

Results

Age was significantly associated with normalized aortic diameter (R = 0.73, P < 0.001), skewness (R = 0.76, P < 0.001), and kurtosis (R = 0.74, P < 0.001), all adjusted by heart rate. Aortic peak velocity and velocity distribution descriptors, adjusted by heart rate, were significantly different between age groups (P < 0.001, analysis of covariance). Skewness and kurtosis significantly increased (P < 0.001) during adulthood (>40 years) as compared with childhood (<21 years). Men and women revealed significant differences (P ≤ 0.05) for peak velocity, incidence, mean, median, standard deviation, and skewness, all adjusted by heart rate.

Conclusion

Aortic hemodynamics significantly change with age and gender, indicating the importance of age‐ and gender‐matched control cohorts for the assessment of the impact of cardiovascular disease on aortic blood flow.

Level of Evidence: 3

Technical Efficacy: Stage 5

J. Magn. Reson. Imaging 2018;47:487–498.
Multiresidue analysis of glucocorticoids in milk by LC–MS/MS with low‐temperature purification and dispersive solid‐phase extraction
Authors: Ma Lili , Fan Xiaojing , Jia Li , Wang Jiaqi , Wang Suli , Zhao Liuwei
Published: May 2017

A multiresidue method for the determination of 12 glucocorticoids (clobetasol propionate, budesonide, triamcinolone, triamcinolone acetonide, fludrocortisone acetate, flumethasone, beclomethasone, prednisone acetate, 6‐α‐methylprednisolone, hydrocortisone, cortisone, and prednisone) in bovine milk was developed using liquid chromatography with tandem mass spectrometry. Isoflupredone was used as an internal standard. Milk samples were treated with ethyl acetate to extract glucocorticoids and were frozen at −20°C for 6 h to precipitate fat. The extract was dried under nitrogen, and residues were dissolved in an acetonitrile/water solution. A further clean‐up step was used by dispersive solid‐phase extraction, with octadecyl silica and primary secondary amine as the absorbents. The recoveries of glucocorticoids spiked at 0.5, 1.0, 10.0 μg/kg ranged from 75.7 to 117.3%, except for clobetasol propionate and budesonide (16.1–49.5%). The limits of quantification were 0.01–0.5 μg/kg in milk. This method has been successfully applied in real samples. The results demonstrated that this method is simple, robust, and suitable for identification of glucocorticoid residues in milk.
Histological Grade and Immunohistochemical Biomarkers of Breast Cancer: Correlation to Ultrasound Features
Authors: Au Frederick Wing‐Fai , Ghai Sandeep , Lu Fang‐I , Moshonov Hadas , Crystal Pavel
Published: May 2017

Objectives

The purpose of this study is to correlate various features of breast cancers on ultrasound to their histological grade and immunohistochemical biomarkers.

Methods

Seventy‐three patients with 77 invasive breast cancers, diagnosed between August 2011 and December 2014, were included in this prospective analysis. Margin, posterior features, shape, and vascularity were determined from ultrasound and classified according to the Breast Imaging Reporting and Data System lexicon. Histological grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status (positive [+] or negative [−]) were determined from surgical pathology reports. The cancers were categorized into low grade (grades 1 or 2) and high grade (grade 3). Correlation of ultrasound features of the cancers to their histological grade and receptor status was performed.

Results

There were 47 low‐grade and 29 high‐grade cancers. There was a significant difference in margin and posterior features between the low and high grade, ER + and ER−, and PR + and PR− (all P < .05), but not between HER2 + and HER2− cancers (both P > .05). There was no significant difference in shape and vascularity among the different subtypes (all P > .05). Spiculated margin was significantly associated with low‐grade, ER+, PR + status; angular margin with high grade; microlobulated margin with ER− status; shadowing with PR + status; and enhancement with high grade, ER− status (all P < .05, all odds ratios ≥ 3.94).

Conclusions

There was significant association of margin and posterior features of breast cancers with their histological grade and receptor status.
Value of Sonography in the Diagnosis of Sialolithiasis: Comparison With the Reference Standard of Direct Stone Identification
Authors: Goncalves Miguel , Schapher Mirco , Iro Heinrich , Wuest Wolfgang , Mantsopoulos Konstantinos , Koch Michael
Published: May 2017

Objectives

The aim of this study was to assess the effectiveness of sonography for diagnosing sialolithiasis in comparison with the existing reference standard of direct identification of a stone.

Methods

A total of 659 glands with signs of obstructive sialadenopathy were evaluated retrospectively. Sonographic examinations of the large head salivary glands had been performed initially in all cases. Direct depiction of a stone during sialoendoscopy or transoral ductal surgery or observation of stone fragmentation with discharge of concrements after extracorporeal shock wave lithotripsy, was regarded as definitive evidence and as the reference standard for the presence of sialolithiasis. The sonographic results were compared with those for direct identification of stones.

Results

The sensitivity of sonography was 94.7%, with specificity of 97.4%, a positive predictive value of 99.4%, and a negative predictive value of 79.6%. Stones that were not diagnosed correctly on sonography were most often located in the distal area of the duct.

Conclusions

These results show that sialolithiasis can be diagnosed by sonography with a high degree of certainty. Sonography thus appears to be highly appropriate as the examination method of choice.
Sonography of Scrotal Wall Lesions and Correlation With Other Modalities
Authors: Conzi Raffaella , Damasio Maria Beatrice , Bertolotto Michele , Secil Mustafa , Ramanathan Subramaniyan , Rocher Laurence , Cuthbert Faye , Richenberg Jonathan , Derchi Lorenzo E. ,   on Behalf of the Scrotal Imaging Group of the European Society of Urogenital Radiology
Published: May 2017

The scrotal wall may be involved in a variety of pathologic processes. Such lesions may rise primarily from the layers of the scrotum or may be due to a process arising from scrotal content. Imaging is not needed in most cases, but it may be useful for making such differentiations and for evaluation of possible involvement of the testes and epididymides in cases of primary wall abnormalities. This pictorial essay will show the imaging findings observed in a variety of pathologic conditions affecting the scrotal wall, both common and unusual ones, with an emphasis on clinically relevant findings and features that lead to a specific diagnosis.
Three‐Dimensional Power Doppler Vascularization in Women With Ovarian Endometriomas and Relationship With Associated Painful Symptoms
Authors: Rizzello Francesca , Capezzuoli Tommaso , D'Amato Scherbatoff Ippolita , Cozzolino Mauro , Gandini Loredana , Coccia Maria Elisabetta
Published: May 2017

Objectives

The objective of the study was to evaluate the correlation between endometrioma‐associated pain and lesion vascularization as measured with 3‐dimensional power Doppler transvaginal sonography.

Methods

Endometriomas were examined, and 4 indices were obtained: mean grayness, flow index, vascularization index, and vascularization‐flow index. Dysmenorrhea, chronic pelvic pain, and dyspareunia were analyzed in terms of severity, presence/absence, and duration.

Results

Twenty‐nine women were selected. The univariable association of painful symptoms in terms of presence/absence and duration was low with the exception of mean grayness with the presence of chronic pelvic pain (β = –0.106;P = .047; 95% confidence interval, 0.810 to 0.998). TheR2value increased to 0.226 for dysmenorrhea (β = –0.475;P = .029) when analyzing the association between the vascularization index and the severity of painful symptoms. The visual analog scale scores for chronic pelvic pain and dyspareunia were higher (R2 = 0.300; β = –0.547 and –0.548, respectively;P = .028 and .053).

Conclusions

We observed an inverse association between the severity of pain and endometrioma vascularization. Further larger studies are required to confirm our findings.
Contrast‐Enhanced Ultrasound Differentiation Between Low‐ and High‐ Grade Bladder Urothelial Carcinoma and Correlation With Tumor Microvessel Density
Authors: Guo Suping , Xu Pan , Zhou Aiyun , Wang Gongxian , Chen Weimin , Mei Jinhong , Xiao Fan , Liu Juan , Zhang Cheng
Published: May 2017

Objectives

Time‐intensity curves (TICs) of contrast‐enhanced ultrasound (CEUS) were analyzed retrospectively to differentiate between low‐grade and high‐grade bladder urothelial carcinoma, and to investigate correlation with tumor microvessel density (MVD).

Methods

The data of 105 patients with pathologically confirmed bladder urothelial carcinoma (55 low‐grade and 50 high‐grade) were reviewed. Lesions were examined before surgery using conventional ultrasound and CEUS with TIC analysis. The TIC parameters time from peak to one‐half the signal intensity (TPH) and the corresponding descending slope (DS) of the low‐grade and high‐grade groups were compared, and receiver operating characteristic curves constructed. The MVDs of the resectioned tissue specimens were quantified via immunohistochemistry for CD34.

Results

Based on conventional ultrasound, the low‐grade and high‐grade groups were similar in tumor shape, number, topography, internal echo, height, width, and vascularity. The TPH of the high‐grade group was significantly longer than that of the low‐grade group, and the DS was lower. The cutoff points of TPH and DS for differentiating low‐grade and high‐grade bladder urothelial carcinoma were 48.06 seconds and 0.15 dB/seconds, respectively (area under the receiver operating characteristic curve = 0.79 for both). The mean MVDs per high‐power field of the low‐grade and high‐grade groups were 41.39 16.65 and 51.03 20.16, respectively (P = .009). The TPH correlated linearly with MVD (P < .01), as did the DS (P < .01).

Conclusions

Contrast‐enhanced ultrasound can be used to differentiate low from high‐grade bladder urothelial carcinoma. The TIC parameters of CEUS reflect the MVD of bladder urothelial tumors and may be helpful for evaluating tumor angiogenesis, with implications for clinical diagnosis, treatment, and prognosis.
In the process babel: Definitions, concepts, and tools in a disordered field
Authors: Rocha Gustavo Silva , Lacerda Daniel Pacheco , Veit Douglas Rafael , Rodrigues Luis Henrique , Dresch Aline
Published: May 2017

The purpose of this article is to increase the understanding of this methodology by showing its main advantages, disadvantages, difficulties, adaptation of the people, people management, the implementation steps, and the choice of software. Another objective is to pinpoint some differences between process automation and Workflow. To that end, a field research was conducted consisting of semistructured interviews to gather the perceptions of both clients (analysts) and implementers on business process automation as the main motivators, advantages, disadvantages, and changes that took place in the organization as this methodology was implemented. The interviews were carried out with implementers and users who applied the process automation across their organizations. The conclusion that can be drawn from this paper is that automation of the business process is a methodology that improves the processes in organizations, increases their agility, reduces costs, assures the integrity of processes, and, mainly, keeps track of the activities performed.
Impact of liver disease on outcomes of patients hospitalized for epistaxis
Authors: Mohamed Omar M. , Govindan Aparna , Filimonov Andrey , Sylvester Michael J. , Zaki Michael , Baredes Soly , Eloy Jean Anderson
Published: May 2017

Objectives

Liver disease (LD) often results in coagulation abnormalities that may predispose to more severe epistaxis. The purpose of this analysis was to examine characteristics of patients hospitalized for epistaxis with LD and explore the impact of LD on patient outcomes.

Methods

The 2002 to 2013 National Inpatient Sample was queried for cases with a primary diagnosis of epistaxis. Cases with additional codes meeting the Agency for Healthcare Research and Quality's definition of LD were identified and compared to the non‐LD cohort.

Results

Out of 39,879 cases meeting inclusion criteria, 3.6% had LD. LD was associated with younger age (55.7 years vs. 67.5 years; P < 0.001), longer hospital stay (3.9 days vs. 3.2 days; P < 0.001), and greater hospital charges ($26,141 vs. $18,200; P < 0.001) compared to the non‐LD cohort. LD patients had higher rates of alcohol abuse, coagulopathy, chronic blood loss anemia, and renal failure. LD patients also had higher rates of sepsis, urinary/renal complications, respiratory failure, and infectious pneumonia. LD was associated with decreased rates of aggressive management (defined as ligation or embolization) (6.6%–9.0%; P < 0.002) and anterior or posterior nasal packing. In our multivariate logistic regression model correcting for age, gender, race, and significant comorbidities, LD was associated with 1.520 (1.336–1.729; P < 0.001) greater odds of transfusion and 2.264 (1.372–3.736; P = 0.001) greater odds of in‐hospital mortality.

Conclusion

Among patients hospitalized for epistaxis, LD resulted in greater morbidity and mortality. Clinicians should be aware of the particular risk that LD bears on the hospitalized epistaxis patient.

Level of Evidence

2C. Laryngoscope, 127:2691–2697, 2017
Urbanization Development under Climate Change: Hydrological Responses in a Peri‐Urban Mediterranean Catchment
Authors: Kalantari Zahra , Ferreira Carla Sofia Santos , Walsh Rory Peter Dominic , Ferreira António José Dinis , Destouni Georgia
Published: May 2017

Relatively few studies have so far investigated the hydrological impacts of urbanization in Mediterranean catchments, and particularly in peri‐urban catchments experiencing relatively rapid and large changes in their land‐use mosaic. This study uses data‐based model simulations to investigate such impacts, with the Ribeira dos Covões catchment in Portugal as a concrete Mediterranean peri‐urban catchment example. We distinguish the impacts of urbanization from those of climatic change on the water flux partitioning and connectivity in the catchment over the period 1958–2013. Decrease in precipitation over this period has primarily driven decreases in annual runoff and actual evapotranspiration, while the urbanization development has primarily changed the relative flux partitioning and connectivity pattern in the catchment. The relative contribution of overland flow to annual and seasonal runoff has increased, keeping the absolute overland flow more or less intact, while the baseflow contribution to the stream network has decreased. Methodologically, the present simulation approach provides a relevant means for distinguishing main drivers of change in hydrological flux partitioning and connectivity under concurrent urbanization and climatic changes. © 2017 The Authors. Land Degradation & Development Published by John Wiley & Sons Ltd.
Online UV Curing of Electrospun Polysulfone Fibers Containing an Acrylate as Cross‐Linker
Authors: Mehmood Mian Farrukh , Sangermano Marco , Gule Nonjabulo Prudence , Tiraferri Alberto , Mallon Peter E.
Published: May 2017

In this work, a sustainable, in situ UV‐induced reactive electrospinning technique is demonstrated to produce solvent stable electrospun membranes in a single operation. This approach is based on the addition of an acrylated cross‐linker into the polysulfone‐based dope solution and on the online irradiation of the solution while it is electrospun, thus allowing reaction during formation of the fibers. The electrospinning parameters and UV curing conditions are thoroughly optimized. Mats are also prepared via an offline approach in which UV curing is performed on the previously electrospun mats and compared with the membranes fabricated via the online curing method. As opposed to pristine polysulfone fibers, the electrospun mats containing acrylate are stable in a variety of solvents, such as tetrahydrofurane (THF), acetone, ethyl acetate, dimethylsulfoxide (DMSO), and toluene. The online irradiated mats of desired thickness are produced in a single step operation and the sustainability of the process is achieved through the optimization of electrospinning and solution parameters.

image
Cerebral compensation during motor function in Friedreich ataxia: The IMAGE‐FRDA study
Authors: Harding Ian H. , Corben Louise A. , Delatycki Martin B. , Stagnitti Monique R. , Storey Elsdon , Egan Gary F. , Georgiou‐Karistianis Nellie
Published: May 2017

Background: Friedreich ataxia is characterized by progressive motor incoordination that is linked to peripheral, spinal, and cerebellar neuropathology. Cerebral abnormalities are also reported in Friedreich ataxia, but their role in disease expression remains unclear.

Methods: In this cross‐sectional functional magnetic resonance imaging study, 25 individuals with Friedreich ataxia and 33 healthy controls performed simple (self‐paced single‐finger) and complex (visually cued multifinger) tapping tasks to respectively gauge basic and attentionally demanding motor behavior. For each task, whole brain functional activations were compared between groups and correlated with disease severity and offline measures of motor dexterity.

Results: During simple finger tapping, cerebral hyperactivation in individuals with Friedreich ataxia at the lower end of clinical severity and cerebral hypoactivation in those more severely affected was observed in premotor/ventral attention brain regions, including the supplementary motor area and anterior insula. Greater activation in this network correlated with greater offline finger tapping precision. Complex, attentionally demanding finger tapping was also associated with cerebral hyperactivation, but in this case within dorsolateral prefrontal regions of the executive control network and superior parietal regions of the dorsal attention system. Greater offline motor precision was associated with less activation in the dorsal attention network.

Discussion: Compensatory activity is evident in the cerebral cortex in individuals with Friedreich ataxia. Early compensation followed by later decline in premotor/ventral attention systems demonstrates capacity‐limited neural reserve, while the additional engagement of higher order brain networks is indicative of compensatory task strategies. Network‐level changes in cerebral brain function thus potentially serve to mitigate the impact of motor impairments in Friedreich ataxia. © 2017 International Parkinson and Movement Disorder Society
Viral‐mediated oligodendroglial alpha‐synuclein expression models multiple system atrophy
Authors: Bassil Fares , Guerin Paul A. , Dutheil Nathalie , Li Qin , Klugmann Matthias , Meissner Wassilios G. , Bezard Erwan , Fernagut Pierre‐Olivier
Published: May 2017

Background: MSA is a fatal neurodegenerative disorder characterized by a combination of autonomic dysfunction, cerebellar ataxia, and l‐dopa unresponsive parkinsonism. The hallmark of MSA is the accumulation of α‐synuclein, forming cytoplasmic inclusions in oligodendrocytes. Adeno‐associated viruses allow efficient targeting of disease‐associated genes in selected cellular ensembles and have proven efficient for the neuronal overexpression of α‐synuclein in the substantia nigra in the context of PD.

Objectives: We aimed to develop viral‐based models of MSA.

Methods: Chimeric viral vectors expressing either human wild‐type α‐synuclein or green fluorescent protein under the control of mouse myelin basic protein were injected in the striatum of rats and monkeys. Rats underwent a longitudinal motor assessment before histopathological analysis at 3 and 6 months.

Results: Injection of vectors expressing α‐synuclein in the striatum resulted in >80% oligodendroglial selectivity in rats and >60% in monkeys. Rats developed progressive motor deficits that were l‐dopa unresponsive when assessed at 6 months. Significant loss of dopaminergic neurons occurred at 3 months, further progressing at 6 months, together with a loss of striatal neurons. Prominent α‐synuclein accumulation, including phosphorylated and proteinase‐K–resistant α‐synuclein, was detected in the striatum and substantia nigra.

Conclusions: Viral‐mediated oligodendroglial expression of α‐synuclein allows replicating some of the key features of MSA. This flexible strategy can be used to investigate, in several species, how α‐synuclein accumulation in selected oligodendroglial populations contributes to the pathophysiology of MSA and offers a new framework for preclinical validation of therapeutic strategies. © 2017 International Parkinson and Movement Disorder Society
Patient‐reported outcomes in Huntington's disease: Quality of life in neurological disorders (Neuro‐QoL) and Huntington's disease health‐related quality of life (HDQLIFE) physical function measures
Authors: Carlozzi Noelle E. , Ready Rebecca E. , Frank Samuel , Cella David , Hahn Elizabeth A. , Goodnight Siera M. , Schilling Stephen G. , Boileau Nicholas R. , Dayalu Praveen
Published: May 2017

Background: There is a need for patient‐reported outcome measures that capture the impact that motor impairments have on health‐related quality of life in individuals with Huntington's disease.

Objectives: The objectives of this study were to establish the reliability and validity of new physical functioning patient‐reported outcome measures in Huntington's disease.

Methods: A total of 510 individuals with Huntington's disease completed 2 Quality of Life in Neurological Disorders (Lower Extremity Function and Upper Extremity Function) and 3 Huntington's Disease Health‐Related Quality of Life (Chorea, Speech Difficulties, and Swallowing Difficulties) measures. Clinician‐rated and generic self‐report measures were also administered.

Results: Reliabilities for the new patient reported physical functioning measures were excellent (all Cronbach's α > .92). Convergent, discriminant validity and known group validity was supported.

Conclusions: The results provide psychometric support for new patient‐reported physical functioning measures and the fact that these measures can be used as clinically meaningful endpoints in Huntington's disease research and clinical practice. © 2017 International Parkinson and Movement Disorder Society
Coherence enhancement in quantitative susceptibility mapping by means of anisotropic weighting in morphology enabled dipole inversion
Authors: Kee Youngwook , Cho Junghun , Deh Kofi , Liu Zhe , Spincemaille Pascal , Wang Yi
Published: May 2017

Purpose

To investigate an anisotropic structural prior in morphology enabled dipole inversion (MEDI) for improving accuracy in quantitative susceptibility mapping (QSM).

Theory and Methods

Anisotropic weighting (AW) was devised and implemented to incorporate orientation information into the edge agreement in the MEDI method. AW performance was compared with isotropic weighting by testing and validating on in vivo brain multiple orientation MRI data using COSMOS and the (33) component of the susceptibility tensor as reference.

Results

Suppressing streaking artifacts, AW improved not only QSM image quality but also accuracy in terms of RMSE (root mean square error), HFEN (high frequency error norm), SSIM (structural similarity index), and GDA (gradient direction agreement). In addition, it outperformed isotropic weighting in region of interest‐based analysis. From a computational perspective, AW was as fast as isotropic weighting, taking approximately the same central processing unit times.

Conclusion

Using AW in MEDI improves QSM accuracy compared with isotropic weighting. Magn Reson Med 79:1172–1180, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Effects of hemodialysis on intraneural blood flow in end‐stage kidney disease
Authors: Borire Adeniyi A. , Arnold Ria , Pussell Bruce A. , Kwai Natalie C. , Visser Leo H. , Simon Neil G. , Kiernan Matthew C. , Krishnan Arun V.
Published: May 2017

Introduction: We quantified intraneural blood flow (INBF) in 18 patients with end‐stage kidney disease (ESKD) and examined its relationship with nerve size, neuropathy severity, and nerve excitability parameters. Methods: Sonographic measurements of the median nerve were performed at the same site before and after hemodialysis. INBF was quantified by analyzing power Doppler sonograms to obtain the vessel score (VSc) and maximum perfusion intensity (MPI). Corresponding median motor nerve excitability studies were performed. Neuropathy severity was assessed using Total Neuropathy Score. Results: A total of 39% of ESKD patients had detectable INBF compared with none in the control group (P < 0.0001). Patients with detectable INBF had larger nerves and more severe neuropathy (P < 0.01). INBF parameters were significantly reduced after a session of dialysis (VSc: P < 0.01; MPI: P < 0.01). A significant relationship was found between interdialytic change in INBF and changes in nerve excitability. Conclusions: Increased INBF is a potential marker for neuropathy severity in ESKD patients. Muscle Nerve 57: 287–293, 2018
Soluble activin receptor type IIB decoy receptor differentially impacts murine osteogenesis imperfecta muscle function
Authors: Jeong Youngjae , Daghlas Salah A. , Kahveci Alp S. , Salamango Daniel , Gentry Bettina A. , Brown Marybeth , Rector R. Scott , Pearsall R. Scott , Phillips Charlotte L.
Published: May 2017

Introduction: Osteogenesis imperfecta (OI) is characterized by skeletal fragility and muscle weakness. In this study we investigated the effects of soluble activin type IIB receptor (sActRIIB‐mFc) on muscle mass and function in 2 distinct mouse models of OI: osteogenesis imperfecta murine (oim) and +/G610C. Methods: Wild‐type (WT), +/G610C, and oim/oim mice were treated from 2 to 4 months of age with Tris‐buffered saline (vehicle) or sActRIIB‐mFc and their hindlimb muscles evaluated for mass, morphology, and contractile function. Results: sActRIIB‐mFc‐treated WT, +/G610C, and oim/oim mice had increased hindlimb muscle weights and myofiber cross‐sectional area compared with vehicle‐treated counterparts. sActRIIB‐mFc‐treated oim/oim mice also exhibited increased contractile function relative to vehicle‐treated counterparts. Discussion: Blocking endogenous ActRIIB was effective at increasing muscle size in mouse models of OI, and increasing contractile function in oim/oim mice. ActRIIB inhibitors may provide a potential mutation‐specific therapeutic option for compromised muscle function in OI. Muscle Nerve 57: 294–304, 2018
Recovery of rat muscle size but not function more than 1 year after a single botulinum toxin injection
Authors: Ward Samuel R. , Minamoto Viviane B. , Suzuki Kentaro P. , Hulst Jonah B. , Bremner Shannon N. , Lieber Richard L.
Published: May 2017

Introduction

Neurotoxin injection is used to treat a wide variety of neuromuscular disorders. The purpose of this study was to measure the functional and structural properties of botulinum toxin–injected adult rat skeletal muscle over nearly the entire lifespan.

Methods

Ten groups of animals were subjected to either neurotoxin injection [Botox, Type A (BT‐A); Allergan, Irvine, California] or saline solution injection. Neurotoxin‐injected animals (n = 90) were analyzed at different time‐points: 1 week; 1 month; 3 months; 6 months; 12 months; or 18 months.

Results

In spite of the recovery of structural features, such as muscle mass and fiber area, dorsiflexion torque production remained significantly depressed by 25%, even at 12 months after neurotoxin injection.

Discussion

The data demonstrate that, after a single BT‐A injection, although gross muscle morphology recovered over a 12‐month time period, loss of contractile function did not recover. Muscle Nerve 57: 435–441, 2018
Effect of adding nanosilica particulate filler on the wear behavior of dental composite
Authors: Sonal   , Kumar Shiv Ranjan , Patnaik Amar , Meena Anoj , Godara Manish
Published: May 2017

The aim of this study was to fabricate BisGMA based nanosilica filled dental composites and to study the effect of varying nanosilica filler content on their wear characteristics. The composites were developed by varying filler content of silane treated nanosilica from 0 to 9 wt%, into the resin matrix consisting of 51 wt% Bisphenol‐A glycidyl methacrylate, 46.5 wt% Tri‐ethylene glycol dimethacrylate, 0.24 wt% Camphorquinone, 1.5 wt% Butyl hydroxyl toluene and 0.76 wt% Dimethylamino ethyl methacrylate. The hardness was determined using Vickers's micro hardness tester. The two body abrasive wear experiments were performed in the artificial saliva medium as per Taguchi Orthogonal Array and steady state condition by varying parameters such as filler content, normal load, and chewing speed. The finding of results indicated that the wear resistance and hardness were improved with increase in filler fraction. The dental composite filled with 9 wt% of nanosilica filler exhibited maximum hardness (31.4 HV), maximum compression strength (360.5 MPa) and flexural strength (120.5 MPa) and minimum volumetric wear rate. Also, the wear volume increased with the increase in normal load, chewing speed and number of cycles but decreased with the increase in filler content. Statistical significance of each factor as per generalized linear model of Analysis of Variance showed that filler content was the most influencing factor followed by applied normal load, numbers of cycle and chewing speed. Worn surfaces were studied using a scanning electron microscope (SEM) to give an insight into the wear mechanisms. POLYM. COMPOS., 39:E332–E341, 2018. © 2017 Society of Plastics Engineers
Macroporous polyacrylamide hydrogels with tailored porosity and mechanical properties via microphase separation in the presence of hydroxyethylcellulose
Authors: Bignotti Fabio , Agnelli Silvia , Baldi Francesco , Sartore Luciana , Peroni Isabella
Published: May 2017

In this work hydroxyethylcellulose (HEC) was employed to prepare macroporous polyacrylamide (PAAm) hydrogels with different porosities and degrees of interconnectivity. The porosity and the equilibrium mass swelling ratio of hydrogels equilibrated in 0.1 M NaCl increased with the amount of HEC employed in the reaction mixture. Tensile and fracture tests were performed to investigate the mechanical behavior of both as prepared hydrogels and of hydrogels equilibrated in 0.1 M NaCl. As prepared hydrogels displayed invariably better mechanical properties than the corresponding equilibrated hydrogels. The mechanical stiffness decreased regularly as the amount of HEC (and porosity) was increased. A more complex trend was observed for the ultimate properties (elongation and stress at break) and for the fracture resistance, which displayed a maximum at intermediate HEC contents. POLYM. ENG. SCI., 57:764–771, 2017. © 2017 Society of Plastics Engineers
Decreased Absorption of Dolutegravir and Tenofovir Disoproxil Fumarate, But Not Emtricitabine, in anHIV‐Infected Patient Following Oral and Jejunostomy‐Tube Administration
Authors: Brooks Kristina M. , Garrett Katy L. , Kuriakose Safia S. , George Jomy M. , Balba Gayle , Bailey Bria , Anderson Megan , Lane H. Clifford , Maldarelli Frank , Pau Alice K.
Published: May 2017

The use of enteral feeding tubes to administer antiretroviral medications is necessary in certain patients with human immunodeficiency virus (HIV) infection. However, adequacy of drug exposures after these administration routes are largely unknown, making dosing recommendations and the attainment of viral suppression challenging in this patient population. This report describes a patient with advancedHIVinfection and a complicated medical history including long‐term intractable nausea/vomiting necessitating antiretroviral medication administration via a Roux‐en‐Y jejunostomy (J)‐tube. Pharmacokinetic assessments were performed to compare differences in antiretroviral drug absorption and plasma exposure following oral and J‐tube administration of dolutegravir, tenofovir disoproxil fumarate, and emtricitabine. Results were also compared with published pharmacokinetic data inHIV‐infected individuals. Exposure to dolutegravir and tenofovir were similar between J‐tube and oral administration routes, whereas emtricitabine exposure was 38% lower when administered via J‐tube. However, in comparison with reference data inHIV‐infected individuals taking these medications orally, exposure to dolutegravir and tenofovir was 75–76% and 55–61% lower, respectively, following both routes of administration. Emtricitabine exposure was similar to and 71% higher than reference data following J‐tube and oral administration, respectively. This report highlights the importance of performing pharmacokinetic assessments in patients with the potential for impaired drug absorption to ensure antiretroviral treatment success.
Prevalence rates of childhood protective factors in adolescents with BPD, psychiatrically healthy adolescents and adults with BPD
Authors: Borkum Dana B. , Temes Christina M. , Magni Laura R. , Fitzmaurice Garrett M. , Aguirre Blaise A. , Goodman Marianne , Zanarini Mary C.
Published: May 2017

Objective

Existing literature on the aetiology of borderline personality disorder (BPD) has primarily focused on pathological childhood experiences, while little to no research has been conducted on protective factors that may serve to ameliorate these symptoms. The current study attempts to fill this gap in the literature by comparing the rates of childhood protective factors among adolescents with BPD, psychiatrically healthy adolescents and adults with BPD.

Methods

One hundred and four subjects were adolescent inpatients between the ages of 13 and 17 who met Revised Diagnostic Interview for Borderlines and Diagnostic and Statistical Manual of Mental Disorders Fourth Edition criteria for BPD. Sixty were age‐matched psychiatrically healthy comparison subjects. Two hundred and ninety subjects were adult inpatients between the ages of 18 and 35 who met Revised Diagnostic Interview for Borderlines and Revised Diagnostic and Statistical Manual of Mental Disorders Third Edition criteria for BPD. All three groups were interviewed by using the Revised Childhood Experiences Questionnaire, a semi‐structured interview that assesses pathological and protective childhood experiences.

Results

Psychiatrically healthy adolescents reported significantly higher rates of 4 out of 18 protective factors than adolescents with BPD. Adolescents with BPD reported significantly higher rates of 5 of these 18 protective factors than adults with BPD. Adults with BPD were significantly more likely to endorse having a steady after school or weekend work record than adolescents with BPD.

Conclusions

Taken together, the results of this study suggest that adolescents meeting criteria for BPD report lower rates of some protective factors than psychiatrically healthy adolescents. They also suggest that they have higher rates of some protective factors than adults with BPD. Copyright © 2017 John Wiley & Sons, Ltd.
SWATH‐based quantitative proteomics reveals the mechanism of enhanced Bombyx mori nucleopolyhedrovirus‐resistance in silkworm reared on UV‐B treated mulberry leaves
Authors: Hu Jin , Zhu Wei , Li Yaohan , Guan Qijie , Yan Haijian , Yu Jiaojiao , Fu Zhirong , Lu Xingmeng , Tian Jingkui
Published: May 2017

Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the most acute infectious diseases in silkworm, which has led to great economic loss in sericulture. Previous study showed that the content of secondary metabolites in mulberry leaves, particularly for moracin N, was increased after UV‐B irradiation. In this study, the BmNPV resistance of silkworms reared on UV‐B treated and moracin N spread mulberry leaves was improved. To uncover the mechanism of enhanced BmNPV resistance, silkworm midguts from UV‐B treated mulberry leaves (BUM) and moracin N (BNM) groups were analyzed by SWATH‐based proteomic technique. Of note, the abundance of ribosomal proteins in BUM and BNM groups was significantly changed to maintain the synthesis of total protein levels and cell survival. While, cytochrome c oxidase subunit II, calcium ATPase and programmed cell death 4 involved in apoptotic process were up‐regulated in BNM group. Expressions of lipase‐1, serine protease precursor, Rab1 protein, and histone genes were increased significantly in BNM group. These results suggest that moracin N might be the main active component in UV‐B treated mulberry leaves which could improve the BmNPV‐resistance of silkworm through promoting apoptotic cell death, enhancing the organism immunity, and regulating the intercellular environment of cells in silkworm. It also presents an innovative process to reduce the mortality rate of silkworms infected with BmNPV.
Quantitative proteome‐based systematic identification of SIRT7 substrates
Authors: Zhang Chaohua , Zhai Zichao , Tang Ming , Cheng Zhongyi , Li Tingting , Wang Haiying , Zhu Wei‐Guo
Published: May 2017

SIRT7 is a class III histone deacetylase that is involved in numerous cellular processes. Only six substrates of SIRT7 have been reported thus far, so we aimed to systematically identify SIRT7 substrates using stable‐isotope labeling with amino acids in cell culture (SILAC) coupled with quantitative mass spectrometry (MS). Using SIRT7+/+ and SIRT7−/− mouse embryonic fibroblasts as our model system, we identified and quantified 1493 acetylation sites in 789 proteins, of which 261 acetylation sites in 176 proteins showed ≥2‐fold change in acetylation state between SIRT7−/− and SIRT7+/+ cells. These proteins were considered putative SIRT7 substrates and were carried forward for further analysis. We then validated the predictive efficiency of the SILAC–MS experiment by assessing substrate acetylation status in vitro in six predicted proteins. We also performed a bioinformatic analysis of the MS data, which indicated that many of the putative protein substrates were involved in metabolic processes. Finally, we expanded our list of candidate substrates by performing a bioinformatics‐based prediction analysis of putative SIRT7 substrates, using our list of putative substrates as a positive training set, and again validated a subset of the proteins in vitro. In summary, we have generated a comprehensive list of SIRT7 candidate substrates.
Select human cancer mutants of NRMT1 alter its catalytic activity and decrease N‐terminal trimethylation
Authors: Shields Kaitlyn M. , Tooley John G. , Petkowski Janusz J. , Wilkey Daniel W. , Garbett Nichola C. , Merchant Michael L. , Cheng Alan , Schaner Tooley Christine E.
Published: May 2017

A subset of B‐cell lymphoma patients have dominant mutations in the histone H3 lysine 27 (H3K27) methyltransferase EZH2, which change it from a monomethylase to a trimethylase. These mutations occur in aromatic resides surrounding the active site and increase growth and alter transcription. We study the N‐terminal trimethylase NRMT1 and the N‐terminal monomethylase NRMT2. They are 50% identical, but differ in key aromatic residues in their active site. Given how these residues affect EZH2 activity, we tested whether they are responsible for the distinct catalytic activities of NRMT1/2. Additionally, NRMT1 acts as a tumor suppressor in breast cancer cells. Its loss promotes oncogenic phenotypes but sensitizes cells to DNA damage. Mutations of NRMT1 naturally occur in human cancers, and we tested a select group for altered activity. While directed mutation of the aromatic residues had minimal catalytic effect, NRMT1 mutants N209I (endometrial cancer) and P211S (lung cancer) displayed decreased trimethylase and increased monomethylase/dimethylase activity. Both mutations are located in the peptide‐binding channel and indicate a second structural region impacting enzyme specificity. The NRMT1 mutants demonstrated a slower rate of trimethylation and a requirement for higher substrate concentration. Expression of the mutants in wild type NRMT backgrounds showed no change in N‐terminal methylation levels or growth rates, demonstrating they are not acting as dominant negatives. Expression of the mutants in cells lacking endogenous NRMT1 resulted in minimal accumulation of N‐terminal trimethylation, indicating homozygosity could help drive oncogenesis or serve as a marker for sensitivity to DNA damaging chemotherapeutics or γ‐irradiation.
Translational Modeling to Guide Study Design and Dose Choice in Obesity Exemplified by AZD1979, a Melanin‐concentrating Hormone Receptor 1 Antagonist
Authors: Gennemark P , Trägårdh M , Lindén D , Ploj K , Johansson A , Turnbull A , Carlsson B , Antonsson M
Published: May 2017

In this study, we present the translational modeling used in the discovery of AZD1979, a melanin‐concentrating hormone receptor 1 (MCHr1) antagonist aimed for treatment of obesity. The model quantitatively connects the relevant biomarkers and thereby closes the scaling path from rodent to man, as well as from dose to effect level. The complexity of individual modeling steps depends on the quality and quantity of data as well as the prior information; from semimechanistic body‐composition models to standard linear regression. Key predictions are obtained by standard forward simulation (e.g., predicting effect from exposure), as well as non‐parametric input estimation (e.g., predicting energy intake from longitudinal body‐weight data), across species. The work illustrates how modeling integrates data from several species, fills critical gaps between biomarkers, and supports experimental design and human dose‐prediction. We believe this approach can be of general interest for translation in the obesity field, and might inspire translational reasoning more broadly.