bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Bladder Matrix Does Not Improve Tenogenesis in an In Vitro Equine Model
Authors: Khatibzadeh Sarah M. , Menarim Bruno C. , Nichols Anne E. C. , Werre Stephen R. , Dahlgren Linda A.
Published: May 2019

Extracellular matrix (ECM) is responsible for tendon strength and elasticity. Healed tendon ECM lacks structural integrity, leading to reinjury. Porcine urinary bladder matrix (UBM) provides a scaffold and source of bioactive proteins to improve tissue healing, but has received limited attention for treating tendon injuries. The objective of this study was to evaluate the ability of UBM to induce matrix organization and tenogenesis using a novel in vitro model. We hypothesized that addition of UBM to tendon ECM hydrogels would improve matrix organization and cell differentiation. Hydrogels seeded with bone marrow cells (n = 6 adult horses) were cast using rat tail tendon ECM ± UBM, fixed under static tension and harvested at 7 and 21 days for construct contraction, cell viability, histology, biochemistry, and gene expression. By day 7, UBM constructs contracted significantly from baseline, whereas control constructs did not. Both control and UBM constructs contracted significantly by day 21. In both groups, cells remained viable over time and changed from round and randomly oriented to elongated along lines of tension with visible compaction of the ECM. There were no differences over time or between treatments for nuclear aspect ratio, DNA, or glycosaminoglycan content. Decorin, matrix metalloproteinase 13, and scleraxis expression increased significantly over time, but not in response to UBM treatment. Mohawk expression was constant over time. Cartilage oligomeric matrix protein expression decreased over time in both groups. Using a novel ECM hydrogel model, substantial matrix organization and cell differentiation occurred; however, the addition of UBM failed to induce greater matrix organization than tendon ECM alone. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1848–1859, 2019
Scaffold‐Based Delivery of Nucleic Acid Therapeutics for Enhanced Bone and Cartilage Repair
Authors: Kelly Domhnall C. , Raftery Rosanne M. , Curtin Caroline M. , O’Driscoll Caitriona M. , O’Brien Fergal J.
Published: May 2019

Recent advances in tissue engineering have made progress toward the development of biomaterials capable of the delivery of growth factors, such as bone morphogenetic proteins, in order to promote enhanced tissue repair. However, controlling the release of these growth factors on demand and within the desired localized area is a significant challenge and the associated high costs and side effects of uncontrolled delivery have proven increasingly problematic in clinical orthopedics. Gene therapy may be a valuable tool to avoid the limitations of local delivery of growth factors. Following a series of setbacks in the 1990s, the field of gene therapy is now seeing improvements in safety and efficacy resulting in substantial clinical progress and a resurgence in confidence. Biomaterial scaffold‐mediated gene therapy provides a template for cell infiltration and tissue formation while promoting transfection of cells to engineer therapeutic proteins in a sustained but ultimately transient fashion. Additionally, scaffold‐mediated delivery of RNA‐based therapeutics can silence specific genes associated with orthopedic pathological states. This review will provide an overview of the current state‐of‐the‐art in the field of gene‐activated scaffolds and their use within orthopedic tissue engineering applications. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1671–1680, 2019
Platelet‐Rich Plasma (PRP) From Older Males With Knee Osteoarthritis Depresses Chondrocyte Metabolism and Upregulates Inflammation
Authors: O’Donnell Christian , Migliore Eleonora , Grandi Fiorella Carla , Koltsov Jayme , Lingampalli Nithya , Cisar Cecilia , Indelli Pier F. , Sebastiano Vittorio , Robinson William H. , Bhutani Nidhi , Chu Constance R.
Published: May 2019

There is intense clinical interest in the potential effects of platelet‐rich plasma (PRP) for the treatment of osteoarthritis (OA). This study tested the hypotheses that (i) “lower” levels of the inflammatory mediators (IMs), interleukin‐1β, and tumor necrosis factor α (TNF‐α) and (ii) “higher” levels of the growth factors (GFs), insulin‐like growth factor 1, and transforming growth factor β1 within leukocyte‐poor PRP correlate with more favorable chondrocyte and macrophage responses in vitro. Samples were collected from 10 “healthy” young male (23–33 years old) human subjects (H‐PRP) and nine older (62–85 years old) male patients with severe knee OA (OA‐PRP). The samples were separated into groups of “high” or “low” levels of IM and GF based on multiplex cytokine and enzyme‐linked immunosorbent assay data. Three‐dimensional (3D) alginate bead chondrocyte cultures and monocyte‐derived macrophage cultures were treated with 10% PRP from donors in different groups. Gene expression was analyzed by quantitative polymerase chain reaction. Contrary to our hypotheses, the effect of PRP on chondrocytes and macrophages was mainly influenced by the age and disease status of the PRP donor as opposed to the IM or GF groupings. While H‐PRP showed similar effects on expression of chondrogenic markers (Col2a1 and Sox9) as the negative control group (p > 0.05), OA‐PRP decreased chondrocyte expression of Col2a1 and Sox‐9 messenger RNA by 40% and 30%, respectively (Col2a1, p = 0.015; Sox9, p = 0.037). OA‐PRP also upregulated TNF‐α and matrix metallopeptidase 9 (p < 0.001) gene expression in macrophages while H‐PRP did not. This data suggests that PRP from older individuals with OA contain factors that may suppress chondrocyte matrix synthesis and promote macrophage inflammation in vitro. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1760–1770, 2019
Associations Between Intervertebral Disc Degeneration Grading Schemes and Measures of Disc Function
Authors: Zehra Uruj , Noel‐Barker Natasha , Marshall John , Adams Michael A. , Dolan Patricia
Published: May 2019

Disc degeneration is a major cause of spinal dysfunction and pain, but grading schemes concentrate on tissue changes rather than altered function. The aim of this study was to compare disc degeneration grading systems with each other, and with biomechanical measures of disc function. Sixty‐six motion segments (T8–9 to L5–S1) were dissected from cadavers aged 48–98 years. Disc function was assessed by measuring nucleus pressure (IDP) and maximum stresses in the annulus under 1 kN of compression. Detailed “scores” of disc degeneration were based on independent radiographic, macroscopic, and microscopic evaluations. For each evaluation, scores were used to assign a degeneration “grade” (I–IV), and functional measures were then correlated with degeneration scores and grades. Results showed that all measures were reliable (intraclass correlation coefficients: 0.82–0.99). Macroscopic and microscopic assessments were highly correlated with each other (r: 0.57–0.89, p < 0.001) but only weakly correlated with radiographic features. The overall macroscopic and microscopic scores of degeneration increased significantly with age and at lower spinal levels, although the influence of age was less marked in the case of the microscopic scores. IDP decreased with age and at lower spinal levels, but annulus stresses were more variable. Importantly, IDP and annulus stresses decreased consistently with all measures of disc degeneration, and these associations remained strong after controlling for age, gender, and spinal level. We conclude that radiographic and tissue‐based assessments of disc degeneration are consistent with each other, and are more closely related to mechanical (dys)function than to age or spinal level. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1946–1955, 2019
Ultrasound‐Guided Dry Needling of the Healthy Rat Supraspinatus Tendon Elicits Early Healing Without Causing Permanent Damage
Authors: Riggin Corinne N. , Chen Mengcun , Gordon Joshua A. , Schultz Susan M. , Soslowsky Louis J. , Khoury Viviane
Published: May 2019

Overuse‐induced tendinopathy is highly prevalent in the general population. Percutaneous fenestration, or dry needling, techniques have been increasing in popularity, but despite their current use, there are no controlled laboratory studies to provide fundamental support for this practice. The objective of this study was to establish a model for percutaneous needling of the rat supraspinatus tendon using ultrasound guidance and to evaluate the biological response of needling healthy tendon. A total of 44 male Sprague–Dawley rats (477 ± 39 g) were used to evaluate the effect of dry needling on healthy supraspinatus tendon properties. Ten rats were reserved as un‐needled control animals, and the remaining animals underwent either mild or moderate bilateral needling protocols and were sacrificed at 1 or 6 weeks post‐needling (n = 8–10/group). Color Doppler ultrasound imaging was performed to analyze blood flow within the tendon. Histological and immunohistochemical analyses were used to determine cellular, inflammatory, and extracellular matrix properties of the tissue. Finally, quasi‐static tensile mechanical analysis was performed to obtain viscoelastic, structural, and material properties to evaluate the tendon healing outcome. Data were tested for normality, and then two‐way analysis of variance tests were performed followed by post hoc tests for multiple comparisons. Both the mild and moderate needling groups caused a transient healing response at early time points as shown by a statistically significant (p < 0.05) reduction in mechanical properties, and increase in blood flow, inflammation, and production of collagen III and glycosaminoglycans as compared to the control. Furthermore, mild needling properties returned to or exceeded pre‐needling values at the 6‐week time point. Clinical significance: Needling the rat supraspinatus tendon is a feasible technique that causes a transient healing response followed by a return to, or improvement of, normal tendon properties, indicating potential applicability in understanding the effects of current practices utilizing dry needling of tendons in humans. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2035–2042, 2019
Muscle and Joint Function After Anatomic and Reverse Total Shoulder Arthroplasty Using a Modular Shoulder Prosthesis
Authors: Ackland David C. , Wu Wen , Thomas Richard , Patel Minoo , Page Richard , Sangeux Morgan , Richardson Martin
Published: May 2019

Changes in joint architecture and muscle loading resulting from total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RSA) are known to influence joint stability and prosthesis survivorship. This study aimed to measure changes in muscle moment arms, muscle lines of action, as well as muscle and joint loading following TSA and RSA using a metal‐backed uncemented modular shoulder prosthesis. Eight cadaveric upper extremities were assessed using a customized testing rig. Abduction, flexion, and axial rotation muscle moment arms were quantified using the tendon‐excursion method, and muscle line‐of‐force directions evaluated radiographically pre‐operatively, and after TSA and revision RSA. Specimen‐specific musculoskeletal models were used to estimate muscle and joint loading pre‐ and post‐operatively. TSA lateralized the glenohumeral joint center by 4.3 ± 3.2 mm, resulting in small but significant increases in middle deltoid force (2.0%BW) and joint compression during flexion (2.1%BW) (p < 0.05). Revision RSA significantly increased the moment arms of the major abductors, flexors, adductors, and extensors, and reduced their peak forces (p < 0.05). The superior inclination of the deltoid significantly increased while the inferior inclination of the rotator cuff muscles decreased (p < 0.05). TSA using an uncemented metal‐backed modular shoulder prosthesis effectively restores native joint function; however, lateralization of the glenoid component should be minimized intra‐operatively to mitigate increased glenohumeral joint loading and polyethylene liner contact stresses. Revision RSA reduces muscle forces required during shoulder function but produces greater superior joint shear force and less joint compression. The findings may help to guide component selection and placement to mitigate joint instability after arthroplasty. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1988–2003, 2019
Typical Shape Differences in the Subtalar Joint Bones Between Subjects with Chronic Ankle Instability and Controls
Authors: Tümer Nazlı , Vuurberg Gwendolyn , Blankevoort Leendert , Kerkhoffs Gino M M. J. , Tuijthof Gabrielle J. M. , Zadpoor Amir A.
Published: May 2019

Bone shapes, particularly those defining the subtalar joint (STJ), have not received much attention yet as a risk factor for developing chronic ankle instability (CAI) after sustaining a lateral ankle sprain (LAS). This study aimed to compare three‐dimensional (3D) shape variations in the STJ bones within individuals with CAI and healthy controls. 3D statistical shape models (SSMs) of the STJ bones were built to describe the bone shape variations observed within a population consisting of 26 individuals with unilateral CAI and 26 healthy controls. Using the SSMs and analysis of covariance test, age‐ and gender‐adjusted shape variations in the bones were compared within individuals with CAI and healthy controls. The mean age of the CAI patients (14 males and 12 females) and healthy controls (12 males and 14 females) was 29 (standard deviation [SD] = 11) and 36 years (SD = 11), respectively. Tali and calcanei did not significantly vary between ipsilateral CAI and their contralateral ankle. Two shape modes, one for the talus (p = 0.015, variations in the curvature of the talar lateral process and the inclination angle of the talar neck relative to the body) and one for the calcaneus (p = 0.003, variations in the medial and lateral tuberosities, and the contour of the anterior articular surface), described significant shape differences between the CAI patients and healthy controls. The CAI patients generally had flatter talar joint surfaces and a flattened calcaneal ground‐contact surface. These findings suggest that specific bone shapes may increase the risk of developing CAI after sustaining a LAS. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:1892–1902, 2019
A kinked meta‐regression model for publication bias correction
Authors: Bom Pedro R. D. , Rachinger Heiko
Published: May 2019

Publication bias distorts the available empirical evidence and misinforms policymaking. Evidence of publication bias is mounting in virtually all fields of empirical research. This paper proposes the endogenous kink (EK) meta‐regression model as a novel method of publication bias correction. The EK method fits a piecewise linear meta‐regression of the primary estimates on their standard errors, with a kink at the cutoff value of the standard error below which publication selection is unlikely. We provide a simple method of endogenously determining this cutoff value as a function of a first‐stage estimate of the true effect and an assumed threshold of statistical significance. Our Monte Carlo simulations show that EK is less biased and more efficient than other related regression‐based methods of publication bias correction in a variety of research conditions.
S‐(E)‐Elenolide: a new constituent of extra virgin olive oil
Authors: Rigakou Aimilia , Diamantakos Panagiotis , Melliou Eleni , Magiatis Prokopios
Published: May 2019

BACKGROUND

Extra virgin olive oil is a food with a recognized health claim in the EU related to its phenolic content. Based on nuclear magnetic resonance (NMR) analysis, we observed for the first time that most high‐phenolic olive oils also contain significant quantities of another potential beneficial ingredient, S‐(E)‐elenolide, which is a non‐phenolic compound related to oleuropein or ligstroside. Elenolide had only been found in olive leaves and fruits as the Z isomer or had been synthesized and had been recognized as an antihypertensive agent.

RESULTS

(E)‐Elenolide was isolated from olive oil and its structure was elucidated and completely characterized for the first time using 1D and 2D NMR and gas chromatography–mass spectrometry. In addition, we developed a method of quantitative measurement based on qNMR. Investigation of 2120 olive oil samples showed that elenolide was present in the majority of samples, in quantities ranging from 0 to 2821 mg kg−1. Although elenolic acid, which is a hydrated derivative of elenolide, had been reported as an olive oil ingredient, this is the first time that elenolide has proved to be transformed to elenolic acid after reaction with water. Finally, it was found that the quantity of elenolide in olive oil depends on the quantity of water remaining in the olive oil during storage.

CONCLUSION

S‐(E)‐Elenolide is a new important substance of olive oil and could be used as marker of high‐quality oils with low water content. © 2019 Society of Chemical Industry
Dissolvable layered double hydroxide as a sorbent in dispersive micro‐solid phase extraction for the determination of acidic quinolones in honey by HPLC
Authors: Di Xin , Wang Xin , Liu Youping , Guo Xingjie , Di Xin
Published: May 2019

This study presents a simple and green dispersive micro‐solid phase extraction method for preconcentration of acidic quinolones from honey prior to high performance liquid chromatography determination. A two‐dimensional nanostructured zinc‐aluminum layered double hydroxide was synthesized and used as the sorbent for dispersive micro‐solid phase extraction. Its different characteristics from conventional sorbents is that it is dissolvable in acidic solution (pH < 4). After the extraction, the analyte elution step was omitted and thus the use of organic solvents was avoided. The key parameters influencing the extraction efficiency such as the amount of sorbent, pH of sample solution, vortex time, type and volume of acidic solution were investigated and optimized. The method exhibited low limits of detection (3.0−5.0 ng/g), good linearity (10−2000 ng/g) with coefficients of determinations higher than 0.9991, acceptable precision (RSD<9.1%) and accuracy (RE<5.8%). The proposed method is fast, efficient, eco‐friendly, and suitable for the determination of acidic quinolones in honey samples.
Which Is the Best Reference Tissue for Strain Elastography in Predicting Malignancy in Thyroid Nodules, the Sternocleidomastoid Muscle or the Thyroid Parenchyma?
Authors: Görgülü Feride Fatma
Published: May 2019

Objectives

This study aimed to compare 2 types of strain ratios (SRs) in thyroid nodules. Two reference points were used: the sternocleidomastoid (SCM) muscle and the thyroid parenchyma.

Methods

A total of 101 nodules in 83 patients were prospectively enrolled in the study. For the semiquantitative analysis, 2 types of SRs were used: SR1, the ratio of the SCM muscle strain to the thyroid nodule strain; and SR2, the ratio of the surrounding normal thyroid tissue strain to the thyroid nodule strain. For each nodule, the SR1 and SR2 elastographic values were calculated, and their averages were compared.

Results

Eighty‐one (80.2%) of 101 thyroid nodules were benign, and 20 (19.8%) were malignant. In both benign and malignant histopathologic types, the SR1 averages were significantly higher than the SR2 averages (P = .001; P < .001, respectively). Both the SR1 and SR2 values were found to be significantly successful in differentiating benign from malignant histopathologic types (P < .001 for both). The areas under the curve were then compared for the methods, and the difference was found to be statistically significant (P = .046). The diagnostic accuracy of the SR1 was superior to that of the SR2.

Conclusions

The SR1 and SR2 are effective adjunctive diagnostic tools for identifying malignant thyroid nodules. Using the SCM muscle as a reference point instead of thyroid tissue may be a more valuable way to measure SRs.
Predicting Pouch of Douglas Obliteration Using Ultrasound and Laparoscopic Video Sets: An Interobserver and Diagnostic Accuracy Study
Authors: Chiu Le Chi , Leonardi Mathew , Lu Chuan , Mein Brendan , Nadim Batool , Reid Shannon , Ludlow Joanne , Casikar Ishwari , Condous George
Published: May 2019

Objectives

To investigate the diagnostic accuracy and interobserver agreement among sonologists when assessing offline ultrasound (US) video sets of the “sliding sign” and among gynecologic surgeons when assessing corresponding laparoscopic video sets to predict pouch of Douglas (POD) obliteration and to compare the performance of the groups.

Methods

A diagnostic and reproducibility study was conducted, including 15 observers in 4 groups: (1) senior sonologists, (2) junior sonologists, (3) general gynecologists, and (4) advanced laparoscopists. The sonologists viewed 25 offline preoperative US video sets of the sliding sign, and the surgeons viewed the corresponding intraoperative laparoscopic videos of the same patients. Each observer was asked to classify POD obliteration in the video sets and was compared to the reference standard POD state determined at real‐time laparoscopy by a single investigator (G.C.). The interobserver correlation and diagnostic accuracy were evaluated among the 15 observers and 4 groups. The Cohen κ coefficient and Fleiss κ coefficient were used for the analysis.

Results

The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for senior sonologists were 93.3%, 100%, 89.6%, 84.4%, and 100%, respectively; for junior sonologists, 70.0%, 88.9%, 59.4%, 55.2%, and 90.5%; for general gynecologists, 75.2%, 88.1%, 78.1%, 69.8%, and 91.9%; and for advanced laparoscopists, 82.4%, 91.9%, 90.8%, 82.9%, and 95.8%. The overall agreement between senior sonologists was almost perfect (Fleiss κ = 0.876); for junior sonologists and general gynecologists, it was moderate (Fleiss κ = 0.589 and 0.528); and for advanced laparoscopists, it was substantial (Fleiss κ = 0.652).

Conclusions

Interobserver agreement was superior among senior sonologists. Prediction of POD obliteration using offline US videos by senior sonologists is comparable to offline assessments of laparoscopic videos by advanced laparoscopists for prediction of POD obliteration.
Guidelines on the surgical management of sleep disorders: A systematic review
Authors: Mandavia Rishi , Mehta Nishchay , Veer Vik
Published: May 2019

Objective

To facilitate the development of U.K. guidelines for sleep surgery and to guide sleep surgeons to existing guidelines relevant to their practice, we provide a systematic review and quality assessment of all existing guidelines on the surgical management of sleep disorders.

Methods

Systematic review using preferred reporting items for systematic reviews and meta‐analyses (PRISMA) recommendations. Medline and Embase databases were searched from inception to April 2018. Publications were included if they described a guideline for the surgical management of sleep disorders. Three assessors used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument to evaluate included guidelines.

Results

The systematic search revealed 1,161 publications. Twenty‐two guidelines from eight countries were included. Fourteen focused on adults, five on children, and three on both. The guidelines discussed nasal, tonsillar, palatal, tongue, hyoid, maxillomandibular, tracheal, bariatric, and multilevel surgeries. The mean overall AGREE II quality score of included guidelines was 3.5 (range = 2 to 5.3; maximum possible score = 7).

Conclusion

This article provides a summary and quality assessment of all published guidelines on the surgical management of sleep disorders. No U.K. guidelines were identified, and existing guidelines have several shortcomings. This highlights the need for robust U.K. national guidelines on sleep surgery to promote clinical and cost‐effective care in this field. Our findings can be used by stakeholders as a foundation for the development of new guidelines and can be used by sleep surgeons to direct them to existing guidelines relevant to their practice, promoting evidence‐based clinical care. Laryngoscope, 130:1070–1084, 2020
Measuring Flap Oxygen Using Electron Paramagnetic Resonance Oximetry
Authors: Polacco Marc A. , Hou Huagang , Kuppusamy Periannan , Chen Eunice Y.
Published: May 2019

Objectives/Hypothesis

To determine if electron paramagnetic resonance (EPR) oximetry is a viable technology to aid in flap monitoring.

Study Design

Prospective cohort.

Methods

This was a cohort study assessing accuracy and speed of EPR oximetry in detecting ischemia of a saphenous artery–based flap in a rat model, using transcutaneous oximetry as a control. Measurements were obtained under both resting and ischemic conditions for nine Sprague Dawley rats (18 flaps), for 3 postoperative days following flap elevation.

Results

The mean partial pressure of oxygen prior to tourniquet application was 66.9 ± 8.9 mm Hg with EPR oximetry and 64.7 ± 5.2 mm Hg with transcutaneous oximetry (P = .45). Mean partial pressures of oxygen during tourniquet application were 8.9 ± 3.2 mm Hg and 8.5 ± 2.9 mm Hg for EPR oximetry and transcutaneous oximetry, respectively (P = .48), and 67.2 ± 6.9 mm Hg and 65.3 ± 6.1 mm Hg after tourniquet release for EPR oximetry and transcutaneous oximetry, respectively (P = .44). The mean ischemia detection time of EPR oximetry was 49 ± 21 seconds.

Conclusions

Offering timely, accurate, and noninvasive tissue oxygen measurements, EPR oximetry is a promising adjunct in flap monitoring.

Level of Evidence

NA Laryngoscope, 129:E415–E419, 2019
Electrochemical evaluation of the corrosion protectiveness and porosity of vacuum annealed CrAlN and TiAlN cathodic arc physical vapor deposited coatings
Authors: Adesina Akeem Yusuf , Gasem Zuhair M. , Kumar A. Madhan
Published: May 2019

The corrosion behavior of cathodic arc physical vapor deposited CrAlN and TiAlN coatings were examined in 1 M HCl solution before and after vacuum annealing at 700, 800, 900, and 1000 °C. Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP) methods were used to study the corrosion behavior and porosity of the coatings in comparison with the bare steel substrate (304SS). Structural and mechanical characterization of the coatings were also conducted. It is found that with increasing annealing temperature, the mechanical properties of TiAlN increased due to age hardening caused by spinodal decomposition while the hardness of CrAlN decreased as result of relaxation. Similarly, EIS and PDP results revealed that the as‐deposited and annealed coatings offer higher corrosion resistance as compared to the bare 304SS substrate. The coatings susceptibility to corrosion is reduced after annealing as indicated by the increasing nobility of Ecorr. Both PDP and EIS tests revealed that CrAlN coating annealed at 1000°C exhibited superior corrosion resistance properties. It is found that the reduced current density for CrAlN coating annealed at 1000°C was due to the reduction in the porosity. Annealed TiAlN coating follows similar behavior until an optimum annealing temperature of 800°C. Beyond this temperature, porosity enlargement and an increase in the number of pores subsequent to structural changes deteriorated the corrosion resistance of TiAlN coating.
Cationic Polymerization of (3‐Aminopropyl)‐tris‐furfuryloxysilane Derivatives—a New Strategy for Complex Hybrid Material Synthesis
Authors: Uhlig Daniel , Seifert Andreas , Schreiter Katja , Rüffer Tobias , Lang Heinrich , Thielbeer Frank , Stoll Ragnar , Müller Philipp , Spange Stefan
Published: May 2019

The trifunctional (3‐aminopropyl)‐tris‐furfuryloxysilane monomer (1) is able to undergo both twin polymerization and reaction with electrophilic compounds such as isocyanates. 1 can be readily synthesized from 3‐aminopropyptrimethoxysilane (APTMS) and furfuryl alcohol (FA). The reaction of 1 with three different aromatic isocyanates, namely phenyl isocyanate, diphenylmethane‐4,4′‐diisocyanate (MDI), and a prepolymer consisting of MDI end‐capped polytetramethylene ether glycole (PTMEG), to the corresponding substituted urea derivatives is presented. Three urea derivatives 1‐phenyl‐3‐(3‐tris‐furfuryloxysilyl)propylurea (2), diphenylmethan‐4,4′‐bis[3(tris‐furfuryloxysilyl)propyl]urea (3), bis[3(tris‐furfuryloxysilyl)‐propyl]urea‐capped PTMEG‐MDI‐prepolymer (4) as well as 1 were polymerized to multicomponent organic/inorganic hybrid materials in a one step procedure using methane sulfonic acid as catalyst. The simultaneous formations of poly furfuryl alcohol and polysiloxane networks within the hybrid material are proven by means of solid‐state NMR spectroscopic measurements. The homogeneous distribution of silicon within the solidified hybrid materials is analyzed by scanning electron microscopy, energy dispersive X‐ray spectroscopy, and high‐angle annular dark field‐scanning transmission electron microscopy (HAADF)‐STEM. Homogeneous nanostructured hybrid materials with silicon cluster sizes in the range of 2 nm have been obtained by polymerization of the urea derivatives 2, 3, and 4.
The use of transcranial magnetic stimulation as a treatment for movement disorders: A critical review
Authors: Latorre Anna , Rocchi Lorenzo , Berardelli Alfredo , Bhatia Kailash P. , Rothwell John C.
Published: May 2019

Background

Transcranial magnetic stimulation is a safe and painless non‐invasive brain stimulation technique that has been largely used in the past 30 years to explore cortical function in healthy participants and, inter alia, the pathophysiology of movement disorders. During the years, its use has evolved from primarily research purposes to treatment of a large variety of neurological and psychiatric diseases. In this article, we illustrate the basic principles on which the therapeutic use of transcranial magnetic stimulation is based and review the clinical trials that have been performed in patients with movement disorders.

Methods

A search of the PubMed database for research and review articles was performed on therapeutic applications of transcranial magnetic stimulation in movement disorders. The search included the following conditions: Parkinson's disease, dystonia, Tourette syndrome and other chronic tic disorders, Huntington's disease and choreas, and essential tremor. The results of the studies and possible mechanistic explanations for the relatively minor effects of transcranial magnetic stimulation are discussed. Possible ways to improve the methodology and achieve greater therapeutic efficacy are discussed.

Conclusion

Despite the promising and robust rationales for the use of transcranial magnetic stimulations as a treatment tool in movement disorders, the results taken as a whole are not as successful as were initially expected. There is encouraging evidence that transcranial magnetic stimulation may improve motor symptoms and depression in Parkinson's disease, but the efficacy in other movement disorders is unclear. Possible improvements in methodology are on the horizon but have yet to be implemented in large clinical studies. © 2019 International Parkinson and Movement Disorder Society © 2019 International Parkinson and Movement Disorder Society
Structural stability and stabilization of solutions of the reversible three‐component Gray‐Scott system
Authors: Kalantarova Jamila , Uğurlu Davut
Published: May 2019

This paper is concerned with the structural stability and stabilization of solutions to the three‐component reversible Gray‐Scott system under the Dirichlet or Neumann boundary conditions defined in a bounded domain of
for 1  ≤  n  ≤  3. We prove that each solution depends on changes in a coefficient of the ratio of the reverse and forward reaction rates for the autocatalytic reaction as well as proving the continuous dependence on the initial data. We also prove that under Dirichlet's boundary conditions, the system is stabilized to the stationary solution by finitely many Fourier modes.
Numerical modeling of the immune response to human papillomavirus infection
Authors: Solis Francisco J. , Gonzalez Luz M. , Jerez Silvia
Published: May 2019

In this work, we develop mathematical models describing the interactions between Human papillomavirus (HPV)‐infected cells and the immune system. We start with simple models in order to capture the most important features of such interactions. Then, we proceed to consider fundamental immunological characteristics for the models. For the numerical counterpart, we develop and implement efficient numerical discretizations of our models in order to illustrate the behavior of the schemes using different initial conditions, which represent the degree of infection of the disease. Understanding such interactions is of paramount importance for the prevention and the potential eradication of the infection. One main goal of this research is to analyze how and under what circumstances the immune system succeeds in eliminating HPV‐infected cells.
Whole‐brain B1‐mapping using three‐dimensional DREAM
Authors: Ehses Philipp , Brenner Daniel , Stirnberg Rüdiger , Pracht Eberhard D. , Stöcker Tony
Published: May 2019

Purpose

Demonstration of a 3D version of the DREAM sequence (3DREAM) for rapid 3D flip angle and mapping of the human brain.

Methods

A rectangular non‐selective STE preparation is followed by a 3D readout with a Cartesian center‐out spiral phase encoding order. This enables parallel imaging acceleration in both phase encoding dimensions as well as early capture of the prepared magnetization.

Results

mapping of the whole human head is demonstrated on a 7T system at a nominal resolution of 5 mm with and without parallel imaging acceleration. Artifacts caused by the different signal decay of the FID and STE signal during the long imaging train is suppressed by appropriate filtering of the FID image. Remaining blurring can be controlled by adjusting the echo train length and readout flip angle.

Conclusions

3DREAM provides a whole‐brain flip angle map in a few seconds or individual maps for an 8‐channel array in about a minute.
Transverse relaxation‐based assessment of mammographic density and breast tissue composition by single‐sided portable NMR
Authors: Ali Tonima S. , Tourell Monique C. , Hugo Honor J. , Pyke Chris , Yang Samuel , Lloyd Thomas , Thompson Erik W. , Momot Konstantin I.
Published: May 2019

Purpose

Elevated mammographic density (MD) is an independent risk factor for breast cancer (BC) as well as a source of masking in X‐ray mammography. High‐frequency longitudinal monitoring of MD could also be beneficial in hormonal BC prevention, where early MD changes herald the treatment’s success. We present a novel approach to quantification of MD in breast tissue using single‐sided portable NMR. Its development was motivated by the low cost of portable‐NMR instrumentation, the suitability for measurements in vivo, and the absence of ionizing radiation.

Methods

Five breast slices were obtained from three patients undergoing prophylactic mastectomy or breast reduction surgery. Carr‐Purcell‐Meiboom‐Gill (CPMG) relaxation curves were measured from (1) regions of high and low MD (HMD and LMD, respectively) in the full breast slices; (2) the same regions excised from the full slices; and (3) excised samples after H2O‐D2O replacement. T2 distributions were reconstructed from the CPMG decays using inverse Laplace transform.

Results

Two major peaks, identified as fat and water, were consistently observed in the T2 distributions of HMD regions. The LMD T2 distributions were dominated by the fat peak. The relative areas of the two peaks exhibited statistically significant (P < .005) differences between HMD and LMD regions, enabling their classification as HMD or LMD. The relative‐area distributions exhibited no statistically significant differences between full slices and excised samples.

Conclusion

T2‐based portable‐NMR analysis is a novel approach to MD quantification. The ability to quantify tissue composition, combined with the low cost of instrumentation, make this approach promising for clinical applications.
Characterization of MRI techniques to assess neonatal brain oxygenation and blood flow
Authors: Liu Peiying , Parkinson Charlamaine , Jiang Dengrong , Ouyang Minhui , De Vis Jill B. , Northington Frances J. , Tekes Aylin , Huang Hao , Huisman Thierry A.G.M. , Golden W. Christopher
Published: May 2019

There is increasing interest in applying physiological MRI in neonates, based on the premise that physiological parameters may provide an early biomarker of neonatal brain health and injury. Two commonly used techniques are oxygen extraction fraction (OEF) measurement using T2‐relaxation‐under‐spin‐tagging (TRUST) MRI and cerebral blood flow measurement using phase‐contrast (PC) quantitative flow MRI, which collectively provide an assessment of the brain's oxygen consumption. However, prior research has only demonstrated proof of principle of these methods in neonates, without characterization or benchmarking of the techniques. This is because available time is limited in neonatal subjects, especially when scans are performed as add‐ons to clinical scans (typically less than 5 min). The work presented aims to examine the TRUST and PC MRI sequences systematically in normal neonates, through research‐dedicated scan sessions. A series of characterization and optimization studies were conducted in a total of 26 radiographically normal neonates on 3 T systems. Our results show that TRUST MRI at the superior sagittal sinus (SSS) provides an OEF measurement equivalent to that at the internal jugular vein (r = 0.80, n = 10), yet with shorter scan time. Lower resolution provided better precision in the TRUST measurement (p = 0.001, n = 9). Therefore, the preferred OEF measurement is to apply TRUST MRI at the SSS using a spatial resolution of 2.5 mm. For PC MRI, our results showed that non‐gated PC MRI yielded blood flow measurements comparable to those from the more time‐consuming gated approach in neonates (r = 0.89, n = 7). It was also found that blood flow could be overestimated by 18% when imaging resolution is larger than 0.3 mm (n = 7). Therefore, non‐gated PC MRI with a spatial resolution of 0.3 mm is recommended for neonatal applications. In conclusion, this study verifies consistency of neonatal brain oxygenation and flow measurements across acquisition schemes and points to optimal strategies in parameter selection when using these sequences.
Guiding carbon farming using interdisciplinary mixed methods mapping
Authors: Brockett Beth F. T. , Browne Alison L. , Beanland Andy , Whitfield Mike G. , Watson Nigel , Blackburn George Alan , Bardgett Richard D.
Published: May 2019

In recognition of the need to address complex environmental problems, some ecological studies have adopted social research methods to better understand the complexity of social‐ecological systems management. The overwhelming majority of these studies stop short of fully embracing qualitative methodologies.

The lack of integrative social and natural science data for a topic such as soil carbon farming is problematic as theoretical carbon sequestration opportunities identified through soil mapping and process‐based models can fail to deliver the sequestration levels promised when introduced on‐the‐ground. Such mapping needs to account for the human factors involved in delivering increased soil carbon on‐farm.

Here, we develop a mixed methods mapping approach to explore the potential for increasing soil carbon stocks on upland farms in the UK. Our approach considers ecological and social complexity through application of soil science, ecology, participant observation, interviews and a focus group.

Our maps revealed landscapes that are full of carbon farming opportunity, but contain previously hidden barriers to the delivery of increased soil carbon. For example, they revealed that carbon farming can be considered by farmers to work in opposition to perceived ‘good farming’ practices and be correlated with increased incidents of livestock disease. We also discovered that the use of maps in research can be problematic as they can close down discussion and exclude local representation of an area.

Trialling an interdisciplinary mixed methods approach produced new, deeper and more richly‐textured understandings about how soil carbon management is produced socially as well as ecologically on upland livestock farms. Our findings have potential to improve the success of future carbon farming initiatives by incorporating farmer knowledge and social drivers of implementation.

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Serotonin synthesis protects the mouse colonic crypt from DNA damage and colorectal tumorigenesis
Authors: Sakita Juliana Y , Bader Michael , Santos Emerson S , Garcia Sergio B , Minto Stefania B , Alenina Natalia , Brunaldi Mariângela O , Carvalho Milene C , Vidotto Thiago , Gasparotto Bianca , Martins Ronaldo B , Silva Wilson A , Brandão Marcus L , Leite Caio A , Cunha Fernando Q , Karsenty Gerard , Squire Jeremy A , Uyemura Sergio A , Kannen Vinicius
Published: May 2019

Serotonin (5‐HT) signaling pathways are thought to be involved in colorectal tumorigenesis (CRT), but the role of 5‐HT synthesis in the early steps of this process is presently unknown. In this study, we used carcinogen treatment in the tryptophan hydroxylase 1 knockout (Tph1KO) and transgenic (Tph1fl/flVillinCre) mouse models defective in 5‐HT synthesis to investigate the early mutagenic events associated with CRT. Our observations of the colonic crypt post‐treatment followed a timeline designed to understand how disruption of 5‐HT synthesis affects the initial steps leading to CRT. We found Tph1KO mice had decreased development of both allograft tumors and colitis‐related CRT. Interestingly, carcinogenic exposure alone induced multiple colon tumors and increased cyclooxygenase‐2 (Ptgs2) expression in Tph1KO mice. Deletion of interleukin 6 (Il6) in Tph1KO mice confirmed that inflammation was a part of the process. 5‐HT deficiency increased colonic DNA damage but inhibited genetic repair of specific carcinogen‐related damage, leading to CRT‐related inflammatory reactions and dysplasia. To validate a secondary effect of 5‐HT deficiency on another DNA repair pathway, we exposed Tph1KO mice to ionizing radiation and found an increase in DNA damage associated with reduced levels of ataxia telangiectasia and Rad3 related (Atr) gene expression in colonocytes. Restoring 5‐HT levels with 5‐hydroxytryptophan treatment decreased levels of DNA damage and increased Atr expression. Analysis of Tph1fl/flVillinCre mice with intestine‐specific loss of 5‐HT synthesis confirmed that DNA repair was tissue specific. In this study, we report a novel protective role for 5‐HT synthesis that promotes DNA repair activity during the early stages of colorectal carcinogenesis. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Four‐jointed knock‐out delays renal failure in an ADPKD model with kidney injury
Authors: Formica Chiara , Happé Hester , Veraar Kimberley AM , Vortkamp Andrea , Scharpfenecker Marion , McNeill Helen , Peters Dorien JM
Published: May 2019

Autosomal Dominant Polycystic Kidney Disease is characterised by the development of fluid‐filled cysts in the kidneys which lead to end‐stage renal disease (ESRD). In the majority of cases, the disease is caused by a mutation in the Pkd1 gene. In a previous study, we demonstrated that renal injury can accelerate cyst formation in Pkd1 knock‐out (KO) mice. In that study, we found that after injury four‐jointed (Fjx1), an upstream regulator of planar cell polarity and the Hippo pathway, was aberrantly expressed in Pkd1 KO mice compared to WT. Therefore, we hypothesised a role for Fjx1 in injury/repair and cyst formation. We generated single and double deletion mice for Pkd1 and Fjx1, and we induced toxic renal injury using the nephrotoxic compound 1,2‐dichlorovinyl‐cysteine. We confirmed that nephrotoxic injury can accelerate cyst formation in Pkd1 mutant mice. This caused Pkd1 KO mice to reach ESRD significantly faster; unexpectedly, double KO mice survived significantly longer. Cyst formation was comparable in both models, but we found significantly less fibrosis and macrophage infiltration in double KO mice. Taken together, these data suggest that Fjx1 disruption protects the cystic kidneys against kidney failure by reducing inflammation and fibrosis. Moreover, we describe, for the first time, an interesting (yet unidentified) mechanism that partially discriminates cyst growth from fibrogenesis. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
High sensitivity and clonal stability of the genomic fusion as single marker for response monitoring in ETV6‐RUNX1‐positive acute lymphoblastic leukemia
Authors: Hoffmann Jana , Krumbholz Manuela , Gutiérrez Helia Pimentel , Fillies Marion , Szymansky Annabell , Bleckmann Kirsten , zur Stadt Udo , Köhler Rolf , Kuiper Roland P. , Horstmann Martin , von Stackelberg Arend , Eckert Cornelia , Metzler Markus
Published: May 2019

Background

Assessment of minimal residual disease (MRD) is an integral component for response monitoring and treatment stratification in acute lymphoblastic leukemia (ALL). We aimed to evaluate the genomic ETV6‐RUNX1 fusion sites as a single marker for MRD quantification.

Procedure

In a representative, uniformly treated cohort of pediatric relapsed ALL patients (n = 52), ETV6‐RUNX1 fusion sites were compared to the current gold standard, immunoglobulin/T‐cell receptor (Ig/TCR) gene rearrangements.

Results

Primer/probe sets designed to ETV6‐RUNX1 fusions achieved significantly more frequent a sensitivity and a quantitative range of at least 10–4 compared to the gold standard with 100% and 73% versus 76% and 47%, respectively. The breakpoint sequence was identical at diagnosis and relapse in all tested cases. There was a high degree of concordance between quantitative MRD results assessed using ETV6‐RUNX1 and the highest Ig/TCR marker (Spearman's 0.899, P < .01) with differences >½ log‐step in only 6% of patients. A high proportion of ETV6‐RUNX1‐positive ALL relapses (40%) in our cohort showed a poor response to induction treatment at relapse, and therefore had an indication for hematopoietic stem cell transplantation, demonstrating the need of accurate identification of this subgroup.

Conclusions

ETV6‐RUNX1 fusion sites are highly sensitive and reliable MRD markers. Our data confirm that they are unaffected by clonal evolution and selection during front‐line and second‐line chemotherapy in contrast to Ig/TCR rearrangements, which require several markers per patient to compensate for the observed loss of target clones. In future studies, the genomic ETV6‐RUNX1 fusion can be used as single MRD marker.