bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dehydroepiandrosterone Stimulation of Osteoblastogenesis in Human MSCs Requires IGF‐I Signaling
Authors: Liang Xiaonan , Glowacki Julie , Hahne Jochen , Xie Li , LeBoff Meryl S. , Zhou Shuanhu 
Published: December 2015

ABSTRACTDehydroepiandrosterone (DHEA) is an adrenal steroid that circulates in high concentrations in humans in its sulfated form, DHEAS. Clinical and epidemiological studies suggested that low DHEAS levels may be associated with low bone mass. Previously, we and others showed that the effects of DHEA on the skeleton may be conferred partly by their ability to inhibit skeletal catabolic agents, for example, bone resorptive cytokine IL‐6. In this study, we tested the hypothesis that the anabolic effects of DHEA on osteoblastogenesis require IGF‐I signaling pathways. Using both primary cultures and a cell line of human bone marrow‐derived mesenchymal stem cells (hMSCs), we show that DHEA and other steroids stimulate osteoblastogenesis as shown by alkaline phosphatase activity and osteoblast gene induction. The stimulation by DHEA on both IGF‐I gene expression and osteoblastogenesis in hMSCs requires IGF‐I receptor, PI3K, p38 MAPK, or p42/44 MAPK signaling pathways. This study adds information to indicate that DHEA may be useful for treating bone diseases through its inhibition of skeletal catabolic IL‐6 and stimulation of anabolic IGF‐I‐mediated mechanisms. J. Cell. Biochem. 117: 1769–1774, 2016. © 2015 Wiley Periodicals, Inc.
Enhanced phase‐sensitive SSFP reconstruction for fat‐water separation in phased‐array acquisitions
Authors: Yilmaz Ozgur , Saritas Emine Ulku , Çukur Tolga 
Published: December 2015

PurposeTo propose and assess a method to improve the reliability of phase‐sensitive fat–water separation for phased‐array balanced steady‐state free precession (bSSFP) acquisitions. Phase‐sensitive steady‐state free precession (PS‐SSFP) is an efficient fat–water separation technique that detects the phase difference between neighboring bands in the bSSFP magnetization profile. However, large spatial variations in the sensitivity profiles of phased‐array coils can lead to noisy phase estimates away from the coil centers, compromising tissue classification.Materials and MethodsWe first perform region‐growing phase correction in individual coil images via unsupervised selection of a fat‐voxel seed near the peak of each coil's sensitivity profile. We then use an optimal linear combination of phase‐corrected images to segregate fat and water signals. The proposed method was demonstrated on noncontrast‐enhanced SSFP angiograms of the thigh, lower leg, and foot acquired at 1.5T using an 8‐channel coil. Individual coil PS‐SSFP with a common seed selection for all coils, individual coil PS‐SSFP with coil‐wise seed selection, PS‐SSFP after coil combination, and IDEAL reconstructions were also performed. Water images reconstructed via PS‐SSFP methods were compared in terms of the level of fat suppression and the similarity to reference IDEAL images (signed‐rank test).ResultsWhile tissue misclassification was broadly evident across regular PS‐SSFP images, the proposed method achieved significantly higher levels of fat suppression (P < 0.005) and increased similarity to reference IDEAL images (P < 0.005).ConclusionThe proposed method enhances fat–water separation in phased‐array acquisitions by producing improved phase estimates across the imaging volume. J. Magn. Reson. Imaging 2016;44:148–157.
Attenuation of cartilage degeneration by calcitonin gene‐related paptide receptor antagonist via inhibition of subchondral bone sclerosis in osteoarthritis mice
Authors: Nakasa Tomoyuki , Ishikawa Masakazu , Takada Tsuyoshi , Miyaki Shigeru , Ochi Mitsuo 
Published: December 2015

ABSTRACTOsteoarthritis (OA) is a progressive joint disorder which affects cartilage and subchondral bone. Calcitonin gene‐related peptide (CGRP) plays a role in bone metabolism. The purpose of this study is to examine the therapeutic effect of the blocking CGRP on OA progression in mice by inhibition of subchondral bone sclerosis. OA was induced by the resection of the medial meniscotibial ligament of the knee in C57/BL6 mice. An intraperitoneal injection of the CGRP receptor antagonist (BIBN4096) was administered after OA surgery. At 1, 4, and 8 weeks after injection, histological analysis were performed. In vitro, the effect of CGRP and BIBN4096 on osteogenesis and osteoclastogenesis was analyzed. BIBN4096 could prevent cartilage degeneration and subchondral bone sclerosis. The OARSI score in the BIBN4096 group was significantly lower than that in the control. In vitro, CGRP up regulated osteocalcin expression, but its expression was down regulated by BIBN4096. CGRP inhibited osteoclastogenesis of raw 267.4 cells, but its effect was reduced by the addition of BIBN4096.The current study showed that subchondral bone sclerosis and increasing expression of CGRP occurs in the early phase of OA in relation to cartilage degeneration, and that BIBN4096 could effectively attenuate OA progression. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1177–1184, 2016.
Relative motion between the flexor digitorum superficialis tendon and paratenon in zone V increases with wrist flexion angle
Authors: Kociolek Aaron M. , Keir Peter J. 
Published: December 2015

ABSTRACTCarpal tunnel syndrome is characterized by non‐inflammatory fibrosis of the subsynovial connective tissue (SSCT), a paratenon‐like structure inside the carpal tunnel. This pathology suggests repetitive and/or excessive shear forces are involved in injury development. We assessed relative motion between the flexor digitorum superficialis (FDS) tendon and adjacent paratenon in Zone V using colour Doppler imaging as 16 healthy participants completed three long finger movements (metacarpophalangeal joint flexion, proximal and distal interphalangeal joint flexion, full finger flexion) in three wrist postures (30° extension, 0°, 30° flexion). While the type of finger movement did not affect tendon‐paratenon relative motion, we found a significant main effect of wrist posture (p < 0.001). Relative displacement between the FDS tendon and paratenon (as a percentage of tendon displacement) increased from 27.2% (95%CI = 24.8–29.5%) in 30° wrist extension to 39.9% (95%CI = 37.3–42.4%) in 30° wrist flexion. Optical motion capture confirmed that wrist posture did not affect metacarpophalangeal joint range of motion (p = 0.265) or proximal interphalangeal joint range of motion (p = 0.582). These results indicate that relative motion increased due to paratenon strain when the wrist was flexed. While our findings agree with previous cadaveric research in wrist flexion, we found that relative displacement decreased in 30° wrist extension (compared to 0°). These results differ from cadaveric research, possibly due to challenges maintaining anatomic fidelity of the viscoelastic paratenon tissue in vitro. Overall, our study suggests a greater susceptibility to shear injury during repetitive finger movements, particularly when the wrist is flexed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1248–1255, 2016.
Antagonism of the Met5‐enkephalin‐opioid growth factor receptor‐signaling axis promotes MSC to differentiate into osteoblasts
Authors: Thakur Nikhil A. , DeBoyace Sean D. , Margulies Bryan S. 
Published: December 2015

ABSTRACTChronic opioid therapy is associated with bone loss. This led us to hypothesize that the opioid antagonists, that include naloxone, would stimulate bone formation by regulating MSC differentiation. The opioid growth factor receptor (OGFR) is a non‐canonical opioid receptor that binds naloxone with high affinity whereas the native opioid growth factor, met5‐enkephalin (met5), binds both the OGFR and the canonical delta opioid receptor (OPRD). Naloxone and an shRNA OGFR lentivirus were employed to disrupt the OGFR‐signaling axis in cultured MSC. In parallel, naloxone was administered to bone marrow using a mouse unicortical defect model. OPRD, OGFR, and the met5‐ligand were highly expressed in MSC and osteoblasts. A pulse‐dose of naloxone increased mineral formation in MSC cultures in contrast to MSC treated with continuous naloxone or OGFR deficient MSC. Importantly, SMAD1 and SMAD8/9 expression increased after a pulse dose of naloxone whereas SMAD1, SMAD7, and ID1 were increased in the OGFR deficient MSC. Inhibited OGFR signaling decreased proliferation and increased p21 expression. The addition of naloxone to the unicortical defect resulted in increased bone formation within the defect. Our data suggest that novel mechanism through which signaling through the OGFR regulates osteogenesis via negative regulation of SMAD1 and p21. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1195–1205, 2016.
High‐throughput screening of measuring conditions for an optimized SERS detection
Authors: Kämmer Evelyn , Olschewski Konstanze , Rösch Petra , Weber Karina , Cialla‐May Dana , Popp Jürgen 
Published: December 2015

Surface‐enhanced Raman spectroscopy (SERS) is a perfect method for analytical applications because of delivering specific molecular information combined with a high sensitivity when applying rational design metallic nanostructures. However, the pH level and the activation of ctheir mutual influence. Besidesolloidal SERS substrates influence the sensitivity and comparability of the SERS analysis. In this study, a routine is presented that allows for a fast and effective recognition of the influences of pH and activating agents on the SERS signal of an analyte molecule. To do so, a citrate‐reduced Ag colloid served as SERS substrate. The influence of four activating agents as well as five pH levels on the SERS signal of the model analyte melamine was investigated. Here, not only the influence of the anion but also that of the cation of the activating agents was examined. In addition to different signal intensities, a shift of the dominant melamine signal occurred depending on the adjusted conditions. At pH 11, the lowest intensities of the SERS signal from the model analyte melamine were detected. The maximal enhancement of the ring breathing II mode in combination with this specific colloid was achieved using sodium chloride as an activating agent at a pH level of 5. Thus, the study introduces a routine, which can be applied on various analyte molecules to optimize the SERS intensity by changing the activation agent as well as the pH. Copyright © 2015 John Wiley & Sons, Ltd.
Development and Validation of an Artificial Mechanical Skin Model for the Study of Interactions between Skin and Microneedles
Authors: Ranamukhaarachchi Sahan A. , Schneider Thomas , Lehnert Sarah , Sprenger Lisa , Campbell Jonathon R. , Mansoor Iman , Lai Jacqueline C. Y. , Rai Kimit , Dutz Jan , Häfeli Urs O. , Stoeber Boris 
Published: December 2015

Microneedles are small needle‐like structures that are almost invisible to the naked eye. They have an immense potential to serve as a valuable tool in many medical applications, such as painless vaccination. Microneedles work by breaking through the stratum corneum, the outermost barrier layer of the skin, and providing a direct path for drug delivery into the skin. A lot of research has been presented over the past two decades on the applications of microneedles, yet the fundamental mechanism of how they interact, pressure, and penetrate the skin in its native state is worth examining further. As such, a major difficulty with understanding the mechanism of microneedle–skin interaction is the lack of an artificial mechanical human skin model to use as a standardized substrate. In this research news, the development of an artificial mechanical skin model based on a thorough mechanical study of fresh human and porcine skin samples is presented. The artificial mechanical skin model can be used to study the mechanical interactions between microneedles and skin, but not diffusion of molecules across skin. This model can assist in improving the performance of microneedles by enhancing the reproducibility of microneedle depth insertions for optimal drug delivery and biosensing.
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ICS teaching module: Detrusor leak point pressures in patients with relevant neurological abnormalities
Authors: Tarcan Tufan , Demirkesen Oktay , Plata Mauricio , Castro‐Diaz David 
Published: December 2015

AimsThis manuscript serves as a scientific background review; the evidence base, for the presentation made available on ICS website to summarize current knowledge and recommendations for the measurement and use of the DLPP.MethodsThis review has been prepared by a Working Group of The ICS Urodynamics Committee. The methodology used included comprehensive literature review, consensus formation by the members of the Working Group, and review by members of the ICS Urodynamics Committee core panel.ResultsDLPP has been recommended and utilized in the urodynamic evaluation of N‐LUTD for many years, but it lacks standardization and there are numerous pitfalls in its measurement. EFP and LPP associated with N‐DO are frequently and mistakenly reported as DLPP. The information that high DLPP predicts UUTD originates from retrospective cohort studies of a low level of evidence (LoE 3). Existing data confirm that patients with lower DLPP do better than patients with higher DLPP in terms of their upper urinary tract. However, there appears to be no reliable ‘safe/no safe’ cut‐off for DLPP since there are other urodynamic factors that influence UUTD such as bladder compliance and more.ConclusionAlthough higher DLPP is associated with a greater risk of UUTD, there is no reliable cut‐off level to undoubtedly discriminate the risky group, including the traditional cut‐off level of 40 cm H2O. Therefore, DLPP should not be used as the sole urodynamic parameter. Future research should be directed to standardization of the technique and better classification of DLPP cut‐offs in N‐LUTD. Neurourol. Urodynam. 36:259–262, 2017. © 2015 Wiley Periodicals, Inc.
Validity, reliability, and responsiveness of the ICIQ‐UI SF and ICIQ‐LUTSqol in the Malaysian population
Authors: Lim Renly , Liong Men Long , Lau Yong Khee , Yuen Kah Hay 
Published: December 2015

AimsTo enable the use of the International Consultation on Incontinence Questionnaire‐Urinary Incontinence Short Form (ICIQ‐UI SF) and ICIQ‐Lower Urinary Tract Symptoms Quality of Life (ICIQ‐LUTSqol) in Southeast Asia, we translated and subsequently evaluated their validity (content and discriminant validity), reliability (internal consistency and test–retest reliability), and responsiveness in female patients with stress urinary incontinence.MethodsPermission was obtained to translate the English versions into Malay and subsequently validate them, and to validate the existing Chinese versions. The translated questionnaires were taken for pilot testing. Validation was carried out for the face/content and discriminant validity. Reliability was assessed for test–retest and internal consistency using Cronbach's alpha and intraclass correlation coefficient respectively. The responsiveness was calculated via effect size and standardized response mean.ResultsTen patients were recruited for the pilot testing. The English and Chinese versions had “substantial” or “almost perfect” agreement as measured by weighted Kappa. 284 participants (139 patients with stress urinary incontinence and 145 healthy volunteers) were included in the subsequent phases. The ICIQ‐UI SF and ICIQ‐LUTSqol had good discriminant validity. The ICIQ‐UI SF had moderate internal consistency although the ICIQ‐LUTSqol had good internal consistency. Both questionnaires had high test–retest reliability. Responsiveness was established with a moderate to large effect size and a standardized response mean.ConclusionsThe English, Chinese, and Malay versions each proved to be valid and reliable in our Malaysian population, thereby enabling more cross‐cultural research in this region. Neurourol. Neurourol. Urodynam. 36:438–442, 2017. © 2015 Wiley Periodicals, Inc.
Inter‐function anomaly analysis for correct SDN/NFV deployment
Authors: Basile Cataldo , Canavese Daniele , Lioy Antonio , Pitscheider Christian , Valenza Fulvio 
Published: December 2015

SummaryImplementing the security of a network consists in individually configuring several network functions. Network functions are configured by means of a policy composed of a set of rules, but their actual behaviour is influenced by the other policies implemented by all the other network functions around them. This paper proposes a formal model that can be used to detect inter‐function anomalies, which are defined as the interferences between two or more functions deployed in the same network. We have proved with experiments that the proposed model is fast and scalable. Copyright © 2015 John Wiley & Sons, Ltd.
Copayments for prescription medicines on a public health insurance scheme in Ireland
Authors: Sinnott Sarah‐Jo , Normand Charles , Byrne Stephen , Woods Noel , Whelton Helen 
Published: December 2015

AbstractPurposeWe assessed the impact of the introduction of a €0.50 prescription copayment, and its increase to €1.50, on adherence to essential and less‐essential medicines in a publicly insured population in Ireland.MethodsWe used a pre‐post longitudinal repeated measures design. We included new users of essential medicines: blood pressure lowering, lipid lowering and oral diabetic agents, thyroid hormone, anti‐depressants, and less‐essential medicines: non‐steroidal anti‐inflammatory drugs (NSAIDs), Proton Pump Inhibitors/H2 antagonists (PPIs/H2), and anxiolytics/hypnotics. The outcome was change in adherence, measured using Proportion of Days Covered. We used segmented regression with generalised estimating equations to allow for repeated measurements.ResultsSample sizes ranged from 7145 (thyroid hormone users) to 136 111 (NSAID users). The €0.50 copayment was associated with reductions in adherence ranging from −2.1%[95% CI, −2.8 to −1.5] (thyroid hormone) to −8.3%[95% CI, −8.7 to −7.9] (anti‐depressants) for essential medicines and reductions in adherence of −2%[95% CI, −2.3 to −1.7] (anxiolytics/hypnotics) to −9.5%[95% CI, −9.8 to −9.1] (PPIs/H2) for less‐essential medicines. The €1.50 copayment generally resulted in smaller reductions in adherence to essential medicines. Anti‐depressant medications were the exception with a decrease of −10.0% [95% CI, −10.4 to −9.6] after the copayment increase. Larger decreases in adherence were seen for most less‐essential medicines; the largest was for PPIs/H2 at −13.5% [95% CI, −13.9 to −13.2] after the €1.50 copayment.ConclusionBoth copayments had a greater impact on adherence to less‐essential medicines than essential medicines. The major exception was for anti‐depressant medicines. Further research is required to explore heterogeneity across different socio‐economic strata and to elicit the impact on clinical outcomes. Copyright © 2015 John Wiley & Sons, Ltd.
Boosting protein stability with the computational design of β‐sheet surfaces
Authors: Kim Doo Nam , Jacobs Timothy M. , Kuhlman Brian 
Published: December 2015

Abstractβ‐sheets often have one face packed against the core of the protein and the other facing solvent. Mutational studies have indicated that the solvent‐facing residues can contribute significantly to protein stability, and that the preferred amino acid at each sequence position is dependent on the precise structure of the protein backbone and the identity of the neighboring amino acids. This suggests that the most advantageous methods for designing β‐sheet surfaces will be approaches that take into account the multiple energetic factors at play including side chain rotamer preferences, van der Waals forces, electrostatics, and desolvation effects. Here, we show that the protein design software Rosetta, which models these energetic factors, can be used to dramatically increase protein stability by optimizing interactions on the surfaces of small β‐sheet proteins. Two design variants of the β‐sandwich protein from tenascin were made with 7 and 14 mutations respectively on its β‐sheet surfaces. These changes raised the thermal midpoint for unfolding from 45°C to 64°C and 74°C. Additionally, we tested an empirical approach based on increasing the number of potential salt bridges on the surfaces of the β‐sheets. This was not a robust strategy for increasing stability, as three of the four variants tested were unfolded.
Semiconductor nanostructures towards electronic and opto‐electronic device applications V
Authors: Moreels Iwan , André Pascal , Climente Juan I. , Reece Peter , Ribierre Jean‐Charles 
Published: December 2015

AbstractIn 2015, the E‐MRS spring meeting in Lille hosted the fifth installment of the bi‐annual symposium “Semiconductor nanostructures towards electronic and opto‐electronic device applications ”.Organized for the first time in 2007, the symposium brought together researchers from different fields working on nanostructured materials and their application in opto‐electronics and photonics. Several sessions discussed the latest developments in the growth of CuInS2, InP, and group‐IV nanocrystals, III–V quantum dots and nanowires, and 2D materials such as graphene, MoS2 and BN. These were accompanied by presentations dedicated to the characterization of the electronic, optical and plasmonic properties, and charge transport in nanostructured films. New applications of these materials were also discussed, with an emphasis on nanostructured organic and inorganic transistors and LEDs, lasers, detectors and sensors.Selected papers of the symposium are published in this special issue. Next to the contributed articles and proceedings, a feature article by Pavesi et al. highlights recent progress on silicon nanocrystals for optical communications [DOI: 10.1002/pssa.201532528].
The non‐conservation of potential vorticity by a dynamical core compared with the effects of parametrized physical processes
Authors: Saffin L. , Methven J. , Gray S. L. 
Published: December 2015

Numerical models of the atmosphere combine a dynamical core, which approximates solutions to the adiabatic, frictionless governing equations for fluid dynamics, with tendencies arising from the parametrization of other physical processes. Since potential vorticity (PV) is conserved following fluid flow in adiabatic, frictionless circumstances, it is possible to isolate the effects of non‐conservative processes by accumulating PV changes in an air‐mass‐relative framework. This ‘PV tracer technique’ is used to accumulate separately the effects on PV of each of the different non‐conservative processes represented in a numerical model of the atmosphere. Dynamical cores are not exactly conservative because they introduce, explicitly or implicitly, some level of dissipation and adjustment of prognostic model variables which acts to modify PV. Here, the PV tracers technique is extended to diagnose the cumulative effect of the non‐conservation of PV by a dynamical core and its characteristics relative to the PV modification by parametrized physical processes.Quantification using the Met Office Unified Model reveals that the magnitude of the non‐conservation of PV by the dynamical core is comparable to those from physical processes. Moreover, the residual of the PV budget, when tracing the effects of the dynamical core and physical processes, is at least an order of magnitude smaller than the PV tracers associated with the most active physical processes. The implication of this work is that the non‐conservation of PV by a dynamical core can be assessed in case‐studies with a full suite of physics parametrizations and directly compared with the PV modification by parametrized physical processes. The non‐conservation of PV by the dynamical core is shown to move the position of the extratropical tropopause while the parametrized physical processes have a lesser effect at the tropopause level.