bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity
Authors: Ahmed Zeshan , Cooper Jane , Murray Tracey K. , Garn Katya , McNaughton Emily , Clarke Hannah , Parhizkar Samira , Ward Mark A. , Cavallini Annalisa , Jackson Samuel , Bose Suchira , Clavaguera Florence , Tolnay Markus , Lavenir Isabelle , Goedert Michel , Hutton Michael L. , O’Neill Michael J. 
Published: February 2014

Abstract
Intracellular inclusions composed of hyperphosphorylated filamentous tau are a hallmark of Alzheimer’s disease, progressive supranuclear palsy, Pick’s disease and other sporadic neurodegenerative tauopathies. Recent in vitro and in vivo studies have shown that tau aggregates do not only seed further tau aggregation within neurons, but can also spread to neighbouring cells and functionally connected brain regions. This process is referred to as ‘tau propagation’ and may explain the stereotypic progression of tau pathology in the brains of Alzheimer’s disease patients. Here, we describe a novel in vivo model of tau propagation using human P301S tau transgenic mice infused unilaterally with brain extract containing tau aggregates. Infusion-related neurofibrillary tangle pathology was first observed 2 weeks post-infusion and increased in a stereotypic, time-dependent manner. Contralateral and anterior/posterior spread of tau pathology was also evident in nuclei with strong synaptic connections (efferent and afferent) to the site of infusion, indicating that spread was dependent on synaptic connectivity rather than spatial proximity. This notion was further supported by infusion-related tau pathology in white matter tracts that interconnect these regions. The rapid and robust propagation of tau pathology in this model will be valuable for both basic research and the drug discovery process.
Efficacy and safety of ipilimumab in patients with advanced melanoma and brain metastases
Authors: Queirolo Paola , Spagnolo Francesco , Ascierto Paolo Antonio , Simeone Ester , Marchetti Paolo , Scoppola Alessandro , Del Vecchio Michele , Di Guardo Lorenza , Maio Michele , Di Giacomo Anna Maria , Antonuzzo Andrea , Cognetti Francesco , Ferraresi Virginia , Ridolfi Laura , Guidoboni Massimo , Guida Michele , Pigozzo Jacopo , Chiarion Sileni Vanna 
Published: February 2014

Abstract

Patients with melanoma brain metastases have a poor prognosis and historically have been excluded from clinical trials. The Expanded Access Program (EAP) provided an opportunity to evaluate the feasibility of ipilimumab (3 mg/kg every 3 weeks for four doses) in patients with stage 3 (unresectable) or 4 melanoma and asymptomatic brain metastases, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Tumor assessments were conducted at baseline and week 12 using immune-related response criteria and patients were monitored for adverse events (AEs). Of 855 patients participating in the EAP in Italy, 146 had asymptomatic brain metastases. With a median follow-up of 4 months, the global disease control rate was 27 %, including 4 patients with a complete response and 13 with a partial response. Median progression-free survival and overall survival were 2.8 and 4.3 months, respectively and approximately one-fifth of patients were alive 1 year after starting ipilimumab. In total, 29 % of patients reported a treatment-related AE of any grade, which were grade 3/4 in 6 % of patients. AEs were generally reversible with treatment as per protocol-specific guidelines. Ipilimumab shows durable benefits in some patients with advanced melanoma metastatic to the brain, with safety results consistent with those previously reported in clinical trials.
Curvatures of the DIP Joints of the Hand
Authors: Graham Kraig S. , Goitz Robert J. , Kaufmann Robert A. 
Published: February 2014

Background The distal interphalangeal (DIP) joints of the hand are highly susceptible to osteoarthritis and trauma. Surgical treatment options mandate accurate characterization of their osseous anatomy; however, there are few studies that describe this. We describe the curvatures of the DIP joints by measuring the bone morphology using advanced imaging and modeling methods. Methods The fingers of 16 right hand fresh frozen human cadavers were analyzed. Fingers showing signs of DIP joint arthritis were excluded. The fingers were scanned using microtomography (microCT). Measurements of the bony morphology were made using models created from the scans. Results In each finger, there is no statistically significant difference between the radii of curvature of the ulnar and radial condyles of the middle phalanx head. Conversely, the radius of curvature of the distal phalanx ulnar groove is significantly greater than that of the radial groove. The radii of curvature of the groove of the distal phalanx and the condyles of the middle phalanx displayed nonconformity with disparity increasing from the index to small fingers. Remarkably, the radius of curvature of the distal phalanx central ridge and the mean radius of the middle phalanx condyles are essentially the same. Conclusion The purpose of this study is to gain better insight into the DIP joints of the hand. The asymmetry between the distal phalanx grooves and the middle phalanx condyles suggests that there may be a translational component to DIP joint motion. Our understanding of morphology may lend insight into the biomechanics and disease progression within the DIP joints.
Structure and Physical Properties of Plant Wax Crystal Networks and Their Relationship to Oil Binding Capacity
Authors: Blake Alexia I. , Co Edmund D. , Marangoni Alejandro G. 
Published: February 2014

AbstractThe microstructure, melting and crystallization behavior, rheological properties and oil binding capacity of crystalline networks of plant‐derived waxes in edible oil were studied and then compared amongst different wax types. The critical concentrations for oleogelation of canola oil by rice bran wax (RBX), sunflower wax, candelilla wax, and carnauba wax were 1, 1, 2, and 4 %, respectively, suggesting RBX and sunflower wax are more efficient structurants. A phenomenological two‐phase exponential decay model was implemented to quantify the oil‐binding capacity of these oleogels. Parameters obtained from this empirical model were then evaluated against microscale structural attributes such as crystal size, mass distribution and porosity to determine the structural dependence of oil‐binding capacity. Gels containing candelilla wax exhibited the greatest oil‐binding capacity, as they retained nearly 90 % of their oil. This is due to the small crystal size as well as the spatial distribution of these crystals. Using a microscopic to macroscopic approach, this study examines how the structural characteristics unique to each wax and resulting oleogel system affect functionality and macroscopic behavior.
Assessing skeletal muscle mass: historical overview and state of the art
Authors: Heymsfield Steven B. , Adamek Michael , Gonzalez M. Cristina , Jia Guang , Thomas Diana M. 
Published: February 2014

BackgroundEven though skeletal muscle (SM) is the largest body compartment in most adults and a key phenotypic marker of sarcopenia and cachexia, SM mass was until recently difficult and often impractical to quantify in vivo. This review traces the historical development of SM mass measurement methods and their evolution to advances that now promise to provide in‐depth noninvasive measures of SM composition.MethodsKey steps in the advancement of SM measurement methods and their application were obtained from historical records and widely cited publications over the past two centuries. Recent advances were established by collecting information on notable studies presented at scientific meetings and their related publications.ResultsThe year 1835 marks the discovery of creatine in meat by Chevreul, a finding that still resonates today in the D3‐creatine method of measuring SM mass. Matiegka introduced an anthropometric approach for estimating SM mass in 1921 with the vision of creating a human “capacity” marker. The 1940s saw technological advances eventually leading up to the development of ultrasound and bioimpedance analysis methods of quantifying SM mass in vivo. Continuing to seek an elusive SM mass “reference” method, Burkinshaw and Cohn introduced the whole‐body counting‐neutron activation analysis method and provided some of the first detailed reports of cancer cachexia in the late 1970s. Three transformative breakthroughs leading to the current SM mass reference methods appeared in the 1970s and early 1980s as follows: the introduction of computed tomography (CT), photon absorptiometry, and magnetic resonance (MR) imaging. Each is advanced as an accurate and/or practical approach to quantifying whole‐body and regional SM mass across the lifespan. These advances have led to a new understanding of fundamental body size‐SM mass relationships that are now widely applied in the evaluation and monitoring of patients with sarcopenia and cachexia. An intermediate link between SM mass and function is SM composition. Advances in water‐fat MR imaging, diffusion tensor imaging, MR elastography, imaging of connective tissue structures by ultra‐short echo time MR, and other new MR approaches promise to close the gap that now exists between SM anatomy and function.ConclusionsThe global efforts of scientists over the past two centuries provides us with highly accurate means by which to measure SM mass across the lifespan with new advances promising to extend these efforts to noninvasive methods for quantifying SM composition.
Medical students with low self-efficacy bolstered by calling to medical speciality
Authors: Goodin Joel B. , D’Brot Vanessa M. , Duffy Ryan D. , Borges Nicole J. , Ulman Catherine A. , Manuel R. Stephen 
Published: February 2014

This study was performed to understand the degree to which medical students’ self-efficacy (SE) moderates the influence of calling on students’ speciality commitment, emphasizing the need to understand variables that predict primary care specialization. The researchers hypothesized that students who perceived their career as a calling would be more committed to their speciality, especially when students had high SE. Medical students (Years 1–4; N = 152) completed an online survey to rate their calling, speciality commitment, and SE. Calling was measured by the Brief Calling scale (Dik et al., J Career Assess 20:242–263, 2012), while speciality choice was measured by Hollenbeck et al. (J Appl Psychol 74:18–23, 1989) measure of commitment. SE was measured by the Jerusalem and Schwarzer's general SE scale (see Scholz et al., Eur J Psychol Assess 18:242–51, 2002). Calling (r = 0.24, p < 0.01) and SE (r = 0.20, p < 0.05) were found to moderately correlate with speciality commitment, thus emphasizing the possibility that they may have an interaction. The interaction of calling and SE significantly predicted speciality commitment (β = −0.20, t(148) = −2.55, p < 0.05) and explained a significant proportion of variance in speciality commitment (R 2 = 0.12, F(3, 148) = 6.875, p < 0.001). Students with a high presence of calling may have high speciality commitment, despite low SE.
Global gene expression changes induced by prolonged cold ischemic stress and preservation method of breast cancer tissue
Authors: Aktas Bilge , Sun Hongxia , Yao Hui , Shi Weiwei , Hubbard Rebekah , Zhang Ya , Jiang Tingting , Ononye Sophia N. , Wali Vikram B. , Pusztai Lajos , Symmans W. Fraser , Hatzis Christos 
Published: February 2014

BackgroundTissue handling can alter global gene expression potentially affecting the analytical performance of genomic signatures, but such effects have not been systematically evaluated.MethodsTissue samples from 11 previously untreated breast tumors were minced and aliquots were either snap frozen or placed in RNAlater immediately or after 20, 40, 60, 120 or 180 min at room temperature. RNA was profiled on Affymetrix HG‐U133A arrays. We used probe‐set‐wise hierarchical models to evaluate the effect of preservation method on transcript expression and linear mixed effects models to assess the effect of cold ischemic delay on the expression of individual probe sets. Gene set enrichment analysis identified pathways overrepresented in the affected transcripts. We combined the levels of 41 most sensitive transcripts to develop an index of ischemic stress.ResultsConcordance in global gene expression between the baseline and 40 min delay was higher for samples preserved in RNAlater (average concordance correlation coefficient CCC = 0.92 compared to 0.88 for snap frozen). Overall, 481 transcripts (3%) were significantly affected by the preservation method, most of them involved in processes important in cancer. Prolonged cold ischemic delay of up to 3 h induced marginal global gene expression changes (average CCC = 0.90 between baseline and 3 h delay). However 41 transcripts were significantly affected by cold ischemic delay. Among the induced transcripts were stress response genes, apoptotic response genes; among the downregulated were genes involved in metabolism, protein processing and cell cycle regulation. An index combining the expression levels of these genes was proportional to the cold ischemic delay.ConclusionsProlonged cold ischemia induces significant transcriptional changes in a small subset of transcripts in the tissue. Furthermore, the expression level of about 3% of the transcripts is affected by the preservation method. These sensitive transcripts should not be included in genomic signatures for more reliable analytical performance.
Instability of an inhomogeneous bacterial suspension subjected to a chemo-attractant gradient
Authors: Kasyap T. V. , Koch Donald L. 
Published: February 2014

AbstractThe stability of a suspension of chemotactic bacteria confined in an infinitely long channel and subjected to a stationary, linear chemo-attractant gradient is investigated. While swimming, individual bacteria exert force dipoles on the fluid, which at the continuum level lead to a stress depending upon the bacterial orientation and number density fields. The presence of the attractant gradient causes bacteria to tumble less frequently when swimming along the gradient, leading to a mean orientation and a non-zero chemotactic drift velocity$U_0$in that direction. At long length and time scales compared to those associated with the persistence of bacterial swimming, fluxes due to chemotaxis and the random run–tumble motion of bacteria balance to yield an exponentially varying number density profile across the channel in the base state. The associated bacterial stress field is also exponentially varying and is normal. This spatially non-uniform base state is unstable to fluctuations in the bacterial concentration field when the scaled bacterial concentration$\beta = (3 C/8) \langle n_0\rangle L^2 H$exceeds a critical value determined by a Péclet number defined as${\mathit{Pe}} = U_0 H/\kappa $. Here,$C$is a non-dimensional dipole strength, which depends on the geometry of the bacterium,$\langle n_0\rangle $is the bacterial concentration averaged across the channel of depth$H$,$L$is the total length of the bacterium,$\kappa $is the bacterial diffusivity, and$\beta _{\mathit{crit}}$is a monotonically decreasing function of${\mathit{Pe}}$, with$\beta _{\mathit{crit}} \sim 720/{\mathit{Pe}}^3$for${\mathit{Pe}} \ll 1$and$\beta _{\mathit{crit}} \sim 2$for${\mathit{Pe}} \gg 1$. The instability is the result of the coupling between the active stress-driven fluid flow and the bacterial concentration, and manifests as rectangular convection patterns. When$\beta $first exceeds$\beta _{\mathit{crit}}$, the unstable wavelengths are large with$\lambda \gg H$and the mode of instability is stationary. Although oscillatory modes appear when$\lambda \leq O(H)$and$\beta > 247$, the most dangerous mode of instability is found to be always stationary with a wavelength$\lambda _m/H \sim {\mathit{Pe}}^{-1}$. To study the coupling between the previously analysed orientation shear instability mechanism of bacterial suspensions and the new chemotaxis-driven instability, a new set of continuum equations that consistently account for weak chemotaxis, rotation of bacteria by weak fluid shear and weak non-continuum effects along with their coupled effects has been derived. The stability analysis of those equations showed that the orientation shear mechanism has only a negligible influence on the critical concentration for the present chemotaxis-induced instability when the suspension depth is large, and it is the latter that has the lowest critical concentration.
Absolute instabilities in eccentric Taylor–Couette–Poiseuille flow
Authors: Leclercq Colin , Pier Benoît , Scott Julian F. 
Published: February 2014

AbstractThe effect of eccentricity on absolute instabilities (AI) in the Taylor–Couette system with pressure-driven axial flow and fixed outer cylinder is investigated. Five modes of instability are considered, characterized by a pseudo-angular order $m$, with here $\vert m\vert \leq 2$. These modes correspond to toroidal ($m=0$) and helical structures ($m\neq 0$) deformed by the eccentricity. Throughout the parameter range, the mode with the largest absolute growth rate is always the Taylor-like vortex flow corresponding to $m=0$. Axial advection, characterized by a Reynolds number ${\mathit{Re}_z}$, carries perturbations downstream, and has a strong stabilizing effect on AI. On the other hand, the effect of the eccentricity $e$ is complex: increasing $e$ generally delays AI, except for a range of moderate eccentricites ${0.3\lesssim e \lesssim 0.6}$, where it favours AI for large enough ${\mathit{Re}_z}$. This striking behaviour is in contrast with temporal instability, always inhibited by eccentricity, and where left-handed helical modes of increasing $\vert m\vert $ dominate for larger ${\mathit{Re}_z}$. The instability mechanism of AI is clearly centrifugal, even for the larger values of ${\mathit{Re}_z}$ considered, as indicated by an energy analysis. For large enough ${\mathit{Re}_z}$, critical modes localize in the wide gap for low $e$, but their energy distribution is shifted towards the diverging section of the annulus for moderate $e$. For highly eccentric geometries, AI are controlled by the minimal annular clearance, and the critical modes are confined to the vicinity of the inner cylinder. Untangling the AI properties of each $m$ requires consideration of multiple pinch points.
Sidewall effects in Rayleigh–Bénard convection
Authors: Stevens Richard J. A. M. , Lohse Detlef , Verzicco Roberto 
Published: February 2014

AbstractWe investigate the influence of the temperature boundary conditions at the sidewall on the heat transport in Rayleigh–Bénard (RB) convection using direct numerical simulations. For relatively low Rayleigh numbers $Ra$ the heat transport is higher when the sidewall is isothermal, kept at a temperature $T_c+\Delta /2$ (where $\Delta $ is the temperature difference between the horizontal plates and $T_c$ the temperature of the cold plate), than when the sidewall is adiabatic. The reason is that in the former case part of the heat current avoids the thermal resistance of the fluid layer by escaping through the sidewall that acts as a short-circuit. For higher $Ra$ the bulk becomes more isothermal and this reduces the heat current through the sidewall. Therefore the heat flux in a cell with an isothermal sidewall converges to the value obtained with an adiabatic sidewall for high enough $Ra$ (${\simeq }10^{10}$). However, when the sidewall temperature deviates from $T_c+\Delta /2$ the heat transport at the bottom and top plates is different from the value obtained using an adiabatic sidewall. In this case the difference does not decrease with increasing $Ra$ thus indicating that the ambient temperature of the experimental apparatus can influence the heat transfer. A similar behaviour is observed when only a very small sidewall region close to the horizontal plates is kept isothermal, while the rest of the sidewall is adiabatic. The reason is that in the region closest to the horizontal plates the temperature difference between the fluid and the sidewall is highest. This suggests that one should be careful with the placement of thermal shields outside the fluid sample to minimize spurious heat currents. When the physical sidewall properties (thickness, thermal conductivity and heat capacity) are considered the problem becomes one of conjugate heat transfer and different behaviours are possible depending on the sidewall properties and the temperature boundary condition on the ‘dry’ side. The problem becomes even more complicated when the sidewall is shielded with additional insulation or temperature-controlled surfaces; some particular examples are illustrated and discussed. It has been observed that the sidewall temperature dynamics not only affects the heat transfer but can also trigger a different mean flow state or change the temperature fluctuations in the flow and this could explain some of the observed differences between similar but not fully identical experiments.
What happens to food choices when a gluten-free diet is required? A prospective longitudinal population-based study among Swedish adolescent with coeliac disease and their peers
Authors: Kautto E. , Rydén P. J. , Ivarsson A. , Olsson C. , Norström F. , Högberg L. , Carlsson A. , Hagfors L. , Hörnell A. 
Published: February 2014

AbstractA dietary survey was performed during a large screening study in Sweden among 13-year-old adolescents. The aim was to study how the intake of food groups was affected by a screening-detected diagnosis of coeliac disease (CD) and its gluten-free (GF) treatment. Food intake was reported using a FFQ, and intake reported by the adolescents who were diagnosed with CD was compared with the intake of two same-aged referent groups: (i) adolescents diagnosed with CD prior to screening; and (ii) adolescents without CD. The food intake groups were measured at baseline before the screening-detected cases were aware of their CD, and 12–18 months later. The results showed that food intakes were affected by screen-detected CD and its dietary treatment. Many flour-based foods were reduced such as pizza, fish fingers and pastries. The results also indicated that bread intake was lower before the screened diagnosis compared with the other studied groups, but increased afterwards. Specially manufactured GF products (for example, pasta and bread) were frequently used in the screened CD group after changing to a GF diet. The present results suggest that changing to a GF diet reduces the intake of some popular foods, and the ingredients on the plate are altered, but this do not necessarily include a change of food groups. The availability of manufactured GF replacement products makes it possible for adolescents to keep many of their old food habits when diagnosed with CD in Sweden.