bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG‐782 and INT0133—A Report From the Children's Oncology Group Bone Tumor Committee
Authors: Bishop Michael W. , Chang Yu‐Chen , Krailo Mark D. , Meyers Paul A. , Provisor Arthur J. , Schwartz Cindy L. , Marina Neyssa M. , Teot Lisa A. , Gebhardt Mark C. , Gorlick Richard , Janeway Katherine A. , Chou Alexander J.
Published: May 2016

Background

The prognostic value of histologic response for osteosarcoma may have changed with induction chemotherapy schedules over time. We hypothesized that the increased intensity of induction therapy provided on INT0133 compared to the Children's Cancer Group study CCG‐782 would diminish the impact of histologic response on the risk of events after definitive surgery.

Methods

Retrospective analysis was performed for patients aged <22 with newly diagnosed nonmetastatic osteosarcoma enrolled on CCG‐782 and INT0133. Clinical factors were evaluated for association with response and outcome. Good response was defined as <5% viable tumor at resection. Associations of response, study, and postdefinitive surgery event‐free survival (EFS‐DS) were determined using Cox proportional hazard models. EFS‐DS was estimated by Kaplan–Meier methodology.

Results

Data were available for 814 patients (206 CCG‐782, 608 INT0133). For good responders, 10‐year EFS‐DS (±SE) was 75.4% ± 7.7% for CCG‐782 and 70.8% ± 3.1% for INT0133. For poor responders, 10‐year EFS‐DS was 39.9% ± 4.9% for CCG‐782 and 58.4% ± 3.1% for INT0133. Histologic response predicted outcome across studies (P < 0.0001). Significant interaction between study and histologic response was observed for EFS‐DS (P = 0.011). Using proportional hazards regression, INT0133 poor responders had less risk of events compared to CCG‐782 poor responders (relative hazard ratio (RHR) = 0.6:1), but good responders on INT0133 had a greater risk of events compared to CCG‐782 good responders (RHR = 1.53:1).

Conclusion

We observed an inverse relationship between the predictive value of tumor necrosis and intensity of induction therapy, raising questions about the true prognostic value of histologic response. This highlights the need for novel markers to develop strategies for treatment in future trials.
Vacuum‐assisted microwave processing of glass‐epoxy composite laminates using novel microwave absorbing molds
Authors: Rao Sandhya , Chiranjeevi M.C. , Rajendra Prakash M.
Published: May 2016

For polymer composite product manufacture, curing is a critical step in achieving desired thermal and mechanical properties. The conventional thermal cure processes using hot air ovens and autoclaves are time and energy intensive. Microwave (MW) assisted curing is one of the alternative, most promising methods of curing polymer matrix composites, that could lead to substantial reduction in cure cycle time, energy requirements and operational costs due to its volumetric mode of heating. In the present work, studies were carried out on vacuum assisted microwave curing of glass‐epoxy composite laminates using novel, in‐house fabricated, silica based microwave susceptible molds inside a conveyor type microwave cure facility. Comparison of the cure process parameters with those of conventional thermally cured composite laminates revealed that vacuum assisted microwave curing resulted in ∼ 90% time savings and ∼ 60% energy savings, thus revealing the dual benefits of microwave processing as well as the novel microwave susceptible molds employed. The temperature uniformity of the molds as well as the curing laminate was assessed using a non‐invasive, thermal imaging camera. Cure completion of microwave‐cured laminates was ascertained by glass transition temperature (Tg) measurements across the laminates as well as mechanical property determination. Tgs as well as the mechanical properties obtained for vacuum assisted microwave‐cured laminates (VMCL) were comparable or superior to those of thermally cured laminates (THCL). POLYM. COMPOS., 39:1152–1160, 2018. © 2016 Society of Plastics Engineers
Three‐dimensional analysis of carbon nanotube‐reinforced cylindrical shells with temperature‐dependent properties under thermal environment
Authors: Pourasghar A. , Moradi‐Dastjerdi R. , Yas M.H. , Ghorbanpour Arani A. , Kamarian S.
Published: May 2016

In this article, the three‐dimensional thermo‐elastic deformation of cylindrical shells reinforced by single‐walled carbon nanotubes (SWCNTs), subjected to thermal load is analyzed. The cylindrical shell has been reinforced by Carbon Nanotube (CNT) in the radial direction and the material properties are estimated by the extended rule of mixture. The material properties are temperature dependent and suitable temperature and displacement functions that identically satisfy boundary conditions at the edges are used to reduce the equilibrium equations to a set of coupled ordinary differential equations (ODE) with variable coefficients, which are solved by Generalized Differential Quadrature (GDQ) method. Accuracy of the presents approach is validated by comparing the numerical results with the available published results in the literature. POLYM. COMPOS., 39:1161–1171, 2018. © 2016 Society of Plastics Engineers
Effect of waste glass content on the physico‐chemical and mechanical properties of styrene acrylic ester blended cement mortar composites
Authors: Abdel‐Rahman H.A. , Younes M.M. , Khattab Magdy M.
Published: May 2016

This study focuses on the partial substitution effect of ordinary Portland cement (OPC) by different ratios of waste glass powder (5%, 10%, and 20% by weight of cement) on the performance of blended cement mortars. The hardened blended cement mortars were first cured under tap water for different time intervals 3, 7, 28, and 90 days. However, the effect of addition of 10% styrene‐acrylic ester as well as the influence of different doses of gamma rays on the physico‐chemical and mechanical properties of polymer modified blended cement mortar specimens were discussed. Compressive strength, total porosity, and water absorption percentages were measured. The experimental results showed that the physico‐chemical and mechanical properties of blended cement mortars specimens improved as the waste glass content increases up to 20%. In addition, irradiated SAE blended cement mortar composites containing 20% waste glass showed an enhancement in its properties as compared to neat cement (0%WG content) composites. The results were confirmed by X‐ray diffraction, thermogravimetric analysis, and scanning electron microscopy. POLYM. COMPOS., 39:985–996, 2018. © 2016 Society of Plastics Engineers
Chromosomal microarray use among women undergoing invasive prenatal diagnosis
Authors: Naqvi Mariam , Goldfarb Ilona T. , Hanmer Kaitlin J. , Bryant Allison
Published: May 2016

Objective

To study the offer and uptake of chromosomal microarray analysis (CMA) among women undergoing invasive prenatal testing.

Methods

This is a retrospective cohort study of women who underwent chorionic villus sampling (CVS) or amniocentesis. Charts were reviewed for CMA offer and uptake, in additional to clinical and demographic variables.

Results

One hundred forty‐one women underwent CVS (n = 53) or amniocentesis (n = 91) over the study period. Overall, 41% of women underwent CMA. Women who underwent invasive testing for a fetal structural abnormality were more likely to undergo CMA than women who underwent invasive testing for all other indications (aOR 43.18, 95% CI 4.64 – 401.58). Chromosomal microarray was offered more often to women who primarily spoke English (p < 0.001), self‐identified as white (p = 0.046) and did not receive prenatal care in a community health center (p = 0.044). Statistically significant differences in CMA uptake by race/ethnicity, language, insurance or provider type were not noted. Multiparous women were less likely to accept this test than nulliparas (aOR 0.39, 95% CI 0.17 – 0.86).

Conclusion

Women who undergo invasive fetal testing are more likely to undergo CMA if the indication is for a fetal structural anomaly. There may be important demographic disparities in the offering of CMA which bear further exploration. © 2016 John Wiley & Sons, Ltd.
Measurements of slip velocity and frictional heating in the capillary extrusion of linear‐low‐density polyethylene with a fluoropolymer processing aid
Authors: Zamora‐López H.S. , Pérez‐González J. , Marín‐Santibáñez B.M. , Ortega‐Avila J.F.
Published: May 2016

The slip velocity and frictional or slip heating of linear‐low density polyethylene with a fluoropolymer processing aid in capillary flow were measured by rheo‐particle image velocimetry and thermal imaging. The pure polymer did not show slip before the stick‐slip regime but exhibited strong slip when blended with the processing additive. However, for shear stresses beyond the stick‐slip regime, the pure polymer and the blend exhibited the same flow behavior with slip. The slip velocity increased with the shear stress at two different rates before and after the stick‐slip and the contribution of slip to the total flow rate exhibited a minimum. Significant rises in temperature were measured under slip and no slip conditions, being these much higher than the values predicted by the adiabatic flow assumption. Clear difference was made between viscous and frictional heating before the stick‐slip regime, even though they could not be distinguished from one another at higher stresses. Overall, in the presence of slip, frictional and viscous heating act synergistically producing higher temperature rises in the melt. Finally, in contrast to predictions by numerical simulations of viscous heating, measured velocity profiles did not evidence the heating effects in the shear stress range analyzed in this work. POLYM. ENG. SCI., 56:837–845, 2016. © 2016 Society of Plastics Engineers
Impact of Isotope Dilution Mass Spectrometry (IDMS) Standardization on Carboplatin Dose and Adverse Events
Authors: Lawson Justin , Switchenko Jeffrey M. , McKibbin Trevor , Donald Harvey R.
Published: May 2016

Background

When using area under the concentration–time curve–based strategies for dosing carboplatin, accurate estimation of glomerular filtration rate is required for determining dose. Commonly, the Cockcroft–Gault equation is used, which is dependent on measurement of serum creatinine (SCr). Because analysis of SCr changed to an isotope dilution mass spectrometry (IDMS) standard, we sought to determine the impact of this assay change on carboplatin dosing and related toxicity.

Methods

This was a single‐center, retrospective chart review of adults treated with carboplatin between April 2008 and April 2010 divided into cohorts that initiated carboplatin before or after IDMS standardization. End points included grade 3 thrombocytopenia, decrease in platelet count, and hospitalization and were evaluated in cohorts based on concomitant chemotherapy.

Results

The chart review identified 158 patients, with 63 patients in the pre‐IDMS group and 95 patients in the post‐IDMS group. Average SCr (pre 1.01 mg/dl vs post 0.86 mg/dl, p<0.001) and average carboplatin dose (pre 580 mg vs post 703 mg, p<0.001) were significantly different between the groups. The frequency of grade 3 thrombocytopenia was not statistically significant across three partner chemotherapy cohorts before and after IDMS implementation.

Conclusion

IDMS standardization led to an overall decrease in SCr with subsequent increase in carboplatin doses. However, no increase in recorded adverse events was observed, suggesting that the clinical relevance in toxicity from higher doses was minimal.
Immobilized metal affinity chromatography optimized for the analysis of extracellular phosphorylation
Authors: Klement Eva , Raffai Timea , Medzihradszky Katalin F.
Published: May 2016

Phosphorylation is the most widely studied posttranslational modification. Its role within the cell has been the focus of numerous large‐scale studies. Recently there is growing evidence on the biological significance of extracellular phosphorylation. The analysis of these phosphopeptides is complicated by the abundance of glycosylation in the extracellular space, since glycopeptides are also enriched by the methods used for phosphopeptide isolation. Thus, we optimized IMAC for phosphorylation analysis of secreted proteins, specifically in human serum. Selectivity and efficiency of different enrichment conditions used in earlier large‐scale phosphoproteomic studies were evaluated. We found that minimizing hydrophilic interactions in the enrichment allowed selective phosphopeptide isolation. Using a two‐step IMAC enrichment protocol under these conditions led to the identification of ∼100 phosphorylation sites from the tryptic digest of as little as 40 μL human serum.
Post‐functionalization of perfluorophenyl ester‐functional acyclic diene metathesis polymer
Authors: Daglar Ozgun , Durmaz Hakan , Hizal Gurkan , Tunca Umit
Published: May 2016

The acyclic diene metathesis (ADMET) polymerization was utilized for the design of the ADMET polymer (Mn = 21,200 g/mol, Mw/Mn = 1.74) with pendant perfluorophenyl ester functionality using Grubbs first generation catalysis overnight in bulk at 80 °C. Next, a wide variety of functional groups, like benzyl, octyl, propargyl, allyl, and furfuryl was quantitatively incorporated to the ADMET polymer backbone through various amines using activated ester substitution reaction. The ADMET polymers studied in this work were characterized using 1H, 13C, and 19F NMR, GPC and DSC and displayed a monomodal distribution and a rather broad polydispersity index in the range of −1.33 to 1.90. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 2593–2598
Competition between the phytophagous stink bugs Euschistus heros and Piezodorus guildinii in soybeans
Authors: Tuelher Edmar S , Silva Éder H , Hirose Edson , Guedes Raul Narciso C , Oliveira Eugênio E
Published: May 2016

BACKGROUND

The abundance and contribution of the neotropical brown stink bug, Euschistus heros (F.), and the redbanded stink bug, Piezodorus guildinii (West.), to the composition of insect pests of soybean, Glycine max (L.), fields have changed both spatially and temporally in neotropical soybean production areas. Therefore, we assessed the competitiveness of each species in direct competition experiments following an additive series. We performed mixed (adult) insect infestations in soybean plants and evaluated the fitness of each species and the soybean yield.

RESULTS

While the competitive ability of E. heros was significantly compromised by increments in conspecifics and heterospecifics (i.e. P. guildinii), the competitive ability of P. guildinii was compromised by the presence of heterospecifics (i.e. E. heros). The reproductive output of P. guildinii remained unaffected by increments in E. heros or of P. guildinii. Intriguingly, despite the fact that P. guildinii apparently lost the competition with E. heros, almost no pod production was observed in any plant colonised by the former.

CONCLUSIONS

The higher abundance of E. heros in neotropical soybean fields seems to result from higher competitive ability than its heterospecific competitor P. guildinii, which may prevent the higher losses caused by P. guildinii. © 2016 Society of Chemical Industry
Diagnostic study of a HyMeX heavy precipitation event over Spain by investigation of moisture trajectories
Authors: Röhner Luisa , Nerding Kai‐Uwe , Corsmeier Ulrich
Published: May 2016

The western Mediterranean area is often affected by heavy precipitation events (HPEs). To understand these events, the research programme ‘Hydrological Cycle in the Mediterranean Experiment’ (HyMeX) was established. We investigated a HyMeX HPE over Spain that took place between 28 and 29 September 2012. Due to extreme local precipitation that occurred over the Spanish Mediterranean coast and amounted to over 200 mm rain in a few hours, this event not only is of scientific interest but also had a large social impact. A detailed process study of the scale dependence of the HPE's triggering is performed with the numerical weather prediction (NWP) model Consortium for Small‐scale Modeling (COSMO) and the Lagrangian Analysis Tool (LAGRANTO). Large‐scale lifting is reasonably well captured by global‐scale models and local‐scale convection is tackled by convection‐permitting models. Between these phenomena, there is still a scale where uplift takes place and convective clouds can lead to partly severe precipitation. For the investigated case study, mesoscale horizontal moisture convergence and orographic enhancement over land are identified as the two triggering mechanisms leading to severe precipitation. Vertical profiles of equivalent potential temperature are used to explain the evolution of stability at two selected sites over land and sea. Moisture trajectories indicate the pathways of air masses involved in the HPE. On the one hand, the synoptic flow and the mesoscale convergence line are well represented by the trajectories; on the other hand, additional information about moisture sources was found. Two moisture uptake regions could be identified for this convective HPE: the early part of the event was fed from the eastern Atlantic Ocean, the latter part from the Mediterranean Sea itself. Compared with other cases with strong dynamic forcing, this event is governed mainly by regional diabatic processes.
The October 2011 devastating flash flood event of Antalya: triggering mechanisms and quantitative precipitation forecasting
Authors: Demirtaş Meral
Published: May 2016

The Gulf of Antalya was affected by very heavy precipitation (238 mm in 6 h) that resulted in a devastating flash flood on 9 October 2011. Analysis of numerical model products, based on diagnostics and comparison with conventional and remote‐sensing observations, indicates that the remarkable amount of accumulated precipitation was strongly modulated by mesoscale effects induced on the synoptic‐scale flow. There was a sustained co‐alignment of an upper‐tropospheric tongue of high potential vorticity (PV) over a pre‐existing low‐level baroclinic region. Thermal advection by the low‐level circulation at 925 hPa formed a warm equivalent potential temperature (EPT) anomaly ahead of the PV‐streamer, enhancing the effects of pre‐existing warm‐moist advection. Interaction between the PV‐streamer and thermodynamic processes at low levels set the scene for an enhanced dynamical feedback from the warm low‐level anomaly to upper levels, and the tighter coupling led to further reinforcement of low‐level warm‐moist advection. A southwesterly low‐level jet (LLJ) with high EPT transported conditionally unstable and moist air from the relatively warm Mediterranean Sea, and the sustained northeastward moisture flux was directed toward the concave segment of the Taurus Mountains.

Quantitative precipitation forecasting (QPF) of the phenomenon is explored using the recently developed mesoscale ensemble prediction system – which is constructed by combining the Weather Research and Forecasting model with various ensemble approaches. QPF studies give the timing, location and amount reasonably well 72 h in advance. Sensitivity experiments have been carried out to explore the mesoscale aspects of the precipitating structures and their dependence on orography, surface (sensible and latent heat) fluxes and latent heating due to convection.
Physicochemical, morphological, thermal and pasting properties of marama (Tylosema esculentum) storage root starch
Authors: Adeboye Adedola S. , Emmambux Naushad M.
Published: May 2016

Starch from marama (Tylosema esculentum) storage roots were isolated and characterized for physicochemical, micro‐ and molecular structure, pasting, and thermal properties, and were compared to commercial cassava, maize, and potato starches. The amylose content of marama root starch was 192 g/kg starch; and was close to cassava (196 g/kg), but lower in comparison to maize (250 g/kg) and higher than potato (161 g/kg). Marama root starch granules were found to be simple; spherical, lenticular, and oval in shape with granule size range of about 5–38 µm. The peak viscosity (5350–5475 mPa · s) of marama root starch paste is about twice as high as those of cassava and maize. Marama root starch has higher gel firmness than cassava but half that of potato and maize starches. Gelatinization temperature range (67.5–79.0°C) of marama root starch was close to commercial cassava and maize starches. Marama root starch exhibited type A molecular arrangement (X‐ray diffraction) pattern similar to the cassava and maize starches, but different to type B exhibited by the potato starch. Granule size, amylose:amylopectin ratio and molecular arrangement pattern seem to account for the differences and or similarities between marama root starch and the commercial starches. Marama starch has potential as thickeners in food compared to maize and cassava due to the high viscosity.
Using Children's Picture Books About Autism as Resources in Inclusive Classrooms
Authors: Sigmon Miranda L. , Tackett Mary E. , Azano Amy Price
Published: May 2016

This article focuses on developing teacher understanding of how to carefully select and use children's picture books about autism as a tool for teaching awareness, empathy, and acceptance in an elementary classroom setting. We describe how the increased rate of autism and growing practice of inclusive educational settings affect classroom practice and provide implementation tips for using specific picture books and activities. Knowing that picture books are often used as a teaching tool for elementary educators, the use of books addressing autism could teach empathy while enhancing students' awareness and acceptance of students on the autism spectrum.
Fetal size monitoring and birth‐weight prediction: a new population‐based approach
Authors: Gjessing H. K. , Grøttum P. , Økland I. , Eik‐Nes S. H.
Published: May 2016

Objective

To develop a complete, population‐based system for ultrasound‐based fetal size monitoring and birth‐weight prediction for use in the second and third trimesters of pregnancy.

Methods

Using 31 516 ultrasound examinations from a population‐based Norwegian clinical database, we constructed fetal size charts for biparietal diameter, femur length and abdominal circumference from 24 to 42 weeks' gestation. A reference curve of median birth weight for gestational age was estimated using 45 037 birth weights. We determined how individual deviations from the expected ultrasound measures predicted individual percentage deviations from expected birth weight. The predictive quality was assessed by explained variance of birth weight and receiver–operating characteristics curves for prediction of small‐for‐gestational age. A curve for intrauterine estimated fetal weight was constructed. Charts were smoothed using the gamlss non‐linear regression method.

Results

The population‐based approach, using bias‐free ultrasound gestational age, produces stable estimates of size‐for‐age and weight‐for‐age curves in the range 24–42 weeks' gestation. There is a close correspondence between percentage deviations and percentiles of birth weight by gestational age, making it easy to convert between the two. The variance of birth weight that can be ‘explained’ by ultrasound increases from 8% at 20 weeks up to 67% around term. Intrauterine estimated fetal weight is 0–106 g higher than median birth weight in the preterm period.

Conclusions

The new population‐based birth‐weight prediction model provides a simple summary measure, the ‘percentage birth‐weight deviation’, to be used for fetal size monitoring throughout the third trimester. Predictive quality of the model can be measured directly from the population data. The model computes both median observed birth weight and intrauterine estimated fetal weight. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
The construction of ‘geopolitical spaces’ in Russian foreign policy discourse before and after the Ukraine crisis
Authors: Svarin David
Published: May 2016

Focusing on discourses by the ruling elite, this article examines the construction of ‘geopolitical spaces’ in Russian foreign policy. Based on a critical geopolitical analysis, suggesting that territory, space and geographies are being actively (re)formulated by those in power, this article analyzes how policy-makers define and articulate the importance of a particular geographical region for their foreign policy. It analyzes how the three ‘geopolitical spaces’ – Eurasia, the Euro-Atlantic and the Asia-Pacific – are defined by Russia's political leaders and how each space fulfils a particular function for the pursuit of Russian interests abroad. In a second part, this article takes into account the events in and around Ukraine starting in late 2013 and analyzes how Russia's discourse toward the traditional ‘geopolitical spaces’ changed as a result. It is argued, that while Russia previously strived for membership in each of the three ‘geopolitical spaces’, the Ukraine crisis and its impact on Moscow's relation with the West led to a reorientation of Russia's geopolitical vision toward the East and most importantly toward Eurasia. The establishment of the Eurasian Economic Union was instrumental for the promotion of a new vision of wider Eurasian integration.
Successful medical management of a neonate with spontaneous splenic rupture and severe hemophilia A
Authors: Badawy Sherif M. , Rossoff Jenna , Yallapragada Sushmita , Liem Robert I. , Sharathkumar Anjali A.
Published: May 2016

Splenic rupture in neonates is a rare event, usually occurring in the setting of underlying predisposing conditions. Here, we present the case of a term neonate who presented with worsening anemia in the setting of known hemolytic disease during the newborn period and was later found to have a spontaneous splenic rupture. He was subsequently diagnosed with severe hemophilia A, and was managed medically with recombinant factor VIII replacement therapy without any surgical intervention. This is the first reported case of a neonate who had spontaneous splenic rupture and severe hemophilia A, and underwent successful medical treatment without any surgical intervention.
Profile of pregnant women using delivery hut services of the Ballabgarh Health and Demographic Surveillance System in rural north India
Authors: Kant Shashi , Haldar Partha , Singh Arvind K. , Archana S. , Misra Puneet , Rai Sanjay
Published: May 2016

Objective

To describe women who attended two delivery huts in rural Haryana, India.

Methods

The present observational study assessed routinely collected service provision data from two delivery huts located at primary health centers in the district of Faridabad. Data on sociodemographic characteristics, prenatal care, use of free transport services, and maternal and neonatal indicators at delivery were assessed for all pregnant women who used the delivery hut services from January 2012 to June 2014.

Results

During the study period, 1796 deliveries occurred at the delivery huts. The mean age of the mothers was 23.3 ± 3.3 years (95% confidence interval 23.1–23.5). Of 1648 mothers for whom data were available, 1039 (63.0%) had travelled less than 5 km to the delivery hut. The proportion of mothers who belonged to a lower caste increased from 31.0% (193/622) in 2012 to 41.1% (162/394) in 2014. The proportion of mothers who were illiterate also increased, from 8.1% (53/651) in 2012 to 26.4% (104/394) in 2014.

Conclusion

Belonging to a disadvantaged social group (in terms of caste or education) was not an obstacle to use of delivery hut services. The delivery huts might have satisfied some unmet needs of community members in rural India.
Molecular mechanism of prion‐like tau‐induced neurodegeneration
Authors: Alonso Alejandra D. , Beharry Cindy , Corbo Christopher P. , Cohen Leah S.
Published: May 2016

Introduction

Accumulation of hyperphosphorylated tau and the disruption of microtubules are correlated with synaptic loss and pathology of Alzheimer's disease (AD). Impaired cognitive function and pathology of AD is correlated with this lesion. This review looks at the mechanism of neurodegeneration, the prion‐like behavior of tau in its interaction with normal MAPs in correlation with tau hyperphosphorylation.

Methods

We reviewed our work in the field as well as current literature that pertains to tau phosphorylation and the biological effects.

Results

Hyperphosphorylation of tau in AD, in vitro, in cells, or in animal models converts this protein into a prion‐like protein that is able to propagate the altered conformation.

Discussion

These findings suggest that phosphorylation of tau is a critical event in neurodegeneration. The combination of phosphorylation sites can generate a gain of toxic function for tau. The mechanism of tau toxicity might involve not only the microtubule system but also interference with other cellular compartments such as the nucleus and the actin cytoskeleton.
Early pathologic amyloid induces hypersynchrony of BOLD resting‐state networks in transgenic mice and provides an early therapeutic window before amyloid plaque deposition
Authors: Shah Disha , Praet Jelle , Latif Hernandez Amira , Höfling Corinna , Anckaerts Cynthia , Bard Frédérique , Morawski Markus , Detrez Jan R. , Prinsen Els , Villa Alessandro , De Vos Winnok H. , Maggi Adriana , D'Hooge Rudi , Balschun Detlef , Rossner Steffen , Verhoye Marleen , Van der Linden Annemie
Published: May 2016

Introduction

In Alzheimer's disease (AD), pathologic amyloid‐beta (Aβ) is synaptotoxic and impairs neuronal function at the microscale, influencing brain networks at the macroscale before Aβ deposition. The latter can be detected noninvasively, in vivo, using resting‐state functional MRI (rsfMRI), a technique used to assess brain functional connectivity (FC).

Methods

RsfMRI was performed longitudinally in TG2576 and PDAPP mice, starting before Aβ deposition to determine the earliest FC changes. Additionally, the role of pathologic Aβ on early FC alterations was investigated by treating TG2576 mice with the 3D6 anti‐Aβ‐antibody.

Results

Both transgenic models showed hypersynchronized FC before Aβ deposition and hyposynchronized FC at later stages. Early anti‐Aβ treatment in TG2576 mice prevented hypersynchronous FC and the associated synaptic impairments and excitatory/inhibitory disbalances.

Discussion

Hypersynchrony of FC may be used as a new noninvasive read out of early AD and can be recovered by anti‐Aβ treatment, encouraging preventive treatment strategies in familial AD.
Bidirectional contrast effects between taste perception and simulation: A simulation‐induced adaptation mechanism
Authors: Si Kao , Jiang Yuwei
Published: May 2016

Four experiments reveal that actual taste perception and mental simulation of taste can exert a bidirectional contrast effect on each other. Experiment 1 shows that similar to actual taste experience, simulated taste experience is influenced by a prior actual taste in a contrastive manner. Experiment 2 shows that this contrast effect of actual taste on taste simulation occurs only when people adopt an imagery‐based rather than an analytical processing mode. Experiment 3 demonstrates the bidirectional nature of the current effect and again shows that it depends on people's use of mental simulation. Lastly, experiment 4 replicates the observed effect in a realistic marketing environment. These findings support the proposition of a simulation‐induced adaptation mechanism. Theoretical and practical implications of this research are discussed.
Trends and determinant factors in the use of cardiac resynchronization therapy devices in Japan: Analysis of the Japan cardiac device treatment registry database
Authors: Yokoshiki Hisashi , Shimizu Akihiko , Mitsuhashi Takeshi , Furushima Hiroshi , Sekiguchi Yukio , Manaka Tetsuyuki , Nishii Nobuhiro , Ueyama Takeshi , Morita Norishige , Nitta Takashi , Okumura Ken ,   Members of the Implantable Cardioverter‐Defibrillator (ICD) Committee of the Japanese Heart Rhythm Society
Published: May 2016

Background

The choice of cardiac resynchronization therapy device, with (CRT‐D) or without (CRT‐P) a defibrillator, in patients with heart failure largely depends on the physician's discretion, because it has not been established which subjects benefit most from a defibrillator.

Methods

We examined the annual trend of CRT device implantations between 2006 and 2014, and evaluated the factors related to the device selection (CRT‐D or CRT‐P) for primary prevention of sudden cardiac death in patients with heart failure by analyzing the Japan Cardiac Device Treatment Registry (JCDTR) database from January 2011 and August 2015 (CRT‐D, n=2714; CRT‐P, n=555).

Results

The proportion of CRT‐D implantations for primary prevention among all the CRT‐D recipients was more than 70% during the study period. The number of CRT‐D implantations for primary prevention reached a maximum in 2011 and decreased gradually between 2011 and 2014, whereas CRT‐P implantations increased year by year until 2011 and remained unchanged in recent years. Multivariate analysis identified age (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.90–0.95, P<0.0001), male sex (OR 1.99, 95% CI 1.28–3.11, P<0.005), reduced left ventricular ejection fraction (LVEF) (OR 0.96, 95% CI 0.94–0.98, P<0.0001), and non‐sustained ventricular tachycardia (NSVT) (OR 2.85, 95% CI 1.87–4.35, P<0.0001) as independent factors favoring the choice of CRT‐D.

Conclusions

Younger age, male sex, reduced LVEF, and a history of NSVT were independently associated with the choice of CRT‐D for primary prevention of sudden cardiac death in patients with heart failure in Japan.
Bile acids‐mediated overexpression of MUC4 via FAK‐dependent c‐Jun activation in pancreatic cancer
Authors: Joshi Suhasini , Cruz Eric , Rachagani Satyanarayana , Guha Sushovan , Brand Randall E. , Ponnusamy Moorthy P. , Kumar Sushil , Batra Surinder K.
Published: May 2016

The majority of pancreatic cancer (PC) patients are clinically presented with obstructive jaundice with elevated levels of circulatory bilirubin and alkaline phosphatases. In the current study, we examined the implications of bile acids (BA), an important component of bile, on the pathophysiology of PC and investigated their mechanistic association in tumor‐promoting functions. Integration of results from PC patient samples and autochthonous mouse models showed an elevated levels of BA (p < 0.05) in serum samples compared to healthy controls. Similarly, an elevated BA levels was observed in pancreatic juice derived from PC patients (p < 0.05) than non‐pancreatic non‐healthy (NPNH) controls, further establishing the clinical association of BA with the pathogenesis of PC. The tumor‐promoting functions of BA were established by observed transcriptional upregulation of oncogenic MUC4 expression. Luciferase reporter assay revealed distal MUC4 promoter as the primary responsive site to BA. In silico analysis recognized two c‐Jun binding sites at MUC4 distal promoter, which was biochemically established using ChIP assay. Interestingly, BA treatment led to an increased transcription and activation of c‐Jun in a FAK‐dependent manner. Additionally, BA receptor, namely FXR, which is also upregulated at transcriptional level in PC patient samples, was demonstrated as an upstream molecule in BA‐mediated FAK activation, plausibly by regulating Src activation. Altogether, these results demonstrate that elevated levels of BA increase the tumorigenic potential of PC cells by inducing FXR/FAK/c‐Jun axis to upregulate MUC4 expression, which is overexpressed in pancreatic tumors and is known to be associated with progression and metastasis of PC.
Sildenafil and Exercise Capacity in the Elderly at Moderate Altitude
Authors: Rodway George W. , Lovelace Anne J. , Lanspa Michael J. , McIntosh Scott E. , Bell James , Briggs Ben , Weaver Lindell K. , Yanowitz Frank , Grissom Colin K.
Published: May 2016

Objective

Hypobaric hypoxia decreases exercise capacity and causes hypoxic pulmonary vasoconstriction and pulmonary hypertension. The phosphodiesterase-5 inhibitor sildenafil is a pulmonary vasodilator that may improve exercise capacity at altitude. We aimed to determine whether sildenafil improves exercise capacity, measured as maximal oxygen consumption (peak V̇o2), at moderate altitude in adults 60 years or older.

Methods

The design was a randomized, double-blind, placebo-controlled, crossover study. After baseline cardiopulmonary exercise testing at 1400 m, 12 healthy participants (4 women) aged 60 years or older, who reside permanently at approximately 1400 m and are regularly active in self-propelled mountain recreation above 2000 m, performed maximal cardiopulmonary cycle exercise tests in a hypobaric chamber at a simulated altitude of 2750 m after ingesting sildenafil and after ingesting a placebo.

Results

After placebo, mean peak V̇o2 was significantly lower at 2750 m than 1400 m: 37.0 mL · kg-1 · min-1 (95% CI, 32.7 to 41.3) vs 39.1 mL · kg-1 · min-1 (95% CI, 33.5 to 44.7; P = .020). After placebo, there was no difference in heart rate (HR) or maximal workload at either altitude ( z = 0.182; P = .668, respectively). There was no difference between sildenafil and placebo at 2750 m in peak V̇o2 ( P = .668), O2 pulse ( P = .476), cardiac index ( P = .143), stroke volume index ( z = 0.108), HR ( z = 0.919), or maximal workload ( P = .773). Transthoracic echocardiography immediately after peak exercise at 2750 m showed tricuspid annular plane systolic velocity was significantly higher after sildenafil than after placebo ( P = .019), but showed no difference in tricuspid annular plane systolic excursion ( P = .720).

Conclusions

Sildenafil (50 mg) did not improve exercise capacity in adults 60 years or older at moderate altitude in our study. This might be explained by a “dosing effect” or insufficiently high altitude.
Reconstruction of CMB temperature anisotropies with primordial CMB induced polarization in galaxy clusters
Authors: Liu Guo-Chin , Ichiki Kiyotomo , Tashiro Hiroyuki , Sugiyama Naoshi
Published: May 2016

Scattering of cosmic microwave background (CMB) radiation in galaxy clusters induces polarization signals determined by the quadrupole anisotropy in the photon distribution at the location of clusters. This ‘remote quadrupole’ derived from the measurements of the induced polarization in galaxy clusters provides an opportunity to reconstruct local CMB temperature anisotropies. In this Letter, we develop an algorithm of the reconstruction through the estimation of the underlying primordial gravitational potential, which is the origin of the CMB temperature and polarization fluctuations and CMB induced polarization in galaxy clusters. We found a nice reconstruction for the quadrupole and octopole components of the CMB temperature anisotropies with the assistance of the CMB induced polarization signals. The reconstruction can be an important consistency test on the puzzles of CMB anomalies, especially for the low-quadrupole and axis-of-evil problems reported in Wilkinson Microwave Anisotropy Probe and Planck data.
Spiral-induced velocity and metallicity patterns in a cosmological zoom simulation of a Milky Way-sized galaxy
Authors: Grand Robert J. J. , Springel Volker , Kawata Daisuke , Minchev Ivan , Sánchez-Blázquez Patricia , Gómez Facundo A. , Marinacci Federico , Pakmor Rüdiger , Campbell David J. R.
Published: May 2016

We use a high-resolution cosmological zoom simulation of a Milky Way-sized halo to study the observable features in velocity and metallicity space associated with the dynamical influence of spiral arms. For the first time, we demonstrate that spiral arms, that form in a disc in a fully cosmological environment with realistic galaxy formation physics, drive large-scale systematic streaming motions. In particular, on the trailing edge of the spiral arms the peculiar galactocentric radial and azimuthal velocity field is directed radially outward and azimuthally backward, whereas it is radially inward and azimuthally forward on the leading edge. Owing to the negative radial metallicity gradient, this systematic motion drives, at a given radius, an azimuthal variation in the residual metallicity that is characterized by a metal-rich trailing edge and a metal-poor leading edge. We show that these signatures are theoretically observable in external galaxies with integral field unit instruments such as VLT/MUSE, and if detected, would provide evidence for large-scale systematic radial migration driven by spiral arms.
Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence
Authors: Oladele Rita O. , Akanmu Alani S. , Nwosu Augustina O. , Ogunsola Folasade T. , Richardson Malcolm D. , Denning David W.
Published: May 2016

Background.  Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria.

Methods.  Sera were collected from 214 consenting HIV-infected participants with CD4+ counts <250 cells/mm3, irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes.

Results.  Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 ± 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4+ cell count was 160 cells/mm3 (interquartile range, 90–210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4+ cell counts <100 cells/mm3, 4 of 80 (5.0%) in the 100–200 group, and 9 of 73 (12.3%) in 200–250 cells/mm3 group. Among ART-naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts <100 cells/mm3, which was unrelated to CrAg positivity (P = .018).

Conclusions.  We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We recommend CrAg screening for HIV-infected patients, even for patients on ART.
Genomic positional conservation identifies topological anchor point (tap)RNAs linked to developmental loci
Authors: Amaral Paulo P. , Leonardi Tommaso , Han Namshik , Viré Emmanuelle , Gascoigne Dennis K. , Arias-Carrasco Raúl , Büscher Magdalena , Zhang Anda , Pluchino Stefano , Maracaja-Coutinho Vinicius , Nakaya Helder I. , Hemberg Martin , Shiekhattar Ramin , Enright Anton J. , Kouzarides Tony
Published: May 2016

The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider positional conservation across mammalian genomes as an indicator of functional commonality. We identify 665 conserved lncRNA promoters in mouse and human genomes that are preserved in genomic position relative to orthologous coding genes. The identified ‘positionally conserved’ lncRNA genes are primarily associated with developmental transcription factor loci with which they are co-expressed in a tissue-specific manner. Strikingly, over half of all positionally conserved RNAs in this set are linked to distinct chromatin organization structures, overlapping the binding sites for the CTCF chromatin organizer and located at chromatin loop anchor points and borders of topologically associating domains (TADs). Thesetopologicalanchorpoint (tap)RNAs possess conserved sequence domains that are enriched in potential recognition motifs for Zinc Finger proteins. Characterization of these noncoding RNAs and their associated coding genes shows that they are functionally connected: they regulate each other’s expression and influence the metastatic phenotype of cancer cellsin vitroin a similar fashion. Thus, interrogation of positionally conserved lncRNAs identifies a new subset of tapRNAs with shared functional properties. These results provide a large dataset of lncRNAs that conform to the “extended gene” model, in which conserved developmental genes are genomically and functionally linked to regulatory lncRNA loci across mammalian evolution.
Presenile diffuse familial sebaceous hyperplasia successfully treated with low‐dose isotretinoin: A report of two cases and review of the published work
Authors: Liu You‐Chen Serena , Cheng Yu‐Pin , Liu Chuan‐I , Yang Chin‐Yi , Yang Chia‐Yi
Published: May 2016

Presenile diffuse familial sebaceous hyperplasia (PDFSH) presents as extensive yellowish papules with central umbilication on the face without involvement of periorificial regions and occurs in adolescents or young adults with a positive family history. Thirteen cases of PDFSH have been reported in the English‐language published work, 10 of which responded to oral isotretinoin from 0.5 to 1 mg/kg per day but recurrences were often observed. Herein, we report two cases of PDFSH, which were successfully managed without recurrence with prolonged low‐dose isotretinoin (0.2 mg/kg per day, a cumulative dose of 41 and 64 mg/kg, respectively). Treatment protocols among different published works were reviewed to verify the efficacy of isotretinoin.
Interobserver agreement on dermoscopic features of small basal cell carcinoma (<5 mm) among low‐experience dermoscopists
Authors: di Meo Nicola , Damiani Giovanni , Vichi Silvia , Fadel Mattia , Nan Katiuscia , Noal Cecilia , Trevisini Sara , Trevisan Giusto
Published: May 2016

The basal cell carcinoma (BCC) assessment in dermoscopy is based on the recognition of specific characteristics synthesized and described as classical and non‐classical criteria, but which may not necessarily present all at the same time. Consequently, a deep knowledge in detecting the aforementioned dermoscopic criteria is crucial in diagnosis. The aim of the study was to evaluate which criteria are more frequently recognized among a group of low‐experienced dermoscopists when confronted with the difficult diagnosis of BCC with a diameter lower than 5 mm. We examined 100 BCC finding that data displays a full agreement only for one classical criterion, the lack of pigmented network (Fleiss' κ = 1), while among other classical criteria only arborizing vessels and ulceration exhibit a good agreement among observers (Fleiss' κ > 0.40). Analyzing non‐classical criteria, only blue‐whitish veil and blue in‐focus dots show a good agreement among low‐experience observers (Fleiss' κ > 0.40). It is evident that in small size BCC classic dermoscopic criteria are often substituted by non‐classical criteria, which represent the neoplasm's early phase. Thus, it is of importance, especially for low‐experience dermoscopists, to analyze even the non‐classical criteria in order to obtain a diagnosis of early BCC.