bluuebunny/crossref_metadata_2025 huggingface dataset:
Situations Leading to Reduced Effectiveness of Current Hand Hygiene against Infectious Mucus from Influenza Virus-Infected Patients
Authors: Hirose Ryohei , Nakaya Takaaki , Naito Yuji , Daidoji Tomo , Bandou Risa , Inoue Ken , Dohi Osamu , Yoshida Naohisa , Konishi Hideyuki , Itoh Yoshito
Published: September 2019

Antiseptic hand rubbing (AHR) and antiseptic hand washing (AHW) are important to prevent the spread of influenza A virus (IAV). This study elucidated the situations/mechanisms underlying the reduced efficacy of AHR against infectious mucus derived from IAV-infected individuals and indicated the weaknesses of the current hand hygiene regimens. Due to the low rate of diffusion/convection because of the physical properties of mucus as a hydrogel, the efficacy of AHR using ethanol-based disinfectant against mucus is greatly reduced until infectious mucus adhering to the hands/fingers has completely dried. If there is insufficient time before treating the next patient (i.e., if the infectious mucus is not completely dry), medical staff should be aware that effectiveness of AHR is reduced. Since AHW is effective against both dry and nondry infectious mucus, AHW should be adopted to compensate for these weaknesses of AHR.
Recovirus NS1-2 Has Viroporin Activity That Induces Aberrant Cellular Calcium Signaling To Facilitate Virus Replication
Authors: Strtak Alicia C. , Perry Jacob L. , Sharp Mark N. , Chang-Graham Alexandra L. , Farkas Tibor , Hyser Joseph M.
Published: September 2019

Tulane virus is one of many enteric caliciviruses that cause acute gastroenteritis and diarrheal disease. Globally, enteric caliciviruses affect both humans and animals and amass >65 billion dollars per year in treatment and health care-associated costs, thus imposing an enormous economic burden. Recent progress has resulted in several cultivation systems (B cells, enteroids, and zebrafish larvae) to study human noroviruses, but mechanistic insights into the viral factors and host pathways important for enteric calicivirus replication and infection are still largely lacking. Here, we used Tulane virus, a calicivirus that is biologically similar to human noroviruses and can be cultivated by conventional cell culture, to identify and functionally validate NS1-2 as an enteric calicivirus viroporin. Viroporin-mediated calcium signaling may be a broadly utilized pathway for enteric virus replication, and its existence within caliciviruses provides a novel approach to developing antivirals and comprehensive therapeutics for enteric calicivirus diarrheal disease outbreaks.
Left atrial myxoma: an unusual cause of postpartum tachycardia and shortness of breath
Authors: Nazir Tahir , Ahmed Saad , Ahmed Irfan Munir
Published: September 2019

Primary cardiac tumours are exceedingly rare in clinical practice and a myxoma is certainly not the first suspected diagnosis on a list of differentials in a patient presenting with breathlessness and tachycardia. Naturally, a structured work-up to rule out much more common conditions will take place. Nonetheless, an index of clinical suspicion is required especially when a clear-cut diagnosis is not forthcoming. We describe a case of a postpartum woman who presented with shortness of breath and palpitations, and was eventually diagnosed with a left atrial tumour. She underwent a successful surgical excision of the mass which was found to be a myxoma on histological examination. We review and present an up-to-date literature review on epidemiology, pathophysiology, clinical features, diagnosis and treatment options for cardiac myxomas.
Photoreceptor morphology and correlation with subretinal fluid chronicity associated with choroidal nevus
Authors: Yaghy Antonio , Yu Michael D , Dalvin Lauren A , Mazloumi Mehdi , Ferenczy Sandor R , Shields Carol L
Published: September 2019

Background

Subretinal fluid (SRF) can be associated with choroidal nevus and can cause progressive change in the morphology of overlying photoreceptors.

Methods

A retrospective observational study was performed using optical coherence tomography to assess nevus and SRF features, as well as photoreceptor morphology over time.

Results

There were 232 choroidal nevi that presented with or developed SRF. Photoreceptor morphology at presentation was classified as normal (n=60, 26%), shaggy (elongated) (n=73, 31%), retracted (stalactite appearance) (n=76, 33%), or absent (n=23, 10%). There was a progression in photoreceptor morphology with increasing SRF chronicity (p=0.003). For nevus presenting with normal photoreceptors and later developed SRF (n=60), photoreceptors became shaggy in 29 (48%), retracted in 24 (40%), and absent in 7 (12%) after 15, 19 and 22 months, respectively. For nevus presenting with SRF and shaggy photoreceptors (n=73), progression to retracted photoreceptors occurred in 31 (42%) after a mean of 22 months; for nevus with SRF and retracted photoreceptors (n=76), progression to absent photoreceptors occurred in 19 (25%) after a mean of 34 months; and for nevus with absent photoreceptors (n=23), photoreceptor morphology showed no change after mean follow-up of 33 months. Risk of nevus growth to melanoma was not associated with photoreceptor morphology at presentation (p=0.19).

Conclusion

In eyes with choroidal nevus and SRF, there is a longitudinal evolution in photoreceptor morphology from normal to shaggy to retracted then absent with increasing SRF chronicity. SRF chronicity, as indicated by photoreceptor morphology on presentation, did not correlate with nevus growth to melanoma.
Unusual cause of treatable Parkinsonism
Authors: Wiblin Lou , Mitra Dipayan , Warren Naomi
Published: September 2019

A 78-year-old woman presented with features of bilateral, asymmetric Parkinsonism for 1 year, with prominent difficulties with continence, swallowing and apathy. Brain imaging showed evidence of chronic venous sinus thrombosis with dilated serpiginous vessels over the brain surface in keeping with a dural arteriovenous fistula, together with high T2 signal on MRI in the basal ganglia. Having responded only modestly to levodopa, she received 6 months of anticoagulation followed by embolisation of the dural arteriovenous fistula, with good response. Cerebral dural arteriovenous fistula is a rare, structural cause of atypical Parkinsonism.
Effects of stored whole rice bran treated with organic acids on the performance, nutrient digestibility, intestinal mucosa morphometry, and bone characteristics of broiler chickens
Authors: Gopinger E. , Xavier E.G. , Ziegler V. , Lopes D.C.N. , Krabbe E.L. , Nunes A.P. , Elias M.C.
Published: September 2019

This study evaluated the effects of feeding whole rice bran (WRB) stored for different times and treated with a mixture of organic acids on the growth performance, nutrient digestibility, duodenal morphometry, and bone characteristics of broiler chickens. Three hundred and twenty 1-d-old Cobb broilers were used in a 21 d experiment with a completely randomized design. Whole rice bran with five storage times (0, 30, 60, 90, and 120 d) was included at a 12% level in the diets, with eight replicates of eight birds each. A polynomial regression with a significance level of 5% was used. A reduction in daily weight gain was observed in birds fed WRB stored up to 90 d. A quadratic response was observed in the daily feed intake and average body weight of birds fed diets containing WRB treated with a mixture of organic acids and stored up to 90 d. There was a linear increase in the digestibility of crude protein with increased WRB storage time. Apparent metabolizable energy and apparent metabolizable energy corrected for nitrogen showed an increasing quadratic response for up to 60 d of WRB storage and treated with a mixture of organic acids. A quadratic response for the morphometry of intestinal crypts was found. The crypt depth increased as the birds were fed a diet containing WRB treated with a mixture of organic acids, stored up to 30 d and decreased with storage times. In conclusion, WRB treated with a mixture of acetic and propionic acids and stored up to 60 d may be safely added to broiler chicken diets.
Integrating tagging and fisheries data into a spatial population dynamics model to improve its predictive skills
Authors: Senina Inna , Lehodey Patrick , Sibert John , Hampton John
Published: September 2019

SEAPODYM is a model developed for investigating spatiotemporal dynamics of fish populations under the influence of both fishing and the environment. The model simulates age-structured population dynamics using advection–diffusion–reaction equations describing movement, recruitment, and natural and fishing mortality. The dynamic processes are constrained by environmental data and distributions of prey species. Model parameter estimation using fishing data was implemented earlier based on a maximum likelihood estimation (MLE) approach and adjoint technique. Here, we describe the integration of tagging data into the existing MLE approach with application to skipjack tuna (Katsuwonus pelamis) in the Pacific Ocean. We find that tagging data improve estimates of species habitat parameters and movement rates and hence allow better representation of spatial dynamics of fish population. Due to estimated lower diffusion and higher advection rates, the model predicts less non-observed “cryptic” biomass, which leads to the stock sizes being closer to those estimated by stock assessment models commonly used by tuna commissions.
Existence of dynamical wormholes in f(R) gravity
Authors: Yousaf Z. , Ikram A. , Ilyas M. , Bhatti M.Z.
Published: September 2019

This paper explores spherically symmetrical dynamical traversable wormhole solutions for an anisotropic fluid configuration in the context of f(R) gravity. We construct the corresponding field equations and investigate the wormhole solutions by specifying the redshift and shape functions for three models of f(R) gravity. Graphical analysis shows that ordinary matter satisfies the null as well as weak energy conditions against the time and radial coordinates for each model. It is concluded that dynamical traversable wormholes are supported by this theory.
Effective theories of two T-dual theories are also T-dual
Authors: Davidović Ljubica , Sazdović Branislav
Published: September 2019

We investigate how T-duality and solving the boundary conditions of the open bosonic string are related. We start by considering the T-dualization of the open string moving in the constant background. We take that the coordinates of the initial theory satisfy either Neumann or Dirichlet boundary conditions. It follows that the coordinates of T-dual theory satisfy exactly the opposite set of boundary conditions. We treat the boundary conditions of both theories as constraints, and apply the Dirac procedure to them, which results in forming $$\sigma $$σ-dependent constraints. We solve these constraints and obtain the effective theories for the solution. We show that the effective closed string theories are also T-dual.
Characterizing dynamics of swirling film in gas–liquid cylindrical cyclone separator using multi-scale entropy analysis
Authors: Zhai Lusheng , Xie Hailin , Yang Jie , Wu Yinglin , Lu Xuanzhao
Published: September 2019

Gas–liquid cylindrical cyclone (GLCC) separator is attractive for subsea gas–water separation due to its simplicity and small footprint. In this study, we designed a multi-channel conductance probe and conducted an experiment of gas–liquid separation in a GLCC separator. Local information of the lower swirling liquid film in the GLCC is collected by the multi-channel conductance probe. To uncover the hydrodynamics of swirl liquid film in the lower part of the GLCC, multi-scale distribution entropy (MSDE) in coupled phase space is employed to analyze the multi-channel conductance signals. The results of the MSDE enable to indicate the spatial dynamics of the swirling film, which can provide beneficial insights for uncovering the generation mechanism of gas bubble in the process of gas carry-under.
ENERGY INSECURITY, ECONOMIC GROWTH, AND THE ROLE OF RENEWABLE ENERGY: A CROSS-COUNTRY PANEL ANALYSIS
Authors: XU XIANG , YU JIAN , ZHANG DAYONG , JI QIANG
Published: September 2019

Many countries rely on the international energy market as their main energy supplier, thus leading to issues of insecurity. Energy insecurity can potentially hinder economic growth and cause sustainability problems. This paper builds on cross-country panel data and estimates the relationship between energy insecurity and economic growth. We explore the multi-dimensional feature of energy insecurity through energy dependency, renewable energy share, and price effects. Our results show statistically significant negative impacts on growth due to energy insecurity, but the effects are mostly relevant to developing economies. Moreover, we show that the development renewable energy sector can mitigate the negative effects.
Lifetime estimations from RHIC Au+Au data
Authors: Kasza Gábor , Csörgő Tamás
Published: September 2019

We discuss a recently found family of exact and analytic, finite and accelerating, [Formula: see text]-dimensional solutions of perfect fluid relativistic hydrodynamics to describe the pseudorapidity densities and longitudinal HBT-radii and to estimate the lifetime parameter and the initial energy density of the expanding fireball in Au[Formula: see text]+[Formula: see text]Au collisions at RHIC with [Formula: see text] GeV and 200 GeV colliding energies. From these exact solutions of relativistic hydrodynamics, we derive a simple and powerful formula to describe the pseudorapidity density distributions in high-energy proton–proton and heavy-ion collisions, and derive the scaling of the longitudinal HBT radius parameter as a function of the pseudorapidity density. We improve upon several oversimplifications in Bjorken’s famous initial energy density estimate, and apply our results to estimate the initial energy densities of high-energy reactions with data-driven pseudorapidity distributions. When compared to similar estimates at the LHC energies, our results indicate a surprising and nonmonotonic dependence of the initial energy density on the energy of heavy-ion collisions.
Strongly Nonlinear Vibrations of a Hyperelastic Thin-walled Cylindrical Shell Based on the Modified Lindstedt–Poincaré Method
Authors: Zhang Jing , Xu Jie , Yuan Xuegang , Zhang Wenzheng , Niu Datian
Published: September 2019

Some significant behaviors on strongly nonlinear vibrations are examined for a thin-walled cylindrical shell composed of the classical incompressible Mooney–Rivlin material and subjected to a single radial harmonic excitation at the inner surface. First, with the aid of Donnell’s nonlinear shallow-shell theory, Lagrange’s equations and the assumption of small strains, a nonlinear system of differential equations for the large deflection vibration of a thin-walled shell is obtained. Second, based on the condensation method, the nonlinear system of differential equations is reduced to a strongly nonlinear Duffing equation with a large parameter. Finally, by the appropriate parameter transformation and modified Lindstedt–Poincar[Formula: see text] method, the response curves for the amplitude-frequency and phase-frequency relations are presented. Numerical results demonstrate that the geometrically nonlinear characteristic of the shell undergoing large vibrations shows a hardening behavior, while the nonlinearity of the hyperelastic material should weak the hardening behavior to some extent.
Analysis of Rocking Behavior of Tang-Song Timber Frames under Pulse-Type Excitations
Authors: Gao Chao , Wang Juan , Yang Qingshan , Yang Na
Published: September 2019

This paper investigates the rocking behavior of two free-standing columns capped with a freely supported superstructure in an effort to explain the seismic stability of Tang-Song timber frames subjected to pulse-type excitations. The geometric characteristics of the column determine the acceleration amplitude needed to create uplift of the rocking frame, which also affect the loss of energy during impact along with the mass ratio of the superstructure to the column. Two distinct rocking modes are analyzed according to whether the frame can be limited by the tenon-mortise joint. The expression that yields the minimum acceleration required to overturn the frame is derived within the limits of the linear approximation of the governing equation of motion. Different safety and overturning regions plotted on the stability diagrams indicates that the partially joint limitation may weaken the seismic behavior. The entirely limited frame will rock within the fixed amplitude caused by the joint gap and never topple down. Probability analysis results of the entirely limited frame suggest that a great majority of this type of traditional timber structures have excellent seismic capacity to resist the horizontal excitation.
A space-consistent version of the minimum-contrast estimator for linear stochastic evolution equations
Authors: Kříž Pavel
Published: September 2019

A new modification of the minimum-contrast estimator (the weighted MCE) of drift parameter in a linear stochastic evolution equation with additive fractional noise is introduced in the setting of the spectral approach (Fourier coordinates of the solution are observed). The reweighing technique, which utilizes the self-similarity property, achieves strong consistency and asymptotic normality of the estimator as number of coordinates increases and time horizon is fixed (the space consistency). In this respect, this modification outperforms the standard (non-weighted) MCE. Compared to other drift estimators studied within spectral approach (e.g., maximum likelihood, trajectory fitting), the weighted MCE is rather universal. It covers discrete time as well as continuous-time observations and it is applicable to processes with any value of Hurst index [Formula: see text]. To the author’s best knowledge, this is so far the first space-consistent estimator studied for [Formula: see text].
Filtering of Gaussian processes in Hilbert spaces
Authors: Kubelka Vít , Maslowski Bohdan
Published: September 2019

Linear filtering problem for infinite-dimensional Gaussian processes is studied, the observation process being finite-dimensional. Integral equations for the filter and for covariance of the error are derived. General results are applied to linear SPDEs driven by Gauss–Volterra process observed at finitely many points of the domain.
Synthesis, characterization, OFET, and DFT study of the novel ball-type metallophthalocyanines bridged with four diaminopyrimidine-dithiol
Authors: Molla Fadime , Yazıcı Ayşegül , Selçuki Nursel Acar , Altındal Ahmet , Salih Bekir , Bekaroğlu Özer
Published: September 2019

Co2Pc2 (2) and Zn2Pc2 (3) were obtained in DMF and LuPc2 (4) was obtained in hexanol by the cyclotetramerization of novel diphthalonitrile (1). Synthesized compounds were characterized by FT-IR,1H-NMR, elemental analyses, MALDI-TOF MS and UV-vis spectroscopy techniques. Optimized geometries and electronic structures for compounds 2, 3 and 4 were investigated by Density Functional Theory (DFT) and Time Dependent Density Functional Theory (TD-DFT). In compound 2, a new bond was observed between Co centers forming two Co(III) with the interaction of d orbitals. Computational and experimental UV-vis spectra in DMF were found in agreement for the investigated compounds. Vertical and adiabatic ionization potentials for the studied systems were also calculated. The gate dielectric performances of thin films obtained from these compounds were investigated by fabricating ITO/2–4/Au devices. The observed reverse bias J-V characteristics revealed that the leakage current in ITO/2–4/Au devices is because of the Poole–Frenkel effect. The effect of the gate dielectric on the OFET performance parameters was also investigated by fabricating bottom-gate top-contact OFET using pentacene as the active layer. Maximum field effect mobility was observed with the 2-based OFET device. Calculated HOMO–LUMO gap, hole reorganization energy and ionization energy have also supported the experimental results which indicate that 2 is the most suitable system for OFET devices.
Auditor-Provided Tax Services and Accounting for Tax Uncertainty
Authors: Watrin Christoph , Burggraef Stephan , Weiss Falko
Published: September 2019

This paper investigates the associations of auditor-provided tax services (APTS) with tax planning and audit quality using a German sample. Our findings differ from those of previous U.S. studies, which we attribute to the fact that prior to 2015, the International Financial Reporting Standards (IFRS) did not contain a clear regulation similar to FIN 48, which requires firms to reserve for tax uncertainties. We find for our IFRS sample a negative association between APTS and tax avoidance, which suggests that auditors are aware that firms might not reserve for tax uncertainties and may advise more conservative tax strategies. Additionally, we find a positive relation between the level of APTS and the sustainability of tax strategies in client firms, consistent with this conservative approach. Furthermore, our results show that APTS are positively related to audit quality for our sample. This finding suggests that auditors, being aware of remaining tax uncertainties that are not reserved for, are more reluctant to accept earnings management, which would further increase the risk of restatement. Taken together, the results of our study suggest the importance of accounting standards regarding tax uncertainties for the implications of APTS.
Efficient Generation of Geographically Accurate Transit Maps
Authors: Bast Hannah , Brosi Patrick , Storandt Sabine
Published: September 2019

We present LOOM (Line-Ordering Optimized Maps), an automatic generator of geographically accurate transit maps. The input to LOOM is data about the lines of a transit network: for each line, its station sequence and geographical course. LOOM proceeds in three stages: (1) construct a line graph, where edges correspond to network segments with the same set of lines following the same course; (2) apply a set of local transformation rules that compute an optimal partial ordering of the lines and speed up the next stage; (3) construct an Integer Linear Program (ILP) that yields a line ordering for each edge and minimizes the total number of line crossings and line separations; and (4) based on the line graph and the computed line ordering, draw the map. As our maps respect the geography of the transit network, they can be used as overlays in typical map services. Previous research either did not take the network geography into account or was only concerned with schematic metro map layouting. We evaluate LOOM on six real-world transit networks, with line-ordering search-space sizes up to 2 × 10
267
. Using our transformation rules and an improved ILP formulation, we compute optimal line orderings in a fraction of a second for all networks. This enables interactive use of our method in map editors.
Future of IOT: Design and deployment challenges
Authors: Ravi Prashant
Published: September 2019

The article touches upon the various design considerations for IoT devices, and discusses the various challenges faced in the design and deployment of such devices.
How to do a naked presentation
Authors: Yaffe Philip
Published: September 2019

Each "Communication Corner" essay is self-contained; however, they build on each other. For best results, before reading this essay and doing the exercise, go to the first essay "How an Ugly Duckling Became a Swan," then read each succeeding essay.

A "naked" presentation solely relies upon good storytelling. Learn how to enrapture an audience without the use of visual aids.
A Case of 14-Year-Old Male with Fibroma of Tendon Sheath of the Hand with Novel Chromosomal Translocation 4;10
Authors: Rubinstein Aaron , Fitzhugh Valerie , Ahmed Irfan , Vosbikian Michael
Published: September 2019

Fibroma of tendon sheath (FTS) is an uncommonly encountered soft tissue mass, which is morphologically distinct from the more commonly seen giant cell tumor of tendon sheath (GCTTS). Initially described in 1936, FTS is typically a slow growing, painless, firm mass with a predilection for the upper extremity, frequently involving the hand. Cases of associated triggering or compression neuropathies have been described when underlying tendons or nerves are affected. Currently, the literature on FTS is sparse and largely limited to case reports. More recently, few reports of cytogenetic analysis on FTS have been reported in the literature. Cellular and chromosomal analysis of FTS tissue revealed chromosomal translocations with yet unknown clinical significance. Here, we present a case report of FTS in a 14-year-old male with a painless enlarging mass on the palmar side of the left hand treated by excision. Subsequent karyotypic analysis revealed a chromosomal translocation t(4;10) (p16;q24), add (10)(q22)[24]. To our knowledge, this is the first description of this chromosomal aberration in the literature.
Long‐Term Deformation Analysis of Recycled Construction Waste Subgrade Filler
Authors: Li Zhe , Yan Shihao , Liu Lulu , Dai Baosen , Dong Wenjing
Published: September 2019

The application of construction waste to subgrade has important economic and environmental significance. In order to study the long‐term deformation characteristics of recycled construction waste filler, a series of laboratory tests and field measurement have been carried out. Through compaction, sieving, and California bearing ratio (CBR) tests, the gradation and CBR value of recycled construction waste filler meet the requirements of expressway subgrade. Long‐term deformation tests include laboratory creep tests and field settlement measurement. The creep tests were carried out for about 500 days by a self‐made consolidation creep instrument, the creep type of recycled construction waste filler under the test load is stable creep, as the load increases, not only the creep deformation increases but also the time to reach creep stability is longer, and the breakage and compaction of particles are the main reasons for long‐term deformation. Through measurement and analysis, it is found that the settlement stability of the construction waste subgrade takes a long time; after the operation of road, the settlement of the subgrade has grown rapidly. Furthermore, the Burgers model can be used to predict the deformation of creep tests, and the maximum settlement of construction waste subgrade can be predicted. The research can provide reference for the application of recycled construction waste filler, and it is conducive to the promotion of construction waste subgrade.
Abdominal Lymphangioma and Hemangioma in a Newborn
Authors: Demiri Charikleia D. , Kaselas Christos , Godosis Dimitrios , Neofytou Andreas , Spyridakis Ioannis
Published: September 2019

Abdominal hemangiolymphangioma (HLA) in neonates is a rare condition that demands surgical intervention after a complete preoperative diagnostic approach. The differential diagnosis and the establishment of a therapeutic algorithm is a challenge, both for the neonatologists and the pediatric surgeons, because there is no consensus in the management of HLAs in infancy according to the literature. We report a rare case of abdominal HLA in a female newborn that was admitted to our pediatric surgery department with a prenatal diagnosis of an abdominal cystic tumor. After a thorough preoperative diagnostic approach, the neonate underwent an explorative laparotomy and lesion excision with simultaneous splenectomy due to the operative findings. The neonate had an uncomplicated postoperative period and is free of recurrence a year after. Only the pathology examination can reveal the HLA diagnosis. When a total surgical excision is evitable, a close follow-up follows an uncomplicated postoperative hospitalization.
Numerical Study of Particle Morphology Effect on the Angle of Repose for Coarse Assemblies Using DEM
Authors: Chen Jing , Gao Rui , Liu Yangzepeng
Published: September 2019

The morphologies of coarse particles are usually irregular and play a dominant role in the mechanical behaviors of the particle assemblies. This paper quantitatively studies the effect of particle shape on the angle of repose, which is an important macroscopic parameter for ballast materials, via laboratory tests and numerical simulations by means of the discrete element method (DEM). Forty ballast particle templates and four simply created clump templates are reconstructed using an image-based method and quantified with two shape factors, sphericity and convexity. A series of simulations are conducted with the coefficient of sliding friction between particles changing from 0.2 to 0.6 at an interval of 0.1 to study its influence on various shapes of particles, and an appropriate value of sliding friction coefficient is chosen for the comparison of particle shape effect. The results show that increasing sphericity and convexity can significantly decrease the angle of repose, and the real ballast model gives a more realistic angle of repose behaviors as that of laboratory tests compared to simply created models. By analyzing the characteristics of particle motions and contacts from a microscopic perspective, the mechanism of particle shape attributed to the formation of granular aggregation is also discussed and revealed in this research.
PEG10 Promoter–Driven Expression of Reporter Genes Enables Molecular Imaging of Lethal Prostate Cancer
Authors: Shapovalova Mariya , Lee John K. , Li Yingming , Vander Griend Donald J. , Coleman Ilsa M. , Nelson Peter S. , Dehm Scott M. , LeBeau Aaron M.
Published: September 2019

The retrotransposon-derived paternally expressed gene 10 (PEG10) protein is ordinarily expressed at high levels in the placenta. Recently, it was discovered that PEG10 isoforms promote the progression of prostate cancer to a highly lethal androgen receptor (AR)-negative phenotype. The presence of PEG10 in other subtypes of prostate cancer has not been explored and a utility for PEG10 overexpression has not been developed. Here, we found that in addition to AR-null disease, PEG10 was also expressed in prostate cancer with constitutively active AR-splice variants. A molecular genetic imaging strategy for noninvasive imaging of AR-splice variant prostate cancer was developed by utilizing the cancer specificity of the PEG10 promoter to drive the expression of reporter genes. Plasmid insertion of a PEG10 promoter sequence optimized for enhanced output upstream of a reporter gene allowed detection of prostate cancer by near-infrared and positron emission tomography imaging after systemic administration of the plasmid in vivo. PEG10 expressing subcutaneous xenograft and intratibial tumor models were imaged by both modalities using this molecular genetic imaging strategy. This study demonstrates a preclinical proof-of-concept that the PEG10 promoter is a powerful and specific tool that can be utilized for noninvasive detection of aggressive prostate cancer subtypes.

Significance:

PEG10 is expressed by prostate cancer with constitutively active AR-splice variants that can be exploited for noninvasive molecular imaging of this aggressive prostate cancer subytpe.
Guadecitabine Plus Ipilimumab in Unresectable Melanoma: The NIBIT-M4 Clinical Trial
Authors: Di Giacomo Anna Maria , Covre Alessia , Finotello Francesca , Rieder Dietmar , Danielli Riccardo , Sigalotti Luca , Giannarelli Diana , Petitprez Florent , Lacroix Laetitia , Valente Monica , Cutaia Ornella , Fazio Carolina , Amato Giovanni , Lazzeri Andrea , Monterisi Santa , Miracco Clelia , Coral Sandra , Anichini Andrea , Bock Christoph , Nemc Amelie , Oganesian Aram , Lowder James , Azab Mohammad , Fridman Wolf H. , Sautès-Fridman Catherine , Trajanoski Zlatko , Maio Michele
Published: September 2019

Purpose:

The immunomodulatory activity of DNA hypomethylating agents (DHAs) suggests they may improve the effectiveness of cancer immunotherapies. The phase Ib NIBIT-M4 trial tested this hypothesis using the next-generation DHA guadecitabine combined with ipilimumab.

Patients and Methods:

Patients with unresectable stage III/IV melanoma received escalating doses of guadecitabine 30, 45, or 60 mg/m2/day subcutaneously on days 1 to 5 every 3 weeks, and ipilimumab 3 mg/kg intravenously on day 1 every 3 weeks, starting 1 week after guadecitabine, for four cycles. Primary endpoints were safety, tolerability, and MTD of treatment; secondary were immune-related (ir) disease control rate (DCR) and objective response rate (ORR); and exploratory were changes in methylome, transcriptome, and immune contextures in sequential tumor biopsies, and pharmacokinetics.

Results:

Nineteen patients were treated; 84% had grade 3/4 adverse events, and neither dose-limiting toxicities per protocol nor overlapping toxicities were observed. Ir-DCR and ir-ORR were 42% and 26%, respectively. Median CpG site methylation of tumor samples (n = 8) at week 4 (74.5%) and week 12 (75.5%) was significantly (P < 0.05) lower than at baseline (80.3%), with a median of 2,454 (week 4) and 4,131 (week 12) differentially expressed genes. Among the 136 pathways significantly (P < 0.05; Z score >2 or ←2) modulated by treatment, the most frequently activated were immune-related. Tumor immune contexture analysis (n = 11) demonstrated upregulation of HLA class I on melanoma cells, an increase in CD8+, PD-1+ T cells and in CD20+ B cells in posttreatment tumor cores.

Conclusions:

Treatment of guadecitabine combined with ipilimumab is safe and tolerable in advanced melanoma and has promising immunomodulatory and antitumor activity.
Outcome-Related Differences in Gene Expression Profiles of High-Grade Serous Ovarian Cancers Following Neoadjuvant Chemotherapy
Authors: Octeau David , Kessous Roy , Klein Kathleen , Kogan Liron , Pelmus Manuella , Ferenczy Alex , Greenwood Celia M.T. , Van Kempen Leon C. , Salvador Shannon , Lau Susie , Tonin Patricia N. , Yasmeen Amber , Gotlieb Walter H.
Published: September 2019

Large-scale genomic studies have detailed the molecular landscape of tumors from patients with high-grade serous ovarian cancers (HGSC) who underwent primary debulking surgery and correlated the identified subgroups to survival. In recent years, there is increased use of neoadjuvant chemotherapy (NACT) for patients with HGSC and while abundant data exist for patients who underwent primary debulking, little data are available on the cancer cells remaining after NACT that could lead to recurrences. We aimed to analyze gene expression profiles of NACT-treated HGSC tumor samples, and correlate them to treatment response and outcome. Tumor samples were collected from patients with stage III or IV HGSC (NACT cohort, N = 57) at the time of surgery and diagnosis (biopsy samples N = 8). Tumor content was validated by histologic examination and bioinformatics. Gene expression analysis was performed using a tailored NanoString-based assay, while sequencing was performed using MiSeq. A cross-validated survival classifier revealed patient clusters with either a “Better” or “Worse” prognostic outcome. The association with overall survival remained significant after controlling for clinical variables, and differential gene expression, gene set enrichment analyses, and the appropriate survival models were used to assess the associations between alterations in gene expression in cancer cells remaining after NACT and outcome. Pathway-based analysis of the differentially expressed genes revealed comparatively high levels of cell cycle and DNA repair gene expression in the poor outcome group.

Implications:

Our work suggests mRNA expression patterns in key genes following NACT may reflect response to treatment and outcome in patient with HGSC.
Last Common Ancestor of Apes and Humans: Morphology and Environment
Authors: Andrews Peter
Published: September 2019

For much of their history, fossil apes retained many monkey-like features in posture and body structure. They also occupied a range of habitats, of which tropical forest was only a part, and there is evidence of increasing terrestriality in the fossil record as it is known at present (2019). In the early Miocene (18–20 million years ago, Ma), fossil apes were pronograde arboreal slow climbers, associated mainly with forest environments and deciduous woodland and with some indications of terrestrial behaviour, particularly the larger species. Their hands had long and opposable thumbs, and the phalanges were curved. In the early middle Miocene (15–16 Ma), apes were still monkey-like in body plan and posture and were associated almost entirely with non-forest, deciduous woodland habitats, with increasing evidence of terrestrial adaptations. Hand proportions remained the same. Towards the end of the middle Miocene (12 Ma), some fossil ape species had broadened chests, long clavicles, medial torsion of the humerus and re-positioning of the scapula to the back. These adaptations may have been linked with more upright posture, as in the living apes, but unlike them, the hand phalanges were short, robust and less curved, and the thumb remained long. Associated environments were deciduous woodland rather than forest. This body plan was retained in part in some later Miocene apes (10 Ma), some of which also had more elongated limbs and hands (thumb length not known), and hind limbs modified for greater flexibility, analogous with the orang utan. Associated environments were subtropical deciduous woodlands and subtropical evergreen laurophyllous woodland in southern Europe. Other late Miocene European apes had adaptations for living on the ground, and some of these also shared characters of the skull with orang utans. They are associated with more open deciduous woodland habitats. This body plan and environment were retained in the early hominin, Ardipithecus ramidus, but with a more robust postcranial skeleton and incipient bipedalism. Based on shared character states in fossil apes, living apes and early hominins, 27 characters are identified as probable attributes of the last common ancestor (LCA) of apes and humans. The likely environment of the LCA was tropical deciduous woodland with some evidence of more open habitats, and this remained unchanged in the transition from apes to early hominins.
Peach Tree Pollen and Prunus persica 9 Sensitisation and Allergy in Children and Adolescents
Authors: Victorio Puche Laura , Somoza Maria Luisa , López-Sánchez José Damián , Garrido-Arandia María , Díaz-Perales Araceli , Blanca Miguel
Published: September 2019

Background: Although plant and fruit pollens are entomophilous and relevant in exposed workers, we have shown a high frequency of sensitisation and symptoms induction of peach tree pollen (PTP) and Prunus persica 9 (Pru p 9) in adults from areas of peach cultivars. Methods: We studied the sensitisation and clinical relevance of PTP and Pru p 9 in a large group of children and adolescents aged 3–19 years. A detailed questionnaire plus skin prick testing to prevalent allergens, PTP, and Pru p 9 were carried out. The clinical relevance was established by nasal provocation test (NPT) and symptom score index. Results: We evaluated 685 children (mean age 8.75 ± 3.3 years, median 9 years), 52% of them female. Sensitisation to PTP occurred in 20% of the cases following olive tree (33%) and Phleum pratense (26%). In a randomly selected subgroup of subjects sensitised to PTP, 30% were skin prick test-positive to Pru p 9. Most cases had rhinitis or rhinoconjunctivitis. NPT showed the relevance of PTP and Pru p 9 in the induction of symptoms. Conclusion: PTP and Pru p 9 are relevant in the induction of sensitisation and respiratory symptoms in children and adolescents. This allergen should be evaluated in children living in regions of peach tree cultivars.
Metastatic Breast Cancer as a Chronic Disease: Evidence-Based Data on a Theoretical Concept
Authors: Elfgen Constanze , Montagna Giacomo , Schmid Seraina Margaretha , Bierbauer Walter , Güth Uwe
Published: September 2019

Background: We challenge the concept of metastatic breast cancer (MBC) as a chronic disease. Methods: We analyzed an unselected cohort of 367 patients who were diagnosed with MBC over a 22-year period (1990–2011). Results: In order to create a “chronic disease subgroup”, we separated those patients from the entire cohort in whom systemic therapy was not applied after the diagnosis of MBC (n = 53; 14.4%). Three hundred fourteen patients (85.6%) comprised the “chronic disease subgroup”. The vast majority of those patients (89.8%) died of progressive disease after a median metastatic disease survival (MDS) of 25 months. Twenty patients (6.4%) died of non-MBC-related causes (MDS 38.5 months). Approximately 1 in 4 patients (26.8%) died within the first year after the MBC diagnosis. The 3- and 5-year MDS rates were 35.4 and 16.2%, respectively. Only 12 patients (3.8%) were exceptional survivors (MDS >10 years). Conclusion: The term “chronic disease” might be appropriate in selected MBC cases, bringing MBC into alignment with “classical” chronic diseases such as diabetes and hypertension. However, most cases display fundamental differences with regard to temporal progression and above all the case fatality rate. More than 90% of patients in the “chronic disease subgroup” died of the disease with a MDS of 2–3 years (even those who underwent systemic palliative therapies). Doctors and patients might understand the term “chronic disease” differently. The term must be used sparingly and explained carefully in order to create a common level of communication based on a shared understanding which avoids awakening false hopes and fostering misleading expectations.
LZTR1: Genotype Expansion in Noonan Syndrome
Authors: Güemes María , Martín-Rivada Álvaro , Ortiz-Cabrera Neimar Valentina , Martos-Moreno Gabriel Ángel , Pozo-Román Jesús , Argente Jesús
Published: September 2019

Background: LZTR1 participates in RAS protein degradation, hence limiting the RAS/MAPK cascade. Pathogenic mutations in LZTR1 (MIM:600574) have been described in a few patients with Noonan syndrome (NS). Three patients with LZTR1 mutations of different genetic transmission and NS phenotype are herein characterized. Clinical Cases: Case 1 is a 5-year-old boy with NS phenotype. Sanger sequencing of PTPN11 and SOS1 identified no mutations. Whole exome sequencing (WES) detected a heterozygous missense mutation in LZTR1:c.742G>A (p.Gly248Arg) (exon 8, Kelch 4 functional domain). Bioinformatic algorithms predict a deleterious effect of this variant, previously described to cause NS. Case 2 is a 4-year-old boy with NS phenotype. Direct sequencing of 8 genes associated with NS identified no mutations. WES localized a homozygous missense mutation in LZTR1:c.2074T>C (p.Phe692Leu, exon 18). This mutation has not been reported before and is predicted to have a deleterious effect on the protein. Case 3 is an 8-year-old boy who shares NS phenotype with his mother. A multigene panel for RASopathies showed a heterozygous missense variant in LZTR1:c.730T>C (p.Ser244Pro) (exon 8; Kelch 4 functional domain) that was maternally inherited. This variant has not been previously described; however, in silico predictors classify it as deleterious. Familial segregation suggests its pathogenicity. Conclusions: The molecular approach for syndromic phenotypes associated with various genes should involve complete/updated panels or WES rather than gene-by-gene sequencing. RASopathy genetic panels should incorporate LZTR1. Patients with pathogenic mutations in LZTR1 exhibit a characteristic NS gestalt but variable cardiac, height, and neurodevelopment expressions, with recessive inheritance possibly associating with a more severe phenotype.
Food and health: the scientific evidence informing the dietary guidelines for the Brazilian population
Authors:   Universidade Federal de São Paulo, Louzada Maria Laura da Costa , Canella Daniela Silva ,   Universidade de São Paulo. Faculdade de Saúde Pública, Jaime Patrícia Constante ,   Universidade de São Paulo. Faculdade de Saúde Pública, Monteiro Carlos Augusto ,   Universidade de São Paulo. Faculdade de Saúde Pública
Published: September 2019

The Dietary Guidelines for the Brazilian Population is an official document from the Ministry of Health of Brazil that addresses the principles and recommendations of an adequate and healthy diet for the Brazilian population, and is a tool to guide food and nutritional education actions and health programs and policies in the Unified Health System (SUS) and in other sectors. In seeking to make content accessible to the entire population, the Guideline did not, however, set out to provide an exhaustive description of the evidence used in its making, nor to present a long list of references at the end of the document. The purpose of this book is to present the scientific evidence that supported the development of the 2014 Dietary Guidelines for the Brazilian Population.
CREATE a Revolution in Undergraduates' Understanding of Science: Teach through Close Analysis of Scientific Literature
Authors: Hoskins Sally G.
Published: September 2019

The teaching of science to undergraduates aligns poorly with the practice of science, leading many students to conclude that research is boring and researchers themselves are antisocial geniuses. Creativity, a key driver of scientific progress, is underemphasized or ignored altogether in many classrooms, as teaching focuses on the complex integrated concepts and voluminous amounts of information typical of STEM curricula. Faculty, largely untrained in science education per se, teach largely as they were taught, through lectures based in textbooks. This situation could change, and students' understanding of research practice could be fostered relatively easily, if faculty began teaching classes focused on the journal articles they read in their professional lives. In this essay, I outline a novel scaffolded approach to guiding students in a) deciphering the complexities of scientific literature and b) the process of gaining new understanding of who scientists are, what they do, how they do it, and why.
The False Dichotomy between Academic Learning & Occupational Skills
Authors: Bailey Thomas R. , Belfield Clive R.
Published: September 2019

What distinctions are there between vocational (career and technical) education and academic learning in college? In this essay, we compare broad academic and vocational program goals, embodied skills, tasks, and jobs, with a focus primarily on community college students. There is considerable overlap between the two types of education, so a separation of tracks presents a false dichotomy. In addition, vocational certificates, which often have little academic content, have attracted attention lately as a path to good jobs. New evidence indicates that degrees offer more substantial advantages than certificates in the labor market. We argue for an alternative framework for thinking about the optimal accumulation of skills in college. Rejecting the traditional distinction between vocational education and academic learning, we posit that educational paths are best understood as accumulations of general education followed by terminal work-related education. We label this the Gen-Tech framework and consider its explanatory power and implications for colleges and students.
‘Wishing You a Speedy Termination of Existence’
Authors: Djurdjevic Gordan
Published: September 2019

Aleister Crowley was considerably influenced by the doctrines of Theravāda Buddhism, which he studied in his youth, both theoretically and practically. He correlated its principles to the principles of scientific agnosticism and considered that its objectives could also be achieved through the practice of ceremonial magic. His eventual acceptance of Thelema’s religious philosophy led to his ultimate renunciation of Buddhism as a worldview. This essay examines Crowley’s early writings on the subject of Buddhism and suggests that the presence of Buddhist theories remains quite significant in his formulation of the doctrine of Thelema.