bluuebunny/crossref_metadata_2025 huggingface dataset:
Salvage treatment for children with relapsed/refractory germ cell tumors: The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience
Authors: De Pasquale Maria Debora , D'Angelo Paolo , Crocoli Alessandro , Boldrini Renata , Conte Massimo , Bisogno Gianni , Spreafico Filippo , Inserra Alessandro , Biasoni Davide , Dall'Igna Patrizia , Siracusa Fortunato , Miele Evelina , Terenziani Monica
Published: December 2019

Background

Malignant germ cell tumors (GCTs) are a heterogeneous group of rare neoplasms in children. Optimal outcome is achieved with multimodal therapies for patients with both localized and advanced disease, especially after the introduction of platinum‐based chemotherapy regimens. In this respect, data on salvage treatment for children with relapsed or platinum‐refractory disease are still limited.

Methods

Retrospective analysis of data regarding patients affected by malignant GCTs with platinum‐refractory or relapsed disease after first‐line treatment according to AIEOP TCGM 2004 protocol was conducted.

Results

Twenty‐one patients, 15 females and 6 males, were considered for the analysis. All 21 patients received second‐line conventional chemotherapy (SLCT), two of these immediately after surgery for local relapse removal. Two patients showed a progression of disease during SLCT and died of disease shortly thereafter, whereas 19 patients were in partial remission (PR) or complete remission (CR) after SLCT. Treatment after SLCT consisted in surgery on residual tumor mass (9/19) followed by high dose of chemotherapy (HDCT) with autologous hematopoietic stem cell support (16/19). The overall survival (OS) and event‐free survival of the whole populations are 71% and 66.6%, respectively. Platinum‐refractory patients OS is 54.5% compared with 91.5% of the relapsed group. There were no treatment‐related deaths.

Conclusion

SLCT followed or not by HDCT is an effective salvage treatment for children with relapsed/refractory GCTs. However, the role of HDCT following SLCT needs to be further investigated, especially regarding the identification of specific patient subgroups, which can benefit from this more intensive treatment.
Establishment of extraction design space for ursolic acid from Paulowniae Flos based on the concept of quality by design
Authors: Meng Xiaoyan , Liu Donghao , Yang Manli , Shi Yi , He Hua
Published: December 2019

Introduction

The application of quality by design (QbD) concept needs to be strengthened in the field of traditional Chinese medicine research. The extraction process has an important influence on the effectiveness of the drug, and the combination of QbD and the extraction process of the active ingredient helps to improve the effectiveness of the drug.

Objective

To establish the extraction design space for ursolic acid (UA) from Paulowniae Flos based on the concept of QbD.

Methods

The extraction yield of the target component UA was taken as critical quality attributes (CQAs), extraction time, extraction temperature, ethanol concentration and liquid–solid ratio, as critical process parameters (CPPs). Box–Behnken design (BBD) was applied to optimise the design space and the chromatographic conditions were performed on a Shimadzu C18 reversed‐phase column with 0.1% (v/v) acetic acid aqueous water–acetonitrile (7:13, v/v) as the mobile phase at a 1 mL/min flow rate, using UA standard as a control and detection at 210 nm.

Results

The single factor investigation and BBD experiment were used to construct the design space, while verification experiments and methodological validation were used to demonstrate that the space was robust and analytical methods were appropriate. The operating space of ethanol concentration 93–98%, liquid–solid ratio 28–37 mL/g and extraction temperature 70–78.3°C was recommended.

Conclusion

The proposed methodology can help to promote the quality control of the Chinese medicine extraction process and facilitate the production operation of the enterprise easier.
A review on the recent advances in HPLC, UHPLC and UPLC analyses of naturally occurring cannabinoids (2010–2019)
Authors: Nahar Lutfun , Onder Alev , Sarker Satyajit D.
Published: December 2019

Introduction

Organic molecules that bind to cannabinoid receptors are called cannabinoids, and they have similar pharmacological properties like the plant, Cannabis sativa L. Hyphenated liquid chromatography (LC), incorporating high‐performance liquid chromatography (HPLC) and ultra‐performance liquid chromatography (UPLC, also known as ultrahigh‐performance liquid chromatography, UHPLC), usually coupled to an ultraviolet (UV), UV‐photodiode array (PDA) or mass spectrometry (MS) detector, has become a popular analytical tool for the analysis of naturally occurring cannabinoids in various matrices.

Objective

To review literature on the use of various LC‐based analytical methods for the analysis of naturally occurring cannabinoids published since 2010.

Methodology

A comprehensive literature search was performed utilising several databases, like Web of Knowledge, PubMed and Google Scholar, and other relevant published materials including published books. The keywords used, in various combinations, with cannabinoids being present in all combinations, in the search were Cannabis, hemp, cannabinoids, Cannabis sativa, marijuana, analysis, HPLC, UHPLC, UPLC, quantitative, qualitative and quality control.

Results

Since 2010, several LC methods for the analysis of naturally occurring cannabinoids have been reported. While simple HPLC‐UV or HPLC‐UV‐PDA‐based methods were common in cannabinoids analysis, HPLC‐MS, HPLC‐MS/MS, UPLC (or UHPLC)‐UV‐PDA, UPLC (or UHPLC)‐MS and UPLC (or UHPLC)‐MS/MS, were also used frequently. Applications of mathematical and computational models for optimisation of different protocols were observed, and pre‐analyses included various environmentally friendly extraction protocols.

Conclusions

LC‐based analysis of naturally occurring cannabinoids has dominated the cannabinoids analysis during the last 10 years, and UPLC and UHPLC methods have been shown to be superior to conventional HPLC methods.
Effects of Sintering Method and BiAlO3 Dopant on Dielectric Relaxation and Energy Storage Properties of BaTiO3–BiYbO3 Ceramics
Authors: Yi Xin , Ji Cong , Chen Gang , Yang Hongqi , Yong Hualei , Fu Chunlin , Cai Wei , Gao Rongli , Fan Tao , Wang Zhenhua , Deng Xiaoling
Published: December 2019

(0.9 – x)BaTiO3–0.1BiYbO3–xBiAlO3 (x = 0, 0.02, 0.04, and 0.08) lead‐free ferroelectric ceramics are synthesized using conventional sintering (CS) and microwave sintering (MWS) methods. The microstructure, dielectric and ferroelectric properties, relaxation behavior, and energy storage properties are investigated systematically. X‐ray diffraction (XRD) patterns show a single perovskite phase for all samples. Scanning electron microscope (SEM) images indicate that MWS method can impede the grain growth, whereas the introduction of BiAlO3 can lead to the increase in the grain size. Dielectric measurements reveal that an obvious dielectric relaxation behavior can be strengthened by MWS, and the improvement of the dielectric constant (εr) of ceramics is realized by MWS. Incorporated with BiAlO3 contributes to enhancement of the frequency and temperature stabilities of the dielectric constant for BaTiO3–BiYbO3 ceramics. The slim hysteresis loops are observed, and the maximum polarization of the sample sintered by MWS is higher than that sintered by CS. The MWS samples possess a higher energy density which is about 2 times larger than that of CS samples, and the largest energy storage density ≈0.86 J cm−3 and energy storage efficiency ≈97.44% are, respectively, obtained at x = 0 and 0.04 for MWS ceramics.
A Novel Optical Method for Nondestructive Determination of Binary Diffusion Coefficients in Metal Nanoalloy Films
Authors: Pashaki Elahe Rastegar , Falamaki Cavus
Published: December 2019

A new optical method for the indirect determination of binary diffusion coefficients of metals in binary nanoalloys is presented. Beginning with an initial nano‐bilayer of two pure metals, the method is based on the measurement of the visible‐light surface plasmon resonance (SPR) characteristic of the final alloy nanolayer as a function of the diffusion process that occurred due to heat treatment at a constant temperature for a definite time. The theory behind is described and an algorithm is developed that takes the initial thickness of the deposited metal layers and the measured SPR angle of the final sample as input and accordingly calculates the binary diffusion coefficient. The proposed algorithm has been coded in the MATLAB simulator and applied to a fabricated initial Au–Ag bi‐nanolayer (Au thickness 23 nm and Ag thickness 15 nm) which is subjected to a specific heat‐treatment process (1 h at 100 °C). The binary diffusion coefficient is estimated as 6.94 × 10−17 cm2 s−1, in agreement with reported values for thin films. The novel method is nondestructive, simple, fast, and highly sensitive to changes of concentration profiles throughout multilayers, a few tens of nanometer that exhibit the SPR phenomenon.
A Study of Temperature‐Dependent Photoluminescence from As‐Deposited and Heavy‐Ion‐Irradiated Plasma‐Enhanced Chemical Vapor Deposition‐Grown Si‐Rich a‐SiNx:H Thin Films
Authors: Gupta Harsh , Plantevin Olivier , Bommali Ravi K. , Ghosh Santanu , Srivastava Pankaj
Published: December 2019

Temperature‐dependent photoluminescence (PL) measurements in the range of 10–300 K are carried out on silicon‐rich hydrogenated silicon nitride films deposited by plasma‐enhanced chemical vapor deposition. The in situ formation of Si quantum dots (QDs) with an average size of 3.5 nm is observed. The composition of thin films is estimated by Rutherford backscattering and ellipsometry. Broad PL spectra from thin films are decomposed into contributions from Si QDs, N dangling bonds (DBs), and Si DBs (K‐centers). At a low temperature, a strong PL can be observed, its quenching with increase in temperature is explained by the thermal activation of nonradiative decay mechanisms. Further, temperature‐dependent PL for swift heavy‐ion‐irradiated films shows similar quenching with increase in temperature. However, the effect of irradiation on the luminescence mechanisms of a‐SiNx:H is revealed at low temperatures (<120 K) only, whereby a relatively narrow peak around 2.0 eV emerges. These results clearly show the role of radiative defects in the luminescence from Si‐rich silicon nitride.
Electronic Properties of Defective MoS2 Monolayers Subject to Mechanical Deformations: A First‐Principles Approach
Authors: Bahmani Mohammad , Faghihnasiri Mahdi , Lorke Michael , Kuc Agnieszka-Beata , Frauenheim Thomas
Published: December 2019

Monolayers (MLs) of group‐6 transition‐metal dichalcogenides (TMDs) are semiconducting 2D materials with direct bandgap, showing promising applications in various fields of science and technology, such as nanoelectronics and optoelectronics. These MLs can undergo strong elastic deformations, up to about 10%, without any bond breaking. Moreover, the electronic structure and transport properties, which define the performance of these TMD MLs in nanoelectronic devices, can be strongly affected by the presence of point defects, which are often present in the synthetic samples. Thus, it is important to understand both effects on the electronic properties of such MLs. Herein, the electronic structure and energetic properties of defective MoS2 MLs are investigated as subject to various strains, using density functional theory simulations. The results indicate that strain leads to strong modifications of the defect levels inside the bandgap and their orbital characteristics. Strain also splits the degenerate defect levels up to an amount of 450 meV, proposing novel applications.
Re‐establishment of fish passage for conserving threatened migratory species of West‐Indian Himalayas
Authors: Raut Shailendra , Gupta Nishikant , Nautiyal Prakash , Everard Mark
Published: December 2019

Fish passes are structures (natural or manmade) bypassing barriers (e.g., dams), enabling satisfactory movement of migratory fish species. Reestablishment of fish passage, including facilitating overcoming barriers presented by impoundments or restoration of defunct structures, is attracting interest among scientists and policymakers as a mechanism to enable recovery of target fish species or fish communities. However, it is also important to note that fish passes may also act as ecological traps in some large neotropical rivers. A diversity of multispecies fish passage designs have been implemented in North and South America, Europe, and Australia, with varying efficacy for different species. However, field surveys between 2010 and 2018 supported by a review of published literature (N = 217) using Google Scholar search engine using six key terms reveal that few fish passes have been constructed in dams in the Indian Himalayan region, and their efficacy is largely unproven. Major problems associated with fish pass designs include uneven success across a range of species and largely untested effectiveness at the large scale of many major dams. The objective of this paper is to stress upon the requirement of a new approach to understand the operational drawbacks of different types of fish pass and to take an adaptive approach to both design and operation using field data to improve fish pass efficiency. These measures could contribute significantly to the conservation of threatened migratory fish in the increasingly impounded rivers of the Indian Himalayan region.
N‐Directed Pd‐Catalyzed Direct ortho‐Acetoxylation and ortho‐tert‐Butoxylation of 2‐Phenyl‐4H‐benzo[d][1,3]oxazin‐4‐ones via C‐H Activation
Authors: Gupta Mohit , Kumar Sandeep , Kumar Prashant , Kumar Singh Amit , Bahadur Vijay , K. Singh Brajendra
Published: December 2019

A highly efficient, palladium‐catalyzed protocol for the regioselective ortho‐acyloxylation of 4H‐Benzo[d][1,3]oxazin‐4‐ones and various other heterocycles which includes indoline, 3,4‐dihydro‐2H‐benzo[b][1,4]oxazine, and 1‐methyl‐3‐phenylquinoxalin‐2(1H)‐one has been developed using C−H activation strategy. The protocol exploits the directing group property of nitrogen present in the heterocyclic framework to introduce the acyloxyl group onto heterocyclic compounds with excellent regioselectivity. The developed method offers a wide substrate and excellent functional group tolerance.
On the Amazing Reactivity of the Ranelate Ion: New Applications of an Old Antiosporotic Drug
Authors: Rocha Julio C. , Sihn Luca M. , Uchiyama Mayara K. , Ribeiro Marcos A. , Franco Maurício P. , Braga Ataualpa A. C. , Silveira Alceu T. , Toma Henrique E.
Published: December 2019

Ranelate ion, the major component of an old antiosporotic drug, exhibits a unusual chemical structure encompassing a thiophene ring with two carboxylic groups, a cyanonitrile substituent, and a nitrile diacetate group; it undergoes decarboxylation at the thiophene carbon‐5 position in acidic solutions, yielding a photoreactive (H5Ran) species which converts into a remarkably stable blue dithiophene dye in the presence of UV light and air.
Chiromagnetic Plasmonic Nanoassemblies with Magnetic Field Modulated Chiral Activity
Authors: Wu Xiaoling , Hao Changlong , Xu Liguang , Kuang Hua , Xu Chuanlai
Published: December 2019

Chiral plasmonic nanoassemblies, which exhibit outstanding chiroptical activity in the visible or near‐infrared region, are popular candidates in molecular sensing, polarized nanophotonics, and biomedical applications. Their optical chirality can be modulated by manipulating chemical molecule stimuli or replacing the building blocks. However, instead of irreversible chemical or material changes, real‐time control of optical activity is desired for reversible and noninvasive physical regulating methods, which is a challenging research field. Here, the directionally and reversibly switching optical chirality of magneto‐plasmonic nanoassemblies is demonstrated by the application of an external magnetic field. The gold‐magnetic nanoparticles core–satellite (Au@Fe3O4) nanostructures exhibit chiral activity in the UV–visible range, and the circular dichroism signal is 12 times greater under the magnetic field. Significantly, the chiral signal can be reversed by regulating the direction of the applied magnetic field. The attained magnetic field‐regulated chirality is attributed to the large contributions of the magnetic dipole moments to polarization rotation. This magnetic field‐modulated optical activity may be pivotal for photonic devices, information communication, as well as chiral metamaterials.
SEWMS: An edge‐based smart wearable maintenance system in communication network
Authors: Rui Lanlan , Qin Yabin , Li Biyao , Wang Ying , Huang Haoqiu
Published: December 2019

The development of the Internet of Things (IoT) and wearable technology provides an opportunity for the development of maintenance of communication. The use of wearable technology and instant messaging technology of IoT can improve the support capabilities and data interaction ability of on‐site maintenance of the communication network. Existing communication maintenance systems lack real‐time operation and maintenance of data interaction. In the field operation decision‐making and execution process, there are problems of lack of field links and inconvenient information interaction. On‐site maintenance mainly relies on maintenance personnel to actively search for information, and the retrieval results are lacking of personalization, which makes it difficult to meet the needs of on‐site maintenance of the communication network. Edge computing and information push technology can solve these problems to some extent. In this paper, we focus on the current low level in information, complicated scenes, and various information of on‐site maintenance and propose a dynamic context‐aware information push algorithm. The simulation results demonstrate that the algorithm delivers good performance in terms of precision, recall, and F1. Besides, we present a smart wearable maintenance system, an edge computing–assisted IoT platform for the real‐time guidance of technical experts and systems for on‐site maintenance personnel, aiming to improve the efficiency and quality of on‐site maintenance.
Re‐evaluating composite scores: Adaptive Lasso variable selection for non‐linear models
Authors: Kravitz Eli S. , Carroll Raymond J.
Published: December 2019

In nutrition, epidemiology, and other public health fields, composite scores are a common tool used to assess a health behaviour. These composite scores compare an individual's health behaviour to an idealized standard and provide a number, often between 0 and 100, to indicate their compliance to a health behaviour. Crucially, this measure of health behaviour is applied across populations (gender, smoking status, etc.) and health outcomes (colon cancer, breast cancer, etc.) to create a single interpretable score. One such composite score is the 2005 Healthy Eating Index that breaks diet into 12 components and evaluates nutritional intake by adherence to these components. We provide a general method that can be used to reassess the importance of these 12 components using flexible non‐linear models, across populations and diseases, based on an asymptotic least squares approximation. We establish oracle properties of this variable selection technique in our context, which is different from the usual one population and one disease context. Although our methods are motivated by the Healthy Eating Index, they are broad enough to be applied to any composite score and a broad range of non‐linear models.
A note on cyclic shift permutation testing for large eigenvalues
Authors: Zhou Yi‐Hui
Published: December 2019

Recent publications have described the problem of testing for the “significance” of large sample (empirical) matrix eigenvalues in the presence of modest variation of underlying true eigenvalues. This modest variation often can be ascribed to endemic dependence in one matrix dimension (e.g., rows), whereas the null hypothesis concerns the other dimension (columns). The need for such testing frequently arises in genomics, time‐series analysis, and a variety of other fields. However, the tools available for testing are underdeveloped, with statistical properties that may be sensitive to the true eigenvalues. The purpose of this note is to point the reader to this emerging literature and to suggest that the tool of cyclic shift permutation may be well‐suited to the problem.
Salivary neoplasia in dogs and cats: 1996–2017
Authors: Cray Megan , Selmic Laura E. , Ruple Audrey
Published: December 2019

Objective

The objectives of this study were to report the contemporary demographical information, provide the incidence of and to assess sex and breed predisposition of salivary gland neoplasia in dogs and cats.

Materials and Methods

Information was collected from cats or dogs with salivary neoplasia (cases) and controls from the 26 university veterinary teaching hospitals within the Veterinary Medical Data Base. A total of 56 dogs and 24 cats were identified as having been diagnosed with salivary neoplasia.

Results

The incidence of salivary neoplasia in this population was calculated to be 15.3 per 100,000 dogs and 26.3 per 100,000 cats. The specific anatomic location of the salivary neoplasia was unable to be determined in 90.8% of cases in both dogs and cats. Results of the univariable conditional logistic regression models revealed no increased risk of salivary neoplasia in dogs or cats of any sex or neuter status (dogs:p = .26; cats:p = .45). There was no breed disposition within the feline species for salivary neoplasia. However, in the conditional logistic regression for dogs, poodles (toy and standard) trended towards significance (p = .075) with an odds ratio of 6.83 (95% CI: 1.16–40.10) compared to mixed breeds.

Conclusions and clinical relevance

The present study's results differ from previous conclusions made in regards to predisposed breeds and tumour location. Additional epidemiological studies should be performed to help in determining risk factors for salivary gland neoplasia.
PIXE data analysis by two‐dimensional correlation mapping techniques: Analysis of chloride and sulfate ions attack in homemade mortar samples
Authors: Al Lafi Abdul G. , Rihawy Mohamed Salah
Published: December 2019

Chloride and sulfate ions ingress behaviors in concrete are more complex and complicated processes than can be described by Fick's law of diffusion. A new approach based on two‐dimensional correlation mapping (2D‐CM) and particle‐induced X‐ray emission (PIXE) spectra was successfully applied to describe their transportation process. The use of hybrid 2D correlation enabled a fast comparison of ions ingress, whereas multiple perturbation correlation spectroscopy enabled the study of compositional factor affecting the ingress process. It was shown that by rearranging the same data in different ways, different techniques of 2D‐CM could be applied and new information could be derived. The 2D‐CM findings were in line with the classical PIXE analysis and consistent with the underlying physics of the experiments, which suggested that it will be a powerful and fast data analysis tool for PIXE spectra.
Superluminal chaos after a quantum quench
Authors: Balasubramanian Vijay , Craps Ben , De Clerck Marine , Nguyen Kévin
Published: December 2019

Abstract

Thermal states holographically dual to black holes in Einstein gravity display maximal Lyapunov growth as well as “butterfly effect cones”. We study these effects in highly non-equilibrium states, obtained from an initial thermal state by the sudden injection of energy. We do this by computing out-of-time-order correlators (OTOCs) in BTZ-Vaidya spacetimes, which describe transitions between black holes at different temperatures. If both pairs of boundary operators appearing in the OTOC are inserted before the energy injection, we recover standard results, with butterfly effect cones displaying a light-cone structure. But when one pair of operators is inserted before and the other pair after the energy injection, the Lyapunov growth saturates the chaos bounds set by the local temperatures and the butterfly effect cones can “open up”, becoming superluminal, albeit in a way that does not violate causality. In the limiting case, in which the initial state is the vacuum, Lyapunov growth only starts after the energy injection. Our computations of the OTOCs are phrased in terms of gravitationally interacting particles, where fields are treated in a geodesic approximation and the eikonal phase shift is expressed in terms of stress tensors and shock waves associated to geodesics.
Dmc1 is a candidate for temperature tolerance during wheat meiosis
Authors: Draeger Tracie , C. Martin Azahara , Alabdullah Abdul Kader , Pendle Ali , Rey María-Dolores , Shaw Peter , Moore Graham
Published: December 2019

Key message

The meiotic recombination geneDmc1on wheat chromosome 5D has been identified as a candidate for the maintenance of normal chromosome synapsis and crossover at low and possibly high temperatures.

We initially assessed the effects of low temperature on meiotic chromosome synapsis and crossover formation in the hexaploid wheat (Triticum aestivumL.) variety ‘Chinese Spring’. At low temperatures, asynapsis and chromosome univalence have been observed before in Chinese Spring lines lacking the long arm of chromosome 5D (5DL), which led to the proposal that 5DL carries a gene (Ltp1) that stabilises wheat chromosome pairing at low temperatures. In the current study, Chinese Spring wild type and 5DL interstitial deletion mutant plants were exposed to low temperature in a controlled environment room during a period from premeiotic interphase to early meiosis I. A 5DL deletion mutant was identified whose meiotic chromosomes exhibit extremely high levels of asynapsis and chromosome univalence at metaphase I after 7 days at 13 °C, suggesting thatLtp1is deleted in this mutant. Immunolocalisation of the meiotic proteins ASY1 and ZYP1 onltp1mutants showed that low temperature results in a failure to complete synapsis at pachytene. KASP genotyping revealed that theltp1mutant has a 4-Mb deletion in 5DL. Of 41 genes within this deletion region, the strongest candidate for the stabilisation of chromosome pairing at low temperatures is the meiotic recombination geneDmc1.Theltp1mutants were subsequently treated at 30 °C for 24 h during meiosis and exhibited a reduced number of crossovers and increased univalence, though to a lesser extent than at 13 °C. We therefore renamed ourltp1mutant ‘ttmei1’ (temperature-tolerantmeiosis1) to reflect this additional loss of high temperature tolerance.
Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers
Authors: Family Neiloufar , Maillet Emeline L. , Williams Luke T. J. , Krediet Erwin , Carhart-Harris Robin L. , Williams Tim M. , Nichols Charles D. , Goble Daniel J. , Raz Shlomi
Published: December 2019

Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT2A receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease.

Objective

This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally repeated administration of 5 μg, 10 μg, and 20 μg LSD in older healthy individuals. In the current paper, we present safety, tolerability, pharmacokinetics, and pharmacodynamic measures that relate to safety, tolerability, and dose response.

Methods

This was a phase 1 double-blind, placebo-controlled, randomized study. Volunteers were randomly assigned to 1 of 4 dose groups (5 μg, 10 μg, 20 μg LSD, and placebo), and received their assigned dose on six occasions (i.e., every 4 days).

Results

Forty-eight older healthy volunteers (mean age = 62.9 years) received placebo (n = 12), 5 μg (n = 12), 10 μg (n = 12), or 20 μg (n = 12) LSD. LSD plasma levels were undetectable for the 5 μg group and peak blood plasma levels for the 10 μg and 20 μg groups occurred at 30 min. LSD was well tolerated, and the frequency of adverse events was no higher than for placebo. Assessments of cognition, balance, and proprioception revealed no impairment.

Conclusions

Our results suggest safety and tolerability of orally administered 5 μg, 10 μg, and 20 μg LSD every fourth day over a 21-day period and support further clinical development of LSD for the treatment and prevention of Alzheimer’s disease (AD).
Inotersen preserves or improves quality of life in hereditary transthyretin amyloidosis
Authors: Coelho Teresa , Yarlas Aaron , Waddington-Cruz Marcia , White Michelle K. , Sikora Kessler Asia , Lovley Andrew , Pollock Michael , Guthrie Spencer , Ackermann Elizabeth J. , Hughes Steven G. , Karam Chafic , Khella Sami , Gertz Morie , Merlini Giampaolo , Obici Laura , Schmidt Hartmut H. , Polydefkis Michael , Dyck P. James B. , Brannagan III Thomas H. , Conceição Isabel , Benson Merrill D. , Berk John L.
Published: December 2019

Objective

To examine the impact on quality of life (QOL) of patients with hATTR amyloidosis with polyneuropathy treated with inotersen (Tegsedi™) versus placebo.

Methods

Data were from the NEURO-TTR trial (ClinicalTrials.gov Identifier: NCT01737398), a phase 3, multinational, randomized, double-blind, placebo-controlled study of inotersen in patients with hATTR amyloidosis with polyneuropathy. At baseline and week 66, QOL measures—the Norfolk-QOL-Diabetic Neuropathy (DN) questionnaire and SF-36v2® Health Survey (SF-36v2)—were assessed. Treatment differences in mean changes in QOL from baseline to week 66 were tested using mixed-effect models with repeated measures. Responder analyses compared the percentages of patients whose QOL meaningfully improved or worsened from baseline to week 66 in inotersen and placebo arms. Descriptive analysis of item responses examined treatment differences in specific activities and functions at week 66.

Results

Statistically significant mean differences between treatment arms were observed for three of five Norfolk-QOL-DN domains and five of eight SF-36v2 domains, with better outcomes for inotersen than placebo in physical functioning, activities of daily living, neuropathic symptoms, pain, role limitations due to health problems, and social functioning. A larger percentage of patients in the inotersen arm than the placebo arm showed preservation or improvement in Norfolk-QOL-DN and SF-36v2 scores from baseline to week 66. Responses at week 66 showed more substantial problems with daily activities and functioning for patients in the placebo arm than in the inotersen arm.

Conclusion

Patients with hATTR amyloidosis with polyneuropathy treated with inotersen showed preserved or improved QOL at 66 weeks compared to those who received placebo.
Design and tailoring of an artificial DNA scaffolding system for efficient lycopene synthesis using zinc-finger-guided assembly
Authors: Xu Xian , Tian Liqing , Tang Susu , Xie Chengjia , Xu Jiali , Jiang Ling
Published: December 2019

A highly efficient lycopene production system was constructed by assembling enzymes fused to zinc-finger motifs on DNA scaffolds in vitro and in vivo. Three key enzymes of the lycopene synthesis pathway, geranylgeranyl diphosphate synthase, phytoene synthase, and phytoene desaturase, were fused with zinc-finger proteins, expressed and purified. Recombinant plasmids of the pS series containing DNA scaffolds that the zinc-finger proteins can specifically bind to were constructed. In the in vitro system, the production efficiency of lycopene was improved greatly after the addition of the scaffold plasmid pS231. Subsequently, the plasmid pET-AEBI was constructed and introduced into recombinant Escherichia coli BL21 (DE3) for expression, together with plasmids of the pS series. The lycopene production rate and content of the recombinant strain pp231 were higher than that of all strains carrying the DNA scaffold and the control. With the addition of cofactors and substrates in the lycopene biosynthesis pathway, the lycopene yield of pp231 reached 632.49 mg/L at 40 h, representing a 4.7-fold increase compared to the original recombinant strain pA1A3. This DNA scaffold system can be used as a platform for the construction and production of many biochemicals synthesized via multi-enzyme cascade reactions.
Genomics-driven discovery of the biosynthetic gene cluster of maduramicin and its overproduction in Actinomadura sp. J1-007
Authors: Liu Ran , Fang Fang , An Ziheng , Huang Renqiong , Wang Yong , Sun Xiao , Fu Shuai , Fu Aisi , Deng Zixin , Liu Tiangang
Published: December 2019

Maduramicin is the most efficient and possesses the largest market share of all anti-coccidiosis polyether antibiotics (ionophore); however, its biosynthetic gene cluster (BGC) has yet to been identified, and the associated strains have not been genetically engineered. Herein, we performed whole-genome sequencing of a maduramicin-producing industrial strain of Actinomadura sp. J1-007 and identified its BGC. Additionally, we analyzed the identified BGCs in silico to predict the biosynthetic pathway of maduramicin. We then developed a conjugation method for the non-spore-forming Actinomadura sp. J1-007, consisting of a site-specific integration method for gene overexpression. The maduramicin titer increased by 30% to 7.16 g/L in shake-flask fermentation following overexpression of type II thioesterase MadTE that is the highest titer at present. Our findings provide insights into the biosynthetic mechanism of polyethers and provide a platform for the metabolic engineering of maduramicin-producing microorganisms for overproduction and development of maduramicin analogs in the future.
The Gray Monoidal Product of Double Categories
Authors: Böhm Gabriella
Published: December 2019

The category of double categories and double functors is equipped with a symmetric closed monoidal structure. For any double category $${\mathbb {A}}$$A, the corresponding internal hom functor "Equation missing" sends a double category $${\mathbb {B}}$$B to the double category whose 0-cells are the double functors $${\mathbb {A}} \rightarrow {\mathbb {B}}$$A→B, whose horizontal and vertical 1-cells are the horizontal and vertical pseudo transformations, respectively, and whose 2-cells are the modifications. Some well-known functors of practical significance are checked to be compatible with this monoidal structure.
Positive Psychology of Malaysian University Students: Impacts of Engagement, Motivation, Self-Compassion, and Well-being on Mental Health
Authors: Kotera Yasuhiro , Ting Su-Hie
Published: December 2019

Malaysia plays a key role in education of the Asia Pacific, expanding its scholarly output rapidly. However, mental health of Malaysian students is challenging, and their help-seeking is low because of stigma. This study explored the relationships between mental health and positive psychological constructs (academic engagement, motivation, self-compassion, and well-being), and evaluated the relative contribution of each positive psychological construct to mental health in Malaysian students. An opportunity sample of 153 students completed the measures regarding these constructs. Correlation, regression, and mediation analyses were conducted. Engagement, amotivation, self-compassion, and well-being were associated with, and predicted large variance in mental health. Self-compassion was the strongest independent predictor of mental health among all the positive psychological constructs. Findings can imply the strong links between mental health and positive psychology, especially self-compassion. Moreover, intervention studies to examine the effects of self-compassion training on mental health of Malaysian students appear to be warranted.
Focused Audification and the optimization of its parameters
Authors: Groß-Vogt Katharina , Frank Matthias , Höldrich Robert
Published: December 2019

We present a sonification method which we call Focused Audification (FA; previously: Augmented Audification) that allows to expand pure audification in a flexible way. It is based on a combination of single-side-band modulation and a pitch modulation of the original data stream. Based on two free parameters, the sonification’s frequency range is adjustable to the human hearing range and allows to interactively zoom into the data set at any scale. The parameters have been adjusted in a multimodal experiment on cardiac data by laypeople. Following from these results we suggest a procedure for parameter optimization to achieve an optimal listening range for any data set, adjusted to human speech.
Biomarker Application for Precision Medicine in Stroke
Authors: Simpkins Alexis N. , Janowski Miroslaw , Oz Helieh S. , Roberts Jill , Bix Gregory , Doré Sylvain , Stowe Ann M.
Published: December 2019

Stroke remains one of the leading causes of long-term disability and mortality despite recent advances in acute thrombolytic therapies. In fact, the global lifetime risk of stroke in adults over the age of 25 is approximately 25%, with 24.9 million cases of ischemic stroke and 18.7 million cases of hemorrhagic stroke reported in 2015. One of the main challenges in developing effective new acute therapeutics and enhanced long-term interventions for stroke recovery is the heterogeneity of stroke, including etiology, comorbidities, and lifestyle factors that uniquely affect each individual stroke survivor. In this comprehensive review, we propose that future biomarker studies can be designed to support precision medicine therapeutic interventions after stroke. The current challenges in defining ideal biomarkers for stroke are highlighted, including consideration of disease course, age, lifestyle factors, and subtypes of stroke. This overview of current clinical trials includes biomarker collection, and concludes with an example of biomarker design for aneurysmal subarachnoid hemorrhage. With the advent of “-omics” studies, neuroimaging, big data, and precision medicine, well-designed stroke biomarker trials will greatly advance the treatment of a disease that affects millions globally every year.
Screening for personality disorders in geriatric medicine outpatients
Authors: Meuwissen-van Pol E. C. H. , Rossi G. , de Weerd-Spaetgens C. M. E. E. , van Alphen S. P. J.
Published: December 2019

Purpose

Personality disorder (PD) assessment in older adults is challenging. In geriatric medicine, older adults with multi-morbidity are treated for their somatic, psychogeriatric, functional and social complaints and the presence of a PD can be a complicating factor in this treatment. Therefore, this study evaluates the diagnostic accuracy of a PD screening instrument, the Gerontological Personality disorder Scale (GPS) in a Dutch geriatric medicine population.

Methods

Using an informant-based personality questionnaire (HAP) as a reference criterion, the psychometric properties of the GPS-informant version were assessed in a sample of N = 160 (62 male) outpatients (mean age = 81.7).

Results

The internal consistency of the GPS (total score), Cronbach’s alpha, was α = 0.69. And the average inter-item correlation (total score) was 0.14. The test–retest reliability was rs = 0.68. The sensitivity and specificity for the GPS were 0.91 and 0.67, respectively. The GPS items showed predictive validity for PD status with 87.4% of predictions being accurate based on a logistic regression analysis.

Conclusions

This is the first psychometric study to use the GPS as an age-specific screening instrument for PDs in Dutch geriatric medicine outpatients. The GPS is an adequate screening tool for PDs in geriatric medicine, given the high sensitivity. The diagnostic accuracy of the GPS-informant version is fair to excellent.
Differences in self‐reported character strengths across adolescence
Authors: Brown Mitch , Blanchard Tamar , McGrath Robert E.
Published: December 2019

Introduction

Although typically considered a stable trait, character strengths may be subject to temporal changes. Whereas research has investigated these changes across adulthood, the pivotal period of adolescence remains relatively understudied.

Method

To identify potential developmental differences in character strengths, we conducted a cross‐sectional exploratory analysis of 24 Character strengths, assessed by the VIA‐Youth, across youth between ages 10 and 17 from four highly represented countries (N = 12,871).

Results

The general pattern was for older adolescents to generate lower scores in many traits compared to younger adolescents. When considering gender as a potential moderator, girls, on average, scored higher on most strengths, but also showed more consistently lower scores across ages.

Conclusion

Findings provide a nuanced understanding of developmental differences in character across adolescence in a large‐scale study. We frame these findings in the context of recent work investigating how character strengths develop throughout adolescence and offer suggestions for future research and interventions.
Interpretations of sustainability beyond the middle class
Authors: Beasy Kim
Published: December 2019

Critical discourses of sustainability challenge modern rhetoric of economic growth and challenge current modes of social development. Yet sustainability discourses are shaped predominantly by the perspectives and interests of middle-class, tertiary-educated urban policy makers or environmentalists, and have insufficiently engaged people beyond these cohorts, even in the advanced capitalist societies where they have originated. This article shares findings from a study that investigated how people who are not strongly engaged with sustainability discourses understand and engage with many of the underlying concerns that animate these discourses from the context of their situated, everyday experiences. This is important information for sustainability educators, because it challenges dominant ideas of what sustainabilityisand offers new and alternate ways of engaging different groups of people in actions for sustainability. Bourdieu’s concepts of habitus, field and capital were used to inform the research design that employed focus groups and interviews with people from a range of socio-economic and cultural backgrounds and life stages in Tasmania, Australia. The findings provide insight into the ways in which people who are disengaged from discourses of sustainability may be actively engaged in practices of sustainability that may provide practical guidance for environmentalists and policy makers concerning how current discourses of sustainability reflect specific social contexts and experiences.
Wet subglacial bedforms of the NE Greenland Ice Stream shear margins
Authors: Riverman Kiya L. , Anandakrishnan Sridhar , Alley Richard B. , Holschuh Nicholas , Dow Christine F. , Muto Atsuhiro , Parizek Byron R. , Christianson Knut , Peters Leo E.
Published: December 2019

We describe elongate, wet, subglacial bedforms in the shear margins of the NE Greenland Ice Stream and place some constraints on their formation. Lateral shear margin moraines have been observed across the previously glaciated landscape, but little is known about the ice-flow conditions necessary to form these bedforms. Here we describe in situ sediment bedforms under the NE Greenland Ice Stream shear margins that are observed in active-source seismic and ground-penetrating radar surveys. We find bedforms in the shear margins that are ~500 m wide, ~50 m tall, and elongated nearly parallel to ice-flow, including what we believe to be the first subglacial observation of a shear margin moraine. Acoustic impedance analysis of the bedforms shows that they are composed of unconsolidated, deformable, water-saturated till. We use these geophysical observations to place constraints on the possible formation mechanism of these subglacial features.
The nutritional content of children’s breakfast cereals: a cross-sectional analysis of New Zealand, Australia, the UK, Canada and the USA
Authors: Chepulis Lynne , Everson Nadine , Ndanuko Rhoda , Mearns Gael
Published: December 2019

Objective:

To compare the Nutrition Information Panel (NIP) content, serving size and package size of children’s ready-to-eat breakfast cereals (RTEC) available in five different Western countries.

Design:

NIP label information was collected from RTEC available for purchase in major supermarket chains. Kruskal–Wallis, Mann–WhitneyUandχ2tests were applied to detect differences between countries on manufacturer-declared serving size, total energy (kJ), total protein, fat, saturated fat, carbohydrate, total sugar, Na and fibre content. The Nutrient Profiling Scoring Criterion (NPSC) was used to evaluate the number of products deemed to be ‘unhealthy’.

Setting:

Supermarkets in Australia, Canada, New Zealand, the UK and the USA.

Participants:

Children’s breakfast cereals (n636), including those with and without promotional characters.

Results:

The majority of children’s RTEC contained substantial levels of total sugar and differences were apparent between countries. Median sugar content per serving was higher in US cereals than all other countries (10·0v. 7·7–9·1 g;P< 0·0001). Median fat and saturated fat content were lowest in Australia and New Zealand RTEC, while the Na content of RTEC was 60–120 % higher in the USA and Canada than in Australia and the UK (allP≤ 0·01).

Conclusions:

Across all countries, there was a high proportion of RTEC marketed for children that had an unhealthy nutrient profile. Strategies and policies are needed to improve the nutrient value of RTEC for children, so they provide a breakfast food that meets nutrition guidelines.
A review of traditional and machine learning methods applied to animal breeding
Authors: Nayeri Shadi , Sargolzaei Mehdi , Tulpan Dan
Published: December 2019

The current livestock management landscape is transitioning to a high-throughput digital era where large amounts of information captured by systems of electro-optical, acoustical, mechanical, and biosensors is stored and analyzed on a daily and hourly basis, and actionable decisions are made based on quantitative and qualitative analytic results. While traditional animal breeding prediction methods have been used with great success until recently, the deluge of information starts to create a computational and storage bottleneck that could lead to negative long-term impacts on herd management strategies if not handled properly. A plethora of machine learning approaches, successfully used in various industrial and scientific applications, made their way in the mainstream approaches for livestock breeding techniques, and current results show that such methods have the potential to match or surpass the traditional approaches, while most of the time they are more scalable from a computational and storage perspective. This article provides a succinct view on what traditional and novel prediction methods are currently used in the livestock breeding field, how successful they are, and how the future of the field looks in the new digital agriculture era.