bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased CSF clearance and increased brain amyloid in Alzheimer’s disease
Authors: li yi , Rusinek Henry , Butler Tracy , Glodzik Lidia , Pirraglia Elizabeth , Babich John , Mozley P. David , Nehmeh Sadek , Pahlajani Silky , Wang Xiuyuan , Tanzi Emily B. , Zhou Liangdong , Strauss Sara , Carare Roxana , Theise Neil , Okamura Nobuyuki , de Leon Mony J. 
Published: September 2021

Abstract
In sporadic Alzheimer’s disease (AD), brain amyloid-beta (Aβ) deposition is believed to be a consequence of impaired Aβ clearance, but this relationship is not well established in living human subjects. CSF clearance, a major feature of brain glymphatic clearance (BGC), has been shown to be abnormal in AD murine models. Prior MRI phase contrast studies have reported reduced aqueductal CSF flow in AD. Using PET and tau tracer 18F-THK5117, we previously reported that the ventricular CSF clearance of the PET tracer was reduced in AD and associated with elevated brain Aβ levels. In the present study, using two PET tracers, 18F-THK5351 and 11C-PiB to estimate CSF clearance, we observe that the ventricular CSF clearance measures were correlated (r = .66, p < .01), with reductions in AD of 18 and 27%, respectively. We also replicated a significant relationship between ventricular CSF clearance (18F-THK5331) and brain Aβ load (r = −.64, p < .01). With a larger sample size, we extended our observations to show that reduced CSF clearance is associated with reductions in cortical thickness and cognitive performance. Overall, the findings support the hypothesis that failed CSF clearance is a feature of AD that is related to Aβ deposition and to the pathology of AD. Longitudinal studies are needed to determine whether failed CSF clearance is a predictor of progressive amyloidosis or its consequence.
The road beyond licensing: The impact of a driver licensing support program on employment outcomes for Aboriginal and Torres Strait Islander Australians
Authors: Porykali Bobby , Cullen Patricia , Hunter Kate , Rogers Kris , Kang Melissa , Young Nareen , Senserrick Teresa , Clapham Kathleen , Ivers Rebecca 
Published: September 2021

Abstract
Background: With increasingly tough graduated driver licensing laws in all Australian States and Territories, driver licensing support programs are recognised as being important to support Aboriginal and Torres Strait Islander peoples to obtain a driver licence. Such programs appear to improve licensing attainment rates, but few studies have examined the broader impact that these programs can have. This research aims to examine the impact of a NSW based driver licensing support program (Driving Change) on client employment outcomes. Methods: Driving Change was delivered from February 2013 to August 2016 in 4 urban and 7 regional Aboriginal communities of New South Wales. Clients were followed-up at 6 months or more following contact with the program as part of routine program operations. Descriptive statistics and regression models were used to analyse data.Results: From 933 clients contacted 254 agreed to provide feedback, a response rate of 27%. Those that responded were mostly female (57%), aged 24 years and under (72%), unemployed (85%) with secondary education or less (71%) and from a regional area (74%). Adjusted logistic regression indicated that clients who achieved an independent licence were more likely (OR: 2.5, 95% CI: 1.22 – 5.24, p=0.001) of reporting a new job or change in job than those who did not attain a licence. Clients from regional areas were more likely (OR: 1.72, 95% CI: 1.27 – 2.33, p=0.001) to gain an independent licence than those from urban areas. Clients from regional areas were also more likely to report an improvement in employment outcomes (OR: 1.2, 95% CI: 0.52 – 2.52, p=0.72,) compared to those from urban areas, though results were not statistically significant. Discussion: This licensing support program increased licensing attainment particularly in regional areas and also had a beneficial effect on employment for those who gained a licence through the program. Clients were predominantly young and unemployed, which are often a hard to reach cohort. There is a need for future licensing programs to collect client employment data and explore approaches for sustainable collaboration between employment agencies and Governments.Conclusion: Licensing programs appear to be effective in improving employment outcomes. Future licensing programs being delivered in regional areas need integrated pathways into employment opportunities to provide holistic services that address the social and economic challenges faced by Aboriginal and Torres Strait Islander Australians.
Multi-shuttle AS/RS Dimensions Optimization Using a Genetic Algorithm – Case of the Multi-aisle Configuration
Authors: FANDI wahiba , KOULOUGHLI Sihem , GHOMRI Latefa 
Published: September 2021

Abstract
Over the past few years, automated storage and retrieval systems (AS/RSs) have been increasingly improving. It is worth mentioning that multi-shuttle storage/retrieval (S/R) machines were gradually introduced to the market some years ago. These machines, which possess a high speed of execution, are able to transport several pallets at a time during the same trip, as opposed to single-shuttle S/R machines which can carry only one pallet at a time. It should be noted that the installation of this type of system requires a significant financial investment, and therefore it is highly recommended that this system be well studied and designed prior to its installation. It is widely acknowledged that one of the most important objectives while designing an AS/RS is to achieve the shortest time for one single cycle. The present work aims at designing an AS/RS with optimal dimensions for the purpose of minimizing the time in a multi-cycle implementation. To do this, it was decided to consider a multi-aisle automated storage/ retrieval system (AS/RS) with a multi-shuttle S/R machine. In addition, a genetic algorithm (GA) was used for the optimization of the system.
Research on the Optimal Allocation of Tolerances of CNC Machine Tools Based on Small Deformation of Grinding Wheel
Authors: Fan Jinwei , Xie Bentian , Zhao Qinzhi , Wang Junjian 
Published: September 2021

Abstract
In order to solve the problem of precision optimization design of CNC machine tools, this paper proposes an optimized allocation method of machine tool tolerance parameters that takes into account the slight deformation of the machine tool. First, establish a tolerance-based geometric error prediction model, and establish a spatial motion error model based on the theory of multi-body systems(MBS); Homogeneously, perform finite element analysis(FEA) on the CNC internal cylindrical compound grinding machine to obtain the slight deformation of the machine tool, and apply the result to the optimal tolerance allocation In the constraint conditions, the final optimal allocation plan is obtained; Finally, the genetic algorithm is used to simulate and analyze the plan, and the optimal tolerance allocation result is obtained. The result shows that most of the tolerance parameters have been relaxed, which means that the machine tool’s manufacturing cost. Through experiments, it is verified that the optimized machine tool machining accuracy pass rates are 98.5%, 98.25%, and 97.85%, respectively. Therefore, the optimal allocation method of tolerances that considers small deformations proposed in this paper is effective.
Effect of Density on Mediterranean Pine Seedlings Using the Nelder Wheel Design: Analysis of Survival and Early Growth
Authors: Ruano Irene , Pando Valentín , Bravo Felipe 
Published: September 2021

Abstract
Background: There is growing interest in mixed-species forests but a lack of studies that analyse them for regeneration phases or any stage other than mature stands. Information is scarce about relatively unproductive species such as Pinus pinaster and Pinus halepensis in Mediterranean ecosystems. The objective of this study was to investigate inter- and intra-specific interactions of both species in different tree densities during the first years of establishment. Five Nelder wheel plots were planted to test densities ranging from 1000 to 80000 seedlings/ha and simulate establishment sub-processes at high densities. Pinus pinaster and Pinus halepensis were mixed along the spokes, to obtain three mixture levels in which 100%, 80% or 60% of the seedlings were of the same species. Cox proportional-hazards models and binomial logistic regressions were fitted to analyse seedling survival. Early growth (basal diameter and height at one and four years after plantation) was analysed by fitting linear mixed-effects models. Results: Pinus halepensis showed higher survival rates and basal diameter increments but more time is needed to know how Pinus pinaster responds to density and mixture. Conclusions: Both competitive and facilitating seedling interactions were observed at higher densities, which facilitate seedling survival but decrease early growth. Pinus halepensis showed higher survival rates and basal diameter increments but more time is necessary to determine Pinus pinaster response to density and mixture.
Axial-Ligand-Cleavable Silicon Phthalocyanines Triggered by Near-Infrared Light toward Design of Photosensitizers for Photoimmunotherapy
Authors: Takakura Hideo , Matsuhiro Shino , Kobayashi Masato , Goto Yuto , Harada Mei , Taketsugu Tetsuya , Ogawa Mikako 
Published: September 2021

Abstract
Near-infrared photoimmunotherapy (NIR-PIT) is a novel phototherapy for the treatment of cancer that uses NIR light and conjugates of antibody-IR700, a silicon phthalocyanine photosensitizer. A key feature of NIR-PIT is light-induced axial ligand cleavage of IR700, which finally causes cytotoxicity. Here, we focused on protonation of the axial ligand on the IR700 anion radical during the photochemical process. The Gibbs energy in the protonation reaction of IR700 derivatives with different axial ligands was calculated. These calculations suggested the order of the cleavage efficiency corresponds to the basicity of the axial ligand (i.e. alkoxy > siloxy (IR700) > phenoxy ≈ oxycarbonyl), which was confirmed by the photoirradiation experiments with synthesized compounds. Thus, axial ligand cleavage is significantly dependent on the basicity of the axial ligand. Our findings suggest that PIT reagent with an IR700 derivative bearing alkoxy group would show better efficacy than IR700.
Isolation of Nannocystis species from Iran and exploring their natural products
Authors: Moradi Azam , Yaghoubi-Avini Mohammad , Wink Joachim 
Published: September 2021

Abstract
Several different techniques were employed for the isolation of Nannocystis from various sources. A polyphasic approach was used for identification. Twelve strains of N. pusilla, N. exedens, and N. konarekensis with distinctive distribution between climates were identified. The bioactivity was examined against a panel of eight bacteria, two yeasts, and one fungus; cytotoxicity was tested on the L929 fibroblast cell line. Eleven strains mainly inhibit Gram-positive bacteria, and only one isolate was cytotoxic. The extracts analysis by HPLC and LC-MS were compared to Myxobase, and eight different compounds were detected; a correlation was observed between compounds and producing species. 70% of strains had the potential to produce structurally diverse compounds. Nannochelins and althiomycin were the most abundant metabolites. The discovery of a new species of Nannocystis and the high potentiality of strains to produce secondary metabolites encourage further sampling and in-depth analysis of extracts to find new active metabolites.
Integrated metabolomic and transcriptomic analysis of the anthocyanin regulatory networks in red walnut
Authors: Wang Lei , Li Lin , Zhao Wei , Meng Haijun , Zhang Ganggang , Wu Wenjiang , Shi Jiangli , Wu Guoliang 
Published: September 2021

Abstract
Background

Walnut is one of the most important dry fruit crops worldwide, typically green leaves and yellow-brown or gray-yellow seed coats. A specific walnut type, red walnut ‘RW-1’ with red leaves and seed coats was selected as plant material because of higher anthocyanins contents. Anthocyanins are important colorants with strong antioxidant activity, especially, benefic for human health. However, few studies focused on the molecular mechanism of anthocyanin biosynthesis in walnut.
Results

From the results of Widely Targeted Metabolome and anthocyanidin detection analysis, 395 substances, including 4 procyanidins and 26 anthocyanins, were identified from the red-leaf walnuts of RW-1 natural hybrid progenies (SR) and the green-leaf walnuts of RW-1 natural hybrid progenies (SG). Among these, all the anthocyanins in SR were significantly up-accumulated comparing with SG. Also, delphinidin 3-O-galactoside, cyanidin 3-O-galactoside, delphinidin 3-O-glucoside and cyanidin 3-O-glucoside were identified to the primary components of anthocyanidins because of the higher contents. It was noted that 9 anthocyanins including malvidin 3-O-galactoside, malvidin 3-O-arabinoside, cyanidin 3-O-(6-O-malonyl-beta-D-glucoside), delphinidin 3-O-glucoside, delphinidin 3,5-O-diglucoside (Delphin), peonidin 3-O-(6-O-malonyl-beta-D-glucoside), petunidin 3-O-(6-O-malonyl-beta-D-glucoside), petunidin 3-O-arabinoside and pelargonidin 3-O-(6-O-malonyl-beta-D-glucoside) were detected only in SR walnut. Furthermore, transcriptome analysis demonstrated that the expression of structural genes (C4H, F3H, F3’5’H and UFGTs), and four MYBs in anthocyanin biosynthetic pathway were significantly higher in SR walnut.
Conclusions

We identified the color formation of SR leaves is due to the accumulation of anthocyanins. And our results obtained the valuable information on the anthocyanin metabolites and candidate genes in anthocyanin biosynthesis, which provided new insights into the anthocyanin biosynthesis in walnuts.
Research designs and instruments to detect physiotherapy overuse of low-value care services in low back pain management: A scoping review protocol
Authors: Kühn Lukas , Lindert Lara , Choi Kyung-Eun (Anna) 
Published: September 2021

Abstract
BackgroundThe provision of low value care services in low back pain management is a problem of global scope. Inappropriate imaging, overmedication and overused invasive therapies are prevalent in physician services. Yet, little is known about overused low-value physiotherapy services. Most studies addressing physiotherapy overuse in low back pain management arose from countries in which physiotherapy is established in primary care. However, measures and instruments addressing physiotherapy overuse limitedly fit legislative conditions of health systems in which physiotherapy is a service of secondary care. Thus, this scoping review’s purpose is to map existing research designs and instruments aiming to detect overused low-value physiotherapy services taking specific healthcare settings and aspects of the medical overuse into account.MethodsThe development of this scoping review is guided by the Arksey and O’Malley framework. A three-step, peer reviewed search strategy in accordance to the PRESS checklist will be conducted on Medline (PubMed), Web of Science and CINHAL. Additionally, grey literature will be searched on googlescholar. Preprints of empirical studies will be included. Initially, two reviewers will independently screen articles for eligibility by title and abstract. A third reviewer will mediate discrepancies. Uncertainties will be eliminated by full text analysis or by contacting the corresponding authors. A four-step analytical process will guide result reporting focusing on major research questions outlined in this protocol. Numerical and narrative tables, graphics and narrative summaries will be methods to summarize and collate results. In the final step, the German health system will serve as an exemplary setting and frame to practically apply results.DiscussionResults of this scoping review will help researchers to systematically select overuse measures referring to aspects of the overuse typology, specific healthcare settings and physiotherapy services. It will further provide information on limitations of present studies and will give advice how to address them. Moreover, this review will illustrate to what degree existing studies succeed to comprehensively cover the concept of the overuse typology.RegistrationThis protocol has been registered on open science framework. (https://osf.io/vzq7k DOI: 10.17605/OSF.IO/PMF2G)
Balanced modulation of neuromuscular synaptic transmission via M1 and M2 muscarinic receptors during inhibition of cholinesterases
Authors: Lenina Oksana A. , Petrov Konstantin A. 
Published: September 2021

Abstract
Organophosphorus (OP) compounds that inhibit acetylcholinesterase are a common cause of poisoning worldwide, resulting in several hundred thousand deaths each year. The pathways activated during OP compound poisoning via overstimulation of muscarinic acetylcholine receptors (mAChRs) play a decisive role in toxidrome. The antidotal therapy includes atropine, which is a nonspecific blocker of all mAChR subtypes. Atropine is efficient for mitigating depression in respiratory control centers but does not benefit patients with OP-induced skeletal muscle weakness. By using an ex vivo model of OP-induced muscle weakness, we studied the effects of the M1/M4 mAChR antagonist pirenzepine and the M2/M4 mAChR antagonist methoctramine on the force of mouse diaphragm muscle contraction. It was shown that weakness caused by the application of paraoxon can be significantly prevented by methoctramine (1 µM). However, neither pirenzepine (0.1 µM) nor atropine (1 µM) was able to prevent muscle weakness. Moreover, the application of pirenzepine significantly reduced the positive effect of methoctramine. Thus, balanced modulation of neuromuscular synaptic transmission via M1 and M2 mAChRs contributes to paraoxon-induced muscle weakness. It was shown that methoctramine (10 µM/kg, i.p.) and atropine (50 µM/kg, i.p.) were equieffective toward increasing the survival of mice poisoned with a 2xLD50 dose of paraoxon.
Superconductivity in In-doped AgSnBiTe3 with possible band inversion
Authors: Mitobe Tsubasa , Hoshi Kazuhisa , Kasem Md. Riad , Kiyama Ryosuke , Usui Hidetomo , Yamashita Aichi , Higashinaka Ryuji , Matsuda Tatsuma D. , Aoki Yuji , Goto Yosuke , Mizuguchi Yoshikazu 
Published: September 2021

Abstract
We investigated the chemical pressure effects on structural and electronic properties of SnTe-based material using partial substitution of Sn by Ag0.5Bi0.5, which results in lattice shrinkage. For Sn1-2x(AgBi)xTe, single-phase polycrystalline samples were obtained with a wide range of x. On the basis of band calculations, we confirmed that the Sn1-2x(AgBi)xTe system is basically possessing band inversion and topologically preserved electronic states. To explore new superconducting phases related to the topological electronic states, we investigated the In-doping effects on structural and superconducting properties for x = 0.33 (AgSnBiTe3). For (AgSnBi)(1-y)/3InyTe, single-phase polycrystalline samples were obtained for y = 0–0.5 by high-pressure synthesis. Superconductivity was observed for y = 0.2–0.5. For y = 0.4, specific heat investigation confirmed the emergence of bulk superconductivity. Because the parameters obtained from specific heat analyses were comparable to In-doped SnTe, we expect that the (AgSnBi)(1-y)/3InyTe and other (Ag,In,Sn,Bi)Te phases are a candidate system for studying topological superconductivity.
Further delineation of the phenotypic spectrum of pathogenic variants in MED13
Authors: Povolotskaya Inna S. , Vetrova Natalya V. , Zhikrivetskaya Svetlana O. , Musatova Elizaveta V. , Klestova Valeriia S. , Shirokova Natalya A. , Tveleneva Aleksandra A. , Kotov Ilya N. , Isaev Artur A. , Pomerantseva Ekaterina A. 
Published: September 2021

Abstract
Introduction:Diagnostic yield of the genetic testing in search for the molecular basis of neurodevelopmental diseases remains low due to incomplete knowledge of the phenotypic spectrum of pathogenic variants in a specific gene. Recently the MED13 gene was linked to neurodevelopmental disease. Methods:Four families with children affected by autism spectrum disorder (ASD) were recruited to the study. Extensive genetic testing was performed for each proband: CGG repeat expansion analysis in FMR1 gene; whole exome sequencing (WES); array comparative genomic hybridization (aCGH); maternity and paternity confirmation. Genetic variants which were revealed by WES were verified with Sanger sequencing or aCGH in probands and their relatives. Results:Four rare heterozygous genetic variants in MED13 gene were identified in four unrelated patients with clinical features matching MED13-associated phenotype: intellectual disability (ID) of various degrees, speech delay, ASD and mild facial dysmorphisms. Three of the variants occurred de novo, while one was inherited maternally, in accordance with previous findings, suggesting incomplete penetrance. A patient with a de novo missense mutation in the intrinsic disordered region of MED13 developed seizures similarly to the only other reported patient with a pathogenic missense variant in this region. Limitations:Additional functional studies are needed to elucidate molecular mechanisms of the disease and distinguish between pathogenic and non-pathogenic variation.Conclusion:Our data strongly support the role of MED13 in neurodevelopmental disease by eliminating other common genetic defects. We expand the phenotypic spectrum of the disease causing variants: pathogenic missense variants in the intrinsic disordered region of MED13 may lead to a phenotype with seizures and incomplete penetrance of the maternally inherited variants may occur.
Metagenomics-informed soil biogeochemical models projected less carbon loss in tropical soils in response to climate warming
Authors: song Yang , Yao Qiuming , Yang Xiaojuan , Wright Stuart , Wang Gangsheng , Hazen Terry , Turner Benjamin , Tfaily Malak , Pasa-Tolic Ljiljana , Jonston Eric , Kim Minjae , Konstantinidis Konstantinos , Pan Chongle , Mayes Melanie 
Published: September 2021

Abstract
A major challenge of quantifying feedback between microbial communities and climate is the vast diversity of microbial communities and the intricacy of soil biogeochemical processes they mediate. We overcome this challenge by simplifying the representation of diverse enzyme functions from metagenomics data. We developed a dynamic allocation scheme for enzyme functional classes (EFCs) based on the premise that microbial communities act to maximize acquisition of limiting resources while minimizing energy expenditure for acquiring unlimited resources. We incorporated this scheme into a biogeochemical model to explicitly represent microbial functional diversity and simulate responses of microbially-mediated soil biogeochemical processes to varying environmental and nutrient conditions. Representing microbial functional diversity and environmental acclimation improved predictions of the stoichiometry of microbial biomass and mitigated the sensitivity of soil organic carbon to warming in nutrient-deficient regions. Our results indicate the importance of microbial functional diversity and environmental acclimation for projecting climate feedbacks of nutrient-limited soils.