bluuebunny/crossref_metadata_2025 huggingface dataset:
The Diversity and Community Assembly Process of Wetland Plants from Lakeshores on the Qinghai-Tibetan Plateau
Authors: Cui Shasha , Ouyang Jian , Lu Yu , Liu Wenzhi , Li Wenyang , Liu Guihua , Zhou Wen
Published: December 2021

Unravelling the patterns, potential processes and mechanisms underlying biodiversity has always been a crucial issue in community ecology. It is also a necessary first step for any conservation and restoration to better adapt fragile ecosystems to a changing climate. However, little is known regarding the structure and maintenance of plant communities in typical high-altitude wetlands. Here, we made a comprehensive analysis of the diversity and composition of wetland plant communities based on the distribution of plants near the shorelines of 19 lakes across the Qinghai-Tibetan Plateau. The latitude, mean annual temperature (MAT) and mean annual precipitation (MAP), along with the edaphic properties, were the dominant predictors affecting the taxonomic and phylogenetic α-diversity. Besides diversification, ecological drift, mixing with weak dispersal and weak selection shaped the community composition of wetland plants in our study. The latitude and MAP predictors, although modest, showed an impact on the community structure.
BatchBMD as an Efficient and Accurate Dual-Energy X-ray Absorptiometry Report Generator
Authors: Chan Chun-Hsiang , Huang Wen-Chi , Lu Yi-Chien , Hsiao Hsing-Fen , Chan Wing P.
Published: December 2021

Dual-energy X-ray absorptiometry is the gold standard for evaluating Bone Mineral Density (BMD); however, a typical BMD report is generated in a time-inefficient manner and is prone to error. We developed a rule-based automated reporting system, BatchBMD, that accelerates DXA reporting while improving its accuracy over current systems. BatchBMD generates a structured report, customized to the specific clinical purpose. To compare BatchBMD to a Web-based Reporting (WBR) system for efficiency and accuracy, 500 examinations were randomly chosen from those performed at the Taipei Municipal Wanfang Hospital from January to March 2021. The final assessment included all 2326 examinations conducted from September 2020 to March 2021. The average reporting times were 6.7 and 10.8 min for BatchBMD and the WBR system, respectively, while accuracy was 99.4% and 98.2%, respectively. Most of the errors made by BatchBMD were digit errors in the appendicular skeletal muscle index. After correcting this, 100% accuracy across all 2326 examinations was validated. This automated and accurate BMD reporting system significantly reduces report production workload for radiologists and technicians while increasing productivity and quality. Additionally, the portable software, which employs a simple framework, can reduce deployment costs in clinical practice.
Analysis of Microbial Communities: An Emerging Tool in Forensic Sciences
Authors: Gouello Audrey , Dunyach-Remy Catherine , Siatka Christian , Lavigne Jean-Philippe
Published: December 2021

The objective of forensic sciences is to find clues in a crime scene in order to reconstruct the scenario. Classical samples include DNA or fingerprints, but both have inherent limitations and can be uninformative. Another type of sample has emerged recently in the form of the microbiome. Supported by the Human Microbiome Project, the characteristics of the microbial communities provide real potential in forensics. They are highly specific and can be used to differentiate and classify the originating body site of a human biological trace. Skin microbiota is also highly specific and different between individuals, leading to its possibility as an identification tool. By extension, the possibilities of the microbial communities to be deposited on everyday objects has also been explored. Other uses include the determination of the post-mortem interval or the analysis of soil communities. One challenge is that the microbiome changes over time and can be influenced by many environmental and lifestyle factors. This review offers an overview of the main methods and applications to demonstrate the benefit of the microbiome to provide forensically relevant information.
Experimental Investigation and Fault Diagnosis for Buckled Wet Clutch Based on Multi-Speed Hilbert Spectrum Entropy
Authors: Xue Jiaqi , Ma Biao , Chen Man , Zhang Qianqian , Zheng Liangjie
Published: December 2021

The multi-disc wet clutch is widely used in transmission systems as it transfers the torque and power between the gearbox and the driving engine. During service, the buckling of the friction components in the wet clutch is inevitable, which can shorten the lifetime of the wet clutch and decrease the vehicle performance. Therefore, fault diagnosis and online monitoring are required to identify the buckling state of the friction components. However, unlike in other rotating machinery, the time-domain features of the vibration signal lack efficiency in fault diagnosis for the wet clutch. This paper aims to present a new fault diagnosis method based on multi-speed Hilbert spectrum entropy to classify the buckling state of the wet clutch. Firstly, the wet clutch is classified depending on the buckling degree of the disks, and then a bench test is conducted to obtain vibration signals of each class at varying speeds. By comparing the accuracy of different classifiers with and without entropy, Hilbert spectrum entropy shows higher efficiency than time-domain features for the wet clutch diagnosis. Thus, the classification results based on multi-speed entropy achieve even better accuracy.
Quantum Information in Relativity: The Challenge of QFT Measurements
Authors: Anastopoulos Charis , Savvidou Ntina
Published: December 2021

Proposed quantum experiments in deep space will be able to explore quantum information issues in regimes where relativistic effects are important. In this essay, we argue that a proper extension of quantum information theory into the relativistic domain requires the expression of all informational notions in terms of quantum field theoretic (QFT) concepts. This task requires a working and practicable theory of QFT measurements. We present the foundational problems in constructing such a theory, especially in relation to longstanding causality and locality issues in the foundations of QFT. Finally, we present the ongoing Quantum Temporal Probabilities program for constructing a measurement theory that (i) works, in principle, for any QFT, (ii) allows for a first- principles investigation of all relevant issues of causality and locality, and (iii) it can be directly applied to experiments of current interest.
A Grouping Differential Evolution Algorithm Boosted by Attraction and Repulsion Strategies for Masi Entropy-Based Multi-Level Image Segmentation
Authors: Mousavirad Seyed Jalaleddin , Zabihzadeh Davood , Oliva Diego , Perez-Cisneros Marco , Schaefer Gerald
Published: December 2021

Masi entropy is a popular criterion employed for identifying appropriate threshold values in image thresholding. However, with an increasing number of thresholds, the efficiency of Masi entropy-based multi-level thresholding algorithms becomes problematic. To overcome this, we propose a novel differential evolution (DE) algorithm as an effective population-based metaheuristic for Masi entropy-based multi-level image thresholding. Our ME-GDEAR algorithm benefits from a grouping strategy to enhance the efficacy of the algorithm for which a clustering algorithm is used to partition the current population. Then, an updating strategy is introduced to include the obtained clusters in the current population. We further improve the algorithm using attraction (towards the best individual) and repulsion (from random individuals) strategies. Extensive experiments on a set of benchmark images convincingly show ME-GDEAR to give excellent image thresholding performance, outperforming other metaheuristics in 37 out of 48 cases based on cost function evaluation, 26 of 48 cases based on feature similarity index, and 20 of 32 cases based on Dice similarity. The obtained results demonstrate that population-based metaheuristics can be successfully applied to entropy-based image thresholding and that strengthening both exploitation and exploration strategies, as performed in ME-GDEAR, is crucial for designing such an algorithm.
An Exponential Endogenous Switching Regression with Correlated Random Coefficients
Authors: Keay Myoung-Jin
Published: December 2021

This paper presents a method for estimating the average treatment effects (ATE) of an exponential endogenous switching model where the coefficients of covariates in the structural equation are random and correlated with the binary treatment variable. The estimating equations are derived under some mild identifying assumptions. We find that the ATE is identified, although each coefficient in the structural model may not be. Tests assessing the endogeneity of treatment and for model selection are provided. Monte Carlo simulations show that, in large samples, the proposed estimator has a smaller bias and a larger variance than the methods that do not take the random coefficients into account. This is applied to health insurance data of Oregon.
Research on the Cross-Platform Co-Simulation Strategy of Power Systems Based on the Model-Segmentation Algorithm
Authors: Yu Dachuan , Zhou Niancheng , Luo Yongjie , Dong Le , Jia Zan
Published: December 2021

In recent years, cross-platform co-simulation has become an important development direction of the real-time simulation of power systems. Model segmentation is at the core of the realization of cross-platform joint simulation and parallel real-time simulation of these systems. In essence, it is based on the deep application of a system-decoupling algorithm. In order to solve problems that a single interface cannot, it considers the data interaction of large- and small-step systems at the same time This paper proposes an improved joint-simulation strategy based on the model-segmentation method for the cross-platform joint-simulation technology of a large-scale, flexible direct-power grid sent by the wind farms of RT-lab and Hypersim. Firstly, by studying several common interface algorithms in the current project, the adaptability of different interface algorithms is analyzed. Secondly, the problem of high-frequency oscillation caused by the inductance-decoupling algorithm is improved, and an improved segmentation-model algorithm is proposed. Finally, according to the adaptability, each interface algorithm is applied to the wind-power-based, flexible direct-transmission, dual-platform simulation model that was built for this study. The simulation results verify the feasibility of the improved interface in system decoupling and platform interfacing, and indicate the significantly improved accuracy and stability of the system.
Non-Dimensional Analysis of Diffusion Characteristics in Polymer Electrolyte Membrane Fuel Cells with Mismatched Anodic and Cathodic Flow Channels
Authors: Kim Hyeok , Kim Geonhwi , Kim Jaeyeon , Kim Dasol , Kwon Obeen , Yoo Hongnyoung , Cha Hyeonjin , Choi Heesoo , Park Taehyun
Published: December 2021

Polymer electrolyte membrane fuel cells were analyzed to investigate changes in the structure of the flow field and operating conditions. The cell performance, which was controlled by adjusting the width of the cathodic channel, improved as the backpressure increases. With the anodic and cathodic flow channels mismatched, the maximum power densities at 3.0 bar for a narrow cathodic channel were 1115 and 1024 mW/cm2, and those for a wide cathodic channel were 959 and 868 mW/cm2, respectively. The diffusion characteristics were investigated using the non-dimensional numbers Re (Reynolds), Sc (Schmidt), and Sh (Sherwood) to confirm the improvement of mass transport. The narrower the channel or the higher the operating pressure, the larger Re was and the smaller Sc and Sh became. In particular, the wider the anodic channel, the larger the value of Sh.
A Review on Unit Commitment Algorithms for the Italian Electricity Market
Authors: Falvo Maria , Panella Stefano , Caprabianca Mauro , Quaglia Federico
Published: December 2021

This paper focuses on the state-of-the-art of unit commitment (UC) and economic dispatch (ED) algorithms suitable for the Italian electricity market. In view of the spread of renewable energy systems (RES), the desired UC algorithm should be able to properly consider the uncertainty affecting key input variables into the formulation of the problem, as well as the different capabilities of dispatched power plants to provide ancillary services (e.g., voltage regulation). The goal of this paper is to resume the developments in UC and ED algorithms which occurred in the last decades, having a particular focus on alternating current (AC) security constrained (SC) approaches and stochastic ones, highlighting the advantages and weakness of each technique. This review is useful for the Italian TSO (Terna) to investigate what is the best solution to formulate a new algorithm to be potentially adopted in the framework of the Italian Ancillary Service Market, striving for an explicit modelization of stochastic variables and voltage constraints. This review is also useful to all system operators (SOs), independently to the market environment in which they operate, because UC algorithms are widely adopted to ensure real-time security of power systems. In conclusion, an SC-UC algorithm which takes into account both stochastic variables and AC formulation does not exist.
Experiencing the Unprecedented COVID-19 Lockdown: Abu Dhabi Older Adults’ Challenges and Concerns
Authors: Badri Masood A. , Alkhaili Mugheer A. , Aldhaheri Hamad , Yang Guang , Albahar Muna , Alrashdi Asma , Almulla Bushra , Alhyas Layla
Published: December 2021

This study focused on older adults (60+ years old) of both genders in Abu Dhabi during the COVID-19 pandemic before vaccines were made available (age ranged from 60 years to 75 years). They faced more strict rules of movement restriction and isolation that might have resulted in certain psychological feelings and social reactions. The main objective was to understand Abu Dhabi older adults’ psychological feelings during the pandemic and to identify their main concerns and challenges considering the various COVID-19-related policies and restrictions. The psychological feelings focused on fear, loneliness, sadness, irritability, emotional exhaustion, depressive symptoms, sleeping disorders, overeating, and excessive screen use. The objectives also included the changes in the psychological feelings concerning time. Other objectives covered better understanding the differences in (some activities) compared to the other age categories. Data were gathered through an online survey of community members from February to July 2020 as part of government initiatives (Department of Community Development). Responses were collected from 574 older adults in Abu Dhabi (60.1% male and 39.9% female). The analysis mainly used descriptive analysis, t-tests, analysis of variance (ANOVA), and simple trend analysis. For all tests, a p-value less than 0.05 was used for significance. The results pointed to the significant rise in feelings related to excessive screen use, fear, loneliness, and stress. The most significant concerns were related to more restrictions being imposed and not being able to see the grandchildren.The impact of new technologies on their quality of life was significantly reflected by respondents. The influence of the pandemic on older adults’ health and weight was also investigated. Analysis of variance, t-tests, and regression analysis with relevant tests were employed. The relevant results showed that some negative psychological feelings were common among older adults during the pandemic. However, the psychological feelings did not portray significant changes with time, except for sleeping disorders and overeating. Overall, older adults scored significantly different from other age groups on many challenges, concerns, and views regarding new technologies during the pandemic. No significant differences were observed regarding gender and marital status for the challenges and concerns. The research summarizes some policy guidance while noting some limitations of this study and future research directions.
Impact of Economic Policy Uncertainty on Carbon Emissions: Evidence from 137 Multinational Countries
Authors: Wang Hai-Jie , Geng Yong , Xia Xi-Qiang , Wang Quan-Jing
Published: December 2021

With growing economic policy uncertainty (EPU) and the importance of protecting the natural environment worldwide, the relationship between EPU and carbon emissions should be investigated further. However, conclusions in the existing literature on the relationship between EPU and carbon emission are inconclusive. This paper aims to examine the influence of EPU on carbon emissions according to the Stochastic Impacts by Regression on Population, Affluence and Technology (STIRPAT) model. To investigate such essential issues, we conduct GMM estimations by utilizing cross-country data covering 137 countries during the period 1970–2018, obtained from World Bank and OECD statistics. Our empirical estimations support that EPU would bring about more carbon emissions, while we conduct empirical analysis by changing the system of measurement, employing alternative estimation and constructing new samples. Our study provides substantial policy implications for government participation in international treaties on environmental protection to mitigate environmental degradation.
Place of Residence and Cognitive Function in Older Adults in China: The Mediating Role of Social Participation
Authors: Yang Le , Cheng Jingmin , Wang Hongman
Published: December 2021

Background: Cognitive impairment is a severe health problem faced by older adults and their families, as well as the countries in which they live. Differences in place of residence may contribute to differences in the cognitive function of older adults, and the mediating effect of social participation has rarely been studied in China. Methods: A total of 10,014 older adult participants were included, using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Place of residence was described as either a city, town, or rural area. The frequency of participation in organized social activities and visits and interactions with friends was used to assess both formal and informal social participation. The Chinese version of a Mini-Mental State Examination (MMSE) was used as a measure of cognitive function. The mediation analysis was conducted using Hayes’ process version 3.4 on SPSS (IBM, Armonk, NY, USA). Results: Place of residence had a negative effect on cognitive function in older adults. The mediating functions of both informal (a1b1 = 0.199) and formal (a2b2 = −0.056) social participation indicate a suppression effect on the part of informal social participation and a partial mediation effect on the part of formal social participation in terms of the association between place of residence and cognitive function in older adults. Promoting both informal and formal social participation seems to be an important strategy for preventing a decline in the cognitive function of older adults, especially for those living in rural areas.
Child-Friendly Legal Aid and Individual Assessment of Children in Conflict with the Law: Building the Basis for Effective Participation
Authors: Limantė Agnė , Vaičiūnienė Rūta , Apolevič Jolanta
Published: December 2021

This article focuses on the importance of the right to effective participation of children in conflict with the law in criminal (youth justice) proceedings. In particular, it explores two procedural aspects which are closely related to the right to child-friendly legal aid and the role of individual assessment. The authors claim that qualitatively identifying the needs of the child (through the instrument of individual assessment) and establishing a relationship of trust with a specifically trained legal aid lawyer is critical in raising the child’s status to that of an active participant in the proceedings and ensuring that the best interests of the child are observed. The authors also suggest that such an initial encounter within the justice system forms an attitude (of either confidence or rejection) of the child towards public institutions and, accordingly, directly affects the effectiveness of further interventions. To support their position, the authors of the paper bring several examples from the comparative research carried out in two European projects, noting, regretfully, that the initial interventions often suffer from formal implementation and lack a systemic approach.
Adverse Selection in P2P Lending: Does Peer Screening Work Efficiently?—Empirical Evidence from a P2P Platform
Authors: Wang Yao , Drabek Zdenek
Published: December 2021

The rapid development of online lending in the past decade, while providing convenience and efficiency, also generates large hidden credit risk for the financial system. Will removing financial intermediaries really provide more efficiency to the lending market? This paper used a large dataset with 251,887 loan listings from a pioneer P2P lending platform to investigate the efficiency of the credit-screening mechanism on the P2P lending platform. Our results showed the existence of a TYPE II error in the investors’ decision-making process, which indicated that the investors were predisposed to making inaccurate diagnoses of signals, and gravitated to borrowers with low creditworthiness while inadvertently screening out their counterparts with high creditworthiness. Due to the growing size of the fintech industry, this may pose a systematic risk to the financial system, necessitating regulators’ close attention. Since, investors can better diagnose soft signals, an effective and transparent enlargement of socially related soft information together with a comprehensive and independent credit bureau could mitigate adverse selection in a disintermediation environment.
Over-Expression of Rose RrLAZY1 Negatively Regulates the Branch Angle of Transgenic Arabidopsis Inflorescence
Authors: Li Dan , Zhao Mingyuan , Yu Xiaoyan , Zhao Lanyong , Xu Zongda , Han Xu
Published: December 2021

Branch angle is a key shoot architecture trait that strongly influences the ornamental and economic value of garden plants. However, the mechanism underlying the control of branch angle, an important aspect of tree architecture, is far from clear in roses. In the present study, we isolated the RrLAZY1 gene from the stems of Rosa rugosa ‘Zilong wochi’. Sequence analysis showed that the encoded RrLAZY1 protein contained a conserved GΦL (A/T) IGT domain, which belongs to the IGT family. Quantitative real-time PCR (qRT-PCR) analyses revealed that RrLAZY1 was expressed in all tissues and that expression was highest in the stem. The RrLAZY1 protein was localized in the plasma membrane. Based on a yeast two-hybrid assay and bimolecular fluorescence complementation experiments, the RrLAZY1 protein was found to interact with auxin-related proteins RrIAA16. The over-expression of the RrLAZY1 gene displayed a smaller branch angle in transgenic Arabidopsis inflorescence and resulted in changes in the expression level of genes related to auxin polar transport and signal transduction pathways. This study represents the first systematic analysis of the LAZY1 gene family in R. rugosa. The results of this study will provide a theoretical basis for the improvement of rose plant types and molecular breeding and provide valuable information for studying the regulation mechanism of branch angle in other woody plants.
Glycolysis under Circadian Control
Authors: Zlacká Jana , Zeman Michal
Published: December 2021

Glycolysis is considered a main metabolic pathway in highly proliferative cells, including endothelial, epithelial, immune, and cancer cells. Although oxidative phosphorylation (OXPHOS) is more efficient in ATP production per mole of glucose, proliferative cells rely predominantly on aerobic glycolysis, which generates ATP faster compared to OXPHOS and provides anabolic substrates to support cell proliferation and migration. Cellular metabolism, including glucose metabolism, is under strong circadian control. Circadian clocks control a wide array of metabolic processes, including glycolysis, which exhibits a distinct circadian pattern. In this review, we discuss circadian regulations during metabolic reprogramming and key steps of glycolysis in activated, highly proliferative cells. We suggest that the inhibition of metabolic reprogramming in the circadian manner can provide some advantages in the inhibition of oxidative glycolysis and a chronopharmacological approach is a promising way to treat diseases associated with up-regulated glycolysis.
Biological Activity, Lipophilicity and Cytotoxicity of Novel 3-Acetyl-2,5-disubstituted-1,3,4-oxadiazolines
Authors: Paruch Kinga , Biernasiuk Anna , Berecka-Rycerz Anna , Hordyjewska Anna , Popiołek Łukasz
Published: December 2021

Antibiotic resistance is now a global problem, and the lack of effective antimicrobial agents for the treatment of diseases caused by resistant microbes is increasing. The 3-acetyl-2,5-disubstituted-1,3,4-oxadiazolines presented in this article may provide a good starting point for the development of potential new effective antimicrobial agents useful in the treatment of bacterial and fungal infections. Particular attention is drawn to the 1,3,4-oxadiazole derivative marked with the number 29 with 5-nitrofuran-2-yl substituent in its chemical structure. This substance showed a strong bactericidal effect, especially against Staphylococcus spp., and no cytotoxicity to the L929 normal cell line.
Physiological Ovarian Aging Is Associated with Altered Expression of Post-Translational Modifications in Mice
Authors: Wei Minli , Li Jia , Yan Huilin , Luo Tao , Huang Jiang , Yuan Yangyang , Hu Liaoliao , Zheng Liping
Published: December 2021

Post-translational modifications (PTMs) have been confirmed to be involved in multiple female reproductive events, but their role in physiological ovarian aging is far from elucidated. In this study, mice aged 3, 12 or 17 months (3M, 12M, 17M) were selected as physiological ovarian aging models. The expression of female reproductive function-related genes, the global profiles of PTMs, and the level of histone modifications and related regulatory enzymes were examined during physiological ovarian aging in the mice by quantitative real-time PCR and western blot, respectively. The results showed that the global protein expression of Kbhb (lysineβ-hydroxybutyryllysine), Khib (lysine 2-hydroxyisobutyryllysine), Kglu (lysineglutaryllysine), Kmal (lysinemalonyllysine), Ksucc (lysinesuccinyllysine), Kcr (lysinecrotonyllysine), Kbu (lysinebutyryllysine), Kpr (lysinepropionyllysine), SUMO1 (SUMO1 modification), ub (ubiquitination), P-Typ (phosphorylation), and 3-nitro-Tyr (nitro-tyrosine) increased significantly as mice aged. Moreover, the modification level of Kme2 (lysinedi-methyllysine) and Kac (lysineacetyllysine) was the highest in the 3M mice and the lowest in 12M mice. In addition, only trimethylation of histone lysine was up-regulated progressively and significantly with increasing age (p < 0.001), H4 ubiquitination was obviously higher in the 12M and 17M mice than 3M (p < 0.001), whereas the modification of Kpr (lysinepropionylation) and O-GlcNA in 17M was significantly decreased compared with the level in 3M mice (p < 0.05, p < 0.01). Furthermore, the expression levels of the TIP60, P300, PRDM9, KMT5B, and KMT5C genes encoding PTM regulators were up-regulated in 17M compared to 3M female mice (p < 0.05). These findings indicate that altered related regulatory enzymes and PTMs are associated with physiological ovarian aging in mice, which is expected to provide useful insights for the delay of ovarian aging and the diagnosis and treatment of female infertility.
HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2
Authors: Jeong Seho , Kim Soo-A , Ahn Sang-Gun
Published: December 2021

Homeobox C6 (HOXC6) is a transcription factor that plays a role in the malignant progression of various cancers. However, the roles of HOXC6 and its regulatory mechanism remain unclear. In this study, we used microRNA (miRNA) regulatory networks to identify key regulatory interactions responsible for HOXC6-mediated cancer progression. In microarray profiling of miRNAs, the levels of miRNAs such as hsa-miR-188-5p, hsa-miR-8063, and hsa-miR-8064 were significantly increased in HOXC6-overexpressing cells. Higher positive expression rates of HOXC6 and miR-188-5p were observed in malignant cancer. We also found that HOXC6 significantly upregulated miR-188-5p expression. The underlying function of HOXC6-mediated miR-188-5p expression was predicted through TargetScan and the MiRNA Database. Overexpression of mir-188-5p inhibited the expression of forkhead box N2 (FOXN2), a tumor suppressor gene. Furthermore, in the luciferase assay, miR-188-5p bound to the 3′-UTR of FOXN2 and was mainly responsible for the dysregulation of FOXN2 expression. Silencing FOXN2 induced cell migration, and the effect of FOXN2 silencing was enhanced when the HOXC6/miR-188-5p axis was induced. These results suggest that HOXC6/miR-188-5p may induce malignant progression in cancer by inhibiting the activation of the FOXN2 signaling pathway.
Rare Trafficking CFTR Mutations Involve Distinct Cellular Retention Machineries and Require Different Rescuing Strategies
Authors: Ramalho Sofia S. , Silva Iris A. L. , Amaral Margarida D. , Farinha Carlos M.
Published: December 2021

Most of the ~2100 CFTR variants so far reported are very rare and still uncharacterized regarding their cystic fibrosis (CF) disease liability. Since some may respond to currently approved modulators, characterizing their defect and response to these drugs is essential. Here we aimed characterizing the defect associated with four rare missense (likely Class II) CFTR variants and assess their rescue by corrector drugs. We produced CFBE cell lines stably expressing CFTR with W57G, R560S, H1079P and Q1100P, assessed their effect upon CFTR expression and maturation and their rescue by VX-661/VX-445 correctors. Results were validated by forskolin-induced swelling assay (FIS) using intestinal organoids from individuals bearing these variants. Finally, knock-down (KD) of genes previously shown to rescue F508del-CFTR was assessed on these mutants. Results show that all the variants preclude the production of mature CFTR, confirming them as Class II mutations. None of the variants responded to VX-661 but the combination rescued H1079P- and Q1100P-CFTR. The KD of factors that correct F508del-CFTR retention only marginally rescued R560S- and H1079P-CFTR. Overall, data evidence that Class II mutations induce distinct molecular defects that are neither rescued by the same corrector compounds nor recognized by the same cellular machinery, thus requiring personalized drug discovery initiatives.
Metabolic Therapy of Heart Failure: Is There a Future for B Vitamins?
Authors: Piquereau Jérôme , Boitard Solène E. , Ventura-Clapier Renée , Mericskay Mathias
Published: December 2021

Heart failure (HF) is a plague of the aging population in industrialized countries that continues to cause many deaths despite intensive research into more effective treatments. Although the therapeutic arsenal to face heart failure has been expanding, the relatively short life expectancy of HF patients is pushing towards novel therapeutic strategies. Heart failure is associated with drastic metabolic disorders, including severe myocardial mitochondrial dysfunction and systemic nutrient deprivation secondary to severe cardiac dysfunction. To date, no effective therapy has been developed to restore the cardiac energy metabolism of the failing myocardium, mainly due to the metabolic complexity and intertwining of the involved processes. Recent years have witnessed a growing scientific interest in natural molecules that play a pivotal role in energy metabolism with promising therapeutic effects against heart failure. Among these molecules, B vitamins are a class of water soluble vitamins that are directly involved in energy metabolism and are of particular interest since they are intimately linked to energy metabolism and HF patients are often B vitamin deficient. This review aims at assessing the value of B vitamin supplementation in the treatment of heart failure.
Effects of Aluminium Contamination on the Nervous System of Freshwater Aquatic Vertebrates: A Review
Authors: Closset Marie , Cailliau Katia , Slaby Sylvain , Marin Matthieu
Published: December 2021

Aluminium (Al) is the most common natural metallic element in the Earth’s crust. It is released into the environment through natural processes and human activities and accumulates in aquatic environments. This review compiles scientific data on the neurotoxicity of aluminium contamination on the nervous system of aquatic organisms. More precisely, it helps identify biomarkers of aluminium exposure for aquatic environment biomonitoring in freshwater aquatic vertebrates. Al is neurotoxic and accumulates in the nervous system of aquatic vertebrates, which is why it could be responsible for oxidative stress. In addition, it activates and inhibits antioxidant enzymes and leads to changes in acetylcholinesterase activity, neurotransmitter levels, and in the expression of several neural genes and nerve cell components. It also causes histological changes in nerve tissue, modifications of organism behaviour, and cognitive deficit. However, impacts of aluminium exposure on the early stages of aquatic vertebrate development are poorly described. Lastly, this review also poses the question of how accurate aquatic vertebrates (fishes and amphibians) could be used as model organisms to complement biological data relating to the developmental aspect. This “challenge” is very relevant since freshwater pollution with heavy metals has increased in the last few decades.
Application of Graphene in Tissue Engineering of the Nervous System
Authors: Ławkowska Karolina , Pokrywczyńska Marta , Koper Krzysztof , Kluth Luis Alex , Drewa Tomasz , Adamowicz Jan
Published: December 2021

Graphene is the thinnest two-dimensional (2D), only one carbon atom thick, but one of the strongest biomaterials. Due to its unique structure, it has many unique properties used in tissue engineering of the nervous system, such as high strength, flexibility, adequate softness, electrical conductivity, antibacterial effect, and the ability to penetrate the blood–brain barrier (BBB). Graphene is also characterized by the possibility of modifications that allow for even wider application and adaptation to cell cultures of specific cells and tissues, both in vitro and in vivo. Moreover, by using the patient’s own cells for cell culture, it will be possible to produce tissues and organs that can be re-transplanted without transplant rejection, the negative effects of taking immunosuppressive drugs, and waiting for an appropriate organ donor.
Nicotine Exposure during Adolescence Leads to Changes of Synaptic Plasticity and Intrinsic Excitability of Mice Insular Pyramidal Cells at Later Life
Authors: Toyoda Hiroki , Koga Kohei
Published: December 2021

To find satisfactory treatment for nicotine addiction, synaptic and cellular mechanisms should be investigated comprehensively. Synaptic transmission, plasticity and intrinsic excitability in various brain regions are known to be altered by acute nicotine exposure. However, it has not been addressed whether and how nicotine exposure during adolescence alters these synaptic events and intrinsic excitability in the insular cortex in adulthood. To address this question, we performed whole-cell patch-clamp recordings to examine the effects of adolescent nicotine exposure on synaptic transmission, plasticity and intrinsic excitability in layer V pyramidal neurons (PNs) of the mice insular cortex five weeks after the treatment. We found that excitatory synaptic transmission and potentiation were enhanced in these neurons. Following adolescent nicotine exposure, insular layer V PNs displayed enhanced intrinsic excitability, which was reflected in changes in relationship between current strength and spike number, inter-spike interval, spike current threshold and refractory period. In addition, spike-timing precision evaluated by standard deviation of spike timing was decreased following nicotine exposure. Our data indicate that adolescent nicotine exposure enhances synaptic transmission, plasticity and intrinsic excitability in layer V PNs of the mice insular cortex at later life, which might contribute to severe nicotine dependence in adulthood.
Gastric Xanthelasma, Microsatellite Instability and Methylation of Tumor Suppressor Genes in the Gastric Mucosa: Correlation and Comparison as a Predictive Marker for the Development of Synchronous/Metachronous Gastric Cancer
Authors: Fukushima Masashi , Fukui Hirokazu , Watari Jiro , Ito Chiyomi , Hara Ken , Eda Hirotsugu , Tomita Toshihiko , Oshima Tadayuki , Miwa Hiroto
Published: December 2021

A predictive marker for the development of synchronous/metachronous gastric cancer (GC) would be highly desirable in order to establish an effective strategy for endoscopic surveillance. Herein, we examine the significance of gastric xanthelasma (GX) and molecular abnormalities for the prediction of synchronous/metachronous GC. Patients (n = 115) were followed up (range, 12–122; median, 55 months) in whom the presence of GX and molecular alterations, including microsatellite instability (MSI) and methylation of human mutL homolog 1 (hMLH1), cyclin-dependent kinase inhibitor 2A (CDKN2A) and adenomatous polyposis coli (APC) genes, had been confirmed in non-neoplastic gastric mucosa when undergoing endoscopic submucosal dissection (ESD) for early GC. At the start of surveillance, the numbers of positive subjects were as follows: GX, 59 (51.3%); MSI, 48 (41.7%); hMLH1, 37 (32.2%); CDKN2A, 7 (6.1%); APC, 18 (15.7%). After ESD treatment, synchronous/metachronous GCs occurred in patients with the following positive factors: GX, 16 (27.1%); MSI, 7 (14.6%); hMLH1, 6 (16.2%); CDKN2A, 3 (42.9%); APC, 3 (16.7%). The presence of GX had no significant relationship to positivity for MSI or methylation of hMLH1, CDKN2A or APC. GX was significantly (p = 0.0059) and independently (hazard ratio, 3.275; 95% confidence interval, 1.134–9.346) predictive for the development of synchronous/metachronous GC, whereas those genetic alterations were not predictive. GX is a simple and powerful marker for predicting the development of synchronous or metachronous GC.
Validation of an Automated Screening System for Diabetic Retinopathy Operating under Real Clinical Conditions
Authors: Jimenez-Carmona Soledad , Alemany-Marquez Pedro , Alvarez-Ramos Pablo , Mayoral Eduardo , Aguilar-Diosdado Manuel
Published: December 2021

Background. Retinopathy is the most common microvascular complication of diabetes mellitus. It is the leading cause of blindness among working-aged people in developed countries. The use of telemedicine in the screening system has enabled the application of large-scale population-based programs for early retinopathy detection in diabetic patients. However, the need to support ophthalmologists with other trained personnel remains a barrier to broadening its implementation. Methods. Automatic diagnosis of diabetic retinopathy was carried out through the analysis of retinal photographs using the 2iRetinex software. We compared the categorical diagnoses of absence/presence of retinopathy issued by family physicians (PCP) with the same categories provided by the algorithm (ALG). The agreed diagnosis of three specialist ophthalmologists is used as the reference standard (OPH). Results. There were 653 of 3520 patients diagnosed with diabetic retinopathy (DR). Diabetic retinopathy threatening to vision (STDR) was found in 82 patients (2.3%). Diagnostic sensitivity for STDR was 94% (ALG) and 95% (PCP). No patient with proliferating or severe DR was misdiagnosed in both strategies. The k-value of the agreement between the ALG and OPH was 0.5462, while between PCP and OPH was 0.5251 (p = 0.4291). Conclusions. The diagnostic capacity of 2iRetinex operating under normal clinical conditions is comparable to screening physicians.
Cancer Type Classification in Liquid Biopsies Based on Sparse Mutational Profiles Enabled through Data Augmentation and Integration
Authors: Danyi Alexandra , Jager Myrthe , de Ridder Jeroen
Published: December 2021

Identifying the cell of origin of cancer is important to guide treatment decisions. Machine learning approaches have been proposed to classify the cell of origin based on somatic mutation profiles from solid biopsies. However, solid biopsies can cause complications and certain tumors are not accessible. Liquid biopsies are promising alternatives but their somatic mutation profile is sparse and current machine learning models fail to perform in this setting. We propose an improved method to deal with sparsity in liquid biopsy data. Firstly, data augmentation is performed on sparse data to enhance model robustness. Secondly, we employ data integration to merge information from: (i) SNV density; (ii) SNVs in driver genes and (iii) trinucleotide motifs. Our adapted method achieves an average accuracy of 0.88 and 0.65 on data where only 70% and 2% of SNVs are retained, compared to 0.83 and 0.41 with the original model, respectively. The method and results presented here open the way for application of machine learning in the detection of the cell of origin of cancer from liquid biopsy data.
Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy
Authors: Ługowska Agnieszka , Purzycka-Olewiecka Joanna K. , Płoski Rafał , Truszkowska Grażyna , Pronicki Maciej , Felczak Paulina , Śpiewak Mateusz , Podlecka-Piętowska Aleksandra , Sitek Martyna , Bilińska Zofia T. , Leszek Przemysław , Bednarska-Makaruk Małgorzata
Published: December 2021

We report on a 36-year-old man with cerebellar-extrapyramidal syndrome and severe heart failure because of dilated cardiomyopathy of unknown origin. Dysarthria and cardiac arrhythmia began at early childhood (4 years of age). Brain MRI (28 years of age) demonstrated severe cerebellar atrophy. At the age 32, he presented with dysarthria, ataxia, dystonia, and tremor of the right hand, bilateral slowed neural conduction in the visual pathways, and decreased mental acuity. At the age of 33 years, the patient underwent cardiac transplantation because of severe dilated cardiomyopathy. In the TPP1 gene, biallelic variants were identified: previously reported p.(Leu13Pro) and novel p.(Tyr508Cys) variant. Additionally, hemizygous novel missense variant in the ABCD1 gene was inherited from the mother p.(Arg17His). Normal very-long-chain fatty acids (VLCFA) levels both in patient and his mother excluded ABCD1 mutation as the pathogenic one. Tripeptidyl peptidase 1 (TPP1) activity was reduced (8,8 U/mg protein/h; reference range: 47.4 ± 10.7). In light microscopy the biopsy specimens obtained from explanted heart showed severe myocyte hypertrophy with perinuclear vacuolization with inclusions. Electron microscopy revealed absence of lipofuscin accumulation, no ultrastructural curvilinear profiles, fingerprint bodies, or granular osmiophilic deposits (GRODs) in lysosomes. As described here, the patient presents clinical symptoms observed in benign forms of ceroid lipofuscinosis type 2 (CLN2) and simultaneously some features of autosomal recessive spinocerebellar ataxia type 7 (SCAR7), which is also caused by mutations in the TPP1 gene.
Conformable Fractional Martingales and Some Convergence Theorems
Authors: Hammad Ma’mon Abu
Published: December 2021

In this paper, we define conformable Lebesgue measure and conformable fractional countable martingales. Some convergence theorems are proved.
The Improved Element-Free Galerkin Method for 3D Helmholtz Equations
Authors: Cheng Heng , Peng Miaojuan
Published: December 2021

The improved element-free Galerkin (IEFG) method is proposed in this paper for solving 3D Helmholtz equations. The improved moving least-squares (IMLS) approximation is used to establish the trial function, and the penalty technique is used to enforce the essential boundary conditions. Thus, the final discretized equations of the IEFG method for 3D Helmholtz equations can be derived by using the corresponding Galerkin weak form. The influences of the node distribution, the weight functions, the scale parameters of the influence domain, and the penalty factors on the computational accuracy of the solutions are analyzed, and the numerical results of three examples show that the proposed method in this paper can not only enhance the computational speed of the element-free Galerkin (EFG) method but also eliminate the phenomenon of the singular matrix.
Structure Revision and Protein Tyrosine Phosphatase Inhibitory Activity of Drazepinone
Authors: Cao Fei , Pan Li , Gao Wenbin , Liu Yunfeng , Zheng Caijuan , Zhang Yahui
Published: December 2021

From the marine-derived fungus Penicillium sumatrense (Trichocomaceae), a pair of enantiomers [(+)-1 and (−)-1] were isolated with identical 1D NMR data to drazepinone, which was originally reported to have a trisubstituted naphthofuroazepinone skeleton. In this study, we confirmed the structures of the two enantiomers as drazepinone and revised their structures by detailed analysis of extensive 2D NMR data and a comparison of the calculated 13C chemical shifts, ECD, VCD, and ORD spectra with those of the experiment ones. (+)-1 and (−)-1 were evaluated for their PTP inhibitory activity in vitro. (−)-1 showed selective PTP inhibitory activity against PTP1B and TCPTP with IC50 values of 1.56 and 12.5 μg/mL, respectively.
A Novel Agarase, Gaa16B, Isolated from the Marine Bacterium Gilvimarinus agarilyticus JEA5, and the Moisturizing Effect of Its Partial Hydrolysis Products
Authors: Lee Youngdeuk , Jo Eunyoung , Lee Yeon-Ju , Eom Tae-Yang , Gang Yehui , Kang Yoon-Hyeok , Marasinghe Svini Dileepa , Hettiarachchi Sachithra Amarin , Kang Do-Hyung , Oh Chulhong
Published: December 2021

We recently identified a β-agarase, Gaa16B, in the marine bacterium Gilvimarinus agarilyticus JEA5. Gaa16B, belonging to the glycoside hydrolase 16 family of β-agarases, shows less than 70.9% amino acid similarity with previously characterized agarases. Recombinant Gaa16B lacking the carbohydrate-binding region (rGaa16Bc) was overexpressed in Escherichia coli and purified. Activity assays revealed the optimal temperature and pH of rGaa16Bc to be 55 ∘C and pH 6–7, respectively, and the protein was highly stable at 55 ∘C for 90 min. Additionally, rGaa16Bc activity was strongly enhanced (2.3-fold) in the presence of 2.5 mM MnCl2. The Km and Vmax of rGaa16Bc for agarose were 6.4 mg/mL and 953 U/mg, respectively. Thin-layer chromatography analysis revealed that rGaa16Bc can hydrolyze agarose into neoagarotetraose and neoagarobiose. Partial hydrolysis products (PHPs) of rGaa16Bc had an average molecular weight of 88–102 kDa and exhibited > 60% hyaluronidase inhibition activity at a concentration of 1 mg/mL, whereas the completely hydrolyzed product (CHP) showed no hyaluronidase at the same concentration. The biochemical properties of Gaa16B suggest that it could be useful for producing functional neoagaro-oligosaccharides. Additionally, the PHP of rGaa16Bc may be useful in promoting its utilization, which is limited due to the gel strength of agar.