bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-Attentional Effects on Global Precedence Processing in Children with Autism Spectrum Disorder and Those with Typical Development on a Tablet-Based Modified Navon’s Paradigm Task
Authors: Ju Yumi , Kang Soyoung , Chung Jin-Wook , Ryu Jeh-Kwang
Published: January 2023

This study aimed to characterize the pre-attentional effects on global precedence processing in children with autism spectrum disorder (ASD) and those with typical development (TD). A sample of 17 participants, comprising eight children with ASD and nine TD children, were recruited for the study. A tablet-based assessment utilizing a global and local visual processing paradigm task was developed to investigate the participant’s abilities. The task consisted of verbal instructions to locate and touch either a global or local figure, presented in five conditions: neutral, congruent, and incongruent. The percentage of correct answers and reaction time (RT) for each task were measured and analyzed statistically. Results revealed that children with ASD exhibited statistically significant differences in both the percentage of correct scores and RT among various conditions, while TD children displayed differences in RT but not in the percentage of correct answers. These findings suggest that conflicting processes affect both behavioral and cognitive processes in children with ASD, and that cognitive effort is still involved for children with TD, but does not affect behavioral processes. In children with ASD, the RT was the shortest in the congruent (report local figure) condition; in children with TD, the RT was the shortest in the congruent (report global figure) condition. This implies that children with TD exhibit a pre-attentive effect on global precedence processing, while children with ASD do not. These visual-processing-function characteristics may aid in screening for visual perception problems in children with ASD.
Comparison of COVID-19 Severity in Vaccinated and Unvaccinated Patients during the Delta and Omicron Wave of the Pandemic in a Romanian Tertiary Infectious Diseases Hospital
Authors: Briciu Violeta , Topan Adriana , Calin Mihai , Dobrota Roxana , Leucuta Daniel-Corneliu , Lupse Mihaela
Published: January 2023

Romania has a poor uptake of COVID-19 vaccination in its population. The study objectives were to evaluate the differences between vaccinated and unvaccinated hospitalized COVID-19 patients with regard to disease severity, intensive care need, and mortality during the fourth and the fifth wave of the pandemic associated with the Delta and Omicron variants of concern. A retrospective study on a cohort of hospitalized COVID-19 patients was performed in a Romanian tertiary hospital for infectious diseases. Multivariate logistic regression models were built predicting severe/critical COVID-19, intensive care need, and death as a function of vaccination status and adjusted for age, comorbidities, and wave of the pandemic. 2235 COVID-19 patients were included, and vaccination status, as a primary vaccination or a booster dose, was described in 750 (33.5%). Unvaccinated patients were older, with more cardiovascular and endocrine diseases, a longer duration of hospitalization, a higher percentage of severe/critical COVID-19, need for intensive care, and death (p < 0.05). The multivariate logistic regression models adjusted for age and comorbidities showed higher odds ratio for severe/critical COVID-19, intensive care need, and mortality in unvaccinated versus vaccinated patients. Our results support vaccination to prevent severe outcomes associated with COVID-19 due to both variants of concern.
Impact of Endodontic Irrigant Activation on Smear Layer Removal and Surface Disintegration of Root Canal Dentine In Vitro
Authors: Widbiller Matthias , Rosendahl Andreas , Schlichting Ralf , Schuller Christine , Lingl Benedikt , Hiller Karl-Anton , Buchalla Wolfgang , Galler Kerstin M.
Published: January 2023

The objective of this study was to compare the ability of different endodontic irrigation activation methods to enable irrigant penetration, remove the smear layer from root canal walls after preparation, and investigate surface effects on dentine. Root canals of 90 single-rooted teeth were prepared and irrigated with EDTA (17%) and sodium hypochlorite (5%), where both irrigants or sodium hypochlorite only were activated as follows: conventional needle irrigation, ultrasonic activation, sonic activation (EDDY), or laser-based activation (photon-induced photoacoustic streaming/PIPS). For the evaluation of irrigant penetration into dentinal tubules, methylene blue was injected and activated as well. Subsequently, teeth were sectioned horizontally, and dye penetration depths were measured. Alternating sections were split in halves and randomly selected for scanning electron microscopic analysis. Root canal dentine was assessed for smear layer removal and surface disintegration according to a defined scoring system. The data were analyzed statistically with nonparametric and chi-squared tests for whole teeth and separately for coronal, middle, and apical thirds. All the tested activation methods removed a thicker smear layer than needle irrigation only. Additional activation of EDTA improved penetration depths of the irrigants, but not the smear layer removal. Surface disintegration of root canal dentine was observed with the additional activation of EDTA and particularly after laser-based techniques. Additional activation of EDTA does not seem to offer any convincing advantages in terms of irrigant penetration or smear layer removal but disrupts the dentine surface. Especially laser-based activation resulted in undesirable destruction of root canal wall dentine.
Improved Wireless Medical Cyber-Physical System (IWMCPS) Based on Machine Learning
Authors: Alzahrani Ahmad , Alshehri Mohammed , AlGhamdi Rayed , Sharma Sunil Kumar
Published: January 2023

Medical cyber-physical systems (MCPS) represent a platform through which patient health data are acquired by emergent Internet of Things (IoT) sensors, preprocessed locally, and managed through improved machine intelligence algorithms. Wireless medical cyber-physical systems are extensively adopted in the daily practices of medicine, where vast amounts of data are sampled using wireless medical devices and sensors and passed to decision support systems (DSSs). With the development of physical systems incorporating cyber frameworks, cyber threats have far more acute effects, as they are reproduced in the physical environment. Patients’ personal information must be shielded against intrusions to preserve their privacy and confidentiality. Therefore, every bit of information stored in the database needs to be kept safe from intrusion attempts. The IWMCPS proposed in this work takes into account all relevant security concerns. This paper summarizes three years of fieldwork by presenting an IWMCPS framework consisting of several components and subsystems. The IWMCPS architecture is developed, as evidenced by a scenario including applications in the medical sector. Cyber-physical systems are essential to the healthcare sector, and life-critical and context-aware health data are vulnerable to information theft and cyber-okayattacks. Reliability, confidence, security, and transparency are some of the issues that must be addressed in the growing field of MCPS research. To overcome the abovementioned problems, we present an improved wireless medical cyber-physical system (IWMCPS) based on machine learning techniques. The heterogeneity of devices included in these systems (such as mobile devices and body sensor nodes) makes them prone to many attacks. This necessitates effective security solutions for these environments based on deep neural networks for attack detection and classification. The three core elements in the proposed IWMCPS are the communication and monitoring core, the computational and safety core, and the real-time planning and administration of resources. In this study, we evaluated our design with actual patient data against various security attacks, including data modification, denial of service (DoS), and data injection. The IWMCPS method is based on a patient-centric architecture that preserves the end-user’s smartphone device to control data exchange accessibility. The patient health data used in WMCPSs must be well protected and secure in order to overcome cyber-physical threats. Our experimental findings showed that our model attained a high detection accuracy of 92% and a lower computational time of 13 sec with fewer error analyses.
Factors Influencing the Aged in the Use of Mobile Healthcare Applications: An Empirical Study in China
Authors: Wang Xiang , Lee Chang-Franw , Jiang Jiabei , Zhu Xiaoyang
Published: January 2023

Mobile healthcare applications are of significant potential value in the development of the aged-care industry due to their great convenience, high efficiency, and low cost. Since the cognition and utilization rates of mobile healthcare applications for the elderly are still low, this study explored the factors that affect the elderly’s adoption of mobile healthcare applications. This study conducted a questionnaire survey on the elderly in China and received 365 valuable responses. This study combined the technology acceptance model, protection motivation theory, and perceived risk theory to build a research model of factors affecting the use of mobile healthcare applications by the elderly. The data were analyzed using a structural equation model. The results were as follows: according to the empirical research, (1) perceived usefulness and perceived ease of use positively affect the use attitude of the elderly; perceived usefulness and user attitude positively affect the behavior intention of the elderly; perceived ease of use positively affects perceived usefulness; (2) perceived severity has a significant positive correlation with use attitude; perceived susceptibility and attitude to use have no significant impact; (3) perceived risk is negatively correlated with the use attitude and behavioral intention. The above-mentioned factors should be taken into consideration during the development of mobile healthcare applications for the aged to upgrade the overall service quality of mobile healthcare applications, thus enhancing the operational level of mobile healthcare applications and the health literacy of the aged.
Trend in STEAM Careers in the Depopulated Spain
Authors: Fernández-Arias Pablo , Sánchez-Jiménez María , Antón-Sancho Álvaro , Vergara Diego
Published: January 2023

Spain has a serious depopulation problem in large part of its territory and mainly in rural areas, where the population density is even lower than ten inhabitants per km2. An example of this depopulation phenomenon, known as “depopulated Spain”, is the region of Castilla y León. STEAM knowledge areas (Sciences, Technologies, Engineering, Art, and Mathematics) are essential to achieve the socio-economic growth of the territories and, with it, the desired population growth. Faced with this challenge, STEAM graduates can help to strengthen the industrial fabric and increase economic development. The main objectives of this research are the analysis (i) of the trend and (ii) of the gender gap in STEAM degrees and Ph.D. programs in Castilla y León. The evolution of the number of enrolled and graduated students in STEAM knowledge areas in the last years was analyzed to achieve these objectives, as well as the future trend. The results obtained showed a lack of STEAM graduates in Castilla y León, as well as the existence of a gender gap. Given this scenario, it is difficult to affirm the sustainability of the research, economic, and industrial systems in the region.
Studies on the Identification of Resistance to Fusarium oxysporum (Schlecht.) in Different Genetic Backgrounds of Asparagus officinalis (L.) and Its Defense Responses
Authors: Jacobi Julia , Budahn Holger , Nothnagel Thomas , König Janine
Published: January 2023

Due to the restricted genetic diversity among current asparagus cultivars, wild relatives are of particular interest as a source of resistance. In this study, seventeen cultivars and wild relatives were tested for their resistance to Fusarium oxysporum in the seedling test. Two isolates differing in virulence (single spore lines with high and low virulence) were used for testing. Most of the tested genotypes showed high infestation, whereby Asparagus aethiopicus caused no browning of the roots or growth depression. This wild relative was evaluated for its defence response after infection with F. oxysporum. For comparison, the wild relative Asparagus densiflorus and Asparagus officinalis cv. Thielim were tested. Like A. densiflorus, A. aethiopicus showed accumulation of hydrogen peroxide as a defence mechanism, while Asparagus officinalis cv. Thielim showed no storage of hydrogen compounds.
Impact of Foliar Application of Zinc and Zinc Oxide Nanoparticles on Growth, Yield, Nutrient Uptake and Quality of Tomato
Authors: Ahmed Razu , Uddin Md. Kamal , Quddus Md. Abdul , Samad Mohd Yusoff Abd , Hossain M. A. Motalib , Haque Ahmad Numery Ashfaqul
Published: January 2023

Appropriate foliar application of zinc (Zn) and zinc oxide nanoparticles (ZnO-NPs) is important for the proper growth and yield of tomato. However, the effects of foliar application of Zn and ZnO-NPs were not well-studied on tomato production. A pot experiment was conducted at glasshouse (8D) conditions under the Faculty of Agriculture, Universiti Putra Malaysia (UPM) to evaluate the effectiveness of Zn and ZnO-NPs on growth, yield, nutrient uptake, and fruit quality of tomatoes and to compare between the Zn nutrient and ZnO-NPs. Treatment combinations were 14 viz. T1 = 0 (control), T2 = 1500 ppm (mg/L) Zn nutrient, T3 = 2000 ppm (mg/L) Zn nutrient, T4 = 2500 ppm (mg/L) Zn nutrient, T5 = 75 ppm ZnO nanoparticle, T6 = 100 ppm ZnO nanoparticle, and T7 = 125 ppm ZnO nanoparticle along with two tomato varieties. The experimental design was a split plot with four replications. Results indicated that foliar application of 100 ppm ZnO-NPs performed best in terms of growth parameters, physiological traits, yield attributes, yield, and quality traits of tomatoes. The same treatment (100 ppm ZnO-NPs) contributed to attain the highest nutrient uptake. Recovery use efficiency of Zn was highest with foliar application of 75 ppm ZnO-NPs. The highest yield increment (200%) over control was from foliar sprayed with 100 ppm ZnO-NPs. Comparing the two varieties, MARDI Tomato-3 (MT3) showed better than MARDI Tomato-1 (MT1). As is appears from the results, foliar application of zinc oxide nanoparticles was more efficient than conventional zinc fertilizer. Therefore, the foliar sprayed with 100 ppm ZnO-NPs can be suggested to improve quantity and quality of tomato in glasshouse soil conditions.
Evaluation of Compost and Biochar as Partial Substitutes of Peat in Growing Media and Their Influence in Microbial Counts, Enzyme Activity and Lactuca sativa L. Seedling Growth
Authors: Rozas Amanda , Aponte Humberto , Maldonado Carlos , Contreras-Soto Rodrigo , Medina Jorge , Rojas Claudia
Published: January 2023

The main organic input for the elaboration of growing media is peat (Sphagnum spp.), due to its physical and chemical characteristics. However, the mining of this material creates a considerable impact in the local ecosystems from which this is obtained, along with a global impact because of the emission of greenhouse gasses. Thus, sustainable materials that can replace, or reduce the use of peat, while maintaining or improving attributes in the growing media and plant growth, are greatly needed. Therefore, this work aims to evaluate the effects of the use of different proportions of compost and biochar on the biological characteristics of growing media and (Lactuca sativa L.) seedling growth prior to transplanting. Out of the biological variables evaluated, the β-glucosidase activity showed the greatest results in growing media based on 80% peat and based on 70% peat, 5% compost and 5% biochar. Moreover, growing media based on the combination of compost, biochar and peat maintained most of the Lactuca sativa L. (Oak Leaf variety) seedling traits obtained in the growing media based on only peat. These findings emphasize the need to further investigate further biological conditions for alternative materials to peat, and the need to pay attention to feedstock initial characteristics and processing in order to obtain high quality organic inputs for optimum growing media.
The Parasitoid Hyposoter didymator Can Transmit a Broad Host Range Baculovirus in a Two Host System
Authors: Morel Ariel , Leigh Brendan , Muñoz Delia , Caballero Primitivo , Medina Pilar , Dáder Beatriz
Published: January 2023

Hyposoter didymator (Thunberg) (Hymenoptera: Ichneumonidae) and baculovirus (BV) might be used jointly to provide effective control of the Spodoptera genus. The literature has mostly covered the safe compatibility between natural enemies and BV-based insecticides, but research on the potential dispersal of BV by natural enemies is lacking. Thus, the goal of this manuscript was to ascertain if H. didymator was able to disperse the broad host range of Autographa californica nucleopolyhedrovirus (AcMNPV) to Spodoptera littoralis and Spodoptera exigua in choice and non-choice conditions and whether the preference of the parasitoid by one of these noctuids could mediate this dispersion. It was previously needed to improve the rearing of the parasitoid in the laboratory, concerning the optimal host age and length of parasitization, parasitoid competition, and influence of parasitization on the longevity of females. The best rearing conditions for S. littoralis are collective parasitization of mature L3 larvae for 24 h, after at least one day of copulation. Hyposoter didymator transmits AcMNPV to both lepidopterans, but its efficiency is mediated by host preference and the pathogenicity of the BV in each host. In this particular case, H. didymator as well as AcMNPV showed a clear preference towards S. exigua.
Behavior, Characteristics and Sources of Microplastics in Tea
Authors: Xing Daiman , Hu Yang , Sun Binmei , Song Fan , Pan Yiyu , Liu Shaoqun , Zheng Peng
Published: January 2023

Microplastics have become a widespread environmental concern because they are found in most tested places, including the air we breathe and the food and beverages we consume. To explore the current status of microplastic pollution and future research trends in tea, we reviewed the distribution, abundance, shape, size and sources of microplastics in tea. Microplastics are plastic particles that are 5 mm in diameter or less. Those found in tea and tea gardens originate from agricultural plastic films, plastic packaging of products and tools used in tea production, organic fertilizers, even atmospheric deposition. The microplastics in tea gardens are typically fragments and fibers, mainly composed of polyethylene, polypropylene and polyethylene terephthalate. The prevention and control of microplastics in tea planting, tea processing and packaging should be strengthened, and reduce the input of products containing microplastics. Future research on microplastic detection methods in tea and determination of safety thresholds should be prioritized to provide a reference for microplastic contamination risk, control, and management in tea.
Hydroalcoholic Extracts of Campomanesia lineatifolia R. & P. Seeds Inhibit the Germination of Rumex crispus and Amaranthus hybridus
Authors: Maestre Rodríguez Laura , Palacios Ortega Edgar , Moreno Medina Brigitte Liliana , Balaguera-López Helber Enrique , Hernandez Juan Pablo
Published: January 2023

This study explores how hydroalcoholic extracts of Campomanesia lineatifolia R. and P. seeds affect the germination and viability of seeds from two weeds, Rumex crispus and Amaranthus hybridus. The phenolic compounds were initially characterized using ultra-high-performance liquid chromatography. In seeds sown in Petri dishes, four concentrations of hydroalcoholic extracts (0%, 3%, 6%, and 9% w/v) were used for single and continuous applications. The mean germination speed, mean germination time, germination percentage, and seed viability were evaluated. Epigallocatechin gallate, quercetin-3-glucoside, epicatechin gallate, ursolic acid, epigallocatechin, and trans-cinnamic acid were the main compounds discovered in that order. Notably, while the germination percentages of both species were reduced with a single application (38.5% for R. crispus and 52% for A. hybridus), they were reduced by 76.2% and 58.34% with a continuous application, respectively. A delay in germination was also observed, which produced changes in germination speed throughout the experiment. With a 9% application, the number of nonviable seeds of R. crispus increased by 40.53%, whereas in A. hybridus, viability decreased by at least 70.8%. Overall, the phenolic compounds in C. lineatifolia extract are thought to inhibit the germination process of the evaluated species.
A Qualitative Assessment of River Plumes Coupling SWAT Model Simulations and a Beach Optical Monitoring System
Authors: Joumar Nada , Nabih Soumaya , Chatzipavlis Antonis , Velegrakis Adonis , Hasiotis Thomas , Tzoraki Ourania , Stitou El Messari Jamal Eddine , Benaabidate Lahcen
Published: January 2023

The study of plumes occurring at the mouth of small rivers of temporal flow is a challenging task due to the lack of sedimentological and flow data of appropriate spatiotemporal scales. The present contribution examined the case of a typical un-gauged intermittent Mediterranean stream located in Northern Crete (Xiropotamos river). The SWAT (soil and water assessment tool) model was used to simulate and reproduce the hydrological behavior of the adjacent intermittent (Giofyros) river discharging at the same beach, the basin of which has the same geomorphological and hydrological characteristics. The output of the calibrated SWAT model was used to simulate daily flow data for the year 2014. The results were then considered together with the results of the RGB analysis of optical datasets of high spatio-temporal resolution for the same period, derived from a beach optical monitoring system (BOMS). The RGB analysis of the optical (TIMEX) imagery was shown to be a useful technique to identify and classify coastal plumes by using the spatio-temporal variability of pixel properties. The technique was also shown to be useful for the (qualitative) validation of the SWAT output and could be further improved by the collection of ‘ground truth’ data.
Increasing Income Generation: The Role of Staff Participation and Awareness
Authors: Mahmud Amir , Susilowati Nurdian , Anisykurlillah Indah , Sari Puji Novita
Published: January 2023

The policy of educational autonomy through legal entity state universities is a very interesting issue. Universities have the authority to manage finances and collect additional income, specifically generated income. Its successful implementation also provides more significant income to everyone in the institution through greater incentives, thereby helping to improve the economic conditions of staff, institutions, and all academics. This study examines the empirical evidence of factors influencing university income-generating performance. This study presents the direct and indirect effects of staff awareness, staff participation, and top management support on income-generating performance. This research used a quantitative approach utilizing the structural equation model with WarpPLS. A questionnaire-based survey collected 111 valid responses. Surveys were distributed to the appointed persons in charge of each unit, faculty, and university. The results show that staff awareness influences top management support. Top management support also affects income-generating performance, so it impacts the role of top management support, which can mediate the influence of managers’ awareness on income-generating performance. On the other hand, staff participation cannot influence top management support and income-generating performance. This means that top management support cannot mediate the effect of staff participation on income-generating performance.
SABRE Hyperpolarization with up to 200 bar Parahydrogen in Standard and Quickly Removable Solvents
Authors: Duchowny Anton , Denninger Johannes , Lohmann Lars , Theis Thomas , Lehmkuhl Sören , Adams Alina
Published: January 2023

Parahydrogen (p-H2)-based techniques are known to drastically enhance NMR signals but are usually limited by p-H2 supply. This work reports p-H2-based SABRE hyperpolarization at p-H2 pressures of hundreds of bar, far beyond the typical ten bar currently reported in the literature. A recently designed high-pressure setup was utilized to compress p-H2 gas up to 200 bar. The measurements were conducted using a sapphire high-pressure NMR tube and a 43 MHz benchtop NMR spectrometer. In standard methanol solutions, it could be shown that the signal intensities increased with pressure until they eventually reached a plateau. A polarization of about 2%, equal to a molar polarization of 1.2 mmol L−1, could be achieved for the sample with the highest substrate concentration. While the signal plateaued, the H2 solubility increased linearly with pressure from 1 to 200 bar, indicating that p-H2 availability is not the limiting factor in signal enhancement beyond a certain pressure, depending on sample composition. Furthermore, the possibility of using liquefied ethane and compressed CO2 as removable solvents for hyperpolarization was demonstrated. The use of high pressures together with quickly removable organic/non-organic solvents represents an important breakthrough in the field of hyperpolarization, advancing SABRE as a promising tool for materials science, biophysics, and molecular imaging.
Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance
Authors: Zerlotin Roberta , Fornaro Marco , Errede Mariella , Pignataro Patrizia , Suriano Clelia , Ruggieri Maddalena , Colucci Silvia , Iannone Florenzo , Grano Maria , Colaianni Graziana
Published: January 2023

Dermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM) are two rare diseases belonging to the group of idiopathic inflammatory myopathies (IIM). Muscle involvement in DM is characterized by perifascicular atrophy and poor myofiber necrosis, while IMNM is characterized by myofiber necrosis with scarce inflammatory infiltrates. Muscle biopsies and laboratory tests are helpful in diagnosis, but currently, few biomarkers of disease activity and progression are available. In this context, we conducted a cohort study of forty-one DM and IMNM patients, aged 40–70 years. In comparison with control subjects, in the muscle biopsies of these patients, there was a lower expression of FNDC5, the precursor of irisin, a myokine playing a key role in musculoskeletal metabolism. Expectedly, the muscle cross-sectional areas of these patients were reduced, while, surprisingly, serum irisin levels were higher than in CTRL, as were mRNA levels of ADAM10, a metalloproteinase recently shown to be the cleavage agent for FNDC5. We hypothesize that elevated expression of ADAM10 in the skeletal muscle of DM and IMNM patients might be responsible for the discrepancy between irisin levels and FNDC5 expression. Future studies will be needed to understand the mechanisms underlying exacerbated FNDC5 cleavage and muscle irisin resistance in these inflammatory myopathies.
Mechanical Properties of Twisted Carbon Nanotube Bundles with Carbon Linkers from Molecular Dynamics Simulations
Authors: Pedrielli Andrea , Dapor Maurizio , Gkagkas Konstantinos , Taioli Simone , Pugno Nicola Maria
Published: January 2023

The manufacturing of high-modulus, high-strength fibers is of paramount importance for real-world, high-end applications. In this respect, carbon nanotubes represent the ideal candidates for realizing such fibers. However, their remarkable mechanical performance is difficult to bring up to the macroscale, due to the low load transfer within the fiber. A strategy to increase such load transfer is the introduction of chemical linkers connecting the units, which can be obtained, for example, using carbon ion-beam irradiation. In this work, we investigate, via molecular dynamics simulations, the mechanical properties of twisted nanotube bundles in which the linkers are composed of interstitial single carbon atoms. We find a significant interplay between the twist and the percentage of linkers. Finally, we evaluate the suitability of two different force fields for the description of these systems: the dihedral-angle-corrected registry-dependent potential, which we couple for non-bonded interaction with either the AIREBO potential or the screened potential ReboScr2. We show that both of these potentials show some shortcomings in the investigation of the mechanical properties of bundles with carbon linkers.
The Journey of Mitochondrial Protein Import and the Roadmap to Follow
Authors: Haastrup Mary Oluwadamilola , Vikramdeo Kunwar Somesh , Singh Seema , Singh Ajay Pratap , Dasgupta Santanu
Published: January 2023

Mitochondria are double membrane-bound organelles that play critical functions in cells including metabolism, energy production, regulation of intrinsic apoptosis, and maintenance of calcium homeostasis. Mitochondria are fascinatingly equipped with their own genome and machinery for transcribing and translating 13 essential proteins of the oxidative phosphorylation system (OXPHOS). The rest of the proteins (99%) that function in mitochondria in the various pathways described above are nuclear-transcribed and synthesized as precursors in the cytosol. These proteins are imported into the mitochondria by the unique mitochondrial protein import system that consists of seven machineries. Proper functioning of the mitochondrial protein import system is crucial for optimal mitochondrial deliverables, as well as mitochondrial and cellular homeostasis. Impaired mitochondrial protein import leads to proteotoxic stress in both mitochondria and cytosol, inducing mitochondrial unfolded protein response (UPRmt). Altered UPRmt is associated with the development of various disease conditions including neurodegenerative and cardiovascular diseases, as well as cancer. This review sheds light on the molecular mechanisms underlying the import of nuclear-encoded mitochondrial proteins, the consequences of defective mitochondrial protein import, and the pathological conditions that arise due to altered UPRmt.
A Comparative Study between Lycorine and Galantamine Abilities to Interact with AMYLOID β and Reduce In Vitro Neurotoxicity
Authors: Kola Arian , Lamponi Stefania , Currò Francesco , Valensin Daniela
Published: January 2023

Galantamine is a natural alkaloid extracted from the Amaryllidaceae plants and is used as the active ingredient of a drug approved for the treatment of the early stages of Alzheimer’s disease. It mainly acts as an acetylcholinesterase (AChE) inhibitor, increasing concentrations of the acetylcholine neurotransmitter. Recent cellular studies have also shown the ability of galantamine to protect SH-SY5Y cell lines against amyloid-β (Aβ)-induced toxicity. Such investigations have supported and validated further in-depth studies for understanding the chemical and molecular features associated with galantamine-protective abilities. In addition to galantamine, other natural alkaloids are known to possess AChE inhibitory activity; among them lycorine has been extensively investigated for its antibacterial, anti-inflammatory and antitumoral activities as well. Despite its interesting biological properties, lycorine’s neuroprotective functions against Aβ-induced damages have not been explored so far. In this research study, the ability of galantamine and lycorine to suppress Aβ-induced in vitro neuronal toxicity was evaluated by investigating the chemical interactions of the two alkaloids with Aβ peptide. A multi-technique spectroscopic analysis and cellular cytotoxicity assays were applied to obtain new insights on these molecular associations. The comparison between the behaviors exhibited by the two alkaloids indicates that both compounds possess analogue abilities to interact with the amyloidogenic peptide and protect cells.
TRPA1 as Target in Myocardial Infarction
Authors: Hoebart Clara , Kiss Attila , Pilz Patrick M. , Szabo Petra L. , Podesser Bruno K. , Fischer Michael J. M. , Heber Stefan
Published: January 2023

Transient receptor potential cation channel subfamily A member 1 (TRPA1), an ion channel primarily expressed on sensory neurons, can be activated by substances occurring during myocardial infarction. Aims were to investigate whether activation, inhibition, or absence of TRPA1 affects infarcts and to explore underlying mechanisms. In the context of myocardial infarction, rats received a TRPA1 agonist, an antagonist, or vehicle at different time points, and infarct size was assessed. Wild type and TRPA1 knockout mice were also compared in this regard. In vitro, sensory neurons were co-cultured with cardiomyocytes and subjected to a model of ischemia-reperfusion. Although there was a difference between TRPA1 activation or inhibition in vivo, no experimental group was different to control animals in infarct size, which also applies to animals lacking TRPA1. In vitro, survival probability of cardiomyocytes challenged by ischemia-reperfusion increased from 32.8% in absence to 45.1% in presence of sensory neurons, which depends, at least partly, on TRPA1. This study raises doubts about whether TRPA1 is a promising target to reduce myocardial damage within a 24 h period. The results are incompatible with relevant enlargements of infarcts by TRPA1 activation or inhibition, which argues against adverse effects when TRPA1 is targeted for other indications.
Annotation-Free Deep Learning-Based Prediction of Thyroid Molecular Cancer Biomarker BRAF (V600E) from Cytological Slides
Authors: Wang Ching-Wei , Muzakky Hikam , Lee Yu-Ching , Lin Yi-Jia , Chao Tai-Kuang
Published: January 2023

Thyroid cancer is the most common endocrine cancer. Papillary thyroid cancer (PTC) is the most prevalent form of malignancy among all thyroid cancers arising from follicular cells. Fine needle aspiration cytology (FNAC) is a non-invasive method regarded as the most cost-effective and accurate diagnostic method of choice in diagnosing PTC. Identification of BRAF (V600E) mutation in thyroid neoplasia may be beneficial because it is specific for malignancy, implies a worse prognosis, and is the target for selective BRAF inhibitors. To the authors’ best knowledge, this is the first automated precision oncology framework effectively predict BRAF (V600E) immunostaining result in thyroidectomy specimen directly from Papanicolaou-stained thyroid fine-needle aspiration cytology and ThinPrep cytological slides, which is helpful for novel targeted therapies and prognosis prediction. The proposed deep learning (DL) framework is evaluated on a dataset of 118 whole slide images. The results show that the proposed DL-based technique achieves an accuracy of 87%, a precision of 94%, a sensitivity of 91%, a specificity of 71% and a mean of sensitivity and specificity at 81% and outperformed three state-of-the-art deep learning approaches. This study demonstrates the feasibility of DL-based prediction of critical molecular features in cytological slides, which not only aid in accurate diagnosis but also provide useful information in guiding clinical decision-making in patients with thyroid cancer. With the accumulation of data and the continuous advancement of technology, the performance of DL systems is expected to be improved in the near future. Therefore, we expect that DL can provide a cost-effective and time-effective alternative tool for patients in the era of precision oncology.
Comparison between Sickle Cell Disease Patients and Healthy Donors: Untargeted Lipidomic Study of Erythrocytes
Authors: Alabed Husam B. R. , Gorello Paolo , Pellegrino Roberto Maria , Lancioni Hovirag , La Starza Roberta , Taddei Anna Aurora , Urbanelli Lorena , Buratta Sandra , Fernandez Anair Graciela Lema , Matteucci Caterina , Caniglia Maurizio , Arcioni Francesco , Mecucci Cristina , Emiliani Carla
Published: January 2023

Sickle cell disease (SCD) is one of the most common severe monogenic disorders in the world caused by a mutation on HBB gene and characterized by hemoglobin polymerization, erythrocyte rigidity, vaso-occlusion, chronic anemia, hemolysis, and vasculopathy. Recently, the scientific community has focused on the multiple genetic and clinical profiles of SCD. However, the lipid composition of sickle cells has received little attention in the literature. According to recent studies, changes in the lipid profile are strongly linked to several disorders. Therefore, the aim of this study is to dig deeper into lipidomic analysis of erythrocytes in order to highlight any variations between healthy and patient subjects. 241 lipid molecular species divided into 17 classes have been annotated and quantified. Lipidomic profiling of SCD patients showed that over 24% of total lipids were altered most of which are phospholipids. In-depth study of significant changes in lipid metabolism can give an indication of the enzymes and genes involved. In a systems biology scenario, these variations can be useful to improve the understanding of the biochemical basis of SCD and to try to make a score system that could be predictive for the severity of clinical manifestations.
Mathematical Optimisation of Magnetic Nanoparticle Diffusion in the Brain White Matter
Authors: Yuan Tian , Yang Yi , Zhan Wenbo , Dini Daniele
Published: January 2023

Magnetic nanoparticles (MNPs) are a promising drug delivery system to treat brain diseases, as the particle transport trajectory can be manipulated by an external magnetic field. However, due to the complex microstructure of brain tissues, particularly the arrangement of nerve fibres in the white matter (WM), how to achieve desired drug distribution patterns, e.g., uniform distribution, is largely unknown. In this study, by adopting a mathematical model capable of capturing the diffusion trajectories of MNPs, we conducted a pilot study to investigate the effects of key parameters in the MNP delivery on the particle diffusion behaviours in the brain WM microstructures. The results show that (i) a uniform distribution of MNPs can be achieved in anisotropic tissues by adjusting the particle size and magnetic field; (ii) particle size plays a key role in determining MNPs’ diffusion behaviours. The magnitude of MNP equivalent diffusivity is reversely correlated to the particle size. The MNPs with a dimension greater than 90 nm cannot reach a uniform distribution in the brain WM even in an external magnitude field; (iii) axon tortuosity may lead to transversely anisotropic MNP transport in the brain WM; however, this effect can be mitigated by applying an external magnetic field perpendicular to the local axon track. This study not only advances understanding to answer the question of how to optimise MNP delivery, but also demonstrates the potential of mathematical modelling to help achieve desired drug distributions in biological tissues with a complex microstructure.
NMDA Receptor and Its Emerging Role in Cancer
Authors: Gallo Simona , Vitacolonna Annapia , Crepaldi Tiziana
Published: January 2023

Glutamate is a key player in excitatory neurotransmission in the central nervous system (CNS). The N-methyl-D-aspartate receptor (NMDAR) is a glutamate-gated ion channel which presents several unique features and is involved in various physiological and pathological neuronal processes. Thanks to great efforts in neuroscience, its structure and the molecular mechanisms controlling its localization and functional regulation in neuronal cells are well known. The signaling mediated by NMDAR in neurons is very complex as it depends on its localization, composition, Ca2+ influx, and ion flow-independent conformational changes. Moreover, NMDA receptors are highly diffusive in the plasma membrane of neurons, where they form heterocomplexes with other membrane receptors and scaffold proteins which determine the receptor function and activation of downstream signaling. Interestingly, a recent paper demonstrates that NMDAR signaling is involved in epithelial cell competition, an evolutionary conserved cell fitness process influencing cancer initiation and progress. The idea that NMDAR signaling is limited to CNS has been challenged in the past two decades. A large body of evidence suggests that NMDAR is expressed in cancer cells outside the CNS and can respond to the autocrine/paracrine release of glutamate. In this review, we survey research on NMDAR signaling and regulation in neurons that can help illuminate its role in tumor biology. Finally, we will discuss existing data on the role of the glutamine/glutamate metabolism, the anticancer action of NMDAR antagonists in experimental models, NMDAR synaptic signaling in tumors, and clinical evidence in human cancer.
Dalbavancin Boosts the Ability of Neutrophils to Fight Methicillin-Resistant Staphylococcus aureus
Authors: Scutera Sara , Sparti Rosaria , Comini Sara , Menotti Francesca , Musso Tiziana , Cuffini Anna Maria , Allizond Valeria , Banche Giuliana
Published: January 2023

Polymorphonuclear leukocytes (PMNs) are the most important cell type involved in the early nonspecific host response to bacterial pathogens. Staphylococcus aureus has evolved mechanisms to evade immune responses that contribute to its persistence in PMNs, and acquired resistance to several antimicrobials. Additionally, methicillin-resistant S. aureus (MRSA) is one of the most common causes of acute bacterial skin and skin-structure infections (ABSSSIs). Dalbavancin (DBV), a lipoglycopeptide, is indicated for the treatment of ABSSSIs, and has a broad spectrum of action against most microorganisms. Here, we sought to determine the effect of DBV on the neutrophil killing of MRSA and its potential immunomodulating activity. Our results revealed that DBV boosts MRSA killing by acting on both bacteria and PMNs. DBV pre-treatment of PMNs did not change the respiratory burst or degranulation, while an increased trend in neutrophil extracellular traps-associated elastase and in the production of TNFα and CXCL8 was revealed. In parallel, DBV caused a delay in the apoptosis of MRSA-infected neutrophils. In conclusion, we demonstrated a cooperative effect between the antimicrobial properties of PMNs and DBV, thus owing to their immunomodulatory activity. In the choice of the treatment management of serious S. aureus infections, DBV should be considered as an outstanding option since it reinforces PMNs pathogen clearance capability by exerting its effect directly, not only on MRSA but also on neutrophils.
Genome-Wide Identification and Posttranscriptional Regulation Analyses Elucidate Roles of Key Argonautes and Their miRNA Triggers in Regulating Complex Yield Traits in Rapeseed
Authors: Zhang Liyuan , Yang Bo , Zhang Chao , Chen Huan , Xu Jinxiong , Qu Cunmin , Lu Kun , Li Jiana
Published: January 2023

Argonautes (AGOs) interact with microRNAs (miRNAs) to form the RNA-induced silencing complex (RISC), which can posttranscriptionally regulate the expression of targeted genes. To date, however, the AGOs and their miRNA triggers remain elusive in rapeseed (Brassica napus). Here, we systematically performed a phylogenetic analysis and examined the collinear relationships of the AGOs among four Brassicaceae species. Their physicochemical properties, gene structures, and expression patterns among 81 tissues from multiple materials and developmental stages were further analyzed. Additionally, their posttranscriptional regulation was analyzed using psRNATarget prediction, miRNA-/mRNA-Seq analyses, and a qRT-PCR verification. We finally identified 10 AtAGOs, 13 BolAGOs, 11 BraAGOs, and 24 BnaAGOs. An expression analysis of the BnaAGOs in the B. napus cultivar ZS11, as well as genotypes with extreme phenotypes in various yield-related traits, revealed the conservation and diversity of these genes. Furthermore, we speculated the posttranscriptional regulation of the B. napus miR168a–AGO1s and miR403–AGO2s modules. Combining miRNA-Seq and mRNA-Seq analyses, we found that the B. napus miR168a–AGO1s module may play an essential role in negatively regulating yield traits, whereas the miR403–AGO2s module positively impacts yield. This is the first attempt to comprehensively analyze the AGOs and their miRNA triggers in B. napus and provides a theoretical basis for breeding high-yielding varieties through the manipulation of the miRNA–AGOs modules.
Characterization of Stress Granule Protein Turnover in Neuronal Progenitor Cells Using Correlative STED and NanoSIMS Imaging
Authors: Rabasco Stefania , Lork Alicia A. , Berlin Emmanuel , Nguyen Tho D. K. , Ernst Carl , Locker Nicolas , Ewing Andrew G. , Phan Nhu T. N.
Published: January 2023

Stress granules (SGs) are stress-induced biomolecular condensates which originate primarily from inactivated RNA translation machinery and translation initiation factors. SG formation is an important defensive mechanism for cell survival, while its dysfunction has been linked to neurodegenerative diseases. However, the molecular mechanisms of SG assembly and disassembly, as well as their impacts on cellular recovery, are not fully understood. More thorough investigations into the molecular dynamics of SG pathways are required to understand the pathophysiological roles of SGs in cellular systems. Here, we characterize the SG and cytoplasmic protein turnover in neuronal progenitor cells (NPCs) under stressed and non-stressed conditions using correlative STED and NanoSIMS imaging. We incubate NPCs with isotopically labelled (15N) leucine and stress them with the ER stressor thapsigargin (TG). A correlation of STED and NanoSIMS allows the localization of individual SGs (using STED), and their protein turnover can then be extracted based on the 15N/14N ratio (using NanoSIMS). We found that TG-induced SGs, which are highly dynamic domains, recruit their constituents predominantly from the cytoplasm. Moreover, ER stress impairs the total cellular protein turnover regimen, and this impairment is not restored after the commonly proceeded stress recovery period.
Investigation of Glucose–Water Mixtures as a Function of Concentration and Temperature by Infrared Spectroscopy
Authors: Caccamo Maria Teresa , Magazù Salvatore
Published: January 2023

The main aim of the present paper is to characterize the hydration properties of glucose and the hydrogen bond network in glucose–water mixtures. For these purposes, temperature scans on ten concentration values of glucose–water mixtures were performed by means of Fourier Transform InfraRed (FTIR) spectroscopy. More specifically, in order to get this information an analysis of the intramolecular OH stretching mode, investigating the 3000–3700 cm−1 spectral range, was performed by means of an innovative approach based on the evaluation of the Spectral Distance (SD). The adopted procedure allows evaluating the glucose hydration number as well as characterizing the temperature behavior of the hydrogen bond network in the glucose–water mixtures. The obtained results for the hydration number are in excellent agreement with literature data and suggest the existence of a particular concentration value for which the hydrogen bond network shows a maximum strength.