bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-COVID Symptoms in Occupational Cohorts: Effects on Health and Work Ability
Authors: Magnavita Nicola , Arnesano Gabriele , Di Prinzio Reparata Rosa , Gasbarri Martina , Meraglia Igor , Merella Marco , Vacca Maria Eugenia
Published: April 2023

Post-acute COVID-19 syndrome is frequently observed in workers and has a substantial impact on work ability. We conducted a health promotion program to identify cases of post-COVID syndrome, analyze the distribution of symptoms and their association with work ability. Of the 1422 workers who underwent routine medical examination in 2021, 1378 agreed to participate. Among the latter, 164 had contracted SARS-CoV-2 and 115 (70% of those who were infected) had persistent symptoms. A cluster analysis showed that most of the post-COVID syndrome cases were characterized by sensory disturbances (anosmia and dysgeusia) and fatigue (weakness, fatigability, tiredness). In one-fifth of these cases, additional symptoms included dyspnea, tachycardia, headache, sleep disturbances, anxiety, and muscle aches. Workers with post-COVID were found to have poorer quality sleep, increased fatigue, anxiety, depression, and decreased work ability compared with workers whose symptoms had rapidly disappeared. It is important for the occupational physician to diagnose post-COVID syndrome in the workplace since this condition may require a temporary reduction in work tasks and supportive treatment.
An Evaluation of Community Health Workers’ Knowledge, Attitude and Personal Lifestyle Behaviour in Non-Communicable Disease Health Promotion and Their Association with Self-Efficacy and NCD-Risk Perception
Authors: Yenit Melaku Kindie , Kolbe-Alexander Tracy L. , Gelaye Kassahun Alemu , Gezie Lemma Derseh , Tesema Getayeneh Antehunegn , Abebe Solomon Mekonnen , Azale Telake , Shitu Kegnie , Gyawali Prajwal
Published: April 2023

Community health workers, also known as health extension workers (HEWs), play an important role in health promotion. This study evaluates HEWs’ knowledge, attitude, and self-efficacy for non-communicable diseases (NCD) health promotion. HEWs (n = 203) completed a structured questionnaire on knowledge, attitude, behaviour, self-efficacy and NCD risk perception. Regression analysis was used to determine the association between self-efficacy and NCD risk perception with knowledge (high, medium, low), attitude (favourable/unfavourable) and physical activity (sufficient/insufficient). HEWs with higher self-efficacy were more likely to have high NCD knowledge (AOR: 2.21; 95% CI: 1.21. 4.07), favourable attitude towards NCD health promotion (AOR: 6.27; 95% CI: 3.11. 12.61) and were more physically active (AOR: 2.27; 95% CI: 1.08. 4.74) than those with lower self-efficacy. HEWs with higher NCD susceptibility (AOR: 1.89; 95% CI: 1.04. 3.47) and perceived severity (AOR: 2.69; 95% CI: 1.46, 4.93) had higher odds of NCD knowledge than their counterparts. Moreover, sufficient physical activity was influenced by HEWs’ perceived NCD susceptibility and perceived benefits of lifestyle change. Therefore, HEWs need to adopt healthy lifestyle choices to become effective role models for the community. Our findings highlight the need to include a healthy lifestyle when training HEWs, which might increase self-efficacy for NCD health promotion.
Group-Based Patterns of Life Satisfaction and Functional Independence over the 10 Years after Traumatic Brain Injury in Older Adults: A Model Systems Study
Authors: Tyler Carmen M. , Dini Mia E. , Perrin Paul B.
Published: April 2023

Background: Older adults who sustain a traumatic brain injury (TBI) have been shown to have reduced functional independence and life satisfaction relative to younger individuals with TBI. The purpose of this study was to examine the covarying patterns of functional independence and life satisfaction over the 10 years after TBI in adults who were 60 years of age or older upon injury. Method: Participants were 1841 individuals aged 60 or older at the time of TBI, were enrolled in the longitudinal TBI Model Systems database, and had Functional Independence Measure and Satisfaction with Life Scale scores during at least one time point at 1, 2, 5, and 10 years after TBI. Results: A k-means cluster analysis identified four distinct group-based longitudinal patterns of these two variables. Three cluster groups suggested that functional independence and life satisfaction generally traveled together over time, with one group showing relatively high functional independence and life satisfaction over time (Cluster 2), one group showing relatively moderate functional independence and life satisfaction (Cluster 4), and one group showing relatively low functional independence and life satisfaction (Cluster 1). Cluster 3 had relatively high functional independence over time but, nonetheless, relatively low life satisfaction; they were also the youngest group upon injury. Participants in Cluster 2 generally had the highest number of weeks of paid competitive employment but lower percentages of underrepresented racial/ethnic minority participants, particularly Black and Hispanic individuals. Women were more likely to be in the cluster with the lowest life satisfaction and functional independence (Cluster 1). Conclusion: Functional independence and life satisfaction generally accompany one another over time in older adults, although this does not always occur, as life satisfaction can still be low in a subgroup of older individuals after TBI with higher functioning. These findings contribute to a better understanding of post-TBI recovery patterns in older adults over time that may inform treatment considerations to improve age-related discrepancies in rehabilitation outcomes.
Personality Traits and Coping Strategies as Psychological Factors Associated with Health-Related Quality of Life in Highly Sensitive Persons
Authors: Pérez-Chacón Manuela , Borda-Mas Mercedes , Chacón Antonio , Avargues-Navarro María Luisa
Published: April 2023

Sensory-Processing Sensitivity (SPS) is the reactivity to different stimuli that occurs in some people with sufficient intensity to cause interference in daily life. There are not many previous studies that determine the influence of adaptive and maladaptive coping strategies on health-related quality of life through indicators of mental (anxiety and depression) and physical (vitality) health and functioning in their lives in different contexts (emotional role functioning). In this sense, contexts that promote the use of successful stress-coping strategies are related to the presence of positive mental health outcomes. This study focuses on the analysis of indicators of health-related quality of life in people with SPS in relation to certain personality traits and coping strategies. Participants (N = 10,525) completed HSPS-S, NEO-FFI, CSI, and SF-36. Differences were observed between men and women. Differences indicated that women had higher SPS scores compared to men and poorer health-related quality of life. The results showed significant relationships with the three indicators of health-related quality of life. Finally, it is confirmed that neuroticism and the use of maladaptive coping strategies act as risk factors, whereas extraversion, conscientiousness, and adaptive coping strategies act as protective factors. These findings highlight the need to develop prevention programs for highly sensitive persons.
Non-Performing Loans and Net Interest Margin in the MENA Region: Linear and Non-Linear Analyses
Authors: Alnabulsi Khalil , Kozarević Emira , Hakimi Abdelaziz
Published: April 2023

This paper analyzes the linear and non-linear relationship between non-performing loans and bank profitability measured by the Net Interest Margin for a sample of 74 Middle Eastern and North African banks over the period of 2005–2020. We used the System Generalized Method of Moments (SGMM) as a linear approach and the Panel Smooth Transition Regression (PSTR) model as a non-linear approach. The empirical results of the SGMM approach indicated that the ratio of NPLs negatively affects bank profitability. The findings of the non-linear relationship based on the PSTR model confirmed the existence of a threshold effect. We found that below the threshold of 4.42%, the effect of NPLs is negative but not significant, while after surpassing this threshold, the effect becomes negative and significant. As for bank specifics, we revealed that bank size is positively and significantly associated with bank profitability. For industry factors, we found that more bank concentration decreases bank profitability. Regarding the financial environment, we concluded that the global financial crisis exerted a negative impact on bank profitability. Moreover, we revealed a positive and significant impact of GDP on bank profitability as well as a negative impact of inflation on bank profitability. This study has some limitations regarding the social, economic, and financial differences of the whole sample, which includes banks from the Middle East and others from North Africa. Hence, decomposing the whole sample into two sub-samples could improve the results of this paper.
MAC-GAN: A Community Road Generation Model Combining Building Footprints and Pedestrian Trajectories
Authors: Yang Lin , Wei Jing , Zuo Zejun , Zhou Shunping
Published: April 2023

Community roads are crucial to community navigation. There are automatic methods to obtain community roads using trajectories, but the sparsity and uneven density distribution of community trajectories present significant challenges in identifying community roads. To overcome these challenges, we propose a conditional generative adversarial network (MAC-GAN) supervised by pedestrian trajectories and neighborhood building footprints for road generation. MAC-GAN packs the “road trajectory–building footprint” pairs into images to characterize implicit ternary relations and sets up a multi-scale skip-connected and asymmetric convolution-based generator to incorporate such a relationship, in which the generator and discriminator mutually learn to optimize the network parameters and then derive approximate optimal results. Experiments on 37 real-world community datasets in Wuhan, China, are conducted to verify the effectiveness of the proposed model. The experimental results show that the F1 score of our model increases by 1.7–6.8%, and the IOU of our model increases by 2.2–7.5% compared with three baselines (i.e., Pix2pix, GANmapper, and DLinkGAN (configured by DLinknet)). In areas with sparse and missing trajectory data, the generated fine roads have high accuracy with the supervision of building footprints.
The Use of Decision Support in Search and Rescue: A Systematic Literature Review
Authors: Nasar Wajeeha , Da Silva Torres Ricardo , Gundersen Odd Erik , Karlsen Anniken T.
Published: April 2023

Whenever natural and human-made disasters strike, the proper response of the concerned authorities often relies on search and rescue services. Search and rescue services are complex multidisciplinary processes that involve several degrees of interdependent assignments. To handle such complexity, decision support systems are used for decision-making and execution of plans within search and rescue operations. Advances in data management solutions and artificial intelligence technologies have provided better opportunities to make more efficient and effective decisions that can lead to improved search and rescue operations. This paper provides findings from a bibliometric mapping and a systematic literature review performed to: (1) identify existing search and rescue processes that use decision support systems, data management solutions, and artificial intelligence technologies; (2) do a comprehensive analysis of existing solutions in terms of their research contributions to the investigated domain; and (3) investigate the potential for knowledge transfer between application areas. The main findings of this review are that non-conventional data management solutions are commonly used in land rescue operations and that geographical information systems have been integrated with various machine learning approaches for land rescue. However, there is a gap in the existing research on search and rescue decision support at sea, which can motivate future studies within this specific application area.
Atorvastatin Attenuates Diet-Induced Non-Alcoholic Steatohepatitis in APOE*3-Leiden Mice by Reducing Hepatic Inflammation
Authors: Inia José A. , Stokman Geurt , Pieterman Elsbet J. , Morrison Martine C. , Menke Aswin L. , Verschuren Lars , Caspers Martien P. M. , Giera Martin , Jukema J. Wouter , van den Hoek Anita M. , Princen Hans M. G.
Published: April 2023

Patients with metabolic syndrome are often prescribed statins to prevent the development of cardiovascular disease. Conversely, data on their effects on non-alcoholic steatohepatitis (NASH) are lacking. We evaluated these effects by feeding APOE*3-Leiden mice a Western-type diet (WTD) with or without atorvastatin to induce NASH and hepatic fibrosis. Besides the well-known plasma cholesterol lowering (−30%) and anti-atherogenic effects (severe lesion size −48%), atorvastatin significantly reduced hepatic steatosis (−22%), the number of aggregated inflammatory cells in the liver (−80%) and hepatic fibrosis (−92%) compared to WTD-fed mice. Furthermore, atorvastatin-treated mice showed less immunohistochemically stained areas of inflammation markers. Atorvastatin prevented accumulation of free cholesterol in the form of cholesterol crystals (−78%). Cholesterol crystals are potent inducers of the NLRP3 inflammasome pathway and atorvastatin prevented its activation, which resulted in reduced expression of the pro-inflammatory cytokines interleukin (IL)-1β (−61%) and IL-18 (−26%). Transcriptome analysis confirmed strong reducing effects of atorvastatin on inflammatory mediators, including NLRP3, NFκB and TLR4. The present study demonstrates that atorvastatin reduces hepatic steatosis, inflammation and fibrosis and prevents cholesterol crystal formation, thereby precluding NLRP3 inflammasome activation. This may render atorvastatin treatment as an attractive approach to reduce NAFLD and prevent progression into NASH in dyslipidemic patients.
Identification and Characterization of Proteins That Are Involved in RTP1S-Dependent Transport of Olfactory Receptors
Authors: Inoue Ryosuke , Fukutani Yosuke , Niwa Tatsuya , Matsunami Hiroaki , Yohda Masafumi
Published: April 2023

Olfaction is mediated via olfactory receptors (ORs) that are expressed on the cilia membrane of olfactory sensory neurons in the olfactory epithelium. The functional expression of most ORs requires the assistance of receptor-transporting proteins (RTPs). We examined the interactome of RTP1S and OR via proximity biotinylation. Deubiquitinating protein VCIP135, the F-actin-capping protein sub-unit alpha-2, and insulin-like growth factor 2 mRNA-binding protein 2 were biotinylated via AirID fused with OR, RTP1S-AirID biotinylated heat shock protein A6 (HSPA6), and double-stranded RNA-binding protein Staufen homolog 2 (STAU2). Co-expression of HSPA6 partially enhanced the surface expression of Olfr544. The surface expression of Olfr544 increased by 50–80%. This effect was also observed when RTP1S was co-expressed. Almost identical results were obtained from the co-expression of STAU2. The interactions of HSPA6 and STAU2 with RTP1S were examined using a NanoBit assay. The results show that the RTP1S N-terminus interacted with the C-terminal domain of HSP6A and the N-terminal domain of STAU2. In contrast, OR did not significantly interact with STAU2 and HSPA6. Thus, HSP6A and STAU2 appear to be involved in the process of OR traffic through interaction with RTP1S.
Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/β5 in Parkinson’s Disease
Authors: Tang Chuanxi , Liu Mengting , Zhou Zihang , Li Hao , Yang Chenglin , Yang Li , Xiang Jie
Published: April 2023

Parkinson’s disease with cognitive impairment (PD-CI) results in several clinical outcomes for which specific treatment is lacking. Although the pathogenesis of PD-CI has not yet been fully elucidated, it is related to neuronal plasticity decline in the hippocampus region. The dopaminergic projections from the substantia nigra to the hippocampus are critical in regulating hippocampal plasticity. Recently, aerobic exercise has been recognized as an effective therapeutic strategy for enhancing plasticity through the secretion of various muscle factors. The exact role of FNDC5—an upregulated, newly identified myokine produced after exercise—in mediating hippocampal plasticity and regional dopaminergic projections in PD-CI remains unclear. In this study, the effect of treadmill exercise on hippocampal synaptic plasticity was evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced chronic PD models. The results showed that treadmill exercise substantially alleviated the motor dysfunction, cognition disorder, and dopaminergic neuron degeneration induced by MPTP. Here, we discovered that the quadriceps, serum, and brain FNDC5 levels were lower in PD mice and that intervention with treadmill exercise restored FNDC5 levels. Moreover, treadmill exercise enhanced the synaptic plasticity of hippocampal pyramidal neurons via increased dopamine levels and BDNF in the PD mice. The direct protective effect of FNDC5 is achieved by promoting the secretion of BDNF in the hippocampal neurons via binding the integrin αVβ5 receptor, thereby improving synaptic plasticity. Regarding the indirect protection effect, FNDC5 promotes the dopaminergic connection from the substantia nigra to the hippocampus by mediating the interaction between the integrin αVβ5 of the hippocampal neurons and the CD90 molecules on the membrane of dopaminergic terminals. Our findings demonstrated that treadmill exercise could effectively alleviate cognitive disorders via the activation of the FNDC5–BDNF pathway and enhance the dopaminergic synaptic connection from SNpc to the hippocampus in the MPTP-induced chronic PD model.
Amino-Pyrazoles in Medicinal Chemistry: A Review
Authors: Lusardi Matteo , Spallarossa Andrea , Brullo Chiara
Published: April 2023

A pyrazole nucleus is an easy-to-prepare scaffold with large therapeutic potential. Consequently, the search for new pyrazole-based compounds is of great interest to the academic community as well as industry. In the last ten years, a large number of papers and reviews on the design, synthesis, and biological evaluation of different classes of pyrazoles and many pyrazole-containing compounds have been published. However, an overview of pyrazole derivatives bearing a free amino group at the 3, 4, or 5 position (namely, 3-aminopyrazoles, 4-aminopyrazoles, and 5-aminopyrazoles, respectively) and their biological properties is still missing, despite the fact that aminopyrazoles are advantageous frameworks able to provide useful ligands for receptors or enzymes, such as p38MAPK, and different kinases, COX and others, as well as targets important for bacterial and virus infections. With the aim to fill this gap, the present review focuses on aminopyrazole-based compounds studied as active agents in different therapeutic areas, with particular attention on the design and structure-activity relationships defined by each class of compounds. In particular, the most relevant results have been obtained for anticancer/anti-inflammatory compounds, as the recent approval of Pirtobrutinib demonstrates. The data reported here are collected from different databases (Scifinder, Web of Science, Scopus, Google Scholar, and Pubmed) using “aminopyrazole” as the keyword.
Recent Advances in NMR Protein Structure Prediction with ROSETTA
Authors: Koehler Leman Julia , Künze Georg
Published: April 2023

Nuclear magnetic resonance (NMR) spectroscopy is a powerful method for studying the structure and dynamics of proteins in their native state. For high-resolution NMR structure determination, the collection of a rich restraint dataset is necessary. This can be difficult to achieve for proteins with high molecular weight or a complex architecture. Computational modeling techniques can complement sparse NMR datasets (<1 restraint per residue) with additional structural information to elucidate protein structures in these difficult cases. The Rosetta software for protein structure modeling and design is used by structural biologists for structure determination tasks in which limited experimental data is available. This review gives an overview of the computational protocols available in the Rosetta framework for modeling protein structures from NMR data. We explain the computational algorithms used for the integration of different NMR data types in Rosetta. We also highlight new developments, including modeling tools for data from paramagnetic NMR and hydrogen–deuterium exchange, as well as chemical shifts in CS-Rosetta. Furthermore, strategies are discussed to complement and improve structure predictions made by the current state-of-the-art AlphaFold2 program using NMR-guided Rosetta modeling.
Apostasia Mitochondrial Genome Analysis and Monocot Mitochondria Phylogenomics
Authors: Ke Shi-Jie , Liu Ding-Kun , Tu Xiong-De , He Xin , Zhang Meng-Meng , Zhu Meng-Jia , Zhang Di-Yang , Zhang Cui-Li , Lan Si-Ren , Liu Zhong-Jian
Published: April 2023

Apostasia shenzhenica belongs to the subfamily Apostasioideae and is a primitive group located at the base of the Orchidaceae phylogenetic tree. However, the A. shenzhenica mitochondrial genome (mitogenome) is still unexplored, and the phylogenetic relationships between monocots mitogenomes remain unexplored. In this study, we discussed the genetic diversity of A. shenzhenica and the phylogenetic relationships within its monocotyledon mitogenome. We sequenced and assembled the complete mitogenome of A. shenzhenica, resulting in a circular mitochondrial draft of 672,872 bp, with an average read coverage of 122× and a GC content of 44.4%. A. shenzhenica mitogenome contained 36 protein-coding genes, 16 tRNAs, two rRNAs, and two copies of nad4L. Repeat sequence analysis revealed a large number of medium and small repeats, accounting for 1.28% of the mitogenome sequence. Selection pressure analysis indicated high mitogenome conservation in related species. RNA editing identified 416 sites in the protein-coding region. Furthermore, we found 44 chloroplast genomic DNA fragments that were transferred from the chloroplast to the mitogenome of A. shenzhenica, with five plastid-derived genes remaining intact in the mitogenome. Finally, the phylogenetic analysis of the mitogenomes from A. shenzhenica and 28 other monocots showed that the evolution and classification of most monocots were well determined. These findings enrich the genetic resources of orchids and provide valuable information on the taxonomic classification and molecular evolution of monocots.
Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches
Authors: Monti Alessandra , Vitagliano Luigi , Caporale Andrea , Ruvo Menotti , Doti Nunzianna
Published: April 2023

Protein–protein interfaces play fundamental roles in the molecular mechanisms underlying pathophysiological pathways and are important targets for the design of compounds of therapeutic interest. However, the identification of binding sites on protein surfaces and the development of modulators of protein–protein interactions still represent a major challenge due to their highly dynamic and extensive interfacial areas. Over the years, multiple strategies including structural, computational, and combinatorial approaches have been developed to characterize PPI and to date, several successful examples of small molecules, antibodies, peptides, and aptamers able to modulate these interfaces have been determined. Notably, peptides are a particularly useful tool for inhibiting PPIs due to their exquisite potency, specificity, and selectivity. Here, after an overview of PPIs and of the commonly used approaches to identify and characterize them, we describe and evaluate the impact of chemical peptide libraries in medicinal chemistry with a special focus on the results achieved through recent applications of this methodology. Finally, we also discuss the role that this methodology can have in the framework of the opportunities, and challenges that the application of new predictive approaches based on artificial intelligence is generating in structural biology.
Detecting Pre-Analytically Delayed Blood Samples for Laboratory Diagnostics Using Raman Spectroscopy
Authors: Hunold Pascal , Fischer Markus , Olthoff Carsten , Hildebrand Peter W. , Kaiser Thorsten , Staritzbichler René
Published: April 2023

In this proof-of-principle study, we systematically studied the potential of Raman spectroscopy for detecting pre-analytical delays in blood serum samples. Spectra from 330 samples from a liver cirrhosis cohort were acquired over the course of eight days, stored one day at room temperature, and stored subsequently at 4 °C. The spectra were then used to train Convolutional Neural Networks (CNN) to predict the delay to sample examination. We achieved 90% accuracy for binary classification of the serum samples in the groups “without delay” versus “delayed”. Spectra recorded on the first day could be distinguished clearly from all subsequent measurements. Distinguishing between spectra taken in the range from the second to the last day seems to be possible as well, but currently, with an accuracy of approximately 70% only. Importantly, filtering out the fluorescent background significantly reduces the precision of detection.
Hypoxic Stress-Dependent Regulation of Na,K-ATPase in Ischemic Heart Disease
Authors: Baloglu Emel
Published: April 2023

In cardiomyocytes, regular activity of the Na,K-ATPase (NKA) and its Na/K pump activity is essential for maintaining ion gradients, excitability, propagation of action potentials, electro-mechanical coupling, trans-membrane Na+ and Ca2+ gradients and, thus, contractility. The activity of NKA is impaired in ischemic heart disease and heart failure, which has been attributed to decreased expression of the NKA subunits. Decreased NKA activity leads to intracellular Na+ and Ca2+ overload, diastolic dysfunction and arrhythmias. One signal likely related to these events is hypoxia, where hypoxia-inducible factors (HIF) play a critical role in the adaptation of cells to low oxygen tension. HIF activity increases in ischemic heart, hypertension, heart failure and cardiac fibrosis; thus, it might contribute to the impaired function of NKA. This review will mainly focus on the regulation of NKA in ischemic heart disease in the context of stressed myocardium and the hypoxia–HIF axis and argue on possible consequences of treatment.
Mechanisms of Phytochemicals in Anti-Inflammatory and Anti-Cancer
Authors: Jang Ji-Hoon , Lee Tae-Jin
Published: April 2023

Phytochemicals are chemical compounds that exist in plants and serve various functions such as protecting against pests, UV radiation, and diseases [...]
A Systematic Review of the Role of Purinergic Signalling Pathway in the Treatment of COVID-19
Authors: Korb Vitoria Guero , Schultz Iago Carvalho , Beckenkamp Liziane Raquel , Wink Márcia Rosângela
Published: April 2023

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health concern. Three years since its origin, despite the approval of vaccines and specific treatments against this new coronavirus, there are still high rates of infection, hospitalization, and mortality in some countries. COVID-19 is characterised by a high inflammatory state and coagulation disturbances that may be linked to purinergic signalling molecules such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine (ADO), and purinergic receptors (P1 and P2). These nucleotides/nucleosides play important roles in cellular processes, such as immunomodulation, blood clot formation, and vasodilation, which are affected during SARS-CoV-2 infection. Therefore, drugs targeting this purinergic pathway, currently used for other pathologies, are being evaluated in preclinical and clinical trials for COVID-19. In this review, we focus on the potential of these drugs to control the release, degradation, and reuptake of these extracellular nucleotides and nucleosides to treat COVID-19. Drugs targeting the P1 receptors could have therapeutic efficacy due to their capacity to modulate the cytokine storm and the immune response. Those acting in P2X7, which is linked to NLRP3 inflammasome activation, are also valuable candidates as they can reduce the release of pro-inflammatory cytokines. However, according to the available preclinical and clinical data, the most promising medications to be used for COVID-19 treatment are those that modulate platelets behaviour and blood coagulation factors, mainly through the P2Y12 receptor.
Renewable Biopolymers Combined with Ionic Liquids for the Next Generation of Supercapacitor Materials
Authors: Shamshina Julia L. , Berton Paula
Published: April 2023

The search for biocompatible and renewable materials for the next generation of energy devices has led to increasing interest in using biopolymers as a matrix component for the development of electric double-layer capacitors (EDLCs). However, using biopolymers as host matrices presents limitations in performance and scalability. At the same time, ionic liquids (ILs) have shown exceptional properties as non-aqueous electrolytes. This review intends to highlight the progress in integrating ILs and biopolymers for EDLC. While ILs have been used as solvents to process biopolymers and electrolyte materials, biopolymers have been utilized to provide novel chemistries of electrolyte materials via one of the following scenarios: (1) acting as host polymeric matrices for IL-support, (2) performing as polymeric fillers, and (3) serving as backbone polymer substrates for synthetic polymer grafting. Each of these scenarios is discussed in detail and supported with several examples. The use of biopolymers as electrode materials is another topic covered in this review, where biopolymers are used as a source of carbon or as a flexible support for conductive materials. This review also highlights current challenges in materials development, including improvements in robustness and conductivity, and proper dispersion and compatibility of biopolymeric and synthetic polymeric matrices for proper interface bonding.
Modulation of EZH2 Activity Induces an Antitumoral Effect and Cell Redifferentiation in Anaplastic Thyroid Cancer
Authors: de Mello Diego Claro , Saito Kelly Cristina , Cristovão Marcella Maringolo , Kimura Edna Teruko , Fuziwara Cesar Seigi
Published: April 2023

Anaplastic thyroid cancer (ATC) is a rare and lethal form of thyroid cancer that requires urgent investigation of new molecular targets involved in its aggressive biology. In this context, the overactivation of Polycomb Repressive Complex 2/EZH2, which induces chromatin compaction, is frequently observed in aggressive solid tumors, making the EZH2 methyltransferase a potential target for treatment. However, the deregulation of chromatin accessibility is yet not fully investigated in thyroid cancer. In this study, EZH2 expression was modulated by CRISPR/Cas9-mediated gene editing and pharmacologically inhibited with EZH2 inhibitor EPZ6438 alone or in combination with the MAPK inhibitor U0126. The results showed that CRISPR/Cas9-induced EZH2 gene editing reduced cell growth, migration and invasion in vitro and resulted in a 90% reduction in tumor growth when EZH2-edited cells were injected into an immunocompromised mouse model. Immunohistochemistry analysis of the tumors revealed reduced tumor cell proliferation and less recruitment of cancer-associated fibroblasts in the EZH2-edited tumors compared to the control tumors. Moreover, EZH2 inhibition induced thyroid-differentiation genes’ expression and mesenchymal-to-epithelial transition (MET) in ATC cells. Thus, this study shows that targeting EZH2 could be a promising neoadjuvant treatment for ATC, as it promotes antitumoral effects in vitro and in vivo and induces cell differentiation.
Vermicompost Amendments Disrupt Feeding Behavior of Diaphorina citri Kuwayama and Boost Activities of Salicylic Acid and Jasmonic Acid Pathway-Related Enzymes in Citrus
Authors: Tao Tonglai , Wang Zhaohong , Mao Runqian , Hussain Mubasher , Arthurs Steven P. , Ye Fengxian , An Xincheng , Gao Jing
Published: April 2023

Plants grown with vermicompost amendments are known to be harmful to sap-sucking insects, but the underlying mechanism remains to be determined. Here we investigated the feeding behavior of Diaphorina citri Kuwayama on Citrus limon (L.) Burm. F using the electrical penetration graph technique. Plants were grown in soil with different vermicompost rates (0%, 20%, 40%, and 60% w/w). Additionally, plants were tested for the activity of salicylic acid (SA) and jasmonic acid (JA) pathway-related enzymes. When compared to the control, vermicompost treatments (40% and 60%) decreased duration of phloem sap feeding and increased duration of the pathway phase of D. citri, and the 60% vermicompost made it more difficult for D. citri to reach and gain access to phloem sap. Enzymatic assays indicated that the 40% amendment rate increased phenylalanine ammonia lyase (involved in the SA pathway) and polyphenol oxidase (involved in the JA pathway), while the 60% amendment rate increased -1,3-glucanases (involved in the SA pathway) and lipoxygenase (involved in the JA pathway). The 20% amendment rate had no effect on feeding or enzyme activities. This study revealed that vermicompost amendments can reduce the efficiency of D. citri feeding, which may result from increased plant resistance via the SA and JA pathway.
Temperature and Host Plant Impacts on the Development of Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae): Linear and Nonlinear Modeling
Authors: Maharjan Rameswor , Hong Seoyeon , Ahn Jeongjoon , Yoon Youngnam , Jang Yunwoo , Kim Jungin , Lee Myounghee , Park Kido , Yi Hwijong
Published: April 2023

The tobacco cutworm, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae), is one of the most serious pests in field crops, vegetables, and ornamentals. Temperatures (15, 20, 25, 27, 30, 35, and 40 °C), host plants (soybean (Glycine max (L.)), maize (Zea mays L.), groundnut (Arachis hypogaea L.) and azuki bean (Vigna angularis (Willd.) Ohwi & H. Ohashi,), and the artificial diet-dependent developmental parameters and survival of S. litura were examined in this study. Stage-specific parameters such as threshold development temperature (LDT) and thermal constant (K) (Degree day (DD)) were determined by linear and nonlinear models (Sharpe–Schoolfield–Ikemoto), respectively. The total developmental time (egg–adult) decreased with increasing temperature on host plants and with an artificial diet. The total immature developmental time varied from 106.29, 107.57, 130.40, 111.82, and 103.66 days at 15 °C to 22.47, 21.25, 25.31, 18.30, and 22.50 days at 35 °C on soybean, maize, groundnut, azuki bean, and artificial diet, respectively. The LDT for the total immature completion was 7.50, 9.48, 11.44, 12.32, and 7.95 °C on soybean, maize, groundnut, azuki bean, and artificial diet, respectively. The K for the total immature completion was 587.88, 536.84, 517.45, 419.44, and 586.95 DD on soybean, maize, groundnut, azuki bean, and artificial diet, respectively. Temperature and host plant interaction also influenced the longevity and survival of adults. The findings of this study can be used to predict the number of generations, spring emergence, and population dynamics of S. litura. The nutrient content analysis of the host plants is discussed in terms of the developmental patterns of S. litura.
Gestational Diabetes Mellitus Does Not Worsen Obstetrical and Neonatal Outcomes of Twin Pregnancy
Authors: Ronco Alice , Roero Sofia , Arduino Silvana , Arese Arianna , Ferrando Isabella , Scaltrito Gabriella , Casula Viola , Fea Teresa , Mazza Mattia , Bossotti Carlotta , Zizzo Roberto , Revelli Alberto
Published: April 2023

The specific effects of gestational diabetes mellitus (GDM) on twin pregnancy outcomes, which are at high risk per se, are unclear. The present study analyzes outcomes of twin pregnancies complicated by GDM (n = 227) by comparing them with GDM singleton pregnancies (n = 1060) and with twin pregnancies without GDM (n = 1008), all followed up at Sant’Anna Hospital, Turin (Italy), between January 2010 and March 2020. The prevalence of GDM among twin pregnancies (n = 1235) was 18.4%. Compared to GDM singletons, GDM twins had higher rates of preeclampsia (aOR 2.0; 95% CI 1.2–3.8), cesarean section (aOR 7.5; 95% CI 5.2–10.8), and neonatal hypoglycemia (aOR 2.5; 95% CI 1.1–5.3). They had a higher incidence of abnormal 2 h OGTT values (aOR 7.1; 95% CI: 3.2–15.7) and were less likely to require insulin therapy (aOR 0.5; 95% CI: 0.3–0.7). In comparison with twin pregnancies without GDM, women with GDM twins were significantly older (35.0 vs. 33.0 years; p < 0.001) and had higher BMI (23.0 versus 22.0 kg/m2; p < 0.001); they had a higher incidence of LGA newborns (aOR 5.3; 95% CI 1.7–14.8), and lower incidence of low APGAR scores (0.5; 95% CI 0.3–0.9). Overall, GDM does not worsen outcomes of twin pregnancy, which is per se at high risk for adverse outcomes.
Umbilical Vein Blood Flow in Uncomplicated Pregnancies: Systematic Review of Available Reference Charts and Comparison with a New Cohort
Authors: Barbieri Moira , Zamagni Giulia , Fantasia Ilaria , Monasta Lorenzo , Lo Bello Leila , Quadrifoglio Mariachiara , Ricci Giuseppe , Maso Gianpaolo , Piccoli Monica , Di Martino Daniela Denis , Ferrazzi Enrico Mario , Stampalija Tamara
Published: April 2023

The objectives of the study were (1) to perform a systematic review of the available umbilical vein blood flow volume (UV-Q) reference ranges in uncomplicated pregnancies; and (2) to compare the findings of the systematic review with UV-Q values obtained from a local cohort. Available literature in the English language on this topic was identified following the PRISMA guidelines. Selected original articles were further grouped based on the UV sampling sites and the formulae used to compute UV-Q. The 50th percentiles, the means, or the best-fitting curves were derived from the formulae or the reported tables presented by authors. A prospective observational study of uncomplicated singleton pregnancies from 20+0 to 40+6 weeks of gestation was conducted to compare UV-Q with the results of this systematic review. Fifteen sets of data (fourteen sets belonging to manuscripts identified by the research strategy and one obtained from our cohort) were compared. Overall, there was a substantial heterogeneity among the reported UV-Q central values, although when using the same sampling methodology and formulae, the values overlap. Our data suggest that when adhering to the same methodology, the UV-Q assessment is accurate and reproducible, thus encouraging further investigation on the possible clinical applications of this measurement in clinical practice.
Antibacterial-Based Hydrogel Coatings and Their Application in the Biomedical Field—A Review
Authors: Peng Tai , Shi Qi , Chen Manlong , Yu Wenyi , Yang Tingting
Published: April 2023

Hydrogels exhibit excellent moldability, biodegradability, biocompatibility, and extracellular matrix-like properties, which make them widely used in biomedical fields. Because of their unique three-dimensional crosslinked hydrophilic networks, hydrogels can encapsulate various materials, such as small molecules, polymers, and particles; this has become a hot research topic in the antibacterial field. The surface modification of biomaterials by using antibacterial hydrogels as coatings contributes to the biomaterial activity and offers wide prospects for development. A variety of surface chemical strategies have been developed to bind hydrogels to the substrate surface stably. We first introduce the preparation method for antibacterial coatings in this review, which includes surface-initiated graft crosslinking polymerization, anchoring the hydrogel coating to the substrate surface, and the LbL self-assembly technique to coat crosslinked hydrogels. Then, we summarize the applications of hydrogel coating in the biomedical antibacterial field. Hydrogel itself has certain antibacterial properties, but the antibacterial effect is not sufficient. In recent research, in order to optimize its antibacterial performance, the following three antibacterial strategies are mainly adopted: bacterial repellent and inhibition, contact surface killing of bacteria, and release of antibacterial agents. We systematically introduce the antibacterial mechanism of each strategy. The review aims to provide reference for the further development and application of hydrogel coatings.
Digital Twin Based SUDIHA Architecture to Smart Shopfloor Scheduling
Authors: Khadiri Hassan , Sekkat Souhail , Herrou Brahim
Published: April 2023

Standing on the brink of the fourth industrial revolution, Cyber Physical Systems (CPS) are considered the basic components of the Smart Factory. One important challenge in cyber physical production systems is dynamic scheduling that can handle random disruptions such as failures, raw material shortages and quality defects. To achieve dynamic scheduling, we have proposed a Supervised and Distributed Holonic architecture we called SUDIHA. This architecture incorporates three Holons: Product Holon, Resource Holon and Order Holon and combines global supervision, achieved by Product Holon, with dynamic local control, achieved by Resource Holon. The Digital Twin (DT) concept is generally used to design CPS; it is virtual copies of the system that can interact with the physical counterparts in a bi-directional way. It seems to be promising to tackle the complexity and increase manufacturing system flexibility. In this paper, we use a DT Model to improve the SUDIHA architecture. We propose a Digital Twin based SUDIHA architecture (DT-SUDIHA). The paper will describe Digital Twins’ configuration of each Holon of the SUDIHA Architecture, and the intelligent and real time data driven operation control of this architecture. A case study is carried out at the ENSAM-Meknes flexible workshop to prove the effectiveness of the proposed approach.
Process Map Definition for Laser Metal Deposition of VDM Alloy 780 on the 316L Substrate
Authors: Paulus Pascal , Ruppert Yannick , Vielhaber Michael , Griebsch Juergen
Published: April 2023

VDM Alloy 780 is a novel Ni-based superalloy that allows for approximately 50 °C higher operating temperatures, compared to Inconel 718, without a significant decrease in mechanical properties. The age hardenable NiCoCr Alloy combines increased temperature strength with oxidation resistance, as well as improved microstructural stability due to γ′-precipitation. These advantages make it suitable for wear- and corrosion-resistant coatings that can be used in high temperature applications. However, VDM Alloy 780 has not yet been sufficiently investigated for laser metal deposition applications. A design of experiments with single tracks on 316L specimens was carried out to evaluate the influence of the process parameters on clad quality. Subsequently, the quality of the clads was evaluated by means of destructive and non-destructive testing methods, in order to verify the suitability of VDM Alloy 780 for laser metal deposition applications. The single-track experiments provide a basis for coating or additive manufacturing applications. For conveying the results, scatter plots with regression lines are presented, which illustrate the influence of specific energy density on the resulting porosity, dilution, powder efficiency, aspect ratio, width and height. Finally, the clad quality, in terms of porosity, is visualized by two process maps with different mass per unit lengths.
The Prognostic Role of the Immune Microenvironment in Sinonasal Intestinal-Type Adenocarcinoma: A Computer-Assisted Image Analysis of CD3+ and CD8+ Tumor-Infiltrating Lymphocytes
Authors: Ferrari Marco , Alessandrini Lara , Savietto Enrico , Cazzador Diego , Schiavo Gloria , Taboni Stefano , Carobbio Andrea L. C. , Calvanese Leonardo , Contro Giacomo , Gaudioso Piergiorgio , Emanuelli Enzo , Sbaraglia Marta , Zanoletti Elisabetta , Marioni Gino , Dei Tos Angelo P. , Nicolai Piero
Published: April 2023

The prognostic value of conventional histopathological parameters in the sinonasal intestinal-type adenocarcinoma (ITAC) has been debated and novel variables should be investigated. Increasing evidence demonstrated that the evolution of cancer is strongly dependent upon the complex interactions within tumor microenvironment. The aim of this retrospective study was to assess the features of immune microenvironment in terms of CD3+ and CD8+ cells in a series of ITAC and explore their prognostic role, as well as their relations with clinicopathological variables. A computer-assisted image analysis of CD3+ and CD8+ tumor-infiltrating lymphocytes (TIL) density was conducted on surgical specimens of 51 patients with ITAC that underwent a curative treatment including surgery. ITAC displays variable TIL density, which is associated with OS. In a univariate model, the density of CD3+ TIL was significantly related to OS (p = 0.012), whereas the association with CD8+ TIL density resulted in being non-significant (p = 0.056). Patients with intermediate CD3+ TIL density were associated with the best outcome, whereas 5-year OS was the lowest for intermediate CD8+ TIL density. CD3+ TIL density maintained a significant association with OS in the multivariable analysis. TIL density was not significantly related to demographic and clinicopathological variables. CD3+ TIL density was independently associated with OS in a non-linear fashion and patients with intermediate CD3+ TIL density had the best outcome. Though based on a preliminary analysis on a relatively small series of patients, this finding makes TIL density a potential independent prognostic factor of ITAC.
Integration of Square Fiducial Markers in Patient-Specific Instrumentation and Their Applicability in Knee Surgery
Authors: León-Muñoz Vicente J. , Moya-Angeler Joaquín , López-López Mirian , Lisón-Almagro Alonso J. , Martínez-Martínez Francisco , Santonja-Medina Fernando
Published: April 2023

Computer technologies play a crucial role in orthopaedic surgery and are essential in personalising different treatments. Recent advances allow the usage of augmented reality (AR) for many orthopaedic procedures, which include different types of knee surgery. AR assigns the interaction between virtual environments and the physical world, allowing both to intermingle (AR superimposes information on real objects in real-time) through an optical device and allows personalising different processes for each patient. This article aims to describe the integration of fiducial markers in planning knee surgeries and to perform a narrative description of the latest publications on AR applications in knee surgery. Augmented reality-assisted knee surgery is an emerging set of techniques that can increase accuracy, efficiency, and safety and decrease the radiation exposure (in some surgical procedures, such as osteotomies) of other conventional methods. Initial clinical experience with AR projection based on ArUco-type artificial marker sensors has shown promising results and received positive operator feedback. Once initial clinical safety and efficacy have been demonstrated, the continued experience should be studied to validate this technology and generate further innovation in this rapidly evolving field.