bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatio-Temporal Heterogeneity of Carbon Emissions and Its Key Influencing Factors in the Yellow River Economic Belt of China from 2006 to 2019
Authors: Zhang Jingxue , Feng Yanchao , Zhu Ziyi
Published: April 2022

The Yellow River Economic Belt (YREB) performs an essential function in the low-carbon development of China as an important ecological protection barrier, and it is of great importance to identify its spatio-temporal heterogeneity and key influencing factors. In this study, we propose a comprehensively empirical framework to conduct this issue. The STIRPAT model was applied to determine the influencing factors of carbon emissions in the YREB from 2006 to 2019. The results show that the carbon emissions in the YREB had significant clustering characteristics in the spatial auto-correlation analysis. In addition, the estimation results of the spatial panel analysis demonstrate that the carbon emissions showed a distinct spatial lag effect and temporal lag effect. Moreover, the three traditional factors including population, affluence, technology are identified as the key influencing factors of carbon emissions in the YREB of China. Furthermore, the spatio-temporal heterogeneity is illustrated vividly by employing the GTWR-STIRPAT model. Finally, policy implications are provided to respond to the demand for low-carbon development.
Drug Prescriptions among Italian and Immigrant Pregnant Women Resident in Italy: A Cross-Sectional Population-Based Study
Authors: D’Aloja Paola , Da Cas Roberto , Belleudi Valeria , Fortinguerra Filomena , Poggi Francesca Romana , Perna Serena , Trotta Francesco , Donati Serena ,   MoM-Net Group
Published: April 2022

Ensuring drug safety for pregnant women through prescription drug monitoring is essential. The aim of this study was to describe the prescription pattern of medicines among pregnant immigrant women from countries with high migratory pressure (HMPCs) compared to pregnant Italian women. The prevalence of drug prescriptions among the two study populations was analysed through record linkage procedures applied to the administrative databases of eight Italian regions, from 2016 to 2018. The overall prevalence of drug prescription was calculated considering all women who received at least one prescription during the study period. Immigrants had a lower prevalence of drug prescriptions before (51.0% vs. 58.6%) and after pregnancy (55.1% vs. 60. 3%). Conversely, during pregnancy, they obtained a slightly higher number of prescriptions (74.9% vs. 72.8%). The most prescribed class of drugs was the blood and haematopoietic organs category (category ATC B) (56.4% vs. 45.9%, immigrants compared to Italians), followed by antimicrobials (31.3% vs. 33.7%). Most prescriptions were appropriate, while folic acid administration 3 months before conception was low for both study groups (3.9% immigrants and 6.2% Italians). Progesterone seemingly was prescribed against early pregnancy loss, more frequently among Italians (16.5% vs. 8.1% immigrants). Few inappropriate medications were prescribed among antihypertensives, statins and anti-inflammatory drugs in both study groups.
An Occupancy Information Grid Model for Path Planning of Intelligent Robots
Authors: Zhang Jinming , Wang Xun , Xu Lianrui , Zhang Xin
Published: April 2022

Commonly used robot map models include occupancy grid maps, topological maps, and semantic maps. Among these, an occupancy grid map is mainly represented as a quadrilateral grid. This paper proposes an occupancy information grid for intelligent robots by exploiting the advantages of the occupancy grid map and spatial information grid. In terms of geometric structure, a regular hexagonal grid is used instead of a regular quadrilateral grid. In terms of attribute structure, the single obstacle attribute is replaced by the grid terrain characteristics, grid element attributes, and grid edge attributes. Thus, the occupancy information grid model is transformed into a new data structure describing the spatial environment, and it can be effectively applied to map construction and path planning of intelligent robots. For the map construction application of intelligent robots, this paper describes the basic process of laser sensor-based grid model construction. For the path planning application of intelligent robots, this paper extends the A* algorithm based on a regular hexagonal grid. Additionally, map construction and path planning applications for intelligent robots are experimentally verified. Several experimental results were obtained. First, the experimental results confirmed the theoretical conclusion that the minimum sampling density of the hexagonal structure was 13.4% lower than that of the quadrilateral structure. Second, the regular hexagonal grid is clearly more advantageous in describing environmental scenes, which can ameliorate the "undercompleteness" phenomenon. Third, there were large differences in the planning paths based on two types of grids, as shown by the fact that the distance of the planning paths obtained by the regular hexagonal grid was reduced by at least 10.8% and at most 15.6% compared with the regular quadrilateral grid.
Upregulation of p75NTR by Histone Deacetylase Inhibitors Sensitizes Human Neuroblastoma Cells to Targeted Immunotoxin-Induced Apoptosis
Authors: Dedoni Simona , Olianas Alessandra , Manconi Barbara , Collu Maria , Tuveri Barbara , Vincis Maria Elena , Olianas Maria C. , Onali Pierluigi
Published: April 2022

Histone deacetylase (HDAC) inhibitors are novel chemotherapy agents with potential utility in the treatment of neuroblastoma, the most frequent solid tumor of childhood. Previous studies have shown that the exposure of human neuroblastoma cells to some HDAC inhibitors enhanced the expression of the common neurotrophin receptor p75NTR. In the present study we investigated whether the upregulation of p75NTR could be exploited to render neuroblastoma cells susceptible to the cytotoxic action of an anti-p75NTR antibody conjugated to the toxin saporin-S6 (p75IgG-Sap). We found that two well-characterized HDAC inhibitors, valproic acid (VPA) and entinostat, were able to induce a strong expression of p75NTR in different human neuroblastoma cell lines but not in other cells, with entinostat, displaying a greater efficacy than VPA. Cell pretreatment with entinostat enhanced p75NTR internalization and intracellular saporin-S6 delivery following p75IgG-Sap exposure. The addition of p75IgG-Sap had no effect on vehicle-pretreated cells but potentiated the apoptotic cell death that was induced by entinostat. In three-dimensional neuroblastoma cell cultures, the subsequent treatment with p75IgG-Sap enhanced the inhibition of spheroid growth and the impairment of cell viability that was produced by entinostat. In athymic mice bearing neuroblastoma xenografts, chronic treatment with entinostat increased the expression of p75NTR in tumors but not in liver, kidney, heart, and cerebellum. The administration of p75IgG-Sap induced apoptosis only in tumors of mice that were pretreated with entinostat. These findings define a novel experimental strategy to selectively eliminate neuroblastoma cells based on the sequential treatment with entinostat and a toxin-conjugated anti-p75NTR antibody.
Molecular Advances in Preeclampsia and HELLP Syndrome
Authors: Gardikioti Angeliki , Venou Theodora-Maria , Gavriilaki Eleni , Vetsiou Evangelia , Mavrikou Ioulia , Dinas Konstantinos , Daniilidis Angelos , Vlachaki Efthymia
Published: April 2022

Preeclampsia (PE) constitutes one of the principal reasons for maternal and perinatal morbidity and mortality worldwide. The circumstance typically implicates formerly healthful normotensive women, after 20 weeks of gestation, typically withinside the third trimester, without regarded threat elements or past deliveries. PE can be further complicated with hemolysis and thrombocytopenia, leading to the emergence of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low platelets). Both conditions are classified as hypertensive diseases of pregnancy (HDP), and their pathogenesis has been linked to an excessive maternal inflammatory response, accompanied by enhanced endothelial activation. Several studies have found that in pregnancies affected by PE/HELLP, von Willebrand factor (vWF) antigen levels (vWF:Ag) are significantly elevated, while its cleaving protease (ADAMTS-13, A Disintegrin-like and Metalloprotease with Thrombospondin type 1 motif, member 13) activity is normal to decreased. Furthermore, the higher urine excretion of the terminal complement complex C5b-9, as well as its greater deposition in the placental surface in preeclamptic women, imply that the utero-placental unit’s distinctive deficits are intimately tied to disproportionate complement activation. The goal of this updated evaluation is to provide the most up-to-date molecular advances in the pathophysiology of PE/HELLP syndromes. Recent medical data on vWF:Ag levels in patients with PE, ADAMTS-13, and dysregulation of the complement system, are highlighted and evaluated. Furthermore, we discuss the relationship between those entities and the progression of the disease, as well as their significance in the diagnostic process. Finally, considering the difficulties in analyzing and controlling those symptoms in pregnant women, we can provide a current diagnostic and therapeutic algorithm.
Sensing the Messenger: Potential Roles of Cyclic-di-GMP in Rickettsial Pathogenesis
Authors: Narra Hema P. , Sahni Abha , Sepuru Krishna Mohan , Alsing Jessica , Sahni Sanjeev K.
Published: April 2022

Pathogenic bacteria causing human rickettsioses, transmitted in nature by arthropod vectors, primarily infect vascular endothelial cells lining the blood vessels, resulting in ‘endothelial activation’ and onset of innate immune responses. Nucleotide second messengers are long presumed to be the stimulators of type I interferons, of which bacterial cyclic-di-GMP (c-di-GMP) has been implicated in multiple signaling pathways governing communication with other bacteria and host cells, yet its importance in the context of rickettsial interactions with the host has not been investigated. Here, we report that all rickettsial genomes encode a putative diguanylate cyclase pleD, responsible for the synthesis of c-di-GMP. In silico analysis suggests that although the domain architecture of PleD is apparently well-conserved among different rickettsiae, the protein composition and sequences likely vary. Interestingly, cloning and sequencing of the pleD gene from virulent (Sheila Smith) and avirulent (Iowa) strains of R. rickettsii reveals a nonsynonymous substitution, resulting in an amino acid change (methionine to isoleucine) at position 236. Additionally, a previously reported 5-bp insertion in the genomic sequence coding for pleD (NCBI accession: NC_009882) was not present in the sequence of our cloned pleD from R. rickettsii strain Sheila Smith. In vitro infection of HMECs with R. rickettsii (Sheila Smith), but not R. rickettsii (Iowa), resulted in dynamic changes in the levels of pleD up to 24 h post-infection. These findings thus provide the first evidence for the potentially important role(s) of c-di-GMP in the determination of host-cell responses to pathogenic rickettsiae. Further studies into molecular mechanisms through which rickettsial c-di-GMP might regulate pathogen virulence and host responses should uncover the contributions of this versatile bacterial second messenger in disease pathogenesis and immunity to human rickettsioses.
Lactadherin: From a Well-Known Breast Tumor Marker to a Possible Player in Extracellular Vesicle-Mediated Cancer Progression
Authors: Durán-Jara Eduardo , Vera-Tobar Tamara , Lobos-González Lorena De Lourdes
Published: April 2022

Lactadherin is a secreted glycoprotein associated with the milk fat globule membrane, which is highly present in the blood and in the mammary tissue of lactating women. Several biological functions have been associated with this protein, mainly attributable to its immunomodulatory role promoting phagocyte-mediated clearance of apoptotic cells. It has been shown that lactadherin also plays important roles in cell adhesion, the promotion of angiogenesis, and tissue regeneration. On the other hand, this protein has been used as a marker of breast cancer and tumor progression. Recently, high levels of lactadherin has been associated with poor prognosis and decreased survival, not only in breast cancer, but also in melanoma, ovarian, colorectal, and other types of cancer. Although the mechanisms responsible for the tumor-promoting effects attributed to lactadherin have not been fully elucidated, a growing body of literature indicates that lactadherin could be a promising therapeutic target and/or biomarker for breast and other tumors. Moreover, recent studies have shown its presence in extracellular vesicles derived from cancer cell lines and cancer patients, which was associated with cancer aggressiveness and worse prognosis. Thus, this review will focus on the link between lactadherin and cancer development and progression, its possible use as a cancer biomarker and/or therapeutic target, concluding with a possible role of this protein in cellular communication mediated by extracellular vesicles
Dynamic Changes in Reactive Oxygen Species in the Shoot Apex Contribute to Stem Cell Death in Arabidopsis thaliana
Authors: Wang Yukun , Shirakawa Makoto , Ito Toshiro
Published: April 2022

In monocarpic plants, stem cells are fated to die. However, the potential mechanism of stem cell death has remained elusive. Here, we reveal that the levels of two forms of reactive oxygen species (ROS), superoxide anion free radical (O2·−) and hydrogen peroxide (H2O2), show dynamic changes in the shoot apex during the plant life cycle of Arabidopsis thaliana. We found that the level of O2·− decreased and disappeared at four weeks after bolting (WAB), while H2O2 appeared at 3 WAB and showed a burst at 5 WAB. The timing of dynamic changes in O2·− and H2O2 was delayed for approximately three weeks in clv3-2, which has a longer lifespan. Moreover, exogenous application of H2O2 inhibited the expression of the stem cell determinant WUSCHEL (WUS) and promoted the expression of the developmentally programmed cell death (dPCD) marker gene ORESARA 1 (ORE1). These results indicate that H2O2 triggers an important signal inducing dPCD in stem cells. Given that O2·− plays roles in maintaining WUS expression and stem cell activity, we speculate that the dynamic shift from O2·− to H2O2 in the shoot apex results in stem cell death. Our findings provide novel insights for understanding ROS-mediated regulation during plant stem cell death.
Lysophosphatidylserine Induces MUC5AC Production via the Feedforward Regulation of the TACE-EGFR-ERK Pathway in Airway Epithelial Cells in a Receptor-Independent Manner
Authors: Sim Myeong Seong , Kim Hye Jeong , Jo Sang Hee , Kim Chun , Chung Il Yup
Published: April 2022

Lysophosphatidylserine (LysoPS) is an amphipathic lysophospholipid that mediates a broad spectrum of inflammatory responses through a poorly characterized mechanism. Because LysoPS levels can rise in a variety of pathological conditions, we sought to investigate LysoPS’s potential role in airway epithelial cells that actively participate in lung homeostasis. Here, we report a previously unappreciated function of LysoPS in production of a mucin component, MUC5AC, in the airway epithelial cells. LysoPS stimulated lung epithelial cells to produce MUC5AC via signaling pathways involving TACE, EGFR, and ERK. Specifically, LysoPS- dependent biphasic activation of ERK resulted in TGF-α secretion and strong EGFR phosphorylation leading to MUC5AC production. Collectively, LysoPS induces the expression of MUC5AC via a feedback loop composed of proligand synthesis and its proteolysis by TACE and following autocrine EGFR activation. To our surprise, we were not able to find a role of GPCRs and TLR2, known LyoPS receptors in LysoPS-induced MUC5AC production in airway epithelial cells, suggesting a potential receptor-independent action of LysoPS during inflammation. This study provides new insight into the potential function and mechanism of LysoPS as an emerging lipid mediator in airway inflammation.
Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation
Authors: Mandel Jonathan , Casari Martina , Stepanyan Maria , Martyanov Alexey , Deppermann Carsten
Published: April 2022

There is accumulating evidence that platelets play roles beyond their traditional functions in thrombosis and hemostasis, e.g., in inflammatory processes, infection and cancer, and that they interact, stimulate and regulate cells of the innate immune system such as neutrophils, monocytes and macrophages. In this review, we will focus on platelet activation in hemostatic and inflammatory processes, as well as platelet interactions with neutrophils and monocytes/macrophages. We take a closer look at the contributions of major platelet receptors GPIb, αIIbβ3, TLT-1, CLEC-2 and Toll-like receptors (TLRs) as well as secretions from platelet granules on platelet–neutrophil aggregate and neutrophil extracellular trap (NET) formation in atherosclerosis, transfusion-related acute lung injury (TRALI) and COVID-19. Further, we will address platelet–monocyte and macrophage interactions during cancer metastasis, infection, sepsis and platelet clearance.
The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration
Authors: Wan Rou , Hussain Arif , Behfar Atta , Moran Steven L. , Zhao Chunfeng
Published: April 2022

Soft tissue defects are common following trauma and tumor extirpation. These injuries can result in poor functional recovery and lead to a diminished quality of life. The healing of skin and muscle is a complex process that, at present, leads to incomplete recovery and scarring. Regenerative medicine may offer the opportunity to improve the healing process and functional outcomes. Barriers to regenerative strategies have included cost, regulatory hurdles, and the need for cell-based therapies. In recent years, exosomes, or extracellular vesicles, have gained tremendous attention in the field of soft tissue repair and regeneration. These nanosized extracellular particles (30–140 nm) can break the cellular boundaries, as well as facilitate intracellular signal delivery in various regenerative physiologic and pathologic processes. Existing studies have established the potential of exosomes in regenerating tendons, skeletal muscles, and peripheral nerves through different mechanisms, including promoting myogenesis, increasing tenocyte differentiation and enhancing neurite outgrowth, and the proliferation of Schwann cells. These exosomes can be stored for immediate use in the operating room, and can be produced cost efficiently. In this article, we critically review the current advances of exosomes in soft tissue (tendons, skeletal muscles, and peripheral nerves) healing. Additionally, new directions for clinical applications in the future will be discussed.
The Interplay between PARP Inhibitors and Immunotherapy in Ovarian Cancer: The Rationale behind a New Combination Therapy
Authors: Maiorano Brigida Anna , Lorusso Domenica , Maiorano Mauro Francesco Pio , Ciardiello Davide , Parrella Paola , Petracca Antonio , Cormio Gennaro , Maiello Evaristo
Published: April 2022

Ovarian cancer (OC) has a high impact on morbidity and mortality in the female population. Survival is modest after platinum progression. Therefore, the search for new therapeutic strategies is of utmost importance. BRCA mutations and HR-deficiency occur in around 50% of OC, leading to increased response and survival after Poly (ADP-ribose) polymerase inhibitors (PARPis) administration. PARPis represent a breakthrough for OC therapy, with three different agents approved. On the contrary, immune checkpoint inhibitors (ICIs), another breakthrough therapy for many solid tumors, led to modest results in OC, without clinical approvals and even withdrawal of clinical trials. Therefore, combinations aiming to overcome resistance mechanisms have become of great interest. Recently, PARPis have been evidenced to modulate tumor microenvironment at the molecular and cellular level, potentially enhancing ICIs responsiveness. This represents the rationale for the combined administration of PARPis and ICIs. Our review ought to summarize the preclinical and translational features that support the contemporary administration of these two drug classes, the clinical trials conducted so far, and future directions with ongoing studies.
Development of a Smart Fluorescent Probe Specifically Interacting with C-Myc I-Motif
Authors: Wei Zuzhuang , Liu Bobo , Lin Xiaomin , Wang Jing , Huang Zhi-Shu , Li Ding
Published: April 2022

I-motifs play key regulatory roles in biological processes, holding great potential as attractive therapeutic targets. In the present study, we developed a novel fluorescent probe G59 with strong and selective binding to the c-myc gene promoter i-motif. G59 had an i-motif-binding carbazole moiety conjugated with naphthalimide fluorescent groups. G59 could differentiate the c-myc i-motif from other DNA structures through selective activation of its fluorescence, with its apparent visualization in solution. The smart probe G59 showed excellent sensitivity, with a low fluorescent detection limit of 154 nM and effective stabilization to the c-myc i-motif. G59 could serve as a rapid and sensitive probe for label-free screening of selective c-myc i-motif binding ligands under neutral crowding conditions. To the best of our knowledge, G59 is the first fluorescent probe with high sensitivity for recognizing the i-motif structure and screening for selective binding ligands.
A Novel Morphine Drinking Model of Opioid Dependence in Rats
Authors: Berríos-Cárcamo Pablo , Quezada Mauricio , Santapau Daniela , Morales Paola , Olivares Belén , Ponce Carolina , Ávila Alba , De Gregorio Cristian , Ezquer Marcelo , Quintanilla María Elena , Herrera-Marschitz Mario , Israel Yedy , Ezquer Fernando
Published: April 2022

An animal model of voluntary oral morphine consumption would allow for a pre-clinical evaluation of new treatments aimed at reducing opioid intake in humans. However, the main limitation of oral morphine consumption in rodents is its bitter taste, which is strongly aversive. Taste aversion is often overcome by the use of adulterants, such as sweeteners, to conceal morphine taste or bitterants in the alternative bottle to equalize aversion. However, the adulterants’ presence is the cause for consumption choice and, upon removal, the preference for morphine is not preserved. Thus, current animal models are not suitable to study treatments aimed at reducing consumption elicited by morphine itself. Since taste preference is a learned behavior, just-weaned rats were trained to accept a bitter taste, adding the bitterant quinine to their drinking water for one week. The latter was followed by allowing the choice of quinine or morphine (0.15 mg/mL) solutions for two weeks. Then, quinine was removed, and the preference for morphine against water was evaluated. Using this paradigm, we show that rats highly preferred the consumption of morphine over water, reaching a voluntary morphine intake of 15 mg/kg/day. Morphine consumption led to significant analgesia and hyperlocomotion, and to a marked deprivation syndrome following the administration of the opioid antagonist naloxone. Voluntary morphine consumption was also shown to generate brain oxidative stress and neuroinflammation, signs associated with opioid dependence development. We present a robust two-bottle choice animal model of oral morphine self-administration for the evaluation of therapeutic interventions for the treatment of morphine dependence.
TNF-α Induced Myotube Atrophy in C2C12 Cell Line Uncovers Putative Inflammatory-Related lncRNAs Mediating Muscle Wasting
Authors: Powrózek Tomasz , Pigoń-Zając Dominika , Mazurek Marcin , Ochieng Otieno Michael , Rahnama-Hezavah Mansur , Małecka-Massalska Teresa
Published: April 2022

Background: Muscle atrophy is a complex catabolic condition developing under different inflammatory-related systemic diseases resulting in wasting of muscle tissue. While the knowledge of the molecular background of muscle atrophy has developed in recent years, how the atrophic conditions affect the long non-coding RNA (lncRNAs) machinery and the exact participation of the latter in the mediation of muscle loss are still unknown. The purpose of the study was to assess how inflammatory condition developing under the tumor necrosis factor alpha (TNF-α) treatment affects the lncRNAs’ expression in a mouse skeletal muscle cell line. Materials and method: A C2C12 mouse myoblast cell line was treated with TNF-α to develop atrophy, and inflammatory-related lncRNAs mediating muscle loss were identified. Bioinformatics was used to validate and analyze the discovered lncRNAs. The differences in their expression under different TNF-α concentrations and treatment times were investigated. Results: Five lncRNAs were identified in a discovery set as atrophy related and then validated. Three lncRNAs, Gm4117, Ccdc41os1, and 5830418P13Rik, were selected as being significant for inflammatory-related myotube atrophy. Dynamics changes in the expression of lncRNAs depended on both TNF-α concentration and treatment time. Bioinformatics analysis revealed the mRNA and miRNA target for selected lncRNAs and their putative involvement in the molecular processes related to muscle atrophy. Conclusions: The inflammatory condition developing in the myotube under the TNF-α treatment affects the alteration of lncRNAs’ expression pattern. Experimental and bioinformatics testing suggested the prospective role of lncRNAs in the mediation of muscle loss under an inflammatory state.
Asthma and Allergy: Unravelling a Tangled Relationship with a Focus on New Biomarkers and Treatment
Authors: Rodriguez del Rio Pablo , Liu Andrew H. , Borres Magnus P. , Södergren Eva , Iachetti Fabio , Casale Thomas B.
Published: April 2022

Asthma is a major driver of health care costs across ages. Despite widely disseminated asthma-treatment guidelines and a growing variety of effective therapeutic options, most patients still experience symptoms and/or refractoriness to standard of care treatments. As a result, most patients undergo a further intensification of therapy to optimize symptom control with a subsequent increased risk of side effects. Raising awareness about the relevance of evaluating aeroallergen sensitizations in asthmatic patients is a key step in better informing clinical practice while new molecular tools, such as the component resolved diagnosis, may be of help in refining the relationship between sensitization and therapeutic recommendations. In addition, patient care should benefit from reliable, easy-to-measure and clinically accessible biomarkers that are able to predict outcome and disease monitoring. To attain a personalized asthma management and to guide adequate treatment decisions, it is of paramount importance to expand clinicians’ knowledge about the tangled relationship between asthma and allergy from a molecular perspective. Our review explores the relevance of allergen testing along the asthma patient’s journey, with a special focus on recurrent wheezing children. Here, we also discuss the unresolved issues regarding currently available biomarkers and summarize the evidence supporting the eosinophil-derived neurotoxin as promising biomarker.
Exploring the Contribution of Autophagy to the Excess-Sucrose Response in Arabidopsis thaliana
Authors: Laloum Daniel , Magen Sahar , Soroka Yoram , Avin-Wittenberg Tamar
Published: April 2022

Autophagy is an essential intracellular eukaryotic recycling mechanism, functioning in, among others, carbon starvation. Surprisingly, although autophagy-deficient plants (atg mutants) are hypersensitive to carbon starvation, metabolic analysis revealed that they accumulate sugars under such conditions. In plants, sugars serve as both an energy source and as signaling molecules, affecting many developmental processes, including root and shoot formation. We thus set out to understand the interplay between autophagy and sucrose excess, comparing wild-type and atg mutant seedlings. The presented work showed that autophagy contributes to primary root elongation arrest under conditions of exogenous sucrose and glucose excess but not during fructose or mannitol treatment. Minor or no alterations in starch and primary metabolites were observed between atg mutants and wild-type plants, indicating that the sucrose response relates to its signaling and not its metabolic role. Extensive proteomic analysis of roots performed to further understand the mechanism found an accumulation of proteins essential for ROS reduction and auxin maintenance, which are necessary for root elongation, in atg plants under sucrose excess. The analysis also suggested mitochondrial and peroxisomal involvement in the autophagy-mediated sucrose response. This research increases our knowledge of the complex interplay between autophagy and sugar signaling in plants.
The DnaJ-like Zinc Finger Protein ORANGE Promotes Proline Biosynthesis in Drought-Stressed Arabidopsis Seedlings
Authors: Ali Farman , Wang Qi , Fazal Aliya , Wang Lin-Juan , Song Shuyan , Kong Meng-Juan , Mahmood Tariq , Lu Shan
Published: April 2022

Orange (OR) is a DnaJ-like zinc finger protein with both nuclear and plastidial localizations. OR, and its orthologs, are highly conserved in flowering plants, sharing a characteristic C-terminal tandem 4× repeats of the CxxCxxxG signature. It was reported to trigger chromoplast biogenesis, promote carotenoid accumulation in plastids of non-pigmented tissues, and repress chlorophyll biosynthesis and chloroplast biogenesis in the nucleus of de-etiolating cotyledons cells. Its ectopic overexpression was found to enhance plant resistance to abiotic stresses. Here, we report that the expression of OR in Arabidopsis thaliana was upregulated by drought treatment, and seedlings of the OR-overexpressing (OE) lines showed improved growth performance and survival rate under drought stress. Compared with the wild-type (WT) and OR-silencing (or) lines, drought-stressed OE seedlings possessed lower contents of reactive oxygen species (such as H2O2 and O2−), higher activities of both superoxide dismutase and catalase, and a higher level of proline content. Our enzymatic assay revealed a relatively higher activity of Δ1-pyrroline-5-carboxylate synthase (P5CS), a rate-limiting enzyme for proline biosynthesis, in drought-stressed OE seedlings, compared with the WT and or lines. We further demonstrated that the P5CS activity could be enhanced by supplementing exogenous OR in our in vitro assays. Taken together, our results indicated a novel contribution of OR to drought tolerance, through its impact on proline biosynthesis.
A Game-Based Learning Approach in Digital Design Course to Enhance Students’ Competency
Authors: Velaora Chrysoula , Dimos Ioannis , Tsagiopoulou Sofia , Kakarountas Athanasios
Published: April 2022

Digital Design is a laboratory course, and the educator must focus on the students’ need to know why they study the theory and mainly on the transition from knowledge-based learning to competency-based learning. This study consists of five surveys that were conducted during 2017–2021. First, we evaluated students’ learning outcomes in order to define possible learning problems. According to the literature, gamification can have a positive impact on students’ motivation and learning outcomes. Therefore, we used ready-made digital games in order to evaluate students’ satisfaction and willingness toward their integration in the educational process. This process was repeated in the next academic year. The feedback we received from the previous surveys has helped us to adapt to the new approaches of teaching due to the current pandemic caused by COVID-19. We proposed an online holistic environment based on Keller’s (1987) ARCS model and Malone’s (1981) motivational model, which was applied in distance learning. Each student participated in a student-centered learning experience. He took an active role and was self-manager of his learning process. He was given the opportunity to develop capabilities and strategies through practice and engagement in higher-order cognitive activities, acquire self-learning skills, learn how to solve problems, and participate in teamwork. This study’s innovation is that students experienced a combination of learning approaches: (a) a virtual lab consisting of simulation-based activities, which allowed students to access new laboratory experiences, (b) a project-based digital game without a processor, which developed their motivation, creativity, and hands-on ability, as opposed to the other relevant studies that use ready-made games, and (c) asynchronous videos as feedback, which ensured the educator’s emotional support and social presence. Finally, this study developed research to evaluate the effectiveness of this online holistic environment and used a questionnaire, which was created based on Keller’s Instructional Materials Motivation Survey tool. The results showed that its integration in distance learning is probable to motivate students to learn and affect positively their attention, relevance, confidence, and satisfaction.
Ionic Conductivity of LiSiON and the Effect of Amorphization/Heterovalent Doping on Li+ Diffusion
Authors: Wu Siyuan , Xiao Ruijuan , Li Hong , Chen Liquan
Published: April 2022

The search for and design of suitable superior lithium ion conductors is a key process for developing solid state batteries. In order to realize a large range of applications, we researched the ionic conductivity of LiSiON, an example oxynitride mainly composed of elements with high abundance and a similar mixed anion size. Both its amorphous and heterovalent-doped phases were studied through density functional theory simulations. The Li+ ion diffusion behaviors and related properties are discussed. These elements are abundant in nature, and we found that amorphization or doping with P obviously enhanced the ionic conductivity of the system. General strategies to improve the kinetic properties of a candidate structure are presented, to help in the design of solid state electrolytes for lithium batteries.
Cross-Latitude Behavioural Axis in an Adult Damselfly Calopteryx splendens (Harris, 1780)
Authors: Golab Maria J. , Sniegula Szymon , Brodin Tomas
Published: April 2022

Behavioural variation is important for evolutionary and ecological processes, but can also be useful when predicting consequences of climate change and effects on species ranges. Latitudinal differences in behaviour have received relatively limited research interest when compared to morphological, life history and physiological traits. This study examined differences in expression of three behavioural axes: activity, courtship and boldness, and their correlations, along a European latitudinal gradient spanning ca. 1500 km. The study organism was the temperate damselfly Calopteryx splendens (Harris). We predicted that the expression of both behavioural traits and behavioural syndromes would be positively correlated to latitude, with the lowest values in the southern populations, followed by central and the highest in the north, because animals usually compensate behaviourally for increasing time constraints and declining environmental conditions. We found that behavioural expression varied along the latitudinal cline, although not always in the predicted direction. Activity was the only behaviour that followed our prediction and gradually increased northward. Whereas no south-to-north gradient was seen in any of the behavioural syndromes. The results, particularly for activity, suggest that climatic differences across latitudes change behavioural profiles. However, for other traits such as courtship and boldness, local factors might invoke stronger selection pressures, disrupting the predicted latitudinal pattern.
New Genus and New Subgenera of Camerobiid Mites (Acari: Prostigmata: Camerobiidae) with a Key to World Species of the Genus
Authors: Mirza Jawwad Hassan , Kamran Muhammad , Alatawi Fahad Jaber
Published: April 2022

A new genus, Monobius Alatawi and Kamran, is hereby proposed for the two already described species, viz; M. electrus (Żmudziński) and M. meyerae (Bolland). In addition, the monospecific genus Tillandsobius Bolland is synonymized with the genus Tycherobius Bolland due to variations in the setae number of tibiae I–IV. Further, the genus Neophyllobius Berlese is categorized in two new subgeneric divisions as Neophyllobius Berlese and Monophyllobius Mirza. The number and position of the midventral setae on tarsi I–IV are considered as strong diagnostic generic and subgeneric diagnostic characters. The present study also includes the key to all known species of the genus Neophyllobius. The morphological characters of ten poorly described Neophyllobius species were studied in detail through published literature. The ambiguities in the ventral idiosoma setal notation are highlighted and discussed. It is concluded that two intercoxal setae 3a–4a are always present on small platelets, paired aggenital setae (ag) are present anteriorly and paired genital setae (g) present posteriorly on genital shield. In addition, five records of new species for Saudi Arabia are reported along with re–descriptions of three species.
Can Acute Exercise Lower Cardiovascular Stress Reactivity? Findings from a Scoping Review
Authors: Chen Wei Joo , Mat Ludin Arimi Fitri , Farah Nor M. F.
Published: April 2022

Exaggerated cardiovascular reactivity to and delayed recovery from stress increase the risk of cardiovascular diseases in the future. While exercise training has been shown to attenuate stress-induced cardiovascular reactivity and enhance recovery from stress, the effects with acute exercise are less characterized. The aim of this scoping review was to explore the range and characteristics of published evidence regarding acute exercise on cardiovascular reactivity and stress recovery. The secondary objective was to highlight research gaps and implications for future research. A total of 36 articles met the review inclusion/exclusion criteria, involving 1200 participants from various age groups, fitness and health status. Blood pressure (BP) reactivity was the most measured outcome, followed by heart rate (HR) reactivity, and to some extent, heart rate variability. Overall, acute exercise particularly of the moderate-intensity aerobic type effectively reduced stress-induced BP reactivity in the general population. The effects on HR reactivity and cardiovascular recovery were inconclusive. Further research would be recommended to establish if other forms of exercise intensity or type are equally beneficial to lower exaggerated cardiovascular responses to stress. Despite methodological differences and limitations, the available evidence supports the therapeutic potential of acute exercise in addressing the ill effects of stress on cardiovascular health.
The Impact of Atrial Fibrillation on One-Year Mortality in Patients with Severe Lower Extremity Arterial Disease
Authors: Su Min-I , Cheng Ying-Chih , Huang Yu-Chen , Liu Cheng-Wei
Published: April 2022

Atrial fibrillation (Afib) is associated with the presence of lower extremity arterial disease (LEAD), but its effect on a severe LEAD prognosis remains unclear. We investigated the association between Afib and clinical outcomes. We retrospectively enrolled consecutive severe LEAD patients undergoing percutaneous transluminal angioplasty between 1 January 2013 and 31 December 2018. Patients were divided according to the history of any type of Afib and followed for at least one year. The primary outcome was all-cause mortality. Secondary outcomes were cardiac-related mortality and major adverse cardiovascular events (MACEs). The study included 222 patients aged 74 ± 11 years (54% male), and 12.6% had acute limb ischemia. The Afib group had significantly higher rates of all-cause mortality (42.9% vs. 20.1%, p = 0.014) and MACEs (32.1% vs. 14.4%, p = 0.028) than the non-Afib group. Afib was independently associated with all-cause mortality (adjusted HR: 2.153, 95% CI: 1.084–4.276, p = 0.029) and MACEs (adjusted HR: 2.338, 95% CI: 1.054–2.188, p = 0.037). The other factors associated with all-cause mortality included acute limb ischemia (adjusted HR: 2.898, 95% CI: 1.504–5.586, p = 0.001), Rutherford classification, and heart rate. Afib was significantly associated with increased risks of one-year all-cause mortality and MACEs in patients with severe LEAD. Future studies should investigate whether oral anticoagulants benefit these patients.
Pelvic Floor Dysfunctions and Their Rehabilitation in Multiple Sclerosis
Authors: Sparaco Maddalena , Bonavita Simona
Published: April 2022

Urinary, bowel, and sexual dysfunctions are the most frequent and disabling pelvic floor (PF) disorders in patients with multiple sclerosis (MS). PF dysfunction negatively impacts the performance of daily living activities, walking, and the physical dimension of quality of life (QoL) in people with MS. Patient-reported outcomes on sphincteric functioning could be useful to detect PF disorders and their impact on patients’ lives. PF rehabilitation proposed by Kegel is based on a series of regularly repeated exercises for “the functional restoration of the perineal muscles”. Over time, various therapeutic modalities have been added to PF muscles exercises, through the application of physical or instrumental techniques, such as intravaginal neuromuscular electrical stimulation, electromyographic biofeedback, transcutaneous tibial nerve stimulation. PF rehabilitation has been applied in MS treatment, with improvements of lower urinary tract symptoms severity, QoL, level of anxiety and depression, and sexual dysfunction. This review aims to examine the different PF disorders in MS to evaluate the application of PF rehabilitation in MS and to highlight its advantages and limits, suggesting a multidisciplinary management of PF disorders, with a well-deserved space reserved for PF rehabilitation.
Efficacy and Safety of Laparoscopy for Mild and Moderate Pediatric Abdominal Trauma: A Systematic Review and Meta-Analysis
Authors: Park Yun Chul , Jo Young Goun , Ki Young-Jun , Kang Wu Seong , Kim Joongsuck
Published: April 2022

In this systematic review and meta-analysis, we aimed to investigate the efficacy and safety of laparoscopy for pediatric patients with abdominal trauma. Relevant articles were obtained by searching the MEDLINE PubMed, EMBASE, and Cochrane databases until 7 December 2021. Meta-analyses were performed using odds ratio (OR) for binary outcomes, standardized mean differences (SMDs) for continuous outcome measures, and overall proportion for single proportional outcomes. Nine studies examining 12,492 patients were included in our meta-analysis. Our meta-analysis showed younger age (SMD −0.47, 95% confidence interval (CI) −0.52 to −0.42), lower injury severity score (SMD −0.62, 95% CI −0.67 to −0.57), shorter hospital stay (SMD −0.55, 95% CI −0.60 to −0.50), less complications (OR 0.375, 95% CI 0.309 to 0.455), and lower mortality rate (OR 0.055, 95% CI 0.0.28 to 0.109) in the laparoscopy group compared to the laparotomy group. The majority of patients were able to avoid laparotomy (0.816, 95% CI 0.800 to 0.833). There were no missed injuries during the laparoscopic procedures in seven eligible studies. Laparoscopy for stable pediatric patients showed favorable outcomes in terms of morbidity and mortality. There were no missed injuries, and laparotomy could be avoided for the majority of patients.
Unified Probabilistic Deep Continual Learning through Generative Replay and Open Set Recognition
Authors: Mundt Martin , Pliushch Iuliia , Majumder Sagnik , Hong Yongwon , Ramesh Visvanathan
Published: April 2022

Modern deep neural networks are well known to be brittle in the face of unknown data instances and recognition of the latter remains a challenge. Although it is inevitable for continual-learning systems to encounter such unseen concepts, the corresponding literature appears to nonetheless focus primarily on alleviating catastrophic interference with learned representations. In this work, we introduce a probabilistic approach that connects these perspectives based on variational inference in a single deep autoencoder model. Specifically, we propose to bound the approximate posterior by fitting regions of high density on the basis of correctly classified data points. These bounds are shown to serve a dual purpose: unseen unknown out-of-distribution data can be distinguished from already trained known tasks towards robust application. Simultaneously, to retain already acquired knowledge, a generative replay process can be narrowed to strictly in-distribution samples, in order to significantly alleviate catastrophic interference.
The Impact of Quality of Public Administration on Local Economic Growth in Vietnam
Authors: Pham Thanh , Hoang Thi , Thalassinos Eleftherios , Le Hoang
Published: April 2022

This study examines how the quality of public administration influenced local economic growth in Vietnam from 2011 to 2019. Based on previous studies, we evaluate this impact through the Cobb–Douglas function includes government capital, thereby examining both the individual and interactive effects of local government expenditures and quality of public administration on local economic growth in Vietnam. The system GMM method (SGMM) was used to estimate the model with data collected from 61 provinces and cities in Vietnam in the period 2011–2019. The findings suggest that local government expenditures and quality of public administration positively influence local economic growth in Vietnam. Thereby, the authors propose policy implications to improve the efficiency of local government expenditures on local economic growth in Vietnam in terms of public administration.
Post-COVID-19 Condition: Where Are We Now?
Authors: Boaventura Paula , Macedo Sofia , Ribeiro Filipa , Jaconiano Sónia , Soares Paula
Published: April 2022

COVID-19 is currently considered a systemic infection involving multiple systems and causing chronic complications. Compared to other post-viral fatigue syndromes, these complications are wider and more intense. The most frequent symptoms are profound fatigue, dyspnea, sleep difficulties, anxiety or depression, reduced lung capacity, memory/cognitive impairment, and hyposmia/anosmia. Risk factors for this condition are severity of illness, more than five symptoms in the first week of the disease, female sex, older age, the presence of comorbidities, and a weak anti-SARS-CoV-2 antibody response. Different lines of research have attempted to explain these protracted symptoms; chronic persistent inflammation, autonomic nervous system disruption, hypometabolism, and autoimmunity may play a role. Due to thyroid high ACE expression, the key molecular complex SARS-CoV-2 uses to infect the host cells, thyroid may be a target for the coronavirus infection. Thyroid dysfunction after SARS-CoV-2 infection may be a combination of numerous mechanisms, and its role in long-COVID manifestations is not yet established. The proposed mechanisms are a direct effect of SARS-CoV-2 on target cells, an indirect effect of systemic inflammatory immune response, and a dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis leading to decreased serum TSH. Only a few studies have reported the thyroid gland status in the post-COVID-19 condition. The presence of post-COVID symptoms deserves recognition of COVID-19 as a cause of post-viral fatigue syndrome. It is important to recognize the affected individuals at an early stage so we can offer them the most adequate treatments, helping them thrive through the uncertainty of their condition.