bluuebunny/crossref_metadata_2025 huggingface dataset:
circSnx12 Is Involved in Ferroptosis During Heart Failure by Targeting miR-224-5p
Authors: Zheng Haoyuan , Shi Lin , Tong Changci , Liu Yunen , Hou Mingxiao
Published: April 2021

Circular RNA (circRNA) is a subclass of non-coding RNAs that enables the circular transcripts resistant to the exonuclease digestion. Iron homeostasis is essential for the body to maintain normal physiological functions. At present, the relationship among circRNA, iron metabolism and heart failure remains largely unknown. This study aimed to explore the regulatory mechanism of circRNA and iron metabolism in heart failure. We obtained circRNA, miRNA and mRNA data from public databases and built a ceRNA network. The prediction results were verified in the myocardial tissues of pressure overload-induced heart failure mice through the use of histopathological staining methods, iron and malondialdehyde (MDA) measurement tests, quantitative real-time PCR (qRT-PCR), Western blot analysis and luciferase reporter assay. A total of 4 genes related to iron metabolism and oxidative stress were identified, and a ceRNA network involving 7 circRNAs, 7 miRNAs, and 4 mRNAs was constructed using bioinformatics tools. The results of qRT-PCR and Western blot analyses indicated that the expression level of FTH1 was similar with that predicted by bioinformatics analysis. Echocardiographic measurement showed that heart failure mice have lower fractional shortening and ejection fraction. Moreover, the myocardium of heart failure mice displayed obvious fibrosis as well as increased levels of iron and MDA compared to control mice. Besides, circSnx12 could act as an endogenous sponge to bind with miR-224-5p, and the 3'UTR region of FTH1 also had miRNA binding sites. A circRNA-miRNA-mRNA regulatory network was successfully constructed by identifying differentially expressed genes related to iron metabolism. This new approach reveals potential circRNA targets for the treatment of heart failure.
Development of Interdisciplinary STEM Impact Measures of Student Attitudes and Reasoning
Authors: Mayes Robert , Rittschof Kent
Published: April 2021

The integration of Science, Technology, Engineering and Mathematics (STEM) programs is a national trend. The goal of implementing STEM in schools is to prepare students for the demands of the 21st century, while addressing future workforce needs. The Real STEM project focused on the development of interdisciplinary STEM experiences for students. The project was characterized by sustained professional development which was job-embedded, competency-based, and focused on the development of five STEM reasoning abilities within real-world contexts. The project promoted inclusion of tasks that drew on multiple STEM disciplines, embraced the use of authentic teaching strategies, and supported development of collaboration through interdisciplinary STEM professional learning communities and engaging STEM experts from the community. The four tenets of the project are presented and research on developing and characterizing measures of student impact are provided. Key outcomes include the construction and evaluation of measures supporting interdisciplinary STEM to assess both the impact of intervention on student attitudes toward STEM and students’ STEM reasoning abilities. Findings include reliability and validity evidence supporting attitude measurement and reasoning measurement as well as exploratory results that highlight a disconnection between STEM attitudes and STEM reasoning with the interdisciplinary STEM intervention examined.
Low-Cost Radiant Heater for Rapid Response, High-Temperature Heating
Authors: Gao Xiang , von Boecklin Matt , Ermanoski Ivan , Stechel Ellen B.
Published: April 2021

High-temperature processing has an irreplaceable role in many research and industrial applications. Despite remarkable development spanning over a century, the pursuit of even higher thermal flux density and more rapid thermal transients has not slowed down. As part of the ongoing energy evolution, many industrial applications are transitioning from direct combustion of fossil fuels as primary energy sources to increasing electrification, capable of adapting to renewable power grids. Thus, there is an emerging need for electrical heaters that can replace burners and supply the heat demand, especially at the highest temperatures. In this study, we report on a radiant heater design that can achieve cyclic heating/cooling rates of up to 400 K min–1 and a temperature range in excess of 1,800 K, comparable to those of commercial infrared gold image furnaces, at high surface and volumetric power densities. The heater consists of a modular unit of incandescent tungsten filament and is enclosed in an evacuated ceramic envelope, chemically inert, tolerant of thermal shock, and impervious to gasses. The material and manufacture cost of such heaters, which is estimated at ∼$0.05/W, is less than 0.03% of that for infrared gold image furnaces, which is at >$2/W. Tests of more than 10,000 demanding cycles (high temperature and high heating/cooling rate) over 350 h of total operational time and in different temperature ranges confirm the robust performance of radiant heater prototypes. The design is widely applicable to high-temperature reactor and furnace designs. In thermochemistry research and practice, these radiant heaters could offer multiple benefits compared to solar simulators, lasers, infrared gold furnaces, ceramic heaters, or direct concentration of solar input.
Application of Blockchain Technology in Energy Trading: A Review
Authors: Li Hongbiao , Xiao Fan , Yin Lixin , Wu Fengtong
Published: April 2021

As blockchain and energy trading have become hot topics in industry and academia, this paper presents a brief literature regarding the blockchain-based energy trading in the fields of energy trading with blockchain. At first, the background and development process is presented, and then the applications of blockchain in energy trading are surveyed and analyzed. Finally, conclusions are summarized and important directions are highlighted in this field.
Predation and Resource Availability Interact to Drive Life-History Evolution in an Adaptive Radiation of Livebearing Fish
Authors: Hulthén Kaj , Hill Jacob S. , Jenkins Matthew R. , Langerhans Randall Brian
Published: April 2021

Predation risk and resource availability are two primary factors predicted by theory to drive the evolution of life histories. Yet, disentangling their roles in life-history evolution in the wild is challenging because (1) the two factors often co-vary across environments, and (2) environmental effects on phenotypes can mask patterns of genotypic evolution. Here, we use the model system of the post-Pleistocene radiation of Bahamas mosquitofish (Gambusia hubbsi) inhabiting blue holes to provide a strong test of the roles of predation and resources in life-history evolution, as the two factors do not co-vary in this system and we attempted to minimize environmental effects by raising eight populations under common laboratory conditions. We testeda prioripredictions of predation- and resource-driven evolution in five life-history traits. We found that life-history evolution in Bahamas mosquitofish largely reflected complex interactions in the effects of predation and resource availability. High predation risk has driven the evolution of higher fecundity, smaller offspring size, more frequent reproduction, and slower growth rate—but this predation-driven divergence primarily occurred in environments with relatively high resource availability, and the effects of resources on life-history evolution was generally greater within environments having high predation risk. This implies that resource-driven selection on life histories overrides selection from predators when resources are particularly scarce. While several results matcheda prioripredictions, with the added nuance of interdependence among selective agents, some did not. For instance, only resource levels, not predation risk, explained evolutionary change in male age at maturity, with more rapid sexual maturation in higher-resource environments. We also found faster (not slower) juvenile growth rates within low-resource and low-predation environments, probably caused by selection in these high-competition scenarios favoring greater growth efficiency. Our approach, using common-garden experiments with a natural system of low- and high-predation populations that span a continuum of resource availability, provides a powerful way to deepen our understanding of life-history evolution. Overall, it appears that life-history evolution in this adaptive radiation has resulted from a complex interplay between predation and resources, underscoring the need for increased attention on more sophisticated interactions among selective agents in driving phenotypic diversification.
Identification of a Potentially Functional circRNA-miRNA-mRNA Regulatory Network in Melanocytes for Investigating Pathogenesis of Vitiligo
Authors: Li Lili , Xie Zhi , Qian Xiliang , Wang Tai , Jiang Minmin , Qin Jinglin , Wang Chen , Wu Rongqun , Song Canling
Published: April 2021

CircRNAs have been reported to play essential roles in regulating immunity and inflammation, which may be an important regulatory factor in the development of vitiligo. However, the expression profile of circRNAs and their potential biological functions in vitiligo have not been reported so far. In our study we found there are 64 dysregulated circRNAs and 14 dysregulated miRNAs in the patients with vitiligo. Through the correlation analysis, we obtained 12 dysregulated circRNAs and 5 dysregulated miRNAs, forming 48 relationships in the circRNA-miRNA-mRNA regulatory network. Gene Ontology analysis indicated dysregulated circRNAs in vitiligo is closely related to the disorder of the metabolic pathway. The KEGG pathway of dysregulation of circRNAs mainly enriched in the biological processes such as ubiquitin mediated proteolysis, endocytosis and RNA degradation, and in Jak-STAT signaling pathway. Therefore, we found the circRNA-miRNA-mRNA regulatory network are involved in the regulation of numerous melanocyte functions, and these dysregulated circRNAs may closely related to the melanocyte metabolism. Our study provides a theoretical basis for studying the vitiligo pathogenesis from the perspective of circRNA-miRNA-mRNA network.
Plasmodium falciparum VAR2CSA-Specific IgG Subclass Responses Reflect Protection Against Low Birth Weight and Pregnancy-Associated Malaria
Authors: Tornyigah Bernard , d’Almeida Tania , Escriou Guillaume , Viwami Firmine , Fievet Nadine , Luty Adrian J. F. , Massougbodji Achille , Nielsen Morten A. , Deloron Philippe , Tuikue Ndam Nicaise
Published: April 2021

Sequestration ofPlasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen in the placenta results in poor pregnancy outcomes, including low birth weight and maternal anemia. Antigen-specific antibody-mediated immunity is acquired during successive pregnancies. Thus, evaluating VAR2CSA-specific IgG profiles among pregnant women will increase knowledge on the immunological mechanisms associated with protection, and help in the development of VAR2CSA-based placental malaria vaccines. Using the PAMVAC candidate vaccine antigen, we assessed anti-VAR2CSA IgG subclass responses of a cohort of pregnant Beninese, and analyzed their relationships with pregnancy outcomes. Cytophilic IgG1 and IgG3 responses were the most frequent, with prevalences ranging from 28% (IgG3) up to 50% (IgG1). Elevated levels of VAR2CSA-specific total IgG and cytophilic IgG3 during pregnancy were consistently associated with higher birth weights, whilst high levels of IgG4 were associated with a reduced risk of placental infections. This suggests that protective anti-VAR2CSA IgG responses are coordinated between both cytophilic and non-cytophilic antibodies.
Vaccine-Induced Immunological Memory in Invasive Fungal Infections – A Dream so Close yet so Far
Authors: Biswas Partha S.
Published: April 2021

The invasive fungal infections (IFIs) are a major cause of mortality due to infectious disease worldwide. Majority of the IFIs are caused by opportunistic fungi including Candida, Aspergillus and Cryptococcus species. Lack of approved antifungal vaccines and the emergence of antifungal drug-resistant strains pose major constraints in controlling IFIs. A comprehensive understanding of the host immune response is required to develop novel fungal vaccines to prevent death from IFIs. In this review, we have discussed the challenges associated with the development of antifungal vaccines. We mentioned how host-pathogen interactions shape immunological memory and development of long-term protective immunity to IFIs. Furthermore, we underscored the contribution of long-lived innate and adaptive memory cells in protection against IFIs and summarized the current vaccine strategies.
Variation in Population Structure and Standing Stocks of Kelp Along Multiple Environmental Gradients and Implications for Ecosystem Services
Authors: Gundersen Hege , Rinde Eli , Bekkby Trine , Hancke Kasper , Gitmark Janne K. , Christie Hartvig
Published: April 2021

There is an increasing focus on ecosystem services provided by macroalgae worldwide, many which depend on its structural and morphological characteristics. Here we investigated how characteristics of canopy kelp plants of Laminaria hyperborea varies along the Norwegian part of the NE Atlantic. Ten characteristics related to size, allometry, density, biomass and epiphytes were analyzed along wide gradients of depth, wave exposure and latitude. The analyses were performed on a compiled dataset of 630 scuba samples from different research and monitoring projects along the Norwegian coast (58-71°N). The largest kelps, highest biomass, and highest biomass of epiphytic algae was found in Mid-Norway (63-65°N). While most size-related kelp characteristics were reduced with water depth, they were enlarged with wave exposure. The developed statistical models can be used to calculate site-specific values (and their variation) of the different characteristics at any location based on latitude, depth and wave exposure. These can further be used to map kelp derived ecosystem services. We predicted region-specific estimates of total plant weight, kelp density and kelp biomass. Moreover, the models were applied to estimate living biomass (56 million tonnes fresh weight), carbon standing stock (2.6 million tonnes carbon or 9.5 million tonnes CO2), and carbon sequestration potential (0.46 million tonnes per year) for the Norwegian kelp forests, that were estimated to cover about 5 355 km2. The site- and region-specific estimates are relevant to kelp forest management and for blue carbon accountings.
Disentangling Natural and Anthropogenic Forms of Mortality and Serious Injury in a Poorly Studied Pelagic Dolphin
Authors: Ashe Erin , Williams Rob , Morton Alexandra , Hammond Philip S.
Published: April 2021

Killer whale (Orcinus orca) populations specialize in both prey and prey acquisition tactics around the world and may be a primary evolutionary driver of the habits of small cetaceans. Entanglement in fishing gear is the most significant anthropogenic threat to the survival of cetaceans worldwide. Distinguishing between natural and human-caused sources of mortality and injury is a key task in marine mammal conservation and management. In British Columbia (BC), Canada, mammal-eating killer whales co-occur with Pacific white-sided dolphins (Lagenorhynchus obliquidens). Bycatch mortality rates are unknown here due to lack of systematic fisheries observer coverage. Drawing from more than three decades of first-hand observations of killer whale attacks on Pacific white-sided dolphins, we identify common themes with respect to predatory behavior of killer whales and anti-predatory responses of dolphins. With input from veterinary pathologists, we outline clues to distinguish killer whale rake marks from scars and wounds likely to be caused by fishery interactions. We examined photographs of 415 well-marked Pacific white-side dolphins for evidence of injuries and scars consistent with either killer whale attacks or fishery interactions. In this case study, healed scars from interactions with killer whale predators were ∼8× more common than scars from fishery interactions (3.9 vs. 0.5%), suggesting that predation is a much bigger threat to Pacific white-sided dolphins in the study area than anthropogenic impacts, or that dolphins are much less likely to survive a fishery interaction than a predation attempt. To advance our knowledge on poorly studied species, multiple lines of evidence will be needed.
Optically Active Polyurethane/Silica Aerogel Coated Cotton Fabrics for Thermal Protection
Authors: Lin Ling , Li Ziyin , Mao Haiyan , Li Wenyao , Wang Chaoxia
Published: April 2021

Application of SiO2 aerogel in thermal protective clothing has been limited due to its brittle nature, ordinary mechanical properties, and poor film forming performance. This work is aimed to develop thermal protective cotton fabrics by coating blended OPU/SiO2 aerogel with enhanced mechanical properties and thermal protection performance. The OPU/SiO2 aerogel composites with different ratio were applied onto cotton fabrics by knife-coating. The morphology, chemical component, crystalline structure, thermal stability and compression strength were characterized by scanning electron microscopy (SEM), Fourier transfer Infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG) and compression test, respectively. Besides, the warmth retention performance and heat protection performance together with air and moisture permeability of the coated fabrics were studied. The results showed that OPU/SiO2 aerogel were successfully coated onto cotton fabrics with enhanced mechanical properties and thermal stability together with better film forming capacity. The heat transfer coefficient of the coated cotton fabrics was distinctly dropped due to the synergistic effect of OPU and SiO2 aerogel, which resulted in higher warmth retention. The OPU/SiO2 aerogel coated fabrics exhibited obvious heat insulation performance with its surface temperate almost 4°C than the uncoated fabrics. This work demonstrates a new strategy of fabricating stronger thermal insulating textiles using OPU/SiO2 aerogel composites.
Sumoylation of the Carboxy-Terminal of Human Cytomegalovirus DNA Polymerase Processivity Factor UL44 Attenuates Viral DNA Replication
Authors: Chen Jun , Li Guanlie , He Haiqing , Li Xin , Niu Wenjing , Cao Di , Shen Ao
Published: April 2021

Controlled regulation of genomic DNA synthesis is a universally conserved process for all herpesviruses, including human cytomegalovirus (HCMV), and plays a key role in viral pathogenesis, such as persistent infections. HCMV DNA polymerase processivity factor UL44 plays an essential role in viral DNA replication. To better understand the biology of UL44, we performed a yeast two-hybrid screen for host proteins that could interact with UL44. The most frequently isolated result was the SUMO-conjugating enzyme UBC9, a protein involved in the sumoylation pathway. The UBC9-UL44 interaction was confirmed by in vitro His-tag pull-down and in vivo co-immunoprecipitation assays. Using deletion mutants of UL44, we mapped two small regions of UL44, aa 11–16, and 260–269, which might be critical for the interaction with UBC9. We then demonstrated that UL44 was a target for sumoylation by in vitro and in vivo sumoylation assays, as well as in HCMV-infected cells. We further confirmed that 410lysine located within a ψKxE consensus motif on UL44 carboxy-terminal was the major sumoylation site of UL44. Interestingly, although 410lysine had no effects on subcellular localization or protein stability of UL44, the removal of 410lysine sumoylation site enhanced both viral DNA synthesis in transfection-replication assays and viral progeny production in infected cells for HCMV, suggesting sumoylation can attenuate HCMV replication through targeting UL44. Our results suggest that sumoylation plays a key role in regulating UL44 functions and viral replication, and reveal the crucial role of the carboxy-terminal of UL44, for which little function has been known before.
High Potential for Biomass-Degrading Enzymes Revealed by Hot Spring Metagenomics
Authors: Reichart Nicholas J. , Bowers Robert M. , Woyke Tanja , Hatzenpichler Roland
Published: April 2021

Enzyme stability and activity at elevated temperatures are important aspects in biotechnological industries, such as the conversion of plant biomass into biofuels. In order to reduce the costs and increase the efficiency of biomass conversion, better enzymatic processing must be developed. Hot springs represent a treasure trove of underexplored microbiological and protein chemistry diversity. Herein, we conduct an exploratory study into the diversity of hot spring biomass-degrading potential. We describe the taxonomic diversity and carbohydrate active enzyme (CAZyme) coding potential in 71 publicly available metagenomic datasets from 58 globally distributed terrestrial geothermal features. Through taxonomic profiling, we detected a wide diversity of microbes unique to varying temperature and pH ranges. Biomass-degrading enzyme potential included all five classes of CAZymes and we described the presence or absence of genes encoding 19 glycosyl hydrolases hypothesized to be involved with cellulose, hemicellulose, and oligosaccharide degradation. Our results highlight hot springs as a promising system for the further discovery and development of thermo-stable biomass-degrading enzymes that can be applied toward generation of renewable biofuels. This study lays a foundation for future research to further investigate the functional diversity of hot spring biomass-degrading enzymes and their potential utility in biotechnological processing.
Hippocampal and Hippocampal-Subfield Volumes From Early-Onset Major Depression and Bipolar Disorder to Cognitive Decline
Authors: Hansen Niels , Singh Aditya , Bartels Claudia , Brosseron Frederic , Buerger Katharina , Cetindag Arda C. , Dobisch Laura , Dechent Peter , Ertl-Wagner Birgit B. , Fliessbach Klaus , Haynes John D. , Heneka Michael T. , Janowitz Daniel , Kilimann Ingo , Laske Christoph , Metzger Coraline D. , Munk Matthias H. , Peters Oliver , Priller Josef , Roy Nina , Scheffler Klaus , Schneider Anja , Spottke Annika , Spruth Eike J. , Teipel Stefan , Tscheuschler Maike , Vukovich Ruth , Wiltfang Jens , Duezel Emrah , Jessen Frank , Goya-Maldonado Roberto
Published: April 2021

Background: The hippocampus and its subfields (HippSub) are reported to be diminished in patients with Alzheimer's disease (AD), bipolar disorder (BD), and major depressive disorder (MDD). We examined these groups vs healthy controls (HC) to reveal HippSub alterations between diseases.

Methods: We segmented 3T-MRI T2-weighted hippocampal images of 67 HC, 58 BD, and MDD patients from the AFFDIS study and 137 patients from the DELCODE study assessing cognitive decline, including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and AD, via Free Surfer 6.0 to compare volumes across groups.

Results: Groups differed significantly in several HippSub volumes, particularly between patients with AD and mood disorders. In comparison to HC, significant lower volumes appear in aMCI and AD groups in specific subfields. Smaller volumes in the left presubiculum are detected in aMCI and AD patients, differing from the BD group. A significant linear regression is seen between left hippocampus volume and duration since the first depressive episode.

Conclusions: HippSub volume alterations were observed in AD, but not in early-onset MDD and BD, reinforcing the notion of different neural mechanisms in hippocampal degeneration. Moreover, duration since the first depressive episode was a relevant factor explaining the lower left hippocampal volumes present in groups.
In vitro Toxico-genomics of Etoposide Loaded Gelatin Nanoparticles and Its in-vivo Therapeutic Potential: Pharmacokinetics, Biodistribution and Tumor Regression in Ehrlich Ascites Carcinoma (EAC) Mice Model
Authors: Moin Imran , Biswas Largee , Zafaryab Md , Kumari Namrata , Leekha Ankita , Mittal Disha , Verma Anita Kamra
Published: April 2021

Globally, breast cancer is the foremost cause of mortality among women detected with cancer, with 21% diagnosed in India alone. Etoposide loaded gelatin nanoparticles (EGNP) were prepared and its physical characterization (size:150nm±0.241; zeta potential −29.32 mV) was done along with in-vitro studies to assess biotoxicity, intracellular ROS, cell cycle arrest and death caused by EGNPs. We report the molecular pathways induced by EGNP in-vitro, pharmacokinetics, biodistribution and tumor regression in-vivo in Balb/c mice.Gene expression profiling of Bax, Bcl2, p53, Caspase-3, RIPK1, RIPK3 and ß-actin as internal control were done by RT-PCR wherein Etoposide and EGNP treated MCF-7 cells showed higher expressions of apoptotic genes-Bax, p53, caspase-3, lower expression of anti-apoptotic gene-Bcl2 when compared to control. Enhanced expression of necroptosis-RIPK1 were observed, while RIPK3 was insignificant. Since, RIPK1 regulates necroptosis and apoptosis, expression of apoptotic markers confirmed apoptotic molecular mechanisms. Negligible hemolysis of Gelatin nanoparticles (GNP), and EGNP at selected dosages confirmed biocompatibility. In vivo pharmacokinetics and biodistribution were done by 99Tc-labelled nanoparticles indicating increased circulation of EGNPs, allowing accumulation at the tumor site by Enhanced permeability and retention (EPR) phenomena. Tumor regression indicates the efficacy of EGNP by reducing the tumor burden when compared to void GNP and Etop per se, resulting in increased life span. High biocompatibility and bio-efficacy of EGNPs prove their therapeutic potential in cancer treatment.
Detectable Unmetabolized Folic Acid and Elevated Folate Concentrations in Folic Acid-Supplemented Canadian Children With Sickle Cell Disease
Authors: Williams Brock A. , Mayer Cara , McCartney Heather , Devlin Angela M. , Lamers Yvonne , Vercauteren Suzanne M. , Wu John K. , Karakochuk Crystal D.
Published: April 2021

Sickle cell disease (SCD) is an inherited hemoglobinopathy caused by a variant (rs344) in the HBB gene encoding the β-globin subunit of hemoglobin. Chronic hemolytic anemia and increased erythropoiesis and RBC turnover in individuals with SCD can result in increased needs for folate and other B-vitamins. We assessed B-vitamin status, and the distribution of folate forms, including unmetabolized folic acid (UMFA), in Canadian children with SCD supplemented with 1 mg/d folic acid (current routine practice). Non-fasted serum and plasma samples were analyzed for concentrations of folate, and vitamins B-2, B-6, and B-12. Eleven individuals (45% male; SCD type: HbSS n = 8, HbSC n = 2, HbSβ0-Thal n = 1), with a median (IQR) age of 14 (7, 18) years, were included. Total folate concentrations were 3–27 times above the deficiency cut-off (10 nmol/L), and 64% of children had elevated folate levels (>45.3 nmol/L). UMFA (>0.23 nmol/L) was detected in all children, and 36% of participants had elevated levels of UMFA (>5.4 nmol/L). All children were vitamin B-12 sufficient (>150 pmol/L), and the majority (55%) had sufficient B-6 status (>30 nmol/L). Among this sample of Canadian children with SCD, there was limited evidence of B-vitamin deficiencies, but UMFA was detectable in all children.
Communication Between Epithelial–Mesenchymal Plasticity and Cancer Stem Cells: New Insights Into Cancer Progression
Authors: Zheng Xiaobo , Dai Fuzhen , Feng Lei , Zou Hong , Feng Li , Xu Mingqing
Published: April 2021

The epithelial–mesenchymal transition (EMT) is closely associated with the acquisition of aggressive traits by carcinoma cells and is considered responsible for metastasis, relapse, and chemoresistance. Molecular links between the EMT and cancer stem cells (CSCs) have indicated that EMT processes play important roles in the expression of CSC-like properties. It is generally thought that EMT-related transcription factors (EMT-TFs) need to be downregulated to confer an epithelial phenotype to mesenchymal cells and increase cell proliferation, thereby promoting metastasis formation. However, the genetic and epigenetic mechanisms that regulate EMT and CSC activation are contradictory. Emerging evidence suggests that EMT need not be a binary model and instead a hybrid epithelial/mesenchymal state. This dynamic process correlates with epithelial–mesenchymal plasticity, which indicates a contradictory role of EMT during cancer progression. Recent studies have linked the epithelial–mesenchymal plasticity and stem cell-like traits, providing new insights into the conflicting relationship between EMT and CSCs. In this review, we examine the current knowledge about the interplay between epithelial–mesenchymal plasticity and CSCs in cancer biology and evaluate the controversies and future perspectives. Understanding the biology of epithelial–mesenchymal plasticity and CSCs and their implications in therapeutic treatment may provide new opportunities for targeted intervention.
Intraoperative Ultrasound-Assisted Extent of Resection Assessment in Pediatric Neurosurgical Oncology
Authors: Carai Andrea , De Benedictis Alessandro , Calloni Tommaso , Onorini Nicola , Paternò Giovanni , Randi Franco , Colafati Giovanna Stefania , Mastronuzzi Angela , Marras Carlo Efisio
Published: April 2021

Central nervous system tumors represent the most frequent solid malignancy in the pediatric population. Maximal safe surgical resection is a mainstay of treatment, with significant prognostic impact for the majority of histotypes. Intraoperative ultrasound (ioUS) is a widely available tool in neurosurgery to assist in intracerebral disease resection. Despite technical caveats, preliminary experiences suggest a satisfactory predictive ability, when compared to magnetic resonance imaging (MRI) studies. Most of the available evidence on ioUS applications in brain tumors derive from adult series, a scenario that might not be representative of the pediatric population. We present our preliminary experience comparing ioUS-assisted resection assessment to early post-operative MRI findings in 154 consecutive brain tumor resections at our pediatric neurosurgical unit. A high concordance was observed between ioUS and post-operative MRI. Overall ioUS demonstrated a positive predictive value of 98%, a negative predictive value of 92% in assessing the presence of tumor residue compared to postoperative MRI. Overall, sensibility and specificity were 86% and 99%, respectively. On a multivariate analysis, the only variable significantly associated to unexpected tumor residue on postoperative MRI was histology. Tumor location, patient positioning during surgery, age and initial tumor volume were not significantly associated with ioUS predictive ability. Our data suggest a very good predictive value of ioUS in brain tumor resective procedures in children. Low-grade glioma, high-grade glioma and craniopharyngioma might represent a setting deserving specific endeavours in order to improve intraoperative extent of resection assessment ability.
Radiotherapy in the Era of Immunotherapy With a Focus on Non-Small-Cell Lung Cancer: Time to Revisit Ancient Dogmas?
Authors: Khalifa Jonathan , Mazieres Julien , Gomez-Roca Carlos , Ayyoub Maha , Moyal Elizabeth Cohen-Jonathan
Published: April 2021

Radiation-induced immune effects have been extensively deciphered over the last few years, leading to the concept of the dual immune effect of radiotherapy with both immunostimulatory and immunosuppressive effects. This explains why radiotherapy alone is not able to drive a strong anti-tumor immune response in most cases, hence underlining the rationale for combining both radiotherapy and immunotherapy. This association has generated considerable interest and hundreds of trials are currently ongoing to assess such an association in oncology. However, while some trials have provided unprecedented results or shown much promise, many hopes have been dashed. Questions remain, therefore, as to how to optimize the combination of these treatment modalities. This narrative review aims at revisiting the old, well-established concepts of radiotherapy relating to dose, fractionation, target volumes and organs at risk in the era of immunotherapy. We then propose potential innovative approaches to be further assessed when considering a radio-immunotherapy association, especially in the field of non-small-cell lung cancer (NSCLC). We finally propose a framework to optimize the association, with pragmatic approaches depending on the stage of the disease.
Trans-Ancestry Mutation Landscape of Hepatoblastoma Genomes in Children
Authors: Liu Jie , Gao Chengwen , Wang Liping , Jian Xuemin , Ma Mingdi , Li Tong , Hao XiWei , Zhang Qian , Chen Yuanbin , Zhao Jing , Niu Haitao , Zhu Chengzhan , Zhao Jie , Xia Nan , Li Zhiqiang , Dong Qian
Published: April 2021

Hepatoblastoma (HB) is the most common malignant tumor in the liver of infants and young children. The incidence rate varies among different populations. However, genetic differences in HB patients with different epidemiological and ancestral backgrounds have not been found. In this study, we aim to analyze data from 16 patients treated at our center and collected published data from whole-exome sequencing studies on HB, and to explore the genetic differences between races. Data from a total of 75 HB patients of three races (24 Asian, 37 Caucasian and 14 Hispanic) were analyzed. We identified 16 genes with recurrent somatic mutations and 7 core pathway modules. Among them, the Wnt/β-catenin pathway had the highest mutation rate, and the mutation frequency in Caucasians and Hispanics was approximately twice as high as that in Asians. In addition, this study compared the characteristics of gene mutations between patients who underwent preoperative chemotherapy and those who did not and found that there was no significant difference in gene mutations between the two groups. We also preliminarily verified the function of cancer-associated candidate genes (CTNNB1 and KMT2D). In conclusion, we found ethnic differences in HB biology at the genomic level, which expands our understanding of the genetics of HB in children.
Children With Inflammatory Bowel Disease in the COVID-19 Main Endemic Focus: The Lombardy Experience
Authors: Sansotta Naire , Norsa Lorenzo , Zuin Giovanna , Panceri Roberto , Dilillo Dario , Pozzi Elena , Giacomo Costantino De , Moretti Chiara , Celano Rosaria , Nuti Federica , Sgaramella Paola , Stefano Marina Di , Salvatore Silvia , Arrigo Serena , Motta Valentina , D'Antiga Lorenzo
Published: April 2021

Objectives: In the era of Coronavirus 2019 (COVID-19), concern has been raised for immunosuppressed patients, including children with inflammatory bowel diseases (IBD). We aimed to collect data from IBD tertiary centers of Lombardy during pandemic.

Methods: A cross-sectional survey enrolling IBD children has been completed by seven major IBD centers in Lombardy during lockdown. The clinical form included questions on any symptom consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the IBD adherence treatment. Furthermore, we have reviewed all IBD medical records including new IBD diagnoses and flares in known IBD patients after the lockdown.

Results: Questionnaires of 290 IBD children were returned during lockdown. Out of them, 24 children (8%) complained of mild symptoms suspicious of SARS-CoV-2 infection without needing hospitalization or changing IBD treatment. During the lockdown, one patient presented with IBD flare and one had infectious colitis, with no new IBD cases. Conversely, after lockdown, 12/290 (4%) children relapsed and 15 children were newly diagnosed with IBD. Last year, in the same timeframe, 20/300 (7%) children presented with IBD flare, while 17 children had IBD onset with no statistical difference.

Conclusions: Our data on children with IBD in a high COVID-19 prevalence region are reassuring. Only a minority of IBD children had mild symptoms, and no hospitalization or treatment modification was needed. Standard IBD treatments including biologics were safely continued. New IBD diagnoses and flares in known IBD children occurred after the lockdown phase, although no significant difference was found compared with the previous year.
Anti-Apoptotic Role of Sanhuang Xiexin Decoction and Anisodamine in Endotoxemia
Authors: Liu Zixuan , Wang Wenxiang , Luo Jie , Zhang Yingrui , Zhang Yunsen , Gan Zhiqiang , Shen Xiaofei , Zhang Yi , Meng Xianli
Published: April 2021

Endotoxemia is characterized by initial uncontrollable inflammation, terminal immune paralysis, significant cell apoptosis and tissue injury, which can aggravate or induce multiple diseases and become one of the complications of many diseases. Therefore, anti-inflammatory and anti-apoptotic therapy is a valuable strategy for the treatment of endotoxemia-induced tissue injury. Traditional Chinese medicine exhibits great advantages in the treatment of endotoxemia. In this review, we have analyzed and summarized the active ingredients and their metabolites of Sanhuang Xiexin Decoction, a famous formula in endotoxemia therapy. We then have summarized the mechanisms of Sanhuang Xiexin Decoction against endotoxemia and its mediated tissue injury. Furthermore, silico strategy was used to evaluate the anti-apoptotic mechanism of anisodamine, a well-known natural product that widely used to improve survival in patients with septic shock. Finally, we also have summarized other anti-apoptotic natural products as well as their therapeutic effects on endotoxemia and its mediated tissue injury.
Influence of Context and Setting on the Mental Health and Wellbeing Outcomes of Ayahuasca Drinkers: Results of a Large International Survey
Authors: Perkins Daniel , Schubert Violeta , Simonová Hana , Tófoli Luís Fernando , Bouso José Carlos , Horák Miroslav , Galvão-Coelho Nicole Leite , Sarris Jerome
Published: April 2021

Ayahuasca is a traditional plant decoction containing N,N-dimethyltryptamine (DMT) and various β-carbolines including harmine, harmaline, and tetrahydroharmine, which has been used ceremonially by Amazonian Indigenous groups for healing and spiritual purposes. Use of the brew has now spread far beyond its original context of consumption to North America, Europe, and Australia in neo-shamanic settings as well as Christian syncretic churches. While these groups have established their own rituals and protocols to guide use, it remains unknown the extent to which the use of traditional or non-traditional practices may affect drinkers’ acute experiences, and longer term wellbeing and mental health outcomes. Hence, this study aimed to provide the first detailed assessment of associations between ceremony/ritual characteristics, additional support practices, motivations for drinking, and mental health and wellbeing outcomes. The paper uses data from a large cross-sectional study of ayahuasca drinkers in more than 40 countries who had used ayahuasca in various contexts (n= 6,877). It captured detailed information about participant demographics, patterns and history of ayahuasca drinking, the setting of consumption, and ritualistic practices employed. Current mental health status was captured via the Kessler 10 psychological distress scale and the mental health component score of the SF-12 Health Questionnaire, while reported change in prior clinically diagnosed anxiety or depression (n= 1276) was evaluated using a (PGIC) Patient Global Impression of Change tool. Various intermediate outcomes were also assessed including perceived change in psychological wellbeing, number of personal self-insights attained, and subjective spiritual experience measured via the spirituality dimension of the Persisting Effects Questionnaire (PEQ) and Short Index of Mystical Orientation. Regression models identified a range of significant associations between set and setting variables, and intermediate and final mental health and wellbeing outcomes. A generalized structural equation model (GSEM) was then used to verify relationships and associations between endogenous, mediating and final outcome variables concurrently. The present study sheds new light on the influence of ceremonial practices, additional supports and motivations on the therapeutic effects of ayahuasca for mental health and wellbeing, and ways in which such factors can be optimized in naturalistic settings and clinical studies.
Bilateral Motor Cortex tDCS Effects on Post-Stroke Pain and Spasticity: A Three Cases Study
Authors: Molero-Chamizo Andrés , Salas Sánchez Ángeles , Álvarez Batista Belén , Cordero García Carlos , Andújar Barroso Rafael , Rivera-Urbina G. Nathzidy , Nitsche Michael A. , Alameda Bailén José R.
Published: April 2021

Stroke patients frequently suffer from chronic limb pain, but well-suited treatment approaches have been not established so far. Transcranial direct current stimulation (tDCS) is a safe and non-invasive brain stimulation technique that alters cortical excitability, and it has been shown that motor cortex tDCS can reduce pain. Some data also suggest that spasticity may be improved by tDCS in post-stroke patients. Moreover, multiple sessions of tDCS have shown to induce neuroplastic changes with lasting beneficial effects in different neurological conditions. The aim of this pilot study was to explore the effect of multiple anodal tDCS (atDCS) sessions on upper limb pain and spasticity of stroke patients, using a within-subject, crossover, sham-controlled design. Brain damage was of similar extent in the three patients evaluated, although located in different hemispheres. The results showed a significant effect of 5 consecutive sessions of atDCS, compared to sham stimulation, on pain evaluated by the Adaptive Visual Analog Scales -AVAS-, and spasticity evaluated by the Fugl-Meyer scale. In two of the patients, pain was completely relieved and markedly reduced, respectively, only after verum tDCS. The pain improvement effect of atDCS in the third patient was considerably lower compared to the other two patients. Spasticity was significantly improved in one of the patients. The treatment was well-tolerated, and no serious adverse effects were reported. These findings suggest that multiple sessions of atDCS are a safe intervention for improving upper limb pain and spasticity in stroke patients, although the inter-individual variability is a limitation of the results. Further studies including longer follow-up periods, more representative patient samples and individualized stimulation protocols are required to demonstrate the efficacy and safety of tDCS for improving limb symptoms in these patients.
Control of Neuronal Excitability by Cell Surface Receptor Density and Phosphoinositide Metabolism
Authors: Kruse Martin , Whitten Rayne J.
Published: April 2021

Phosphoinositides are members of a family of minor phospholipids that make up about 1% of all lipids in most cell types. Despite their low abundance they have been found to be essential regulators of neuronal activities such as action potential firing, release and re-uptake of neurotransmitters, and interaction of cytoskeletal proteins with the plasma membrane. Activation of several different neurotransmitter receptors can deplete phosphoinositide levels by more than 90% in seconds, thereby profoundly altering neuronal behavior; however, despite the physiological importance of this mechanism we still lack a profound quantitative understanding of the connection between phosphoinositide metabolism and neuronal activity. Here, we present a model that describes phosphoinositide metabolism and phosphoinositide-dependent action potential firing in sympathetic neurons. The model allows for a simulation of activation of muscarinic acetylcholine receptors and its effects on phosphoinositide levels and their regulation of action potential firing in these neurons. In this paper, we describe the characteristics of the model, its calibration to experimental data, and use the model to analyze how alterations of surface density of muscarinic acetylcholine receptors or altered activity levels of a key enzyme of phosphoinositide metabolism influence action potential firing of sympathetic neurons. In conclusion, the model provides a comprehensive framework describing the connection between muscarinic acetylcholine signaling, phosphoinositide metabolism, and action potential firing in sympathetic neurons which can be used to study the role of these signaling systems in health and disease.
Physical and Chemical Traits of Grape Varieties Influence Drosophila suzukii Preferences and Performance
Authors: Weißinger Lisa , Arand Katja , Bieler Evi , Kassemeyer Hanns-Heinz , Breuer Michael , Müller Caroline
Published: April 2021

The cuticle-covered surface forms the interface between plant parts, including fruits, and their environment. The physical and chemical properties of fruit surfaces profoundly influence plant-frugivore interactions by shaping the susceptibility and suitability of the host for the attacker. Grapevine (Vitis vinifera, Vitaceae) serves as one of the various host plants of the spotted wing drosophila,Drosophila suzukiiMatsumura (Diptera: Drosophilidae), which is invasive in several parts of the world and can cause major crop losses. The susceptibility of wine towards this pest species differs widely among varieties. The objective of our study was to identify physical and chemical traits of the berry surface that may explain the differences in susceptibility of five grape varieties toD. suzukii. Both preferences of adultD. suzukiiand offspring performance on intactversusdewaxed (epicuticular wax layer mechanically removed) grape berries were investigated in dual-choice assays. Moreover, the morphology and chemical composition of cuticular waxes and cutin of the different varieties were analyzed. Bioassays revealed that the epicuticular wax layer of most tested grape varieties influenced the preference behavior of adult flies; even less susceptible varieties became more susceptible after removal of these waxes. In contrast, neither offspring performance nor berry skin firmness were affected by the epicuticular wax layer. The wax morphology and the composition of both epi- and intracuticular waxes differed pronouncedly, especially between more and less susceptible varieties, while cutin was dominated by ω-OH-9/10-epoxy-C18 acid and the amount was comparable among varieties within sampling time. Our results highlight the underestimated role of the epicuticular surface and cuticle integrity in grape susceptibility toD. suzukii.