bluuebunny/crossref_metadata_2025 huggingface dataset:
An Overview of Research Opportunities to Increase the Impact of Nutrition Intervention Research in Early Childhood and Education Care Settings According to the RE-AIM Framework
Authors: Yoong Sze Lin , Jones Jannah , Pearson Nicole , Swindle Taren , Barnes Courtney , Delaney Tessa , Lum Melanie , Golley Rebecca , Matwiejczyk Louisa , Kelly Bridget , Kerr Erin , Love Penelope , Esdaile Emma , Ward Dianne , Grady Alice
Published: March 2021

Objective: To highlight opportunities for future nutrition intervention research within early childhood and education care (ECEC) settings, with a focus on generating evidence that has applicability to real-world policy and practice. Methods: An overview of opportunities to progress the field was developed by the authors using a collaborative writing approach and informed by recent research in the field. The group developed a list of recommendations aligned with the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework. Pairs of authors drafted individual sections of the manuscript, which were then reviewed by a separate pair. The first and senior author consolidated all sections of the manuscript and sought critical input on the draft iterations of the manuscript. Results: Interventions that employ digital platforms (reach) in ECEC settings, as well as research in the family day care setting (effectiveness) were identified as areas of opportunities. Research understanding the determinants of and effective strategies for dissemination (adoption), the implementation of nutrition programs, in addition to de-implementation (implementation) of inappropriate nutrition practices, is warranted. For maintenance, there is a need to better understand sustainability and the sustainment of interventions, in addition to undertaking policy-relevant research. Conclusions: The ECEC setting is prime for innovative and practical nutrition intervention research.
A Cellular Automata Model for Integrated Simulation of Land Use and Transport Interactions
Authors: Pinto Nuno , Antunes António P. , Roca Josep
Published: March 2021

Cellular automata (CA) models have been used in urban studies for dealing with land use change. Transport and accessibility are arguably the main drivers of urban change and have a direct influence on land use. Land use and transport interaction models deal with the complexity of this relationship using many different approaches. CA models incorporate these drivers, but usually consider transport (and accessibility) variables as exogenous. Our paper presents a CA model where transport variables are endogenous to the model and are calibrated along with the land use variables to capture the interdependent complexity of these phenomena. The model uses irregular cells and a variable neighborhood to simulate land use change, taking into account the effect of the road network. Calibration is performed through a particle swarm algorithm. We present an application of the model to a comparison of scenarios for the construction of a ring road in the city of Coimbra, Portugal. The results show the ability of the CA model to capture the influence of change of the transport network (and thus in accessibility) in the land use dynamics.
Effects of Virtual Reality Locomotion Techniques on Distance Estimations
Authors: Keil Julian , Edler Dennis , O’Meara Denise , Korte Annika , Dickmann Frank
Published: March 2021

Mental representations of geographic space are based on knowledge of spatial elements and the spatial relation between these elements. Acquiring such mental representations of space requires assessing distances between pairs of spatial elements. In virtual reality (VR) applications, locomotion techniques based on real-world movement are constrained by the size of the available room and the used room scale tracking system. Therefore, many VR applications use additional locomotion techniques such as artificial locomotion (continuous forward movement) or teleporting (“jumping” from one location to another). These locomotion techniques move the user through virtual space based on controller input. However, it has not yet been investigated how different established controller-based locomotion techniques affect distance estimations in VR. In an experiment, we compared distance estimations between artificial locomotion and teleportation before and after a training phase. The results showed that distance estimations in both locomotion conditions improved after the training. Additionally, distance estimations were found to be more accurate when teleportation locomotion was used.
Advancing Drug Discovery for Neurological Disorders Using iPSC-Derived Neural Organoids
Authors: Costamagna Gianluca , Comi Giacomo Pietro , Corti Stefania
Published: March 2021

In the last decade, different research groups in the academic setting have developed induced pluripotent stem cell-based protocols to generate three-dimensional, multicellular, neural organoids. Their use to model brain biology, early neural development, and human diseases has provided new insights into the pathophysiology of neuropsychiatric and neurological disorders, including microcephaly, autism, Parkinson’s disease, and Alzheimer’s disease. However, the adoption of organoid technology for large-scale drug screening in the industry has been hampered by challenges with reproducibility, scalability, and translatability to human disease. Potential technical solutions to expand their use in drug discovery pipelines include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to create isogenic models, single-cell RNA sequencing to characterize the model at a cellular level, and machine learning to analyze complex data sets. In addition, high-content imaging, automated liquid handling, and standardized assays represent other valuable tools toward this goal. Though several open issues still hamper the full implementation of the organoid technology outside academia, rapid progress in this field will help to prompt its translation toward large-scale drug screening for neurological disorders.
How Macrophages Become Transcriptionally Dysregulated: A Hidden Impact of Antitumor Therapy
Authors: Medvedeva Galina F. , Kuzmina Daria O. , Nuzhina Julia , Shtil Alexander A. , Dukhinova Marina S.
Published: March 2021

Tumor-associated macrophages (TAMs) are the essential components of the tumor microenvironment. TAMs originate from blood monocytes and undergo pro- or anti-inflammatory polarization during their life span within the tumor. The balance between macrophage functional populations and the efficacy of their antitumor activities rely on the transcription factors such as STAT1, NF-κB, IRF, and others. These molecular tools are of primary importance, as they contribute to the tumor adaptations and resistance to radio- and chemotherapy and can become important biomarkers for theranostics. Herein, we describe the major transcriptional mechanisms specific for TAM, as well as how radio- and chemotherapy can impact gene transcription and functionality of macrophages, and what are the consequences of the TAM-tumor cooperation.
Potential of Exosomes for Diagnosis and Treatment of Joint Disease: Towards a Point-of-Care Therapy for Osteoarthritis of the Knee
Authors: Maehara Miki , Toyoda Eriko , Takahashi Takumi , Watanabe Masahiko , Sato Masato
Published: March 2021

In the knee joint, articular cartilage injury can often lead to osteoarthritis of the knee (OAK). Currently, no point-of-care treatment can completely address OAK symptoms and regenerate articular cartilage to restore original functions. While various cell-based therapies are being developed to address OAK, exosomes containing various components derived from their cells of origin have attracted attention as a cell-free alternative. The potential for exosomes as a novel point-of-care treatment for OAK has been studied extensively, especially in the context of intra-articular treatments. Specific exosomal microRNAs have been identified as possibly effective in treating cartilage defects. Additionally, exosomes have been studied as biomarkers through their differences in body fluid composition between joint disease patients and healthy subjects. Exosomes themselves can be utilized as a drug delivery system through their manipulation and encapsulation of specific contents to be delivered to specific cells. Through the combination of exosomes with tissue engineering, novel sustained release drug delivery systems are being developed. On the other hand, many of the functions and activities of exosomes are unknown and challenges remain for clinical applications. In this review, the possibilities of intra-articular treatments utilizing exosomes and the challenges in using exosomes in therapy are discussed.
The Role of Mitochondria in Immune-Cell-Mediated Tissue Regeneration and Ageing
Authors: Su Yu-Jih , Wang Pei-Wen , Weng Shao-Wen
Published: March 2021

During tissue injury events, the innate immune system responds immediately to alarms sent from the injured cells, and the adaptive immune system subsequently joins in the inflammatory reaction. The control mechanism of each immune reaction relies on the orchestration of different types of T cells and the activators, antigen-presenting cells, co-stimulatory molecules, and cytokines. Mitochondria are an intracellular signaling organelle and energy plant, which supply the energy requirement of the immune system and maintain the system activation with the production of reactive oxygen species (ROS). Extracellular mitochondria can elicit regenerative effects or serve as an activator of the immune cells to eliminate the damaged cells. Recent clarification of the cytosolic escape of mitochondrial DNA triggering innate immunity underscores the pivotal role of mitochondria in inflammation-related diseases. Human mesenchymal stem cells could transfer mitochondria through nanotubular structures to defective mitochondrial DNA cells. In recent years, mitochondrial therapy has shown promise in treating heart ischemic events, Parkinson’s disease, and fulminating hepatitis. Taken together, these results emphasize the emerging role of mitochondria in immune-cell-mediated tissue regeneration and ageing.
The Roles of Superoxide on At-Level Spinal Cord Injury Pain in Rats
Authors: Lee Bong Hyo , Kang Jonghoon , Kim Hee Young , Gwak Young S.
Published: March 2021

Background: In the present study, we examined superoxide-mediated excitatory nociceptive transmission on at-level neuropathic pain following spinal thoracic 10 contusion injury (SCI) in male Sprague Dawley rats. Methods: Mechanical sensitivity at body trunk, neuronal firing activity, and expression of superoxide marker/ionotropic glutamate receptors (iGluRs)/CamKII were measured in the T7/8 dorsal horn, respectively. Results: Topical treatment of superoxide donor t-BOOH (0.4 mg/kg) increased neuronal firing rates and pCamKII expression in the naïve group, whereas superoxide scavenger Tempol (1 mg/kg) and non-specific ROS scavenger PBN (3 mg/kg) decreased firing rates in the SCI group (* p < 0.05). SCI showed increases of iGluRs-mediated neuronal firing rates and pCamKII expression (* p < 0.05); however, t-BOOH treatment did not show significant changes in the naïve group. The mechanical sensitivity at the body trunk in the SCI group (6.2 ± 0.5) was attenuated by CamKII inhibitor KN-93 (50 μg, 3.9 ± 0.4) or Tempol (1 mg, 4 ± 0.4) treatment (* p < 0.05). In addition, the level of superoxide marker Dhet showed significant increase in SCI rats compared to the sham group (11.7 ± 1.7 vs. 6.6 ± 1.5, * p < 0.05). Conclusions: Superoxide and the pCamKII pathway contribute to chronic at-level neuropathic pain without involvement of iGluRs following SCI.
Characterization of Long Non-Coding RNA Profiles in Porcine Granulosa Cells of Healthy and Atretic Antral Follicles: Implications for a Potential Role in Apoptosis
Authors: Meng Li , Zhao Kun , Wang Chi Chiu , Tao Jian , Wu Zhenfang , Teerds Katja , Zhang Shouquan
Published: March 2021

Long non-coding RNAs (lncRNAs) play important roles in multiple biological processes including ovarian follicular development. Here we aimed to gain novel information regarding lncRNAs transcriptome profiles in porcine granulosa cells of advanced atretic antral (AA) and healthy antral (HA) follicles using RNA-seq. A total of 11,321 lncRNAs including 10,813 novel and 508 annotated lncRNAs were identified, of which 173 lncRNAs were differentially expressed (DE-lncRNAs); ten of these were confirmed by qRT-PCR. Gene Ontology indicated that DE-lncRNAs associated with developmental processes were highly enriched. Pathway analysis demonstrated predicted cis- and trans-targets of DE-lncRNAs. Potential mRNA targets of up-regulated DE-lncRNAs were mainly enriched in apoptosis related pathways, while targeted genes of downregulated DE-lncRNAs were primarily enriched in metabolism and ovarian steroidogenesis pathways. Linear regression analyses showed that expression of upregulated DE-lncRNAs was significantly associated with apoptosis related genes. NOVEL_00001850 is the most-downregulated DE-lncRNA (FDR = 0.04, FC = −6.53), of which miRNA binding sites were predicted. KEGG analysis of its downregulated target genes revealed that ovarian steroidogenesis was the second most highlighted pathway. qRT-PCR and linear regression analysis confirmed the expression and correlation of its potential targeted gene, CYP19A1, a key gene involved in estradiol synthesis. Our results indicate that lncRNAs may participate in granulosa cells apoptosis and thus antral follicular atresia.
Sperm Methylome Profiling Can Discern Fertility Levels in the Porcine Biomedical Model
Authors: Pértille Fabio , Alvarez-Rodriguez Manuel , da Silva Arthur Nery , Barranco Isabel , Roca Jordi , Guerrero-Bosagna Carlos , Rodriguez-Martinez Heriberto
Published: March 2021

A combined Genotyping By Sequencing (GBS) and methylated DNA immunoprecipitation (MeDIP) protocol was used to identify—in parallel—genetic variation (Genomic-Wide Association Studies (GWAS) and epigenetic differences of Differentially Methylated Regions (DMR) in the genome of spermatozoa from the porcine animal model. Breeding boars with good semen quality (n = 11) and specific and well-documented differences in fertility (farrowing rate, FR) and prolificacy (litter size, LS) (n = 7) in artificial insemination programs, using combined FR and LS, were categorized as High Fertile (HF, n = 4) or Low Fertile (LF, n = 3), and boars with Unknown Fertility (UF, n = 4) were tested for eventual epigenetical similarity with those fertility-proven. We identified 165,944 Single Nucleotide Polymorphisms (SNPs) that explained 14–15% of variance among selection lines. Between HF and LF individuals (n = 7, 4 HF and 3 LF), we identified 169 SNPs with p ≤ 0.00015, which explained 58% of the variance. For the epigenetic analyses, we considered fertility and period of ejaculate collection (late-summer and mid-autumn). Approximately three times more DMRs were observed in HF than in LF boars across these periods. Interestingly, UF boars were clearly clustered with one of the other HF or LF groups. The highest differences in DMRs between HF and LF experimental groups across the pig genome were located in the chr 3, 9, 13, and 16, with most DMRs being hypermethylated in LF boars. In both HF and LF boars, DMRs were mostly hypermethylated in late-summer compared to mid-autumn. Three overlaps were detected between SNPs (p ≤ 0.0005, n = 1318) and CpG sites within DMRs. In conclusion, fertility levels in breeding males including FR and LS can be discerned using methylome analyses. The findings in this biomedical animal model ought to be applied besides sire selection for andrological diagnosis of idiopathic sub/infertility.
Mediator-Related Symptoms and Anaphylaxis in Children with Mastocytosis
Authors: Brockow Knut , Plata-Nazar Katarzyna , Lange Magdalena , Nedoszytko Bogusław , Niedoszytko Marek , Valent Peter
Published: March 2021

Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier’s sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.
Neuroinflammation and Hypothalamo-Pituitary Dysfunction: Focus of Traumatic Brain Injury
Authors: Mele Chiara , Pingue Valeria , Caputo Marina , Zavattaro Marco , Pagano Loredana , Prodam Flavia , Nardone Antonio , Aimaretti Gianluca , Marzullo Paolo
Published: March 2021

The incidence of traumatic brain injury (TBI) has increased over the last years with an important impact on public health. Many preclinical and clinical studies identified multiple and heterogeneous TBI-related pathophysiological mechanisms that are responsible for functional, cognitive, and behavioral alterations. Recent evidence has suggested that post-TBI neuroinflammation is responsible for several long-term clinical consequences, including hypopituitarism. This review aims to summarize current evidence on TBI-induced neuroinflammation and its potential role in determining hypothalamic-pituitary dysfunctions.
Expression and Prognostic Significance of CD47–SIRPA Macrophage Checkpoint Molecules in Colorectal Cancer
Authors: Sugimura-Nagata Akane , Koshino Akira , Inoue Satoshi , Matsuo-Nagano Aya , Komura Masayuki , Riku Miho , Ito Hideaki , Inoko Akihito , Murakami Hideki , Ebi Masahide , Ogasawara Naotaka , Tsuzuki Toyonori , Takahashi Satoru , Kasugai Kunio , Kasai Kenji , Inaguma Shingo
Published: March 2021

Despite the confirmed anti-cancer effects of T-cell immune checkpoint inhibitors, in colorectal cancer (CRC) they are only effective in a small subset of patients with microsatellite-unstable tumors. Thus, therapeutics targeting other types of CRCs or tumors refractory to T-cell checkpoint inhibitors are desired. The binding of aberrantly expressed CD47 on tumor cells to signal regulatory protein-alpha (SIRPA) on macrophages allows tumor cells to evade immune destruction. Based on these observations, drugs targeting the macrophage checkpoint have been developed with the expectation of anti-cancer effects against T-cell immune checkpoint inhibitor-refractory tumors. In the present study, 269 primary CRCs were evaluated immunohistochemically for CD47, SIRPA, CD68, and CD163 expression to assess their predictive utility and the applicability of CD47–SIRPA axis-modulating drugs. Thirty-five percent of the lesions (95/269) displayed CD47 expression on the cytomembrane of CRC cells. CRCs contained various numbers of tumor-associated immune cells (TAIs) with SIRPA, CD68, or CD163 expression. The log-rank test revealed that patients with CD47-positive CRCs had significantly worse survival than CD47-negative patients. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio (R) = 0.23), age < 70 years (HR = 0.48), and high SIRPA-positive TAI counts (HR = 0.55) as potential favorable factors. High tumor CD47 expression (HR = 1.75), lymph node metastasis (HR = 2.26), and peritoneal metastasis (HR = 5.80) were cited as potential independent risk factors. Based on our observations, CD47–SIRPA pathway-modulating therapies may be effective in patients with CRC.
The Rationale for the Intra-Articular Administration of Clodronate in Osteoarthritis
Authors: Moretti Antimo , Paoletta Marco , Liguori Sara , Ilardi Walter , Snichelotto Francesco , Toro Giuseppe , Gimigliano Francesca , Iolascon Giovanni
Published: March 2021

Background: Several pharmacological therapeutic approaches have been proposed to manage osteoarthritis (OA), including intra-articular (IA) injections. Although the discovery of clodronate, a bisphosphonate, dates back to the 1960s and the effects of its IA administration have been investigated for decades in animal models, mechanisms of action of this drug are not quite clear, particularly in OA. This scoping review is an overview of the biological as well as the clinical role of clodronic acid in OA. Method: A scoping review based on the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model was performed to characterize the mechanisms of action of IA clodronate in OA and to evaluate its efficacy from a clinical point of view. Results: Several effects of clodronate have been observed in animal models of OA, including depletion of synovial lining cells that results in reduced production of chemokines (IL-1, TNF- α), growth factors (TGF-β, BMP 2/4), and metalloproteases (MMP 2/3/9); prevention of cartilage damage, synovial hyperplasia, and proteoglycans loss; reduction in joint inflammation, joint swelling, and osteophyte formation. From a clinical perspective, patients with knee OA treated with IA clodronate experienced improvements in pain and joint mobility. Conclusion: Clodronate appears to have different mechanisms of action interfering with the pathogenic processes contributing to OA development and progression. This intervention demonstrated positive effects for patients affected by knee OA.
Lung Surfactant Decreases Biochemical Alterations and Oxidative Stress Induced by a Sub-Toxic Concentration of Carbon Nanoparticles in Alveolar Epithelial and Microglial Cells
Authors: Caruso Giuseppe , Fresta Claudia G. , Costantino Angelita , Lazzarino Giacomo , Amorini Angela M. , Lazzarino Giuseppe , Tavazzi Barbara , Lunte Susan M. , Dhar Prajnaparamita , Gulisano Massimo , Caraci Filippo
Published: March 2021

Carbon-based nanomaterials are nowadays attracting lots of attention, in particular in the biomedical field, where they find a wide spectrum of applications, including, just to name a few, the drug delivery to specific tumor cells and the improvement of non-invasive imaging methods. Nanoparticles inhaled during breathing accumulate in the lung alveoli, where they interact and are covered with lung surfactants. We recently demonstrated that an apparently non-toxic concentration of engineered carbon nanodiamonds (ECNs) is able to induce oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial dysfunction in microglial and alveolar basal epithelial cells. Therefore, the complete understanding of their “real” biosafety, along with their possible combination with other molecules mimicking the in vivo milieu, possibly allowing the modulation of their side effects becomes of utmost importance. Based on the above, the focus of the present work was to investigate whether the cellular alterations induced by an apparently non-toxic concentration of ECNs could be counteracted by their incorporation into a synthetic lung surfactant (DPPC:POPG in 7:3 molar ratio). By using two different cell lines (alveolar (A549) and microglial (BV-2)), we were able to show that the presence of lung surfactant decreased the production of ECNs-induced nitric oxide, total reactive oxygen species, and malondialdehyde, as well as counteracted reduced glutathione depletion (A549 cells only), ameliorated cell energy status (ATP and total pool of nicotinic coenzymes), and improved mitochondrial phosphorylating capacity. Overall, our results on alveolar basal epithelial and microglial cell lines clearly depict the benefits coming from the incorporation of carbon nanoparticles into a lung surfactant (mimicking its in vivo lipid composition), creating the basis for the investigation of this combination in vivo.
P25 Gene Knockout Contributes to Human Epidermal Growth Factor Production in Transgenic Silkworms
Authors: Wu Meiyu , Ruan Jinghua , Ye Xiaogang , Zhao Shuo , Tang Xiaoli , Wang Xiaoxiao , Li Huiping , Zhong Boxiong
Published: March 2021

Transgenic silkworm expression systems have been applied for producing various recombinant proteins. Knocking out or downregulating an endogenous silk protein is considered a viable strategy for improving the ability of transgenic expression systems to produce exogenous proteins. Here, we report the expression of human epidermal growth factor (hEGF) in a P25 gene knockout silkworm. The hEGF gene regulated by the P25 gene promoter was integrated into a silkworm’s genome. Five transgenic positive silkworm lineages were generated with different insertion sites on silkworm chromosomes and the ability to synthesize and secrete proteins into cocoons. Then, a cross-strategy was used to produce transgenic silkworms with a P25 gene knockout background. The results of the protein analysis showed that the loss of an endogenous P25 protein can increase the hEGF production to about 2.2-fold more than normal silkworms. Compared to those of transgenic silkworms with wild type (non-knockout) background, the morphology and secondary structure of cocoon silks were barely changed in transgenic silkworms with a P25 gene knockout background, indicating their similar physical properties of cocoon silks. In conclusion, P25 gene knockout silkworms may become an efficient bioreactor for the production of exogenous proteins and a promising tool for producing various protein-containing silk biomaterials.
Macrophage Polarization in Cardiac Tissue Repair Following Myocardial Infarction
Authors: Kim Yevgeniy , Nurakhayev Sanzhar , Nurkesh Ayan , Zharkinbekov Zharylkasyn , Saparov Arman
Published: March 2021

Cardiovascular disease is the leading cause of mortality and morbidity around the globe, creating a substantial socio-economic burden as a result. Myocardial infarction is a significant contributor to the detrimental impact of cardiovascular disease. The death of cardiomyocytes following myocardial infarction causes an immune response which leads to further destruction of tissue, and subsequently, results in the formation of non-contractile scar tissue. Macrophages have been recognized as important regulators and participants of inflammation and fibrosis following myocardial infarction. Macrophages are generally classified into two distinct groups, namely, classically activated, or M1 macrophages, and alternatively activated, or M2 macrophages. The phenotypic profile of cardiac macrophages, however, is much more diverse and should not be reduced to these two subsets. In this review, we describe the phenotypes and functions of macrophages which are present in the healthy, as well as the infarcted heart, and analyze them with respect to M1 and M2 polarization states. Furthermore, we discuss therapeutic strategies which utilize macrophage polarization towards an anti-inflammatory or reparative phenotype for the treatment of myocardial infarction.
A Web Server for Designing Molecular Switches Composed of Two Interacting RNAs
Authors: Taneda Akito , Sato Kengo
Published: March 2021

The programmability of RNA–RNA interactions through intermolecular base-pairing has been successfully exploited to design a variety of RNA devices that artificially regulate gene expression. An in silico design for interacting structured RNA sequences that satisfies multiple design criteria becomes a complex multi-objective problem. Although multi-objective optimization is a powerful technique that explores a vast solution space without empirical weights between design objectives, to date, no web service for multi-objective design of RNA switches that utilizes RNA–RNA interaction has been proposed. We developed a web server, which is based on a multi-objective design algorithm called MODENA, to design two interacting RNAs that form a complex in silico. By predicting the secondary structures with RactIP during the design process, we can design RNAs that form a joint secondary structure with an external pseudoknot. The energy barrier upon the complex formation is modeled by an interaction seed that is optimized in the design algorithm. We benchmarked the RNA switch design approaches (MODENA+RactIP and MODENA+RNAcofold) for the target structures based on natural RNA-RNA interactions. As a result, MODENA+RactIP showed high design performance for the benchmark datasets.
Endothelial Nox5 Expression Modulates Glucose Uptake and Lipid Accumulation in Mice Fed a High-Fat Diet and 3T3-L1 Adipocytes Treated with Glucose and Palmitic Acid
Authors: García Jorge G. , Ansorena Eduardo , Milagro Fermín I. , Zalba Guillermo , de Miguel Carlos
Published: March 2021

Obesity is a global health issue associated with insulin resistance and altered lipid homeostasis. It has been described that reactive oxygen species (ROS) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity are involved in the development of these pathologies. The present study describes the role of endothelial NOX5 expression over adipose tissue by using two experimental systems: NOX5 conditional knock-in mice fed with a high-fat diet and 3T3-L1 adipocytes cultured with conditioned media of NOX5-expressing endothelial cells previously treated with glucose and palmitic acid. Animals expressing NOX5 presented lower body weight gain and less mesenteric and epididymal adipose mass compared to control mice fed with the same diet. NOX5-expressing mice also showed significantly lower glycaemia and improved insulin-induced glucose uptake. In addition, Glut4 and Caveolin 1 (Cav1) expression were significantly increased in the adipose tissue of these animals. Likewise, 3T3-L1 adipocytes treated with conditioned media from NOX5-expressing endothelial cells, incubated with high glucose and palmitic acid, presented a reduction in lipid accumulation and an increase in glucose uptake. Moreover, a significant increase in the expression of Glut4 and Cav1 was also detected in these cells. Taken together, all these data support that, in response to a highly caloric diet, NOX5 endothelial activity may regulate glucose sensitivity and lipid homeostasis in the adipose tissue.
Flowering and Seed Production across the Lemnaceae
Authors: Fourounjian Paul , Slovin Janet , Messing Joachim
Published: March 2021

Plants in the family Lemnaceae are aquatic monocots and the smallest, simplest, and fastest growing angiosperms. Their small size, the smallest family member is 0.5 mm and the largest is 2.0 cm, as well as their diverse morphologies make these plants ideal for laboratory studies. Their rapid growth rate is partially due to the family’s neotenous lifestyle, where instead of maturing and producing flowers, the plants remain in a juvenile state and continuously bud asexually. Maturation and flowering in the wild are rare in most family members. To promote further research on these unique plants, we have optimized laboratory flowering protocols for 3 of the 5 genera: Spirodela; Lemna; and Wolffia in the Lemnaceae. Duckweeds were widely used in the past for research on flowering, hormone and amino acid biosynthesis, the photosynthetic apparatus, and phytoremediation due to their aqueous lifestyle and ease of aseptic culture. There is a recent renaissance in interest in growing these plants as non-lignified biomass sources for fuel production, and as a resource-efficient complete protein source. The genome sequences of several Lemnaceae family members have become available, providing a foundation for genetic improvement of these plants as crops. The protocols for maximizing flowering described herein are based on screens testing daylength, a variety of media, supplementation with salicylic acid or ethylenediamine-N,N′-bis(2-hydroxyphenylacetic acid) (EDDHA), as well as various culture vessels for effects on flowering of verified Lemnaceae strains available from the Rutgers Duckweed Stock Cooperative.
A Comprehensive Review on Chemotaxonomic and Phytochemical Aspects of Homoisoflavonoids, as Rare Flavonoid Derivatives
Authors: Mottaghipisheh Javad , Stuppner Hermann
Published: March 2021

Homoisoflavonoids (3-benzylidene-4-chromanones) are considered as an infrequent flavonoid class, possessing multi-beneficial bioactivities. The present study gives an overview on phytochemical aspects of homoisoflavonoids, including utilized plant species, parts, extracts, and separation techniques. Overall, these compounds have mainly been isolated and identified from bulbs and rhizomes of the plants belonging to Asparagaceae and Fabaceae families, particularly the genera of Ophiopogon, Dracaena, Scilla, Polygonatum, and Caesalpinia.
Dynamic Community Structure in Online Social Groups
Authors: Guidi Barbara , Michienzi Andrea
Published: March 2021

One of the main ideas about the Internet is to rethink its services in a user-centric fashion. This fact translates to having human-scale services with devices that will become smarter and make decisions in place of their respective owners. Online Social Networks and, in particular, Online Social Groups, such as Facebook Groups, will be at the epicentre of this revolution because of their great relevance in the current society. Despite the vast number of studies on human behaviour in Online Social Media, the characteristics of Online Social Groups are still unknown. In this paper, we propose a dynamic community detection driven study of the structure of users inside Facebook Groups. The communities are extracted considering the interactions among the members of a group and it aims at searching dense communication groups of users, and the evolution of the communication groups over time, in order to discover social properties of Online Social Groups. The analysis is carried out considering the activity of 17 Facebook Groups, using 8 community detection algorithms and considering 2 possible interaction lifespans. Results show that interaction communities in OSGs are very fragmented but community detection tools are capable of uncovering relevant structures. The study of the community quality gives important insights about the community structure and increasing the interaction lifespan does not necessarily result in more clusterized or bigger communities.
Maximizing Image Information Using Multi-Chimera Transform Applied on Face Biometric Modality
Authors: Mohammad Ahmad Saeed , Zaghar Dhafer , Khalaf Walaa
Published: March 2021

With the development of mobile technology, the usage of media data has increased dramatically. Therefore, data reduction represents a research field to maintain valuable information. In this paper, a new scheme called Multi Chimera Transform (MCT) based on data reduction with high information preservation, which aims to improve the reconstructed data by producing three parameters from each 16×16 block of data, is proposed. MCT is a 2D transform that depends on constructing a codebook of 256 picked blocks from some selected images which have a low similarity. The proposed transformation was applied on solid and soft biometric modalities of AR database, giving high information preservation with small resulted file size. The proposed method produced outstanding performance compared with KLT and WT in terms of SSIM and PSNR. The highest SSIM was 0.87 for the proposed scheme MCT of the full image of AR database, while the existed method KLT and WT had 0.81 and 0.68, respectively. In addition, the highest PSNR was 27.23 dB for the proposed scheme on warp facial image of AR database, while the existed methods KLT and WT had 24.70 dB and 21.79 dB, respectively.
A Qualitative Analysis of Beekeepers’ Perceptions and Farm Management Adaptations to the Impact of Climate Change on Honey Bees
Authors: Vercelli Monica , Novelli Silvia , Ferrazzi Paola , Lentini Giada , Ferracini Chiara
Published: March 2021

(1) Background: Bees are the primary animal pollinators in most ecosystems, and honey bees (Apis mellifera L.) are important providers of pollination ecosystem services and products. Climate change is one of the major threats for honey bees. (2) Objectives and methods: Qualitative research using focus group discussions was carried out in northwestern Italy, to investigate the beekeepers’ perceptions of climate change effects, the relevant management adaptations, and the main issues affecting the sector. (3) Results: Beekeepers reported several consequences related to severe weather events (weakening or loss of colonies; scarcity of nectar, pollen, and honeydew; decrease or lack of honey and other bee products; greater infestation by varroa; decline in pollination), making it necessary to provide supplemental sugar feeding, intensive transhumance, more effective and sustainable techniques for varroa control, and increased production of nuclei. A strengths, weaknesses, opportunities, and threats (SWOT) analysis was completed, displaying the factors able to strengthen or weaken the resilience of the beekeeping sector to climate change. (4) Conclusions: Thanks to their strong motivation and collaborative attitude, beekeepers succeed in adopting farm and bee hive adaptation strategies that are able to limit the climatic adverse effects. However, these findings highlight how the institutional and financial support for the beekeeping sector should be strengthened and better targeted.
Sonodynamic Therapy for the Treatment of Intracranial Gliomas
Authors: D’Ammando Antonio , Raspagliesi Luca , Gionso Matteo , Franzini Andrea , Porto Edoardo , Di Meco Francesco , Durando Giovanni , Pellegatta Serena , Prada Francesco
Published: March 2021

High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, prognosis still remains poor; hence, new therapeutic options for malignant gliomas are currently researched. Sonodynamic Therapy (SDT) has proven to be a promising treatment combining the effects of low-intensity ultrasound waves with various sound-sensitive compounds, whose activation leads to increased immunogenicity of tumor cells, increased apoptotic rates and decreased angiogenetic potential. In addition, this therapeutic technique only exerts its cytotoxic effects on tumor cells, while both ultrasound waves and sensitizing compound are non-toxic per se. This review summarizes the present knowledge regarding mechanisms of action of SDT and currently available sonosensitizers and focuses on the preclinical and clinical studies that have investigated its efficacy on malignant gliomas. To date, preclinical studies implying various sonosensitizers and different treatment protocols all seem to confirm the anti-tumoral properties of SDT, while first clinical trials will soon start recruiting patients. Accordingly, it is crucial to conduct further investigations regarding the clinical applications of SDT as a therapeutic option in the management of intracranial gliomas.
Use of a Machine Learning Method in Predicting Refraction after Cataract Surgery
Authors: Yamauchi Tomofusa , Tabuchi Hitoshi , Takase Kosuke , Masumoto Hiroki
Published: March 2021

The present study aims to describe the use of machine learning (ML) in predicting the occurrence of postoperative refraction after cataract surgery and compares the accuracy of this method to conventional intraocular lens (IOL) power calculation formulas. In total, 3331 eyes from 2010 patients were assessed. The objects were divided into training data and test data. The constants for the IOL power calculation formulas and model training for ML were optimized using training data. Then, the occurrence of postoperative refraction was predicted using conventional formulas, or ML models were calculated using the test data. We evaluated the SRK/T formula, Haigis formula, Holladay 1 formula, Hoffer Q formula, and Barrett Universal II formula (BU-II); similar to ML methods, we assessed support vector regression (SVR), random forest regression (RFR), gradient boosting regression (GBR), and neural network (NN). Among the conventional formulas, BU-II had the lowest mean and median absolute error of prediction. Therefore, we compared the accuracy of our method with that of BU-II. The absolute errors of some ML methods were lower than those of BU-II. However, no statistically significant difference was observed. Thus, the accuracy of our method was not inferior to that of BU-II.
Effect of Acupuncture in Pain Management of Head and Neck Cancer Radiotherapy: Prospective Randomized Unicentric Study
Authors: Dymackova Radana , Selingerova Iveta , Kazda Tomas , Slavik Marek , Halamkova Jana , Svajdova Michaela , Slampa Pavel , Slama Ondrej
Published: March 2021

This prospective randomized open-label trial aimed to evaluate the role of acupuncture in the treatment of pain related to curative and adjuvant (chemo)radiotherapy of head and neck cancer. Patients in two arms (30 patients in each arm) underwent standard oncology therapy and standard supportive care with or without acupuncture. The stratification factors were the type of treatment and chemotherapy indication. The toxicity assessed was represented by pain rated on a 10-point pain scale and analgesic use. Average pain (AP) and the worst pain during the day (WP) were significantly lower in the acupuncture arm during radiotherapy (AP median 0.16 vs. 1.36, p < 0.001; WP median 0.90 vs. 1.96, p < 0.001) and three months after radiotherapy (AP median 0.07 vs. 0.50, p < 0.001; WP median 0.30 vs. 0.83, p = 0.002). The analgesic consumption between arms was statistically significantly different. A median of the proportion of days when the patients used analgesics was 8% and 32.5% during radiotherapy (p = 0.047) and 0% and 20.8% during three months after radiotherapy (p = 0.006) for the acupuncture and control arm, respectively. Results point out lower analgesic consumption and milder pain in acupuncture arm. Acupuncture consequently offers another alternative to standard treatment leading to a reduction in the toxicity of oncological treatment.
Efficacy of the XEN-Implant in Glaucoma and a Meta-Analysis of the Literature
Authors: Poelman Huub , Pals Jan , Rostamzad Parinaz , Bramer Wichor , Wolfs Roger , Ramdas Wishal
Published: March 2021

Background: To assess the efficacy of XEN-implant surgery in patients with glaucoma, and to perform a meta-analysis of previously published results and compare these to our data. Methods: Prospective case-control study, in which all eyes that underwent XEN-implant surgery were included from 2015 onwards. Sub-analyses were performed for eyes that underwent XEN-implant as standalone procedure and as cataract-combined procedure. To compare our results, a systematic review was performed using the Embase, PubMed, Web of Science, and Cochrane database. Meta-analyses were performed by combining data (intraocular pressure (IOP), IOP-lowering medication, and complications) from the retrieved studies. Results: A total of 221 eyes underwent XEN-implant surgery (124 standalone and 97 cataract-combined). The mean ± standard deviation IOP declined from 18.8 ± 6.5 to 13.5 ± 4.3 mmHg at the last follow-up (p < 0.001; 28.9%). Postoperative, no significant differences in IOP or IOP-lowering medication were found between patients with and without combined procedure. Secondary surgeries were performed in 20.8% of eyes, most of them (63.0%) within six months. A meta-analysis of 19 studies retrieved from the systematic review showed a two-years postoperative pooled mean (weighted mean difference) of 14.5 (7.3) mmHg and 1.0 (1.6) for IOP and IOP-lowering medications, respectively (compared to 13.5 (5.3) mmHg and 3.2 (2.4) in the current study). Conclusion: XEN-implant surgery was effective and safe in lowering IOP and the number of IOP-lowering medications. There were no differences between standalone and combined procedures.
Is It Time for Machine Learning Algorithms to Predict the Risk of Kidney Failure in Patients with Chronic Kidney Disease?
Authors: Thongprayoon Charat , Kaewput Wisit , Choudhury Avishek , Hansrivijit Panupong , Mao Michael A. , Cheungpasitporn Wisit
Published: March 2021

Chronic kidney disease (CKD) is a common clinical problem affecting more than 800 million people with different kidney diseases [...]
Hodgkin Lymphoma—Review on Pathogenesis, Diagnosis, Current and Future Treatment Approaches for Adult Patients
Authors: Momotow Jesko , Borchmann Sven , Eichenauer Dennis A. , Engert Andreas , Sasse Stephanie
Published: March 2021

Hodgkin lymphoma (HL) is a rare malignancy accounting for roughly 15% of all lymphomas and mostly affecting young patients. A second peak is seen in patients above 60 years of age. The history of HL treatment represents a remarkable success story in which HL has turned from an incurable disease to a neoplasm with an excellent prognosis. First-line treatment with stage-adapted treatment consisting of chemotherapy and/or radiotherapy results in cure rates of approximately 80%. Second-line treatment mostly consists of intensive salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Novel approaches such as antibody drug conjugates and immunomodulatory drugs have shown impressive results in clinical trials in refractory and relapsed HL and are now increasingly implemented in earlier treatment lines. This review gives a comprehensive overview on HL addressing epidemiology, pathophysiology and current treatment options as well as recent developments and perspectives.
Reconstruction of Marine Traffic from Sémaphore Data: A Python-GIS Procedure to Build Synthetic Navigation Routes and Analyze Their Temporal Variation
Authors: Minelli Annalisa , Berre Iwan Le , Peuziat Ingrid , Rouan Mathias
Published: March 2021

Originally designed as a mode of telecommunication, the network of French sémaphore is now dedicated to the continuous monitoring and recording of marine traffic along the entire French coast. Although the observation data collected by sémaphores cover 7/7 days and 24/24 h and could provide precious information regarding marine traffic, they remain underexploited. Indeed, these data concern all types of traffic, including leisure boating and smaller craft that are not usually recorded by the most common means of observation, such as AIS, radar and satellite. Based on sémaphore data, traffic pressure and its spatiotemporal distribution can be fully measured to better analyze its interactions with human activities and the environment. One drawback of these data is their initially semantic nature, which requires the development of an original processing method. The protocol developed to analyze the marine traffic of the Iroise Sea and its first results are presented in this article. It is based on a semi-automatic method aimed to clean the original data and quantify the marine traffic along synthetic routes. It includes a procedure that takes into account the temporal evolution of the traffic based on the Allen’s time framework. The results proved interesting as they provide an overview of marine traffic, including all types of vessels, and may be defined for different time periods and granularity. A description of the numerical and geographic instruments created is given; all the written code is released as Open Source software and freely available for download and testing.