bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between Standing Trunk Extension Angle and Medial Elbow Injuries in Young Baseball Pitchers
Authors: Gonno Megumi , Kida Noriyuki , Nomura Teruo , Matsui Tomoyuki , Azuma Yoshikazu , Hiramoto Machiko , Hashimoto Ruo , Miyazaki Tetsuya , Tanaka Maki , Watanabe Yuya , Kai Yoshihiro , Morihara Toru
Published: March 2022

Purpose: The purpose of this study was to investigate the relationship between the standing trunk extension angle and medial elbow injuries. Subjects and methods: The study participants were 90 male baseball pitchers (10–12 years) belonging to youth baseball teams. Pitching elbow injuries were evaluated by an orthopedic surgeon using ultrasound scans and physical examination findings. A single optical three-dimensional motion analysis system was used for the trunk extension measurements, with three-dimensional coordinates captured. The overall, upper, and lower trunk angles were then analyzed. Results: Trunk extension angle during standing trunk extension was significantly smaller among participants who were positive for medial elbow injuries on ultrasound scans (positive: 71.4° ± 10.3°; negative: 75.7° ± 9.2°; t = 2.05, p < 0.05). The upper trunk extension angle was significantly smaller than the lower trunk extension angle among participants who were positive for medial elbow injuries on physical examination (upper: 33.0° ± 6.9°; lower: 41.2° ± 8.2°; t = −2.42, p < 0.05). Conclusions: Trunk extension angle during standing trunk extension is associated with medial elbow injuries. Evaluating the trunk extension angle as multiple segments rather than a single rigid body is valuable.
Development and Evaluation of Interactive Flipped e-Learning (iFEEL) for Pharmacy Students during the COVID-19 Pandemic
Authors: Shahba Ahmad A. , Alashban Zaid , Sales Ibrahim , Sherif Abdelrahman Y. , Yusuf Osman
Published: March 2022

Background: Distance learning has come to the forefront of educational delivery throughout the world due to the COVID-19 pandemic. Presently, there is a paucity of studies that have utilized interactive e-lectures as a model for remote flipped learning. Objectives: To compare educational outcomes for the remote interactive flipped e-learning (iFEEL) activity versus paper-based in-class group learning (PICkLE). Methods: During the spring 2021 semester, tutorials in pharmaceutical quality control and good manufacturing practice were remotely delivered to students by two different approaches: PICkLE and iFEEL. In the latter activity, interactive e-lectures were software-designed and included several audiovisual enhanced illustrations to encourage students to interact with the lecture material prior to attending the virtual class. The class time was reserved for in-class quizzes and discussion. Mean exam scores were compared and voluntary questionnaires were distributed among the participating students as well as healthcare faculty members in 29 Saudi universities. Data from the remotely-delivered course was compared with data from previous course offerings (2018–2020) that used the live PICkLE method. Results: The mean score of post-lecture tests significantly (p < 0.05) increased compared to pre-lecture tests in remote PICkLE and iFEEL, respectively. iFEEL activity showed higher mean post-tests score (95.2%) compared to live PICkLE (90.2%, p = 0.08) and remote PICkLE (93.5%, p = 0.658). Mean comprehensive exam scores increased from 83.8% for remote PICkLE to 89.2% for iFEEL (p = 0.449). On average, 92% of students and 85% of faculty members reported positive feedback on the five quality attributes of the e-lecture. Over 75% of students preferred the iFEEL over PICkLE activity for future course offerings and 84% of faculty members recommend the integration of interactive e-lectures in their future courses. Conclusion: iFEEL represents a novel model of remote flipped learning and shows promising potential to be incorporated into live blended-learning classroom activities.
Under Pressure: The Chronic Effects of Lower-Body Compression Garment Use during a 6-Week Military Training Course
Authors: Edgar David T. , Beaven Christopher Martyn , Gill Nicholas D. , Driller Matthew W.
Published: March 2022

Background: Previous studies have shown that compression garments may aid recovery in acute settings; however, less is known about the long-term use of compression garments (CG) for recovery. This study aimed to assess the influence of wearing CG on changes in physical performance, subjective soreness, and sleep quality over 6 weeks of military training. Methods: Fifty-five officer-trainees aged 24 ± 6 y from the New Zealand Defence Force participated in the current study. Twenty-seven participants wore CG every evening for 4–6 h, and twenty-eight wore standard military attire (CON) over a 6-week period. Subjective questionnaires (soreness and sleep quality) were completed weekly, and 2.4 km run time-trial, maximum press-ups, and curl-ups were tested before and after the 6 weeks of military training. Results: Repeated measures ANOVA indicated no significant group × time interactions for performance measures (p > 0.05). However, there were small effects in favour of CG over CON for improvements in 2.4 km run times (d = −0.24) and press-ups (d = 0.36), respectively. Subjective soreness also resulted in no significant group × time interaction but displayed small to moderate effects for reduced soreness in favour of CG. Conclusions: Though not statistically significant, CG provided small to moderate benefits to muscle-soreness and small benefits to aspects of physical-performance over a 6-week military training regime.
Challenges of Data Availability and Use in Conducting Health-EDRM Research in a Post-COVID-19 World
Authors: Chan Emily Ying Yang , Guha-Sapir Debarati , Dubois Caroline , Shaw Rajib , Wong Chi Sing
Published: March 2022

Disasters disrupt communication channels, infrastructure, and overburden health systems. This creates unique challenges to the functionality of surveillance tools, data collection systems, and information sharing platforms. The WHO Health Emergency and Disaster Risk Management (Health-EDRM) framework highlights the need for appropriate data collection, data interpretation, and data use from individual, community, and global levels. The COVID-19 crisis has evolved the way hazards and risks are viewed. No longer as a linear event but as a protracted hazard, with cascading and compound risks that affect communities facing complex risks such as climate-related disasters or urban growth. The large-scale disruptions of COVID-19 show that disaster data must evolve beyond mortality and frequency of events, in order to encompass the impact on the livelihood of communities, differentiated between population groups. This includes relative economic losses and psychosocial damage. COVID-19 has created a global opportunity to review how the scientific community classifies data, and how comparable indicators are selected to inform evidence-based resilience building and emergency preparedness. A shift into microlevel data, and regional-level information sharing is necessary to tailor community-level interventions for risk mitigation and disaster preparedness. Real-time data sharing, open governance, cross-organisational, and inter-platform collaboration are necessary not just in Health-EDRM and control of biological hazards, but for all natural hazards and man-made disasters.
Mechanical Differences between Men and Women during Overground Load Carriage at Self-Selected Walking Speeds
Authors: Middleton Kane , Vickery-Howe Danielle , Dascombe Ben , Clarke Anthea , Wheat Jon , McClelland Jodie , Drain Jace
Published: March 2022

Few studies have directly compared physical responses to relative loading strategies between men and women during overground walking. This study aimed to compare gait mechanics of men and women during overground load carriage. A total of 30 participants (15 male, 15 female) completed three 10-min walking trials while carrying external loads of 0%, 20% and 40% of body mass at a self-selected walking speed. Lower-body motion and ground reaction forces were collected using a three-dimensional motion capture system and force plates, respectively. Female participants walked with a higher cadence (p = 0.002) and spent less absolute time in stance (p = 0.010) but had similar self-selected walking speed (p = 0.750), which was likely due to the female participants being shorter than the male participants. Except for ankle plantarflexion moments, there were no sex differences in spatiotemporal, kinematic, or kinetic variables (p > 0.05). Increasing loads resulted in significantly lower self-selected walking speed, greater stance time, and changes in all joint kinematics and kinetics across the gait cycle (p < 0.05). In conclusion, there were few differences between sexes in walking mechanics during overground load carriage. The changes identified in this study may inform training programs to increase load carriage performance.
Environmental Substances Associated with Chronic Obstructive Pulmonary Disease—A Scoping Review
Authors: Elonheimo Hanna Maria , Mattila Tiina , Andersen Helle Raun , Bocca Beatrice , Ruggieri Flavia , Haverinen Elsi , Tolonen Hanna
Published: March 2022

Chronic obstructive pulmonary disease (COPD) is a slowly developing non-communicable disease (NCD), causing non-reversible obstruction and leading to marked morbidity and mortality. Besides traditional risk factors such as smoking, some environmental substances can augment the risk of COPD. The European Human Biomonitoring Initiative (HBM4EU) is a program evaluating citizens’ exposure to various environmental substances and their possible health impacts. Within the HBM4EU, eighteen priority substances or substance groups were chosen. In this scoping review, seven of these substances or substance groups are reported to have an association or a possible association with COPD. Main exposure routes, vulnerable and high-exposure risk groups, and matrices where these substances are measured are described. Pesticides in general and especially organophosphate and carbamate insecticides, and some herbicides, lead (Pb), and polycyclic aromatic hydrocarbons (PAHs) showed an association, and cadmium (Cd), chromium (Cr and CrVI), arsenic (As), and diisocyanates, a possible association with COPD and/or decreased lung function. Due to long latency in COPD’s disease process, the role of chemical exposure as a risk factor for COPD is probably underestimated. More research is needed to support evidence-based conclusions. Generally, chemical exposure is a growing issue of concern, and prompt action is needed to safeguard public health.
Perspective Charts in a Multi-Foci Globe-Based Visualization of COVID-19 Data
Authors: MacTavish Mia , Wecker Lakin , Samavati Faramarz
Published: March 2022

The use of perspective projection in data visualization has been shown to potentially aid with the perception of small values in datasets with important variations at multiple scales. We integrate perspective charts, which use perspective projection in their designs, into a geospatial visualization application for global COVID-19 data. We perform an evaluation through Amazon Mechanical Turk to evaluate the readability of these visualizations compared to traditional methods, when tools such as interactive techniques are used. Results of our evaluation show that participants more accurately retrieved small values from perspective chart visualizations than traditional bar charts on the globe. The use of perspective projection in an interactive system allows for users to read data with important variations at multiple scales without affecting the overall perception of scale in datasets.
Investigating the Potential Use of Chemical Biopsy Devices to Characterize Brain Tumor Lipidomes
Authors: Bogusiewicz Joanna , Kupcewicz Bogumiła , Goryńska Paulina Zofia , Jaroch Karol , Goryński Krzysztof , Birski Marcin , Furtak Jacek , Paczkowski Dariusz , Harat Marek , Bojko Barbara
Published: March 2022

The development of a fast and accurate intraoperative method that enables the differentiation and stratification of cancerous lesions is still a challenging problem in laboratory medicine. Therefore, it is important to find and optimize a simple and effective analytical method of enabling the selection of distinctive metabolites. This study aims to assess the usefulness of solid-phase microextraction (SPME) probes as a sampling method for the lipidomic analysis of brain tumors. To this end, SPME was applied to sample brain tumors immediately after excision, followed by lipidomic analysis via liquid chromatography-high resolution mass spectrometry (LC-HRMS). The results showed that long fibers were a good option for extracting analytes from an entire lesion to obtain an average lipidomic profile. Moreover, significant differences between tumors of different histological origin were observed. In-depth investigation of the glioma samples revealed that malignancy grade and isocitrate dehydrogenase (IDH) mutation status impact the lipidomic composition of the tumor, whereas 1p/19q co-deletion did not appear to alter the lipid profile. This first on-site lipidomic analysis of intact tumors proved that chemical biopsy with SPME is a promising tool for the simple and fast extraction of lipid markers in neurooncology.
GLP1 Exerts Paracrine Activity in the Intestinal Lumen of Human Colon
Authors: Grau-Bové Carme , González-Quilen Carlos , Cantini Giulia , Nardini Patrizia , Espina Beatriz , Bani Daniele , Terra Ximena , Blay MTeresa , Rodríguez-Gallego Esther , Luconi Michaela , Ardévol Anna , Pinent Montserrat
Published: March 2022

GLP1 produced in the upper part of the gut is released after food intake and acts by activating insulin secretion, but the role of GLP1 in the colon, where it is predominantly produced, remains unknown. Here we characterized the apical versus basolateral secretion of GLP1 and PYY and the paracrine mechanisms of action of these enterohormones in the human colon. We stimulated human colon tissue in different ex vivo models with meat peptone and we used immunofluorescence to study the presence of canonical and non-canonical receptors of GLP1. We found that PYY and GLP1 are secreted mainly at the gut lumen in unstimulated and stimulated conditions. We detected DPP4 activity and found that GLP1R and GCGR are widely expressed in the human colon epithelium. Unlike GLP1R, GCGR is not expressed in the lamina propria, but it is located in the crypts of Lieberkühn. We detected GLP1R expression in human colon cell culture models. We show that the apical secretion of PYY and GLP1 occurs in humans, and we provide evidence that GLP1 has a potential direct paracrine function through the expression of its receptors in the colon epithelium, opening new therapeutic perspectives in the use of enterohormones analogues in metabolic pathologies.
The Role of Endoplasmic Reticulum Stress and NLRP3 Inflammasome in Liver Disorders
Authors: Lu Xueqin , Huang Haitao , Fu Xiaodi , Chen Chaoran , Liu Huiyang , Wang Honggang , Wu Dongdong
Published: March 2022

The endoplasmic reticulum (ER) is a key organelle responsible for the synthesis, modification, folding and assembly of proteins; calcium storage; and lipid synthesis. When ER homeostatic balance is disrupted by a variety of physiological and pathological factors—such as glucose deficiency, environmental toxins, Ca2+ level changes, etc.—ER stress can be induced. Abnormal ER stress can be involved in many diseases. NOD-like receptor family pyrin domain-containing 3 (NLRP3), an intracellular receptor, can perceive internal and external stimuli. It binds to apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 to assemble into a protein complex called the NLRP3 inflammasome. Evidence indicates that ER stress and the NLRP3 inflammasome participate in many pathological processes; however, the exact mechanism remains to be understood. In this review, we summarized the role of ER stress and the NLRP3 inflammasome in liver disorders and analyzed the mechanisms, to provide references for future related research.
Immune Checkpoint Receptors Signaling in T Cells
Authors: Baldanzi Gianluca
Published: March 2022

The characterization of the receptors negatively modulating lymphocyte function is rapidly advancing, driven by success in tumor immunotherapy. As a result, the number of immune checkpoint receptors characterized from a functional perspective and targeted by innovative drugs continues to expand. This review focuses on the less explored area of the signaling mechanisms of these receptors, of those expressed in T cells. Studies conducted mainly on PD-1, CTLA-4, and BTLA have evidenced that the extracellular parts of some of the receptors act as decoy receptors for activating ligands, but in all instances, the tyrosine phosphorylation of their cytoplasmatic tail drives a crucial inhibitory signal. This negative signal is mediated by a few key signal transducers, such as tyrosine phosphatase, inositol phosphatase, and diacylglycerol kinase, which allows them to counteract TCR-mediated activation. The characterization of these signaling pathways is of great interest in the development of therapies for counteracting tumor-infiltrating lymphocyte exhaustion/anergy independently from the receptors involved.
An Updated Model of the Divisome: Regulation of the Septal Peptidoglycan Synthesis Machinery by the Divisome
Authors: Attaibi Mohamed , den Blaauwen Tanneke
Published: March 2022

The synthesis of a peptidoglycan septum is a fundamental part of bacterial fission and is driven by a multiprotein dynamic complex called the divisome. FtsW and FtsI are essential proteins that synthesize the peptidoglycan septum and are controlled by the regulatory FtsBLQ subcomplex and the activator FtsN. However, their mode of regulation has not yet been uncovered in detail. Understanding this process in detail may enable the development of new compounds to combat the rise in antibiotic resistance. In this review, recent data on the regulation of septal peptidoglycan synthesis is summarized and discussed. Based on structural models and the collected data, multiple putative interactions within FtsWI and with regulators are uncovered. This elaborates on and supports an earlier proposed model that describes active and inactive conformations of the septal peptidoglycan synthesis complex that are stabilized by these interactions. Furthermore, a new model on the spatial organization of the newly synthesized peptidoglycan and the synthesis complex is presented. Overall, the updated model proposes a balance between several allosteric interactions that determine the state of septal peptidoglycan synthesis.
Drenched Silicon Suppresses Disease and Insect Pests in Coffee Plant Grown in Controlled Environment by Improving Physiology and Upregulating Defense Genes
Authors: Yang Jingli , Song Jinnan , Jeong Byoung Ryong
Published: March 2022

Plant disease and insect pests are major limiting factors that reduce crop production worldwide. The ornamental indoor cultivation cash crop dwarf coffee Punica arabica ‘Pacas’ is also troubled by these issues. Silicon (Si) is one of the most abundant elements in the lithosphere and positively impacts plant health by effectively mitigating biotic and abiotic stresses. Several studies have shown that Si activates plant defense systems, although the specific nature of the involvement of Si in biochemical processes that lead to resistance is unclear. In our study, Si significantly promoted the growth and development of dwarf coffee seedlings grown in plant growth chambers. More than that, through natural infection, Si suppressed disease and insect pests by improving physiology (e.g., the strong development of the internal structures of roots, stems, and leaves; higher photosynthetic efficiency; more abundant organic matter accumulation; the promotion of root activity; the efficient absorption and transfer of mineral elements; and various activated enzymes) and up-regulating defense genes (CaERFTF11 and CaERF13). Overall, in agriculture, Si may potentially contribute to global food security and safety by assisting in the creation of enhanced crop types with optimal production as well by mitigating plant disease and insect pests. In this sense, Si is a sustainable alternative in agricultural production.
In Silico Characterisation of the Late Embryogenesis Abundant (LEA) Protein Families and Their Role in Desiccation Tolerance in Ramonda serbica Panc
Authors: Pantelić Ana , Stevanović Strahinja , Komić Sonja Milić , Kilibarda Nataša , Vidović Marija
Published: March 2022

Ramonda serbica Panc. is an ancient resurrection plant able to survive a long desiccation period and recover metabolic functions upon watering. The accumulation of protective late embryogenesis abundant proteins (LEAPs) is a desiccation tolerance hallmark. To propose their role in R. serbica desiccation tolerance, we structurally characterised LEAPs and evaluated LEA gene expression levels in hydrated and desiccated leaves. By integrating de novo transcriptomics and homologues LEAP domains, 318 R. serbica LEAPs were identified and classified according to their conserved motifs and phylogeny. The in silico analysis revealed that hydrophilic LEA4 proteins exhibited an exceptionally high tendency to form amphipathic α-helices. The most abundant, atypical LEA2 group contained more hydrophobic proteins predicted to fold into the defined globular domains. Within the desiccation-upregulated LEA genes, the majority encoded highly disordered DEH1, LEA1, LEA4.2, and LEA4.3 proteins, while the greatest portion of downregulated genes encoded LEA2.3 and LEA2.5 proteins. While dehydrins might chelate metals and bind DNA under water deficit, other intrinsically disordered LEAPs might participate in forming intracellular proteinaceous condensates or adopt amphipathic α-helical conformation, enabling them to stabilise desiccation-sensitive proteins and membranes. This comprehensive LEAPs structural characterisation is essential to understanding their function and regulation during desiccation aiming at crop drought tolerance improvement.
IL11 Activates Pancreatic Stellate Cells and Causes Pancreatic Inflammation, Fibrosis and Atrophy in a Mouse Model of Pancreatitis
Authors: Ng Benjamin , Viswanathan Sivakumar , Widjaja Anissa A. , Lim Wei-Wen , Shekeran Shamini G. , Goh Joyce Wei Ting , Tan Jessie , Kuthubudeen Fathima , Lim Sze Yun , Xie Chen , Schafer Sebastian , Adami Eleonora , Cook Stuart A.
Published: March 2022

Interleukin-11 (IL11) is important for fibrosis and inflammation, but its role in the pancreas is unclear. In pancreatitis, fibrosis, inflammation and organ dysfunction are associated with pancreatic stellate cell (PSC)-to-myofibroblast transformation. Here, we show that IL11 stimulation of PSCs, which specifically express IL11RA in the pancreas, results in transient STAT3 phosphorylation, sustained ERK activation and PSC activation. In contrast, IL6 stimulation of PSCs caused sustained STAT3 phosphorylation but did not result in ERK activation or PSC transformation. Pancreatitis factors, including TGFβ, CTGF and PDGF, induced IL11 secretion from PSCs and a neutralising IL11RA antibody prevented PSC activation by these stimuli. This revealed an important ERK-dependent role for autocrine IL11 activity in PSCs. In mice, IL11 was increased in the pancreas after pancreatic duct ligation, and in humans, IL11 and IL11RA levels were elevated in chronic pancreatitis. Following pancreatic duct ligation, administration of anti-IL11RA to mice reduced pathologic (ERK, STAT, NF-κB) signalling, pancreatic atrophy, fibrosis and pro-inflammatory cytokine (TNFα, IL6 and IL1β) levels. This is the first description of IL11-mediated activation of PSCs, and the data suggest IL11 as a stromal therapeutic target in pancreatitis.
Calcium- and Integrin-Binding Protein 2 (CIB2) in Physiology and Disease: Bright and Dark Sides
Authors: Dal Cortivo Giuditta , Dell’Orco Daniele
Published: March 2022

Calcium- and integrin-binding protein 2 (CIB2) is a small EF-hand protein capable of binding Mg2+ and Ca2+ ions. While its biological function remains largely unclear, an increasing number of studies have shown that CIB2 is an essential component of the mechano-transduction machinery that operates in cochlear hair cells. Mutations in the gene encoding CIB2 have been associated with non-syndromic deafness. In addition to playing an important role in the physiology of hearing, CIB2 has been implicated in a multitude of very different processes, ranging from integrin signaling in platelets and skeletal muscle to autophagy, suggesting extensive functional plasticity. In this review, we summarize the current understanding of biochemical and biophysical properties of CIB2 and the biological roles that have been proposed for the protein in a variety of processes. We also highlight the many molecular aspects that remain unclarified and deserve further investigation.
Macrophage-like Cells Are Responsive to Titania Nanotube Intertube Spacing—An In Vitro Study
Authors: Necula Madalina Georgiana , Mazare Anca , Negrescu Andreea Mariana , Mitran Valentina , Ozkan Selda , Trusca Roxana , Park Jung , Schmuki Patrik , Cimpean Anisoara
Published: March 2022

With the introduction of a new interdisciplinary field, osteoimmunology, today, it is well acknowledged that biomaterial-induced inflammation is modulated by immune cells, primarily macrophages, and can be controlled by nanotopographical cues. Recent studies have investigated the effect of surface properties in modulating the immune reaction, and literature data indicate that various surface cues can dictate both the immune response and bone tissue repair. In this context, the purpose of the present study was to investigate the effects of titanium dioxide nanotube (TNT) interspacing on the response of the macrophage-like cell line RAW 264.7. The cells were maintained in contact with the surfaces of flat titanium (Ti) and anodic TNTs with an intertube spacing of 20 nm (TNT20) and 80 nm (TNT80), under standard or pro-inflammatory conditions. The results revealed that nanotube interspacing can influence macrophage response in terms of cell survival and proliferation, cellular morphology and polarization, cytokine/chemokine expression, and foreign body reaction. While the nanostructured topography did not tune the macrophages’ differentiation into osteoclasts, this behavior was significantly reduced as compared to flat Ti surface. Overall, this study provides a new insight into how nanotubes’ morphological features, particularly intertube spacing, could affect macrophage behavior.
Protein Kinases: Function, Substrates, and Implication in Diseases
Authors: Cipak Lubos
Published: March 2022

Protein kinases are important enzymes, involved in the regulation of various cellular processes [...]
Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response
Authors: Milosevic Katarina , Stevanovic Ivana , Bozic Iva D. , Milosevic Ana , Janjic Marija M. , Laketa Danijela , Bjelobaba Ivana , Lavrnja Irena , Savic Danijela
Published: March 2022

Neuroinflammation and microglial activation, common components of most neurodegenerative diseases, can be imitated in vitro by challenging microglia cells with Lps. We here aimed to evaluate the effects of agmatine pretreatment on Lps-induced oxidative stress in a mouse microglial BV-2 cell line. Our findings show that agmatine suppresses nitrosative and oxidative burst in Lps-stimulated microglia by reducing iNOS and XO activity and decreasing O2− levels, arresting lipid peroxidation, increasing total glutathione content, and preserving GR and CAT activity. In accordance with these results, agmatine suppresses inflammatory NF-kB, and stimulates antioxidant Nrf2 pathway, resulting in decreased TNF, IL-1 beta, and IL-6 release, and reduced iNOS and COX-2 levels. Together with increased ARG1, CD206 and HO-1 levels, our results imply that, in inflammatory conditions, agmatine pushes microglia towards an anti-inflammatory phenotype. Interestingly, we also discovered that agmatine alone increases lipid peroxidation end product levels, induces Nrf2 activation, increases total glutathione content, and GPx activity. Thus, we hypothesize that some of the effects of agmatine, observed in activated microglia, may be mediated by induced oxidative stress and adaptive response, prior to Lps stimulation.
Correction: Koh et al. Targeting MicroRNA-485-3p Blocks Alzheimer’s Disease Progression. Int. J. Mol. Sci. 2021, 22, 13136
Authors: Koh Han Seok , Lee SangJoon , Lee Hyo Jin , Min Jae-Woong , Iwatsubo Takeshi , Teunissen Charlotte E. , Cho Hyun-Jeong , Ryu Jin-Hyeob
Published: March 2022

The authors wish to make the following corrections to this paper [...]
Zafirlukast Induces VHL- and HIF-2α-Dependent Oxidative Cell Death in 786-O Clear Cell Renal Carcinoma Cells
Authors: Wolf Christopher , Smith Sonja , van Wijk Sjoerd J. L.
Published: March 2022

Mutations in the Von Hippel–Lindau (VHL) gene are the driving force in many forms of clear cell renal cell carcinoma (ccRCC) and promote hypoxia-inducible factor (HIF)-dependent tumor proliferation, metastasis and angiogenesis. Despite the progress that has already been made, ccRCC generally remain resistant to conventional therapies and ccRCC patients suffer from metastasis and acquired resistance, highlighting the need for novel therapeutic options. Cysteinyl leukotriene receptor 1 (CysLTR1) antagonists, like zafirlukast, are administered in bronchial asthma to control eicosanoid signaling. Intriguingly, long-term use of zafirlukast decreases cancer risk and leukotriene receptor antagonists inhibit tumor growth, but the mechanisms still remain unexplored. Therefore, we aim to understand the mechanisms of zafirlukast-mediated cell death in ccRCC cells. We show that zafirlukast induces VHL-dependent and TNFα-independent non-apoptotic and non-necroptotic cell death in ccRCC cells. Cell death triggered by zafirlukast could be rescued with antioxidants and the PARP-1 inhibitor Olaparib, and additionally relies on HIF-2α. Finally, MG-132-mediated proteasome inhibition sensitized VHL wild-type cells to zafirlukast-induced cell death and inhibition of HIF-2α rescued zafirlukast- and MG-132-triggered cell death. Together, these results highlight the importance of VHL, HIF and proteasomal degradation in zafirlukast-induced oxidative cell death with potentially novel therapeutic implications for ccRCC.
Mast Cells: When the Best Defense Is an Attack?
Authors: Martin Margarita
Published: March 2022

The main goal of this Special Issue was to highlight the recent advances made on the role of mast cells (MCs) in host defense and pathology [...]
Distinctive Toll-like Receptors Gene Expression and Glial Response in Different Brain Regions of Natural Scrapie
Authors: García-Martínez Mirta , Cortez Leonardo M. , Otero Alicia , Betancor Marina , Serrano-Pérez Beatriz , Bolea Rosa , Badiola Juan J. , Garza María Carmen
Published: March 2022

Prion diseases are chronic and fatal neurodegenerative diseases characterized by the accumulation of disease-specific prion protein (PrPSc), spongiform changes, neuronal loss, and gliosis. Growing evidence shows that the neuroinflammatory response is a key component of prion diseases and contributes to neurodegeneration. Toll-like receptors (TLRs) have been proposed as important mediators of innate immune responses triggered in the central nervous system in other human neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. However, little is known about the role of TLRs in prion diseases, and their involvement in the neuropathology of natural scrapie has not been studied. We assessed the gene expression of ovine TLRs in four anatomically distinct brain regions in natural scrapie-infected sheep and evaluated the possible correlations between gene expression and the pathological hallmarks of prion disease. We observed significant changes in TLR expression in scrapie-infected sheep that correlate with the degree of spongiosis, PrPSc deposition, and gliosis in each of the regions studied. Remarkably, TLR4 was the only gene upregulated in all regions, regardless of the severity of neuropathology. In the hippocampus, we observed milder neuropathology associated with a distinct TLR gene expression profile and the presence of a peculiar microglial morphology, called rod microglia, described here for the first time in the brain of scrapie-infected sheep. The concurrence of these features suggests partial neuroprotection of the hippocampus. Finally, a comparison of the findings in naturallyinfected sheep versus an ovinized mouse model (tg338 mice) revealed distinct patterns of TLRgene expression.
CD44 Receptor-Mediated/Reactive Oxygen Species-Sensitive Delivery of Nanophotosensitizers against Cervical Cancer Cells
Authors: Yoon Jieun , Kim Howard , Jeong Young-IL , Yang Hoe Saeng
Published: March 2022

Stimulus-sensitive, nanomedicine-based photosensitizer delivery has an opportunity to target tumor tissues since oxidative stress and the expression of molecular proteins, such as CD44 receptors, are elevated in the tumor microenvironment. The aim of this study is to investigate the CD44 receptor- and reactive oxygen species (ROS)-sensitive delivery of nanophotosensitizers of chlorin e6 (Ce6)-conjugated hyaluronic acid (HA) against HeLa human cervical cancer cells. For the synthesis of nanophotosensitizers, thioketal diamine was conjugated with the carboxyl group in HA and then the amine end group of HA-thioketal amine conjugates was conjugated again with Ce6 (Abbreviated as HAthCe6). The HAthCe6 nanophotosensitizers were of small diameter, with sizes less than 200. Their morphology was round-shaped in the observations using a transmission electron microscope (TEM). The HAthCe6 nanophotosensitizers responded to oxidative stress-induced changes in size distribution when H2O2 was added to the nanophotosensitizer aqueous solution, i.e., their monomodal distribution pattern at 0 mM H2O2 was changed to dual- and/or multi-modal distribution patterns at higher concentrations of H2O2. Furthermore, the oxidative stress induced by the H2O2 addition contributed to the disintegration of HAthCe6 nanophotosensitizers in morphology, and this phenomenon accelerated the release rate of Ce6 from nanophotosensitizers. In a cell culture study using HeLa cells, nanophotosensitizers increased Ce6 uptake ratio, ROS generation and PDT efficacy compared to free Ce6. Since HA specifically bonds with the CD44 receptor of cancer cells, the pretreatment of free HA against HeLa cells decreased the Ce6 uptake ratio, ROS generation and PDT efficacy of HAthCe6 nanophotosensitizers. These results indicated that intracellular delivery of HAthCe6 nanophotosensitizers can be controlled by the CD44 receptor-mediated pathway. Furthermore, these phenomena induced CD44 receptor-controllable ROS generation and PDT efficacy by HAthCe6 nanophotosensitizers. During in vivo tumor imaging using HeLa cells, nanophotosensitizer administration showed that the fluorescence intensity of tumor tissues was relatively higher than that of other organs. When free HA was pretreated, the fluorescence intensity of tumor tissue was relatively lower than those of other organs, indicating that HAthCe6 nanophotosensitizers have CD44 receptor sensitivity and that they can be delivered by receptor-specific manner. We suggest that HAthCe6 nanophotosensitizers are promising candidates for PDT in cervical cancer.
The Effects of Omni-Channel Retailing on Promotional Strategy
Authors: Schrotenboer Dana , Constantinides Efthymios , Herrando Carolina , de Vries Sjoerd
Published: March 2022

The objective of this study is to ascertain the effects of omni-channel retailing on the promotional strategy of retail organisations in order to better understand how to alter the promotional strategy in accordance with the ever-changing needs of customers and ultimately provide the customer with a seamless experience. This research is based on a critical systematic literature review of articles related to the topics of ‘omni-channel retailing’ and ‘promotional strategy’. The analysis made evident that most literature is focused on developing an understanding of omni-channel retailing; uncovering consumer behaviours in omni-channel retailing; and ways to adapt promotional strategies related to merchandising, sales promotion, selling, and word of mouth. Past research is quite fractured and does not represent a holistic picture of the implications of omni-channel retailing for promotional strategy. The analysis provided in this paper provides a general guideline for researchers and practitioners concerning promotional strategies that can be adopted in omni-channel retailing.
Managing Wildfire Risk in Mosaic Landscapes: A Case Study of the Upper Gata River Catchment in Sierra de Gata, Spain
Authors: Bertomeu Manuel , Pineda Javier , Pulido Fernando
Published: March 2022

Fire prevention and suppression approaches that exclusively rely on silvicultural measures and containment infrastructure have become increasingly ineffective in stopping the spread of wildfires. As agroforestry landscape mosaics consisting of a mix of different land cover and use types are considered less prone to fire than forests, approaches that support the involvement of rural people in agriculture and forestry activities have been proposed. However, it is unknown whether, in the current socio-economic context, these land-use interventions will nudge fire-prone landscapes towards more fire-resistant ones. We report on a case study of the Gata river catchment in Sierra de Gata, Spain, which is a fire-prone area that has been a pilot site for Mosaico-Extremadura, an innovative participatory fire-risk-mitigation strategy. Our purpose is to assess the efficacy of project interventions as “productive fuel breaks” and their potential for protecting high-risk areas. Interventions were effective in reducing the flame length and the rate of spread, and almost 40% of the intervention area was in sub-catchments with high risk. Therefore, they can function as productive fuel breaks and, if located strategically, contribute to mitigating wildfire risk. For these reasons, and in view of other economic and social benefits, collaborative approaches for land management are highly recommended.
Two-Step Geometry Design Method, Numerical Simulations and Experimental Studies of Bioresorbable Stents
Authors: Molęda Natalia , Kokot Grzegorz , Kuś Wacław , Sobota Michał , Włodarczyk Jakub , Stojko Mateusz
Published: March 2022

The stent-implantation process during angioplasty procedures usually involves clamping the stent onto a catheter to a size that allows delivery to the place inside the artery. Finding the right geometrical form of the stent to ensure good functionality in the open form and to enable the clamping process is one of the key elements in the stent-design process. In the first part of the work, an original two-step procedure for stent-geometry design was proposed. This was due to the necessary selection of a geometry that would provide adequate support to the blood-vessel wall without causing damage to the vessel. Numerical simulations of the crimping and deployment processes were performed to verify the method. At the end of this stage, the optimal stent was selected for further testing. In addition, numerical simulations of selected experimental tests (catheter-crimping process, compression process) were used to verify the obtained geometrical forms. The results of experimental tests on stents produced by the microinjection method are presented. The digital image correlation (DIC) method was used to compare the results of numerical simulation and experimental tests. The two-step modeling approach was found to help select the appropriate geometry of the expanded stent, which is an extremely important step in the design of the crimping process. In the part of the paper where the results obtained by numerical simulation were compared with those gained by experiment and using the DIC method, a good compatibility of the displacement results can be observed. For both longitudinal and transverse (pinch) stent compression, the results practically coincide. The paper presents also the application of the DIC method which significantly expands the research possibilities, allowing for a detailed inspection of the deformation state and, above all, verification of local dangerous areas. This approach significantly increases the possibility of assessing the quality of the stents.
Investigation of Phase Transitions in Ferromagnetic Nanofilms on a Non-Magnetic Substrate by Computer Simulation
Authors: Belim Sergey V.
Published: March 2022

Magnetic properties of ferromagnetic nanofilms on non-magnetic substrate are examined by computer simulation. The substrate influence is modeled using the two-dimensional Frenkel-Kontorova potential. The film has a cubic crystal lattice. Cases of different ratio for substrate period and ferromagnetic film period are considered. The difference in film and substrate periods results in film deformations. These deformations result in a change in the magnetic properties of the film. The Ising model and the Metropolis algorithm are used for the study of magnetic properties. The dependence of Curie temperature on film thickness and substrate potential parameters is calculated. Cases of different values for the coverage factor are considered. The deformation of the film layers is reduced away from the substrate when it is compressed or stretched. The Curie temperature increases when the substrate is compressed and decreases when the substrate is stretched. This pattern is performed for films with different thicknesses. If the coating coefficient for the film is different from one, periodic structures with an increased or reduced concentration of atoms are formed in the film first layer. These structures are absent in higher layers.
Printing Accuracy and Flexural Properties of Different 3D-Printed Denture Base Resins
Authors: al-Qarni Faisal D. , Gad Mohammed M.
Published: March 2022

Digital dentures can be fabricated by subtractive milling or, more recently, by 3D-printing technology. Several different 3D-printing technologies and materials are commercially available, and the differences in printing accuracy and mechanical behavior among them are unknown. Aim: This study evaluated the printing accuracy of 3D-printed denture base resins and assessed their flexural properties when compared with conventional heat-polymerized ones. Methods: A total of 40 acrylic specimens were prepared with four different materials: three 3D-printed resins, and a conventional heat polymerized resin was used as a control. The printing accuracy was evaluated by calculating the error rate of 3D-printed specimens compared with dimensions of the virtual design. Flexural strength and elastic modulus were assessed with a universal testing machine. One-way ANOVA and Kruskal–Wallis tests were used for analysis. Results: Printing accuracy across the tested materials was statistically different. Specimen length showed error rates between 1.3% and 2.4%, specimen width had error rates between 0.2% and 0.7%, and specimen thickness had error rates between 0.2% and 0.6%. Three-dimensional-printed specimens had lower flexural strength and elastic modulus values when compared with heat-polymerized specimens. Conclusions: The choice of material seems to influence printing accuracy, and to a lesser extent, flexural strength. However, it has no effect on the elastic modulus.
Purification, Chemical Characterization and Immunomodulatory Activity of a Sulfated Polysaccharide from Marine Brown Algae Durvillaea antarctica
Authors: Qin Ling , Xu Hui , He Yingying , Liang Chen , Wang Kai , Cao Junhan , Qu Changfeng , Miao Jinlai
Published: March 2022

An immunomodulatory polysaccharide (DAP4) was extracted, purified, and characterized from Durvillaea antarctica. The results of chemical and spectroscopic analyses demonstrated that the polysaccharide was a fucoidan, and was mainly composed of (1→3)-α-l-Fucp and (1→4)-α-l-Fucp residues with a small degree of branching at C-3 of (1→4)-α-l-Fucp residues. Sulfate groups were at C-4 of (1→3)-α-l-Fucp, C-2 of (1→4)-α-l-Fucp and minor C-6 of (1→4)-β-d-Galp. Small amounts of xylose and galactose exist in the forms of β-d-Xylp-(1→ and β-d-Gal-(1→. The immunomodulatory activity of DAP4 was measured on RAW 264.7 cells, the results proved that DAP4 exhibited excellent immunomodulatory activities, such as promoted the proliferation of spleen lymphocytes, increased NO production, as well as enhanced phagocytic of macrophages. Besides, DAP4 could also produce better enhancement on the vitality of NK cells. For the high immunomodulatory activity, DAP4 might be a potential source of immunomodulatory fucoidan with a novel structure.
Evaluation of Host Cell Impurity Effects on the Performance of Sterile Filtration Processes for Therapeutic Viruses
Authors: Wright Evan , Kawka Karina , Medina Maria Fe C. , Latulippe David R.
Published: March 2022

Efficient downstream processing represents a significant challenge in the rapidly developing field of therapeutic viruses. While it is known that the terminal sterile filtration step can be a major cause of product loss, there is little known about the effect of host cell impurities (DNA and protein) on filtration performance. In this study, fractions of relatively pure Vero host cell protein and DNA were spiked into a highly pure preparation of vesicular stomatitis virus (VSV). Then, the resulting solutions were sterile filtered using two commercially available 0.22 µm rated microfiltration membranes. A combination of transmembrane pressure measurements, virus recovery measurements, and post-filtration microscopy images of the microfiltration membranes was used to evaluate the sterile filtration performance. It was found that increasing the amount of host cell protein from approximately 1 µg/mL (in the un-spiked VSV preparation) to 25 µg/mL resulted in a greater extent of membrane fouling, causing the VSV recovery to decrease from 89% to 65% in experiments conducted with the highly asymmetric Express PLUS PES membrane and to go as low as 48% in experiments conducted with the symmetric Durapore PVDF membrane. Similar effects were not seen when bovine serum albumin, a common model protein used in filtration studies, was spiked into the VSV preparation, which indicates that the sterile filtration performance is critically dependent on the complex composition of the mixture of host cell proteins rather than the presence of any protein. The results presented in this work provide important insights into the role of host cell impurities on the performance of sterile filtration processes for therapeutic viruses.
Thermal-Structural Characteristics of Multi-Layer Vacuum-Insulated Pipe for the Transfer of Cryogenic Liquid Hydrogen
Authors: Kim Jeong Hwan , Park Dae Kyeom , Kim Tae Jin , Seo Jung Kwan
Published: March 2022

As the world’s hydrocarbon supplies are gradually being depleted, the search for alternative energy sources with acceptably low emissions of environmentally harmful pollutants is a growing concern. Hydrogen has been proposed by numerous researchers as a fuel source for ships. Liquid hydrogen (LH2) has been shown to be particularly attractive as a ship fuel with respect to its ability to reduce pollution, density, high performance in engines, and high caloric value per unit mass. However, working with hydrogen in the liquid phase requires very low (i.e., cryogenic) temperatures. The design of a cryogenic LH2 pipeline is very different from the design of a normal fluid pipe due to the change between the liquid and gas states involved and the effect of thermal and structural characteristics on the cryogenic temperature during LH2 transportation through the transfer pipeline. This study investigated the material and thermal-structural characteristics of a multi-layer vacuum-insulated pipeline system through experiments and finite element analysis. The experimental and numerical results can be used as a database of material parameters for thermal-structural analysis when designing applications such as LH2 pipeline systems for hydrogen carriers and hydrogen-fuelled ships.