bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Thermal O2 Plasma Efficacy on C. albicans and Its Effect on Denture Base Resin Color
Authors: Maillet Christina , Odof Serge , Meuret Mikaël , Le Bras Florian , Velard Frédéric , Gelle Marie-Paule
Published: November 2021

Denture stomatitis is a disease involving C. albicans, which can affect elderly and immuno-compromised people. To avoid any recurrence of this pathology, it is necessary to treat patients regularly and disinfect dentures. However, the denture cleansers’ efficacy is not optimal and often leads to adverse color effects on the denture base resins. The aim of this study was to investigate the efficacy of a low-pressure non-thermal O2 plasma (NTP) treatment on C. albicans seeded on ProBase®Hot resin (Ivoclar Vivadent). The viability reduction of C. albicans was assessed by colony forming units (CFU) analysis and by scanning electron microscopy (SEM). The effect of repeated treatments on the resin color was evaluated by spectrophotometry. The resin samples were placed in a sealed bag in which O2 plasma was generated in low-pressure conditions. The results showed that a 120-min O2 NTP treatment led to a 6-log reduction of C. albicans viability (p < 0.05) and to yeasts’ major alterations observed by SEM. Furthermore, significant slight color changes of the resin (∆E00 = 1.33) were noted only after six plasma treatments (p < 0.05). However, the denture aesthetic was preserved, as the color changes were not perceptible and remained below the acceptability threshold (∆E00 < 4).
Opoka—Sediment Rock as New Type of Hybrid Mineral Filler for Polymer Composites
Authors: Przekop Robert E. , Jakubowska Paulina , Sztorch Bogna , Kozera Rafał , Dydek Kamil , Jałbrzykowski Marek , Osiecki Tomasz , Marciniak Piotr , Martyła Agnieszka , Kloziński Arkadiusz , Brząkalski Dariusz
Published: November 2021

The work presents a comprehensive profile of the physicochemical characteristics of opoka sedimentary rock in the context of its use as a hybrid filler for thermoplastics. Determining the functional parameters of the studied filler was the main aim of this research. Thermal treatment leads to changes in its morphology and phase composition. A wide range of physicochemical techniques was used, such as low-temperature nitrogen adsorption, FT-IR, TGA, XRD, optical, and electron microscopy. The susceptibility of the material to micronisation was also tested (ball milling). Due to its widespread occurrence, opoka can be an attractive alternative to fillers such as silica or chalk. In order to verify this statement, polypropylene composites thereof were prepared by melt blending and injection molding, and studied by mechanical testing and microscopic imaging.
Cordon Pricing, Daily Activity Pattern, and Exposure to Traffic-Related Air Pollution: A Case Study of New York City
Authors: Baghestani Amirhossein , Tayarani Mohammad , Allahviranloo Mahdieh , Gao H. Oliver
Published: November 2021

Road pricing is advocated as an effective travel demand management strategy to alleviate traffic congestion and improve environmental conditions. This paper analyzes the impacts of cordon pricing on the population’s daily activity pattern and their exposure to particulate matter by integrating activity-based models with air quality and exposure models in the case of New York City. To estimate changes in public exposure under cordon pricing scenarios, we take a sample of employees and study their mobility behavior during the day, which is mainly attributed to the location of the work and the time spent at work. The selection of employees and their exposure during the duration of their work is due to the unavailability of exact activity patterns for each individual. We show that the Central Business District (CBD) experiences a high concentration of PM2.5 emissions. Results indicate that implementing cordon pricing scenarios can reduce the population-weighted mean of exposure to PM2.5 emissions by 7% to 13% for our sample and, in particular, by 22% to 28% for those who work in the CBD. Furthermore, using an experimental model and assuming constant conditions, we point out the positive influence on indoor exposure for two locations inside and outside the CBD in response to cordon pricing. Considering the correlation between long-term exposure to fine particulate matter and the risks of developing cardiovascular disease and lung cancer, our findings suggest that improved public health conditions could be provided by implementing cordon pricing in the New York City CBD.
Survey of Eight Modern Methods of Hamiltonian Mechanics
Authors: Bruno Alexander D. , Batkhin Alexander B.
Published: November 2021

Here we describe eight new methods, arisen in the last 60 years, to study solutions of a Hamiltonian system with n degrees of freedom. The first six of them are intended for systems with small parameters or without them. The methods allow to find families of periodic solutions and families of invariant n-dimensional tori by means of analytic computation near a stationary solution, near a periodic solution and near an invariant torus, using the corresponding normal form of a Hamiltonian. Then we can continue the founded families by means of numerical computation. In a Hamiltonian system without parameters, only periodic solutions and invariant n-dimensional tori form one-parameter families. The last two methods are intended for systems with not small parameters, which do not depend on time. They allow computing sets of parameters, which guarantee the stability of some solutions for linear (method seven) and nonlinear (method eight) systems. We do not consider chaotic behaviors, but only regular ones.
Oxford Nanopore MinION Direct RNA-Seq for Systems Biology
Authors: Pyatnitskiy Mikhail A. , Arzumanian Viktoriia A. , Radko Sergey P. , Ptitsyn Konstantin G. , Vakhrushev Igor V. , Poverennaya Ekaterina V. , Ponomarenko Elena A.
Published: November 2021

Long-read direct RNA sequencing developed by Oxford Nanopore Technologies (ONT) is quickly gaining popularity for transcriptome studies, while fast turnaround time and low cost make it an attractive instrument for clinical applications. There is a growing interest to utilize transcriptome data to unravel activated biological processes responsible for disease progression and response to therapies. This trend is of particular interest for precision medicine which aims at single-patient analysis. Here we evaluated whether gene abundances measured by MinION direct RNA sequencing are suited to produce robust estimates of pathway activation for single sample scoring methods. We performed multiple RNA-seq analyses for a single sample that originated from the HepG2 cell line, namely five ONT replicates, and three replicates using Illumina NovaSeq. Two pathway scoring methods were employed—ssGSEA and singscore. We estimated the ONT performance in terms of detected protein-coding genes and average pairwise correlation between pathway activation scores using an exhaustive computational scheme for all combinations of replicates. In brief, we found that at least two ONT replicates are required to obtain reproducible pathway scores for both algorithms. We hope that our findings may be of interest to researchers planning their ONT direct RNA-seq experiments.
Immunocytometric Analysis of Oral Pemphigus vulgaris Patients after Treatment with Rituximab as Adjuvant
Authors: Fortuna Giulio , Calabria Elena , Aria Massimo , Giudice Amerigo , Mignogna Michele Davide
Published: November 2021

Background: B-cell depletion therapy was demonstrated to be a valid and safe alternative as an adjuvant in oral-pharyngeal pemphigus vulgaris (OPV) patients. We aimed to assess its effects on anti-desmoglein (Dsg) 1 and 3 and leukocytes subsets profile in these patients’ population. Methods and Materials: We evaluated the immunologic profile of 10 OPV patients treated with RTX as adjuvant by using the ELISA testing for anti-Dsg-1 and -3 titers and the immunophenotyping for B and T-cell lymphocyte subpopulations and compared them with the PDAI score for clinical remission. Results: A significant difference in medians between baseline, end of RTX therapy, and 6 months after RTX therapy was observed in Dsg-3 titer (p < 0.001), in the CD8 (p = 0.009), and CD20 counts (p < 0.001). Multiple comparisons after Bonferroni adjustment confirmed such significant differences mainly between baseline and the end of RTX therapy and baseline and 6 months after RTX therapy. Only the anti-Dsg-3 titer at the end of RTX therapy demonstrated a slight positive correlation with the PDAI score at baseline (p = 0.046, r = 0.652). Conclusions: B-cell depletion adjuvant therapy in OPV patients demonstrated a significant impact on anti-Dsg-3 titer and B and T-cell lymphocyte subpopulations profile.
Immunological Targets of Biologic Drugs in Allergic Skin Diseases in Children
Authors: Di Filippo Paola , Russo Daniele , Attanasi Marina , Di Pillo Sabrina , Chiarelli Francesco
Published: November 2021

Atopic dermatitis and urticaria are two invalidating skin disorders that are very common in children. Recent advances in the understanding of their specific intracellular molecular pathways have permitted the development of precise biological molecules, targeting inflammatory mediators and arresting the pathogenetic pathways of skin diseases. Many biologics with promising results have been studied, although few are currently approved in children. In this review, we aim to provide the latest evidence about the use, indications, efficacy and safety of biologic therapies to treat atopic dermatitis and chronic urticaria in children and adolescents.
Experimental Bioactive Glass-Containing Composites and Commercial Restorative Materials: Anti-Demineralizing Protection of Dentin
Authors: Par Matej , Gubler Andrea , Attin Thomas , Tarle Zrinka , Tarle Andro , Tauböck Tobias T.
Published: November 2021

The purpose of this in vitro study was to investigate whether different types of experimental and commercial restorative dental materials can protect dentin against acid-induced softening. Experimental composites were prepared with a photocurable mixture of methacrylates and two types of bioactive glass (45S5 and a customized low-Na F-containing formulation). Human dentin samples were prepared from mid-coronal tooth slices and immersed in lactic acid solution (pH = 4.0) at 5 mm from set specimens of restorative material. After 4, 8, 12, 16, 20, 24, 28, and 32 days, surface microhardness of dentin samples and pH of the immersion solution were measured, followed by replenishing of the immersion medium. Microstructural analysis was performed using scanning electron microscopy. The protective effect of restorative materials was determined as dentin microhardness remaining statistically similar to initial values for a certain number of acid additions. Scanning electron microscopy showed a gradual widening of dentinal tubules and proved less discriminatory than microhardness measurements. To produce a protective effect on dentin, 20 wt% of low-Na F-containing bioactive glass was needed, whereas 10 wt% of bioactive glass 45S5 was sufficient to protect dentin against acid-induced demineralization. The anti-demineralizing protective effect of experimental and commercial restoratives on dentin was of shorter duration than measured for enamel in a previous study using the same experimental approach.
Residual Strength of Reinforced Concrete Beams under Sequential Small Impact Loads
Authors: Hansapinyo Chayanon , Limkatanyu Suchart , Zhang Hexin , Imjai Thanongsak
Published: November 2021

Sequential small impact loads may not collapse structures directly but could weaken the strength of structures. This study aimed to investigate the impact of these sequential small impact loads on the strength of the reinforced concrete beams. First, six sequential impact loads were applied to the test specimens. Then, the residual static capacity of the impacted specimens was determined by the ultimate static load test, compared with those of undamaged specimens. The experiment was composed of 12 specimens having identical dimensions. The variable parameters were the magnitude of the axial load and shear reinforcement. Under the sequential small impacts, the axial load improves the impact performance. It reduces the tensile strain of the longitudinal reinforcement. Hence, the flexural tensile crack propagation is limited. In addition, the local damage at the impact location is minimized and the shear plug induced diagonal shear crack is prevented. The axial force is also able to diminish the adverse effect of the large spacing stirrups. Large impact load could alter the failure of a designed flexural critical reinforced concrete beam without axial load to the shear failure. Although the axial load improves the impact response, the Residual Resistance Index (RRI) decreases with axial load. For the damaged specimens with axial load, the ultimate static load is lower than the calculated concrete shear capacity and more severe diagonal shear cracks were found. It can be obviously said that the prior impact damage decreases the concrete shear capacity.
Management of VEGFR-Targeted TKI for Thyroid Cancer
Authors: Enokida Tomohiro , Tahara Makoto
Published: November 2021

Recent advances in the development of multitarget tyrosine kinase inhibitors (MTKIs), which mainly target the vascular endothelial growth factor receptor (VEGFR), have improved prognoses and dramatically changed the treatment strategy for advanced thyroid cancer. However, adverse events related to this inhibition can interrupt treatment and sometimes lead to discontinuation. In addition, they can be annoying and potentially jeopardize the subjects’ quality of life, even allowing that the clinical outcome of patients with advanced thyroid cancer remains limited. In this review, we summarize the potential mechanisms underlying these adverse events (hypertension, proteinuria and renal impairment, hemorrhage, fistula formation/gastrointestinal perforation, wound healing, cardiovascular toxicities, hematological toxicity, diarrhea, fatigue, and acute cholecystitis), their characteristics, and actual management. Furthermore, we also discuss the importance of related factors, including alternative treatments that target other pathways, the necessity of subject selection for safer administration, and patient education.
Serum Total Bilirubin and Risk of Cancer: A Swedish Cohort Study and Meta-Analysis
Authors: Monroy-Iglesias Maria J. , Moss Charlotte , Beckmann Kerri , Hammar Niklas , Walldius Goran , Bosco Cecilia , Van Hemelrijck Mieke , Santaolalla Aida
Published: November 2021

Bilirubin has strong antioxidant properties that have been hypothesized to be preventive against the development of cancer. Thus, we aimed to investigate the association between serum total bilirubin (STB) and risk of overall and site-specific cancers in the large Swedish Apolipoprotein Mortality Risk (AMORIS) cohort. We also performed a systematic review and meta-analysis for specific cancer types (colorectal, breast and lung). We found no association between high levels of STB and risk of overall cancer. Regarding site-specific cancer, there was an inverse association between increased STB and lung cancer (Hazard Ratio (HR) for the 4th quartile (Q4) vs. Q1: 0.50; 95%CI: 0.44–0.59) and gynecological cancer (HR for Q4 vs. Q1: 0.86; 95%CI: 0.76–0.99). A positive association was found with melanoma (HR for Q4 vs. Q1: 1.25; 95%CI: 1.06–1.47) and breast cancer (HR for Q4 vs. Q1: 1.13; 95%CI: 1.01–1.25) risk. The meta-analysis showed an inverse association between high levels of STB and risk of lung cancer (Relative risk (RR): 0.69; 95%CI: 0.55–0.86). No associations were seen for colorectal and breast cancer risk. Further studies are required to establish if bilirubin can be used as a biomarker for risk assessment and/or as a novel therapeutic target.
Dysfunction of RNA/RNA-Binding Proteins in ALS Astrocytes and Microglia
Authors: Rossi Simona , Cozzolino Mauro
Published: November 2021

Amyotrophic Lateral Sclerosis is a neurological disease that primarily affects motor neurons in the cortex, brainstem, and spinal cord. The process that leads to motor neuron degeneration is strongly influenced by non-motor neuronal events that occur in a variety of cell types. Among these, neuroinflammatory processes mediated by activated astrocytes and microglia play a relevant role. In recent years, it has become clear that dysregulation of essential steps of RNA metabolism, as a consequence of alterations in RNA-binding proteins (RBPs), is a central event in the degeneration of motor neurons. Yet, a causal link between dysfunctional RNA metabolism and the neuroinflammatory processes mediated by astrocytes and microglia in ALS has been poorly defined. In this review, we will discuss the available evidence showing that RBPs and associated RNA processing are affected in ALS astrocytes and microglia, and the possible mechanisms involved in these events.
Mesenchymal Stem Cell Induced Foxp3(+) Tregs Suppress Effector T Cells and Protect against Retinal Ischemic Injury
Authors: Agrawal Mona , Rasiah Pratheepa Kumari , Bajwa Amandeep , Rajasingh Johnson , Gangaraju Rajashekhar
Published: November 2021

Mesenchymal stem/stromal cells (MSC) are well known for immunomodulation; however, the mechanisms involved in their benefits in the ischemic retina are unknown. This study tested the hypothesis that MSC induces upregulation of transcription factor forkhead box protein P3 (Foxp3) in T cells to elicit immune modulation, and thus, protect against retinal damage. Induced MSCs (iMSCs) were generated by differentiating the induced pluripotent stem cells (iPSC) derived from urinary epithelial cells through a noninsertional reprogramming approach. In in-vitro cultures, iMSC transferred mitochondria to immune cells via F-actin nanotubes significantly increased oxygen consumption rate (OCR) for basal respiration and ATP production, suppressed effector T cells, and promoted differentiation of CD4+CD25+ T regulatory cells (Tregs) in coculture with mouse splenocytes. In in-vivo studies, iMSCs transplanted in ischemia-reperfusion (I/R) injured eye significantly increased Foxp3+ Tregs in the retina compared to that of saline-injected I/R eyes. Furthermore, iMSC injected I/R eyes significantly decreased retinal inflammation as evidenced by reduced gene expression of IL1β, VCAM1, LAMA5, and CCL2 and improved b-wave amplitudes compared to that of saline-injected I/R eyes. Our study demonstrates that iMSCs can transfer mitochondria to immune cells to suppress the effector T cell population. Additionally, our current data indicate that iMSC can enhance differentiation of T cells into Foxp3 Tregs in vitro and therapeutically improve the retina’s immune function by upregulation of Tregs to decrease inflammation and reduce I/R injury-induced retinal degeneration in vivo.
FGFR1 Overexpression Induces Cancer Cell Stemness and Enhanced Akt/Erk-ER Signaling to Promote Palbociclib Resistance in Luminal A Breast Cancer Cells
Authors: Cheng Qiong , Ma Zhikun , Shi Yujie , Parris Amanda B. , Kong Lingfei , Yang Xiaohe
Published: November 2021

Resistance to CDK4/6 inhibitors (CDKis) is emerging as a clinical challenge. Identification of the factors contributing to CDKi resistance, with mechanistic insight, is of pivotal significance. Recent studies linked aberrant FGFR signaling to CDKi resistance. However, detailed mechanisms are less clear. Based on control and FGFR1 overexpressing luminal A cell line models, we demonstrated that FGFR1 overexpression rendered the cells resistant to palbociclib. FGFR1 overexpression abolished palbociclib-mediated cell cycle arrest, as well as the attenuated palbociclib-induced inhibition of G1/S transition regulators (pRb, E2F1, and cyclin D3) and factors that promote G2/M transition (cyclin B1, cdc2/CDK1, and cdc25). Importantly, FGFR1-induced palbociclib resistance was associated with promotion of cancer cell stemness and the upregulation of Wnt/β-catenin signaling. We found that palbociclib may function as an ER agonist in MCF-7/FGFR1 cells. Upregulation of the ER-mediated transcription in MCF-7/FGFR1 cells was associated with ERα phosphorylation and enhanced receptor tyrosine kinase signaling. The combination of palbociclib with FGFR-targeting AZD4547 resulted in remarkable synergistic effects on MCF-7/FGFR1 cells, especially for the inhibition of cancer cell stemness. Our findings of FGFR1-induced palbociclib resistance, promotion of cancer stem cells and associated molecular changes advance our mechanistic understanding of CDKi resistance, which will facilitate the development of strategies targeting CDKi resistance in breast cancer treatment.
Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory
Authors: Zhou Susan , Jia Zhengping
Published: November 2021

P21-activated kinase 3 (PAK3) gene mutations are linked to several neurodevelopmental disorders, but the underlying mechanisms remain unclear. In this study, we used a tetracycline-inducible system to control the expression of a mutant PAK3 (mPAK3) protein in immediate early gene, namely cFos, positive cells to disrupt PAK signaling, specifically in cells activated by social interaction in transgenic mice. We show that the expression of mPAK3-GFP proteins was in cFos-expressing excitatory and inhibitory neurons in various brain regions, such as the cortex and hippocampus, commonly activated during learning and memory. Basal expression of mPAK3-GFP proteins in cFos-positive cells resulted in social recognition memory deficits in the three-chamber social interaction test, without affecting locomotor activity or other forms of memory. The social memory deficit was rescued by doxycycline to halt the mPAK3-GFP transgene expression. In addition, we show that the expression of mPAK3-GFP proteins in a subset of cFos-positive cells, induced by an antecedent short social interaction, termed social pairing, was sufficient to impair social recognition memory. These results indicate that normal PAK signaling in cFos-positive cells activated during social interaction is critical for social memory.
Development and Characterization of Alkaline Phosphatase-Positive Human Umbilical Cord Perivascular Cells
Authors: Nonoyama Shun , Karakida Takeo , Chiba-Ohkuma Risako , Yamamoto Ryuji , Ujiie Yuko , Nagano Takatoshi , Yamakoshi Yasuo , Gomi Kazuhiro
Published: November 2021

Human umbilical cord perivascular cells (HUCPVCs), harvested from human umbilical cord perivascular tissue, show potential for future use as an alternative to mesenchymal stromal cells. Here, we present the results for the characterization of the properties alkaline phosphatase-positive HUCPVCs (ALP(+)-HUCPVCs). These ALP(+)-HUCPVCs were created from HUCPVCs in this study by culturing in the presence of activated vitamin D3, an inhibitor of bone morphogenetic protein signaling and transforming growth factor-beta1 (TGF-β1). The morphological characteristics, cell proliferation, gene expression, and mineralization-inducing ability of ALP(+)-HUCPVCs were investigated at the morphological, biological, and genetic levels. ALP(+)-HUCPVCs possess high ALP gene expression and activity in cells and a slow rate of cell growth. The morphology of ALP(+)-HUCPVCs is fibroblast-like, with an increase in actin filaments containing alpha-smooth muscle actin. In addition to ALP expression, the gene expression levels of type I collagen, osteopontin, elastin, fibrillin-1, and cluster of differentiation 90 are increased in ALP(+)-HUCPVCs. ALP(+)-HUCPVCs do not have the ability to induce mineralization nodules, which may be due to the restriction of phosphate uptake into matrix vesicles. Moreover, ALP(+)-HUCPVCs may produce anti-mineralization substances. We conclude that ALP(+)-HUCPVCs induced from HUCPVCs by a TGF-β1 stimulation possess myofibroblast-like properties that have little mineralization-inducing ability.
The Response of Mitochondrial Respiration and Quantity in Skeletal Muscle and Adipose Tissue to Exercise in Humans with Prediabetes
Authors: Szczerbinski Lukasz , Taylor Mark Alan , Puchta Urszula , Konopka Paulina , Paszko Adam , Citko Anna , Szczerbinski Karol , Goscik Joanna , Gorska Maria , Larsen Steen , Kretowski Adam
Published: November 2021

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes, but its contribution to the early stages of dysglycemia remains poorly understood. By collecting a high-resolution stage-based spectrum of dysglycemia, our study fills this gap by evaluating derangement in both the function and quantity of mitochondria. We sampled mitochondria in skeletal muscle and subcutaneous adipose tissues of subjects with progressive advancement of dysglycemia under a three-month exercise intervention. Methods: We measured clinical metabolic parameters and gathered skeletal muscle and adipose tissue biopsies before and after the three-month exercise intervention. We then assayed the number of mitochondria via citrate synthase (CS) activity and functional parameters with high-resolution respirometry. Results: In muscle, there were no differences in mitochondrial quantity or function at baseline between normoglycemics and prediabetics. However, the intervention caused improvement in CS activity, implying an increase in mitochondrial quantity. By contrast in adipose tissue, baseline differences in CS activity were present, with the lowest CS activity coincident with impaired fasting glucose and impaired glucose tolerance (IFG + IGT). Finally, CS activity, but few of the functional metrics, improved under the intervention. Conclusions: We show that in prediabetes, no differences in the function or amount of mitochondria (measured by CS activity) in skeletal muscle are apparent, but in adipose tissue of subjects with IFG + IGT, a significantly reduced activity of CS was observed. Finally, metabolic improvements under the exercise correlate to improvements in the amount, rather than function, of mitochondria in both tissues.
Comprehensive Analysis of microRNAs in Human Adult Erythropoiesis
Authors: Nath Aneesha , Rayabaram Janakiram , Ijee Smitha , Bagchi Abhirup , Chaudhury Anurag Dutta , Roy Debanjan , Chambayil Karthik , Singh Jyoti , Nakamura Yukio , Velayudhan Shaji R.
Published: November 2021

MicroRNAs (miRNAs) are small non-coding RNAs, which play an important role in various cellular and developmental processes. The study of miRNAs in erythropoiesis is crucial to uncover the cellular pathways that are modulated during the different stages of erythroid differentiation. Using erythroid cells derived from human CD34+ hematopoietic stem and progenitor cells (HSPCs)and small RNA sequencing, our study unravels the various miRNAs involved in critical cellular pathways in erythroid maturation. We analyzed the occupancy of erythroid transcription factors and chromatin accessibility in the promoter and enhancer regions of the differentially expressed miRNAs to integrate miRNAs in the transcriptional circuitry of erythropoiesis. Analysis of the targets of the differentially expressed miRNAs revealed novel pathways in erythroid differentiation. Finally, we described the application of Clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-Cas9) based editing of miRNAs to study their function in human erythropoiesis.
Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes
Authors: Nicolay Wiebke , Moeller Rebecca , Kahl Sina , Vondran Florian , Pietschmann Thomas , Kunz Stefan , Gerold Gisa
Published: November 2021

The liver is targeted by several human pathogenic RNA viruses for viral replication and dissemination; despite this, the extent of innate immune sensing of RNA viruses by human hepatocytes is insufficiently understood to date. In particular, for highly human tropic viruses such as hepatitis C virus, cell culture models are needed to study immune sensing. However, several human hepatoma cell lines have impaired RNA sensing pathways and fail to mimic innate immune responses in the human liver. Here we compare the RNA sensing properties of six human hepatoma cell lines, namely Huh-6, Huh-7, HepG2, HepG2-HFL, Hep3B, and HepaRG, with primary human hepatocytes. We show that primary liver cells sense RNA through retinoic acid-inducible gene I (RIG-I) like receptor (RLR) and Toll-like receptor 3 (TLR3) pathways. Of the tested cell lines, Hep3B cells most closely mimicked the RLR and TLR3 mediated sensing in primary hepatocytes. This was shown by the expression of RLRs and TLR3 as well as the expression and release of bioactive interferon in primary hepatocytes and Hep3B cells. Our work shows that Hep3B cells partially mimic RNA sensing in primary hepatocytes and thus can serve as in vitro model to study innate immunity to RNA viruses in hepatocytes.
Decreased Trabecular Bone Mass in Col22a1-Deficient Mice
Authors: Zhao Wenbo , Wiedemann Philip , Wölfel Eva Maria , Neven Mona , Peters Stephanie , Imhof Thomas , Koch Manuel , Busse Björn , Amling Michael , Schinke Thorsten , Yorgan Timur Alexander
Published: November 2021

The bone matrix is constantly remodeled by the coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. Whereas type I collagen is the most abundant bone matrix protein, there are several other proteins present, some of them specifically produced by osteoblasts. In a genome-wide expression screening for osteoblast differentiation markers we have previously identified two collagen-encoding genes with unknown function in bone remodeling. Here we show that one of them, Col22a1, is predominantly expressed in bone, cultured osteoblasts, but not in osteoclasts. Based on this specific expression pattern we generated a Col22a1-deficient mouse model, which was analyzed for skeletal defects by µCT, undecalcified histology and bone-specific histomorphometry. We observed that Col22a1-deficient mice display trabecular osteopenia, accompanied by significantly increased osteoclast numbers per bone surface. In contrast, cortical bone parameters, osteoblastogenesis or bone formation were unaffected by the absence of Col22a1. Likewise, primary osteoblasts from Col22a1-deficient mice did not display a cell-autonomous defect, and they did not show altered expression of Rankl or Opg, two key regulators of osteoclastogenesis. Taken together, we provide the first evidence for a physiological function of Col22a1 in bone remodeling, although the molecular mechanisms explaining the indirect influence of Col22a1 deficiency on osteoclasts remain to be identified.
Willin/FRMD6: A Multi-Functional Neuronal Protein Associated with Alzheimer’s Disease
Authors: Chen Doris , Yu Wanjia , Aitken Laura , Gunn-Moore Frank
Published: November 2021

The FERM domain-containing protein 6 (FRMD6), also known as Willin, is an upstream regulator of Hippo signaling that has recently been shown to modulate actin cytoskeleton dynamics and mechanical phenotype of neuronal cells through ERK signaling. Physiological functions of Willin/FRMD6 in the nervous system include neuronal differentiation, myelination, nerve injury repair, and vesicle exocytosis. The newly established neuronal role of Willin/FRMD6 is of particular interest given the mounting evidence suggesting a role for Willin/FRMD6 in Alzheimer’s disease (AD), including a series of genome wide association studies that position Willin/FRMD6 as a novel AD risk gene. Here we describe recent findings regarding the role of Willin/FRMD6 in the nervous system and its actions in cellular perturbations related to the pathogenesis of AD.
Association of Birth Weight with Central and Peripheral Corneal Thickness in Adulthood—Results from the Population-Based German Gutenberg Health Study
Authors: Fieß Achim , Urschitz Michael S. , Marx-Groß Susanne , Nagler Markus , Wild Philipp S. , Münzel Thomas , Beutel Manfred E. , Lackner Karl J. , Pfeiffer Norbert , Schuster Alexander K.
Published: November 2021

Purpose: Low birth weight (BW) is associated with altered ocular geometry such as a steeper corneal shape in adulthood. However, it is unclear whether low birth weight affects corneal thickness development in the center or periphery in adulthood which may contribute to ocular disease. The purpose of this study was to investigate corneal thickness in former low birth weight individuals in adulthood. Methods: The German Gutenberg Health Study is a prospective, population-based study in which every participant (age range 40–80 years) was measured with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). BW was collected by self-reports. The relationship between birth weight and corneal thickness at different locations were assessed. Linear regression models were carried out including uni- and multivariable analyses with adjustment for age, sex, mean corneal radius, and white-to-white distance. Main outcome measures were corneal thickness at the apex, at the pupil center, and at the corneal periphery. Results: Overall, 5657 participants were successfully measured (3019 females, aged 56.0 ± 10.3 years). In multivariable analyses a lower BW was associated with a thinner corneal thickness at the apex (B = 1.71 µm/500 g, p < 0.001) and at the pupil (B = 1.69 µm/500 g, p < 0.001). These effects diminished towards the corneal periphery resulting in no differences in the perilimbal regions. Conclusion: The present study provides evidence that lower birth weight goes along with corneal thickness alterations even into adult ages of 40 to 80 years. Thinner measurements of the cornea were particularly found in the corneal center and diminished in the periphery. This indicates that there may be fetal origins affecting corneal thickness development particularly in the corneal center.
Patterns of Response to Methylphenidate Administration in Children with ADHD: A Personalized Medicine Approach through Clustering Analysis
Authors: Grazioli Silvia , Rosi Eleonora , Mauri Maddalena , Crippa Alessandro , Tizzoni Federica , Tarabelloni Arianna , Villa Filippo Maria , Chiapasco Federica , Reimers Maria , Gatti Erika , Bertella Silvana , Molteni Massimo , Nobile Maria
Published: November 2021

Individual responses to methylphenidate (MPH) can significantly differ in children with attention-deficit/hyperactivity disorder (ADHD) in terms of the extent of clinical amelioration, optimal dosage needed, possible side effects, and short- and long-term duration of the benefits. In the present repeated-measures observational study, we undertook a proof-of-concept study to determine whether clustering analysis could be useful to characterize different clusters of responses to MPH in children with ADHD. We recruited 33 children with ADHD who underwent a comprehensive clinical, cognitive, and neurophysiological assessment before and after one month of MPH treatment. Symptomatology changes were assessed by parents and clinicians. The neuropsychological measures used comprised pen-and-paper and computerized tasks. Functional near-infrared spectroscopy was used to measure cortical hemodynamic activation during an attentional task. We developed an unsupervised machine learning algorithm to characterize the possible clusters of responses to MPH in our multimodal data. A symptomatology improvement was observed for both clinical and neuropsychological measures. Our model identified distinct clusters of amelioration that were related to symptom severity and visual-attentional performances. The present findings provide preliminary evidence that clustering analysis can potentially be useful in identifying different responses to MPH in children with ADHD, highlighting the importance of a personalized medicine approach within the clinical framework.
Research Progress in Corrosion Mechanism of Reinforced Alkali-Activated Concrete Structures
Authors: Zhang Feng , Xi Xun , Yang Shangtong
Published: November 2021

In this paper, the recent research progress on the corrosion of reinforced alkali-activated materials (AAMs) concrete structures is reviewed. The corrosion mechanisms induced by carbonation and chloride ingress in AAMs concrete are discussed, from the perspectives of composition, microstructure and pore solution chemistry, in comparison to ordinary Portland cement (OPC) concrete. The steel–alkali-activated concrete interface is a key to investigating corrosion initiation and propagation, which has different physical and chemical characteristics of the steel–concrete interface in OPC concrete. Moreover, the electrochemical process testing methods including half-cell potential and linear polarization resistance are critically discussed with a focus on what could be inherited from the OPC concrete and what criteria are no longer suitable for AAMs concrete due to underestimation in most cases. New data and theories are urgently needed for using AAMs in concrete structures to replace OPC. At the end of this paper, the research gaps and future research needs are summarised for the sake of widespread application of AAMs in concrete structures for sustainable and low-carbon construction.
Charge Carriers Density, Temperature, and Electric Field Dependence of the Charge Carrier Mobility in Disordered Organic Semiconductors in Low Density Region
Authors: Shukri Seyfan Kelil , Deja Lemi Demeyu
Published: November 2021

We investigate the transport properties of charge carriers in disordered organic semiconductors using a model that relates a mobility with charge carriers (not with small polarons) hopping by thermal activation. Considering Miller and Abrahams expression for a hopping rate of a charge carrier between localized states of a Gaussian distributed energies, we employ Monte Carlo simulation methods, and calculate the average mobility of finite charge carriers focusing on a lower density region where the mobility was shown experimentally to be independent of the density. There are Monte Carlo simulation results for density dependence of mobility reported for hopping on regularly spaced states neglecting the role of spatial disorder, which does not fully mimic the hopping of charge carriers on randomly distributed states in disordered system as shown in recent publications. In this work we include the spatial disorder and distinguish the effects of electric field and density which are not separable in the experiment, and investigate the influence of density and electric field on mobility at different temperatures comparing with experimental results and that found in the absence of the spatial disorder. Moreover, we analyze the role of density and localization length on temperature and electric field dependence of mobility. Our results also give additional insight regarding the value of localization length that has been widely used as 0.1b where b is a lattice sites spacing.
Analysis and Quantification of Alkyl (C12-22) Trimethyl Ammonium Chloride Content in Cosmetics: Regulatory Compliance Gap Analysis
Authors: Jairoun Ammar Abdulrahman , Al-Hemyari Sabaa Saleh , Shahwan Moyad , Zyoud Sa’ed H.
Published: November 2021

Background: Exceeding the recommended Alkyl (C12-22) trimethyl ammonium bromide and chloride levels in cosmetics and personal care products is a serious health threat. Objectives: To quantify and investigate Cetrimonium chloride and Behentrimonium chloride in cosmetics and personal care products in the UAE market to gauge whether or not they adhered to requirements for safety and health. Methods: A total of 164 cosmetics products were collected and analyzed in this study. The gas chromatography–mass spectrometry (GC–MS) method was developed and validated for the determination of Cetrimonium chloride and Behentrimonium chloride surfactants in cosmetics products. With each product, Cetrimonium chloride and Behentrimonium chloride (%) were calculated. To test cross-group differences in Cetrimonium chloride and Behentrimonium chloride (%), Kruskal–Wallis test was applied. Results: Of the 125 tested cosmetics and personal care products, five (4%) exceeded the recommended Cetrimonium chloride level in rinse-off hair products (2.5%), 10 (8%) exceeded the recommended Cetrimonium chloride level in leave-on hair products (1%), and 24 (61.5%) exceeded the recommended Cetrimonium chloride level used as a preservative in cosmetics products. Moreover, of the 125 tested cosmetics and personal care products, 21 (53.8%) exceeded the recommended Behentrimonium chloride level used as preservatives in cosmetics products. Conclusions: Although several structures for cosmetics quality and control across the globe are fairly comprehensive and intricate, there is a need to make them more rigorous to apply compliance with GMP and ensure regulatory control. Doing so would help enhance the inspection and regulation of cosmetics containing Behentrimonium chloride/Cetrimonium chloride preservatives. Furthermore, there is a dire need to establish a unified cosmetovigilance worldwide.
Medical Infrared Thermography in Odontogenic Facial Cellulitis as a Clinical Decision Support Tool. A Technical Note
Authors: Derruau Stéphane , Bogard Fabien , Exartier-Menard Guillaume , Mauprivez Cédric , Polidori Guillaume
Published: November 2021

Background: Odontogenic cellulitis are frequent infections of the head and neck fascial spaces that can sometimes spread and be life-threatening, requiring urgent hospitalization. Early diagnosis of facial cellulitis with diffuse inflammatory process is crucial in patient management but not always obvious in the field. Medical infrared thermography (MIT) is a noninvasive tool increasingly used to evaluate skin temperature maps and delineate inflammatory lesions. Objective: The aim of this work was to evaluate the use of MIT to improve the clinical examination of patients with facial cellulitis. Methods: Image processing work was carried out to highlight the thermal gradient resulting from inflammation linked to infection, in 2 patients with facial cellulitis. Results: In real-time, MIT allowed to precisely locate the inflammatory focus linked to cellulitis with no propagation to danger areas such as infraorbital space or around pharyngeal axis. Conclusion: Here, we show the first cases using MIT as a powerful complementary tool in the clinical evaluation of patients with facial cellulitis. Significance: This technology could help optimize the hospitalization decision through a facilitated assessment of infection spread in head and neck tissues and helping to incision for drainage.
Real-Time Monitoring and Quantitative Evaluation of Resin In-Filtrant Repairing Enamel White Spot Lesions Based on Optical Coherence Tomography
Authors: Zeng Sujuan , Huang Yuhang , Huang Wenyan , Pathak Janak L. , He Yanbing , Gao Weijian , Huang Jing , Zhang Yiqing , Zhang Jian , Dong Huixian
Published: November 2021

The aim of the present study was to explore the feasibility of real-time monitoring and quantitative guiding the repair of enamel white spot lesions (WSLs) with resin infiltration by optical coherence tomography (OCT). Seven New Zealand rabbits were treated with 37% phosphoric acid etchant for 15 min to establish the model of enamel demineralization chalk spots of upper incisors, which were repaired by Icon resin infiltrant. OCT, stereo microscope (SM) imaging, scanning electron microscope (SEM) imaging and hematoxylin eosin (HE) staining were used to image each operation step. The changes of WSLs of enamel before and in the process of restoration with resin infiltrant showed specific performance in OCT images, which were consistent with the corresponding results of stereomicroscope and SEM. OCT can non-invasively and accurately image the whole process of repairing enamel demineralization layer with resin infiltration real-time, which can effectively guide the clinical use of resin infiltrant to repair enamel WSLs and be used as an imaging tool to evaluate the process and effect of restoration with resin infiltrant at the same time.
Impact of Disturbances on Species Diversity and Regeneration of Nepalese Sal (Shorea robusta) Forests Managed under Different Management Regimes
Authors: Chapagain Uttam , Chapagain Binod P. , Nepal Sunil , Manthey Michael
Published: November 2021

Sal (Shorea robusta) forests, a dominant forest type in Nepal, experience different disturbance intensities depending on management regimes. This study compares the impact of disturbance on Nepalese Sal forests, which are managed on three major management regimes: protected area, state-managed forest, and buffer zone community forest. Using a systematic sampling approach, we sampled 20 plots, each covering 500 square meters, and nested plots within each main plot to measure pole and regeneration for each management regime. We recorded forest characteristics including tree species, counts, diameter, height, crown cover, and disturbance indicators. We compared forest attributes such as diversity indices, species richness, and stand structure by management regime using analysis of variance and regression analysis. The forest management regimes were classified into three disturbance levels based on disturbance factor bundles, and the buffer zone community forest was found to have the highest disturbance while the protected forest had the lowest disturbance. Species richness, diversity, evenness, abundance, density and basal area were higher, but regeneration was lower in protected area and state-managed forest compared to the buffer zone community forests. This suggests positive impacts of moderate disturbance on regeneration. The management plan should prioritize the minimization of excessive disturbance to balance forest conservation and provide forest resources to local users.
A Bourdieusian Analysis of Good Practice Partnerships: Implications for Private, Voluntary and Independent Early Childcare Leaders
Authors: McMahon Samantha , Firth Nicola , Youde Andrew
Published: November 2021

This article applies the theoretical lens of Bourdieu to explore leadership and the distribution of power between teachers and early childhood practitioners in the private voluntary and independent (PVI) sector in a good practice partnership. It questions the effectiveness of such partnerships in bringing about sustained improvements to practice in this sector. Data were collected in three focus groups with practitioners from 10 settings that were recruited by a consortium of schools to the partnership to take part in a 10-week intervention. The findings showed that the power imbalance between teachers and early childhood practitioners cancelled out collaborative pedagogical models of leadership intended to underpin the good practice partnership. Furthermore, this power imbalance contributed to the lack of sustainability of the intervention. In conclusion, leadership practices need to be more closely aligned between early childhood practitioners and teachers by drawing on ideas of moral leadership elicited from a symbolic frame. The article has relevance for leaders operating in collaborative contexts where existing power imbalances are evident.