bluuebunny/crossref_metadata_2025 huggingface dataset:
Merkel Cells Are Multimodal Sensory Cells: A Review of Study Methods
Authors: Bataille Adeline , Le Gall Christelle , Misery Laurent , Talagas Matthieu
Published: November 2022

Merkel cells (MCs) are rare multimodal epidermal sensory cells. Due to their interactions with slowly adapting type 1 (SA1) Aβ low-threshold mechanoreceptor (Aβ-LTMRs) afferents neurons to form Merkel complexes, they are considered to be part of the main tactile terminal organ involved in the light touch sensation. This function has been explored over time by ex vivo, in vivo, in vitro, and in silico approaches. Ex vivo studies have made it possible to characterize the topography, morphology, and cellular environment of these cells. The interactions of MCs with surrounding cells continue to be studied by ex vivo but also in vitro approaches. Indeed, in vitro models have improved the understanding of communication of MCs with other cells present in the skin at the cellular and molecular levels. As for in vivo methods, the sensory role of MC complexes can be demonstrated by observing physiological or pathological behavior after genetic modification in mouse models. In silico models are emerging and aim to elucidate the sensory coding mechanisms of these complexes. The different methods to study MC complexes presented in this review may allow the investigation of their involvement in other physiological and pathophysiological mechanisms, despite the difficulties in exploring these cells, in particular due to their rarity.
Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment
Authors: Piquet Léo , Coutant Kelly , Mitchell Andrew , Ben Anes Amel , Bollmann Enola , Schoonjans Nathan , Bérubé Julie , Bordeleau François , Brisson Alain , Landreville Solange
Published: November 2022

Uveal melanoma (UM) is the most common primary intraocular tumor and often spreads to the liver. Intercellular communication though extracellular vesicles (EVs) plays an important role in several oncogenic processes, including metastasis, therapeutic resistance, and immune escape. This study examines how EVs released by UM cells modify stellate and endothelial cells in the tumor microenvironment. The surface markers, and the concentration and size of EVs derived from UM cells or choroidal melanocytes were characterized by high-resolution flow cytometry, electron microscopy, and Western blotting. The selective biodistribution of EVs was studied in mice by fluorescence imaging. The activation/contractility of stellate cells and the tubular organization of endothelial cells after exposure to melanomic EVs were determined by traction force microscopy, collagen gel contraction, or endothelial tube formation assays. We showed that large EVs from UM cells and healthy melanocytes are heterogenous in size, as well as their expression of phosphatidylserine, tetraspanins, and Tsg101. Melanomic EVs mainly accumulated in the liver and lungs of mice. Hepatic stellate cells with internalized melanomic EVs had increased contractility, whereas EV-treated endothelial cells developed more capillary-like networks. Our study demonstrates that the transfer of EVs from UM cells leads to a pro-fibrotic and pro-angiogenic phenotype in hepatic stellate and endothelial cells.
Iron Brain Menace: The Involvement of Ferroptosis in Parkinson Disease
Authors: Lin Kai-Jung , Chen Shang-Der , Lin Kai-Lieh , Liou Chia-Wei , Lan Min-Yu , Chuang Yao-Chung , Wang Pei-Wen , Lee Jong-Jer , Wang Feng-Sheng , Lin Hung-Yu , Lin Tsu-Kung
Published: November 2022

Parkinson disease (PD) is the second-most common neurodegenerative disease. The characteristic pathology of progressive dopaminergic neuronal loss in people with PD is associated with iron accumulation and is suggested to be driven in part by the novel cell death pathway, ferroptosis. A unique modality of cell death, ferroptosis is mediated by iron-dependent phospholipid peroxidation. The mechanisms of ferroptosis inhibitors enhance antioxidative capacity to counter the oxidative stress from lipid peroxidation, such as through the system xc−/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis and the coenzyme Q10 (CoQ10)/FSP1 pathway. Another means to reduce ferroptosis is with iron chelators. To date, there is no disease-modifying therapy to cure or slow PD progression, and a recent topic of research seeks to intervene with the development of PD via regulation of ferroptosis. In this review, we provide a discussion of different cell death pathways, the molecular mechanisms of ferroptosis, the role of ferroptosis in blood–brain barrier damage, updates on PD studies in ferroptosis, and the latest progress of pharmacological agents targeting ferroptosis for the intervention of PD in clinical trials.
Sorting and Manipulation of Human PGC-LC Using PDPN and Hanging Drop Cultures
Authors: Arkoun Brahim , Moison Pauline , Guerquin Marie-Justine , Messiaen Sébastien , Moison Delphine , Tourpin Sophie , Monville Christelle , Livera Gabriel
Published: November 2022

The generation of oocytes from induced pluripotent stem cells (iPSCs) was proven efficient with mouse cells. However, no human iPSCs have yet been reported to generate cells able to complete oogenesis. Additionally, efficient sorting of human Primordial Germ Cell-like Cells (hPGC-LCs) without genomic integration of fluorescent reporter for their downstream manipulation is still lacking. Here, we aimed to develop a model that allows human germ cell differentiation in vitro in order to study the developing human germline. The hPGC-LCs specified from two iPS cell lines were sorted and manipulated using the PDPN surface marker without genetic modification. hPGC-LCs obtained remain arrested at early stages of maturation and no further differentiation nor meiotic onset occurred when these were cultured with human or mouse fetal ovarian somatic cells. However, when cultured independently of somatic ovarian cells, using BMP4 and the hanging drop-transferred EBs system, early hPGC-LCs further differentiate efficiently and express late PGC (DDX4) and meiotic gene markers, although no SYCP3 protein was detected. Altogether, we characterized a tool to sort hPGC-LCs and an efficient in vitro differentiation system to obtain pre-meiotic germ cell-like cells without using a gonadal niche.
Delivery of Active AKT1 to Human Cells
Authors: Siddika Tarana , Balasuriya Nileeka , Frederick Mallory I. , Rozik Peter , Heinemann Ilka U. , O’Donoghue Patrick
Published: November 2022

Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Thr308, Ser473), yet cell stimulation also activates many other kinases. To produce cells with specific AKT1 activity, we developed a novel system to deliver active AKT1 to human cells. We recently established a method to produce AKT1 phospho-variants from Escherichia coli with programmed phosphorylation. Here, we fused AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) protein. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308 induced selective phosphorylation of the known AKT1 substrate GSK-3α, but not GSK-3β, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Ser240/244. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on AKT1 activity.
Correction: Zheng et al. Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis. Cells 2021, 10, 3424
Authors: Zheng Yizhou , Xiao Yaosheng , Zhang Di , Zhang Shanshan , Ouyang Jing , Li Linfu , Shi Weimei , Zhang Rui , Liu Hai , Jin Qi , Chen Zhixi , Xu Daohua , Wu Longhuo
Published: November 2022

The authors wish to make the following changes to their paper [...]
Do Tumor Mechanical Stresses Promote Cancer Immune Escape?
Authors: Onwudiwe Killian , Najera Julian , Siri Saeed , Datta Meenal
Published: November 2022

Immune evasion—a well-established cancer hallmark—is a major barrier to immunotherapy efficacy. While the molecular mechanisms and biological consequences underpinning immune evasion are largely known, the role of tissue mechanical stresses in these processes warrants further investigation. The tumor microenvironment (TME) features physical abnormalities (notably, increased fluid and solid pressures applied both inside and outside the TME) that drive cancer mechanopathologies. Strikingly, in response to these mechanical stresses, cancer cells upregulate canonical immune evasion mechanisms, including epithelial–mesenchymal transition (EMT) and autophagy. Consideration and characterization of the origins and consequences of tumor mechanical stresses in the TME may yield novel strategies to combat immunotherapy resistance. In this Perspective, we posit that tumor mechanical stresses—namely fluid shear and solid stresses—induce immune evasion by upregulating EMT and autophagy. In addition to exploring the basis for our hypothesis, we also identify explicit gaps in the field that need to be addressed in order to directly demonstrate the existence and importance of this biophysical relationship. Finally, we propose that reducing or neutralizing fluid shear stress and solid stress-induced cancer immune escape may improve immunotherapy outcomes.
Identification and Validation of RELN Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung Cancer
Authors: Li Zhenpeng , Wang Xin , Yang Yi , Shi Fuyan , Zhang Wenjing , Wang Qinghua , Wang Suzhen
Published: November 2022

Remarkable clinical benefits in several advanced cancers are observed under the treatment of immune checkpoint inhibitor (ICI) agents. However, only a smaller proportion of patients respond to the treatments. Reelin (RELN) is frequently mutated in the cancer genome. In this study, the RELN mutation association with ICI treatment efficacy in melanoma and non-small cell lung cancer (NSCLC) was elucidated. Data from 631 melanoma and 109 NSCLC patients with both ICI treatment data and pre-treatment mutational profiles were collected. In addition, from the Cancer Genome Atlas (TCGA) project, we also obtained both tumors to explore the immunologic features behind RELN mutations. Melanoma patients with RELN mutations exhibited a favorable ICI survival benefit when compared with wild-type patients (HR: 0.66, 95% CI: 0.51–0.87, p = 0.003). A higher response rate was also noticed in RELN-mutated patients (38.9% vs. 28.3%, p = 0.017). The association of RELN mutations with a preferable immunotherapy outcome and response was further confirmed in NSCLC. Further exploration demonstrated that favorable immunocyte infiltration and immune response signaling pathways were found in patients with RELN mutations. In this study, RELN mutations were identified to connect with a better immune microenvironment and an improved ICI efficacy in melanoma and NSCLC, which provides a potential biomarker for immunological feature evaluation and immunotherapeutic outcome prediction at the molecular level.
A Review on Autophagy in Orofacial Neuropathic Pain
Authors: Shrivastava Mayank , Ye Liang
Published: November 2022

Orofacial neuropathic pain indicates pain caused by a lesion or diseases of the somatosensory nervous system. It is challenging for the clinician to diagnose and manage orofacial neuropathic pain conditions due to the considerable variability between individual clinical presentations and a lack of understanding of the mechanisms underlying the etiology and pathogenesis. In the last few decades, researchers have developed diagnostic criteria, questionnaires, and clinical assessment methods for the diagnosis of orofacial neuropathic pain. Recently, researchers have observed the role of autophagy in neuronal dysfunction as well as in the modulation of neuropathic pain. On this basis, in the present review, we highlight the characteristics, classification, and clinical assessment of orofacial neuropathic pain. Additionally, we introduce autophagy and its potential role in the modulation of orofacial neuropathic pain, along with a brief overview of the pathogenesis, which in future may reveal new possible targets for treating this condition.
The Role of Oxidative Stress in Atherosclerosis
Authors: Batty Matthew , Bennett Martin R. , Yu Emma
Published: November 2022

Atherosclerosis is a chronic inflammatory disease of the vascular system and is the leading cause of cardiovascular diseases worldwide. Excessive generation of reactive oxygen species (ROS) leads to a state of oxidative stress which is a major risk factor for the development and progression of atherosclerosis. ROS are important for maintaining vascular health through their potent signalling properties. However, ROS also activate pro-atherogenic processes such as inflammation, endothelial dysfunction and altered lipid metabolism. As such, considerable efforts have been made to identify and characterise sources of oxidative stress in blood vessels. Major enzymatic sources of vascular ROS include NADPH oxidases, xanthine oxidase, nitric oxide synthases and mitochondrial electron transport chains. The production of ROS is balanced by ROS-scavenging antioxidant systems which may become dysfunctional in disease, contributing to oxidative stress. Changes in the expression and function of ROS sources and antioxidants have been observed in human atherosclerosis while in vitro and in vivo animal models have provided mechanistic insight into their functions. There is considerable interest in utilising antioxidant molecules to balance vascular oxidative stress, yet clinical trials are yet to demonstrate any atheroprotective effects of these molecules. Here we will review the contribution of ROS and oxidative stress to atherosclerosis and will discuss potential strategies to ameliorate these aspects of the disease.
Primary Investigation of Phenotypic Plasticity in Fritillaria cirrhosa Based on Metabolome and Transcriptome Analyses
Authors: Wang Ye , Xie Huigan , Yang Tiechui , Gao Dan , Li Xiwen
Published: November 2022

Phenotypic plasticity refers to the adaptability of an organism to a heterogeneous environment. In this study, the differential gene expression and compositional changes in Fritillaria cirrhosa during phenotypic plasticity were evaluated using transcriptomic and metabolomic analyses. The annotation profiles of 1696 differentially expressed genes from the transcriptome between abnormal and normal phenotypes revealed that the main annotation pathways were related to the biosynthesis of amino acids, ABC transporters, and plant–pathogen interactions. According to the metabolome, the abnormal phenotype had 36 upregulated amino acids, including tryptophan, proline, and valine, which had a 3.77-fold higher relative content than the normal phenotype. However, saccharides and vitamins were found to be deficient in the abnormal phenotypes. The combination profiles demonstrated that phenotypic plasticity may be an effective strategy for overcoming potential stress via the accumulation of amino acids and regulation of the corresponding genes and transcription factors. In conclusion, a pathogen attack on F. cirrhosa may promote the synthesis of numerous amino acids and transport them into the bulbs through ABC transporters, which may further result in phenotypic variation. Our results provide new insights into the potential mechanism of phenotypic changes.
Dietary Choline Mitigates High-Fat Diet-Impaired Chylomicrons Assembly via UPRer Modulated by perk DNA Methylation
Authors: Bai Zhen-Yu , Zheng Hua , Luo Zhi , Hogstrand Christer , Wang Ling-Jiao , Song Yu-Feng
Published: November 2022

High-fat diets (HFD) lead to impairment of chylomicrons (CMs) assembly and adversely influence intestinal lipid homeostasis. However, the mechanisms of HFD impairing CMs assembly have yet to be fully understood. Additionally, although choline, as a lipid-lowering agent, has been widely used and its deficiency has been closely linked to non-alcoholic steatohepatitis (NASH), the contribution of choline by functioning as a methyl donor in alleviating HFD-induced intestinal lipid deposition is unknown. Thus, this study was conducted to determine the mechanism of HFD impairing CMs assembly and also tested the effect of choline acting as a methyl donor in this process. To this end, in this study, four diets (control, HFD, choline and HFD + choline diet) were fed to yellow catfish for 10 weeks in vivo and their intestinal epithelial cells were isolated and incubated for 36 h in fatty acids (FA) with or without choline solution combining si-perk transfection in vitro. The key findings from this study as follows: (1) HFD caused impairment of CMs assembly main by unfolded protein response (UPRer). HFD activated perk and then induced UPRer, which led to endoplasmic reticulum dysfunction and further impaired CMs assembly via protein–protein interactions between Perk and Apob48. (2) Choline inhibited the transcriptional expression level of perk via activating the −211 CpG methylation site, which initiated the subsequent ameliorating effect on HFD-impaired CMs assembly and intestinal lipid dysfunction. These results provide a new insight into direct crosstalk between UPRer and CMs assembly, and also emphasize the critical contribution of choline acting as a methyl donor and shed new light on choline-deficient diet-induced NASH.
The Biological Effects of Compound Microwave Exposure with 2.8 GHz and 9.3 GHz on Immune System: Transcriptomic and Proteomic Analysis
Authors: Yao Chuanfu , Wang Hui , Sun Liu , Ren Ke , Dong Ji , Wang Haoyu , Zhang Jing , Xu Xinping , Yao Binwei , Zhou Hongmei , Zhao Li , Peng Ruiyun
Published: November 2022

It is well-known that microwaves produce both thermal and nonthermal effects. Microwave ablation can produce thermal effects to activate the body’s immune system and has been widely used in cancer therapy. However, the nonthermal effects of microwaves on the immune system are still largely unexplored. In the present study, we exposed rats to multifrequency microwaves of 2.8 GHz and 9.3 GHz with an average power density of 10 mW/cm2, which are widely used in our daily life, to investigate the biological effects on the immune system and its potential mechanisms. Both single-frequency microwaves and multifrequency microwaves caused obvious pathological alterations in the thymus and spleen at seven days after exposure, while multifrequency microwaves produced more pronounced injuries. Unexpectedly, multifrequency microwave exposure increased the number of both leukocytes and lymphocytes in the peripheral blood and upregulated the proportion of B lymphocytes among the total lymphocytes, indicating activation of the immune response. Our data also showed that the cytokines associated with the proliferation and activation of B lymphocytes, including interleukin (IL)-1α, IL-1β and IL-4, were elevated at six hours after exposure, which might contribute to the increase in B lymphocytes at seven days after exposure. Moreover, multifrequency microwave exposure upregulated the mRNA and protein expression of B cell activation-associated genes in peripheral blood. In addition to immune-associated genes, multifrequency microwaves mainly affected the expression of genes related to DNA duplication, cellular metabolism and signal transduction in the peripheral blood and spleen. In conclusion, multifrequency microwaves with 2.8 GHz and 9.3 GHz caused reversible injuries of the thymus and spleen but activated immune cells in the peripheral blood by upregulating mRNA and protein expression, as well as cytokine release. These results not only uncovered the biological effects of multifrequency microwave on the immune system, but also provide critical clues to explore the potential mechanisms.
Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation
Authors: Mathis Bryan J. , Kato Hideyuki , Hiramatsu Yuji
Published: November 2022

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the endogenous antioxidant response to reactive oxygen species as well as a controller of Phase II detoxification in response to xenobiotics. This amenity to specific external manipulation exploits the binding affinity of Nrf2 for its constitutive repressor and degradation facilitator Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1). Derived from both natural and synthesized origins, these compounds have been extensively tested without definitive beneficial results. Unfortunately, multiple terminated trials have shown a negative side to Nrf2 with regard to cardiac pathologies while animal-based studies have demonstrated cardiomyocyte hypertrophy and heart failure after chronic Nrf2 upregulation. Putatively based on autophagic control of Nrf2 activity-modulating upstream factors, new evidence of miRNA involvement has added complexity to this mechanism. What follows is an extensive survey of Nrf2-regulating exogenous compounds that may promote cardiomyopathy, clinical trial evidence, and a comparison to exercise-induced factors that also upregulate Nrf2 while preventing cardiac pathologies.
CAF-Released Exosomal miR-20a-5p Facilitates HCC Progression via the LIMA1-Mediated β-Catenin Pathway
Authors: Qi Yong , Wang Haibo , Zhang Qikun , Liu Zhiqiang , Wang Tianbing , Wu Zhengsheng , Wu Wenyong
Published: November 2022

Currently, exosomes derived from Cancer-associated fibroblast (CAF) have reportedly been involved in regulating hepatocellular carcinoma (HCC) tumour microenvironment (TME). LIM domain and actin binding 1 (LIMA1) is an actin-binding protein that is involved in controlling the biological behaviour and progression of specific solid tumours. We aimed to determine the effect of LIMA1 and exosome-associated miR-20a-5p in HCC development. LIMA1 and miR-20a-5p expression levels were examined by real-time quantitative PCR (qRT-PCR), western blotting or immunohistochemistry (IHC). Functional experiments, including Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU) assays, colony formation assays, wound healing assays, and Transwell invasion assays, were performed to investigate the effect of LIMA1 and miR-20a-5p. A dual-luciferase reporter gene assay was performed to confirm the interaction of miR-20a-5p and LIMA1. Exosomes were characterised by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. We noted that LIMA1 was downregulated in human HCC tissues and cells and remarkably correlated with overall survival (OS) and recurrence-free survival (RFS). LIMA1 overexpression suppressed HCC cell proliferation and metastasis in vitro and in vivo, while LIMA1 knockdown had the opposite effects. A mechanistic investigation showed that LIMA1 inhibited the Wnt/β-catenin signalling pathway by binding to BMI1 and inducing its destabilisation. Additionally, we found that LIMA1 expression in HCC cells could be suppressed by transferring CAF-derived exosomes harbouring oncogenic miR-20a-5p. In summary, LIMA1 is a tumour suppressor that inhibits the Wnt/β-catenin signalling pathway and is downregulated by CAF-derived exosomes carrying oncogenic miR-20a-5p in HCC.
MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A
Authors: Soederberg Agnes , Meißgeier Tina , Bosserhoff Anja Katrin , Linck-Paulus Lisa
Published: November 2022

Cutaneous malignant melanoma is a highly proliferative and aggressive skin cancer with a steadily increasing incidence and a low long-term survival rate after metastatic progression. The protein MAGOH and its highly identical homologue MAGOHB are core components of the exon junction complex (EJC), which regulates splicing, stability and translation of mRNAs. The EJC, and especially MAGOH, has been shown to be involved in the development and progression of several cancers. In melanoma, the expression and function of both homologues remain essentially unexplored. This study identifies high MAGOH and MAGOHB protein expression in cutaneous melanoma cell lines and patient derived tissue samples. An siRNA-mediated knockdown of MAGOH significantly inhibits melanoma cell proliferation. The loss of MAGOH does not affect cell cycle progression, but induces apoptosis, an effect that is enhanced by a simultaneous knockdown of MAGOH and MAGOHB. MAGOH and MAGOHB do not influence the expression of the pro-apoptotic protein Bcl-XS or exon skipping. However, the knockdown of MAGOH and MAGOHB strongly decreases nonsense-mediated decay (NMD) activity, leading to an upregulation of the pro-apoptotic protein GADD45A. In conclusion, simultaneous inhibition of MAGOH and MAGOHB expression substantially affects cell survival, indicating both MAGOH homologues as promising new targets for the treatment of melanoma.
GABAA and GABAB Receptors Mediate GABA-Induced Intracellular Ca2+ Signals in Human Brain Microvascular Endothelial Cells
Authors: Negri Sharon , Scolari Francesca , Vismara Mauro , Brunetti Valentina , Faris Pawan , Terribile Giulia , Sancini Giulio , Berra-Romani Roberto , Moccia Francesco
Published: November 2022

Numerous studies recently showed that the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), can stimulate cerebral angiogenesis and promote neurovascular coupling by activating the ionotropic GABAA receptors on cerebrovascular endothelial cells, whereas the endothelial role of the metabotropic GABAB receptors is still unknown. Preliminary evidence showed that GABAA receptor stimulation can induce an increase in endothelial Ca2+ levels, but the underlying signaling pathway remains to be fully unraveled. In the present investigation, we found that GABA evoked a biphasic elevation in [Ca2+]i that was initiated by inositol-1,4,5-trisphosphate- and nicotinic acid adenine dinucleotide phosphate-dependent Ca2+ release from neutral and acidic Ca2+ stores, respectively, and sustained by store-operated Ca2+ entry. GABAA and GABAB receptors were both required to trigger the endothelial Ca2+ response. Unexpectedly, we found that the GABAA receptors signal in a flux-independent manner via the metabotropic GABAB receptors. Likewise, the full Ca2+ response to GABAB receptors requires functional GABAA receptors. This study, therefore, sheds novel light on the molecular mechanisms by which GABA controls endothelial signaling at the neurovascular unit.
Monitoring of MSW Incinerator Leachate Using Electronic Nose Combined with Manifold Learning and Ensemble Methods
Authors: Zhang Zhongyuan , Qiu Shanshan , Zhou Jie , Huang Jingang
Published: November 2022

Waste incineration is regarded as an ideal method for municipal solid waste disposal (MSW), with the advantages of waste-to-energy, lower secondary pollution, and greenhouse gas emission mitigation. For incineration leachate, the information from the headspace gas that varies at different processing processes and might be useful for chemical analysis, is ignored. The study applied a novel electronic nose (EN) to mine the information from leachate headspace gas. By combining manifold learnings (principal component analysis (PCA) and isometric feature mapping (ISOMAP), and uniform manifold approximation and projection (UMAP) and ensemble techniques (light gradient boosting machine (lightGBM) and extreme gradient boosting (XGBT)), EN based on the UMAP-XGBT model had the best classification performance with a 99.95% accuracy rate in the training set and a 95.83% accuracy rate in the testing set. The UMAP-XGBT model showed the best prediction ability for leachate chemical parameters (pH, chemical oxygen demand, biochemical oxygen demand, ammonia, and total phosphorus), with R2 higher than 0.99 both in the training and testing sets. This is the first study of the EN application for leachate monitoring, offering an easier and quicker detection method than traditional instrumental measurements for the enforcement and implementation of effective monitoring programs.
Family Influences on the Dental Caries Status of Children with Special Health Care Needs: A Systematic Review
Authors: Anwar Diyana Shereen , Mohd Yusof Mohd Yusmiaidil Putera , Ahmad Mas Suryalis , Md Sabri Budi Aslinie
Published: November 2022

Oral health is a likely source of health inequalities in children with special health care needs (CSHCN), according to multiple studies. This systematic review aimed to explore the evidence of family influence—as well as family features, such as societal variables and parents’ perspectives—on these children’s dental caries status. Embase, Ebsco, Scopus, PubMed, and Web of Science databases were all searched. All cross-sectional research published on the variables of family impact ranging from 2010 to 2021 were considered. The DMFT and dmft index was utilised for the report data of dental caries, whereas the National Heart, Lung, and Blood Institute (NHLBI) was used for the purposes of assessing quality. Of the 3861 records identified, 14 were eligible. Further, most of the studies had a caries prevalence of over 50%, (p-value < 0.005). Family influences imparted a significant relationship and association towards the dental caries status of the demographic being studied. The influences on the children included tooth brushing behaviour, parents’ education level, parents’ occupation level, diet pattern, dental visit, snacking frequency, parents’ psychological status, family size, and parents’ knowledge towards oral health. Future research should further explore the family functioning domains, specifically among the CSHCN population. This study was registered on PROSPERO, number CRD42021274923.
Dysphagia Management in Children: Implementation and Perspectives of Flexible Endoscopic Evaluation of Swallowing (FEES)
Authors: Printza Athanasia , Sdravou Katerina , Triaridis Stefanos
Published: November 2022

Dysphagia is any impairment of swallowing that compromises the safety, efficiency, or adequacy of nutritional or liquid intake. It is common in children, especially in some clinical populations, and may result in failure to thrive and respiratory problems due to pulmonary aspiration. Swallowing disorders have a severe impact on children’s health, growth, and development, and on the quality of life of the child and family. Clinical evaluation cannot validly predict aspiration, which is mostly silent. A team management approach is advocated, including instrumental swallowing assessments. FEES has been proven to be safe and valid and is increasingly used in children of all ages. It allows the identification of structural abnormalities, assessment of the child’s diet with real-life food and liquids while the child holds the optimal or preferred position, examination during breastfeeding, and assessment of fatigue and treatment strategies. FEES is carried out following a protocol that comprises three parts: the evaluation of the anatomical and physiological parameters of swallowing, testing of food and liquids of a range of different consistencies, and evaluation of treatment methods. Pediatric FEES involves adaptations for infants, and special considerations about readiness for nutritive trials and the infant’s ability to sustain a coordinated feeding pattern. Varying consistencies and volumes of food or liquids are tried. Care of the dysphagic child involves team work. FEES, as a part of the assessment and management of dysphagia, enables the evaluation of the safety, efficiency, and adequacy of oral food and liquid intake. Future perspectives include standardized training in clinical FEES protocols to ensure clinical competency of the pediatric FESS team members and the development and validation of standardized examination and interpretation protocols for pediatric FEES.
Extraosseous Ewing Sarcoma in Children: A Systematic Review and Meta-Analysis of Clinicodemographic Characteristics
Authors: Ghandour Maher , Lehner Burkhard , Klotz Matthias , Geisbüsch Andreas , Bollmann Jakob , Renkawitz Tobias , Horsch Axel
Published: November 2022

Background: We conducted this systematic review to provide comprehensive evidence on the prevalence, clinical features and outcomes of young extraosseous Ewing sarcoma (EES) cases. Methods: PubMed, Scopus, Web of Science, and Google Scholar were searched for articles reporting the occurrence of EES among children and adolescents (<21 years). The primary outcome included the rate of occurrence of EES among children and adolescents, while the secondary outcomes included the descriptive analyses of the demographic characteristics, tumor characteristics, and clinical outcomes of the affected cases. The data are reported as the effect size (ES) and its corresponding 95% confidence interval (CI). Results: A total of 29 studies were included. Twenty-four reported instances of childhood disease among all the EES cases [ES = 30%; 95%CI: 29–31%], while five studies reported extraosseous cases among the pediatric EES cases [ES = 22%; 95%CI: 13–31%]. The thorax is the most common location of childhood EES [33%; 95%CI: 20–46%] followed by the extremities [31%; 95%CI: 22–40%]. Concurrent chemotherapy and radiotherapy [57%; 95%CI: 25–84%] was the most commonly implemented management protocol in the pediatric EES cases. The rate of no evidence of disease and 5-year overall survival was 69% for both outcomes. Mortality occurred in 29% of cases, while recurrence and secondary metastasis occurred in 35% and 16% of cases, respectively. Conclusions: Our findings provide insight into the clinical features and outcomes of EES among children and adolescents.
Grouping of Ankyloglossia According to Coryllos Anatomical Classification and Follow-Up Results for Breastfeeding: Single-Center, Cross-Sectional Study
Authors: Narsat Mehmet Ali , Beygirci Abdulvehhap , Özdönmez Gökçen Tuğçe , Yıldız Eren
Published: November 2022

Ankyloglossia is a condition of limited tongue mobility caused by a short lingual frenulum. The diagnosis and treatment of ankyloglossia are still controversial. The main clinical problems encountered during breastfeeding are difficulty in sucking and its clinical reflections. This study aims to evaluate the infant population born with ankyloglossia and to determine the results of frenotomy. We conducted an observational, cross-sectional study among infants born in a tertiary hospital. We included all infants born between 1 January and 30 June 2022. The neonatal follow-up protocol for ankyloglossia was determined before the defined dates, and data were recorded during the screening period. The recorded data were retrospectively collected from the files. Within six months, 705 infants were born. Due to additional problems and other conditions that prevent breastfeeding, evaluable data of 207 (29.3%) infants could not be provided. Of the remaining 498 infants, 234 (33.2%) had ankyloglossia. While none of the infants without ankyloglossia had a breastfeeding problem after appropriate training, 28.6% of the ankyloglossia group had a breastfeeding problem (p < 0.001). The need for frenotomy differed significantly between Coryllos groups (p < 0.001). Breastfeeding was unsuccessful before frenotomy in 12 Coryllos type-1 patients, and all had difficulty in sucking. Frenotomy was performed within the three-month follow-up period in all patients with complaints of inability to firmly grasp the breast, nipple slipping from the mouth, and nipple biting during the first 24 h. In terms of breastfeeding problems, regardless of the anatomical typology, frenotomy can be performed safely in early life with successful results. If deficiencies or difficulties in breastfeeding are noticed in ankyloglossia patients even at the first control, frenotomy should be recommended in clinical conditions.
The Effects of Soccer Specific Exercise on Countermovement Jump Performance in Elite Youth Soccer Players
Authors: Lyons Donegan Max , Eustace Steven , Morris Rhys , Penny Ryan , Tallis Jason
Published: November 2022

The aims of the study were to examine the test–retest reliability of force-time (F-T) characteristics and F-T curve waveform of bilateral and unilateral countermovement jumps (CMJ) in elite youth soccer players and to evaluate the effects of competitive match-play on CMJ performance. 16 male youth soccer players completed CMJs on two separate occasions to determine reliability, and immediately pre, post and 48 h following a competitive match. Coefficient of variation (CV%), Intra-class correlation coefficient (ICC) and limits of agreement were used to assess reliability of discreate CMJ variables. Single factor repeated measures ANOVA were used to determine the effects of match play. Statistical parametric mapping was used to evaluate the repeatability of the CMJ force-time waveform and the effects of match play. Jump height had limited reliability in all three jumps and only a select few jump specific F-T variables were found to be reliable (CV < 10%, ICC > 0.5). Select variables were reduced immediately post game but recovered 48 h post game. The F-T curve waveform was found to be repeatable but did not differ following match-play. This study suggest that select F-T variables change following match-play and may be suitable tools to allow practitioners to detect decrements in performance. These data may help inform practitioners to use the most appropriate F-T variables to assess fatigue and recovery, with implications for performance and injury risk.
Lockdown Fatigue in Pediatric Respiratory Patients: Lessons from the First COVID-19 Year
Authors: Cahal Michal , Amirav Israel , Rochman Mika , Be’er Moria , Besor Omri , Lavie Moran
Published: November 2022

Lockdown policies have been implemented worldwide to limit the spread of COVID-19. “Lockdown fatigue” is a state of exhaustion related to the accumulating effects of repeated lockdowns. The aim of the current study was to examine the effects of repeated lockdowns on children with respiratory disorders. Data on children aged 0–18 years old with respiratory disorders were collected by an electronic survey during the third lockdown in Israel. The retrieved information included demographics and baseline medical status, respiratory clinical status during the third lockdown compared to pre-lockdown periods, lockdown adherence, lifestyle modifications and caregiver emotional status. The results were compared to those of a similar questionnaire distributed during the first lockdown. A total of 234 patients (62% males, 37% females, mean age 6.8 years (confidence interval 6.1–7.5)) were enrolled. Respiratory symptoms and exacerbation frequency were reduced in 76 (35.5%) and 58 (27.4%) patients, respectively, compared to the pre-lockdown period and similar to the first lockdown (p = 0.840 and p = 0.063, respectively). However, compared to the first lockdown, the third lockdown was associated with greater use of reliever medications (p = 0.006), less use of inhaled corticosteroids as routine treatment (p = 0.027), and more pediatric emergency room visits and hospitalizations (p = 0.001 and p < 0.001, respectively). The results also showed an increase in sedentary lifestyle (e.g., reduced physical activity (p = 0.025), less healthy eating habits (p = 0.001)) and reduced adherence to lockdown policies (p < 0.001). These data show that the continuing stability of clinical improvement during lockdown was accompanied by deleterious sequelae that potentially indicate “lockdown fatigue” among children with respiratory disorders.
The Impact of the ‘Planning Health in School’ Programme on a Pair of Twins with Obesity
Authors: Vieira Margarida , Carvalho Graça S.
Published: November 2022

This case study describes the impact of the ‘Planning Health in School’ programme (PHS-pro) on the nutritional status and lifestyle behaviours of two twins with obesity. As part of a larger research project involving 449 adolescents in grade-6, PHS-pro aims at preventing obesity and guiding children towards healthy behaviours. Twins were evaluated for anthropometric measurements—height, weight, body mass index (BMI), waist circumference (WC), and lifestyle behaviours before (baseline) and after (8 months) PHS-pro and at a follow-up (one-year later). At the baseline, both twins were obese according to the international cut-off points of Cole. After PHS-pro, improvements in anthropometric parameters were found: the boy decreased his BMI by 10% and lost 9.0 cm in WC, while remaining obese; the girl decreased her BMI by 8% and lost 8.7 cm in WC, changing to the overweight category. At the follow-up, a slight increase in the anthropometric parameters was found in both twins; however, they did not return to the baseline values. The programme successfully promoted positive changes in behaviours and improved nutritional status, showing the long-term effects of the PHS-pro. Although it is a school-based intervention to prevent obesity, the PHS-pro is helpful in weight reduction even in children already with obesity.
Oral Immunotherapy for Children with Cow’s Milk Allergy: A Practical Approach
Authors: Tosca Maria Angela , Olcese Roberta , Marinelli Guido , Schiavetti Irene , Ciprandi Giorgio
Published: November 2022

Cow milk allergy (CMA) is a prevalent disease in childhood. Natural history is usually favorable as CMA can disappear by school age in many subjects. Diagnosis corresponds to treatment, as an elimination diet is a solution. However, cow’s milk (CM) is real food, hardly replaceable. Thus, CM reintroduction represents a demanding challenge in clinical practice. The induction of CM tolerance could be achievable using oral immunotherapy (OIT), such as the administration of increasing milk quantities until reaching tolerance. However, the OIT schedule and procedure need to be better standardized, and performance may vary widely. Therefore, the present study reports the practical experience of a third-level pediatric allergy center in managing children with CMA and submitting them to OIT. OFC and OIT are relatively safe procedures as the reaction rate is low. Almost two-thirds of the OIT subjects tolerated CM. Reactions were associated with high IgE levels. Therefore, the present experience, developed by a qualified center, may suggest and propose a practical approach for managing children with CMA. After the initial workup, including a thorough history, physical examination, and laboratory tests, OFC and, when indicated, OIT could be performed in most children with CMA.
Vision Therapy: A Primer and Caution for Pediatricians
Authors: Wang Bo , Kuwera Edward
Published: November 2022

Vision therapy, also known as behavioral therapy, is theorized by its practitioners to treat a variety of visual disorders, including learning disability in children. However, the utility of vision therapy to treat various learning disabilities is challenged by the American Academy of Pediatrics, American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, and the American Association of Certified Orthoptists. The purpose of this review is to (1) provide an overview of vision therapy, (2) evaluate the evidence for vision therapy, and (3) give practical recommendations for pediatric primary care providers regarding vision therapy. A review of the literature demonstrates evidence that vision therapy is useful in the management of convergence insufficiency only. There is insufficient evidence to recommend in-office vision therapy for the management of other types of strabismus, amblyopia, or learning disability in the pediatric population.
Role of Cardiovascular Imaging in the Follow-Up of Patients with Fontan Circulation
Authors: Moscatelli Sara , Borrelli Nunzia , Sabatino Jolanda , Leo Isabella , Avesani Martina , Montanaro Claudia , Di Salvo Giovanni
Published: November 2022

Since its first description in 1971, the Fontan procedure and its modifications have led to a substantial improvement in the survival rates of patients with a variety of types of complex Congenital Heart Disease (CHD) characterised by the presence of a single, dominant ventricle. However, despite the significant improvement of the prognosis over the years, Fontan patients are still exposed to several cardiovascular and systemic complications. It is, therefore, important to fully understand the pitfalls hidden behind a Fontan anatomy and the potential predictors of ventricular failure. Cardiovascular imaging plays a key role in this context, allowing for the early identification of complications with important prognostic implications. Echocardiography remains the first-line imaging modality for serial evaluation of Fontan patients. However, there is a growing role of cardiovascular magnetic resonance and cardiac computed tomography from pre-operative assessment to longitudinal follow-up. The aim of this paper will be to provide a comprehensive overview of the role, strengths, and weaknesses of each imaging modality in the assessment of congenital cardiac conditions palliated with the Fontan procedure.
Assessing Children’s Dental Age with Panoramic Radiographs
Authors: Ratson Tal , Dagon Nurit , Aderet Netta , Dolev Eran , Laviv Amir , Davidovitch Moshe , Blumer Sigalit
Published: November 2022

(1) Background: The aim of the study was to assess the dental age of the subjects and compare it to their chronological age; to assess the dominant tooth for evaluation of dental age; and to investigate possible individual differences between the left and right side of the dental arch. (2) Methods: This study involved evaluating panoramic radiographs of patients aged 7–13 years. A separate assessment was performed for each tooth according to the degree of germ development. Each subject’s dental age was estimated. (3) Results: The study involved evaluating 349 panoramic radiographs. No difference was found between stages of tooth development on the right side and left side. Correlation between the stages of tooth development and the chronological age was found to be highest in the second permanent molar teeth. The age can be predicted with the estimated age of tooth #37 and the gender of the patient. (4) Conclusions: The chronological age of children aged 7–13 may be estimated based on a modified seven-stage London Atlas of tooth development, where the most accurate landmark(s) of use are second molars.
The Nocardia Rubra Cell Wall Skeleton Regulates Macrophages and Promotes Wound Healing
Authors: Hu Kai , Xu Yan , Li Xiaoxiao , Du Pan , Lu Yichi , Lyu Guozhong
Published: November 2022

The Nocardia rubra cell wall skeleton (Nr-CWS) is an immunomodulator used clinically for its ability to modulate the body’s immune function. Macrophages are an important hub of the immune response during wound healing. In this study, we hypothesized that a Nr-CWS could modulate macrophage physiological activities, polarize macrophages toward M2, and promote wound healing. Through in vivo experiments, we made two full-thickness excisional wounds on the backs of mice; one was treated with a Nr-CWS, and the other was treated with saline. We photographed and recorded the wound change every other day. We observed the histopathological examination and collagen deposition using H&E and Masson staining, then analyzed the macrophage surface markers using immunofluorescence. Through in vitro experiments, we studied the effect of the Nr-CWS on RAW264.7 cells through CCK8, transwell, flow cytometry, western blot, immunofluorescence, and ELISA. We found that the Nr-CWS can enhance the proliferation, migration, and phagocytosis of macrophages. In addition, it can promote the recruitment of macrophages on the wound surface, polarize macrophages to M2, and increase the expression of pro-healing cytokines. Ultimately, the Nr-CWS accelerated wound healing.