bluuebunny/crossref_metadata_2025 huggingface dataset:
DUOX1 Gene Missense Mutation Confers Susceptibility on Type 2 Amiodarone-Induced Thyrotoxicosis
Authors: Biakina Olga , Mitina Yulia , Gognieva Daria , Axenova Marina , Ermolaeva Alexandra , Bestavashvili Afina , Fadeev Valentin , Syrkin Abram , Kopylov Philipp
Published: February 2023

Possible triggers and genetic markers involved in pathogenesis of amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH) are currently unknown. This study aimed to analyze the association between polymorphisms in the genes involved in thyroid hormones biosynthesis and metabolism. Thirty-nine consecutive patients with confirmed type 2 amiodarone-induced thyrotoxicosis were enrolled; 39 patients on the same therapy for at least 6 months without thyroid pathology were included as a control group. A comparative study was carried out to determine the distribution and genotypes of polymorphic markers of the (Na)-iodide symporter (NIS) genes (rs7250346, C/G substitution), thyroid stimulating hormone receptor (TSHR) (rs1991517, C/G substitution), thyroid peroxidase (TPO) (rs 732609, A/C substitution), DUOX 1-1 (C/T substitution), DUOX 1-2 (G/T substitution), DUOX 1-3 (C/T substitution), glutathione peroxidase 3 (GPX3) (C/T substitution), glutathione peroxidase 4 (GPX4) (C/T substitution). Statistical analysis was performed using Prism (Version 9.0.0 (86)). This study showed that the risk of AIT2 is 3.18 times higher in the G/T of the DUOX1 gene carriers. This study is the first report of genetic markers associated with amiodarone-related adverse events conducted in humans. The obtained results indicate the necessity for a personalized approach to amiodarone administration.
Cytosolic Release of Mitochondrial DNA and Associated cGAS Signaling Mediates Radiation-Induced Hematopoietic Injury of Mice
Authors: Guan Hua , Zhang Wen , Xie Dafei , Nie Yuehua , Chen Shi , Sun Xiaoya , Zhao Hongling , Liu Xiaochang , Wang Hua , Huang Xin , Bai Chenjun , Huang Bo , Zhou Pingkun , Gao Shanshan
Published: February 2023

Mitochondrion is an important organelle of eukaryotic cells and a critical target of ionizing radiation (IR) outside the nucleus. The biological significance and mechanism of the non-target effect originating from mitochondria have received much attention in the field of radiation biology and protection. In this study, we investigated the effect, role, and radioprotective significance of cytosolic mitochondrial DNA (mtDNA) and its associated cGAS signaling on hematopoietic injury induced by IR in vitro culture cells and in vivo total body irradiated mice in this study. The results demonstrated that γ-ray exposure increases the release of mtDNA into the cytosol to activate cGAS signaling pathway, and the voltage-dependent anion channel (VDAC) may contribute to IR-induced mtDNA release. VDAC1 inhibitor DIDS and cGAS synthetase inhibitor can alleviate bone marrow injury and ameliorate hematopoietic suppression induced by IR via protecting hematopoietic stem cells and adjusting subtype distribution of bone marrow cells, such as attenuating the increase of the F4/80+ macrophage proportion in bone marrow cells. The present study provides a new mechanistic explanation for the radiation non-target effect and an alternative technical strategy for the prevention and treatment of hematopoietic acute radiation syndrome.
Computational Analysis of the Ligand-Binding Sites of the Molecular Chaperone OppA from Yersinia pseudotuberculosis
Authors: Ramírez Mirian Becerril , Urzúa Lucía Soto , Martínez María de los Ángeles Martínez , Morales Luis Javier Martínez
Published: February 2023

The function of chaperones is to correct or degrade misfolded proteins inside the cell. Classic molecular chaperones such as GroEL and DnaK have not been found in the periplasm of Yersinia pseudotuberculosis. Some periplasmic substrate-binding proteins could be bifunctional, such as OppA. Using bioinformatic tools, we try to elucidate the nature of the interactions between OppA and ligands from four proteins with different oligomeric states. Using the crystal structure of the proteins Mal12 alpha-glucosidase from Saccharomyces cerevisiae S288C, LDH rabbit muscle lactate dehydrogenase, EcoRI endonuclease from Escherichia coli and THG Geotrichum candidum lipase, a hundred models were obtained in total, including five different ligands from each enzyme with five conformations of each ligand. The best values for Mal12 stem from ligands 4 and 5, with conformation 5 for both; for LDH, ligands 1 and 4, with conformations 2 and 4, respectively; for EcoRI, ligands 3 and 5, with conformation 1 for both; and for THG, ligands 2 and 3, with conformation 1 for both. The interactions were analyzed with LigProt, and the length of the hydrogen bridges has an average of 2.8 to 3.0 Å. The interaction within the OppA pocket is energetically favored due to the formation of hydrogen bonds both of OppA and of the selected enzymes. The Asp 419 residue is important in these junctions.
Pancreatic Organoids: A Frontier Method for Investigating Pancreatic-Related Diseases
Authors: Liu Yuxiang , Li Nianshuang , Zhu Yin
Published: February 2023

The pancreas represents an important organ that has not been comprehensively studied in many fields. To fill this gap, many models have been generated, and traditional models have shown good performance in addressing pancreatic-related diseases, but are increasingly struggling to keep up with the need for further research due to ethical issues, genetic heterogeneity and difficult clinical translation. The new era calls for new and more reliable research models. Therefore, organoids have been proposed as a novel model for the evaluation of pancreatic-related diseases such as pancreatic malignancy, diabetes, and pancreatic cystic fibrosis. Compared with common traditional models, including 2D cell culture and gene editing mice, organoids derived from living humans or mice cause minimal harm to the donor, raise fewer ethical concerns, and reasonably address the claims of heterogeneity, which allows for the further development of pathogenesis studies and clinical trial analysis. In this review, we analyse studies on the use of pancreatic organoids in research on pancreatic-related diseases, discuss the advantages and disadvantages, and hypothesize future trends.
Comparative Proteomics Analysis of Exosomes Identifies Key Pathways and Protein Markers Related to Breast Cancer Metastasis
Authors: Shen Shichen , Tu Chengjian , Shen He , Li Jun , Frangou Costa , Zhang Jianmin , Qu Jun
Published: February 2023

Proteomics analysis of circulating exosomes derived from cancer cells represents a promising approach to the elucidation of cell–cell communication and the discovery of putative biomarker candidates for cancer diagnosis and treatment. Nonetheless, the proteome of exosomes derived from cell lines with different metastatic capabilities still warrants further investigation. Here, we present a comprehensive quantitative proteomics investigation of exosomes isolated from immortalized mammary epithelial cells and matched tumor lines with different metastatic potentials in an attempt to discover exosome markers specific to breast cancer (BC) metastasis. A total of 2135 unique proteins were quantified with a high confidence level from 20 isolated exosome samples, including 94 of the TOP 100 exosome markers archived by ExoCarta. Moreover, 348 altered proteins were observed, among which several metastasis-specific markers, including cathepsin W (CATW), magnesium transporter MRS2 (MRS2), syntenin-2 (SDCB2), reticulon-4 (RTN), and UV excision repair protein RAD23 homolog (RAD23B), were also identified. Notably, the abundance of these metastasis-specific markers corresponds well with the overall survival of BC patients in clinical settings. Together, these data provide a valuable dataset for BC exosome proteomics investigation and prominently facilitate the elucidation of the molecular mechanisms underlying primary tumor development and progression.
Changes of RAS Pathway Phosphorylation in Lymphoblastoid Cell Lines from Noonan Syndrome Patients Carrying Hypomorphic Variants in Two NS Genes
Authors: Tritto Viviana , Capitanio Daniele , Gelfi Cecilia , Riva Paola
Published: February 2023

Noonan syndrome (NS) is an autosomal dominant multisystem disorder, characterized by variable expressivity and locus heterogeneity, being caused by mutations in one of a subset of RAS pathway genes. Nevertheless, for 20–30% of patients it is not possible to provide molecular diagnosis, suggesting that further unknown genes or mechanisms are involved in NS pathogenesis. Recently, we proposed a digenic inheritance of subclinical variants as an alternative NS pathogenic model in two NS patients negative for molecular diagnosis. They showed hypomorphic variants of RAS pathway genes co-inherited from both their healthy parents that we hypothesized to generate an additive effect. Here, we report on the phosphoproteome and proteome analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) performed on the immortalized peripheral blood mononuclear cells (PBMCs) from the two above trios. Our results indicate that the two unrelated patients show overlapped profiles in both protein abundances and their phosphorylation levels not reached by their parents. IPA software predicted RAS-related pathways as significantly activated in the two patients. Interestingly, they remained unchanged or only slightly activated in both patients’ parents. These findings suggest that the presence of one subclinical variant can activate the RAS pathway below the pathological threshold, which can instead be exceeded by the additive effect due to the co-presence of two subclinical variants causing NS, supporting our digenic inheritance hypothesis.
Melatonin in Dermatologic Allergic Diseases and Other Skin Conditions: Current Trends and Reports
Authors: Bešlić Iva , Lugović-Mihić Liborija , Vrtarić Alen , Bešlić Ante , Škrinjar Ivana , Hanžek Milena , Crnković Danijel , Artuković Marinko
Published: February 2023

Melatonin is the main hormone that regulates the sleep cycle, and it is mostly produced by the pineal gland from the amino acid tryptophan. It has cytoprotective, immunomodulatory, and anti-apoptotic effects. Melatonin is also one of the most powerful natural antioxidants, directly acting on free radicals and the intracellular antioxidant enzyme system. Furthermore, it participates in antitumor activity, hypopigmentation processes in hyperpigmentary disorders, anti-inflammatory, and immunomodulating activity in inflammatory dermatoses, maintaining the integrity of the epidermal barrier and thermoregulation of the body. Due predominantly to its positive influence on sleep, melatonin can be used in the treatment of sleep disturbances for those with chronic allergic diseases accompanied by intensive itching (such as atopic dermatitis and chronic spontaneous urticaria). According to the literature data, there are also many proven uses for melatonin in photoprotection and skin aging (due to melatonin’s antioxidant effects and role in preventing damage due to DNA repair mechanisms), hyperpigmentary disorders (e.g., melasma) and scalp diseases (such as androgenic alopecia and telogen effluvium).
Association of FANCM Mutations with Familial and Early-Onset Breast Cancer Risk in a South American Population
Authors: Morales-Pison Sebastian , Morales-González Sarai , Fernandez-Ramires Ricardo , Tapia Julio C. , Maldonado Edio , Calaf Gloria M. , Jara Lilian
Published: February 2023

Breast cancer (BC) is the most common cancer among women worldwide. BRCA1/2 are responsible for 16–20% of the risk for hereditary BC. Other susceptibility genes have been identified; Fanconi Anemia Complementation Group M (FANCM) being one of these. Two variants in FANCM, rs144567652 and rs147021911, are associated with BC risk. These variants have been described in Finland, Italy, France, Spain, Germany, Australia, the United States, Sweden, Finnish, and the Netherlands, but not in the South American populations. Our study evaluated the association of the SNPs rs144567652 and rs147021911 with BC risk in non-carriers of BRCA1/2 mutations from a South American population. The SNPs were genotyped in 492 BRCA1/2-negative BC cases and 673 controls. Our data do not support an association between FANCM rs147021911 and rs144567652 SNPs and BC risk. Nevertheless, two BC cases, one with a family history of BC and the other with sporadic early-onset BC, were C/T heterozygotes for rs144567652. In conclusion, this is the first study related contribution of FANCM mutations and BC risk in a South American population. Nevertheless, more studies are necessary to evaluate if rs144567652 could be responsible for familial BC in BRCA1/2-negatives and for early-onset non-familial BC in Chilean BC cases.
Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies
Authors: Wnuk Agnieszka , Przepiórska Karolina , Pietrzak Bernadeta Angelika , Kajta Małgorzata
Published: February 2023

Nuclear- and membrane-initiated estrogen signaling cooperate to orchestrate the pleiotropic effects of estrogens. Classical estrogen receptors (ERs) act transcriptionally and govern the vast majority of hormonal effects, whereas membrane ERs (mERs) enable acute modulation of estrogenic signaling and have recently been shown to exert strong neuroprotective capacity without the negative side effects associated with nuclear ER activity. In recent years, GPER1 was the most extensively characterized mER. Despite triggering neuroprotective effects, cognitive improvements, and vascular protective effects and maintaining metabolic homeostasis, GPER1 has become the subject of controversy, particularly due to its participation in tumorigenesis. This is why interest has recently turned toward non-GPER-dependent mERs, namely, mERα and mERβ. According to available data, non-GPER-dependent mERs elicit protective effects against brain damage, synaptic plasticity impairment, memory and cognitive dysfunctions, metabolic imbalance, and vascular insufficiency. We postulate that these properties are emerging platforms for designing new therapeutics that may be used in the treatment of stroke and neurodegenerative diseases. Since mERs have the ability to interfere with noncoding RNAs and to regulate the translational status of brain tissue by affecting histones, non-GPER-dependent mERs appear to be attractive targets for modern pharmacotherapy for nervous system diseases.
Bone Differentiation Ability of CD146-Positive Stem Cells from Human Exfoliated Deciduous Teeth
Authors: Kunimatsu Ryo , Rikitake Kodai , Yoshimi Yuki , Putranti Nurul Aisyah Rizky , Hayashi Yoko , Tanimoto Kotaro
Published: February 2023

Regenerative therapy for tissues by mesenchymal stem cell (MSCs) transplantation has received much attention. The cluster of differentiation (CD)146 marker, a surface-antigen of stem cells, is crucial for angiogenic and osseous differentiation abilities. Bone regeneration is accelerated by the transplantation of CD146-positive deciduous dental pulp-derived mesenchymal stem cells contained in stem cells from human exfoliated deciduous teeth (SHED) into a living donor. However, the role of CD146 in SHED remains unclear. This study aimed to compare the effects of CD146 on cell proliferative and substrate metabolic abilities in a population of SHED. SHED was isolated from deciduous teeth, and flow cytometry was used to analyze the expression of MSCs markers. Cell sorting was performed to recover the CD146-positive cell population (CD146+) and CD146-negative cell population (CD146-). CD146 + SHED without cell sorting and CD146-SHED were examined and compared among three groups. To investigate the effect of CD146 on cell proliferation ability, an analysis of cell proliferation ability was performed using BrdU assay and MTS assay. The bone differentiation ability was evaluated using an alkaline phosphatase (ALP) stain after inducing bone differentiation, and the quality of ALP protein expressed was examined. We also performed Alizarin red staining and evaluated the calcified deposits. The gene expression of ALP, bone morphogenetic protein-2 (BMP-2), and osteocalcin (OCN) was analyzed using a real-time polymerase chain reaction. There was no significant difference in cell proliferation among the three groups. The expression of ALP stain, Alizarin red stain, ALP, BMP-2, and OCN was the highest in the CD146+ group. CD146 + SHED had higher osteogenic differentiation potential compared with SHED and CD146-SHED. CD146 contained in SHED may be a valuable population of cells for bone regeneration therapy.
Impact of Vancomycin Treatment and Gut Microbiota on Bile Acid Metabolism and the Development of Non-Alcoholic Steatohepatitis in Mice
Authors: Kasai Kaichi , Igarashi Naoya , Tada Yuki , Kani Koudai , Takano Shun , Yanagibashi Tsutomu , Usui-Kawanishi Fumitake , Fujisaka Shiho , Watanabe Shiro , Ichimura-Shimizu Mayuko , Takatsu Kiyoshi , Tobe Kazuyuki , Tsuneyama Koichi , Furusawa Yukihiro , Nagai Yoshinori
Published: February 2023

The potential roles of the gut microbiota in the pathogenesis of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH), have attracted increased interest. We have investigated the links between gut microbiota and NASH development in Tsumura-Suzuki non-obese mice fed a high-fat/cholesterol/cholate-based (iHFC) diet that exhibit advanced liver fibrosis using antibiotic treatments. The administration of vancomycin, which targets Gram-positive organisms, exacerbated the progression of liver damage, steatohepatitis, and fibrosis in iHFC-fed mice, but not in mice fed a normal diet. F4/80+-recruited macrophages were more abundant in the liver of vancomycin-treated iHFC-fed mice. The infiltration of CD11c+-recruited macrophages into the liver, forming hepatic crown-like structures, was enhanced by vancomycin treatment. The co-localization of this macrophage subset with collagen was greatly augmented in the liver of vancomycin-treated iHFC-fed mice. These changes were rarely seen with the administration of metronidazole, which targets anaerobic organisms, in iHFC-fed mice. Finally, the vancomycin treatment dramatically modulated the level and composition of bile acid in iHFC-fed mice. Thus, our data demonstrate that changes in inflammation and fibrosis in the liver by the iHFC diet can be modified by antibiotic-induced changes in gut microbiota and shed light on their roles in the pathogenesis of advanced liver fibrosis.
Non-ROS-Mediated Cytotoxicity of ZnO and CuO in ML-1 and CA77 Thyroid Cancer Cell Lines
Authors: Peters Alyse N. , Weaver Nakaja A. , Monahan Kathryn S. , Kim Kyoungtae
Published: February 2023

Metal oxide nanoparticles (MONPs) are widely used in agriculture and food development but there is little understanding of how MONPs, including ZnO, CuO, TiO2, and SnO2, impact human health and the environment. Our growth assay revealed that none of these (up to 100 µg/mL) negatively affect viability in the budding yeast, Saccharomyces cerevisiae. In contrast, both human thyroid cancer cells (ML-1) and rat medullary thyroid cancer cells (CA77) displayed a significant reduction in cell viability with the treatment of CuO and ZnO. The production of reactive oxygen species (ROS) in these cell lines, when treated with CuO and ZnO, was found to be not significantly altered. However, levels of apoptosis with ZnO and CuO were increased, which led us to conclude that the decreased cell viability is mainly caused by non-ROS-mediated cell death. Consistently, data from our RNAseq studies identified differentially regulated pathways associated with inflammation, Wnt, and cadherin signaling across both cell lines, ML-1, and CA77, after ZnO or CuO MONP treatment. Results from gene studies further support non-ROS-mediated apoptosis being the main factor behind decreased cell viability. Together, these findings provide unique evidence that the apoptosis in response to treatment of CuO and ZnO in these thyroid cancer cells was not mainly due to oxidative stress, but to the alteration of a range of signal cascades that promotes cell death.
Expanding the Spectrum of BRAF Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre
Authors: De Leo Antonio , Serban Daniela , Maloberti Thais , Sanza Viviana , Coluccelli Sara , Altimari Annalisa , Gruppioni Elisa , Chiarucci Federico , Corradini Angelo Gianluca , Repaci Andrea , Colapinto Alessandra , Nannini Margherita , Pantaleo Maria A. , de Biase Dario , Tallini Giovanni
Published: February 2023

The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. BRAF alterations other than the p.V600E are less common in thyroid carcinoma and represent an alternative mechanism of BRAF activation with unclear clinical significance. The study aims to describe the frequency and clinicopathologic characteristics of BRAF non-V600E mutations in a large cohort (1654 samples) of thyroid lesions characterized by next-generation sequencing. BRAF mutations have been found in 20.3% (337/1654) of thyroid nodules, including classic (p.V600E) mutation in 19.2% (317/1654) of samples and non-V600E variants in 1.1% of cases (19/1654). BRAF non-V600E alterations include 5 cases harboring p.K601E, 2 harboring p.V600K substitutions, 2 with a p.K601G variant, and 10 cases with other BRAF non-V600E alterations. BRAF non-V600E mutations have been reported in one case of follicular adenoma, three cases of conventional papillary thyroid carcinoma, eight cases of follicular variant of papillary carcinomas, one case of columnar cell variant papillary thyroid carcinoma, one case of oncocytic follicular carcinoma, and two bone metastasis of follicular thyroid carcinoma. We confirm that BRAF non-V600E mutations are uncommon and typically found in indolent follicular-patterned tumors. Indeed, we show that BRAF non-V600E mutations can be found in tumors with metastatic potential. However, in both aggressive cases, the BRAF mutations were concomitant with other molecular alterations, such as TERT promoter mutation.
Conceptual Approach to the Pedagogy of Serious Games
Authors: Fernández-Sánchez María Rosa , González-Fernández Alberto , Acevedo-Borrega Jesús
Published: February 2023

The transformation of educational processes, derived from the technological disruption that has taken place in the educational field, has allowed for the development of certain methodologies and techniques that place emphasis on the students as an active element in their own learning. Among these methodologies is learning based on video games. Serious games are video games with an explicit educational objective, that facilitate the generation of motivating contexts, promoting relevant experiences, and with the possibility of creating challenges of a systemic nature. With a systematic literature review (SLR) methodology, this study analysed the pedagogical models and/or approaches that are implemented in the teaching–learning processes brought about by the use of serious games, with the aim of evidencing the potentialities derived from the conception of the video game as an educational resource. The results show a clear conceptual network in relation to the analysed subject, with little interaction between selected studies. A variety of pedagogical models were identified, pertaining to the use of serious games as an educational resource in the classroom context. As an overall conclusion, there is no one reference model able to generate a single pedagogy for serious games.
Normotensive Glaucoma in the Fellow Eye of Patient with Unilateral Pseudoexfoliation
Authors: Shin Da Young , Park Chan Kee , Jung Kyoung In , Park Hae Young Lopilly , Lee Na Young
Published: February 2023

Purpose: To investigate the characteristics of normotensive glaucoma (NTG) in the fellow eye of patients with unilateral pseudoexfoliation syndrome (PXS). Methods: This study is a retrospective chart review. We included 313 patients with NTG. Using the 1:1 matched propensity score, only 94 well-matched patients were selected. A total of 47 NTG patients who had PXS in their contralateral eye (PXS group) and 47 NTG patients who did not (control group) were compared. The propensity score was matched based on age, mean intraocular pressure (IOP), baseline retinal nerve fiber layer (RNFL) thickness and baseline mean deviation (MD) of visual field (VF) score. The diagnosis of NTG was based on the presence of glaucomatous optic nerve head injury with VF defect, intraocular pressure less than 22 mmHg, open angles and no pseudoexfoliation material. Results: The PXS group had a higher ratio of males (34.0%) than the control group (17.0%). No significant differences were observed between the two groups in terms of CCT, axial length, untreated baseline IOP, baseline PSD of VF, systemic blood pressure and follow-up duration. The rate of RNFL thinning was significantly faster in the PXS group (−1.88 ± 2.83 μm/year) compared with the control group (−0.27 ± 5.29 μm/year) (p = 0.02). The progression rate of VF MD was slightly faster in PXS than in the control group, but there was no statistically significant difference (PXS group, −0.33 ± 0.90 dB/year; control group, −0.11 ± 0.84 dB/year; p = 0.236). Conclusions: NTG eyes with PXS showed faster RNFL thinning than did control NTG eyes.
Low-Dose Atropine Induces Changes in Ocular Biometrics in Myopic Children: Exploring Temporal Changes by Linear Mixed Models and Contribution to Treatment Effect by Mediation Analyses
Authors: Hvid-Hansen Anders , Jacobsen Nina , Hjortdal Jesper , Møller Flemming , Ozenne Brice , Kessel Line
Published: February 2023

This study aimed to investigate changes in non-cycloplegic ocular biometrics during the initial six months of treatment with a 0.1% atropine loading dose and 0.01% atropine compared with a placebo and analyze their contribution to the treatment effect on cycloplegic spherical equivalent (SE) progression. The study was based on a randomized, double-masked, placebo-controlled, multicenter trial evaluating a 0.1% atropine six-month loading dose and 0.01% atropine in reducing myopic progression in Danish children. The treatment phase was 24 months, and the washout phase was 12 months. Parameters measured included changes in axial length (AL), anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and choroidal thickness (ChT), while cycloplegic SE and lens power were calculated. Longitudinal changes and contributions to treatment effects were analyzed using constrained linear mixed models and mediation analyses, respectively. After six months, AL was 0.13 mm shorter (95% confidence interval [CI], −0.18 to −0.07 [adjusted p < 0.001]) and 0.06 mm shorter (95% CI, −0.11 to −0.01 [adjusted p = 0.060]) with a 0.1% atropine loading dose and 0.01% atropine, respectively, compared to the placebo group. Similar concentration-dependent changes were found with ACD, LT, VCD, ChT, and cycloplegic SE. Although the treatment effects trended toward concentration-dependent responses, only the treatment effect mediated by AL at three months differed significantly between 0.01% atropine and a 0.1% atropine loading dose (adjusted p = 0.023). Several ocular biometrics, including AL, ACD, and LT, changed dose-dependently during low-dose atropine treatment. Moreover, the treatment effect of atropine on SE progression was mediated by a subset of ocular biometrics, mainly AL, with trends toward concentration dependency and distributional shifts over time.
A Retrospective Cohort Study of Red Cell Alloimmunisation in Rural, Remote, and Aboriginal and Torres Strait Islander Peoples Admitted to Intensive Care in the Northern Territory, Australia
Authors: Noutsos Tina , Perry Maree A. , Secombe Paul J. , Roxby David J. , Sinha Romi , Campbell Lewis T.
Published: February 2023

Red cell (RC) alloantibodies occur on exposure to non-self RC antigens in transfusion and pregnancy (typically IgG and clinically significant) or in association with non-RC immune environmental factors (typically IgM and not clinically significant). In Australia, the risk of RC alloimmunisation in First Nations peoples is unknown. We assessed the epidemiology, specificity, and antecedents of RC alloimmunisation via a data linkage retrospective cohort study of Northern Territory (NT) intensive care unit (ICU) patients (2015–2019). Of 4183 total patients, 50.9% were First Nations. In First Nations versus non-First Nations patients, the period prevalence of alloimmunisation was 10.9% versus 2.3%, with 390 versus 72 prevalent alloantibodies detected in 232 versus 48 alloimmunised patients, of which 135 (34.6%) versus 52 (72.2%) were clinically significant specificities. Baseline and follow-up alloantibody testing were available for 1367 patients, in whom new incident clinically significant alloantibodies developed in 4.5% First Nations versus 1.1% non-First Nations patients. On Cox proportional hazards modelling, adjusted hazard ratios (HR) showed First Nations status (HR 2.67 (95% CI 1.05–6.80), p = 0.04) and cumulative RC unit transfusion exposure (HR 1.03 (95% CI 1.01–1.05), p = 0.01) were independent predictors of clinically significant alloimmunisation. First Nations Australian patients are at increased risk of alloimmunisation due to RC transfusion, underscoring the importance of very judicious use of RC transfusions and shared decision-making with patients. Further studies are recommended to explore the role of other (non-RC) immune host factors, given the relative high prevalence of non-clinically significant IgM alloantibodies within alloimmunised First Nations patients.
Effectiveness of BMP-2 and PDGF-BB Adsorption onto a Collagen/Collagen-Magnesium-Hydroxyapatite Scaffold in Weight-Bearing and Non-Weight-Bearing Osteochondral Defect Bone Repair: In Vitro, Ex Vivo and In Vivo Evaluation
Authors: Xu Jietao , Fahmy-Garcia Shorouk , Wesdorp Marinus A. , Kops Nicole , Forte Lucia , De Luca Claudio , Misciagna Massimiliano Maraglino , Dolcini Laura , Filardo Giuseppe , Labberté Margot , Vancíková Karin , Kok Joeri , van Rietbergen Bert , Nickel Joachim , Farrell Eric , Brama Pieter A. J. , van Osch Gerjo J. V. M.
Published: February 2023

Despite promising clinical results in osteochondral defect repair, a recently developed bi-layered collagen/collagen-magnesium-hydroxyapatite scaffold has demonstrated less optimal subchondral bone repair. This study aimed to improve the bone repair potential of this scaffold by adsorbing bone morphogenetic protein 2 (BMP-2) and/or platelet-derived growth factor-BB (PDGF-BB) onto said scaffold. The in vitro release kinetics of BMP-2/PDGF-BB demonstrated that PDGF-BB was burst released from the collagen-only layer, whereas BMP-2 was largely retained in both layers. Cell ingrowth was enhanced by BMP-2/PDFG-BB in a bovine osteochondral defect ex vivo model. In an in vivo semi-orthotopic athymic mouse model, adding BMP-2 or PDGF-BB increased tissue repair after four weeks. After eight weeks, most defects were filled with bone tissue. To further investigate the promising effect of BMP-2, a caprine bilateral stifle osteochondral defect model was used where defects were created in weight-bearing femoral condyle and non-weight-bearing trochlear groove locations. After six months, the adsorption of BMP-2 resulted in significantly less bone repair compared with scaffold-only in the femoral condyle defects and a trend to more bone repair in the trochlear groove. Overall, the adsorption of BMP-2 onto a Col/Col-Mg-HAp scaffold reduced bone formation in weight-bearing osteochondral defects, but not in non-weight-bearing osteochondral defects.
Data Augmentation in Classification and Segmentation: A Survey and New Strategies
Authors: Alomar Khaled , Aysel Halil Ibrahim , Cai Xiaohao
Published: February 2023

In the past decade, deep neural networks, particularly convolutional neural networks, have revolutionised computer vision. However, all deep learning models may require a large amount of data so as to achieve satisfying results. Unfortunately, the availability of sufficient amounts of data for real-world problems is not always possible, and it is well recognised that a paucity of data easily results in overfitting. This issue may be addressed through several approaches, one of which is data augmentation. In this paper, we survey the existing data augmentation techniques in computer vision tasks, including segmentation and classification, and suggest new strategies. In particular, we introduce a way of implementing data augmentation by using local information in images. We propose a parameter-free and easy to implement strategy, the random local rotation strategy, which involves randomly selecting the location and size of circular regions in the image and rotating them with random angles. It can be used as an alternative to the traditional rotation strategy, which generally suffers from irregular image boundaries. It can also complement other techniques in data augmentation. Extensive experimental results and comparisons demonstrated that the new strategy consistently outperformed its traditional counterparts in, for example, image classification.
Correction: Hamin et al. (2022). Understanding Organisational Risks and Opportunities Associated with Implementing Australia’s National Disability Insurance Scheme from the Nonprofit Service Provider Perspective—Findings from Quantitative Research. Journal of Risk and Financial Management 15: 614
Authors: Hamin Hamin , Rosenbaum David , More Elizabeth
Published: February 2023

In our original publication (Hamin et al [...]
Fractures in CKD Patients—Risk Analysis in RRT Lombardy Patients
Authors: Conte Ferruccio , Roggeri Daniela Paola , Cozzolino Mario Gennaro , Rossi Carlotta , Zocchetti Carlo , Roggeri Alessandro
Published: February 2023

The increase in the number of patients with CKD starting dialysis treatment has become a major health problem in recent years. Osteoporosis is a typical feature of advanced age, which, in the dialysis population, is almost always accompanied by uremic osteodystrophy (CKD-MBD). These two factors are involved in the pathogenesis of fractures, which represent an important risk factor for the outcome of patients. The real consistency of fractures in CKD patients on kidney replacement therapy (KRT) requiring hospitalization in the Lombardy region (over 9,000,000 inhabitants) was analyzed using data from the regional administrative databases in the years 2011–2012. Among 8109 prevalent patients, 251 (45.8% women), with fractures after 1 January 2011, entered the analysis. A follow-up of two years (2011–2012) was considered to evaluate the incidence of more frequent fractures (femur, pelvis, hip, and spine) using ICD-9-CM codes. The most frequent sites of fractures were the femur (68.5%), hip and pelvis (47.4%), and vertebrae (12%). The patients on hemodialysis (HD) had more events than PD (3.3% vs. 1.4%; p = 0.03), while patients undergoing kidney transplantation (KTx) had a significantly lower percentage of fractures (0.6% vs. 3.3%; p < 0.001). Observed mortality was very high: the estimated gross mortality rate for any cause was 25.9% at 90 days and 34.7% at 180 days. Diabetes, peripheral vasculopathy, and heart failure were associated with a numerical increase in fractures, although this was not significant. Proton pump inhibitor drugs (PPI), vitamin K antagonists, and diphosphonates were more frequently associated with fracture occurrence. The average total cost of fractured patients was 11.4% higher than that of non-fractured patients. On multivariate analysis, age >65 years, female gender, PPI therapy, and cerebrovascular disease were found to be strongly associated with fractures in dialysis patients, whereas undergoing renal transplantation presented a reduced risk.
Orthologs of Human-Disease-Associated Genes in Plants Are Involved in Regulating Leaf Senescence
Authors: Wang Hou-Ling , Yin Weilun , Xia Xinli , Li Zhonghai
Published: February 2023

As eukaryotes, plants and animals have many commonalities on the genetic level, although they differ greatly in appearance and physiological habits. The primary goal of current plant research is to improve the crop yield and quality. However, plant research has a wider aim, exploiting the evolutionary conservatism similarities between plants and animals, and applying discoveries in the field of botany to promote zoological research that will ultimately serve human health, although very few studies have addressed this aspect. Here, we analyzed 35 human-disease-related gene orthologs in plants and characterized the genes in depth. Thirty-four homologous genes were found to be present in the herbaceous annual plant Arabidopsis thaliana and the woody perennial plant Populus trichocarpa, with most of the genes having more than two exons, including the ATM gene with 78 exons. More surprisingly, 27 (79.4%) of the 34 homologous genes in Arabidopsis were found to be senescence-associated genes (SAGs), further suggesting a close relationship between human diseases and cellular senescence. Protein–protein interaction network analysis revealed that the 34 genes formed two main subnetworks, and genes in the first subnetwork interacted with 15 SAGs. In conclusion, our results show that most of the 34 homologs of human-disease-associated genes in plants are involved in the leaf senescence process, suggesting that leaf senescence may offer a means to study the pathogenesis of human diseases and to screen drugs for the treat of diseases.
2,9-Dimethyl-4H-oxazolo[5’,4’:4,5]pyrano[3,2-f]quinolin-4-one
Authors: Vlachou Evangelia-Eirini N. , Balalas Thomas D. , Hadjipavlou-Litina Dimitra J. , Litinas Konstantinos E. , Douka Matina
Published: February 2023

The new 2,9-dimethyl-4H-oxazolo[5’,4’:4,5]pyrano[3,2-f]quinolin-4-one was successfully prepared through the three-component iodine-catalyzed reaction of n-butyl vinyl ether with the new 8-amino-2-methyl-4H-chromeno[3,4-d]oxazol-4-one. The latter was prepared by the reduction of 2-methyl-8-nitro-4H-chromeno[3,4-d]oxazol-4-one with Pd/C in a hydrogen atmosphere. The above nitro compound was synthesized by the condensation of N-(4-hydroxy-6-nitro-2-oxo-2H-chromen-3-yl)acetamide with P2O5 under microwave irradiation. The above acetamide derivative was prepared during the nitration of 2-methyl-4H-chromeno[3,4-d]oxazol-4-one with H2SO4 and KNO3. The structure of the newly synthesized compounds was confirmed by FT-IR, LC-MS, 1H-NMR, and 13C-NMR analyses. Preliminary biological tests show significant anti-lipid peroxidation activity for the title compound and the other synthesized new intermediates, as well as interesting soybean lipoxygenase inhibition for acetamide 2 (IC50 55 μM) and nitro-compound 3 (IC50 27 μM).
Assessment Effect of Nanometer-Sized Al2O3 Fillers in Polylactide on Fracture Probability of Filament and 3D Printed Samples by FDM
Authors: Smirnov Anton , Peretyagin Pavel , Nikitin Nikita
Published: February 2023

In this paper, a mathematical model for the description of the failure probability of filament and fused deposition modeling (FDM)-printed products is considered. The model is based on the results of tensile tests of filament samples made of polyacrylonitrile butadiene styrene (ABS), polylactide (PLA), and composite PLA filled with alumina (Al2O3) as well after FDM-printed products of “spatula” type. The application of probabilistic methods of fracture analysis revealed that the main contribution to the reduction of fracture probability is made by the elastic and plastic stages of the fracture curve under static loading. Particle distribution analysis of Al2O3 combined with fracture probability analysis shows that particle size distributions on the order of 10−5 and 10−6 mm decrease the fracture probability of the sample, whereas uniform particle size distributions on the order of 10−1 and 10−2 mm do not change the distribution probability. The paper shows that uneven distribution of Al2O3 fillers in composite samples made using FDM printing technology leads to brittle fracture of the samples.
Synthesis of Carbon Microspheres from Inedible Crystallized Date Palm Molasses: Influence of Temperature and Reaction Time
Authors: El-Harbawi Mohanad , Alhawtali Saeed , Al-Awadi Abdulrhman S. , El Blidi Lahssen , Alrashed Maher M. , Alzobidi Abdulrahman , Yin Chun-Yang
Published: February 2023

In this work, carbon microspheres (CMs) were prepared by hydrothermal carbonization (HTC) of inedible crystallized date palm molasses. The effects of temperature and reaction time on the prepared materials were studied. Experiments were carried out at different temperatures (180, 200, 230 and 250 °C) with reaction times ranging from 2 to 10 h. It was found that temperature had the greatest influence on the mass yield of the CMs. No solid products were observed at a temperature of 180 °C and a reaction time less than 2 h. The highest yield was found to be 40.4% at 250 °C and a reaction time of 6 h. The results show that the CMs produced were approximately 5–9 μm in diameter. The results also show that the largest diameter of the CMs (8.9 μm) was obtained at a temperature of 250 °C and a reaction time of 6 h. Nonetheless, if the reaction time was extended beyond 6 h at 250 °C, the CMs fused and their shapes were deformed (non-spherical shapes). The synthesized materials were characterized using Scanning Electron Microscopy (SEM), Fourier Transform Infrared (FTIR), Branuer-Emmett-Teller (BET) and thermogravimetric analysis (TGA). BET surface areas for the four samples were found to be less than 1 m2/g. The methylene blue adsorption studies indicated that the equilibrium adsorption capacity was reached after 15 min, with a maximum adsorption capacity of 12 mg/g. The recycling of date palm molasses (a known processed waste) to generate a useable carbon microsphere represents a beneficial step in the application of sustainable processing industries in the Middle East.
Supramolecular Weaving by Halogen-Bonding in Functionality-Rich Hexasubstituted Aromatic Synthons
Authors: Catenazzi Matteo , Nitti Andrea , Boiocchi Massimo , Bianchi Gabriele , Po Riccardo , Pasini Dario
Published: February 2023

Hexasubstituted benzenes are interesting platforms for the generation of functional materials, whose applications span from supramolecular recognition to organic electronics. Their synthesis is difficult to achieve by controlling multiple substitution steps of all hydrogen atoms on the aromatic benzene skeleton, so, often, cycloaddition reactions from disubsituted alkynes are used. In this work, we report a novel, straightforward route to C3-symmetrical hexasubstituted aromatic synthons with a diverse and rich pattern of functionalities, and we report about their packing mode in the crystals, in which, unprecedentedly, directional, strong halogen bonding interactions are capable of forming bidimensional supramolecular weaving.
Microstructural Degradation and Creep Property Damage of a Second-Generation Single Crystal Superalloy Caused by High Temperature Overheating
Authors: Guo Xiaotong , He Hao , Chen Fangzhou , Liu Jiahao , Li Wendao , Zhao Hao
Published: February 2023

Nickel base superalloys are widely used to manufacture turbine blades, and overheating poses a serious threat to the safe service of turbine blades. In this study, a second-generation nickel base single crystal superalloy was taken as the research object, and we carried out the overheating treatment at 1100 °C and 1300 °C, and then tested the creep properties at 1000 °C/300 MPa and 1100 °C/130 MPa. Through systematic analysis of creep properties, γ/γ’ phases, and creep voids, the effects of overheating on the microstructures and creep properties of the experimental superalloy were revealed. The results demonstrate that the effect of overheating at 1100 °C on the microstructure of the experimental superalloy can be ignored, and the effect on the creep property is limited. The degree of γ’ dissolution is gradually increased and the creep property is reduced with overheating time extending at the overheating temperature of 1300 °C.
Application of the Variational Method to the Large Deformation Problem of Thin Cylindrical Shells with Different Moduli in Tension and Compression
Authors: He Xiao-Ting , Wang Xiao-Guang , Sun Jun-Yi
Published: February 2023

In this study, the variational method concerning displacement components is applied to solve the large deformation problem of a thin cylindrical shell with its four sides fully fixed and under uniformly distributed loads, in which the material that constitutes the shell has a bimodular effect, in comparison to traditional materials, that is, the material will present different moduli of elasticity when it is in tension and compression. For the purpose of the use of the displacement variational method, the physical equations on the bimodular material model and the geometrical equation under large deformation are derived first. Thereafter, the total strain potential energy is expressed in terms of the displacement component, thus bringing the possibilities for the classical Ritz method. Finally, the relationship between load and central deflection is obtained, which is validated with the numerical simulation, and the jumping phenomenon of thin cylindrical shell with a bimodular effect is analyzed. The results indicate that the bimodular effect will change the stiffness of the shell, thus resulting in the corresponding change in the deformation magnitude. When the shell is relatively thin, the bimodular effect will influence the occurrence of the jumping phenomenon of the cylindrical shell.
Quantitative Measurement of Morphological Characteristics of PTFE Composite Transfer Films Based on Computer Graphics
Authors: Qi Yuan , Sun Bugong , Wang Honggang , Zhang Yang , Gao Gui , Zhang Peng , Zheng Xiaobao
Published: February 2023

In this paper, the tribological properties of polytetrafluoroethylene (PTFE) composites filled with Nano-ZrO2 and polyetheretherketone (PEEK) particles were tested for sliding friction against a counterpart metal (ASTM 1045 steel) using a linear reciprocating friction and wear experimental machine. Data on tribological performance and optical images of the transfer film were obtained at various friction stages for the material. MATLAB software was employed to develop quantitative analysis procedures for the morphological characteristics of the transfer film. The program enables image enhancement and morphological processing of transfer film images, then identifies, extracts, and quantifies the geometric and textural properties of the transfer film as a foundation for analyzing the variation of the characteristics and their relationship to the tribological properties of the material. The results demonstrated that the geometric, morphological, and textural characteristics of the transfer film were dynamically developing during the friction process, with noticeable differences between various friction stages and a significant impact on the tribological properties of the material. Quantitative analysis revealed a good correlation between the trends of some morphological and textural characteristics (the coverage, area, diameter, roundness, consistency, and texture entropy) of the transfer film and the wear resistance of the PTFE composite. Therefore, these morphological and textural characteristics can thus be used to quantify the transfer film quality and utilized as an indirect indicator of the tribological properties of the material.