bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of the Synthesis of Fungus-Mediated Bi-Metallic Ag-Cu Nanoparticles
Authors: Ameen Fuad
Published: January 2022

Bi-metallic nanoparticles (NPs) have appeared to be more efficient as antimicrobials than mono-metallic NPs. The fungus Aspergillus terreus-mediated synthesis of bi-metallic Ag-Cu NPs was optimized using response surface methodology (RSM) to reach the maximum yield of NPs. The optimal conditions were validated using ANOVA. The optimal conditions were 1.5 mM total metal (Ag + Cu) concentration, 1.25 mg fungal biomass, 350 W microwave power, and 15 min reaction time. The structure and shape of the synthesized NPs (mostly 20–30 nm) were characterized using several analytical tools. The biological activities of the synthesized NPs were assessed by studying their antioxidant, antibacterial, and cytotoxic activity in different NP concentrations. A dose-dependent response was observed in each test. Bi-metallic Ag-Cu NPs inhibited three clinically relevant human pathogens: Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa. Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus were inhibited less. The DPPH and hydrogen peroxide scavenging activities of the NPs were high, reaching 90% scavenging. Ag-Cu NPs could be studied as antimicrobials in different applications. The optimization procedure using statistical analyses was successful in improving the yield of nanoparticles.
Culturable Filamentous Fungi in the Air of Recreational Areas and Their Relationship with Bacteria and Air Pollutants during Winter
Authors: Góralska Katarzyna , Lis Szymon , Gawor Weronika , Karuga Filip , Romaszko Krystian , Brzeziańska-Lasota Ewa
Published: January 2022

One of the greatest environmental health problems to arise in recent years is air pollution. Inorganic and organic particles are important components of air aerosol. The potential of air microbiota as an indicator of air quality is gaining increasing research interest. The aim of the present study was to determine the relationship between the level of fungal contamination and the levels of bacteria and smog particles in outdoor air in recreational areas during the heating season. A quantitative and qualitative mycological evaluation and quantitative bacteriological evaluation of air quality in 10 selected parks were performed. The numbers of microorganisms in the air were correlated with smog levels. The mean prevalence of fungi was 18.96 ± 15.43–23.30 ± 26.70 CFU/m3 of air and the mean bacterial count was 74.06 ± 130.89–268.04 ± 126.10 CFU/m3. Among the isolated fungi, clinically significant species were identified: four species belonged to Risk Group 2, and 17 to Risk Group 1. The predominant genera were Aspergillus, Penicillium and Alternaria. The total number of bacteria demonstrated a positive correlation with the size of the park, air temperature and ozone level during sampling, and a negative correlation with humidity, pressure and smog parameters (CO, NO, NO2 and NOx). The qualitative and quantitative composition of bioaerosols can be used as a bioindicator for environmental monitoring. There is a need for more efficient monitoring of airborne pollutants and microorganisms to learn about the structure of the air biota, the mechanisms regulating their occurrence, and to identify potential threats to human health.
On the Structure of Topological Spaces
Authors: Martins-Ferreira Nelson
Published: January 2022

The structure of topological spaces is analysed here through the lenses of fibrous preorders. Each topological space has an associated fibrous preorder and those fibrous preorders which return a topological space are called spatial. A special class of spatial fibrous preorders consisting of an interconnected family of preorders indexed by a unitary magma is called Cartesian and is studied here. Topological spaces that are obtained from those fibrous preorders, with a unitary magma I, are called I-Cartesian and are characterized. The characterization reveals a hidden structure on such spaces. Several other characterizations are obtained, and special attention is drawn to the case of a monoid equipped with a topology. A wide range of examples is provided, as well as general procedures to obtain topologies from other data types such as groups and their actions. Metric spaces and normed spaces are considered as well.
Neural Differentiation of Human Dental Mesenchymal Stem Cells Induced by ATRA and UDP-4: A Comparative Study
Authors: Koutsoumparis Anastasios E. , Patsiarika Anastasia , Tsingotjidou Anastasia , Pappas Ioannis , Tsiftsoglou Asterios S.
Published: January 2022

Human mesenchymal stem cells (MSC) are multipotent stem cells, which are isolated from various sources. Currently, there is a worldwide interest for dental MSC to be used against neurodegenerative diseases, since they derive from the neural crest and express embryonic stem cell markers. This fact prompted us to explore their potential for neural trans-differentiation in culture. We employed all-trans-retinoic acid (ATRA) and 2-(3-ethylureido)-6-methylpyridine (UDP-4) to induce neural differentiation of human MSC from the dental apical papilla (SCAP). The SCAP were exposed to either agent separately and assessed for proliferation, viability, morphology, and gene expression of the following neural-specific markers: neuron-specific enolase (ENO2), neurofibromin 1 (NF1), choline acetyltransferase (CHAT), tyrosine hydroxylase (TH), and the vesicular GABA transporter (SLC32A1). They were also assessed for the expression of glial fibrillary acidic protein (GFAP) and neuronal nuclear antigen (NeuN) by immunofluorescence. ATRA or UDP-4 treatment inhibited the cell growth and promoted limited cell death, but to a different extent. The addition of the neuroprotective agent recombinant human erythropoietin-alpha (rhEPO-α) enhanced the UDP-4-inducing capacity for more than three weeks. ATRA or UDP-4 treatment significantly upregulated ENO2 and NF1 expression, indicating neuronal differentiation. Moreover, the ATRA treatment significantly induced the upregulation of the GABAergic-specific SLC32A1, while the UDP-4 treatment led to the significant upregulation of the adrenergic-specific TH. The UDP-4 treatment induced the expression of NeuN and GFAP after four and three weeks, respectively, while the ATRA-treatment did not. Our findings indicate that SCAP can be differentiated into neural-like cells after treatment with ATRA or UDP-4 by exhibiting a disparate pattern of differentiation. Therefore, UDP-4 is suggested here as a new potent neural-differentiation-inducing compound, which, when combined with rhEPO-α, could lay the foundation for robust stem-cell-based therapies of neurodegeneration.
A Stepwise Framework for the Systematic Development of Lipid Nanoparticles
Authors: Basso João , Mendes Maria , Cova Tânia , Sousa João , Pais Alberto , Fortuna Ana , Vitorino Rui , Vitorino Carla
Published: January 2022

A properly designed nanosystem aims to deliver an optimized concentration of the active pharmaceutical ingredient (API) at the site of action, resulting in a therapeutic response with reduced adverse effects. Due to the vast availability of lipids and surfactants, producing stable lipid dispersions is a double-edged sword: on the one hand, the versatility of composition allows for a refined design and tuning of properties; on the other hand, the complexity of the materials and their physical interactions often result in laborious and time-consuming pre-formulation studies. However, how can they be tailored, and which premises are required for a “right at first time” development? Here, a stepwise framework encompassing the sequential stages of nanoparticle production for disulfiram delivery is presented. Drug in lipid solubility analysis leads to the selection of the most suitable liquid lipids. As for the solid lipid, drug partitioning studies point out the lipids with increased capacity for solubilizing and entrapping disulfiram. The microscopical evaluation of the physical compatibility between liquid and solid lipids further indicates the most promising core compositions. The impact of the outer surfactant layer on the colloidal properties of the nanosystems is evaluated recurring to machine learning algorithms, in particular, hierarchical clustering, principal component analysis, and partial least squares regression. Overall, this work represents a comprehensive systematic approach to nanoparticle formulation studies that serves as a basis for selecting the most suitable excipients that comprise solid lipid nanoparticles and nanostructured lipid carriers.
Quantitative Proteomic Study Unmasks Fibrinogen Pathway in Polycystic Liver Disease
Authors: Cordido Adrian , Vizoso-Gonzalez Marta , Nuñez-Gonzalez Laura , Molares-Vila Alberto , Chantada-Vazquez Maria del Pilar , Bravo Susana B. , Garcia-Gonzalez Miguel A.
Published: January 2022

(1) Background: Polycystic liver disease (PLD) is a heterogeneous group of congenital disorders characterized by bile duct dilatation and cyst development derived from cholangiocytes. Nevertheless, the cystogenesis mechanism is currently unknown and the PLD treatment is limited to liver transplantation. Novel and efficient therapeutic approaches are th6us needed. In this context, the present work has a principal aim to find novel molecular pathways, as well as new therapeutic targets, involved in the hepatic cystogenesis process. (2) Methods: Quantitative proteomics based on SWATH–MS technology were performed comparing hepatic proteomes of Wild Type and mutant/polycystic livers in a polycystic kidney disease (PKD) murine model (Pkd1cond/cond;Tam-Cre−/+). (3) Results: We identified several proteins altered in abundance, with two-fold cut-off up-regulation or down-regulation and an adjusted p-value significantly related to hepatic cystogenesis. Then, we performed enrichment and a protein–protein analysis identifying a cluster focused on hepatic fibrinogens. Finally, we validated a selection of targets by RT-qPCR, Western blotting and immunohistochemistry, finding a high correlation with quantitative proteomics data and validating the fibrinogen complex. (4) Conclusions: This work identified a novel molecular pathway in cystic liver disease, highlighting the fibrinogen complex as a possible new therapeutic target for PLD.
Relationship between Macrophage and Radiosensitivity in Human Primary and Recurrent Glioblastoma: In Silico Analysis with Publicly Available Datasets
Authors: Jang Bum-Sup , Kim In Ah
Published: January 2022

The glioblastoma microenvironment predominantly contains tumor-associated macrophages that support tumor growth and invasion. We investigated the relationship between tumor radiosensitivity and infiltrating M1/M2 macrophage profiles in public datasets of primary and recurrent glioblastoma. We estimated the radiosensitivity index (RSI) score based on gene expression rankings. Macrophages were profiled using the deconvolution algorithm CIBERSORTx. Samples from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), the Ivy Glioblastoma Atlas Project dataset, a single-cell RNA sequencing dataset (GSE84465), Glioma Longitudinal Analysis Consortium (GLASS), and an immunotherapy trial dataset (GSE121810) were included. RSI-high radioresistant tumors were associated with worse overall survival in TCGA and CGGA than RSI-low tumors. M1/M2 macrophage ratios and RSI scores were inversely associated, indicating that radioresistant glioblastoma tumor microenvironments contain more M2 than M1 macrophages. In the single-cell RNA sequencing dataset, the mean RSI of neoplastic cells was positively correlated with high M2 macrophages proportions. A favorable response to programmed cell death protein 1 (PD-1) therapy was observed in recurrent glioblastomas with high M1/M2 macrophage ratios and low RSI scores. In patients with recurrent glioblastoma, fewer M2 macrophages and low RSI scores were associated with improved overall survival. High M2 macrophage proportions may be involved in radioresistant glioblastoma.
Effects of Therapeutic Antibodies on Gene and Protein Signatures in Asthma Patients: A Comparative Systematic Review
Authors: Martin Maria J. , Estravís Miguel , García-Sánchez Asunción , Pérez-Pazos Jacqueline , Isidoro-García María , Dávila Ignacio , Sanz Catalina
Published: January 2022

Several biologic therapies that target inflammatory modulators are now used for treating patients with uncontrolled, severe asthma. Knowledge about how this type of treatment modifies the molecular milieu is rapidly increasing. Thus, this systematic review aimed to compile the reported effects of therapeutic antibodies on the transcriptome or proteome of asthma patients. Studies of asthmatic patients under biological treatment describing transcriptomic or proteomic changes upon treatment were included. Preclinical or single gene/protein studies were not considered. PubMed and Scopus search was performed in August and September 2021. Following PRISMA guidelines and GRADE recommendations, we selected 12 studies on gene or protein expression changes in patients treated with the antibodies currently approved by EMA and the FDA. All studies were at low risk of bias as per the RoB2 tool. Different gene clusters have been identified to change upon omalizumab treatment, found a reduction in eosinophil-associated gene signatures after benralizumab treatment, and protein profiles were different in patients treated with mepolizumab and in those treated with benralizumab. The main potential biomarkers proposed by the selected studies are shown. These results may contribute to discovering biomarkers of response and selecting the best therapy for each patient.
Nasal Rifampicin Halts the Progression of Tauopathy by Inhibiting Tau Oligomer Propagation in Alzheimer Brain Extract-Injected Mice
Authors: Umeda Tomohiro , Uekado Rumi , Shigemori Keiko , Eguchi Hiroshi , Tomiyama Takami
Published: January 2022

The cell-to-cell transmission of tau aggregates is considered a mechanism underlying the intracerebral spreading of tau pathology in Alzheimer’s disease (AD) and other tauopathies. Recent studies suggest that tau oligomers, rather than fibrils, participate in this process. We previously showed that intranasal rifampicin inhibits tau oligomer accumulation and improves cognition in tauopathy mice. In the present study, we examined the effects of nasal rifampicin on tau propagation in a new mouse model of tauopathy. A tau oligomer-rich fraction prepared from the brain of an AD patient was injected into a unilateral hippocampus of tau264 mice that express both 3-repeat and 4-repeat wild-type human tau. Rifampicin administration was started one week after the injection and performed three times a week for 24 weeks. Cognitive function and tau pathology were assessed by the Morris water maze test and brain section staining. Rifampicin treatment inhibited the spreading of tau oligomers from the injection site to other brain regions and neurofibrillary tangle formation in the entorhinal cortex. Synapse and neuronal loss in the hippocampus were also prevented, and cognitive function remained normal. These results suggest that intranasal rifampicin could be a promising remedy that halts the progression of tauopathy by inhibiting tau oligomer propagation.
Effective CpG Delivery Using Zwitterion-Functionalized Dendrimer-Entrapped Gold Nanoparticles to Promote T Cell-Mediated Immunotherapy of Cancer Cells
Authors: Chen Huan , Zhang Yiming , Li Lulu , Guo Rui , Shi Xiangyang , Cao Xueyan
Published: January 2022

Recently, cell-based immunotherapy has become one of the most promising ways to completely eliminate cancer. The major challenge is to effectively promote a proper immune response to kill the cancer cells by activated T cells. This study investigated the effect of T cell-mediated immunotherapy trigged by Au DENPs-MPC (zwitterion 2-methacryloyloxyethyl phosphorylcholine (MPC)-functionalized dendrimer-entrapped gold nanoparticles) loading oli-godeoxynucleotides (ODN) of unmethylated cytosine guanine dinucleotide (CPG). Here, we first synthesized Au DENPs-MPC, evaluated their capability to compress and transfect CpG-ODN to bone marrow dendritic cells (BMDCs), and investigated the potential to use T cells stimulated by matured BMDCs to inhibit the growth of tumor cells. The developed Au DENPs-MPC could apparently reduce the toxicity of Au DENPs, and enhanced transfer CpG-ODN to the BMDCs for the maturation as demonstrated by the 44.41–48.53% increase in different surface maturation markers. The transwell experiments certificated that ex vivo activated T cells display excellent anti-tumor ability, which could effectively inhibit the growth of tumor cells. These results suggest that Au DENPs-MPC can deliver CpG-ODN efficiently to enhance the antigen presentation ability of BMDCs to activate T cells, indicating that T cells-based immunotherapy mediated by Au DENPs-MPC loaded with CpG-ODN may become the most promising treatment of cancer.
Graph Analysis of Verbal Fluency Tests in Schizophrenia and Bipolar Disorder
Authors: Chrobak Adrian Andrzej , Turek Aleksander , Machalska Karolina , Arciszewska-Leszczuk Aleksandra , Starowicz-Filip Anna , Krupa Anna Julia , Dudek Dominika , Siwek Marcin
Published: January 2022

Verbal Fluency Tests (VFT) are one of the most common neuropsychological tasks used in bipolar disorder (BD) and schizophrenia (SZ) research. Recently, a new VFT analysis method based on graph theory was developed. Interpreting spoken words as nodes and every temporal connection between consecutive words as edges, researchers created graph structures, allowing the extraction of more data from participants’ speech, called Speech Graph Attributes (SGA). The aim of our study was to compare speech graphs, derived from Phonemic and Semantic VFT, between SZ, BD, and healthy controls (HC). Twenty-nine SZ patients, twenty-nine BD patients, and twenty-nine HC performed Semantic and Phonemic VFT. Standard measures (SM) and 13 SGA were analyzed. SZ patients’ Semantic VFT graphs showed lower total word count and correct responses. Their graphs presented less nodes and edges, higher density, smaller diameter, average shortest path (ASP), and largest strongly connected component than the HC group. SM did not differentiate BD and HC groups, and patients’ Semantic VFT graphs presented smaller diameter and ASP than HC. None of the parameters differentiated BD and SZ patients. Our results encourage the use of speech graph analysis, as it reveals verbal fluency alterations that remained unnoticed in the routine comparisons of groups with the use SM.
Direct and Indirect Effects of Blood Levels of Omega-3 and Omega-6 Fatty Acids on Reading and Writing (Dis)Abilities
Authors: Borasio Francesca , Syren Marie-Louise , Turolo Stefano , Agostoni Carlo , Molteni Massimo , Antonietti Alessandro , Lorusso Maria Luisa
Published: January 2022

The purpose of the present study was to investigate whether there are associations between polyunsaturated fatty acid (PUFA) blood levels, reading/writing performance and performance in neuropsychological tasks. Moderate to strong correlations were found between PUFA levels (specific omega-6/omega-3 ratios) and reading/writing abilities, and the former and neuropsychological test scores. Mediation models analyzing the direct and indirect effects of PUFA on reading and writing scores showed that the effects of fatty acids on learning measures appear to be direct rather than mediated by the investigated visual and auditory neuropsychological mechanisms. The only significant indirect effect was found for the difference in accuracy between the left and right visual fields in visual-spatial cueing tasks, acting as a mediator for the effect of PUFA ratios on writing accuracy. Regression analyses, by contrast, confirmed the roles of phonological awareness and other visual attentional factors as predictors of reading and writing skills. Such results confirm the crucial role of visual-spatial attention mechanisms in reading and writing, and suggest that visual low-level mechanisms may be more sensitive to the effects of favorable conditions related to the presence of higher omega-3 blood levels.
Investigating the Role of Insight, Decision-Making and Mentalizing in Functional Outcome in Schizophrenia: A Cross-Sectional Study
Authors: Escobedo-Aedo Paula Jhoana , Forjan-González Ana , Sánchez-Escribano Martínez Adela , Ruiz-Ruano Verónica González , Sánchez-Alonso Sergio , Mata-Iturralde Laura , Muñoz-Lorenzo Laura , Baca-García Enrique , David Anthony S. , Lopez-Morinigo Javier-David
Published: January 2022

Background: Recovery has become a priority in schizophrenia spectrum disorders (SSDs). This study aimed to investigate predictors of objective—general functioning and disability—and subjective—quality of life (QoL)—measures of functional outcomes in SSD. Methods: Sample: n = 77 SSD outpatients (age 18–64, IQ > 70) participating in a randomised controlled trial. Baseline data were used to build three multivariable linear regression models on: (i) general functioning—General Assessment of Functioning (GAF); (ii) disability—the World Health Organization Disability Assessment Schedule (WHODAS-2.0); and (iii) QoL—Satisfaction Life Domains Scale (SLDS). Results: Young age and being employed (R2 change = 0.211; p = 0.001), late adolescence premorbid adjustment (R2 change = 0.049; p = 0.0050), negative symptoms and disorganization (R2 change = 0.087; p = 0.025) and Theory of Mind (R2 change = 0.066, p = 0.053) predicted general functioning. Previous suicidal behaviour (R2 change = 0.068; p = 0.023) and negative and depressive symptoms (R2 change = 0.167; p = 0.001) were linked with disability. Previous suicidal behaviour (R2 change = 0.070, p = 0.026), depressive symptoms (R2 change = 0.157; p < 0.001) and illness recognition (R2 change = 0.046, p = 0.044) predicted QoL. Conclusions: Negative, disorganization and depressive symptoms, older age, unemployment, poor premorbid adjustment, previous suicide attempts and illness awareness appear to underlie a poor global functional outcome in SSD. Achieving recovery in SSD appears to require both symptomatic remission (e.g., through antipsychotics) and measures to improve mastery and relieve low mood.
Fish Consumption and Colorectal Cancer Risk: Meta-Analysis of Prospective Epidemiological Studies and Review of Evidence from Animal Studies
Authors: Caini Saverio , Chioccioli Sofia , Pastore Elisa , Fontana Miriam , Tortora Katia , Caderni Giovanna , Masala Giovanna
Published: January 2022

Background: Epidemiological studies on the association between fish consumption and colorectal cancer (CRC) risk have yielded inconsistent results, despite evidence from preclinical studies that long-chain ω-3 polyunsaturated fatty acids inhibit colorectal carcinogenesis. We conducted a meta-analysis of prospective epidemiological studies investigating the association between fish consumption and CRC risk among humans and reviewed studies examining the link between fish components and colorectal carcinogenesis in animal models. Methods: We included studies published until November 2020. We calculated the summary risk ratio (SRR) and 95% confidence intervals (CI) through random effects meta-analysis models in order to summarize evidence from studies among humans. Results: Twenty-five prospective epidemiological studies encompassing 25,777 CRC cases were included. Individuals in the highest (vs. lowest) category of fish consumption had a significantly reduced risk of CRC (SRR 0.94, 95%CI 0.89–0.99). In dose–response meta-analysis, a 50-g increment in the daily consumption of fish was associated with a statistically significant 4% reduction in CRC risk (SRR 0.96, 95%CI 0.92–0.99). Preclinical studies (n = 25) identified multiple mechanisms of action of fish and fish components on colorectal carcinogenesis. Conclusions: Dietary recommendations for cancer prevention should take into account the evidence from epidemiological and preclinical studies that increasing fish consumption may be effective in preventing CRC.
RBM22, a Key Player of Pre-mRNA Splicing and Gene Expression Regulation, Is Altered in Cancer
Authors: Soubise Benoît , Jiang Yan , Douet-Guilbert Nathalie , Troadec Marie-Bérengère
Published: January 2022

RNA-Binding Proteins (RBP) are very diverse and cover a large number of functions in the cells. This review focuses on RBM22, a gene encoding an RBP and belonging to the RNA-Binding Motif (RBM) family of genes. RBM22 presents a Zinc Finger like and a Zinc Finger domain, an RNA-Recognition Motif (RRM), and a Proline-Rich domain with a general structure suggesting a fusion of two yeast genes during evolution: Cwc2 and Ecm2. RBM22 is mainly involved in pre-mRNA splicing, playing the essential role of maintaining the conformation of the catalytic core of the spliceosome and acting as a bridge between the catalytic core and other essential protein components of the spliceosome. RBM22 is also involved in gene regulation, and is able to bind DNA, acting as a bona fide transcription factor on a large number of target genes. Undoubtedly due to its wide scope in the regulation of gene expression, RBM22 has been associated with several pathologies and, notably, with the aggressiveness of cancer cells and with the phenotype of a myelodysplastic syndrome. Mutations, enforced expression level, and haploinsufficiency of RBM22 gene are observed in those diseases. RBM22 could represent a potential therapeutic target in specific diseases, and, notably, in cancer.
Combination of Anti-Angiogenics and Checkpoint Inhibitors for Renal Cell Carcinoma: Is the Whole Greater Than the Sum of Its Parts?
Authors: Jonasch Eric , Atkins Michael B. , Chowdhury Simon , Mainwaring Paul
Published: January 2022

Anti-angiogenic agents, such as vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors and anti-VEGF antibodies, and immune checkpoint inhibitors (CPIs) are standard treatments for advanced renal cell carcinoma (aRCC). In the past, these agents were administered as sequential monotherapies. Recently, combinations of anti-angiogenic agents and CPIs have been approved for the treatment of aRCC, based on evidence that they provide superior efficacy when compared with sunitinib monotherapy. Here we explore the possible mechanisms of action of these combinations, including a review of relevant preclinical data and clinical evidence in patients with aRCC. We also ask whether the benefit is additive or synergistic, and, thus, whether concomitant administration is preferred over sequential monotherapy. Further research is needed to understand how combinations of anti-angiogenic agents with CPIs compare with CPI monotherapy or combination therapy (e.g., nivolumab and ipilimumab), and whether the long-term benefit observed in a subset of patients treated with CPI combinations will also be realised in patients treated with an anti-angiogenic therapy and a CPI. Additional research is also needed to establish whether other elements of the tumour microenvironment also need to be targeted to optimise treatment efficacy, and to identify biomarkers of response to inform personalised treatment using combination therapies.
Clinicopathologic vs. Molecular Integrated Prognostication of Endometrial Carcinoma by European Guidelines
Authors: Loukovaara Mikko , Pasanen Annukka , Bützow Ralf
Published: January 2022

This was a retrospective study of 604 patients with endometrial carcinoma, classified into ESGO-ESTRO-ESP 2021 clinicopathologic and molecular integrated risk groups. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) and Leiden classifier were employed for molecular classification. Median follow-up time was 81 months. Clinicopathologic and molecular integrated risk groups were similarly associated with distinct prognoses (p < 0.001). Disease-specific survival was similar for all molecular subgroups within clinicopathologic intermediate-risk, high-risk, and advanced/metastatic groups. In contrast, the p53 abnormal subgroup (hazard ratio 9.1, 95% confidence interval 2.0–41; p = 0.004) and mismatch repair deficient subgroup (hazard ratio 3.5, 95% confidence interval 1.2–10; p = 0.024) were associated with disease-related death within clinicopathologic low-risk and high-intermediate-risk carcinomas, respectively. A risk-group shift occurred in 6.0% (36/604) and 7.4% (38/515) of patients classified by ProMisE and Leiden, respectively (p = 0.341). Of the 36 patients shifted in the ProMisE cohort, 27 were upshifted and 9 downshifted. Based on the Leiden classifier, polymerase-ϵ sequencing could be omitted in 60% (311/515) of patients without affecting the risk-group assessment. ESGO-ESTRO-ESP 2021 guidelines provide a platform for risk classification in future trials on molecularly directed treatment of endometrial carcinoma.
Treatment with Idelalisib in Patients with Relapsed or Refractory Follicular Lymphoma: The Observational Italian Multicenter FolIdela Study
Authors: Casadei Beatrice , Argnani Lisa , Broccoli Alessandro , Patti Caterina , Stefani Piero Maria , Cuneo Antonio , Margiotta Casaluci Gloria , Visco Carlo , Gini Guido , Pane Fabrizio , D’Alò Francesco , Luzi Debora , Cantonetti Maria , Pozzi Samantha , Musuraca Gerardo , Rosignoli Chiara , Arcari Annalisa , Kovalchuk Sofya , Tani Monica , Tisi Maria Chiara , Petrini Mario , Stefoni Vittorio , Zinzani Pier Luigi
Published: January 2022

Follicular lymphoma (FL) is an indolent hematological disease, often responsive to the first line of treatment, but characterized by repeated relapses. The therapeutic algorithm for relapsed/refractory FL patients comprises phosphatidylinositol 3-kinase inhibitors. Idelalisib showed anticancer activity, while inducing a significant rate of toxicities. Since the evidence in the literature on its use in normal clinical practice is scarce, a retrospective multicenter study was conducted to evaluate effectiveness and tolerability in a real-life context. Seventy-two patients with a median age at diagnosis of 57.2 years—mostly with an advanced stage (88.9%) and relapsed to the most recent therapy (79.1%)—were enrolled. The median number of prior therapies was three (20.8% refractory to the last therapy before idelalisib). With a median number of 4 months of treatment, the overall response rate was 41.7% (20.8% complete responses). Median disease-free survival and overall survival were achieved at 8.4 months and at 4 years, respectively. Forty-four percent of patients experienced at least one drug-related toxicity: 6.9% hematological ones and 43% non-hematological. The study confirmed that idelalisib has anticancer effectiveness and an acceptable safety profile in relapsed/refractory FL with unfavorable prognostic characteristics, even in the context of normal clinical practice.
Propane Dehydrogenation over PtSn/Al2O3 Catalysts: Influence of Urea to Al(NO3)3·9H2O Ratio
Authors: Wang Xiaohan , Cui Jing , Zhang Ning , Song Jiaxin , Fan Xiaoqiang , Zhao Zhen , Kong Lian , Xiao Xia , Xie Zean
Published: January 2022

Al2O3 supports were synthesized by the hydrothermal method and PtSn/Al2O3 catalysts were prepared by incipient-wetness impregnation method. The influence of the ratio of urea to Al(NO3)3·9H2O on the structure and catalytic performance for propane dehydrogenation was investigated. The catalysts were characterized by XRD, N2 adsorption–desorption, SEM, H2-TPR, NH3-TPD and Raman. The results show that the ratios of urea to Al(NO3)3·9H2O influence the morphology and phy-chemical properties of Al2O3 support, which influence the dispersion of PtSn active sites and the interaction of Pt and Sn on PtSn/Al2O3 catalysts. The PtSn/Al2O3-9 catalyst possesses the highest interaction of Pt and Sn, which result in high dispersion of active sites. The PtSn/Al2O3-9 catalyst shows high propane conversion and low deactivation rate among these catalysts.
Use of CRISPR/Cas9-Based Gene Editing to Simultaneously Mutate Multiple Homologous Genes Required for Pollen Development and Male Fertility in Maize
Authors: Liu Xinze , Zhang Shaowei , Jiang Yilin , Yan Tingwei , Fang Chaowei , Hou Quancan , Wu Suowei , Xie Ke , An Xueli , Wan Xiangyuan
Published: January 2022

Male sterility represents an important trait for hybrid breeding and seed production in crops. Although the genes required for male fertility have been widely studied and characterized in many plant species, most of them are single genic male-sterility (GMS) genes. To investigate the role of multiple homologous genes in anther and pollen developments of maize, we established the CRISPR/Cas9-based gene editing method to simultaneously mutate the homologs in several putative GMS gene families. By using the integrated strategies of multi-gene editing vectors, maize genetic transformation, mutation-site analysis of T0 and F1 plants, and genotyping and phenotyping of F2 progenies, we further confirmed gene functions of every member in ZmTGA9-1/-2/-3 family, and identified the functions of ZmDFR1, ZmDFR2, ZmACOS5-1, and ZmACOS5-2 in controlling maize male fertility. Single and double homozygous gene mutants of ZmTGA9-1/-2/-3 did not affect anther and pollen development, while triple homozygous gene mutant resulted in complete male sterility. Two single-gene mutants of ZmDFR1/2 displayed partial male sterility, but the double-gene mutant showed complete male sterility. Additionally, only the ZmACOS5-2 single gene was required for anther and pollen development, while ZmACOS5-1 had no effect on male fertility. Our results show that the CRISPR/Cas9 gene editing system is a highly efficient and convenient tool for identifying multiple homologous GMS genes. These findings enrich GMS genes and mutant resources for breeding of maize GMS lines and promote deep understanding of the gene family underlying pollen development and male fertility in maize.
Transcriptional and Post-Transcriptional Regulation of Autophagy
Authors: Ma Qiuqin , Long Shihui , Gan Zhending , Tettamanti Gianluca , Li Kang , Tian Ling
Published: January 2022

Autophagy is a widely conserved process in eukaryotes that is involved in a series of physiological and pathological events, including development, immunity, neurodegenerative disease, and tumorigenesis. It is regulated by nutrient deprivation, energy stress, and other unfavorable conditions through multiple pathways. In general, autophagy is synergistically governed at the RNA and protein levels. The upstream transcription factors trigger or inhibit the expression of autophagy- or lysosome-related genes to facilitate or reduce autophagy. Moreover, a significant number of non-coding RNAs (microRNA, circRNA, and lncRNA) are reported to participate in autophagy regulation. Finally, post-transcriptional modifications, such as RNA methylation, play a key role in controlling autophagy occurrence. In this review, we summarize the progress on autophagy research regarding transcriptional regulation, which will provide the foundations and directions for future studies on this self-eating process.
The Relative Influence of Family and Neighborhood Factors on Child Maltreatment at Critical Stages of Child Development
Authors: Maguire-Jack Kathryn , Yoon Susan , Chang Yujeong , Hong Sunghyun
Published: January 2022

This study examines the impact of family and neighborhood factors on physical and psychological abuse across three developmental stages of children: early childhood (age 3), young school age (age 5), and middle childhood (age 9). Data from the Fragile Families and Child Wellbeing Study, a longitudinal national cohort study of children from 20 urban U.S. cities, are used. Path analysis is employed to investigate the longitudinal relationships between family and neighborhood context variables and abuse risk, as well as the importance of different factors at key developmental stages. Economic hardship, maternal substance use, intimate partner violence, and exposure to community violence are found to be related to child abuse risk regardless of developmental stage, while maternal depression and neighborhood informal social control are found to have impacts only within certain child development stages. Findings suggest the need for early intervention and prevention strategies that specifically target economic hardship, poverty, intimate partner violence, and exposure to community violence.
Impact of Engineering Surface Treatment on Surface Properties of Biomedical TC4 Alloys under a Simulated Human Environment
Authors: Deng Hongyun , Xu Kuixue , Liu Shuguang , Zhang Chaofeng , Zhu Xiongwei , Zhou Haoran , Xia Chaoqun , Shi Chunbao
Published: January 2022

The impact of sandblasting, anodic oxidation, and anodic oxidation after sandblasting on the surface structure and properties of titanium alloys was investigated. It was found that the surface treatments had a significant influence on the surface roughness values, contact angle values, Vickers hardness, wear resistance, and corrosion resistance of titanium alloys. The surface roughness of titanium alloys with sandblasting treatment was increased by 67% compared to untreated specimen. The Vickers hardness of titanium alloys treated with anodic oxidation after sandblasting was found to increase from 380.8 HV to 408.5 HV, which was increased by 7.3%. The surface treatments in this work improved the wear resistance of the titanium alloys to some extent, and it can be found that the wear scar width is reduced by up to 18.6%. The corrosion resistance of the titanium alloys was found to improve on anodic oxidation. Sandblasting was found to increase surface roughness and promote the formation of a porous layer during the anodization process, resulting in a slight decrease in corrosion resistance. The corrosion current density was increased by 21% compared to the untreated specimen. The corrosion current density of the titanium alloy treated with anodic oxidation decreased to 7.01 × 10−8 A/cm2. The corrosion current density was decreased by 24% compared to the untreated specimen. The corrosion current density of the titanium alloys treated with anodic oxidation after sandblasting decreased to 7.63 × 10−8 A/cm2. The corrosion current density was decreased by 8.8% compared to the specimen with anodic oxidation. The anodic oxidation provided a hydrophilic property for the surface of Ti alloys, which could show a better osseointegration characteristic than that of sandblasting. The impact of the surface treatments on surface structure and properties of titanium alloys was studied.
Gadoxetic Acid-Based MRI for Decision-Making in Hepatocellular Carcinoma Employing Perfusion Criteria Only—A Post Hoc Analysis from the SORAMIC Trial Diagnostic Cohort
Authors: Seidensticker Max , Steffen Ingo G. , Bargellini Irene , Berg Thomas , Benito Alberto , Gebauer Bernhard , Iezzi Roberto , Loewe Christian , Karçaaltincaba Musturay , Pech Maciej , Sengel Christian , van Delden Otto , Vandecaveye Vincent , Zech Christoph J. , Ricke Jens
Published: January 2022

The value of gadoxetic acid in the diagnosis of hepatocellular carcinoma (HCC), based on perfusion criteria, is under dispute. This post-hoc analysis of the prospective, phase II, randomized, controlled SORAMIC study compared the accuracy of gadoxetic acid-enhanced dynamic magnetic resonance imaging (MRI) (arterial, portovenous, and venous phase only) versus contrast-enhanced computed tomography (CT) for stratifying patients with HCC to curative ablation or palliative treatment. Two reader groups (radiologists, R1 and R2) performed blind reads of CT and gadoxetic acid-enhanced MRI (contrast dynamics only). A truth panel, with access to clinical and imaging follow-up data, served as reference. Primary endpoint was non-inferiority (margin: 5% points) of MRI vs. CT (lower 95% confidence interval [CI] > 0.75) in a first step and superiority (complete 95% CI > 1) in a second step. The intent-to-treat population comprised 538 patients. Accuracy of treatment decisions was 73.4% and 70.8% for CT (R1 and R2, respectively) and 75.1% and 70.3% for gadoxetic acid-enhanced dynamic MRI. Non-inferiority but not superiority of gadoxetic acid-enhanced dynamic MRI versus CT was demonstrated (odds ratio 1.01; CI 0.97–1.05). Despite a theoretical disadvantage in wash-out depiction, gadoxetic acid-enhanced dynamic MRI is non-inferior to CT in accuracy of treatment decisions for curative ablation versus palliative strategies. This outcome was not subject to the use of additional MR standard sequences.
Modeling the Potential Distribution of Two Species of Shrews (Chodsigoa hypsibia and Anourosorex squamipes) under Climate Change in China
Authors: Hu Wenhao , Onditi Kenneth Otieno , Jiang Xuelong , Wu Hailong , Chen Zhongzheng
Published: January 2022

Understanding how the direct and indirect effects of climate change may affect species distributions is a key topic in ecology. We used maximum entropy models to explore the distribution of two species of shrews (Chodsigoa hypsibia and Anourosorex squamipes) in China and analyzed the main environmental factors affecting their current distribution and potential distribution changes under two future climate scenarios. The results showed that the major environmental factors determining the current distribution of C. hypsibia were the mean temperature of the coldest quarter (contributing 47.4%), annual mean temperature (contributing 24.7%), precipitation of the driest quarter (contributing 21.1%) and isothermality (contributing 6%). Annual precipitation (contributing 42.9%), precipitation of the driest month (contributing 28.1%), annual mean temperature (contributing 14.8%) and temperature seasonality (contributing 12.6%) had the highest contributions to the distribution of A. squamipes. Under future climate scenarios, the suitable habitat range of C. hypsibia increased while that of A. squamipes decreased. These findings demonstrate that different small mammal species respond differently to climate change.
Optimization and Design of a Flexible Droop-Nose Leading-Edge Morphing Wing Based on a Novel Black Widow Optimization Algorithm—Part I
Authors: Bashir Musavir , Longtin-Martel Simon , Botez Ruxandra Mihaela , Wong Tony
Published: January 2022

An aerodynamic optimization for a Droop-Nose Leading-Edge (DNLE) morphing of a well-known UAV, the UAS-S45, is proposed, using a novel Black Widow Optimization (BWO) algorithm. This approach integrates the optimization algorithm with a modified Class-Shape Transformation (CST) parameterization method to enhance aerodynamic performance by minimizing drag and maximizing aerodynamic endurance at the cruise flight condition. The CST parameterization technique is used to parameterize the reference airfoil by introducing local shape changes and provide skin flexibility to obtain various optimized morphing airfoil configurations. The optimization framework uses an in-house MATLAB algorithm, while the aerodynamic calculations use the XFoil solver with flow transition estimation criteria. These results are validated with a CFD solver utilizing the Transition (γ−Reθ) Shear Stress Transport (SST) turbulence model. Numerical studies verified the effectiveness of the optimization strategy, and the optimized airfoils have shown a significant improvement in overall aerodynamic performance by up to 12.18% drag reduction compared to the reference airfoil, and an increase in aerodynamic endurance of up to 10% for the UAS-S45 optimized airfoil configurations over its reference airfoil. These results indicate the importance of leading-edge morphing in enhancing the aerodynamic efficiency of the UAS-S45 airfoil.
A Comparative Study for Measuring Serum Ferritin Levels with Three Different Laboratory Methods: Enzyme-Linked Immunosorbent Assay versus Cobas e411 and Cobas Integra 400 Methods
Authors: Dahman Lotfi S. Bin , Sumaily Khalid M. , Sabi Essa M. , Hassan Mohammed A. , Thalab Abeer M. Bin , Sayad Asrar S. , Kolaib Saleh M. Bin , Alhadhrmi Fatima M.
Published: January 2022

Different laboratory methods are used to measure serum ferritin levels as a marker of iron status in the general population. This study aimed to compare serum ferritin levels using enzyme-linked immunosorbent assay (ELISA) versus immunochemiluminescence (Cobas e411) and immunoturbidimetric (Cobas Integra 400) methods in terms of sensitivity, specificity and accuracy, and whether they can be used interchangeably. A comparative cross-sectional study enrolled one hundred and six adult Yemeni patients (33 males and 73 females) aged 18–55 years, recruited from the dermatology and cosmetic center of Hadhramout Modern Hospital, Mukalla, Yemen. Serum ferritin levels were measured using ELISA, Cobas e411, and Cobas Integra 400 methods. For method comparison, a paired-sample t-test was used. For the consistency between the three methods, they were analyzed with regression and Pearson correlation coefficient. For determining accuracy, a receiver operating curve (ROC) was used. Bias error between the methods was determined through a Bland–Altman plot analysis. Our results did not show any significant statistical difference between ELISA and Cobas e411 (52.55 ± 7.4 µg/L vs. 52.58 ± 7.5 µg/L, p = 0.967), while there were significantly higher values from Cobas Integra 400 results than Cobas e411 (56.31 ± 7.8 µg/L vs. 52.58 ± 7.5 µg/L, p < 0.001) and ELISA (52.55 ± 7.4 µg/L vs. 56.31 ± 7.8 µg/L, p < 0.001). According to the correlation coefficient and linear regression analysis, a strong association between ELISA with Cobas e411 (r = 0.993, p < 0.001) and Cobas Integra 400 results (r = 0.994, p < 0.001) were revealed. For determining accuracy, Cobas e411 and Cobas Integra 400 results showed higher sensitivity (92.0%; 90.0%) and specificity (97.7%; 99.9%) respectively. Additionally, the Bland–Altman plot analysis showed a high agreement between the ELISA and Cobas e411 methods (bias: −0.035). In contrast, there was a low agreement between the ELISA and Cobas Integra 400 methods (bias: −3.75). Similarly, the agreement between Cobas e411 and Cobas Integra 400 methods was low (bias: −3.72). Serum ferritin levels were measured by Cobas e411, and Cobas Integra 400 methods were strongly correlated with the ELISA results, with higher sensitivity, specificity, and accuracy. However, further investigations with larger samples are required for improved accuracy and more precise results, and to determine whether they can be used interchangeably.
Cardiac Computed Tomography Radiomics-Based Approach for the Detection of Left Ventricular Remodeling in Patients with Arterial Hypertension
Authors: Cavallo Armando Ugo , Troisi Jacopo , Muscogiuri Emanuele , Cavallo Pierpaolo , Rajagopalan Sanjay , Citro Rodolfo , Bossone Eduardo , McVeigh Niall , Forte Valerio , Di Donna Carlo , Giannini Francesco , Floris Roberto , Garaci Francesco , Sperandio Massimiliano
Published: January 2022

The aim of the study is to verify the feasibility of a radiomics based approach for the detection of LV remodeling in patients with arterial hypertension. Cardiac Computed Tomography (CCT) and clinical data of patients with and without history of arterial hypertension were collected. In one image per patient, on a 4-chamber view, left ventricle (LV) was segmented using a polygonal region of interest by two radiologists in consensus. A total of 377 radiomics features per region of interest were extracted. After dataset splitting (70:30 ratio), eleven classification models were tested for the discrimination of patients with and without arterial hypertension based on radiomics data. An Ensemble Machine Learning (EML) score was calculated from models with an accuracy >60%. Boruta algorithm was used to extract radiomic features discriminating between patients with and without history of hypertension. Pearson correlation coefficient was used to assess correlation between EML score and septum width in patients included in the test set. EML showed an accuracy, sensitivity and specificity of 0.7. Correlation between EML score and LV septum width was 0.53 (p-value < 0.0001). We considered LV septum width as a surrogate of myocardial remodeling in our population, and this is the reason why we can consider the EML score as a possible tool to evaluate myocardial remodeling. A CCT-based radiomic approach for the identification of LV remodeling is possible in patients with past medical history of arterial hypertension.