bluuebunny/crossref_metadata_2025 huggingface dataset:
Compositing Fullerene-Derived Porous Carbon Fibers with Reduced Graphene Oxide for Enhanced ORR Catalytic Performance
Authors: He Zhimin , Guo Ziqian , Guo Kun , Akasaka Takeshi , Lu Xing
Published: February 2022

Compositing all-carbon materials with distinct dimensions and structures has demonstrated the great potential to bring synergistic promotion to individual components for the electrocatalytic activity of oxygen reduction reaction (ORR). Fullerene-derived porous carbon fibers (FPCFs) offer unique one-dimensional (1D) nanostructures with abundant defects and a large specific surface area while graphene features two-dimensional (2D) nanostructures with fast electron transfer. Both carbon materials are promising alternatives to Pt-based electrocatalysts for ORR. Herein, a novel hierarchical composite (FPCFs@rGO) composed of FPCFs and reduced graphene oxide (rGO) is constructed by sonication-assisted mixing and high-temperature pyrolysis. When tested as an electrocatalyst for ORR, the 1D/2D FPCFs@rGO composite presents significantly enhanced performance compared to each individual component, indicating an eminent synergistic effect between FPCFs and rGO. The improved ORR performance of FPCFs@rGO is attributed to the unique hierarchical structure with abundant structural defects, a large specific surface area, and high porosity.
CD26/DPP-4 in Chronic Myeloid Leukemia
Authors: Sicuranza Anna , Raspadori Donatella , Bocchia Monica
Published: February 2022

CD26 expression is altered in many solid tumors and hematological malignancies. Recently, it has been demonstrated that it is a specific marker expressed on LSCs of CML, both in BM and PB samples, and absent on CD34+/CD38− stem cells in normal subjects or on LSCs of other myeloid neoplasms. CD26+ LSCs have been detected by flow-cytometry assays in all PB samples of Chronic-Phase CML patients evaluated at diagnosis. Additionally, it has been demonstrated that most CML patients undergoing Tyrosine Kinase Inhibitors (TKIs) treatment still harbored circulating measurable residual CD26+ LSCs, even when displaying a consistent deep molecular response without any significant association among the amounts of BCR-ABL transcript and CD26+ LSCs. Preliminary data of our Italian prospective multicenter study showed that CML patients with a poorer response presented with a higher number of CD26+ LSCs at diagnosis. These data confirmed that CD26 is a specific marker of CML and suggest that it could be considered for the monitoring of therapeutic responses.
A Tailored Approach for Appendicular Impending and Pathologic Fractures in Solid Cancer Metastases
Authors: Soares do Brito Joaquim , Lopes-Brás Raquel , Abrunhosa-Branquinho André , Fernandes Isabel , Gomes Inês , Casimiro Sandra , Costa Luís
Published: February 2022

Advances in medical and surgical treatment have played a major role in increasing the survival rates of cancer patients with metastatic bone disease. The clinical course of patients with bone metastases is often impaired by bone complications, such as bone fractures, which have a substantial negative impact on clinical outcomes. To optimize clinical results and prevent a detrimental impact on patients’ health, a tailored approach should be defined for any given patient. The optimal management of impending or pathologic fractures is unknown and relies on a multidisciplinary approach to tailor clinical decisions to each individual patient. The ability to control systemic disease, the extent, location and nature of bone metastases, and the biology of the underlying tumor, are the main factors that will define the strategy to follow. The present review covers the most recent data regarding impending and pathologic fractures in patients with bone metastases, and discusses the medical and surgical management of patients presenting with metastatic bone disease in different clinical settings.
Tissue miRNA Combinations for the Differential Diagnosis of Adrenocortical Carcinoma and Adenoma Established by Artificial Intelligence
Authors: Turai Péter István , Herold Zoltán , Nyirő Gábor , Borka Katalin , Micsik Tamás , Tőke Judit , Szücs Nikolette , Tóth Miklós , Patócs Attila , Igaz Peter
Published: February 2022

The histological analysis of adrenal tumors is difficult and requires great expertise. Tissue microRNA (miRNA) expression is distinct between benign and malignant tumors of several organs and can be useful for diagnostic purposes. MiRNAs are stable and their expression can be reliably reproduced from archived formalin-fixed, paraffin-embedded (FFPE) tissue blocks. Our purpose was to assess the potential applicability of combinations of literature-based miRNAs as markers of adrenocortical malignancy. Archived FFPE tissue samples from 10 adrenocortical carcinoma (ACC), 10 adrenocortical adenoma (ACA) and 10 normal adrenal cortex samples were analyzed in a discovery cohort, while 21 ACC and 22 ACA patients were studied in a blind manner in the validation cohort. The expression of miRNA was determined by RT-qPCR. Machine learning and neural network-based methods were used to find the best performing miRNA combination models. To evaluate diagnostic applicability, ROC-analysis was performed. We have identified three miRNA combinations (hsa-miR-195 + hsa-miR-210 + hsa-miR-503; hsa-miR-210 + hsa-miR-375 + hsa-miR-503 and hsa-miR-210 + hsa-miR-483-5p + hsa-miR-503) as unexpectedly good predictors to determine adrenocortical malignancy with sensitivity and specificity both of over 90%. These miRNA panels can supplement the histological examination of removed tumors and could even be performed from small volume adrenal biopsy samples preoperatively.
Glycans as Targets for Drug Delivery in Cancer
Authors: Diniz Francisca , Coelho Pedro , Duarte Henrique O. , Sarmento Bruno , Reis Celso A. , Gomes Joana
Published: February 2022

Innovative strategies have been proposed to increase drug delivery to the tumor site and avoid cytotoxicity, improving the therapeutic efficacy of well-established anti-cancer drugs. Alterations in normal glycosylation processes are frequently observed in cancer cells and the resulting cell surface aberrant glycans can be used as direct molecular targets for drug delivery. In the present review, we address the development of strategies, such as monoclonal antibodies, antibody–drug conjugates and nanoparticles that specific and selectively target cancer-associated glycans in tumor cells. The use of nanoparticles for drug delivery encompasses novel applications in cancer therapy, including vaccines encapsulated in synthetic nanoparticles and specific nanoparticles that target glycoproteins or glycan-binding proteins. Here, we highlight their potential to enhance targeting approaches and to optimize the delivery of clinically approved drugs to the tumor microenvironment, paving the way for improved personalized treatment approaches with major potential importance for the pharmaceutical and clinical sectors.
Prevalence of Sleep Disorders, Risk Factors and Sleep Treatment Needs of Adolescents and Young Adult Childhood Cancer Patients in Follow-Up after Treatment
Authors: Peersmann Shosha H. M. , Grootenhuis Martha A. , van Straten Annemieke , Kerkhof Gerard A. , Tissing Wim J. E. , Abbink Floor , de Vries Andrica C. H. , Loonen Jacqueline , Kremer Leontien C. M. , Kaspers Gertjan J. L. , van Litsenburg Raphaële R. L.
Published: February 2022

Background: Sleep disorders negatively impact adolescent and young adult childhood cancer patients’ physical and psychosocial health. Early recognition improves timely treatment. We therefore studied the prevalence of subjective sleep disorders, risk factors and sleep treatment needs after completion of childhood cancer treatment. Methods: Childhood cancer patients (12–26 years old), ≥6 months after treatment, were invited to fill out the Holland Sleep Disorders Questionnaire, which distinguishes six sleep disorders in substantial agreement with the International Classification of Sleep Disorders, second edition (ICSD-2). They additionally indicated sleep treatment needs. Prevalence rates and needs were displayed in percentages. Logistic regression models were used for risk factors. Results: 576 patients participated (response rate 55.8%)—49.5% females, mean age 17.0 years, 44.4% hemato-oncology, 31.9% solid tumors, 23.6% neuro-oncology. Prevalence rates were: insomnia (9.6%), circadian rhythm sleep disorder (CRSD; 8.1%), restless legs syndrome (7.6%), parasomnia (3.5%), hypersomnia (3.5%) and sleep-related breathing disorders (1.8%). Female sex, comorbid health conditions and young adulthood seem to be risk factors for sleep disorders, but cancer-related factors were not. Differing per sleep disorder, 42–72% wanted help, but only 0–5.6% received sleep treatment. Conclusions: Insomnia and CRSD were most prevalent. An unmet need for sleep treatment was reported by childhood cancer patients during follow-up. Screening for sleep disorders after cancer might improve access to treatment and patient wellbeing.
Bone Marrow Stroma-Induced Transcriptome and Regulome Signatures of Multiple Myeloma
Authors: Dziadowicz Sebastian A. , Wang Lei , Akhter Halima , Aesoph Drake , Sharma Tulika , Adjeroh Donald A. , Hazlehurst Lori A. , Hu Gangqing
Published: February 2022

Multiple myeloma (MM) is a hematological cancer with inevitable drug resistance. MM cells interacting with bone marrow stromal cells (BMSCs) undergo substantial changes in the transcriptome and develop de novo multi-drug resistance. As a critical component in transcriptional regulation, how the chromatin landscape is transformed in MM cells exposed to BMSCs and contributes to the transcriptional response to BMSCs remains elusive. We profiled the transcriptome and regulome for MM cells using a transwell coculture system with BMSCs. The transcriptome and regulome of MM cells from the upper transwell resembled MM cells that coexisted with BMSCs from the lower chamber but were distinctive to monoculture. BMSC-induced genes were enriched in the JAK2/STAT3 signaling pathway, unfolded protein stress, signatures of early plasma cells, and response to proteasome inhibitors. Genes with increasing accessibility at multiple regulatory sites were preferentially induced by BMSCs; these genes were enriched in functions linked to responses to drugs and unfavorable clinic outcomes. We proposed JUNB and ATF4::CEBPβ as candidate transcription factors (TFs) that modulate the BMSC-induced transformation of the regulome linked to the transcriptional response. Together, we characterized the BMSC-induced transcriptome and regulome signatures of MM cells to facilitate research on epigenetic mechanisms of BMSC-induced multi-drug resistance in MM.
Discoidin Domain Receptor 1 Expression in Colon Cancer: Roles and Prognosis Impact
Authors: Ben Arfi Kaouther , Schneider Christophe , Bennasroune Amar , Bouland Nicole , Wolak-Thierry Aurore , Collin Guillaume , Le Cuong Cao , Toussaint Kevin , Hachet Cathy , Lehrter Véronique , Dedieu Stéphane , Bouché Olivier , Morjani Hamid , Boulagnon-Rombi Camille , Appert-Collin Aline
Published: February 2022

Extracellular matrix components such as collagens are deposited within the tumor microenvironment at primary and metastatic sites and are recognized to be critical during tumor progression and metastasis development. This study aimed to evaluate the clinical and prognostic impact of Discoidin Domain Receptor 1 (DDR1) expression in colon cancers and its association with a particular molecular and/or morphological profile and to evaluate its potential role as a prognosis biomarker. Immunohistochemical expression of DDR1 was evaluated on 292 colonic adenocarcinomas. DDR1 was highly expressed in 240 (82.2%) adenocarcinomas. High DDR1 immunostaining score was significantly associated, on univariate analysis, with male sex, left tumor location, BRAF wild type status, KRAS mutated status, and Annexin A10 negativity. High DDR1 immunohistochemical expression was associated with shorter event free survival only. Laser capture microdissection analyses revealed that DDR1 mRNA expression was mainly attributable to adenocarcinoma compared to stromal cells. The impact of DDR1 expression on cell invasion was then evaluated by modified Boyden chamber assay using cell types with distinct mutational profiles. The invasion capacity of colon adenocarcinoma is supported by DDR1 expression. Thus, our results showed that DDR1 was highly expressed in most colon adenocarcinomas and appears as an indicator of worse event free survival.
Fabrication of Pt-Loaded Catalysts Supported on the Functionalized Pyrolytic Activated Carbon Derived from Waste Tires for the High Performance Dehydrogenation of Methylcyclohexane and Hydrogen Production
Authors: Ye Hongli , Wang Tianci , Liu Shuangxi , Zhang Cui , Cai Youqiong
Published: February 2022

The pyrolytic activated carbon derived from waste tires (PTC) was functionalized to fabricate the high performance of Pt-based catalysts in the dehydrogenation of methylcyclohexane and hydrogen production. Structural characterizations evidenced that the modification partially influenced the surface area, the pore structure, and the oxygen-containing functional groups of the supports. The techniques of CO pulse, transmission electron microscopy, and hydrogen temperature-programmed reduction were utilized to investigate the dispersion degrees and particle sizes of the active component Pt, and its interaction with the various functionalized supports, respectively. The results manifested that Pt particles loaded on the functionalized PTC-S had the largest dispersion degree and the smallest size among those loaded on PTC and other functionalized PTC (i.e., PTC-K and PTC-NH). Finally, the Pt-based catalysts were successfully applied in the dehydrogenation reaction of methylcyclohexane to yield hydrogen. The results revealed that the Pt catalyst over the functional PTC-S support exhibited a more excellent conversion of methylcyclohexane (84.3%) and a higher hydrogen evolution rate (991.5 mmol/gPt/min) than the other resulting Pt-based catalysts.
Modified 7-Chloro-11H-indeno[1,2-b]quinoxaline Heterocyclic System for Biological Activities
Authors: Kumar Nakul , Inwati Gajendra Kumar , Ahmed Emad M. , Lal Chhagan , Makwana Bharat , Yadav Virendra K. , Islam Saiful , Ahn Hyun-Jo , Yadav Krishna K. , Jeon Byong-Hun
Published: February 2022

Recent advances in functionalized organic Spiro heterocyclic compounds composed of nitrogen bonded five- and six-membered rings have been made, establishing them as a synthetic target in organic-based biomedical applications. In this work, we report a synthesis of spirocyclic compounds under a one-pot reaction using 1,3-dipolar cycloaddition in a regio and diastereoselective manner. The higher atomic economy with higher yield (95%) and regio and stereoselectivity were achieved by a multi-component reaction of L-proline (1), Indenoquinoxaline (2), and the dipolarophile of malononitrile (3) solvents followed by reflux conditions. The reaction intermediate comprised azomethineylides derived from reactive primary amines, and the spiro derivatives were synthesized up to a ≈ 95% yield. The structural and characteristic chemical components of the as-prepared Spiro compounds were characterized by 1H-NMR, FTIR, and Mass spectroscopy. The functionalized spiro-pyrrolizidines were found to be effective for biological uses by considering their in vitro screening and antimicrobial impacts. Spiro constituents were found to be much more effective for Gram-positive bacteria due to the stronger lipophilic character of the molecules, and they resulted feasible membrane permeation in a biological system. Based on the planarity geometry of the Spiro pyrrolizidines, meta-substitution possesses steric hindrance and hence shows less effectiveness compared to para-substitution on the same nucleus, which shows a marginal steric effect. The biological studies showed that the derived spiro heterocyclic systems have an inhibitory effect of 50%.
The ACE2 Receptor for Coronavirus Entry Is Localized at Apical Cell—Cell Junctions of Epithelial Cells
Authors: Rouaud Florian , Méan Isabelle , Citi Sandra
Published: February 2022

Transmembrane proteins of adherens and tight junctions are known targets for viruses and bacterial toxins. The coronavirus receptor ACE2 has been localized at the apical surface of epithelial cells, but it is not clear whether ACE2 is localized at apical Cell—Cell junctions and whether it associates with junctional proteins. Here we explored the expression and localization of ACE2 and its association with transmembrane and tight junction proteins in epithelial tissues and cultured cells by data mining, immunoblotting, immunofluorescence microscopy, and co-immunoprecipitation experiments. ACE2 mRNA is abundant in epithelial tissues, where its expression correlates with the expression of the tight junction proteins cingulin and occludin. In cultured epithelial cells ACE2 mRNA is upregulated upon differentiation and ACE2 protein is widely expressed and co-immunoprecipitates with the transmembrane proteins ADAM17 and CD9. We show by immunofluorescence microscopy that ACE2 colocalizes with ADAM17 and CD9 and the tight junction protein cingulin at apical junctions of intestinal (Caco-2), mammary (Eph4) and kidney (mCCD) epithelial cells. These observations identify ACE2, ADAM17 and CD9 as new epithelial junctional transmembrane proteins and suggest that the cytokine-enhanced endocytic internalization of junction-associated protein complexes comprising ACE2 may promote coronavirus entry.
Modeling Down Syndrome Myeloid Leukemia by Sequential Introduction of GATA1 and STAG2 Mutations in Induced Pluripotent Stem Cells with Trisomy 21
Authors: Barwe Sonali P. , Sebastian Aimy , Sidhu Ishnoor , Kolb Edward Anders , Gopalakrishnapillai Anilkumar
Published: February 2022

Children with Down syndrome (DS) have a high risk for acute myeloid leukemia (DS-ML). Genomic characterization of DS-ML blasts showed the presence of unique mutations in GATA1, an essential hematopoietic transcription factor, leading to the production of a truncated from of GATA1 (GATA1s). GATA1s, together with trisomy 21, is sufficient to develop a pre-leukemic condition called transient abnormal myelopoiesis (TAM). Approximately 30% of these cases progress into DS-ML by acquisition of additional somatic mutations in a stepwise manner. We previously developed a model for TAM by introducing disease-specific GATA1 mutation in trisomy 21-induced pluripotent stem cells (iPSCs), leading to the production of N-terminally truncated short form of GATA1 (GATA1s). In this model, we used CRISPR/Cas9 to introduce a co-operating mutation in STAG2, a member of the cohesin complex recurrently mutated in DS-ML but not in TAM. Hematopoietic differentiation of GATA1 STAG2 double-mutant iPSC lines confirmed GATA1s expression and the loss of functional STAG2 protein, leading to enhanced production of immature megakaryocytic population compared to GATA1 mutant alone. Megakaryocyte-specific lineage expansion of the double-mutant HSPCs exhibited close resemblance to the DS-ML immunophenotype. Transcriptome analysis showed that GATA1 mutation resulted in downregulation of megakaryocytic and erythrocytic differentiation pathways and interferon α/β signaling, along with an upregulation of pathways promoting myeloid differentiation such as toll-like receptor cascade. The co-occurrence of STAG2 knockout partially reverted the expression of genes involved in myeloid differentiation, likely leading to enhanced self-renewal and promoting leukemogenesis. In conclusion, we developed a DS-ML model via hematopoietic differentiation of gene-targeted iPSCs bearing trisomy 21.
The Role of Extracellular Vesicles in Idiopathic Pulmonary Fibrosis Progression: An Approach on Their Therapeutics Potential
Authors: Ramírez-Hernández Alma Aurora , Velázquez-Enríquez Juan Manuel , Santos-Álvarez Jovito Cesar , López-Martínez Armando , Reyes-Jiménez Edilburga , Carrasco-Torres Gabriela , González-García Karina , Vásquez-Garzón Verónica Rocío , Baltierrez-Hoyos Rafael
Published: February 2022

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease of unknown etiology. Different types of cells are involved in fibrogenesis, which is persistently physical and molecular stimulation, either directly or by interacting with bioactive molecules and extracellular vesicles (EVs). Current evidence suggests that EVs play an essential role in IPF development. EVs are released by a variety of cells, including fibroblasts, epithelial cells, and alveolar macrophages. In addition, EVs can transport bioactive molecules, such as lipids, proteins, and nucleic acids, which play a pivotal role in cellular communication. Several proposed mechanisms show that an acceptor cell can capture, absorb, or interact with EVs through direct fusion with the plasma membrane, ligand–receptor interaction, and endocytotic process, modifying the target cell. During fibrogenesis, the release of EVs is deregulated, increases the EVs amount, and the cargo content is modified. This alteration is closely associated with the maintenance of the fibrotic microenvironment. This review summarizes the current data on the participation of EVs secreted by the cells playing a critical role in IPF pathogenesis.
Drug Resistance and Endoplasmic Reticulum Stress in Hepatocellular Carcinoma
Authors: Khaled Jaafar , Kopsida Maria , Lennernäs Hans , Heindryckx Femke
Published: February 2022

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide. It is usually diagnosed in an advanced stage and is characterized by a high intrinsic drug resistance, leading to limited chemotherapeutic efficacy and relapse after treatment. There is therefore a vast need for understanding underlying mechanisms that contribute to drug resistance and for developing therapeutic strategies that would overcome this. The rapid proliferation of tumor cells, in combination with a highly inflammatory microenvironment, causes a chronic increase of protein synthesis in different hepatic cell populations. This leads to an intensified demand of protein folding, which inevitably causes an accumulation of misfolded or unfolded proteins in the lumen of the endoplasmic reticulum (ER). This process is called ER stress and triggers the unfolded protein response (UPR) in order to restore protein synthesis or—in the case of severe or prolonged ER stress—to induce cell death. Interestingly, the three different arms of the ER stress signaling pathways have been shown to drive chemoresistance in several tumors and could therefore form a promising therapeutic target. This review provides an overview of how ER stress and activation of the UPR contributes to drug resistance in HCC.
Glucose Transporter 9 (GLUT9) Plays an Important Role in the Placental Uric Acid Transport System
Authors: Lüscher Benjamin P. , Albrecht Christiane , Stieger Bruno , Surbek Daniel V. , Baumann Marc U.
Published: February 2022

Background: Hyperuricemia is a common laboratory finding in pregnant women compromised by preeclampsia. A growing body of evidence suggests that uric acid is involved in the pathogenesis of preeclampsia. Glucose transporter 9 (GLUT9) is a high-capacity uric acid transporter. The aim of this study was to investigate the placental uric acid transport system, and to identify the (sub-) cellular localization of GLUT9. Methods: Specific antibodies against GLUT9a and GLUT9b isoforms were raised, and human villous (placental) tissue was immunohistochemically stained. A systemic GLUT9 knockout (G9KO) mouse model was used to assess the placental uric acid transport capacity by measurements of uric acid serum levels in the fetal and maternal circulation. Results: GLUT9a and GLUT9b co-localized with the villous (apical) membrane, but not with the basal membrane, of the syncytiotrophoblast. Fetal and maternal uric acid serum levels were closely correlated. G9KO fetuses showed substantially higher uric acid serum concentrations than their mothers. Conclusions: These findings demonstrate that the placenta efficiently maintains uric acid homeostasis, and that GLUT9 plays a key role in the placental uric acid transport system, at least in this murine model. Further studies investigating the role of the placental uric acid transport system in preeclampsia are eagerly needed.
Analysis of the Glucose-Dependent Transcriptome in Murine Hypothalamic Cells
Authors: Webert Leonhard , Faro Dennis , Zeitlmayr Sarah , Gudermann Thomas , Breit Andreas
Published: February 2022

Glucose provides vital energy for cells and contributes to gene expression. The hypothalamus is key for metabolic homeostasis, but effects of glucose on hypothalamic gene expression have not yet been investigated in detail. Thus, herein, we monitored the glucose-dependent transcriptome in murine hypothalamic mHypoA-2/10 cells by total RNA-seq analysis. A total of 831 genes were up- and 1390 genes were downregulated by at least 50%. Key genes involved in the cholesterol biosynthesis pathway were upregulated, and total cellular cholesterol levels were significantly increased by glucose. Analysis of single genes involved in fundamental cellular signaling processes also suggested a significant impact of glucose. Thus, we chose ≈100 genes involved in signaling and validated the effects of glucose on mRNA levels by qRT-PCR. We identified Gnai1–3, Adyc6, Irs1, Igfr1, Hras, and Elk3 as new glucose-dependent genes. In line with this, cAMP measurements revealed enhanced noradrenalin-induced cAMP levels, and reporter gene assays elevated activity of the insulin-like growth factor at higher glucose levels. Key data of our studies were confirmed in a second hypothalamic cell line. Thus, our findings link extra cellular glucose levels with hypothalamic lipid synthesis and pivotal intracellular signaling processes, which might be of particular interest in situations of continuously increased glucose levels.
Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review
Authors: Wilkowska Alina , Wiglusz Mariusz S. , Jakuszkowiak-Wojten Katarzyna , Cubała Wiesław J.
Published: February 2022

Background and Objectives: Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented. Materials and Methods: PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied. Results: Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms. Conclusions: The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine’s side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine–lamotrigine combination in bipolar patients.
Role of Integrins in Modulating Smooth Muscle Cell Plasticity and Vascular Remodeling: From Expression to Therapeutic Implications
Authors: Jain Manish , Chauhan Anil K.
Published: February 2022

Smooth muscle cells (SMCs), present in the media layer of blood vessels, are crucial in maintaining vascular homeostasis. Upon vascular injury, SMCs show a high degree of plasticity, undergo a change from a “contractile” to a “synthetic” phenotype, and play an essential role in the pathophysiology of diseases including atherosclerosis and restenosis. Integrins are cell surface receptors, which are involved in cell-to-cell binding and cell-to-extracellular-matrix interactions. By binding to extracellular matrix components, integrins trigger intracellular signaling and regulate several of the SMC function, including proliferation, migration, and phenotypic switching. Although pharmacological approaches, including antibodies and synthetic peptides, have been effectively utilized to target integrins to limit atherosclerosis and restenosis, none has been commercialized yet. A clear understanding of how integrins modulate SMC biology is essential to facilitate the development of integrin-based interventions to combat atherosclerosis and restenosis. Herein, we highlight the importance of integrins in modulating functional properties of SMCs and their implications for vascular pathology.
Hypothesis: Emerging Roles for Aryl Hydrocarbon Receptor in Orchestrating CoV-2-Related Inflammation
Authors: Guarnieri Tiziana
Published: February 2022

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the pathogenic agent of Coronavirus-Induced Disease-2019 (COVID-19), a multi-organ syndrome which primarily targets the respiratory system. In this review, considering the large amount of data pointing out the role of the Aryl hydrocarbon Receptor (AhR) in the inflammatory response and in the modulation of innate and adaptive immunity, we describe some mechanisms that strongly suggest its involvement in the management of COVID-19′s inflammatory framework. It regulates both the expression of Angiotensin Converting Enzyme-2 (ACE-2) and its stabilizing partner, the Broad neutral Amino acid Transporter 1 (B0AT1). It induces Indolamine 2,3 dioxygenase (IDO-1), the enzyme which, starting from Tryptophan (Trp), produces Kynurenine (Kyn, Beta-Anthraniloyl-L-Alanine). The accumulation of Kyn and the depletion of Trp arrest T cell growth and induce apoptosis, setting up an immune-tolerant condition, whereas AhR and interferon type I (IFN-I) build a mutual inhibitory loop that also involves NF-kB and limits the innate response. AhR/Kyn binding boosts the production of Interleukin-6 (IL-6), thus reinforcing the inflammatory state and counteracting the IDO-dependent immune tolerance in the later stage of COVID-19. Taken together, these data depict a framework where sufficient clues suggest the possible participation of AhR in the management of COVID-19 inflammation, thus indicating an additional therapeutic target for this disease.
Phenylamine/Amide Grafted in Silica as Sensing Nanocomposites for the Removal of Carbamazepine: A DFT Approach
Authors: Algarra Manuel , Jodeh Shehdeh , Aqel Israa , Hanbali Ghadir , Radi Smaail , Tighadouini Said , Alkowni Raed , Soto Juan , Samhan Subhi , Kaya Savaş , Katin Konstantin
Published: February 2022

This study aimed to remove carbamazepine from aqueous solutions, using functional silica phenylamine (SiBN), which is characterized and showed excellent chemical and thermal stability. Adsorbents based on silica were developed due to their unusually large surface area, homogenous pore structure, and well-modified surface properties, as silica sparked tremendous interest. It was determined to develop a novel silica adsorbent including phenylamine and amide (SiBCON). The adsorbents obtained were analyzed by various spectroscopy devices, including SEM, FT-IR and TGA analysis. The maximum removal rates for carbamazepine were 98.37% and 98.22% for SiBN and SiBCON, respectively, when optimized at room temperature, pH 9.0, initial concentration of 10 mg·L−1 and contact time of 15 min. Theoretical tools are widely used in the prediction of the power of interactions between chemical systems. The computed data showed that new amine modified silica is quite effective in terms of the removal of carbamazepine from aqueous solution. Calculation binding energies and DFT data showed that there is a powerful interaction between amine-modified silica and carbamazepine.
Self-Referenced Optical Fiber Sensor Based on LSPR Generated by Gold and Silver Nanoparticles Embedded in Layer-by-Layer Nanostructured Coatings
Authors: Martínez-Hernández María Elena , Sandúa Xabier , Rivero Pedro J. , Goicoechea Javier , Arregui Francisco J.
Published: February 2022

In this work, an optical fiber sensor based on the localized surface plasmon resonance (LSPR) phenomenon has been designed for the detection of two different chemical species (mercury and hydrogen peroxide) by using Layer-by-Layer Embedding (LbL-E) as a nanofabrication technique. In the first step, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) have been synthesized by using a chemical protocol as a function of the strict control of three main parameters, which were polyelectrolyte concentration, a loading agent, and a reducing agent. In the second step, their incorporation into nanometric thin films have been demonstrated as a function of the number of bilayers, which shows two well-located absorption peaks associated to their LSPR in the visible region at 420 nm (AgNPs) and 530 nm (AuNPs). Finally, both plasmonic peaks provide a stable real-time reference measurement, which can be extracted from the spectral response of the optical fiber sensor, which shows a specific sensing mechanism as a function of the analyte of study.
The Frequency of Clinical Seizures in Paroxysmal Events in a Neonatal Intensive Care Unit
Authors: Chan Oi-Wa , Chen Wan-Hsuan , Lin Jainn-Jim , Chiang Ming-Chou , Hsia Shao-Hsuan , Wang Huei-Shyong , Lee En-Pei , Wang Yi-Shan , Kuo Cheng-Yen , Lin Kuang-Lin ,   iCNS Group
Published: February 2022

Background: In general clinical practice, neonatal seizures are identified visually by direct clinical observation. The study aimed to examine the frequency of clinical seizures in paroxysmal events in a neonatal intensive care unit. Methods: We conducted a prospective study of continuous video-EEG monitoring in a neonatal intensive care unit between January 2017 and December 2020. The demographic data were also reviewed. Results: Sixty-four neonates were enrolled. The median total video-EEG monitoring duration was 24.1 h (IQR 17.5–44.8 h). There were 309 clinically suspected seizure episodes, of which 181 (58.6%) were the motor type and 128 (41.4%) were the non-motor type. Only 63 (20.4%) of these events were confirmed to be clinical seizures on a simultaneous video-EEG recording. In terms of the impact of continuous video-EEG monitoring on clinical management, the anti-epileptic drugs were changed in 42 (65.6%) of the 64 neonates. Conclusion: In the identification of neonatal seizures, a clinical diagnosis by direct observation alone is not enough. The use of continuous video-EEG monitoring plays an important role in the diagnosis of neonatal seizures and in guiding clinical management decisions.
Mental Health, Bullying, and Victimization among Chinese Adolescents
Authors: Wen Yang , Zhu Xihe , Haegele Justin A. , Yu Fangliang
Published: February 2022

The purpose of this study was to examine if adolescents who experience anxiety or depression have higher levels of reported bullying victimization or perpetration than those who do not. Based on the existing research, we hypothesized that those who experienced moderate or severe depression and anxiety would have higher rates of bullying victimization and perpetration when compared to those who experienced mild or no depression. This study used an observational design, and data were collected from a convenience sample of adolescents in a large regional high school in an Eastern province of China. The final sample included 1481 adolescents aged 14–19 years who provided complete data for each of the study variables. Demographic data were collected through a four-item demographic survey, bullying perpetration and victimization data were collected using subscales from the Illinois Bully Scale, and anxiety and depression were measured using the Chinese version of the General Anxiety Disorder-7 scale and the Patient Health Questionnaire, respectively. Descriptive analyses, correlational analyses, and multivariate analysis of covariance were used to analyze the data. About 7.1% and 15.2% of participants reported moderate-to-severe depression or moderate-to-severe anxiety, respectively. Pairwise comparisons indicated that adolescents with no or mild depression had significantly lower bullying perpetration than those with moderate-to-severe depression, but those with no or mild anxiety had significantly higher perpetration than those with moderate-to-severe anxiety. There was no statistically significant difference in victimization among different anxiety or depression levels alone (all p-values ≥ 0.05). This is among the first studies to examine reported levels of bullying perpetration and victimization among adolescents experiencing anxiety and depression. The findings help to identify adolescents who experience moderate-to-severe levels of depression as an at-risk group for bullying perpetration, who should therefore be a focus of bullying intervention work.
The Associations of Child’s Clinical Conditions and Behavioral Problems with Parenting Stress among Families of Preschool-Aged Children: 2018–2019 National Survey of Child Health
Authors: Kwon Soyang , O’Neill Meghan E. , Foster Carolyn C.
Published: February 2022

To understand parental stress resulting from parenting young children, the current literature has primarily focused on families of children with clinical conditions, but has placed far less attention on the general population. The aim of this study was to examine parenting stress related to children’s clinical conditions and behavioral problems in a nationally representative sample of US children aged 3 to 5 years. The study sample included 8454 children aged 3 to 5 years and their parents who participated in the 2018–2019 US National Survey of Child Health (NSCH). Using online/paper NSCH questionnaires, parents reported their children’s special health care needs (SHCN), clinically diagnosed mental, emotional, developmental, and behavioral (MEDB) problems (e.g., anxiety problem, developmental delay), and externalizing behaviors. Parents also reported the frequency of feeling aggravated from parenting the participating child as an indicator of elevated parenting stress. In the sample, the prevalence of elevated parenting stress was 5.1% overall (95% CI = 4.2, 6.0); however, it was significantly higher among parents of children with SHCN (20.8%; 95% CI = 16.7, 24.9), with MEDB problems (24.8%; 95% CI = 19.9, 29.8), and with externalizing behavior problems (14.7%; 95% CI = 11.8, 17.6). A multivariable logistic regression model showed that elevated parenting stress was associated with the child’s SHCN (adjusted odds ratio [AOR] = 2.3; 1.3, 3.9), MEDB problems (AOR = 4.8; 95% CI = 2.5, 9.1), and externalizing behavior problems (AOR = 5.4; 95% CI = 3.1, 9.4). Even in children without SHCN or MEDB problems, externalizing behavior problems were associated with elevated parenting stress (AOR = 6.4; 95% CI = 3.3, 12.7). The findings call for greater attention to subclinical or yet to be diagnosed externalizing behavior problems among the general preschool-aged child population and their underestimated impact on parenting stress.
COVID-19 Infection in Children and Infants: Current Status on Therapies and Vaccines
Authors: Malcangi Giuseppina , Inchingolo Alessio Danilo , Inchingolo Angelo Michele , Piras Fabio , Settanni Vito , Garofoli Grazia , Palmieri Giulia , Ceci Sabino , Patano Assunta , Mancini Antonio , Vimercati Luigi , Nemore Damiano , Scardapane Arnaldo , Rapone Biagio , Semjonova Alexandra , D’Oria Maria Teresa , Macchia Luigi , Bordea Ioana Roxana , Migliore Giovanni , Scarano Antonio , Lorusso Felice , Tartaglia Gianluca Martino , Giovanniello Delia , Nucci Ludovica , Maggialetti Nicola , Parisi Antonio , Domenico Marina Di , Brienza Nicola , Tafuri Silvio , Stefanizzi Pasquale , Curatoli Luigi , Corriero Alberto , Contaldo Maria , Inchingolo Francesco , Dipalma Gianna
Published: February 2022

Since the beginning in December 2019, the SARS-CoV-2 outbreak appeared to affect mostly the adult population, sparing the vast majority of children who only showed mild symptoms. The purpose of this investigation is to assess the status on the mechanisms that give children and infants this variation in epidemiology compared to the adult population and its impact on therapies and vaccines that are aimed towards them. A literature review, including in vitro studies, reviews, published guidelines and clinical trials was performed. Clinical trials concerned topics that allowed a descriptive synthesis to be produced. Four underlying mechanisms were found that may play a key role in providing COVID-19 protection in babies. No guidelines are available yet for therapy due to insufficient data; support therapy remains the most used. Only two vaccines are approved by the World Health Organization to be used in children from 12 years of age, and there are currently no efficacy or safety data for children below the age of 12 years. The COVID-19 clinical frame infection is milder in children and adolescents. This section of the population can act as vectors and reservoirs and play a key role in the transmission of the infection; therefore, vaccines are paramount. More evidence is required to guide safely the vaccination campaign.
A Preliminary Study of Assessing Gaze, Interoception and School Performance among Children with Neurodevelopmental Disorders: The Feasibility of VR Classroom
Authors: Ide-Okochi Ayako , Matsunaga Nobutomo , Sato Hiro
Published: February 2022

Children with developmental disabilities (DDs) have sensory modulation disorders that interrelate school performance. Virtual reality (VR) has demonstrated the potential to become a neuropsychological assessment modality. This study was conducted to explore the feasibility of the VR classroom for assessing their characteristics of gaze, school performance, and interoception. School-aged children were assigned to the DD group or control group. A VR classroom was designed to evaluate their gaze patterns to distracting events. Interoception was assessed using the Heart Rate Perception test and the Multidimensional Assessment of Interoceptive Awareness (MAIA). The DD group had a significantly longer gaze duration on the virtual teacher during 30–45 s of the VR classroom event (p < 0.05). The mean score of the quiz and the Heart Rate Perception test showed a significant tendency to be lower than the children of the control group. The DD group scored significantly lower in six of eight subscales of the MAIA. These results showed the potential of VR classroom to evaluate the difference of sensory modulation between school-aged children with DDs and typically developed children. Future research is necessary to investigate the validity of the VR environment used in this study.
Effects of Serine/Arginine Enriched Protein BmUP on the Development of Male Silkworm Reproductive Organs
Authors: Chen Chun-Bing , Li Juan , Deng Xuan , Liu Lian-Lian , Deng Jing , Zha Xing-Fu
Published: February 2022

Serine/arginine-rich proteins are a class of highly conserved splicing factor proteins involved in constitutive and alternative splicing. We screened a low molecular weight serine/arginine rich protein from silkworms and named it BmUP. Temporal and spatial expression analysis indicated that the BmUP gene was specifically expressed in the silkworm testis, and the highest expression occurred in the pre-pupa stage from the fifth instar to the moth stages. Here, we generated BmUP knockout individuals with the CRISPR/Cas9 system. Both the internal and external genitalia of knockout individuals were abnormal in knockout compared with wild-type male silkworms. In transgenic silkworms overexpressing BmUP, male silkworms showed a phenotype similar to that of the knockout individuals, whereas female individuals showed no significant differences from the wild type. In addition, by conducting promoter analysis, we identified Bmachi, a transcription factor that regulates the BmUP gene. Gel migration experiments revealed that BmAchi specifically binds the BmUP promoter. Quantitative real-time PCR showed that an increase in Bmachi expression up-regulated the expression of BmUP. In contrast, when the expression of Bmachi decreased, the expression of BmUP also downregulated in the experimental group compared with the control group. These results provide new insights for studying the effects of serine/arginine-rich proteins on the development of silkworm genitals.
Antifungal Activity of Squid Pen Chitosan Nanoparticles against Three Fungal Pathogens in Various Citrus Fruits In Vitro and In Vivo
Authors: Cuong Hoang Ngoc , Minh Nguyen Cong , Hoa Nguyen Van , Giang Dang Ha , Hieu Nguyen Van , Nam Pham Viet
Published: February 2022

Fungal infections have been considered a primary cause of the postharvest losses of citrus fruits. Therefore, it is necessary to find low-cost and high antifungal activity materials for preventing the decay of citrus fruits after harvest. In this study, squid chitosan nanoparticles (SCNs) were prepared from squid pen chitosan and used as a biofungicide against three citrus fungal pathogens in both in vitro and in vivo evaluations. The prepared SCNs had a mean size of ca. 56 nm and a high zeta potential of +98.7 eV with a narrow size distribution. At a range of 50–250 ppm, the SCN concentration of 200 ppm exhibited the highest activity in totally inhibiting the growth of Lasiodiplodia pseudotheobromae, Alternaria alternate, and Penicillium digitatum in in vitro tests where these fungi were isolated from symptomatic fruits and identified. Furthermore, after 12 days of incubation at 30 ± 0.2 °C and high relative humidity in in vivo studies, the infection area of the sample treated at 250 ppm completely suppressed fruit disease symptoms. The results demonstrate that prepared SCNs efficiently control postharvest citrus fruit diseases. These findings recommend applying SCNs as a potential candidate for citrus fruit storage.
Sustainable and Resistant Road Infrastructures: The Role of the Envision Framework as a Guide to a New Design Approach
Authors: Censorii Francesco , Cotignoli Luca , Vignali Valeria , Bartoli Alberto
Published: February 2022

In Italy, resilience and sustainability concepts are generally applied to road infrastructures (mainly in terms of pavements) in order to minimize the environmental impacts of their construction and maintenance. In this paper the Envision framework has been adopted to evaluate the sustainability of a road project, optimizing its resilience for both short-term and long-term impacts. The rating approach has been applied considering not only pavements analysis but also the complete project process. The authors have upgraded the original Envision framework to road infrastructures, in compliance with the Italian regulatory framework. Four scenarios have been considered. The first allowed us to understand which credits can be evaluated with the available project documentation. The second represents a snapshot of the state of the project. The third evaluates the effect of the improvement in the performance level obtained by analyzing the potential increases. Finally, the last considers also for “pending” credits.