bluuebunny/crossref_metadata_2025 huggingface dataset:
How Classmates’ Gender Stereotypes Affect Students’ Math Self-Concepts: A Multilevel Analysis
Authors: Wolff Fabian
Published: May 2021

The present research is the first to examine how students’ individual and their classmates’ math-related gender stereotypes, endorsing that math would be a typically male domain, relate to students’ math self-concepts. To this end, data of N = 1,424 secondary school students from Germany were analyzed using multilevel analyses. As expected, strong individual beliefs in the math-related gender stereotype were related to lower math self-concepts for girls, but to higher math self-concepts for boys. Moreover, classmates’ shared beliefs in this stereotype showed a negative relation to girls’ self-concepts, whereas no significant relation between classmates’ shared beliefs and boys’ self-concepts was found. These relations also persisted after controlling for students’ math grades and age. In sum, the results demonstrated that gender stereotypes shared by students’ classmates can have a substantial impact on students’ math self-concepts, beyond their individual gender stereotypes. This finding emphasizes the significance of classmates as important socializing peers in the process of students’ self-concept formation.
Social Media Exposure, Psychological Distress, Emotion Regulation, and Depression During the COVID-19 Outbreak in Community Samples in China
Authors: Zhang Yu-ting , Li Rui-ting , Sun Xiao-jun , Peng Ming , Li Xu
Published: May 2021

The outbreak of coronavirus disease 2019 (COVID-19) has been a global emergency, affecting millions of individuals both physically and psychologically. The present research investigated the associations between social media exposure and depression during the COVID-19 outbreak by examining the mediating role of psychological distress and the moderating role of emotion regulation among members of the general public in China. Participants (N = 485) completed a set of questionnaires online, including demographic information, self-rated physical health, and social media exposure to topics related to COVID-19. The Impact of Event Scale-Revised (IES-R), the Beck Depression Inventory-II (BDI-II), and the Emotion Regulation Questionnaire (ERQ) were utilized to measure psychological distress about COVID-19, depression, and emotion regulation strategies, respectively. Results found that older age and greater levels of social media exposure were associated with more psychological distress about the virus (r = 0.14, p = 0.003; r = 0.22, p < 0.001). Results of the moderated mediation model suggest that psychological distress mediated the relationship between social media exposure and depression (β = 0.10; Boot 95% CI = 0.07, 0.15). Furthermore, expressive suppression moderated the relationship between psychological distress and depression (β = 0.10, p = 0.017). The findings are discussed in terms of the need for mental health assistance for individuals at high risk of depression, including the elderly and individuals who reported greater psychological distress and those who showed preference usage of suppression, during the COVID-19 crisis.
Is Encephalitozoon cuniculi of Significance in Young Dogs With Neurological Signs?
Authors: Boer Tamar S. de , Diaz Espineira Montse M. , Mandigers Paul J. J.
Published: May 2021

Encephalitozoon cuniculi is a microsporidium belonging to the phylum Microspora. A few reports have described the clinical significance of E. cuniculi infection in young dogs. In American and Japanese household dog populations, the seroprevalence was found to be 21%, indicating its wide-spread existence. To evaluate the clinical significance of E. cuniculi in a cohort of young dogs with neurological signs, the presence of the organism and possible response to treatment were studied. Over a 1-year period, all young dogs (<3 years old) that were referred with neurological signs were examined for the presence of E. cuniculi. Dogs were selected if serology revealed a clearly elevated IgM titer (>100) and/or if an EDTA-blood sample and/or urine sample tested positive by polymerase chain reaction (PCR). Sixteen dogs with various neurological signs were included in this study. Additional work-up included magnetic resonance imaging and cerebrospinal fluid analysis, but these revealed no abnormalities or indication of infection. All dogs were treated with fenbendazole for 10–30 days. Neurological signs disappeared completely in five dogs, 11 dogs continued to show neurological signs, and five dogs deteriorated and were euthanized, after which necropsy was performed in three. At necropsy no evidence of an E. cuniculi infection was found. We concluded that, although IgM titers and PCR indicated an E. cuniculi infection, it is most likely of limited clinical significance in young dogs.
Sound and Safe: The Role of Leader Motivating Language and Follower Self-Leadership in Feelings of Psychological Safety
Authors: Mayfield Milton , Mayfield Jacqueline
Published: May 2021

This manuscript presents a study on how leader motivating language and follower self-leadership act to influence a follower’s feelings of psychological safety. This study found that both constructs significantly influenced psychological safety in samples from India and the USA. Additionally, this study found that this influence occurred through the mediating processes of trust in leadership, leader inclusiveness, and role clarity. These mediators fully explained motivating language’s relationship with psychological safety, but only partially explained self-leadership’s relationship. Differences existed in the model between samples, but self-leadership showed an overall consistency between the samples for most relationships. Follow-up analysis indicated that self-leadership without leader communication support lead to a weak or non-existent relationship between self-leadership and psychological safety, but a positive and relatively strong relationship in the presence of motivating language.
The Ruminant Farm Systems Animal Module: A Biophysical Description of Animal Management
Authors: Hansen Tayler L. , Li Manfei , Li Jinghui , Vankerhove Chris J. , Sotirova Militsa A. , Tricarico Juan M. , Cabrera Victor E. , Kebreab Ermias , Reed Kristan F.
Published: May 2021

Dairy production is an important source of nutrients in the global food supply, but environmental impacts are increasingly a concern of consumers, scientists, and policy-makers. Many decisions must be integrated to support sustainable production—which can be achieved using a simulation model. We provide an example of the Ruminant Farm Systems (RuFaS) model to assess changes in the dairy system related to altered animal feed efficiency. RuFaS is a whole-system farm simulation model that simulates the individual animal life cycle, production, and environmental impacts. We added a stochastic animal-level parameter to represent individual animal feed efficiency as a result of reduced residual feed intake and compared High (intake = 94% of expected) and Very High (intake = 88% of expected) efficiency levels with a Baseline scenario (intake = 100% of expected). As expected, the simulated total feed intake was reduced by 6 and 12% for the High and Very High efficiency scenarios, and the expected impact of these improved efficiencies on the greenhouse gas emissions from enteric methane and manure storage was a decrease of 4.6 and 9.3%, respectively.
The Challenges of Bringing Up a Child with Autism Spectrum Disorders: Editorial for Brain Sciences Special Issue “Connections between Parental Involvement and Treatment of Children with Autism Spectrum Disorders (ASD)”
Authors: Samadi Sayyed Ali
Published: May 2021

There is no unique scientific method to guide parents in bringing up a child with autism spectrum disorders (ASD) [...]
The FIB-4 Index Is a Useful Predictor for the Development of Hepatocellular Carcinoma in Patients with Coexisting Nonalcoholic Fatty Liver Disease and Chronic Hepatitis B
Authors: Kim Minah , Lee Yeonju , Yoon Jun Sik , Lee Minjong , Kye So Shin , Kim Sun Woong , Cho Yuri
Published: May 2021

Background: The FIB-4 index, a noninvasive tool (FIB-4 index = age × aspartate transaminase (AST)/(platelet count × √alanine aminotransferase (ALT)), is a useful assessment for liver fibrosis. Patients with a high FIB-4 index were reported to have a high risk of developing hepatocellular carcinoma (HCC). This study analyzed the clinical association of the FIB-4 index with HCC development in patients with coexisting nonalcoholic fatty liver disease and chronic hepatitis B (NAFLD–CHB). Methods: This retrospective study analyzed 237 consecutive patients with NAFLD–CHB between January 2006 and December 2010 at the National Police Hospital in Korea. Patients with HCC at baseline and those diagnosed with HCC within 6 months from baseline were excluded. Propensity score matching analysis (PSM) was adopted to balance the baseline characteristics between patients with low and high FIB-4 index values. The cumulative rates of HCC development were compared between the two groups using the Kaplan–Meier method in the matched population. Results: The median follow-up duration was 13 years (interquartile range, 8.2–15.7). The optimal cutoff for the FIB-4 index of 1.77 was calculated based on the maximum Youden index value, with an AUC of 0.70. Among a total of 237 patients with NAFLD–CHB, HCC developed in 20 patients (8.4%) (14 of the 90 patients with a high FIB-4 index vs. 6 of the 147 patients (4.1%) with a low FIB-4 index; log-rank p = 0.003). Patients with a high FIB-4 index had a significantly and independently higher risk of HCC than those with a low FIB-4 index (adjusted hazard ratio, 4.35; 95%; confidence interval, 1.42–13.24; log-rank test, p = 0.006). Conclusion: A high FIB-4 index (≥1.77) might be a useful marker for predicting the development of HCC in patients with NAFLD–CHB.
Evidence of Cooperation between Hippo Pathway and RAS Mutation in Thyroid Carcinomas
Authors: Carneiro Thaise Nayane Ribeiro , Bim Larissa Valdemarin , Buzatto Vanessa Candiotti , Galdeno Vanessa , Asprino Paula Fontes , Lee Eunjung Alice , Galante Pedro Alexandre Favoretto , Cerutti Janete Maria
Published: May 2021

Thyroid cancer incidences have been steadily increasing worldwide and are projected to become the fourth leading cancer diagnosis by 2030. Improved diagnosis and prognosis predictions for this type of cancer depend on understanding its genetic bases and disease biology. RAS mutations have been found in a wide range of thyroid tumors, from benign to aggressive thyroid carcinomas. Based on that and in vivo studies, it has been suggested that RAS cooperates with other driver mutations to induce tumorigenesis. This study aims to identify genetic alterations or pathways that cooperate with the RAS mutation in the pathogenesis of thyroid cancer. From a cohort of 120 thyroid carcinomas, 11 RAS-mutated samples were identified. The samples were subjected to RNA-Sequencing analyses. The mutation analysis in our eleven RAS-positive cases uncovered that four genes that belong to the Hippo pathway were mutated. The gene expression analysis revealed that this pathway was dysregulated in the RAS-positive samples. We additionally explored the mutational status and expression profiling of 60 RAS-positive papillary thyroid carcinomas (PTC) from The Cancer Genome Atlas (TCGA) cohort. Altogether, the mutational landscape and pathway enrichment analysis (gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genome (KEGG)) detected the Hippo pathway as dysregulated in RAS-positive thyroid carcinomas. Finally, we suggest a crosstalk between the Hippo and other signaling pathways, such as Wnt and BMP.
Gene Expression Levels of the Prolyl Hydroxylase Domain Proteins PHD1 and PHD2 but Not PHD3 Are Decreased in Primary Tumours and Correlate with Poor Prognosis of Patients with Surgically Resected Non-Small-Cell Lung Cancer
Authors: Koren Ana , Rijavec Matija , Krumpestar Tomaž , Kern Izidor , Sadikov Aleksander , Čufer Tanja , Korošec Peter
Published: May 2021

Background: Hypoxia correlates with poor prognosis in several cancer types, including lung cancer. Prolyl hydroxylase domain proteins (PHDs) play a role in cell oxygen sensing, negatively regulating the hypoxia-inducible factor (HIF) pathway. Our study aim was to evaluate PHD1, PHD2 and PHD3 mRNA expression levels in primary tumours and normal lungs of non-small-cell lung cancer (NSCLC) patients and to correlate it with selected regulators of HIF signalling, with clinicopathological characteristics and overall survival (OS). Methods: Tumour tissue samples were obtained from 60 patients with surgically resected NSCLC who were treated with radical surgery. In 22 out of 60 cases, matching morphologically normal lung tissue was obtained. PHD1, PHD2 and PHD3 mRNA expressions were measured using RT-qPCR. Results: The PHD1 and PHD2 mRNA levels in primary tumours were significantly decreased compared to those in normal lungs (both p < 0.0001). PHD1 and PHD2 expression in tumours was positively correlated (rs = 0.82; p < 0.0001) and correlated well with HIF pathway downstream genes HIF1A, PKM2 and PDK1. Decreased PHD1 and PHD2 were associated with larger tumour size, higher tumour stage (PHD1 only) and squamous cell carcinoma. Patients with low PHD1 and patients with low PHD2 expression had shorter OS than patients with high PHD1 (p = 0.02) and PHD2 expression (p = 0.01). PHD1 showed borderline independent prognostic values in multivariate analysis (p = 0.06). In contrast, we found no associations between PHD3 expression and any of the observed parameters. Conclusions: Our results show that reduced expression of PHD1 and PHD2 is associated with the development and progression of NSCLC. PHD1 could be further assessed as a prognostic marker in NSCLC.
Current Views on the Interplay between Tyrosine Kinases and Phosphatases in Chronic Myeloid Leukemia
Authors: Boni Christian , Sorio Claudio
Published: May 2021

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by BCR-ABL1 oncogene expression. This dysregulated protein-tyrosine kinase (PTK) is known as the principal driver of the disease and is targeted by tyrosine kinase inhibitors (TKIs). Extensive documentation has elucidated how the transformation of malignant cells is characterized by multiple genetic/epigenetic changes leading to the loss of tumor-suppressor genes function or proto-oncogenes expression. The impairment of adequate levels of substrates phosphorylation, thus affecting the balance PTKs and protein phosphatases (PPs), represents a well-established cellular mechanism to escape from self-limiting signals. In this review, we focus our attention on the characterization of and interactions between PTKs and PPs, emphasizing their biological roles in disease expansion, the regulation of LSCs and TKI resistance. We decided to separate those PPs that have been validated in primary cell models or leukemia mouse models from those whose studies have been performed only in cell lines (and, thus, require validation), as there may be differences in the manner that the associated pathways are modified under these two conditions. This review summarizes the roles of diverse PPs, with hope that better knowledge of the interplay among phosphatases and kinases will eventually result in a better understanding of this disease and contribute to its eradication.
Orai3-Mediates Cisplatin-Resistance in Non-Small Cell Lung Cancer Cells by Enriching Cancer Stem Cell Population through PI3K/AKT Pathway
Authors: Daya Hiba Abou , Kouba Sana , Ouled-Haddou Hakim , Benzerdjeb Nazim , Telliez Marie-Sophie , Dayen Charles , Sevestre Henri , Garçon Loïc , Hague Frédéric , Ouadid-Ahidouch Halima
Published: May 2021

The development of the resistance to platinum salts is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). Among the reasons underlying this resistance is the enrichment of cancer stem cells (CSCs) populations. Several studies have reported the involvement of calcium channels in chemoresistance. The Orai3 channel is overexpressed and constitutes a predictive marker of metastasis in NSCLC tumors. Here, we investigated its role in CSCs populations induced by Cisplatin (CDDP) in two NSCLC cell lines. We found that CDDP treatment increased Orai3 expression, but not Orai1 or STIM1 expression, as well as an enhancement of CSCs markers. Moreover, Orai3 silencing or the reduction of extracellular calcium concentration sensitized the cells to CDDP and led to a reduction in the expression of Nanog and SOX-2. Orai3 contributed to SOCE (Store-operated Calcium entry) in both CDDP-treated and CD133+ subpopulation cells that overexpress Nanog and SOX-2. Interestingly, the ectopic overexpression of Orai3, in the two NSCLC cell lines, lead to an increase of SOCE and expression of CSCs markers. Furthermore, CD133+ cells were unable to overexpress neither Nanog nor SOX-2 when incubated with PI3K inhibitor. Finally, Orai3 silencing reduced Akt phosphorylation. Our work reveals a link between Orai3, CSCs and resistance to CDDP in NSCLC cells.
Syndecan-1 Promotes Angiogenesis in Triple-Negative Breast Cancer through the Prognostically Relevant Tissue Factor Pathway and Additional Angiogenic Routes
Authors: Nassar Eyyad , Hassan Nourhan , El-Ghonaimy Eslam A. , Hassan Hebatallah , Abdullah Mahmoud Salah , Rottke Theresa V. , Kiesel Ludwig , Greve Burkhard , Ibrahim Sherif Abdelaziz , Götte Martin
Published: May 2021

Triple-negative breast cancer (TNBC) is characterized by increased angiogenesis, metastasis, and poor survival. Dysregulation of the cell surface heparan sulfate proteoglycan and signaling co-receptor Syndecan-1 is linked to poor prognosis. To study its role in angiogenesis, we silenced Syndecan-1 in TNBC cell lines using a 3D human umbilical vein endothelial cell (HUVEC) co-culture system. Syndecan-1 siRNA depletion in SUM-149, MDA-MB-468, and MDA-MB-231 cells decreased HUVEC tubule network formation. Angiogenesis array revealed reduced VEGF-A and tissue factor (TF) in the Syndecan-1-silenced secretome. qPCR independently confirmed altered expression of F3, F7, F2R/PAR1, F2RL1/PAR2, VEGF-A, EDN1, IGFBP1, and IGFBP2 in SUM-149, MDA-MB-231, and MDA-MB-468 cells. ELISA revealed reduced secreted endothelin-1 (SUM-149, MDA-MB-468) and TF (all cell lines) upon Syndecan-1 depletion, while TF pathway inhibitor treatment impaired angiogenesis. Survival analysis of 3951 patients demonstrated that high expression of F3 and F7 are associated with better relapse-free survival, whereas poor survival was observed in TNBC and p53 mutant basal breast cancer (F3) and in ER-negative and HER2-positive breast cancer (F2R, F2RL1). STRING protein network analysis revealed associations of Syndecan-1 with VEGF-A and IGFBP1, further associated with the TF and ET-1 pathways. Our study suggests that TNBC Syndecan-1 regulates angiogenesis via the TF and additional angiogenic pathways and marks its constituents as novel prognostic markers and therapeutic targets.
Frequency of CDH1 Germline Mutations in Non-Gastric Cancers
Authors: Massari Giulia , Magnoni Francesca , Favia Giorgio , Peradze Nickolas , Veronesi Paolo , La Vecchia Carlo , Corso Giovanni
Published: May 2021

Hereditary Diffuse Gastric Cancer (HDGC) is a complex inherited syndrome caused by CDH1 germline mutations. DGC is the hallmark cancer of this genetic predisposition, but several other cancers are associated with these CDH1 mutations. In this review, we revised all studies reporting CDH1 mutations in non-GC patients. The selected studies included: (a) families aggregating with GC and other cancers, both, and (b) families presenting only non-gastric tumors association. Among non-gastric tumors, our results show that CDH1 mutations are most frequently identified in breast cancer. The frequency of missense mutations is higher in the non-GC group, as the age at diagnosis in this group. Moreover, the predominant CDH1 mutation affects the extracellular domain. Our data suggest that CDH1 genetic testing should be considered also in other cancers, especially breast tumors.
The Ratio of GrzB+ − FoxP3+ over CD3+ T Cells as a Potential Predictor of Response to Nivolumab in Patients with Metastatic Melanoma
Authors: Scognamiglio Giosuè , Capone Mariaelena , Sabbatino Francesco , Di Mauro Annabella , Cantile Monica , Cerrone Margherita , Madonna Gabriele , Grimaldi Antonio Maria , Mallardo Domenico , Palla Marco , Sarno Sabrina , Anniciello Anna Maria , Di Bonito Maurizio , Ascierto Paolo Antonio , Botti Gerardo
Published: May 2021

The understanding of the molecular pathways involved in the dynamic modulation of the tumor microenvironment (TME) has led to the development of innovative treatments for advanced melanoma, including immune checkpoint blockade therapies. These approaches have revolutionized the treatment of melanoma, but are not effective in all patients, resulting in responder and non-responder populations. Physical interactions among immune cells, tumor cells and all the other components of the TME (i.e., cancer-associated fibroblasts, keratinocytes, adipocytes, extracellular matrix, etc.) are essential for effective antitumor immunotherapy, suggesting the need to define an immune score model which can help to predict an efficient immunotherapeutic response. In this study, we performed a multiplex immunostaining of CD3, FOXP3 and GRZB on both primary and unmatched in-transit metastatic melanoma lesions and defined a novel ratio between different lymphocyte subpopulations, demonstrating its potential prognostic role for cancer immunotherapy. The application of the suggested ratio can be useful for the stratification of melanoma patients that may or may not benefit from anti-PD-1 treatment.
The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology
Authors: Fan Fengjuan , Podar Klaus
Published: May 2021

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the clonal expansion of malignant plasma cells within the bone marrow. Activator Protein-1 (AP-1) transcription factors (TFs), comprised of the JUN, FOS, ATF and MAF multigene families, are implicated in a plethora of physiologic processes and tumorigenesis including plasma cell differentiation and MM pathogenesis. Depending on the genetic background, the tumor stage, and cues of the tumor microenvironment, specific dimeric AP-1 complexes are formed. For example, AP-1 complexes containing Fra-1, Fra-2 and B-ATF play central roles in the transcriptional control of B cell development and plasma cell differentiation, while dysregulation of AP-1 family members c-Maf, c-Jun, and JunB is associated with MM cell proliferation, survival, drug resistance, bone marrow angiogenesis, and bone disease. The present review article summarizes our up-to-date knowledge on the role of AP-1 family members in plasma cell differentiation and MM pathophysiology. Moreover, it discusses novel, rationally derived approaches to therapeutically target AP-1 TFs, including protein-protein and protein-DNA binding inhibitors, epigenetic modifiers and natural products.
Neurofibromin Deficiency and Extracellular Matrix Cooperate to Increase Transforming Potential through FAK-Dependent Signaling
Authors: Errico Andrea , Stocco Anna , Riccardi Vincent M. , Gambalunga Alberto , Bassetto Franco , Grigatti Martina , Ferlosio Amedeo , Tadini Gianluca , Garozzo Debora , Ferraresi Stefano , Trevisan Andrea , Giustini Sandra , Rasola Andrea , Chiara Federica
Published: May 2021

Plexiform neurofibromas (Pnfs) are benign peripheral nerve sheath tumors that are major features of the human genetic syndrome, neurofibromatosis type 1 (NF1). Pnfs are derived from Schwann cells (SCs) undergoing loss of heterozygosity (LOH) at the NF1 locus in an NF1+/− milieu and thus are variably lacking in the key Ras-controlling protein, neurofibromin (Nfn). As these SCs are embedded in a dense desmoplastic milieu of stromal cells and abnormal extracellular matrix (ECM), cell–cell cooperativity (CCC) and the molecular microenvironment play essential roles in Pnf progression towards a malignant peripheral nerve sheath tumor (MPNST). The complexity of Pnf biology makes treatment challenging. The only approved drug, the MEK inhibitor Selumetinib, displays a variable and partial therapeutic response. Here, we explored ECM contributions to the growth of cells lacking Nfn. In a 3D in vitro culture, NF1 loss sensitizes cells to signals from a Pnf-mimicking ECM through focal adhesion kinase (FAK) hyperactivation. This hyperactivation correlated with phosphorylation of the downstream effectors, Src, ERK, and AKT, and with colony formation. Expression of the GAP-related domain of Nfn only partially decreased activation of this signaling pathway and only slowed down 3D colony growth of cells lacking Nfn. However, combinatorial treatment with both the FAK inhibitor Defactinib (VS-6063) and Selumetinib (AZD6244) fully suppressed colony growth. These observations pave the way for a new combined therapeutic strategy simultaneously interfering with both intracellular signals and the interplay between the various tumor cells and the ECM.
Chemical Stimulation of Rodent and Human Cortical Synaptosomes: Implications in Neurodegeneration
Authors: Ahmad Faraz , Jing Yu , Lladó Albert , Liu Ping
Published: May 2021

Synaptic plasticity events, including long-term potentiation (LTP), are often regarded as correlates of brain functions of memory and cognition. One of the central players in these plasticity-related phenomena is the α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR). Increased levels of AMPARs on postsynaptic membranes thus constitute a biochemical measure of LTP. Isolated synaptic terminals (synaptosomes) are an excellent ex vivo tool to monitor synaptic physiology in healthy and diseased brains, particularly in human research. We herein describe three protocols for chemically-induced LTP (cLTP) in synaptosomes from both rodent and human brain tissues. Two of these chemical stimulation protocols are described for the first time in synaptosomes. A pharmacological block of synaptosomal actin dynamics confirmed the efficiency of the cLTP protocols. Furthermore, the study prototypically evaluated the deficiency of cLTP in cortical synaptosomes obtained from human cases of early-onset Alzheimer’s disease (EOAD) and frontotemporal lobar degeneration (FLTD), as well as an animal model that mimics FLTD.
3,3′-Diindolylmethane Suppresses the Growth of Hepatocellular Carcinoma by Regulating Its Invasion, Migration, and ER Stress-Mediated Mitochondrial Apoptosis
Authors: Munakarmi Suvesh , Shrestha Juna , Shin Hyun-Beak , Lee Geum-Hwa , Jeong Yeon-Jun
Published: May 2021

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide with limited treatment options. Biomarker-based active phenolic flavonoids isolated from medicinal plants might shed some light on potential therapeutics for treating HCC. 3,3′-diindolylmethane (DIM) is a unique biologically active dimer of indole-3-carbinol (I3C), a phytochemical compound derived from Brassica species of cruciferous vegetables—such as broccoli, kale, cabbage, and cauliflower. It has anti-cancer effects on various cancers such as breast cancer, prostate cancer, endometrial cancer, and colon cancer. However, the molecular mechanism of DIM involved in reducing cancer risk and/or enhancing therapy remains unknown. The aim of the present study was to evaluate anti-cancer and therapeutic effects of DIM in human hepatoma cell lines Hep3B and HuhCell proliferation was measured with MTT and trypan blue colony formation assays. Migration, invasion, and apoptosis were measured with Transwell assays and flow cytometry analyses. Reactive oxygen species (ROS) intensity and the loss in mitochondrial membrane potential of Hep3B and Huh7 cells were determined using dihydroethidium (DHE) staining and tetramethylrhodamine ethyl ester dye. Results showed that DIM significantly suppressed HCC cell growth, proliferation, migration, and invasion in a concentration-dependent manner. Furthermore, DIM treatment activated caspase-dependent apoptotic pathway and suppressed epithelial–mesenchymal transition (EMT) via ER stress and unfolded protein response (UPR). Taken together, our results suggest that DIM is a potential anticancer drug for HCC therapy by targeting ER-stress/UPR.
Adipose-Derived Mesenchymal Stromal Cells Treated with Interleukin 1 Beta Produced Chondro-Protective Vesicles Able to Fast Penetrate in Cartilage
Authors: Colombini Alessandra , Ragni Enrico , Mortati Leonardo , Libonati Francesca , Perucca Orfei Carlotta , Viganò Marco , Brayda-Bruno Marco , de Girolamo Laura
Published: May 2021

The study of the miRNA cargo embedded in extracellular vesicles (EVs) released from adipose-derived mesenchymal stromal cells (ASC) preconditioned with IL-1β, an inflammatory stimulus driving osteoarthritis (OA), along with EVs-cartilage dynamic interaction represent poorly explored fields and are the purpose of the present research. ASCs were isolated from subcutaneous adipose tissue and EVs collected by ultracentrifugation. Shuttled miRNAs were scored by high-throughput screening and analyzed through bioinformatics approach that predicted the potentially modulated OA-related pathways. Fluorescently labeled EVs incorporation into OA cartilage explants was followed in vitro by time-lapse coherent anti-Stokes Raman scattering; second harmonic generation and two-photon excited fluorescence. After IL-1β preconditioning, 7 miRNA were up-regulated, 4 down-regulated, 37 activated and 17 silenced. Bioinformatics allowed to identify miRNAs and target genes mainly involved in Wnt, Notch, TGFβ and Indian hedgehog (IHH) pathways, cartilage homeostasis, immune/inflammatory responses, cell senescence and autophagy. As well, ASC-EVs steadily diffuse in cartilage cells and matrix, reaching a plateau 16 h after administration. Overall, ASCs preconditioned with IL-1β allows secretion of EVs embedded with a chondro-protective miRNA cargo, able to fast penetrate in collagen-rich areas of cartilage with tissue saturation in a day. Further functional studies exploring the EVs dose-effects are needed to achieve clinical relevance.
Does Dental Fear in Children Predict Untreated Dental Caries? An Analytical Cross-Sectional Study
Authors: Panda Suman , Quadri Mir Faeq Ali , Hadi Imtinan H. , Jably Rafaa M. , Hamzi Aisha M. , Jafer Mohammed A.
Published: May 2021

Despite free health care services in Saudi Arabia, the prevalence of caries in children is substantially greater in comparison to other high-income countries. Dental fear in children may be an important issue that needs attention. Therefore, the aim was to investigate the role of dental fear in predicting untreated dental caries in schoolchildren. This analytical cross-sectional study included children aged 8–10 years residing in Saudi Arabia. Dental status via oral examinations was surveyed with the WHO standardized chart and the Children Fear Survey Schedule—Dental Subscale was used to score dental fear. Descriptive, binary, and multivariable logistic regression analyses were performed to report the findings at 5% statistical significance. Overall, there were 798 schoolchildren with an average fear score of 36. Nearly 70.4% reported fear of someone examining their mouth. About 76.9% had at least one carious tooth in their oral cavity. Children with dental fear were 1.8 times (OR = 1.80; 95% CI = 1.26, 2.56) more likely to have at least one untreated carious tooth in their oral cavity than those who did not express fear during oral examinations and dental procedures. Thus, the current study concludes that fear of dentists and dental treatment procedures successfully predicts untreated carious teeth in schoolchildren.
Improved Corrosion Resistance of Magnesium Alloy AZ31 in Ringer Lactate by Bilayer Anodic Film/Beeswax–Colophony
Authors: Anawati Anawati , Fitriana Medio Febby , Gumelar Muhammad Dikdik
Published: May 2021

A bilayer anodic film/beeswax–colophony is proposed for improving the corrosion resistance of magnesium alloy surface. The bilayer was synthesized on the AZ31 alloy by anodization and subsequent dip coating, and the corrosion behavior was investigated by electrochemical measurements and weight loss test in Ringer lactate at 37 °C. The bilayer improved the electrochemical corrosion resistance by four orders of magnitude, as demonstrated by ~104 times lower corrosion current density in the polarization curves and ~104 higher film resistance in the impedance spectra. The tremendous surface area of the porous anodic film led to a strong attachment of the topcoat beeswax–colophony. Most of the coating remained attached to the surface after 14 days soaking in Ringer lactate. A few small blisters developed under the bilayer contributed to the low mass loss of 0.07 mg/cm2/day compared to the bare substrate, with an average loss rate of 0.25 mg/cm2/day. Local detachment of topcoat layer exposed the underlying anodic film that triggered the deposition of Ca and further nucleation of the Ca–P compound on the surface. The existence of a Ca−P compound with a Ca/P ratio of 1.68 indicated the ability of the bilayer to promote the formation of bone mineral apatite.
A Comprehensive Life-Cycle Cost Analysis Approach Developed for Steel Bridge Deck Pavement Schemes
Authors: Liu Changbo , Qian Zhendong , Liao Yang , Ren Haisheng
Published: May 2021

This study aims to evaluate the economy of a steel bridge deck pavement scheme (SBDPS) using a comprehensive life-cycle cost (LCC) analysis approach. The SBDPS are divided into the “epoxy asphalt concrete system” (EA system) and “Gussasphalt concrete system” (GA system) according to the difference in the material in the lower layer of the SBDPS. A targeted LCC checklist, including manager cost and user cost was proposed, and a Markov-based approach was applied to establish a life-cycle performance model with clear probability characteristics for SBDPS. Representative traffic conditions were designed using a uniform design method, and the LCC of SBDPS under representative traffic conditions and different credibility (construction quality as a random factor) was compared. The reliability of the LCC analysis approach was verified based on the uncertainty analysis method. Based on an expert-scoring approach, a user cost weight was obtained to ensure it is considered reasonably in the LCC analysis. Compared with the cumulative traffic volume, the cumulative equivalent single axle loads (CESAL) have a closer relationship with the LCC. The GA system has better LCC when the CESAL is less, while the EA system is just the opposite. The breaking point of CESAL for the LCC of the EA system and the GA system is 15 million times. The LCC analysis of SBDPS should consider the influence of random factors such as construction quality. The comprehensive LCC analysis approach in this paper can provide suggestions for bridge-management departments to make a reasonable selection on SBDPS.
On the Analysis of the Non-Newtonian Fluid Flow Past a Stretching/Shrinking Permeable Surface with Heat and Mass Transfer
Authors: Khan Shahid , Selim Mahmoud M. , Khan Aziz , Ullah Asad , Abdeljawad Thabet , Ikramullah  , Ayaz Muhammad , Mashwani Wali Khan
Published: May 2021

The 3D Carreau fluid flow through a porous and stretching (shrinking) sheet is examined analytically by taking into account the effects of mass transfer, thermal radiation, and Hall current. The model equations, which consist of coupled partial differential equations (PDEs), are simplified to ordinary differential equations (ODEs) through appropriate similarity relations. The analytical procedure of HAM (homotopy analysis method) is employed to solve the coupled set of ODEs. The functional dependence of the hydromagnetic 3D Carreau fluid flow on the pertinent parameters are displayed through various plots. It is found that the x-component of velocity gradient (f′(η)) enhances with the higher values of the Hall and shrinking parameters (m,ϱ), while it reduces with magnetic parameter and Weissenberg number (M,We). The y-component of fluid velocity (g(η)) rises with the augmenting values of m and M, while it drops with the augmenting viscous nature of the Carreau fluid associated with the varying Weissenberg number. The fluid temperature θ(η) enhances with the increasing values of radiation parameter (Rd) and Dufour number (Du), while it drops with the rising Prandtl number (Pr). The concentration field (ϕ(η)) augments with the rising Soret number (Sr) while drops with the augmenting Schmidt number (Sc). The variation of the skin friction coefficients (Cfx and Cfz), Nusselt number (Nux) and Sherwood number (Shx) with changing values of these governing parameters are described through different tables. The present and previous published results agreement validates the applied analytical procedure.
Analytical Validation and Clinical Application of Rapid Serological Tests for SARS-CoV-2 Suitable for Large-Scale Screening
Authors: De Nicolò Amedeo , Avataneo Valeria , Cusato Jessica , Palermiti Alice , Mula Jacopo , De Vivo Elisa , Antonucci Miriam , Bonora Stefano , Calcagno Andrea , Di Perri Giovanni , De Rosa Francesco Giuseppe , D’Avolio Antonio
Published: May 2021

Recently, large-scale screening for COVID-19 has presented a major challenge, limiting timely countermeasures. Therefore, the application of suitable rapid serological tests could provide useful information, however, little evidence regarding their robustness is currently available. In this work, we evaluated and compared the analytical performance of a rapid lateral-flow test (LFA) and a fast semiquantitative fluorescent immunoassay (FIA) for anti-nucleocapsid (anti-NC) antibodies, with the reverse transcriptase real-time PCR assay as the reference. In 222 patients, LFA showed poor sensitivity (55.9%) within two weeks from PCR, while later testing was more reliable (sensitivity of 85.7% and specificity of 93.1%). Moreover, in a subset of 100 patients, FIA showed high sensitivity (89.1%) and specificity (94.1%) after two weeks from PCR. The coupled application for the screening of 183 patients showed satisfactory concordance (K = 0.858). In conclusion, rapid serological tests were largely not useful for early diagnosis, but they showed good performance in later stages of infection. These could be useful for back-tracing and/or to identify potentially immune subjects.
Short-Term N-Fertilization Differently Affects the Leaf and Leaf Litter Chemistry of the Dominant Species in a Mediterranean Forest under Drought Conditions
Authors: Vallicrosa Helena , Sardans Jordi , Ogaya Romà , Fernández Pere Roc , Peñuelas Josep
Published: May 2021

Nitrogen (N) deposition is a key driver of global change with significant effects on carbon (C) cycling, species fitness, and diversity; however, its effects on Mediterranean ecosystems are unclear. Here, we simulated N deposition in an N-fertilization experiment with 15N-labeled fertilizer in a montane evergreen Mediterranean holm oak forest, in central Catalonia, to quantify short-term impacts on leaf, leaf litter elemental composition, and resorption efficiency in three dominant species (Quercus ilex, Phillyrea latifolia, and Arbutus unedo). We found that even under drought conditions, 15N isotope analysis of leaf and leaf litter showed a rapid uptake of the added N, suggesting an N deficient ecosystem. Species responses to N fertilization varied, where A. unedo was unaffected and the responses in P. latifolia and Q. ilex were similar, albeit with contrasting magnitude. P. latifolia benefited the most from N fertilization under drought conditions of the experimental year. These differences in species response could indicate impacts on species fitness, competition, and abundance under increased N loads in Mediterranean forest ecosystems. Further research is needed to disentangle interactions between long-term N deposition and the drought predicted under future climate scenarios in Mediterranean ecosystems.
Gap-Fillers for Wooden Artefacts Exposed Outdoors—A Review
Authors: Broda Magdalena , Kryg Paulina , Ormondroyd Graham Alan
Published: May 2021

Conservation of wooden artefacts that are exposed outdoors, mainly in open-air museums, is a very complex and difficult issue that aims to preserve both the integrity and aesthetics of valuable objects. Unceasingly subjected to several factors, such as alternating weather conditions and the activities of microorganisms, algae, and insects, they undergo continuous changes and inevitable deterioration. Their biological and physical degradation often results in the formation of gaps and cracks in the wooden tissue, which creates a need not only for wood consolidation, but also for using specialist materials to fill the holes and prevent further degradation of an object. To ensure effective protection for a wooden artefact, a filling material must both protect the wood against further degradation and adapt to changes in wood dimensions in response to humidity variations. A variety of substances, both organic and inorganic, have been used for conservation and gap filling in historic wooden objects over the years. The filling compounds typically consist of two components, of which one is a filler, and the second a binder. In the case of inorganic fillers, plaster has been traditionally used, while the most popular organic fillers were wood powder, wood shavings, and powdered cork. As with binders, mainly natural substances have been used, such as animal glues or waxes. Nowadays, however, due to the lower biodegradability and better physicochemical properties, synthetic materials are gaining popularity. This article discusses the types of filling compounds currently used for gap filling in wooden artefacts exposed outdoors, outlining their advantages and drawbacks, as well as future perspective compounds. It appears that particularly composite materials based on natural polymers deserve attention as promising filling materials due to their high elasticity, as well as similarity and good adhesion to the wooden surface. Their main shortcomings, such as susceptibility to biodegradation, could be eliminated by using some modern, bio-friendly preservatives, providing effective protection for historic wooden artefacts.
Seven Complete Chloroplast Genomes from Symplocos: Genome Organization and Comparative Analysis
Authors: Kim Sang-Chul , Lee Jei-Wan , Choi Byoung-Ki
Published: May 2021

In the present study, chloroplast genome sequences of four species of Symplocos (S. chinensis for. pilosa, S. prunifolia, S. coreana, and S. tanakana) from South Korea were obtained by Ion Torrent sequencing and compared with the sequences of three previously reported Symplocos chloroplast genomes from different species. The length of the Symplocos chloroplast genome ranged from 156,961 to 157,365 bp. Overall, 132 genes including 87 functional genes, 37 tRNA genes, and eight rRNA genes were identified in all Symplocos chloroplast genomes. The gene order and contents were highly similar across the seven species. The coding regions were more conserved than the non-coding regions, and the large single-copy and small single-copy regions were less conserved than the inverted repeat regions. We identified five new hotspot regions (rbcL, ycf4, psaJ, rpl22, and ycf1) that can be used as barcodes or species-specific Symplocos molecular markers. These four novel chloroplast genomes provide basic information on the plastid genome of Symplocos and enable better taxonomic characterization of this genus.
Effects of Moisture Content and Grain Direction on the Elastic Properties of Beech Wood Based on Experiment and Finite Element Method
Authors: Fu Wei-Lian , Guan Hui-Yuan , Kei Sawata
Published: May 2021

Beech wood (Fagus sylvatica L.) is used in a wide range of wood products. However, the influence of the wood’s moisture content on its mechanical functions will affect its structural strength. It would be complicated and time-consuming to experimentally measure wood’s mechanical functions under different moisture contents. Therefore, it is necessary to establish a prediction formula between the moisture content and elastic constants, and then verify whether its mechanical functions within a wide range of moisture content can be studied by using FEM (finite element method). In this study, which was based on experimentation, we studied the influence of a wide range of moisture contents and grain direction on the compressive yield strength, modulus of elasticity and shear modulus of beech wood. The relationship between the moisture content and elastic constants was established; the moisture sensitivities of different elastic parameters were obtained. Ultimately, compression curves under different moisture contents were plotted out, using both FEM and experimentation. According to the results, the interaction of moisture with the grain direction had a significant effect on the elastic constants of wood, with grain direction having a greater effect on the elastic properties than the moisture content. Moreover, the decay function can be used to fit these experimental results well. The elastic constants of beech wood responded differently to the moisture content, depending on whether it was in the longitude or transverse directions. Finally, this study proved the feasibility of using FEM to simulate wood’s compressive performance with a wide range of moisture contents.
Patient-Reported Outcomes in Inflammatory Bowel Disease: A Measurement of Effect in Research and Clinical Care
Authors: Fletcher Jane , Cooper Sheldon C. , Swift Amelia
Published: May 2021

The measurement of outcomes is key in evaluating healthcare or research interventions in inflammatory bowel disease (IBD). In patient-centred care, patient-reported outcome measures (PROMs) are central to this evaluation. In this review, we provide an overview of validated, adult disease-specific PROMs developed for use in IBD. Our aim is to assist clinicians and researchers in selection of PROMs to measure outcomes in their patient cohort. The Consensus-based Standards for the Selection of Health Measurement Instruments database of systematic reviews was the primary resource used to identify PROMs used in IBD. Search terms were ‘Crohn’s disease’, ‘ulcerative colitis’, and ‘IBD’. Seven systematic reviews were identified from this search. In addition, the publication by the IBD Core Outcome Set Working Group was used to identify further PROMs. Three systematic reviews were excluded as they did not meet the inclusion criteria. From the five included systematic reviews, we identified 21 PROMs and their shortened versions. In conclusion, it does not appear that any one PROM is entirely suitable for both research and clinical practice. Overall, the IBDQ-32 is most widely used in research but has the limitation of cost, whereas the IBD-Control has been recommended in the clinical core outcome set.