bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 Disease and Vaccination: Knowledge, Fears, Perceptions and Feelings of Regret for Not Having Been Vaccinated among Hospitalized Greek Patients Suffering SARS-CoV-2 Infection
Authors: Ioannou Petros , Tzalis Sotiris , Pasparaki Eirini , Spentzouri Despoina , Konidaki Myrto , Papakitsou Ioanna , Spernovasilis Nikolaos , Papanikolaou Nikolaos , Samonis George , Kofteridis Diamantis P.
Published: August 2022

Background: The development of vaccines against COVID-19 has greatly altered the natural course of this infection, reducing the disease’s severity and patients’ hospitalization. However, hesitancy against vaccination remains an obstacle in the attempt to achieve appropriate herd immunity that could reduce the spread of SARS-CoV-2. The aim of this study was to investigate the perceptions and attitudes of COVID-19 patients hospitalized during the fourth pandemic wave in two Greek hospitals and assess whether their experience had changed their intentions regarding vaccination against COVID-19. Methods: This is a cross-sectional, questionnaire-based survey, conducted from 31 August 2021 to 18 February 2022 in the COVID-19 departments of two tertiary care hospitals. The questionnaire included questions regarding the patients’ educational level, knowledge and beliefs regarding SARS-CoV-2, personal protection measures, beliefs regarding vaccination, vaccination status, reasons for not been vaccinated against SARS-CoV-2, feelings of regret for not been vaccinated, and willingness to be vaccinated in the future. All adult patients with COVID-19 were eligible, regardless of their vaccination status against SARS-CoV-2. Results: In total, 162 patients agreed and participated in the study, with 97% of them suffering severe COVID-19. Their median age was 56 years, and 59.9% (97 patients) were male. Among them, 43.8% had been vaccinated against COVID-19. When unvaccinated patients were asked the reasons for not being vaccinated, the most frequent responses were that they were waiting for more scientific data, due to uncertainty about long-term consequences of the vaccine, and their fear of thrombosis. When at discharge, unvaccinated hospitalized COVID-19 patients were asked whether they would get vaccinated if they could turn time back, and 64.7% of them replied positively. Conclusions: The study reveals several patients’ fears and misconceptions and suggests that there is room for implementing measures that could reduce knowledge gaps allowing for improvement of vaccination rates against COVID-19.
Wet Nurse or Milk Bank? Evolution in the Model of Human Lactation: New Challenges for the Islamic Population
Authors: Espina-Jerez Blanca , Romera-Álvarez Laura , de Dios-Aguado Mercedes , Cunha-Oliveira Aliete , Siles-Gonzalez José , Gómez-Cantarino Sagrario
Published: August 2022

(1) Introduction: The establishment of milk banks in the Islamic world as well as donation to Islamic families in Western countries remains a challenge in the context of human lactation. Religious reservations established since the Qur’an and regulated at the legal–religious and medical level equate milk kinship with consanguinity, which prevents donation. The aim of the study was to analyse the evolution in the model of breastfeeding and care in Islamic society. (2) Methods: The methodology of comparative history was applied, following the structural–dialectical model of care. Historical manuals, articles and databases were analysed. (3) Results: Paediatric care in medical manuals from the 10th–15th centuries is similar to that practiced by the Muslim population today, some beneficial, some harmful; the wet nurse had to follow a series of dietary habits and have a series of physical, moral and educational characteristics in order to be hired. They constituted a beginning of pseudo-professionalisation, in a domestic–family framework. Human milk was used as a remedy for different health problems. (4) Conclusions: Islamic society and nursing have to evolve towards transnational care adapted to the needs of the population.
Air Quality Assessment by the Determination of Trace Elements in Lichens (Xanthoria calcicola) in an Industrial Area (Sicily, Italy)
Authors: Varrica Daniela , Lo Medico Federica , Alaimo Maria Grazia
Published: August 2022

This study provides data on variation in the content of metals and metalloids measured in the lichens (Xanthoria calcicola Oxner) collected in the Syracusan petrochemical complex (Sicily, Italy) which is considered one of the largest in Europe. Concentrations of eighteen trace elements measured in the lichens that were collected from 49 different points were analyzed using an inductively coupled plasma (ICP-MS) device. The concentrations of the typical elements of industrial emissions (As, Cr, Ni, and V) highlight the environmental criticality that exists in the study area. The interpretation of the data in terms of multi-element statistical analysis (FA) and enrichment factor (EFs) proved to be particularly useful in identifying several sources that contribute to the presence of trace elements in the atmospheric particulate between anthropogenic emissions and geogenic emissions. The results of this study reveal the versatility of the lichen species Xanthoria calcicola Oxner in the search for trace elements in highly anthropized environments, so the approach followed in this study can also be applied to other industrial contexts.
Regional Research-Practice-Policy Partnerships in Response to Climate-Related Disparities: Promoting Health Equity in the Pacific
Authors: Palinkas Lawrence A. , O’Donnell Meaghan , Kemp Susan , Tiatia Jemaima , Duque Yvonette , Spencer Michael , Basu Rupa , Del Rosario Kristine Idda , Diemer Kristin , Doma Bonifacio , Forbes David , Gibson Kari , Graff-Zivin Joshua , Harris Bruce M. , Hawley Nicola , Johnston Jill , Lauraya Fay , Maniquiz Nora Elizabeth F. , Marlowe Jay , McCord Gordon C. , Nicholls Imogen , Rao Smitha , Saunders Angela Kim , Sortino Salvatore , Springgate Benjamin , Takeuchi David , Ugsang Janette , Villaverde Vivien , Wells Kenneth B. , Wong Marleen
Published: August 2022

Although climate change poses a threat to health and well-being globally, a regional approach to addressing climate-related health equity may be more suitable, appropriate, and appealing to under-resourced communities and countries. In support of this argument, this commentary describes an approach by a network of researchers, practitioners, and policymakers dedicated to promoting climate-related health equity in Small Island Developing States and low- and middle-income countries in the Pacific. We identify three primary sets of needs related to developing a regional capacity to address physical and mental health disparities through research, training, and assistance in policy and practice implementation: (1) limited healthcare facilities and qualified medical and mental health providers; (2) addressing the social impacts related to the cooccurrence of natural hazards, disease outbreaks, and complex emergencies; and (3) building the response capacity and resilience to climate-related extreme weather events and natural hazards.
The Association of Attending Physicians’ Publications and Patients’ Readmission Rates: Evidence from Tertiary Hospitals in China Using a Retrospective Data Analysis
Authors: Shen Menghan , Liang Xiaoxia , Li Linyan , Wu Yushan , Yang Yuanfan , Zingg Raphael
Published: August 2022

Background: Physicians play a unique role in scientific and clinical research, which is the cornerstone of evidence-based medical practice. In China, tertiary public hospitals link promotions and bonuses with publications. However, the weight placed on research in the clinician’s evaluation process and its potential impact on clinical practice have come under controversy. Despite the heated debate about physicians’ role in research, there is little empirical evidence about the relationship between physicians’ publications and their clinical outcomes. Method: This paper examines the association of the quantity and quality of tertiary hospitals’ attending physicians’ publications and inpatient readmission rates in China. We analyzed a 20% random sample of inpatient data from the Urban Employee Basic Medical Health Insurance scheme in one of the largest cities in China from January 2018 through October 2019. We assessed the relationship between the quantity and impact factor of physicians’ publications and 30-day inpatient readmission rates using logistic regression. There were 111,965 hospitalizations treated by 5794 physicians in our sample. Results: Having any first-author publications was not associated with the rate of readmission. Among internists, having clinical studies published in journals with an average impact factor of 3 or above was associated with lower readmission rates (OR = 0.849; 95% CI (0.740, 0.975)), but having basic science studies published in journals with an average impact factor of 3 or above was not associated with the rate of readmission. Among surgeons, having clinical studies published in journals with an average impact factor of 3 or above was likewise associated with lower readmission rates (OR = 0.708 (0.531, 0.946)), but having basic science studies published in journals with an average impact factor of 3 or above was associated with higher readmission rates (OR = 1.230 (1.051, 1.439)).
Tempo-Spatial Modelling of the Spread of COVID-19 in Urban Spaces
Authors: Galacho-Jiménez Federico Benjamín , Carruana-Herrera David , Molina Julián , Ruiz-Sinoga José Damián
Published: August 2022

The relationship between the social structure of urban spaces and the evolution of the COVID-19 pandemic is becoming increasingly evident. Analyzing the socio-spatial structure in relation to cases may be one of the keys to explaining the ways in which this contagious disease and its variants spread. The aim of this study is to propose a set of variables selected from the social context and the spatial structure and to evaluate the temporal spread of infections and their different degrees of intensity according to social areas. We define a model to represent the relationship between the socio-spatial structure of the urban space and the spatial distribution of pandemic cases. We draw on the theory of social area analysis and apply multivariate analysis techniques to check the results in the urban space of the city of Malaga (Spain). The proposed model should be considered capable of explaining the functioning of the relationships between societal structure, socio-spatial segregation, and the spread of the pandemic. In this paper, the study of the origins and consequences of COVID-19 from different scientific perspectives is considered a necessary approach to understanding this phenomenon. The personal and social consequences of the pandemic have been exceptional and have changed many aspects of social life in urban spaces, where it has also had a greater impact. We propose a geostatistical analysis model that can explain the functioning of the relationships between societal structure, socio-spatial segregation, and the temporal evolution of the pandemic. Rather than an aprioristic theory, this paper is a study by the authors to interpret the disparity in the spread of the pandemic as shown by the infection data.
DLKN-MLC: A Disease Prediction Model via Multi-Label Learning
Authors: Li Bocheng , Zhang Yunqiu , Wu Xusheng
Published: August 2022

With the increasingly available electronic health records (EHR), disease prediction has recently gained immense research attention, where an accurate classifier needs to be trained to map the input prediction signals (e.g., symptoms, auxiliary examination results, etc.) to the estimated diseases for each patient. However, most of the current disease prediction models focus on the prediction of a single disease; in the medical field, a patient often suffers from multiple diseases (especially multiple chronic diseases) at the same time. Therefore, multi-disease prediction is of greater significance for patients’ early intervention and treatment, but there is no doubt that multi-disease prediction has higher requirements for data extraction ability and greater complexity of classification. In this paper, we propose a novel disease prediction model DLKN-MLC. The model extracts the information in EHR through deep learning combined with a disease knowledge network, quantifies the correlation between diseases through NodeRank, and completes multi-disease prediction. in addition, we distinguished the importance of common disease symptoms, occasional disease symptoms and auxiliary examination results in the process of disease diagnosis. In empirical and comparative experiments on real EHR datasets, the Hamming loss, one-error rate, ranking loss, average precision, and micro-F1 values of the DLKN-MLC model were 0.2624, 0.2136, 0.2190, 88.21%, and 87.86%, respectively, which were better compared with those from previous methods. Extensive experiments on a real-world EHR dataset have demonstrated the state-of-the-art performance of our proposed model.
Development and Use of a Kinetical and Real-Time Monitoring System to Analyze the Replication of Hepatitis C Virus
Authors: Li Xiaoyu , Ito Masahiko , Aoyagi Haruyo , Murayama Asako , Aizaki Hideki , Fukasawa Masayoshi , Kato Takanobu , Wakita Takaji , Suzuki Tetsuro
Published: August 2022

In microbiological research, it is important to understand the time course of each step in a pathogen’s lifecycle and changes in the host cell environment induced by infection. This study is the first to develop a real-time monitoring system that kinetically detects luminescence reporter activity over time without sampling cells or culture supernatants for analyzing the virus replication. Subgenomic replicon experiments with hepatitis C virus (HCV) showed that transient translation and genome replication can be detected separately, with the first peak of translation observed at 3–4 h and replication beginning around 20 h after viral RNA introduction into cells. From the bioluminescence data set measured every 30 min (48 measurements per day), the initial rates of translation and replication were calculated, and their capacity levels were expressed as the sums of the measured signals in each process, which correspond to the areas on the kinetics graphs. The comparison of various HuH-7-derived cell lines showed that the bioluminescence profile differs among cell lines, suggesting that both translation and replication capacities potentially influence differences in HCV susceptibility. The effects of RNA mutations within the 5′ UTR of the replicon on viral translation and replication were further analyzed in the system developed, confirming that mutations to the miR-122 binding sites primarily reduce replication activity rather than translation. The newly developed real-time monitoring system should be applied to the studies of various viruses and contribute to the analysis of transitions and progression of each process of their life cycle.
mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity
Authors: Mota-Martorell Natalia , Jové Mariona , Pamplona Reinald
Published: August 2022

Decreased content and activity of the mechanistic target of rapamycin (mTOR) signalling pathway, as well as the mTOR complex 1 (mTORC1) itself, are key traits for animal species and human longevity. Since mTORC1 acts as a master regulator of intracellular metabolism, it is responsible, at least in part, for the longevous phenotype. Conversely, increased content and activity of mTOR signalling and mTORC1 are hallmarks of ageing. Additionally, constitutive and aberrant activity of mTORC1 is also found in age-related diseases such as Alzheimer’s disease (AD) and cancer. The downstream processes regulated through this network are diverse, and depend upon nutrient availability. Hence, multiple nutritional strategies capable of regulating mTORC1 activity and, consequently, delaying the ageing process and the development of age-related diseases, are under continuous study. Among these, the restriction of calories is still the most studied and robust intervention capable of downregulating mTOR signalling and feasible for application in the human population.
New Organic–Inorganic Salt Based on Fluconazole Drug: TD-DFT Benchmark and Computational Insights into Halogen Substitution
Authors: Ferjani Hela , Bechaieb Rim , Alshammari Marzook , Lemine O. M. , Dege Necmi
Published: August 2022

In this study, we report the synthesis of a new organic–inorganic molecular salt of the clinically used antifungal drug fluconazole, (H2Fluconazole).SnCl6.2H2O. By detailed investigation and analysis of its structural properties, we show that the structure represents a 0D structure built of alternating organic and inorganic zig-zag layers along the crystallographic c-axis and the primary supramolecular synthons in this salt are hydrogen bonding, F···π and halogen bonding interactions. Magnetic measurements reveal the co-existence of weak ferromagnetic behavior at low magnetic field and large diamagnetic contributions, indicating that the synthesized material behaves mainly as a diamagnetic material, with very low magnetic susceptibility and with a band gap energy of 3.6 eV, and the salt is suitable for semiconducting applications. Extensive theoretical study is performed to explain the acceptor donor reactivity of this compound and to predict the Cl-substitution effect by F, Br and I. The energy gap, frontier molecular orbitals (FMOs) and the different chemical reactivity descriptors were evaluated at a high theoretical level. Calculations show that Cl substitution by Br and I generates compounds with more important antioxidant ability and the intramolecular charge transfer linked to the inorganic anion.
A Systematic Study of Restorative Crown-Materials Combinations for Dental Implants: Characterization of Mechanical Properties under Dynamic Loads
Authors: Marimon Xavier , Cerrolaza Miguel , Ferrer Miquel , Cantó-Navés Oriol , Cabratosa-Termes Josep , Pérez Román
Published: August 2022

This study aimed to find the optimum mechanical characteristics of the restorative materials for the manufacture of implant crowns subjected to impact loading when different combinations of materials are used for the inner and outer crown. Several combinations of external–internal crown restorative materials were analyzed. The dynamic stresses at eight different zones of a dental implant subjected to an impact load and the influence of several mechanical properties, such as the Young’s modulus, Poisson’s ratio, density, and initial velocity, were analyzed and compared. A detailed 3D model was created, including the crown, the retention screw, the implant, and a mandible section. The model was then built by importing the 3D geometries from CAD software. The whole 3D model was carefully created in order to guarantee a finite element mesh that produced results adjusted to physical reality. Then, we conducted a numerical simulation using the finite element method (FEM). The results of the FEM analysis allowed for evaluating the effect that different combinations of restorative materials and mechanical properties had on the stress distribution in various regions of the implant. The choice of restorative material is a factor to be considered in order to preserve the integrity of osseointegration. Restorative materials transfer more or less stress to the dental implant and surrounding bone, depending on their stiffness. Therefore, an inadequate Young’s modulus of the rehabilitation material can affect the survival of the implant over time. Eight interactive graphics were provided on a web-based surface platform to help clinical dentists, researchers, and manufacturers to select the best restorative materials combination for the crown.
Synthesis of Four Steroidal Carbamates with Antitumor Activity against Mouse Colon Carcinoma CT26WT Cells: In Vitro and In Silico Evidence
Authors: Pacheco Daylin Fernández , Alonso Dayana , Ceballos Leonardo González , Castro Armando Zaldo , Brown Roldán Sheila , García Díaz Mairelys , Villa Testa Anabel , Wagner Sarah Fuentes , Piloto-Ferrer Janet , García Yamilet Coll , Olea Andrés F. , Espinoza Luis
Published: August 2022

Colorectal cancer (CRC) is one of the most lethal cancers worldwide. If detected on time, surgery can expand life expectations of patients up to five more years. However, if metastasis has grown deliberately, the use of chemotherapy can play a crucial role in CRC control. Moreover, the lack of selectivity of current anticancer drugs, plus mutations that occur in cancerous cells, demands the development of new chemotherapeutic agents. Several steroids have shown their potentiality as anticancer agents, while some other compounds, such as Taxol and its derivatives bearing a carbamate functionality, have reached the market. In this article, the synthesis, characterization, and antiproliferative activity of four steroidal carbamates on mouse colon carcinoma CT26WT cells are described. Carbamate synthesis occurred via direct reaction between diosgenin, its B-ring modified derivative, and testosterone with phenyl isocyanate under a Brønsted acid catalysis. All obtained compounds were characterized by 1H and 13C Nuclear Magnetic Resonance (NMR), High Resolution Mass Spectroscopy (HRMS); their melting points are also reported. Results obtained from antiproliferative activity assays indicated that carbamates compounds have inhibitory effects on the growth of this colon cancer cell line. A molecular docking study carried out on Human Prostaglandin E Receptor (EP4) showed a high affinity between carbamates and protein, thus providing a valuable theoretical explanation of the in vitro results.
Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant
Authors: Boschetti Elisa , Caporali Leonardo , D’Angelo Roberto , Malagelada Carolina , Accarino Anna , Dotti Maria Teresa , Costa Roberta , Cenacchi Giovanna , Pironi Loris , Rinaldi Rita , Stanghellini Vincenzo , Ratti Stefano , Manzoli Lucia , Carelli Valerio , De Giorgio Roberto
Published: August 2022

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.
Discovery of the First Highly Selective Antagonist of the GluK3 Kainate Receptor Subtype
Authors: Chałupnik Paulina , Vialko Alina , Pickering Darryl S. , Hinkkanen Markus , Donbosco Stephanie , Møller Thor C. , Jensen Anders A. , Nielsen Birgitte , Bay Yasmin , Kristensen Anders S. , Johansen Tommy N. , Łątka Kamil , Bajda Marek , Szymańska Ewa
Published: August 2022

Kainate receptors belong to the family of glutamate receptors ion channels, which are responsible for the majority of rapid excitatory synaptic transmission in the central nervous system. The therapeutic potential of kainate receptors is still poorly understood, which is also due to the lack of potent and subunit-selective pharmacological tools. In search of selective ligands for the GluK3 kainate receptor subtype, a series of quinoxaline-2,3-dione analogues was synthesized and pharmacologically characterized at selected recombinant ionotropic glutamate receptors. Among them, compound 28 was found to be a competitive GluK3 antagonist with submicromolar affinity and unprecedented high binding selectivity, showing a 400-fold preference for GluK3 over other homomeric receptors GluK1, GluK2, GluK5 and GluA2. Furthermore, in functional assays performed for selected metabotropic glutamate receptor subtypes, 28 did not show agonist or antagonist activity. The molecular determinants underlying the observed affinity profile of 28 were analyzed using molecular docking and molecular dynamics simulations performed for individual GluK1 and GluK3 ligand-binding domains.
PEBP4 Directs the Malignant Behavior of Hepatocellular Carcinoma Cells via Regulating mTORC1 and mTORC2
Authors: Chen Qiongfeng , Jin Jingguang , Guo Wenhui , Tang Zhimin , Luo Yunfei , Ying Ying , Lin Hui , Luo Zhijun
Published: August 2022

Phosphatidylethanolamine binding protein 4 (PEBP4) is an understudied multifunctional small protein. Previous studies have shown that the expression of PEBP4 is increased in many cancer specimens, which correlates to cancer progression. The present study explored the mechanism by which PEBP4 regulates the growth and progression of hepatocellular carcinoma cells. Thus, we showed that knockdown of PEBP4 in MHCC97H cells, where its expression was relatively high, diminished activities of serine/threonine protein kinase B (PKB, also known as Akt), mammalian target of rapamycin complex 1(mTORC1), and mTORC2, events that were not restored by insulin-like growth factor 1 (IGF-1). Conversely, overexpression of PEBP4 in MHCC97L cells with the low endogenous level yielded opposite effects. Furthermore, physical association of PEBP4 with Akt, mTORC1, and mTORC2 was observed. Interestingly, introduction of AktS473D mutant, bypassing phosphorylation by mTORC2, rescued mTORC1 activity, but without effects on mTORC2 signaling. In contrast, the effect of PEBP4 overexpression on the activity of mTORC1 but not that of mTORC2 was suppressed by MK2206, a specific inhibitor of Akt. In conjunction, PEBP4 knockdown-engendered reduction of cell proliferation, migration and invasion was partially rescued by Akt S473D while increases in these parameters induced by overexpression of PEBP4 were completely abolished by MK2206, although the expression of epithelial mesenchymal transition (EMT) markers appeared to be fully regulated by the active mutant of Akt. Finally, knockdown of PEBP4 diminished the growth of tumor and metastasis, whereas they were enhanced by overexpression of PEBP4. Altogether, our study suggests that increased expression of PEBP4 exacerbates malignant behaviors of hepatocellular cancer cells through cooperative participation of mTORC1 and mTORC2.
A Comprehensive Prognostic Analysis of Tumor-Related Blood Group Antigens in Pan-Cancers Suggests That SEMA7A as a Novel Biomarker in Kidney Renal Clear Cell Carcinoma
Authors: Wang Yange , Li Chenyang , Qi Xinlei , Yao Yafei , Zhang Lu , Zhang Guosen , Xie Longxiang , Wang Qiang , Zhu Wan , Guo Xiangqian
Published: August 2022

Blood group antigen is a class of heritable antigenic substances present on the erythrocyte membrane. However, the role of blood group antigens in cancer prognosis is still largely unclear. In this study, we investigated the expression of 33 blood group antigen genes and their association with the prognosis of 30 types of cancers in 31,870 tumor tissue samples. Our results revealed that blood group antigens are abnormally expressed in a variety of cancers. The high expression of these antigen genes was mainly related to the activation of the epithelial-mesenchymal transition (EMT) pathway. High expression of seven antigen genes, i.e., FUT7, AQP1, P1, C4A, AQP3, KEL and DARC, were significantly associated with good OS (Overall Survival) in six types of cancers, while ten genes, i.e., AQP1, P1, C4A, AQP3, BSG, CD44, CD151, LU, FUT2, and SEMA7A, were associated with poor OS in three types of cancers. Kidney renal clear cell carcinoma (KIRC) is associated with the largest number (14 genes) of prognostic antigen genes, i.e., CD44, CD151, SEMA7A, FUT7, CR1, AQP1, GYPA, FUT3, FUT6, FUT1, SLC14A1, ERMAP, C4A, and B3GALT3. High expression of SEMA7A gene was significantly correlated with a poor prognosis of KIRC in this analysis but has not been reported previously. SEMA7A might be a putative biomarker for poor prognosis in KIRC. In conclusion, our analysis indicates that blood group antigens may play functional important roles in tumorigenesis, progression, and especially prognosis. These results provide data to support prognostic marker development and future clinical management.
The Antimicrobial Peptides Human β-Defensins Induce the Secretion of Angiogenin in Human Dermal Fibroblasts
Authors: Umehara Yoshie , Takahashi Miho , Yue Hainan , Trujillo-Paez Juan Valentin , Peng Ge , Nguyen Hai Le Thanh , Okumura Ko , Ogawa Hideoki , Niyonsaba François
Published: August 2022

The skin produces a plethora of antimicrobial peptides that not only show antimicrobial activities against pathogens but also exhibit various immunomodulatory functions. Human β-defensins (hBDs) are the most well-characterized skin-derived antimicrobial peptides and contribute to diverse biological processes, including cytokine production and the migration, proliferation, and differentiation of host cells. Additionally, hBD-3 was recently reported to promote wound healing and angiogenesis, by inducing the expression of various angiogenic factors and the migration and proliferation of fibroblasts. Angiogenin is one of the most potent angiogenic factors; however, the effects of hBDs on angiogenin production in fibroblasts remain unclear. Here, we investigated the effects of hBDs on the secretion of angiogenin by human dermal fibroblasts. Both in vitro and ex vivo studies demonstrated that hBD-1, hBD-2, hBD-3, and hBD-4 dose-dependently increased angiogenin production by fibroblasts. hBD-mediated angiogenin secretion involved the epidermal growth factor receptor (EGFR), Src family kinase, c-Jun N-terminal kinase (JNK), p38, and nuclear factor-kappa B (NF-κB) pathways, as evidenced by the inhibitory effects of specific inhibitors for these pathways. Indeed, we confirmed that hBDs induced the activation of the EGFR, Src, JNK, p38, and NF-κB pathways. This study identified a novel role of hBDs in angiogenesis, through the production of angiogenin, in addition to their antimicrobial activities and other immunomodulatory properties.
A Novel Cell-Based Model for a Rare Disease: The Tks4-KO Human Embryonic Stem Cell Line as a Frank-Ter Haar Syndrome Model System
Authors: László Loretta , Maczelka Hédi , Takács Tamás , Kurilla Anita , Tilajka Álmos , Buday László , Vas Virag , Apáti Ágota
Published: August 2022

Tyrosine kinase substrate with four SH3 domains (Tks4) scaffold protein plays roles in cell migration and podosome formation and regulates systemic mechanisms such as adult bone homeostasis and adipogenesis. Mutations in the Tks4 gene (SH3PXD2b) cause a rare developmental disorder called Frank-Ter Haar syndrome (FTHS), which leads to heart abnormalities, bone tissue defects, and reduced adiposity. We aimed to produce a human stem cell-based in vitro FTHS model system to study the effects of the loss of the Tks4 protein in different cell lineages and the accompanying effects on the cell signalome. To this end, we used CRISPR/Cas9 (clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR associated (Cas9)) to knock out the SH3PXD2b gene in the HUES9 human embryonic stem cell line (hESC), and we obtained stable homo- and heterozygous knock out clones for use in studying the potential regulatory roles of Tks4 protein in embryonic stem cell biology. Based on pluripotency marker measurements and spontaneous differentiation capacity assays, we concluded that the newly generated Tks4-KO HUES9 cells retained their embryonic stem cell characteristics. We propose that the Tks4-KO HUES9 cells could serve as a tool for further cell differentiation studies to investigate the involvement of Tks4 in the complex disorder FTHS. Moreover, we successfully differentiated all of the clones into mesenchymal stem cells (MSCs). The derived MSC cultures showed mesenchymal morphology and expressed MSC markers, although the expression levels of mesodermal and osteogenic marker genes were reduced, and several EMT (epithelial mesenchymal transition)-related features were altered in the Tks4-KO MSCs. Our results suggest that the loss of Tks4 leads to FTHS by altering cell lineage differentiation and cell maturation processes, rather than by regulating embryonic stem cell potential.
Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome
Authors: Xue Xiang , Li Xiaoli , Yao Jinmeng , Zhang Xue , Ren Xu , Xu Shan
Published: August 2022

Asherman’s Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the Wnt signaling pathway and the progression of AS after initial endometrial damage. Endometria with and without adhesion as well as from the intrauterine devices three months after the surgery were collected to compare the area of fibrosis. The area% of fibrosis did not vary significantly. Significantly higher expression of non-phosphorylated β-catenin, Wnt5a and Wnt7a was identified in the endometria with adhesion. The CD140b+CD146+ endometrial stem-like cells were present in the endometria with adhesion. Both Wnt5a and Wnt7a promoted stem cell proliferation. However, only Wnt7a preserved stem cell population by stimulating self-renewal. A rat endometrial injury model was established to investigate the effect of the activated Wnt/β-catenin signaling pathway on endometrial healing. We found that a transient activation of the Wnt/β-catenin signaling pathway promoted angiogenesis and increased the number of glands. In conclusion, transient activation of the Wnt/β-catenin signaling pathway during the acute endometrial damage may help the tissue regeneration, while prolonged activation may correlate to fibrosis formation.
Forest Biomass as a Promising Source of Bioactive Essential Oil and Phenolic Compounds for Alzheimer’s Disease Therapy
Authors: Moreira Patrícia , Matos Patrícia , Figueirinha Artur , Salgueiro Lígia , Batista Maria Teresa , Branco Pedro Costa , Cruz Maria Teresa , Pereira Cláudia Fragão
Published: August 2022

Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting elderly people worldwide. Currently, there are no effective treatments for AD able to prevent disease progression, highlighting the urgency of finding new therapeutic strategies to stop or delay this pathology. Several plants exhibit potential as source of safe and multi-target new therapeutic molecules for AD treatment. Meanwhile, Eucalyptus globulus extracts revealed important pharmacological activities, namely antioxidant and anti-inflammatory properties, which can contribute to the reported neuroprotective effects. This review summarizes the chemical composition of essential oil (EO) and phenolic extracts obtained from Eucalyptus globulus leaves, disclosing major compounds and their effects on AD-relevant pathological features, including deposition of amyloid-β (Aβ) in senile plaques and hyperphosphorylated tau in neurofibrillary tangles (NFTs), abnormalities in GABAergic, cholinergic and glutamatergic neurotransmission, inflammation, and oxidative stress. In general, 1,8-cineole is the major compound identified in EO, and ellagic acid, quercetin, and rutin were described as main compounds in phenolic extracts from Eucalyptus globulus leaves. EO and phenolic extracts, and especially their major compounds, were found to prevent several pathological cellular processes and to improve cognitive function in AD animal models. Therefore, Eucalyptus globulus leaves are a relevant source of biological active and safe molecules that could be used as raw material for nutraceuticals and plant-based medicinal products useful for AD prevention and treatment.
Soil and Soilless Tomato Cultivation Promote Different Microbial Communities That Provide New Models for Future Crop Interventions
Authors: Anzalone Alice , Mosca Alexandros , Dimaria Giulio , Nicotra Daniele , Tessitori Matilde , Privitera Grete Francesca , Pulvirenti Alfredo , Leonardi Cherubino , Catara Vittoria
Published: August 2022

The cultivation of soilless tomato in greenhouses has increased considerably, but little is known about the assembly of the root microbiome compared to plants grown in soil. To obtain such information, we constructed an assay in which we traced the bacterial and fungal communities by amplicon-based metagenomics during the cultivation chain from nursery to greenhouse. In the greenhouse, the plants were transplanted either into agricultural soil or into coconut fiber bags (soilless). At the phylum level, bacterial and fungal communities were primarily constituted in all microhabitats by Proteobacteria and Ascomycota, respectively. The results showed that the tomato rhizosphere microbiome was shaped by the substrate or soil in which the plants were grown. The microbiome was different particularly in terms of the bacterial communities. In agriculture, enrichment has been observed in putative biological control bacteria of the genera Pseudomonas and Bacillus and in potential phytopathogenic fungi. Overall, the study describes the different shaping of microbial communities in the two cultivation methods.
OsWRKY114 Inhibits ABA-Induced Susceptibility to Xanthomonas oryzae pv. oryzae in Rice
Authors: Son Seungmin , Im Jong Hee , Song Giha , Nam Suhyeon , Park Sang Ryeol
Published: August 2022

The phytohormone abscisic acid (ABA) regulates various aspects of plant growth, development, and stress responses. ABA suppresses innate immunity to Xanthomonas oryzae pv. oryzae (Xoo) in rice (Oryza sativa), but the identity of the underlying regulator is unknown. In this study, we revealed that OsWRKY114 is involved in the ABA response during Xoo infection. ABA-induced susceptibility to Xoo was reduced in OsWRKY114-overexpressing rice plants. OsWRKY114 attenuated the negative effect of ABA on salicylic acid-dependent immunity. Furthermore, OsWRKY114 decreased the transcript levels of ABA-associated genes involved in ABA response and biosynthesis. Moreover, the endogenous ABA level was lower in OsWRKY114-overexpressing plants than in the wild-type plants after Xoo inoculation. Taken together, our results suggest that OsWRKY114 is a negative regulator of ABA that confers susceptibility to Xoo in rice.
Salicylaldehyde Suppresses IgE-Mediated Activation of Mast Cells and Ameliorates Anaphylaxis in Mice
Authors: Ashikari Tsubasa , Hachisu Masakazu , Nagata Kazuki , Ando Daisuke , Iizuka Yuki , Ito Naoto , Ito Kandai , Ikeda Yuki , Matsubara Hiroki , Yashiro Takuya , Kasakura Kazumi , Nishiyama Chiharu
Published: August 2022

Mast cells (MCs) play key roles in IgE-mediated immunoresponses, including in the protection against parasitic infections and the onset and/or symptoms of allergic diseases. IgE-mediated activation induces MCs to release mediators, including histamine and leukotriene, as an early response, and to produce cytokines as a late phase response. Attempts have been made to identify novel antiallergic compounds from natural materials such as Chinese medicines and food ingredients. We herein screened approximately 60 compounds and identified salicylaldehyde, an aromatic aldehyde isolated from plant essential oils, as an inhibitor of the IgE-mediated activation of MCs. A degranulation assay, flow cytometric analyses, and enzyme-linked immunosorbent assays revealed that salicylaldehyde inhibited the IgE-mediated degranulation and cytokine expression of bone-marrow-derived MCs (BMMCs). The salicylaldehyde treatment reduced the surface expression level of FcεRI, the high affinity receptor for IgE, on BMMCs, and suppressed the IgE-induced phosphorylation of tyrosine residues in intercellular proteins, possibly Lyn, Syk, and Fyn, in BMMCs. We also examined the effects of salicylaldehyde in vivo using passive anaphylaxis mouse models and found that salicylaldehyde administration significantly enhanced the recovery of a reduced body temperature due to systemic anaphylaxis and markedly suppressed ear swelling, footpad swelling, and vascular permeability in cutaneous anaphylaxis.
Deletion of Meg8-DMR Enhances Migration and Invasion of MLTC-1 Depending on the CTCF Binding Sites
Authors: Han Xiao , He Hongjuan , Shao Lan , Cui Shuang , Yu Haoran , Zhang Ximeijia , Wu Qiong
Published: August 2022

The Dlk1-Dio3 imprinted domain on mouse chromosome 12 contains three well-characterized paternally methylated differentially methylated regions (DMRs): IG-DMR, Gtl2-DMR, and Dlk1-DMR. These DMRs control the expression of many genes involved in embryonic development, inherited diseases, and human cancer in this domain. The first maternal methylation DMR discovered in this domain was the Meg8-DMR, the targets and biological function of which are still unknown. Here, using an enhancer-blocking assay, we first dissected the functional parts of the Meg8-DMR and showed that its insulator activity is dependent on the CCCTC-binding factor (CTCF) in MLTC-1. Results from RNA-seq showed that the deletion of the Meg8-DMR and its compartment CTCF binding sites, but not GGCG repeats, lead to the downregulation of numerous genes on chromosome 12, in particular the drastically reduced expression of Dlk1 and Rtl1 in the Dlk1-Dio3 domain, while differentially expressed genes are enriched in the MAPK pathway. In vitro assays revealed that the deletion of the Meg8-DMR and CTCF binding sites enhances cell migration and invasion by decreasing Dlk1 and activating the Notch1-Rhoc-MAPK/ERK pathway. These findings enhance research into gene regulation in the Dlk1-Dio3 domain by indicating that the Meg8-DMR functions as a long-range regulatory element which is dependent on CTCF binding sites and affects multiple genes in this domain.
Ketogenic and Low FODMAP Diet in Therapeutic Management of a Young Autistic Patient with Epilepsy and Dysmetabolism Poorly Responsive to Therapies: Clinical Response and Effects of Intestinal Microbiota
Authors: Bertuccioli Alexander , Cardinali Marco , Di Pierro Francesco , Zonzini Giordano Bruno , Matera Maria Rosaria
Published: August 2022

Autism spectrum disorder (ASD) is often associated with several intestinal and/or metabolic disorders as well as neurological manifestations such as epilepsy (ASD-E). Those presenting these neuropathological conditions share common aspects in terms of gut microbiota composition. The use of microbiota intervention strategies may be an approach to consider in the management of these cases. We describe the case of a 17-year-old girl affected by ASD, reduced growth, neurological development delay, mutations in the PGM1 and EEF1A2 genes (in the absence of clinically manifested disease) and, intestinal disorders such as abdominal pain and diarrhea associated with weight loss. As she demonstrated poor responsiveness to the therapies provided, we attempted two specific dietary patterns: a ketogenic diet, followed by a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, with the aim of improving her neurological, metabolic, and intestinal symptoms through modulation of the gut microbiota’s composition. The ketogenic diet (KD) provided a reduction in Firmicutes, Bacteroidetes, and Proteobacteria. Although her intestinal symptoms improved, KD was poorly tolerated. On the other hand, the passage to a low FODMAPs diet produced a significant improvement in all neurological, intestinal, and metabolic symptoms and was well-tolerated. The following gut microbiota analysis showed reductions in Actinobacteria, Firmicutes, Lactobacilli, and Bifidobacteria. The alpha biodiversity was consistently increased and the Firmicutes/Bacteroidetes ratio decreased, reducing the extent of fermentative dysbiosis. Gut microbiota could be a therapeutic target to improve ASD-related symptoms. Further studies are needed to better understand the correlation between gut microbiota composition and ASD, and its possible involvement in the physiopathology of ASD.
Facile Microwave Assisted Synthesis of Silver Nanostars for Ultrasensitive Detection of Biological Analytes by SERS
Authors: Revnic Radu Nicolae , Știufiuc Gabriela Fabiola , Toma Valentin , Onaciu Anca , Moldovan Alin , Țigu Adrian Bogdan , Fischer-Fodor Eva , Tetean Romulus , Burzo Emil , Știufiuc Rareș Ionuț
Published: August 2022

We report a very simple, rapid and reproducible method for the fabrication of anisotropic silver nanostars (AgNS) that can be successfully used as highly efficient SERS substrates for different bioanalytes, even in the case of a near-infra-red (NIR) excitation laser. The nanostars have been synthesized using the chemical reduction of Ag+ ions by trisodium citrate. This is the first research reporting the synthesis of AgNS using only trisodium citrate as a reducing and stabilizing agent. The key elements of this original synthesis procedure are rapid hydrothermal synthesis of silver nanostars followed by a cooling down procedure by immersion in a water bath. The synthesis was performed in a sealed bottom flask homogenously heated and brought to a boil in a microwave oven. After 60 s, the colloidal solution was cooled down to room temperature by immersion in a water bath at 35 °C. The as-synthesized AgNS were washed by centrifugation and used for SERS analysis of test molecules (methylene blue) as well as biological analytes: pharmaceutical compounds with various Raman cross sections (doxorubicin, atenolol & metoprolol), cell lysates and amino acids (methionine & cysteine). UV-Vis absorption spectroscopy, (Scanning) Transmission Electron Microscopy ((S)TEM) and Atomic Force Microscopy (AFM) have been employed for investigating nanostars’ physical properties.
Design of a Fuzzy Logic Controller for the Double Pendulum Inverted on a Cart
Authors: Maraslidis George S. , Kottas Theodore L. , Tsipouras Markos G. , Fragulis George F.
Published: August 2022

The double-inverted pendulum (DIP) constitutes a classical problem in mechanics, whereas the control methods for stabilizing around the equilibrium positions represent the classic standards of control system theory and various control methods in robotics. For instance, it functions as a typical model for the calculation and stability of walking robots. The present study depicts the controlling of a double-inverted pendulum (DIP) on a cart using a fuzzy logic controller (FLC). A linear-quadratic controller (LQR) was used as a benchmark to assess the effectiveness of our method, and the results showed that the proposed FLC can perform significantly better than the LQR under a variety of initial system conditions. This performance is considered very important when the reduction of the peak system output is concerned. The proposed controller equilibration and velocity tracking performance were explored through simulation, and the results obtained point to the validity of the control method.