bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Management Interventions for Adults Living with Type II Diabetes to Improve Patient-Important Outcomes: An Evidence Map
Authors: Song Yang , Beltran Puerta Jessica , Medina-Aedo Melixa , Canelo-Aybar Carlos , Valli Claudia , Ballester Marta , Rocha Claudio , Garcia Montserrat León , Salas-Gama Karla , Kaloteraki Chrysoula , Santero Marilina , Niño de Guzmán Ena , Spoiala Cristina , Gurung Pema , Willemen Fabienne , Cools Iza , Bleeker Julia , Poortvliet Rune , Laure Tajda , Gaag Marieke van der , Pacheco-Barrios Kevin , Zafra-Tanaka Jessica , Mavridis Dimitris , Angeliki Veroniki Areti , Zevgiti Stella , Seitidis Georgios , Alonso-Coello Pablo , Groene Oliver , González-González Ana Isabel , Sunol Rosa , Orrego Carola , Heijmans Monique
Published: December 2023

Self-management interventions (SMIs) may be promising in the treatment of Diabetes Mellitus Type 2 (T2DM). However, accurate comparisons of their relative effectiveness are challenging, partly due to a lack of clarity and detail regarding the intervention content being evaluated. This study summarizes intervention components and characteristics in randomized controlled trials (RCTs) related to T2DM using a taxonomy for SMIs as a framework and identifies components that are insufficiently incorporated into the design of the intervention or insufficiently reported. Following evidence mapping methodology, we searched MEDLINE, CINAHL, Embase, Cochrane, and PsycINFO from 2010 to 2018 for randomized controlled trials (RCTs) on SMIs for T2DM. We used the terms ‘self-management’, ‘adult’ and ‘T2DM’ for content. For data extraction, we used an online platform based on the taxonomy for SMIs. Two independent reviewers assessed eligible references; one reviewer extracted data, and a second checked accuracy. We identified 665 RCTs for SMIs (34% US, 21% Europe) including 164,437 (median 123, range 10–14,559) adults with T2DM. SMIs highly differed in design and content, and characteristics such as mode of delivery, intensity, location and providers involved were poorly described. The majority of interventions aimed to improve clinical outcomes like HbA1c (83%), weight (53%), lipid profile (45%) or blood pressure (42%); 27% (also) targeted quality of life. Improved knowledge, health literacy, patient activation or satisfaction with care were hardly used as outcomes (<16%). SMIs most often used education (98%), self-monitoring (56%), goal-setting (48%) and skills training (42%) to improve outcomes. Management of emotions (17%) and shared decision-making (5%) were almost never mentioned. Although diabetes is highly prevalent in some minority groups, in only 13% of the SMIs, these groups were included. Our findings highlight the large heterogeneity that exists in the design of SMIs for T2DM and the way studies are reported, making accurate comparisons of their relative effectiveness challenging. In addition, SMIs pay limited attention to outcomes other than clinical, despite the importance attached to these outcomes by patients. More standardized and streamlined research is needed to better understand the effectiveness and cost-effectiveness of SMIs of T2DM and benefit patient care.
Using the Expanded Andersen Model to Determine Factors Associated with Mexican Adolescents’ Utilization of Dental Services
Authors: Galicia-Diez Barroso Daniela , Abeijón-Malvaez Luis David , Moreno Altamirano Gloria Alejandra , Irigoyen-Camacho María Esther Josefina , Finlayson Tracy L. , Borges-Yáñez Socorro Aída
Published: December 2023

Many factors contribute as facilitators of or barriers to adolescents’ use of dental services. Guided by the expanded Andersen model for dental service utilization, the aim of this study was to identify factors associated with the use of dental services among adolescents ages 12–16 in south Mexico City (n = 247). Adolescents answered a questionnaire on predisposing factors (age and gender), enabling factors (socioeconomic status, oral health support, parental years of education, and previous dental treatments), and psychosocial and behavioral factors (attitudes towards oral health; knowledge of gingivitis; alcohol, drug, and tobacco use; and depressive symptoms), and they underwent a visual clinical exam to determine their need factors (caries and gingivitis). The adolescents reported whether or not they had attended a dental visit in the last year for any reason. Multiple logistic regression was used to evaluate these factors. Having oral health support increased the odds of a dental visit by 2.69 (95% CI = 1.24–5.84). Previous dental treatment increased the odds of a dental visit by 2.25 (95% CI = 1.12–4.52). The presence of depressive symptoms reduced the odds of a dental visit by 4% (OR = 0.96, 95% CI = 0.94–0.99). Enabling and psychosocial factors of oral health support and previous dental treatment were positively associated with the utilization of dental services, while depressive symptoms were negatively associated.
Modeling and Simulating Rainfall and Temperature Using Rotated Bivariate Copulas
Authors: De Luca Giovanni , Rivieccio Giorgia
Published: December 2023

Climate change is a significant environmental challenge that affects water resources, agriculture, health, and other aspects of human life. Bivariate modeling is a statistical method used to analyze the relationship between variables such as rainfall and temperature. The Pearson correlation coefficient, Kendall’s tau, or Spearman’s rank correlation are some measures used for bivariate modeling. However, copula functions can describe the dependence structure between two or more variables and can be effectively used to describe the relationship between rainfall and temperature. Despite the literature on bivariate modeling of rainfalls and temperature being extensive, finding flexible and sophisticated bivariate models is sometimes difficult. In this paper, we use rotated copula functions that can arrange any type of dependence that is empirically detected, especially negative dependence. The methodology is applied to an Italian municipality’s bivariate daily time series of rainfall and temperature. The estimated rotated copula is significant and, therefore, can be used for simulating the effects of extreme events.
Identifying Challenges and Solutions to Early Childhood Education and the Perceived Importance of Outdoor Time: A Mixed Methods Approach in a Socioeconomically Diverse Population
Authors: Butcher Maria B. , Haakenstad Magdalena K. , Noonan Carolyn J. , Fyfe-Johnson Amber L.
Published: December 2023

The current literature supports the positive relationship between time in nature and the improvement in children’s health and identifies early childhood education (ECE) settings as an avenue for intervention. Unfortunately, access to both outdoor time and ECE opportunities is lower in communities facing economic adversity. Efforts are needed to identify the best approaches to incorporate outdoor time in ECE settings, especially in communities facing socioeconomic adversity. The objectives of this research were to use a mixed methods approach to identify (1) barriers and solutions to the integration of outdoor time in ECE settings, (2) if outdoor time is a priority in ECE settings compared to other ECE priorities, and (3) how socioeconomic status influences ECE priorities and barriers for outdoor time, and health outcomes. Fourteen focus groups were conducted (n = 50) in the United States (US) with participants from three stakeholder groups: outdoor educators, parents of children attending outdoor preschool, and community members with children. Participants completed a survey (n = 49) to evaluate demographics, views on ECE and outdoor time, and health characteristics. Exploratory analyses of F as an effect modifier were conducted. The survey results showed that parents prioritized social and emotional learning and outdoor time when selecting an ECE setting for their child. The barriers identified include financial challenges and the limited availability of ECE programs. The solutions discussed included increased availability and financial support. Low income was correlated with higher rates of anxiety and increased outdoor time was a potential protective factor. These insights inform interventions to enhance outdoor time in ECE settings, with the goal of reducing disparities and promoting children’s overall health.
Introduction to this Special Issue on New Thinking on Psychological Health: Find Purpose and Meaning in Life
Authors: Ryff Carol D. , Soren Andrew
Published: December 2023

As illustrated by the articles in this Special Issue [1,2], research on meaning and purpose in life has grown exponentially in recent years [...]
Do MD&A Risk Disclosures Reduce Stock Price Crash Risk? Evidence from China
Authors: Su Fei , Zhai Lili , Liu Jianmei
Published: December 2023

This study examines whether and how risk disclosures in Management Discussion and Analysis (MD&A) affected the stock price crash risk of China’s publicly listed firms over the period of 2017–2021. The empirical results show that risk disclosures within the MD&A section are significantly and negatively associated with the future stock price crash risk, even after controlling for a broad set of well-known factors of crash risk. Additional tests revealed that the impact of MD&A risk disclosures on the stock price crash risk is accentuated when the MD&A disclosure contains more incremental information. The negative association between MD&A risk disclosures and stock price crash risk is also more pronounced for firms with poorer information environments, for firms with weaker external monitoring, and for firms with more investor attention. Our findings are robust to alternative measures of the stock price crash risk, controlling for firm-fixed effects and endogeneity issues, and excluding certain samples. The results indicate that MD&A risk disclosures could help alleviate information asymmetry and mitigate stock price crash risk.
What Drives the Spatial Heterogeneity of Urban Leisure Activity Participation? A Multisource Big Data-Based Metrics in Nanjing, China
Authors: Liu Shaojun , Chen Xiawei , Zhang Fengji , Liu Yiyan , Ge Junlian
Published: December 2023

With the rapid pace of urbanization, enhancing the quality of life has become an urgent demand for the general public in both developed and developing countries. This study addresses the pressing need to understand the spatial distribution and underlying mechanisms of urban leisure activity participation. To achieve this, we propose a novel methodological framework that integrates diverse big data sources, including mobile phone signaling data, urban geospatial data, and web-crawled data. By applying this framework to the urban area of Nanjing, our study reveals both the temporal and spatial patterns of urban leisure activity participation in the city. Notably, leisure activity participation is significantly higher on weekends, with distinctive daily peaks. Moreover, we identify spatial heterogeneity in leisure activity participation across the study area. Leveraging the OLS regression model, we design and quantify a comprehensive set of 12 internal and external indicators to explore the formation mechanisms of leisure participation for different leisure activity types. Our findings offer valuable guidance for urban planners and policymakers to optimize the allocation of resources, enhance urban street environments, and develop leisure resources in a rational and inclusive manner. Ultimately, this study contributes to the ongoing efforts to improve the quality of urban life and foster vibrant and sustainable cities.
Quantification of Antiphospholipid Antibodies: The Importance of Using an Appropriate Methodology for Each Clinical Profile
Authors: Cabrera-Marante Oscar , Garcinuño Sara , Pleguezuelo Daniel Enrique , Gil-Etayo Francisco J. , Tenica Iulian , Rodríguez de Frías Edgard , Zafra Denis , Castro Nerea , Paz-Artal Estela , Serrano Antonio , Serrano Manuel
Published: December 2023

The presence of antiphospholipid antibodies (aPLs) is associated with antiphospholipid syndrome (APS), characterized by thrombosis and obstetric morbidity. aPLs included in APS classification criteria are lupus anticoagulant, anti-cardiolipin and anti-beta-2-glycoprotein-I of IgG or IgM isotypes. Enzyme-linked immunosorbent assay is the most used diagnostic technique to determine aPLs. Recently, new automated technologies mainly based in antigen-coated beads have been developed. The aim is to compare a fluorescence enzyme immunoassay (M1) and an antigen-coated bead assay (M2) in obstetric and thrombotic APS patients. All samples from the first 1020 patients received in the Immune Service Laboratory (Hospital 12 de Octubre) during the recruitment period, without exclusions, were analysed for aPLs. The weighted kappa for both methods in all the patients was 0.39 (0.30–0.47). Agreement increased to 0.56 (0.38–0.73) in patients with autoimmune disease. Sensitivity and specificity obtained for M1 were 17.1% and 89.3%, respectively, and 12.7% and 91.4% for M2. The sensibility and specificity of IgG isotypes were higher than the IgM ones. Regarding obstetric patients, M1 obtained significant diagnostic performance and had more sensitivity 23.75 (14.95–34.58) compared to M2 12.50 (6.16–21.79). In conclusion, clinical suspicion-based method selection for aPLs should be considered. To identify obstetric APS patients, solid phase methods remain more preferable.
Identification and Functional Analysis of an Epsilon Class Glutathione S-Transferase Gene Associated with α-Pinene Adaptation in Monochamus alternatus
Authors: Xue Mingyu , Xia Xiaohong , Deng Yadi , Teng Fei , Zhao Shiyue , Li Hui , Hao Dejun , Chen Wei-Yi
Published: December 2023

Alpha-pinene is one of the main defensive components in conifers. Monochamus alternatus (Coleoptera: Cerambycidae), a wood borer feeding on Pinaceae plants, relies on its detoxifying enzymes to resist the defensive terpenoids. Here, we assayed the peroxide level and GST activity of M. alternatus larvae treated with different concentrations of α-pinene. Meanwhile, a gst gene (MaGSTe3) was isolated and analyzed. We determined its expression level and verified its function. The results showed that α-pinene treatment led to membrane lipid peroxidation and thus increased the GST activity. Expression of MaGSTe3 was significantly upregulated in guts following exposure to α-pinene, which has a similar pattern with the malonaldehyde level. In vitro expression and disk diffusion assay showed that the MaGSTe3 protein had high antioxidant capacity. However, RNAi treatment of MaGSTe3 did not reduce the hydrogen peroxide and malonaldehyde levels, while GST activity was significantly reduced. These results suggested MaGSTe3 takes part in α-pinene adaptation, but it does not play a great role in the resistance of M. alternatus larvae to α-pinene.
Sex-Chromosome-Related Dimorphism in Steroidogenic Enzymes and Androgen Receptor in Response to Testosterone Treatment: An In Vitro Study on Human Primary Skeletal Muscle Cells
Authors: Di Luigi Luigi , Antinozzi Cristina , Duranti Guglielmo , Dimauro Ivan , Sgrò Paolo
Published: December 2023

Gender-related methodology in biomedical sciences receives considerable attention, with numerous studies highlighting biological differences between cisgender males and females. These differences influence the clinical symptoms of various diseases and impact therapeutic approaches. In this in vitro study, we investigate the potential role of sex-chromosome-related dimorphism on steroidogenic enzymes, androgen receptor (AR) expression, and cellular translocation in primary human skeletal muscle cells before and after exposure to testosterone. We analyzed 46XY and 46XX cells for 17β-hydroxysteroid dehydrogenase (17β-HSD), 5α-reductase (5α-R2), aromatase (Cyp-19), and AR gene expression. We also compared AR expression and intracellular translocation after increasing exposure to testosterone. At baseline, we observed higher mRNA expression for 5α-R2 and AR in 46XY cells and higher Cyp-19 mRNA expression in 46XX cells. Following testosterone exposure, we observed an increase in AR expression and translocation in 46XX cells, even at the lowest dose of 0.5 nM, while significant changes in 46XY cells were observed only from 10 nM. Our in vitro results demonstrate that the diverse sex chromosome assets reflect important differences in muscle steroidogenesis. They support the concept that chromosomal disparities between males and females, even in vitro, lead to pivotal variations in cellular physiology and response. This understanding represents a crucial starting point in gender medicine, ensuring a precise approach in clinical practice, sports, and exercise settings and facilitating the translation of in vitro data to in vivo applicability.
Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors
Authors: Jovanović Aleksa , Tošić Nataša , Marjanović Irena , Komazec Jovana , Zukić Branka , Nikitović Marina , Ilić Rosanda , Grujičić Danica , Janić Dragana , Pavlović Sonja
Published: December 2023

Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an “in-house” gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine.
Bacterial Virus Forcing of Bacterial O-Antigen Shields: Lessons from Coliphages
Authors: Letarov Andrey V.
Published: December 2023

In most Gram-negative bacteria, outer membrane (OM) lipopolysaccharide (LPS) molecules carry long polysaccharide chains known as the O antigens or O polysaccharides (OPS). The OPS structure varies highly from strain to strain, with more than 188 O serotypes described in E. coli. Although many bacteriophages recognize OPS as their primary receptors, these molecules can also screen OM proteins and other OM surface receptors from direct interaction with phage receptor-binding proteins (RBP). In this review, I analyze the body of evidence indicating that most of the E. coli OPS types robustly shield cells completely, preventing phage access to the OM surface. This shield not only blocks virulent phages but also restricts the acquisition of prophages. The available data suggest that OPS-mediated OM shielding is not merely one of many mechanisms of bacterial resistance to phages. Rather, it is an omnipresent factor significantly affecting the ecology, phage–host co-evolution and other related processes in E. coli and probably in many other species of Gram-negative bacteria. The phages, in turn, evolved multiple mechanisms to break through the OPS layer. These mechanisms rely on the phage RBPs recognizing the OPS or on using alternative receptors exposed above the OPS layer. The data allow one to forward the interpretation that, regardless of the type of receptors used, primary receptor recognition is always followed by the generation of a mechanical force driving the phage tail through the OPS layer. This force may be created by molecular motors of enzymatically active tail spikes or by virion structural re-arrangements at the moment of infection.
The Molecular Aspects of Functional Activity of Macrophage-Activating Factor GcMAF
Authors: Kirikovich Svetlana S. , Levites Evgeniy V. , Proskurina Anastasia S. , Ritter Genrikh S. , Peltek Sergey E. , Vasilieva Asya R. , Ruzanova Vera S. , Dolgova Evgeniya V. , Oshihmina Sofya G. , Sysoev Alexandr V. , Koleno Danil I. , Danilenko Elena D. , Taranov Oleg S. , Ostanin Alexandr A. , Chernykh Elena R. , Kolchanov Nikolay A. , Bogachev Sergey S.
Published: December 2023

Group-specific component macrophage-activating factor (GcMAF) is the vitamin D3-binding protein (DBP) deglycosylated at Thr420. The protein is believed to exhibit a wide range of therapeutic properties associated with the activation of macrophagal immunity. An original method for GcMAF production, DBP conversion to GcMAF, and the analysis of the activating potency of GcMAF was developed in this study. Data unveiling the molecular causes of macrophage activation were obtained. GcMAF was found to interact with three CLEC10A derivatives having molecular weights of 29 kDa, 63 kDa, and 65 kDa. GcMAF interacts with high-molecular-weight derivatives via Ca2+-dependent receptor engagement. Binding to the 65 kDa or 63 kDa derivative determines the pro- and anti-inflammatory direction of cytokine mRNA expression: 65 kDa—pro-inflammatory (TNF-α, IL-1β) and 63 kDa—anti-inflammatory (TGF-β, IL-10). No Ca2+ ions are required for the interaction with the canonical 29 kDa CLEC10A. Both forms, DBP protein and GcMAF, bind to the 29 kDa CLEC10A. This interaction is characterized by the stochastic mRNA synthesis of the analyzed cytokines. Ex vivo experiments have demonstrated that when there is an excess of GcMAF ligand, CLEC10A forms aggregate, and the mRNA synthesis of analyzed cytokines is inhibited. A schematic diagram of the presumable mechanism of interaction between the CLEC10A derivatives and GcMAF is provided. The principles and elements of standardizing the GcMAF preparation are elaborated.
Can CD133 Be Regarded as a Prognostic Biomarker in Oncology: Pros and Cons
Authors: Gisina Alisa , Kim Yan , Yarygin Konstantin , Lupatov Alexey
Published: December 2023

The CD133 cell membrane glycoprotein, also termed prominin-1, is expressed on some of the tumor cells of both solid and blood malignancies. The CD133-positive tumor cells were shown to exhibit higher proliferative activity, greater chemo- and radioresistance, and enhanced tumorigenicity compared to their CD133-negative counterparts. For this reason, CD133 is regarded as a potential prognostic biomarker in oncology. The CD133-positive cells are related to the cancer stem cell subpopulation in many types of cancer. Recent studies demonstrated the involvement of CD133 in the regulation of proliferation, autophagy, and apoptosis in cancer cells. There is also evidence of its participation in the epithelial–mesenchymal transition associated with tumor progression. For a number of malignant tumor types, high CD133 expression is associated with poor prognosis, and the prognostic significance of CD133 has been confirmed in a number of meta-analyses. However, some published papers suggest that CD133 has no prognostic significance or even demonstrate a certain correlation between high CD133 levels and a positive prognosis. This review summarizes and discusses the existing evidence for and against the prognostic significance of CD133 in cancer. We also consider possible reasons for conflicting findings from the studies of the clinical significance of CD133.
Prioritization of Fluorescence In Situ Hybridization (FISH) Probes for Differentiating Primary Sites of Neuroendocrine Tumors with Machine Learning
Authors: Pietan Lucas , Vaughn Hayley , Howe James R. , Bellizzi Andrew M. , Smith Brian J. , Darbro Benjamin , Braun Terry , Casavant Thomas
Published: December 2023

Determining neuroendocrine tumor (NET) primary sites is pivotal for patient care as pancreatic NETs (pNETs) and small bowel NETs (sbNETs) have distinct treatment approaches. The diagnostic power and prioritization of fluorescence in situ hybridization (FISH) assay biomarkers for establishing primary sites has not been thoroughly investigated using machine learning (ML) techniques. We trained ML models on FISH assay metrics from 85 sbNET and 59 pNET samples for primary site prediction. Exploring multiple methods for imputing missing data, the impute-by-median dataset coupled with a support vector machine model achieved the highest classification accuracy of 93.1% on a held-out test set, with the top importance variables originating from the ERBB2 FISH probe. Due to the greater interpretability of decision tree (DT) models, we fit DT models to ten dataset splits, achieving optimal performance with k-nearest neighbor (KNN) imputed data and a transformation to single categorical biomarker probe variables, with a mean accuracy of 81.4%, on held-out test sets. ERBB2 and MET variables ranked as top-performing features in 9 of 10 DT models and the full dataset model. These findings offer probabilistic guidance for FISH testing, emphasizing the prioritization of the ERBB2, SMAD4, and CDKN2A FISH probes in diagnosing NET primary sites.
The Profiling of 179 miRNA Expression in Serum from Limb Girdle Muscular Dystrophy Patients and Healthy Controls
Authors: Magri Francesca , Napoli Laura , Ripolone Michela , Ciscato Patrizia , Moggio Maurizio , Corti Stefania , Comi Giacomo Pietro , Sciacco Monica , Zanotti Simona
Published: December 2023

Limb girdle muscular dystrophies (LGMDs) are a group of genetically inherited neuromuscular diseases with a very variable clinical presentation and overlapping traits. Over the last few years there has been an increasing interest in the use of non-invasive circulating biomarkers to monitor disease progression and to evaluate the efficacy of therapeutic approaches. Our aim was to identify the miRNA signature with potential value for LGMD patient screening and stratification. Using miRCURY LNA miRNA qPCR Serum/Plasma Panel, we analyzed 179 miRNAs from 16 patients, divided in four pools based on their genetic diagnosis, and from healthy controls. The miRNAs analysis showed a total of 107 dysregulated miRNAs in LGMD patients when compared to the healthy controls. After filtering via skeletal tissue expression and gene/pathways target analysis, the number of dysregulated miRNAs drastically reduced. Six selected miRNAs—let-7f-5p (in LGMDR1), miR-20a-5p (in LGMDR2), miR-130b-5p, miR-378a-5p (both in LGMDR3), miR-376c-3p and miR-382-5p (both in LGMDR4)—whose expression was significantly lower compared to controls in the different LGMD pools, were further investigated. The bioinformatic analysis of the target genes in each selected miRNA revealed ECM–receptor interaction and TGF-beta signaling as the most involved pathways. The correlation analysis showed a good correlation of let-7f-5p with fibrosis and with the cross sectional area of type I and type II fibers, while miR-130b-5p showed a good correlation with the age of onset of the disease. The receiver operating characteristic curves showed how single miRNAs were able to discriminate a specific group of LGMD patients and how the combination of six miRNAs was able to discriminate LGMD patients from controls.
High-Performance Hydrogen-Selective Pd-Ag Membranes Modified with Pd-Pt Nanoparticles for Use in Steam Reforming Membrane Reactors
Authors: Petriev Iliya , Pushankina Polina , Andreev Georgy , Ivanin Sergei , Dzhimak Stepan
Published: December 2023

A unique method for synthesizing a surface modifier for metallic hydrogen permeable membranes based on non-classic bimetallic pentagonally structured Pd-Pt nanoparticles was developed. It was found that nanoparticles had unique hollow structures. This significantly reduced the cost of their production due to the economical use of metal. According to the results of electrochemical studies, a synthesized bimetallic Pd-Pt/Pd-Ag modifier showed excellent catalytic activity (up to 60.72 mA cm−2), long-term stability, and resistance to COads poisoning in the alkaline oxidation reaction of methanol. The membrane with the pentagonally structured Pd-Pt/Pd-Ag modifier showed the highest hydrogen permeation flux density, up to 27.3 mmol s−1 m−2. The obtained hydrogen flux density was two times higher than that for membranes with a classic Pdblack/Pd-Ag modifier and an order of magnitude higher than that for an unmodified membrane. Since the rate of transcrystalline hydrogen transfer through a membrane increased, while the speed of transfer through defects remained unchanged, a one and a half times rise in selectivity of the developed Pd-Pt/Pd-Ag membranes was recorded, and it amounted to 3514. The achieved results were due to both the synergistic effect of the combination of Pd and Pt metals in the modifier composition and the large number of available catalytically active centers, which were present as a result of non-classic morphology with high-index facets. The specific faceting, defect structure, and unusual properties provide great opportunities for the application of nanoparticles in the areas of membrane reactors, electrocatalysis, and the petrochemical and hydrogen industries.
Recent Advances in the HPPH-Based Third-Generation Photodynamic Agents in Biomedical Applications
Authors: Fan Lixiao , Jiang Zheng , Xiong Yu , Xu Zepeng , Yang Xin , Gu Deying , Ainiwaer Mailudan , Li Leyu , Liu Jun , Chen Fei
Published: December 2023

Photodynamic therapy has emerged as a recognized anti-tumor treatment involving three fundamental elements: photosensitizers, light, and reactive oxygen species. Enhancing the effectiveness of photosensitizers remains the primary avenue for improving the biological therapeutic outcomes of PDT. Through three generations of development, HPPH is a 2-(1-hexyloxyethyl)-2-devinyl derivative of pyropheophorbide-α, representing a second-generation photosensitizer already undergoing clinical trials for various tumors. The evolution toward third-generation photosensitizers based on HPPH involves structural modifications for multimodal applications and the combination of multifunctional compounds, leading to improved imaging localization and superior anti-tumor effects. While research into third-generation HPPH is beneficial for advancing PDT treatment, equal attention should also be directed toward the other two essential elements and personalized diagnosis and treatment methodologies.
Polymer Biocompositions and Nanobiocomposites Based on P3HB with Polyurethane and Montmorillonite
Authors: Krzykowska Beata , Czerniecka-Kubicka Anna , Białkowska Anita , Bakar Mohamed , Hęclik Karol , Dobrowolski Lucjan , Longosz Michał , Zarzyka Iwona
Published: December 2023

Due to the growing interest in biopolymers, biosynthesizable and biodegradable polymers currently occupy a special place. Unfortunately, the properties of native biopolymers make them not good enough for use as substitutes for conventional polymers. Therefore, attempts are being made to modify their properties. In this work, in order to improve the properties of the poly(3-hydroxybutyrate) (P3HB) biopolymer, linear aliphatic polyurethane (PU) based on 1,4-butanediol (BD) and hexamethylene 1,6-diisocyanate (HDI) was used. The conducted studies on the effect of the amount of PU used (5, 10, 15 and 20 m/m%) showed an improvement in the thermal properties of the prepared polymer blends. As part of the tested mechanical properties of the new polymer blends, we noted the desired increase in the tensile strength, and the impact strength showed a decrease in hardness, in particular at the presence of 5 m/m% PU. Therefore, for further improvement, hybrid nanobiocomposites with 5 m/m% PU and organically modified montmorillonite (MMT) (Cloisite 30®B) were produced. The nanoadditive was used in a typical amount of 1–3 m/m%. It was found that the obtained nanobiocomposites containing the smallest amount of nanofillers, i.e., 1 m/m% Cloisite®30B, exhibited the best mechanical and thermal properties.
Macrophage Polarization: Learning to Manage It 2.0
Authors: Lampiasi Nadia
Published: December 2023

The aim of this Special Issue is to investigate macrophages’ high plasticity and ability to differentiate/polarize in response to numerous stimuli in the context of diseases, infections, and biomolecules exposition (immunomodulators) [...]
Surface Modification of Polylactic Acid Bioscaffold Fabricated via 3D Printing for Craniofacial Bone Tissue Engineering
Authors: Liu Yao-Chang , Lo Guan-Jie , Shyu Victor Bong-Hang , Tsai Chia-Hsuan , Chen Chih-Hao , Chen Chien-Tzung
Published: December 2023

Bone tissue engineering is a promising solution for advanced bone defect reconstruction after severe trauma. In bone tissue engineering, scaffolds in three-dimensional (3D) structures are crucial components for cell growth, migration, and infiltration. The three-dimensional printing technique is well suited to manufacturing scaffolds since it can fabricate scaffolds with highly complex designs under good internal structural control. In the current study, the 3D printing technique was utilized to produce polylactic acid (PLA) scaffolds. BMSCs were seeded onto selected scaffolds, either hydrogel-mixed or not, and cultivated in vitro to investigate the osteogenic potential in each group. After osteogenic incubation in vitro, BMSC-seeded scaffolds were implanted onto rat cranium defects, and bone regeneration was observed after 12 weeks. Our results demonstrated that BMSCs were able to seed onto 3D-printed PLA scaffolds under high-resolution observation. Real-time PCR analysis showed their osteogenic ability, which could be further improved after BMSCs were mixed with hydrogel. The in vivo study showed significantly increased bone regeneration when rats’ cranium defects were implanted with a hydrogel-mixed BMSC-seeded scaffold compared to the control and those without cell or hydrogel groups. This study showed that 3D-printed PLA scaffolds are a feasible option for BMSC cultivation and osteogenic differentiation. After mixing with hydrogel, BMSC-seeded 3D-printed scaffolds can facilitate bone regeneration.
Drosophila melanogaster Transcriptome Response to Different Wolbachia Strains
Authors: Gruntenko Nataly E. , Deryuzhenko Maksim A. , Andreenkova Olga V. , Shishkina Olga D. , Bobrovskikh Margarita A. , Shatskaya Natalja V. , Vasiliev Gennady V.
Published: December 2023

Wolbachia is a maternally inherited, intercellular bacterial symbiont of insects and some other invertebrates. Here, we investigated the effect of two different Wolbachia strains, differing in a large chromosomal inversion, on the differential expression of genes in D. melanogaster females. We revealed significant changes in the transcriptome of the infected flies compared to the uninfected ones, as well as in the transcriptome of flies infected with the Wolbachia strain, wMelPlus, compared to flies infected with the wMelCS112 strain. We linked differentially expressed genes (DEGs) from two pairwise comparisons, “uninfected—wMelPlus-infected” and “uninfected—wMelCS112-infected”, into two gene networks, in which the following functional groups were designated: “Proteolysis”, “Carbohydrate transport and metabolism”, “Oxidation–reduction process”, “Embryogenesis”, “Transmembrane transport”, “Response to stress” and “Alkaline phosphatases”. Our data emphasized similarities and differences between infections by different strains under study: a wMelPlus infection results in more than double the number of upregulated DEGs and half the number of downregulated DEGs compared to a wMelCS112 infection. Thus, we demonstrated that Wolbachia made a significant contribution to differential expression of host genes and that the bacterial genotype plays a vital role in establishing the character of this contribution.
Plant Secondary Compounds Promote White Adipose Tissue Browning via Modulation of the Gut Microbiota in Small Mammals
Authors: Ren Shien , Zhang Liangzhi , Tang Xianjiang , Fan Chao , Zhao Yaqi , Cheng Qi , Zhang Yanming
Published: December 2023

The browning of white adipose tissue (WAT) is a promising area of research for treating metabolic disorders and obesity in the future. However, studies on plant secondary compounds promoting WAT browning are limited. Herein, we explored the effects of swainsonine (SW) on gut microbiota and WAT browning in captive pikas. SW inhibited body mass gain, increased brown adipose tissue (BAT) mass, and induced WAT browning in pikas. The 16S rDNA sequencing revealed a significant reduction in the alpha diversity and altered community structure of the gut microbiota in captive pikas. However, the addition of SW to the diet significantly increased the alpha diversity of gut microbiota and the relative abundance of Akkermansia, Prevotella, and unclassified_f__Lachnospiraceae, along with the complexity of the microbial co-occurrence network structure, which decreased in the guts of captive pikas. Functional profiles showed that SW significantly decreased the relative abundances of energy metabolism, lipid metabolism, and glycan biosynthesis and metabolism, which were enriched in captive pikas. Furthermore, SW decreased deterministic processes of gut microbiota assembly in July and increased them in November. Finally, the genera Prevotella and unclassified_f__Prevotellaceae were positively correlated with BAT mass. Our results highlighted that plant secondary compounds promote WAT browning by modulating the gut microbiota in small mammals.
Systematic Review and Meta-Analysis of Dietary Interventions and Microbiome in Phenylketonuria
Authors: Ubaldi Francesca , Frangella Claudia , Volpini Veronica , Fortugno Paola , Valeriani Federica , Romano Spica Vincenzo
Published: December 2023

Inborn errors of metabolism (IEMs) comprise a diverse group of monogenic disorders caused by enzyme deficiencies that result either in a toxic accumulation of metabolic intermediates or a shortage of essential end-products. Certain IEMs, like phenylketonuria (PKU), necessitate stringent dietary intervention that could lead to microbiome dysbiosis, thereby exacerbating the clinical phenotype. The objective of this systematic review was to examine the impact of PKU therapies on the intestinal microbiota. This research was conducted following the PRISMA Statement, with data from PubMed, Scopus, ScienceDirect, and Web of Science. A total of 18 articles meeting the inclusion criteria were published from 2011 to 2022. Significant reductions in several taxonomic groups in individuals with PKU when compared to the control group were detected in a quantitative analysis conducted across seven studies. The meta-analysis synthesis indicates a contrast in biodiversity between PKU subjects and the control population. Additionally, the meta-regression results, derived from the Bacillota/Bacteroidota ratio data, suggest a potential influence of diet in adult PKU populations (p = 0.004). It is worth noting that the limited number of studies calls for further research and analysis in this area. Our findings indicate the necessity of enhancing understanding of microbiota variability in reaction to treatments among PKU subjects to design tailored therapeutic and nutritional interventions to prevent complications resulting from microbiota disruption.
RSV Induces Activation of Intracellular EGFR on the Mitochondrial Membrane for Virus Propagation
Authors: Noh Se Sil , Shin Hye Jin
Published: December 2023

Respiratory syncytial virus (RSV) infects people of all ages and is one of the most common causative agents of lower respiratory tract infections, such as pneumonia, especially in infants under one year of age. However, no direct treatment has been developed for RSV infections. Maintenance of mitochondrial homeostasis and epidermal growth factor receptor (EGFR) activity is important for human cell growth. This study reported that RSV infection maintained the total cellular ATP levels and promoted the intracellular activity of EGFR to replicate RSV. RSV activates the intracellular EGFR-mediated cell survival signaling cascade and maintains mitochondrial EGFR expression for viral production during early events after infection. The approved EGFR inhibitor, vandetanib, markedly reduces RSV propagation, suggesting that EGFR is an attractive host target for RSV therapeutics. Our results suggest that RSV infection maintains cellular ATP levels and promotes the activation of intracellular EGFR in the mitochondrial membrane, significantly contributing to robust RSV propagation.
Angiotensin-Converting Enzyme 2 (ACE2) Signaling in Pulmonary Arterial Hypertension: Underpinning Mechanisms and Potential Targeting Strategies
Authors: Papavassiliou Kostas A. , Gogou Vassiliki A. , Papavassiliou Athanasios G.
Published: December 2023

Pulmonary arterial hypertension (PAH) is a debilitating progressive disease characterized by excessive pulmonary vasoconstriction and abnormal vascular remodeling processes that lead to right-ventricular heart failure and, ultimately, death. Although our understanding of its pathophysiology has advanced and several treatment modalities are currently available for the management of PAH patients, none are curative and the prognosis remains poor. Therefore, further research is required to decipher the molecular mechanisms associated with PAH. Angiotensin-converting enzyme 2 (ACE2) plays an important role through its vasoprotective functions in cardiopulmonary homeostasis, and accumulating preclinical and clinical evidence shows that the upregulation of the ACE2/Angiotensin-(1-7)/MAS1 proto-oncogene, G protein-coupled receptor (Mas 1 receptor) signaling axis is implicated in the pathophysiology of PAH. Herein, we highlight the molecular mechanisms of ACE2 signaling in PAH and discuss its potential as a therapeutic target.
Taxonomic Structure and Wing Pattern Evolution in the Parnassius mnemosyne Species Complex (Lepidoptera, Papilionidae)
Authors: Lukhtanov Vladimir A. , Zakharov Evgeny V.
Published: December 2023

In our study, using the analysis of DNA barcodes and morphology (wing color, male genitalia, and female sphragis shape), we show that the group of species close to P. mnemosyne comprises the western and eastern phylogenetic lineages. The eastern lineage includes P. stubbendorfii, P. glacialis, and P. hoenei. The western lineage includes three morphologically similar species: P. mnemosyne (Western Eurasia), P. turatii (southwestern Europe), and P. nubilosus stat. nov. (Turkmenistan and NE Iran), as well as the morphologically differentiated P. ariadne (Altai). The latter species differs from the rest of the group in the presence of red spots on the wings. Parnassius mnemosyne s.s. is represented by four differentiated mitochondrial clusters that show clear association with specific geographic regions. We propose to interpret them as subspecies: P. mnemosyne mnemosyne (Central and Eastern Europe, N Caucasus, N Turkey), P. mnemosyne adolphi (the Middle East), P. mnemosyne falsa (Tian Shan), and P. mnemosyne gigantea (Gissar-Alai in Central Asia). We demonstrate that in P. ariadne, the red spots on the wing evolved as a reversion to the ancestral wing pattern. This reversion is observed in Altai, where the distribution areas of the western lineage, represented by P. ariadne, and the eastern lineage, represented by P. stubbendorfii, overlap. These two species hybridize in Altai, and we hypothesize that the color change in P. ariadne is the result of reinforcement of prezygotic isolation in the contact zone. The lectotype of Parnassius mnemosyne var. nubilosus Christoph, 1873, is designated.
Antithrombotic Management for Transcatheter Aortic Valve Implantation
Authors: Ya’Qoub Lina , Arnautovic Jelena , Sharkawi Musa , AlAasnag Mirvat , Jneid Hani , Elgendy Islam Y.
Published: December 2023

Background: There have been significant changes in the optimal antithrombotic regimen post transcatheter aortic valve implantation (TAVI) after the results of major clinical trials in the past few years. Given the clinical importance of the optimal antithrombotic therapy post TAVI, we performed a narrative description of the major clinical trials behind the scientific evidence supporting these changes, as well the current guideline recommendations and knowledge gaps. Methods: We performed a narrative description of the major clinical trials behind the scientific evidence supporting these changes. We used PubMed as a major source to collect the major clinical trials including the following key words: “transcatheter aortic valve replacement”, “transcatheter aortic valve implantation”, “antithrombotic”, “antiplatelet” and “anticoagulation”. We selected the major clinical trials on this topic. This is not a systematic review or meta-analysis. Results: We describe the results of the major clinical trials on antithrombotic therapy post TAVI: POPULAR-TAVI A, POPULAR-TAVI B, ENVISAGE-TAVI AF, GALILEO, ATLANTIS and ADAPT-TAVR trials. Based on the results of these trials, single antiplatelet therapy is recommended post TAVI in patients without concomitant indication for oral anticoagulation or dual antiplatelet therapy, especially in elderly patients. In younger patients, it is advised to evaluate the patient’s bleeding and thrombotic risk, and dual antiplatelet therapy may be reasonable in patients with a high thrombotic risk and low bleeding risk. In patients with a concurrent indication for oral anticoagulation or dual antiplatelet therapy, it is recommended to continue oral anticoagulation or dual antiplatelet therapy post TAVI. Conclusion: In most patients without concomitant indication for oral anticoagulation, single antiplatelet therapy is recommended post TAVI.
Anticoagulants versus Left Atrial Appendage Occlusion in Patients with Atrial Fibrillation and Co-Morbid Thrombocytopenia
Authors: Kowalska Wiktoria , Mitręga Katarzyna , Olma Anna , Podolecki Tomasz , Kalarus Zbigniew , Streb Witold
Published: December 2023

Left atrial appendage closure (LAAC) is an alternative approach to anticoagulants. Nonetheless, data regarding the outcomes of LAAC procedures in patients with thrombocytopenia remain lacking. The primary objective was to determine the incidence of the composite endpoint comprising ischemic stroke, intracranial hemorrhage, major bleeding, and cardiac cause of death among patients with atrial fibrillation (AF) and thrombocytopenia who were either undergoing LAAC or receiving oral anticoagulants. The secondary endpoint was the determination of total mortality. Data from a prospective, single-center registry of patients undergoing LAAC procedures were analyzed. A subset of 50 consecutive patients with thrombocytopenia were selected. Thrombocytopenia was defined as a thrombocyte count below 150,000. Subsequently, from patients hospitalized with AF receiving oral anticoagulants, 50 patients were further chosen based on propensity score matching, ensuring comparability with the study group. The primary endpoint occurred in 2% of patients in the LAAC group and 10% of patients in the non-LAAC group (p = 0.097). Additionally, a significant difference was noted in the occurrence of the secondary endpoint, which was observed in 0% of patients in the LAAC group and 10% of patients in the non-LAAC group (p = 0.025). In patients with thrombocytopenia the LAAC procedure improves prognosis compared with continued anticoagulant treatment.