bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Novel Independent Correlations between Cellular Components of the Immune System and Strain-Related Indices of Myocardial Dysfunction in CKD Patients and Kidney Transplant Recipients without Established Cardiovascular Disease
Authors: Duni Anila , Kitsos Athanasios , Bechlioulis Aris , Lakkas Lampros , Markopoulos Georgios , Tatsis Vasileios , Koutlas Vasileios , Tzalavra Eirini , Baxevanos Gerasimos , Vartholomatos Georgios , Mitsis Michail , Naka Katerina K. , Dounousi Evangelia
Published: August 2024

The role of immune system components in the development of myocardial remodeling in chronic kidney disease (CKD) and kidney transplantation remains an open question. Our aim was to investigate the associations between immune cell subpopulations in the circulation of CKD patients and kidney transplant recipients (KTRs) with subclinical indices of myocardial performance. We enrolled 44 CKD patients and 38 KTRs without established cardiovascular disease. A selected panel of immune cells was measured by flow cytometry. Classical and novel strain-related indices of ventricular function were measured by speckle-tracking echocardiography at baseline and following dipyridamole infusion. In CKD patients, the left ventricular (LV) relative wall thickness correlated with the CD14++CD16− monocytes (β = 0.447, p = 0.004), while the CD14++CD16+ monocytes were independent correlates of the global radial strain (β = 0.351, p = 0.04). In KTRs, dipyridamole induced changes in global longitudinal strain correlated with CD14++CD16+ monocytes (β = 0.423, p = 0.009) and CD4+ T-cells (β = 0.403, p = 0.01). LV twist and untwist were independently correlated with the CD8+ T-cells (β = 0.405, p = 0.02 and β = −0.367, p = 0.03, respectively) in CKD patients, whereas the CD14++CD16+ monocytes were independent correlates of LV twist and untwist in KTRs (β = 0.405, p = 0.02 and β = −0.367, p = 0.03, respectively). Immune cell subsets independently correlate with left ventricular strain and torsion-related indices in CKD patients and KTRs without established CVD.
Temporal and Spatial Variations in Zebrafish Hairy/E(spl) Gene Expression in Response to Mib1-Mediated Notch Signaling During Neurodevelopment
Authors: Chen Yi-Chieh , Hsieh Fu-Yu , Chang Chia-Wei , Sun Mu-Qun , Cheng Yi-Chuan
Published: August 2024

Notch signaling is a conserved pathway crucial for nervous system development. Disruptions in this pathway are linked to neurodevelopmental disorders, neurodegenerative diseases, and brain tumors. Hairy/E(spl) (HES) genes, major downstream targets of Notch, are commonly used as markers for Notch activation. However, these genes can be activated, inhibited, or function independently of Notch signaling, and their response to Notch disruption varies across tissues and developmental stages. MIB1/Mib1 is an E3 ubiquitin ligase that enables Notch receptor activation by processing ligands like Delta and Serrate. We investigated Notch signaling disruption using the zebrafish Mib1 mutant line, mib1ta52b, focusing on changes in the expression of Hairy/E(spl) (her) genes. Our findings reveal significant variability in her gene expression across different neural cell types, regions, and developmental stages following Notch disruption. This variability questions the reliability of Hairy/E(spl) genes as universal markers for Notch activation, as their response is highly context-dependent. This study highlights the complex and context-specific nature of Notch signaling regulation. It underscores the need for a nuanced approach when using Hairy/E(spl) genes as markers for Notch activity. Additionally, it provides new insights into Mib1’s role in Notch signaling, contributing to a better understanding of its involvement in Notch signaling-related disorders.
Metabolic Function and Therapeutic Potential of CD147 for Hematological Malignancies: An Overview
Authors: Spinello Isabella , Labbaye Catherine , Saulle Ernestina
Published: August 2024

Hematological malignancies refer to a heterogeneous group of neoplastic conditions of lymphoid and hematopoietic tissues classified in leukemias, Hodgkin and non-Hodgkin lymphomas and multiple myeloma, according to their presumed cell of origin, genetic abnormalities, and clinical features. Metabolic adaptation and immune escape, which influence various cellular functions, including the proliferation and survival of hematological malignant tumor cells, are major aspects of these malignancies that lead to therapeutic drug resistance. Targeting specific metabolic pathways is emerging as a novel therapeutic strategy in hematopoietic neoplasms, particularly in acute myeloid leukemia and multiple myeloma. In this context, CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or Basigin, is one target candidate involved in reprograming metabolism in different cancer cells, including hematological malignant tumor cells. CD147 overexpression significantly contributes to the metabolic transformation of these cancer cells, by mediating signaling pathway, growth, metastasis and metabolic reprogramming, through its interaction, direct or not, with various membrane proteins related to metabolic regulation, including monocarboxylate transporters, integrins, P-glycoprotein, and glucose transporter 1. This review explores the metabolic functions of CD147 and its impact on the tumor microenvironment, influencing the progression and neoplastic transformation of leukemias, myeloma, and lymphomas. Furthermore, we highlight new opportunities for the development of targeted therapies against CD147, potentially improving the treatment of hematologic malignancies.
Spatial Transcriptomics Identifies Cellular and Molecular Characteristics of Scleroderma Skin Lesions: Pilot Study in Juvenile Scleroderma
Authors: Liu Tianhao , Esencan Deren , Salgado Claudia M. , Zhao Chongyue , Lai Ying-Ju , Hutchins Theresa , Sanyal Anwesha , Chen Wei , Torok Kathryn S.
Published: August 2024

Juvenile localized and systemic scleroderma are rare autoimmune diseases which cause significant disability and morbidity in children. The mechanisms driving juvenile scleroderma remain unclear, necessitating further cellular and molecular level studies. The Visium CytAssist spatial transcriptomics (ST) platform, which preserves the spatial location of cells and simultaneously sequences the whole transcriptome, was employed to profile the histopathological slides from skin lesions of juvenile scleroderma patients. (1) Spatial domains were identified from ST data and exhibited strong concordance with the pathologist’s annotations of anatomical structures. (2) The integration of paired ST data and single-cell RNA sequencing (scRNA-seq) from the same patients validated the comparable accuracy of the two platforms and facilitated the estimation of cell type composition in ST data. (3) The pathologist-annotated immune infiltrates, such as perivascular immune infiltrates, were clearly delineated by the ST analysis, underscoring the biological relevance of the findings. This is the first study utilizing spatial transcriptomics to investigate skin lesions in juvenile scleroderma patients. The validity of the ST data was corroborated by gene expression analyses and the pathologist’s assessments. Integration with scRNA-seq data facilitated the cell type-level analysis and validation. Analyses of immune infiltrates through combined ST data and pathological review enhances our understanding of the pathogenesis of juvenile scleroderma.
Toxicological and Pharmacological Activities, and Potential Medical Applications, of Marine Algal Toxins
Authors: Gao Xinyu , Wang Hanyi , Chen Kuilin , Guo Yifan , Zhou Jin , Xie Weidong
Published: August 2024

Marine algal toxins have garnered significant attention in the research community for their unique biochemical properties and potential medical applications. These bioactive compounds, produced by microalgae, pose significant risks due to their high toxicity, yet offer promising therapeutic benefits. Despite extensive research identifying over 300 marine algal toxins, including azaspiracids, brevetoxins, cyclic imines, and yessotoxins, gaps remain in the understanding of their pharmacological potential. In this paper, we critically review the classification, bioactive components, toxicology, pharmacological activities, and mechanisms of these toxins, with a particular focus on their clinical applications. Our motivation stems from the increasing interest in marine algal toxins as candidates for drug development, driven by their high specificity and affinity for various biological receptors. We aim to bridge the gap between toxicological research and therapeutic application, offering insights into the advantages and limitations of these compounds in comparison to other bioactive substances. This review not only enhances the understanding of marine algal toxins’ complexity and diversity, but also highlights their extensive application potential in medicine and bioscience, providing a foundation for future research and development in this field.
Exploring Genetic Interactions in Colombian Women with Polycystic Ovarian Syndrome: A Study on SNP-SNP Associations
Authors: Alarcón-Granados Maria Camila , Camargo-Villalba Gloria Eugenia , Forero-Castro Maribel
Published: August 2024

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with high prevalence in women around the world. The identification of single-nucleotide polymorphisms (SNPs) through genome-wide association studies has classified it as a polygenic disease. Most studies have independently evaluated the contribution of each SNP to the risk of PCOS. Few studies have assessed the effect of epistasis among the identified SNPs. Therefore, this exploratory study aimed to evaluate the interaction of 27 SNPs identified as risk candidates and their contribution to the pathogenesis of PCOS. The study population included 49 control women and 49 women with PCOS with a normal BMI. Genotyping was carried out through the MassARRAY iPLEX single-nucleotide polymorphism typing platform. Using the multifactor dimensionality reduction (MDR) method, the interaction between SNPs was evaluated. The analysis showed that the best interaction model (p < 0.0001) was composed of three loci (rs11692782-FSHR, rs2268361-FSHR, and rs4784165-TOX3). Furthermore, a tendency towards synergy was evident between rs2268361 and the SNPs rs7371084–rs11692782–rs4784165, as well as a redundancy in rs7371084–rs11692782–rs4784165. This pilot study suggests that epistasis may influence PCOS pathophysiology. Large-scale analysis is needed to deepen our understanding of its impact on this complex syndrome affecting thousands of women.
Discovery of Aloperine as a Potential Antineoplastic Agent for Cholangiocarcinoma Harboring Mutant IDH1
Authors: Wu Xingkang , Li Yang , Han Chenchen , Li Shifei , Qin Xuemei
Published: August 2024

Intrahepatic cholangiocarcinoma (ICC) is a universally lethal malignancy with increasing incidence. However, ICC patients receive limited benefits from current drugs; therefore, we must urgently explore new drugs for treating ICC. Quinolizidine alkaloids, as essential active ingredients extracted from Sophora alopecuroides Linn, can suppress cancer cell growth via numerous mechanisms and have therapeutic effects on liver-related diseases. However, the impact of quinolizidine alkaloids on intrahepatic cholangiocarcinoma has not been fully studied. In this article, the in vitro anti-ICC activities of six natural quinolizidine alkaloids were explored. Aloperine was the most potent antitumor compound among the tested quinolizidine alkaloids, and it preferentially inhibited RBE cells rather than HCCC-9810 cells. Mechanistically, aloperine can potentially decrease glutamate content by inhibiting the hydrolysis of glutamine, reducing D-2-hydroxyglutarate levels and, consequently, leading to preferential growth inhibition in isocitrate dehydrogenase (IDH)-mutant ICC cells. In addition, aloperine preferentially resensitizes RBE cells to 5-fluorouracil, AGI-5198 and olaparib. This article demonstrates that aloperine shows preferential antitumor effects in intrahepatic cholangiocarcinoma cells harboring the mutant IDH1 by decreasing D-2-hydroxyglutarate, suggesting that aloperine could be used as a lead compound or adjuvant chemotherapy drug to treat ICC harboring the mutant IDH.
Immune-Enhancing Effects of Gwakhyangjeonggi-san in RAW 264.7 Macrophage Cells through the MAPK/NF-κB Signaling Pathways
Authors: Jeong Yun Hee , Yang Hye Jin , Li Wei , Oh You-Chang , Choi Jang-Gi
Published: August 2024

Gwakhyangjeonggi-san (GJS) is a traditional herbal medicine used in East Asia for the treatment of symptoms involving lower intestinal abnormalities; however, the effects of GJS on innate immunity and its cellular mechanisms of action have not been elucidated. In this study, we assessed the immune-enhancing activity and underlying mechanisms of GJS using RAW 264.7 murine macrophages. The results showed that GJS treatment significantly increased the secretion of nitric oxide and cytokines and their mRNA expression in macrophage RAW 264.7 cells without causing cytotoxicity. GJS treatment also significantly increased the production of reactive oxygen species, as well as inducing phagocytic activity, adhesion function, and migration ability, all of which improved the immune response. In addition, GJS activated nuclear factor-κB by promoting the phosphorylation and degradation of inhibitor of nuclear factor-κB alpha. Furthermore, GJS markedly increased the phosphorylation of mitogen-activated protein kinase in RAW 264.7 cells. These findings indicate that GJS has potential value as a dietary supplement for strengthening immunity.
Exploring the Antimicrobial Potential of Hallachrome, a Defensive Anthraquinone from the Marine Worm Halla parthenopeia (Polychaeta)
Authors: Ferri Anita , Simonini Roberto , Sabia Carla , Iseppi Ramona
Published: August 2024

Antimicrobial resistance is a critical global health issue, with rising resistance among bacteria and fungi. Marine organisms have emerged as promising, but underexplored, sources of new antimicrobial agents. Among them, marine polychaetes, such as Halla parthenopeia, which possess chemical defenses, could attract significant research interest. This study explores the antimicrobial properties of hallachrome, a unique anthraquinone found in the purple mucus of H. parthenopeia, against Gram-negative bacteria (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027), Gram-positive bacteria (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228), and the most common human fungal pathogen Candida albicans ATCC 10231. Antibacterial susceptibility testing revealed that Gram-negative bacteria were not inhibited by hallachrome at concentrations ≤2 mM. However, Gram-positive bacteria showed significant growth inhibition at 0.12–0.25 mM, while C. albicans was inhibited at 0.06 mM. Time-kill studies demonstrated dose-dependent growth inhibition of susceptible strains by hallachrome, which exerted its effect by altering the membrane permeability of C. albicans, E. faecalis, and S. epidermidis after 6 h and S. aureus after 24 h. Additionally, hallachrome significantly reduced biofilm formation and mature biofilm in S. aureus, E. faecalis, and C. albicans. Additionally, it inhibited hyphal growth in C. albicans. These findings highlight hallachrome’s potential as a novel antimicrobial agent, deserving further exploration for clinical experimentation.
New Bioactive Polyketides from the Mangrove-Derived Fungus Penicillium sp. SCSIO 41411
Authors: Chen Yi , Cai Jian , Xia Ziwei , Chen Chunmei , Liu Yonghong , Jayasinghe Lalith , Wang Xueni , Zhou Xuefeng
Published: August 2024

Three new polyketides, including three ester derivatives (1, 3, and 5) and a new natural product, which was a benzoquinone derivative, embelin A (4), together with nine known ones (2 and 6–13), were isolated from the mangrove-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by detailed NMR and MS spectroscopic analyses. The X-ray single-crystal diffraction analysis of 4 was described for the first time. Compound 9 displayed obvious inhibition against PDE4 with an inhibitory ratio of 40.78% at 10 μM. Compound 12 showed DPPH radical scavenging activity, with an EC50 of 16.21 µg/mL, compared to the positive control (ascorbic acid, EC50, 11.22 µg/mL). Furthermore, compound 4 exhibited cytotoxicity against PC-3 and LNCaP with IC50 values of 18.69 and 31.62 µM, respectively.
Machine Learning-Driven Discovery and Evaluation of Antimicrobial Peptides from Crassostrea gigas Mucus Proteome
Authors: Song Jingchen , Liu Kelin , Jin Xiaoyang , Huang Ke , Fu Shiwei , Yi Wenjie , Cai Yijie , Yu Ziniu , Mao Fan , Zhang Yang
Published: August 2024

Marine antimicrobial peptides (AMPs) represent a promising source for combating infections, especially against antibiotic-resistant pathogens and traditionally challenging infections. However, traditional drug discovery methods face challenges such as time-consuming processes and high costs. Therefore, leveraging machine learning techniques to expedite the discovery of marine AMPs holds significant promise. Our study applies machine learning to develop marine AMPs, focusing on Crassostrea gigas mucus rich in antimicrobial components. We conducted proteome sequencing of C. gigas mucous proteins, used the iAMPCN model for peptide activity prediction, and evaluated the antimicrobial, hemolytic, and cytotoxic capabilities of six peptides. Proteomic analysis identified 4490 proteins, yielding about 43,000 peptides (8–50 amino acids). Peptide ranking based on length, hydrophobicity, and charge assessed antimicrobial potential, predicting 23 biological activities. Six peptides, distinguished by their high relative scores and promising biological activities, were chosen for bactericidal assay. Peptides P1 to P4 showed antimicrobial activity against E. coli, with P2 and P4 being particularly effective. All peptides inhibited S. aureus growth. P2 and P4 also exhibited significant anti-V. parahaemolyticus effects, while P1 and P3 were non-cytotoxic to HEK293T cells at detectable concentrations. Minimal hemolytic activity was observed for all peptides even at high concentrations. This study highlights the potent antimicrobial properties of naturally occurring oyster mucus peptides, emphasizing their low cytotoxicity and lack of hemolytic effects. Machine learning accurately predicted biological activity, showcasing its potential in peptide drug discovery.
Regolith-Hosted Rare Earth Element Mineralization in the Esperance Region, Western Australia: Major Characteristics and Potential Controls
Authors: Sergeev Nikita , Collins Tiffany
Published: August 2024

A number of regolith-hosted REE occurrences have recently been discovered in the Esperance region in southern Western Australia. This paper summarizes major characteristics of REE mineralization and discusses contributing factors and potential controls. The main aim is to explain why there is a lack of highly sought-after ion-adsorption-clay-type REE deposits across the region despite the presence of the regolith-hosted REE mineralization on a regional scale. Local mineralization mostly occurs as continuous flat-lying enrichment “blankets” within the residual regolith developed over Archaean–Proterozoic granite gneisses and granitoids with elevated REE content. The enriched horizon is commonly located in the lower saprolite and saprock and is accompanied by an overlying REE-depleted zone. This distribution pattern, together with the data on HREE fractionation and the presence of the supergene REE minerals, indicates chemogenic type enrichment formed by supergene REE mobilization into groundwater, downward transport, and accumulation in the lower part of the weathering profile. Residual REE accumulation processes due to bulk rock volume and mass reduction during weathering also contribute to mineralization. It is proposed that climate and groundwater chemistry are the critical regional controls on the distribution of REEs in the weathering profile and on their speciation in the enrichment zone. Cenozoic aridification of climate in southwest Australia heavily overprinted pre-existing REE distributions in the weathering profile. Acidic (pH < 4), highly saline groundwaters intensely leached away any relatively weakly bound, adsorbed or colloidal REE forms, moving them downward. Dissolved REEs precipitated as secondary phosphates in neutral to alkaline environment at lower Eh near the base of the weathering profile forming the supergene enrichment zone. Low denudation rates, characteristic of areas of low relief under the arid climate, are favourable for the preservation of the existing weathering profiles with REE mineralization.
Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation on Clinical Outcome of Atopic Dermatitis in Children
Authors: Niseteo Tena , Hojsak Iva , Ožanić Bulić Suzana , Pustišek Nives
Published: August 2024

The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while others show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA from fish oil in combination with gamma-linolenic acid (GLA) from blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period throughout autumn, winter, and spring, avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing a specific blend of omega-3 and omega-6 fatty acids or placebo. The primary outcomes were changes in severity of AD measured using SCORing Atopic Dermatitis (SCORAD), patient-oriented SCORAD (PO-SCORAD) and the difference in topical corticosteroid (TCS) use. The secondary outcomes were changes in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving the active product, intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and the use of topical corticosteroids (from median 30 to 10 mg/month, p < 0.001), but also significant improvements in itch, sleep quality, and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D may decrease symptoms and were associated with an improvement clinical picture of AD in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that may significantly reduce the severity of AD in pediatric patients.
Influence of Northern Wild Rice on Gut Dysbiosis and Short Chain Fatty Acids: Correlation with Metabolic and Inflammatory Markers in Mice on High Fat Diet
Authors: Zhao Ruozhi , Fajardo Janice , Shen Garry X.
Published: August 2024

Wild rice (WLD) attenuated hyperglycemia, hyperlipidemia and chronic inflammation in mice receiving a high-fat diet (HFD) versus white rice (WHR), but the underlying mechanism is not well understood. We examined the influence of HFD + WLD on gut microbiota, short chain fatty acids (SCFAs) and the correlation with metabolic or inflammatory markers in mice versus HFD + WHR. C57BL/6J mice received HFD + 26 g weight (wt) % WHR or WLD or 13 g wt% WHR + 13 g wt% WLD (WTWD) for 12 weeks. Plasma levels of glucose, cholesterol and triglycerides, insulin resistance and inflammatory markers after overnight fasting were lower, and the abundances of fecal Lactobacillus gasseri and propionic acid were higher in HFD + WLD-fed mice than in HFD + WHR-fed mice. The anti-inflammatory effects of HFD + WTWD were weaker than HFD + WLD but were greater than those in HFD + WHR-fed mice. Abundances of fecal Lactobacillus gasseri and propionic acid in mice receiving HFD + WLD were higher than those in mice fed with HFD + WHR. The abundances of fecal L. gasseri and propionic acid negatively correlated with metabolic and inflammatory markers. The findings of the present study suggest that WLD attenuated metabolic and inflammatory disorders in mice on HFD. Interactions between WLD components and gut microbiota may upregulate fecal SCFAs, and the latter may be attributed to the benefits of WLD on metabolism and inflammation in mice on HFD.
Role of Low Amount of Iron Intake from Groundwater for Prevention of Anemia in Children: A Cross-Sectional Study in Rural Bangladesh
Authors: Rahman Sabuktagin , Lee Patricia , Biswas Nezam Uddin , Khan Moududur Rahman , Ahmed Faruk
Published: August 2024

In Bangladesh, groundwater, the principal source of drinking water, contains predominantly high levels of iron. Drinking groundwater is associated with good iron status in populations. Against this backdrop, iron supplementation is often associated with side effects, which reduces its intake compliance. However, the level of iron in groundwater is not consistent, and low levels exist in many areas of the country. In the present study, we examined the role of groundwater with a low concentration of iron in the prevention of anemia in Bangladeshi children. In 2018, a cross-sectional study was conducted in Bangladesh among children aged 2–5 years (n = 122) who drank groundwater containing a low level of iron (0–<2 mg/L). The combined intake of iron was calculated from the key sources—diet, groundwater, and the simulated intake of MNPs. The intakes of iron were compared against the standard reference intake. The children’s hemoglobin levels were measured using a photometer. The combined intake of iron from diet, groundwater with low levels of iron, and the simulated consumption of low-iron MNP in children was 5.8 ± 2.0 and 6.9 ± 2.5 mg/day, comprising 193% and 169% of the Estimated Average Requirements in the 2–3-year-old and 4–5-year-old subgroups, respectively. The combined intake of bioavailable iron from dietary and low-iron groundwater was 0.42 ± 0.023 and 0.22 ± 0.019 mg/day in children exposed to groundwater concentrations of 0.8–<2.0 mg/L and 0.0–<0.8 mg/L, respectively (p < 0.001). The mean concentration of hemoglobin in the respective groups was 12.17 ± 0.94 g/dL and 11.91 ± 0.91 g/dL (p = 0.30). The combined intake of iron from diet and the low-iron groundwater was associated with maintenance of hemoglobin concentration at the non-anemic level in > 90% of the children. The findings highlight the protective influence of the low concentration of iron in the drinking groundwater against childhood anemia in Bangladesh.
From Struggle to Strength: A Multicentric Study on How Public Policies for Celiac Disease Transform Lives
Authors: Falcomer Ana Luísa , Pratesi Claudia B. , Nakano Eduardo Yoshio , Chaves Cláudia , Rostami-Nejad Mohammad , Guennouni Morad , Aksan Ayşegül , Pouchot Jacques , Häuser Winfried , Zandonadi Renata Puppin
Published: August 2024

This multicenter study aims to assess the impact of public policies (PPs) on the health-related quality of life (HRQoL) of individuals with celiac disease (CD) using the Celiac Disease Questionnaire (CDQ) and PPs for Celiac Disease Score (PPCDS). This cross-sectional exploratory study was conducted in four stages: first, standardizing data from countries using the CDQ; second, analyzing PPs aimed at CD patients; third, statistically examining these data; and fourth, associating HRQoL indicators with corresponding PPs. This study analyzed 15 CDQ assessments from 12 countries from 2007 to 2023. It found that comprehensive PPs positively correlated with HRQoL outcomes (Spearman correlation of 0.358). However, policies specifically targeting gluten-free meals and certification did not significantly improve HRQoL individually, suggesting they may be more effective when implemented together. Additionally, specialized health services did not notably reduce gastrointestinal symptoms, underscoring the necessity for improved patient education to enhance the effectiveness of these services. This study concludes that implementing and rigorously monitoring regulations to support CD patients is crucial for enhancing their HRQoL.
Toward Model-Informed Precision Dosing for Remimazolam: A Population Pharmacokinetic–Pharmacodynamic Analysis
Authors: Chen Yueting , Gong Cansheng , Liu Feng , Jiao Zheng , Zheng Xiaochun
Published: August 2024

Remimazolam, widely used for procedural sedation and general anesthesia, is a new ultra short-acting benzodiazepine for intravenous sedation and anesthesia. We aim to characterize the pharmacokinetics/pharmacodynamics (PK/PD) of remimazolam and its metabolite CNS 7054 in healthy Chinese volunteers using population analysis and suggest an optimal dosing regimen for sedation therapy. Data were collected from a single-center, placebo-controlled, randomized, and dose–escalation clinical pharmacology study. Forty-six healthy volunteers received a single infusion dose of remimazolam, while nine healthy subjects received a continuous infusion of remimazolam. A population PK/PD model was established and RxODE and Shiny in R were used to design the remimazolam dosing regimens. A three-compartment model best described the PK of remimazolam and a two-compartment model with one transit compartment was adopted for CNS 7054. The relationship between exposure and the bispectral index was best described using an effect compartment model with an inhibitory sigmoid model. Additionally, a web-based dashboard was developed to provide individualized dosing regimens, complemented by a graphical illustration of the PK/PD profiles of the proposed dosing regimen. The established population PK/PD model characterized the dose–exposure–response relationship of remimazolam well, which could be applied to optimize individual dosing regimens.
Imaging-Based Drug Penetration Profiling in an Excised Sheep Cornea Model
Authors: Viehmeister Karla , Manuelli Aurélie , Guerin Camille , Kappes Sebastian , Lamprecht Alf
Published: August 2024

Formulations designed to address ocular conditions and diseases are predominantly administered topically. While in vitro test systems have been developed to assess corneal permeation under extended contact conditions, methods focusing on determining the penetration depth and kinetics of a substance within the cornea itself rather than through it, are scarce. This study introduces a method for time-dependent penetration depth analysis (10 and 60 min) by means of a semiquantitative imaging method in comparison with a quantitative corneal depth-cut technique, employing fluorescein sodium at concentrations of 0.2 and 0.4 mg/mL as a small molecule model substance and sheep cornea as a human surrogate. Excised tissues exhibited sustained viability in modified artificial aqueous humor and maintained thickness (746 ± 43 µm) and integrity (electrical resistance 488 ± 218 Ω∙cm2) under the experimental conditions. Both methods effectively demonstrated the expected concentration- and time-dependent depth of penetration of fluorescein sodium, displaying a significantly strong correlation. The traceability of the kinetic processes was validated with polysorbate 80, which acted as a penetration enhancer. Furthermore, the imaging-based method enabled detecting the retention of larger structures, such as hyaluronic acid and nanoemulsions from the commercial eyedrop formulation NEOVIS® TOTAL multi, inside the lacrimal layer.
Financial Risk Management in Healthcare in the Provision of High-Tech Medical Assistance for Sustainable Development: Evidence from Russia
Authors: Chililov Abdula M.
Published: August 2024

The research determines the level of financial risk in the Russian healthcare system and identifies prospects for improving the current Russian practice of financial risk management in healthcare when providing high-tech medical care for sustainable development (using Russia as an example). The author summarizes the advanced experience of the top 20 largest healthcare organizations in Russia by revenue in 2022. Based on this experience, the author developed an SEM model of the financial risks in healthcare during the provision of high-tech medical care in Russia from a sustainable development perspective. The theoretical significance of the developed model lies in uncovering the previously unknown causal relationships between the implementation of the ICT, sustainable development support, and financial risks in healthcare. The model reveals a new market dimension of financial risks for healthcare organizations in Russia. The main conclusion is that implementing the ICT and support for sustainable development helps to reduce the financial risks in healthcare. The identified potential for reducing financial risks in providing high-tech medical care in Russia until 2026 is practically significant. This prospect can be practically applied as a roadmap for the digital modernization and sustainable development of healthcare until 2026, enhancing the state healthcare policy in Russia. The established systemic relationship between ICT implementation, sustainable development support, and financial risks in healthcare is of managerial importance because it will increase the predictability of the financial risks in the market dimension of healthcare in Russia. The newly developed approach to risk management in healthcare during the provision of high-tech medical care in Russia has expanded the instrumental framework of risk management for healthcare organizations in Russia and revealed further opportunities for improving its efficiency.
IoT-Based Assessment of a Driver’s Stress Level
Authors: Mattioli Veronica , Davoli Luca , Belli Laura , Gambetta Sara , Carnevali Luca , Sgoifo Andrea , Raheli Riccardo , Ferrari Gianluigi
Published: August 2024

Driver Monitoring Systems (DMSs) play a key role in preventing hazardous events (e.g., road accidents) by providing prompt assistance when anomalies are detected while driving. Different factors, such as traffic and road conditions, might alter the psycho-physiological status of a driver by increasing stress and workload levels. This motivates the development of advanced monitoring architectures taking into account psycho-physiological aspects. In this work, we propose a novel in-vehicle Internet of Things (IoT)-oriented monitoring system to assess the stress status of the driver. In detail, the system leverages heterogeneous components and techniques to collect driver (and, possibly, vehicle) data, aiming at estimating the driver’s arousal level, i.e., their psycho-physiological response to driving tasks. In particular, a wearable sensorized bodice and a thermal camera are employed to extract physiological parameters of interest (namely, the heart rate and skin temperature of the subject), which are processed and analyzed with innovative algorithms. Finally, experimental results are obtained both in simulated and real driving scenarios, demonstrating the adaptability and efficacy of the proposed system.
Innovative Detection and Segmentation of Mobility Activities in Patients Living with Parkinson’s Disease Using a Single Ankle-Positioned Smartwatch
Authors: Goubault Etienne , Duval Christian , Martin Camille , Lebel Karina
Published: August 2024

Background: The automatic detection of activities of daily living (ADL) is necessary to improve long-term home-based monitoring of Parkinson’s disease (PD) symptoms. While most body-worn sensor algorithms for ADL detection were developed using laboratory research systems covering full-body kinematics, it is now crucial to achieve ADL detection using a single body-worn sensor that remains commercially available and affordable for ecological use. Aim: to detect and segment Walking, Turning, Sitting-down, and Standing-up activities of patients with PD using a Smartwatch positioned at the ankle. Method: Twenty-two patients living with PD performed a Timed Up and Go (TUG) task three times before engaging in cleaning ADL in a simulated free-living environment during a 3 min trial. Accelerations and angular velocities of the right or left ankle were recorded in three dimensions using a Smartwatch. The TUG task was used to develop detection algorithms for Walking, Turning, Sitting-down, and Standing-up, while the 3 min trial in the free-living environment was used to test and validate these algorithms. Sensitivity, specificity, and F-scores were calculated based on a manual segmentation of ADL. Results: Sensitivity, specificity, and F-scores were 96.5%, 94.7%, and 96.0% for Walking; 90.0%, 93.6%, and 91.7% for Turning; 57.5%, 70.5%, and 52.3% for Sitting-down; and 57.5%, 72.9%, and 54.1% for Standing-up. The median of time difference between the manual and automatic segmentation was 1.31 s for Walking, 0.71 s for Turning, 2.75 s for Sitting-down, and 2.35 s for Standing-up. Conclusion: The results of this study demonstrate that segmenting ADL to characterize the mobility of people with PD based on a single Smartwatch can be comparable to manual segmentation while requiring significantly less time. While Walking and Turning were well detected, Sitting-down and Standing-up will require further investigation to develop better algorithms. Nonetheless, these achievements increase the odds of success in implementing wearable technologies for PD monitoring in ecological environments.
Holo-U2Net for High-Fidelity 3D Hologram Generation
Authors: Yang Tian , Lu Zixiang
Published: August 2024

Traditional methods of hologram generation, such as point-, polygon-, and layer-based physical simulation approaches, suffer from substantial computational overhead and generate low-fidelity holograms. Deep learning-based computer-generated holography demonstrates effective performance in terms of speed and hologram fidelity. There is potential to enhance the network’s capacity for fitting and modeling in the context of computer-generated holography utilizing deep learning methods. Specifically, the ability of the proposed network to simulate Fresnel diffraction based on the provided hologram dataset requires further improvement to meet expectations for high-fidelity holograms. We propose a neural architecture called Holo-U2Net to address the challenge of generating a high-fidelity hologram within an acceptable time frame. Holo-U2Net shows notable performance in hologram evaluation metrics, including an average structural similarity of 0.9988, an average peak signal-to-noise ratio of 46.75 dB, an enhanced correlation coefficient of 0.9996, and a learned perceptual image patch similarity of 0.0008 on the MIT-CGH-4K large-scale hologram dataset.
AI-Based Prediction of Ultrasonic Vibration-Assisted Milling Performance
Authors: El-Asfoury Mohamed S. , Baraya Mohamed , El Shrief Eman , Abdelgawad Khaled , Sultan Mahmoud , Abass Ahmed
Published: August 2024

The current study aims to evaluate the performance of the ultrasonic vibration-assisted milling (USVAM) process when machining two different materials with high deviations in mechanical properties, specifically 7075 aluminium alloy and Ti-6Al-4V titanium alloy. Additionally, this study seeks to develop an AI-based model to predict the process performance based on experimental data for the different workpiece characteristics. In this regard, an ultrasonic vibratory setup was designed to provide vibration oscillations at 28 kHz frequency and 8 µm amplitude in the cutting feed direction for the two characterised materials of 7075 aluminium alloy (150 BHN) and Ti-6Al-4V titanium alloy (350 BHN) workpieces. A series of slotting experiments were conducted using both conventional milling (CM) and USVAM techniques. The axial cutting force and machined slot surface roughness were evaluated for each method. Subsequently, Support Vector Regression (SVR) and artificial neural network (ANN) models were built, tested and compared. AI-based models were developed to analyse the experimental results and predict the process performance for both workpieces. The experiments demonstrated a significant reduction in cutting force by up to 30% and an improvement in surface roughness by approximately four times when using USVAM compared to CM for both materials. Validated by the experimental findings, the ANN model accurately and better predicted the performance metrics with RMSE = 0.11 µm and 0.12 N for Al surface roughness and cutting force. Regarding Ti, surface roughness and cutting force were predicted with RMSE of 0.12 µm and 0.14 N, respectively. The results indicate that USVAM significantly enhances milling performance in terms of a reduced cutting force and improved surface roughness for both 7075 aluminium alloy and Ti-6Al-4V titanium alloy. The ANN model proved to be an effective tool for predicting the outcomes of the USVAM process, offering valuable insights for optimising milling operations across different materials.
Mobile Government Service Promotion Strategies: Exploring Sustainable Development Pathways Based on Provincial Government Practices in China
Authors: Zhang Huiying , Zhu Zijian
Published: August 2024

The level of mobile government services has become a crucial metric for modernizing a government’s governance capabilities, and it plays a significant role in promoting sustainable development. This study aims to explore the key factors influencing the level of mobile government services across 31 provinces in China, along with their combinatory pathways. Using the technology–organization–environment (TOE) framework and employing fuzzy-set qualitative comparative analysis (fsQCA), this study conducts an in-depth analysis of mobile government service levels across these provinces, focusing on the dimensions of technology, organization, and environment. The results identify three pathways that promote high levels of mobile government services: technology–organization, technology–environment, and internal–external linkage-driven pathways. These pathways offer viable strategies for achieving sustainable development in mobile government services. Additionally, this study identifies two pathways associated with lower service levels, technology deficiency, and organization–environment misalignment, highlighting key factors that hinder sustainable development. The findings suggest that organizational and environmental factors can complement each other based on technological conditions, internet penetration rates, and citizen participation levels. Based on these insights, this study recommends that provincial governments proactively explore sustainable development pathways, optimize the “technology–organization–environment” conditions to harness synergies, and work towards enhancing mobile government service levels, thereby reducing inter-provincial disparities and advancing sustainable development.
Refining Environmental Sustainability Governance Reports through Fuzzy Systems Evaluation and Scoring
Authors: Yang Yung-Fa , Chen Haon-Yao , Chen Yun-Hsiang , Ho Shih-Ping , Wang Chuan-San , Lin Cheng-Fang
Published: August 2024

Environmental, Social, and Governance (ESG) reports have become essential tools for enterprises to showcase their commitment to sustainable development and social responsibility. However, discrepancies persist regarding the criteria, assessments, and ratings disclosed in these reports. Moreover, there is a need for more objective methods to determine the weight distribution of indicator items. This study introduces a novel approach utilizing semantic variables in fuzzy theory and a multiple logic fuzzy inference system to develop an ESG environmental management performance assessment model. Therefore, this paper aims to develop a novel approach utilizing semantic variables and a multiple logic fuzzy inference system to quantitatively evaluate the sustainable performance of an environmental management plan. This research also aims to ensure fair and objective assessment outcomes, providing valuable guidance for enterprises in implementing performance management strategies. Key aspects investigated include the impact of membership functions, the extended utilization of semantic variables and logical rules, a comparative analysis of traditional weight assessments, and the limitations of applying fuzzy theory. Through comprehensive discussions and calculations, it is evident that fuzzy theory offers considerable flexibility in application. By tailoring fuzzy rules and selecting appropriate membership functions, diverse application scenarios can be accommodated. The Fuzzy systems evaluation and scoring EMP model generates EMP evaluation scores ranging from 1.76 to 8.29 for Gaussian membership, 1.80 to 8.19 for Triangular membership-A, 1.92 to 8.00 for Triangular membership-B, and 1.81 to 8.19 for Quadrilateral trapezoidal membership, based on simulated rating scenarios using the semantic variables of completeness and feasibility. This approach successfully incorporates distribution logic from subjective membership degrees to evaluate EMP scores. The findings demonstrate that fuzzy theory enables the consideration of multiple factors and facilitates the provision of objective-level membership, underscoring its potential in addressing complex evaluation challenges. This study illuminates the versatility of the fuzzy system theory, with its applications poised to extend across various domains.
Industry Experts’ Perspectives on the Difficulties and Opportunities of the Integration of Bio-Based Insulation Materials in the European Construction Sector
Authors: Zerari Salima , Franchino Rossella , Pisacane Nicola
Published: August 2024

This paper explores the current status of bio-based insulation materials (BbIMs) integration in Europe, through structured online questionnaires. with industry experts. The findings show that the main common difficulties are obtaining European Conformity (CE) marking, high costs, a skills gap, a lack of trained builders, and slow acceptance from industry decision-makers. On the other hand, the main common opportunities are the gradual improvement with certain supportive policies and incentives, the growing environmental awareness, thermal, acoustic, and environmental performance, long-term cost savings and value, and increasing educational initiatives, advertising, and awareness campaigns. The finding also emphasizes the critical role that users and buyers play in the adoption of these materials as a potential driver and barrier. The professionals suggest strengthening environmentally friendly standards, integrating natural materials into construction databases, leading by example, withdrawing subsidies for hazardous waste disposal, providing continuing education, workshops, collaboration among stakeholders, and referencing exemplary projects in France. Further insights on bio-based building materials integration in building information modeling (BIM) practices indicate that the rate of their integration is very low. This research contributes to the scientific literature on BbIMs, by highlighting the barriers to the widespread use of these materials in practice and promoting the drivers of their widespread use. Future research should address more insights from other uncovered countries and the countries with limited insight (The Netherlands, Switzerland, and Portugal) in the current study as well as End-users’ perceptions.