bluuebunny/crossref_metadata_2025 huggingface dataset:
DIAFM: An Improved and Novel Approach for Incremental Frequent Itemset Mining
Authors: Shaikh Mohsin , Akram Sabina , Khan Jawad , Khalid Shah , Lee Youngmoon
Published: December 2024

Traditional approaches to data mining are generally designed for small, centralized, and static datasets. However, when a dataset grows at an enormous rate, the algorithms become infeasible in terms of huge consumption of computational and I/O resources. Frequent itemset mining (FIM) is one of the key algorithms in data mining and finds applications in a variety of domains; however, traditional algorithms do face problems in efficiently processing large and dynamic datasets. This research introduces a distributed incremental approximation frequent itemset mining (DIAFM) algorithm that tackles the mentioned challenges using shard-based approximation within the MapReduce framework. DIAFM minimizes the computational overhead of a program by reducing dataset scans, bypassing exact support checks, and incorporating shard-level error thresholds for an appropriate trade-off between efficiency and accuracy. Extensive experiments have demonstrated that DIAFM reduces runtime by 40–60% compared to traditional methods with losses in accuracy within 1–5%, even for datasets over 500,000 transactions. Its incremental nature ensures that new data increments are handled efficiently without needing to reprocess the entire dataset, making it particularly suitable for real-time, large-scale applications such as transaction analysis and IoT data streams. These results demonstrate the scalability, robustness, and practical applicability of DIAFM and establish it as a competitive and efficient solution for mining frequent itemsets in distributed, dynamic environments.
Failure Mode and Effect Analysis Using Interval Type-2 Fuzzy and Multiple-Criteria Decision-Making Methods
Authors: Liou James J. H. , Guo Bruce H. T. , Huang Sun-Weng , Yang Yi-Tien
Published: December 2024

In recent years, Failure Mode and Effects Analysis (FMEA) has become an essential preventive tool widely applied across various fields. As a structured system analysis method, FMEA aids in identifying potential failure modes in product or process design, allowing for preventive measures to be taken in advance. However, traditional FMEA has certain limitations, as it does not comprehensively consider all potential failure factors. This study proposes an improved FMEA method that addresses these shortcomings by integrating it with a Multiple-Criteria Decision Making (MCDM) model, thereby enhancing the comprehensiveness of the assessment framework. Notably, this research introduces an economic risk factor—Expected Cost (EC)—to make the analysis results more aligned with real-world conditions. Additionally, to manage the uncertainty in expert opinions, this study applies Interval Type-2 Trapezoidal Fuzzy Numbers (IT2TFNs) and combines them with the Best-Worst Method (BWM) to calculate the weights of risk factors. Furthermore, the Decision-Making Trial and Evaluation Laboratory (DEMATEL) method is employed to explore the interrelationships between failure modes. Finally, the Multi-Attribute Ideal-Real Comparative Analysis (MAIRCA) method is used to rank risk factors, determining the priorities for improvement. This paper uses an air purifier as a case study to validate the effectiveness of the improved FMEA method, successfully addressing the shortcomings of traditional FMEA regarding uncertainty in expert opinions and the calculation of Risk Priority Numbers (RPNs). It provides a more practical and accurate risk assessment framework.
Real-World Clinical Utility of a Methylated DNA Biomarker Assay on Samples Collected with a Swallowable Capsule-Balloon for Detection of Barrett’s Esophagus (BE)
Authors: Lister Dan , Fine Andy , Maheshwari Shail , Bradley Paul S. , Lister Kimberly , Lee Victoria T. , deGuzman Brian J. , Verma Suman , Aklog Lishan
Published: December 2024

Background: Barrett’s Esophagus (BE) is the only known precursor for esophageal adenocarcinoma (EAC). Patients with multiple risk factors for BE/EAC are recommended for screening; however, few eligible patients undergo evaluation by endoscopy. EsoGuard® (EG) is a commercially available biomarker assay used to analyze esophageal cells collected non-endoscopically with EsoCheck® (EC) for the qualitative detection of BE/EAC. This study evaluates the real-world clinical utility of EG on cells collected with EC in patients defined by U.S. gastroenterology societies to be at-risk for BE and EAC. Methods: This multi-center, observational CLinical Utility of EsoGuard (CLUE) study enrolled screening-eligible patients as defined by the American College of Gastroenterology (ACG) and the American Gastroenterological Association (AGA). Clinical utility was evaluated by the provider decision impact of EG and additionally by assessing patient compliance outcomes with recommended follow-up testing. Results: There were 551 patients enrolled, with a mean age of 62.0 ± 12.4 years and 56.1% (309/551) meeting ACG guideline criteria for BE screening. EC cell collection was successful in 97.1% (535/551), among which the EG positivity rate was 27.3% (n = 146). The provider decision impact was high, with 100% of EG-positive patients being referred for esophagogastroduodenoscopy (EGD), while 98% of EG negative patients were not referred. Among the EG-positive patients, the overall compliance with follow-up EGD was 85.4%. Conclusions: Combining EC non-endoscopic esophageal cell collection with the EG biomarker assay is effective in guiding provider decision-making for the detection of BE and EAC. Patients with positive EG results demonstrate high compliance with recommended follow-up EGD.
Long-Term Outcomes of Modified Expansive Open-Door Laminoplasty Combined with Short-Level Anterior Cervical Fusion in Multilevel Cervical Spondylotic Myelopathy
Authors: Chen Szu-Wei , Yeh Kuang-Ting , Peng Cheng-Huan , Chang Chia-Ming , Chen Hao-Wen , Yu Tzai-Chiu , Chen Ing-Ho , Wang Jen-Hung , Yang Wan-Ting , Wu Wen-Tien
Published: December 2024

Background and Objectives: Multilevel cervical spondylotic myelopathy (MCSM) presents complex challenges for surgical management, particularly in patients with kyphosis or significant anterior pathology. This study aimed to assess the long-term efficacy of modified expansive open-door laminoplasty (MEOLP) combined with short-level anterior cervical fusion (ACF) in providing decompression, preserving alignment, and maintaining range of motion (ROM) over a nine-year follow-up. Materials and Methods: A retrospective analysis was conducted on 124 MCSM patients treated with MEOLP combined with ACF between 2011 and 2015. MEOLP, a muscle-sparing posterior approach, was combined with ACF to correct sagittal misalignment and address anterior compression. Key outcome measures included the Pavlov ratio, C2–C7 angle, Japanese Orthopedic Association (JOA) score, and Visual Analog Scale (VAS) for neck pain. Patients were monitored for adjacent segment degeneration (ASD) and other postoperative changes over the long-term follow-up. Results: At nine years post-surgery, patients demonstrated significant improvements in decompression and cervical alignment. The mean C2–C7 angle increased, reflecting enhanced lordotic curvature, while the Pavlov ratio showed maintained canal expansion. JOA scores improved significantly, indicating reduced myelopathy symptoms, and VAS scores for neck pain decreased, reflecting symptom relief. Despite these positive outcomes, ASD was noted, especially in patients with reduced preoperative disk height, highlighting the need for strategies to mitigate degeneration at adjacent segments. Conclusions: MEOLP combined with short-level ACF is a viable and durable option for managing complex MCSM cases, offering effective decompression, alignment correction, and ROM preservation. The limitations of this study, including its retrospective, single-center design and the lack of quality-of-life assessments, underscore the need for future multi-center studies with broader outcome measures. These findings support MEOLP with ACF as an alternative approach in cases where traditional laminoplasty may be insufficient.
Influence of the Microbial Metabolite Acetyl Phosphate on Mitochondrial Functions Under Conditions of Exogenous Acetylation and Alkalization
Authors: Beloborodova Natalia V. , Fedotcheva Nadezhda I.
Published: December 2024

Background. Acetyl phosphate (AcP) is a microbial intermediate involved in the central bacterial metabolism. In bacteria, it also functions as a donor of acetyl and phosphoryl groups in the nonenzymatic protein acetylation and signal transduction. In host, AcP was detected as an intermediate of the pyruvate dehydrogenase complex, and its appearance in the blood was considered as an indication of mitochondrial breakdown. In vitro experiments showed that AcP is a powerful agent of nonenzymatic acetylation of proteins. The influence of AcP on isolated mitochondria has not been previously studied. Methods. In this work, we tested the influence of AcP on the opening of the mitochondrial permeability transition pore (mPTP), respiration, and succinate dehydrogenase (SDH) activity under neutral and alkaline conditions stimulating the nonenzymatic acetylation using polarographic, cation-selective, and spectrophotometric methods. Results. It was found that AcP slowed down the opening of the mPTP by calcium ions and decreased the efficiency of oxidative phosphorylation and the activity of SDH. These effects were observed only at neutral pH, whereas alkaline pH by itself caused a decrease in these functions to a much greater extent than AcP. AcP at a concentration of 0.5–1 mM decreased the respiratory control and the swelling rate by 20–30%, while alkalization decreased them twofold, thereby masking the effect of AcP. Presumably, the acetylation of adenine nucleotide translocase involved in both the opening of mPTP and oxidative phosphorylation underlies these changes. The intermediate electron carrier phenazine methosulfate (PMS), removing SDH inhibition at the ubiquinone-binding site, strongly activated SDH under alkaline conditions and, partially, in the presence of AcP. It can be assumed that AcP weakly inhibits the oxidation of succinate, while alkalization slows down the electron transfer from the substrate to the acceptor. Conclusions. The results show that both AcP and alkalization, by promoting nonmetabolic and nonenzymatic acetylation from the outside, retard mitochondrial functions.
Dual-Band High-Throughput and High-Contrast All-Optical Topology Logic Gates
Authors: Zhang Jinying , Si Yulin , Zhang Yexiaotong , Wang Bingnan , Wang Xinye
Published: December 2024

Optical computing offers advantages such as high bandwidth and low loss, playing a crucial role in signal processing, communication, and sensing applications. Traditional optical logic gates, based on nonlinear fibers and optical amplifiers, suffer from poor robustness and large footprints, hindering their on-chip integration. All-optical logic gates based on topological photonic crystals have emerged as a promising approach for developing robust and monolithic optical computing systems. Expanding topological photonic crystal logic gates from a single operating band to dual bands can achieve high throughput, significantly enhancing parallel computing capabilities. This study integrates the topological protection offered by valley photonic crystals with linear interference effects to design and implement seven optical computing logic gates on a silicon substrate. These gates, based on dual-band valley photonic crystal topological protection, include OR, XOR, NOT, NAND, NOR, and AND. The robustness of the implemented OR logic gates was verified in the presence of boundary defects. The results demonstrate that multi-band parallel computing all-optical logic gates can be achieved using topological photonic crystals, and these gates exhibit high robustness. The all-optical logic gates designed in this study hold significant potential for future applications in optical signal processing, optical communication, optical sensing, and other related areas.
Complete Genome Sequence Analysis of a Dengue Case Co-Infected with Type I and Type II Imported into Jiaxing in 2023
Authors: Zhou Yamei , Lv Shencong , Yan Hao , Ren Ganglin , Song Yin , Jj Jimei , Li Lina , Yan Yong , Zhu Guoying
Published: December 2024

In 2023, one case of coinfection with type I and type II dengue virus of imported origin was first reported in Jiaxing city. Therefore, we analysed the results of the molecular tracing analysis of this case. We collected serum samples for whole-genome amplification and sequencing and further analysed the whole-genome sequence for homology analysis, evolutionary tree analysis, and protein amino acid mutation site analysis. The results revealed that the JX202301 DENV-1 sequence had the highest homology with the epidemic strains in Guangdong (PP563909, PP563875, PP563840, and PP563879) in 2023, with nucleotide homology ranging from 99.5 to 99.8% and amino acid homology of 100%. The JX202301 DENV-2 sequence had the highest homology with the epidemic strains of 2019 Thailand (MZ636805, MZ636802, MZ636803, MW512454, and MW512419), with nucleotide homology ranging from 98.4 to 99.2% and amino acid homology of 99.7%. By analysing the amino acid mutation sites, we found that, compared with the corresponding reference strains and the epidemic strains in the same branch, there were 52 amino acid difference sites in the viral coding region of the DENV-1 sequence and 51 amino acid difference sites in the viral coding region of the DENV-2 sequence, which were mainly concentrated in the NS1 and NS5 region of the nonstructural proteins. In this study, we described for the first time the genome-wide sequence, genetic variation, and phylogenetic analysis of imported DENV-1 and DENV-2 mixed cases in Jiaxing city. These results provide a scientific basis for dengue fever outbreak surveillance, viral evolution studies, and prevention and control strategy development in Jiaxing city.
Antifungal Activity on Botrytis fabae and Response of Agronomic Variables of Plant Extracts in Faba Beans
Authors: Mora-Baez Guadalupe , Torres-Rueda Lucia , Morgado-Gonzalez Antonio , Nava-Díaz Cristian , Soto-Hernández Ramón Marcos , Carrillo-López Luis Manuel
Published: December 2024

Chocolate spot (Botrytis fabae) is a disease that threatens faba bean production in Mexico, as it can cause up to 70% yield losses. Currently, indiscriminate fungicides combat this disease, leading to environmental and human health problems. In this context, the effect of applying ethanolic extracts of two native plants of Mexico (Litsea glaucescens and Tagetes erecta), and Ruta graveolens was evaluated under in vitro and field conditions, in comparison to a commercial fungicide (Benomyl®) on the percentage of inhibition, incidence, severity, and relevant agronomic variables (plant height, number of secondary stems, number of flowers, and number and weight of pods). Applications with ethyl alcohol and water were used as controls. Both the bay laurel extract and Benomyl® achieved 100% inhibition under in vitro conditions, while in the field, they reduced severity by up to 51% at the beginning and end of the experiment. Plants treated with the marigold extract showed greater plant height (90.3 cm), while those treated with ethyl alcohol (control 1) had the lowest height (76.5 cm). The fungicide and bay laurel extract produced pods with higher weight (166.3 g and 139.2 g, respectively), while the water control produced pods weighing only 33.1 g. The ethanolic extract of bay laurel could potentially replace the chemical control of chocolate spot without affecting faba bean crop yield.
High Prevalence of High-Risk HPV Among People with and Without HIV: Insights into Risk Factors for Tailored Screening Approaches
Authors: Bruzzesi Elena , Gandini Federica , Diotallevi Sara , Lolatto Riccardo , Cernuschi Massimo , Candela Caterina , Raccagni Angelo Roberto , Passini Flavia , Tamburini Andrea Marco , Burioni Roberto , Castagna Antonella , Nozza Silvia
Published: December 2024

Men who have sex with men (MSM) and people with HIV are at increased risk of anal HPV infection and cancer. This study aimed to assess the prevalence of anal HPV among MSM with HIV (MWH) and without HIV (MWoH), as well as among MSM under and over 35 years. Factors associated with infection from high-risk (HR) HPV were investigated. This retrospective cohort analysis included MSM receiving care at IRCCS San Raffaele, Milan, Italy, with at least one HPV test collected from 2014 to 2023. Among 1577 MSM, 1427 (90%) were MWH. At first screening, 87.6% were had HR-HPV and MWoH were significantly younger, as compared to MWH. Cytological abnormalities were more frequent among younger MSM, while high-grade lesions were more frequent among those over 35 years of age. In multivariate regressions, the risk of ≥1 HR-HPV genotype at first and last screening was associated with younger age (adjusted odds ratio, aOR (95% confidence interval): 0.33 (0.18, 0.59); 0.34 (0.18, 0.58), p < 0.001) and concomitant STI (aOR 2.74 (1.59, 5.08), p < 0.001; 1.68 (1.09, 2.67), p: 0.023). A discrepancy between the recommend and actual age for screening was found. As a younger age and concomitant STIs were associated with infection by ≥1 HR-HPV, we promote a more tailored screening approach for both MWH and MWoH.
CuO-TiO2–Saponite Ternary Nanocomposite for Efficient Removal of Bromocresol Green Dye
Authors: Trigueiro Pollyana , Albuquerque Willams A. , Jerônimo Aimée G. , Rodrigues Monica Sá , França Emanoel L. Tavares , Peña-Garcia Ramón Raudel
Published: December 2024

This study presents the synthesis of a CuO-TiO2–saponite ternary nanocomposite via a hydrothermal method, designed to efficiently remove bromocresol green dye. Characterization techniques, including X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy, confirmed significant interactions between metal oxide nanoparticles and the clay mineral matrix. Diffuse reflectance and photoluminescence analyses revealed a narrow band gap and surface defects, such as oxygen vacancies, enhancing the material’s photocatalytic properties. Under UV irradiation, the nanocomposite achieved 83% discoloration of bromocresol green dye within 150 min. The inhibitor studies identified hydroxyl and superoxide radicals as key species in the degradation mechanism. This work underscores the potential of clay-mineral-based nanocomposites, where clay minerals function both as structural support and as enhancers of the semiconductor’s photocatalytic activity.
Aqueous Carbonation of Waste Incineration Residues: Comparing BA, FA, and APCr Across Production Scenarios
Authors: Wehrung Quentin , Bernasconi Davide , Destefanis Enrico , Caviglia Caterina , Curetti Nadia , Di Felice Sara , Bicchi Erica , Pavese Alessandro , Pastero Linda
Published: December 2024

This study investigates the reactivity of municipal solid waste incineration residues to aqueous carbonation, focusing on CO2 absorption rates, uptakes, and heavy metal (HM) leachability. Various combinations of boiler, electrofilter, and bag filter residues were assessed under typical incineration conditions. Bag filter residues from lime-sorbent plants exhibited the highest CO2 uptake (244.5 gCO2/kg), while bottom ash (BA) fine fraction, boiler/electrofilter fly ash (FA), and other mixed air pollution control residue (APCr) demonstrated uptakes of 101, 0, 93, and 167 gCO2/kg, respectively. Carbonation kinetics revealed that high calcium content FA and APCr, followed similar CO2 absorption trends. Notably, BA carbonation was predominantly driven by Ca-aluminates rather than lime. Carbonation reduces leaching of Al, As, Cd, Co, Cu, Ni, Pb and Zn compared to water washing, though significant concerns arise with anions such as Sb and Cr. In BA, critical behaviours of Cr, Mn, and Fe were observed, with Cr leaching likely controlled by Fe-Mn-Cr oxide particle dissolution. These findings highlight the potential of integrating enhanced metal recovery (EMR) through density or magnetic separation in BA prior to carbonation to reduce HM leaching and recycle critical metals (Ag, Cu, Cr, Ni, Mn, etc).
Dual-Valence Copper Nanostructures with Cu+/Cu2+ Interfaces for High-Sensitivity Glucose Electrochemical Sensing
Authors: Yu Zhipeng , Yan Pengxu , Sheng Yilei , Zhang Chengwei , Qiao Zhun , Fan Qikui , Kong Chuncai , Yang Zhimao
Published: December 2024

Copper-based materials, renowned for their redox versatility and conductivity, have extensive applications in electrochemical sensing. Herein, we construct stable Cu+/Cu2+ interfaces within dual-valence copper nanostructures to achieve enhanced sensitivity in glucose sensing. By employing a hydrolysis method to tune Cu2+/Cu+ ratios precisely, we achieved an optimal electrochemical interface with heightened stability and reactivity. The Cu+/Cu2+ interface-based flexible electrode demonstrated excellent glucose sensitivity (332.4 µA mmol/L−1 cm−2 at +0.65 V), wide linear range (up to 10 mmol), a low detection limit of 1.02 nmol/L, and strong selectivity, including detection in human sweat, making this study significant for advanced electrochemical sensors.
Enhanced Visible Light Controlled Glucose Photo-Reforming Using a Composite WO3/Ag/TiO2 Photoanode: Effect of Incorporated Plasmonic Ag Nanoparticles
Authors: Jakubow-Piotrowska Katarzyna , Witkowski Bartlomiej , Wrobel Piotr , Miecznikowski Krzysztof , Augustynski Jan
Published: December 2024

WO3/Ag/TiO2 composite photoelectrodes were formed via the high-temperature calcination of a WO3 film, followed by the sputtering of a very thin silver film and deposition of an overlayer of commercial TiO2 nanoparticles. These synthetic photoanodes were characterized in view of the oxidation of a model organic compound glucose combined with the generation of hydrogen at a platinum cathode. During prolonged photoelectrolysis under simulated solar light, these photoanodes demonstrated high and stable photocurrents of ca. 4 mA cm−2 due, on one hand, to the occurrence of the so-called photocurrent doubling and, on the other hand, to the plasmonic effect of Ag nanoparticles. The post-photoelectrolysis analyses of the electrolyte demonstrated the formation of high-value final glucose photo-reforming products, principally gluconic acid, erythrose and formic acid.
Burden of Wasting and Stunting in Colombia and Its Economic Impact: A Society’s Perspective Analysis, 2021
Authors: Londoño Trujillo Darío , Taborda Restrepo Paula Andrea , De la Hoz María Camila , Burgos Castro Juan Carlos , Arbelaez Vargas Joan Sebastian , Pineda Ruiz Diana María
Published: December 2024

Background/Objectives: Child malnutrition is a critical public health concern that significantly hampers children’s physical and mental development and imposes serious economic burdens. The World Health Organization (WHO) estimates that malnutrition is responsible for half of all deaths among children under five, leading to long-term consequences such as lower educational achievement, decreased productivity, and deepened poverty. This study aims to estimate the burden of child malnutrition in Colombia for children up to four years old, assessing both direct and indirect costs from a societal perspective. Methods: A Markov chain model was utilized to simulate six health states related to malnutrition, integrating direct and indirect costs. Epidemiological data and international literature informed the transition probabilities between states, while caregiver surveys were conducted to capture the indirect costs. Results: The study found that malnutrition accounted for 419.84 disability-adjusted life years (DALYs) per 1000 inhabitants. The total cost of malnutrition over a four-year period was approximately USD 243.58 million, with an annual average of USD 60.89 million, of which 65% of the burden fell on households. Conclusions: Child malnutrition in Colombia presents a considerable burden on health systems, households, and the national economy, demonstrating the need for robust interventions to mitigate its long-term socioeconomic impact.
Enhancing Performance in Young Athletes: A Systematic Review of Acute Supplementation Effects
Authors: Gruska Nina , Sarmento Hugo , Martinho Diogo , Field Adam , Massart Alain
Published: December 2024

Background/Objectives: The increasing popularity of acute supplementation among young athletes is concerning, given the limited scientific evidence to guide recommendations specific to this group. Therefore, the aim of this systematic review was to synthesize the available scientific evidence on the acute effects of supplementation in young athletes to understand the impact on physical and cognitive performance. Methods: Following pre-registration on INPLASY (INPLASY202310017) and according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, systematic searches of three electronic databases (Web of Science, PubMed, and Scopus) were conducted by independent researchers from inception until July 2024. Only original studies in English that examined the acute effects of supplementation on young athletes’ physical and/or cognitive performance, specifically when taken on the same day as exercise (before or during), were included. The risk of bias was individually assessed for each study using the revised Cochrane risk of bias tool for randomized trials (RoB 2.0). Results: A total of 16 studies were included in the review. A range of ages, participants, sports, and methodological approaches were involved in the studies included in the current review. The studies mainly used carbohydrates, beetroot juice, and sodium citrate, with carbohydrates being the most used acute supplementation. Carbohydrate supplementation enhanced endurance capacity and increased blood glucose, but mixed results were found for anaerobic performance. Mixed results were found for beetroot juice, with one study finding increases in power production. One study used sodium citrate supplementation, with improvements in technical performance observed. Conclusions: Since this review identified only three substances meeting our eligibility criteria, further research is needed to confirm the acute effects of supplements in young athletes and to better understand their benefits and limitations. Carbohydrate supplementation shows strong evidence for enhancing endurance performance, particularly during prolonged activities, while sodium citrate appears to support the preservation of skill performance. In contrast, the effects of beetroot juice are less consistent. Additional research is required to confirm the acute effects of supplements like beetroot juice in young athletes.
Bovine Colostrum in Pediatric Nutrition and Health
Authors: Canbolat Ahmet Alperen , Lombardo Mauro , Mondragon Alicia del Carmen , López Jose Manuel Miranda , Bechelany Mikhael , Karav Sercan
Published: December 2024

Bovine colostrum (BC), the first milk secreted by mammals after birth, is a trending alternative source for supplementing infants and children, offering benefits for gut and immune health. Its rich components, such as proteins, immunoglobulins, lactoferrin, and glycans, are used to fortify diets and support development. Preterm development is crucial, especially in the maturation of essential systems, and from 2010 to 2020, approximately 15% of all premature births occurred at less than 32 weeks of gestation worldwide. This review explores the composition, benefits, and effects of BC on general infants and children, along with preterm infants who require special care, and highlights its role in growth and development. BC is also associated with specific pediatric diseases, including necrotizing enterocolitis (NEC), infectious diarrhea, inflammatory bowel disease (IBD), short-bowel syndrome (SBS), neonatal sepsis, gastrointestinal and respiratory infections, and some minor conditions. This review also discusses the clinical trials regarding these specific conditions which are occasionally encountered in preterm infants. The anti-inflammatory, antimicrobial, immunomodulatory, and antiviral properties of BC are discussed, emphasizing its mechanisms of action. Clinical trials, particularly in humans, provide evidence supporting the inclusion of BC in formulas and diets, although precise standards for age, feeding time, and amounts are needed to ensure safety and efficacy. However, potential adverse effects, such as allergic reactions to caseins and immunoglobulin E, must be considered. More comprehensive clinical trials are necessary to expand the evidence on BC in infant feeding, and glycans, important components of BC, should be further studied for their synergistic effects on pediatric diseases. Ultimately, BC shows promise for pediatric health and should be incorporated into nutritional supplements with caution.
Evaluating the Clinical Impact of a Polyphenol-Rich Extract from Salicornia ramosissima on Patients with Transient Ischemic Attack and Minor Stroke
Authors: Nájar Ana M. , López Azcárate Cristina , Domínguez Ruiz Carmen , Núñez-Jurado David , de Torres Reyes , López Reyes , Camino-Moya Miriam , Magni Eleonora , Montero-Ramirez Emilio , Bocero Antonio , Laviana Álvaro , Busquier Cerdán Teresa , León Antonio , del Rio Carmen , Montaner Joan , Pérez-Sánchez Soledad
Published: December 2024

Transient ischemic attack (TIA) is a well-established risk factor for future strokes, making interventions that target recovery and vascular risk crucial. This study aimed to assess the safety and clinical effects of a polyphenol-rich Salicornia ramosissima extract in post-TIA patients. A randomized, triple-blind, placebo-controlled trial was conducted with participants who had a history of TIA or minor stroke and who received 1 g of Salicornia extract or placebo over 11 months. Biochemical analyses, neuropsychological assessments (MOCA test), and gait and aerobic performance tests were conducted at the beginning and the end of the study. A total of 118 individuals were screened, with 80 finally included. Importantly, no significant adverse events were reported throughout the study. A neurological analysis showed an improvement in MOCA scores in patients treated with the Salicornia extract for 11 months. The treatment did not affect spatiotemporal gait parameters, but it significantly reduced blood pressure at baseline and after the aerobic performance test. Biochemically, both groups exhibited mild hyperhomocysteinemia at baseline; however, Salicornia treatment significantly lowered homocysteine levels, bringing them within the normal range. These findings highlight the safety of the Salicornia extract in patients at a high cerebrovascular risk and suggest it as a potential therapeutic option for managing vascular risk factors, such as hyperhomocysteinemia and hypertension. However, further studies are required to confirm the underlying mechanisms and explore broader clinical applications.
Mindful Eating, BMI, Sleep, and Vitamin D: A Cross-Sectional Study of Cypriot and Greek Adults
Authors: Andreou Eleni , Mouski Christiana , Georgaki Evridiki , Andreou Nayia , Christoforou Christoforos , Abboud Myriam , Korfiati Persa , Kaxiri Fani , Papaioannou Marilena , Philippou Christiana , Papandreou Dimitrios , Papaneophytou Christos
Published: December 2024

Background: Obesity and related health challenges remain significant concerns in Cyprus and Greece. Mindful eating (ME) has emerged as a behavioral approach to address these issues, yet its relationship with BMI, vitamin D levels, and sleep duration in Mediterranean populations is underexplored. Objectives: This study aimed to examine associations between ME subcategories (Awareness, Distraction, Disinhibition, Emotional, and External Cues), BMI, vitamin D levels, and sleep duration among Cypriot and Greek adults across two cohorts. Methods: A cross-sectional design was employed with data collected in 2022 (N1 = 438) and 2023 (N2 = 174). Participants completed the validated Cyprus Mindful Eating Questionnaire (CyMEQ). Vitamin D levels, sleep duration, and BMI were self-reported. Statistical analyses included Mann–Whitney U Tests for ME subcategory comparisons, chi-square tests for categorical variables, and Spearman correlations to examine associations. Results: Significant differences were found between cohorts in ME subcategories, with N1 scoring higher in Awareness [Median (IQR): 2.60 (2.20–3.00) vs. 2.00 (1.80–2.30), p = 0.02], Disinhibition [2.70 (2.50–3.00) vs. 2.50 (2.20–2.70), p = 0.03], and External Cues [2.50 (2.10–2.90) vs. 2.10 (1.80–2.50), p = 0.01]. ME scores were negatively correlated with BMI (r = −0.25, p = 0.01) and positively associated with vitamin D levels and sleep duration. Differences in vitamin D supplementation practices were observed across groups; however, these differences did not reach statistical significance (p = 0.07). Conclusions: ME behaviors, particularly Awareness and Disinhibition, are associated with BMI, highlighting their potential in obesity management. The interplay between ME, vitamin D, and sleep underscores the need for integrative health interventions in Mediterranean populations.
Transcriptional and Metabolic Changes Following Repeated Fasting and Refeeding of Adipose Stem Cells Highlight Adipose Tissue Resilience
Authors: Galigniana Natalia M. , Abdelhalim Mohamed , Collas Philippe , Sæther Thomas
Published: December 2024

Background: Obesity and related metabolic disorders have reached epidemic levels, calling for diverse therapeutic strategies. Altering nutrient intake, timing and quantity by intermittent fasting seems to elicit beneficial health effects by modulating endocrine and cell signaling networks. This study explores the impact of cyclic nutrient availability in the form of every-other-day fasting (EODF) on human adipose stem cells (ASCs). Methods: We subjected ASCs to repeated fasting/refeeding (F/R) cycles, mimicking low glucose/high fatty acid (LGHF) conditions, and assessed phenotypic and transcriptomic changes, lipid storage capacity, insulin sensitivity, and differentiation potential. Results: Four consecutive F/R cycles induced significant changes in adipogenic gene expression, with upregulation of FABP4 and PLIN1 during fasting, and increased lipid storage in the ASCs. Upon differentiation, ASCs exposed to LGHF conditions retained a transient increase in lipid droplet size and altered fatty acid metabolism gene expression until day 9. However, these changes dissipated by day 15 of differentiation, suggesting a limited duration of fasting-induced transcriptional and adipogenic memory. Despite initial effects, ASCs showed resilience, returning to a physiological trajectory during differentiation, with respect to gene expression and lipid metabolism. Conclusions: These findings suggest that the long-term effects of EODF on the ASC niche may be transient, emphasizing the ability of the adipose tissue to adapt and restore homeostasis.
Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B
Authors: He Wei , Zheng Zhijin , Zhao Qian , Zhang Renxia , Zheng Hui
Published: December 2024

Chronic hepatitis B (CHB) caused by HBV infection has brought suffering to numerous people. Due to the stable existence of HBV cccDNA, the original template for HBV replication, chronic hepatitis B (CHB) is difficult to cure completely. Despite current antiviral strategies being able to effectively limit the progression of CHB, complete CHB cure requires directly targeting HBV cccDNA. In this review, we discuss strategies that may achieve a complete cure of CHB, including inhibition of cccDNA de novo synthesis, targeting cccDNA degradation through host factors and small molecules, CRISP-Cas9-based cccDNA editing, and silencing cccDNA epigenetically.
The Mosquito Microbiota: A Key Player in Vector Competence and Disease Dynamics
Authors: Palinauskas Vaidas , Abdelali Salma Kaoutar , Cabezas-Cruz Alejandro
Published: December 2024

Mosquitoes are well-known vectors for a range of pathogens, including Plasmodium parasites, which cause malaria in reptiles, birds, and mammals [...]
FISH–Flow Cytometry Reveals Microbiome-Wide Changes in Post-Translational Modification and Altered Microbial Abundance Among Children with Inflammatory Bowel Disease
Authors: Ulas Mevlut , Hussey Seamus , Broderick Annemarie , Fitzpatrick Emer , Dunne Cara , Cooper Sarah , Dominik Anna , Bourke Billy
Published: December 2024

Metaproteomic analysis of microbiome post-translation modifications (PTMm) is challenging, and little is known about the effects of inflammation on the bacterial PTM landscape in IBD. Here, we adapted and optimised fluorescence in situ hybridisation–flow cytometry (FISH-FC) to study microbiome-wide tyrosine phosphorylation (p-Tyr) in children with and without inflammatory bowel disease (IBD). Microbial p-Tyr signal was significantly higher in children with IBD, compared to those without. Faecalibacterium prausnitzii, Bacteroidota, Gammaproteobacteria and Bifidobacteria tended to be more abundant in IBD than in non-IBD control children but there were only minor differences in p-Tyr among these bacterial communities in those with and without IBD. p-Tyr was significantly lower in non-IBD children older than 9 yrs compared with those less than 9 yrs, and the effect was seen in all four bacterial subgroups studied. The opposite trend was seen in patients with IBD. p-Tyr overall is higher in children with IBD but the effects of inflammation on p-Tyr vary according to the bacterial community. The overall microbiome p-Tyr signal changes with age in healthy children. FISH-FC can be used to study the microbiome-wide PTM landscape.
Centella asiatica Promotes Antioxidant Gene Expression and Mitochondrial Oxidative Respiration in Experimental Autoimmune Encephalomyelitis
Authors: Kundu Payel , Yasuhara Kanon , Brandes Mikah S. , Zweig Jonathan A. , Neff Cody J. , Holden Sarah , Kessler Kat , Matsumoto Steven , Offner Halina , Waslo Carin S. , Vandenbark Arthur , Soumyanath Amala , Sherman Larry S. , Raber Jacob , Gray Nora E. , Spain Rebecca I.
Published: December 2024

Background/Objectives: Centella asiatica (L.) Urban (family Apiaceae) (C. asiatica) is a traditional botanical medicine used in aging and dementia. Water extracts of C. asiatica (CAW) have been used to treat neuropsychiatric symptoms in related animal models and are associated with increases in antioxidant response element (ARE) genes and improvements in mitochondrial respiratory function and neuronal health. Because multiple sclerosis (MS) shares its neurogenerative pathology of oxidative stress and mitochondrial dysfunction with aging and dementia, neuropsychiatric symptoms in MS may also benefit from C. asiatica. To determine whether CAW similarly benefits neuropsychiatric symptoms, ARE gene expression, and mitochondrial respiration in inflammatory models of MS, and to determine the effects of CAW on clinical disability and inflammation, we tested CAW using experimental autoimmune encephalomyelitis (EAE). Methods: C57BL/6J mice induced with EAE were treated with CAW or a placebo for 2 weeks. The outcomes were clinical disability, signs of anxiety (open field test), ARE gene expression, mitochondrial respiration, and inflammation and demyelination. Results: At the dosing schedule and concentrations tested, CAW-treated mice with EAE demonstrated increased ARE gene expression and mitochondrial respiratory activity compared to those of placebo-treated mice with EAE. CAW was also associated with reduced inflammatory infiltrates in the spinal cord, but the differences between the populations of activated versus quiescent microglia were equivocal. CAW did not improve behavioral performance, EAE motor disability, or demyelination. Conclusions: In the inflammatory EAE model of MS, CAW demonstrates similar neuroprotective effects to those it exhibits in aging and dementia mouse models. These benefits, along with the anti-inflammatory effects of CAW, support further investigation of its neuropsychiatric effects in people with MS.
p53: The Multifaceted Roles of Covalent Modifications in Cancer
Authors: Grigoreva Tatiana A. , Romanova Angelina A. , Tribulovich Vyacheslav G. , Pestov Nikolay B. , Oganov Ruslan A. , Kovaleva Diana K. , Korneenko Tatyana V. , Barlev Nickolai A.
Published: December 2024

The p53 protein has attracted huge research interest over several decades due to its role as one of the most important tumor suppressors in mammals, which orchestrates a synchronous response from normal cells in the body to various forms of stress. The diverse cellular activities of the p53 protein are regulated mainly via its post-translational modifications (PTMs). PTMs affect p53 on several levels: at the level of the assembly of tetrameric complexes on DNA to transactivate its target genes, at the level of the assembly of tetrameric complexes on DNA to transactivate its target genes; at the level of proteolysis in the absence of stress; and on the contrary, at the level of augmented protein stability in response to stress signals. Disruptions in these regulatory mechanisms can lead to deviations from normal cellular function, boosting tumor initiation and progression. Conversely, targeted interventions in these pathways could prove beneficial for the development of antitumor therapies. Advancing our understanding of p53 modifiers and the proteins involved in its regulation equips researchers with an expanded toolkit for studying cellular processes and for developing biologically active molecules that influence p53-mediated responses.
A Comprehensive Review: Mesoporous Silica Nanoparticles Greatly Improve Pharmacological Effectiveness of Phytoconstituent in Plant Extracts
Authors: Aulifa Diah Lia , Amarilis Bunga , Ichsani Luthfia Nur , Maharani Devita Salsa , Shabrina Ayunda Myela , Hanifah Hanifah , Wulandari Rizky Prasiska , Rusdin Agus , Subra Laila , Budiman Arif
Published: December 2024

Medicinal plants are increasingly being explored due to their possible pharmacological properties and minimal adverse effects. However, low bioavailability and stability often limit efficacy, necessitating high oral doses to achieve therapeutic levels in the bloodstream. Mesoporous silica nanoparticles (MSNs) offer a potential solution to these limitations. Due to their large surface area, substantial pore volume, and ability to precisely control pore size. MSNs are also capable of efficiently incorporating a wide range of therapeutic substances, including herbal plant extracts, leading to potential use for drug containment and delivery systems. Therefore, this review aimed to discuss and summarize the successful developments of herbal plant extracts loaded into MSN, focusing on preparation, characterization, and the impact on efficacy. Data were collected from publications on Scopus, PubMed, and Google Scholar databases using the precise keywords “mesoporous silica nanoparticle” and “herbal extract”. The results showed that improved phytoconstituent bioavailability, modified release profiles, increased stability, reduced dose and toxicity are the primary benefits of this method. This review offers insights on the significance of integrating MSNs into therapeutic formulations to improve pharmacological characteristics and effectiveness of medicinal plant extracts. Future prospects show favorable potential for therapeutic applications using MSNs combined with herbal medicines for clinical therapy.
Comparative Analyses of the Safety Profiles of Vitamin D Receptor Agonists: A Pharmacovigilance Study Based on the EudraVigilance Database
Authors: Gáll Zsolt , Kolcsar Melinda
Published: December 2024

Background/Objectives: Vitamin D receptor (VDR) agonists are commonly used in clinical practice for their roles in calcium regulation and potential benefits in various diseases. However, their safety profiles, particularly for compounds available as food supplements, remain underexplored in real-world settings. This study aimed to analyze the safety profiles of VDR agonists using the EudraVigilance database, focusing on adverse drug reactions (ADRs) reported between 1 January 2004 and 23 June 2024. Methods: Data for ten VDR agonists were collected, de-duplicated, and analyzed to identify specific safety signals. Risk factors for specific ADRs were assessed using multiple logistic regression. Results: This study analyzed 5,369,581 reports in the EudraVigilance system, from which 17,947 reports (0.33%) involving 80,050 ADRs were linked to VDR agonists. The most-reported drugs were cholecalciferol (12,944 cases) and calcitriol (1355 cases). Serious ADRs were more prevalent with paricalcitol, alfacalcidol, and calcitriol than with cholecalciferol (p < 0.05). Hypercalcemia was a hallmark ADR for all VDR agonists, with the highest risk linked to dihydrotachysterol (ROR = 5668; 95%CI = 3332 to 9641; p < 0.0001), alfacalcidol (ROR = 965.7; 95%CI = 843.6 to 1106; p < 0.0001), and calcitriol (ROR = 726.0; 95%CI = 634.6 to 830.5; p < 0.0001). Logistic regression highlighted dehydration, overdose, and concomitant administration of calcium salts as major predictors of hypercalcemia. The co-administration of multiple VDR agonists was also found to increase hypercalcemia risk. However, the disproportionality analysis showed that only active VDR agonists (e.g., calcitriol, alfacalcidol) were associated with severe complications like renal and urinary disorders and cardiac issues due to hypercalcemia. Natural precursors (cholecalciferol, ergocalciferol) were more often linked to non-calcemic ADRs such as gastrointestinal symptoms, which were more prevalent in infants and children compared to adults. Conclusions: The safety profiles of VDR agonists differ significantly between compounds. Active derivatives require close monitoring for serious calcemia-related complications, whereas cholecalciferol is associated with less severe ADRs, primarily in at-risk populations. These findings highlight the need for targeted safety monitoring and further research into the real-world uses of VDR agonists.
Editorial on Special Issue “State-of-Art in mRNA Therapeutics and Gene Delivery”
Authors: Mendonça Liliana S.
Published: December 2024

RNA therapeutics are a class of medicines based on the insertion of a specific genetic message (mRNA) into the cells and the silencing or gene editing of a specific mRNA [...]
Performance Analysis of Chirped Graded Photonic Crystal Resonator for Biosensing Applications
Authors: Saini Jasmine , Kumar Ajay , Goyal Amit Kumar
Published: December 2024

In this manuscript, a chirped graded photonic crystal (PhC) resonator structure is optimized for biosensing applications. The proposed structure comprises a bilayer PhC with an aqueous defect layer, where the thickness grading within the material is introduced, considering alpha (α) as a grading parameter. The device performance is analytically evaluated using the finite element method (FEM). The impact of α, the resonator thickness, and the incidence angle on the device performance is analyzed. Further, the device’s ability to be used as a biosensor is evaluated, considering cholesterol as an analyte. The analytical results demonstrate an average sensitivity of 410 nm/RIU, a quality factor of 0.91 × 103, and a figure of merit (FOM) of 2.47 × 102RIU−1, showing 88.5% and 43% improvements in sensitivity and FOM compared to recently reported devices. The device’s superior sensing performance makes it suitable for medical and commercial applications, while the use of thickness grading addresses fabrication limitations, offering a robust framework for advanced photonic device design.