bluuebunny/crossref_metadata_2025 huggingface dataset:
The Multivariate Fusion Distribution Characteristics in Physician Demand Prediction
Authors: Zhang Jiazhen , Chen Wei , Wang Xiulai
Published: January 2025

Aiming at the optimization of the big data infrastructure in China’s healthcare system, this study proposes a lightweight time series physician demand prediction model, which is especially suitable for the field of telemedicine. The model incorporates multi-head attention mechanisms and generates statistical information, which significantly improves the ability to process nonlinear data, adapt to different data sources, improve the computational efficiency, and process high-dimensional features. By combining variational autoencoders and LSTM units, the model can effectively capture complex nonlinear relationships and long-term dependencies, and the multi-head attention mechanism overcomes the limitations of traditional algorithms. This lightweight architecture design not only improves the computational efficiency but also enhances the stability in high-dimensional data processing and reduces feature redundancy by combining the normalization process with statistics. The experimental results show that the model has wide applicability and excellent performance in a telemedicine consulting service system.
Application of Evolutionary Game to Analyze Dual-Channel Decisions: Taking Consumer Loss Aversion into Consideration
Authors: Zhang Shuang , Du Yueping
Published: January 2025

Manufacturers and consumers are boundedly rational and ultimately seek evolutionarily stable strategies through trial and error, imitation, and learning. It is important to study the pricing strategies of manufacturers and the purchasing channel decisions of consumers in the context of increasingly fierce competition in online channels, in addition to consumers’ loss aversion due to increasingly confusing promotional strategies; accordingly, in this paper, an evolutionary game including both parties is constructed, and the loss aversion factor from prospect theory is introduced. Based on data from Chinese media reports on the cosmetics industry, simulation and sensitivity analyses were conducted using Matlab R2024a. The results indicate that—in addition to channel services affecting the evolutionarily stable strategy for purchasing channel selection—a decrease in consumer loss aversion will help consumers reach the evolutionarily stable strategy faster. For manufacturers, channel services do not affect their evolution to a unified pricing strategy; however, when consumer loss aversion increases, manufacturers’ evolutionarily stable strategy will shift from a unified pricing strategy to a differentiated pricing strategy.
The Multi-Soliton Solutions for the (2+1)-Dimensional Caudrey–Dodd–Gibbon–Kotera–Sawada Equation
Authors: Xu Li-Jun , Ma Zheng-Yi , Fei Jin-Xi , Wu Hui-Ling , Cheng Li
Published: January 2025

The (2+1)-dimensional integrable Caudrey–Dodd–Gibbon–Kotera–Sawada equation is a higher-order generalization of the Kadomtsev–Petviashvili equation, which can be applied in some physical branches such as the nonlinear dispersive phenomenon. In this paper, we first present the bilinear form for this equation after constructing one Bäcklund transformation. As a result, the one-soliton solution, two-soliton solution, and three-soliton solution are shown successively and the corresponding soliton structures are constructed. These solitons and their interactions illustrate that the obtained solutions have powerful applications.
Antioxidant and Anti-Obesity Properties of Acidic and Alkaline Seaweed Extracts Adjusted to Different pH Levels
Authors: Ghelichi Sakhi , Hajfathalian Mona , Falcione Sara , Jacobsen Charlotte
Published: January 2025

This research examined antioxidant and anti-obesity effects of Palmaria palmata extracts obtained through acidic or alkaline treatments and subsequent pH adjustments. After two rounds of acidic or alkaline extraction, the extracts were separated from biomass and adjusted to different pH values: for acidic extracts, pH 3 (no adjustment), pH 6, pH 9, and pH 12; for alkaline extracts, pH 12 (no adjustment), pH 9, pH 6, and pH 3. The findings revealed that extraction medium as well as subsequent pH adjustments significantly influenced composition of the extracts in terms of protein content and recovery, amino acids, and phenolic compounds (p < 0.05). Acidic conditions produced extracts with potent radical scavenging, especially at pH 6 (IC50 = 0.30 ± 0.04 mg.mL−1), while alkaline conditions favored metal chelating, with the highest Fe2+ chelation at pH 12 (IC50 = 0.65 ± 0.03 mg.mL−1). Moreover, extracts showed inhibitory activities against porcine pancreatic lipase and α-amylase, with the acidic extract at pH 9 showing the best anti-obesity properties (IC50 = 5.38 ± 0.34 mg.mL−1 for lipase and IC50 = 5.79 ± 0.30 mg.mL−1 for α-amylase). However, the highest α-amylase activity was in the alkaline extract at pH 12 (IC50 = 3.05 ± 0.66 mg.mL−1). In conclusion, adjusting the pH of seaweed extracts notably influences their bioactive properties, likely due to changes in the reactivity and interactions of bioactive compounds such as peptides, carbohydrates, and polyphenols.
Involvement of HLADQA1*05 in Patients with Inflammatory Bowel Disease Treated with Anti-TNF Drugs
Authors: Pau Anna , Galliano Ilaria , Barnini Elisa , Dini Maddalena , Pizzol Antonio , Ponte Alice , Gambarino Stefano , Calvo Pier Luigi , Bergallo Massimiliano
Published: January 2025

Background: Over the past decade, TNF inhibitors such as Infliximab and Adalimumab have become central to Inflammatory Bowel Diseases treatment, greatly enhancing patient outcomes. However, immunogenicity—where anti-drug antibodies diminish effectiveness—remains an issue, often requiring dose changes or combination therapies. Pharmacogenomics is increasingly applied in IBD to personalise treatment, especially since genetic factors like the HLA-DQA1*05 variant heighten the immunogenicity risk with IFX. This study aims to examine the relationship between the HLA-DQA1*05 variant and response loss or antibody development in patients regularly monitored on IFX or ADA. Methods: Sixty-five paediatric IBD patients were enrolled, with therapeutic drug monitoring (TDM) of IFX and ADA, conducted using immunoenzymatic assays. The presence of the HLA-DQA1*05 T>C allele variant was also tested using a Biomole HLA-DQA1 Real-time PCR kit. Results: The HLA-DQA1*05 rs2097432 T>C allele was present in 54% of patients on IFX and 69% of those on ADA. No statistically significant differences were found between HLA carriers and non-carriers across any of the three analysed groups: IFX, ADA and the overall anti-TNFα. Conclusions: Our study suggests that the HLA-DQA1*05 allele does not increase the risk of secondary loss of response to anti-TNF therapy, likely because most patients were on a combination of anti-TNF agents and immunomodulators, which can lower anti-drug antibody production. Testing for HLA-DQA105 can aid in personalising treatment and optimising therapy to minimise immunogenicity risks.
Separation of Short-Chain Fatty Acids from Primary Sludge into a Particle-Free Permeate by Coupling Chamber Filter-Press and Cross-Flow Microfiltration: Optimization, Semi-Continuous Operation, and Evaluation
Authors: Shylaja Prakash Nikhil , Maurer Peter , Horn Harald , Saravia Florencia , Hille-Reichel Andrea
Published: January 2025

Short-chain fatty acids (SCFAs) are valuable metabolic intermediates that are produced during dark fermentation of sludge, which, when capitalized on, can be used as chemical precursors for biotechnological applications. However, high concentrations of solids with SCFAs in hydrolyzed sludge can be highly detrimental to downstream recovery processes. This pilot-scale study addresses this limitation and explores the recovery of SCFAs from primary sludge into a particle-free permeate through a combination of chamber filter-press (material: polyester; mesh size: 100 µm) and cross-flow microfiltration (material: α-Al2O3; pore size: 0.2 µm; cross-flow velocity: 3 m∙s−1; pressure = 2.2 bars). Firstly, primary sludge underwent dark fermentation yielding a hydrolyzate with a significant concentration of SCFAs along with total solids (TS) concentration in the range of 20 to 30 g∙L−1. The hydrolyzate was conditioned with hydroxypropyl trimethyl ammonium starch (HPAS), and then dewatered using a filter press, reducing TS by at least 60%, resulting in a filtrate with a suspended solids concentration ranging from 100 to 1300 mg∙L−1. Despite the lower suspended solids concentration, the microfiltration membrane underwent severe fouling due to HPAS’s electrostatic interaction. Two methods were optimized for microfiltration: (1) increased backwashing frequency to sustain a permeate flux of 20 L∙m−2∙h−1 (LMH), and (2) surface charge modification to maintain the flux between 70 and 80 LMH. With backwashing, microfiltration can filter around 900 L∙meff−2 (without chemical cleaning), with the flux between 50 and 60 LMH under semi-continuous operation. Evaluating the particle-free permeate obtained from the treatment chain, around 4 gCSCFAs∙capita−1∙d−1 can be recovered from primary sludge with a purity of 0.85 to 0.97 CSCFAs∙DOC−1.
A Comprehensive Machine Learning Approach for COVID-19 Target Discovery in the Small-Molecule Metabolome
Authors: Sumon Md. Shaheenur Islam , Hossain Md Sakib Abrar , Al-Sulaiti Haya , Yassine Hadi M. , Chowdhury Muhammad E. H.
Published: January 2025

Background/Objectives: Respiratory viruses, including Influenza, RSV, and COVID-19, cause various respiratory infections. Distinguishing these viruses relies on diagnostic methods such as PCR testing. Challenges stem from overlapping symptoms and the emergence of new strains. Advanced diagnostics are crucial for accurate detection and effective management. This study leveraged nasopharyngeal metabolome data to predict respiratory virus scenarios including control vs. RSV, control vs. Influenza A, control vs. COVID-19, control vs. all respiratory viruses, and COVID-19 vs. Influenza A/RSV. Method: We proposed a stacking-based ensemble technique, integrating the top three best-performing ML models from the initial results to enhance prediction accuracy by leveraging the strengths of multiple base learners. Key techniques such as feature ranking, standard scaling, and SMOTE were used to address class imbalances, thus enhancing model robustness. SHAP analysis identified crucial metabolites influencing positive predictions, thereby providing valuable insights into diagnostic markers. Results: Our approach not only outperformed existing methods but also revealed top dominant features for predicting COVID-19, including Lysophosphatidylcholine acyl C18:2, Kynurenine, Phenylalanine, Valine, Tyrosine, and Aspartic Acid (Asp). Conclusions: This study demonstrates the effectiveness of leveraging nasopharyngeal metabolome data and stacking-based ensemble techniques for predicting respiratory virus scenarios. The proposed approach enhances prediction accuracy, provides insights into key diagnostic markers, and offers a robust framework for managing respiratory infections.
Correction: Tai et al. Sea Bass Essence from Lates calcarifer Improves Exercise Performance and Anti-Fatigue in Mice. Metabolites 2022, 12, 531
Authors: Tai Hong-Jun , Lee Mon-Chien , Hsu Yi-Ju , Kuo Chun-Yen , Huang Chi-Chang , Wang Ming-Fu
Published: January 2025

First, in the original publication [...]
Photonic and Optoelectronic Devices and Systems, Second Edition
Authors: Butt Muhammad A.
Published: January 2025

Photonic and optoelectronic devices and systems are at the forefront of modern technology, enabling the precise manipulation of light for a wide range of applications [...]
W-Band GaAs pHEMT Power Amplifier MMIC Stabilized Using Network Determinant Function
Authors: Han Seong-Hee , Kim Dong-Wook
Published: January 2025

This paper presents a W-band power amplifier monolithic microwave integrated circuit (MMIC) that is designed for high-precision millimeter-wave systems and fabricated using a 0.1 µm GaAs pHEMT process. The amplifier’s stability was evaluated using the network determinant function, ensuring robust performance under both linear and nonlinear conditions. Simultaneous matching for gain and output power was achieved with minimal passive elements. The developed power amplifier MMIC exhibits a linear gain exceeding 20 dB and an input return loss greater than 6 dB across the 88–98 GHz range. It delivers an output power of 23.8–24.1 dBm with a power gain of 17.3–17.9 dB in the 88–97 GHz range and achieves a maximum power-added efficiency (PAE) of 24% at 94 GHz.
Efficient Particle Manipulation Using Contraction–Expansion Microchannels Embedded with Hook-Shaped Arrays
Authors: Huang Di , Zhao Yan , Cao Chao , Zhao Jiyun
Published: January 2025

Inertial microfluidics, as an efficient method for the manipulation of micro-/nanoparticles, has garnered significant attention due to its advantages of high throughput, structural simplicity, no need for external fields, and sheathless operation. Common structures include straight channels, contraction–expansion array (CEA) channels, spiral channels, and serpentine channels. In this study, we developed a CEA channel embedded with hook-shaped microstructures to modify the characteristics of vortices. Through experimental studies, we investigated the particles’ migration mechanisms within the proposed structure. The findings indicated that, in comparison to conventional rectangular microstructures, the particles within the hook-shaped microstructured CEA channels experienced a more pronounced influence from inertial lift forces. Moreover, the magnitude of the second flow within the novel configuration was directly proportional to the channel width, the length of the expansion segment, and the embedding depth of the microstructure. The innovative structure was subsequently employed for particle trapping, focusing, and separation. The experimental outcomes revealed focusing efficiency of up to 99.1% and sorting efficiency of up to 97%. This research holds the potential to enhance the foundational theory of Dean flows and broaden the application spectrum of inertial contraction–expansion microfluidic chips.
Genomic and Metabolomic Analyses of Streptomyces albulus with Enhanced ε-Poly-l-lysine Production Through Adaptive Laboratory Evolution
Authors: Ren Xidong , Sun Xinjie , Chen Yan , Xi Xiangheng , Ma Yunzhe , Jiang Xinyue , Zhang Xian , Wang Chenying , Zhu Deqiang , Liu Xinli
Published: January 2025

ε-poly-l-lysine (ε-PL), a natural food preservative, has garnered widespread attention. It is mainly produced by Streptomyces albulus, but the production by wild-type strains fails to meet the demands of industrialization. To address this issue, adaptive laboratory evolution (ALE) was successfully employed in this study, subjecting S. albulus CICC 11022 to environmental stresses such as acidic pH and antibiotics (rifampicin, gentamicin, and streptomycin). As a result of ALE, an evolutionary strain S. albulus C214 was obtained, exhibiting an increase in ε-PL production and cell growth by 153.23% and 234.51%, respectively, as compared with the original strain. Genomic and metabolic analyses revealed that mutations occurred in genes responsible for transcriptional regulation, transporter, cell envelope, energy metabolism, and secondary metabolite synthesis, as well as the enrichment of metabolites involved in the biosynthesis of ε-PL. These findings hold great significance for elucidating the mechanism underlying ε-PL synthesis.
Comparative Analysis of γ-Cyclodextrin, Perilla Oil, and Their Inclusion Complexes on Liver Injury and Dyslipidemia Associated with Elevated Gastrointestinal 12-Hydroxylated Bile Acid Levels
Authors: Yoshikiyo Keisuke , Shimizu Hidehisa , Nagato Edward G. , Ishizuka Satoshi , Yamamoto Tatsuyuki
Published: January 2025

Our previous study demonstrated that γ-cyclodextrin (γ-CD)–perilla oil inclusion complexes increase plasma α-linolenic acid and eicosapentaenoic acid levels in healthy rats without adverse effects. The present study examined the effects of perilla oil, γ-CD, and their inclusion complexes on rats fed cholic acid (CA) to mimic the elevated gastrointestinal 12-hydroxylated (12OH) bile acid levels in high-fat diet-fed rats. Rats fed CA (CA group) tended to have higher AST, ALT, plasma total cholesterol (T-CHO), and triglyceride (TG) levels compared to controls fed a standard diet without CA. Rats fed CA and perilla oil (CA+LP group) showed a tendency for lower AST and plasma TG levels than those in the CA group. Rats fed CA and γ-CD (CA+CD group) had significantly higher AST, ALT, plasma T-CHO, and TG levels than the controls, indicating severe liver injury and dyslipidemia. Rats fed CA and the γ-CD–perilla oil inclusion complex (CA+IC group) had significantly lower AST and ALT levels than the CA+CD rats, with a trend towards lower plasma T-CHO and TG levels. Plasma α-linolenic acid and eicosapentaenoic acid levels were significantly higher in the CA+LP and CA+IC groups than in the controls and CA+CD groups. However, the CA+IC group tended to have lower α-linolenic acid levels and significantly lower eicosapentaenoic acid levels than the CA+LP group. This suggests an accelerated conversion of α-linolenic acid to eicosapentaenoic acid in the CA+IC group, which may contribute to the attenuation of liver injury and dyslipidemia. These findings suggest that γ-CD may exacerbate liver injury and dyslipidemia caused by elevated gastrointestinal 12OH bile acid levels, whereas γ-CD–perilla oil inclusion complexes may ameliorate these effects by altering fatty acid metabolism. Furthermore, we recommend evaluating γ-CD safety in both healthy and pathological models and carefully selecting compounds co-ingested with γ-CD.
Genetic Algorithm-Enhanced Direct Method in Protein Crystallography
Authors: Fu Ruijiang , Su Wu-Pei , He Hongxing
Published: January 2025

Direct methods based on iterative projection algorithms can determine protein crystal structures directly from X-ray diffraction data without prior structural information. However, traditional direct methods often converge to local minima during electron density iteration, leading to reconstruction failure. Here, we present an enhanced direct method incorporating genetic algorithms for electron density modification in real space. The method features customized selection, crossover, and mutation strategies; premature convergence prevention; and efficient message passing interface (MPI) parallelization. We systematically tested the method on 15 protein structures from different space groups with diffraction resolutions of 1.35∼2.5 Å. The test cases included high-solvent-content structures, high-resolution structures with medium solvent content, and structures with low solvent content and non-crystallographic symmetry (NCS). Results showed that the enhanced method significantly improved success rates from below 30% to nearly 100%, with average phase errors reduced below 40°. The reconstructed electron density maps were of sufficient quality for automated model building. This method provides an effective alternative for solving structures that are difficult to predict accurately by AlphaFold3 or challenging to solve by molecular replacement and experimental phasing methods. The implementation is available on Github.
Insights into the Mode of Action of Novel Morpholinated Curcumin Derivatives Exhibiting Potent Antitumor Activity in Bladder Cancer Cells In Vitro
Authors: Kobylka Paulina , Bakun Pawel , Kuzminska Joanna , Goslinski Tomasz , Murias Marek , Kucinska Malgorzata
Published: January 2025

Although curcumin is a well-known natural polyphenol with many biological activities, its clinical application has been limited by low aqueous solubility and stability. Therefore, curcumin derivatives have been proposed to overcome these limitations and increase anticancer activity. This study tested curcumin derivatives with modified feruloyl moieties (2a and 2a-B) and the β-diketo moiety (2a-B) to better understand their anticancer mechanism against human bladder cancer cells. The anticancer activity of 2a and 2a-B was determined using MTT (hypoxic conditions) and LDH (normoxic conditions) assays. An ELISA-based protein panel was used to find the potential molecular targets, while flow cytometric, colorimetric, fluorescent, and luminescent assays were used to investigate the cell death mechanism. It was shown that compound 2a exerted a more potent cytotoxic effect under hypoxic conditions, while compound 2a-B demonstrated a comparable effect in normoxic and hypoxic conditions. The potential molecular targets modified by 2a and 2a-B depending on oxygen concentration were also proposed. Both compounds alter cell cycle progression by blocking the cell cycle in the G2/M phase and decreasing the percentage of cells in the G0/G1 phase. Compound 2a-B led to phosphatidylserine translocation, increased caspase 3/7 activity, and decreased mitochondrial membrane potential, suggesting a mitochondrial apoptosis pathway. We found that the Akt signaling pathway may modulate the activity of compound 2a-B, as evidenced by enhanced cytotoxic activity in combination with MK-2206, an Akt 1/2/3 inhibitor. Thus, our results provide new insights into the anticancer activity of compounds 2a and 2a-B; however, further studies are needed to better understand their therapeutic potential.
Advancements in Superhydrophobic Paper-Based Materials: A Comprehensive Review of Modification Methods and Applications
Authors: Tang Yin , Ban Shouwei , Xu Zhihan , Sun Jing , Ning Zhenxin
Published: January 2025

Superhydrophobic paper-based functional materials have emerged as a sustainable solution with a wide range of applications due to their unique water-repelling properties. Inspired by natural examples like the lotus leaf, these materials combine low surface energy with micro/nanostructures to create air pockets that maintain a high contact angle. This review provides an in-depth analysis of recent advancements in the development of superhydrophobic paper-based materials, focusing on methodologies for modification, underlying mechanisms, and performance in various applications. The paper-based materials, leveraging their porous structure and flexibility, are modified to achieve superhydrophobicity, which broadens their application in oil–water separation, anti-corrosion, and self-cleaning. The review describes the use of these superhydrophobic paper-based materials in diagnostics, environmental management, energy generation, food testing, and smart packaging. It also discusses various superhydrophobic modification techniques, including surface chemical modification, coating technology, physical composite technology, laser etching, and other innovative methods. The applications and development prospects of these materials are explored, emphasizing their potential in self-cleaning materials, oil–water separation, droplet manipulation, and paper-based sensors for wearable electronics and environmental monitoring.
The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation
Authors: Kala Srishti , Strutz Andrew G. , Katt Moriah E.
Published: January 2025

Neuroinflammation is a blanket term that describes the body’s complex inflammatory response in the central nervous system (CNS). It encompasses a phenotype shift to a proinflammatory state, the release of cytokines, the recruitment of peripheral immune cells, and a wide variety of other processes. Neuroinflammation has been implicated in nearly every major CNS disease ranging from Alzheimer’s disease to brain cancer. Understanding and modeling neuroinflammation is critical for the identification of novel therapeutic targets in the treatment of CNS diseases. Unfortunately, the translation of findings from non-human models has left much to be desired. This review systematically discusses the role of human pluripotent stem cell (hPSC)-derived glia and supporting cells within the CNS, including astrocytes, microglia, oligodendrocyte precursor cells, pericytes, and endothelial cells, to describe the state of the field and hope for future discoveries. hPSC-derived cells offer an expanded potential to study the pathobiology of neuroinflammation and immunomodulatory cascades that impact disease progression. While much progress has been made in the development of models, there is much left to explore in the application of these models to understand the complex inflammatory response in the CNS.
Risk Factors of Standalone and Coexisting Forms of Undernutrition Among Children in Sub-Saharan Africa: A Study Using Data from 26 Country-Based Demographic and Health Surveys
Authors: Worku Misganaw Gebrie , Mohanty Itismita , Mengesha Zelalem , Niyonsenga Theo
Published: January 2025

Introduction: Undernutrition in low- and middle-income countries (LMICs) remains a leading public health challenge. It accounts for one-third of the under-five mortality rate in sub-Saharan Africa (SSA). This study applied the composite index of anthropometric failure (CIAF) to assess the prevalence of various standalone and coexisting forms of undernutrition and identify associated risk factors. Methods: Nationally representative demographic health survey (DHS) data from 26 SSA countries were used. A multilevel multinomial logistic regression analysis was conducted considering the hierarchical nature of DHS data and more than two categories of outcome variable. Four models were fitted and the model with the highest log-likelihood and lowest deviance was chosen as the best-fitted model. The adjusted relative risk ratio (aRRR) with its corresponding 95% confidence interval (CI) was presented as a measure of the effect. Results: The overall prevalence of undernutrition among under-five children in SSA was 34.59% (95% CI: 34.35–34.82). Additionally, 20.49% (95% CI: 20.30–20.69) and 14.09% (95% CI: 13.92–14.26) of under-five children had standalone and coexisting undernutrition, respectively. The mother’s educational level and household wealth status were the most significant shared drivers for standalone and coexisting undernutrition. On the other hand, child and health service factors were differentiating factors between standalone and coexisting undernutrition. Age of the child, sex of the child, type of birth, birth weight, adherence to age-appropriate feeding, antenatal care visit (ANC), place of delivery, and maternal educational status were the most significant determinants of various undernutrition forms in 0–23-month-old children. For 24–59-month-old children, age of the child, sex of the child, type of birth, household wealth status, and maternal education were identified as the main determinants of different forms of undernutrition. Conclusions: Our analysis revealed that distal factors were shared risk factors among standalone and coexisting forms of undernutrition. However, proximal and intermediate factors varied in the type and strength of the association between standalone and coexisting undernutrition. This implies that holistic and category-specific strategies are needed to significantly reduce undernutrition among under-five children in SSA.
Maternal Glycemia and Its Pattern Associated with Offspring Neurobehavioral Development: A Chinese Birth Cohort Study
Authors: Yuan Zhichao , Su Tao , Yang Li , Xi Lei , Wang Hai-Jun , Ji Yuelong
Published: January 2025

Background/Objectives: This study investigates the impact of maternal glycemic levels during early and late pregnancy on offspring neurodevelopment in China. Methods: Fasting plasma glucose (FPG) and triglyceride (TG) levels were measured in maternal blood during pregnancy, and the TyG index was calculated to assess insulin resistance. Hyperglycemia was defined as FPG > 5.1 mmol/L. Neurodevelopmental outcomes in offspring aged 6–36 months were evaluated using the China Developmental Scale for Children, focusing on developmental delay (DD) and developmental quotient (DQ). Mothers were categorized into four glycemic groups: healthy glycemia group (HGG), early pregnancy hyperglycemia group (EHG), late pregnancy hyperglycemia group (LHG), and full-term hyperglycemia group (FHG). Linear and logistic regression models were applied. Results: Among 1888 mother–child pairs, hyperglycemia and FPG were associated with an increased risk of overall DD (aOR = 1.68; 95% CI 1.07–2.64) and lower DQ (aBeta = −1.53; 95% CI −2.70 to −0.36). Elevated FPG was linked to DD in fine motor and social behaviors. Compared to HGG, LHG and FHG significantly increased the risk of overall DD (aOR = 2.18; 95% CI 1.26–3.77; aOR = 2.64; 95% CI 1.38–5.05), whereas EHG did not. Male offspring were particularly vulnerable to early pregnancy hyperglycemia (aBeta = −2.80; 95% CI −4.36 to −1.34; aOR = 2.05; 95% CI 1.10–3.80). Conclusions: Maternal glycemic levels during pregnancy influence offspring neurodevelopment, with persistent hyperglycemia significantly increasing DD risk. Early pregnancy hyperglycemia particularly affects male offspring, underscoring the need for glycemic management during pregnancy.
Eosinophilic Esophagitis and Cow’s Milk: Mechanisms, Challenges, and Treatment Perspectives
Authors: Dinardo Giulio , Fiocchi Alessandro , Artesani Maria Cristina , De Angelis Paola , Rea Francesca , Tambucci Renato , Dahdah Lamia , Fierro Vincenzo , Valluzzi Rocco Luigi , Arasi Stefania , Pecora Valentina , Cafarotti Arianna , Mazzuca Carmen , Indolfi Cristiana , Miraglia del Giudice Michele , Urbani Sara
Published: January 2025

Eosinophilic esophagitis is a chronic, antigen-driven, immune-mediated disease characterized by esophageal dysfunction and significant eosinophilic infiltration. Its rising incidence and prevalence over recent decades reflect both increased clinical awareness and the influence of environmental factors such as dietary patterns and allergen exposure. Among food allergens, cow’s milk proteins are the most commonly implicated triggers, contributing to esophageal inflammation through complex immunological pathways involving both IgE-mediated and non-IgE-mediated mechanisms. Dietary elimination of cow’s milk has been shown to induce histologic remission in over 60% of pediatric patients, underscoring its pivotal role in eosinophilic esophagitis management. Despite these promising results, challenges persist, including variability in individual responses, the burden of adherence to restrictive diets, and gaps in understanding the molecular mechanisms driving cow’s milk-induced esophageal inflammation. This review examines the complex relationship between eosinophilic esophagitis and cow’s milk, focusing on its role in disease pathogenesis and management, offering insights into its therapeutic implications. Understanding the interplay between eosinophilic esophagitis and dietary allergens, particularly cow’s milk, may inform the development of targeted interventions and improve clinical outcomes for affected patients.
Impact of Maternal Macronutrient Intake on Large for Gestational Age Neonates’ Risk Among Women with Gestational Diabetes Mellitus: Results from the Greek BORN2020 Cohort
Authors: Siargkas Antonios , Tranidou Antigoni , Magriplis Emmanuela , Tsakiridis Ioannis , Apostolopoulou Aikaterini , Xenidis Theodoros , Pazaras Nikolaos , Chourdakis Michail , Dagklis Themistoklis
Published: January 2025

Background/Objectives: The effect of maternal macronutrient composition on the risk of large for gestational age (LGA) neonates among women with gestational diabetes mellitus (GDM) is not well understood. This study aimed to investigate these associations in a pregnant cohort in Northern Greece, considering both pre-pregnancy and early pregnancy dietary intake, and stratifying women by pre-pregnancy body mass index (BMI). Methods: From a total of 797 eligible pregnant women, the 117 (14.7%) who developed GDM (and thus were included in the study) completed the validated Food Frequency Questionnaires (FFQs). Macronutrient intake was assessed for the six months before pregnancy and until mid-gestation, prior to the oral glucose tolerance test. Data were compared with European Food Safety Authority (EFSA) guidelines, and participants were stratified by pre-pregnancy BMI (normal vs. overweight/obese). Multivariate logistic regression was used to estimate adjusted odds ratios (aORs) for LGA risk. Results: In normal-BMI women with GDM, higher dietary fiber (aOR = 1.39) and vegetable protein (aOR = 1.61) intake before pregnancy were both significantly associated with an increased risk of LGA. During early pregnancy, the elevated risk from vegetable protein persisted (aOR = 1.51). Among overweight/obese women, no significant pre-pregnancy associations were observed. However, during early pregnancy, a higher percentage of total carbohydrate intake was linked to increased LGA risk (aOR = 1.11), while maintaining saturated fatty acids “as low as possible” reduced the odds of LGA (aOR = 0.71). Elevated vegetable protein intake also increased LGA risk (aOR = 1.61). Conclusions: Maternal macronutrient intake prior to and during early pregnancy may influence LGA risk in GDM, with distinct patterns according to pre-pregnancy BMI. These findings underscore the importance of tailoring dietary recommendations—especially regarding fiber, vegetable protein, carbohydrates, and saturated fat—to mitigate the risk of LGA in women with GDM.
Near-Death Quality of Life in Cancer Patients on Home Parenteral Nutrition
Authors: Cotogni Paolo , De Carli Luca
Published: January 2025

Background: The impact of home parenteral nutrition (HPN) on the quality of life (QoL) of cancer patients has been previously investigated. However, scarce data are available regarding near-death QoL in patients with cancer receiving HPN. This study aims to investigate the changes of QoL in these patients in the last two months before death. Methods: This is a secondary analysis of a previous, prospective, longitudinal, observational study. QoL was assessed using the EORTC QLQ-C30 questionnaire. Results: Eighty-four adult cancer patients who died on HPN and had filled out the questionnaire between 31 and 60 days (M2) and within 30 days prior (M1) to death were included in this analysis. The questionnaires filled out at M2 and M1 were compared with those filled out by the same patients at HPN start (T0). At M2, there was a significant improvement in both the global QoL and symptoms scales (p < 0.001 and p < 0.033, respectively), while at M1, a significant improvement in the global QoL scale persisted (p < 0.035) compared with T0. Conclusions: Our study first reports that HPN, if started early and according to European guidelines, is associated with an improvement in the QoL of patients with cancer even in the last two months before death.
Development of a Hydrocortisone Orodispersible Thin Film Containing Its Succinate Prodrug
Authors: Boisseillier Clément , Demange-Labriet Lucas , Kariyawasam Dulanjalee , Marchadour Pauline , Fauqueur Anne-Sophie , Annereau Maxime , Denis Lucas , Cotteret Camille , Cisternino Salvatore , Schweitzer-Chaput Arnaud
Published: January 2025

Orodispersible thin film (ODF) is an innovative dosage form that allows for adjustable dosing and improved patient compliance. It is administered by mouth, where it dissolves, making it suitable for children. Objectives: The aim of the study was to develop and characterize an optimal ODF formulation containing equivalent hydrocortisone at 0.5 mg/cm2 using the solvent-casting method. A stability-indicating assay for the simultaneous quantification of hydrocortisone and hydrocortisone 21-hemissucinate (HMS) was developed. ODFs were characterized by organoleptic properties and by testing for uniformity of mass, content, stability, thickness, and dissolution. Results: When optimized, ODF is thin, flexible, and transparent, making it suitable for production in hospital pharmacies using standard equipment. In contrast to the water-insoluble hydrocortisone, the HMS-loaded cast gel successfully satisfied the tests, including content uniformity. Disintegration appeared acceptable as compared to the commercial grade ondansetron ODF (Setofilm®). The physicochemical stability of the active ingredients (i.e., HMS, hydrocortisone) contained in the ODF at 0.5 mg/cm2 is demonstrated for at least 84 days at 23 °C. Conclusion: The ODF formulated with the water-soluble hydrocortisone prodrug HMS allows accurate drug level to be achieved, thus opening up new opportunities for use in pediatric patients.
Non-Viral Delivery Systems to Transport Nucleic Acids for Inherited Retinal Disorders
Authors: Jony Md Jobair , Joshi Ameya , Dash Alekha , Shukla Surabhi
Published: January 2025

Inherited retinal disorders (IRDs) represent a group of challenging genetic conditions that often lead to severe visual impairment or blindness. The complexity of these disorders, arising from their diverse genetic causes and the unique structural and functional aspects of retinal cells, has made developing effective treatments particularly challenging. Recent advancements in gene therapy, especially non-viral nucleic acid delivery systems like liposomes, solid lipid nanoparticles, dendrimers, and polymersomes, offer promising solutions. These systems provide advantages over viral vectors, including reduced immunogenicity and enhanced targeting capabilities. This review delves into introduction of common IRDs such as Leber congenital amaurosis, retinitis pigmentosa, Usher syndrome, macular dystrophies, and choroideremia and critically assesses current treatments including neuroprotective agents, cellular therapy, and gene therapy along with their limitations. The focus is on the emerging role of non-viral delivery systems, which promise to address the current limitations of specificity, untoward effects, and immunogenicity in existing gene therapies. Additionally, this review covers recent clinical trial developments in gene therapy for retinal disorders.
Synthesis of Anti-Inflammatory Drugs’ Chalcone Derivatives and a Study of Their Conformational Properties Through a Combination of Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling
Authors: Georgiou Nikitas , Tzani Andromachi , Vavougyiou Kyriaki , Papadopoulos Christos , Eleftheriadis Nikolaos , Šket Primož , Tzeli Demeter , Niemi-Aro Tuomas , Detsi Anastasia , Mavromoustakos Thomas
Published: January 2025

Background: In this study, two chalcone analogs were synthesized through in silico and experimental methods, and their potential to inhibit the lipoxygenase enzyme, which plays a role in the inflammation pathway, was assessed. Specifically, this study is a continuation of previous research in which chalcone derivatives were synthesized and characterized. Objectives/Methods: In the current work, we present the re-synthesis of two chalcones, with a focus on their docking studies, NMR analysis, and dynamic simulations. The structure of each chalcone was elucidated through a combination of Nuclear Magnetic Resonance (NMR) and Density Functional Theory (DFT). The substituent effect on the absorption spectrum of the two chalcone derivatives was studied. Results: A “LOX–chalcone” complex, predicted by docking studies, was further examined using molecular dynamics (MD) simulations to evaluate the stability of the complex. After fully characterizing the “LOX–chalcone” complexes in silico, the atomic details of each chalcone’s interaction with LOX-1 and 5-LOX were revealed through Saturation Transfer Difference (STD) NMR (Nuclear Magnetic Resonance). Finally, their selectivity profile was investigated against human 15-LOX-1 and general Lipoxidase activity. Conclusions: The in silico methods suggest that chalcones could be promising lead compounds for drug designs targeting the LOX enzyme.
Scalable Manufacturing Method for Model Protein-Loaded PLGA Nanoparticles: Biocompatibility, Trafficking and Release Properties
Authors: Akpinar Adscheid Selin , Rojas-Rodríguez Marta , Abdel-Hafez Salma M. , Pavone Francesco S. , Schneider Marc , Türeli Akif E. , Calamai Martino , Günday-Türeli Nazende
Published: January 2025

Background and Objectives: Drug delivery systems (DDSs) offer efficient treatment solutions to challenging diseases such as central nervous system (CNS) diseases by bypassing biological barriers such as the blood–brain barrier (BBB). Among DDSs, polymeric nanoparticles (NPs), particularly poly(lactic-co-glycolic acid) (PLGA) NPs, hold an outstanding position due to their biocompatible and biodegradable qualities. Despite their potential, the translation of PLGA NPs from laboratory-scale production to clinical applications remains a significant challenge. This study aims to address these limitations by developing scalable PLGA NPs and evaluating their potential biological applications. Methods: We prepared blank and model-protein-loaded (albumin–FITC and wheat germ agglutinin-488 (WGA-488)) fluorescent PLGA NPs using the traditional double-emulsion method combined with the micro-spray-reactor system, a novel approach that enables fine particle production enabling scale-up applications. We tested the biocompatibility of the NPs in living RPMI 2650 and neuroblastoma cell lines, as well as their trafficking and uptake. Release kinetics of the encapsulated proteins were investigated through confocal microscopy and in vitro release studies, providing insights into the stability and functionality of the released proteins. Results: The formulation demonstrated sustained and prolonged protein release profiles. Importantly, cellular uptake studies revealed that the NPs were not internalized. Furthermore, encapsulated WGA-488 protein retained its functional activity after release, validating the integrity of the encapsulation and release processes. Conclusions: The proof-of-concept study on NP manufacturing and an innovative drug trafficking and release approach can bring new perspectives on scalable preparations of PLGA NPs and their biological applications.
Stability of Ternary Drug–Drug–Drug Coamorphous Systems Obtained Through Mechanochemistry
Authors: D’Abbrunzo Ilenia , Venier Elisabetta , Selmin Francesca , Škorić Irena , Bernardo Enrico , Procida Giuseppe , Perissutti Beatrice
Published: January 2025

Background/Objectives: This study investigates the preparation of coamorphous systems composed entirely of active pharmaceutical ingredients (APIs), namely praziquantel, niclosamide, and mebendazole. The objective was to formulate and characterize binary and ternary coamorphous systems to evaluate their structural, thermal, and stability properties. Methods: Ten different mixtures (binary and ternary) were designed through a mixture design approach and prepared using a sustainable, one-step neat grinding process in a lab-scale vibrational mill. The systems were prepared reproducibly within 4 h across the entire experimental domain. Structural characterization was performed using PXRD and FTIR to confirm the absence of crystalline domains and the presence of molecular interactions. The glass transition temperature (Tg) was theoretically calculated using the Gordon–Taylor equation for three-component systems and determined experimentally via DSC. Stability studies were conducted on seven systems under different storage conditions (−30 °C, 5 °C, 25 °C, and 40 °C) for six months. Results: PXRD analysis confirmed the formation of coamorphous systems with no crystalline phases. DSC revealed a single Tg for most systems, indicating homogeneity. Stability studies demonstrated that five out of seven systems adhered to the “Tg—50 °C” stability rule, remaining physically stable over six months. Recrystallization studies indicated diverse pathways: some systems reverted to their original crystalline phases, while others formed new entities such as cocrystals. Conclusions: This study highlights the feasibility of coamorphous systems composed of multiple APIs using a simple, solvent-free grinding approach. The findings underscore the importance of molecular interactions in determining stability and recrystallization behavior, offering insights for designing robust coamorphous formulations.
A Whale Optimization Algorithm-Based Data Fitting Method to Determine the Parameters of Films Measured by Spectroscopic Ellipsometry
Authors: Ma Liyuan , Xu Xipeng , Cui Changcai , Gao Mai , Li Tukun , Lou Shan , Scott Paul J. , Jiang Xiangqian , Zeng Wenhan
Published: January 2025

A data-fitting method based on the whale optimization algorithm (WOA) is proposed to determine the thickness and refractive index of films measured by spectroscopic ellipsometry (SE). To demonstrate this method, tin oxide (SnO2) films with transparent wavelength coverage (400–800 nm) are evaluated. The comparative analysis indicates that Psi and Delta parameter curves based on WOA fitting align more closely with those obtained through experiments. Furthermore, the thickness and refractive index of films obtained by WOA are in nearly agreement with the results from the well-known Levenberg–Marquardt (LM) algorithm. This validation confirms that it has great potential in the determination of film parameters in ellipsometry data fitting.
Focusing Hemispherical Waves
Authors: Sheppard Colin J. R.
Published: January 2025

The field in the focal plane of a hemispherically focused wave in an aplanatic optical system can be expressed in an analytical form. In fact, many different cases of hemispherically focused scalar and vectorial waves can be analytically expressed. We consider focusing with linear or circular polarized illumination as well as other cases such as electric dipole, transverse electric, and radial polarizations. We also investigate 4Pi focusing and the focusing of vortex waves. These results can be applied to focusing with microscope objectives of high numerical aperture.
Prohexadione-Calcium Reduced Stem and Tiller Damage and Maintained Yield by Improving the Photosynthetic and Antioxidant Capacity of Rice (Oryza sativa L.) Under NaCl Stress
Authors: Mei Wanqi , Yang Shaoxia , Xiong Jian , Khan Aaqil , Zhao Liming , Du Xiaole , Huo Jingxin , Zhou Hang , Sun Zhiyuan , Yang Xiaohui , Yue Nana , Feng Naijie , Zheng Dianfeng
Published: January 2025

Salt stress is a vital environmental stress that severely limits plant growth and productivity. Prohexadione-calcium (Pro-Ca) has been extensively studied to regulate plant growth, development, and stress responses. However, the constructive role of Pro-Ca in alleviating damages and enhancing rice tillers’ morph-physiological characteristics under salt stress remains largely unknown. The results showed that Pro-Ca significantly improved Changmaogu’s (CMG’s) productive tillering rate and the total yield per plant by 17.1% and 59.4%, respectively. At tillering stage, the results showed that Pro-Ca significantly improved the morph-physiological traits, i.e., leaf area, and photosynthetic traits of the rice variety with salt tolerance, under NaCl stress. Pro-Ca significantly increased the seedling index of the main stem and tiller by 10.3% and 20.0%, respectively. Pro-Ca significantly increased the chlorophyll a (chl a), chlorophyll b (chl b) and carotenoid contents by 32.8%, 58.4%, and 33.2%, respectively under NaCl stress. Moreover, Pro-Ca significantly enhanced the net photosynthetic rate (A) by 25.0% and the non-photochemical (NPQ) by 9.0% under NaCl stress. Furthermore, the application of Pro-Ca increased the activities of antioxidant enzymes by 7.5% and 14.7% in superoxide dismutase (SOD), 6.76% and 18.0% in peroxidase (POD), 26.4% and 58.5% in catalase (CAT), 11.0% and 15.9% in ascorbate peroxidase (APX), and Pro-Ca reduced the membrane damage index by 10.8% and 2.19% in malondialdehyde (MDA) content, respectively, for main stem and tiller leaves under NaCl stress. Pro-Ca significantly enhanced the soluble protein content of the main stem and tiller leaves by 2.60% and 6.08%, respectively. The current findings strongly suggested that exogenous application of Pro-Ca effectively alleviated the adverse impact of NaCl stress on the main stem and tillers by enhancing the photosynthetic capacity and antioxidant enzyme activity, and ultimately increased the productive tillering rate and grain yield.