bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Reconstruction of the Nickel Ions’ Behavior in Different Orthodontic Archwires Following Clinical Application in an Intraoral Environment
Authors: Georgieva Mirela , Petkov George , Petrov Valeri , Andreeva Laura , Martins Jorge N. R. , Georgiev Velizar , Stoyanova-Ivanova Angelina
Published: January 2025

Rationale: Orthodontic archwires undergo chemical and structural changes in the complex intraoral environment. The present work aims to investigate the safe duration for intraoral use (related to the nickel release hypothesis) of different types of nickel-containing wires. By analyzing how the nickel content (NC) varies over time, we aim to provide practical recommendations for the optimal use of said archwires. Materials and Methods: Our analysis focuses on the following nickel-containing archwires: stainless steel, Ni-Ti superelastic, heat-activated NiTi and CuNiTi, and multi-force archwires. The studied archwires of each type were divided into three groups: group 1, as received; group 2, retrieved after intraoral exposure for less than 6 weeks; group 3, used for more than 8 weeks. To assess NC, measurements using scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), and laser-induced breakdown spectroscopy (LIBS) were performed in multiple regions of each wire. Statistical analysis of the measured values using one-way ANOVA and multiple group comparisons showed significant differences in nickel content between groups. The dynamic behavior of the statistical results for NC was then modeled using logistic regression and fitted with cubic splines. Conclusions: The proposed behavior model, with further refinement, could enable orthodontists to make informed, patient-specific decisions regarding the safe and effective use of orthodontic floss. The overall conclusion of the study is that due to stability, SS-CrNi, HA-Ni-Ti with Cu, and TriTaniumTM are suitable for long-term use, and due to higher nickel release, Ni-Ti-Superelastic, HA-Ni-Ti without Cu, and Bio-ActiveTM are better for short- to medium-term use.
Analyzing the Vibration Response of Adhesively Bonded Composite Cantilevers
Authors: Chełmecki Jarosław , Szeptyński Paweł , Jasińska Dorota , Kwiecień Arkadiusz
Published: January 2025

In this study, we investigated the vibration of adhesively bonded composite cantilevers consisting of two beech wood lamella and a bondline of flexible polyurethane. The beams had a constant total height, while the thickness of the adhesive layer varied. We analyzed both the driven and free vibration of a single cantilever beam and a cantilever with an additional mass attached to its end. The eigenfrequencies were determined using Fourier analysis of a sweep load response, the response to an impact load excited using an impact hammer, and the response observed via the manual displacement of the beam’s tip. The system’s damping was estimated according to the recorded logarithmic decrement. Theoretical estimates of the fundamental natural frequency were obtained using the γ-method and employing a linear elastic theory of composite beams. A numerical modal analysis was carried out using the finite element method. Upon comparing the results of our experiments with the numerical estimates and theoretical predictions, a fair agreement was found.
A Dynamic Tensile Method Using a Modified M-Typed Specimen Loaded by Split Hopkinson Pressure Bar
Authors: Lin Yuan , Fan Jitang , Yu Xinlu , Fu Yingqian , Zhou Gangyi , Wang Xu , Dong Xinlong
Published: January 2025

Obtaining reliable dynamic mechanical properties through experiments is essential for developing and validating constitutive models in material selection and structural design. This study introduces a dynamic tensile method using a modified M-type specimen loaded by a split Hopkinson pressure bar (SHPB). A closed M-type specimen was thus employed. Finite element simulations and experiments were used to validate the design of the M-type specimen, which was fabricated using 17-4PH (precipitation hardening) stainless steel powder with a 3D (three-dimensional) selected laser melting (SLM) printer. After verifying force balance and uniform deformation in the tensile region, tensile tests were conducted across strain rates from quasi-static to a strain rate of 5900 s−1. The results demonstrated that this method effectively assessed the dynamic tensile behaviors of stainless steel at high strain rates, and achieved both ultra-high strain rates and large plastic deformation.
An Investigation of the Indentation Elastic Modulus for Metal Films on Flexible Substrates Considering the Substrate Effect
Authors: Lee Jong-Hyup , Ham Ju-Been , Kim Young-Cheon
Published: January 2025

The accurate measurement of the elastic modulus of thin metal films on flexible substrates is critical for understanding the mechanical reliability of flexible electronics. However, conventional methods, such as the Oliver–Pharr model, often underestimate the modulus due to substrate effects, particularly with low-modulus substrates like polyimide (PI). In this study, we propose an improved weighting model that replaces the empirical weighting factor with a variable X to better account for substrate contributions. Nanoindentation experiments were performed on Cu and Al films with thicknesses of 0.5, 1, and 1.5 μm, deposited on PI and silicon substrates. The results show a significant underestimation of the elastic modulus when traditional methods were applied, especially on PI substrates, where values decreased by up to 95%. Using the proposed X-based model, the corrected elastic modulus aligned with the inherent properties of the films, with errors reduced to within 2%. A finite element analysis (FEA) validated the stress and displacement distributions, demonstrating the substrate’s influence on indentation behavior. This study provides a robust framework for accurately measuring the elastic modulus of thin films on flexible substrates, paving the way for a more reliable mechanical characterization in flexible electronics.
Investigation of Chloride Salt Erosion on Asphalt Binders and Mixtures: Performance Evaluation and Correlation Analysis
Authors: Qiu Xin , Deng Jianghui , Fu Qinghong , Lou Yunxi , Ye Yingci , Zhang Dingchuan
Published: January 2025

Asphalt pavement, widely utilized in transportation infrastructure due to its favourable properties, faces significant degradation from chloride salt erosion in coastal areas and winter deicing regions. In this study, two commonly used asphalt binders, 70# base asphalt and SBS (Styrene–Butadiene–Styrene)-modified asphalt, were utilized to study the chloride salt erosion effect on asphalt pavement by immersing materials in laboratory-prepared chloride salt solutions. The conventional properties and adhesion of asphalt were assessed using penetration, softening point, ductility, and pull-off tests, while Fourier transform infrared spectroscopy (FTIR) elucidated the erosion mechanism. The Marshall stability test, freeze–thaw splitting test, and Cantabro test were applied to study the effects of chloride exposure on the strength, water stability, and structural integrity of the asphalt mixture. Finally, the grey correlation analysis was employed to assess the impact of chloride salt erosion on the performance of asphalt binders and mixtures. The findings highlight that chloride salt erosion reduces penetration and ductility in both types of asphalt binders, raises the softening point, and weakens asphalt–aggregate adhesion, confirmed as a primarily physical effect by FTIR analysis. Asphalt mixtures showed decreased strength and water stability, intensifying these impacts at higher chloride concentrations and longer erosion duration. SBS-modified asphalt binders and mixtures exhibited greater resistance to chloride salt erosion, particularly in adhesion, as demonstrated by the Cantabro and pull-out tests. Grey relational analysis revealed that erosion duration is the most influential factor, with TSR and softening point emerging as the most responsive indicators of chloride-induced changes. These findings offer critical insights for practice, providing evidence-based guidance for designing and constructing asphalt pavements in environments with high chloride levels.
Exponential Growth and Properties of Solutions for a Forced System of Incompressible Navier–Stokes Equations in Sobolev–Gevrey Spaces
Authors: Díaz Palencia José Luis
Published: January 2025

One problem of interest in the analysis of Navier–Stokes equations is concerned with the behavior of solutions for certain conditions in the forcing term or external force. In this work, we consider an external force of a maximum exponential growth, and we investigate the local existence and uniqueness of solutions to the incompressible Navier–Stokes equations within the Sobolev–Gevrey space Ha,σ1(R3). Sobolev–Gevrey spaces are well suited for our purposes, as they provide high regularity and control over derivative growth, and this is particularly relevant for us, given the maximum exponential growth in the forcing term. Additionally, the structured bounds in Gevrey spaces help monitor potential solution blow-up by maintaining regularity, though they do not fully prevent or resolve global blow-up scenarios. Utilizing the Banach fixed-point theorem, we demonstrate that the nonlinear operator associated with the Navier–Stokes equations is locally Lipschitz continuous in Ha,σ1(R3). Through energy estimates and the application of Grönwall’s inequality, we establish that solutions exist, are unique, and also exhibit exponential growth in their Sobolev–Gevrey norms over time under certain assumptions in the forcing term. This analysis in intended to contribute in the understanding of the behavior of fluid flows with forcing terms in high-regularity function spaces.
Genomic Characterization of Laodelphax striatellus Permutotetra-like Virus and Self-Cleavage Function of Viral Capsid Protein
Authors: Piao Jun , Zhang Jiarui , Zhang Lujie , Piao Jingai , Wang Haitao , Xie Yilin , Li Shuo
Published: January 2025

Laodelphax striatellus permutotetra-like virus (LsPLV) is a novel insect virus identified via small RNA deep sequencing. At present, there is a lack of awareness of LsPLV, restricting research on its utilization in biocontrol. In this paper, the full-length genome of LsPLV was cloned and analyzed, then viral capsid protein (CP) was expressed and prepared as an antibody, and CP property was tested. It was found that the LsPLV genome was 4667 nt in length, encoding two proteins, RNA-dependent RNA polymerase (RdRP) and CP, and the palm subdomain conserved region in RdRp was arranged in a “C–A–B” permutation pattern, exhibiting the typical characteristics of permutotetra-like viruses. Phylogenetic analysis suggested that LsPLV shared the highest homology (excluding LsPLV1) with a Nodaviridae virus (QLI47702.1), and their nucleotide identities of RdRP and CP were 55.4% and 59.2%, respectively. After expression, purified CP exhibited two bands of 60 kDa and 47 kDa, suggesting a potential cleavage in the protein. LsPLV CP in L. striatellus was detected by Western blot, and except for the complete CP band, the specific bands with molecular weights lower than CP were also detected, indicating that CP underwent cleavage. Detection of purified CP in vitro showed that the cleavage could occur independent of any protease, confirming that CP has self-cleavage characteristics.
Bayesian Estimation of the True Bovine Brucellosis Prevalence in Vaccinated and Non-Vaccinated Ecuadorian Cattle Populations, and the Sensitivity and Specificity of a Competitive and Indirect ELISA Using a New Synthetic Antigen
Authors: Garrido Haro Ana Dolores , Barrionuevo Samaniego Margoth Yolanda , Moreno-Caballeros Paola , Burbano-Enríquez Alexandra , Salas Torres Verónica Alexandra , Galante Mulki María Cristina , Wielick Constance , Ron-Román Jorge , Saegerman Claude
Published: January 2025

Bovine brucellosis (bB) is a zoonosis mainly caused by the Brucella abortus species in cattle. Bovine brucellosis can present with either a range of clinical symptoms, including spontaneous abortions in the last trimester of pregnancy, retained fetal membranes, and decreased milk production, or it can be asymptomatic. In Ecuador, vaccination against bB with S19 and/or RB51 is not mandatory and is the responsibility of the farmer. As serology is a convenient method for detecting antibodies against Brucella, evaluating the diagnostic performance and discriminative ability of such tests in various epidemiological settings is required. To estimate and compare the diagnostic sensitivity (Se) and specificity (Sp) of two screening tests, a new competitive (cELISA) and an indirect ELISA based on a new synthetic antigen (iELISA), a randomized, stratified, cross-sectional, serological survey was performed on the cattle population (3299 bovine sera from 223 farms) in continental Ecuador. A Bayesian approach was used to evaluate the two tests by estimating their respective diagnostic Se and Sp, as well as the true prevalence of bB in different sub-populations (non-vaccinated, vaccinated with S19 or RB51). The Se of both tests was similar across Bayesian models, with values around 94%. In contrast, the Sp of the iELISA, ranging between 97 and 98%, was significantly higher than that of the cELISA, which was approximately 94–95%. The true prevalence of bB was 1.63% (95% CrI: 0.56–2.54) in non-vaccinated cattle, decreased to 0.97% (95% CrI: 0.005–2.54) in S19-vaccinated cattle and was 2.75% (95% CrI: 0.50–5.32) in RB51-vaccinated cattle. The results of this study suggest that, with similar Se and higher Sp, the iELISA based on an innovative synthetic antigen (which is more standardizable) should be recommended as a possible screening test for bB in Ecuador. Also, the proposed approach suggests insights into the quality of the vaccination campaign and highlights the need for refining the Ecuadorian national brucellosis control program.
Fungi in the Gut Microbiota: Interactions, Homeostasis, and Host Physiology
Authors: Liu Hao-Yu , Li Shicheng , Ogamune Kennedy Jerry , Ahmed Abdelkareem A. , Kim In Ho , Zhang Yunzeng , Cai Demin
Published: January 2025

The mammalian gastrointestinal tract is a stage for dynamic inter-kingdom interactions among bacteria, fungi, viruses, and protozoa, which collectively shape the gut micro-ecology and influence host physiology. Despite being a modest fraction, the fungal community, also referred to as mycobiota, represents a critical component of the gut microbiota. Emerging evidence suggests that fungi act as early colonizers of the intestine, exerting a lasting influence on gut development. Meanwhile, the composition of the mycobiota is influenced by multiple factors, with diet, nutrition, drug use (e.g., antimicrobials), and physical condition standing as primary drivers. During its establishment, the mycobiota forms both antagonistic and synergistic relationships with bacterial communities within the host. For instance, intestinal fungi can inhibit bacterial colonization by producing alcohol, while certain bacterial pathogens exploit fungal iron carriers to enhance their growth. However, the regulatory mechanisms governing these complex interactions remain poorly understood. In this review, we first introduce the methodologies for studying the microbiota, then address the significance of the mycobiota in the mammalian intestine, especially during weaning when all ‘primary drivers’ change, and, finally, discuss interactions between fungi and bacteria under various influencing factors. Our review aims to shed light on the complex inter-kingdom dynamics between fungi and bacteria in gut homeostasis and provide insights into how they can be better understood and managed to improve host health and disease outcomes.
The Silent Threat of Human Metapneumovirus: Clinical Challenges and Diagnostic Insights from a Severe Pneumonia Case
Authors: Costa-Filho Rubens Carmo , Saddy Felipe , Costa João Luiz Ferreira , Tavares Leandro Reis , Castro Faria Neto Hugo Caire
Published: January 2025

Background: Human metapneumovirus (hMPV) is a respiratory pathogen that has gained increasing recognition due to advancements in molecular diagnostic tools, which have improved its detection and characterization. While severe disease manifestations are traditionally associated with pediatric, elderly, or immunocompromised patients, hMPV-related pneumonia in immunocompetent adults remains underexplored. Methods: This case report describes a 68-year-old male who developed severe community-acquired pneumonia (CAP) caused by hMPV despite being immunocompetent and having no significant comorbidities. The diagnosis was confirmed via multiplex RT-PCR, excluding bacterial and viral coinfections. Laboratory and imaging findings supported a viral etiology, while empirical antibiotics were initially prescribed due to diagnostic uncertainty. Results: The patient presented with respiratory symptoms that progressed to hypoxia, productive cough, and fatigue, requiring hospitalization. Imaging revealed bilateral ground-glass opacities and consolidations typical of viral pneumonia. Molecular diagnostics enabled accurate pathogen identification and guiding appropriate management, and the patient fully recovered with supportive care. Conclusion: This case underscores the importance of rapid molecular diagnostics for hMPV, reducing unnecessary antibiotics and enhancing management. Routine incorporation of hMPV testing into clinical protocols could improve the diagnosis and resource use. The development of vaccines, such as the IVX-A12 in phase II trials, offers hope for targeted prevention, underscoring the need for further research and therapeutic innovations.
New Gold(I) Complexes as Potential Precursors for Gas-Assisted Methods: Structure, Volatility, Thermal Stability, and Electron Sensitivity
Authors: Butrymowicz-Kubiak Aleksandra , Muzioł Tadeusz M. , Madajski Piotr , Szymańska Iwona B.
Published: January 2025

We report the synthesis and characterization of new, user-friendly gold(I) [Au4(μ-(NH)2CC2F5)4]n coordination polymer and [Au2Cl2(NH2(NH=)CC2F5)2]n complex. These compounds were investigated for potential application as precursors in chemical vapor deposition (CVD) and focused electron/ion beam-induced deposition (FEBID/FIBID), which are additive methods to produce nanomaterials. Single-crystal X-ray diffraction, elemental analysis, and infrared spectroscopy were used to determine the complexes’ composition and structure. We studied their thermal stability and volatility using thermal analysis and variable-temperature infrared spectroscopy (VT IR) and by conducting sublimation experiments. The gold(I) amidinate [Au2(μ-(NH)2CC2F5)2]n sublimates at 413 K under 10−2 mbar pressure. The electron-induced decomposition of the complexes’ molecules in the gas phase and of their thin layers on silicon substrates was analyzed using electron impact mass spectrometry (EI MS) and microscopy studies (SEM/EDX), respectively, to provide insights for FEBID and FIBID precursor design. The [Au2Cl2(NH2(NH=)CC2F5)2]n hydrogen chloride molecules evolved during heating, with the formation of gold(I) amidinate. The obtained results revealed that the new gold(I) amidinate may be a promising source of metal for nanomaterial fabrication by gas-assisted methods.
Rh(III)-Catalyzed Double Annulation of 3-Phenyl-1,2,4-oxadiazoles with 2-Diazo-1,3-diketones: Access to Pyran-Fused Isoquinolines
Authors: Zhang Enshen , Sun Mei , Gao Lvlv
Published: January 2025

Efficient access to pyranoisoquinoline derivatives via rhodium-catalyzed double C-H functionalization of phenyl oxadiazoles and diazo compounds has been developed. Two C-C bonds and one C-O and C-N bond formation was realized by this tandem reaction, along with the formation of two heterocycles, affording diversified pyran-fused isoquinolines in moderate to good yields with broad functional group tolerance under mild reaction conditions.
Monitoring the Calibration Status of a Universal Testing Machine Through the Implementation of Acoustic Methods: Development of Equipment and a Suitable Interface
Authors: Subadra Sharath , Skaria Roy , Hasselmann Andrea , Mayer Eduard , Sheikhi Shahram
Published: January 2025

The calibration of a universal testing machine (UTM) verifies the accuracy of the system instruments responsible for obtaining force and displacement measurements. This process involves comparing the instrument to equipment that has already been calibrated to a known traceable standard. The limit of accuracy is then certified and the traceability of the measurements is determined. There are several internationally recognized standards that are used to calibrate the cross-head speed and displacement (ASTM E2658 and E2309, respectively), strain and load rate (ASTM E2309), measurement of tension, compression (ASTM E4) and dynamic force (ASTM E467). The current study aims to monitor the calibration status of UTMs through the implementation of acoustic methods. A methodology is developed whereby a reference sample is initially identified with suitable material properties, enabling it to be used continuously. The sample is used simultaneously with acoustic instruments to check its natural frequencies, which enables the monitoring of the UTM calibration status. An algorithm is developed that enables the user to interact with the system, thus forming an interface and helping the user to check the calibration status of the equipment. The entire system is validated to check if the equipment and the inbuilt algorithm can predict the calibration status of the machine. It was found that the geometric constraints imposed on the sample influence the output from the algorithm, and hence correct values should be fed to the system. Our sample never lost its elastic characteristics through continuous use, demonstrating that it can be used to continuously monitor the machine’s status.
Dietary Nutrient Adequacy in Aeronautical Military Personnel in Spain: Strengths and Weaknesses
Authors: Carretero-Krug Alejandra , Montero-Bravo Ana , Úbeda Natalia
Published: January 2025

Background/Objectives: Aeronautical military personnel operate under intense physical and mental stress, requiring high psychophysical aptitude. Adequate nutrition is essential to sustain operational readiness and mitigate the risk of chronic diseases and other health issues. This study aims to evaluate the nutritional status of aeronautical military personnel group in Spain through dietary parameters. Methods: A total of 390 male aeronautical military personnel, who attended the Centro de Instrucción de Medicina Aeroespacial (Madrid, Spain), were evaluated. Energy and nutrient intakes were estimated by three non-consecutive 24-h dietary recalls (DIAL® program). Results: The median energy intake was 2134 kcal/day, with significant variations across professional groups, highest in parachutists (2347 kcal/day). Protein intake was 18.2% TE, while carbohydrate intake was 37.6% TE, below standards, with 83.8% of participants not meeting the EFSA guidelines. However, a high intake of added sugars was observed (10% TE). Fat intake (38.3% TE) and saturated fats (11.7% TE) exceeded recommendations. Micronutrient deficiencies were notable for vitamin D (98% below recommendations), folate (56.4%), vitamin C (40.2%), calcium (50.3%), iodine (76.6%), and zinc (59%). Elevated cholesterol intake (352 mg/day) and inadequate fiber intake (18.5 g/day) were also observed. Conclusions: This study highlights imbalanced dietary patterns among Spanish aeronautical military personnel, with high protein, fat, cholesterol and added sugar consumption, low carbohydrate, and inadequate intake of critical micronutrients and fiber. These findings emphasize the need for targeted dietary interventions, nutritional monitoring protocols, and specific guidelines to enhance health and performance in this specialized group.
Unplanned Weight Loss and Sarcopenia Across Body Mass Index Categories in Nursing Homes—A Cross-Sectional Study
Authors: Klaassen Laura , Christoffersen Tenna , Aaslyng Margit Dall , Tetens Inge
Published: January 2025

Background: Nutritional risks in older adults, such as malnutrition and sarcopenia, are often underdiagnosed. Screening practices frequently rely on Unplanned Weight Loss (UPWL), potentially overlooking at-risk individuals. This study aims to assess the prevalence of nutritional risk, identified by UPWL and sarcopenia, across different body mass index categories in a nursing home (NH) population. Methods: Cross-sectional data were collected from an NH in a Danish municipality, including those of all self-reliant participants who consented and excluding those of terminally ill older adults. Data on age, sex, height, weight, and chronic diseases were extracted from medical records. Nutritional risk was assessed using two markers: a UPWL of ≥1 kg during the last six months and muscle strength via a modified 30 s chair stand test as a marker of sarcopenia. An ANOVA and Fisher’s Exact Test were used to assess differences, followed by a post hoc Tukey test. Results: In our study of older adults (n = 93, mean age 83.2 ± 9.12 years, 63% female), 17 individuals (19%) had UPWL, and 27 (29%) had sarcopenia. Among those with obesity, twelve (48%) had sarcopenia, but only two (8%) had UPWL. In contrast, seven (21%) of those with normal weight had sarcopenia, while eleven (33%) experienced UPWL. Conclusions: Older adults in NHs are at nutritional risk, but the prevalence varies significantly depending on whether UPWL or sarcopenia markers are applied for categorization. Sarcopenia prevalence was the highest in the obesity group, suggesting a need for integrating muscle strength or quantity assessments into community care to identify older adults at nutritional risk better.
Reason’s Triumph over Passion? Chinese Adults’ Attention to Information on Ultra-Processed Foods’ Fat and Sodium Contents in Nutrition Facts Tables
Authors: Huang Zeying
Published: January 2025

Background: It is common for consumers to purchase ultra-processed foods that are perceived to have health risks, and this phenomenon is rarely explained in the existing literature from the perspective of consumers’ responses to the intuitive marketing of flavor labels and the packaging. Methods: This study aimed to fill this knowledge gap and investigated the attention of 920 participants aged 18~59 across China toward fat and sodium content information for six ultra-processed foods (pastry foods, quick-frozen foods, dessert foods, puffed foods, beverages, and sauces) presented in nutrition facts tables based on the theoretical analysis framework for purchasing decisions on ultra-processed foods by using the binary logit model. Results: It was found that the respondent’ s attention to fat and sodium content information was positively influenced by health risk perception levels and levels of knowledge about fat and sodium but negatively influenced by the interaction term between flavor labels (or the packaging) that stimulated the purchase desire and health risk perception levels (or levels of knowledge about fat and sodium). Conclusions: The stimulation of purchase desire by flavor labels and the packaging weakened the consumer’ s increased attention to fat and sodium content information being enhanced by the health risk perception level and the level of knowledge about fat and sodium, especially the probability of attention to such information for dessert foods, puffed foods, quick-frozen foods, and sauces, which dropped the most. Additionally, the attention of females, youth, low-income individuals, those with below-college education, and non-overweight and obese individuals to such information dropped more, and the decrease was the largest for dessert foods, puffed foods, quick-frozen foods, and sauces.
How Do Maternal Gestational Diabetes and Other Concomitant Maternal Factors Determine the Perinatal Outcomes of Pregnancy?—A Retrospective Analysis
Authors: Karcz Karolina , Królak-Olejnik Barbara
Published: January 2025

Objectives: Gestational diabetes mellitus (GDM) is associated with an increased risk of both neonatal and maternal morbidity. The aim of this retrospective study was to evaluate the frequency of perinatal complications due to GDM in the Department of Neonatology at the Medical University of Wroclaw, Poland, considering the treatment of GDM—diet and physical activity versus insulin therapy. The influence of maternal comorbidities and the COVID-19 pandemic on pregnancy outcomes was assessed. Methods: A retrospective analysis of medical records was conducted. Statistics were calculated using a range of methods, with p < 0.05 considered significant. A sample of n = 625 mothers with n = 646 newborns were included in this study. Results: The newborns of insulin-treated mothers had cardiovascular defects more often (p < 0.05). A higher prevalence of vaginal infections was found in the diet-treated mothers (p < 0.05), while insulin-treated mothers had a higher prevalence of pregnancy-induced hypertension, pregnancy-induced hypothyroidism and obesity (p < 0.05). The mode of delivery, maternal age and maternal pregnancy-induced hypertension, obesity and cholestasis were found to influence neonatal outcomes (p < 0.05). Conclusions: The maternal management of GDM is not the main determinant of pregnancy outcomes, which might be affected by other maternal comorbidities. Effective initiatives are needed to control GDM, support breastfeeding and prevent adverse pregnancy outcomes
Dual Approaches in Oncology: The Promise of siRNA and Chemotherapy Combinations in Cancer Therapies
Authors: Sousa Carolina , Videira Mafalda
Published: January 2025

The integration of small interfering RNA (siRNA) with traditional cancer therapies represents a promising frontier in oncology aimed at enhancing treatment effectiveness, reducing side effects, and overcoming drug resistance. This review highlights the potential of siRNA to selectively silence genes that are overexpressed or uniquely expressed in cancer cells, thereby disrupting critical pathways that support tumor growth and survival. Key target genes discussed include survivin, VEGF, EGFR, c-MET, HER2, MUC1, and Bcl-2, all of which play vital roles in tumor proliferation, angiogenesis, and resistance to therapies. Clinical trials investigating various siRNA candidates, such as EZN-3042 and ALN-VSP, indicate that these therapies are generally well-tolerated; however, significant challenges persist, including the effective delivery and stability of siRNA. Recent advancements in nanoparticle-based delivery systems have shown promise in addressing these issues. Future research will focus on optimizing siRNA delivery methods, personalizing therapies based on individual genetic profiles, and establishing clearer regulatory guidelines for approval. As the field evolves, siRNA-based combination therapies are poised to become an integral part of precision oncology, offering new therapeutic options and hope for patients with difficult-to-treat cancers.
Serological Diagnosis of Brucella Infection in Cetaceans by Rapid Serum Agglutination Test and Competitive ELISA with Brucella abortus and Brucella ceti as Antigens
Authors: Di Febo Tiziana , Di Francesco Gabriella , Grattarola Carla , Sonsini Luigina , Di Renzo Ludovica , Lucifora Giuseppe , Puleio Roberto , Di Francesco Cristina Esmeralda , Smoglica Camilla , Di Guardo Giovanni , Tittarelli Manuela
Published: January 2025

Rose Bengal antigen and smooth lipopolysaccharide (s-LPS) were produced from a field strain of Brucella ceti (“homologous” antigens) and from the reference strain B. abortus S99 (“heterologous” antigens); they are currently used for the diagnosis of brucellosis in cattle, water buffaloes, sheep, goats, and pigs, as recommended in the Manual of Diagnostic Tests and Vaccines for Terrestrial Animals of the World Organization for Animal Health (WOAH). “Homologous” and “heterologous” antigens were used in a rapid serum agglutination test (Rose Bengal test, RBT) and a competitive ELISA assay (c-ELISA) to test a panel of sera, blood, and other body fluids (cerebrospinal fluid, pericardial fluid, tracheal fluid, and aqueous humor) collected from 71 individuals belonging to five cetacean species (Stenella coeruleoalba; Tursiops truncatus; Grampus griseus; Globicephala melas; and Ziphius cavirostris), which were found stranded on the Italian coastline. Six animals were positive for Brucella spp. for bacterial isolation and/or PCR, and 55 animals were negative; for the remaining 10 animals, no PCR/isolation data were available. A total of 90 samples were tested. Results obtained from the two tests were compared in order to identify the most suitable antigen for the serological diagnosis of Brucella infection in cetaceans. The RBT performed with the “homologous” antigen showed the best results in comparison with the “heterologous” antigen: diagnostic sensitivity, specificity, and accuracy were 80.0%, 44.1%, and 46.9% for the “homologous” antigen and 80.0%, 17.0%, and 21.9% for the “heterologous” antigen. For the c-ELISA, “homologous” and “heterologous” s-LPS showed similar results (diagnostic sensitivity 66.7%, diagnostic specificity 97.3%, and diagnostic accuracy 95.0%). Therefore, the RBT using the “homologous” antigen and c-ELISA with “homologous” or “heterologous” s-LPS could be used in parallel for the detection of antibodies against Brucella spp. in cetaceans.
Multi-Omics and Network-Based Drug Repurposing for Septic Cardiomyopathy
Authors: Liu Pei-Pei , Yu Xin-Yue , Pan Qing-Qing , Ren Jia-Jun , Han Yu-Xuan , Zhang Kai , Wang Yan , Huang Yin , Ban Tao
Published: January 2025

Background/Objectives: Septic cardiomyopathy (SCM) is a severe cardiac complication of sepsis, characterized by cardiac dysfunction with limited effective treatments. This study aimed to identify repurposable drugs for SCM by integrated multi-omics and network analyses. Methods: We generated a mouse model of SCM induced by lipopolysaccharide (LPS) and then obtained comprehensive metabolic and genetic data from SCM mouse hearts using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) and RNA sequencing (RNA-seq). Using network proximity analysis, we screened for FDA-approved drugs that interact with SCM-associated pathways. Additionally, we tested the cardioprotective effects of two drug candidates in the SCM mouse model and explored their mechanism-of-action in H9c2 cells. Results: Network analysis identified 129 drugs associated with SCM, which were refined to 14 drug candidates based on strong network predictions, proven anti-infective effects, suitability for ICU use, and minimal side effects. Among them, acetaminophen and pyridoxal phosphate significantly improved cardiac function in SCM moues, as demonstrated by the increased ejection fraction (EF) and fractional shortening (FS), and the reduced levels of cardiac injury biomarkers: B-type natriuretic peptide (BNP) and cardiac troponin I (cTn-I). In vitro assays revealed that acetaminophen inhibited prostaglandin synthesis, reducing inflammation, while pyridoxal phosphate restored amino acid balance, supporting cellular function. These findings suggest that both drugs possess protective effects against SCM. Conclusions: This study provides a robust platform for drug repurposing in SCM, identifying acetaminophen and pyridoxal phosphate as promising candidates for clinical translation, with the potential to improve treatment outcomes in septic patients with cardiac complications.
Fabrication of Thymoquinone and Ascorbic Acid-Loaded Spanlastics Gel for Hyperpigmentation: In Vitro Release, Cytotoxicity, and Skin Permeation Studies
Authors: Zaid Alkilani Ahlam , Alkhaldi Rua’a , Basheer Haneen A. , Amro Bassam I. , Alhusban Maram A.
Published: January 2025

Background/Objectives: The demand for a safe compound for hyperpigmentation is continuously increasing. Bioactive compounds such as thymoquinone (TQ) and ascorbic acid (AA) induce inhibition of melanogenesis with a high safety profile. The aim of this study was to design and evaluate spanlastics gel loaded with bioactive agents, TQ and AA, for the management of hyperpigmentation. Methods: Several spanlastics formulations were successfully fabricated and characterized in terms of morphology, vesicle size, zeta potential, and release. Results: The optimized TQ-loaded spanlastic formulation showed an average size of 223.40 ± 3.50 nm, and 133.00 ± 2.80 nm for AA-loaded spanlastic formulation. The optimized spanlastics formulation showed the highest entrapment efficiency (EE%) of 97.18 ± 2.02% and 93.08 ± 1.95%, for TQ and AA, respectively. Additionally, the edge activator concentration had a significant effect (p < 0.05) on EE%; it was found that by increasing the amount of EA, the EE% increases. Following that, the optimal spanlastics fomulation loaded with TQ and AA were incorporated into gel and explored for appearance, pH, spreadability, stability, rheology, in vitro release, ex vivo permeation study, and MTT cytotoxicity. The formulated spanlastics gel (R-1) has a pH of 5.53. Additionally, R-1 gel was significantly (p < 0.05) more spreadable than control gel, and exhibited a shear thinning behavior. Most importantly, ex vivo skin deposition studies confirmed superior skin deposition of TQ and AA from spanlastic gels. Additionally, results indicated that tyrosinase inhibition was primarily due to TQ. When comparing TQ alone with the TQ-AA combination, inhibition ranged from 18.35 to 42.73% and 24.28 to 42.53%, respectively. Both TQ spanlastics and the TQ-AA combination showed a concentration-dependent inhibition of tyrosinase. Conclusions: Spanlastic gel might represent a promising carrier for the dermal delivery of TQ and AA for the management of hyperpigmentation conditions.
Non-Steroidal Anti-Inflammatory Drugs Are Inhibitors of the Intestinal Proton-Coupled Amino Acid Transporter (PAT1): Ibuprofen and Diclofenac Are Non-Translocated Inhibitors
Authors: Nielsen Carsten Uhd , Jakobsen Sebastian , Pedersen Maria L.
Published: January 2025

Background/Objectives: The proton-coupled amino acid transporter (PAT1) is an intestinal absorptive solute carrier responsible for the oral bioavailability of some GABA-mimetic drug substances such as vigabatrin and gaboxadol. In the present work, we investigate if non-steroidal anti-inflammatory drug substances (NSAIDs) interact with substrate transport via human (h)PAT1. Methods: The transport of substrates via hPAT1 was investigated in Caco-2 cells using radiolabeled substrate uptake and in X. laevis oocytes injected with hPAT1 cRNA, measuring induced currents using the two-electrode voltage clamp technique. The molecular interaction between NSAIDs and hPAT1 was investigated using an AlphaFold2 model and molecular docking. Results: NSAIDs such as ibuprofen, diclofenac, and flurbiprofen inhibited proline uptake via hPAT1, with IC50 values of 954 (logIC50 2.98 ± 0.1) µM, 272 (logIC50 2.43 ± 0.1) µM, and 280 (logIC50 2.45 ± 0.1) µM, respectively. Ibuprofen acted as a non-competitive inhibitor of hPAT1-mediated proline transport. In hPAT1-expressing oocytes, ibuprofen and diclofenac did not induce inward currents, and inhibited inward currents caused by proline. Molecular modeling pointed to a binding mode involving an allosteric site. Conclusions: NSAIDs interact with hPAT1 as non-translocated non-competitive inhibitors, and molecular modeling points to a binding mode involving an allosteric site distinct from the substrate binding site. The present findings could be used as a starting point for developing specific hPAT1 inhibitors.
Sorafenib-Loaded Silica-Containing Redox Nanoparticle Decreases Tumorigenic Potential of Lewis Lung Carcinoma
Authors: Shashni Babita , Tran Hao Thi , Vong Long Binh , Chung Ren-Jei , Nagasaki Yukio
Published: January 2025

Background: Orally administered sorafenib has shown limited improvement in overall survival for non-small-cell lung cancer patients, likely due to poor pharmacokinetics and adverse effects, including gastrointestinal toxicity. To address these issues, we developed silica-containing antioxidant nanoparticles (siRNP) as a carrier to enhance the therapeutic efficacy of lipophilic sorafenib. Methods: Sorafenib was loaded into siRNP via dialysis (sora@siRNP). The therapeutic efficacy and safety of sora@siRNP (20 and 40 mg-sora/kg) were evaluated in a xenograft mouse model of Lewis lung carcinoma (subcutaneous tumors and experimental metastasis) following oral administration. Results: Crosslinking nanosilica in siRNP improved drug stability, enabling 8.9% sorafenib loading and pH resilience. Oral sora@siRNP exhibited dose-dependent tumor growth suppression by downregulating pMEK, outperforming free sorafenib, which showed inconsistent efficacy likely due to formulation variability. Intestinal damage, a major adverse effect of free sorafenib, was significantly reduced with sora@siRNP, attributed to siRNP’s antioxidant property of mitigating oxidative damage. Survival rates in the experimental metastasis model were 66–74% for sorafenib but reached 100% for sora@siRNP, highlighting its superior efficacy and safety. Conclusions: These findings demonstrate that nanosilica-crosslinked antioxidant nanoparticles (siRNP) enhance the stability, delivery efficiency, and safety of lipophilic drugs like sorafenib for oral administration. This platform holds promise for improving therapeutic outcomes in lung cancer while minimizing adverse effects.
White-Seeded Culinary Poppy (Papaver somniferum L.) Se Biofortification: Oil Quality, Fatty Acid Profile, and Seed Yield
Authors: Varga Ivana , Moslavac Tihomir , Flanjak Ivana , Iljkić Dario , Pospišil Milan , Lončarić Zdenko , Antunović Manda
Published: January 2025

The culinary poppy (Papaver somniferum L.) has been used for centuries in everyday diets, especially for food, but also as a non-food source of health-promoting ingredients. In the present study, a field trial was set with white-seeded poppy varieties collected from farmers in Croatia. The poppies were sown as a winter crop. Selenium biofortification was applied using different selenium sources, such as selenite, SeO32−, and selenate SeO42−. In the flowering stage, biofortification was carried out as follows: (1) Se-0: control; (2) SeO3_30: 30 g ha−1; (3) SeO3_60: 60 g ha−1; (4) SeO4_30: 30 g ha−1; and (5) SeO4_60: 60 g ha−1. Plants formed an average of four capsules per plant, with an average seed mass per capsule of 3.52 g. The seed yield varied from 0.91 (SeO3_30) to 1.26 t ha−1 (SeO4_30). The cold-pressed oil was characterized as good-quality since the average water content was 0.38%, insoluble impurities consisted of 0.013%, iodine number value was 135.81 g, I2 was 100 g−1, and saponification number was 188.51 mg KOH g−1, and it was on average 0.93% free fatty acids. Selenium biofortification had a significant (p ≤ 0.05) impact on Se accumulation in the seeds. Thus, the selenite form increased Se content in the seeds by about 7% compared to the control, whereas for the (4) SeO4_30 treatment, the increase was about 50%, and for (5) SeO4_60, it was even higher, about 91% compared to the control treatment. The highest content of fatty acids in the cold-pressed oil was determined for linoleic (76.31%), oleic (13.49), and palmitic (7.86%) acids.
Phytochemicals and Biological Properties of Azorean Camellia sinensis Black Tea Samples from Different Zones of Tea Plantation
Authors: Paiva Lisete Sousa , Dias Ana Paula , Motta Madalena Hintze , Baptista José António Bettencourt
Published: January 2025

Camellia sinensis tea has received considerable attention due to its beneficial effects on health, particularly due to its antioxidant properties that are affected by several factors, which have a high influence on the final quality of black tea. The objective of this study was to investigate the biological properties of Azorean C. sinensis black tea from five different zones of tea plantation in order to select specific areas to cultivate tea rich in targeted compounds beneficial to human health. The free radical scavenging activity (FRSA), ferric reducing antioxidant power (FRAP), ferrous ion chelating (FIC) activities, total phenolic content (TPC), total flavonoid content (TFC), and tannins were determined by colorimetric methods, and catechin and theaflavin contents were analyzed by high-pressure liquid chromatography. The results indicated that samples from Zone E (341 m above the sea level) presented higher values of FRSA (EC50 = 7.22 µg/mL), FRAP (EC50 = 9.06 µg/mL), and FIC activities (79.83%) and higher values of total phenolics (264.76 mg GAE/g DE) and almost all catechins. For TFC, the values were very similar between zones, and for theaflavins content, Zone A showed the best levels, followed by Zone E. In general, these results clearly highlight that altitude plays a significant role in enhancing certain compounds of tea, thereby influencing its quality.
Comparative Study on Growth Characteristics and Early Selection Efficiency of Hybrid Offspring of Populus deltoides ‘DD-109’ and P. maximowiczii in Liaoning, China
Authors: Liu Wei , Liu Chenggong , Zhang Yan , Li Jinhua , Ji Jiabao , Qin Xiaorui , Liu Fenfen , Gao Chengcheng , Wang Nairui , Zhang Xueli , Liu Ning , Peng Rusheng , Huang Qinjun
Published: January 2025

Poplar is an important tree species for timber supply and ecological protection in northern China. Cultivating and selecting high-quality varieties and germplasm resources suitable for cultivation are key factors in enhancing the quality and productivity of poplar plantations in the arid and semi-arid northern regions with shorter growing seasons. This study conducted a field cultivation experiment on 10 progeny clones from the direct cross (D × M) of imported Populus deltoides ‘DD-109’ with Populus maximowiczii and 7 progeny clones from the reciprocal cross (M × D) using one-year-old rooted cuttings planted at a 4 m × 8 m spacing. Based on 17 years of annual growth observations, the study systematically compared growth characteristics, age of quantitative maturity, path relationships between traits, and early selection efficiency in the hybrid offspring. The results indicated that the D × M population had superior diameter at breast height (DBH), tree height (H), and volume (V) compared to the M × D population, while the height-to-diameter ratio (HDR) was lower. The growth rate of the 17 clones peaked from 10 to 14 years, with annual volume growth increments (PAIs) higher than mean annual volume increments (MAIs) during the early growth stages; the quantitative maturity age ranged between 12 and 16 years. The D × M population generally reached quantitative maturity earlier than the M × D population, with the fastest clone maturing in 12 years. Four clones (DM-9-17, DM-9-18, DM-9-14, and MD-61) showed values for V, DBH, H, and HDR above the hybrid group average. Path analysis demonstrated that DBH had the most significant direct and indirect effects on V, suggesting it as the best predictor for V. Using DBH as a reference, correlation and early selection efficiency analysis showed a strong relationship between growth characteristics at planting years 4–5 and later-stage performance, indicating this as the optimal period for early selection. These findings contribute to evaluating the production potential of P. deltoides ‘DD-109’ and P. maximowiczii germplasm in northern China and provide valuable guidance for selecting poplar clones suitable for local cultivation, accelerating breeding processes, and informing management planning for poplar plantations.