bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep Quality and Stress Experienced with Quality of Life Among Nurses Working in Private Hospitals in Kathmandu, Nepal: A Cross-sectional Study
Authors: Kafle Birat Raj , Pradhan Simran , Bartaula Manita , Karki Rajesh , Dhungana Prakriti , Devkota Nishchal
Published: April 2024

Sleep and stress significantly affect emotions, productivity, and overall well-being, crucial for optimal health and performance. However, limited research examines how Nepalese nurses' quality of life relates to their sleep quality and stress levels. This study aims to assess this relationship among nurses in private hospitals in Kathmandu. Three private hospitals were selected for this cross-sectional analytical study. Eligible nurses were chosen through purposive sampling, and data were analysed using IBM SPSS v25, employing Chi-square tests and logistic regression analysis. Research revealed a high rate of poor sleep quality (83.9%) among individuals with a mean age of 24.33 ± 3.08 years. Initially, significant associations were found with the factors like bachelor's degree, no tobacco use, absence of insomnia, good sleep quality, and low stress with good quality of life. After adjustment, the association with bachelor's degree [AOR:2.025, CI at 95%: 1.021-4.016, p
Simple Determination of Affinity Constants of Antibodies by Competitive Immunoassays
Authors: Fischer Janina , Kaufmann Jan Ole , Weller Michael G.
Published: April 2024

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (Kd), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC50 approaches the Kd value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to Kd. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.
Spectroscopic Study of a Novel Binaphthyl Amine Fluorescent Probe for Chiral Recognition of DL-Lysine
Authors: Wu Liji , Lu Xiangyu , Cai Wentao , Zou Yajun , Zhang Xiaoyu , Yang Jialiang , Zhao Gang
Published: April 2024

Lysine plays a crucial role in promoting development, enhancing immune function, and improving the function of central nervous system tissues. The two configurational isomers of amino acids have significantly different effects. Currently, methods for chiral recognition of lysine all have drawbacks such as expensive equipment and complicated detection processes, whereas fluorescence analysis boasts high sensitivity, strong selectivity, and simple operation. In this study, we synthesized four novel Binaphthyl-Amine (BINAM)-based fluorescent probes capable of specifically identifying the L-configuration of lysine among the twenty amino acids constituting human proteins. The enantiomeric fluorescence enhancement ratio (ef or ΔIL/ΔID) reached up to 15.29, demonstrating high enantioselectivity. We also evaluated the probe's recognition ability under different pH, reaction times, and metal ion conditions, as well as the Limit of Detection of the probe. Our findings indicate that this probe is a highly stable tool for detecting chiral lysine.
The Prescribed Observation Problem: The Empirical Genesis of Quantum Physics
Authors: Harvey-Tremblay Alexandre
Published: April 2024

Quantum mechanics, despite its remarkable empirical success, has been subject to longstanding interpretational challenges. This work introduces the Prescribed Observation Problem (POP) framework, which derives the complete formulation of quantum theory from the empirical basis of measurement outcomes, treated as an optimization constraint. Rather than postulating quantum principles axiomatically, the POP framework formulates quantum mechanics as the solution to an entropy maximization problem subject to this constraint, resulting in quantum theory's axioms emerging as theorems – the optimal, least biased probability measure consistent with the given measurement data. Notably, the POP framework is sufficiently powerful to reduce the foundation of quantum mechanics to a single axiom. Conventionally, interpretations of quantum mechanics need only align with the theory's postulated axioms, allowing for a plurality of viable interpretations that cannot definitively rule each other out. In contrast, the POP framework derives the axioms as theorems directly from empirical first principles, grounding them in observational constraints from the outset. This substantially restricts the allowable theoretical landscape, imposing stringent requirements for the viability of interpretations and invalidating all those that contradict this genesis. By engendering quantum theory from a formal empirical footing, the POP framework offers a compelling resolution to the enduring interpretational puzzles that have long plagued the field, effectively eliminating all but one interpretation consistent with both the axioms and their empirical genesis.
Eigenvalue Distributions in Random Confusion Matrices: Applications to Machine Learning Evaluation
Authors: Olaniran Oyebayo Ridwan , Alzahrani Ali Rashash R. , Alzahrani Mohammed R.
Published: April 2024

In this paper, we derive the distribution of eigenvalues for a 2×2 random confusion matrix stemming from a machine learning (ML) evaluation problem. Additionally, we present the distributions of both the matrix’s trace and the difference between the two traces of random confusion matrices. We also illustrate the application of these derived distributions in calculating the superiority probability of four baseline ML models.
Nutraceuticals Modulating Mitophagy May Combat the Mitochondrial Dysfunction and Redox Stress in Several Cardiac Disorders
Authors: Nakashima Moeka , Suga Naoko , Matsuda Satoru
Published: April 2024

It has been proposed that procedures which up-regulate mitochondrial biogenesis and autophagy by replacing damaged mitochondria with healthy ones, may prevent the development of several heart diseases. A member of serine and threonine kinases, AMPK, could play essential roles in the autophagy and/or mitophagy. AMPK is widely distributed in various cells, which might play diverse regulatory roles in different tissues and/or organs. In fact, changes in the kinase function of AMPK due to alteration of activity have been linked with diverse pathologies including cardiac disorders. AMPK can regulate mitochondrial biogenesis via PGC1α signaling and also improve oxidative mitochondrial metabolism through inhibition of mTOR pathway, which may also modulate the autophagy/mitophagy through ULK1 and/or TGF-β signaling. Therefore, the modulation of AMPK in autophagy/mitophagy pathway might be considered as a therapeutic tactic for several cardiac disorders. As kinases are amongst the most controllable proteins, in general, the design of small molecules targeting kinases might be an eye-catching avenue to modulate the cardiac function. Some analyses of the molecular biology underlying mitophagy suggests that nutraceuticals and/or drugs including specific AMPK modulator as well as physical exercise and/or dietary restriction that could modulate AMPK may be useful against several heart diseases. In particular, some nutraceutical regimens may have encouraging potential for controlling some of cardiac disorders.
Discovering Data Domains and Products in Data Meshes Using Semantic Blueprints
Authors: Pingos Michalis , Andreou Andreas S.
Published: April 2024

Nowadays, one of the greatest challenges in Data Meshes revolves around detecting and creating Data Domains and Data Products for providing the ability to adapt easily and quickly to changing business needs. This requires a disciplined approach to identify, differentiate and prioritize distinct data sources according to their content and diversity. The current paper tackles this highly com-plicated issue and suggests a standardized approach that integrates the concept of Data Blueprints with Data Meshes. In essence, a novel standardization framework is proposed that creates Data Products using a metadata semantic enrichment mechanism, the latter also offering Data Domain readiness and alignment. The approach is demonstrated using real-world data produced by mul-tiple sources in a poultry meat production factory. A set of functional attributes is used to compare qualitatively the proposed approach against existing data structures utilized in storage architectures with quite promising results. Finally, experimentation with different scenarios varying in data product complexity and granularity suggests successful performance.
A Contribution to the Integration of International, National and Local Cultural Heritage Protection through a Multilevel Approach to Planning: A Case Study of the Djerdap Area
Authors: Niković Ana , Manić Božidar , Čolić Marković Nataša , Krunić Nikola
Published: April 2024

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.
Pre-infection Nutritional Status, Oxidative Stress, and One-Year Long COVID Persistence in Patients Undergoing Hemodialysis: A Prospective Cohort Study
Authors: Stepanova Natalia , Korol Lesya , Ostapenko Tetyana , Marchenko Valeriia , Belousova Olga , Snisar Lyudmila , Shifris Iryna , Kolesnyk Mykola
Published: April 2024

Background: Nutritional status and oxidative stress have been implicated in the pathogenesis and persistence of long COVID, but data in patients undergoing hemodialysis (HD) are limited. The present study aimed to investigate the association between pre-infection nutritional status, oxidative stress, and one-year long COVID persistence in HD patients. Methods: This prospective observational cohort study enrolled 115 HD patients with confirmed COVID-19. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score twice: before infection and three months post-infection. Oxidative markers included malondialdehyde (MDAs), ceruloplasmin, transferrin, and sulfhydryl groups. The endpoint was one-year long COVID persistence. Results: Moderate pre-infection CONUT scores were associated with heightened severe undernutrition risk (p < 0.0001), elevated MDAs (p < 0.0001), and reduced ceruloplasmin levels (p = 0.0009) at three months post-COVID-19 compared to light CONUT scores. Pre-infection CONUT score independently predicted post-COVID oxidative damage [OR 2.3 (95%CI 1.2; 4.6), p < 0.0001] and one-year long COVID persistence [HR 4.6 (95%CI 1.4; 9.9), p < 0.0001], even after adjusting for potential confounders. Conclusion: Moderate pre-infection undernutrition in patients undergoing HD associated with increased post-COVID oxidative stress intensity and heightened risk of one-year long COVID persistence.
2D Shear Wave Elastography of the Thyroid in Clinically Healthy Dogs of Different Age Groups
Authors: Ramos Denise J. , Disseli Tamiris , Gomes Diego R. , Aires Luiz Paulo N. , Tinto Stefany T. , Salazar Diana V. V. , Pereira Mariane M. F. , Miranda Brenda S. P. , Oliveira Ana Paula L. , Lima Bruna B. , Uscategui Ricardo A. R. , Feliciano Marcus Antônio R.
Published: April 2024

Considering the age of the dogs, it was expected that elderly animals would have stiffer thyroids than adults. The aim of this study was to evaluate the thyroid glands of healthy dogs using 2D shear wave elastography in order to establish qualitative and quantitative parameters of tissue stiffness in dogs of different age groups. The B-mode ultrasound and elastography findings were correlated with the weight and sex of the patients, allowing a reference range to be established for different groups of dogs. 31 dogs of different breeds, sexes and sizes were evaluated. Animals with clinical signs or ultrasound findings indicative of endocrine disease or thyroid lesions were not included in the study. Using QelaXtoTM 2D software, shear wave velocity data in m/s and color elastograms were evaluated and calculated. A healthy thyroid has a blue color elastogram, indicative of low stiffness, and there was no distinction between adult and elderly dogs, genders or sizes. The reference range for the shear wave velocity of thyroid tissue assessed by 2D shear wave elastography can be between 1.6 and 2.0 m/s with a variation of ±0.889 in adult and elderly dogs.
Findings and Challenges Replacing the Traditional Uterine Cervical Cancer Diagnosis with Molecular Tools in the Private Gynecological Practice in Mexico
Authors: Barrera-Saldaña Hugo A , Castrillo José L , Rivera Santiago Carolina , Avila Silvia M , Barrera-Barrera Silvia A.
Published: April 2024

We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as an alternative enabled by these platforms to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test and still one more for the p16/Ki67 dual stain cytology. A total of 4,499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% got a positive HR HPV-PCR result. Dual staining with the p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Of the PCR results positive for any of these high-risk HPV subtypes, n 68.3% we did not to find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR, to avoid unnecessary colposcopies. Encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists, we still believe that colposcopy continues to be a preferred procedure over dual staining protocol.
Perceptions of COVID-19 Vaccination among Organ Transplant Recipients
Authors: Lerner River , Arvanitis Panos , Guermazi Dorra , Farmakiotis Dimitrios
Published: April 2024

Understanding vaccine hesitancy in organ transplant recipients (OTR) is critical, given clear, alt-hough attenuated, benefits from vaccination. Adult OTR were surveyed regarding vaccine-related values and a novel outcome variable called Vaccine Acceptance Composite Score (VACS) was built as the average Likert score of 7 domains of vaccination confidence. Of 46 OTR included (93.5% kidney transplant recipients), 32.6% were female, 13.3% Black, 6.77% Hispan-ic/Latino/a/x; median age was 58 years. Patients were most concerned about COVID-19 vac-cine-associated risks (46.3%), its potential effect on allograft (47.6%) and motives of government officials involved with vaccine policy (55.6%). Politically conservative patients were likely to have a significantly lower VACS, while those who lived with someone ≥65 had a higher VACS. The VACS was not significantly associated with race, income, religious beliefs, comorbidities, COVID-19 history, or influenza vaccination status. Higher VACS was significantly associated with ≥3 and ≥4 COVID-19 immunizations. This study highlighted political beliefs and elderly household members as correlates of vaccine acceptance among OTR. The VACS may be a useful tool to help standardize multifaceted analyses in vaccination-focused behavioral research, as well as identify individuals and groups at risk for vaccine hesitancy, who may benefit from tai-lored outreach and educational interventions.
Effectiveness of a Dual-Task Intervention Involving Exercise and Vocalized Cognitive Tasks
Authors: Abo Masahiro , Hamaguchi Toyohiro
Published: April 2024

Background/Objectives: Population aging is rapidly increasing, and the importance of preventive medicine has been stressed. Health checkup, diet, and exercise are of paramount importance. This study aimed to evaluate the effectiveness of a personalized dual-task intervention that combined exercise with cognitive tasks in improving physical and cognitive functions among independently living elderly individuals. Methods: Participants were aged >65 years who were mostly independent in their activities of daily living, divided into 2 groups. The group receiving the 20-min robot-assisted session was compared to the group receiving traditional functional restoration training. This randomized trial assessed the impact of this intervention on the 30-s chair stand test score and Montreal Cognitive Assessment-Japanese version score of the participants. Results: Both scores significantly improved in the intervention group, indicating enhanced lower-limb function and cognitive capabilities. Conclusions: These findings suggest that integrating cognitive tasks with physical exercise can be a potent strategy to improve overall well-being in the elderly, offering valuable insights for designing comprehensive preventive health programs tailored to this demographic.
Selenium Levels and Sources on Performance, Digestibility, Intestinal Integrity, Serum Parameters and Gene Expression of Selenoproteins in Weaned Piglets
Authors: de Almeida Jorge Luiz Santos , Pascoal Leonardo Augusto Fonseca , Guerra Ricardo Romão , Martins Terezinha Domiciano Dantas , Givisiez Patricia Emília Naves , Watanabe Pedro Henrique , Almeida Jonathan Mádson dos Santos , Batista João Marcos Monteiro , Hermínio Maria Pricila Ferreira , Santos Verônica Lisboa , de Araújo Wydemberg José
Published: April 2024

This study was conducted with the objective of investigating the enrichment of weaned piglet diets with organic selenium (proteinate selenium) and inorganic selenium (sodium selenite) with two addition levels (0.15 and 0.30 mg/kg). A total of 40 piglets (20 castrated males and 20 females) weaned at 28 days of age with an average initial weight of 6.60±1.06 kg were used. The treatments were: Control diet (Control diet); Selenium-enriched control diet proteinate with 0.15 mg/kg of selenium added (SeOrg-0.15); Selenium-enriched control diet proteinate with 0.30 mg/kg of selenium added (SeOrg-0.30); Control diet enriched with sodium selenite with 0.15 mg/kg of selenium added (SeInorg-0.15); and Control diet enriched with sodium selenite with 0.30 mg/kg of selenium added (SeInorg-0.30). The presence of selenium in the control diet came from the ingredients and the mineral supplement. The following data were analyzed: productive performance; digestibility of nutrients and energy; morphometry and intestinal integrity; serum biochemical parameters; and gene expression of selenoproteins in intestinal epithelium and liver tissue of piglets. The SeOrg-0.30 treatment caused a reduction (P
More than 30 Years of PVC Recycling – Need for Regulation
Authors: Lahl Uwe , Zeschmar-Lahl Barbara
Published: April 2024

On the basis of a stocktaking on PVC in Europe and on a current ECHA investigation report, we conclude that regulatory action at EU level is recommended. We support ECHA's regulatory proposals in the main, but come to a more comprehensive proposal for the phasing-out of PVC beyond the area of electrical installations. PVC stored in buildings and infrastructure to date amounts to around 160 million tonnes ("stock") and this mass is still increasing. Parts from the stock have entered the waste management sector for years and their mass is gradually increasing. Neither material, chemical nor energy recovery will be able to absorb these incoming quantities. We therefore come to the conclusion that PVC should be collected separately and disposed of in an infrastructure designed for chlorine recovery. The required infrastructure should be set up and operated by the chemical industry. So, PVC will lose its status as a particularly economically favorable plastic. In view of the constantly increasing stock, we recommend phasing-out the production of virgin PVC as early as possible. In our opinion, this would also be justifiable because the effects of the closed loop recycling announced by VinylPlus ('Vinyl') would go in the same direction.
Performance and Cost-Efficiency of Single Hormonal Treatment Protocols in Tropical Anestrous Dairy Cows
Authors: Changtes Thitiwich , Sanchez Javier , Arunvipas Pipat , Patanasatienkul Thitiwan , Thammahakin Passawat , Jaroensawat Jiranit , Hall David , Heider Luke , Rukkwamsuk Theera
Published: April 2024

This retrospective study aimed to evaluate the performance of the hormone treatment protocols, determine the factors associated with pregnancy success after hormone treatment, and compare the cost-efficiencies of two types of hormone treatment among cyclic and noncyclic anestrous dairy cows. The clinical records of 279 anestrous cows who received hormone treatment for artificial insemination (AI) from 64 herds in the western region of Thailand were obtained from Kasetsart University Veterinary Teaching Hospital from January to August 2017. The performance of the hormone treatment protocols, fixed-time AI (TAI) and estrus detection before AI (EAI), showed that the pregnancy risk for the TAI protocol was higher than for the EAI protocol, but pregnancy per AI did not differ significantly between the two protocols in cyclic and noncyclic cows. Multivariate logistic regression analysis showed that cows receiving the TAI protocol were more likely to be pregnant compared to those treated with the EAI protocol. Cows with a 3.00 body condition score (BCS) <3.75 after treatment and loose-housing cows were more likely to become pregnant. Treatment during winter showed higher pregnancy success than in the summer and rainy seasons. The cost-efficiency analysis showed that the TAI protocol was the most cost-efficient option for noncyclic cows, whereas the EAI protocol was the most cost-efficient option for cyclic cows.
Genetics and Molecular Mechanisms of Idiopathic Dilated Cardiomyopathy, a Possible Guide to Individualized Management
Authors: Arnautu Diana-Aurora , Cretu Octavian-Marius , Lighezan Daniel Florin , Andor Minodora , Citu Ioana , Cozma Dragoș , Bernad Brenda-Cristiana , Trifa Adrian-Pavel , Lighezan Diana , Bernad Elena-Silvia , Jianu Dragos Catalin , Oancea Cristian , Lala Ioan-Radu , Arnautu Sergiu-Florin , Tomescu Mirela-Cleopatra
Published: April 2024

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both hereditary and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variations that can be transmitted from one generation to another can be a significant contributor to causing family or isolated DCM. Genetic variation also plays a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a diverse range of phenotypic expressions. It is crucial to select the most probable patients to have advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the crucial relationships between genotype and phenotype, and the usefulness of genetic testing in the therapeutic care of both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications.
Penrose Scattering in Quantum Vacuum
Authors: Mendonça José Tito
Published: April 2024

Scattering of a probe laser pulse by an intense light spring in QED vacuum is considered. This new scattering configuration can be seen as the vacuum equivalent to the process originally associated with scattering of light by a rotating black hole, usually called Penrose superradiance. Here the rotating object is an intense laser beam containing two different components of orbital angular momentum. Due to these two components with slightly different frequencies, the energy profile of the intense laser beam rotates with a frequency that depends on the frequency difference. The nonlinear properties of quantum vacuum are described by first order Euler-Heisenberg Lagrangian. It is shown that, in such a configuration, nonlinear photon-photon coupling leads to scattered radiation, with frequency shift and angular dispersion. These two distinct properties, of frequency and propagation direction, could eventually be favourable for possible experimental observations. In principle, this new scattering configuration can also be reproduced in a nonlinear optical medium.
Advanced Voltametric Characterization of Polyphenols in Wine Using a Modified Carbon Paste Electrode with TiO2 Nanoparticles
Authors: Mićin Saša , DeNardis Nadica Ivošević , Martinez Sanja , Špada Vedrana , Malinović Borislav N.
Published: April 2024

Polyphenols are the most common organic compounds in wine. They improve both the sensory aspects of wine and human health by activating antioxidant systems. Therefore, there is a great need for a simple, fast and accessible method to determine the polyphenol content of wine. The aim of this study is to characterize polyphenolic compounds in natural wine samples using an electrochemical method and a modified carbon paste electrode with TiO2 nanoparticles. This work is motivated by the promising improvement of the sensing properties of a TiO2 nanoparticle-modified carbon paste electrode observed in the electrooxidation of different polyphenols. Since the voltammetric response of wine is largely irreversible, another motivation was the possibility of improving the processing of voltammograms to obtain data indicative of wine polyphenols, based on the approach described in the seminal work by Espinoza et al. The modified electrode studied provides an improved and reproducible voltammetric response of gallic acid in wine samples and provides a good basis for further development of an integrated sensor/data system with the possibility of wider application for the quantification of gallic acid as a flavor and visually relevant parameter in winemaking.
The Platform Technology Approach to mRNA Product Development and Regulation
Authors: SKERRITT John Howard , Tucek-Szabo Carolyn , Sutton Brett , Nolan Terry
Published: April 2024

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods utilised often for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This Review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products and mRNA therapeutics.

Providing a predictable development pathway for academic and commercial groups, so they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission, has many potential benefits. These include reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review.
Anti‐Candida Phytochemicals and Isolated Compounds in Anacardiaceae Family—An Updated Review and In‐Silico Analysis
Authors: Oliveira Aluisio Silva , Farias Josivan Regis , Franco Danielle Cristine Gomes , Costa Arthur Andre Castro da , Santos Pamela Gomes , Silva Mayara Cristina Pinto , Nascimento Flavia Raquel Fernandes , Guerra Rosane Nassar Meireles
Published: April 2024

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.
Development of Sensitive Anti-mouse CCR5 Monoclonal Antibodies Using the N-terminal Peptide Immunization
Authors: Ubukata Rena , Suzuki Hiroyuki , Tanaka Tomohiro , Ouchida Tsunenori , Li Guanjie , Kaneko Mika K , Kato Yukinari
Published: April 2024

One of the G protein-coupled receptors, C-C chemokine receptor 5 (CCR5), is an important regulator for the activation of T and B lymphocytes, dendritic cells, natural killer cells, and macrophages. Upon binding to the ligands, CCR5 activates downstream signaling, which plays critical roles in the innate and adaptive immune response through the promotion of lymphocyte migration and the secretion of pro-inflammatory cytokines. Anti-CCR5 monoclonal antibodies (mAbs) have been developed and evaluated in clinical trials for tumors and inflammatory diseases. In this study, we developed novel mAbs for mouse CCR5 (mCCR5) using the N-terminal peptide immunization. Among the established anti-mCCR5 mAbs, C5Mab-4 (rat IgG2a, kappa) and C5Mab-8 (rat IgG1, kappa), recognized mCCR5-overexpressed Chinese hamster ovary-K1 (CHO/mCCR5) and an endogenously mCCR5-expressing cell line (L1210) by flow cytometry. The dissociation constant (KD) values of C5Mab-4 and C5Mab-8 for CHO/mCCR5 were determined as 3.5 × 10−8 M and 7.3 × 10−9 M, respectively. Furthermore, both C5Mab-4 and C5Mab-8 could detect mCCR5 by western blotting. These results indicated that C5Mab-4 and C5Mab-8 are useful for detecting mCCR5 by flow cytometry and western blotting and provide a possibility to obtain the proof of concept in preclinical studies.
The Acceptability and Validity of AI-Generated Psycholinguistic Stimuli
Authors: Alzahrani Alaa
Published: April 2024

Sentence stimuli pervade psycholinguistics research. Yet limited attention has been paid to the automatic construction of sentence stimuli. Given their linguistic capabilities, this study investigated the efficacy of ChatGPT/AI tools in generating sentence stimuli. In three psycholinguistic experiments, this study examined the acceptability and validity of AI-formulated auditory sentences and written sentences in two languages: English and Arabic. Participants gave English AI-generated stimuli similar to or higher acceptability ratings than human-composed stimuli, but the opposite was observed for Arabic AI-generated stimuli. The validity of AI-developed stimuli relied on the study design, with only Experiment 2 demonstrating the target psycholinguistic effect (L1/L2 morphosyntactic prediction). These results highlight the promising role of AI as a stimuli developer which could facilitate psycholinguistic research and increase its diversity. Implications for psycholinguistic research were discussed.
Genomic Approaches for Drug Repurposing
Authors: Dave Kirtan , Sharma Meenakshi , Patel Dahavl , Dhanda Parmdeep Singh , Yadav Alpa , Jain Mukul
Published: April 2024

Functional genomics, a multidisciplinary subject, investigates the functions of genes and their products in biological systems to better understand diseases and find new drugs. Drug repurposing is an economically efficient approach that entails discovering novel therapeutic applications for already-available medications. Genomics enables the identification of illness and therapeutic molecular characteristics and interactions, which in turn facilitates the process of drug repurposing. Techniques like gene expression profiling and Mendelian randomization are helpful in identifying possible medication candidates. Progress in computer science allows for the investigation and modelling of gene expression networks that involve large amounts of data. The integration of data from DNA, RNA, and protein activities has resemblance to pharmacogenomics, which is of utmost importance in the development of cancer drugs. Functional genomics in drug discovery, particularly for cancer, is still not thoroughly investigated, despite the existence of a significant amount of literature on the subject. Next-generation sequencing and proteomics present highly intriguing opportunities. Publicly available databases and mining techniques facilitate the development of cancer treatments based on functional genomics. Expanding the study and application of functional genomics has great promise to advance the process of discovering and repurposing drugs, especially in the field of oncology.
Detection of Individual Crop and Canopy Delineation from UAV Imagery
Authors: Dorbu Freda , Hashemi-Beni Leila
Published: April 2024

Precise monitoring of individual crop growth and health status is crucial for precision agriculture practices. However, traditional manual inspection methods are time-consuming, labor-intensive, and often lack the spatial resolution required for detailed analysis. This research addresses the need for efficient and high-resolution crop monitoring by leveraging Unmanned Aerial Vehicle (UAV) imagery and advanced computational techniques. The primary objective was to develop a methodology for precise identification, extraction, and monitoring of individual corn crops throughout their growth cycle. This was achieved by integrating UAV-derived data with image processing, computational geometry, and machine learning techniques. UAV imagery was ac-quired bi-weekly at altitudes of 40m and 70m, capturing the entire growth cycle of a corn crop from planting to harvest. A time-series Canopy Height Model (CHM) was generated by analyzing the differences between the Digital Terrain Model (DTM) and the Digital Surface Model (DSM) derived from the UAV data. Local spatial analysis and image processing techniques were em-ployed to determine the local maximum height of each crop. Subsequently, a Voronoi data model was developed to delineate individual crop canopies, successfully identifying 13,000 out of 13,050 corn crops in the study area. For enhanced accuracy in canopy size delineation, vegetation indices were incorporated into the Voronoi model segmentation, refining the initial canopy area esti-mates by eliminating interference from soil and shadows. The proposed methodology enables precise estimation and monitoring of crop canopy size, height, biomass reduction, lodging, and stunted growth over time, providing valuable insights for precision agriculture practices. This work contributes to the scientific community by demonstrating the potential of integrating UAV technology, computational geometry, and machine learning for accurate and efficient crop mon-itoring at the individual plant level.
Impact of Nutrient Intake on Body Composition in Very Low Birth Weight Infants Following Early Progressive Enteral Feeding
Authors: Brinkis Rasa , Albertsson-Wikland Kerstin , Šmigelskas Kastytis , Vanckavičienė Aurika , Aldakauskienė Ilona , Tamelienė Rasa , Verkauskienė Rasa
Published: April 2024

Preterm infants have increased body adiposity at term equivalent age and risk for adverse metabolic outcomes. The aim of the study was to define how nutrient intake may impact body composition (BC) of very low birth weight infants fed with early progressive enteral feeding and standard fortification. Eighty-six infants with
Phenolic Compounds from Cherries and Berries for Chronic Disease Management and Cardiovascular Risk Reduction
Authors: Carvalho Filomena , Lahlou Radhia Aitfella , Silva Luís Manuel Lopes Rodrigues da
Published: April 2024

Cardiovascular diseases (CVDs) a leading cause of mortality worldwide. Therefore, there is in-creasing interest in dietary interventions to reduce risk factors associated with these conditions. Cherries and berries are rich sources of bioactive compounds and have attracted attention for their potential cardiovascular benefits. This review summarizes the current research on the effects of cherries and berries consumption on cardiovascular health, including in vivo studies and clinical trials. These red fruits are rich in phenolic compounds, such as anthocyanins and flavonoids, which have multiple bioactive properties. These properties include antioxidant, anti-inflammatory, and vasodilatory effects. Studies suggest that regular consumption of these fruits may reducing in-flammation and oxidative stress, leading to lower blood pressure, improved lipid profiles, and enhanced endothelial function. However, interpreting findings and establishing optimal dosages is challenge due to the variability in fruit composition, processing methods, and study design. Despite these limitations, the evidence highlights the potential of cherries and berries as components of preventive strategies against CVD. Further research is needed to maximize their health benefits and improve clinical practice.
Efficacy and Tolerability of Radiosurgery in Treating Benign Meningioma: A Dose Comparison Study from a Single-Center Analysis
Authors: Cho Hyun Jeong , Lee Jong Min , Park Sung Ho , Park Jun Bum , Jung Na Young
Published: April 2024

This retrospective study aimed to evaluate the impact of radiation dose on the outcomes of stereotactic radiosurgery (SRS) for benign meningiomas and determine an optimal dosing strategy for balancing tumor control and treatment-related toxicity. Clinical data of 147 patients with 164 lesions treated between 2014 and 2022 were reviewed. Primary outcomes included progression-free survival (PFS), local control rate (LCR), and radiation-induced toxicity, with secondary outcomes focusing on LCR and radiation-induced peritumoral edema (PTE) in two dose groups (≥14 Gy and <14 Gy). Results revealed a median follow-up duration of 47 months, with 1-year, 2-year, and 5-year PFS rates of 99.3%, 96.7%, and 93.8% respectively, and an overall LCR of 95.1%. Radiation-induced toxicity was observed in 24.5% of patients, primarily presenting mild symptoms. Notably, no significant difference in LCR was found between the two dose groups (P = 0.628), while Group 2 (<14 Gy) exhibited significantly lower PTE (P = 0.039). The study concludes that SRS with a radiation dose <14 Gy demonstrates comparable tumor control with reduced toxicity, advocating for consideration of such dosing to achieve a balance between therapeutic efficacy and safety.
Raising Awareness of the Importance of Early Diagnosis of Children with Autism Spectrum Disorders (ASD)
Authors: DAN Adrian-Nicolae , Stănescu Nina
Published: April 2024

The article discusses early diagnosis and intervention for developmental delays in children, emphasizing the role of specialized services and personnel in supporting recovery and development. It presents findings from a pilot project initiated in Bucharest, aiming to assess the incidence of developmental delays in children aged 1-3 years in selected kindergartens, including ASD. The study involved children, parents, and specialists, utilizing systematic behavior observation (SBO) and semi-structured interviews. Results indicate that out of 613 evaluated children, 81 received specialized control recommendations, with 4 cases showing potential risk of ASD. Additionally, 8 children were diagnosed with autism. The incidence of autism in children aged 1-3 years was 1 in 51. Although exploratory, these findings suggest a model of good practice for future early diagnosis campaigns nationally. Conclusively, the study underscores the importance of early diagnosis and intervention for developmental delays, advocating for a responsive community and emphasizing the significance of national-level efforts to address these issues effectively.
An Uplifting Avenue upon Mealworm Chitosan for Hemodialysis Application
Authors: Martingo Maria , Baptista-Silva Sara , Mesquita Raquel , Ferreira João Paulo , Borges Sandra , Pintado Manuela
Published: April 2024

Chronic kidney disease (CKD) is characterized by a continuous decline in kidney function, often persisting for years or even a lifetime. This study presents a new exploration into the extraction and application of insect chitosan (Tenebrio molitor) targeting hemodialysis (HD). Initially, the potential of insect-derived chitosan as a sustainable and effective alternative to traditional sources (i.e. crustaceans) is demonstrated. Efficient extraction methods were developed (totaling between 6 h and 12 h), producing chitosan. Firstly, chitin was efficiently isolated from T. molitor through deproteinization and demineralization, with yields of approximately 5% (w/w). Subsequently, chitosan was obtained from the extracted chitin resulting in yields of between 65.0 ± 0.8% (w/w) and 79.3 ± 0.8% (w/w). Characterization using Fourier Transform Infrared Spectroscopy (FTIR) confirmed structural similarities with commercial chitosan and degrees of deacetylation in the 73 - 75% range. The bioactive properties of chitosan obtained from T. molitor, including antimicrobial and antioxidant activities, were evaluated. All the microorganisms tested were inhibited, exhibiting minimum lethal concentrations between 2 and 8 mg/mL, confirming the antimicrobial activity of the extracted chitosan. In addition, chitosan showed antioxidant activity in the range of 60 to 65 µmol Trolox equivalent/g, suggesting its viability for various medical applications.This study also developed a chitosan-based membrane (CH - M) culminating in a proof-of-concept phase for hemodialysis. The permeation characteristics of CH-M for urea and albumin were studied in vitro to assess their suitability as HD membranes. Urea was permeable to values of over 70% and albumin was retained.
Significance of Cellular Lipid Metabolism for the Replication of Rotaviruses and Other RNA Viruses
Authors: Desselberger Ulrich
Published: April 2024

The replication of species A rotaviruses (RVAs) and other RNA viruses involves recruitment of and inter-action with the cellular organelles lipid droplets (LDs), both physically and functionally. Inhibition of en-zymes involved in the cellular fatty acid biosynthesis pathway or of cellular lipases that degrade LDs re-duces the functions of ‘viral factories’ (viroplasms for rotaviruses or replication compartments of other RNA viruses) and decreases the production of infectious progeny virus. Similarly, disturbance of the cellular lipid homeostasis in various ways blocks the replication of flaviviruses (hepatitis C viruses, Zikavirus, others), HIV-1, SARS-CoV-2, picornaviruses, noroviruses, influenza viruses and other negative-strand RNA viruses.
Liquid Moisture Transport in Multilayer Fabric Sets for Firefighters Protective Clothing
Authors: Matusiak Małgorzata , Sukhbat Otgonsuren
Published: April 2024

Firefighters Protective Clothing consist of several layers of different properties and functions. The layers create barriers against dangerous outer factor. However, they are also barriers to transport of sweat produced by human organism. It causes that very often sweat in the form of vapor is not transferred effectively from the human organism through the FPC to environment. This leads to sweat condensation on the skin of the FPC user causing his discomfort. In order to ensure as good as possible physiological comfort of firefighter while firefighting and other rescue actions it is necessary to take into consideration the transport of condensed sweat in the multilayer textile set creating the FPC. In the presented work four variants of multilayer textile sets for the FPC have been tested in the aspect of liquid moisture transport. Measurement was performed by means of the Moisture Management Tester (MMT290) – innovative instrument manufactured by the SDL Atlas. Obtained results showed that the transfer of sweat in liquid form occurs only in the inner, next to skin layer of the multilayer sets for the FPC.