bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Freeze–Thaw Cycles on the Freshness of Prepackaged Penaeus vannamei
Authors: Liu Shouchun , Zhang Luyao , Chen Jing , Li Zhuyi , Liu Meijiao , Hong Pengzhi , Zhong Saiyi , Li Haifeng
Published: January 2024

The effect of temperature fluctuations on the freshness of shrimp in simulated trays was investigated by setting a freeze–thaw (F-T) cycle of 12 h after freezing at −20 °C and thawing at 1 °C under refrigeration. The results showed that the shrimp’s physicochemical properties deteriorated to different extents with the increase in F-T cycles. The total colony count of shrimp was 6.07 lg CFU/g after 21 cycles, and the volatile saline nitrogen content reached 30.36 mg/100 g, which exceeded the edible standard. In addition, the sensory quality and textural properties (hardness, elasticity, chewiness, and adhesion) declined to different degrees with increased F-T cycles. LF-NMR and protein property measurements showed that F-T cycles resulted in reduced water holding capacity and protein denaturation, which were the main factors leading to the deterioration of shrimp quality. Furthermore, flavor changes were analyzed using an electronic nose sensor to establish a freshness model. The W1W, W1S, W2S, and W5S sensors were correlated with the quality changes in shrimp and used as the main sensors for detecting the freshness of Penaeus vannamei. As a result, to better maintain the overall freshness, temperature fluctuations should be minimized in sales and storage, and fewer than 8 F-T cycles should be performed.
Metabolomics Reveals the Response Mechanisms of Potato Tubers to Light Exposure and Wounding during Storage and Cooking Processes
Authors: Wang Xin , Yang Shuiyan , Sun Jinghan , Chen Guoyan , Wen Yunman , Yang Jin , Nie Xuheng , Liu Chao
Published: January 2024

Potato is susceptible to light exposure and wounding during harvesting and transportation. However, the metabolite profile changes in these potato tubers are unclear. The potato cultivars in this study included Hezuo88 (HZ88), Shida6 (SD6), and Jianchuanhong (JCH); the effects of light exposure (L), wounding (W), and the cooking process on potato metabolites were determined. In total, 973 metabolites were identified, with differential metabolites (mainly alkaloids, flavonoids, and phenolic acids) accumulated on days 0 and 2 (0 d and 2 d) in the 0dHZ88 vs. 0dJCH (189), 0dHZ88 vs. 0dSD6 (147), 0dSD6 vs. 0dJCH (91), 0dJCH vs. 2dIJCH (151), 0dJCH vs. 2dWDJCH (250), 0dJCH vs. 2dWLJCH (255), 2dIJCH vs. 2dWDJCH (234), and 2dIJCH vs. 2dWLJCH (292) groups. The flavonoid content in the light exposure group was higher than that in the dark group. The alkaloid content in the wounded group was higher than that in the uninjured potato tuber group, but the lipid content in the wounded group was lower. Importantly, only 5.54% of the metabolites changed after potato tuber steaming. These results provide valuable information for the breeding and consumption of potato tubers.
Consumer Perception and Liking of Parmigiano Reggiano Protected Designation of Origin (PDO) Cheese Produced with Milk from Cows Fed Fresh Forage vs. Dry Hay
Authors: Tura Matilde , Gagliano Mara Antonia , Soglia Francesca , Bendini Alessandra , Patrignani Francesca , Petracci Massimiliano , Gallina Toschi Tullia , Valli Enrico
Published: January 2024

This study aimed to investigate consumer sensory profiles and liking of Parmigiano Reggiano PDO cheese produced with milk from cows reared indoors and fed with different forage sources, i.e., dry hay and fresh forage. Two cheese samples were tested by 119 Italian subjects, following a protocol that included a Check-All-That-Apply method to assess the sensory profile, a Just-About-Right scale to evaluate the adequacy of attributes, and questions on liking (9-point hedonic scale). A questionnaire related to personal information and consumption habits was also submitted. The color of the two samples, based on image analysis, was different: the sample produced with milk from the dairy cows fed fresh forage had a higher intensity of yellow than the other; they were also described differently (p ≤ 0.05) by participants in the consumer test. Indeed, Parmigiano Reggiano produced with milk from the cows that were fed dry hay was mainly characterized by a “fresh milk” and “solubility”, while the sample produced with milk from cows fed fresh forage was described as “yellow”, “seasoned”, “pungent”, and with a “cheese crust” flavor. Even if no significant differences were observed between the two samples in terms of liking (p ≤ 0.05), the attribute “graininess” showed a great impact on liking ratings together with “yellow” (p ≤ 0.05), apparently corresponding to a specific expectation regarding the intensity of these attributes. Data were also analyzed according to the gender of consumers, highlighting that for women, the adequacy of “fresh milk”, “sweet”, and “graininess” greatly impacted liking for the cheese from cows fed dry hay.
Use of Glutathione, Pure or as a Specific Inactivated Yeast, as an Alternative to Sulphur Dioxide for Protecting White Grape Must from Browning
Authors: Bustamante Marco , Giménez Pol , Just-Borràs Arnau , Solé-Clua Ignasi , Gombau Jordi , Heras José M. , Sieczkowski Nathalie , Gil Mariona , Pérez-Navarro José , Gómez-Alonso Sergio , Canals Joan Miquel , Zamora Fernando
Published: January 2024

One of the problems that most seriously affects oenology today is enzymatic browning, especially when grapes are infected by grey rot. We studied the capacity of glutathione (GSH) and a specific inactivated dry yeast rich in glutathione (IDY-GSH) to protect white grape must from browning compared to that of sulphur dioxide (SO2). The results indicate that SO2 drastically reduces the oxygen consumption rate (by around 72%), protects hydroxycinnamic acids from oxidation and prevents grape must against browning even in the presence of laccase. Specifically, the presence of SO2 reduced the colour’s blue–yellow component (b*) by around 91% in control conditions and around 76% in the presence of laccase. GSH, pure or in the form of IDY-GSH, also reduces the oxygen consumption rate (by 23% and 36%, respectively) but to a lesser extent than SO2. GSH also favours the formation of grape reaction product (GRP) from hydroxycinnamic acids and effectively protects grape must against browning in healthy grape conditions. Specifically, the presence of GSH reduced b* by around 81% in control conditions. Nevertheless, in the presence of laccase, it was not effective enough, reducing b* by around 39% in the case of pure GSH and 24% in the case of IDY-GSH. Therefore, both forms of GSH can be considered as interesting alternative tools to SO2 for preventing browning in white grape must, but only when the grapes are healthy.
Yeast Starter Culture Identification to Produce of Red Wines with Enhanced Antioxidant Content
Authors: Romano Giuseppe , Taurino Marco , Gerardi Carmela , Tufariello Maria , Lenucci Marcello , Grieco Francesco
Published: January 2024

Grape variety, quality, geographic origins and phytopathology can influence the amount of polyphenols that accumulate in grape tissues. Polyphenols in wine not only shape their organoleptic characteristics but also significantly contribute to the positive impact that this beverage has on human health. However, during the winemaking process, the total polyphenol content is substantially reduced due to the adsorption onto yeast wall polymers and subsequent lees separation. Despite this, limited information is available regarding the influence of the yeast starter strain on the polyphenolic profile of wine. To address this issue, a population consisting of 136 Saccharomyces cerevisiae strains was analyzed to identify those with a diminished ability to adsorb polyphenols. Firstly, the reduction in concentration of polyphenolic compounds associated to each strain was studied by assaying Total Phenolic Content (TPC) and Trolox Equivalent Antioxidant Capacity (TEAC) in the wines produced by micro-scale must fermentation. A total of 29 strains exhibiting a TPC and TEAC reduction ≤ 50%, when compared to that detected in the utilized grape must were identified and the nine most-promising strains were further validated by larger-scale vinification. Physico-chemical analyses of the resulting wines led to the identification of four strains, namely ITEM6920, ITEM9500, ITEM9507 and ITEM9508 which showed, compared to the control wine, a TPC and TEAC reduction ≤ 20 in the produced wines. They were denoted by a significant (p < 0.05) increased amount of anthocyanin, quercetin and trans-coutaric acid, minimal volatile acidity (<0.2 g/L), absence of undesirable metabolites and a well-balanced volatile profile. As far as we know, this investigation represents the first clonal selection of yeast strains aimed at the identifying “functional” fermentation starters, thereby enabling the production of regional wines with enriched polyphenolic content.
Exploring the Characteristics of Δh Bivariate Appell Polynomials: An In-Depth Investigation and Extension through Fractional Operators
Authors: Almusawa Musawa Yahya
Published: January 2024

The objective of this article is to introduce the ∆h bivariate Appell polynomials ∆hAs[r](λ,η;h) and their extended form via fractional operators. The study described in this paper follows the line of study in which the monomiality principle is used to develop new results. It is further discovered that these polynomials satisfy various well-known fundamental properties and explicit forms. The explicit series representation of ∆h bivariate Gould–Hopper polynomials is first obtained, and, using this outcome, the explicit series representation of the ∆h bivariate Appell polynomials is further given. The quasimonomial properties fulfilled by bivariate Appell polynomials ∆h are also proved by demonstrating that the ∆h bivariate Appell polynomials exhibit certain properties related to their behavior under multiplication and differentiation operators. The determinant form of ∆h bivariate Appell polynomials is provided, and symmetric identities for the ∆h bivariate Appell polynomials are also exhibited. By employing the concept of the forward difference operator, operational connections are established, and certain applications are derived. Different Appell polynomial members can be generated by using appropriate choices of functions in the generating expression obtained in this study for ∆h bivariate Appell polynomials. Additionally, generating relations for the ∆h bivariate Bernoulli and Euler polynomials, as well as for Genocchi polynomials, are established, and corresponding results are obtained for those polynomials.
New Generalized Jacobi Galerkin Operational Matrices of Derivatives: An Algorithm for Solving Multi-Term Variable-Order Time-Fractional Diffusion-Wave Equations
Authors: Ahmed Hany Mostafa
Published: January 2024

The current study discusses a novel approach for numerically solving MTVO-TFDWEs under various conditions, such as IBCs and DBCs. It uses a class of GSJPs that satisfy the given conditions (IBCs or DBCs). One of the important parts of our method is establishing OMs for Ods and VOFDs of GSJPs. The second part is using the SCM by utilizing these OMs. This algorithm enables the extraction of precision and efficacy in numerical solutions. We provide theoretical assurances of the treatment’s efficacy by validating its convergent and error investigations. Four examples are offered to clarify the approach’s practicability and precision; in each one, the IBCs and DBCs are considered. The findings are compared to those of preceding studies, verifying that our treatment is more effective and precise than that of its competitors.
Prospective Teachers’ Knowledge of Physical Activity in Children and Adolescents
Authors: Moreno-Lavaho Sandra Milena , Pérez-Gómez Jorge , Polo-Campos Irene , Gómez-Paniagua Santiago , Rojo-Ramos Jorge
Published: January 2024

Over the past few years, organizations around the world have tried to reach different populations with recommendations about physical activity (PA), due to this subject playing an important role in the phases of intention development and in preparation for it. Thus, the knowledge of future educators in the fields of health and PA is of vital importance when improving the levels of the latter in students. The objective of this research is to determine what knowledge future teachers have about health and PA, examining possible disparities according to the gender, age, and level of physical exercise of the participants. In addition, the psychometric properties of the instrument used were explored. A total of 321 Colombian university students from the Faculty of Education between the ages of sixteen and thirty-five participated in this study, providing sociodemographic information by filling out the CUAFYS-A questionnaire. Significant differences were found in the scale items according to sex and self-perception of being physically active. Also, the findings revealed a single-factor structure with nine items that had satisfactory reliability (α = 0.71; CR = 0.72) and excellent goodness-of-fit indices (RMSEA = 0.055 (90% CI (0.3, 0.8), RMSR = 0.02, CFI = 0.935, NNFI = 0.912, CMIN/DF = 1.97). Therefore, strategies and campaigns to promote PA knowledge in prospective teachers should be tailored according to gender and PA levels. Similarly, the CUAFYS-A questionnaire can be considered a valid and reliable instrument to identify the PA knowledge of future educators.
A Network Analysis Study on the Structure and Gender Invariance of the Satisfaction with Life Scale among Spanish University Students
Authors: Diaz-Milanes Diego , Salado Vanesa , Santín Vilariño Carmen , Andrés-Villas Montserrat , Pérez-Moreno Pedro Juan
Published: January 2024

Introduction: The psychometric properties of the Satisfaction With Life Scale (SWLS) have been evaluated across numerous languages and population groups, primarily from a factor analysis perspective. In some studies, inconsistencies in structural invariance have been identified. Objective: This study aims to analyze the properties and gender invariance of the SWLS from a network analysis perspective. Method: A total of 857 Spanish university students were obtained through a stratified random cluster sampling method in a cross-sectional survey design study. Descriptive analysis of the items, partial-correlation network, Bayesian network model estimation, and invariance analysis by gender were conducted. Results: The instrument did not exhibit any floor or ceiling effects. Each item can be considered univariately normally distributed, and all items clustered in a single and stable community. The partial-correlation network model and centrality measures were stable in the full sample and invariant across genders. Item 3 emerged as the most central node in the network with the highest predictability. The Bayesian network indicated that items 2 and 4 initiate the process, while item 5 acts as the sink, and items 1 and 3 act as mediators. Conclusions: The SWLS can be used as a unidimensional measure, and the total score and relationships among items are stable and reliable. Any potential differences among genders cannot be associated with the functioning of the instrument. The predictability of every item was high, and the Bayesian network clearly identified different roles among the items.
A Life Course Perspective on the Sexual Development of Young Intersex People
Authors: Marinus Mir Abe , Cense Marianne
Published: January 2024

Previous research has indicated that intersex people face specific challenges in their sexual development, including uncertainties or confusion about their gender, a negative genital self-image, and hesitance to engage in romantic and sexual relationships. However, in-depth knowledge regarding a central period in this development, adolescence, is missing. In our qualitative study, we explore which factors influence the relational and sexual development of intersex youth and what elements contribute to positive development. We interviewed eighteen intersex persons aged 18–38. We identified three main themes: (1) intersex experiences, (2) the described sexual and relational life course, and (3) factors influencing a positive development. Our findings show that intersex youth face many obstacles in their relational and sexual development, many of which are related to healthcare. However, their life stories also illuminate how healthcare professionals, as well as parents, friends, partners, teachers, and others, can make a substantial difference in intersex lives by breaking normative, binary thinking on sex and gender.
Drug-Related Problems Detected in Complex Chronic Patients by Community Pharmacists of Catalonia: Perception of the Person-Centred Approach Necessity
Authors: Torres-Novellas Berta , Rius Pilar , Figueiredo-Escribá Carlos , Mariño Eduardo L. , Modamio Pilar
Published: January 2024

Community pharmacies are healthcare settings in which pharmacists are in an ideal position to carry out pharmaceutical care. The aim of this study was to analyse the number, type and groups of drugs that caused drug-related problems (DRPs) detected in complex chronic patients who are outpatients, the interventions and actions of community pharmacists and their impact on patient medication adherence. The study was designed as a secondary analysis of a multicentre study in the field of primary healthcare and community pharmacies in Catalonia (Spain). The patients who took part were divided into two groups by the primary care physician depending on whether or not they were considered likely to receive their medication through a monitored dosage system (MDS) based on pre-established criteria. Patients underwent 12 months of follow-up by community pharmacists. The prevalence of DRPs among the studied complex chronic patients was high (n = 689). The most identified DRP was nonadherence (31.20%). In the MDS group, results showed a statistically significant increase of 21% in the number of adherent patients with respect to the baseline visit (p-value = 0.0008). Community pharmacists can have an important role in addressing DRPs and optimizing the safety and effectiveness of medications for these patients and in involving them in their own health conditions.
Real-World Dispensing of Buprenorphine in California during Prepandemic and Pandemic Periods
Authors: Wang Yun , Chan Alexandre , Beuttler Richard , Fleming Marc L. , Schneberk Todd , Nichol Michael , Lu Haibing
Published: January 2024

Introduction: The opioid overdose crisis in the United States has become a significant national emergency. Buprenorphine, a primary medication for individuals coping with opioid use disorder (OUD), presents promising pharmacokinetic properties for use in primary care settings, and is often delivered as a take-home therapy. The COVID-19 pandemic exacerbated the scarcity of access to buprenorphine, leading to dire consequences for those with OUD. Most existing studies, primarily focused on the immediate aftermath of the COVID-19 outbreak, highlight the challenges in accessing medications for opioid use disorder (MOUDs), particularly buprenorphine. However, these studies only cover a relatively short timeframe. Methods: To bridge this research gap, in our study, we utilized 33 months of California’s prescription drug monitoring program (PDMP) data to provide insights into real-world buprenorphine dispensing trends since the onset of the pandemic from 2018 to 2021, focusing on outcomes such as patient counts, prescription volumes, prescriber involvement, days’ supply, and dosage. Statistical analysis employed interrupted time series analysis to measure changes in trends before and during the pandemic. Results: We found no significant impact on patient counts or prescription volumes during the pandemic, although it impeded the upward trajectory of prescriber numbers that was evident prior to the onset of the pandemic. An immediate increase in days’ supply per prescription was observed post-pandemic. Conclusion: Our findings differ in comparison to previous data regarding the raw monthly count of patients and prescriptions. The analysis encompassed uninsured patients, offering a comprehensive perspective on buprenorphine prescribing in California. Our study’s insights contribute to understanding the impact of COVID-19 on buprenorphine access, emphasizing the need for policy adjustments.
Predicting the Length of Stay of Cardiac Patients Based on Pre-Operative Variables—Bayesian Models vs. Machine Learning Models
Authors: Abdurrab Ibrahim , Mahmood Tariq , Sheikh Sana , Aijaz Saba , Kashif Muhammad , Memon Ahson , Ali Imran , Peerwani Ghazal , Pathan Asad , Alkhodre Ahmad B. , Siddiqui Muhammad Shoaib
Published: January 2024

Length of stay (LoS) prediction is deemed important for a medical institution’s operational and logistical efficiency. Sound estimates of a patient’s stay increase clinical preparedness and reduce aberrations. Various statistical methods and techniques are used to quantify and predict the LoS of a patient based on pre-operative clinical features. This study evaluates and compares the results of Bayesian (simple Bayesian regression and hierarchical Bayesian regression) models and machine learning (ML) regression models against multiple evaluation metrics for the problem of LoS prediction of cardiac patients admitted to Tabba Heart Institute, Karachi, Pakistan (THI) between 2015 and 2020. In addition, the study also presents the use of hierarchical Bayesian regression to account for data variability and skewness without homogenizing the data (by removing outliers). LoS estimates from the hierarchical Bayesian regression model resulted in a root mean squared error (RMSE) and mean absolute error (MAE) of 1.49 and 1.16, respectively. Simple Bayesian regression (without hierarchy) achieved an RMSE and MAE of 3.36 and 2.05, respectively. The average RMSE and MAE of ML models remained at 3.36 and 1.98, respectively.
Physiological and Productivity Responses in Two Chili Pepper Morphotypes (Capsicum annuum L.) under Different Soil Moisture Contents
Authors: Pedroza-Sandoval Aurelio , Minjares-Fuentes José Rafael , Trejo-Calzada Ricardo , Gramillo-Avila Isaac
Published: January 2024

The aim of this study was to explore some physiological and productivity responses of two chili pepper morphotypes (Capsicum annum L.) exposed to different soil moisture contents. A randomized block design in a split-plot arrangement with four replicates was used. The large plots (32 m long and 3.2 m width) were 25% ± 2 as the optimum soil moisture content (OSMC), and 20% ± 2 as the suboptimum soil moisture content (SSMC); the small plots (16 m long and 3.2 m width) were two chili pepper morphotypes: Jalapeño and Chilaca, respectively. Jalapeño plants showed more stability in relative water content (RWC), photosynthetic activity (µmol CO2/m2/s), and a relatively low transpiration (mmol H2O/m2/s) and stomatal conductance (µmol H2O/m2/s); therefore, it had a higher number of flowers per plant and number of fruits per plant, consequently recording a high fruit production of 3.94 and 2.99 kg/m2 in OSMC and SSMC, respectively. In contrast, the Chilaca chili showed low stability in water relative content (WRC), photosynthesis, and transpiration, going from OSMC to SSMC, as well as showed a lower yield in SSMC; however, all of that was compensated by its size and weight of the fruit per plant, with a yield of 4.95 kg/m2 in OSMC. Therefore, the Jalapeño chili pepper could be an option when the irrigation water is limited, and the Chilaca chili pepper when this resource is not limited.
Fabricating Polymer/Surfactant/Cyclodextrin Hybrid Particles for Possible Nose-to-Brain Delivery of Ropinirole Hydrochloride: In Vitro and Ex Vivo Evaluation
Authors: Saitani Elmina-Marina , Pippa Natassa , Perinelli Diego Romano , Forys Aleksander , Papakyriakopoulou Paraskevi , Lagopati Nefeli , Bonacucina Giulia , Trzebicka Barbara , Gazouli Maria , Pispas Stergios , Valsami Georgia
Published: January 2024

Ropinirole is a non-ergolinic dopamine agonist used to manage Parkinson’s disease and it is characterized by poor oral bioavailability. This study aimed to design and develop advanced drug delivery systems composed of poloxamer 407, a non-ionic surfactant (Tween 80), and cyclodextrins (methyl-β-CD or hydroxy-propyl-β-CD) for possible brain targeting of ropinirole after nasal administration for the treatment of Parkinson’s disease. The hybrid systems were formed by the thin-film hydration method, followed by an extensive physicochemical and morphological characterization. The in vitro cytotoxicity of the systems on HEK293 cell lines was also tested. In vitro release and ex vivo mucosal permeation of ropinirole were assessed using Franz cells at 34 °C and with phosphate buffer solution at pH 5.6 in the donor compartment, simulating the conditions of the nasal cavity. The results indicated that the diffusion-controlled drug release exhibited a progressive increase throughout the experiment, while a proof-of-concept experiment on ex vivo permeation through rabbit nasal mucosa revealed a better performance of the prepared hybrid systems in comparison to ropinirole solution. The encouraging results in drug release and mucosal permeation indicate that these hybrid systems can serve as attractive platforms for effective and targeted nose-to-brain delivery of ropinirole with a possible application in Parkinson’s disease. Further ex vivo and in vivo studies to support the results of the present work are ongoing.
Gas Phase Transformations in Carbon-11 Chemistry
Authors: Lu Shuiyu , Telu Sanjay , Siméon Fabrice G. , Cai Lisheng , Pike Victor W.
Published: January 2024

The short-lived positron-emitter carbon-11 (t1/2 = 20.4 min; β+, 99.8%) is prominent for labeling tracers for use in biomedical research with positron emission tomography (PET). Carbon-11 is produced for this purpose with a cyclotron, nowadays almost exclusively by the 14N(p,α)11C nuclear reaction, either on nitrogen containing a low concentration of oxygen (0.1–0.5%) or hydrogen (~5%) to produce [11C]carbon dioxide or [11C]methane, respectively. These primary radioactive products can be produced in high yields and with high molar activities. However, only [11C]carbon dioxide has some utility for directly labeling PET tracers. Primary products are required to be converted rapidly and efficiently into secondary labeling synthons to provide versatile radiochemistry for labeling diverse tracer chemotypes at molecular positions of choice. This review surveys known gas phase transformations of carbon-11 and summarizes the important roles that many of these transformations now play for producing a broad range of labeling synthons in carbon-11 chemistry.
Salivary Biomarkers for Alzheimer’s Disease: A Systematic Review with Meta-Analysis
Authors: Nijakowski Kacper , Owecki Wojciech , Jankowski Jakub , Surdacka Anna
Published: January 2024

Alzheimer’s Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the noninvasive collection of saliva, we designed the systematic review to answer the question “Are salivary biomarkers reliable for the diagnosis of Alzheimer’s Disease?” Following the inclusion and exclusion criteria, 30 studies were included in this systematic review (according to the PRISMA statement guidelines). Potential biomarkers include mainly proteins, metabolites and even miRNAs. Based on meta-analysis, in AD patients, salivary levels of beta-amyloid42 and p-tau levels were significantly increased, and t-tau and lactoferrin were decreased at borderline statistical significance. However, according to pooled AUC, lactoferrin and beta-amyloid42 showed a significant predictive value for salivary-based AD diagnosis. In conclusion, potential markers such as beta-amyloid42, tau and lactoferrin can be detected in the saliva of AD patients, which could reliably support the early diagnosis of this neurodegenerative disease.
Oncolytic Virotherapy: A New Paradigm in Cancer Immunotherapy
Authors: Volovat Simona Ruxandra , Scripcariu Dragos Viorel , Vasilache Ingrid Andrada , Stolniceanu Cati Raluca , Volovat Constantin , Augustin Iolanda Georgiana , Volovat Cristian Constantin , Ostafe Madalina-Raluca , Andreea-Voichița Slevoacă-Grigore , Bejusca-Vieriu Toni , Lungulescu Cristian Virgil , Sur Daniel , Boboc Diana
Published: January 2024

Oncolytic viruses (OVs) are emerging as potential treatment options for cancer. Natural and genetically engineered viruses exhibit various antitumor mechanisms. OVs act by direct cytolysis, the potentiation of the immune system through antigen release, and the activation of inflammatory responses or indirectly by interference with different types of elements in the tumor microenvironment, modification of energy metabolism in tumor cells, and antiangiogenic action. The action of OVs is pleiotropic, and they show varied interactions with the host and tumor cells. An important impediment in oncolytic virotherapy is the journey of the virus into the tumor cells and the possibility of its binding to different biological and nonbiological vectors. OVs have been demonstrated to eliminate cancer cells that are resistant to standard treatments in many clinical trials for various cancers (melanoma, lung, and hepatic); however, there are several elements of resistance to the action of viruses per se. Therefore, it is necessary to evaluate the combination of OVs with other standard treatment modalities, such as chemotherapy, immunotherapy, targeted therapies, and cellular therapies, to increase the response rate. This review provides a comprehensive update on OVs, their use in oncolytic virotherapy, and the future prospects of this therapy alongside the standard therapies currently used in cancer treatment.
Reanalysis of Trio Whole-Genome Sequencing Data Doubles the Yield in Autism Spectrum Disorder: De Novo Variants Present in Half
Authors: Bar Omri , Vahey Elizabeth , Mintz Mark , Frye Richard E. , Boles Richard G.
Published: January 2024

Autism spectrum disorder (ASD) is a common condition with lifelong implications. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole-genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV), additionally, were present in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes (p = 0.0002), validating that most are indeed disease related. Sequence reanalysis increased diagnostic yield from 28% to 68%, mostly through inclusion of de novo PDVs in genes not yet reported as ASD associated. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate a high yield of trio-WGS for revealing molecular diagnoses in ASD, which is greatly enhanced by reanalyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.
Enhanced Stability and Improved Oral Absorption of Enzalutamide with Self-Nanoemulsifying Drug Delivery System
Authors: Lee Su-Min , Lee Jeong-Gyun , Yun Tae-Han , Cho Jung-Hyun , Kim Kyeong-Soo
Published: January 2024

The purpose of this study is to develop and evaluate a self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral absorption of poorly water-soluble enzalutamide (ENZ). Considering the rapid recrystallization of the drug, based on solubility and crystallization tests in various oils, surfactants and co-surfactants, Labrafac PG 10%, Solutol HS15 80%, and Transcutol P 10%, which showed the most stable particle size and polydispersity index (PDI) without drug precipitation, were selected as the optimal SNEDDS formulation. The optimized SNEDDS formulation showed excellent dissolution profiles for all the drugs released at 10 min of dissolution due to the increased surface area with a small particle size of approximately 16 nm. Additionally, it was confirmed to be stable without significant differences in physical and chemical properties for 6 months under accelerated conditions (40 ± 2 °C, 75 ± 5% RH) and stressed conditions (60 ± 2 °C). Associated with the high dissolutions of ENZ, pharmacokinetic parameters were also greatly improved. Specifically, the AUC was 1.9 times higher and the Cmax was 1.8 times higher than those of commercial products (Xtandi® soft capsule), resulting in improved oral absorption. Taken together with the results mentioned above, the SNEDDS could be an effective tool as a formulation for ENZ and other similar drugs.
Fluid Status Assessment in Critically Ill Patients with COVID-19: A Retrospective Cohort Study
Authors: Rodríguez-Moguel Nadia , Osuna-Padilla Ivan Armando , Piekarska Karolina Bozena , Negrete-García María-Fernanda , Hernández-Muñoz Andrea , Contreras-Marín Julián Andrés , Montaño-Mattar Roberto , Casas-Aparicio Gustavo
Published: January 2024

Fluid status (FS) is a diagnostic challenge in critically ill patients with COVID-19. Here, we compared parameters related to FS derived from cumulative fluid balance (CFB), bioelectrical impedance analysis (BIA) and venous congestion assessed by ultrasound (VExUS) to predict mortality. We retrospectively reviewed the medical records of individuals with severe pneumonia due to COVID-19 between July and November 2021 in a single center. Comorbidities, demographic, clinical and laboratory data as well as results from CFB, BIA and VExUS measurements were collected on admission and weekly afterwards for two consecutive evaluations. Seventy-nine patients were included, of which eighteen (14.2%) died. Abnormalities of FS were only identified by BIA. Extracellular water/total body water ratio (ECW/TBW) > 0.394 (overhydrated) by BIA was a good predictor of mortality (AUC = 0.78, 95% CI: 0.067–0.89). Mortality risk was higher in overhydrated patients (OR: 6.2, 95% CI: 1.2–32.6, p = 0.02) and in persistently overhydrated patients (OR: 9.57, 95% CI: 1.18–77.5, p = 0.03) even after adjustment to age, serum albumin and acute kidney injury (AKI) in stages 2–3. Time to death was shorter in overhydrated patients (HR: 2.82, 95% CI: 1.05–7.5, log-rank test p = 0.03). Abnormalities in FS associated with mortality were only identified by BIA in critically ill patients with COVID-19.
Deep Infiltrating Endometriosis in Adolescence: Early Diagnosis and Possible Prevention of Disease Progression
Authors: Martire Francesco Giuseppe , Giorgi Matteo , D’Abate Claudia , Colombi Irene , Ginetti Alessandro , Cannoni Alberto , Fedele Francesco , Exacoustos Caterina , Centini Gabriele , Zupi Errico , Lazzeri Lucia
Published: January 2024

Endometriosis has a prevalence of 10% worldwide in premenopausal women. Probably, endometriosis begins early in the life of young girls, and it is commonly diagnosed later in life. The prevalence of deep infiltrating endometriosis (DIE) in adolescence is currently unknown due to diagnostic limits and underestimation of clinical symptoms. Dysmenorrhea is a common symptom in adolescents affected by DIE, often accompanied by dyspareunia and chronic acyclic pelvic pain. Ultrasonography—either performed transabdominal, transvaginal or transrectal—should be considered the first-line imaging technique despite the potential for missed diagnosis due to early-stage disease. Magnetic resonance imaging should be preferred in the case of virgo patients or when ultrasonographic exam is not accepted. Diagnostic laparoscopy is deemed acceptable in the case of suspected DIE not responding to conventional hormonal therapy. An early medical and/or surgical treatment may reduce disease progression with an immediate improvement in quality of life and fertility, but at the same time, painful symptoms may persist or even recur due to the surgery itself. The aim of this narrative review is to report the prevalence of DIE in adolescents, describe the pathogenetic theories and discuss the management in adolescent women, including the challenging road to diagnosis and the treatment alternatives.
Fusiform versus Saccular Intracranial Aneurysms—Hemodynamic Evaluation of the Pre-Aneurysmal, Pathological, and Post-Interventional State
Authors: Korte Jana , Marsh Laurel M. M. , Saalfeld Sylvia , Behme Daniel , Aliseda Alberto , Berg Philipp
Published: January 2024

Minimally-invasive therapies are well-established treatment methods for saccular intracranial aneurysms (SIAs). Knowledge concerning fusiform IAs (FIAs) is low, due to their wide and alternating lumen and their infrequent occurrence. However, FIAs carry risks like ischemia and thus require further in-depth investigation. Six patient-specific IAs, comprising three position-identical FIAs and SIAs, with the FIAs showing a non-typical FIA shape, were compared, respectively. For each model, a healthy counterpart and a treated version with a flow diverting stent were created. Eighteen time-dependent simulations were performed to analyze morphological and hemodynamic parameters focusing on the treatment effect (TE). The stent expansion is higher for FIAs than SIAs. For FIAs, the reduction in vorticity is higher (Δ35–75% case 2/3) and the reduction in the oscillatory velocity index is lower (Δ15–68% case 2/3). Velocity is reduced equally for FIAs and SIAs with a TE of 37–60% in FIAs and of 41–72% in SIAs. Time-averaged wall shear stress (TAWSS) is less reduced within FIAs than SIAs (Δ30–105%). Within this study, the positive TE of FDS deployed in FIAs is shown and a similarity in parameters found due to the non-typical FIA shape. Despite the higher stent expansion, velocity and vorticity are equally reduced compared to identically located SIAs.
Images, Words, and Imagination: Accessible Descriptions to Support Blind and Low Vision Art Exploration and Engagement
Authors: Doore Stacy A. , Istrati David , Xu Chenchang , Qiu Yixuan , Sarrazin Anais , Giudice Nicholas A.
Published: January 2024

The lack of accessible information conveyed by descriptions of art images presents significant barriers for people with blindness and low vision (BLV) to engage with visual artwork. Most museums are not able to easily provide accessible image descriptions for BLV visitors to build a mental representation of artwork due to vastness of collections, limitations of curator training, and current measures for what constitutes effective automated captions. This paper reports on the results of two studies investigating the types of information that should be included to provide high-quality accessible artwork descriptions based on input from BLV description evaluators. We report on: (1) a qualitative study asking BLV participants for their preferences for layered description characteristics; and (2) an evaluation of several current models for image captioning as applied to an artwork image dataset. We then provide recommendations for researchers working on accessible image captioning and museum engagement applications through a focus on spatial information access strategies.
Fucanases Related to the GH107 Family from Members of the PVC Superphylum
Authors: Gonzalez Jessica A. , Ponce Nora M. A. , Lozada Mariana , Daglio Yasmín , Stortz Carlos A. , Dionisi Hebe M.
Published: January 2024

The glycoside hydrolase 107 (GH107) family includes fucanase enzymes from only two bacterial phyla, Bacteroidota and Pseudomonadota. The goal of this work was to explore the diversity of putative fucanase enzymes related to this family in organisms of the PVC superphylum (Planctomycetota, Verrucomicrobiota, Chlamydiota), in order to expand our knowledge of the fucoidan-degrading potential in this ecologically and biotechnologically relevant group. Using hidden Markov model- and peptide-based annotation tools, 26 GH107 homolog sequences were identified in metagenome and genome datasets. The sequences formed two distinct clusters in a phylogenetic analysis, only one including members of the GH107 family. The endo-acting fucoidan degrading activity was confirmed in an enzyme included in the most divergent cluster. The fucanase, which probably originated in an uncultured planctomycete from the sampled subantarctic sediments, was cloned and expressed in Escherichia coli. The enzyme catalyzed the rapid hydrolysis of internal glycosidic bonds of fucoidan from Macrocystis pyrifera, a macroalgae species abundant at the site. It was active in a wide range of temperatures (5–45 °C), salinities (9.5–861 mM NaCl), and pH values (4.5–9), mainly producing sulfated α-(1,3)-linked fuco-oligosaccharides of various lengths. The PVC superphylum represents a promising source of fucanase enzymes with various biotechnological applications.
Neurocutaneous Melanosis with Meningeal Melanocytosis: A Rare Case of Intracranial Hypertension and Cutaneous Manifestations
Authors: Chen Hsien-Chung , Hsu Tsung-I , Chao Tsu-Yi , Yang Shun-Tai
Published: January 2024

A 50-year-old male presented to the emergency room after experiencing sudden right upper limb facial numbness and dysphasia, followed by full recovery. A brain CT scan showed hyperdense lesions within the left hemispheric sulcus, which raised suspicion of spontaneous subarachnoid hemorrhage. A T1-weighted MRI showed multiple tiny leptomeningeal enhancements in the same area, and a digital subtraction angiography showed no signs of vascular abnormality. Cerebrospinal fluid cytology revealed atypical melanin-containing cells with minimal pleomorphism. One month later, the patient developed sixth nerve palsy, which was determined to be due to intracranial hypertension. Multiple giant nevi on the legs, trunk, and scalp were also observed. A skin biopsy showed well-defined and symmetrical proliferation of melanocytic nevus cell nests in the dermis. An open biopsy was performed due to the suspicious leptomeningeal lesions, which surprisingly revealed diffuse and thick black-colored tissue infiltration of the leptomeninges. Pathology confirmed the diagnosis of meningeal melanocytosis. A ventriculoperitoneal shunt was then placed, and the patient’s neurological symptoms gradually improved. Based on the presence of multiple giant nevi on the patient’s skin and the finding of diffuse meningeal melanocytosis during the open biopsy, the patient was diagnosed with neurocutaneous melanosis. The patient received 6 cycles triweekly of Ipilimumab and Nivolumab 8 months after initial diagnosis. Unfortunately, the disease progressed and the patient passed away 14 months after initial diagnosis.
Riemann Integral on Fractal Structures
Authors: Gálvez-Rodríguez José Fulgencio , Martín-Aguado Cristina , Sánchez-Granero Miguel Ángel
Published: January 2024

In this work we start developing a Riemann-type integration theory on spaces which are equipped with a fractal structure. These topological structures have a recursive nature, which allows us to guarantee a good approximation to the true value of a certain integral with respect to some measure defined on the Borel σ-algebra of the space. We give the notion of Darboux sums and lower and upper Riemann integrals of a bounded function when given a measure and a fractal structure. Furthermore, we give the notion of a Riemann-integrable function in this context and prove that each μ-measurable function is Riemann-integrable with respect to μ. Moreover, if μ is the Lebesgue measure, then the Lebesgue integral on a bounded set of Rn meets the Riemann integral with respect to the Lebesgue measure in the context of measures and fractal structures. Finally, we give some examples showing that we can calculate improper integrals and integrals on fractal sets.
The Heteromorphic Approach to Adjunctions: Theory and History
Authors: Ellerman David
Published: January 2024

Mallios and Zafiris emphasize that adjoint functors, or adjunctions, are not only “ubiquitous” in category theory but also characterize the naturality of their approach to physical geometry. Hence, in this paper, the history and theory of adjoint functors is investigated. Where do adjoint functors come from mathematically, and how did the concept develop historically?
Observer-Based Adaptive Fuzzy Quantized Control for Fractional-Order Nonlinear Time-Delay Systems with Unknown Control Gains
Authors: Dong Yuwen , Song Shuai , Song Xiaona , Tejado Inés
Published: January 2024

This paper investigates the observer-based adaptive fuzzy quantized control problem for a class of fractional-order nonlinear time-delay systems with unknown control gains based on a modified fractional-order dynamic surface control (FODSC) technique and an indirect Lyapunov method. First, a fractional-order, high-gain state observer is constructed to estimate unavailable state information. Furthermore, the Nussbaum gain technique and a fractional-order filter are adopted to cope with the problem of unknown control gains and to reduce the computational complexity of the conventional recursive procedure, respectively. Moreover, through integration with the compensation mechanism and estimation model, the adaptive fuzzy quantized controllers and adaptive laws are designed to ensure that all the signals of the closed-loop system are bounded. In the end, the proposed controller is applied to a numerical example and a single-machine-infinite bus (SMIB) power system; the simulation results show the validity, superiority, and application potential of the developed control strategy.
Nine-Stage Runge–Kutta–Nyström Pairs Sharing Orders Eight and Six
Authors: Alharbi Hadeel , Yadav Kusum , Ramadan Rabie A. , Jerbi Houssem , Simos Theodore E. , Tsitouras Charalampos
Published: January 2024

We explore second-order systems of non-stiff initial-value problems (IVPs), particularly those cases where the first derivatives are absent. These types of problems are of significant interest and have applications in various domains, such as astronomy and physics. Runge–Kutta–Nyström (RKN) pairs stand out as highly effective methods of addressing these IVPs. In order to create a pair with eighth and sixth orders, we need to address a certain known set of equations concerning the coefficients. When constructing such pairs for use in double-precision arithmetic, we often need to meet various conditions. Primarily, we aim to maintain small coefficient magnitudes to prevent a loss of accuracy. Nevertheless, in the context of quadruple precision, we can tolerate larger coefficients. This flexibility enables us to establish pairs with eighth and sixth orders that exhibit significantly reduced truncation errors. Traditionally, these pairs are constructed to go through eight stages per step. Here, we propose using nine stages per step. Then we have available more coefficients in order to further reduce truncation errors. As a result, we construct a novel pair that, as anticipated, achieves superior performance compared to equivalent-order pairs in various significant problem scenarios.