bluuebunny/crossref_metadata_2025 huggingface dataset:
PrecivityAD2™ Blood Test: Analytical Validation of an LC-MS/MS Assay for Quantifying Plasma Phospho-tau217 and Non-Phospho-tau217 Peptide Concentrations That Are Used with Plasma Amyloid-β42/40 in a Multianalyte Assay with Algorithmic Analysis for Detecting Brain Amyloid Pathology
Authors: Eastwood Stephanie M. , Meyer Matthew R. , Kirmess Kristopher M. , Wente-Roth Traci L. , Irvin Faith , Holubasch Mary S. , Verghese Philip B. , West Tim , Braunstein Joel B. , Yarasheski Kevin E. , Contois John H.
Published: August 2024

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography–tandem mass spectrometry (LC-MS/MS) multiplex method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS multiplex assay for plasma Aβ42/40 into a new multianalyte assay with algorithmic analysis (MAAA; PrecivityAD2™ test) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found (a) the %p-tau217 assay is precise, accurate, sensitive, and linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage, and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or from negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.
Comparing Clinicopathological and Immunohistochemical Features of Colorectal Carcinoma between Young and Old Age Groups
Authors: Awad Heyam , Elshebli Sanad , Hasan Khaled , Eid Yousef , Obeidat Fatima , Alzyoud Mohammad , Alakhras Basheer , AlShammas Faris
Published: August 2024

The incidence of colorectal carcinoma (CRC) is increasing among individuals younger than 50, and some studies suggest the presence of differences in CRC among old and young individuals regarding clinical and histopathological features. The aim of this study was to compare clinicopathological features, mismatch repair protein status, and expression of certain immunohistochemical stains between young and old groups. The study included 180 cases and found significant histological and immunohistochemical differences between the two groups. CRC in the young tends to be more right-sided and has a higher percentage of dMMR proteins, but less expression of p53 mutations. These features are commoner in Lynch syndrome, and more investigations to study the relationship between young-onset CRC and hereditary syndromes are needed. Young-onset CRC also tends to show higher expression of tumor cell PD-L1, which is an expected finding, as dMMR cases are more likely to be immunogenic. Two other significant differences are the higher percentage of mucinous carcinoma and the higher tumor grade in young-onset CRC. These two features suggest a more advanced disease with possibly worse outcomes; however, there is no difference in disease stage between the two age groups.
Pain from Internal Organs and Headache: The Challenge of Comorbidity
Authors: Affaitati Giannapia , Costantini Raffaele , Fiordaliso Michele , Giamberardino Maria Adele , Tana Claudio
Published: August 2024

Headache and visceral pain are common clinical painful conditions, which often co-exist in the same patients. Numbers relative to their co-occurrence suggest possible common pathophysiological mechanisms. The aim of the present narrative review is to describe the most frequent headache and visceral pain associations and to discuss the possible underlying mechanisms of the associations and their diagnostic and therapeutic implications based on the most recent evidence from the international literature. The conditions addressed are as follows: visceral pain from the cardiovascular, gastrointestinal, and urogenital areas and primary headache conditions such as migraine and tension-type headache. The most frequent comorbidities involve the following: cardiac ischemic pain and migraine (possible shared mechanism of endothelial dysfunction, oxidative stress, and genetic and hormonal factors), functional gastrointestinal disorders, particularly IBS and both migraine and tension-type headache, primary or secondary dysmenorrhea and migraine, and painful bladder syndrome and headache (possible shared mechanisms of peripheral and central sensitization processes). The data also show that the various visceral pain–headache associations are characterized by more than a simple sum of symptoms from each condition but often involve complex interactions with the frequent enhancement of symptoms from both, which is crucial for diagnostic and treatment purposes.
Germplasm Resource Status and Seed Adaptability of Nypa fruticans Wurmb, an Endangered Species in China
Authors: Zhang Mengwen , Zhong Cairong , Lv Xiaobo , Fang Zanshan , Cheng Cheng , Hao Jiewei
Published: August 2024

Nypa fruticans, commonly known as the Nipa palm, belongs to the true mangrove plants of the Arecaceae family. In China, it is naturally distributed only on Hainan Island and designated as a second-class National Key Protected Wild Plants List. Field research and indoor simulation experiments were systematically employed to study the resource status of N. fruticans and the adaptation of seed germination to environmental factors. The results showed that: (1) Four natural populations of N. fruticans, approximately 9319 trees within a total area of 3.96 hm2, were distributed in Haikou, Wenchang, Qionghai, and Wanning on Hainan Island. Only the Wanning population was developed in small patches, while other populations were scattered sporadically. (2) A total of 23 mangrove species belonged to 19 genera in 13 families, which were recorded in all study sites, of which 18 were true mangroves and 5 were semi-mangrove species. The vertical structures of 4 N. fruticans communities exhibited the consistent pattern, characterized by distinct layers including the tree, shrub, and herb layers. However, notable differences in species composition and dominant species were observed among the layers of each community. (3) The population dynamics of N. fruticans in Haikou, Qionghai, and Wanning were declining, while the population in Wenchang was growing. (4) Seed germination of N. fruticans was not resistant to strong light and required some shade treatment with an optimal light intensity of 60%. The suitable salinity range for seed germination was 0‰ to 10‰. With the increase of salinity, the germination rate and seedling rate showed an increasing and then decreasing trend with maximum values of 63.3% and 50.0% at 5‰, which showed the sensitivity of seed germination to salinity, with low salinity promoting germination whereas high salinity inhibiting germination. Around 8 h/d of flooding time was most suitable for the seed germination, and 10 h/d was a critical flooding time. This study provides a theoretical basis for population recovery, resource utilization, and other further research of N. fruticans.
Effect of Polyethylene Glycol with Different Molecular Weights on the Properties of Mytilaria laosensis Timber
Authors: He Linhan , Liu Xiaoling , Kuang Yin , Wang Liuliu , Chen Songwu , Luo Yufen , Chen Yao
Published: August 2024

Mytilaria laosensis, a common fast-growing tree species in southern China, boasts excellent growth speed and attractive color and texture. However, due to its short growth cycle and high proportion of juvenile wood, it typically exhibits poor dimensional stability and low strength, which significantly limits its practical applications. This study uses vacuum impregnation to modify M. laosensis wood with polyethylene glycol (PEG), focusing on the effects and mechanisms of PEG with different molecular weights on wood properties. The results indicate that PEG enters the wood cell walls through capillary action and diffusion, forming hydrogen bonds with the free hydroxyl groups on cellulose and hemicellulose, which keeps the cell walls swollen and enhances dimensional stability. Post modification, the dimensional stability of M. laosensis wood improved, with an anti-swelling efficiency ranging from 61.43% to 71.22%, showing an initial increase followed by a decrease with increasing PEG molecular weight. The optimal PEG molecular weight for anti-swelling efficiency was 1500 Da, achieving 71.22%. The flexural modulus of elasticity and flexural strength of the treated wood also first decreased and then increased with increasing PEG molecular weight. Among them, the PEG1000-treated material showed the best performance, with the flexural modulus of elasticity increased by about 29% and the flexural strength increased by about 5% compared to untreated wood. Additionally, PEG, having a higher pyrolysis temperature than wood, raised the initial pyrolysis temperature and maximum pyrolysis rate temperature of M. laosensis wood, thus improving its thermal stability. These findings provide scientific evidence and technical support for the efficient utilization and industrialization of M. laosensis wood, promoting its widespread application and industrial development.
Can CSR Strategy Classes Determined by StrateFy Explain the Species Dominance and Diversity of a Forest Community?
Authors: Peng Ye , Cui Gansha , Li Hengyi , Wang Ningjie , Zheng Xiao , Ding Hui , Lv Ting , Fang Yanming
Published: August 2024

Plant ecological strategies are essential for assessing habitat stress and disturbance and evaluating community productivity. These strategies provide theoretical frameworks for maintaining the natural state of vegetation and enhancing productivity. The functional traits of leaves reflect a plant’s responses to environmental changes and contribute to understanding ecosystem stability, providing a basis for species diversity maintenance and effective conservation efforts. The Wuyishan National Park, a biodiversity hotspot in China, is a focal point for ecological research. Its evergreen, broad-leaved forest, the zonal vegetation of Mt. Wuyi, underpins plant diversity protection in the region. This study investigates the CSR (competitor, stress-tolerator, ruderal) strategy of 126 species on Wuyi Mountain to elucidate prevalent ecological strategies. The main ecological strategy of plants in the study area is the CS (competitor, stress-tolerator) strategy. The species exhibit nine categories. The most abundant ecological strategy is S/CS (plants from Fagaceae), accounting for 38%, followed by S/CSR at 23% (plants from Theaceae), CS at 20% (plants from Fagaceae and Theaceae), and the remaining strategies collectively at 19%. The different growth habit categories showed variations in the CSR strategies. The trees clustered around a CS median strategy, with no R-selected trees observed. Shrubs and lianas centered around an S/CSR strategy, while grasses and understory shrubs clustered around CS/CSR. Redundancy analysis results indicate that leaf functional traits are primarily influenced by temperature, suggesting that temperature is the key environmental factor driving the differentiation of plant functional traits. This study provides insights into the ecological strategies of plant species in the Mt. Wuyi region, highlighting the importance of considering both biotic and abiotic factors in maintaining biodiversity and ecosystem stability.
Thermal Treatment and Fermentation of Legume Flours with Leuconostoc citreum TR116 for the Development of Spreadable Meat Alternatives
Authors: Sahin Aylin W. , Gautheron Ophélie , Galle Sandra
Published: August 2024

The demand for meat alternatives in different forms is increasing due to consumers’ awareness of climate change and the health benefits of plant-based ingredients compared to animals. However, current alternatives on the market do not fulfil consumers’ acceptance for taste and texture. Hence, different physical and biological processes, such as thermal treatment and fermentation, need to be investigated. This study reveals that the thermal treatment of legume flours (soy, pea and lentil) prior to single-strain fermentation with Leuconostoc citreum TR116 has a major impact on acidification, colour, texture and sensory properties due to the pregelatinisation of starch and denaturation of proteins. The thermal treatment of soy flour resulted in liquification, and it could not be used as a fermentation substrate. However, non-heat-treated soy flour was fermented for comparison. The highest total titratable acidity (TTA) was determined in fermented pea flour (PF) and fermented lentil flour (LF) after 48 h with 24.35 ± 0.29 mL 0.1 M NaOH/10 g and 24.98 ± 0.33 mL 0.1 M NaOH/10 g, respectively. Heat treatment prior to fermentation led to a reduction in TTA by 20 mL 0.1 M NaOH/10 g for both PF and LF. The loss of colour pigments during thermal treatment led to a lighter colour of the spreadable alternatives. Moreover, a harder texture (+13.76 N in LF; +15.13 N in PF) and a lower adhesiveness (−0.88 N in LF; −0.43 N in PF) were detected in spreadable meat alternatives that were treated with heat prior to fermentation. Cohesiveness was decreased by thermal treatment, and fermentation did not impact it. Fermentation without pre-heat treatment increased adhesiveness by 4.37 N in LF and by 2.36 N in PF—an attribute typical for spreadable meat. Descriptive sensory analysis showed that thermal treatment significantly decreased bitterness but increased crumbliness and reduced juiciness. On the other hand, fermentation without pre-heat treatment mainly influenced flavour by increasing fruitiness and decreasing beaniness, earthiness and off-flavours. In summary, thermal treatment prior to fermentation is powerful in reducing legume-typical off-flavours but is not suitable for the development of spreadable meat alternatives due to texture changes. However, this process can be very beneficial when producing sausage-like alternatives.
Optimizing the Extraction of Protein from Defatted Schizochytrium Cell Residues and Studying the Emulsification Characteristics of Protein
Authors: Yang Yingying , Zhao Xiangying , Liu Liping , Wang Xinyu , Li Ruiguo , Zhang Jiaxiang
Published: August 2024

In this study, proteins were prepared from Schizochytrium pombe residue after oil extraction using isoelectric point precipitation, and their physicochemical and emulsifying properties were investigated. Our objective was to assess the suitability of these proteins for functional ingredient applications. Through a one-way experiment and optimization using response surface design, the effects of time, temperature, pH, and the material–liquid ratio of NaOH alkaline extraction were explored. The isoelectric point is verified by isoelectric point precipitation; the results revealed that crude protein from Schizochytrium (SCP) is minimally soluble at pH 4.2. Compared with whey protein (WP), it promotes better emulsion stability through the emulsification test. This study suggests that Schizochytrium oil-processing byproducts represent a promising source of protein, with potential applications as functional ingredients, offering implications for the usage of these byproducts in various industries.
Impact of Navier’s Slip and MHD on a Hybrid Nanofluid Flow over a Porous Stretching/Shrinking Sheet with Heat Transfer
Authors: Maranna Thippaiah , Sachin Gadhigeppa Myacher , Mahabaleshwar Ulavathi Shettar , Pérez Laura M. , Shevchuk Igor V.
Published: August 2024

The main objective of this study is to explore the inventive conception of the magnetohydrodynamic flow of a hybrid nanofluid over-porous stretching/shrinking sheet with the effect of radiation and mass suction/injection. The hybrid nanofluid advances both the manufactured nanofluid of the current region and the base fluid. For the current investigation, hybrid nanofluids comprising two different kinds of nanoparticles, aluminium oxide and ferrofluid, contained in water as a base fluid, are considered. A collection of highly nonlinear partial differential equations is used to model the whole physical problem. These equations are then transformed into highly nonlinear ordinary differential equations using an appropriate similarity technique. The transformed differential equations are nonlinear, and thus it is difficult to analytically solve considering temperature increases. Then, the outcome is described in incomplete gamma function form. The considered physical parameters namely, magnetic field, Inverse Darcy number, velocity slip, suction/injection, temperature jump effects on velocity, temperature, skin friction and Nusselt number profiles are reviewed using plots. The results reveal that magnetic field, and Inverse Darcy number values increase as the momentum boundary layer decreases. Moreover, higher values of heat sources and thermal radiation enhance the thermal boundary layer. The present problem has various applications in manufacturing and technological devices such as cooling systems, condensers, microelectronics, digital cooling, car radiators, nuclear power stations, nano-drag shipments, automobile production, and tumour treatments.
Sunflower Meal Valorization through Enzyme-Aided Fractionation and the Production of Emerging Prebiotics
Authors: Simović Milica , Banjanac Katarina , Veljković Milica , Nikolić Valentina , López-Revenga Paula , Montilla Antonia , Moreno Francisco Javier , Bezbradica Dejan
Published: August 2024

Recently, there has been a burgeoning interest in harnessing the potential of biomass and industry byproducts for the development of novel products and materials. In particular, this study explored the efficient valorization of sunflower meal (SFM), an underutilized byproduct of the oil extraction industry, usually discarded or used as low-value animal feed through enzyme-aided fractionation, specifically targeting the extraction and conversion of its abundant carbohydrate component, xylan, into emerging prebiotic compounds—xylo-oligosaccharides (XOSs)—which are recognized as promotors of a healthy gut microbiome and overall human wellbeing. An enzymatic treatment using Alcalase® 2.4 L was implemented for facilitating the recovery of a highly pure hemicellulosic fraction (92.2% carbohydrates) rich in β-(1→4)-linked xylose residues with arabinose and glucuronic acid substitutions (DP-xylan). A further enzymatic treatment of this substrate, using ROHALASE® SEP-VISCO under optimized conditions (70 °C, pH 6, 0.005% v/v enzyme concentration), produced 52.3% of XOSs with a polymerization degree (DP) less than 20 after two hours. Further analyses demonstrated that the majority of the obtained product had a DP less than 6, predominantly consisting of di- and trisaccharides (XOS2 and XOS3) without the significant generation of xylose. These findings highlight the significant potential of SFM for the generation of valuable prebiotic compounds in a sustainable manner.
Clusters of Sociodemographic Characteristics and Their Association with Food Insecurity in Mexican University Students
Authors: Nava-Amante Pablo Alejandro , Betancourt-Núñez Alejandra , Díaz-López Andrés , Bernal-Orozco María Fernanda , De la Cruz-Mosso Ulises , Márquez-Sandoval Fabiola , Vizmanos Barbara
Published: August 2024

Food insecurity (FI) expresses irregular access to sufficient, safe, and nutritious food. We analyze the association between clusters of sociodemographic characteristics and FI in university students from Mexico. The Latin American and Caribbean Food Security Scale was applied, and household type, socioeconomic status (SES), and the characteristics of the head of the household, among others, were asked in a cross-sectional study. We performed Two-Step cluster analysis and logistic regression models. We included 466 university students (72.5% women, 47% with FI). We identified three clusters; Cluster-1 (n = 163) included a single-parent (37.4%) or co-resident/roommate (27%) household type, middle SES (63.2%); the head of the household is usually a woman (76.1%), single (71.8%), and with bachelor’s degree (41.7%) or less educational level (46.6%). Cluster-2 (n = 144) included the nuclear (89.6%) household type, high SES (76.4%); the head of the household is usually a man (79.2%), in a relationship (99.3%), and with a bachelor’s degree (63.2%) or graduate level (33.3%). Cluster-3 (n = 147) is very similar to Cluster-2. The difference is that Cluster-3 includes middle SES (70.1%), and the head of the household’s educational level is high school or less (100%). Only belonging to Cluster-1 was positively associated with FI (OR = 1.96, 95%CI: 1.24, 3.09). These results show the interrelationships between multiple sociodemographic characteristics and should contribute to developing interventions that simultaneously address numerous sociodemographic factors to diminish FI in university students.
Beyond the Classroom: The Influence of Food Insecurity, Mental Health, and Sleep Quality on University Students’ Academic Performance
Authors: Betancourt-Núñez Alejandra , Díaz Rosa , Nava-Amante Pablo Alejandro , Bernal-Orozco María Fernanda , Díaz-López Andrés , González Palacios Aaron , Márquez-Sandoval Fabiola , Velarde-Camaqui Davis , Vizmanos Barbara
Published: August 2024

We aimed to analyze the association between food insecurity (FI) and academic performance in university students, including mental health and sleep quality (SQ), in an association model. A cross-sectional design included university students (n = 466, 72.5% women) from Mexico. We applied the Latin American and Caribbean Food Security Scale, the Depression Anxiety and Stress Scale (DASS-21), and the Pittsburgh Sleep Quality Index. Students self-reported their academic grading (AG) and perceptions about their academic performance. Spearman’s rho and multiple logistic regression models were used. Almost half (47%) experienced some level of FI. The median AG was 95. AG was not significantly (p > 0.05) correlated with FI, nor with depression, anxiety, stress, and SQ. Considering mental health and SQ, moderate/severe FI remained significantly associated with perceived overall progress in college (OR: 2.96; 95%CI: 1.49, 5.88) and attendance to classes (OR:3.14; 95%CI: 1.19, 8.28) as poor or regular, and it was positively related to perceiving difficulties in completing their studies (OR:2.75; 95%CI: 1.43, 5.29). Stress, anxiety, depression symptoms, and poor SQ were also significantly associated with poor/regular perception of academic performance. These findings highlight the need to address psychological and nutritional factors in university students to promote their well-being and academic success.
Extraction and Chromatographic Approaches for Coumarin, Furocoumarin, and Polymethoxyflavone Characterization in Foods
Authors: Cafeo Giovanna , Irrera Elisa , Russo Marina , Dugo Paola
Published: August 2024

Oxygen heterocyclic compounds play a beneficial role in plants, and their presence in foods, such as Citrus fruits, cinnamon, carrots, and parsley, has been documented in recent years. Published research articles reported several extractions and chromatographic techniques for their determination. The aim of this review was to take into consideration the research articles published from 2016 to 2024 in which the authors developed extraction and chromatographic analysis methods of oxygen heterocyclic compounds in foods. The objective of this review was to assist researchers in choosing the best approach for their future work by identifying all the possible approaches to characterize coumarins, furocoumarins, and polymethoxyflavones in foodstuffs.
Utilization of Infrared Drying as Alternative to Spray- and Freeze-Drying for Low Energy Consumption in the Production of Powdered Gelatin
Authors: Cansu Ümran
Published: August 2024

This study evaluated possible utilization of infrared drying (ID) as an alternative to spray- (SD) and freeze-drying (FD) for fish skin-derived gelatins. Physical, functional, thermal, and spectroscopic analyses were conducted for characterization of the resulting gelatin powders. Energy consumption for the applied drying methods were 3.41, 8.46 and 25.33 kWh/kg for ID, SD and FD respectively, indicating that ID had the lowest energy consumption among the studied methods. Gel strength, on the other hand, was lower (398.4 g) in infrared-dried gelatin (ID-FG) compared to that (454.9 g) of freeze-dried gelatin (FD-FG) and that (472.7 g) of spray-dried gelatin (SD-FG). TGA curves indicated that ID-FG showed more resilience to thermal degradation. SDS-PAGE and UV-Vis spectra indicated that slight degradation was observed in the β-configuration of ID-FG. ID-FG and SD-FG gelatins had the highest water holding capacity (WHC), protein solubility and transparency values compared to that of FD-FG. Morphological structures of the samples were quite different as shown by SEM visuals. Ultimately, the findings showed that infrared drying may be a promising alternative for gelatin processing, maintaining product quality and supporting sustainable practices in food and other industries.
Viscoelastic Reversibility of Carrageenan Hydrogels under Large Amplitude Oscillatory Shear: Hybrid Carrageenans versus Blends
Authors: Moraes Izabel Cristina Freitas , Hilliou Loic
Published: August 2024

The viscoelastic response of carrageenan hydrogels to large amplitude oscillatory shear (LAOS) has not received much attention in the literature in spite of its relevance in industrial application. A set of hybrid carrageenans with differing chemical compositions are gelled in the presence of KCl or NaCl, and their nonlinear viscoelastic responses are systematically compared with mixtures of kappa- and iota-carrageenans of equivalent kappa-carrageenan contents. Two categories of LAOS response are identified: strain softening and strain hardening gels. Strain softening gels show LAOS non-reversibility: when entering the nonlinear viscoelastic regime, the shear storage modulus G′ decreases with increasing strain, and never recovers its linear value G0 after successive LAOS sweeps. In contrast to this, strain hardening carrageenan gels show a certain amount of LAOS reversibility: when entering the nonlinear regime, G′ increases with strain and shows a maximum at strain γH. For strains applied below γH, G0 shows good reversibility and the strain hardening behavior is maintained. For strains larger than γH, G0 decreases significantly indicating an irreversible structural change in the elastic network. Strain hardening and elastic recovery after LAOS prevail for hybrid carrageenan and iota-carrageenan gels, but are only achieved when blends are gelled in NaCl, suggesting a phase separated structure with a certain degree of co-aggregated interface for mixed gels.
Plant-Based Nanovesicular Gel Formulations Applied to Skin for Ameliorating the Anti-Inflammatory Efficiency
Authors: Atia Hanan Abdelmawgoud , Shahien Mona M. , Ibrahim Somaia , Ahmed Enas Haridy , Elariny Hemat A. , Abdallah Marwa H.
Published: August 2024

Inflammation is a vascular response that occurs when the immune system responds to a range of stimuli including viruses, allergens, damaged cells, and toxic substances. Inflammation is accompanied by redness, heat, swelling, discomfort, and loss of function. Natural products have been shown to have considerable therapeutic benefits, and they are increasingly being regarded as feasible alternatives for clinical preventative, diagnostic, and treatment techniques. Natural products, in contrast to developed medications, not only contain a wide variety of structures, they also display a wide range of biological activities against a variety of disease states and molecular targets. This makes natural products appealing for development in the field of medicine. In spite of the progress that has been made in the application of natural products for clinical reasons, there are still factors that prevent them from reaching their full potential, including poor solubility and stability, as well limited efficacy and bioavailability. In order to address these problems, transdermal nanovesicular gel systems have emerged as a viable way to overcome the hurdles that are encountered in the therapeutic use of natural products. These systems have a number of significant advantages, including the ability to provide sustained and controlled release, a large specific surface area, improved solubility, stability, increased targeting capabilities and therapeutic effectiveness. Further data confirming the efficacy and safety of nanovesicles–gel systems in delivering natural products in preclinical models has been supplied by extensive investigations conducted both in vitro and in vivo. This study provides a summary of previous research as well as the development of novel nanovesicular gel formulations and their application through the skin with a particular emphasis on natural products used for treatment of inflammation.
Elastin-Derived Peptide-Based Hydrogels as a Potential Drug Delivery System
Authors: Al Musaimi Othman , Ng Keng Wooi , Gavva Varshitha , Mercado-Valenzo Oscar M. , Haroon Hajira Banu , Williams Daryl R.
Published: August 2024

A peptide-based hydrogel sequence was computationally predicted from the Ala-rich cross-linked domains of elastin. Three candidate peptides were subsequently synthesised and characterised as potential drug delivery vehicles. The elastin-derived peptides are Fmoc-FFAAAAKAA-NH2, Fmoc-FFAAAKAA-NH2, and Fmoc-FFAAAKAAA-NH2. All three peptide sequences were able to self-assemble into nanofibers. However, only the first two could form hydrogels, which are preferred as delivery systems compared to solutions. Both of these peptides also exhibited favourable nanofiber lengths of at least 1.86 and 4.57 µm, respectively, which are beneficial for the successful delivery and stability of drugs. The shorter fibre lengths of the third peptide (maximum 0.649 µm) could have inhibited their self-assembly into the three-dimensional networks crucial to hydrogel formation.
Analyzing Runs of Homozygosity Reveals Patterns of Selection in German Brown Cattle
Authors: Wirth Anna , Duda Jürgen , Emmerling Reiner , Götz Kay-Uwe , Birkenmaier Franz , Distl Ottmar
Published: August 2024

An increasing trend in ancestral and classical inbreeding coefficients as well as inbreeding depression for longevity were found in the German Brown population. In addition, the proportion of US Brown Swiss genes is steadily increasing in German Browns. Therefore, the aim of the present study was to analyze the presence and genomic localization of runs of homozygosity (ROH) in order to evaluate their associations with the proportion of US Brown Swiss genes and survival rates of cows to higher lactations. Genotype data were sampled in 2364 German Browns from 258 herds. The final data set included 49,693 autosomal SNPs. We identified on average 35.996 ± 7.498 ROH per individual with a mean length of 8.323 ± 1.181 Mb. The genomic inbreeding coefficient FROH was 0.122 ± 0.032 and it decreased to 0.074, 0.031 and 0.006, when genomic homozygous segments > 8 Mb (FROH>8), >16 Mb (FROH>16) and >32 Mb (FROH>32) were considered. New inbreeding showed the highest correlation with FROH>32, whereas ancestral inbreeding coefficients had the lowest correlations with FROH>32. The correlation between the classical inbreeding coefficient and FROH was 0.572. We found significantly lower FROH, FROH>4, FROH>8 and FIS for US Brown Swiss proportions <60% compared to >80%. Cows surviving to the 2nd, 4th, 6th, 8th, and 10th lactation had lower genomic inbreeding for FROH and up to FROH>32, which was due to a lower number of ROH and a shorter average length of ROH. The strongest ROH island and consensus ROH shared by 50% of the animals was found on BTA 6 at 85–88 Mb. The genes located in this genomic region were associated with longevity (NPFFR2 and ADAMTS3), udder health and morphology (SLC4A4, NPFFR2, GC and RASSF6), milk production, milk protein percentage, coagulation properties of milk and milking speed (CSN3). On BTA 2, a ROH island was detected only in animals with <60% US Brown Swiss genes. Genes within this region are predominantly important for dual-purpose cattle breeds including Original Browns. For cows reaching more than 9 lactations, an exclusive ROH island was identified on BTA 7 with genes assumed to be associated with longevity. The analysis indicated that genomic homozygous regions important for Original Browns are still present and also ROH containing genes affecting longevity may have been identified. The breeding of German Browns should prevent any further increase in genomic inbreeding and run a breeding program with balanced weights on production, robustness and longevity.
Hsa-miR-874-3p Reduces Endogenous Expression of RGS4-1 Isoform In Vitro
Authors: Xu Feng-Ling , Wang Bao-Jie
Published: August 2024

Background: The level of the regulator of G-protein signaling 4-1 (RGS4-1) isoform, the longest RGS4 isoform, is significantly reduced in the dorsolateral prefrontal cortex (DLPFC) of people with schizophrenia. However, the mechanism behind this has not been clarified. The 3′untranslated regions (3′UTRs) are known to regulate the levels of their mRNA splice variants. Methods: We constructed recombinant pmir-GLO vectors with a truncated 3′ regulatory region of the RGS4 gene (3R1, 3R2, 3R3, 3R4, 3R5, and 3R6). The dual-luciferase reporter assay was conducted to find functional regions in HEK-293, SK-N-SH, and U87cells and then predicted miRNA binding to these regions. We performed a dual-luciferase reporter assay and a Western blot analysis after transiently transfecting the predicted miRNAs. Results: The dual-luciferase reporter assay found that regions +401–+789, +789–+1152, and +1562–+1990 (with the last base of the termination codon being +1) might be functional regions. Hsa-miR-874-3p, associated with many psychiatric disorders, might target the +789–+1152 region in the 3′UTR of the RGS4 gene. In the dual-luciferase reporter assay, the hsa-miR-874-3p mimic, co-transfected with 3R1, down-regulated the relative fluorescence intensities. However, this was reversed when the hsa-miR-874-3p mimic was co-transfected with m3R1 (deletion of +853–+859). The hsa-miR-874-3p mimic significantly decreased the endogenous expression of the RGS4-1 isoform in HEK-293 cells. Conclusions: Hsa-miR-874-3p inhibits the expression of the RGS4-1 isoform by targeting +853–+859.
Optimization of Phycocyanobilin Synthesis in E. coli BL21: Biotechnological Insights and Challenges for Scalable Production
Authors: Esclapez Julia , Matarredona Laura , Zafrilla Guillermo , Camacho Mónica , Bonete María-José , Zafrilla Basilio
Published: August 2024

Phycocyanobilin (PCB) is a small chromophore found in certain phycobiliproteins, such as phycocyanins (PCs) and allophycocyanins (APCs). PCB, along with other phycobilins (PBs) and intermediates such as biliverdin (BV) or phycoerythrobilin (PEB), is attracting increasing biotechnological interest due to its fluorescent and medicinal properties that allow potential applications in biomedicine and the food industry. This study aims to optimize PCB synthesis in Escherichia coli BL21 (DE3) and scale the process to a pre-industrial level. Parameters such as optimal temperature, inducer concentration, initial OD600, and stirring speed were analyzed in shake flask cultures to maximize PCB production. The best results were obtained at a temperature of 28 °C, an IPTG concentration of 0.1 mM, an initial OD600 of 0.5, and an orbital shaking speed of 260 rpm. Furthermore, the optimized protocol was scaled up into a 2 L bioreactor batch, achieving a maximum PCB concentration of 3.8 mg/L. Analysis of the results revealed that biosynthesis of exogenous PBs in Escherichia coli BL21 (DE3) is highly dependent on the metabolic burden of the host. Several scenarios, such as too rapid growth, high inducer concentration, or mechanical stress, can advance entry into the stationary phase. That progressively halts pigment synthesis, leading, in some cases, to its excretion into the growth media and ultimately triggering rapid degradation by the host. These conclusions provide a promising protocol for scalable PCB production and highlight the main biotechnological challenges to increase the yields of the process.
Post-COVID Myocarditis in Patients with Primary Cardiomyopathies: Diagnosis, Clinical Course and Outcomes
Authors: Blagova Olga , Lutokhina Yulia , Kogan Evgeniya , Savina Polina , Aleksandrova Svetlana , Zaklyazminskaya Elena
Published: August 2024

The aim of this study was to evaluate the clinical course and outcomes of post-COVID myocarditis in patients with cardiomyopathies (CMP). This case series includes 10 patients with different CMPs who had COVID-19 (seven men; 48.4 ± 11.4 yr.): left ventricular non-compaction (n = 2), arrhythmogenic right ventricular CMP in combination with a heterozygous form of hemochromatosis (n = 1, HFE), restrictive CMP (n = 1, MyBPC3), laminopathy (n = 1, LMNA), dilated cardiomyopathy (n = 1, MYH7 + MyBPC3), Danon’s disease (n = 1, LAMP2) and AL cardiac amyloidosis (n = 3). Myocardial morphological examination with immunohistochemical staining and PCR for SARS-CoV-2 and cardiotropic viruses was performed in six patients, while cardiac MRI and anti-cardiac antibody titres were evaluated in all patients. Post-COVID lymphocytic myocarditis was confirmed morphologically in six patients (with LVNC, RCM, ARCV, Danon’s disease, and AL amyloidosis). Spike and nucleocapsid coronavirus proteins were detected in cell infiltrates, endothelium and cardiomyocytes in all biopsies; SARS-CoV-2 RNA was found in five out of six. In four patients, the diagnosis of myocarditis was based on MRI, high titres of anti-cardiac antibodies and clinical data. The mean time from COVID-19 to the diagnosis of myocarditis was 7 (5; 10.5) months. Myocarditis manifested with the onset/increase of arrhythmias and heart failure. Immunosuppressive therapy with corticosteroids was administered to six patients and led to an increase in ejection fraction and improvement of heart failure symptoms in five of them. CMPs are a favourable background for the development of post-COVID myocarditis. The onset or deterioration of heart failure and/or arrhythmias in patients with CMPs after COVID-19 requires the exclusion of myocarditis and, if present, the administration of immunosuppressive therapy.
Validation of a Questionnaire to Assess Patient Satisfaction with an Automated Drug Dispensing System
Authors: Amirthalingam Palanisamy , Alharbe Umar Abdolah , Almfalh Hanad S. S. , Alqifari Saleh F. , Alatawi Ahmed D. , Aljabri Ahmed , Ali Mostafa A. Sayed
Published: August 2024

Background and objectives: Automated drug dispensing systems (ADDs) have been introduced to improve the efficiency of dispensing and patient safety. The available questionnaires measure patient satisfaction with particular aspects of ADDs. Also, the level of patient satisfaction with ADDs is not widely established. This study aimed to develop and validate a novel questionnaire to assess patient satisfaction with ADDs. Methods: Content and construct validity procedures were used to validate the 20-item questionnaire with four domains, including pharmacy administration, dispensing practice, patient education, and the dispensing system. Two hundred consenting participants took part in this study, from those who visited the outpatient pharmacy in a government hospital. Results: The internal consistency of all four scale items shows acceptable reliability (>0.7). In the exploratory factor analysis, three items were removed due to poor factor loading and cross-loading. In the confirmatory factor analysis, the model has acceptable fit indices, including the comparative fit index (0.937), Tucker–Lewis’s index (0.924), standardized root mean square residual (0.051), root mean square error of approximation (0.057), and χ2/df (1.67). The convergent and discriminant validity were established, since the average variance extracted (AVE) was ≥0.5 and the squared correlation (SC) values of one construct with other constructs were less than the AVE of the specific construct. Conclusion: This study offered a reliable and valid 17-item questionnaire incorporating a multi-dimensional four-factor model to evaluate patient satisfaction with ADDs. The validated questionnaire can be utilized to explore patients’ perspectives on ADDs.
Effects of Community Assets on Major Health Conditions in England: A Data Analytic Approach
Authors: Moustakas Aristides , Thomson Linda J. M. , Mughal Rabya , Chatterjee Helen J.
Published: August 2024

Introduction: The broader determinants of health including a wide range of community assets are extremely important in relation to public health outcomes. Multiple health conditions, multimorbidity, is a growing problem in many populations worldwide. Methods: This paper quantified the effect of community assets on major health conditions for the population of England over six years, at a fine spatial scale using a data analytic approach. Community assets, which included indices of the health system, green space, pollution, poverty, urban environment, safety, and sport and leisure facilities, were quantified in relation to major health conditions. The health conditions examined included high blood pressure, obesity, dementia, diabetes, mental health, cardiovascular conditions, musculoskeletal conditions, respiratory conditions, kidney and liver disease, and cancer. Cluster analysis and dendrograms were calculated for the community assets and major health conditions. For each health condition, a statistical model with all community assets was fitted, and model selection was performed. The number of significant community assets for each health condition was recorded. The unique variance, explained by each significant community asset per health condition, was quantified using hierarchical variance partitioning within an analysis of variance model. Results: The resulting data indicate major health conditions are often clustered, as are community assets. The results suggest that diversity and richness of community assets are key to major health condition outcomes. Primary care service waiting times and distance to public parks were significant predictors of all health conditions examined. Primary care waiting times explained the vast majority of the variances across health conditions, with the exception of obesity, which was better explained by absolute poverty. Conclusions: The implications of the combined findings of the health condition clusters and explanatory power of community assets are discussed. The vast majority of determinants of health could be accounted for by healthcare system performance and distance to public green space, with important covariate socioeconomic factors. Emphases on community approaches, significant relationships, and asset strengths and deficits are needed alongside targeted interventions. Whilst the performance of the public health system remains of key importance, community assets and local infrastructure remain paramount to the broader determinants of health.
Continental Scale Regional Flood Frequency Analysis: Combining Enhanced Datasets and a Bayesian Framework
Authors: Alexandre Duy Anh , Chaudhuri Chiranjib , Gill-Fortin Jasmin
Published: August 2024

Flood frequency analysis at large scales, essential for the development of flood risk maps, is hindered by the scarcity of gauge flow data. Suitable methods are thus required to predict flooding in ungauged basins, a notoriously complex problem in hydrology. We develop a Bayesian hierarchical model (BHM) based on the generalized extreme value (GEV) and the generalized Pareto distribution for regional flood frequency analysis at high resolution across a large part of North America. Our model leverages annual maximum flow data from ≈20,000 gauged stations and a dataset of 130 static catchment-specific covariates to predict extreme flows at all catchments over the continent as well as their associated statistical uncertainty. Additionally, a modification is made to the data layer of the BHM to include peaks over threshold flow data when available, which improves the precision of the discharge level estimates. We validated the model using a hold-out approach and found that its predictive power is very good for the GEV distribution location and scale parameters and improvable for the shape parameter, which is notoriously hard to estimate. The resulting discharge return levels yield a satisfying agreement when compared with the available design peak discharge from various government sources. The assessment of the covariates’ contributions to the model is also informative with regard to the most relevant underlying factors influencing flood-inducing peak flows. According to the developed aggregate importance score, the key covariates in our model are temperature-related bioindicators, the catchment drainage area and the geographical location.
Knowledge Management for Improved Digital Transformation in Insurance Companies: Systematic Review and Perspectives
Authors: Elgargouh Younes , Chbihi Louhdi Mohammed Reda , Zemmouri El Moukhtar , Behja Hicham
Published: August 2024

Knowledge Management (KM) plays a pivotal role in contemporary businesses, facilitating the identification, management, and utilization of existing knowledge for organizational benefit. This article underscores the indispensability of effective KM processes in the insurance industry, which is undergoing profound digital transformation. Through a systematic review utilizing the PRISMA framework, we meta-analyzed 85 high-quality scientific papers sourced from prominent databases spanning 2008 to 2022. Our examination centers on the diverse implementation processes of KM worldwide, emphasizing the integration of information technologies to enhance data collection, analysis, processing, and distribution within insurance companies. The objective of this review is twofold: to devise efficient methods for implementing KM systems in the insurance sector and to delineate practical research directions in this domain.