bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Sustainable Consumption a Sufficient Motivator for Consumers to Adopt Meat Alternatives? A Consumer Perspective on Plant-Based, Cell-Culture-Derived, and Insect-Based Alternatives
Authors: Rehman Nayyer , Edkins Victoria , Ogrinc Nives
Published: May 2024

This study investigates consumer preference and acceptance of three meat alternatives—plant-based, lab-grown, and insect-based—as sustainable choices to meet the demands of a growing population and evolving food systems. Insights were gathered from European consumers regarding their perceptions and consumption patterns using a mixed-methods approach. The approach employed a questionnaire followed by focus group discussions conducted in Slovenia and the UK to understand the motivations and barriers behind their responses. The UK and Slovenia were chosen as they provided the highest response rates to the questionnaire and they have differing legislation. The results show that plant-based alternatives are the most familiar and accepted option, while lab-grown meat and insect-based products are less familiar and have lower acceptance rates. Moreover, they show that although sustainability factors are important to consumers, they are not their only concern; health and nutrition are the primary motivators for choosing meat alternatives. These are followed closely by sensory appeal, pricing, and a preference for natural, minimally processed options. Based on insights from the focus groups, strategies to overcome the barriers to the acceptance of meat alternatives should include targeted product categorisation and placement, educational campaigns, effective use of media, and greater transparency in product information.
Extraction, Characterisation and Evaluation of Antioxidant and Probiotic Growth Potential of Water-Soluble Polysaccharides from Ulva rigida Macroalgae
Authors: Phomkaivon Naraporn , Pongponpai Preeyanut , Kosawatpat Prapat , Thongdang Bussaba , Pan-utai Wanida
Published: May 2024

Ulva rigida green macroalgae contain a variety of polysaccharides. A recent study investigated the optimum concentration and yield of polysaccharide extraction from oven-dried U. rigida biomass using a water-soluble polysaccharide extraction method that adhered to safety standards. This study utilised complete factorial experiments to examine the effects of varying factors on polysaccharide extraction. Results showed a positive correlation between increased levels of all factors and higher polysaccharide extraction yield. This study also found that the main factors and their interaction had a significant impact on the extracted polysaccharides from U. rigida. The highest polysaccharide content and yield were 9.5 mg/mL and 189 mg/g, respectively. Water-soluble polysaccharides demonstrated the presence of reducing sugar (8 mg/g), phenolics (0.69 mg/g) and flavonoids (1.42 mg/g) and exhibited antioxidant properties. Results revealed that freeze-dried polysaccharide powders were primarily composed of the monosaccharide rhamnose. Preliminary results on the effect of these powders on probiotics demonstrated that supplementation of polysaccharides from U. rigida promoted viable Lactobacillus rhamnosus ATCC 53103 growth during cultivation. This discovery has the potential to revolutionise the human food industry and promote the development of functional ingredients for novel and future food products, with numerous applications in the nutraceutical and pharmaceutical industries.
Dynamic Analysis and Sliding Mode Synchronization Control of Chaotic Systems with Conditional Symmetric Fractional-Order Memristors
Authors: Tian Huaigu , Zhao Mingwei , Liu Jindong , Wang Qiao , Yu Xiong , Wang Zhen
Published: May 2024

In this paper, the characteristics of absolute value memristors are verified through the circuit implementation and construction of a chaotic system with a conditional symmetric fractional-order memristor. The dynamic behavior of fractional-order memristor systems is explored using fractional-order calculus theory and the Adomian Decomposition Method (ADM). Concurrently, the investigation probes into the existence of coexisting symmetric attractors, multiple coexisting bifurcation diagrams, and Lyapunov exponent spectra (LEs) utilizing system parameters as variables. Additionally, the system demonstrates an intriguing phenomenon known as offset boosting, where the embedding of an offset can adjust the position and size of the system’s attractors. To ensure the practical applicability of these findings, a fractional-order sliding mode synchronization control scheme, inspired by integer-order sliding mode theory, is designed. The rationality and feasibility of this scheme are validated through a theoretical analysis and numerical simulation.
Efficacy of Chitosan-Carboxylic Acid Hydrogels in Reducing and Chelating Iron for the Removal of Rust from Stone Surface
Authors: Gabriele Francesco , Casieri Cinzia , Spreti Nicoletta
Published: May 2024

In the field of stone conservation, the removal of iron stains is one of the most challenging issues due to the stability and low solubility of the ferrous species. In the present paper, three different chitosan-based hydrogels added with acetic, oxalic or citric acids are applied on different lithotypes, i.e., granite, travertine and marble, widely diffused in monumental heritages, and artificially stained by deposition of a rust dispersion. The reducing power of carboxylic acids is combined with the good chelating properties of chitosan to effectively remove rust from stone surfaces. As evidenced by colorimetry on three samples of each lithotype and confirmed by 1H-NMR relaxometry and SEM/EDS analyses, the chitosan-oxalic acid hydrogel shows the best performance and a single application of 24 h is enough to get a good restoration of the stone original features. Lastly, the chitosan-oxalic acid hydrogel performs well when a rusted iron grid is placed directly on the lithic surfaces to simulate a more realistic pollution. Current work in progress is devoted to finding better formulations for marble, which is the most challenging to clean or, with a different approach, to developing protective agents to prevent rust deposition.
Preparation and Testing of Polyethylenimine-Impregnated Silica Gel for CO2 Capture
Authors: Kyselová Veronika , Havlín Jakub , Ciahotný Karel
Published: May 2024

This work studied the low-temperature sorption of carbon dioxide on impregnated silica gel. An impregnating agent was used polyethyleneimine. The content of the impregnating agent in the silica gel matrix was 33.4 wt.%. Material properties such as the Brunauer–Emmett–Teller (BET) surface area, pore distribution, total pore volume, and thermal stability of the impregnated material were determined for the sample. During the measurement of the adsorption–desorption cycles, the loss of the impregnating agent in the material matrix was also determined. Due to the decrease in the content of polyethyleneimine, the sorption capacity of the adsorbent for CO2 also decreased. It was found that after the 20th adsorption–desorption cycle, the content of the impregnating agent in the adsorbent dropped by 3.15 wt.%, and, as a result, the adsorption capacity for CO2 dropped to almost half.
Neuronal Ceroid Lipofuscinosis in a Mixed-Breed Dog with a Splice Site Variant in CLN6
Authors: Mhlanga-Mutangadura Tendai , Bullock Garrett , Cerda-Gonzalez Sofia , Katz Martin L.
Published: May 2024

A 23-month-old neutered male dog of unknown ancestry presented with a history of progressive neurological signs that included anxiety, cognitive impairment, tremors, seizure activity, ataxia, and pronounced visual impairment. The clinical signs were accompanied by global brain atrophy. Due to progression in the severity of disease signs, the dog was euthanized at 26 months of age. An examination of the tissues collected at necropsy revealed dramatic intracellular accumulations of autofluorescent inclusions in the brain, retina, and cardiac muscle. The inclusions were immunopositive for subunit c of mitochondrial ATP synthase, and their ultrastructural appearances were similar to those of lysosomal storage bodies that accumulate in some neuronal ceroid lipofuscinosis (NCL) diseases. The dog also exhibited widespread neuroinflammation. Based on these findings, the dog was deemed likely to have suffered from a form of NCL. A whole genome sequence analysis of the proband’s DNA revealed a homozygous C to T substitution that altered the intron 3–exon 4 splice site of CLN6. Other mutations in CLN6 cause NCL diseases in humans and animals, including dogs. The CLN6 protein was undetectable with immunolabeling in the tissues of the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the disorder in this dog was classified as an NCL resulting from the absence of the CLN6 protein. Screening the dog’s genome for a panel of breed-specific polymorphisms indicated that its ancestry included numerous breeds, with no single breed predominating. This suggests that the CLN6 disease variant is likely to be present in other mixed-breed dogs and at least some ancestral breeds, although it is likely to be rare since other cases have not been reported to date.
Transcriptomic Analyses Reveal the Effects of Walnut Kernel Cake on Adipose Deposition in Pigs
Authors: Liu Lei , Shang Xiaodan , Ma Li , Yan Dawei , Adetula Adeyinka Abiola , Bai Ying , Dong Xinxing
Published: May 2024

With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenol-, fiber-, protein- and fat-rich byproduct of walnut oil extraction, has been underexplored as a potential protein replacement in pig feed. In this study, we found that feeding large Diqing Tibetan pigs walnut kernel cake promoted adipose deposition and improved pork quality during pig growth. Transcriptome analysis revealed the upregulation of genes ANGPTL8, CCNP, ETV4, and TRIB3, associated with adipose deposition. Pathway analysis highlighted enrichment in adipose deposition-related pathways, including PPAR, insulin, PI3K-Akt, Wnt, and MAPK signaling. Further analysis identified DEGs (differentially expressed genes) positively correlated with adipose-related traits, such as PER2 and PTGES. Single-cell transcriptome data pointed to the specific expression of CD248 and PTGES in adipocyte progenitor/stem cells (APSCs), pivotal for adipocyte differentiation and adipose deposition regulation. This study demonstrates walnut kernel cake’s potential to substitute soybean cake in pig feed, providing high-quality protein and promoting adipose deposition. It offers insights into feed protein replacement, human functional food, fat metabolism, and related diseases, with marker genes and pathways supporting pig breeding and pork quality improvement.
Advances in and Perspectives on Transgenic Technology and CRISPR-Cas9 Gene Editing in Broccoli
Authors: Zhang Li , Meng Sufang , Liu Yumei , Han Fengqing , Xu Tiemin , Zhao Zhiwei , Li Zhansheng
Published: May 2024

Broccoli, a popular international Brassica oleracea crop, is an important export vegetable in China. Broccoli is not only rich in protein, vitamins, and minerals but also has anticancer and antiviral activities. Recently, an Agrobacterium-mediated transformation system has been established and optimized in broccoli, and transgenic transformation and CRISPR-Cas9 gene editing techniques have been applied to improve broccoli quality, postharvest shelf life, glucoraphanin accumulation, and disease and stress resistance, among other factors. The construction and application of genetic transformation technology systems have led to rapid development in broccoli worldwide, which is also good for functional gene identification of some potential traits in broccoli. This review comprehensively summarizes the progress in transgenic technology and CRISPR-Cas9 gene editing for broccoli over the past four decades. Moreover, it explores the potential for future integration of digital and smart technologies into genetic transformation processes, thus demonstrating the promise of even more sophisticated and targeted crop improvements. As the field continues to evolve, these innovations are expected to play a pivotal role in the sustainable production of broccoli and the enhancement of its nutritional and health benefits.
Knotify_V2.0: Deciphering RNA Secondary Structures with H-Type Pseudoknots and Hairpin Loops
Authors: Kolaitis Angelos , Makris Evangelos , Karagiannis Alexandros Anastasios , Tsanakas Panayiotis , Pavlatos Christos
Published: May 2024

Accurately predicting the pairing order of bases in RNA molecules is essential for anticipating RNA secondary structures. Consequently, this task holds significant importance in unveiling previously unknown biological processes. The urgent need to comprehend RNA structures has been accentuated by the unprecedented impact of the widespread COVID-19 pandemic. This paper presents a framework, Knotify_V2.0, which makes use of syntactic pattern recognition techniques in order to predict RNA structures, with a specific emphasis on tackling the demanding task of predicting H-type pseudoknots that encompass bulges and hairpins. By leveraging the expressive capabilities of a Context-Free Grammar (CFG), the suggested framework integrates the inherent benefits of CFG and makes use of minimum free energy and maximum base pairing criteria. This integration enables the effective management of this inherently ambiguous task. The main contribution of Knotify_V2.0 compared to earlier versions lies in its capacity to identify additional motifs like bulges and hairpins within the internal loops of the pseudoknot. Notably, the proposed methodology, Knotify_V2.0, demonstrates superior accuracy in predicting core stems compared to state-of-the-art frameworks. Knotify_V2.0 exhibited exceptional performance by accurately identifying both core base pairing that form the ground truth pseudoknot in 70% of the examined sequences. Furthermore, Knotify_V2.0 narrowed the performance gap with Knotty, which had demonstrated better performance than Knotify and even surpassed it in Recall and F1-score metrics. Knotify_V2.0 achieved a higher count of true positives (tp) and a significantly lower count of false negatives (fn) compared to Knotify, highlighting improvements in Prediction and Recall metrics, respectively. Consequently, Knotify_V2.0 achieved a higher F1-score than any other platform. The source code and comprehensive implementation details of Knotify_V2.0 are publicly available on GitHub.
Cardiac Remodeling and Ventricular Pacing: From Genes to Mechanics
Authors: Malikides Onoufrios , Simantirakis Emmanouel , Zacharis Evangelos , Fragkiadakis Konstantinos , Kochiadakis George , Marketou Maria
Published: May 2024

Cardiac remodeling and ventricular pacing represent intertwined phenomena with profound implications for cardiovascular health and therapeutic interventions. This review explores the intricate relationship between cardiac remodeling and ventricular pacing, spanning from the molecular underpinnings to biomechanical alterations. Beginning with an examination of genetic predispositions and cellular signaling pathways, we delve into the mechanisms driving myocardial structural changes and electrical remodeling in response to pacing stimuli. Insights into the dynamic interplay between pacing strategies and adaptive or maladaptive remodeling processes are synthesized, shedding light on the clinical implications for patients with various cardiovascular pathologies. By bridging the gap between basic science discoveries and clinical translation, this review aims to provide a comprehensive understanding of cardiac remodeling in the context of ventricular pacing, paving the way for future advancements in cardiovascular care.
Evaluation of a New DNA Extraction Method on Challenging Bone Samples Recovered from a WWII Mass Grave
Authors: Di Stefano Barbara , Zupanič Pajnič Irena , Concato Monica , Bertoglio Barbara , Calvano Maria Grazia , Sorçaburu Ciglieri Solange , Bosetti Alessandro , Grignani Pierangela , Addoum Yasmine , Vetrini Raffaella , Introna Francesco , Bonin Serena , Previderè Carlo , Fattorini Paolo
Published: May 2024

Bones and teeth represent a common finding in ancient DNA studies and in forensic casework, even after a long burial. Genetic typing is the gold standard for the personal identification of skeletal remains, but there are two main factors involved in the successful DNA typing of such samples: (1) the set-up of an efficient DNA extraction method; (2) the identification of the most suitable skeletal element for the downstream genetic analyses. In this paper, a protocol based on the processing of 0.5 g of bone powder decalcified using Na2EDTA proved to be suitable for a semi-automated DNA extraction workflow using the Maxwell® FSC DNA IQ™ Casework Kit (Promega, Madison, WI, USA). The performance of this method in terms of DNA recovery and quality was compared with a full demineralisation extraction protocol based on Qiagen technology and kits. No statistically significant differences were scored according to the DNA recovery and DNA degradation index (p-values ≥ 0.176; r ≥ 0.907). This new DNA extraction protocol was applied to 88 bone samples (41 femurs, 19 petrous bones, 12 metacarpals and 16 molars) allegedly belonging to 27 World War II Italian soldiers found in a mass grave on the isle of Cres (Croatia). The results of the qPCR performed by the Quantifiler Human DNA Quantification kit showed values above the lowest Limit of Quantification (lLOQ; 23 pg/µL) for all petrous bones, whereas other bone types showed, in most cases, lower amounts of DNA. Replicate STR-CE analyses showed successful typing (that is, >12 markers) in all tests on the petrous bones, followed by the metacarpals (83.3%), femurs (52.2%) and teeth (20.0%). Full profiles (22/22 autosomal markers) were achieved mainly in the petrous bones (84.2%), followed by the metacarpals (41.7%). Stochastic amplification artefacts such as drop-outs or drop-ins occurred with a frequency of 1.9% in the petrous bones, whereas they were higher when the DNA recovered from other bone elements was amplified (up to 13.9% in the femurs). Overall, the results of this study confirm that petrous bone outperforms other bone elements in terms of the quantity and quality of the recovered DNA; for this reason, if available, it should always be preferred for genetic testing. In addition, our results highlight the need for accurate planning of the DVI operation, which should be carried out by a multi-disciplinary team, and the tricky issue of identifying other suitable skeletal elements for genetic testing. Overall, the results presented in this paper support the need to adopt preanalytical strategies positively related to the successful genetic testing of aged skeletal remains in order to reduce costs and the time of analysis.
EBV-Positive Nodal T- and NK-Cell Lymphoma Mimicking Anaplastic Large Cell Lymphoma: A Case Report
Authors: Abro Brooj , Allen Pamela , Asakrah Saja , Bradley Kyle , Zhang Linsheng
Published: May 2024

EBV-positive nodal T- and NK-cell lymphoma (EBV+ NT/NKCL) is a recently recognized entity in the 5th edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. Notably, CD30 positivity is frequently observed in (EBV+ NT/NKCL), creating diagnostic challenges to distinguish it from ALK-negative anaplastic large cell lymphoma (ALCL). Furthermore, cases of EBV+ ALCL have been documented in the literature, predating the inclusion of EBV+ nodal cytotoxic T-cell lymphoma as a variant of peripheral T-cell lymphoma. We present a case of a 47-year-old male presenting with multiple lymphadenopathies. The histomorphologic and immunophenotypic features of the lymph node closely resemble ALK-negative ALCL, characterized by uniform CD30 expression and a subcapsular distribution of lymphoma cells. However, the lymphoma cells exhibit diffuse positivity for EBV, consistent with EBV+ NT/NKCL. A case of ALK-negative ALCL with an immunophenotype identical to the EBV-positive case is included for comparison. Given that EBV+ NT/NKCL represents an aggressive neoplasm requiring unique clinical management compared to ALK-negative ALCL, it is critical to accurately differentiate EBV+ NT/NKCL from ALK-negative ALCL with a cytotoxic T-cell immunophenotype.
Optimizing Older Adult Mental Health in Support of Healthy Ageing: A Pluralistic Framework to Inform Transformative Change across Community and Healthcare Domains
Authors: Horgan Salinda , Prorok Jeanette , Ellis Katie , Mullaly Laura , Cassidy Keri-Leigh , Seitz Dallas , Checkland Claire
Published: May 2024

This paper describes a pluralistic framework to inform transformative change across community and healthcare domains to optimize the mental health of older adults in support of healthy ageing. An extensive review and analysis of the literature informed the creation of a framework that contextualizes the priority areas of the WHO Decade of Health Ageing (ageism, age-friendly environments, long-term care, and integrated care) with respect to older adult mental health. The framework additionally identifies barriers, facilitators, and strategies for action at macro (social/system), meso (services/supports), and micro (older adults) levels of influence. This conceptual (analytical) framework is intended as a tool to inform planning and decision-making across policy, practice, education and training, research, and knowledge mobilization arenas. The framework described in this paper can be used by countries around the globe to build evidence, set priorities, and scale up promising practices (both nationally and sub-nationally) to optimize the mental health and healthy ageing trajectories of older adults as a population.
Supported Standing and Supported Stepping Devices for Children with Non-Ambulant Cerebral Palsy: An Interdependence and F-Words Focus
Authors: Paleg Ginny S. , Williams Sian A. , Livingstone Roslyn W.
Published: May 2024

Children functioning at Gross Motor Function Classification System (GMFCS) levels IV–V cannot maintain an aligned standing position or take steps without support. Upright positioning and mobility devices have psycho-social significance for these children and their families, enhancing use of vision, communication, functioning and emotional well-being. Standers and supported stepping devices facilitate opportunities for biomechanical loading, potentially helping to build and maintain muscle and bone integrity, and they promote physical development. However, families are often required to choose between these two devices for their young child. This study aims to synthesize evidence for use and benefits of both supported standing and stepping devices through the lens of two contemporary theoretical frameworks to support clinical reasoning and implementation. The F-words for childhood development (functioning, family, fitness, fun, friends, future) and the interdependence-Human Activity Assistive Technology (iHAAT) models were combined to illustrate the complex interactions between the child, family, caregivers, peers and contextual factors when implementing standing and stepping devices with children at GMFCS levels IV and V. Supported standing and stepping devices provide complementary benefits, and both may be necessary starting at 9–15 months. We propose they both be included ON-Time, along with other age-appropriate positioning and mobility devices, to promote more equitable developmental opportunities for children with non-ambulant cerebral palsy.
Anti-Cancer and Anti-Proliferative Potential of Cannabidiol: A Cellular and Molecular Perspective
Authors: Mashabela Manamele Dannies , Kappo Abidemi Paul
Published: May 2024

Cannabinoids, the bioactive compounds found in Cannabis sativa, have been used for medicinal purposes for centuries, with early discoveries dating back to the BC era (BCE). However, the increased recreational use of cannabis has led to a negative perception of its medicinal and food applications, resulting in legal restrictions in many regions worldwide. Recently, cannabinoids, notably Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have gained renewed interest in the medical field due to their anti-cancer properties. These properties include the inhibition of tumour growth and cell invasion, anti-inflammatory effects, and the induction of autophagy and apoptosis. As a result, the use of cannabinoids to treat chemotherapy-associated side effects, like nausea, vomiting, and pain, has increased, and there have been suggestions to implement the large-scale use of cannabinoids in cancer therapy. However, these compounds’ cellular and molecular mechanisms of action still need to be fully understood. This review explores the recent evidence of CBD’s efficacy as an anti-cancer agent, which is of interest due to its non-psychoactive properties. The current review will also provide an understanding of CBD’s common cellular and molecular mechanisms in different cancers. Studies have shown that CBD’s anti-cancer activity can be receptor-dependent (CB1, CB2, TRPV, and PPARs) or receptor-independent and can be induced through molecular mechanisms, such as ceramide biosynthesis, the induction of ER stress, and subsequent autophagy and apoptosis. It is projected that these molecular mechanisms will form the basis for the therapeutic applications of CBD. Therefore, it is essential to understand these mechanisms for developing and optimizing pre-clinical CBD-based therapies.
Apple Glycosyltransferase MdUGT73AR4 Glycosylates ABA to Regulate Stomatal Movement Involved in Drought Stress
Authors: Mu Lijun , Wang Xuekun , Ma Yingxin , Zhao Aijuan , Han Shibo , Li Ru , Lei Kang , Ji Lusha , Li Pan
Published: May 2024

Abscisic acid (ABA) is a drought-stress-responsive hormone that plays an important role in the stomatal activity of plant leaves. Currently, ABA glycosides have been identified in apples, but their glycosyltransferases for glycosylation modification of ABA are still unidentified. In this study, the mRNA expression of glycosyltransferase gene MdUGT73AR4 was significantly up-regulated in mature apple leaves which were treated in drought stress by Real-Time PCR. It was hypothesised that MdUGT73AR4 might play an important role in drought stress. In order to further characterise the glycosylation modification substrate of glycosyltransferase MdUGT73AR4, we demonstrated through in vitro and in vivo functional validation that MdUGT73AR4 can glycosylate ABA. Moreover, the overexpression lines of MdUGT73AR4 significantly enhance its drought stress resistance function. We also found that the adversity stress transcription factor AREB1B might be an upstream transcription factor of MdUGT73AR4 by bioinformatics, EMSA, and ChIP experiments. In conclusion, this study found that the adversity stress transcription factor AREB1B was significantly up-regulated at the onset of drought stress, which in turn positively regulated the downstream glycosyltransferase MdUGT73AR4, causing it to modify ABA by mass glycosylation and promoting the ABA synthesis pathway, resulting in the accumulation of ABA content, and displaying a stress-resistant phenotype.
The Tilapia Cyst Tissue Enclosing the Proliferating Myxobolus bejeranoi Parasite Exhibits Cornified Structure and Immune Barrier Function
Authors: Maor-Landaw Keren , Smirnov Margarita , Lotan Tamar
Published: May 2024

Myxozoa, a unique group of obligate endoparasites within the phylum Cnidaria, can cause emerging diseases in wild and cultured fish populations. Recently, the myxozoan Myxobolus bejeranoi has been identified as a prevalent pathogen infecting the gills of cultured hybrid tilapia, leading to systemic immune suppression and considerable mortality. Here, we employed a proteomic approach to examine the impact of M. bejeranoi infection on fish gills, focusing on the structure of the granulomata, or cyst, formed around the proliferating parasite to prevent its spread to surrounding tissue. Enrichment analysis showed increased immune response and oxidative stress in infected gill tissue, most markedly in the cyst’s wall. The intense immune reaction included a consortium of endopeptidase inhibitors, potentially combating the myxozoan arsenal of secreted proteases. Analysis of the cyst’s proteome and histology staining indicated that keratin intermediate filaments contribute to its structural rigidity. Moreover, we uncovered skin-specific proteins, including a grainyhead-like transcription factor and a teleost-specific S100 calcium-binding protein that may play a role in epithelial morphogenesis and cysts formation. These findings deepen our understanding of the proteomic elements that grant the cyst its distinctive nature at the critical interface between the fish host and myxozoan parasite.
Recent Progress in Innate Immune Responses to Enterovirus A71 and Viral Evasion Strategies
Authors: Wei Jialong , Lv Linxi , Wang Tian , Gu Wei , Luo Yang , Feng Hui
Published: May 2024

Enterovirus A71 (EV-A71) is a major pathogen causing hand, foot, and mouth disease (HFMD) in children worldwide. It can lead to severe gastrointestinal, pulmonary, and neurological complications. The innate immune system, which rapidly detects pathogens via pathogen-associated molecular patterns or pathogen-encoded effectors, serves as the first defensive line against EV-A71 infection. Concurrently, the virus has developed various sophisticated strategies to evade host antiviral responses and establish productive infection. Thus, the virus–host interactions and conflicts, as well as the ability to govern biological events at this first line of defense, contribute significantly to the pathogenesis and outcomes of EV-A71 infection. In this review, we update recent progress on host innate immune responses to EV-A71 infection. In addition, we discuss the underlying strategies employed by EV-A71 to escape host innate immune responses. A better understanding of the interplay between EV-A71 and host innate immunity may unravel potential antiviral targets, as well as strategies that can improve patient outcomes.
Metabolomics and Cardiovascular Risk in Patients with Heart Failure: A Systematic Review and Meta-Analysis
Authors: Neves Leonel Sousa , Saraiva Francisca , Ferreira Rita , Leite-Moreira Adelino , Barros António S. , Diaz Sílvia O.
Published: May 2024

The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Four cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1158 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two studies, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95% CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and a higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting, and sharing.
Advances in Anti-Cancer Drug Development: Metformin as Anti-Angiogenic Supplemental Treatment for Glioblastoma
Authors: Shah Siddharth , Mansour Hadeel M. , Aguilar Tania M. , Lucke-Wold Brandon
Published: May 2024

According to the WHO 2016 classification, glioblastoma is the most prevalent primary tumor in the adult central nervous system (CNS) and is categorized as grade IV. With an average lifespan of about 15 months from diagnosis, glioblastoma has a poor prognosis and presents a significant treatment challenge. Aberrant angiogenesis, which promotes tumor neovascularization and is a prospective target for molecular target treatment, is one of its unique and aggressive characteristics. Recently, the existence of glioma stem cells (GSCs) within the tumor, which are tolerant to chemotherapy and radiation, has been linked to the highly aggressive form of glioblastoma. Anti-angiogenic medications have not significantly improved overall survival (OS), despite various preclinical investigations and clinical trials demonstrating encouraging results. This suggests the need to discover new treatment options. Glioblastoma is one of the numerous cancers for which metformin, an anti-hyperglycemic medication belonging to the Biguanides family, is used as first-line therapy for type 2 diabetes mellitus (T2DM), and it has shown both in vitro and in vivo anti-tumoral activity. Based on these findings, the medication has been repurposed, which has shown the inhibition of many oncopromoter mechanisms and, as a result, identified the molecular pathways involved. Metformin inhibits cancer cell growth by blocking the LKB1/AMPK/mTOR/S6K1 pathway, leading to selective cell death in GSCs and inhibiting the proliferation of CD133+ cells. It has minimal impact on differentiated glioblastoma cells and normal human stem cells. The systematic retrieval of information was performed on PubMed. A total of 106 articles were found in a search on metformin for glioblastoma. Out of these six articles were Meta-analyses, Randomized Controlled Trials, clinical trials, and Systematic Reviews. The rest were Literature review articles. These articles were from the years 2011 to 2024. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on metformin use in the treatment of glioblastoma were searched on clinicaltrials.gov. In this article, we examine and evaluate metformin’s possible anti-tumoral effects on glioblastoma, determining whether or not it may appropriately function as an anti-angiogenic substance and be safely added to the treatment and management of glioblastoma patients.
Cartilage-Specific Gene Expression and Extracellular Matrix Deposition in the Course of Mesenchymal Stromal Cell Chondrogenic Differentiation in 3D Spheroid Culture
Authors: Vakhrushev Igor V. , Basok Yulia B. , Baskaev Konstantin K. , Novikova Victoria D. , Leonov Georgy E. , Grigoriev Alexey M. , Belova Aleksandra D. , Kirsanova Ludmila A. , Lupatov Alexey Y. , Burunova Veronika V. , Kovalev Alexey V. , Makarevich Pavel I. , Sevastianov Victor I. , Yarygin Konstantin N.
Published: May 2024

Articular cartilage damage still remains a major problem in orthopedical surgery. The development of tissue engineering techniques such as autologous chondrocyte implantation is a promising way to improve clinical outcomes. On the other hand, the clinical application of autologous chondrocytes has considerable limitations. Mesenchymal stromal cells (MSCs) from various tissues have been shown to possess chondrogenic differentiation potential, although to different degrees. In the present study, we assessed the alterations in chondrogenesis-related gene transcription rates and extracellular matrix deposition levels before and after the chondrogenic differentiation of MSCs in a 3D spheroid culture. MSCs were obtained from three different tissues: umbilical cord Wharton’s jelly (WJMSC—Wharton’s jelly mesenchymal stromal cells), adipose tissue (ATMSC—adipose tissue mesenchymal stromal cells), and the dental pulp of deciduous teeth (SHEDs—stem cells from human exfoliated deciduous teeth). Monolayer MSC cultures served as baseline controls. Newly formed 3D spheroids composed of MSCs previously grown in 2D cultures were precultured for 2 days in growth medium, and then, chondrogenic differentiation was induced by maintaining them in the TGF-β1-containing medium for 21 days. Among the MSC types studied, WJMSCs showed the most similarities with primary chondrocytes in terms of the upregulation of cartilage-specific gene expression. Interestingly, such upregulation occurred to some extent in all 3D spheroids, even prior to the addition of TGF-β1. These results confirm that the potential of Wharton’s jelly is on par with adipose tissue as a valuable cell source for cartilage engineering applications as well as for the treatment of osteoarthritis. The 3D spheroid environment on its own acts as a trigger for the chondrogenic differentiation of MSCs.
Electrophysiological Effects of the Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitor Dapagliflozin on Human Cardiac Potassium Channels
Authors: Müller Mara Elena , Petersenn Finn , Hackbarth Juline , Pfeiffer Julia , Gampp Heike , Frey Norbert , Lugenbiel Patrick , Thomas Dierk , Rahm Ann-Kathrin
Published: May 2024

The sodium-glucose co-transporter-2 (SGLT2) inhibitor dapagliflozin is increasingly used in the treatment of diabetes and heart failure. Dapagliflozin has been associated with reduced incidence of atrial fibrillation (AF) in clinical trials. We hypothesized that the favorable antiarrhythmic outcome of dapagliflozin use may be caused in part by previously unrecognized effects on atrial repolarizing potassium (K+) channels. This study was designed to assess direct pharmacological effects of dapagliflozin on cloned ion channels Kv11.1, Kv1.5, Kv4.3, Kir2.1, K2P2.1, K2P3.1, and K2P17.1, contributing to IKur, Ito, IKr, IK1, and IK2P K+ currents. Human channels coded by KCNH2, KCNA5, KCND3, KCNJ2, KCNK2, KCNK3, and KCNK17 were heterologously expressed in Xenopus laevis oocytes, and currents were recorded using the voltage clamp technique. Dapagliflozin (100 µM) reduced Kv11.1 and Kv1.5 currents, whereas Kir2.1, K2P2.1, and K2P17.1 currents were enhanced. The drug did not significantly affect peak current amplitudes of Kv4.3 or K2P3.1 K+ channels. Biophysical characterization did not reveal significant effects of dapagliflozin on current–voltage relationships of study channels. In conclusion, dapagliflozin exhibits direct functional interactions with human atrial K+ channels underlying IKur, IKr, IK1, and IK2P currents. Substantial activation of K2P2.1 and K2P17.1 currents could contribute to the beneficial antiarrhythmic outcome associated with the drug. Indirect or chronic effects remain to be investigated in vivo.
Unmasking Banking Fraud: Unleashing the Power of Machine Learning and Explainable AI (XAI) on Imbalanced Data
Authors: Nobel S. M. Nuruzzaman , Sultana Shirin , Singha Sondip Poul , Chaki Sudipto , Mahi Md. Julkar Nayeen , Jan Tony , Barros Alistair , Whaiduzzaman Md
Published: May 2024

Recognizing fraudulent activity in the banking system is essential due to the significant risks involved. When fraudulent transactions are vastly outnumbered by non-fraudulent ones, dealing with imbalanced datasets can be difficult. This study aims to determine the best model for detecting fraud by comparing four commonly used machine learning algorithms: Support Vector Machine (SVM), XGBoost, Decision Tree, and Logistic Regression. Additionally, we utilized the Synthetic Minority Over-sampling Technique (SMOTE) to address the issue of class imbalance. The XGBoost Classifier proved to be the most successful model for fraud detection, with an accuracy of 99.88%. We utilized SHAP and LIME analyses to provide greater clarity into the decision-making process of the XGBoost model and improve overall comprehension. This research shows that the XGBoost Classifier is highly effective in detecting banking fraud on imbalanced datasets, with an impressive accuracy score. The interpretability of the XGBoost Classifier model was further enhanced by applying SHAP and LIME analysis, which shed light on the significant features that contribute to fraud detection. The insights and findings presented here are valuable contributions to the ongoing efforts aimed at developing effective fraud detection systems for the banking industry.
Effects of Occlusal Contact on Maxillary Alveolar Bone Morphology in Patients with and without Anterior Open Bite: A Cross-Sectional Study
Authors: Shimizu-Tomoda Chiyo , Ishida Yuji , Ishizaki-Terauchi Aiko , Mizoguchi Yukari , Oishi Shuji , Ono Takashi
Published: May 2024

Background/Objectives: Anterior open bite (AOB) is characterized by the absence of occlusal contact between the maxillary and mandibular anterior teeth, while the posterior teeth are in contact when occluded. Here, we aimed to clarify the difference in maxillary alveolar bone morphology in adult patients with and without AOB. Methods: This cross-sectional study was conducted on 50 adults aged 18–39 years: 25 patients without AOB (control group; 13 males and 12 females; age: mean ± standard deviation [SD], 22.2 ± 4.5 years) and 25 patients with AOB (9 males and 16 females; age: 24.2 ± 6.4 years). Using cone-beam computed tomography images, the height of the maxillary alveolar bone crest in the anterior and posterior teeth and thickness of the alveolar cortical bone on the labial and palatal sides were measured and compared between the two groups. An independent t-test and Pearson’s correlation analysis were used to examine statistical significance (p < 0.05). Results: The AOB group showed a significantly longer (p = 0.016) posterior alveolar crest and thinner cortical bone on the buccal (p < 0.001) and lingual (p = 0.009) sides of the anterior region and the buccal (p = 0.006) sides of the posterior region than the control group did. Moreover, a significant negative correlation (p = 0.046; r = −0.403) was observed between bite force and cortical bone thickness on the buccal side of the posterior region in the AOB group. Conclusions: It is suggested that the absence of occlusal contact in the anterior area influences the alveolar bone morphology of the maxilla.
Vestibular Schwannoma and Tinnitus: A Systematic Review of Microsurgery Compared to Gamma Knife Radiosurgery
Authors: King Ava M. , Cooper Jaimee N. , Oganezova Karina , Mittal Jeenu , McKenna Keelin , Godur Dimitri A. , Zalta Max , Danesh Ali A. , Mittal Rahul , Eshraghi Adrien A.
Published: May 2024

Background: Vestibular schwannoma (VS) is a benign tumor of the eighth cranial nerve formed from neoplastic Schwann cells. Although VS can cause a variety of symptoms, tinnitus is one of the most distressing symptoms for patients and can greatly impact quality of life. The objective of this systematic review is to comprehensively examine and compare the outcomes related to tinnitus in patients undergoing treatment for VS. Specifically, it evaluates patient experiences with tinnitus following the removal of VS using the various surgical approaches of traditional surgical resection and gamma knife radiosurgery (GKS). By delving into various aspects such as the severity of tinnitus post-treatment, the duration of symptom relief, patient quality of life, new onset of tinnitus after VS treatment, and any potential complications or side effects, this review aims to provide a detailed analysis of VS treatment on tinnitus outcomes. Methods: Following PRISMA guidelines, articles were included from PubMed, Science Direct, Scopus, and EMBASE. Quality assessment and risk of bias analysis were performed using a ROBINS-I tool. Results: Although VS-associated tinnitus is variable in its intensity and persistence post-resection, there was a trend towards a decreased tinnitus burden in patients. Irrespective of the surgical approach or the treatment with GKS, there were cases of persistent or worsened tinnitus within the studied cohorts. Conclusion: The findings of this systematic review highlight the complex relationship between VS resection and tinnitus outcomes. These findings underscore the need for individualized patient counseling and tailored treatment approaches in managing VS-associated tinnitus. The findings of this systematic review may help in guiding clinicians towards making more informed and personalized healthcare decisions. Further studies must be completed to fill gaps in the current literature.
Role of Sport Vision in Performance: Systematic Review
Authors: Buscemi Andrea , Mondelli Flora , Biagini Ilaria , Gueli Stella , D’Agostino Angela , Coco Marinella
Published: May 2024

Sport Vision is a speciality of multidisciplinary interest aimed at improving the performance of the visual system to achieve benefits in practiced sports, as well as in daily life and in preventive care. The type of training practiced by the athlete, his or her physical condition, cognitive level, and level of fatigue condition affects the speed of the reaction time and, consequently, the speed of motor response. Specific orthoptic exercises, the use of technological devices, the recovery of static and dynamic postural stability by using unstable platforms and the dual-task paradigm can help to achieve the expected results. The aim of this systematic review of Sport Vision was to assess the overall existing literature on Sport Vision, paying particular attention to the effects of visual training and its application in different sports and in rehabilitation and preventive settings. We analysed published English language studies about the role of sport vision in athletic performance from 1950 to 2023. We searched through the Medline database. The PRISMA 2020 checklist was used to assess the transparency and reproducibility of this review. The enrolled papers were evaluated with the Jadad Scale, Amstar 2 Scale and Newcastle–Ottawa Scale. 25 (16 studies, 5 reviews, 2 comments, 1 editorial, 1 descriptive paper) out of 476 studies met the inclusion criteria. Due to the variability in the age of the samples, the different techniques, the treatments among the participants in the studies and the finding of non-evaluable articles, a meta-analysis was not conducted. The limitations of this review are the single database research, the studies analyzed contain a non-statistically representative sample size and the lack of a control group. There is no standardized test to measure performance. It was shown that the development of visual skills can benefit athletes in injury prevention, and can lead to improved sports performance and motor function at any age, acquiring adaptive motor behaviour even when the visual system is impaired, due to task repetition and familiarity of the gesture. We intended to identify a multidisciplinary approach and a manual treatment scheme to optimize the circuitry involved in sport vision in order to increase the results that are achieved, but further studies will be needed to this end.