bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimized Spheroid Model of Pancreatic Cancer Demonstrates Influence of Macrophage–T Cell Interaction for Intratumoral T Cell Motility
Authors: Slusny Benedikt , Zimmer Vanessa , Nasiri Elena , Lutz Veronika , Huber Magdalena , Buchholz Malte , Gress Thomas M. , Roth Katrin , Bauer Christian
Published: December 2024

Background: Most spheroid models use size measurements as a primary readout parameter; some models extend analysis to T cell infiltration or perform caspase activation assays. However, to our knowledge, T cell motility analysis is not regularly included as an endpoint in imaging studies on cancer spheroids. Methods: Here, we intend to demonstrate that motility analysis of macrophages and T cells is a valuable functional endpoint for studies on molecular interventions in the tumor microenvironment. In particular, T cell migration analysis represents the final step of effector function, as T cells engage with targets cells upon cytotoxic interaction, which is represented by an arrest within the spheroid volume. Therefore, T cell arrest is a novel readout parameter of T cell effector function in spheroids. Results: Here, we demonstrate that incubation of macrophages with nigericin for NLRP3 activation increases T cell velocity, but results in decreased T cellular arrest. This is paralleled by reduced rejection kinetics of pancreatic cancer spheroids in the presence of antigen-dependent T cells and nigericin-treated macrophages. Our model demonstrates consistent changes in T cell motility upon coculturing of T cells and tumors cells with macrophages, including influences of molecular interventions such as NLRP3 activation. Conclusions: Motility analysis using a spheroid model of pancreatic cancer is a more sophisticated alternative to in vitro cytotoxicity assays measuring spheroid size. Ultimately, an optimized spheroid model might replace at least some aspects of animal experiments investigating T cell effector function.
Experiences of Young Australians with Intellectual and/or Psychosocial Disabilities Sharing Disability-Related Information to Gain Workplace Adjustments
Authors: Devine Alexandra , De Rose Kristy , Jacobs Paul , Dimov Stefanie , White Bella , Cassar Sophie , Jones Rhiannon , McLennan Araminta , Olney Sue , Kavanagh Anne , Vaughan Cathy
Published: December 2024

Sharing disability-related information with an employer to gain workplace adjustments is a complex process for young people with intellectual and/or psychosocial disabilities. We examined the disclosure experiences of young Australians with intellectual and psychosocial disabilities, their subsequent access to workplace adjustments, and their employment outcomes. Using narrative inquiry, we analysed qualitative data collected from 24 interviews with participants with an intellectual (n = 10) and psychosocial disability (n = 14) between 18 and 25 years old recruited as part of an Australian Government-funded Youth Employment Study. Four main narratives emerged among the participants responses. Positions ranged from their having no control over disclosure experiences to a high level of control resulting in access to workplace adjustments. These positions were impingent on their knowledge of rights and adjustments, previous experiences, workplace context, and self-advocacy capacity. Our study provides unique insights into the employment experiences of young people with intellectual and psychosocial disabilities. The findings may inform initiatives aimed at building their capabilities for disclosure to gain workplace adjustments that can improve their employment outcomes in turn.
Winter Diet Pattern of Snow Leopard and Factors Affecting Livestock Depredation in Nubri Valley of Manaslu Conservation Area, Nepal
Authors: Timilsina Sachet , Pandey Bishnu Prasad , Neupane Bijaya , Bhattarai Bishnu Prasad , Silwal Thakur , Tumbahangphe Ajit , Subedi Ashok , Pant Ganesh , Krenova Zdenka , Shrestha Bikram
Published: December 2024

Limited information exists on the diet of snow leopards (SL), factors affecting livestock mortality, and local attitudes toward SL conservation in the Manaslu Conservation Area (MCA), Nepal. Therefore, we aim to investigate the dietary preferences of SL, the factors influencing livestock mortality, and local conservation attitudes. From November 2021 to January 2022, 23 SL scats were collected along 24 transects (total length: 21.6 km) in MCA. Camera traps, set within 4 km × 4 km grids at 28 stations for 661 trap nights, were used to assess prey availability. Jacobs’ index calculated prey preference, while a Generalized Linear Mixed Model (GLMM) assessed factors linked to livestock depredation. Additionally, 65 households from two villages were randomly selected in a survey on depredation and conservation attitudes. Scat analysis identified six wild prey species, including pika (Ochotona sp.), Himalayan tahr (Hemitragus jemlahicus), and blue sheep (Pseudois nayaur), as well as three domestic species: ox/cow, yak, and horse. Himalayan tahr had the highest presence in the SL diet (40%). Despite pika having the highest Relative Abundance Index (RAI), SL strongly preferred horses and avoided pika. Larger prey, such as horses, Himalayan tahr, and blue sheep, were highly preferred. Households with more livestock experienced higher depredation rates. Local attitudes toward SL conservation were generally positive, with an average score of 2.59. We recommend an integrated SL conservation plan in MCA, incorporating local participation, income diversification, and employment programs to mitigate conflicts and promote coexistence.
Intelligent Optimization Scheduling Strategy for Energy Consumption Reduction for Equipment in Open-Pit Mines Based on Enhanced Genetic Algorithm
Authors: Li Fudong , Shi Zonghao , Ding Weiqiang , Gan Yongjun
Published: December 2024

To achieve a rational allocation of real-time operational equipment, such as excavators and dump trucks, in open-pit mines, and thereby enhance truck–shovel coordination, this paper addresses the challenges posed by unreasonable on-site scheduling, which includes excessive truck waiting times and prolonged excavator boom-and-dipper operations. Ultimately, the paper aims to attain optimal truck–shovel coordination efficiency. To this end, we construct a scheduling optimization model, with the production capacities of trucks and shovels serving as constraints. The objective functions of this model focus on minimizing transportation costs, reducing truck waiting times, and shortening excavator boom-and-dipper operation durations. To solve this model, we have developed an improved genetic algorithm that integrates roulette wheel selection and elite preservation strategies. The experimental results of our algorithm demonstrate that it can provide a more refined operational equipment scheduling scheme, effectively decreasing truck transportation costs and enhancing equipment utilization efficiency in open-pit mines.
Research on the Application Potential of New Nano-Oil Displacement Agents to Improve Shale Oil Recovery Rates
Authors: He Haibo , Guo Jixiang , Wang Bo , Zhang Yuzhi , Lei Fan , Wang Tao , Zhang Tiantian , Wang Jing
Published: December 2024

To meet the demand for enhanced oil recovery in shale reservoirs and to improve the fluidity of shale oil while strengthening its imbibition effect, a multifunctional, thermally stable nanofluid agent, SDP-3, was synthesized using acrylamide (AM) and 2-acrylamido-2-methylpropanesulfonicacid (AMPS) as the primary raw materials. A series of characterizations and tests were conducted to evaluate its interfacial properties, stability, viscosity reduction performance, wettability, and imbibition-driven oil recovery capabilities. Furthermore, the mechanisms by which SDP-3 enhances the recovery of shale oil were analyzed. The results demonstrated that a mass concentration of 2% SDP-3 could reduce the oil–water interfacial tension to 0.071 mN/m. When the concentration increased to 2.0%, the interfacial tension further decreased to 0.071 mN/m, at which point the viscosity reduction rate for shale oil reached 92.02%, and the imbibition recovery rate was 36.57%. Microscopic observations revealed that SDP-3 could disperse shale oil into fibrous and spherical forms, effectively detaching the adhering shale oil from minute pores. This nanofluid agent not only exhibits excellent compatibility and stability but also achieves an ideal oil recovery effect while significantly improving recovery rates, showcasing its immense application potential in oilfield development.
The Impact of China’s Natural Forest Logging Ban on Chinese and International Timber Markets: A Counterfactual Analysis Based on Predicted Market Price
Authors: Diao Gang , Shang Di , Wang Donghai
Published: December 2024

China’s implementation of the Comprehensive Commercial Logging Ban in All Natural Forests is deemed as disrupting the stability of both Chinese and international timber markets and has raised widespread concerns about deforestation leakage on a global scale. Clarifying the impact of the logging ban on the Chinese and international timber markets is essential for formulating effective policies and taking collaborative actions to improve the stability of both timber markets and promote the sustainable development of global forest resources. This study examines the causal effects of the logging ban on Chinese and international timber markets by conducting a counterfactual analysis of Chinese domestic and imported timber prices with the synthetic control method. Unlike most previous studies that revealed significant price increases in both markets as a result of the logging ban, our results show that there are no significant causal effects between the logging ban and the price changes in Chinese and international timber markets. As China made extensive efforts in plantation cultivation and harvesting and substantially improved its domestic timber supply capacity, the logging ban has only produced a limited impact on the Chinese domestic timber market and has not disrupted the international timber market through trade. Therefore, China’s logging ban policy has not protected its own forest resources at the expense of deforestation in other countries, and it has provided a practical reference for the formulation of forest protection policies and sustainable forest management.
Leveraging Large Language Models for Enhanced Classification and Analysis: Fire Incidents Case Study
Authors: Alkhammash Eman H.
Published: December 2024

Fire detection and analysis have been a central focus of numerous studies due to their importance in potentially reducing fire’s harmful impact. Fire detection and classification using artificial intelligence (AI) methods have drawn significant attention in the literature. These methods often tackle certain aspects of fire, such as classifying fire versus non-fire images or detecting smoke or flames. However, these studies lack emphasis on integrating the capabilities of large language models for fire classification. This study explores the potential of large language models, especially ChatGPT-4, in fire classification tasks. In particular, we utilize ChatGPT-4 for the first time to develop a classification approach for fire incidents. We evaluate this approach using two benchmark datasets: the Forest Fire dataset and the DFAN dataset. The results indicate that ChatGPT has significant potential for timely fire classification, making it a promising tool to complement existing fire detection technologies. Furthermore, it has the capability to provide users with more thorough information about the type of burning objects and risk level. By integrating ChatGPT, detection systems can benefit from the rapid analysis capabilities of ChatGPT to enhance response times and improve accuracy. Additionally, its ability to provide context-rich information can support better decision-making during fire episodes, making the system more effective overall. The study also examines the limitations of using ChatGPT for classification tasks.
From Species to Varieties: How Modern Sequencing Technologies Are Shaping Medicinal Plant Identification
Authors: Wang Mingcheng , Lin Haifeng , Lin Hongqiang , Du Panyue , Zhang Shuqiao
Published: December 2024

Background/Objectives: Modern sequencing technologies have transformed the identification of medicinal plant species and varieties, overcoming the limitations of traditional morphological and chemical approaches. This review explores the key DNA-based techniques, including molecular markers, DNA barcoding, and high-throughput sequencing, and their contributions to enhancing the accuracy and reliability of plant identification. Additionally, the integration of multi-omics approaches is examined to provide a comprehensive understanding of medicinal plant identity. Methods: The literature search for this review was conducted across databases such as Google Scholar, Web of Science, and PubMed, using keywords related to plant taxonomy, genomics, and biotechnology. Inclusion criteria focused on peer-reviewed studies closely related to plant identification methods and techniques that contribute significantly to the field. Results: The review highlights that while sequencing technologies offer substantial improvements, challenges such as high costs, technical expertise, and the lack of standardized protocols remain barriers to widespread adoption. Potential solutions, including AI-driven data analysis and portable sequencers, are discussed. Conclusions: This review provides a comprehensive overview of molecular techniques, their transformative impact, and future perspectives for more accurate and efficient medicinal plant identification.
Novel LYST Variants Lead to Aberrant Splicing in a Patient with Chediak–Higashi Syndrome
Authors: Aleksenko Maxim , Vlasova Elena , Kieva Amina , Abasov Ruslan , Rodina Yulia , Maschan Michael , Shcherbina Anna , Raykina Elena
Published: December 2024

Background: The advent of next-generation sequencing (NGS) has revolutionized the analysis of genetic data, enabling rapid identification of pathogenic variants in patients with inborn errors of immunity (IEI). Sometimes, the use of NGS-based technologies is associated with challenges in the evaluation of the clinical significance of novel genetic variants. Methods: In silico prediction tools, such as SpliceAI neural network, are often used as a first-tier approach for the primary examination of genetic variants of uncertain clinical significance. Such tools allow us to parse through genetic data and emphasize potential splice-altering variants. Further variant assessment requires precise RNA assessment by agarose gel electrophoresis and/or cDNA Sanger sequencing. Results: We found two novel heterozygous variants in the coding region of the LYST gene (c.10104G>T, c.10894A>G) in an individual with a typical clinical presentation of Chediak–Higashi syndrome (CHS). The SpliceAI neural network predicted both variants as probably splice-altering. cDNA assessment by agarose gel electrophoresis revealed the presence of abnormally shortened splicing products in each variant’s case, and cDNA Sanger sequencing demonstrated that c.10104G>T and c.10894A>G substitutions resulted in a shortening of the 44 and 49 exons by 41 and 47 bp, respectively. Both mutations probably lead to a frameshift and the formation of a premature termination codon. This, in turn, may disrupt the structure and/or function of the LYST protein. Conclusions: We identified two novel variants in the LYST gene, predicted to be deleterious by the SpliceAI neural network. Agarose gel cDNA electrophoresis and cDNA Sanger sequencing allowed us to verify inappropriate splicing patterns and establish these variants as disease-causing.
Genome-Wide Identification and Analysis of the MYC Gene Family in Cotton: Evolution and Expression Profiles During Normal Growth and Stress Response
Authors: Chen Jingxi , Wang Long , Wang Xiufang , Lu Lu , Han Peng , Zhang Caidie , Han Min , Xiang Siyu , Wang Haibiao , Xuan Lizhong , Li Zhibo , Lin Hairong , Nie Xinhui , Wu Yuanlong
Published: December 2024

Background: The gene family of myelomatosis (MYC), serving as a transcription factor in the jasmonate (JA) signaling pathway, displays a significant level of conservation across diverse animal and plant species. Cotton is the most widely used plant for fiber production. Nevertheless, there is a paucity of literature reporting on the members of MYCs and how they respond to biotic stresses in cotton. Methods: Bioinformatics analysis was used to mine the MYC gene family in cotton based on InterPro, cottongen, etc. Results: The gene structure, conserved motifs, and upstream open reading frames of 32 GhMYCs in Gossypium hirsutum were identified. Moreover, it was anticipated that the GT1-motif is the most abundant in GhMYCs, indicating that the GT1-motif plays a significant role in light-responsive GhMYCs. The expression patterns of GhMYCs under biotic stresses including V. dahliae and Aphid gossypii were evaluated, suggesting that GhMYCs in class-1 and -3 GhMYCs, which function as negative regulators, are involved in resistance to verticillium wilt and aphids. The class-3 GhMYCs genes were found to be mostly expressed in female tissues. Interestingly, it was also determined that the homeologous expression bias within GhMYCs in cotton was uncovered, and results showed that the gene expression of class-1A and class-2 GhMYCs in the Dt sub-genome may have a direct impact on gene function. Conclusions: This study provides a research direction for researchers and breeders to enhance cotton traits through manipulating individual or multiple homeologs, which laid a foundation for further study of the molecular characteristics and biological functions of GhMYC gene.
Comparative Transcriptome Analysis of Gene Expression Between Female and Monoecious Spinacia oleracea L.
Authors: Zhao Yingjie , Liu Zhiyuan , She Hongbing , Xu Zhaosheng , Zhang Helong , Zheng Shaowen , Qian Wei
Published: December 2024

Background: Spinach (Spinacia oleracea L.) is an important leafy vegetable with dioecious and occasional monoecious plants. Monoecious lines are more suitable for hybrid production than dioecious lines due to their extended flowering period. However, genetic research on the sex determination of monoecism remains limited. Methods: In this study, RNA-seq analysis of monoecious and female spinach plants was performed at two distinct flowering stages. In total, we identified 4586 differentially expressed genes (DEGs), which were primarily involved in biological processes such as hormone signaling, cell wall biosynthesis, photosynthesis, and flower development, based on Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: Among these DEGs, 354 transcription factors, including 27 genes associated with the ABCDE gene, were discovered. Furthermore, a co-expression gene regulatory network was built, identifying nine key genes that play important roles in regulating sex differentiation between female and monoecious plants. Conclusions: Our findings provide crucial molecular insights into the mechanisms of monoecism in spinach and offer a scientific basis for future spinach breeding.
Genome-Wide Patterns of Homozygosity and Heterozygosity and Candidate Genes in Greek Insular and Mainland Native Goats
Authors: Tsartsianidou Valentina , Otapasidis Antonis , Papakostas Spiros , Karaiskou Nikoleta , Vouraki Sotiria , Triantafyllidis Alexandros
Published: December 2024

Background: Runs of homozygosity (ROHs) and heterozygosity (ROHets) serve for the identification of genomic regions as candidates of selection, local adaptation, and population history. Methods: The present study aimed to comprehensively explore the ROH and ROHet patterns and hotspots in Greek native dairy goats, Eghoria and Skopelos, genotyped with the Illumina Goat SNP50 BeadChip. SNP and functional enrichment analyses were conducted to further characterize hotspots and the candidate genes located within these genomic regions. Genetic relationships between and within breeds and inbreeding coefficients were also evaluated. Results: Clear genetic differentiation and diversified management practices were depicted between the two native populations. The ROH and ROHet average genome coverage for Skopelos (65.35 and 35 Mb) and Eghoria (47.64 and 43 Mb) indicated differences in mainland and insular goats, with Skopelos showing more long ROH fragments, reflecting its geographic isolation and small population size. An ROH hotspot (CHR12: 43.59–44.61 Mb) detected in the Skopelos population has been also reported across European goats and co-localizes with a selection signal detected in the Egyptian Barki goats and sheep adapted to hot–arid conditions. A novel ROH hotspot (CHR18: 60.12–61.81 Mb), shared among the Greek breeds, harbors candidate genes enriched in biosynthesis, metabolism, and immune response. Two well-conserved ROHet islands were detected in Greek goats on chromosomes 1 and 18, with genes participating in development and embryogenesis. The Eghoria population showed the highest number of ROHet islands, potentially reflecting its adaptability to diverse environments. Conclusions: These findings offer new insights into the environmental adaptation and artificial selection in Greek goats and could be utilized in future breeding strategies for sustainable goat farming.
Targeting CD200 in Breast Cancer: Opportunities and Challenges in Immunotherapeutic Strategies
Authors: Baek Sihyang , Cui Kui
Published: December 2024

One of the key factors that contribute to tumor progression and resistance is the immunosuppressive microenvironment of the tumor. CD200 is a recently identified cell surface glycoprotein recognized as an important molecule in breast cancer for its versatile modulation of the immune response via its receptor, CD200R. The interaction between CD200 and CD200R suppresses the immune activities against tumor cells and allows them to be undetected and, in doing so, to escape from the destructive capability of the immune cells. Here, we review recent advances and future trends in CD200-targeted therapies for cancer treatments. We also discuss molecular pathways that include variable expressions across different cancer types and their importance in treatment options.
Exploring the Inhibition of Toxoplasma gondii α-Carbonic Anhydrase by Sulfonamides: Insights into Potential Drug Targeting
Authors: Giovannuzzi Simone , De Luca Viviana , Capasso Clemente , Supuran Claudiu T.
Published: December 2024

Toxoplasma gondii, the causative agent of toxoplasmosis, is a protozoan parasite capable of infecting a wide range of hosts, posing significant health risks, particularly to immunocompromised individuals and congenital transmission. Current therapeutic options primarily target the active tachyzoite stage but are limited by issues such as toxicity and incomplete efficacy. As a result, there is an urgent need for alternative therapies that can selectively target parasite-specific mechanisms critical for metabolic processes and host–parasite interactions. In this context, α-carbonic anhydrase (Tg_CA), an enzyme essential for T. gondii survival has emerged as a promising drug target. Tg_CA was successfully expressed and purified to evaluate its susceptibility to sulfonamide-based inhibitors, represented by compounds 1–24 and the AAZ–HCT series. These inhibitors demonstrated a broad spectrum of activity, with KI values ranging from 17.8 to 8450 nM. Several compounds exhibited moderate to high potency against Tg_CA; however, concerns regarding selectivity arose because of the inhibition of human isoforms, particularly CA I and CA II. Thus, although some inhibitors showed strong activity against Tg_CA, optimizing selectivity remains crucial for minimizing off-target effects and improving therapeutic efficacy. Further structural modifications may enhance selectivity and advance the development of effective treatments for toxoplasmosis.
Hypoxia Regulates Brown Adipocyte Differentiation and Stimulates miR-210 by HIF-1α
Authors: Caca Jan , Bartelt Alexander , Egea Virginia
Published: December 2024

MicroRNAs (miRNAs) are short sequences of single-stranded non-coding RNAs that target messenger RNAs, leading to their repression or decay. Interestingly, miRNAs play a role in the cellular response to low oxygen levels, known as hypoxia, which is associated with reactive oxygen species and oxidative stress. However, the physiological implications of hypoxia-induced miRNAs (“hypoxamiRs”) remain largely unclear. Here, we investigate the role of miR-210 in brown adipocyte differentiation and thermogenesis. We treated the cells under sympathetic stimulation with hypoxia, CoCl2, or IOX2. To manipulate miR-210, we performed reverse transfection with antagomiRs. Adipocyte markers expression, lipid accumulation, lipolysis, and oxygen consumption were measured. Hypoxia hindered BAT differentiation and suppressed sympathetic stimulation. Hypoxia-induced HIF-1α stabilization increased miR-210 in brown adipocytes. Interestingly, miR-210-5p enhanced differentiation under normoxic conditions but was insufficient to rescue the inhibition of brown adipocyte differentiation under hypoxic conditions. Although adrenergic stimulation activated HIF-1α signaling and upregulated miR-210 expression, inhibition of miR-210-5p did not significantly influence UCP1 expression or oxygen consumption. In summary, hypoxia and adrenergic stimulation upregulated miR-210, which impacted brown adipocyte differentiation and thermogenesis. These findings offer new insights for the physiological role of hypoxamiRs in brown adipose tissue, which could aid in understanding oxidative stress and treatment of metabolic disorders.
The SOS Response Activation and the Risk of Antibiotic Resistance Enhancement in Proteus spp. Strains Exposed to Subinhibitory Concentrations of Ciprofloxacin
Authors: Zabłotni Agnieszka , Schmidt Marek , Siwińska Małgorzata
Published: December 2024

The widespread and inappropriate use of antibiotics, for therapeutic and prophylactic purposes, has contributed to a global crisis of rapidly increasing antimicrobial resistance of microorganisms. This resistance is often associated with elevated mutagenesis induced by the presence of antibiotics. Additionally, subinhibitory concentrations of antibiotics can trigger stress responses in bacteria, further exacerbating this problem. In the present study, we investigated the effect of low doses of ciprofloxacin on the induction of the SOS response and the subsequent development of antibiotic resistance in Proteus spp. strains. Our findings revealed an increase in mutation frequencies within the studied strains, accompanied by a significant upregulation of recA expression. These observations were consistent across experiments involving two subinhibitory concentrations of ciprofloxacin. To establish mutation frequencies and assess gene expression changes, we utilized the RifS-to-RifR forward mutagenesis assay and RT-qPCR analysis, respectively. Furthermore, employing the microdilution method, we demonstrated that these changes could promote cross-resistance to multiple classes of antibiotics in Proteus spp. clinical strains. This, combined with the recurrent nature of Proteus-associated infections, poses a substantial risk of therapeutic failure. In conclusion, exposure to low doses of ciprofloxacin can significantly impact the susceptibility of Proteus bacilli, not only reducing their sensitivity to ciprofloxacin itself but also fostering resistance to other antibiotic classes. These findings underscore the importance of cautious antibiotic use and highlight the potential consequences of subinhibitory antibiotic exposure in clinical and environmental settings.
Exceeding the Limits with Nutraceuticals: Looking Towards Parkinson’s Disease and Frailty
Authors: Montanari Martina , Mercuri Nicola Biagio , Martella Giuseppina
Published: December 2024

One of the most pressing challenges facing society today is the rising prevalence of physical and cognitive frailty. This geriatric condition makes older adults more vulnerable to disability, illness, and a heightened risk of mortality. In this scenario, Parkinson’s disease (PD) and geriatric frailty, which share several common characteristics, are becoming increasingly prevalent worldwide, underscoring the urgent need for innovative strategies. Nutraceuticals are naturally occurring bioactive compounds contained in foods, offering health benefits over and above essential nutrition. By examining the literature from the past decade, this review highlights how nutraceuticals can act as complementary therapies, addressing key processes, such as oxidative stress, inflammation, and neuroprotection. Notably, the antioxidant action of nutraceuticals appears particularly beneficial in regard to PD and geriatric frailty. For instance, antioxidant-rich nutraceuticals may mitigate the oxidative damage linked to levodopa therapy in PD, potentially reducing the side effects and enhancing treatment sustainability. Similarly, the antioxidant effects of nutraceuticals may amplify the benefits of physical activity, enhancing muscle function, cognitive health, and resilience, thereby reducing the risk of frailty. This review proposes a holistic approach integrating nutraceuticals with exercise, pharmacotherapy, and lifestyle adjustments. It promises to transform the management of ARD, prolong life, and improve the quality of life and well-being of older people.
Hypertension: A Continuing Public Healthcare Issue
Authors: Goorani Samaneh , Zangene Somaye , Imig John D.
Published: December 2024

Hypertension is a cardiovascular disease defined by an elevated systemic blood pressure. This devastating disease afflicts 30–40% of the adult population worldwide. The disease burden for hypertension is great, and it greatly increases the risk of cardiovascular morbidity and mortality. Unfortunately, there are a myriad of factors that result in an elevated blood pressure. These include genetic factors, a sedentary lifestyle, obesity, salt intake, aging, and stress. Although lifestyle modifications have had limited success, anti-hypertensive drugs have been moderately effective in lowering blood pressure. New approaches to control and treat hypertension include digital health tools and compounds that activate the angiotensin receptor type 2 (AT2), which can promote cardiovascular health. Nonetheless, research on hypertension and its management is vital for lessening the significant health and economic burden of this condition.
Prediction of Composite Clinical Outcomes for Childhood Neuroblastoma Using Multi-Omics Data and Machine Learning
Authors: Wang Panru , Zhang Junying
Published: December 2024

Neuroblastoma is a common malignant tumor in childhood that seriously endangers the health and lives of children, making it essential to find effective prognostic markers to accurately predict their clinical outcomes. The development of high-throughput technology in the biomedical field has made it possible to obtain multi-omics data, whose integration can compensate for missing or unreliable information in a single data source. In this study, we integrated clinical data and two omics data, i.e., gene expression and DNA methylation data, to study the prognosis of neuroblastoma. Since the features in omics data are redundant, it is crucial to conduct feature selection on them. We proposed a two-step feature selection (TSFS) method to quickly and accurately select the optimal features, where the first step aims at selecting candidate features and the second step is to remove redundant features among them using our proposed maximal association coefficient (MAC). Our goal is to predict composite clinical outcomes for neuroblastoma patients, i.e., their survival time and vital status at the last follow-up, which was validated to be two inter-correlated tasks. We conducted a series of experiments and evaluated the experimental results using accuracy and AUC (area under the ROC curve) evaluation metrics, which indicated that by the combination of the integration of the three types of data, our proposed TSFS method and a multi-task learning method can synergistically improve the reliability and accuracy of the prediction models.
Strategic Optimization of the Middle Domain IIIA in RBP-Albumin IIIA-IB Fusion Protein to Enhance Productivity and Thermostability
Authors: Sohn Myungho , Kim Sanggil , Jeong Hyeon Ju , Ko In Young , Moon Ji Wook , Lee Dowon , Oh Junseo
Published: December 2024

The protein therapeutics market, including antibody and fusion proteins, has experienced steady growth over the past decade, underscoring the importance of optimizing amino acid sequences. In our previous study, we developed a fusion protein, R31, which combines retinol-binding protein (RBP) with albumin domains IIIA and IB, linked by a sequence (AAAA), and includes an additional disulfide bond (N227C-V254C) in IIIA. This fusion protein effectively inhibited hepatic stellate cell activation. In this study, we further optimized the sequence. The G176K mutation at the C-terminus of RBP altered the initiation site of the first α-helix in domain IIIA, shifting it from P182 to K176, and promoted polar interactions between K176 and adjacent residues, enhancing the rigidity of the RBP/IIIA interface. The introduction of an additional disulfide bond (V231C/Y250C) connecting helices 3 and 4 in IIIA resulted in a three-fold increase in productivity and a 2 °C improvement in thermal stability compared to R31. Furthermore, combining the G176K mutation with V231C/Y250C further enhanced both productivity and anti-fibrotic activity. These findings suggest that the enhanced stability of domain IIIA, conferred by V231C/Y250C, along with the increased rigidity of the RBP/IIIA interface, optimizes interdomain distance and alignment, facilitating proper protein folding.
Lethal Arrhythmogenic Role of Left Ventricular Myocardial Interstitial Fibrosis in Apolipoprotein E/Low-Density Lipoprotein Receptor Double-Knockout Mice with Metabolic Dysfunction-Associated Steatohepatitis
Authors: Liu Jinyao , Oba Yumiko , Kondo Yosuke , Nakaki Ryo , Yamano Seiko
Published: December 2024

The combination of alcohol and a low-carbohydrate, high-protein, high-fat atherogenic diet (AD) increases the risk of lethal arrhythmias in apolipoprotein E/low-density lipoprotein receptor double-knockout (AL) mice with metabolic dysfunction-associated steatotic liver disease (MASLD). This study investigates whether left ventricular (LV) myocardial interstitial fibrosis (MIF), formed during the progression of metabolic dysfunction-associated steatohepatitis (MASH), contributes to this increased risk. Male AL mice were fed an AD with or without ethanol for 16 weeks, while age-matched AL and wild-type mice served as controls. Liver and heart tissues were analyzed, and susceptibility to lethal arrhythmias was assessed through histopathology, fluorescence immunohistochemistry, RNA-Seq, RT-PCR, and lethal arrhythmia-evoked test. Ethanol combined with an AD significantly induced LV MIF in MASH-affected AL mice, as shown by increased fibrosis-related gene expression, Sirius-Red staining, and elevated collagen 1a1 and 3a1 mRNA levels, alongside a higher incidence of lethal arrhythmias. Cardiac myofibroblasts exhibited sympathetic activation and produced elevated levels of fibrosis-promoting factors. This study highlights the role of cardiac myofibroblasts in LV MIF, contributing to an increased incidence of lethal arrhythmias in MASH-affected AL mice fed ethanol and AD, even after the alcohol was fully metabolized on the day of consumption.
Disrupting SARS-CoV-2 Spike Protein Activity: A Virtual Screening and Binding Assay Study
Authors: Queirós-Reis Luís , Alvites Rui , Maurício Ana Colette , Brancale Andrea , Bassetto Marcella , Mesquita João R.
Published: December 2024

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that emerged in late 2019 and rapidly spread worldwide, causing the COVID-19 pandemic. The spike glycoprotein (S protein) plays a crucial role in viral target recognition and entry by interacting with angiotensin, converting enzyme 2 (ACE2), the functional receptor for the virus, via its receptor binding domain (RBD). The RBD availability for this interaction can be influenced by external factors, such as fatty acids. Linoleic acid (LA), a free fatty acid, has been shown to bind the S protein, modulating the viral infection by reducing initial target recognition. LA interacts with the fatty acid binding pocket (FABP), a potential drug target against SARS-CoV-2. In this study, we aimed to exploit the FABP as a drug target by performing a docking-based virtual screening with a library of commercially available, drug-like compounds. The virtual hits identified were then assessed in in vitro assays for the inhibition of the virus–host interaction and cytotoxicity. Binding assays targeting the spike–ACE2 interaction identified multiple compounds with inhibitory activity and low cytotoxicity.
Special Issue “Effects of Dyslipidemia and Metabolic Syndrome on Cardiac and Vascular Dysfunction”
Authors: Chimenti Isotta , Cammisotto Vittoria
Published: December 2024

The global increase in dysmetabolic conditions such as hyperglycemia, insulin resistance, dyslipidemia, metabolic syndrome, and type 2 diabetes is becoming a significant healthcare concern [...]
The Walk of Guilt: Multimodal Deception Detection from Nonverbal Motion Behaviour
Authors: Alghowinem Sharifa , Caldwell Sabrina , Radwan Ibrahim , Wagner Michael , Gedeon Tom
Published: December 2024

Detecting deceptive behaviour for surveillance and border protection is critical for a country’s security. With the advancement of technology in relation to sensors and artificial intelligence, recognising deceptive behaviour could be performed automatically. Following the success of affective computing in emotion recognition from verbal and nonverbal cues, we aim to apply a similar concept for deception detection. Recognising deceptive behaviour has been attempted; however, only a few studies have analysed this behaviour from gait and body movement. This research involves a multimodal approach for deception detection from gait, where we fuse features extracted from body movement behaviours from a video signal, acoustic features from walking steps from an audio signal, and the dynamics of walking movement using an accelerometer sensor. Using the video recording of walking from the Whodunnit deception dataset, which contains 49 subjects performing scenarios that elicit deceptive behaviour, we conduct multimodal two-category (guilty/not guilty) subject-independent classification. The classification results obtained reached an accuracy of up to 88% through feature fusion, with an average of 60% from both single and multimodal signals. Analysing body movement using single modality showed that the visual signal had the highest performance followed by the accelerometer and acoustic signals. Several fusion techniques were explored, including early, late, and hybrid fusion, where hybrid fusion not only achieved the highest classification results, but also increased the confidence of the results. Moreover, using a systematic framework for selecting the most distinguishing features of guilty gait behaviour, we were able to interpret the performance of our models. From these baseline results, we can conclude that pattern recognition techniques could help in characterising deceptive behaviour, where future work will focus on exploring the tuning and enhancement of the results and techniques.
Phylogenetic and Comparative Genomics Study of Cephalopina titillator Based on Mitochondrial Genomes
Authors: Yao Huaibing , Ma Wanpeng , Su Zhanqiang , Yan Yuanyuan , Li Yang , Cui Weidong , Yang Jie , Zhan Faqiang , Hou Min
Published: December 2024

Camel bot fly (Cephalopina titillator) larvae cause myiasis in domesticated and wild camels, resulting in significant economic losses to the camel industry and posing a serious global public health concern. To date, only one mitochondrial genome (mitogenome) of C. titillator isolated from the Alxa Bactrian camel has been reported. Herein, C. titillator was isolated from the Junggar Bactrian camel to assemble a complete circular mitogenome with a length of 16,552 bp encoding 13 protein-coding genes, 22 tRNA genes, and two rRNA genes. The mitogenome showed a high A + T content (73.31%), positive AT-skew (0.12), and negative GC-skew (−0.34) base composition patterns. All protein-coding genes (PCGs) employed ATG, ATA, ATT, GTG, or TCG as the start codons and TAA, TAG, or single T as the stop codons. Similar to other parasites in the Oestridae subfamily, the mitogenome was structurally conserved, with genes retaining the same order and direction as those in the ancestral insect mitogenome. The phylogenetic analysis clustered this species with the Oestrinae, showing that the subfamily did not exhibit monophyly. C. titillator isolated from the Junggar Bactrian camel was found to be a sister lineage to that isolated from the Alxa Bactrian camel. Despite the lack of data on the mitogenome of C. titillator isolated from dromedaries in the Middle East, phylogenetic analysis of C. titillator isolated from Xinjiang revealed one distinct lineage of the Xinjiang camel nasal bot fly. In conclusion, this study reports the complete mitogenome of Xinjiang C. titillator for the first time, providing valuable data for future studies on the phylogenetic relationships in this subfamily.
Bioconversion of Poultry Litter into Insect Meal and Organic Frasstilizer Using Black Soldier Fly Larvae as a Circular Economy Model for the Poultry Industry: A Review
Authors: Kullan Anand Raj Kumar , Suresh Arumuganainar , Choi Hong Lim , Gabriel Neumann Elke , Hassan Fatima
Published: December 2024

Poultry litter waste management poses a significant global challenge, attributed to its characteristics (odorous, organic, pathogenic, attracting flies). Conventional approaches to managing poultry litter involve composting, biogas generation, or direct field application. Recently, there has been a surge of interest in a novel technology that involves the bioconversion of organic waste utilizing insects (known as entomoremediation), particularly focusing on black soldier fly larvae (BSFL), and has demonstrated successful transformation of various organic waste materials into insect meal and frass (referred to as organic frasstilizer). Black soldier flies have the capacity to consume any organic waste material (ranging from livestock litter, food scraps, fruit and vegetable residues, sewage, sludge, municipal solid waste, carcasses, and defatted seed meal) and convert it into valuable BSFL insect meal (suitable for animal feed) and frass (serving as an organic fertilizer). The bioconversion of poultry litter by black soldier flies offers numerous advantages over traditional methods, notably in terms of reduced land and water requirements, lower emissions, cost-effectiveness, swift processing, and the production of both animal feeds and organic fertilizers. This review focuses on the existing knowledge of BSFL, their potential in bioconverting poultry litter into BSFL meal and frass, and the utilization of BSFL in poultry nutrition, emphasizing the necessity for further innovation to enhance this sustainable circular economy approach.
The Use of Novel Alginate Capsules in a Monitoring System for Drosophila suzukii in a Cherry Orchard in the Region of La Araucanía, Chile
Authors: Lizama Marcelo , Alves-Santos Fernando Manuel , Navas-Gracia Luis Manuel , Martínez-Cisterna Daniel , Medina Cristian , Rebolledo Ramón , Chacón-Fuentes Manuel , Bardehle Leonardo
Published: December 2024

Spotted wing drosophila (SWD) is a pest that causes damage due to the female laying eggs under the skin of ripe fruit, from which a larva emerges, causing its collapse and reducing its commercial value. Due to the importance of this pest, monitoring its population is the starting point for any control program; however, there is no early monitoring plan within management tasks, nor are there studies on behavior, the optimization of traps, or their baits. This research proposes the evaluation of a monitoring system with encapsulated baits and adhesive traps that allow effective control. The encapsulated bait was selected after evaluating three options in olfactometric tests in the laboratory; the most attractive bait was WVM, with 70% of visits to the stimulus and 30% to its control, unlike SAG I and SAG II, whose values did not exceed 40% attraction. Among the expected results is the availability of a new format of attractive bait for SWD with a better release rate over time, and the information obtained will allow the generation of SWD population curves for the area, which is essential for decision-making. This study will contribute from the perspective of nanomaterials, insect biology, agricultural entomology, and pest monitoring.
The Different Paths That Lead to Hypotonic Hyponatremia, and a Safe Approach to Treatment
Authors: Imbriano Louis J. , Grant Candace , Masani Naveed
Published: December 2024

A knowledge gap may exist when attempting to identify the pathogenetic mechanisms resulting in the syndrome of inappropriate antidiuretic hormone (SIADH) or hypotonic hyponatremia. Ectopic secretion of antidiuretic hormone [ADH] is the classic cause of SIADH. But another form of inappropriate secretion of ADH occurs when interleukin 6 is activated. Hypotonic hyponatremia can also occur in patients with cerebral salt wasting, but the secretion of ADH is appropriate, responding to volume depletion induced by excessive natriuresis. Reset osmostat (RO) is another cause of hypotonic hyponatremia caused by an unknown anomaly in the hypothalamus. This review discusses the pathophysiology of and the identical laboratory findings found in classic ectopic ADH secretion, interleukin 6-mediated ADH secretion, cerebral salt wasting-induced ADH secretion, and RO. This review also discusses potential methods to discern which hypotonic hyponatremic syndrome is present and current recommendations for treatment.
Proximal Femur Fractures: Evaluating the Necessity of On-Call Surgery
Authors: Ketter Vanessa , Korschinsky Antonius , Bökeler Ulf , Aigner Rene , Bücking Benjamin , Eschbach Daphne Asimenia , Rascher Katherine , Ruchholtz Steffen , Knauf Tom
Published: December 2024

Background: The decision of the Joint Federal Committee on the treatment of hip fractures stipulates that proximal femur fractures must be treated within the first 24 h. This leads to organizational and personnel difficulties in day-to-day care. Therefore, we investigated the question at what times of day we operate to maintain this timeline and whether there is a difference in the outcome for the patients according to treatment hours. Methods: Data from the DGU’s “AltersTraumaRegister” from 2016 to 2020 were analyzed. For the analysis, the patients were divided into seven cohorts depending on the time of surgery. Pre-operative, operative, and follow-up data were analyzed. Results: A total of 29,470 patients were included in our study. The results showed that 74% of patients were treated within 24 h. 72% of patients operated on between 0–7 h had pertrochanteric fractures, while 56% of all arthroplasties were performed during normal working hours. In supra-regional trauma centers, significantly fewer operations were performed during normal working hours, while significantly more surgeries were carried out in the late evening and at night (p < 0.001). There were no significant differences in mortality and morbidity between the individual groups. Conclusions: Although we manage to treat most patients within 24 h, only 46% of patients are operated on within normal working hours. In terms of the outcome parameters, this does not appear to be a disadvantage for the patients. Nevertheless, night work and fatigue affect concentration and post-operative results in many areas, as we know. Consequently, patient care during normal working hours within 24 h creates the best possible initial situation for the patient, as significantly more personnel resources are available during normal working hours. The aim should be to create the logistical and personnel requirements for this.