bluuebunny/crossref_metadata_2025 huggingface dataset:
Inherited Dyslipidemic Splenomegaly: A Genetic Macrophage Storage Disorder Caused by Disruptive Apolipoprotein E (APOE) Variants
Authors: Ferreira Elise A. , Oud Machteld M. , van der Crabben Saskia N. , Versloot Miranda , Goorden Susan M. I. , van Karnebeek Clara D. M. , Kroon Jeffrey , Langeveld Mirjam
Published: February 2025

Background: Persistent splenomegaly, often an incidental finding, can originate from a number of inherited metabolic disorders (IMDs). Variants of APOE are primarily known as risk factors in terms of cardiovascular disease; however, severe dysfunction of APOE can result in a disease phenotype with considerable overlap with lysosomal storage disorders (LSDs), including splenomegaly and gross elevation of N-palmitoyl-O-phosphocholine-serine (PPCS). Methods: A case study (deep phenotyping, genetic and FACS analysis) and literature study was conducted. Results: The index patient, with a family history of early-onset cardiovascular disease, presented with splenic infarctions in a grossly enlarged spleen. The identified genetic cause was homozygosity for two APOE variants (c.604C>T, p.(Arg202Cys) and c.512G>A, p.(Gly171Asp); ε1/ε1), resulting in a macrophage storage phenotype resembling an LSD that was also present in the brother of the index patient. A FACS analysis of the circulating monocytes showed increased lipid content and the expression of activation markers (CD11b, CCR2, CD36). This activated state enhances lipoprotein intake, which eventually converts these monocytes/macrophages into foam cells, accumulating in tissues (e.g., spleen and vascular wall). A literature search identified seven individuals with splenomegaly caused by APOE variants (deletion of leucine at position 167). The combined data from all patients identified male gender, splenectomy and obesity as potential modifiers determining the severity of the phenotype (i.e., degree of triglyceride increase in plasma and/or spleen size). Symptoms are (partially) reversible by lipid-lowering medication and energy restricted diets and splenectomy is contra-indicated. Conclusions: Inherited dyslipidemic splenomegaly caused by disruptive APOE variants should be included in the differential diagnoses of unexplained splenomegaly with abnormal lipid profiles. A plasma lipid profile consistent with dysbetalipoproteinemia is a diagnostic biomarker for this IMD.
The Emerging Role of MicroRNAs in Nasal Inflammatory Diseases and Tumors: From Bench to Bedside
Authors: Loperfido Antonella , Cavaliere Carlo , Fionda Bruno , Masieri Simonetta , Bellocchi Gianluca , Re Massimo , Tomasetti Marco
Published: February 2025

Background/Objectives: MicroRNAs (miRNAs) play a crucial role in regulating immune responses and have been implicated in the pathogenesis of various nasal diseases, including chronic rhinosinusitis (CRS), allergic rhinitis (AR), and sinonasal tumors. This review comprehensively explores the emerging role of miRNAs in inflammatory and oncological nasal diseases, highlighting their diagnostic, prognostic, and therapeutic potential. Methods: A comprehensive review of the literature was conducted to summarize current findings on miRNA expression in nasal inflammatory conditions and tumors. Key studies evaluating miRNA-mediated regulatory mechanisms, potential biomarker applications, and therapeutic approaches were analyzed. Results: Altered miRNA expression profiles contribute to the pathogenesis of CRS, AR, and sinonasal tumors. Specific miRNAs, such as miR-125b and miR-155 are upregulated in CRS and AR, promoting inflammation and tissue remodeling. In sinonasal tumors, dysregulated miRNAs, including miR-126 and miR-34/miR-449 clusters, influence tumor progression and therapeutic response. Exosome-mediated miRNA delivery emerges as a promising avenue for precision medicine, offering novel strategies for miRNA-based diagnostics and therapies. Conclusions: miRNAs are key regulators of nasal diseases, with potential applications in non-invasive diagnostics and targeted therapies. Further research into miRNA-based interventions may improve treatment outcomes and contribute to the development of personalized medicine approaches for nasal inflammatory disorders and malignancies.
Functional Genomics of Legumes in Bulgaria—Advances and Future Perspectives
Authors: Revalska Miglena , Radkova Mariana , Zhiponova Miroslava , Vassileva Valya , Iantcheva Anelia
Published: February 2025

Members of the Leguminosae family are important crops that provide food, animal feed and vegetable oils. Legumes make a substantial contribution to sustainable agriculture and the nitrogen cycle through their unique ability to fix atmospheric nitrogen in agricultural ecosystems. Over the past three decades, Medicago truncatula and Lotus japonicus have emerged as model plants for genomic and physiological research in legumes. The advancement of innovative molecular and genetic tools, particularly insertional mutagenesis using the retrotransposon Tnt1, has facilitated the development of extensive mutant collections and enabled precise gene tagging in plants for the identification of key symbiotic and developmental genes. Building on these resources, twelve years ago, our research team initiated the establishment of a platform for functional genomic studies of legumes in Bulgaria. In the framework of this initiative, we conducted systematic sequencing of selected mutant lines and identified genes involved in plant growth and development for detailed functional characterization. This review summarizes our findings on the functions of selected genes involved in the growth and development of the model species, discusses the molecular mechanisms underlying important developmental processes and examines the potential for the translation of this fundamental knowledge to improve commercially important legume crops in Bulgaria and globally.
Treat to Target in Gout Management: A Critical Reappraisal of Current Strategies
Authors: Moses Anusha , Voshaar Martijn Oude , Laar Mart van de , Jansen Tim L. Th.
Published: February 2025

Gout management strategies remain a topic of debate, particularly regarding the efficacy of treat-to-target (T2T) and treat-to-avoid-symptoms (T2S) approaches. T2T, endorsed by major rheumatology societies, involves systematic serum urate (sUA) monitoring and urate-lowering therapy (ULT) dose escalation to maintain sUA below a predefined threshold. In contrast, T2S, which focuses on symptom relief rather than routine sUA monitoring, is supported by alternative guidelines. Despite the widespread adoption of T2T in other chronic diseases, its clinical benefits beyond biochemical parameters, such as serum urate reduction, remain uncertain in gout. This study evaluates current evidence on T2T and T2S, analyzing data from a pragmatic multicenter trial comparing both strategies. Findings suggest that while T2T is effective in reducing sUA levels, its superiority in preventing flares and improving patient-reported outcomes remains inconclusive. Some studies report reduced tophus burden and better adherence with T2T, whereas others find negligible differences in pain relief and functional improvement between the two strategies. The lack of high-quality comparative trials underscores the need for further investigation. Future research should prioritize long-term, patient-centered outcomes and pragmatic implementation strategies.
Exploring the Role of Voice Assistants in Managing Noncommunicable Diseases: A Systematic Review on Clinical, Behavioral Outcomes, Quality of Life, and User Experiences
Authors: Bramanti Alessia , Corallo Angelo , Clemente Gennaro , Greco Luca , Garofano Marina , Giordano Massimo , Pascarelli Claudio , Mitrano Gianvito , Di Palo Maria Pia , Di Spirito Federica , Amato Massimo , Bartolomeo Marianna , Del Sorbo Rosaria , Ciccarelli Michele , Bramanti Placido , Ritrovato Pierluigi
Published: February 2025

Background: Non-communicable diseases (NCDs) represent a leading cause of global mortality, demanding innovative approaches to management. Voice assistants (VAs) have emerged as promising tools in healthcare, offering support for self-management, behavioral engagement, and patient care. This systematic review evaluates the role of VAs in NCD management, analyzing their impact on clinical and behavioral outcomes, quality of life, usability, and user experiences while identifying barriers to their adoption. Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science from January 2014 to October 2024. Studies were selected based on predefined inclusion and exclusion criteria using the PRISMA guidelines. Data extraction focused on outcomes such as usability, acceptability, adherence, clinical metrics, and quality of life. The risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2 and ROBINS-I tools. Results: Eight studies involving 541 participants were included, examining VAs across various NCD contexts such as diabetes, cardiovascular diseases, and mental health. While VAs demonstrated good usability and moderate adherence, their clinical and quality-of-life outcomes were modest. Behavioral improvements, such as increased physical activity and problem-solving skills, were noted in some interventions. Key challenges included privacy concerns, speech recognition errors, and accessibility issues. Conclusions: VAs show potential as supportive tools in NCD management, especially for enhancing patient engagement and self-management, and their impact on clinical outcomes and long-term usability requires further investigation. Future research should focus on diverse populations, standardized metrics, and comparative studies with alternative technologies.
Symptoms of Mental Health Conditions and Their Predictors Among U.S. Adults During the First Year of the COVID-19 Pandemic
Authors: Boyle John , Dayton James , ZuWallack Randy , Iachan Ronaldo , Krugipudi Deborah , Blanco Caitlin Flouton
Published: February 2025

Background/Objectives: This study examined the impact of the COVID-19 pandemic on mental health among U.S. adults during its first year, using monthly surveys from March to November 2020. Methods: The primary outcome was the Patient Health Questionnaire four-item (PHQ-4) measure of anxiety and depressive symptoms. Univarite and bivariate analyses were used to provide foundational understanding of key variables. Parametric and non-parametric correlation analyses were conducted to observe the relationship between COVID-19 impacts or risk factors and the frequency of anxiety/depressive symptoms. A series of regression models were fit to assess the impact of pandemic stressors on PHQ-4 scores. Results: There was a statistically significant increase in mean PHQ-4 scores and the proportion of respondents with moderate to severe symptoms (PHQ-4 = 6+) between March–June and July–November 2020. Factors such as fear of contracting the virus, health concerns, and lifestyle disruptions had statistically significant impacts on mental health outcomes; however, these effects were more modest than estimates reported elsewhere. Financial strain, particularly among lower-income households and those experiencing job loss, showed stronger associations with increased anxiety and depressive symptoms, but the overall impact on population-level mental health was limited due to the small proportion severely affected financially. Using regression models, we found that demographic factors and pandemic stressors collectively explained about 21% of the variance in anxiety and depressive symptoms. Conclusions: This study provides a nuanced understanding of the pandemic’s mental health impact, suggesting that while certain subgroups were more affected, the overall population level increase in anxiety and depression was less pronounced than previously assumed.
Risk of Incident Post-Transplantation Diabetes Mellitus After Solid Organ Transplantation in Taiwan: A Population-Based Cohort Study
Authors: Tai Chih-Jaan , Huang Kuang-Hua , Wang Jiun-Yi , Gau Shuo-Yan , Huang Shiang-Wen , Su Kun-Yu , Tsai Tung-Han , Wu Chun-Nan , Lee Chien-Ying
Published: February 2025

Background: Solid organ transplant (SOT) recipients have an elevated risk of diabetes mellitus (DM). This study investigated the risk of posttransplant DM (PTDM) in a retrospective cohort study. Methods: We analyzed patients aged over 18 years who received an SOT between 2002 and 2013. Each patient was matched with four control individuals by age, sex, insured salary, urbanization level, Charlson’s comorbidity index (CCI), and year of inclusion in the study. After matching, the study comprised 6874 patients who underwent an SOT and 27,496 matched general patients as the comparison. The risk of DM among the SOT recipients was assessed using a Cox proportional hazards model after adjustment for all relevant variables. Results: The SOT cohort had a significantly higher risk of DM than general patients (adjusted hazard ratio [aHR], 1.61; 95% confidence interval [CI], 1.51–1.72). Kidney and liver recipients, respectively, had DM incidence rates 1.57 (95% CI, 1.46–1.70) and 1.73 (95% CI, 1.53–1.94) times that of the general patients. Conclusions: SOT recipients had an elevated risk of DM. Among various organ recipients, liver recipients had the highest PTDM risk. Kidney and liver recipients demonstrated the highest DM risk at 6 months after their SOT. The risk of PTDM following an SOT may result in long-term consequences. Hence, we advise the critical need for proper management to mitigate related complications after transplantation.
Footwear Choice and Locomotor Health Throughout the Life Course: A Critical Review
Authors: D’Août Kristiaan , Elnaggar Omar , Mason Lyndon , Rowlatt Adam , Willems Catherine
Published: February 2025

Background/objectives: In this paper, we review and discuss epidemiological and experimental evidence on the effects of daily footwear on gait and life-long health. We consider different types of footwear, including “minimal shoes”, and their design features, comparing them to barefoot walking, with a focus on overall gait and the function of the heel pad. Methods: Narrative review. Results: We find little evidence for health benefits of most typical shoe design features (e.g., cushioning, raised heels or arch support) for normal walking in healthy individuals, and in several cases (e.g., high heels), there is evidence of detrimental health effects. Conclusions: Based on currently available evidence, we recommend minimal footwear as the default for the general population to stimulate healthy biomechanical aging, with other types of footwear used infrequently or when there is an individual or clinical need.
Obesity Among Healthcare Workers in Al Ahsa, Saudi Arabia: Prevalence, Predictors, and Workplace Health Implications
Authors: Hassanein Salwa , Al Khatib Alissar , AlMoosa Omayma , Abdrbo Amany
Published: February 2025

Background/Objectives: Obesity is an emerging public health problem in the world, and health professionals are most likely to be exposed to several occupational determinants thereof. These include long working hours, shift work, high job stress, irregular food intake, poor opportunities for healthy eating, and physical inactivity at work. Healthcare workers’ stressful jobs typically lead to poor eating habits and less opportunity for physical exercise, contributing to obesity risk. The primary objective of this study is to determine the prevalence of obesity among healthcare employees and identify unique predictors that contribute to obesity in this population. Material and Methods: Data were collected between 2021 and 2023 from 557 participants through anthropometric measurement and a structured questionnaire using a stratified random sampling technique. Results: The study found that 18.6% of participants were classified as obese or morbidly obese (12.9% and 5.7%, respectively), while 33.8% were overweight. The strong predictors of obesity included older age (>30 years, AOR = 2.404, p < 0.001) and working in nursing services (AOR = 1.999, p = 0.003). Furthermore, 34.3% of respondents had no physical activity, 71.5% slept less than 8 h per day, and 58.5% consumed fast food one to two times per week. A significant association of obesity was found with gender (p < 0.001), females being at higher risk, and type of department (p = 0.002), nursing staff being at higher risk. However, the predictable factors for obesity did not include nationality, family size, hours of TV watching, and fast-food consumption. Conclusions: These findings highlight a significant burden of obesity among healthcare employees, underscoring the need for workplace interventions. The strategy to address obesity among this highly vulnerable population should be directed toward enhancing physical activities, improving eating habits, and managing occupational stress, particularly for older workers and nursing staff.
Plant Growth-Promoting Microbes for Resilient Farming Systems: Mitigating Environmental Stressors and Boosting Crops Productivity—A Review
Authors: Ansabayeva Assiya , Makhambetov Murat , Rebouh Nazih Y. , Abdelkader Mostafa , Saudy Hani S. , Hassan Karim M. , Nasser Mohamed A. , Ali Mahmoud A. A. , Ebrahim Mohamed
Published: February 2025

This review delves into the role of plant growth-promoting microbes (PGPMs) in sustainable agriculture by enhancing soil health, improving plant stress tolerance, and controlling diseases. PGPMs, which include bacteria, fungi, and other microorganisms, are increasingly recognized as important contributors to promoting eco-friendly agricultural practices. Their ability to improve nutrient availability, stimulate plant growth, and protect crops from environmental stressors makes them a cornerstone for resilient and efficient farming systems. By reducing dependency on synthetic fertilizers and pesticides, PGPMs play a vital role in preserving environmental resources, minimizing greenhouse gas (GHG) emissions, and combating climate change’s negative impacts. This article thoroughly explores the complex interactions between PGPMs, soil nutrients, plant pathogens, and abiotic stressors. It also examines how these interactions influence phytohormone production and signaling pathways, ultimately impacting crop growth and development. Furthermore, this review discusses how PGPMs enhance nutrient uptake, modulate plant immune responses, and improve stress resilience, offering a holistic understanding of their multifaceted contributions to farming. By synthesizing current research and highlighting future directions, this review underscores the potential of PGPMs to revolutionize agricultural activities, ensuring food security and environmental sustainability in the face of global challenges.
Genome-Wide Identification of the SmHD-zip Genes That Respond to Multiple Ripening-Related Signals in Eggplant Fruit
Authors: Jiang Caiqian , Mo Yunrong , Zhang Haoran , Chen Kaiyun , Zhou Ying , Ma Zushuai , Jing Yuhao , Liu Yu , Wang Yanyan , Zhao Kai
Published: February 2025

The homeodomain–leucine zipper (HD-zip) gene family plays a crucial role in plant development and stress responses. However, systematic identification studies of this gene family in eggplant are still lacking. In this study, we systematically identified 44 HD-zip genes in the eggplant genome database using bioinformatics methods and analyzed their expression levels under light and multiple hormones by RT-qPCR. The results show that members of the SmHD-zip gene family were classified into four groups (HD-zip I, II, III, and IV) based on the phylogenetic relationship. Cis-acting elements related to plant development, hormones, and stress were identified in the promoter regions of the SmHD-zip gene family. Furthermore, the expression of the SmHDZ2 gene was upregulated during the fruit development stage, while nine SmHD-zip genes exhibited downregulated expression patterns. Notably, some SmHD-zip genes were identified as key regulators of eggplant responses to light and multiple hormone signals. Overall, these findings not only provide valuable insights into the evolutionary and functional characteristics of eggplant HD-Zips but also suggest that HD-zip genes likely play a significant role in regulating fruit development and ripening by integrating light and multiple hormone signaling pathways. Therefore, this study laid the foundation for further research on eggplant quality.
Emotional Eating and Its Relationship with Symptoms of Anxiety, Depression, and Stress During the COVID-19 Pandemic: A Multicenter Study in College Students
Authors: Silva Isabela , Meireles Adriana Lúcia , Chagas Carolina Martins dos Santos , Cardoso Clareci Silva , Oliveira Helian Nunes de , Freitas Eulilian Dias de , Vidigal Fernanda de Carvalho , Nobre Luciana Neri , Silva Luciana Saraiva da , Paula Waléria de , Ferreira Lívia Garcia
Published: February 2025

Emotional eating refers to overeating triggered by negative emotions, and it is common among those with mental health challenges. Academics are vulnerable to changes in eating habits and mental well-being, especially after the pandemic began. This study aimed to analyze the relationship between emotional eating and the signs and symptoms of mental disorders in undergraduates aged 18 and older. They completed a virtual questionnaire assessing emotional eating using the Three-Factor Eating Questionnaire, and mental health by a reduced version of the Depression Anxiety and Stress Scale. In this cross-sectional, multicenter survey, 8650 students (65.7% female, average age 22) participated, with a median body mass index of 23.3 kg/m2, and 23.8% were enrolled in health-related courses. The median emotional eating score was 44.4 (22.2–66.7), and a large proportion had symptoms of depression (73.2%), stress (68.1%), and anxiety (66.1%). Symptoms of anxiety (CI = 1.291–1.714), depression (CI = 1.469–1.983), and stress (CI = 1.483–2.006) were independently associated with higher emotional eating scores (≥66.7) in multiple regression analyses. Based on the significant associations found, the importance of integrating mental health support and intervention strategies, such as psychological counseling and nutritional guidance, to mitigate emotional eating among university students is highlighted, along with the need for future studies to explore the causal relationships.
Exploring Financial Challenges and University Support Systems for Student Financial Well-Being: A Scoping Review
Authors: Russell Joanna , Austin Kylie , Charlton Karen E. , Igwe Ezinne O. , Kent Katherine , Lambert Kelly , O’Flynn Gabrielle , Probst Yasmine , Walton Karen , McMahon Anne T.
Published: February 2025

Background/Objectives: Financial stress among university students has been widely documented, impacting academic performance, mental health, and overall well-being. This scoping review explores and synthesizes the existing evidence on the extent and impact of financial challenges experienced by university students in Australia and New Zealand and examines approaches implemented by universities in these countries to address these challenges. Methods: The Arksey and O’Malley framework was utilized for comprehensiveness, structure, and reproducibility. Four scientific databases (Scopus, ProQuest, Web of Science, and Informit) were searched until 30 June 2024, and 3542 articles were identified. Following extensive screening, 19 studies were included. The studies were summarized using a narrative synthesis approach. Results: This review suggests that financial stress continues to be experienced by Australian/New Zealand university students. Some studies indicate that over half (8–68%) of students face significant financial issues and 96% of students report high emotional stress. Some groups are more vulnerable than others. Notably, students from low socio-economic status (SES) backgrounds and international students have increased vulnerability due to factors such as inadequate financial support and limited access to job opportunities and support services. Support services available for students included emergency grants, food pantries (including international students), and community gardens but with limited impact in addressing underlying financial hardships. Conclusion: This review highlights the persistent financial challenges faced by vulnerable university students in Australia and New Zealand. It calls for comprehensive strategies to enhance support services and address structural issues in government and institutional policies. Addressing these needs will enable improved student academic success and mental and physical well-being in these vulnerable groups.
Assessing Motivations and Channels for Nutritional Information Verification in Spanish University Communities
Authors: Von-Polheim Paula , Moreno-Castro Carolina
Published: February 2025

This research analyses the results obtained from a survey performed on the nutritional and eating habits of Spanish university communities (students, faculty and administrative staff), involving four multiple-choice questions which determine the respondents’ level of interest in dietary topics. The study sample comprised 124 respondents from three Spanish universities: Complutense University of Madrid, University of Valencia and University of Malaga. The statistical software program R was used to conduct both analyses (quantitative and qualitative), using frequencies and percentages for the multiple-choice questions. The main results reveal that the respondents’ level of interest and motivations were decisive when deciding on whether to verify nutritional information or not. The use of different verification platforms underscores the urgent need for reliable sources and educational intervention in nutrition fields.
New Quality Productivity of Agriculture and Rural Areas at the Provincial Scale in China: Indicator Construction and Spatiotemporal Evolution
Authors: Cao Xiangyang , Lei Jiahui , Shi Donghui , Yu Wenlong , Tao Tianhui , Zhang Xun , Wang An
Published: February 2025

New quality productivity in agriculture and rural areas serves as a critical foundation for addressing the development needs of the times, advancing the comprehensive revitalization of rural regions, and overcoming the urban–rural dual structure. This paper studies the spatial changes and evolutionary trends of new quality productivity in agriculture and rural areas in 31 provinces of mainland China. The main conclusions are as follows: (1) At the provincial level, the development of China’s new quality productivity exhibits a spatial gradient, with a decreasing trend from east to west. (2) At the national scale, while significant spatial autocorrelation exists in the new quality productivity of agriculture and rural areas, internal disparities are gradually narrowing. (3) The eastern region demonstrates significant advantages, the central region is making steady progress, the western region is rapidly catching up, and the northeastern region faces increasingly significant development pressures. This paper extends the research boundary of new quality productivity to the field of agriculture and rural areas, and we introduce a variety of spatial analysis methods to depict its distribution characteristics.
Genome-Wide Identification and Expression Profiling of the Invertase Genes Involved in Sugar Metabolism and Accumulation in Actinidia arguta
Authors: Qiang Xu , Ren Ting , Zhang Ying , Jia Yun
Published: February 2025

Invertase (INV, EC3.2.1.26) is widely recognized as an indispensable enzyme for catalyzing sucrose degradation and plays a central role in plant growth as well as fruit quality improvement. However, no systematic study has been performed in kiwifruit. Here, we identified 102 AaINV genes in the Actinidia arguta “M1” genome. Their physical and chemical properties, subcellular localizations, phylogenetic relationships and expression profiles were characterized. Phylogenetic analysis showed that the INV members were clustered into three groups (vacuole invertases (VINVs) and cell wall invertases (CWINVs) in Group I, alkaline/neutral invertase (NINVs) in Group II and Group III), demonstrating evolutionary conservation in the INV family across Arabidopsis and Actinidia species. Gene replication analysis revealed that many AaINV genes were derived from gene duplication events. Molecular evolution analysis based on Ka/Ks ratios indicated that the INV members have experienced extensive purifying selection during evolution. To explore the potential gene functions, we integrated RNA-seq and metabolomics to analyze AaINV gene expression patterns and sugar accumulation in three A. arguta varieties (“Kukuwa”, “Qinhuang”, “Xianziguang”), respectively. The expression analysis of the 102 genes showed that the expression patterns varied among the three kiwifruit varieties at fruit maturity stage. The expression levels of AaINVs were also investigated via qRT-PCR in these varieties. Specifically, we constructed a complex regulatory network that regulates sugar metabolism in kiwifruit based on the correlation between 42 AaINV genes and 14 sugar metabolites. These findings provide insights into physiological functions of AaINVs in kiwifruit, especially roles in governing sugars accumulation in fruits.
ZmCaM2-1, a Calmodulin Gene, Negatively Regulates Drought Tolerance in Transgenic Arabidopsis Through the ABA-Independent Pathway
Authors: Wu Zhiqiang , Liu Meiyi , Wang Hanqiao , Li Mingrui , Liu Xiaoyue , Zang Zhenyuan , Jiang Liangyu
Published: February 2025

Calmodulin (CaM) family members play crucial roles in the response to various abiotic stresses. However, the functions of CaMs in the response to drought stress in maize are unclear. In this study, a CaM gene, ZmCaM2-1, was isolated from the maize (Zea mays L.) inbred line B73. The coding sequence (CDS) of ZmCaM2-1 was 450 bp with a protein of 149 aa which contains four EF-hand motifs. The ZmCaM2-1 protein was located in the cell nucleus and membrane, and is able to bind to Ca2+. ZmCaM2-1 was strongly induced by drought, NaCl, and low-temperature treatments, except for abscisic acid (ABA) treatment. Overexpression of ZmCaM2-1 in Arabidopsis was found to decrease the drought tolerance with lower antioxidant enzyme activity and greater reactive oxygen species (ROS) production. Moreover, there was no significant difference in the phenotype and ABA-related gene expression levels between ZmCaM2-1-overexpressing Arabidopsis and the wild type (WT) under ABA treatment. These results indicate that ZmCaM2-1 negatively regulates the tolerance of Arabidopsis to drought stress through the ABA-independent pathway.
Scutellarin Alleviates Neuronal Apoptosis in Ischemic Stroke via Activation of the PI3K/AKT Signaling Pathway
Authors: Duan Zhaoda , Peng Yingqi , Xu Dongyao , Yang Yujia , Wu Yuke , Wu Chunyun , Yan Shan , Yang Li
Published: February 2025

Among all stroke types, ischemic stroke (IS) occurs most frequently, resulting in neuronal death and tissue injury within both the central infarct region and surrounding areas. This study explored the neuroprotective mechanisms of scutellarin, a flavonoid compound, through an integrated strategy that merged in silico analyses (including network pharmacology and molecular docking simulations) with both in vitro and in vivo experimental verification. We identified 1887 IS-related targets and 129 scutellarin targets, with 23 overlapping targets. PPI network analysis revealed five core targets, and molecular docking demonstrated strong binding affinities between scutellarin and these targets. Bioinformatic analyses, including GO functional annotation and KEGG pathway mapping, indicated that the PI3K/AKT cascade represents the primary signaling mechanism. An in vitro experimental system was developed using PC12 cells under oxygen-glucose deprivation conditions to investigate how scutellarin regulates neuronal cell death via the PI3K/AKT pathway. Western blot quantification demonstrated that treatment with scutellarin enhanced the expression of p-PI3K, p-AKT, and Bcl-2 proteins, while simultaneously reducing levels of apoptotic markers Bax and cleaved caspase-3. Furthermore, pharmacological intervention with the selective PI3K inhibitor LY294002 attenuated these molecular alterations, resulting in diminished expression of p-PI3K, p-AKT, and Bcl-2, accompanied by elevated levels of Bax and cleaved caspase-3. In a rat model of middle cerebral artery occlusion, scutellarin administration demonstrated comparable neuroprotective effects, maintaining neuronal survival and modulating apoptotic protein expression via PI3K/AKT pathway activation. Collectively, this study demonstrates the therapeutic potential of scutellarin in cerebral ischemia through PI3K/AKT pathway modulation, suggesting its possible application in treating ischemic disorders.
The Role of AaPGRP-LB in the Immune Response of Aedes albopictus Against Bacteria Infection
Authors: Wu Cheng , Chen Yahui , Zheng Chenhua , Huang Xitong , Xie Yuyang , Lin Lingqun , Zhang Xiuli , Xie Lihua
Published: February 2025

The initial phase of an insect’s innate immune response to foreign pathogens is triggered by the identification of exogenous invaders, a mechanism facilitated by pattern recognition receptors. Among these receptors, peptidoglycan recognition proteins (PGRPs), abundant in insects, are essential components of the innate immune system. The roles of PGRPs have been extensively elucidated in Drosophila melanogaster; however, the mechanism underlying the immune response of Aedes albopictus to pathogens is unclear. Herein, we successfully cloned the full-length cDNA of a PGRP gene from Ae. albopictus, designated as the AaPGRP-LB gene. The open reading frame of AaPGRP-LB encodes 203 amino acids, including a secretion signal peptide and a canonical PGRP conserved domain. Multisequence alignment revealed that AaPGRP-LB possesses the amino acid residues essential for zinc binding and amidase activity. Molecular docking studies demonstrated that AaPGRP-LB exhibits a strong binding affinity for DAP-type and LYS-type peptidoglycan. The mRNA expression level of the AaPGRP-LB gene significantly increased after oral infection with Escherichia coli or Staphylococcus aureus. The purified recombinant AaPGRP-LB (rAaPGRP-LB) exhibited strong agglutination properties and demonstrated significant antimicrobial efficacy against E. coli and S. aureus in the presence of zinc ions. This study highlights the critical role of AaPGRP-LB in the immune response of Ae. albopictus. These findings provide a foundation for future research on mosquito immune pathways for innovative vector control and disease prevention strategies.
Insights from the Newborn Screening Program for Very Long-Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency in Kuwait
Authors: Alsharhan Hind , Ahmed Amir A. , Abdullah Marwa , Almaie Moudhi , Marafie Makia J. , Sulaiman Ibrahim , Elshafie Reem M. , Alahmad Ahmad , Alshammari Asma , Cyril Parakkal Xavier , Elkazzaz Usama M. , Ibrahim Samia M. , Elghitany Mohamed , Salloum Ayman M. , Yassen Fahmy , Alsafi Rasha , Bastaki Laila , Albash Buthaina
Published: February 2025

Newborn screening for very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency in Kuwait was initiated in October 2014. Over a 7-year period (January 2015 to December 2021), 43 newborns were diagnosed with VLCAD deficiency out of 356,819 screened, corresponding to an incidence of 1:8290 and 1:5405 among only Kuwaiti newborns. This study represents the first comprehensive review of newborn screening for VLCAD deficiency in Kuwait. The screening process begins with the detection of elevated blood C14:1 levels in dried blood spots, followed by confirmatory testing using dried blood spots acylcarnitine profiling, with or without molecular testing. Furthermore, this study demonstrates that incorporating the C14:1/C2 ratio as a supplementary marker in first-tier testing alongside C14:1 improves the positive predictive value (PPV) of the current newborn screening for VLCAD deficiency. Adding molecular genetic testing for known VLCAD variants as a second-tier strategy to the national program is also recommended to further enhance specificity and improve PPV. Our findings provide evidence that the expanded newborn screening program in Kuwait has successfully facilitated the early detection of VLCAD deficiency, preventing death and disability in affected infants.
Real-Life Comparison of Diagnostic Yield and Sample Adequacy of 22 G and 25 G EBUS-TBNB Needles: A Retrospective Study
Authors: Lanfranchi Filippo , Kalak George , Castelli Gioele , Mancino Laura , Foltran Gabriele , Pavan Alberto , Ciarrocchi Lorenzo , Laurino Licia , Michieletto Lucio
Published: February 2025

Background/Objectives: EBUS-TBNA is a safe and minimally invasive procedure to evaluate hilar and mediastinal lymph nodes (LNs). The Franseen needle provides a transbronchial needle biopsy (TBNB). Various needle sizes are available. In the literature, diagnostic yield (DY) and sample adequacy (SA) between needle sizes are still being debated. Methods: In total, 88 patients with lymphadenopathy were consecutively enrolled from June to December 2021. Chest CT and PET/CT scans were performed. Dimension at imaging and EBUS and the standardized uptake value (SUV) were recorded. EBUS-TBNB was performed with 22 G or 25 G needle sizes. DY for cancer and SA for predictive markers were evaluated. Overall DY (ODY) was also evaluated. Results: A 22 G needle was used in 51 patients and a 25 G needle was used in 37 patients with no differences in sex and age. The 22 G population presented a larger median dimension of LN both at imaging and EBUS compared to the 25 G population. Median LN SUV was higher in the 22 G population. Notably, 70 out of 88 patients had LNs suspicious for malignancy, which was higher in the 22 G group compared to the 25 G group (n = 46, 90% vs. n = 24, 65%; p = 0.004). DY for cancer was similar in both groups (84% for 22 G; 91% for 25 G). Also, SA for predictive markers was similar. ODY values were 78% and 92%, respectively, for the 22 G and 25 G needles. Conclusions: The 25 G needle has a higher DY (even if not statistically significant) and SA for predictive markers similar to the 22 G needle; further studies are necessary to evaluate if 25 G is comparable to the 22 G needle.
Managing Refractory Hypoxemia in Acute Respiratory Distress Syndrome Obese Patients with Veno-Venous Extra-Corporeal Membrane Oxygenation: A Narrative Review
Authors: Robert Arnaud , Honoré Patrick M. , Bulpa Pierre , Michaux Isabelle
Published: February 2025

Veno-venous extracorporeal membrane oxygenation (vvECMO) is a life-saving intervention for severe respiratory failure unresponsive to conventional therapies. However, managing refractory hypoxemia in morbidly obese patients poses significant challenges due to the unique physiological characteristics of this population, including hyperdynamic circulation, elevated cardiac output, and increased oxygen consumption. These factors can limit the effectiveness of vvECMO by diluting arterial oxygen content and complicating oxygen delivery. Refractory hypoxemia in obese patients supported by vvECMO often stems from an imbalance between ECMO blood flow and cardiac output. Hyperdynamic circulation exacerbates the recirculation of oxygenated blood and impairs the efficiency of oxygen transfer. To address these challenges, a stepwise, individualized approach is essential. Strategies to reduce oxygen consumption include deep sedation, neuromuscular blockade, and temperature control. Cardiac output modulation can be achieved through beta-blockers and cautious therapeutic hypothermia. Optimizing oxygen delivery involves improving residual lung function; high positive end-expiratory pressure ventilation guided by esophageal pressure monitoring; prone positioning; and adjustments to the ECMO circuit, such as using dual oxygenators, larger membranes, or additional drainage cannulas. This review highlights the interplay of physiological adaptations and technical innovations required to overcome the challenges of managing refractory hypoxemia in obese patients during vvECMO. By addressing the complexities of high cardiac output and obesity, clinicians can enhance the effectiveness of vvECMO and improve outcomes for this high-risk population.
Current Treatment Strategies for Multiple Myeloma at First Relapse
Authors: Mavrothalassitis Evangelos , Triantafyllakis Konstantinos , Malandrakis Panagiotis , Gavriatopoulou Maria , Kleber Martina , Ntanasis-Stathopoulos Ioannis
Published: February 2025

Multiple myeloma (MM), the second most common hematologic cancer, remains an incurable malignancy, characterized by an initial response to therapy followed by successive relapses. The upfront treatment typically involves induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance therapy. It is important to note that the anticipated duration of myeloma response diminishes with each subsequent relapse. Therefore, the first relapse represents a critical juncture in treatment, where refractoriness to key drug classes emerges as a significant challenge. Addressing the optimal management in this setting requires careful consideration of disease biology, prior therapies, and patient-specific factors to optimize outcomes. Cilta-cel, a chimeric antigen receptor T-cell construct, has emerged as the most promising therapeutic option at first relapse, resulting in long-term remissions with a significant treatment-free interval. However, availability and accessibility are not universal and treatment logistics are complex. Triplet regimens based on carfilzomib, pomalidomide or selinexor, remain the cornerstone of treatment at first relapse, whereas the optimal combination is based on refractoriness to prior drugs, especially anti-CD38 monoclonal antibodies and lenalidomide, and patient comorbidities. With the rapidly expanding therapeutic landscape, clinicians face increasing complexity in selecting the most appropriate regimens for individual patients. This review aims to guide clinicians through these evolving options by consolidating evidence-based strategies and highlighting emerging therapies, ensuring a personalized approach to managing first-relapse MM.
Dynamic Task Allocation for Heterogeneous Multi-Autonomous Underwater Vehicle Collaboration Under Mine Countermeasures Missions
Authors: Li Juan , Liu Baohua , Liu Caiyun , Lin Cong
Published: February 2025

The task allocation of autonomous underwater vehicles (AUVs) is a crucial aspect of ocean exploration and mission execution tasks. In a mine countermeasures (MCM) combat scenario, when a new suspicious mission point is detected in the mission area, the heterogeneous multi-AUV system requires reallocation in real time. To address this, a soft time windows consensus-based bundle algorithm with partial reallocation (SWCBBA-PR) is designed. Based on the consensus-based bundle algorithm (CBBA), this algorithm comprehensively considers the underwater communication limitations and introduces the soft time window mechanism and partial reallocation mechanism. Its aim is to solve the partial reallocation problem that arises when new task points appear under the temporal-coupling constraints of complex underwater tasks. The SWCBBA-PR algorithm has been validated through simulation, demonstrating its ability to generate an optimal allocation scheme in the scenario of MCM mission emergence, and it exhibits good convergence performance.
Research on Coupling Mechanisms of Risk Factors for Collision Accidents Between Merchant Ships and Fishing Vessels Based on the N-K Model
Authors: Dong Chuanming , Guo Xitong , Gong Yongjun
Published: February 2025

Preventing collision accidents between merchant ships and fishing vessels has long been a significant challenge for maritime safety in coastal waters. To quantitatively analyze the relationship between the risk factors contributing to these collisions, identify the key factors leading to such accidents, and develop effective prevention strategies, the N-K model was employed to examine the risk coupling mechanisms involved. The model was based on an analysis of 132 collision incidents between merchant ships and fishing vessels in China’s coastal waters from 2013 to 2023. The characteristics of these collision accidents were investigated, and the risk factors were categorized into four distinct types: human, management, environmental, and ship factors. The coupling of collision risk factors between merchant ships and fishing vessels was mainly considered from the perspective of the overall system, and the N-K model was used to calculate the probability and risk values associated with the coupling of these four risk factors. Modeling results indicated that the coupling value of four factors was 0.1083, which was 1.5 times greater than the maximum coupling value of three factors and 2.1 times greater than the maximum coupling value of two factors. The risk of collision accidents between merchant ships and fishing vessels increases gradually with an increase in the risk coupling factors. Among the four categories of factors, the risk coupling between the ship factors and environmental factors is associated with a relatively large probability of accidents. Appropriate countermeasures were proposed to implement effective preventive measures at the source of collision accidents.
An Adaptive Local Time-Stepping Method Applied to Storm Surge Inundation Simulation
Authors: Yu Pubing , Ji Tao , Wu Xiuguang , Chen Yifan , Liu Guilin
Published: February 2025

This study proposes an adaptive local time stepping (LTS) method based on a two-dimensional shallow water model for simulating multi-scale storm surge inundation in coastal regions. By dynamically monitoring the variation in the proportion of dry/wet cells during the simulation, the method adaptively adjusts the maximum local time step level, improving computational efficiency and minimizing human intervention in traditional LTS schemes. Through a series of idealized cases, this paper derives an empirical criterion for selecting the maximum LTS level and performs detailed analysis for two typical scenarios: in the absence of dry cells, the optimal LTS level is based on the maximum local time step under quiescent conditions; in complex hydrodynamic models with dry cells, the adaptive adjustment strategy based on the dry cell proportion is required to handle the increased computational complexity. The results show that when the proportion of dry cells was between 40% and 70%, the maximum LTS level increased by one level, and when it exceeded 70%, the maximum LTS level increased by two levels, with a recommended maximum limit of 7 levels. In ideal cases, the adaptive LTS method improves efficiency, with speedups of up to 5.83 times compared to traditional methods. Furthermore, the adaptive LTS method is successfully applied to storm surge and seawater inundation simulations, with validation through comparison with observational data. In particular, the simulation of the seawater backflow event in Erjiegou demonstrated the method’s ability to capture both the occurrence time and extent of seawater backflow, confirming its efficiency and reliability in complex hydrodynamic processes. The proposed method holds significant promise for applications in storm surge forecasting, disaster assessment, and emergency management.
Urban Green Spaces as an Effective Tool to Regulate Urban Climate and Biodiversity: Current Research and Challenges
Authors: Proutsos Nikolaos D. , Solomou Alexandra D.
Published: February 2025

Urban green spaces (UGSs) are at the cutting edge of recent research, due to their ability to provide critical ecosystem services, and improve citizens’ quality of life and public health [...]