bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra-Tumoral Lymphocytic Infiltration Is Associated with Favorable Prognosis in Suboptimal Surgery in High-Grade Serous Ovarian Carcinoma
Authors: Harada Hiroshi , Hachisuga Toru , Harada Yoshikazu , Shibahara Mami , Murakami Midori , Nuratdinova Fariza , Higami Shota , Tohyama Atsushi , Kinjo Yasuyuki , Ueda Taeko , Kurita Tomoko , Matsuura Yusuke , Nakayama Toshiyuki , Yoshino Kiyoshi
Published: February 2025

Background: The immunoreactive (IR) subtype is one of the subtypes of high-grade serous ovarian carcinoma (HGSOC) with intra-tumoral lymphocytic infiltration. A positive prognostic correlation between IR subtype and R0 + optimal surgery has been reported. This study investigates the prognostic significance of tumor-infiltrating lymphocytes (TILs) in the suboptimal surgery group of HGSOCs. Methods: After reviewing 318 malignant ovarian tumors detected in our database between 2000 and 2017, 74 HGSOCs with supplemental p53 immunostaining were selected. Differences in progression-free survival (PFS) and overall survival (OS) between the two groups of the IR subtype and the other subtypes were investigated. Based on pathological findings, HGSOCs were divided into two groups: those with or without abundant TILs. Results: Abundant TILs were detected in 17 cases of HGSOC (22.9%). Clinicopathological characteristics including age, CA125, FIGO stage, and residual disease did not show significant differences between the two groups. Lymph node metastasis was more common in the IR subtype group (p = 0.04). In the suboptimal surgery group, the 5-year PFS and OS (Kaplan–Meier estimates) in cases with (n = 10) or without (n = 21) abundant TILs were 10% and 0% (p = 0.097) and 70% and 28.5% (p = 0.012), respectively. The median time (range) to OS in cases with or without abundant TILs were 58 (34–81) months and 39 (22–55) months, respectively. Multivariate analysis in OS showed significant differences in TILs. Conclusions: Abundant intra-tumoral lymphocytic infiltration is an independent and favorable prognostic indicator for the suboptimal surgery group in HGSOCs and is associated with treatment response via cancer immunity.
Urinary Fetuin-A with Specific Post-Translational Modification in Type 1 Diabetes Patients with Normoalbuminuria and Preserved Kidney Function
Authors: Božičević Sandra , Bulum Tomislav , Smirčić Duvnjak Lea , Vučić Lovrenčić Marijana
Published: February 2025

Background/Objectives: Post-translationally modified peptide fragments of fetuin-A (FetA) were identified as a potential biomarker of diabetic kidney disease (DKD). An independent association between urinary FetA-derived peptide levels (uPTM3-FetA) and DKD progression in patients with type 2 diabetes (T2D) was evidenced. This study aimed to explore uPTM3-FetA excretion and its associations with insulin resistance, inflammatory and metabolic biomarkers in patients with type 1 diabetes (T1D), and the normal albuminuria and estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2. Methods: uPTM3-FetA levels in aliquots of 24 h urine specimens, routine laboratory renal, metabolic and inflammatory tests, adipokines (leptin, adiponectin, resistin), and insulin resistance, assessed as the estimated glucose disposal rate (eGDR), were measured in a cohort of 169 adult T1D patients. To evaluate the changes in early renal dysfunction, the cohort was divided according to the median eGFR. Above- and below-median-eGFR groups were considered as having normal and declining kidney function, respectively. Results: The median (IQR) uPTM3-FetA level was 11.7 (8.43–16.65 µg/24 h), with no significant difference between males and females, as well as normal and declining kidney function patients. However, a sex-specific analysis revealed a significantly higher uPTM3-FetA excretion in male T1D patients with lower eGFRs, when compared to those with higher eGFRs, whereas no such difference was observed in female patients. BMI, hs-CRP, resistin and HDL-cholesterol were identified as independent predictors of uPTM3-FetA excretion. Conclusions: Our results implicate the potential role of uPTM3-FetA in the detection of an early renal dysfunction in male patients with T1DM and pinpoint the importance of a sex-specific approach in diabetes diagnostics and research.
A Novel Approach for Maize Straw Type Recognition Based on UAV Imagery Integrating Height, Shape, and Spectral Information
Authors: Liu Xin , Gong Huili , Guo Lin , Gu Xiaohe , Zhou Jingping
Published: February 2025

Accurately determining the distribution and quantity of maize straw types is of great significance for evaluating the effectiveness of conservation tillage, precisely estimating straw resources, and predicting the risk of straw burning. The widespread adoption of conservation tillage technology has greatly increased the diversity and complexity of maize straw coverage in fields after harvest. To improve the precision and effectiveness of remote sensing recognition for maize straw types, a novel method was proposed. This method utilized unmanned aerial vehicle (UAV) multispectral imagery, integrated the Stacking Enhanced Straw Index (SESI) introduced in this study, and combined height, shape, and spectral characteristics to improve recognition accuracy. Using the original five-band multispectral imagery, a new nine-band image of the study area was constructed by integrating the calculated SESI, Canopy Height Model (CHM), Product Near-Infrared Straw Index (PNISI), and Normalized Difference Vegetation Index (NDVI) through band combination. An object-oriented classification method, utilizing a “two-step segmentation with multiple algorithms” strategy, was employed to integrate height, shape, and spectral features, enabling rapid and accurate mapping of maize straw types. The results showed that height information obtained from the CHM and spectral information derived from SESI were essential for accurately classifying maize straw types. Compared to traditional methods that relied solely on spectral information for recognition of maize straw types, the proposed approach achieved a significant improvement in overall classification accuracy, increasing it by 8.95% to reach 95.46%, with a kappa coefficient of 0.94. The remote sensing recognition methods and findings for maize straw types presented in this study can offer valuable information and technical support to agricultural departments, environmental protection agencies, and related enterprises.
Occupation Times on the Legs of a Diffusion Spider
Authors: Salminen Paavo , Stenlund David
Published: February 2025

We study the joint moments of occupation times on the legs of a diffusion spider. Specifically, we give a recursive formula for the Laplace transform of the joint moments, which extends earlier results for a one-dimensional diffusion. For a Bessel spider, of which the Brownian spider is a special case, our approach yields an explicit formula for the joint moments of the occupation times.
Sequence-Aware Vision Transformer with Feature Fusion for Fault Diagnosis in Complex Industrial Processes
Authors: Zhang Zhong , Xu Ming , Wang Song , Guo Xin , Gao Jinfeng , Hu Aiguo Patrick
Published: February 2025

Industrial fault diagnosis faces unique challenges with high-dimensional data, long time-series, and complex couplings, which are characterized by significant information entropy and intricate information dependencies inherent in datasets. Traditional image processing methods are effective for local feature extraction but often miss global temporal patterns, crucial for accurate diagnosis. While deep learning models like Vision Transformer (ViT) capture broader temporal features, they struggle with varying fault causes and time dependencies inherent in industrial data, where adding encoder layers may even hinder performance. This paper proposes a novel global and local feature fusion sequence-aware ViT (GLF-ViT), modifying feature embedding to retain sampling point correlations and preserve more local information. By fusing global features from the classification token with local features from the encoder, the algorithm significantly enhances complex fault diagnosis. Experimental analyses on data segment length, network depth, feature fusion and attention head receptive field validate the approach, demonstrating that a shallower encoder network is better suited for high-dimensional time-series fault diagnosis in complex industrial processes compared to deeper networks. The proposed method outperforms state-of-the-art algorithms on the Tennessee Eastman (TE) dataset and demonstrates excellent performance when further validated on a power transmission fault dataset.
Active Gamification in the Emotional Well-Being and Social Skills of Primary Education Students
Authors: Carcelén-Fraile María del Carmen
Published: February 2025

(1) Background: Gamification has emerged as an innovative strategy in education and involves integrating game elements into pedagogical activities to enhance motivation and the development of cognitive and social skills. The aim was to analyze the effects of active gamification on the emotional well-being and social skills of primary school students. (2) Methods: A total of 120 children with a mean age of 9.40 ± 0.98 years were divided into an experimental group (EG) that carried out a program based on gamification in physical exercise and a control group (CG). (3) Results: The EG improved significantly in self-concept compared to the CG, as did the levels of personal self-esteem, which increased significantly. Likewise, improvements were found in all the subdomains of social skills, except in the subdomain of jealousy/loneliness. (4) Conclusions: The introduction of gamification into Physical Education classes is recommended as an effective tool to improve self-esteem, self-concept, and social skills in primary education.
Self-Esteem and Feelings of Inferiority and Superiority Among Athletes and Non-Athletes
Authors: Stoyanova Stanislava , Ivantchev Nikolay
Published: February 2025

Self-esteem is a central part of personality, related to self-perceptions and evaluation of oneself compared to other people. Self-esteem could be global self-esteem, concerning the whole personality, or partial self-esteem, concerning the different aspects of personality and performance. Global self-esteem, as well as feelings of inferiority and supremacy, were compared among 197 athletes and 198 non-athletes in Bulgaria based on three self-reported questionnaires—the inferiority complex shortened scale COMPIN-10, the superiority complex shortened scale SUCOMP-10, and the single-item self-esteem scale. It was found that the athletes had significantly higher self-esteem and more strongly expressed feelings of superiority, as well as fewer experienced feelings of inferiority than the non-athletes. This may be due to athletes’ achievements and their recognition by society, as well as the social image imposed by media as rich, successful, and representatives of their country. High self-esteem is necessary for athletes to be confident in their ability to perform well during sports competitions. More years of sport experience correlated with a decrease in inferiority feelings and an increase in self-esteem. There were not any statistically significant differences between the athletes practicing individual sports and the athletes practicing team sports in their inferiority feelings, superiority feelings, or self-esteem.
Development and Validation of the War Worry Scale (WWS) in a Sample of Italian Young Adults: An Instrument to Assess Worry About War in Non-War-Torn Environments
Authors: Regnoli Giorgio Maria , Parola Anna , De Rosa Barbara
Published: February 2025

The expansion of wars around the world fosters a macrosocial stress with multilevel effects that also affect the mental health of populations not directly involved, in particular of evolutionary targets in delicate transition. The present study describes the process of development, validation, and evaluation of the psychometric properties of the War Worry Scale (WWS), an instrument that explores the psychological impact of war in contexts not directly involved and, in particular, in the target population of young Italian adults. The process of construct definition and item generation of the WWS is presented here and then verified in Study I, which, using a sample of 250 young adults (40.4% male and 59.6% female), describes the exploration of the factor structure of the instrument through exploratory factor analysis (EFA) and presents preliminary psychometric properties. An independent sample of 500 young adults (39.4% male; 60.6% female) was recruited for Study II, which describes the results of confirmatory factor analysis (CFA) supporting the second-order structure with two first-order dimensions, Worry about the Present (WWP) and Worry about the Future (WWF), composed of 10 items (5 per dimension). The internal consistency of the WWS, convergent, discriminant, and concurrent validity with other validated measures, and measurement invariance between males and females are further described. Finally, significant differences in the levels of Worry about War are found in relation to several sociodemographic variables, i.e., gender, occupational status, relationship status, and political orientation. Overall, the results of Studies I and II confirm the validity, robustness, and reliability of the War Worry Scale.
Precision Modeling of Fuel Consumption to Select the Most Efficient Logging Method for Cut-to-Length Timber Harvesting
Authors: Palander Teijo
Published: February 2025

The fuel consumption of a harvester–operator system was modeled to select logging methods by comparing the forward felling technique (C) and the sideways techniques at the logging edge (A and D) or inside of the stand (B and E). To that end, trees’ logging cycle process data were collected using a drone for time consumption analysis. The fuel consumption data were recorded automatically from the harvester’s digital monitoring system. The fuel consumption averaged 0.22 L during the logging cycle process of trees on flat terrain and 0.25 L for those on sloping terrain. In stands on flat terrain, logging method C consumed 7.9 L E0h−1 more fuel than method A and 4.9 L E0h−1 more fuel than method B, meaning method A consumed 3.0 L E0h−1 less fuel than method B. On sloping terrain, logging method D consumed 1.4 L E0h−1 less fuel than method E. There was a large variation in fuel consumption between the logging methods, which was explained most efficiently (R2 = 0.70) by the stem processing speed (m E0h−1), the tree’s stem length (m), and effective hours of tree logging cycle processes (E0h). The results reveal that logging methods A and D were the most efficient. This precision modeling structure is recommended for the development of working techniques for harvester operators and for environmental efficiency comparisons of logging methods in different timber harvesting conditions.
The Impact of Polydimethylsiloxane (PDMS) in Engineering: Recent Advances and Applications
Authors: Lima Rui A.
Published: February 2025

Since the introduction of polydimethylsiloxane (PDMS) microfluidic devices at the beginning of the 21st century, this elastomeric polymer has gained significant attention in the engineering community due to its biocompatibility, exceptional mechanical and optical properties, thermal stability, and versatility. PDMS has been widely used for in vitro experiments ranging from the macro- to nanoscale, enabling advances in blood flow studies, biomodels improvement, and numerical validations. PDMS devices, including microfluidic systems, have been employed to investigate different kinds of fluids and flow phenomena such as in vitro blood flow, blood analogues, the deformation of individual cells and the cell free layer (CFL). The most recent applications of PDMS involve complex hemodynamic studies such as flow in aneurysms and in organ-on-a-chip (OoC) platforms. Furthermore, the distinctive properties of PDMS, including optical transparency, thermal stability, and versality have inspired innovative applications beyond biomedical applications, such as the development of transparent, virus-protective face masks, including those for SARS-CoV-2 and serpentine heat exchangers to enhance heat transfer and energy efficiency in different kinds of thermal systems. This review provides a comprehensive overview of the current research performed with PDMS and outlines some future directions, in particular applications of PDMS in engineering, including biomicrofluidics, in vitro biomodels, heat transfer, and face masks. Additionally, challenges related to PDMS hydrophobicity, molecule absorption, and long-term stability are discussed alongside the solutions proposed in the most recent research studies.
Advancing Gel Systems with Natural Extracts: Antioxidant, Antimicrobial Applications, and Sustainable Innovations
Authors: Kawee-ai Arthitaya
Published: February 2025

The integration of natural extracts into gel systems has emerged as a transformative approach to enhance functional properties, including antioxidant, antimicrobial, and therapeutic effects. This review underscores the remarkable potential of natural extract-enriched gels, which effectively combine sustainability with improved functionality. These bioactive compounds, sourced from plants and animals, encompass polyphenols, flavonoids, essential oils, chitosan, proteins, and polysaccharides. They provide an eco-friendly alternative to synthetic additives and find applications across various sectors, including pharmaceuticals, cosmetics, and food packaging. Despite their promise, challenges remain, such as the variability in natural extract composition, the stability of bioactive compounds, and scalability for industrial use. To address these issues, innovative strategies like nanoencapsulation, responsive hydrogels, and AI-driven optimization have demonstrated significant progress. Additionally, emerging technologies, such as 3D printing and adherence to circular economy principles, further enhance the versatility, efficiency, and sustainability of these systems. By integrating these advanced tools and methodologies, gel systems enriched with natural extracts are well-positioned to meet contemporary consumer and industrial demands for multifunctional and eco-friendly products. These innovations not only improve performance but also align with global sustainability goals, setting the stage for widespread adoption and continued development in various fields.
Hydrogels for Peripheral Nerve Repair: Emerging Materials and Therapeutic Applications
Authors: Taisescu Oana , Dinescu Venera Cristina , Rotaru-Zavaleanu Alexandra Daniela , Gresita Andrei , Hadjiargyrou Michael
Published: February 2025

Peripheral nerve injuries pose a significant clinical challenge due to the complex biological processes involved in nerve repair and their limited regenerative capacity. Despite advances in surgical techniques, conventional treatments, such as nerve autografts, are faced with limitations like donor site morbidity and inconsistent functional outcomes. As such, there is a growing interest in new, novel, and innovative strategies to enhance nerve regeneration. Tissue engineering/regenerative medicine and its use of biomaterials is an emerging example of an innovative strategy. Within the realm of tissue engineering, functionalized hydrogels have gained considerable attention due to their ability to mimic the extracellular matrix, support cell growth and differentiation, and even deliver bioactive molecules that can promote nerve repair. These hydrogels can be engineered to incorporate growth factors, bioactive peptides, and stem cells, creating a conducive microenvironment for cellular growth and axonal regeneration. Recent advancements in materials as well as cell biology have led to the development of sophisticated hydrogel systems, that not only provide structural support, but also actively modulate inflammation, promote cell recruitment, and stimulate neurogenesis. This review explores the potential of functionalized hydrogels for peripheral nerve repair, highlighting their composition, biofunctionalization, and mechanisms of action. A comprehensive analysis of preclinical studies provides insights into the efficacy of these hydrogels in promoting axonal growth, neuronal survival, nerve regeneration, and, ultimately, functional recovery. Thus, this review aims to illuminate the promise of functionalized hydrogels as a transformative tool in the field of peripheral nerve regeneration, bridging the gap between biological complexity and clinical feasibility.
Dual-Function Hydrogel Coating on Silicone Urinary Catheters with Durable Antibacterial Property and Lubricity
Authors: Gao Shuai , Zeng Wei , Liu Zheng , Zhang Fanjun , Zhang Yunfeng , Liu Xi , Wu Dimeng , Wang Yunbing
Published: February 2025

Silicone urinary catheters are broadly employed in medical practice. However, they are susceptible to inducing catheter-associated urinary tract infections (CAUTIs) due to bacterial adherence to the catheter’s surface, and they exhibit a high friction coefficient, which can greatly affect their effectiveness and functionality. Thus, the development of a silicone urinary catheter with antibacterial properties and lubricity is in strong demand. We hereby developed a poly(vinyl acetate) carrier coating to load chlorhexidine acetate and applied a hydrogel coating primarily composed of polyvinylpyrrolidone (PVP) and poly(ethylene glycol) diacrylate (PEGDA), which was then coated onto the silicone urinary catheters and cured through a thermal curing process and could provide lubricity. Subsequently, we analyzed its surface characteristics and assessed the antibacterial property, lubricity, cytotoxicity, and potential for vaginal irritation. The findings from the Fourier transform infrared spectrometer (FTIR), scanning electron microscope (SEM), water contact angle (WCA), inhibition zone measurements, and friction coefficient analysis confirmed the successful modification of the silicone urinary catheter. Additionally, the outcomes from the cytotoxicity and vaginal irritation assessments demonstrated that the dual-function hydrogel coating-coated silicone urinary catheters exhibit outstanding biocompatibility. This study illustrates that the prepared silicone urinary catheters possess durable antibacterial properties and lubricity, which thus gives them broad clinical application prospects.
Soundscapes of Resistance: Delta Blues and the Transcultural Journeys of the African Diaspora
Authors: Strait John Byron
Published: February 2025

As a distinct musical form, blues music from the Mississippi Delta has been extensively studied across various academic disciplines. While much of this attention has treated blues primarily as an auditory experience, I argue that it represents far more than just sound or entertainment. This research project examines Delta blues as a comprehensive cultural phenomenon, exploring its evolution through a series of distinct diffusionary pathways that reveal complex global interactions and transcultural exchange. This study posits that Delta blues emerged from a broad cultural milieu, shaped by multiple layers of geographical processes ranging from ancient African trade routes to twentieth-century migration patterns. I position Delta blues within the context of the African diaspora, emphasizing not only its strong roots in African and African American cultural traditions but also its crucial role as a vehicle for cultural resistance and consciousness-raising. By mapping the evolution of blues music and culture through specific circuits of exchange, I illuminate the intricate interrelationships between different peoples and places across time and space. This approach reveals how global interactions generated a unique musical and cultural expression that both embodies and transcends the complex social dynamics inherent in the African diaspora.
Self-Reported Medical Errors and Primary Care Physicians’ Performance and Confidence in Delivering Care: A Multilevel Empirical Study in China
Authors: Sun Xueshan , Zhou Zhongliang , Wang Wenhua
Published: February 2025

Background/Objectives: Patient safety is fundamental to primary healthcare, and medical errors impose a considerable burden on patients globally. However, the impact of medical errors on primary healthcare physicians remains understudied, especially in developing countries. This study aimed to examine the associations between self-reported medical errors and physicians’ performance and confidence in Chinese primary care practice. Methods: A cross-sectional survey was conducted from November 2021 to May 2022 with 224 primary care physicians from 38 community health centers (CHCs) across four large cities in China. The quality of clinical and preventative care, and confidence in managing commonly occurring diseases, multimorbidity, and common mental health disorders served as indicators of performance and confidence, respectively. Hierarchical linear regression and linear regression with cluster-robust standard errors were employed. Results: Clinical care quality (β = −0.159, SE = 0.075, p < 0.05), preventive care quality (β = −0.165, SE = 0.068, p < 0.05), confidence in managing multimorbidity (β = −0.175, SE = 0.074, p < 0.05), and confidence in managing common mental health disorders (β = −0.189, SE = 0.076, p < 0.05) were negatively associated with self-reported medical errors, with scores of 4.08 (SD 0.95), 3.59 (SD 0.87), 3.63 (SD 1.04), and 3.10 (SD 1.21) out of 5 (where 5 represents the best possible score), respectively. The association between self-reported medical errors and confidence in managing commonly occurring diseases (β = −0.063, SE = 0.075, p > 0.05) was not statistically significant, with a score of 3.81 (SD 1.00) out of 5 (where 5 represents the best possible score). Conclusions: This study offers new insight into the associations between self-reported medical errors and primary healthcare physicians’ performance and confidence. It is crucial for CHCs to be aware of the impact of self-reported medical errors on physicians’ performance in delivering clinic and preventative care, and confidence in managing multimorbidity and common mental health disorders. Strategies such as strengthening organizational support should be developed to maintain performance and rebuild confidence in delivering care for physicians who were involved in medical errors.
Effect of a Practice-Oriented Electronic Medical Record Education Program for New Nurses
Authors: Ju Jae-Kyun , Jeong Hye-Won
Published: February 2025

Background/Objectives: New nurses often face challenges in adapting to clinical environments, particularly in mastering electronic medical record (EMR) systems, which are critical for effective patient care and communication. This study aimed to evaluate the effectiveness of a practice-oriented EMR education program designed to improve new nurses’ EMR competencies. Methods: A quasi-experimental pretest–post-test design with a non-equivalent control group was employed. Fifty-four new nurses employed for less than a year participated, with 25 in the intervention group and 29 in the comparison group. The intervention group underwent five weekly sessions focused on core EMR tasks, including admission nursing, operation/procedure documentation, patient transfer/discharge, night duties, and SBAR handovers. The program, led by clinical nurse educators, incorporated lectures, practical exercises, and Q&A sessions. EMR competencies were assessed using a validated 5-point Likert scale. Results: The intervention group showed significant improvements across all assessed domains, with post-program scores significantly higher than those of the comparison group. The most notable improvements were in operation/procedure documentation and patient transfer/discharge tasks. The comparison group’s gains were limited, likely reflecting natural skill acquisition through clinical experience. Conclusions: The practice-oriented EMR education program effectively enhanced new nurses’ EMR competencies. The program’s structured approach, which combined theoretical instruction with extensive hands-on practice and department-specific adaptations, proved particularly effective in improving complex documentation tasks. The integration of comprehensive EMR training into nursing curricula and the expansion of such programs to other institutions are recommended for broader implementation.
Assessing the Spread of the Sport of Padel and the Prevalence and Causes of Injuries Among Padel Players
Authors: Alhammad Ayman , Almalki Husam , Ghulam Hussain , Al-harbi Renad , Al-harbi Samia , Al-shareif Shaima , Althomali Omar , Taiar Redha
Published: February 2025

Objectives: To study the prevalence of injuries among padel players in Madinah and investigate potential causes. This study makes an attempt to add to the gaps in the literature regarding injury risks and preventive strategies in this fast-growing sport. Methods: Retrospective cross-sectional study on 305 padel players who come from Madinah, consisting of 193 men and 112 women aged 18–40 years. Data were collected using an online Google Forms questionnaire, including descriptive statistics and non-parametric tests, among which the chi-square test was performed, aiming for the assessment of demographic and injury-related variables. Results: There were significantly different incidences of injuries with regard to gender at the p = 0.001 level. A 44.6% prevalence was recorded among women, while men had a prevalence of 8.2%. With respect to the severity of injuries from moderate to severe, there are higher percentages in women that comprised 40.4% and 5.6%, respectively. The most frequent types of upper body injuries among women were ligament sprains and muscle strains. Stress and poor warm-up practices were some of the lifestyle factors identified to increase the risk of sustaining an injury. Conclusions: This study highlights gender-specific injury patterns among padel players in Madinah, emphasizing the need for targeted injury prevention programs, including structured warm-ups and strength training. The findings contribute valuable insights for enhancing player safety and aligning with public health objectives under Saudi Vision 2030.
West London Healthy Home and Environment (WellHome) Study: Protocol for a Community-Based Study Investigating Exposures Across the Indoor-Outdoor Air Pollution Continuum in Urban Communities
Authors: Varaden Diana , Barratt Benjamin , Dallman Margaret J. , Skillern Adam , Elmi Munira S. , Green David C. , Tremper Anja H. , Hedges Michael , Hicks William , Priestman Max , Barron Leon P. , Fitzgerald Shane P. , Walder Holly M. , Wright Stephanie L. , Mudway Ian S. , Fisher Matthew C. , Hemmings Samuel J. , Poortinga Wouter , Tirotto Francesca , Beevers Sean , Walton Heather , Vu Tuan , Katsouyanni Klea , Evangelopoulos Dimitris , Young George , Wood Dylan , Griffiths Christopher , Kelly Frank J.
Published: February 2025

The relationship between indoor air quality and public health remains under-researched. WellHome is a transdisciplinary community-based study that will engage with residents to co-design feasible and acceptable research to quantify air pollution exposure in 100 homes in West London and examine its potential to exacerbate asthma symptoms in children. Sampling strategies such as using air quality monitors and passive samplers placed in kitchens, children’s bedrooms, and living rooms, will be developed in collaboration with local ambassadors and participating households to measure multiple physical, chemical, microplastic, and biological contaminants. This will provide a comprehensive understanding of indoor air quality across the city’s socio-economic gradient. Other data collected will include housing types and tenure, ventilation practices, occupant behaviours, time-activity, and airway symptoms. Epidemiological analysis will examine air pollution exposure impacts on children’s respiratory health. The particulate mixture’s relative hazard will be evaluated in toxicity studies based on source profiles and activity patterns of participants, focusing on asthma exacerbation related pathways. The study’s findings will be communicated to participants through co-designed reports and inform evidence-based recommendations for reducing indoor air pollution in London and urban areas worldwide. By raising awareness and providing actionable insights, WellHome seeks to contribute to global efforts to improve the health and well-being of vulnerable communities.
Arbuscular Mycorrhizal Fungi Alleviate Cadmium Phytotoxicity by Regulating Cadmium Mobility, Physiological Responses, and Gene Expression Patterns in Malus hupehensis Rehd
Authors: Zhuang Xiaolei , Liu Siyu , Xu Shengzhe , Qin Sijun , Lyu Deguo , He Jiali , Zhou Jiangtao
Published: February 2025

Arbuscular mycorrhizal fungi (AMF) affect cadmium (Cd) accumulation and tolerance in host plants. However, the effects of AMF on Cd accumulation and phytotoxicity and their underlying mechanism in apples remain uncharacterized. In this study, the comprehensive physiological and molecular responses of uninoculated and Rhizophagus intraradices-inoculated Malus hupehensis Rehd. rootstocks exposed to 0 or 300 μM Cd were investigated. AMF inoculation mitigated Cd-induced growth and photosynthesis inhibition and nutrient ion disorders. It also lowered the concentrations of Cd in all tissues and reduced Cd transport to the shoots. Compared to uninoculated apple plants, those inoculated with mycorrhizal fungi reduced the mobility and toxicity of Cd by altering its form and binding it to the cell walls of the roots and leaves. AMF inoculation ameliorated Cd stress by altering endogenous phytohormone levels and triggering enzymatic and non-enzymatic antioxidant systems. Transcriptome analysis revealed that the differentially expressed genes (DEGs) associated with AMF under Cd stress regulated carbohydrate and amino acid biosynthesis and metabolism, as well as phytohormone biosynthesis and signal transduction. Furthermore, AMF inoculation downregulated certain genes involved in Cd uptake and transport while upregulating other genes involved in detoxification. These results suggest that AMF alleviate Cd phytotoxicity by orchestrated physiological and transcriptomic regulation in M. hupehensis Rehd., providing valuable insights into the efficacy of AMF inoculation in improving the heavy metal resistance of fruit trees.
Endothelial Dysfunction in Huntington’s Disease: Pathophysiology and Therapeutic Implications
Authors: Hu Ning , Chen Zihao , Zhao Xinyue , Peng Xin , Wu Yimeng , Yang Kai , Sun Taolei
Published: February 2025

Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. While traditionally viewed through the lens of neuronal dysfunction, emerging evidence highlights the critical role of endothelial dysfunction in HD pathogenesis. This review provides a comprehensive overview of endothelial dysfunction in HD, drawing on findings from both animal models and human studies. Key features of endothelial dysfunction in HD include impaired angiogenesis, altered cerebral blood flow, compromised neurovascular coupling and cerebrovascular reactivity, and increased blood–brain barrier permeability. Genetic factors such as the mutant huntingtin protein, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), Brain-derived neurotrophic factor (BDNF), and the adenosine A2A receptor (ADORA2A) interact to influence endothelial function in complex ways. Various therapeutic approaches targeting endothelial dysfunction, including antioxidants, nitric oxide enhancers, calcium channel blockers, statins, and metformin, have shown promise in preclinical HD models but face translational challenges, particularly regarding optimal timing of intervention and patient stratification. The implications of these findings suggest that reconceptualizing HD as a neurovascular disorder, rather than purely neuronal, could lead to more effective treatment strategies. Future research priorities should include: (1) developing validated vascular biomarkers for disease progression, (2) advancing neuroimaging techniques to monitor endothelial dysfunction in real-time. These directions will be crucial for bridging the current gap between preclinical promise and clinical success in vascular-targeted HD therapeutics.
Engineering of Genetically Encoded Bright Near-Infrared Fluorescent Voltage Indicator
Authors: Xiao Xian , Yang Aimei , Zhang Hanbin , Park Demian , Wang Yangdong , Szabo Balint , Boyden Edward S. , Piatkevich Kiryl D.
Published: February 2025

Genetically encoded voltage indicators (GEVIs) allow for the cell-type-specific real-time imaging of neuronal membrane potential dynamics, which is essential to understanding neuronal information processing at both cellular and circuit levels. Among GEVIs, near-infrared-shifted GEVIs offer faster kinetics, better tissue penetration, and compatibility with optogenetic tools, enabling all-optical electrophysiology in complex biological contexts. In our previous work, we employed the directed molecular evolution of microbial rhodopsin Archaerhodopsin-3 (Arch-3) in mammalian cells to develop a voltage sensor called Archon1. Archon1 demonstrated excellent membrane localization, signal-to-noise ratio (SNR), sensitivity, kinetics, and photostability, and full compatibility with optogenetic tools. However, Archon1 suffers from low brightness and requires high illumination intensities, which leads to tissue heating and phototoxicity during prolonged imaging. In this study, we aim to improve the brightness of this voltage sensor. We performed random mutation on a bright Archon derivative and identified a novel variant, monArch, which exhibits satisfactory voltage sensitivity (4~5% ΔF/FAP) and a 9-fold increase in basal brightness compared with Archon1. However, it is hindered by suboptimal membrane localization and compromised voltage sensitivity. These challenges underscore the need for continued optimization to achieve an optimal balance of brightness, stability, and functionality in rhodopsin-based voltage sensors.
Zebrafish as a Suitable Model for Utilizing the Bioactivity of Coumarins and Coumarin-Based Compounds
Authors: Lachowicz-Radulska Joanna , Widelski Jarosław , Nowaczyński Filip , Serefko Anna , Sobczyński Jan , Ludwiczuk Agnieszka , Kasica Natalia , Szopa Aleksandra
Published: February 2025

The aim of this review is to summarize the current knowledge on the use of coumarin-derived compounds in the zebrafish (Danio rerio) model. Coumarins, a class of naturally occurring compounds with diverse biological activities, including compounds such as coumarin, angelicin, and warfarin, have attracted considerable attention in the study of potential therapeutic agents for cancer, central nervous system disorders, and infectious diseases. The capabilities of coumarins as active compounds have led to synthesizing various derivatives with their own properties. While such variety is certainly promising, it is also cumbersome due to the large amount of research needed to find the most optimal compounds. The zebrafish model offers unique advantages for such studies, including high genetic and physiological homology to mammals, optical transparency of the embryos, and rapid developmental processes, facilitating the assessment of compound toxicity and underlying mechanisms of action. This review provides an in-depth analysis of the chemical properties of coumarins, their mechanisms of biological activity, and the results of previous studies evaluating the toxicity and efficacy of these compounds in zebrafish assays. The zebrafish model allows for a holistic assessment of the therapeutic potential of coumarin derivatives, offering valuable insights for advancing drug discovery and development.
Exploring the Anti-Colorectal Cancer Mechanism of Norcantharidin Through TRAF5/NF-κB Pathway Regulation and Folate-Targeted Liposomal Delivery
Authors: Zhang Fanqin , Chen Xiaodong , Qiao Chuanqi , Yang Siyun , Zhai Yiyan , Zhang Jingyuan , Chai Keyan , Wang Haojia , Zhou Jiying , Guo Meiling , Lu Peiying , Wu Jiarui
Published: February 2025

Colorectal cancer is one of the most common malignant tumors worldwide, significantly impacting human health. Cantharidin (CTD), an active compound derived from the Spanish fly, exhibits antitumor properties. Its derivative, norcantharidin (NCTD), is synthesized by removing methyl groups from positions 1 and 2 of cantharidin. NCTD has demonstrated lower toxicity while maintaining similar antitumor effects compared to CTD. However, the mechanism by which NCTD exerts its effects against colorectal cancer remains unclear. Here, we conducted a comprehensive analysis of the effects of NCTD on colorectal cancer both in vitro and in vivo. Whole-transcriptome sequencing and bioinformatics tools were employed to identify potential key targets of NCTD in the treatment of colorectal cancer. Additionally, we designed folate-receptor-targeting NCTD liposomes (FA-NCTD) and assessed their anticancer efficacy in vivo. NCTD effectively inhibited cell viability, clonal formation, and migration in HCT116 and HT-29 cell lines. NCTD also induced apoptosis, influenced the cell cycle, altered mitochondrial membrane potential, and increased reactive oxygen species levels. The whole-transcriptome sequencing and bioinformatics analysis identified TRAF5 as a key target for NCTD’s action against colorectal cancer. Furthermore, NCTD was found to regulate the TRAF5/NF-κB signaling pathway in both HCT116 and HT-29 cells. The FA-NCTD liposomes demonstrated effective tumor targeting and significantly inhibited tumor growth in vivo. This result showed that NCTD effectively suppresses the malignant proliferation of colon cancer cells by modulating the TRAF5/NF-κB signaling pathway and inducing programmed apoptosis, thereby offering a novel strategy for colorectal cancer treatment. The prepared FA-NCTD liposomes provide a promising approach for achieving the precise targeting and controlled release of NCTD.
Aqueous Humor Cytokine Profiling Reveals Distinct Roles for Serum Amyloid A, Interleukin-8, and Endothelin-1 in Pseudoexfoliation Syndrome and Glaucoma
Authors: Kadoh Yoichi , Takayanagi Yuji , Sugihara Kazunobu , Kaidzu Sachiko , Takai Yasuyuki , Tanito Masaki
Published: February 2025

Pseudoexfoliation syndrome (PE), which is often unilateral in 60% of cases, is a risk for exfoliation glaucoma (EXG) with elevated inflammatory cytokines. This study aimed to clarify the dynamics of these cytokines in unilateral PE (u-PE) patients. This study included 20 eyes from 10 u-PE patients (PE+ eyes and fellow PE− eyes) and 20 eyes from 10 cataract patients without PE (control group). Clinical parameters, including age, visual acuity, and intraocular pressure, were assessed. Anterior chamber aqueous humor cytokine levels (IL-8, SAA, ET-1, VEGF) were measured and compared among groups. SAA was elevated in PE+ eyes compared to PE− and control eyes. IL-8 and ET-1 were elevated in both PE+ and PE− eyes compared to controls. IL-8 was associated with worsening visual acuity, while ET-1 correlated inversely. Our findings suggest that SAA is associated with the manifest disease while IL-8 and ET-1 could be early biomarkers for PE and therapeutic targets to prevent glaucomatous damage, as these markers appear in the aqueous humor even before pseudoexfoliation material becomes clinically evident. These results may enable earlier diagnosis and therapeutic intervention before the clinical onset of PE in patients with risk factors.
Integrating Metabolomics and Network Analyses to Explore Mechanisms of Geum japonicum var. chinense Against Pulmonary Fibrosis: Involvement of Arachidonic Acid Metabolic Pathway
Authors: Ran Junyan , Wang Qian , Lu Tao , Pang Xiuqing , Liao Shanggao , He Xun
Published: February 2025

Pulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Geum japonicum var. chinense (GJC) is used as a traditional Chinese medicine to effectively treat various respiratory conditions. However, the protective effects of GJC against PF remains unclear. In the present study, the anti-PF effect of GJC aqueous extract was studied using a PF mouse model induced by bleomycin (BLM). To characterize the metabolite changes related to PF and reveal therapeutic targets for GJC aqueous extract, we performed metabolomic and network analysis on mice lungs. Finally, key targets were then validated by Western blotting. GJC aqueous extract effectively alleviated the onset and progression of lung fibrosis in PF mice by inhibiting inflammatory responses and regulating oxidative stress levels. Integrating serum metabolomics and network analyses showed the arachidonic acid (AA) pathway to be the most important metabolic pathway of GJC aqueous extract against PF. Further validation of AA pathway protein levels showed a significant rise in the levels of ALOX5, PTGS2, CYP2C9, and PLA2G2A in PF lungs. GJC aqueous extract treatment regulated the above changes in metabolic programming. In conclusion, GJC is a promising botanical drug to delay the onset and progression of PF mice. The primary mechanism of action is associated with the comprehensive regulation of metabolites and protein expression related to the AA metabolic pathway.
Mitigating Water Stress in Plants with Beneficial Bacteria: Effects on Growth and Rhizosphere Bacterial Communities
Authors: Nicotra Daniele , Mosca Alexandros , Dimaria Giulio , Massimino Maria Elena , Di Stabile Massimiliano , La Bella Emanuele , Ghadamgahi Farideh , Puglisi Ivana , Vetukuri Ramesh Raju , Catara Vittoria
Published: February 2025

Climate change has reshaped global weather patterns and intensified extreme events, with drought and soil salinity negatively impacting the yield and quality of crop production. To mitigate the detrimental effects of drought stress, the introduction of beneficial plant growth-promoting rhizobacteria (PGPR) has proven to be a promising approach. In this study, we evaluated a synthetic microbial community (SynCom) comprising bacterial strains belonging to the species Bacillus velezensis, Pseudomonas simiae, P. salmasensis, Glutamicibacter halophytocola, and Leclercia sp., which have been demonstrated to promote tomato growth both individually and collectively. The SynCom and most of its individual bacterial strains were shown to mitigate the detrimental effects of polyethylene glycol (PEG)-induced drought stress in vitro in Arabidopsis thaliana seedlings, either by reducing alterations in xylem elements or promoting the formation of new xylem strands. In a greenhouse trial, soil drenching with the SynCom and two individual strains, B. velezensis PSE31B and P. salmasensis POE54, improved the water stress response in soilless-grown tomato plants under a 40% reduced irrigation regime. Additionally, bacterial treatments positively influenced the diversity of rhizosphere bacterial communities, with distinct changes in bacterial composition, which suggest a treatment-specific interplay between the introduced strains and the native microbiome. These findings highlight the potential of microbial consortia and individual PGPR strains as sustainable tools to improve plant resilience to abiotic stresses.