bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA and RNA Methylation in Rheumatoid Arthritis—A Narrative Review
Authors: Kiełbowski Kajetan , Bakinowska Estera , Gorący-Rosik Anna , Figiel Karolina , Judek Roksana , Rosik Jakub , Dec Paweł , Modrzejewski Andrzej , Pawlik Andrzej
Published: January 2025

Rheumatoid arthritis (RA) is a progressive autoimmune disease leading to structural and functional joint damage and, eventually, to physical disability. The pathogenesis of the disease is highly complex and involves interactions between fibroblast-like synoviocytes (FLSs) and immune cells, which stimulate the secretion of pro-inflammatory factors, leading to chronic inflammation. In recent years, studies have demonstrated the importance of epigenetics in RA. Specifically, epigenetic alterations have been suggested to serve as diagnostic and treatment biomarkers, while epigenetic mechanisms are thought to be involved in the pathogenesis of RA. Epigenetic regulators coordinate gene expression, and in the case of inflammatory diseases, they regulate the expression of a broad range of inflammatory molecules. In this review, we discuss current evidence on the involvement of DNA and RNA methylation in RA.
Assessing Dominant Production Systems in the Eastern Amazon Forest
Authors: Dias Lívia Caroline César , Oliveira-Junior Neil Damas de , Mota Juliana Santos da , Monteiro Erison Carlos dos Santos , Amaral Silvana , Regolin André Luis , Luz Naíssa Batista da , Soler Luciana , Almeida Cláudio Aparecido de
Published: January 2025

The expansion of agricultural frontiers in the Amazon region poses a significant threat to forest conservation and biodiversity persistence. This study focuses on Pará state, Brazil, aiming to identify and characterize the predominant production systems by combining remote sensing data and landscape structure metrics. A rule-based classification tree algorithm is applied to classify hexagonal cells based on land cover, deforestation patterns, and distance from dairy facilities. The results reveal three dominant production systems: Natural Region, Non-Intensive Beef, and Initial Front, with livestock production being prominent. The analysis indicates that there is a correlation between the productive area and deforestation, emphasizing the role of agriculture as a driver of forest loss. Moreover, road networks significantly influence production system spatial distribution, highlighting the importance of infrastructure in land use dynamics. The Shannon diversity index reveals that areas with production systems exhibit greater diversity in land use and land cover classes, reflecting a wider range of modifications. In contrast, natural vegetation areas show lower Shannon values, suggesting that these areas are more intact and are less affected by human activities. These findings underscore the urgent need for sustainable development policies that will mitigate threats to forest resilience and biodiversity in Pará state.
Five Years of Natural Vegetation Recovery in Three Forests of Karst Graben Area and Its Effects on Plant Diversity and Soil Properties
Authors: Yang Xiaorong , Turmuhan Rouzi-Guli , Wang Lina , Li Jiali , Wan Long
Published: January 2025

In recent decades, excessive human activities have led to large-scale rocky desertification in karst areas. Vegetation restoration is one of the most important ways to control rocky desertification. In this study, vegetation surveys were conducted on three typical plantations in Jianshui County, Yunnan Province, a typical karst fault basin area, in 2016 and 2021. The plantations were Pinus massoniana forest (PM), Pinus yunnanensis forest (PY), and mixed forests of Pinus yunnanensis and Quercus variabilis (MF). Plant diversity and soil nutrients were compared during the five-year period. This paper mainly draws the following results: The plant diversity of PM, PY, and MF increased. With the increase of time, new species appeared in the tree layer, shrub layer, and herb layer of the three forests. Tree species with smaller importance values gradually withdrew from the community. In the tree layer, the Patrick index, Simpson index, and Shannon–Wiener index of the three forests increased significantly. The Pielou index changed from the highest for PM in 2016 to the highest for PY in 2021. In the shrub layer, the Pielou index of the three forests increased. The Patrick index changed from the highest for MF in 2016 to the highest for PY in 2021. There was no significant difference in species diversity index for the herb layer. With the increase of vegetation restoration time, the soil bulk density (BD) of the three forests decreased. There was no significant difference in soil total porosity (TP), soil capillary porosity (CP), and non-capillary porosity (NCP). The pH of PM increased significantly from 5.88~6.24 to 7.24~7.34. The pH of PY decreased significantly (p < 0.05). The contents of total nitrogen (TN) and ammonium nitrogen (NH4+-N) in PY and MF decreased. The content of nitrate nitrogen (NO3−-N) in the three forests increased significantly (p < 0.05). Total phosphorus (TP) content decreased in PM and MF. The content of available phosphorus (AP) in PM and PY increased. In general, with the increase of vegetation restoration time, plant diversity and soil physical and chemical properties have also been significantly improved. The results can provide important data support for vegetation restoration in karst areas.
Exploration of Heart Rate Recovery After Maximal Treadmill and Three-Minute All-Out Shuttle Tests in Firefighters
Authors: Mendelson Benjamin J. , Ebersole Kyle T. , Brau Scott D. , Ebersole Nathan T.
Published: January 2025

The purpose of this study was to compare heart rate recovery (HRR) after a maximal treadmill (MAX-TM) and three-minute all-out (3MT) test between firefighters (FF) and a control (CON) group. Nine male CON and nine male FF participants completed height (m), weight (kg), body fat percent (BF%), normalized handgrip (GRIPNORM, kg/kg), and MAX-TM with direct gas analysis to capture aerobic capacity (VO2PEAK, mL/kg/min). A shuttle-sprint 3MT was used to measure critical velocity (CV, m/s) and D′ (m). Non-linear models determined HR decay (HRRτ), HR asymptote (HR∞), and HR amplitude (HRamp). Two-way GROUP (FF vs. CON) by TEST (MAX-TM vs. 3MT) repeated measures ANOVAs indicated a significant TEST (F = 7.004, p = 0.018) effect on HRamp. When divided by VO2PEAK classification (FITNESS), a significant TEST effect was observed (F = 7.661, p = 0.014) on HRamp. VO2PEAK was significantly related to CV (r = 0.583, p = 0.011), GRIPNORM (r = 0.668, p = 0.002), and BF% (r = −0.890, p < 0.001). Complete autonomic nervous system recovery may depend on the intensity of task demands and cardiorespiratory fitness.
Community Dynamics of Fish Larvae in Coastal Zhejiang: Seasonal Variations in Spatiotemporal Distribution and Environmental Driving Factors
Authors: Zhao Peng , Jiang Rijin , Li Qiqun , Yin Rui , He Yuelian , Han Qingxi , Fang Guangjie
Published: January 2025

The coastal waters of Zhejiang feature a complex aquatic environment and abundant biological resources, creating an ideal habitat for various fish species. However, the systematic monitoring of fish larvae in these offshore waters is limited. This study collected 24,232 fish larvae using large plankton nets during April and November 2022, as well as February and July 2023, and identified 93 species, primarily warm-temperate and warm-water species, with a peak occurrence in summer. The dominant species include Larimichthys croceus, Sebastiscus marmoratus, Lateolabrax japonicus, and Odontamblyopus lacepedii, among others, and these species exhibit frequent seasonal changes. Fish larvae are typically found to be aggregated along estuaries and bays in spring, autumn, and summer, while in winter, they tend to shift towards areas near the boundaries of motor trawler fisheries areas. Our cluster analysis revealed spatial heterogeneity in the community structure, driven by an abundance of dominant and important species. Our Mantel tests and canonical correspondence analysis (CCA) identified seawater temperature and salinity as core drivers of the aggregation and distribution of fish larvae, interacting with factors such as the chlorophyll-a concentration, water turbidity, water depth, and dissolved oxygen. This research provides a scientific basis for the dynamic monitoring of spawning grounds and effective management of fishery resources in Zhejiang’s coastal waters.
Quality Preservation and Shelf-Life Extension of Prickly Pear (Opuntia ficus-indica L. Mill) Using Edible Coatings
Authors: Rodrigues Carolina , Polesca Cariny , Bicalho Isabela , Souza Victor Gomes Lauriano , Coelhoso Isabel , Fernando Ana Luísa
Published: January 2025

Prickly pear consumption is increasing across the world due to its rich variety of nutrients and bioactive compounds. Yet, it is a seasonal and highly perishable fruit, and the application of edible coatings emerges as an alternative to extend its shelf life. In this work, the effects of alginate, starch, chitosan, and pectin as coatings on the physicochemical, bioactive, microbiological, and textural properties of two prickly pear varieties (orange and red), kept under refrigeration (5 ± 2 °C) were evaluated for 6 weeks. Coatings proved to be helpful in the maintenance of the fruits’ color and textural properties, especially when pectin was applied. Overall, starch and chitosan can be considered the most effective coatings in preserving the quality of prickly pears among the options studied. A lower weight loss (8–10%) in fruits was achieved when starch and chitosan were applied, while in control fruits (without coating), the loss was 18–23%. Starch and chitosan also contributed to preserving the bioactivity of red fruits and showed good results in the preservation of total phenolic content in the orange fruits. In addition, starch and chitosan coatings also presented the best performance for the reduction of microbial contamination (both yeasts and molds and total mesophilic aerobic microorganisms). These findings highlight the role of edible coatings in preserving prickly pears, for a longer period, meeting consumers’ demand for fresh fruit.
Fish Protein Hydrolysate as Protein Enrichment in Texture-Modified Salmon Products
Authors: Prabhu Leena , Skuland Aase Vorre , Varela Paula , Rosnes Jan Thomas
Published: January 2025

The aim of this study was to develop a chilled, texture-modified salmon product for dysphagia patients, enriched with dairy and fish hydrolysate proteins. The challenge was to create a product with appealing sensory qualities and texture that meets level 5 (minced & moist) of the IDDSI framework. Atlantic salmon (Salmo salar) was heat-treated (95 °C/15 min), blended, and reconstructed by adding texture modifiers, casein and whey protein, and enzymatically derived fish hydrolysate. The products were packaged in oxygen-free plastic trays, heat-treated to a core temperature of 95 °C for 15 min, chilled and stored at 4 °C for 29 days and analyzed for microbiology, instrumental texture, and sensory properties. The texture analyses showed that products with fish protein hydrolysate were softer than those only with casein and whey protein, a result also confirmed by the IDDSI fork pressure test. Quantitative descriptive analysis of salmon products revealed significant differences (p < 0.05) in sensory attributes within flavour (fish flavour), and texture (softness and adhesiveness) but there was no significant change in bitterness. The shelf-life study at 4 °C showed good microbiological quality of the product, and safety after 29 days with appealing sensory and textural properties, i.e., a product at IDDSI level 5 for age care facilities and commercial production was obtained.
Moisture Loss from Cheese During Baking: Influence of Cheese Type, Cheese Mass, and Temperature
Authors: Tarapata Justyna , Szymańska Ewa , van der Meulen Liesbeth , Miltenburg Joost , Huppertz Thom
Published: January 2025

This study examined how temperature, cheese mass and moisture content impact moisture loss rate in various cheeses during baking. Understanding these factors is essential for determining the browning properties of cheese during baking. Eight cheese types, differing in moisture content, were baked at 100–200 °C in a halogen moisture analyzer, and moisture loss over time was recorded. A mixed-effects model analysis showed that temperature had the most significant impact on moisture loss rate (F = 2008.54; p < 0.00001), followed by cheese mass (F = 1973.28; p < 0.00001) and time (F = 278.49; p < 0.00001). Higher temperatures and larger cheese mass accelerated moisture evaporation rate. The moisture content of cheese explained 21.8% of model variation, suggesting that other factors, such as cheese structure, also play a significant role. The cheese baking process involving moisture removal followed by distinct drying stages. Initially, the drying rate increased as the cheese reached the wet bulb temperature; this was followed by a steady rate, and finally, a reduction in dehydration rate as the moisture decreased, limiting further evaporation. Browning, assessed through changes in lightness (L*), was more noticeable at higher temperatures, particularly in Mozzarella and processed Cheddar, after approx. 30% moisture loss in all cheeses.
Comparative Study of Bulgarian Linden Honey (Tilia sp.)
Authors: Yankova-Nikolova Anastasiya , Vlahova-Vangelova Desislava , Balev Desislav , Kolev Nikolay , Dragoev Stefan , Lowndes-Nikolova Biljana
Published: January 2025

The present study aims to evaluate and compare some of the main indicators characterizing Bulgarian linden honey depending on the geographical origin. A total of 18 samples were collected from the six regions of Bulgaria, with 3 samples from each region taken from different producers during the 2023 harvest. The physicochemical indicators: hydroxymethylfurfural content, diastase activity, pH, color, water content and electrical conductivity, as well as organoleptic and pollen characteristics, were analyzed. Antioxidant activity was also investigated by several methods: total phenolic content (TPC), phenolic compounds by the Glories method, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical activity, CUPRAC (Cupric Reducing Antioxidant Capacity), iron-reducing antioxidant capacity (FRAP) assay, and radical scavenging capacity in terms of ABTS•+, ORAC (oxygen radical antioxidant capacity). Differences were found depending on the region. All the studied honeys from the Northern Central Region contained higher Tilia sp. pollen. In the Southwestern Region, Tilia sp. pollen was not detected in any of the honey samples. The highest sensory score was awarded to linden honey from the Northern Central Region. An overall assessment ranks linden honey from the Northern Central region, the richest in linden forests, as the highest quality among the six studied regions. Another key finding was that 39% of linden honey labeled or declared as monofloral linden honey on the Bulgarian market does not meet the established criteria for monofloral honey.
A Time–Frequency Composite Recurrence Plots-Based Series Arc Fault Detection Method for Photovoltaic Systems with Different Operating Conditions
Authors: Yin Zhendong , Ouyang Hongxia , Lu Junchi , Wang Li , Yang Shanshui
Published: January 2025

Series arc faults (SAFs) pose a significant threat to the safety of photovoltaic (PV) systems. However, the complex operating conditions of PV systems make accurate SAF detection challenging. To tackle this issue, this article proposes a SAF detection method based on time–frequency composite recurrence plots (TFCRPs). Initially, variational mode decomposition (VMD) is employed to decompose the current into distinct modes. Subsequently, the proposed TFCRP transforms these modes into two-dimensional matrices, enabling the measurement of composite similarity between different phase states. Lastly, extra tree (ET) is utilized to fuse the fractional recurrence entropy (FRE) and the singular values extracted from the matrices, thereby achieving SAF detection. Experimental results indicate that the proposed method achieves a detection accuracy of 98.75% and can accurately detect SAFs under various operating conditions. Comparisons with different methods further highlight the advancement of the proposed method. Furthermore, the detection time of the proposed method (209 ms) meets the requirements of standard UL1699B.
Expanding the Molecular Spectrum of MMP21 Missense Variants: Clinical Insights and Literature Review
Authors: Pasquetti Domizia , Tesolin Paola , Perino Federica , Zampieri Stefania , Bobbo Marco , Caiffa Thomas , Spedicati Beatrice , Girotto Giorgia
Published: January 2025

Background/Objectives: The failure of physiological left-right (LR) patterning, a critical embryological process responsible for establishing the asymmetric positioning of internal organs, leads to a spectrum of congenital abnormalities characterized by laterality defects, collectively known as “heterotaxy”. MMP21 biallelic variants have recently been associated with heterotaxy syndrome and congenital heart defects (CHD). However, the genotype–phenotype correlations and the underlying pathogenic mechanisms remain poorly understood. Methods: Patients harboring biallelic MMP21 missense variants who underwent diagnostic genetic testing for CHD or heterotaxy were recruited at the Institute for Maternal and Child Health—I.R.C.C.S. “Burlo Garofolo”. Additionally, a literature review on MMP21 missense variants was conducted, and clinical data from reported patients, along with molecular data from in silico and modeling tools, were collected. Results: A total of 18 MMP21 missense variants were reported in 26 patients, with the majority exhibiting CHD (94%) and variable extra-cardiac manifestations (64%). In our cohort, through Whole-Exome Sequencing (WES) analysis, the missense p.(Met301Ile) variant was identified in two unrelated patients, who both presented with heterotaxy syndrome. Conclusions: Our comprehensive analysis of MMP21 missense variants supports the pathogenic role of the p.(Met301Ile) variant and provides significant insights into the disease pathogenesis. Specifically, missense variants are distributed throughout the gene without clustering in specific regions, and phenotype comparisons between patients carrying missense variants in compound heterozygosity or homozygosity do not reveal significant differences. These findings may suggest a potential loss-of-function mechanism for MMP21 missense variants, especially those located in the catalytic domain, and highlight their critical role in the pathogenesis of heterotaxy syndrome.
Quantitative Trait Loci for Phenology, Yield, and Phosphorus Use Efficiency in Cowpea
Authors: Mohammed Saba B. , Ongom Patrick Obia , Belko Nouhoun , Umar Muhammad L. , Muñoz-Amatriaín María , Huynh Bao-Lam , Togola Abou , Ishiyaku Muhammad F. , Boukar Ousmane
Published: January 2025

Background/Objectives: Cowpea is an important legume crop in sub-Saharan Africa (SSA) and beyond. However, access to phosphorus (P), a critical element for plant growth and development, is a significant constraint in SSA. Thus, it is essential to have high P-use efficiency varieties to achieve increased yields in environments where little-to- no phosphate fertilizers are applied. Methods: In this study, crop phenology, yield, and grain P efficiency traits were assessed in two recombinant inbred line (RIL) populations across ten environments under high- and low-P soil conditions to identify traits’ response to different soil P levels and associated quantitative trait loci (QTLs). Single-environment (SEA) and multi-environment (MEA) QTL analyses were conducted for days to flowering (DTF), days to maturity (DTM), biomass yield (BYLD), grain yield (GYLD), grain P-use efficiency (gPUE) and grain P-uptake efficiency (gPUpE). Results: Phenotypic data indicated significant variation among the RILs, and inadequate soil P had a negative impact on flowering, maturity, and yield traits. A total of 40 QTLs were identified by SEA, with most explaining greater than 10% of the phenotypic variance, indicating that many major-effect QTLs contributed to the genetic component of these traits. Similarly, MEA identified 23 QTLs associated with DTF, DTM, GYLD, and gPUpE under high- and low-P environments. Thirty percent (12/40) of the QTLs identified by SEA were also found by MEA, and some of those were identified in more than one P environment, highlighting their potential in breeding programs targeting PUE. QTLs on chromosomes Vu03 and Vu08 exhibited consistent effects under both high- and low-P conditions. In addition, candidate genes underlying the QTL regions were identified. Conclusions: This study lays the foundation for molecular breeding for PUE and contributes to understanding the genetic basis of cowpea response in different soil P conditions. Some of the identified genomic loci, many being novel QTLs, could be deployed in marker-aided selection and fine mapping of candidate genes.
Effect of Health Education Intervention on Knowledge and Adherence to Intermittent Preventive Treatment of Malaria in Pregnancy Among Women
Authors: Atser Pauline N. , Hayat Gommaa , Okafor Uchenna B.
Published: January 2025

Aim: Malaria in pregnancy is a global health problem because it causes anemia in the mother and may result in abortion, stillbirth, uterine growth retardation, and low birth weight in the newborn. The purpose of this study was to assess the effects of HEI on knowledge and adherence to intermittent preventive treatment of malaria among pregnant women at secondary health facilities in Benue State, Nigeria. Methods: This quasi-experimental study included pre-, intervention, and post-intervention. The study recruited 871 pregnant women (436 study and 435 control) using multistage sampling. The study used a semi-structured questionnaire (pre- and post-test), follow-up checklist, and health education module. Participants self-administered the semi-structured questionnaire with 57 open-ended and closed-ended questions. Results: About 41% had high malaria awareness, but 93.9% did throughout pregnancy and intermittent preventive treatment (IPT) after health education intervention (HEI). The majority (93.8%) understood malaria transmission methods after HEI. 95.3% understood malaria symptoms after HEI. The HEI shows 95.6% of participants knew a lot about malaria during pregnancy. Post-HEI, 95% knew malaria prophylaxis. After HEI, 95.4% knew malaria-prevention drugs. Intermittent Preventive treatment (IPT) pregnancy dosages were known by 94.3% of respondents post-HEI. Post-HEI, 95.4% of responders knew the interval between IPT dosages, compared to 59.2% pre-HEI. After HEI, 95% of respondents were aware of IPT adverse effects, up from 29.2% pre-HEI. Pre-HEI showed. Conclusions: Results demonstrate HEI promotes malaria IPT adherence during pregnancy. A health education proves a veritable interventional strategy in influencing a mother’s understanding of malaria IPT, level of adherence to IPT, and drug adherence to directly observed therapy of IP while pregnant. Thus, nurses and midwives should increase IPT health education during antenatal clinic visits to increase its uptake and adherence among pregnant women and reduce malaria burden and death. Sulfadoxine/pyrimethamine (SP) for malaria in pregnancy (MiP) IPT must be distributed by the state health ministry to all health facilities—tertiary, secondary, primary, faith-based, and private.
Preserving the Past, Embracing the Future: Co-Design Strategies for Achieving Harmony Between Heritage Sites and Accessibility Needs
Authors: Lakoud Maryem , Morales Ernesto , Ruiz-Rodrigo Alicia , Feillou Isabelle , Mathieu Samuel , Riendeau Jonathan , Routhier François
Published: January 2025

Canada’s heritage sites, while fewer in number compared to Europe, face significant challenges in accessibility due to strict preservation laws. Many were built before social inclusion became a priority, making them difficult to navigate for individuals with disabilities. For example, cobbled streets with uneven surfaces or significant level differences create obstacles for wheelchair users and others with mobility challenges. This qualitative action research aimed to develop guidelines for shared street designs and innovative solutions that balance heritage preservation with inclusive accessibility. The study involved go along interviews with 21 participants with disabilities in Quebec City’s Petit-Champlain and Place-Royale areas, as well as the Old-Seminary. Insights from these interviews informed a co-design methodology involving three sessions with participants with disabilities, family caregivers, and experts in accessibility and heritage. The co-design sessions generated practical solutions such as lift platforms, accessible signage, and guided handrails, addressing both outdoor and indoor accessibility barriers. For indoor spaces, solutions included integrating acoustic panels and foldable seating, while outdoor recommendations emphasized autonomous access solutions like non-slip coatings and accessible elevators for winter conditions. It was concluded that achieving a balance between preservation and accessibility requires collaboration among architects, designers, heritage experts, and individuals with disabilities. This research highlights the importance of co-design as a method to ensure heritage sites remain culturally significant and universally accessible.
Addressing Vaccine Hesitancy: Validating the PACV Survey for Croatian Parents
Authors: Ćurković Ana , Matana Antonela
Published: January 2025

Background/Objectives: Vaccine hesitancy, recognized by the WHO as a significant global health threat, undermines vaccination efforts. This study aimed to adapt and validate the Parent Attitudes about Childhood Vaccines (PACV) Survey for Croatian parents to understand vaccine hesitancy better. Methods: A cross-sectional study with 1814 Croatian parents was conducted using the PACV survey, translated using a double-back translation method. The psychometrics of the questionnaire were examined, including content validity, dimensionality, construct validity, discriminant validity, and reliability. Confirmatory factor analysis (CFA) assessed the original model’s validity, but the original model fit poorly, prompting exploratory factor analysis (EFA) to identify latent factors. Reliability was measured using Cronbach’s alpha and McDonald’s omega. Results: EFA identified a five-factor model with factors labeled “Safety”, “Schedule”, “Attitudes”, “Behavior”, and “Trust”. Subsequent CFA confirmed this model with acceptable to good fit indices. Discriminant validity was also confirmed. Reliability analyses indicated high internal consistency, with total Cronbach’s alpha at 0.926 and McDonald’s omega at 0.931. Conclusions: The adapted PACV is a valid and reliable tool for identifying vaccine hesitancy among Croatian parents. This study revealed high vaccine hesitancy among Croatian parents, emphasizing the need for targeted interventions.
Mobilising Cross-Sectoral Collaboration in Creating Age-Friendly Cities: Case Studies from Akita and Manchester
Authors: Doran Patty , Yarker Sophie , Buffel Tine , Satake Hisami , Watanabe Fumito , Kimoto Minoru , Kodama Ayuto , Kume Yu , Suzuki Keiko , Makabe Sachiko , Ota Hidetaka
Published: January 2025

Developing Age-Friendly Cities and Communities (AFCCs) is an increasingly popular policy response to supporting ageing populations. AFCC programmes rely on cross-sectoral collaboration, involving partnerships among diverse stakeholders working across sectors to address shared goals. However, there remains a limited understanding of what mechanisms and strategies drive collaboration among diverse actors within age-friendly cities. To address this gap, this empirical paper draws on examples from a comparative case study across Akita (Japan) and Manchester (UK), two cities with distinct demographic profiles but both with a longstanding commitment to the age-friendly approach. Case studies were created through a range of data collection methods, namely, a review of secondary data sources, semi-structured interviews with key stakeholders, and fieldwork in each city. Key insights from the case studies relating to the mobilisation of cross-sectoral collaboration were categorised into three themes: leadership and influencing, co-production, and place-based working. These mechanisms are not mutually exclusive; collaboration building through co-production and place-based working is essential to deliver age-friendly programmes, but these mechanisms rely on leadership and influence. Therefore, it is recommended that all three mechanisms be used to effectively mobilise cross-sectoral collaborations to collectively create AFCC and support healthy ageing.
The Use of Dansyl Chloride to Probe Protein Structure and Dynamics
Authors: Larson James , Tokmina-Lukaszewska Monika , Malone Jadyn , Hasenoehrl Ethan J. , Kelly Will , Fang Xuelan , White Aidan , Patterson Angela , Bothner Brian
Published: January 2025

Dansyl labeling is a widely used approach for enhancing the detection of small molecules by UV spectroscopy and mass spectrometry. It has been successfully applied to identify and quantify a variety of biological and environmental specimens. Despite clear advantages, the dansylation reaction has found very few applications in the study of proteins. We reasoned that the mild labeling conditions, small size, and rapid reaction could be beneficial for studying protein structure and dynamics. To test this, we investigated the impact of dansylation on protein fold, stability, protein–protein, and protein–cofactor interactions. We selected two model proteins, myoglobin and alcohol dehydrogenase, for analysis using native mass spectrometry and ion mobility mass spectrometry. Our work establishes the utility of dansyl chloride as a covalent probe to study protein structure and dynamics under native conditions.
Plasma GlycA, a Glycoprotein Marker of Chronic Inflammation, and All-Cause Mortality in Cirrhotic Patients and Liver Transplant Recipients
Authors: Li Yakun , Chvatal-Medina Mateo , Trillos-Almanza Maria Camila , Connelly Margery A. , Moshage Han , Bakker Stephan J. L. , de Meijer Vincent E. , Blokzijl Hans , Dullaart Robin P. F.
Published: January 2025

Low-grade chronic inflammation may impact liver disease. We investigated the extent to which circulating GlycA, a glycoprotein biomarker of low-grade inflammation, and high-sensitivity C-reactive protein (hs-CRP) are altered in patients with cirrhosis and liver transplant recipients (LTRs) and examined their associations with all-cause mortality. Plasma GlycA (nuclear magnetic resonance spectroscopy) and hs-CRP (nephelometry) were assessed in 129 patients with cirrhosis on the waiting list for liver transplantation and 367 LTRs (TransplantLines cohort study; NCT03272841) and compared with 4837 participants from the population-based PREVEND cohort. GlycA levels were lower, while hs-CRP levels were higher in patients with cirrhosis compared to PREVEND participants (p < 0.001). Notably, GlycA increased, but hs-CRP decreased after transplantation. In LTRs, both GlycA and hs-CRP levels were higher than in PREVEND participants (p < 0.001). Survival was impaired in patients with cirrhosis and LTRs with the highest GlycA and the highest hs-CRP tertiles. In Cox regression analysis, GlycA remained associated with mortality in cirrhotic patients after adjusting for potential confounders and for hs-CRP (HR per 1-SD increment: 2.34 [95% CI 1.07–5.13]), while the association with hs-CRP after adjusting was lost. In LTRs, both GlycA and hs-CRP were also associated with mortality (adjusted HR: 1.60 [95% CI: 1.2–2.14] and 1.64 [95% CI: 1.08–2.51], respectively) but not independent of each other. GlycA increases while hs-CRP decreases after liver transplantation. Both inflammatory markers may be associated with all-cause mortality in cirrhotic patients and LTRs, while the association for GlycA seems at least as strong as that for hs-CRP.
Pre-Clinical Rationale for Amcenestrant Combinations in HER2+/ER+ Breast Cancer
Authors: Mahdi Amira F. , Ashfield Niall , Crown John , Collins Denis M.
Published: January 2025

HER2-positive/oestrogen receptor-positive (HER2+/ER+) represents a unique breast cancer subtype. The use of individual HER2- or ER-targeting agents can lead to the acquisition of therapeutic resistance due to compensatory receptor crosstalk. New drug combinations targeting HER2 and ER could improve outcomes for patients with HER2+/ER+ breast cancer. In this study, the pre-clinical rationale is explored for combining amcenestrant (Amc), a selective oestrogen receptor degrader (SERD), with HER2-targeted therapies including trastuzumab, trastuzumab-emtansine (T-DM1) and tyrosine kinase inhibitors (TKIs). The combination of Amc and anti-HER2 therapies was investigated in a panel of four HER2+/ER+ cell lines: BT-474, MDA-MB-361, EFM-192a and a trastuzumab-resistant variant BT-474-T. Proliferation (IC50 and matrix combination assays) was determined using acid phosphatase assays. HER2/ER and intracellular signalling pathway protein levels/activity were investigated by western blot. Apoptosis was assessed using caspase 3/7 assays. Additivity and synergy were observed between Amc and the TKIs neratinib, lapatinib and tucatinib in all cell lines. Amc increased the anti-proliferative effect of trastuzumab in MDA-MB-361 and BT-474-T. Addition of Amc also increased anti-proliferative efficacy of T-DM1 in BT-474-T. TKI/Amc combinations reduced p-HER2 and ER levels and resulted in increased apoptosis. Higher ER expression in MDA-MB-361 and BT-474-T was associated with greater potential for synergy. In conclusion, the combination of Amc- and HER2-targeted treatments has potential as a therapeutic strategy for the treatment of HER2+/ER+ breast cancer and warrants further clinical investigation to validate safety and efficacy in patients.
Responsivity of Two Pea Genotypes to the Symbiosis with Rhizobia and Arbuscular Mycorrhiza Fungi—A Proteomics Aspect of the “Efficiency of Interactions with Beneficial Soil Microorganisms” Trait
Authors: Frolov Andrej , Shumilina Julia , Etemadi Afshar Sarah , Mashkina Valeria , Rhomanovskaya Ekaterina , Lukasheva Elena , Tsarev Alexander , Sulima Anton S. , Shtark Oksana Y. , Ihling Christian , Soboleva Alena , Tikhonovich Igor A. , Zhukov Vladimir A.
Published: January 2025

It is well known that individual pea (Pisum sativum L.) cultivars differ in their symbiotic responsivity. This trait is typically manifested with an increase in seed weights, due to inoculation with rhizobial bacteria and arbuscular mycorrhizal fungi. The aim of this study was to characterize alterations in the root proteome of highly responsive pea genotype k-8274 plants and low responsive genotype k-3358 ones grown in non-sterile soil, which were associated with root colonization with rhizobial bacteria and arbuscular mycorrhizal fungi (in comparison to proteome shifts caused by soil supplementation with mineral nitrogen salts). Our results clearly indicate that supplementation of the soil with mineral nitrogen-containing salts switched the root proteome of both genotypes to assimilation of the available nitrogen, whereas the processes associated with nitrogen fixation were suppressed. Surprisingly, inoculation with rhizobial bacteria had only a minor effect on the root proteomes of both genotypes. The most pronounced response was observed for the highly responsive k-8274 genotype inoculated simultaneously with rhizobial bacteria and arbuscular mycorrhizal fungi. This response involved activation of the proteins related to redox metabolism and suppression of excessive nodule formation. In turn, the low responsive genotype k-3358 demonstrated a pronounced inoculation-induced suppression of protein metabolism and enhanced diverse defense reactions in pea roots under the same soil conditions. The results of the study shed light on the molecular basis of differential symbiotic responsivity in different pea cultivars. The raw data are available in the PRIDE repository under the project accession number PXD058701 and project DOI 10.6019/PXD058701.
Relative Distribution of DnaA and DNA in Escherichia coli Cells as a Factor of Their Phenotypic Variability
Authors: Namboodiri Sharanya K. , Aranovich Alexander , Hadad Uzi , Gheber Levi A. , Feingold Mario , Fishov Itzhak
Published: January 2025

Phenotypic variability in isogenic bacterial populations is a remarkable feature that helps them cope with external stresses, yet it is incompletely understood. This variability can stem from gene expression noise and/or the unequal partitioning of low-copy-number freely diffusing proteins during cell division. Some high-copy-number components are transiently associated with almost immobile large assemblies (hyperstructures) and may be unequally distributed, contributing to bacterial phenotypic variability. We focus on the nucleoid hyperstructure containing numerous DNA-associated proteins, including the replication initiator DnaA. Previously, we found an increasing asynchrony in the nucleoid segregation dynamics in growing E. coli cell lineages and suggested that variable replication initiation timing may be the main cause of this phenomenon. Here, we support this hypothesis revealing that DnaA/DNA variability represents a key factor leading to the enhanced asynchrony in E. coli. We followed the intra- and intercellular distribution of fluorescently tagged DnaA and histone-like HU chromosomally encoded under their native promoters. The diffusion rate of DnaA is low, corresponding to a diffusion-binding mode of mobility, but still one order faster than that of HU. The intracellular distribution of DnaA concentration is homogeneous in contrast to the significant asymmetry in the distribution of HU to the cell halves, leading to the unequal DNA content of nucleoids and DnaA/DNA ratios in future daughter compartments. Accordingly, the intercellular variabilities in HU concentration (CV = 26%) and DnaA/DNA ratio (CV = 18%) are high. The variable DnaA/DNA may cause a variable replication initiation time (initiation noise). Asynchronous initiation at different replication origins may, in turn, be the mechanism leading to the observed asymmetric intracellular DNA distribution. Our findings indicate that the feature determining the variability of the initiation time in E. coli is the DnaA/DNA ratio, rather than each of them separately. We provide a likely mechanism for the ‘loss of segregation synchrony’ phenomenon.
Differential Impact of Medical Therapies for Acromegaly on Glucose Metabolism
Authors: Gatto Federico , Arecco Anna , Amarù Jessica , Arvigo Marica , Campana Claudia , Milioto Angelo , Esposito Daniela , Johannsson Gudmundur , Cocchiara Francesco , Maggi Davide Carlo , Ferone Diego , Puddu Alessandra
Published: January 2025

Acromegaly is a rare endocrine disorder caused by excessive growth hormone (GH) production, due, in the vast majority of cases, to the presence of a GH-secreting pituitary tumour. The chronic elevation of GH and the resulting high circulating levels of insulin-like growth factor-1 (IGF-1) cause the characteristic tissue overgrowth and a number of associated comorbidities, including several metabolic changes, such as glucose intolerance and overt diabetes mellitus (DM). Elevated GH concentrations directly attenuate insulin signalling and stimulate lipolysis, decreasing glucose uptake in peripheral tissues, thus leading to the development of impaired glucose tolerance and DM. Acromegaly treatment aims to normalize plasma GH and IGF-1 levels using surgery, medical treatment, or radiotherapy. The effect of the different medical therapies on glucose homeostasis varies. This literature review explores the impact of the currently available pharmacological therapies for acromegaly (first- and second-generation somatostatin receptor ligands, a GH receptor antagonist, and dopamine agonists) on glucose homeostasis. We also discuss the underlying biological mechanisms through which they impact glucose metabolism.
Encouraging Sustainable Choices Through Socially Engaged Persuasive Recycling Initiatives: A Participatory Action Design Research Study
Authors: da Silva Emilly Marques , Schneider Daniel , Miceli Claudio , Correia António
Published: January 2025

Human-Computer Interaction (HCI) research has illuminated how technology can influence users’ awareness of their environmental impact and the potential for mitigating these impacts. From hot water saving to food waste reduction, researchers have systematically and widely tried to find pathways to speed up achieving sustainable development goals through persuasive technology interventions. However, motivating users to adopt sustainable behaviors through interactive technologies presents significant psychological, cultural, and technical challenges in creating engaging and long-lasting experiences. Aligned with this perspective, there is a dearth of research and design solutions addressing the use of persuasive technology to promote sustainable recycling behavior. Guided by a participatory design approach, this investigation focuses on the design opportunities for leveraging persuasive and human-centered Internet of Things (IoT) applications to enhance user engagement in recycling activities. The assumption is that one pathway to achieve this goal is to adopt persuasive strategies that may be incorporated into the design of sustainable applications. The insights gained from this process can then be applied to various sustainable HCI scenarios and therefore contribute to HCI’s limited understanding in this area by providing a series of design-oriented research recommendations for informing the development of persuasive and socially engaged recycling platforms. In particular, we advocate for the inclusion of educational content, real-time interactive feedback, and intuitive interfaces to actively engage users in recycling activities. Moreover, recognizing the cultural context in which the technology is socially situated becomes imperative for the effective implementation of smart devices to foster sustainable recycling practices. To this end, we present a case study that seeks to involve children and adolescents in pro-recycling activities within the school environment.
From Biology to Clinical Practice: The Bone Marrow Microenvironment in Multiple Myeloma
Authors: Fotiou Despina , Katodritou Eirini
Published: January 2025

Multiple Myeloma (MM) is a complex hematological malignancy characterized by the clonal proliferation of malignant plasma cells within bone marrow (BM) [...]
Exploring Prognostic Factors and Survival Outcomes in Advanced Non-Small Cell Lung Cancer Patients Undergoing First-Line Chemotherapy in Limited-Resource Settings
Authors: Chayangsu Chawalit , Khorana Jiraporn , Charoentum Chaiyut , Sriuranpong Virote , Patumanond Jayanton , Tantraworasin Apichat
Published: January 2025

Background/Objectives: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality globally, especially in limited-resource countries (LRCs) where access to advanced treatments such as targeted therapy and immunotherapy is constrained. Platinum-based chemotherapy remains a cornerstone of first-line therapy. This study aims to identify prognostic factors influencing survival outcomes and evaluate treatment response to chemotherapy in advanced NSCLC patients in LRCs. Methods: A retrospective cohort study was conducted on 200 advanced NSCLC patients treated with first-line platinum-based doublet chemotherapy at Surin Hospital Cancer Center, Thailand. Prognostic factors were assessed through univariate and multivariate Cox regression analyses. Additionally, restricted mean survival time (RMST) was calculated to compare survival outcomes between responders and non-responders. Results: Independent prognostic factors associated with improved survival included good performance status, ECOG 0–1 (HR 0.50, p = 0.012), serum albumin ≥ 3.5 mg/dL (HR 0.60, p = 0.010), and favorable response to chemotherapy (HR 0.57, p = 0.003). Responders demonstrated significantly longer RMST at 12 months (p < 0.001), 24 months (p < 0.001), and 36 months (p = 0.004) compared to non-responders. Conclusions: Identifying prognostic factors and treatment responses is important for improving outcomes in advanced NSCLC patients, particularly in limited-resource settings where access to novel therapies is restricted.
Risk Stratification of QTc Prolongations in Hospitalized Cardiology and Gastroenterology Patients Using the Tisdale Score—A Retrospective Analysis
Authors: Steinbrech Julian , Amann Ute , Irlbeck Michael , Clauß Sebastian , Strobach Dorothea
Published: January 2025

Background/Objectives: QTc prolongation can result in lethal arrhythmia. Risk scores like the Tisdale score can be used for risk stratification for targeted pharmaceutical interventions. However, the practical usability across different medical specialties has not been sufficiently investigated. The aim of this study was to compare relevant risk factors for QTc prolongation and to investigate the use of the Tisdale score in cardiology and gastroenterology patients. Methods: For patients on a cardiology and a gastroenterology ward receiving a weekly pharmaceutical electronic chart review, risk factors for QTc prolongation, QTc-prolonging drugs, and electrocardiograms (ECGs) were retrospectively collected for a four-month period (07-10/2023), and the Tisdale score and its sensitivity and specificity were calculated. Results: A total of 627 chart reviews (cases) (335 cardiology, 292 gastroenterology) were performed. The median age was 66 (range 20–94) years, and 39% (245) of patients were female. The presence of established risk factors (hypokalemia, renal impairment, age ≥ 68 years, cardiac diseases) differed significantly between the specialties. A median of 2 (range 0–5) QTc-prolonging drugs were prescribed in both groups. Baseline and follow-up ECG were recorded in 166 (50%) cardiology cases, of which prolonged QTc intervals were detected in 38 (23%) cases. In the 27 (9%) gastroenterology cases with baseline and follow-up ECG, no QTc prolongations were detected. Across both specialties, the Tisdale score achieved a sensitivity of 74% and a specificity of 30%. Conclusions: The presence of established risk factors for QTc prolongation differed significantly between cardiology and gastroenterology cases. The Tisdale score showed acceptable sensitivity for risk stratification; however, the limited availability of ECGs for gastroenterology cases was a limiting factor.
A Study of Dizziness or Vertigo Cases Associated with Inflammatory Bowel Disease (Crohn’s Disease and Ulcerative Colitis) in a Vertigo Outpatient Clinic
Authors: Kamogashira Teru , Nakada Tomoaki , Kanaya Kaori
Published: January 2025

Background/Objectives: Dizziness and vertigo are reported in about half of patients with inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Orthostatic dysregulation (OD) is recognized as one of the comorbidities that causes dizziness or vertigo with IBD. Our hospital is affiliated with the Inflammatory Bowel Disease Center, which specializes in diagnosing and treating IBD, so cases with dizziness or vertigo symptoms associated with IBD are sometimes referred to our department, a type of department which is rare in other facilities. The objective of this study is to evaluate IBD cases with dizziness or vertigo symptoms referred to a vertigo outpatient clinic in terms of vestibular function and OD. Methods: The subjects were 221 patients who were referred to the vertigo outpatient clinic of our department from March 2021 to September 2024. Results: Of the 221 patients, 9 cases had CD and 1 case had UC. OD complications were significantly more common in the IBD group than in the non-IBD group, whereas complications of psychogenic vertigo or migraine were not significantly different between groups, and there was no difference in vestibular dysfunction between groups. OD was a complication in all cases using ustekinumab. Conclusions: An orthostatic test will be valuable for diagnosing OD in IBD patients with dizziness or vertigo symptoms.