bluuebunny/crossref_metadata_2025 huggingface dataset:
Life and Quality of Life of Older Adults in Residential Centers in Spain: A Focus Group Analysis Based on Center Quality from the Perspective of Management Stakeholders
Authors: De-la-Fuente-Robles Yolanda María , Rodríguez-Martínez Antonia , Martín-Cano María del Carmen , Jiménez-Delgado Juan José
Published: December 2024

Background/Objectives: New residential models for older adults highlight the need for both public and private institutions to adopt new governance and management approaches. These approaches focus on strategic frameworks that guide decision-making, daily operations, and processes aimed at addressing and resolving the economic and social challenges faced by our society while promoting quality standards that serve the public good. The primary objective of this research is to identify and analyze the quality of residential centers and their impact on improving the quality of life of older adult residents from the perspective of management stakeholders; Methods: This study employed a qualitative methodology, involving systematic literature reviews and the analysis of focus groups. The participants were professionals from various fields working with older adults in Spanish residential centers; Results: The results reveal widespread dissatisfaction among participants regarding the need for change to improve both the quality of the centers and the quality of life for older adult residents; Conclusions: This study suggests that the well-being of older adults residing in these centers requires regulatory changes that focus on person-centered care and are tailored to the specific needs of the residents.
Impact of Hearing Loss Severity on Hearing Aid Benefit Among Adult Users
Authors: Ziemska-Gorczyca Marlena , Dżaman Karolina , Kantor Ireneusz
Published: December 2024

Background: Hearing loss (HL) among older adults is a major global health concern. Hearing aids (HAs) offer an effective solution to manage HL and enhance the quality of life. However, the adoption and the consistent use of HAs remain low, making non-use a significant barrier to successful audiological rehabilitation. The aim of the study was to assess the benefit of HAs among patients with different degrees of HL and to determine the profiles of patients who have the least benefit from HAs. Methods: the HA benefits were assessed by using the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire. Participants were assigned to the study groups based on the pure-tone audiometry. This paper presents the results obtained by using HAs in various listening environments among 167 patients. Results: The majority of individuals benefited from HAs in a noisy environment while a reverberant environment provided the lowest benefit. It was observed that the degree of HL had a statistically significant impact on the benefits of HAs in terms of the communication ease, the reverberation, the background noise, and the global score. A moderately positive correlation was observed between the unaided APHAB and the HL degree. The subjects’ APHAB scores ranged from the 50th to the 65th percentile. Additionally, women had a significantly better improvement than men. Conclusions: HAs improved communication in everyday life situations among 91.6% of HA users. The degree of HL influences APHAB scores. Patients with a severe degree of HL achieved the greatest APHAB scores while male patients with mild HL received the lowest benefits of HAs. Both HL and the age, gender, and HA type are factors that also play important roles. The APHAB questionnaire is a reliable screening test for patients with hearing difficulties.
The Effectiveness and Safety of Tranexamic Acid in Treating Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis
Authors: Al Zayer Mohammed O. , Al Johani Fatima M. , Al ghamdi Shahad A. , Al Hejaili Mohammed D. , Al Mukhtar Fatima H. , Al Ariany Arwa M. , Al Anazi Bashar H. , Al Mutairi Khalid A. , Khoja Rammaz H. , Al Amer Haidar F. , Zeidan Adel A. , Al Faraj Dunya
Published: December 2024

Background/Objectives: Tranexamic acid (TXA) is a synthetic antifibrinolytic agent that inhibits plasminogen activation, thereby reducing bleeding. The aim of this systematic review was to investigate its role in aneurysmal subarachnoid hemorrhage (SAH)—a condition indicated by bleeding between two layers of brain tissue—to stop rebleeding and improve patient outcomes. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from 1981 to 2024, focusing on the efficacy and safety of TXA in treating aneurysmal SAH (PROSPERO registration: CRD42024504834). Our comprehensive search of the PubMed and Cochrane Library databases identified studies assessing TXA at dosages of 3 to 6 g per day and examining outcomes such as rebleeding incidence, mortality, thromboembolic events, and other adverse effects. Results: From six included studies involving 2990 patients, the meta-analysis showed TXA largely lowered rebleeding risk (OR 0.54 95% CI 0.43–0.68; p < 0.00001), yet mortality rates were not largely different between the TXA group (385 out of 1201), and the control group (344 out of 1193) (OR 1.18 95% CI 0.98–1.40; p = 0.07). Likewise, there were no large differences in the occurrence of cerebral ischemia and blood clot-related events between the groups. Conclusions: TXA effectively reduces the risk of rebleeding in SAH patients, but does not significantly alter mortality or the incidence of thromboembolic complications. These findings back the careful use of TXA and demonstrate the need for further research to better its clinical use and assess long-term impacts.
Cross-Cultural Adaptation and Validation of the Person-Centered Therapeutic Relationship in Physiotherapy Scale to European Portuguese
Authors: Moreira João , Domingues Lúcia , Silva Margarida , Caeiro Carmen
Published: December 2024

Background/Objectives: Implementing a person-centered practice is considered a priority in healthcare, and the development of a solid and positive therapeutic relationship is a fundamental element. This study conducted a cross-cultural adaptation of the Person-Centered Therapeutic Relationship in Physiotherapy Scale to European Portuguese and contributed to its validation through the study of its structural validity and internal consistency. Methods: This study was conducted from October 2021 to July 2023 and included two phases: a methodological study of cross-cultural adaptation (phase 1) and a transversal study to assess the psychometric properties (phase 2). Structural validity was analyzed using exploratory factor analysis and internal consistency was estimated using Cronbach’s alpha (α). A p-value < 0.05 was considered to indicate statistical significance. Results: The Person-Centered Therapeutic Relationship in Physiotherapy Scale was successfully culturally adapted to European Portuguese (phase 1). During phase 2, 203 individuals [mean age: 50.16 ± 13.10 years (range 18–80 years)] with musculoskeletal conditions, mostly female (63.1%), were recruited. The factorial solution explained 74.7% of the total variability and retained three factors, grouping items 9 to 15 in a common factor (professional empowerment and therapeutic communication). Adequate internal consistency was found (Cronbach’s α = 0.889). Conclusions: This study culturally adapted an instrument to European Portuguese, which allows the assessment of the person-centered therapeutic relationship in physiotherapy, presenting adequate internal consistency. Future studies should contribute to the remaining validation of the instrument so that it can be available to the Portuguese population.
A Six-Week Smartphone-Based Program for HPV Prevention Among Mothers of School-Aged Boys: A Quasi-Experimental Study in South Korea
Authors: Cho Yun-Hee , Kim Tae-Im
Published: December 2024

Background: Human papilloma virus (HPV) affects both males and females, but in South Korea, vaccination rates for boys are significantly lower due to cultural stigma and limited awareness. Effective strategies are needed to close this gap. Methods: This study evaluated a 6-week smartphone-based HPV prevention program for mothers of school-aged boys, designed using the extended theory of planned behavior (E-TPB). The program aimed to enhance knowledge, attitudes, subjective norms, and self-efficacy, with the goal of increasing vaccination intention and uptake. The E-TPB incorporated knowledge as a key element to improve behavioral intention and vaccination uptake. A nonequivalent control group pre-test–post-test design included 54 mothers (28 in the experimental group and 26 in the control group). Results: The experimental group showed significant improvements in HPV knowledge (p < 0.001; d = 1.41), HPV vaccine knowledge (p < 0.001; d = 1.13), attitudes (p < 0.001; r = 0.48), subjective norms (p = 0.014; d = 0.61), self-efficacy (p < 0.001; r = 0.53), and vaccination intention (p < 0.001; r = 0.58). The experimental group achieved a vaccination uptake rate of 25.0%, compared to 4.0% in the control group, representing a six-fold increase (RR = 6.25; p = 0.033; h = 0.64). Conclusions: The program effectively addressed key factors influencing vaccination behavior, leading to significant increases in HPV vaccination rates among boys. Smartphone-based education shows promise in reducing gender disparities in vaccination uptake, though further studies with larger samples are needed to validate these findings.
Color of Small Ochre Fragments from the Upper Paleolithic Sites Kapova Cave and Kamennaya Balka II (Russia): Combining Visual Color Identification and Cluster Analysis
Authors: Anisovets Yulia , Zhitenev Vladislav , Vinogradova Ekaterina , Statkus Mikhail
Published: December 2024

A technique for characterizing the color of small ochre samples was proposed. The technique includes visual color determination with the aid of a stereomicroscope and a Munsell Soil Color Chart, conversion of Munsell values to CIE L*a*b* coordinates, cluster analysis, and principle component analysis (PCA). The technique was applied to ochre samples from the Kapova Cave and Kamennaya Balka II Upper Paleolithic sites. Characterization of the color of a statistically significant number of pigment samples makes it possible to identify the relationships between different structural features of the cultural layer and reliably identify a wide range of artistic practices in parietal caves in addition to the actual creation of drawings, and it also possibly serves as a chronological marker at multi-layered sites.
Delayed Diagnosis of Disseminated Invasive Aspergillosis with Purulent Myocarditis in an Immunocompromised Host
Authors: Londema Mark , Nijsten Maarten W. N. , Bart Joost , Wiegersma Janke S. , Sinha Bhanu N. M. , Postma Douwe F.
Published: December 2024

Introduction: Invasive aspergillosis (IA) is an opportunistic fungal infection that typically occurs in the immunocompromised host and is associated with severe morbidity and mortality. Myocardial abscess formation is seldomly described. Detailed Case Description: We present a case of IA with purulent myocarditis. The patient was on long-term high-dose corticosteroid and mycophenolate mofetil therapy for severe lupus nephritis. After multiple visits to his general practitioner and nephrologist for general malaise, he was admitted to our hospital with visual complaints. Within several days, he developed atrial fibrillation, respiratory insufficiency, and, finally, a decreased level of consciousness. After admission to the intensive care unit, the broncho alveolar lavage (BAL) fluid galactomannan (GM) index was normal, but the serum GM index was severely elevated. Despite initiation of antifungal therapy, the patient passed away shortly thereafter. Autopsy revealed massive intracranial hemorrhage and disseminated IA affecting the lungs, brain, and myocardium, with macroscopic myocardial abscess formation. Discussion: This classic case of diagnostic uncertainty illustrates how invasive fungal infections can progress to disseminated disease while showing nonspecific symptoms only. It emphasizes the importance of vigilance for opportunistic fungal infections in a growing category of immunocompromised patients. Conclusion: Clinicians should have a low threshold of suspicion for fungal infections in patients on combination immunosuppressive medication, such as high-dose corticosteroid therapy in combination with T-cell inhibitors like MMF.
RNA-Binding S1 Domain in Bacterial, Archaeal and Eukaryotic Proteins as One of the Evolutionary Markers of Symbiogenesis
Authors: Deryusheva Evgenia I. , Machulin Andrey V. , Surin Alexey A. , Kravchenko Sergey V. , Surin Alexey K. , Galzitskaya Oxana V.
Published: December 2024

The RNA-binding S1 domain is a β-barrel with a highly conserved RNA-binding site on its surface. This domain is an important part of the structures of different bacterial, archaeal, and eukaryotic proteins. A distinctive feature of the S1 domain is multiple presences (structural repeats) in proteins and protein complexes. Here, we have analyzed all available protein sequences in the UniProt database to obtain data on the distribution of bacterial, eukaryotic and archaeal proteins containing the S1 domain. Mainly, the S1 domain is found in bacterial proteins with the number of domains varying from one to eight. Eukaryotic proteins contain from one to fifteen S1 domains, while in archaeal proteins, only one S1 domain is identified. Analysis of eukaryotic proteins containing S1 domains revealed a group of chloroplast S1 ribosomal proteins (ChRpS1) with characteristic properties of bacterial S1 ribosomal proteins (RpS1) from the Cyanobacteria. Also, in a separate group, chloroplast and mitochondrial elongation factor Ts containing two S1 structural domains were assigned. For mitochondrial elongation factor Ts, the features of S1 in comparison with the RpS1 from Cyanobacteria phylum and the Alphaproteobacteria class were revealed. The data obtained allow us to consider the S1 domain as one of the evolutionary markers of the symbiogenesis of bacterial and eukaryotic organisms.
Inflammasomes in Intestinal Disease: Mechanisms of Activation and Therapeutic Strategies
Authors: Scalavino Viviana , Piccinno Emanuele , Giannelli Gianluigi , Serino Grazia
Published: December 2024

NOD-like receptors (NLRs) are a family of cytosolic pattern recognition receptors (PRRs) implicated in the innate immune sensing of pathogens and damage signals. NLRs act as sensors in multi-protein complexes called inflammasomes. Inflammasome activity is necessary for the maintenance of intestinal homeostasis, although their aberrant activation contributes to the pathogenesis of several gastrointestinal diseases. In this review, we summarize the main features of the predominant types of inflammasomes involved in gastrointestinal immune responses and their implications in intestinal disease, including Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (IBD), celiac disease, and Colorectal Cancer (CRC). In addition, we report therapeutic discoveries that target the inflammasome pathway, highlighting promising novel therapeutic strategies in the treatment of intestinal diseases. Collectively, our understanding of the mechanisms of intestinal inflammasome activation and their interactions with other immune pathways appear to be not fully elucidated. Moreover, the clinical relevance of the efficacy of inflammasome inhibitors has not been evaluated. Despite these limitations, a greater understanding of the effectiveness, specificity, and reliability of pharmacological and natural inhibitors that target inflammasome components could be an opportunity to develop new therapeutic options for the treatment of intestinal disease.
Novel Mutation Lys30Glu in the TPM1 Gene Leads to Pediatric Left Ventricular Non-Compaction and Dilated Cardiomyopathy via Impairment of Structural and Functional Properties of Cardiac Tropomyosin
Authors: Zaklyazminskaya Elena V. , Nefedova Victoria V. , Koubassova Natalia A. , Kotlukova Natalia P. , Kopylova Galina V. , Kochurova Anastasia M. , Shchepkin Daniil V. , Ryabkova Natalia S. , Katrukha Ivan A. , Kleymenov Sergey Y. , Bershitsky Sergey Y. , Matyushenko Alexander M. , Tsaturyan Andrey K. , Levitsky Dmitrii I.
Published: December 2024

Pediatric dilated cardiomyopathy (DCM) is a rare heart muscle disorder leading to the enlargement of all chambers and systolic dysfunction. We identified a novel de novo variant, c.88A>G (p.Lys30Glu, K30E), in the TPM1 gene encoding the major cardiac muscle tropomyosin (Tpm) isoform, Tpm1.1. The variant was found in a proband with DCM and left ventricular non-compaction who progressed to terminal heart failure at the age of 3 years and 8 months. To study the properties of the mutant protein, we produced recombinant K30E Tpm and used various biochemical and biophysical methods to compare its properties with those of WT Tpm. The K30E substitution decreased the thermal stability of Tpm and its complex with actin and significantly reduced the sliding velocity of the regulated thin filaments over a surface covered by ovine cardiac myosin in an in vitro motility assay across the entire physiological range of Ca2+ concentration. Our molecular dynamics simulations suggest that the charge reversal of the 30th residue of Tpm alters the actin monomer to which it is bound. We hypothesize that this rearrangement of the actin–Tpm interaction may hinder the transition of a myosin head attached to a nearby actin from a weakly to a strongly bound, force-generating state, thereby reducing myocardial contractility. The impaired myosin interaction with regulated actin filaments and the decreased thermal stability of the actin–Tpm complex at a near physiological temperature likely contribute to the pathogenicity of the variant and its causative role in progressive DCM.
Glycosylation Pattern of Serum Clusterin in Psoriatic Arthritis and Rheumatoid Arthritis—The Search for New Diagnostic Glycomarkers
Authors: Kratz Ewa Maria , Kacperczyk Monika , Kokot Izabela , Piwowar Agnieszka , Konopska Bogusława , Sokolik Renata , Korman Lucyna
Published: December 2024

Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are connective tissue autoimmune diseases. The present study aimed to check whether serum clusterin (CLU) concentration and its glycosylation pattern may be markers differentiating these diseases—blood sera of patients with PsA (n = 37), RA (n = 34), and healthy subjects (control, n = 21) were examined. CLU concentration was measured using the ELISA test. Glycosylation was analyzed using lectin-ELISA with sialo-specific lectins from Maackia amurensis (MAA) and Sambucus nigra (SNA) recognizing sialic acid (SA) α2,3- and α2,6-linked, respectively, and fucose-specific lectins from Lotus tetragonolobus (LTA), Ulex europaeus (UEA), and Lens culinaris (LCA) specific to fucose α1,3-linked, α1,2-linked, and core fucose, respectively. Significantly higher CLU concentrations were observed in the PsA than in the RA patients. The expression of α2,6-linked SA was significantly higher in the PsA and RA patients than in the control. The expression of SNA-reactive SA was visibly higher in the PsA compared to the RA and control group but insignificant. Negative significant correlations between CLU concentrations and its glycans reactivity with LTA and UEA were also observed. Significantly higher serum CLU concentration, accompanied by a high expression of SNA-reactive SA and a reduced degree of Lewisx and Lewisy antennary fucosylation, may constitute a promising panel of parameters differentiating PsA from RA.
Chemogenetic Modulation of Preoptic Gabre Neurons Decreases Body Temperature and Heart Rate
Authors: Wang Ziyue , Li Lanxiang , Li Miao , Lu Zhonghua , Qin Lihua , Naumann Robert Konrad , Wang Hong
Published: December 2024

The preoptic area of the hypothalamus is critical for regulation of brain–body interaction, including circuits that control vital signs such as body temperature and heart rate. The preoptic area contains approximately 70 molecularly distinct cell types. The Gabre gene is expressed in a subset of preoptic area cell types. It encodes the GABA receptor ε-subunit, which is thought to confer resistance to anesthetics at the molecular level, but the function of Gabre cells in the brain remains largely unknown. We generated and have extensively characterized a Gabre-cre knock-in mouse line and used chemogenetic tools to interrogate the function of Gabre cells in the preoptic area. Comparison with macaque GABRE expression revealed the conserved character of Gabre cells in the preoptic area. In awake mice, we found that chemogenetic activation of Gabre neurons in the preoptic area reduced body temperature, whereas chemogenetic inhibition had no effect. Furthermore, chemogenetic inhibition of Gabre neurons in the preoptic area decreased the heart rate, whereas chemogenetic activation had no effect under isoflurane anesthesia. These findings suggest an important role of preoptic Gabre neurons in maintaining vital signs such as body temperature and heart rate during wakefulness and under anesthesia.
Integrated Analysis of Neuroendocrine and Neurotransmission Pathways Following Developmental Atrazine Exposure in Zebrafish
Authors: Stradtman Sydney C. , Swihart Jenna N. , Moore Kaylin , Akoro Isabelle N. , Ahkin Chin Tai Janiel K. , Tamagno Wagner Antonio , Freeman Jennifer L.
Published: December 2024

Atrazine is an endocrine-disrupting herbicide, with exposure impacting adverse outcomes along multiple endocrine pathways. This study investigated the neuroendocrine system as the central target of atrazine toxicity, examining effects of early developmental exposures on neurohormones and genes associated with kisspeptin, hypothalamic, pituitary, and dopamine systems. Zebrafish were exposed to 0, 0.3, 3, or 30 ppb (µg/L) atrazine during two developmental time windows. For neurohormone assessments, exposure was ceased at the end of embryogenesis (72 h post-fertilization, hpf) and analyzed immediately or grown to 0.5, 2, or 2.5 years post-fertilization (ypf). Gene expression was measured immediately after 1–72 hpf or 72–120 hpf exposure. Estradiol decreased in the 0.3 and 30 ppb groups in 0.5 ypf female brains, while dopamine decreased in the same treatment groups at 72 hpf. Increases were also observed in 2.5 ypf female brains (3 ppb) for estradiol and in 2 ypf female and male brains (3 and 30 ppb) for dopamine. Gene expression alterations occurred for the follicle-stimulating hormone (fsh) at 72 hpf and the growth hormone (gh1) at 72 and 120 hpf. Overall, results indicated that developmental atrazine exposure has immediate and long-term sex-specific effects on neurohormonal systems.
A 3D-Printable Cell Array for In Vitro Breast Cancer Modeling
Authors: Arciero Ilaria , Buonvino Silvia , Palumbo Valeria , Scimeca Manuel , Melino Sonia
Published: December 2024

Breast cancer is the most common cancer and the second leading cause of cancer-related death in women. In advanced stages of the disease, breast cancer can spread and metastasize to the bone, contributing to malignant progression. The roles of tissue stiffness and remodeling of the tumor microenvironment are relevant in influencing cancer progression and invasiveness, but they are still poorly understood. In this study, we aimed to investigate the effect of bone tissue stiffness on breast cancer cell behavior, using 3D cell–biomaterial systems to model the in vivo conditions. For this purpose, we developed a 3D-printable cell array, which is a tunable and reproducible platform on small scale, where each compartment could mimic the physiological cancer environment with a shape and rigidity close to bone tissue. In this system, we observed that in the highly metastatic breast cancer line MDA-MB-231, embedded in PEG–silk fibroin (PSF) hydrogel spheres in the array’s cavities, increasing stiffness promotes trans-differentiation into osteoblast-like cells and the production of breast microcalcifications. Moreover, we also tested this 3D model as a platform to evaluate the cell response to the therapy, in particular, investigating the drug sensitivity of the cancer cells to chemotherapeutics, observing a decrease in drug resistance over time in the array.
Exosomes Derived from Adipose Mesenhymal Stem Cells Ameliorate Lipid Metabolism Disturbances Following Liver Ischemia-Reperfusion Injury in Miniature Swine
Authors: Lu Xiangyu , Wang Yue , Piao Chenxi , Li Pujun , Cao Lei , Liu Tao , Ma Yajun , Wang Hongbin
Published: December 2024

The liver plays a crucial role in regulating lipid metabolism. Our study examined the impact of Exosomes derived from adipose mesenchymal stem cells (ADSCs-Exo) on lipid metabolism following liver ischemia-reperfusion injury (IRI) combined with partial hepatectomy. We developed a miniature swine model for a minimally invasive hemi-hepatectomy combined with liver IRI. In this study, we administered PBS, ADSCs-Exo, and adipose-derived stem cells (ADSCs) individually through the portal vein. Before and after surgery, we evaluated various factors including hepatocyte ultrastructure, lipid accumulation in liver tissue, and expression levels of genes and proteins associated with lipid metabolism. In addition, we measured serum and liver tissue levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (CHOL). TEM and oil red O stain indicated a significant reduction in liver steatosis following ADSCs-Exo treatment, which also elevated serum levels of HDL, LDL, TG, and CHOL. Additionally, ADSCs-Exo have been shown to significantly decrease serum concentrations of HDL, LDL, TG, and CHOL in the liver (p < 0.05). Finally, ADSCs-Exo significantly downregulated lipid synthesis-related genes and proteins, including SREBP-1, SREBP-2, ACC1, and FASN (p < 0.05), while upregulating lipid catabolism-related genes and proteins, such as PPAR-α and ACOX1 (p < 0.05). ADSCs-Exo as a cell-free therapy highlights its therapeutic potential in hepatic lipid metabolism abnormalities.
AhR-Induced Anti-Inflammatory Effects on a Caco-2/THP-1 Co-Culture Model of Intestinal Inflammation Are Mediated by PPARγ
Authors: da Rocha Gustavo Henrique Oliveira , Müller Claudia , Przybylski-Wartner Susanne , Schaller Heidrun , Riemschneider Sina , Lehmann Jörg
Published: December 2024

The aryl hydrocarbon receptor (AhR) and the peroxisome proliferator-activated receptor γ (PPARγ) are ligand-activated transcription factors that have in recent years been investigated for their anti-inflammatory properties for treatment of inflammatory bowel diseases (IBDs). These are globally prevalent chronic maladies of the gut that lack cost-efficient therapeutical options capable of inducing long-term remission. In the present study, we used an in vitro Transwell® co-culture model composed of Caco-2 epithelial cells in the apical compartment and lipopolysaccharide-treated (LPS) THP-1 macrophages in the basolateral compartment. Secretion of cytokines, disruption of epithelial integrity, and expression of surface markers and junctional proteins were assessed in order to investigate interactions between AhR and PPARγ on the ligand-elicited effects on the control of inflammation. The results revealed that the potent AhR ligand 6-formylindolo[3,2-b]carbazole (FICZ) attenuated LPS-induced IL-6 release by macrophages, which then stabilized Caco-2 monolayer permeability by decreasing claudin-2 expression. These effects were disrupted by GW9662 and to some extent by CH223191, inhibitors of PPARγ and AhR, respectively. Our main findings evidence PPARγ might be a downstream regulator of AhR activation essential for its ligand-based anti-inflammatory effects, suggesting it might be employed as either an auxiliary target or as a biomarker of therapeutical efficacy on AhR-based IBD pharmacotherapy.
Impact of Plant-Based School Meals on Gut Bifidobacterium spp. Abundance and Health Outcomes in Schoolchildren from Bahia, Brazil
Authors: Menezes Camilla Almeida , Zanette Dalila Lucíola , Magalhães Letícia Bastos , Lago Renata Maria Rabello da Silva , Gomes Alexvon Nunes , dos Santos Ronald Alves , Ledeia Ana Marice Teixeira , Vianna Nelzair Araújo , Oliveira Ricardo Riccio
Published: December 2024

Plant-based diets have been linked to various health benefits, including an improved gut microbiota composition, potentially influencing non-communicable diseases. This study investigates the impact of a school meal intervention on the gut microbiota, specifically the abundance of Bifidobacterium spp. (BIF), in Brazilian schoolchildren. A quasi-experimental intervention was conducted in 2019 across four municipalities in the semi-arid region of Bahia, Brazil. The Sustainable School Program aimed to replace animal-based and ultra-processed foods with plant-based options. Clinical, dietary, anthropometric, and laboratory data were collected at the beginning and end of the school year. Fecal samples were analyzed for BIF abundance using RT-PCR. The intervention improved anthropometric and laboratory outcomes, including increased serum hemoglobin levels and reduced LDL-cholesterol. Despite these benefits, no significant change in BIF abundance was observed. However, a negative correlation between BIF abundance and waist-to-height ratio was found. While the intervention positively affected several health parameters, it did not significantly alter BIF abundance. Nevertheless, the abundance of BIF may explain some of these positive outcomes. The findings highlight the potential of plant-based diets to improve overall health, but suggest that further research is needed to understand the role of the gut microbiota in these outcomes. Future studies should explore the influence of factors such as physical activity on the gut microbiota and health.
Drug-Dependent Inhibitory Effects on Corneal Epithelium Structure, Cell Viability, and Corneal Wound Healing by Local Anesthetics
Authors: Foja Sabine , Heinzelmann Joana , Hünniger Susanne , Viestenz Anja , Rüger Christiane , Viestenz Arne
Published: December 2024

Local anesthetics are commonly used in ophthalmic surgery. However, their use can affect the healing process. This study aimed to investigate the potential impact of anesthetic substances at clinically relevant concentrations and incubation times (3 min), specifically oxybuprocaine (OBPC, 0.4%), lidocaine (LIDO, 2%), and bupivacaine (BUPI, 0.5%), either alone or supplemented with hylase (HYLA, 30 I.E.), on corneal epithelium structure, cell viability, and wound healing. To assess the potential cytotoxicity of these anesthetic substances, viability and colony-forming efficiency (CFE) assays were conducted using the human telomerase-immortalized corneal epithelial (hTCEpi) cell line. Additionally, the toxicity of these substances was evaluated using a 3D human tissue-specific corneal epithelial construct as well as a porcine corneal culture model. The results indicate that OBPC (Novesine® 0.4%) exhibited significant cytotoxicity in 2D and 3D corneal epithelial cell culture models and delayed wound healing in the ex vivo porcine corneal organ culture model. In contrast, LIDO, BUPI, and HYLA were less cytotoxic to corneal cells, with no observed impact on wound healing in the porcine corneal organ culture model. In summary, local anesthetics commonly used in eye surgery are generally considered safe. However, the application of OBPC (Novesine® 0.4%) may delay wound healing.
Uncertainty Quantification and Flagging of Unreliable Predictions in Predicting Mass Spectrometry-Related Properties of Small Molecules Using Machine Learning
Authors: Matyushin Dmitriy D. , Burov Ivan A. , Sholokhova Anastasia Yu.
Published: December 2024

Mass spectral identification (in particular, in metabolomics) can be refined by comparing the observed and predicted properties of molecules, such as chromatographic retention. Significant advancements have been made in predicting these values using machine learning and deep learning. Usually, model predictions do not contain any indication of the possible error (uncertainty) or only one criterion is used for this purpose. The spread of predictions of several models included in the ensemble, and the molecular similarity of the considered molecule and the most “similar” molecule from the training set, are values that allow us to estimate the uncertainty. The Euclidean distance between vectors, calculated based on real-valued molecular descriptors, can be used for the assessment of molecular similarity. Another factor indicating uncertainty is the molecule’s belonging to one of the clusters (data set clustering). Together, all three factors can be used as features for the uncertainty assessment model. Classification models that predict whether a prediction belongs to the worst 15% were obtained. The area under the receiver operating curve value is in the range of 0.73–0.82 for the considered tasks: the prediction of retention indices in gas chromatography, retention times in liquid chromatography, and collision cross-sections in ion mobility spectroscopy.
Activation of Bradykinin B2 Receptors in Astrocytes Stimulates the Release of Leukemia Inhibitory Factor for Autocrine and Paracrine Signaling
Authors: Lu Ying , Gu Yishan , Chan Anthony S. L. , Yung Ying , Wong Yung H.
Published: December 2024

Communications between different cell types within a tissue are often critical for the proper functioning of an organ. In the central nervous system, interactions among neurons and glial cells are known to modulate neurotransmission, energy metabolism, extracellular ion homeostasis, and neuroprotection. Here we showed that bradykinin, a proinflammatory neuropeptide, can be detected by astrocytes, resulting in the secretion of cytokines that act on neurons. In astrocytic cell lines and primary astrocytes, bradykinin and several other ligands acting on Gq-coupled receptors stimulated Ca2+ mobilization, which subsequently led to the release of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). The bradykinin B2 receptor antagonist, HOE-140, effectively blocked the ability of bradykinin to mobilize Ca2+ and stimulate mitogen-activated protein kinases (MAPKs) in astrocytes. Interestingly, incubation of neuronal cell lines and primary cortical neurons with conditioned media from bradykinin-treated astrocytes resulted in the activation of STAT3, a key component downstream of LIF and IL-6 receptors. LIF was apparently the major active factor in the conditioned media as the STAT3 response was almost completely neutralized by an anti-LIF antiserum. The presence of kininogen and kallikrein transcripts in neuronal cells but not in astrocytic cells indicates that neurons can produce bradykinin. Correspondingly, conditioned media from neuronal cells stimulated MAPKs in astrocytes in a HOE-140-sensitive manner. These studies demonstrate that paracrine signaling between neurons and astrocytes may involve ligands of Gq-coupled receptors and cytokines such as LIF.
Ameliorative Effect of Ginsenoside Rc on 5-Fluorouracil-Induced Chemotherapeutic Intestinal Mucositis via the PI3K-AKT/NF-κB Signaling Pathway: In Vivo and In Vitro Evaluations
Authors: Xu Liyue , Zhao Xiaolan , Tang Fei , Zhang Jingnan , Peng Cheng , Ao Hui
Published: December 2024

5-Fluorouracil (5-Fu) is a chemotherapeutic agent widely used to treat various cancers, which causes intestinal mucositis as a common side effect. Ginsenoside Rc, an active compound with anti-inflammatory, antioxidant, immunomodulatory, and antitumor properties, has protective effects against chemotherapy-induced mucositis caused by 5-Fu. This study aims to evaluate the protective effects of Rc on 5-Fu-induced chemotherapy-related mucositis and to elucidate its underlying mechanisms. In vivo experiments were conducted to measure intestinal permeability and assess the effects of Rc on body weight loss, diarrhea, and intestinal pathology induced by 5-Fu. Network pharmacology was also employed to explore potential mechanisms. In vitro, IEC-6 cell models were used to validate the cytoprotective effects of Rc, including assessments of cell viability, apoptosis, lactate dehydrogenase (LDH) release, and changes in inflammatory cytokine levels. The results indicate that Rc significantly ameliorated body weight reduction, diarrhea, and intestinal damage in mice treated by 5-Fu. Rc significantly mitigated 5-Fu-induced cellular damage by reducing levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α and decreasing apoptosis and cell permeability. Western blot analysis revealed that Rc upregulated the expression of Bcl-2 and tight junction proteins and downregulated the expression of Bax. Furthermore, Rc exerts anti-inflammatory and anti-apoptotic effects through PI3K-AKT and NF-κB signaling pathways. In conclusion, ginsenoside Rc demonstrated significant protective effects against 5-Fu-induced intestinal mucositis via the PI3K-AKT/NF-κB signaling pathway, suggesting its potential as a therapeutic agent for chemotherapy-related mucositis.
Molecular Biology of Cancer—Interplay of Malignant Cells with Emerging Therapies
Authors: Boussios Stergios , Sheriff Matin , Ovsepian Saak V.
Published: December 2024

Cancer is currently one of the leading causes of death worldwide, and according to data from the World Health Organization reported in 2020, it ranks as the second leading cause of death globally, accounting for 10 million fatalities [...]
Calaspargase-Pegol-Mknl Combined with BCL-2 and MCL-1 Inhibition for Acute Myeloid Leukemia
Authors: Bollino Dominique , Ma Xinrong , Tighe Kayla M. , Casildo Andrea , Richard Katharina , Passaniti Antonino , Carter-Cooper Brandon , Strovel Erin T. , Emadi Ashkan
Published: December 2024

Our previous studies have demonstrated that pegcrisantaspase (PegC), a long-acting Erwinia asparaginase, synergizes with the BCL-2 inhibitor Venetoclax (Ven) in vitro and in vivo; however, the anti-leukemic activity of E. coli-derived asparaginases in combination with BCL-2 inhibition, and potential synergy with inhibitors of MCL-1, a key resistance factor of BCL-2 inhibition, has yet to be determined. Using a combination of human AML cells lines, primary samples, and in vivo xenograft mouse models, we established the anti-leukemic activity of the BCL-2 inhibitor S55746 and the MCL-1 inhibitor S63845, alone and in combination with the long-acting E. coli asparaginase calaspargase pegol-mknl (CalPegA). We report that CalPegA enhances the anti-leukemic effect of S55746 but does not impact the activity of S63845. The S55746-CalPegA combination inhibited protein synthesis and increased eIF4E/4EBP1 interaction, suggesting an inhibition of translational complex formation. These results support the clinical evaluation of CalPegA in combination with BCL-2 inhibition for AML.
Interaction of DDB1 with NBS1 in a DNA Damage Checkpoint Pathway
Authors: Lim Hoe Eun , Lim Hee Jung , Yoo Hae Yong
Published: December 2024

Various DNA damage checkpoint control mechanisms in eukaryotic cells help maintain genomic integrity. Among these, NBS1, a key component of the MRE11-RAD50-NBS1 (MRN) complex, is an essential protein involved in the DNA damage response (DDR). In this study, we discovered that DNA damage-binding protein 1 (DDB1) interacts with NBS1. DDB1 is a DDR sensor protein found in UV-induced DNA replication blocks. Through pull-down and immunoprecipitation assays conducted in Xenopus egg extracts and human cell lines, we demonstrated a specific interaction between NBS1 and DDB1. DDB1 was also found to associate with several proteins that interact with NBS1, including DNA topoisomerase 2-binding protein 1 (TopBP1) and Mediator of DNA damage checkpoint protein 1 (MDC1). Notably, the interaction between DDB1 and NBS1 is disrupted in MDC1-depleted egg extracts, indicating that MDC1 is necessary for this interaction. Furthermore, the depletion of DDB1 leads to increased Chk1 activation upon DNA damage. These novel findings regarding the interaction between NBS1 and DDB1 provide new insights into how DDB1 regulates DNA damage pathways.
Therapeutic Efficacy and Underlying Mechanisms of a Mannoglucan from Hirsutella sinensis Mycelium on Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease in Mice: Modulation of the Intestinal Barrier, Oxidative Stress and Gut Microbiota
Authors: Ni Weihua , Li Yu , Feng Jingyue , Liu Boxuan , Yuan Hongyan , Tai Guixiang , Bi Hongtao
Published: December 2024

Hirsutella sinensis (H. sinensis), a non-sexual form of the valuable Chinese medicinal herb, demonstrates various biological activities, such as immune modulation and antioxidative capabilities. Nonetheless, the effects of bioactive polysaccharides derived from H. sinensis on colitis have yet to be investigated. In our prior research, we extracted a mannoglucan (HSWP-1d) from H. sinensis and found that it attenuates TGF-β1-induced epithelial-mesenchymal transition. The present study investigated the protective effects of HSWP-1d against colitis induced by dextran sulfate sodium (DSS) in mice. The results demonstrate that HSWP-1d effectively ameliorates symptoms of colitis and preserves the intestinal barrier’s stability by enhancing the expression of tight junction proteins. The administration of HSWP-1d results in a reduction in oxidative stress through the augmentation of antioxidative enzyme activities, concomitant with the suppression of oxidative product generation. Simultaneously, HSWP-1d reduced the levels of pro-inflammatory cytokines while elevating the levels of anti-inflammatory cytokines, effectively mitigating the inflammatory response. Furthermore, HSWP-1d influences and alters short-chain-fatty-acid (SCFA) levels, thereby enhancing the intestinal microenvironment. In conclusion, HSWP-1d contributes to intestinal well-being and holds potential as both a therapeutic choice and a supplier of essential nutrients for the amelioration of colitis.
A Human-Centered Approach to Academic Performance Prediction Using Personality Factors in Educational AI
Authors: Aslam Muhammad Adnan , Murtaza Fiza , Haq Muhammad Ehatisham Ul , Yasin Amanullah , Azam Muhammad Awais
Published: December 2024

As artificial intelligence (AI) becomes increasingly integrated into educational environments, adopting a human-centered approach is essential for enhancing student outcomes. This study investigates the role of personality factors in predicting academic performance, emphasizing the need for explainable and ethical AI systems. Utilizing the SAPEx-D (Student Academic Performance Exploration) dataset from Air University, Islamabad, which comprises 494 records, we explore how individual personality traits can impact academic success. We employed advanced regression models, including Gradient Boosting Regressor, K-Nearest Neighbors Regressor, Linear Regression, and Support Vector Regression, to predict students’ Cumulative Grade Point Average (CGPA). Our findings reveal that the Gradient Boosting Regressor achieved an R-squared value of 0.63 with the lowest Mean Squared Error (MSE); incorporating personality factors elevated the R-squared to 0.83, significantly improving predictive accuracy. For letter grade classification, the incorporation of personality factors improved the accuracy for distinct classes to 0.67 and to 0.85 for broader class categories. The integration of the Shapley Additive Explanations (SHAPs) technique further allowed for the interpretation of how personality traits interact with other factors, underscoring their role in shaping academic outcomes. This research highlights the importance of designing AI systems that are not only accurate but also interpretable and aligned with human values, thereby fostering a more equitable educational landscape. Future work will expand on these findings by exploring the interaction effects of personality traits and applying more sophisticated machine learning techniques.
Formal Verification of Business Constraints in Workflow-Based Applications
Authors: Stoica Florin , Stoica Laura Florentina
Published: December 2024

Workflows coordinate a series of computing tasks to create a sophisticated workflow logic. Ensuring the correctness of a workflow specification is essential for automating business processes. Errors in the specification should be identified and resolved as early as possible, during the design phase. In this paper, we propose a verification approach for workflow specifications utilizing model checking techniques. We introduce a method for verifying the correctness properties of workflow processes by utilizing our database-embedded Alternating-time Temporal Logic (ATL) model checker. First, the workflow specification is translated into a concurrent game structure (CGS). Next, the desired property is expressed as an ATL formula. Finally, the ATL model checker is executed to verify whether the correctness properties hold for the model. To support users in the formalization of business constraints, the proposed solution implements an assistant based on generative AI. The experimental results show that employing the chain-of-thought prompting method significantly enhances the reasoning process performance when using the GPT-4o model.
Exploring Intellectual Property in the Digital Realm: A Bibliometric Study on Research on the Management and Protection of Data-Based Intellectual Property
Authors: Sun Hanyue , Liu Jiajia , Chen Bingyuan , Yang Le
Published: December 2024

The management and protection of data-based intellectual property have attracted increasing attention in the academic community due to the rapid development of digital technologies and data-driven industries. However, a comprehensive and multidimensional examination of the research landscape is still required to better understand its structure and evolution. Using CiteSpace software, this study conducts a bibliometric analysis, revealing key trends and patterns in collaboration, co-citation, and keyword co-occurrence in the field of data-based intellectual property. Our findings show a growing body of literature on data IP management, with a significant increase in publications since 2013. We identify that collaboration between regions, especially the United States, China, and the United Kingdom, leads global efforts, but institutional collaboration remains underdeveloped. In terms of co-citation, seminal works by Jaffe, Hall, and Samuelson form the foundation of the current research, while emerging research focuses on technological innovations like blockchain and AI. The analysis further reveals that future research is likely to explore the intersections of data privacy, innovation, and legal frameworks. Compared with previous studies, this paper builds a knowledge framework for data-based intellectual property management from a holistic perspective of bibliometrics, analyses the current challenges, and outlines future research directions, which is of significant reference value to both scholars and practitioners.
Preventing Dysgraphia: Early Observation Protocols and a Technological Framework for Monitoring and Enhancing Graphomotor Skills
Authors: Ceccacci Silvia , Taddei Arianna , Del Bianco Noemi , Giaconi Catia , Forteza Forteza Dolors , Moreno-Tallón Francisca
Published: December 2024

Writing is first-order instrumental learning that develops throughout the life cycle, a complex process evolving from early childhood education. The identification of risk predictors of dysgraphia at age 5 has the potential to significantly reduce the impact of graphomotor difficulties in early primary school, which affects handwriting performance to such an extent that it can become illegible. Building on established scientific literature, this study focuses on screening processes, with particular attention to writing requirements. This paper proposes a novel prevention and intervention system based on new technologies for teachers and educators or therapists. Specifically, it presents a pilot study testing an innovative tactile device to analyze graphomotor performance and motor coordination in real time. The research explores whether this haptic device can be used as an effective pedagogical aid for preventing graphomotor issues in children aged 5 to 6 years. The results showed a high level of engagement and usability among young participants. Furthermore, the quality of graphomotor traces, respectively executed by children after virtual and physical training, were comparable, supporting the use of the tool as a complementary training resource for the observation and enhancement of graphomotor processes.