bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric Assessment of the Communication Skills Scale Among Peruvian Nurses and Factors Associated with Job Insecurity
Authors: Samillán-Yncio Gabriela , Zeladita-Huaman Jhon Alex , Franco-Chalco Eduardo , Zegarra-Chapoñan Roberto , Montes-Iturrizaga Iván , Rivera-Medrano Zulma Jeanette
Published: December 2024

Background/Objectives: The aim of this study was to evaluate the psychometric properties of the Communication Skills Scale (CSS) among Peruvian nurses, as well as the factors associated with job insecurity during the COVID-19 pandemic. Methods: We explored five models of confirmatory factor analysis for the CSS and its four subscales and assessed the convergent validity and criterion validity of the scale by analyzing its connection with job insecurity through stepwise multiple regression. We used insights from a focus group for the cultural adaptation of the scale. In the psychometric phase, 225 nurses participated through a virtual survey. Results: The psychometric analysis revealed that the CSS and its subscales have a robust internal structure—similar to the original questionnaire—and are optimally reliable in the Peruvian population. Furthermore, the results show that job insecurity was associated with contract type, communication skills, empathy, and job satisfaction. Conclusions: The CSS and its subscales are valid and reliable to be applied to Peruvian nurses. Initiatives should be undertaken to strengthen communication skills and increase job satisfaction among nursing professionals by improving their working conditions, especially in times of crisis, to reduce job insecurity and promote well-being.
Exploring the Association Between Adolescents’ Health Literacy and Health Behavior by Using the Short Health Literacy (HLS19-Q12) Questionnaire
Authors: Sukys Saulius , Kuzmarskiene Gerda , Motiejunaite Kristina
Published: December 2024

Background: Health literacy (HL) is an important element of public health that is linked to health behavior in children and adolescents. This study aimed to investigate the structural validity and reliability of the HLS19-Q12 in the adolescent population, to measure the general HL of adolescents, and to assess the relationship between adolescents’ HL and health behavior. Methods: This cross-sectional study involved 825 students aged 15–19 years attending Lithuanian gymnasiums. The participants completed an online survey that collected information on key sociodemographic, HL, and health behavior indicators. Factor analysis, Cronbach’s alpha, and McDonald’s omega were used to validate the Lithuanian version of the HLS19-Q12. Health behavior indicators, including physical activity, smoking, alcohol consumption, self-rated health, and body mass index (BMI), were measured. We used regression analyses to assess the associations. Results: The HLS19-Q12 showed an acceptable reliability index (Cronbach’s α = 0.885, McDonald’s omega ω = 0.877) and adequate structural validity (comparative fit index  =  0.89, Tucker and Lewis’s index of fit  =  0.88, root mean square error of approximation  =  0.06). We found that 67.1% of the adolescents had excellent or sufficient HL, 27.7% had problematic HL, and 5.2% had inadequate HL. Compared with girls, boys had greater HL. HL was positively related to physical activity and self-rated health and negatively related to alcohol use and smoking. Conclusions: HLS19-Q12 is a reliable and valid measure of HL among adolescents in upper grades; higher levels of HL have been found to result in better health behaviors.
Federated Learning in Smart Healthcare: A Comprehensive Review on Privacy, Security, and Predictive Analytics with IoT Integration
Authors: Abbas Syed Raza , Abbas Zeeshan , Zahir Arifa , Lee Seung Won
Published: December 2024

Federated learning (FL) is revolutionizing healthcare by enabling collaborative machine learning across institutions while preserving patient privacy and meeting regulatory standards. This review delves into FL’s applications within smart health systems, particularly its integration with IoT devices, wearables, and remote monitoring, which empower real-time, decentralized data processing for predictive analytics and personalized care. It addresses key challenges, including security risks like adversarial attacks, data poisoning, and model inversion. Additionally, it covers issues related to data heterogeneity, scalability, and system interoperability. Alongside these, the review highlights emerging privacy-preserving solutions, such as differential privacy and secure multiparty computation, as critical to overcoming FL’s limitations. Successfully addressing these hurdles is essential for enhancing FL’s efficiency, accuracy, and broader adoption in healthcare. Ultimately, FL offers transformative potential for secure, data-driven healthcare systems, promising improved patient outcomes, operational efficiency, and data sovereignty across the healthcare ecosystem.
Impact of a Community-Based Health Intervention on Health Knowledge, Lifestyle Goals, Dietary Practices, and Physical Activity in Older Adults: A Multisite Cohort Study
Authors: Lim Shanice Wei En , Chong Jesslyn Hwei Sing , Chee Jia Yi , Lew Charles Chin Han , Lee Hee Hoon , Chua Lancelot Kher Wi , Lim Kian Chong , Koh Hui An , Sow Bao Yin , Wood Janelle , Gui Dorcas , Yap Adrian Ujin
Published: December 2024

Background: Studies on the effectiveness of community-based health interventions (CBHIs) in improving lifestyle practices among older adults are limited. Objectives: This study evaluated the impact of a CBHI on health knowledge, lifestyle goal attainment, and practices among older adults in Singapore. Methods: Older adults (aged ≥60 years) were recruited from 29 senior recreation centres to participate in the “Wise and Well” programme, a 3-month CBHI designed to empower individuals to make healthier lifestyle choices. Pre- and post-programme assessments of health knowledge, goal attainment, and lifestyle behaviours (dietary practices and physical activity levels) were conducted using a health knowledge questionnaire, Goal Attainment Scaling (GAS), the Modified Dietary Practice Questionnaire (DPQ), and the Global Physical Activity Questionnaire (GPAQ), respectively. Statistical analysis was performed using the Wilcoxon signed-rank and McNemar’s tests (α = 0.05). Results: The study comprised 464 participants (mean age 73.1 years [SD 7.6]; 75.9% women). Three months post-program, participants showed significantly increased health knowledge (p < 0.001) and improved lifestyle goal attainment (p < 0.001). Additionally, there was a significant increase in the proportion of participants meeting or exceeding fruit (p < 0.001) and vegetable (p = 0.002) intake recommendations and reductions in sugar-sweetened beverage consumption (p = 0.002). However, no significant changes were observed in fried food consumption or physical activity levels. High health knowledge scores were associated with 2.17 (95% confidence interval 1.02,4.64) times greater odds of increased vegetable intake. Conclusions: The CBHI shows potential as an effective approach to improving health knowledge and enhancing lifestyle goals and practices among older adults
Attributes Desired in a General Practitioner by Adults: Implications for Humanization in Medicine and Enhancement of the Patient Experience
Authors: Szczepek Agnieszka J. , Wrzosek Malgorzata , Makowska Marta
Published: December 2024

Background: Progress in medical education is reflected in healthcare quality and patient satisfaction. However, there are still gaps in knowledge regarding the patients’ expectations of general practitioners (GPs), even though patients’ interactions with GPs are among the most frequent in healthcare. Accordingly, this study investigated the qualities desired by adults in GPs, intending to include them in future medical humanization education to enhance the patients’ experience. Methods: Using an online survey, 1057 respondents (52.8% female; mean age, 46.55 years old, SD 16.03) were asked to rate 15 statements on a scale of 1 to 10 regarding desirable characteristics of general practitioners. In addition to the respondents’ high regard for their GP’s ongoing education and sincerity in conveying both positive and negative information, the findings suggest that the socio-demographic attributes of the respondents influence their expectations of GPs. Results: Women had higher overall expectations than men. In addition, those who reported higher satisfaction with their lives and recent healthcare users had higher expectations of GPs than those who were dissatisfied. The youngest group of respondents exhibited the lowest expectations of the GPs’ attributes, except for their greater willingness to engage in discussions with GPs regarding personal or professional issues, compared with the older groups. Conclusions: The information presented in this work can be utilized during medical students’ humanization training and physicians’ continuing education. The knowledge gained should enhance GPs’ awareness of the distinctions in patients’ expectations, enabling them to adapt their approach and services to align with their patients’ unique needs, expectations, and experiences.
Volunteer Services in Palliative Care by Third Age University Students
Authors: Düzgün Gönül , Kılıç Öztürk Yasemin , Polat Gökşen , Şahin Sevnaz
Published: December 2024

Background: Volunteering is a type of support that provides high motivation and supports social participation during the active aging process without any financial reward. Volunteering services provided by an active older person not only provide free services to the community where needed but also help individuals feel valued by creating a social environment, thereby increasing their resilience. The aim of this study was to determine the views on volunteering in palliative care services among older individuals over the age of sixty who attend the Ege University of the Third Age [U3A] and outline the volunteer profile of older students after receiving palliative care training. Methods: This study was conducted using a qualitative research method. The study population consisted of seventy students from the Ege U3A in İzmir who met the inclusion criteria. Before the training, the U3A students were given a brief pre-test about palliative care and volunteering, followed by 2-day, 16 h basic palliative care training. After the training, the students were asked to respond to written questions about volunteering in palliative care, and their responses were collected in their own handwriting. For the data analysis, a thematic content analysis was conducted using MAXQDA 20, a qualitative data analysis program. Results: In this study, the average age of the 70 University of the Third Age students were 67.47 (60–89) years. The participants were 75% women; 85% were married, 40% lived with their spouse, and 37.14% had been students at the University of the Third Age for 3 years. After the thematic analysis, six main themes emerged: physical and social support, educational support, medical/clinical support, financial support, spiritual support, and caregiving for pediatric patients. Conclusions: In our study, it was clearly observed that older students enrolled in the Ege U3A, who had a high potential for volunteering, were willing to work voluntarily in palliative care within the limits of their physical abilities and resources. This research, which aimed to create a volunteer profile in palliative care, allowed older students to find suitable roles for themselves and increased their motivation to provide this unpaid service. Based on this, it aimed to establish an effective start and an encouraging practice for the development of a pilot study, which is needed for Türkiye.
Cognitive Functioning in Children and Young People with Congenital Heart Disease: A Systematic Review of Meta-Analyses
Authors: Koushiou Maria , Manzoor Sauleha , Jossif Antonis , Ferreira Nuno
Published: December 2024

Objectives: Congenital heart disease (CHD) is a prevalent condition affecting young people that often necessitates complex medical interventions. This study aims to provide a synthesis of existing meta-analyses examining the impact of CHD on the cognitive functioning in children and young people; Methods: A comprehensive literature review was conducted, identifying peer-reviewed meta-analyses from 1 January 1976 to 17 December 2024, focusing on the cognitive outcomes of CHD patients aged 0–24 years. Data extraction covered study details, participant demographics, outcomes, and quality assessments. Quality assessment followed the Scottish Intercollegiate Guidelines Network (SIGN) checklist, and a narrative synthesis was conducted; Results: The narrative synthesis highlighted significant cognitive impairments in children with CHD across domains such as Intelligence Quotient (IQ), executive functions (EF), memory, and alertness. Cognitive impairments were also observed to become worse with increasing age. Furthermore, surgical interventions were found to impact cognitive outcomes, with surgeries at an early age improving survival rates but not entirely mitigating cognitive deficits. Cognitive impairments were more marked in young people assessed at an older age and with a more complex CHD presentation. Conclusions: Children with CHD face persistent cognitive challenges, underscoring the need for early identification and tailored interventions. Routine cognitive assessments and comprehensive care, including educational and psychological support, are crucial for improving neurodevelopmental outcomes. Future research should focus on longitudinal studies to track cognitive development and explore effective rehabilitation programs.
The Role of Reactive Oxygen Species in the In Vivo Germination and Growth of Petunia (Petunia hybrida E. Vilm.) Male Gametophyte in the Progamic Phase of Fertilization
Authors: Zakharova Ekaterina V. , Golivanov Yaroslav Yurievich , Molchanova Tatiana P. , Ulianov Alexei I. , Gazieva Irina I. , Muratova Oksana A.
Published: December 2024

The potential role of reactive oxygen species (ROS) is studied in the male gametophytes of petunia (Petunia hybrida E. Vilm.) grown in vivo with a focus on its germination, growth support in the progamic stage of fertilization, and the function of the mechanism underlying S-RNase-based self-incompatibility. Exogenous treatment with H2O2 influences the in vivo germination and polar growth of pollen tubes (PTs), which manifests as the acceleration or inhibition of these processes depending on its concentration, time interval after pollination, and pollination variant. The H2O2 treatment of the stigma somewhat stimulates the PT elongation in the late stages of self-incompatible pollination (4–8 h) versus the strong PT inhibition observed during the first hour of germination. A different pattern is observable in cross-compatible pollination: the H2O2 treatment of pistils inhibits PT growth during the overall pollination at all tested concentrations. Treatment of pistils with the NADPH oxidase inhibitor diphenylene iodonium chloride (DPI) strongly inhibited the growth of PTs in both pollination variants. In addition, DCF-DA staining confirms that ROS are formed in pollen, PTs, stigma of nonpollinated pistil, and the pistil itself in all pollination variants. The PT growth during the function of the self-incompatibility mechanism is arrested at high ROS concentrations, which is presumably associated with the SI-induced programmed cell death. Our results demonstrate that ROS are a necessary component of pollen, PTs, exudate, and stigma cells and contribute to successful reproduction. This study provides a deeper insight into the ROS functions during the PT growth in an in vivo system.
Potential Effects on the Quinoa Cultivation Yield Based on Different Hydric Scenarios of the Chilean Altiplano
Authors: Sánchez-Monje Matías , Olave Jorge
Published: December 2024

This study evaluates the impact of different irrigation scenarios on the yield of quinoa (Chenopodium quinoa) in the Chilean Altiplano. The research was conducted in Ancovinto, Tarapacá, Chile, using “Pandela” quinoa seeds. Four irrigation treatments were implemented: rainfed (T0) and irrigation at 100% ETc (T1), 66% ETc (T2), and 33% ETc (T3). Various climatic variables, the soil moisture content, and agromorphological parameters were measured. The results indicated that rainfed conditions (T0) led to higher dry matter production in roots, stems, leaves, and panicles at the end of the growth cycle compared to irrigated treatments. The Leaf Area Index (LAI) was also higher in rainfed conditions during the flowering stage, demonstrating the crop’s adaptability to adverse water conditions. Additionally, the ability of quinoa plants under rainfed conditions to tolerate frost during critical growth stages was a key factor in their superior performance, contributing to a higher grain yield and harvest indices. Plants under rainfed conditions reached greater heights and showed higher harvest indices (HI) and grain yield than those under irrigation. The Water Use Efficiency (WUE) was significantly higher in rainfed conditions, suggesting more effective water utilization under water scarcity. This research represents a one-year study that provides orientations for future research, considering the interannual variability of precipitation in the region. The results obtained show that quinoa plants under traditional management (rainfed) exhibited the best response in the measured growth, development, and production variables, leading to higher production and harvest rates. Additionally, there was greater efficiency in water use, equivalent to 15.87 and 12.7 times that of the 100% and 33% ETc treatments, respectively. These findings highlight quinoa’s remarkable adaptability to harsh hydric conditions and the efficiency of traditional rainfed farming practices in the Altiplano.
The First Protocol for In Vitro Propagation of Kalanchoe beharensis Through Adventitious Shoots, a Preliminary Study
Authors: Moreno-García Ignacio , Rodríguez Victoria , García-Sogo Begoña , Ventura Cristhian , Moreno Vicente , Pineda Benito
Published: December 2024

Kalanchoe beharensis, a vulnerable species according to the International Union for Conservation of Nature, is highly prized for its ornamental value and medicinal properties. Therefore, an efficient methodology to propagate this ecologically significant species would be of particular interest. The propagation of K. beharensis has traditionally been achieved by seed or cuttings, but these methods are limited in efficiency. Micropropagation provides a more efficient and controlled alternative by enabling the in vitro production of numerous plants in a small space and in a short period of time. Despite its advantages, no micropropagation protocol for K. beharensis has been reported in the literature. In this study, we report an efficient in vitro regeneration protocol for K. beharensis. In order to implement this, we evaluated the morphogenetic response of leaf and root explants in media supplemented with auxins, cytokinins, or a combination of both growth regulators. Surprisingly, the best results were observed in indole-3-acetic acid-supplemented media. Adventitious shoots were rooted in either hormone-free or auxin-supplemented media, with indole-3-acetic acid yielding the best results. Rooted plants were acclimatized in the greenhouse, achieving over 80% survival during acclimatization. This protocol improves multiplication rate, space utilization, and uniformity, providing a viable alternative to conventional propagation methods.
Plant Morphology and Fruit Quality Traits Affecting Yield and Post-Harvest Behavior of Two Highbush Blueberry Cultivars in Central Chile
Authors: Romero-Bravo Sebastián , Araya-Alman Miguel , Moggia Claudia , Lobos Gustavo A. , Calderon Felipe , Espinoza Sergio
Published: December 2024

In this study, we address the question of the most important factors influencing yield and fruit quality in highbush blueberries. An experiment was carried out to investigate the relationship between yield components and (i) plant yield, (ii) fruit quality traits, and (iii) fruit firmness post-harvest in two Vaccinium corymbosum L. blueberry cultivars (‘Duke’ and ‘Brigitta’). In a field in central Chile (35°15′39″ S; 71°14′32″ W) during the growing season 2018–2019, we measured the number of canes (NC), length of the first shoot (LFS), age of the first shoot (AFS), diameter of the first shoot (DFS), flower buds per cane (FBC), number of one-year shoots per cane (SPC), flowers per bud (FPB), fruit set percentage (FSP), yield (YLD), fruit weight (FW), fruit firmness at harvest (FF), fruit diameter at harvest (FD), soluble solids/acid ratio at harvest (SS:AC), and fruit firmness after harvest (FFpos). The most important factors affecting yield and fruit quality were FBC, SPC, and FF. Our results suggest that FBC and SPC could be managed agronomically to optimize fruit load and light interception.
Application of the Health Belief Model (HBM) to Explore the Quality of Sexual and Reproductive Health (SRH) Education in Sri Lanka
Authors: Rajapakshe Wasantha , Wickramasurendra Anjana Koushani , Amarasinghe Rajini Ranmini , Kohilawatta Arachchige Wijerathne Shynie Lourds Minoli , Wijesinghe Nikini Devindi , Madhavika Naduni
Published: December 2024

Many countries, including Sri Lanka, are taking steps to integrate sex education into their educational systems to combat child abuse. However, this effort is often met with skepticism in Asian nations, including Sri Lanka. This study takes a unique approach by applying the criteria of the health belief model to predict the quality of reproductive health (SRH) education in Sri Lanka, offering a fresh perspective on this issue. A positive philosophical framework and a deductive approach have been employed to provide justification for the underlying assumptions. A structured questionnaire was used as the survey methodology, which included questions about external cues to action, self-efficacy, perceived barriers, perceived susceptibility, and perceived severity. Data was collected from a total of 384 Sri Lankan non-state undergraduate students to test their perception of these factors and how they affect the perceived benefits of quality SRH education. The level of self-efficacy, perceived susceptibility, and perceived severity yielded a coefficient estimate that was statistically significant, thus influencing the perceived benefits of quality SRH education. These results, obtained through a multivariate regression analysis, underscore the importance of one’s role in implementing effective SRH education. Importantly, there is no evidence that external cues to action and perceived barriers predict the perceived benefits of quality SRH education. This underscores the gravity of the situation and the need for immediate action. The findings of this study have significant practical implications. They can be used to develop an effective SRH program that aims to prevent sexual abuse among adolescents. This study also demonstrates that the health belief model can serve as a useful conceptual framework for such intervention programs, providing tangible solutions to the issue of SRH education quality.
Knowledge, Attitudes, and Practice Regarding Physical Exercise in Type 2 Diabetic and Non-Diabetic Staff at a Tertiary Institution
Authors: Sibazo Mbuso , Sookan-Kassie Takshita
Published: December 2024

Type 2 diabetes mellitus (T2DM) has become a global epidemic, where increasing urbanization encourages sedentary lifestyles. Persistent physical inactivity can lead to T2DM and increase the risk of T2DM in the general population. Therefore, the aim of this study was to explore the knowledge, attitudes, and practices (KAP) regarding exercise amongst T2DM and non-diabetic (ND) staff at a tertiary institution in KwaZulu Natal South Africa. A total of 166 responses were received: a total of 16 responses (9.6%) were T2DM, and 150 responses (90.0%) were non-diabetic (ND). The demographics included 66.3% females and 33.7% males who consented to taking part, 62.7% were black, 18.7% were Indian, 12% were white, 5.4% were colored, and 1.2% were other. A cross-sectional descriptive survey design, utilizing a modified validated online knowledge, attitudes, and practice questionnaire, was used to collect data. Descriptive statistics were used for the analysis: inferential statistics; the ordinal (1–5) Likert scale; t-tests; and chi-square tests. The level of statistical significance was set at p ≤ 0.05. No significant differences were found between the T2DM and ND groups except in their attitude towards exercise, which showed three items with significant differences. The ND group agreed significantly more than the T2DM group that they looked forward to exercising (p = 0.002), and even without company, they exercised regularly (p = 0.042). The T2DM group agreed significantly more with the statement that they had asked their doctor if there was medicine available to make them better without doing any exercise (p = 0.002). The overall KAP results of the current study found that both participants diagnosed with T2DM and those in the ND group know about exercise and have a good attitude toward exercise. However, both groups still have poor practice regarding physical activity.
Applying the Surge Capacity Components for Capacity-Building Purposes in the Context of the EMT Initiative
Authors: Echeverri Lina , Salio Flavio , Parker Richard , Relan Pryanka , Storozhenko Oleg , Hubloue Ives , Ragazzoni Luca
Published: December 2024

Background: On 16 January 2021 (EB148/18 Session), the World Health Organization (WHO) and Member States emphasized the importance of expanding the WHO Emergency Medical Teams (EMT) Initiative, investing in a global health workforce and multidisciplinary teams capable of being rapidly deployed, equipped, and fully trained to respond to all-hazard emergencies effectively. This resulted in the need to define a comprehensive framework. To achieve this, the EMT Initiative proposes the application of the four components of Surge Capacity, known as the 4“S” (Staff, Systems, Supplies, and Structure/Space), to build global capacities and capabilities, ensuring rapid mobilization and efficient coordination of national and international medical teams for readiness and response, complying with crisis standards of care defined in an ethical and evidence-based manner. Methods: A mixed-qualitative research approach was used, incorporating expert consensus through focus group discussions (FGDs), between 2021 and July 2022. This facilitated a detailed process analysis for the application of the surge capacity components to build global capacities and capabilities. This research highlighted the similarities between surge capacity and capacity building from an initial desk review and unified these concepts within the EMT Initiative. A standardized formal pathway was developed to enhance local, regional, and global capacities for emergency readiness and response. Results: The results showed that the framework successfully integrated the essential components of surge capacity and capacity building, making it adaptable to various settings. Conclusions: This framework provides a unified and replicable approach for readiness and response for all-hazards emergencies.
Pharmacological Mechanisms of Bile Acids Targeting the Farnesoid X Receptor
Authors: Qi Youchao , Ma Yonggui , Duan Guozhen
Published: December 2024

Bile acids (BAs), a category of amphiphilic metabolites synthesized by liver cells and released into the intestine via the bile duct, serve a vital role in the emulsification of ingested fats during the digestive process. Beyond their conventional emulsifying function, BAs, with their diverse structures, also act as significant hormones within the body. They are pivotal in facilitating nutrient absorption by interacting with the farnesoid X receptor (FXR), and they serve as key regulators of lipid and glucose metabolism, as well as immune system balance. Consequently, BAs contribute to the metabolism of glucose and lipids, enhance the digestion and absorption of lipids, and maintain the equilibrium of the bile pool. Their actions are instrumental in addressing obesity, managing cholestasis, and treating diabetes, and are involved in the onset and progression of cancer. This paper presents an updated systematic review of the pharmacological mechanisms by which BAs target the FXR, incorporating recent findings and discussing their signaling pathways in the context of novel research, including their distinct roles in various disease states and populations. The aim is to provide a theoretical foundation for the continued research and clinical application of BAs.
Whole-Exome Analysis and Osteosarcoma: A Game Still Open
Authors: Chiappetta Caterina , Della Rocca Carlo , Di Cristofano Claudio
Published: December 2024

Osteosarcoma (OS) is the most prevalent malignant bone tumor in adolescents and young adults. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, and drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb and p53), the molecular mechanism of development of OS remains unclear, and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects, along with side effects at high doses. For these reasons, many efforts have been made to characterize the complex genome of OS thanks to the whole-exome analysis, with the aim of identifying predictive biomarkers to give these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.
Different Cytotoxic Effects of Cisplatin on Pancreatic Ductal Adenocarcinoma Cell Lines
Authors: Muscella Antonella , Cossa Luca G. , Stefàno Erika , Rovito Gianluca , Benedetti Michele , Fanizzi Francesco P. , Marsigliante Santo
Published: December 2024

This study examined the response to cisplatin in BxPC-3, Mia-Paca-2, PANC-1, and YAPC pancreatic cancer lines with different genotypic and phenotypic characteristics, and the mechanisms associated with their resistance. BxPC-3 and MIA-PaCa-2 cell lines were the most sensitive to cisplatin, while YAPC and PANC-1 were more resistant. Consistently, in cisplatin-treated BxPC-3 cells, the cleavage patterns of pro-caspase-9, -7, -3, and PARP-1 demonstrated that they were more sensitive than YAPC cells. The autophagic pathway, promoting cisplatin resistance, was active in BxPC-3 cells, as demonstrated by the time-dependent conversion of LC3-I to LC3-II, whereas it was not activated in YAPC cells. In cisplatin-treated BxPC-3 cells, Bcl-2 decreased, while Beclin-1, Atg-3, and Atg-5 increased along with JNK1/2 phosphorylation. Basal levels of phosphorylated ERK1/2 in each cell line were positively correlated with cisplatin IC50 values, and cisplatin caused the activation of ERK1/2 in BxPC-3 and YAPC cells. Furthermore, ERK1/2 pharmacological inactivation increased cisplatin lethality in both BxPC-3 and YAPC cells, suggesting that p-ERK1/2 may be related to cisplatin resistance of PDAC cells. Different mechanisms and strategies are generally required to acquire drug resistance. Here, we partially explain the other response to cisplatin of BxPC-3 and YAPC cell lines by relating it to the role of ERK pathway.
Molecular Research and Treatment of Urologic Cancer
Authors: Yamashita Hironobu
Published: December 2024

Urologic cancers exhibit tumor heterogeneity in their morphology, gene expression, and phenotypic features, and have different responses to drug treatment [...]
Multiomics of Aging and Aging-Related Diseases
Authors: Kiseleva Olga I. , Arzumanian Viktoriia A. , Ikhalaynen Yuriy A. , Kurbatov Ilya Y. , Kryukova Polina A. , Poverennaya Ekaterina V.
Published: December 2024

Despite their astonishing biological diversity, surprisingly few shared traits connect all or nearly all living organisms. Aging, i.e., the progressive and irreversible decline in the function of multiple cells and tissues, is one of these fundamental features of all organisms, ranging from single-cell creatures to complex animals, alongside variability, adaptation, growth, healing, reproducibility, mobility, and, finally, death. Age is a key determinant for many pathologies, shaping the risks of incidence, severity, and treatment outcomes for cancer, neurodegeneration, heart failure, sarcopenia, atherosclerosis, osteoporosis, and many other diseases. In this review, we aim to systematically investigate the age-related features of the development of several diseases through the lens of multiomics: from genome instability and somatic mutations to pathway alterations and dysregulated metabolism.
Probing the Effects of Multisite Mutations in the Lipoic Acid Region of the BCOADC-E2 Protein
Authors: Wang Jinjun , Yang Mingliang , Wei Huixian , Miao Wang , Li Shiyu , Gao Xinru
Published: December 2024

Primary biliary cholangitis (PBC) is a chronic disease, the prevalence of which has been increasing in recent years. And the prevalence of patients who test negative with existing diagnostic techniques remains high. It was found that the antigenic BCOADC-E2 protein could detect patients with a negative original test. And experiments revealed that the lipoyl domain of BCOADC-E2 plays an important role. The present study was carried out to verify the necessity of maintaining the folding conformation of the lipoyl β-sheet of the protein in the lipoyl domain during the recognition of the BCOADC-E2 protein and the importance of the glutamic acid and isoleucine residues at position 4 and position 13, respectively. In order to search for a new pathway for the pre-detection of patients with PBC, firstly, the mutant proteins were subjected to an enzyme-linked immunosorbent assay (ELISA) with serum. Then, MTSSL spin tags were positioned at specific sites of the Cys mutant and reacted with serum samples from PBC patients and controls, and EPR spectroscopic data were measured. The multiple mutant proteins all reacted less specifically with the serum than the wild-type protein in the ELISA; the spectra measured for the pGEX-BCKD-E4A-I13A mutant were severely broadened, and the compactness at the conformational position of the lipoyl β-sheet structural conformation of the proteins of amino acids 4 and 13 remained unchanged. The EPR spectral data validate the importance of the glutamate and isoleucine residues at position 4 and position 13 and their necessity in the maintenance of the lipoyl β-sheet structural conformation of proteins in the lipoyl domain in anti-BCOADC-E2 recognition.
6-Aza-2-Thiothymine as an Alternative Matrix for Spatial Proteomics with MALDI-MSI
Authors: Denti Vanna , Monza Nicole , Bindi Greta , Porto Natalia Shelly , L’Imperio Vincenzo , Pagni Fabio , Piga Isabella , Smith Andrew
Published: December 2024

Matrix Assisted Laser Desorption/Ionisation-Mass Spectrometry Imaging (MALDI-MSI) is a well-established spatial omic technique which enables the untargeted mapping of various classes of biomolecules, including tryptic peptides, directly on tissue. This method relies on the use of matrices for the ionisation and volatilisation of analytes, and α-Cyano-4-hydroxycinnamic acid (CHCA) represents the most widespread matrix for tryptic peptides analysis. However, CHCA also presents certain limitations that foster the quest for novel matrix compounds. 6-aza-2-thiothymine (ATT), traditionally used in MALDI mass spectrometry (MS) for oligonucleotides, small molecules and oxidised phospholipids, has not been thoroughly investigated as a potential matrix for tryptic peptide analysis in MALDI-MS or MALDI-MSI. Therefore, this study addresses this gap by evaluating the capability of ATT to ionise tryptic peptides from Bovine Serum Albumin (BSA) and map in situ-digested peptides from formalin-fixed paraffin-embedded (FFPE) tissue sections in these respective applications. Comparative analysis with CHCA demonstrated the complementary strengths of these matrices for detecting tryptic peptides, establishing ATT as a feasible alternative to CHCA in the MALDI-MSI field and paving the way for future advancements in spatial proteomics.
Somatic Instability Leading to Mosaicism in Fragile X Syndrome and Associated Disorders: Complex Mechanisms, Diagnostics, and Clinical Relevance
Authors: Protic Dragana , Polli Roberta , Bettella Elisa , Usdin Karen , Murgia Alessandra , Tassone Flora
Published: December 2024

Fragile X syndrome (FXS) is a genetic condition caused by the inheritance of alleles with >200 CGG repeats in the 5′ UTR of the fragile X messenger ribonucleoprotein 1 (FMR1) gene. These full mutation (FM) alleles are associated with DNA methylation and gene silencing, which result in intellectual disabilities, developmental delays, and social and behavioral issues. Mosaicism for both the size of the CGG repeat tract and the extent of its methylation is commonly observed in individuals with the FM. Mosaicism has also been reported in carriers of premutation (PM) alleles, which have 55–200 CGG repeats. PM alleles confer risk for the fragile X premutation-associated conditions (FXPAC), including FXTAS, FXPOI, and FXAND, conditions thought to be due to the toxic consequences of transcripts containing large CGG-tracts. Unmethylated FM (UFM) alleles are transcriptionally and translationally active. Thus, they produce transcripts with toxic effects. These transcripts do produce some FMRP, the encoded product of the FMR1 gene, albeit with reduced translational efficiency. As a result, mosaicism can result in a complex clinical presentation. Here, we review the concept of mosaicism in both FXS and in PM carriers, including its potential clinical significance.
Adoptive Transfer of CX3CR1-Transduced Tregs Homing to the Forebrain in Lipopolysaccharide-Induced Neuroinflammation and 3xTg Alzheimer’s Disease Models
Authors: Yang Hyejin , Yang Juwon , Park Namgyeong , Hwang Deok-Sang , Park Seon-Young , Kim Soyoung , Bae Hyunsu
Published: December 2024

CX3CR1-transduced regulatory T cells (Tregs) have shown potential in reducing neuroinflammation by targeting microglial activation. Reactive microglia are implicated in neurological disorders, and CX3CR1-CX3CL1 signaling modulates microglial activity. The ability of CX3CR1-transduced Tregs to inhibit LPS-induced neuroinflammation was assessed in animal models. CX3CR1 Tregs were administered to LPS-induced and 3xTg Alzheimer’s mouse models, resulting in reduced proinflammatory marker expression in both the cortices and hippocampi. In the 3xTg Alzheimer’s model, neuroinflammation was significantly reduced, demonstrating the efficacy of CX3CR1 Tregs even in chronic neuroinflammatory conditions. These findings highlight the therapeutic potential of CX3CR1 Treg therapy in modulating microglial activity and offer promising treatment strategies for neurodegenerative diseases.
Circulating Brain-Reactive Autoantibody Profiles in Military Breachers Exposed to Repetitive Occupational Blast
Authors: Rhind Shawn G. , Shiu Maria Y. , Vartanian Oshin , Tenn Catherine , Nakashima Ann , Jetly Rakesh , Yang Zhihui , Wang Kevin K.
Published: December 2024

Military breachers are routinely exposed to repetitive low-level blast overpressure, placing them at elevated risk for long-term neurological sequelae. Mounting evidence suggests that circulating brain-reactive autoantibodies, generated following CNS injury, may serve as both biomarkers of cumulative damage and drivers of secondary neuroinflammation. In this study, we compared circulating autoantibody profiles in military breachers (n = 18) with extensive blast exposure against unexposed military controls (n = 19). Using high-sensitivity immunoassays, we quantified IgG and IgM autoantibodies targeting glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and pituitary (PIT) antigens. Breachers exhibited significantly elevated levels of anti-GFAP IgG (p < 0.001) and anti-PIT IgG (p < 0.001) compared to controls, while anti-MBP autoantibody levels remained unchanged. No significant differences were observed for any IgM autoantibody measurements. These patterns suggest that repetitive blast exposure induces a chronic, adaptive immune response rather than a short-lived acute phase. The elevated IgG autoantibodies highlight the vulnerability of astrocytes, myelin, and the hypothalamic–pituitary axis to ongoing immune-mediated injury following repeated blast insults, likely reflecting sustained blood–brain barrier disruption and neuroinflammatory processes. Our findings underscore the potential of CNS-targeted IgG autoantibodies as biomarkers of cumulative brain injury and immune dysregulation in blast-exposed populations. Further research is warranted to validate these markers in larger, more diverse cohorts, and to explore their utility in guiding interventions aimed at mitigating neuroinflammation, neuroendocrine dysfunction, and long-term neurodegenerative risks in military personnel and similarly exposed groups.
Synergistic Effects and Mechanisms of Action of Rutin with Conventional Antibiotics Against Escherichia coli
Authors: Yi Lankun , Bai Yubin , Chen Xu , Wang Weiwei , Zhang Chao , Shang Zixuan , Zhang Zhijin , Li Jiajing , Cao Mingze , Zhu Zhen , Zhang Jiyu
Published: December 2024

Rutin is a widely known plant secondary metabolite that exhibits multiple physiological functions. The present study focused on screening for synergistic antibacterial combinations containing rutin, and further explored the mechanisms behind this synergy. In vitro antibacterial test results of rutin showed that the ranges of minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) are 0.125–1 and 0.125–2 mg/mL, respectively. However, rutin and amikacin have a significant synergistic effect, with a fractional inhibitory concentration index (FICI) range of 0.1875–0.5. The time bactericidal curve proved that the combination of rutin and amikacin inhibited bacterial growth within 8 h. Scanning electron microscopy (SEM) revealed that a low-dose combination treatment could disrupt the cell membrane of Escherichia coli (E. coli). A comprehensive analysis using alkaline phosphatase (AKP), K+, and a protein leakage assay revealed that co-treatment destroyed the cell membrane of E. coli, resulting in the significant leakage of AKP, intracellular K+, and proteins. Moreover, confocal laser scanning microscopy (CLSM) and red–green cell ratio analysis indicated severe damage to the E. coli cell membrane following the co-treatment of rutin and amikacin. This study indicates the remarkable potential of strategically selecting antibacterial agents with maximum synergistic effect, which could significantly control antibiotic resistance.
Current Non-Viral-Based Strategies to Manufacture CAR-T Cells
Authors: Gehrke Leon , Gonçalves Vasco Dos Reis , Andrae Dominik , Rasko Tamas , Ho Patrick , Einsele Hermann , Hudecek Michael , Friedel Sabrina R.
Published: December 2024

The successful application of CAR-T cells in the treatment of hematologic malignancies has fundamentally changed cancer therapy. With increasing numbers of registered CAR-T cell clinical trials, efforts are being made to streamline and reduce the costs of CAR-T cell manufacturing while improving their safety. To date, all approved CAR-T cell products have relied on viral-based gene delivery and genomic integration methods. While viral vectors offer high transfection efficiencies, concerns regarding potential malignant transformation coupled with costly and time-consuming vector manufacturing are constant drivers in the search for cheaper, easier-to-use, safer, and more efficient alternatives. In this review, we examine different non-viral gene transfer methods as alternatives for CAR-T cell production, their advantages and disadvantages, and examples of their applications. Transposon-based gene transfer methods lead to stable but non-targeted gene integration, are easy to handle, and achieve high gene transfer rates. Programmable endonucleases allow targeted integration, reducing the potential risk of integration-mediated malignant transformation of CAR-T cells. Non-integrating CAR-encoding vectors avoid this risk completely and achieve only transient CAR expression. With these promising alternative techniques for gene transfer, all avenues are open to fully exploiting the potential of next-generation CAR-T cell therapy and applying it in a wide range of applications.
The Complex Role of Matrix Metalloproteinase-2 (MMP-2) in Health and Disease
Authors: Wolosowicz Marta , Prokopiuk Slawomir , Kaminski Tomasz W.
Published: December 2024

Matrix metalloproteinase-2 (MMP-2), a zinc-dependent enzyme, plays a critical role in the degradation and remodeling of the extracellular matrix (ECM). As a member of the gelatinase subgroup of matrix metalloproteinases, MMP-2 is involved in a variety of physiological processes, including tissue repair, wound healing, angiogenesis, and embryogenesis. It is primarily responsible for the degradation of type IV and V collagen, fibronectin, laminin, and elastin, which are essential components of the ECM. MMP-2 is secreted as an inactive pro-enzyme (proMMP-2) and activated through proteolytic cleavage, with its activity being precisely regulated by tissue inhibitors of metalloproteinases (TIMPs). Dysregulation of MMP-2 has been linked to a variety of pathological conditions, including cardiovascular diseases, diabetic complications, kidney diseases, and cancer. In cardiovascular diseases, it contributes to vascular remodeling, atherosclerosis, and aneurysms, while in fibrotic diseases, it mediates excessive ECM degradation leading to tissue scarring. In diabetes, elevated MMP-2 activity exacerbates complications such as nephropathy, retinopathy, and cardiovascular disease. In cancer, MMP-2 facilitates tumor invasion and metastasis by degrading ECM components and promoting angiogenesis. Despite its essential roles in both physiological and pathological processes, targeting MMP-2 for therapeutic purposes presents challenges due to its dual functions in tissue remodeling and repair, raising concerns about unplanned consequences such as impaired tissue healing or excessive tissue damage. These challenges underscore the need for future research to focus on developing selective modulators that can precisely balance their activity under specific disease environments. Clinical trials targeting MMP-2 modulation highlight the potential of gelatinase inhibitors, including those targeting MMP-2, to reduce tumor progression in fibrosarcoma, breast, and lung cancers. This paper reviews the structure, function, and regulation of MMP-2, its involvement in disease pathogenesis, and the potential challenges in the therapeutic implications of modulating its activity.