Search Results (337)

Brain metastases (BM), which most commonly originate from lung, breast, or skin cancers, remain a major clinical challenge, with standard treatments such as stereotactic radiosurgery (SRS), surgical resection, and whole-brain radiation therapy (WBRT). The prognosis for patients with BM remains poor, with a median overall survival (OS) of just 10–16 months. Although recent advances in systemic therapies, including small molecule inhibitors, monoclonal antibodies, chemotherapeutics, and gene therapies, have demonstrated success in other malignancies, their effectiveness in central nervous system (CNS) cancers is significantly limited by poor blood–brain barrier (BBB) permeability and subtherapeutic drug concentrations in the brain. Nanoparticle-based drug delivery systems have emerged as a promising strategy to overcome these limitations by enhancing CNS drug penetration and selectively targeting metastatic brain tumor cells while minimizing off-target effects. This review summarizes recent preclinical and clinical developments in nanoparticle-based therapies for BM. It is evident from these studies that NPs can carry with them a range of therapeutics, including chemotherapy, immunotherapy, small molecule inhibitors, gene therapies, radiosensitizers, and modulators of tumor microenvironment to the BM. Moreover, preclinical studies have shown encouraging efficacy in murine models, highlighting the potential of these platforms to improve therapeutic outcomes. However, clinical translation remains limited, with few ongoing trials. To close this translational gap, future work must address clinical challenges such as trial design, regulatory hurdles, and variability in BBB permeability while developing personalized nanoparticle-based therapies tailored to individual tumor characteristics. Full article

Echinochloa spp. are among the most problematic malignant weeds in paddy fields. Under long-term herbicide selection pressure, they have developed resistances to multiple herbicides, leading to diminished control efficacy. Precision herbicide application, tailored to the susceptibility disparities among Echinochloa species, has emerged as a promising strategy to enhance weed control efficacy and decelerate herbicide resistance development. Nevertheless, the herbicide susceptibility variation across different Echinochloa taxa remain uncharted. Therefore, in this study, we determined the susceptibility of five Echinochloa species to 15 commonly used herbicides using the whole-plant bioassay method. Additionally, we explored the feasibility of employing the CDDP molecular marker technique for the rapid identification of distinct Echinochloa species. The results showing that five Echinochloa species exhibited differential susceptibility to 12 of the 15 herbicides tested underscore the necessity of personalized herbicide application strategies. Among the seven CDDP markers, KNOX-3 generated a specific band in the Echinochloa caudata population, which can be used to distinguish it from the other four Echinochloa species. The findings of this study will facilitate the precision application of herbicides for Echinochloa management in paddy fields. Full article

The Sustainable Development Goals commit states to Universal Health Coverage (UHC) for all; yet displaced populations—including asylum seekers, refugees, internally displaced persons (IDPs), and undocumented migrants—remain systematically excluded from national health systems across southern and eastern Africa. This paper applies a whole-of-route, rights-based framework to examine how legal status, policy implementation, and structural governance shape healthcare access for displaced populations across South Africa, Kenya, Somalia, and the Democratic Republic of Congo (DRC). Drawing on 70 key informant interviews and policy analysis conducted between 2020 and 2025, the study finds that despite formal commitments to health equity, access remains constrained by restrictive legal regimes, administrative discretion, and fragmented service delivery models. Critical gaps persist in migration-sensitive planning, gender-responsive care, and mental health integration. The findings highlight the limitations of rights-based rhetoric in the absence of legal coherence, intersectoral coordination, and political will. To realise UHC in displacement contexts, health systems must move beyond citizen-centric models and embed migration-aware, inclusive, and sustainable approaches across all stages of displacement. Without such structural reforms, displaced populations will remain at the margins of national health agendas—and the promise of health for all will remain unmet. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental impairment that occurs due to mutations related to the formation of the nervous system, combined with the impact of various epigenetic and environmental factors. This necessitates the identification of the genetic variations involved in ASD pathogenesis. We performed whole exome sequencing (WES) in a cohort of 22 Bulgarian male and female individuals showing ASD features alongside segregation analyses of their families. A targeted panel of genes was chosen and analyzed for each case, based on a detailed examination of clinical data. Gene analyses revealed that specific variants concern key neurobiological processes involving neuronal architecture, development, and function. These variants occur in a number of genes, including SHANK3, DLG3, NALCN, and PACS2 which are critical for synaptic signaling imbalance, CEP120 and BBS5 for ciliopathies, SPTAN1 for spectrins structure, SPATA5, TRAK1, and VPS13B for neuronal organelles trafficking and integrity, TAF6, SMARCB1, DDX3X, MECP2, and SETD1A for gene expression, CDK13 for cell cycle control, ALDH5A1, DPYD, FH, and PDHX for mitochondrial function, and PQBP1, HUWE1, and WDR45 for neuron homeostasis. Novel single nucleotide variants in the SPATA5, CEP120, BBS5, SETD1A, TRAK1, VPS13B, and DDX3X genes have been identified and proposed for use in ASD diagnostics. Our data contribute to a better understanding of the complex neurobiological features of autism and are applicable in the diagnosis and development of personalized therapeutic approaches. Full article

Background: Colorectal cancer (CRC) remains one of the most prevalent and fatal malignancies globally, with radiotherapy playing a crucial role in the treatment of locally advanced rectal cancer (LARC). However, the efficacy of radiotherapy is limited by significant resistance, with only a small proportion of patients achieving a pathologic complete response (PCR) to neoadjuvant chemoradiotherapy (nCRT). This study aims to uncover the genetic and molecular factors contributing to radiotherapy resistance in CRC through an integrated analysis of germline mutations, transcriptomic data, and immune microenvironment characteristics. Methods: Whole-exome sequencing (WES) was performed on tumor samples from 12 LARC patients. Transcriptomic data from the TCGA-READ and GSE150082 (LARC with chemoradiotherapy) cohorts were integrated with WES findings. The independent cohort GSE190826 (neoadjuvant therapy in rectal cancer) dataset was utilized to validate the WES data. Single-cell RNA sequencing (scRNA-seq) analysis of GSE132465 (primary CRC) resolved cellular heterogeneity. A random forest algorithm was employed to develop a predictive gene signature. Results: Our findings reveal a mutational landscape associated with radiotherapy resistance, identifying specific germline mutations linked to treatment outcomes. Differential gene expression analysis highlighted pathways involved in DNA replication, DNA repair, and immune regulation, with a focus on the tumor immune microenvironment (TIME). A gene signature, including CDCA4, FANCA, PBRM1, RPL13, and C12orf43, was developed to predict radiotherapy response. Notably, CDCA4 expression was significantly associated with tumor mutation burden (TMB) and microsatellite instability (MSI), and it plays a crucial role in regulating B cell infiltration in the tumor microenvironment. Conclusions: Our study provides novel insights into the molecular mechanisms of radiotherapy resistance in CRC and proposes CDCA4 and B cell-related immune features as potential biomarkers for patient stratification and personalized treatment strategies. Full article

Background/Objective: The priority task of each country is to ensure the protection of and improvement in its people’s health. One of the key aspects of health is related to food culture, consuming foods that ensure growth and normal development in a person and also prevent diseases. The consumption of foods that contain essential nutrients and functional foods, which include those containing probiotics, is the basis of a healthy diet. Methods: A structured anonymous interview was conducted with 90 parents from the Roma minority group to assess the nutritional culture of children from these families. The knowledge of Roma parents about probiotics, as well as their attitudes to apply them to their children, was examined. The survey was based on a questionnaire that was distributed among the respondents, Roma students, under the guidance of a mentor. Roma students study health specialties and are also participants in a Scholarship Programme. Results: We have established that the daily diet of children from this minority group consists of foods containing hydrogenated fats and sugar, which was indicated by 53.3% of respondents, and only 28.9% of respondents noted that their children consume fresh fruit every day. We have established that less than half of the children (35.6%) consume yoghurt daily as a source of valuable probiotics. We applied a nonparametric Kruskal–Wallis test and found statistically significant differences in the respondents’ knowledge of probiotics (χ² = 16.186, p = 0.001): those receiving secondary specialized education were better informed, but education has not affected their knowledge of the health benefits of probiotics (χ² = 5.462, p = 0.141). Children from minority groups tend to eat unhealthy foods. Conclusions: The role of Roma students studying health specialties as participants in the Scholarship Programme is to assist parents in forming a nutritional culture in their children. Roma students, due to their ethnic and cultural proximity and potential to be health professionals, contribute to sustainable health improvements among the Roma community as a whole. Full article

Education, understood as the process of forming the human person in their integral dimensions—spiritual, intellectual, moral, and social—occupies a key place in the reflection on the evangelizing mission of the Church. This article presents education as a form of integral evangelization based on the thought and activity of the Polish religious sister and mystic Blessed Marcelina Darowska (1827–1911). The initial part outlines the development of the concept of “integral evangelization” in the teachings of the Catholic Church and its relation to personalist pedagogy. The following section presents the figure of Blessed Marcelina Darowska and her educational initiative, situated in the 19th-century socio-historical context of partitioned Poland. The main section of the analysis focuses on Darowska’s concept of education as the formation of the whole person, encompassing the discernment of talents, intellectual, religious, and social development, and preparation for responsible family and civic roles. It also considers to what extent this vision of education can be identified as an expression of integral evangelization in accordance with the criteria of contemporary Church teaching. This article further presents the development of Blessed Marcelina’s educational work and its impact on forming generations of women conscious of their identity. The conclusion offers a reflection on the relevance and potential of this educational method in the context of contemporary social and religious challenges, particularly in the work of new evangelization. Full article

Background: Paramedics and firefighters frequently encounter critical incidents that require both deep learning and emotional processing. This study investigates how reflective writing facilitates these processes, addressing the need to understand professional development in high-stress environments. Methods: The research analyzed reflective writings from 57 second-year Management of Catastrophe Defense undergraduates who were active emergency service workers. Using Mayring’s qualitative content analysis, the study examined participants’ descriptions of critical workplace incidents, emotional responses, and long-term impacts. The theoretical framework combines Paul’s concept of transformative experiences, Schön’s reflective practice, and Jarvis’s experiential learning theory. Results: The analysis revealed three key dimensions: transformative experiences, the role of conversation with the situation in meaning making and the significance of whole-person learning in understanding emotional presence and absence, and the role of reflective writing in understanding learning processes. The study uncovered complex patterns in how professionals process critical incidents and manage emotions in high-stress environments. Conclusions: Reflective writing serves as an effective tool for processing experiences and developing professional resilience, although the process of engaging with traumatic memories through reflection presents its own complexities. These insights contribute to the understanding of learning processes and professional development in high-stress environments. Full article

Reviewing academic curricula requires a significant investment of time and expertise. Beyond accreditation, curriculum may be reviewed in part or in whole during other administrative efforts including the consideration of new elective courses, faculty-student advising, admission of transfer students, internal audits, and more. These activities often require multiple people with deep knowledge of the coursework as well as the discipline(s) involved to pour over scattered documentation and comparatively limited assessment data in order to make an informed decision. In this work, we explored the development of a semi-automated computational approach to visualize a curriculum as described in official course listings at a topic level of detail. We show how our approach can help provide a detailed view of how topics are covered across multiple courses and how these visualizations can show similarities and differences for individual student registration records, paving the way for personalized student support. We also identified opportunities for improvement in this method, including the need to develop more robust topic mapping techniques for short texts. Full article

Background/Objectives: Congenital heart disease (CHD) occurs in ~1% of all live neonates globally, rendering it the most prevalent developmental anomaly affecting humans; this condition confers substantial infant morbidity and mortality worldwide. Although there is ample evidence to suggest a paramount genetic basis for CHD, the genetic etiologies underpinning the majority of CHD remain elusive. In the present study, SOX4 was selected as a significant candidate gene for human CHD, mainly because SOX4 is abundantly expressed in both human and murine hearts during embryogenesis, and the knockout of Sox4 in mice causes embryonic demise predominantly attributable to cardiovascular developmental defects. Methods: Sequencing analysis of SOX4 was fulfilled in 248 probands affected with various types of CHD and the available relatives of the identified variation carrier as well as 262 unrelated healthy individuals. Functional analysis of the mutant SOX4 protein was conducted by utilizing a dual-reporter gene system. Results: a novel heterozygous SOX4 variation, NM_003107.3:c.331G>T;p.(Glu111*), was discovered in a male proband with Coffin–Siris syndromic CHD. Genetic investigation of the proband’s available relatives revealed that the truncating variation co-segregated with the phenotype in the whole family. The nonsense variation was absent from 262 healthy controls. Functional analysis demonstrated that the Glu111*-mutant SOX4 lost transactivation on NKX2.5 and GATA4, two well-established genes that are causative factors for CHD. Moreover, the Glu111* mutation nullified the synergistic transactivation between SOX4 and TBX20, another CHD-causing gene. Conclusions: These findings support SOX4 as a causative gene accountable for familial Coffin–Siris syndromic CHD in humans. These findings may aid in developing personalized preventive and therapeutic strategies for patients with Coffin–Siris syndromic CHD. Full article

CSMD1 is a gene involved in various biological processes and is highly expressed in the central nervous system, where it plays a key role in complement activity, brain circuit development, and cognitive function. It has been implicated as a susceptibility gene for schizophrenia and a causative factor in developmental epileptic encephalopathy, neurodevelopmental disorders, and intellectual disability. However, no MIM phenotype number has been assigned to CSMD1 for a specific disorder. Here, we report an individual presenting with moderate intellectual disability, anxiety disorder, obsessive–compulsive personality traits, and facial dysmorphisms. Trio-based whole-exome sequencing (WES) identified two heterozygous CSMD1 variants, c.8095A>G and c.5315T>C, both classified as variants of uncertain significance (VUS) according to ACMG criteria. Computational analysis using the DOMINO tool supported an autosomal recessive inheritance model for CSMD1. This study contributes to the growing evidence linking CSMD1 to neurodevelopmental phenotypes, highlighting the need for further investigations to clarify its pathogenic role. Full article

Background: Stress affects 45% of NHS staff. More research is needed to explore how to develop resilient mental health nurses who face multiple workplace stressors, including interacting with distressed clients. Higher Education Institutions are uniquely placed to introduce coping skills that help reduce anxiety and increase confidence for pre-registration nurses entering placements for the first time. Methods: A convenience sample of first year mental health student nurses (whole cohort), recruited before their first clinical placement, were invited to participate. Following a mixed methods design, we developed a 360-degree virtual reality (VR) video, depicting a distressed service user across three scenes, filmed in a real-life decommissioned in-patient ward. Participants followed the service user through the scenes, as though in real life. We used the video alongside a cognitive reappraisal/solution-focused/VERA worksheet and supportive clinical supervision technique to explore students’ experiences of VR as an educative tool and to help build emotional coping skills. Results: N = 21 mental health student nurses were recruited to the study. Behavioural responses to the distressed patient scenario were varied. Students that had prior experience in health work were more likely to feel detached from the distress of the service user. Although for some students VR provided a meaningful learning experience in developing emotional awareness, other students felt more like a ‘fly on the wall’ than an active participant. Empathetic and compassionate responses were strongest in those who perceived a strong immersive effect. Overall, the supportive supervision appeared to decrease the anxiety of the small sample involved, but confidence was not affected. Conclusion: The use of 360-degree VR technology as an educative, classroom-based tool to moderate anxiety and build confidence in pre-placement mental health nursing students was partially supported by this study. The effectiveness of such technology appeared to be dependent on the degree to which ‘immersion’ and a sense of presence were experienced by students. Our cognitive reappraisal intervention proved useful in reducing anxiety caused by ‘the patient in distress scenario’ but only for students who achieved a deep immersive effect. Students with prior exposure to distressing events (in their personal lives and in clinical settings) might have developed other coping mechanisms (e.g., detachment). These findings support the idea that ‘presence’ is a subjective VR experience and can vary among users. Full article

Many new technologies focused mainly on improving surgical accuracy were first developed in total knee arthroplasty and have not yet shown significant value. These non-significant clinical improvements could potentially be explained by an inadequate target. In this current concept paper, the authors will describe how artificial intelligence (AI), robotic-assisted surgery, and custom implants allow the definition of new targets and the standardization of the TKA process. As paradoxical as it may be, new technologies in TKA will allow for better standardization in the overall way in which this procedure is carried out. Achieving this goal can be accomplished by incorporating AI-driven tools into the medical field. These tools are intended to enhance decision making, refine surgical planning, and increase the precision and consistency of surgical procedures. Moreover, custom implants with personalized alignment, beyond restoring native anatomy, will define new targets and standardize the whole TKA process. Full article

Insects have been proposed as a sustainable protein alternative to conventional meat sources. However, consumer acceptance of edible insects is still low in the Western Hemisphere. This study examined how product characteristics and consumer beliefs influence the liking and willingness to try cricket-based food products. An online survey was conducted in the province of Alberta, Canada. Alberta is a major site for beef production and plays a vital role in Canada’s agricultural and economic landscape. Participants (n = 548) were asked to indicate their overall liking (OL) and willingness to try (WTT) a cricket-based snack in a conjoint analysis experiment. A 2 × 2 × 5 design was used for the product characteristics (type of product, presence of an image of the product, and product benefit claims). Each participant was assigned five product profiles using a balanced incomplete block design. The type of product (cricket chips and whole roasted crickets) was the most important attribute for participants. Product benefit claims did not effectively increase the OL or WTT of the cricket-based snacks. Higher scores on the Entomophagy Attitude Scale and previous experiences consuming insect-based food products positively influenced WTT and OL. The findings of this study underscore the significance of the type of product and personal attitudes towards entomophagy in shaping consumer preferences for sustainable protein sources and offer valuable insights for the development and marketing of insect-based food products in a Western market where meat products are accessible and affordable for many. Full article

Background: Over the past few decades, the prevalence of obesity has significantly increased worldwide, particularly among children. This trend represents a global health challenge. Considering the pivotal role of obesity in the development of metabolic disorders, the identification and characterization of pathogenic gene variants in children with severe forms of obesity are key priorities in fundamental endocrinology. Methods: We performed whole-exome sequencing (WES) in 163 Russian children with morbid obesity and identified 96 pathogenic or likely pathogenic variants in 61 genes. These variants were clinically significant in 64 children (38.79% of the cohort). Results: Notably, 42 of the identified variants have not been previously described in the literature or reported in existing databases. Conclusions: The findings of this study will enable a more personalized approach to the diagnosis and treatment of patients with syndromic and polygenic forms of obesity. Moreover, these results advance our understanding of the genetic architecture of obesity in the Russian population. Full article