Search Results (1,663)

Copper plays a critical role in cancer biology, with tumor cells exhibiting abnormal copper metabolism that drives proliferation and tumor growth. A limited number of preclinical and clinical studies have reported promising theranostic potential of copper-based radionuclides, such as ⁶⁴Cu, for both diagnostic imaging and targeted radiotherapy in diverse cancers, including prostate cancer (PCa). In this work, we evaluated the cellular uptake and antitumor efficacy of [⁶⁴Cu]Cu-acetate using both cellular and animal models of PCa. Uptake assays revealed that ~70% of the administered dose (10 kBq) was internalized by PC-3 cells within 24 h, predominantly localizing to the cytoplasm, with around 9% detected in the nucleus. These results were corroborated by comparable natural Cu-acetate uptake levels (at equimolar dose) in PC-3 cells, as quantified by ICP-MS. Clonogenic assays revealed a dose-dependent reduction in survival following treatment with [⁶⁴Cu]Cu-acetate (3 and 6 MBq), whereas its non-radioactive counterpart [^NatCu]Cu-acetate, even at excess concentrations (10 µM), had no significant effect. Ex vivo biodistribution studies showed selective tumor accumulation/retention alongside expected hepatic uptake. Clear tumor visualization was achieved using μPET imaging with [⁶⁴Cu]Cu-acetate (10 MBq iv). A single higher dose (65 MBq iv) effectively reduced tumor growth in a subcutaneous PC-3 xenograft mouse model, without systemic toxicity, as evidenced by stable body weight. Together, these results further support the theranostic potential of [⁶⁴Cu]Cu in PCa. Full article

As small–medium-sized enterprises (SMEs) increasingly adopt cloud technologies, understanding the factors influencing this shift is crucial as it helps to optimize cloud integration strategies, enabling SMEs to thrive in today’s digital economy. A cross-sectional, quantitative survey was conducted in February 2022 on 626 employees of SMEs in the USA, based on the TAM-2, TAM-3, and UTAUT-2 models. The questionnaire presented satisfactory reliability, as well as factorial and convergent validity. Employees presented positive behavioral intentions to use cloud technologies, particularly during the COVID-19 period. SMEs were satisfied with the use of Software as a Service (SaaS), Infrastructure as a Service (IaaS), and the public cloud development model in the wake of the COVID-19 period. Behavioral intention to use cloud technologies was linked with higher performance and effort expectancy, price, perceived enjoyment, computer self-efficacy, and social influence. A higher behavioral intention was observed in employees (a) with a mid–top-level role; (b) who worked in finance and insurance, information services data, construction, or software and in an SME with 26–500 employees; (c) who had a master’s degree; (d) were 35–44 years old; and (e) had family obligations. Higher experience with the use of cloud technologies enhanced the positive impacts of effort expectancy, computer self-efficacy, and perceived enjoyment on behavioral intention. Full article

In higher education, institutional quality is traditionally assessed through metrics such as academic programs, research output, educational resources, and community services. However, it is important that their activities align with student expectations, particularly in relation to interactive learning environments, learning management system interaction, curricular and co-curricular activities, accessibility, support services and other learning resources that ensure academic success and, jointly, career readiness. The growing popularity of student engagement metrics as one of the key measures to evaluate institutional efficacy is now a feature across higher education. By monitoring student engagement, institutions assess the impact of existing resources and make necessary improvements or interventions to ensure student success. This study presents a comprehensive analysis of student feedback from the StudentSurvey.ie dataset (2016–2022), which consists of approximately 275,000 student responses, focusing on student self-perception of engagement in the learning process. By using classical topic modelling techniques such as Latent Dirichlet Allocation (LDA) and Bi-term Topic Modelling (BTM), along with the advanced transformer-based BERTopic model, we identify key themes in student responses that can impact institutional strength performance metrics. BTM proved more effective than LDA for short text analysis, whereas BERTopic offered greater semantic coherence and uncovered hidden themes using deep learning embeddings. Moreover, a custom Named Entity Recognition (NER) model successfully extracted entities such as university personnel, digital tools, and educational resources, with improved performance as the training data size increased. To enable students to offer actionable feedback, suggesting areas of improvement, an n-gram and bigram network analysis was used to focus on common modifiers such as “more” and “better” and trends across student groups. This study introduces a fully automated, scalable pipeline that integrates topic modelling, NER, and n-gram analysis to interpret student feedback, offering reportable insights and supporting structured enhancements to the student learning experience. Full article

This study investigated the antimicrobial efficacy of supercritical carbon dioxide (SC-CO₂) plant extracts as a natural preservative, prolonging food shelf-life. The research evaluated the performance of 10 different extracts, including cinnamon, thyme, clove, and dashi, in low-fat food matrices. The results showed that these extracts significantly prolonged the shelf life of a plant-based and animal-based matrixes, with cinnamon and dashi extracts proving highly effective in plant-based matrix against mould and yeast growth for up to 65 days. A key part of the study focused on the interaction between these lipophilic extracts and black soldier fly larvae (BSFL) fat as a potential carrier system. While fats were expected to improve the extracts’ sensory properties and act as a delivery system, in vitro tests revealed an antagonistic effect. The lipophilic nature of the extracts’ active compounds caused them to be trapped within the fat phase, rendering them unavailable to interact with pathogens. These findings highlight the challenges and potential of using lipophilic natural antimicrobials in food systems and underscore the need for new strategies to optimize their efficacy. Full article

Losing a loved one is a painful process that usually diminishes over time. Despite that, one out of ten bereaved adults are at risk of developing Prolonged Grief Disorder (PGD) Internet-delivered cognitive-behavioral therapies (iCBTs) can reach individuals in need of therapy and are both cost-effective and clinically effective. This study aimed to investigate the feasibility of an iCBT for Spanish-speaking individuals with PGD (GROw) compared to the same intervention delivered in a face-to-face videoconferencing format. As a secondary objective, the potential efficacy of GROw was explored. A total of 31 participants were randomized to the experimental group (N = 16) (GROw) and the active control group (N = 15) (videoconferencing treatment). There were four assessment points: baseline, after intervention, and 3- and 12-month follow-ups. Both GROw and videoconferencing treatments were well accepted in terms of preferences, expectations, satisfaction and evaluation about the usefulness of the intervention, and showed significant symptomatology reduction with large effect sizes in most of the outcomes. The dropout rate was 50% in the GROw and 33.33% in the videoconferencing group. GROw is a feasible, well-accepted iCBT for the treatment of PGD with promising results related to its potential efficacy. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) exhibits pronounced biological heterogeneity, aggressive behavior, and a high risk of recurrence and metastasis. The conventional treatments for TNBC have notable limitations: surgical resection may leave residual tumor cells; chemotherapy (CT) frequently induces systemic toxicity and drug resistance; and radiotherapy damages surrounding organs and compromises the patients’ immune function. Methods: Herein, we designed a carrier-free nanodrug delivery system composed of self-assembled Curcumin nanoparticles (NPs) coated with a tannic acid (TA)/Fe(III) network (denoted as CUR@TA-Fe(III) NPs). We systematically evaluated the in vitro cytotoxicity and photothermal–ferroptosis synergistic therapeutic efficacy of CUR@TA-Fe(III) NPs in 4T1 breast cancer cells, as well as the in vivo antitumor activity using 4T1 tumor-bearing mouse models. Results: CUR@TA-Fe(III) NPs had high drug loading efficiency (LE) of 27.99%, good dispersion stability, and photothermal properties. Curcumin could inhibit the growth of 4T1 cancer cells, while TA-Fe(III) efficiently converted light energy into heat upon exposure to near-infrared (NIR) light, leading to direct thermal ablation of 4T1 cells. Additionally, TA-Fe(III) could supply Fe(II) via TA, increase intracellular Fe(II) content, and generate reactive oxygen species (ROS) through the Fenton reaction, in turn inducing lipid peroxidation (LPO), a decrease in mitochondrial membrane potential (MMP), and glutathione depletion, eventually triggering ferroptosis. Conclusions: This treatment strategy, which integrates CT, PTT, and ferroptosis, is expected to overcome the limitations of traditional single-treatment methods and provide a more effective method for the treatment of TNBC. Full article

Treatment-resistant peripartum depression (TRPD) is a significant public health concern due to the dual imperative of maternal symptom relief and fetal/neonatal safety with complex therapeutic challenges, particularly among expecting mothers worldwide. This comprehensive review focused on current pharmacological and non-pharmacological interventions for treatment-resistant depression (TRD)/peripartum depression (PPD), highlighting their mechanisms, efficacy, safety profiles, and practical considerations. The search strategy is based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis), using a systematic search of PubMed, Cochrane Library, and EMBASE for English-language articles published between 2000 and 2024, with a combination of Medical Subject Headings (MeSH) and free-text terms for TRD/TRPD. After screening, the initial search yielded 142 articles; only 67 articles were qualified for eligibility and quality assessment. According to related research, pharmacological treatments such as SSRIs or brexanolone and zuranolone can be effective in addressing TRPD challenges, but they carry concerns regarding fetal and neonatal risk. In contrast, non-pharmacological interventions—such as cognitive behavioral therapy (CBT), repetitive transcranial magnetic stimulation (rTMS), and exercise—offer safe, evidence-based alternatives that are becoming increasingly accessible. Our findings imply that innovative therapeutics and integration of these interventions personalized to individual needs are the optimal clinical approach that may help in balancing maternal symptom control and perinatal safety. Also, expanded mental health infrastructure with enhanced research is essential for advancing TRPD care. Full article

Objective: Type B aortic dissection is a life-threatening medical condition. Endovascular closure of the primary entry by means of TEVAR is considered, nowadays, the gold standard if operative treatment is necessary. The aim of this study is to analyse the theoretical applicability of selective endovascular entry sealing using different occluder systems. Methods: A CT-graphic analysis of 102 patients who received TEVAR from January 2017 to June 2023 was performed. Patients with an intramural haematoma were excluded. The study patients were divided in two groups: type B aortic dissection (n = 87) and distal stent graft-induced new entry (n = 15). The TBAD group included patients with acute (n = 63), subacute (n = 12), and chronic aortic dissections (n = 12). The CTA analysis of the location, length, and width of the entry was performed using Aquarius iNtuition (TeraRecon, Inc., Foster City, CA, USA). After completion of the data collection, the possible application of all three occluder systems (ASD-Occluder, Septal-Occluder, and Amplatzer™-Occluder) was analysed, with reference to the Instructions for Use. Results: The ASD-Occluder from GORE is produced in five different sizes. It can be used in 81.4% (n = 83) of all patients in the overall study, including 82.8% TBAD (n = 72) and 73.3% of dSINE (n = 11) patients. When using the ASD-Occluder, 10.3% (n = 9) of patients are expected to have complete vascular coverage of the LSA based on our CTA analysis. The Septal-Occluder from GORE is offered in three different sizes. Complete entry closure can theoretically be achieved in fifty patients (57.5%) with TBAD and in nine patients (60%) with dSINE, based on CTA analysis and IFU criteria. With the use of the Septal-Occluder, 3.9% (n = 4) of the dSINE patients and 4.6% (n = 4) of the TBAD patients were expected to have complete aortic branch occlusion. The Amplatzer™-Occluder from Abbott is provided in 27 different sizes to effectively seal defects with a diameter of 4 to 56 mm. It can technically be used in 90.1% of patients (n = 92), of which 89.7% with TBAD (n = 78) and 93.3% with dSINE (n = 14) to completely seal the entry. Conclusions: CTA analysis in patients with TBAD and dSINE demonstrated that by the theoretical application of occluder systems, a seal of the entry would be achieved in 57.8% to 90.1% of the patients. However, in addition to entry closure, the use of occluder systems can also lead to unintentional partial (10.7–23.5%) or complete (3.9–22.5%) coverage of adjacent aortic branches. The clinical significance and applicability of the occluder system should be reviewed in future studies and practical applications to evaluate safety, efficacy, and possible complications in order to define the benefit–risk balance. Full article

Purpose: Adolescence is a period of increased vulnerability to addictive behaviors, and Primary Health Care (PHC) plays a crucial role in prevention and intervention (e.g., through Screening, Brief Intervention, and Referral to Treatment), but professionals often face barriers, such as inadequate training and systemic challenges, particularly within the Greek context. Given the lack of data on their needs, this study aimed to investigate the levels of self-perceived knowledge/skills, attitudes regarding communication and readiness, perceived barriers, and educational expectations among PHC professionals in Greece. Method: A cross-sectional descriptive survey was conducted using an anonymous questionnaire with a convenience sample of 331 PHC professionals from 5 Health Regions. Results: Professionals recognized the high importance of effective communication (M = 4.31/5) but reported low preparedness (M = 2.65/5) and moderate confidence in knowledge, especially in screening tools/motivational interviewing (M = 2.25/5). Lack of training was the main barrier (87.6%). A strong positive correlation was found between knowledge and preparedness (rho = 0.68, p < 0.001), but not between age/experience and readiness (p > 0.05). Discussion: The study highlights a significant readiness gap and a substantial need for specialized training for PHC professionals in Greece, regardless of experience. Targeted interventions are required to enhance skills (especially in SBIRT/MI) and self-efficacy, alongside action to address systemic barriers. Full article

Background: Upright position recovery (i.e., verticalization) is crucial in the rehabilitation of severe acquired brain injury (sABI). VErticalization by tilt table equipped with robotic-assisted lower limbs cyclic Mobilization (VEM) may facilitate a safer adaptation to vertical posture, reducing orthostatic hypotension occurrence. This multicenter randomized controlled trial (RCT) aims at investigating efficacy, safety, and usability of VEM compared to Traditional Verticalization (TV) using a conventional tilt table in cognitive-motor rehabilitation of sABI patients; Methods: a total of 118 sABI patients with or emerged from prolonged Disorder of Consciousness (pDoC and eDoC) will be enrolled in six post-acute Neurorehabilitation Units and randomly allocated to VEM or TV arm (for each arm: total 25 sessions of 30 min daily treatment/5 days/week/5 weeks). Patients will undergo clinical–functional assessment, resting EEG recording and blood sampling, before, at the end of treatment, and after 1 month; Results: we will expect possible differences in safety and usability of verticalization between VEM and TV rehabilitative intervention and in their efficacy to improve clinical–functional findings and brain indices; Conclusions: this RCT will provide new insights for the intensive, tailored and safe neurorehabilitation intervention in patients with sABI. Full article

For more than 20 years, after the introduction of the first robotic system, research on prostate cancer (PCa) surgery has mainly focused on evaluating outcomes of Robotic-Assisted Radical Prostatectomy (RARP). In the last few years, however, a new generation of innovative techniques, surgical approaches, and expanded indications have emerged. The Single Port (SP) robotic system was the first real hardware innovation in robotic surgery, and has already demonstrated advantages in terms of shorter length of stay, better cosmetic results and reduced postoperative pain. Artificial Intelligence (AI)-powered algorithms are being proposed as reliable tools for surgical assistance, aiding in standardization and mass implementation of robotic training. New surgical indications are emerging on the basis of patient and tumor characteristics. The extensive adoption of PCa screening and the precision of diagnostic tools have increased the rate of PCa diagnoses in a localized stage. Partial prostatectomy, despite needing further validation, has emerged as a safe and minimally invasive treatment option for confined tumors, able to minimize the side effects of prostate surgery. For locally advanced PCa, radioguided surgery has not only enhanced the oncological effectiveness of lymphadenectomy by enabling the precise identification and extraction of pathological lymph nodes, but has also contributed to minimizing the side effects associated with unnecessarily extensive dissections. Finally, in light of the increased efficacy of modern systemic therapies and the longer life expectancy, RP is currently being evaluated for primary tumor management in the metastatic phase. Despite the novelty of the aforementioned treatment options, they are already set to shape the future evolution of PCa management and international guidelines. Full article

The increasing prevalence of brain metastases in cancer patients due to longer life expectancy and improvements in neuroimaging highlights the need for effective local treatments. Despite advancements in systemic targeted therapies, their low blood–brain barrier (BBB) penetrance limits their intracranial efficacy. Stereotactic radiosurgery (SRS) has largely supplanted whole-brain radiation therapy (WBRT) for patients with up to 10 brain lesions due to superior neurocognitive outcomes and high local control. While single-fraction SRS provides low radiation toxicity with smaller lesions, high-volume metastases necessitate doses above tolerance limits to achieve comparable local control. As tumor volume increases, the number of tumor cells also increases, requiring higher doses of radiation than the maximum tolerated doses reported in the RTOG 9005 study to achieve tumor control. Hypo-fractionated SRS (HySRS) permits the delivery of high radiation doses over 2–5 fractions, thus mitigating the risk of radiation toxicity while maintaining high local control. This review presents the available evidence and ongoing clinical trials on HySRS for the management of brain metastases. Full article

Background: Although DNA vaccines offer a flexible platform for tumor immunotherapy, their weak immunogenicity remains a key limitation. This study aimed to improve the immunogenicity of DNA vaccines by enhancing the efficiency of tumor neoantigen delivery through extracellular vesicles (EVs), thereby promoting stronger dendritic cell (DC) activation and antitumor responses. Methods: A novel DNA vaccine (pCSP) was engineered by fusing tumor-specific neoantigens to the EV-associated protein CD63 and incorporating a SARS-CoV-2 receptor-binding domain (RBD) fragment to facilitate EV uptake by DCs. The resulting EVs were expected to carry neoantigens into the immunoproteasome for major histocompatibility complex I (MHC-I) presentation. The immunological and antitumor effects of pCSP were assessed through in vitro functional assays and in vivo experiments in a murine pancreatic cancer model. Safety was evaluated through histological and biochemical analyses. Results: In vitro, pCSP significantly promoted EV internalization by DCs by approximately twofold and enhanced their immune activation, as evidenced by elevated cytokine production. In vivo, pCSP markedly suppressed tumor growth with a decrease in volume by over 70% relative to controls, boosted CD8+ T cell responses, and increased immune infiltration into the tumor microenvironment. Safety assessments revealed that while liver/kidney function markers were within physiological ranges, mild inflammatory infiltrates were consistently observed in the lungs, indicating a localized safety concern that warrants further monitoring. Conclusions: The pCSP vaccine enhances the immunogenicity of neoantigen DNA vaccines by improving EV uptake and immune activation in DCs. These findings provide a potential strategy for improving DNA vaccine efficacy in the context of cancer immunotherapy while maintaining acceptable safety. Full article

Compound T1089—a novel nitrogen mustard based on an indole-3-carboxylic acid derivative (ICAD)—has been synthesized. The ICAD used as the basis for T1089 is a TLR agonist capable of activating an antitumor immune response. This study describes the synthesis method and presents the results of preliminary investigations of this compound. This research included an assessment of acute toxicity in mice, in vivo clastogenic activity evaluated via the bone marrow chromosome aberration (BMCA) test in mice, in vitro cytotoxicity determined by the MTT assay against human lung carcinoma A549 cells, and in vivo antitumor effects (ATEs) in models of conventional chemotherapy (CCT) of solid tumors in mice. The bifunctional alkylating agent cyclophosphamide (CPA) was used as a reference drug. Toxicological studies revealed that T1089 belongs to toxicity class III (moderately toxic), with acute toxicity values (LD₁₆ and LD₅₀) in mice following intraperitoneal (i.p.) administration being 191 and 202 mg/kg, respectively. The alkylating activity and clastogenic potential of T1089 were demonstrated by its effects in the BMCA test, which were comparable to those of CPA. A single i.p. administration of CPA and T1089 at a dose of 0.064 mmol/kg induced similar stimulation of structural mutagenesis associated with DNA strand breaks. The frequency of karyocytes with aberrations increased 20-fold compared to the control, primarily due to a rise in chromatid breaks and fragments, and to a lesser extent, due to an increase in exchange-type aberrations. In vitro cytotoxicity studies indicated differences in the mechanisms of alkylating activity between CPA and T1089. According to the MTT assay, the cytotoxic effects of CPA were observed only at concentrations exceeding 2 mM (IC₅₀ = 4.2 ± 0.3 mM), corresponding to lethal in vivo doses, which is expected since the formation of CPA’s alkylating metabolite requires hepatic microsomal enzymes. In contrast, significant cytotoxic effects of T1089 were observed at much lower concentrations (15–50 μM, IC₅₀ = 33.4 ± 1.3 μM), corresponding to safe in vivo doses. Differences were also observed in the in vivo ATEs of CPA and T1089 in the Ehrlich solid carcinoma (ESC) CCT model. Following seven i.p. administrations at 48 h intervals (33 mg/kg), both compounds exhibited increasing toxicity, manifested as cumulative body weight loss in treated mice. However, despite the aggressive CCT regimen, ESC showed low sensitivity to CPA. The ATE of CPA developed slowly, reaching a significant level only after four injections, and even after seven administrations, tumor inhibition (TI) did not exceed 30%. In contrast, ESC was significantly more sensitive to T1089 under the same CCT conditions. The ATE of T1089 exhibited a cumulative pattern but developed more rapidly and to a greater extent. A significant antitumor effect was observed after just two injections, with maximal efficacy (TI = 53%) achieved after four injections and sustained until the end of the observation period. A high ATE of T1089 was also observed in the B-16 melanoma CCT model. Following six i.p. administrations at 48 h intervals (28 mg/kg), T1089 treatment was associated with minimal toxicity. Despite this mild CCT regimen, melanoma exhibited high sensitivity to T1089. Maximal ATE (TI = 56%) was achieved after two injections, and subsequent administrations maintained a consistently high efficacy (TI = 52–55%) until the end of the study. In summary, preliminary findings demonstrate that T1089 possesses alkylating activity characteristic of bifunctional agents, accompanied by high in vitro cytotoxicity and in vivo ATEs in CCT models (at high doses). Given that the ICAD used as the basis for T1089 is a TLR agonist capable of stimulating antitumor immunity, T1089 can be considered a dual-action alkylating agent with combined antitumor effects. These results justify further investigation of T1089 in conventional and metronomic chemotherapy regimens, particularly in combination with immune checkpoint inhibitors and antitumor vaccines. Full article

Applying therapeutic elements to prevent injury from potential infections is a promising avenue in the development of novel bone substitutes; however, achieving controllable delivery of therapeutic ions is crucial to realizing their expected functions. In this study, a Ag nanoparticle core wrapped in an MSN shell was successfully synthesized using a one-pot sol–gel process. Subsequently, the produced Ag@MSN was functionalized with amino and carboxylic groups. The experimental results indicated that these core–shell-structured Ag@MSN spheres had a uniform size of ~60 nm and a specific area of 904.6 m²/g. Their release profiles, influenced by different surface charges, were investigated, with the aim of achieving sustainable release of Ag ions. The concentration-dependent biological effects of Ag@MSNs, including their anti-infection properties and biocompatibility, were comprehensively characterized in vitro, considering their potential for use as bioactive bone substitutes. Functionalized mesoporous silica nanoparticles significantly enhanced the sustained release profile of silver ions, achieving a cumulative release efficiency greater than 50% within 24 h. These nanoparticles also demonstrated exceptional antibacterial efficacy, with an inhibition rate surpassing 98% at a concentration of 30 μg/mL, while concurrently maintaining cell viability above 88%, indicating high biocompatibility. We achieved our goal of effectively decreasing the burst release of Ag to satisfy the intrinsic need for long-term resistance to bacteria in bone substitutes and stimulate osteoblast proliferation. Full article