Search Results (431)

Metastatic urothelial carcinoma (mUC) is a lethal cancer with limited therapeutic options. Advances in genomic and transcriptomic research have deepened the understanding of mUC biology, leading to the identification of clinically relevant molecular alterations that represent potential actionable targets. This has broadened the treatment landscape of the disease to include novel agents, such as antibody–drug conjugates (e.g., enfortumab vedotin) and targeted therapies, including the pan-fibroblast growth factor receptor (FGFR) inhibitor erdafitinib. Genomic alterations in FGFR3 are well-established oncogenic drivers in bladder cancer and represent predictive biomarkers of response to FGFR-targeted therapies. The phase III THOR trial demonstrated the clinical benefit of erdafitinib in previously treated mUC patients harboring FGFR3 alterations and supported its subsequent approval by the European Medicines Agency. In this context, accurate molecular profiling is essential to guide patient selection for FGFR inhibitor therapy. Equally important is the standardization and timely implementation of FGFR3 testing in clinical practice to optimize treatment planning. This review addresses key considerations in FGFR3 testing in mUC and discusses how it can be routinely incorporated into clinical practice. Full article

The treatment of central nervous system (CNS) autoimmune diseases has evolved from broad immunosuppression toward targeted disease-modifying therapies (DMTs). While current DMTs effectively control inflammatory activity in many patients, unmet needs remain, including persistent compartmentalised CNS pathology, limited tissue penetration, and the cumulative burden of chronic therapy. Chimeric antigen receptor (CAR) T-cell therapy represents a novel “living” immunotherapy capable of antigen-specific cellular depletion. Although currently approved only for B-cell malignancies, CAR T-cells are increasingly being explored in CNS autoimmunity leveraging their capacity for autonomous cytotoxicity and expected access to immune cells within protected CNS niches following a potentially single intervention. In this review, we examine CAR T-cells in the context of CNS-autoimmunity, we outline principles derived from oncologic applications, assess current DMTs, their limitations and side effects, and define parameters where CAR T-cells may offer added value. We discuss biological and practical requirements for broader clinical application, as currently they are investigated only for the very severe and refractory cases where all alternative treatments have failed. We further review the plasticity of CAR constructs, distinguishing clinically advanced platforms from early proof-of-concept approaches. Finally, we summarise clinical experience from 15 patients with CNS autoimmunity treated with CAR T-cells and review ongoing or planned trials that include such patients. We conclude that CAR T-cell therapy remains investigational for severe, treatment-refractory disease, with future applicability dependent on demonstrable efficacy, safety, cost, and feasibility beyond existing DMTs. Full article

Background: Intimate partner violence (IPV) represents a major public health problem in Europe, with significant physical, psychological, and social consequences. Nurses are often the first professionals capable of detecting early signs of IPV, yet they lack validated instruments to assess their clinical competency in detection, evaluation, documentation, and intervention. This study aimed to develop and validate the Intimate Partner Violence Nursing Competency Scale (IPVNCS), aligned with the Nursing Intervention Classification (NIC 6403). Methods: A cross-sectional psychometric study was conducted among registered nurses in the Community of Madrid. A 30-item Likert-type self-administered instrument (1–5 scale) was developed based on NANDA, NIC 6403, and NOC frameworks. A total of 202 nurses participated. Reliability was assessed through Cronbach’s alpha. Construct validity was examined using exploratory factor analysis (EFA) with Promax rotation and confirmatory factor analysis (CFA) using AMOS 26. Ethical approval was obtained (CEU San Pablo, code 843/24/104). Results: After item refinement, 26 items remained across four dimensions: (1) Intervention and Referral, (2) Detection and Assessment, (3) Documentation and Recording-keeping, (4) Psychosocial Support. The instrument showed excellent reliability ($\alpha$ = 0.97). KMO was 0.947 and Bartlett’s test was significant (p < 0.001). CFA demonstrated satisfactory fit: ${\chi }^2$/df = 2.066, RMSEA = 0.073, CFI = 0.92, TLI = 0.91, NFI = 0.86. The final model adequately represented the latent structure. After debugging, its psychometric properties were significantly improved. Four redundant items were eliminated, achieving internal consistency ($\alpha$ = 0.97), a KMO value of 0.947 and a significant Bartlett’s test of sphericity. It showed a better fit, according to ${\chi }^2$/df = (2.066); Parsimony = (720.736); RMR (0.0529; RMSEA (0.073); NFI (0.860); TLI (0.910) and CFI (0.920). The final model provides an adequate representation of the latent structure of the data. This study provides initial evidence of construct validity and internal consistency reliability of the IPVNCS. Conclusions: The IPVNCS is a valid and reliable tool to assess nursing competencies for clinical management of IPV. It supports structured evaluation across four core nursing domains, enabling improved educational planning, clinical decision-making, and quality of care for victims. The scale fills a gap in clinical nursing assessment tools and can support protocol development in emergency, primary care, and hospital settings. Full article

Children with rare tumours and malformations may benefit from innovative imaging, including patient-specific 3D models that can enhance communication and surgical planning. The primary aim was to evaluate the impact of patient-specific 3D models on communication with families. The secondary aims were to assess their influence on medical management and to establish an efficient post-processing workflow. From 2021 to 2024, we prospectively included patients aged 3 months to 18 years with rare tumours or malformations. Families completed questionnaires before and after the presentation of a 3D model generated from MRI sequences, including peripheral nerve tractography. Treating physicians completed a separate questionnaire before surgical planning. Analyses were performed in R. Among 21 patients, diagnoses included 11 tumours, 8 malformations, 1 trauma, and 1 pancreatic pseudo-cyst. Likert scale responses showed improved family understanding after viewing the 3D model (mean score 3.94 to 4.67) and a high overall evaluation (mean 4.61). Physicians also rated the models positively. An efficient image post-processing workflow was defined. Although manual 3D reconstruction remains time-consuming, these preliminary results show that colourful, patient-specific 3D models substantially improve family communication and support clinical decision-making. They also highlight the need for supporting the development of MRI-based automated segmentation softwares using deep neural networks, which are clinically approved and usable in routine practice. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by decreased amyloid-beta (Aβ) clearance, enhanced Aβ aggregation, an increased risk of amyloid-related imaging abnormalities (ARIA), and blood–brain barrier (BBB) dysfunction. The APOE4 allele, being the leading genetic risk factor for AD, contributes strongly to these symptoms. This review covers the relationship between APOE4 status and the efficacy of FDA-approved monoclonal antibody (mAb) therapies, namely aducanumab, lecanemab, and donanemab. Across several clinical trials, APOE4 carriers exhibited higher rates of ARIA-E and ARIA-H compared to non-carriers. While the therapies did often meet biomarker endpoints (i.e., reduced amyloid), benefits were only observed in early and mild AD, and cognitive benefits were often marginal. Going forward, experimental apoE4-targeted immunotherapies may ease the burden of APOE4-related pathology. The field is shifting towards a more integrated approach, focusing on earlier interventions, biomarker-driven precision treatment, and improved drug delivery systems, such as subcutaneous injections, receptor-mediated transport, and antibodies with enhanced BBB penetration. As it stands, high treatment costs, limited accessibility, and strict eligibility criteria all stand as barriers to treatment. By integrating the APOE4 genotype into treatment planning and focusing on disease-stage-specific approaches, a safer and more effective means of treating AD could be achieved. Full article

Objective: To test whether inpatient electrical muscle stimulation (EMS) using Russian current (5 kHz carrier, 50 Hz modulation; 4 s ON/6 s OFF) improves mobility and balance in elderly people with chronic cerebral ischaemia. Design: Prospective single-centre controlled observational pilot, embedded in routine inpatient rehabilitation; no concealed randomisation (EMS + standard care; sham EMS + standard care; standard care only (control)). Methods: A single-centre controlled observational study with three groups was conducted (EMS n = 27, control n = 10, sham n = 7) with 3–9 sessions over 2 weeks (20 min; quadriceps and calves). Pre/Post Outcomes: Tinetti (balance/gait), Rivermead Mobility Index, Timed Up and Go (TUG), ankle extensor maximal voluntary force (MVF), stabilography (statokinesiogram path length (L), mean velocity of COP (V), sway area (S), and myotonometry; ANOVA, α = 0.05). Ethics approval and informed consent were obtained. Between-group differences in change scores were evaluated descriptively, and no formal hypothesis-testing was planned. Results: EMS showed significant gains versus control/sham—higher Tinetti total and Rivermead scores, faster TUG, higher MVF, and improved stabilography in the eyes-closed condition (reduced L, V, and S), with good tolerability and no serious adverse events (SAEs). Conclusions: Short-course Russian-current EMS is feasible and associated with clinically meaningful improvements in balance, gait, and strength in elderly patients with chronic cerebral ischaemia; however, larger randomised trials are warranted. Full article

Artificial intelligence (AI) is rapidly reshaping thoracic surgery, advancing from decision support to the threshold of autonomous intervention. AI-driven technologies—including machine learning (ML), deep learning (DL), and computer vision—have demonstrated significant improvements in diagnostic accuracy, surgical planning, intraoperative navigation, and postoperative outcome prediction. In lung cancer and thoracic oncology, AI enhances imaging analysis, histopathological classification, and risk stratification, supporting multidisciplinary decision-making and personalized therapy. Robotic-assisted and AI-guided systems are optimizing surgical precision and workflow efficiency, while real-time decision-support tools and augmented reality are improving intraoperative safety. Despite these advances, widespread adoption is limited by challenges in algorithmic bias, data integration, regulatory approval, and ethical transparency. The literature emphasizes the need for multicenter validation, explainable AI, and robust governance frameworks to ensure safe and effective clinical integration. Future research should focus on digital twin technology, federated learning, and transparent AI outputs to further enhance reliability and accessibility. AI is poised to transform thoracic surgery, but responsible implementation and ongoing evaluation are essential for realizing its full potential. The aim of this review is to evaluate and synthesize the current landscape of artificial intelligence (AI) applications across the thoracic surgical pathway, from preoperative decision-support to intraoperative guidance and emerging autonomous interventions. Full article

Prostate cancer remains one of the most common malignancies in men worldwide, with incidence and mortality steadily increasing across diverse populations. While early detection and radical prostatectomy can achieve durable control in a subset of patients, approximately 40% of men will ultimately experience biochemical recurrence often in the absence of clinically detectable disease. Conventional imaging approaches—CT, MRI, and bone scintigraphy—have limited sensitivity for early relapses, frequently leading to delayed diagnosis and suboptimal treatment planning. The discovery of prostate-specific membrane antigen (PSMA) in 1987 and its subsequent clinical translation into positron emission tomography (PET) imaging with [⁶⁸Ga]Ga-PSMA-11 in 2012, followed by U.S. FDA approval in 2020, has transformed the landscape of prostate cancer imaging. PSMA PET has demonstrated superior accuracy over conventional imaging, as highlighted in the landmark proPSMA trial and now serves as the foundation for theranostic approaches that integrate diagnostic imaging with targeted radioligand therapy. The clinical approval of [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto^®: (lutetium Lu 177 vipivotide tetraxetan, Advanced Accelerator Applications USA, Inc., a Novartis company) has established targeted radioligand therapy as a viable option for men with metastatic castration-resistant prostate cancer, extending survival in patients with limited alternatives. Emerging strategies, including next-generation ligands with improved tumor uptake and altered clearance pathways, as well as the integration of artificial intelligence for imaging quantification, are poised to further refine patient selection, dosimetry, and treatment outcomes. This review highlights the evolution of PSMA-based imaging and therapy, discusses current clinical applications and limitations, and outlines future directions for optimizing theranostic strategies in prostate cancer care. Full article

The growing environmental effect of asphalt pavements has fueled interest in sustainable alternatives including the application of recycled materials and self-healing systems. This research investigates the synergistic possibilities of steel slag aggregates and steel wool fibers in hot-mix asphalt compositions to increase sustainability and let crack healing via electromagnetic induction heating. Using either recycled steel slag or natural porphyritic aggregates, two kinds of AC16 Surf S mixtures with 35/50 bitumen were created incorporating two levels of steel fiber content (2% and 4%). Based on repeated semi-circular bending (SCB) testing following regulated induction heating and confinement, a committed self-healing evaluation plan was developed. The results verified that combinations including recycled steel slag met or outperformed traditional mixes in terms of mechanical behavior. Induction heating successfully set off partial recovery of fracture toughness, with more fiber content and repeated heating cycles producing better healing values. Recovery levels ran from 14.6% to 40%, therefore proving the practicality of this approach. These results encourage the creation of asphalt mixtures with improved endurance and environmental advantages. The research offers both an approved approach for assessing healing and real-world recommendations for the construction of low-maintenance, round pavements utilizing induction-based techniques. Full article

Background: Suicidal ideation (SI) represents a clinical challenge in patients with treatment-resistant depression (TRD), and the management of this condition should be as rapid and effective as possible. Intranasal Esketamine has shown promise in patients with TRD due to its rapid onset of action on both SI and depressive symptoms. Since this medication has been recently approved, real-world data on its efficacy remain scarce, and little is known about which patients are most likely to benefit from this approach. Aims: This study aimed (1) to evaluate the efficacy of intranasal Esketamine on SI and depressive symptoms and (2) to find potential predictors of clinical response. Methods: Patients with TRD who received intranasal Esketamine were included in this study. Clinical evaluations and psychometric assessments were made at baseline (T0) and at five subsequent time points (one week [T1], one month [T2], two months [T3], three months [T4], and six months [T5]). SI was assessed using the Columbia Suicide Severity Rating Scale (C-SSRS), and depressive symptoms were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS). Furthermore, sociodemographic, clinical, and pharmacological data were collected. Results: Eighty patients diagnosed with TRD were enrolled. Suicidal ideation (C-SSRS items 1–5) decreased from 1.56 ± 1.65 at baseline to 0.78 ± 1.28 at T1 and 0.12 ± 0.52 at T5 (all p < 0.001). MADRS fell from 31.81 ± 7.94 to 23.62 ± 9.08 and 10.19 ± 7.33 at the same time points (all p < 0.001). By T1, 68.4% achieved an SI response on the C-SSRS. The MADRS response rate increased from 16.7% at T1 to an overall response of 62.5% at T5. Male sex predicted lower odds of early response on the C-SSRS (OR = 0.21, p = 0.031); no other baseline variable was significant as a predictor. Conclusions: Intranasal Esketamine has been shown to be effective in the rapid reduction and lysis of SI in patients with TRD. Male gender was found as a negative predictor of response, suggesting the importance of considering gender differences during treatment planning. Full article

While most prison healthcare litigation seeks individual relief, some cases lead to broader structural reform via consent decrees—court-approved “legally binding performance improvement plans” designed to improve conditions. This study systematically analyzes 121 such settlements from 1970 to 2022 to assess their policy goals and implementation strategies. We identify the substantive areas targeted—general medical care, mental health, dental services, and treatment for specialized conditions like HIV, Hepatitis C, and COVID-19—and trace trends across time and geography. These agreements span 39 states and the federal system, with most states subject to multiple cases. They frequently mandate changes to budgets, staffing, facility infrastructure, training, and patient rights, alongside monitoring for quality improvement. Our findings suggest that consent decrees function not only as judicial remedies but as tools of policy development and institutional reform, shedding light on the role of courts in shaping correctional healthcare delivery. These findings also show how institutional responses to healthcare failures in prisons shape the conditions under which serious harm—and in some cases, preventable death—occur behind bars. Full article

Despite growing technological and economic viability, the adoption of solar energy in the United States remains low. This research synthesizes 96 peer-reviewed publications from 2000 to 2024 to investigate how public perceptions, user psychology, institutional setups, and socioeconomic contexts shape solar energy adoption decisions in the United States. Drawing on a PRISMA systematic review of publications gathered from Scopus and Web of Science databases, the study reveals that solar adoption is influenced not only by environmental concern and perceived economic benefits but also by institutional trust, social norms, cognitive biases, and demographic characteristics. Key findings highlight that while higher income and education levels enable adoption, marginalized communities face persistent barriers, including institutional distrust, limited awareness, and constrained access to financing. Residential rooftop solar projects receive higher public approval than utility-scale developments, with agrivoltaics systems emerging as a promising middle ground. This review identifies critical gaps in public awareness and institutional credibility, calling for integrated policy responses that combine financial incentives with inclusive engagement strategies. By emphasizing the socio-behavioral dimensions of energy transitions, it offers actionable insights for policymakers, energy planners, and researchers aiming to broaden solar accessibility and equity. It underscores the need for future research on identity-driven adoption behavior, participatory energy planning, and depoliticized communication to bridge the intention-action gap and accelerate the just transition to solar energy. Full article

In 2016, the South African government approved free oral PrEP distribution among high-risk groups like female sex workers (FSWs) to reduce new HIV infections. Despite the availability, unique barriers exist that challenge PrEP persistence, including limited knowledge, side effects, stigma, and mobility that hinder adherence. As such, engaging FSWs in the design of an FSW-led intervention program is crucial to promote PrEP uptake, adherence, and retention. Processes of an intervention mapping approach were applied to design and develop the program in KwaZulu-Natal, South Africa. A needs analysis was completed through existing literature and through engagements with FSWs, FSW peer educators, and a healthcare provider. The working group, comprising eight FSW peer educators and a researcher, co-created the intervention following a six-step mapping process. A total of six meetings took place, during which intervention determinants, change objectives, theory-based methods, and the intervention program were discussed and formulated, as well as implementing partners and the evaluation plan identified. The program focuses on the development of agency, self-efficacy, and hope among FSWs and aims to destigmatize PrEP through positive messaging, equipping FSWs with the ability to differentiate PrEP from ARVs given to people living with HIV. Through role-playing, participants will practice discussing PrEP with their intimate partners and friends, receive suggestions on managing pill supply and side effects, and be equipped to become PrEP ambassadors. The introduction of PrEP as a pill for high-risk groups can be stigmatizing. Therefore, it is crucial to involve marginalized groups in the design and implementation of their interventions to foster acceptance and develop a sense of ownership, ensuring the programs’ sustainability. Full article

For patients with relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior lines of therapy, T-cell-redirecting therapies—including the bispecific CD3xCD20 antibody (BsAbs) mosunetuzumab (mosu) and chimeric antigen receptor T-cell (CAR-T) therapies such as axicabtagene ciloleucel (axi-cel), lisocabtagen maraleucel (liso-cel), and tisagenlecleucel (tisa-cel)—are approved by the FDA and EMA. Treatment selection should consider patient-related factors, prior therapeutic exposure, and toxicity profiles. We describe the 20-year history of a patient with R/R FL. At the fourth relapse, both BsAbs and CAR-T cells were available; however, due to the cumulative toxic burden and the high risk of cytopenias, mosu was selected as the preferred option. During mosu, the patient developed pure red cell aplasia unrelated to infections. Despite achieving a partial response after eight cycles of mosu, this complication led to the decision to proceed with allogeneic stem cell transplantation (allo-HSCT). The course was ultimately complicated by severe early toxicity with massive hemoptysis, acute respiratory failure, and hemorrhagic alveolitis, resulting in a fatal outcome. This case illustrates the delicate balance required in selecting between BsAbs and CAR-T therapy in R/R FL. Contributing factors to the patient’s fragility included profound immune status, transfusion-dependent red cell aplasia, prior cumulative chemotherapy, and pulmonary toxicity associated with conditioning regimens. The case underscores the importance of individualized treatment strategies and suggests that earlier integration of novel T-cell-redirecting therapies may mitigate cumulative toxicity and infection risk. Individualized therapeutic planning is critical in heavily pretreated R/R FL. In select cases, bridging strategies using BsAbs can provide disease control and facilitate transplantation. Still, careful assessment of patient fitness, marrow reserve, and cumulative toxicity is essential to minimize the risk of fatal complications. Full article

Ship damage control (DC) is pivotal to platform survivability in the face of battle damage and severe accidents. The DC context features multi-hazard coupling among flooding, fire, and smoke, as well as fast system dynamics and intensive human–machine collaboration, demanding real-time predictive simulation and decision support. Conventional DC simulations fall short in multiphysics fidelity, predictive speed, and integration with onboard sensing and control. A digital twin (DT) framework for predictive shipboard DC is introduced with an explicit capability envelope, observability, and latency requirements, and a cyber-physical mapping to ship systems. Building on this foundation, a three-stage/four-level maturity model charts progression from L1 monitoring, through L2 prediction and L3 human-in-the-loop, override-enabled plan generation, to L4 closed-loop decision control, specifying capability milestones and evaluation metrics. Guided by this model, a four-layer architecture and an end-to-end roadmap are formulated, spanning multi-domain modeling, multi-source sensing and fusion, surrogate-accelerated multiphysics simulation, assisted plan generation with human approval/override, and cyber-physical closed-loop control. The framework aligns interfaces, performance targets, and verification pathways, providing actionable guidance to upgrade shipboard DC toward resilient, efficient, and human-centric operation under multi-hazard coupling. Full article