Search Results (245)

Background/Objectives: Penile urethral stricture is a therapeutically challenging condition that significantly impacts quality of life and is often managed initially with urethral dilation or internal urethrotomy. However, both techniques are associated with high recurrence rates, limited long-term efficacy, and potential adverse effects, particularly in the penile urethra. Urethroplasty remains the gold standard but is invasive and not suitable for all patients. Optilume, a paclitaxel-coated balloon, combines mechanical dilation with localized drug delivery to reduce recurrence rates and the need for re-intervention. This study evaluated its effectiveness in patients with penile urethral strictures. Methods: A retrospective, multicenter study was conducted at two German clinics. Eight male patients (mean age 59) with symptomatic penile urethral strictures underwent Optilume treatment. Symptom severity was assessed using the International Prostate Symptom Score (IPSS) and quality of life (QoL) scores before and after treatment. The primary endpoint was symptom improvement, while the secondary endpoint was the need for reintervention. Patients were followed for a median of 16.5 months. Statistical analyses included Wilcoxon signed-rank and Mann–Whitney U tests. Results: The median IPSS improved from 25.5 to 5.0 and QoL scores from 4.5 to 1.0 after treatment (p < 0.01 for both). No patients required reintervention during follow-up. The subgroup analysis showed slightly better outcomes in patients without prior interventions, although differences were not statistically significant. The stricture length did not correlate with treatment response. Conclusions: Optilume significantly reduces urinary symptoms and improves QoL in penile urethral strictures, and the absence of re-interventions during follow-up underscores its durable mid-term success. It offers a minimally invasive alternative to urethroplasty, particularly for patients seeking symptom relief with a shorter recovery time and no hospital stay or general anesthesia. These preliminary findings suggest that Optilume may be a promising minimally invasive option for selected patients. Larger, controlled studies are warranted to validate these results and refine patient selection criteria. Full article

Genitourinary (GU) cancers, including prostate, bladder, and renal cancers, represent a significant burden on global health. Conventional treatments, while effective in certain contexts, face limitations due to tumor heterogeneity, therapeutic resistance, and relapse. Recent advances in cancer immunotherapy, particularly in the development of personalized mRNA and DNA-based vaccines, have opened new avenues for precise and durable antitumor responses. These vaccines are being developed to leverage neoantigen identification and next-generation sequencing technologies, with the goal of tailoring immunotherapeutic interventions to individual tumor profiles. mRNA vaccines offer rapid, non-integrative, and scalable, with encouraging results reported in infectious diseases and early-phase cancer trials. DNA vaccines, known for their stability and ease of modification, show promise in generating robust cytotoxic T-cell responses. This review discusses the current landscape, preclinical findings, and ongoing clinical trials of mRNA and DNA-based vaccines in GU cancers, highlighting delivery technologies, combination strategies with immune checkpoint inhibitors, and future challenges, including tumor immune evasion and regulatory hurdles. Integrating immunogenomics and artificial intelligence into vaccine design is poised to further enhance precision in cancer vaccine development. As GU malignancies remain a leading cause of cancer-related morbidity and mortality, mRNA and DNA vaccine strategies represent a promising and rapidly evolving area of investigation in oncology. Full article

In 2024, the Americas experienced the largest dengue outbreak on record and Brazil was among the worst affected countries, reporting 6.6 million cases and 6200 deaths. We report the long-term entomological and epidemiological effectiveness of city-wide deployment of wMel-strain Wolbachia-infected Aedes aegypti in Niterói, a city of half a million people in Rio de Janeiro state, where Wolbachia releases across three-quarters of the urban population in 2017–2019 were expanded to remaining populated areas in 2023. wMel was durably established at ≥95% prevalence in Ae. aegypti populations throughout Niterói four years post-release, and up to seven years in the earliest release sites. Notified dengue case incidence in Niterói was 89% lower following Wolbachia releases, compared to the 10-year pre-intervention period of 2007–2016. Dengue incidence in Niterói in 2024, during a period of record high incidence in Brazil and the region, was 374 per 100,000 population, substantially lower than overall in Rio de Janeiro state (1884 per 100,000) and nationwide in Brazil (3157 per 100,000). Our findings show that city-wide Wolbachia coverage in Niterói provided sustained population-level reduction in dengue incidence throughout the five years post-intervention, including during the 2024 epidemic surge, averting an estimated three-quarters of the dengue case burden that may otherwise have been expected in Niterói in 2024. Full article

Accurate prediction and management of the service life of buildings and structural components are crucial for ensuring durability and economic efficiency. This paper investigates both discrete- and continuous-time Markov chains as probabilistic models for representing deterioration processes of building structures. Transition probabilities, fundamental matrices, and absorption times are computed to quantify expected lifespans and degradation pathways. Numerical simulations illustrate how state probabilities evolve, inevitably converging toward structural failure in the absence of maintenance interventions. Additionally, this study explicitly addresses uncertainties inherent in lifecycle predictions through the application of fuzzy set theory. A fuzzy Markov chain model is formulated to represent imprecise deterioration states and transition probabilities, which validate the predictable yet uncertain progression of structural deterioration through graphical analyses and fuzzy simulations. The proposed methodology, including fuzzy modeling, provides building managers and engineers with a robust analytical framework to optimize maintenance scheduling, refurbishment planning, and resource allocation for sustainable lifecycle management under uncertainty. Full article

Background/Objectives: Anosognosia for hemiplegia (AHP) is a multifaceted syndrome in which stroke survivors fail to recognize motor impairments. Although AHP has significant clinical implications, rehabilitation strategies have remained fragmented and underexplored. This systematic review aimed to critically evaluate rehabilitation interventions for AHP published between 2006 and 2025, categorize intervention types, and assess clinical outcomes to inform future research and practice. Methods: A structured search was conducted in the PubMed and PsycINFO databases on 31 March 2025, using predefined keywords related to stroke, anosognosia, and rehabilitation. The eligible studies included randomized controlled trials, case–control studies, and case studies. Following title, abstract, and full-text screening, nine studies focusing on rehabilitation interventions for AHP were selected and analyzed. Results: The interventions reviewed included sensorimotor recalibration techniques, neuromodulatory approaches, error-based cognitive training, and self-observation in video replay strategies. Interventions emphasizing motor intention monitoring, error correction, and self-observation were more consistently associated with durable improvements in motor awareness than neglect-based spatial interventions were. However, many studies were limited by small sample sizes and a lack of standardized outcome measures. Assessment methodologies vary widely, highlighting the need for multidimensional theory-driven evaluation tools. Conclusions: Effective rehabilitation for AHP requires strategies targeting disrupted self-monitoring and agency mechanisms, rather than spatial realignment alone. The video self-observation and error-based learning paradigms show particular promise. Future research should focus on controlled trials, longitudinal tracking, and the integration of individualized, mechanism-specific rehabilitation models to optimize outcomes for stroke survivors with AHP. Full article

Digital interventions are widely promoted as levers of institutional change, yet their effects often prove fragile. We examine why some interventions persist while others fade. Using crisp-set Qualitative Comparative Analysis (csQCA) on 13 large-scale cases from India and abroad, we identify the configurations of conditions under which digital systems become self-sustaining. We conceptualise persistence as a shift in the Nash equilibrium: when incentives realign, the new behaviour maintains itself without continuing external push. The analysis shows that software openness is neither necessary nor sufficient for durable change. Instead, six non-technological conditions—regulatory enablement, a credible revenue model, substantial scale, a clearly targeted systemic barrier, presence of enabling prerequisites, and sufficient time—are each necessary and, in combination, sufficient for an equilibrium shift; no single condition is enough on its own. Successful cases (e.g., Aadhaar, UPI, Chalo, Swiggy) meet these conditions in combination, whereas others (e.g., ONDC, DIKSHA, ICDS-CAS) illustrate how missing elements limit institutional embedding. The paper contributes a theory-informed diagnostic that links game-theoretic stability to configurational evaluation and provides practical “if–then” decision rules for appraisal. We argue that policy and investment decisions should prioritise incentive-compatible ecosystems over software attributes, and judge success by whether interventions reconfigure the rules of the game rather than by short-term uptake. This perspective clarifies when digital systems can contribute to sustainable, inclusive institutional transformation. Full article

Background/Objectives: We compared short- and long-term outcomes of patients with native left-sided infective endocarditis (IE) confined to the valve leaflet (“simple”) versus those with perivalvular extension (“complex”) over two decades. Methods: From 2005 to 2024, 177 patients (mean age 59.6 ± 13.8 years, 71.8% male) underwent surgery for IE. Patients were classified as having simple (n = 129) or complex IE (n = 48) based on imaging and intraoperative findings. Mean follow-up was 86.5 ± 63.3 months (range: 2–232 months). Outcomes included operative and late mortality, recurrent infection, and reoperation. Results: Complex IE was associated with worse preoperative status, longer ICU stays, and mechanical ventilation times. Predictors of early mortality included critical preoperative state (OR 6.35, p = 0.001), chronic renal failure/dialysis (OR 3.01, p = 0.05), and staphylococcal IE (OR 5.62, p = 0.002) but not perivalvular extension. Overall survival at 1, 5, 10, 15, and 20 years was 83%, 74.2%, 59.9%, 51.3%, and 40.7%, with no significant difference between groups (p = 0.18). Female gender (HR 1.93, p = 0.04) and chronic renal failure (HR 3.5, p < 0.01) predicted late mortality. Freedom from re-endocarditis and reoperation d/t relapse of endocarditis was 94.2% and 97.3%, respectively. Freedom from re-intervention d/t structural valve degeneration was 92.1% at 10 years. Repair was performed in 28.2% of cases involving the mitral valve, with 93.1% freedom from reoperation. Conclusions: Surgery for complex IE is not an independent risk factor for long-term mortality. Rates of recurrent endocarditis and reoperation are remarkably low. Excellent durability of bioprostheses and mitral repair was demonstrated. Full article

Architecture can play a pivotal role in addressing the climate crisis by embedding sustainable design principles that reduce environmental impact and enhance resilience. Beyond ecological considerations, architectural interventions are crucial in developing structures capable of withstanding extreme weather events—and thereby mitigating the displacement of vulnerable populations. This study emphasizes the importance of tailoring architectural responses to the specific environmental challenges and evolving needs of rural communities. Drawing on the Perceived Values and Climate Change Resilience Dataset collected in Siaya County, Kenya, the research explores local perceptions of climate change and how these shape housing priorities. Among 300 respondents, 83% express concern about climate change, identifying drought as the most pressing environmental threat. The evolving desire for housing solutions that respond to specific needs highlights the need for more secure housing. This specifically calls for improvements in watertightness, pest resistance (especially against termites), and overall structural durability, as well as reducing maintenance effort, enabling houses to be enlarged, and improving their aesthetics. These findings provide critical insights into how rural populations in western Kenya are experiencing and responding to climate-related stressors. By foregrounding community perspectives, the study informs the development of adaptive, resilient, and contextually appropriate architectural solutions. It contributes to broader discourses on climate adaptation, vernacular design, and inclusive development strategies in Sub-Saharan Africa, reinforcing the imperative to align architectural innovation with both environmental imperatives and cultural realities. Full article

Hemophilias and hemoglobinopathies—including hemophilias A and B, sickle cell disease (SCD), and β-thalassemia—are debilitating genetic disorders associated with significant global health burdens. While traditional management has centered on factor replacement and transfusions, these approaches remain palliative, with limited access and durability in many regions. Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. These therapies offer durable efficacy and improved quality of life, particularly in adult populations. However, implementation remains uneven across global health systems due to high costs, limited infrastructure, and regulatory heterogeneity. Additionally, ethical considerations such as long-term surveillance, informed consent in vulnerable populations, and social perceptions of genetic modification present ongoing challenges. Innovations such as multiplex genome editing, immune-evasive donor platforms, synthetic biology, and AI-driven treatment modeling are poised to expand therapeutic horizons. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic hepatopathy and a leading precursor of hepatocellular carcinoma (HCC) worldwide. Initially attributed to insulin resistance (IR)-driven metabolic imbalance, recent insights highlight a multifactorial pathogenesis involving oxidative stress (OS), chronic inflammation, and immune dysregulation. The hepatic accumulation of free fatty acids (FFAs) initiates mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, culminating in lipotoxic intermediates and mitochondrial DNA damage. These damage-associated molecular patterns (DAMPs), together with gut-derived pathogen-associated molecular patterns (PAMPs), activate innate immune cells and amplify cytokine-mediated inflammation. Kupffer cell activation further exacerbates OS, while ROS-induced transcriptional pathways perpetuate inflammatory gene expression. Traditional immunity refers to the well-established dichotomy of innate and adaptive immune responses, where innate immunity provides immediate but non-specific defense, and adaptive immunity offers long-lasting, antigen-specific protection. However, a paradigm shift has occurred with the recognition of trained immunity (TI)—an adaptive-like memory response within innate immune cells that enables enhanced responses upon re-exposure to stimuli. Following non-specific antigenic stimulation, TI induces durable epigenetic and metabolic reprogramming, leading to heightened inflammatory responses and altered functional phenotypes. These rewired cells acquire the capacity to produce lipid mediators, cytokines, and matrix-modifying enzymes, reinforcing hepatic inflammation and fibrogenesis. In this context, the concept of immunometabolism has gained prominence, linking metabolic rewiring with immune dysfunction. This literature review provides an up-to-date synthesis of emerging evidence on immunometabolism and trained immunity as pathogenic drivers in MASLD. We discuss their roles in the transition from hepatic steatosis to steatohepatitis, fibrosis, and cirrhosis, and explore their contribution to the initiation and progression of MASLD-related HCC. Understanding these processes may reveal novel immunometabolic targets for therapeutic intervention. Full article

Replacement of the retinal pigment epithelium (RPE) is emerging as a promising approach to treat degenerative retinal diseases, including age-related macular degeneration and Stargardt disease, in which RPE function cannot otherwise be restored. Despite the limitations of existing treatments, advances in cell sourcing and surgical methods have enabled initial human trials of RPE transplantation, with early results indicating potential efficacy. This review comprehensively examines the evolution of RPE transplantation in recent decades, highlighting the advantages and limitations of different cell sources and delivery methods. Current clinical trial data are analyzed with a particular focus on immune rejection risks, surgical complications, and long-term safety. Despite encouraging safety profiles, achieving consistent and sustained visual improvement remains a challenge, as vision outcomes might be influenced by factors such as disease stage at intervention, transplantation site, number of cells transplanted, and duration of follow-up. Key challenges, such as cell or graft survival and integration with the host retina, are discussed in depth, as overcoming these obstacles is essential for achieving stable and effective RPE replacement. Future research directions, including innovations in biomaterials, molecular modification strategies, and personalized approaches, hold promise for enhancing the efficacy and durability of RPE transplantation for retinal disease. Full article

Background/Objectives: Lower urinary tract symptoms (LUTSs) due to benign prostatic obstruction (BPO) represent a common condition affecting aging men. Transurethral resection of the prostate represents the gold standard surgical treatment but is not without complications such as retrograde ejaculation, bleeding and urinary retention. The temporary implantable nitinol device (iTIND) is considered a minimally invasive surgical technique, designed to treat LUTS while preserving erectile and ejaculatory function. Herein we report the results of a multi-center, real-world assessment of the iTIND procedure. Methods: Data from five international centers treating LUTS with the iTIND device were collected. We recorded changes through an International Prostatic Symptom Score (IPSS) questionnaire with Quality of Life (QoL), International Index of Erectile Function (IIEF5) questionnaire, antegrade ejaculatory function, maximum flow (QMax), post voiding residual volume (PVR) and freedom from repeat intervention. Results: A total of 74 subjects were enrolled; median follow-up was 12 months. IPSS and QoL changed from a median of 23 and 4 points at baseline to 11 and 2 points, respectively, at the last follow-up. A mean improvement in Qmax and PVR from 9 mL/s and 56 mL at baseline to 13 mL/s and 40 mL was noticed at the last follow-up. Total median operative time was 10 min, and the median time of iTIND indwell time was 7 days. The median device removal time was 5 min. There were no changes in IIEF5 scores and antegrade ejaculation rate. No intraoperative complications were reported, and non-serious postoperative complications occurred in six patients (two urinary retention, two mild haematuria, two urinary tract infection). Finally, four patients underwent reoperation during the follow-up period. All procedures were performed as outpatient day cases. Conclusions: Our results confirms that treatment with the iTIND is effective and safe in terms of improving urinary symptoms and quality of life without impacting sexual function. Longer follow-up is required to better define the durability of this minimally invasive procedure. Full article

Lung cancer (LC), with non-small-cell lung cancer (NSCLC) as its predominant subtype, remains the leading cause of cancer-related mortality worldwide. While immune checkpoint inhibitors (ICIs) have redefined the therapeutic paradigm in advanced NSCLC, durable responses are confined to a limited subset of patients. A major clinical challenge persists: the inability to accurately predict which patients will derive meaningful benefit, which will exhibit primary resistance, and which are at risk for severe immune-related toxicities. The imperative to individualize ICI therapy necessitates robust, dynamic, and accessible biomarkers. Liquid biopsy has emerged as a transformative, minimally invasive tool that enables real-time molecular and immunologic profiling. Through analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and peripheral blood immune components, liquid biopsy offers a window into both tumor intrinsic and host-related determinants of ICI response. These biomarkers not only hold promise for identifying predictive signatures—such as tumor mutational burden, neoantigen landscape, or immune activation states—but also for uncovering mechanisms of acquired resistance and guiding treatment adaptation. Beyond immunotherapy, liquid biopsy plays an increasingly central role in the landscape of targeted therapies, allowing early detection of actionable driver mutations and resistance mechanisms (e.g., EGFR T790M, MET amplification, and ALK fusion variants). Importantly, serial sampling via liquid biopsy facilitates longitudinal disease monitoring and timely therapeutic intervention without the need for repeated tissue biopsies. By guiding therapy selection, monitoring response, and detecting resistance early, liquid biopsy has the potential to significantly improve outcomes in NSCLC. Full article

Obesity presents a significant barrier to transplant eligibility due to increased morbidity associated with higher BMI. Patients with obesity who undergo transplantation face elevated risks of perioperative complications, morbidity from metabolic disease, and delayed graft function. However, recent advances in metabolic and bariatric medicine, endoscopy, and surgery offer promising opportunities for integration with transplant care. This critical review explores the potential benefits of metabolic and bariatric interventions for at-risk transplant patients. Here, we will briefly discuss the implications of obesity in transplant patients, pharmacologic, surgical, and endoscopic interventions, and ultimately, the role of bariatric surgery in different solid organ transplants. The successful implementation of these approaches could dramatically expand access to solid organ transplantation, creating life-saving opportunities for patients who would otherwise be deemed ineligible for this essential treatment. Despite the implications of metabolic and bariatric interventions in transplant care, this review is limited by the need for long-term studies of outcomes to better understand the effects of graft survival and durability of changes in metabolic syndromes. Full article

Systematic Background/Objectives: Type 1 diabetes mellitus (T1DM) is an autoimmune condition in which pancreatic β-cells are selectively destroyed, predominantly by autoreactive T lymphocytes. Despite decades of research, the achievement of durable immune tolerance remains elusive. This review presents a historically grounded and forward-looking perspective on the evolution of immunotherapy in T1DM, from early immunosuppressive interventions to advanced precision-based cellular approaches. Specifically, we focus on systemic immunosuppressants (e.g., corticosteroids, cyclosporine), monoclonal antibodies (e.g., anti-CD3, anti-IL-1, anti-TNF), regulatory cell-based approaches (e.g., Tregs, CAR-Tregs, MDSCs), and β-cell replacement strategies using stem cell-derived islets. Methods: We analyzed major clinical and translational milestones in immunotherapy for T1DM, with particular attention to the transition from broad immunosuppression to targeted modulation of immune pathways. Emerging data on cell-based therapies, artificial intelligence (AI)-driven stratification, and personalized intervention timing have been incorporated to provide a comprehensive overview of current and future directions. Results: Initial therapies such as corticosteroids and cyclosporine offered proof-of-concept for immune modulation, yet suffered from relapse and toxicity. The introduction of monoclonal antibodies (e.g., teplizumab) marked a shift toward immune-specific intervention, particularly in stage 2 preclinical T1DM. More recent approaches include low-dose IL-2, checkpoint modulation, and antigen-specific tolerance strategies. Cellular therapies such as Treg adoptive transfer, chimeric antigen receptor Tregs (CAR-Tregs), and stem cell-derived islet replacements (e.g., VX-880) have shown promise in preserving β-cell function and modulating autoimmunity. Myeloid-derived suppressor cells (MDSCs), although still preclinical, represent a complementary avenue for immune tolerance induction. Concurrently, AI-based models are emerging as tools to stratify risk and personalize immunotherapeutic timing, enhancing trial design and outcome prediction. Conclusions: In conclusion, the historical progression from broad immunosuppression to precision-driven strategies underscores the importance of stage-specific, mechanism-based interventions in T1DM. The convergence of targeted biologics, regenerative cell therapies, and β-cell replacement approaches, supported by AI-enabled patient stratification, offers a realistic path toward durable immune tolerance and functional β-cell preservation. Continued integration of these modalities, coupled with rigorous long-term evaluation, will be essential to transform these scientific advances into sustained clinical benefit. Full article