AbstractInfluenza A viruses (IAVs) cause severe outbreaks with high mortality in birds and humans. A deeper understanding of cell-intrinsic defense mechanisms against influenza viruses is therefore crucial for developing novel antiviral strategies. Herein, we perform a genome-wide CRISPR activation screen to systematically elucidate host restriction factors against influenza A (H7N9) virus. Among multiple candidates, cholesterol 25-hydroxylase (CH25H) is shown to be induced by influenza virus infection and inhibit viral membrane fusion. Notably, our previous work demonstrated that CH25H blocks the entry of plasma membrane-fusing viruses such as coronaviruses. This inhibition occurs by relocating accessible cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER). Here, we extend this finding and show that the same mechanism works against endocytosis-dependent viruses such as influenza viruses. The exogenous supplementation of cholesterol can restore depleted accessible cholesterol and reverse the CH25H-mediated restriction. Additionally, we prove that acyl-CoA:cholesterol acyltransferase (ACAT) is required to recruit the accessible cholesterol in this process. However, how hydrophobic accessible cholesterol is transported remains unclear. Here, we demonstrate that GRAMD1/Aster-mediated non-vesicular cholesterol transport is utilized to mobilize accessible cholesterol upon stimulation of CH25H. 25-hydroxycholesterol (25HC), the catalytic product of CH25H, is a natural metabolite that potently inhibits influenza virus infection both in vitro and in vivo. These findings underscore the promising therapeutic potential of 25HC against influenza viruses.
Youth experiencing homelessness face significant barriers to mental healthcare. To address this gap, the Réseau d'Intervention de Proximité Auprès des Jeunes de la rue (RIPAJ) was established in Montréal in 2003 through collaboration between community and governmental health organizations. In 2016, RIPAJ joined the national Adolescent/Young Adult Connections to Community-driven Early Strengths-based Stigma-free services-Open Minds (ACCESS-OM) initiative, aiming to enhance mental healthcare accessibility for youth experiencing homelessness. This study evaluates the impact of this integrated approach on referral trends and wait times before and during ACCESS-OM RIPAJ implementation. Monthly referrals and wait times for first appointment were recorded for a historical cohort (2014-2015) and the ACCESS-OM RIPAJ period (2016-2020). We used Poisson and Cox regression models to analyze trends in referral rates and wait times, with 2014 as reference period. Seasonality was controlled by incorporating calendar month in the models. Additional Cox regressions examined individual-level sociodemographic and clinical factors associated with post-implementation wait times. We analyzed 158 referrals for 2014 to 2015 and 681 for 2016 to 2020. Monthly referrals increased significantly, peaking at 2.5 times the 2014 level. Wait times remained stable, with 73.5% evaluated within 72 hr. The hazard ratio for wait times during the peak period was 0.87 (95% CI [0.63, 1.20]) indicating no significant change despite the surge in referrals. Older age and self-referral were associated with reduced wait times. This collaborative model successfully increased mental healthcare utilization among youth experiencing homelessness, providing valuable insights for addressing the unmet needs of this vulnerable population and potentially reducing homelessness perpetuation.
Regulatory reliance pathways are increasingly being recognized as essential tools to accelerate patient access to medicines globally while building National Regulatory Authorities (NRA) capacity and capability. Although significant progress has been made in a number of international pilots for Chemistry, Manufacturing and Controls (CMC) post approval changes, there has been more limited application to labelling variations including indication extensions. This paper describes the first reliance pilot for an indication extension, which engaged 21 NRAs across multiple regions. The pilot leveraged the European Medicines Agency (EMA) as a reference agency and incorporated a digital platform, whose use was optional by the NRAs involved, for real-time sharing of questions and responses. The objectives were to reduce approval timelines, promote regulatory convergence, streamline health authority questions and enhance transparency among participating authorities. Results demonstrated significant reduction in approval timelines, with an average reduction of 3 months per country compared to standard timelines across participating countries. This article outlines the process of establishing the pilot, including planning and engagement with regulatory authorities, analysing success factors and challenges encountered including recommendations for optimising the process further. The findings suggest that regulatory reliance for indication extensions can substantially improve efficiency in regulatory processes, reducing approval timelines and ultimately benefiting a wider patient population to access medicines globally and timely.
As remote-access thyroidectomy (RAT) becomes more widely used, evidence on patient- reported outcomes, particularly health-related quality of life (HRQoL), remains scarce and inconsistent. This meta-analysis compared postoperative HRQoL between thyroid cancer (TC) patients undergoing RAT and open thyroidectomy (OT) and assessed changes over time. A comprehensive search of five major databases was conducted from inception to August 2025. Studies reporting HRQoL after RAT or OT were included. Outcomes were grouped by postoperative timepoints. Outcomes were stratified across distinct postoperative timepoints to calculate pooled standardized mean difference (SMD) or mean difference (MD). Heterogeneity was explored through rigorous subgroup analyses encompassing surgical modalities, countries, and assessment instruments. Forty-one studies met the inclusion criteria, and 29 records were included in the quantitative synthesis. RAT demonstrated early advantages in comprehensive quality of life at 1 month and 3 months, and these advantages dissipated long term. Pain trajectories exhibited a biphasic pattern: RAT was associated with lower pain scores on postoperative day 1 but paradoxically higher scores during the 1-2 week period, with subsequent convergence. Cosmetic satisfaction and swallowing function consistently favored RAT from 1-2 weeks through 6 months, while voice outcomes showed no discernible differences. RAT appears to confer selected short- to medium-term patient-reported advantages over OT, particularly in cosmetic satisfaction and swallowing function. But these benefits are heterogeneous and not consistently maintained across all domains or timepoints. Future studies should standardize cross-culturally validated PRO instruments and adopt harmonized follow-up intervals and reporting guidelines to clarify the patient-centered value of RAT.
Redo transcatheter aortic valve replacement (TAVR; TAV-in-TAV procedure) is technically challenging. We report a case of TAV-in-TAV requiring right coronary artery (RCA) protection. An 81-year-old man underwent TAVR with a self-expanding valve in 2021 and presented in 2025 with heart failure symptoms. Multimodality imaging demonstrated severe aortic regurgitation from premature structural valve degeneration. A short-in-tall TAV-in-TAV strategy was planned. Bulky leaflet calcification near the RCA ostium prompted coronary protection. After difficult RCA engagement requiring multiple access changes, the valve was deployed using the engaged guiding catheter as a fluoroscopic landmark. Coronary flow was preserved without bailout stenting. No residual regurgitation was observed on postprocedural imaging. We highlight the importance of preprocedural planning in redo TAVR and illustrate real-world challenges in coronary access despite meticulous planning. Preprocedural planning and access flexibility are essential in redo TAVR. Lifetime coronary access should be considered during index valve selection.
Native Veterans experience disproportionately high rates of PTSD and suicide compared to other Veteran populations and face significant barriers to accessing mental healthcare, particularly in rural areas where many reside. This study aimed to support the delivery of Personalized Implementation of Video Telehealth for Rural Native Veterans (PIVOT-RNV) and examine the longitudinal impact on mental health engagement. PIVOT-RNV involves Implementation Facilitation strategies at the partnering VAMCs focused on technology adoption, cultural considerations, and outreach strategies for RNV communities. For this project, we engaged eight partner VAMCs in fiscal years 2023-2024. Using VA health records data, we conducted linear growth curve models to examine the effects of PIVOT-RNV on overall mental health care encounters and telemental health care specifically and whether this changed over time. Across all sites, telemental health encounters for rural Native Veterans significantly increased over time. Importantly, PIVOT-RNV sites experienced a significantly greater increase in telemental health encounters for RNVs over time compared to control sites. Sites with PIVOT-RNV also demonstrated a marginally significant greater increase in overall mental health encounters over time. These findings indicate PIVOT-RNV shows promise for improving RNV's access to VA healthcare by increasing both access to and engagement in video-based mental health. There is a need to further test and implement PIVOT-RNV across other health systems and to examine additional clinical and access outcomes.
Compatible donor-recipient pairs are increasingly participating in kidney paired donation programs despite eligibility for direct living donor kidney transplant. Beyond addressing overt incompatibility, inclusion of compatible donor-recipient pairs is a strategy to optimize donor-recipient matching, mitigate major anatomical or immunologic disadvantages, and enable multiway or extended exchange chains. Evidence from national and regional registries has suggested that compatible donor-recipient pair participation expands the effective donor pool and improves access for highly sensitized and other hard-to-match recipients. We conducted a structured synthesis of global literature examining compatible pair participation in kidney paired donation programs, focusing on reported clinical outcomes, program-level effects, ethical considerations, and operational models. We comprehensively searched PubMed, Embase, Scopus, and the Cochrane Library and identified studies published between January 2000 and June 2025 reporting on compatible donor-recipient pairs that had specific data. From our search, we included 24 studies from North America, Europe, Asia, and Australia, which encompassed >2500 compatible donor-recipient pairs. Across programs, compatible donor-recipient pairs comprised a proportion of kidney paired donation transplants and were associated with increased program activity. Where reported, participation was driven by the pursuit of superior outcomes, including improved HLA matching, access to younger or lower-risk donors, or avoidance of specific immunologic mismatches, alongside altruistic considerations. Short-term patient and graft outcomes for recipients of compatible donor-recipient pairs were comparable to conventional living donor kidney transplants in reported cohorts. Overall, the evidence supported strategic inclusion of compatible pairs to enhance kidney paired donation program capacity and improve access for highly sensitized and hard-to-match recipients without compromising short-term outcomes.
IntroductionBone resection in minimally invasive procedures requires precise instrument positioning within constrained joint environments. Conventional straight arthroscopic burs (SABs) offer limited mobility due to geometric and soft tissue restrictions, often necessitating portal adjustments or tissue releases. Articulating rotary burs (ARB) incorporate adjustable articulation angles to enhance mobility and minimize collateral damage. This study aimed to quantitatively evaluate the cutting surface area (CSA) of a SAB and an ARB to compare efficiency in bone resection.MethodsA 3D point cloud analysis was performed in SolidWorks (Dassault Systèmes, Vélizy-Villacoublay, France) to compare CSA of a 5.0 mm SAB and a 5.0 mm ARB (Articulator™ Arthroscopic Bur, Joint Preservation Innovations, Naperville, IL), both with ball bur heads. Analyses accounted for continuous rotation about the tool's long axis. The SAB was compared with the ARB at 0°, 15°, and 30° distal articulation. Surface areas are reported in in2 with metric equivalents (mm2). An aggregate motion-envelope CSA (0°-30°) was calculated as the sum of articulated positions.ResultsThe CSA of the SAB was 0.081 in2 (52.3 mm2). The ARB CSA was 0.081 in2 (52.3 mm2) at 0°, 0.203 in2 (131.0 mm2) at 15°, and 0.284 in2 (183.2 mm2) at 30°, totaling 0.568 in2 (366.5 mm2). Overall, the ARB demonstrated a 601% greater CSA.ConclusionIn this geometric modeling study, distal articulation increased accessible CSA across articulated positions. ARBs may expand geometric access in minimally invasive settings; however, translation to surgical performance (eg, resection rate, thermal effects, torque transmission, and safety) requires empirical validation.
BackgroundAlthough perceived distance is a key factor in deciding and reaching healthcare, its impact on antenatal care (ANC) utilisation remains underexplored.ObjectiveThis study aims to examine the effect of perceived distance on ANC uptake, stratified by key maternal characteristics.DesignCross-sectional analysis based on demographic and health survey data (DHS).MethodsThis study analysed the demographic and health survey data of 26 sub-Saharan African countries, comprising 186,873 women who had given birth within the five years preceding the surveys. The exposure variable was perceived distance to a healthcare facility, categorised as "a big problem" or "not a big problem." Whereas the outcome variable was the number of ANC contacts, classified as no, one to three, four to seven and eight or more contacts. A Generalised Structural Equation Model (GSEM) with a multinomial logit link was employed to examine the association. Analyses were further stratified by socio-demographic characteristics.ResultsThe analysis revealed that women who perceived the distance as a major problem had 15% higher odds of receiving only 1-3 contacts (aOR = 1.15, 95% CI: 1.05, 1.25, p = 0.002), and 51% higher odds of receiving no ANC (aOR = 1.51, 95% CI: 1.35, 1.66, p < 0.001), compared to those receiving eight or more contacts. These associations were particularly pronounced among women with lower educational status (aOR=1.48, 95%CI: 1.29, 1.64), rural residents (aOR=1.55, 95%CI: 1.37, 1.74), low household income (aOR=1.47, 95%CI: 1.27,1.68), and younger age (aOR=1.55, 95%CI: 1.31, 1.80).ConclusionPerceived distance remains a significant barrier to the utilisation of antenatal care services in resource-limited settings. Strengthening health system responsiveness and addressing structural barriers, such as transportation infrastructures, through innovations like mobile antenatal care is vital to improving maternal health outcomes and advancing global health equity. Ensuring access to high-quality antenatal care (ANC) is essential for improving maternal and newborn health outcomes. However, evidence on the effect of geographical distance on ANC use in sub-Saharan Africa remains limited and inconclusive. This study examined the relationship between perceived distance to a health facility and ANC utilisation across 26 sub-Saharan African countries. We analysed the Demographic and Health Survey (DHS) data from 186,873 women who had given birth in the five years preceding the survey. Women who reported that distance to a health facility was a major problem had 15% higher odds of attending only 1-3 ANC contacts and 51% higher odds of receiving no ANC, compared with women who attended at least eight contacts. These associations were stronger among women with lower levels of education, those living in rural areas, women from low-income households, and younger women. These findings underscore the importance of addressing perceived distance-related barriers to improve uptake of the WHO-recommended number of ANC contacts and to promote equitable access to maternal health services in sub-Saharan Africa.
Structural heart disease (SHD) encompasses diseases involving the heart valves, chambers, walls, and muscles. Current diagnostic methods have limited accessibility and predictive value. This review aims to present recent advances in artificial intelligence (AI)-guided tools in the screening of SHD and valvular heart disease (VHD), and to present challenges and opportunities for their use in clinical practice. AI-guided models trained on ECGs, chest X-rays, and coronary artery calcium scans have a high accuracy in the diagnosis of SHD, heart failure, low left ventricular ejection fraction, and VHD. Some of these models can highlight the signals that influence their predictions, improving explainability. The use of AI in screening for SHD and VHD could lead to earlier diagnosis, enhanced accuracy, and better accessibility. However, outcome data on earlier diagnosis using these tools is required before broad deployment.
Emergency department (ED) overcrowding and delayed access to care are ongoing challenges in Singapore. The COVID-19 pandemic further underscored the need for scalable virtual care models that go beyond traditional hospital settings, allowing patients to access acute specialist care quickly and efficiently. This study describes the design, implementation, and early outcomes of the National University Health System (NUHS) Virtual Care Centre (VCC), a clinician-led helpline aimed at reducing unnecessary ED visits and supporting community-based acute care. In 2020, the NUHS launched the VCC, a helpline at Alexandra Hospital, as a prehospital triage model. The helpline functions as a nurse-led telephone triage with real-time escalation to doctors for urgent medical issues. It ensures the continuity of care for patients recently discharged and diverts nonemergency cases from the ED. A retrospective analysis of call data from 2020 to 2024 was conducted to evaluate utilization patterns, clinical outcomes, and safety. Over 4 years, the VCC managed 4857 calls, of which 59.3% (n=2879) were clinical in nature. Nearly two-thirds (1834/2879, 63.7%) were resolved remotely, preventing in-person ED visits. Only 13.8% (397/2879) required redirection to an ED, and 3.3% (95/2879) were directly admitted to an acute hospital or hospital at home service. Within 72 hours of call resolution, 69.1% (1990/2879) of the callers avoided an ED visit. Undertriage was 4.9% (110/2232) at 72 hours post call resolution, with no high dependency or intensive care unit admissions during this period. Mortality rates were low (1.0% at 14 days; 2.3% at 30 days). The NUHS VCC provides a feasible and safe model for virtual acute care triage within the public health care system. It effectively diverted lower-acuity cases from the ED and ensured continuity of care, offering a scalable approach aligned with national efforts to extend health care beyond hospital walls.
We present BIOMERO 2.0, a major evolution of the BIOMERO framework that transforms OMERO into a FAIR-compliant (findable, accessible, interoperable, and reusable), provenance-aware bioimaging platform. BIOMERO 2.0 integrates data import, preprocessing, analysis, and workflow monitoring through an OMERO.web plugin and containerised components. The importer subsystem facilitates in-place import using containerised preprocessing and metadata enrichment via forms, while the analyser subsystem coordinates and tracks containerised analyses on high-performance computing systems via the BIOMERO Python library. All imports and analyses are recorded with parameters, versions, and results, ensuring real-time provenance accessible through integrated dashboards. This dual approach places OMERO at the heart of the bioimaging analysis process: the importer ensures provenance from image acquisition through preprocessing and import into OMERO, while the analyser records it for downstream processing. These integrated layers enhance OMERO's FAIRification, supporting traceable, reusable workflows for image analysis that bridge the gap between data import, analysis, and sharing.
The post-translational lipoprotein modification pathway is conserved in bacteria, in which prolipoprotein phosphatidylglycerol diacylglyceryl transferase (Lgt) catalyzes the first and committed step. Due to its essentiality for cell viability in Proteobacteria, its membrane localization, and relative accessibility, Lgt is proposed as a promising target for the development of novel antibiotics. To answer the question of the degree of conservation between Lgt homologs of WHO-listed pathogenic species, we performed evolutionary, structural, and functional analyses. Our data show that Lgt is present in all bacteria and absent from archaea. AlphaFold structural models are similar to the X-ray structure of Lgt from E. coli with most variability and less conserved residues in the arm and head domains between Lgt homologs. Lgt of diderm bacteria, but not of monoderm bacteria, restores growth and viability of an Lgt depletion strain in E. coli. Sequence alignments and site-directed mutagenesis demonstrate that unique conserved residues on arm-2 together with histidine 103 and the periplasmic head domain, determine protein substrate specificity. This large-scale analysis led to the definition of an Lgt motif and an alternative catalytic mechanism. Our results highlight similarities in catalytic mechanism and differences in substrate specificity between Lgt homologs from pathogenic species, with an impact on strategies to develop narrow-spectrum antibiotics targeting Lgt.IMPORTANCEAntimicrobial resistance is a major threat to public health, for which the identification of novel targets and the development of new therapies are urgently needed. The bacterial lipoprotein modification pathway is promising for the exploration of new antibiotics since it is unique to bacteria, essential for bacterial viability and virulence, and accessible to drugs due to the exposed domains of the modification enzymes. In this study, we explored large-scale sequence analysis, structural modeling, and functional assays of the first enzyme in the pathway. Our findings show that the enzyme is highly conserved across distant phyla, that homologous enzymes have similar structures and contain a signature motif composed of invariant essential residues, but that functional conservation divides monoderm and diderm pathogenic bacteria. This correlates with structural variation and differences in substrate specificity, illustrating the potential for the development of narrow-spectrum antibiotics targeting the lipoprotein modification pathway.
Entamoeba histolytica (E. histolytica) is a protozoan parasite that causes amoebiasis in humans. It is prevalent in developing countries, particularly in areas with inadequate sanitation and limited access to clean water. While some data on the infection in the Malaysian population is available, comprehensive data on the overall prevalence is lacking. Our study aimed to determine the prevalence of E. histolytica in Malaysia through systematic review and meta-analysis using data published up to 2025. Fourteen studies covering diverse population groups from various states in Malaysia, including rural and urban residents, schoolchildren, indigenous communities, and high-risk populations were reviewed. We found an overall pooled prevalence of 7% with high heterogeneity (I² = 92.5%). Prevalence varied widely by state and population subgroup, with higher rates in Pahang (18%) and among aboriginal schoolchildren (16%). Lower prevalence was found among urban residents (2%) and patients with gastrointestinal disorders (2%). There was only a slight difference in prevalence between individuals with co-infections (8%) and those without (7%). Studies using microscopy showed higher prevalence (7%) than molecular methods (4%). This is likely due to the misidentification of non-pathogenic Entamoeba species as E. histolytica when using microscopy. These findings contribute to a better understanding of the epidemiology of E. histolytica intestinal infection in Malaysia. Although the overall prevalence is relatively low, the results highlight the need for continued surveillance and more accurate diagnostic approaches to support targeted control.
Pregnant patients were surveyed to determine marijuana use, their interest in additional education of the risks marijuana use in pregnancy, and if they had been educated by their providers about these. Fisher's exact tests were used to determine significant differences in both demographics and survey answers on provider education between those who used and did not use marijuana during pregnancy. 409 patients were surveyed with 367 completing the survey. 87 participants (23.7%) of those surveyed endorsed marijuana use in their current pregnancy. Significant differences between those who used marijuana and those who did not were seen in race/ethnicity (17.1% among White people versus 38.9% among those of other race/ethnicity; p = 0.017), age (with 33.3% of 18-24 year olds reporting the highest use vs. 0.0% of ≥ 40 year olds reporting the lowest use; p = 0.014) and education level (with those who had not completed high school reporting the highest rates of use, p = 0.001). 15.3% of all respondents received counseling on the risks of marijuana use during pregnancy. Among those who used marijuana, 25.3% received the counseling, compared to 12.1% of those who did not use (p = 0.003). 41.4% of those who used marijuana expressed an interest in additional information on this topic, significantly higher than those who did not use (p < 0.001). A gap exists in the area, as only 25%of pregnant patients who used marijuana reported receiving counseling, compared to the 41% who stated a desire for additional information. This emphasizes the need for both accessible resources on how marijuana affects both the pregnant mother and infant, as well as education for providers on this gap in care.
The study investigated the effectiveness of dysgeusia-specific acupuncture combined with self-acupressure compared to supportive acupuncture and self-acupressure for chemotherapy-induced dysgeusia in cancer patients with cancer-related fatigue (CRF) and dysgeusia. This multicenter, randomized, controlled, two-armed parallel-group, single-blind trial included cancer patients with CRF and dysgeusia during chemotherapy. All participants received CRF treatment consisting of eight acupuncture sessions over 8 weeks and had access to an eLearning course for self-acupressure. Patients in the intervention group received additional dysgeusia-specific acupuncture treatment and an eLearning with instructions to acupressure points, whereas the control group received an intervention focused solely on addressing CRF. The main outcome was perceived dysgeusia over 8 weeks, measured weekly after each acupuncture session on a numeric rating scale from 1 to 10. Other outcomes included taste and smell tests, and assessments of perceived dysgeusia, fatigue, distress, and quality of life. Due to a small sample size, results can be only judged exploratory. The study was approved by the Cantonal Ethics Committee (CEC) (Kanton Zürich Kantonale Ethikkommission) (approval no. KEK-ZH-Nr. 2020-01900). Since we included only twenty-one patients (11 intervention, 10 control, 90% female) instead of the target sample size of 130, no confirmatory effectiveness analyses were conducted. All participants showed a substantial decrease in dysgeusia over time, regardless of treatment type (estimated mean reduction per session - 0.30; 95% CI - 0.43 to - 0.18), reflecting a 0.30-point reduction per session. Quality of life and cancer-related fatigue improved over time. The exploratory analyses did not show substantial differences between groups in any outcomes. No serious adverse events occurred. Exploratory findings showed no substantial differences between the study groups in perceived dysgeusia, but both study groups improved over time. DRKS00023348 at 03.11.2020, SNCTP000004128.
High-level competitive golfers often have access to interventions and support systems that include physical, nutritional, and behavioral health. Much focus has been directed to training on the course. There are limited studies describing what competitive golfers do off the course for performance optimization. To describe the training, resources, and lifestyle modifications that competitive golfers use off the course in order to optimize performance on the golf course. Cross-sectional survey study. Online survey. One hundred one high-level competitive golfers (56 collegiate, 45 touring professional; mean age: 25 ± 8 years; 55% male) completed the online survey and were included in the study. Not applicable. Information on golf play, exercise, lifestyle (nutrition, sleep), and alternative interventions was collected from the survey. Participants averaged 4.1 ± 3.5 years of collegiate/professional golf play. Most golfers reported working with swing coaches (78.2%) and athletic trainers (71.3%), and 86.1% participated in golf-specific resistance training for 2.9 ± 2.0 days/week. Massage and Theragun were the most common alternative interventions used to optimize performance. Almost half of all golfers reported working with a sports psychologist. Furthermore, 64.4% of golfers reported changing diet to optimize golf performance, and 41.1% had consulted with nutrition experts. Most golfers reported ≥6 hours of sleep/night (92.1%), and 23.7% had consulted with sleep experts. Compared to collegiate golfers, touring professionals were more likely to make changes to diet, report <6 hours of sleep/night, consult with sleep experts, and use wearable devices to track sleep. Multiple golf-specific and lifestyle interventions were used by high-level competitive golfers off the course to optimize their performance.
The rising incidence of cancer, increasing life expectancy and complex personalized treatment concepts pose considerable challenges for the healthcare system. Artificial intelligence (AI)-in particular machine learning (ML), deep learning (DL), and large language models (LLMs)-offers promising potential for supporting therapeutic decisions in urological oncology. The aim of this review is to present the current state of research on the application of AI in treatment decisions in urological oncology. For this purpose, a systematic review of publications in the PubMed database was carried out. Methodological approaches, performance indicators and challenges with regard to clinical implementation were analysed comparatively. Depending on the entity and treatment category, ML models achieve F1-scores between 0.75 and 0.99. Large language models that access external knowledge sources using retrieval-augmented generation (RAG) demonstrate a high degree of guideline compliance, as evidence-based knowledge is specifically integrated into the treatment recommendations. The explainability of the models is mainly ensured by Shapley additive explanation (SHAP) analyses or transparent guideline referencing. To date, the available evidence predominantly consists of proof-of-concept studies, with a particular emphasis on prostate, urothelial, and renal cell carcinoma. Clinical implementation remains limited, in particular due to a lack of prospective validation studies, unresolved data protection and technical challenges, and limited model transparency and explainability. HINTERGRUND: Die steigende Krebsinzidenz, zunehmende Lebenserwartung und komplexe personalisierte Therapiekonzepte stellen das Gesundheitssystem vor erhebliche Herausforderungen. Künstliche Intelligenz (KI) – insbesondere Machine Learning (ML), Deep Learning (DL) und Large Language Models (LLMs) – bietet ein vielversprechendes Potenzial zur Unterstützung therapeutischer Entscheidungen in der urologischen Onkologie. ZIEL: Ziel dieser Arbeit ist die Darstellung des aktuellen Forschungsstands zur Anwendung von KI im Rahmen von Therapieentscheidungen in der urologischen Onkologie. Hierzu erfolgte eine systematische Auswertung aktueller Publikationen in der Datenbank PubMed. Methodische Ansätze, Leistungskennzahlen sowie Herausforderungen im Hinblick auf eine klinische Implementierung werden vergleichend analysiert. Die ML-Modelle erreichen je nach Entität und Therapiekategorie F1-Scores zwischen 0,75 und 0,99. LLMs, die mittels „retrieval-augmented generation“ (RAG) auf externe Wissensquellen zugreifen, zeigen eine hohe Leitlinienkonformität, da evidenzbasiertes Wissen gezielt in die Therapieempfehlungen integriert wird. Die Erklärbarkeit der Modelle wird u. a. durch „shapley additive explanations“ (SHAP)-Analysen oder durch transparente Leitlinienreferenzierung gewährleistet. Bisher liegen v. a. Proof-of-concept-Studien vor, mit Schwerpunkt auf Prostata‑, Urothel- und Nierenzellkarzinom. Die klinische Implementierung ist derzeit noch limitiert, insbesondere aufgrund fehlender prospektiver Validierung, datenschutzrechtlicher und technischer Herausforderungen sowie begrenzter Modelltransparenz und -erklärbarkeit.
Evaluation of Alzheimer's disease-associated neuronal thread protein (AD7c-NTP) in urine holds significant potential as a noninvasive and accessible biomarker for the early diagnosis of Alzheimer's disease (AD). In this study, a novel label-free and ultrasensitive electrochemiluminescence (ECL) sensor for detection of AD7c-NTP was designed based on a structurally optimized iridium(III) complex ([(piq)2Ir(CH3CN)2]BF4) as the luminescent probe at a boron-doped diamond (BDD) electrode. After modifying the antibody on the surface of the amino-functionalized BDD electrode, AD7c-NTP molecules were first captured, and then a sandwich immunoassay system was constructed by introducing aptamer-modified gold nanoparticles (AuNPs). Subsequently, [(piq)2Ir(CH3CN)2]BF4 was intercalated into the DNA double-helical structure via electrostatic adsorption, thereby enabling ECL signal detection. Based on the metal-to-ligand charge transfer of iridium complexes at the π-π* energy level and the acceleration of electron transfer from the complexes to the BDD electrode by AuNPs, the established ECL immunosensor exhibited high sensitivity, with a linear range of 0.001-100 ng/mL and an ultralow detection limit of 17.7 fg/mL (S/N = 3). The practicability of the assay was confirmed by the test of AD7c-NTP in human urine, providing valuable information for early screening of AD.