Triplet therapy with androgen deprivation therapy (ADT), docetaxel, and androgen receptor pathway inhibitors (ARPIs), either darolutamide or abiraterone, is one of the standard treatments for metastatic hormone-sensitive prostate cancer (mHSPC); however, no randomized trial has directly compared both ARPIs within this regimen. Given practical and financial constraints, a head-to-head randomized trial directly comparing these ARPIs may be unlikely. To compare the real-world effectiveness of darolutamide- versus abiraterone-based triplet therapy in patients with mHSPC. Retrospective cohort study using a multinational electronic health record network. We conducted a retrospective cohort study using the TriNetX research network. Patients with mHSPC treated with darolutamide- or abiraterone-based triplet therapy were identified and balanced using propensity-score matching. The primary outcome was overall survival (OS), and the secondary outcome was time to next treatment (TTNT), defined by treatment switch. Prespecified subgroup analyses focused on age, cardiometabolic comorbidities, and polypharmacy-related medication use. Among 1607 eligible patients, 1252 were included after propensity score matching (626 per group). Darolutamide-based triplet therapy was associated with longer OS compared with abiraterone (hazard ratio (HR) 0.42). A favorable difference in TTNT was also observed (HR 0.66). These associations were consistent across clinically relevant subgroups, including patients aged ⩾65 years and those with ischemic heart disease or diabetes mellitus. In polypharmacy-enriched subgroups, darolutamide-based therapy was consistently associated with more favorable OS and TTNT. In this large real-world analysis, darolutamide-based triplet therapy was associated with longer OS and TTNT compared with abiraterone-based triplet therapy in patients with mHSPC, particularly among older individuals and those with comorbidities. These findings are hypothesis-generating, suggesting that ARPI selection within triplet therapy may have clinically relevant implications, supporting the need for prospective studies. Comparing two three-drug treatment options for advanced prostate cancer: results from a large real-world study Advanced prostate cancer is often treated with a combination of three drugs: hormone therapy, chemotherapy, and a hormone-blocking medicine. Two commonly used hormone-blocking drugs are darolutamide and abiraterone. Although both are recommended treatments, no clinical trial has directly compared these two options when used together with chemotherapy. In this study, we used a large international health database to compare these two treatment approaches in real-world clinical practice. We included over 1,200 patients and used statistical methods to make the two groups as similar as possible. We found that patients treated with darolutamide lived longer and had a longer time before needing another treatment compared with those treated with abiraterone. These benefits were also seen in older patients and in those with other medical conditions, such as heart disease or diabetes. However, because this was not a randomized clinical trial, other factors that we could not fully measure may have influenced the results. In addition, the follow-up period was relatively short. Overall, our findings suggest that darolutamide may be a more effective option than abiraterone when used as part of three-drug therapy for advanced prostate cancer. Further studies are needed to confirm these results.
To assess the real-world clinical outcomes of faricimab in patients receiving treatment for neovascular age-related macular degeneration (nAMD). This real-world prospective observational study included patients with refractory nAMD. In total, 37 patients were analyzed. All patients had previously undergone at least three consecutive intravitreal injections of other anti-vascular endothelial growth factor (anti-VEGF) agents. The primary outcomes were best-corrected visual acuity (BCVA) and anatomical outcomes on optical coherence tomography angiography (OCTA) at a four-month follow-up period. The faricimab regimen resulted in significant improvements in both visual and anatomical parameters among patients with refractory nAMD. LogMAR BCVA decreased substantially from 0.82 ± 0.42 to 0.57 ± 0.32 (p < 0.001). Central subfield thickness (CST) was reduced significantly from 336.89 ± 141.52 μm to 244.19 ± 69.91 μm (p < 0.001). The pigment epithelial detachment (PED) area decreased from 1.30 ± 0.71 to 0.94 ± 0.55 mm2 (p < 0.001), and the choroidal neovascularization (CNV) area shrank from 1.11 ± 0.64 to 0.97 ± 0.56 mm2 (p < 0.001). Both the subretinal fluid (SRF) and SRF & Intraretinal fluid (IRF) subgroups exhibited notable improvements in both vision and anatomical structure. Eyes with isolated SRF achieved longer dosing interval extensions (66.7% reached ≥3 months) compared to the SRF & IRF group (47% reached ≥3 months). Faricimab given as three monthly loading doses demonstrates significant short-term improvement in vision and anatomical outcomes, including rapid gains in BCVA and reductions in CST and retinal fluid. It appears effective and well-tolerated for refractory nAMD, particularly in reducing SRF and improving visual acuity, though its effect on IRF resolution was limited and not statistically significant. However, because the study design confounded drug switch with increased injection frequency, the independent contribution of faricimab itself cannot be determined. No adverse safety signals were observed.
Contact lens (CL) wear may induce changes to the tear film, leading to sensations of ocular dryness and CL discomfort, key reasons for CL discontinuation. CL care solutions can help address underlying mechanisms of CL discomfort, improving wear experience. We report outcomes of an in-home use test of Biotrue® Hydration Plus Multi-Purpose Solution (BHP MPS; Bausch + Lomb, Rochester, NY, USA), which is formulated to maintain ocular surface homeostasis and improve CL comfort. In this IRB-approved, real-world survey study, adult soft CL users used BHP MPS for 7 days before completing a survey rating their experience (agreement/disagreement for attributes including CL cleanliness, comfort [including during extended screen use], prevention of CL dryness, perception of CL hydration, gentleness on eyes, and likelihood to recommend to others). A power analysis estimated sample size for 80% statistical power. Responses were analyzed with 2-sided exact binomial tests for agreement in >50% of responses (significance level α=0.05). Participants (N=435) were demographically balanced (mean age 42.5 years; 52.9% female). Over 60% of participants reported baseline CL dryness and tired eyes; 8.0% were likely to discontinue CL wear. At the end of the trial period, 98.9% were satisfied with how their CLs felt. Individual responses were significantly >50% for all attributes (p<0.05), including 91.7% agreeing that BHP MPS positively impacted CL comfort (and helped to keep CLs feeling clean [96.8%], keep CLs comfortable so that eyes do not feel tired [93.1%], maintain CL comfort [94.7%], prevent CL dryness [93.6%], maintain comfort with extended screen use [92.0%], and maintain hydration [94.7%] while being gentle on eyes [96.6%]); 94.0% would recommend BHP MPS to other CL wearers. No adverse events were reported. BHP MPS demonstrated strong performance across all key criteria evaluated in this real-world cohort of soft CL wearers for improved CL wear experience. Comfort is important to keep people wearing their contact lenses, but some people stop wearing them because their eyes feel uncomfortable and dry over time. For reusable contact lenses especially, the choice of lens cleaning and care solution is important to help keep lenses feeling comfortable. Biotrue® Hydration Plus Multi-Purpose Solution (BHP MPS; Bausch + Lomb, Rochester, NY, USA) is a unique contact lens solution with ingredients that help clean and remove spots off the lenses, which may help keep the eye healthy and help the contact lenses feel more comfortable. The BHP MPS ingredients were chosen based on scientific research and advice from experts. This study looked at how using BHP MPS in daily life made people feel. The study included 435 people who regularly wore reusable contact lenses. Overall, these people agreed that BHP MPS helped keep their contact lenses clean and comfortable, was gentle on their eyes, and stopped their lenses from feeling dry, even if they were using a screen, like a computer, for a long time. Nearly everyone in the study agreed they would recommend BHP MPS to others who wear contact lenses. This study showed that BHP MPS can help reusable contact lens wearers, improving the way people’s eyes feel. This real-life study is important because it builds on what we already know about BHP MPS from other studies and helps people who wear contact lenses and their eye care doctors choose the right contact lens solution to use.
Large language models (LLMs) hold potential value in medical decision support, yet empirical studies systematically comparing multiple models for femoroacetabular impingement (FAI) within Chinese clinical contexts remain scarce. This study aimed to compare the classification performance, decision consistency, and decision confidence of four mainstream LLMs (GPT-5, Gemini 2.5 Pro, DeepSeek-R1, Grok-4) in FAI treatment decision-making tasks for FAI based on real-world hospitalized cases, and to evaluate their clinical adaptability and limitations. We retrospectively included 26 hospitalized FAI cases from our institution (13 surgical group, 13 conservative group), all of which had ethically approved and informed consented. Case information was standardized into two input formats: structured radiology reports only (Group A), and structured radiology reports combined with structured medical records-referred to as multi-source structured text input in this study (Group B). Under both conditions, four LLMs were tasked with providing binary treatment decisions ("surgical" or "conservative") and indicating decision confidence on a scale from 0 to 100%. Primary evaluation metrics included accuracy, precision, sensitivity, specificity, F1 score, and Cohen's kappa. Spearman correlation analysis was used to examine the relationship between LLM decision confidence and accuracy. A hierarchical analysis process (AHP) was employed to derive composite scores through multi-criteria weighting, enabling comprehensive comparison of LLM performance. Under Group B conditions (incorporating structured medical record information), GPT-5 demonstrated optimal performance, with accuracy of 88%, precision of 92%, sensitivity of 85%, specificity of 92%, F1 score of 0.88, and kappa of 0.77, indicating high alignment between its decisions and real-world outcomes. Under the same conditions, the other models showed inferior performance (Gemini 2.5 Pro: 62% accuracy; DeepSeek-R1: 58%; Grok-4: 42%). Across both input modes, GPT-5 exhibited a significant positive correlation between decision confidence and accuracy (Group A: Spearman's r = 0.54; Group B: r = 0.55, both P < 0.01). The confidence-accuracy correlations for the other models were inconsistent and unstable. In the AHP-based composite scoring, GPT-5 achieved the highest Group B score (0.79) and ranked first overall. Overall results indicate that integrating structured radiology reports with structured medical record information (i.e., multi-source structured text information, which simulates a multimodal approach in this study) significantly enhances LLM performance in FAI treatment decision support tasks. In this exploratory, retrospective single-center study with a small sample size, GPT-5 outperformed the other evaluated models in FAI treatment decision support tasks based on Chinese structured clinical information and demonstrated, to some extent, calibrated decision confidence. These preliminary findings suggest the feasibility of LLMs in orthopedic decision support, however, validation in larger, multi-center, prospective studies is required before broader clinical application. Future studies should adopt multi-center, prospective designs to enhance evaluations of model reproducibility, interpretability, and clinical safety, thereby further validating broader applicability.
Clinical remission is an important treatment goal in severe asthma; however, durable remission frameworks generally require sustained disease control over longer periods. Whether dupilumab induces an early response toward this goal in real-world practice remains unclear. We sought to evaluate early response toward clinical remission at 24 weeks after dupilumab initiation and to identify baseline factors associated with this outcome. In this multicenter, prospective cohort at 13 Japanese institutions, adults with severe asthma treated with dupilumab were followed for 24 weeks. Given the limited observation period, an early response toward clinical remission was defined as meeting modified 4-component remission-oriented criteria: Asthma Control Test score 20 or higher, FEV1 % predicted 80% or higher at week 24, no exacerbations, and no oral corticosteroid use (weeks 16-24). Multivariable logistic regression identified baseline factors associated with this outcome, and receiver-operating characteristic analysis evaluated baseline fractional exhaled nitric oxide (Feno). Of 103 enrolled patients, 70 had complete data; 38 (54.3%; 95% CI, 41.9%-66.3%) met the modified remission-oriented criteria at week 24. Higher baseline Feno, higher FEV1 % predicted, and absence of maintenance oral corticosteroid use were associated with this outcome. Baseline Feno showed modest discrimination (area under the curve, 0.65; 95% CI, 0.51-0.78). Approximately half of the patients met the modified remission-oriented criteria at 24 weeks after dupilumab initiation, representing an early response toward clinical remission rather than sustained clinical remission itself. Baseline Feno and lung function may help identify patients more likely to show this response.
Dalbavancin is increasingly used off-label for chronic Gram-positive bone and joint infections (BJIs) requiring prolonged antimicrobial therapy, but optimal dosing strategies and the role of therapeutic drug monitoring (TDM) remain unclear. We evaluated the real-world implementation of a proactive TDM-guided dalbavancin workflow within an outpatient parenteral antimicrobial therapy (OPAT) programme. Single-centre prospective observational implementation study including adult patients with BJIs consecutively treated with dalbavancin in OPAT service between July 2022 and August 2025. A multidisciplinary team developed a workflow incorporating TDM-guided pharmacokinetic modelling to individualize dosing intervals after fixed initial administrations (Days 1, 8 and 43). Target Cmin concentrations were ≥8 mg/L, later increased to ≥15 mg/L after European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint revision. Primary outcomes included implementation metrics (feasibility, fidelity and appropriateness). Secondary outcomes were clinical effectiveness, safety and overall workflow success. The workflow was applied to 101 patients accounting for 418 TDM-guided dalbavancin administrations (feasibility). Three patient-driven treatment discontinuations were observed (3/101, 3.0%), and scheduled administrations occurred within the predefined time window in 335/418 (83.5%) of cases (fidelity). Pharmacological target attainment was achieved in 285/342 (89.6%) of administrations without dosing delays (appropriateness). Clinical effectiveness was achieved in 55/73 (75.3%) patients completing therapy, with 28/101 (28%) still on treatment. Adverse events-related discontinuation occurred in 3/101 (3%) patients. Overall workflow success was observed in 74/101 (73.2%) patients. A multidisciplinary TDM-guided dalbavancin workflow within an OPAT programme was feasible and safe, achieving high target attainment and favourable clinical outcomes. This approach supports individualized long-acting dalbavancin therapy for complex chronic BJIs.
Delayed graft function (DGF) remains a major complication after deceased-donor kidney transplantation. Balanced crystalloid solutions have been associated with lower DGF incidence compared with 0.9% saline, largely based on strategies using Plasma-lyte. However, the role of Ringer lactate compared with other low-chloride solutions, such as hypotonic saline, remains unclear. We therefore evaluated whether a protocol-driven change in perioperative crystalloid strategy was associated with DGF and early posttransplant kidney function. We conducted a retrospective, single-center, quasi-experimental study including recipients of deceased-donor kidney transplants. Patients were exposed to a protocol-driven change in perioperative hydration from a hybrid intraoperative 0.9% saline plus postoperative hypotonic saline (0.45%) strategy to an intraoperative and postoperative Ringer's lactate strategy. The primary outcome was DGF. Secondary outcomes included DGF duration, longitudinal kidney function, electrolyte trajectories, and 12-mo clinical outcomes. Generalized additive mixed models were used to evaluate longitudinal trajectories of graft function and electrolyte balance while accounting for within-subject variability. A total of 257 kidney transplant recipients were included (142 Ringer lactate; 115 hybrid isotonic/hypotonic saline), with comparable baseline characteristics. DGF incidence did not differ between groups (47.9% Ringer lactate versus 52.2% hybrid isotonic/hypotonic; P = 0.49), nor did days to renal graft recovery (5.7 versus 5.7 d; P = 0.96) or DGF duration (10.5 versus 10.2 d; P = 0.78). Mortality, graft loss, and biopsy-proven rejection at 12 mo were also similar. In covariate-adjusted longitudinal analyses, the estimated glomerular filtration rate did not differ between groups. Electrolyte trajectories showed modest differences between groups. In this real-world quasi-experimental study, Ringer lactate was not associated with lower DGF incidence or duration compared with a hybrid isotonic/hypotonic saline-based strategy. No differences were also observed in graft function over the 12-mo follow-up. These findings support further investigation into whether differences in chloride exposure may influence early graft outcomes.
Gastric cancer remains a major cause of cancer mortality worldwide, particularly in middle-income countries, where late diagnosis is frequent and information on its economic impact is limited. We evaluated survival outcomes and direct healthcare costs of adult patients with gastric cancer treated between 2019 and 2024 at Hospital Universitario Mayor Méderi, a tertiary referral hospital in Bogotá, Colombia, using routinely collected clinical and administrative data from a tertiary referral hospital. Overall survival and healthcare resource utilization were described, and cumulative direct medical costs over 5 years were estimated in thousands (k) of 2023 international dollars (Int$). A total of 616 adult patients with gastric cancer were identified in hospital records during the study period. Of these, 388 patients (63.0%) met the eligibility criteria and were included in the final analytic sample, whereas 228 patients (37.0%) were excluded according to the predefined exclusion criteria. The median age was 65 years [interquartile range (IQR): 57-73]; 36.9% women). Using Tumor-Node-Metastasis staging (TNM: tumor extent, regional lymph node involvement, and distant metastasis) recorded in medical charts, 36.3% had stage III and 34.8% stage IV disease. Initial treatment intent was curative in 46.6% and palliative in 53.4%. The estimated cumulative mean direct cost was Int$ 89.3 k (95% CI: 75.9 k-102.8 k) at 2 years and Int$ 161.2 k (95% CI: 92.0 k-230.4 k) at 5 years. Median overall survival was 30.7 months (95% CI: 22.7-38.7), and the estimated 5-year survival probability was 40.0%; it was 45.5% for stage III disease and 12.5% for stage IV disease. Gastric cancer imposes both high mortality and substantial economic burden on the healthcare system, largely determined by the clinical stage at diagnosis. These findings highlight the potential population-level and financial benefits of strategies aimed at earlier detection and timely access to oncologic care in middle-income countries.
Severe alopecia areata (AA) causes substantial psychosocial burden, with suboptimal response rates to approved baricitinib 4 mg. Pharmacologic strategies for dose escalation, supported by inter-specialty evidence, may address this therapeutic gap. To evaluate efficacy and safety of baricitinib 6 mg daily in severe, refractory AA patients who showed suboptimal response to conventional therapies. In this retrospective study, four females (mean age 26.5 years) with severe AA (mean baseline Severity of Alopecia Tool, SALT 64.5) received baricitinib 6 mg between January 2023 and June 2025. Efficacy was assessed via serial SALT score changes; safety through standardized laboratory monitoring. Following escalation to baricitinib 6 mg daily, clinically meaningful SALT improvement was achieved in three patients (75%). Transient laboratory abnormalities occurred in 3 patients (75%), including asymptomatic mild platelet count elevation, self-resolving mild anemia (within normal ranges) and asymptomatic creatinine elevation. No severe adverse events occurred. Baricitinib 6 mg daily demonstrated enhanced efficacy in 75% of patients with severe refractory AA and exhibited an acceptable short-term safety profile under close monitoring. These findings support further investigation of step-up dosing strategies in randomized controlled trials.
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Chronic pancreatitis (CP) is a debilitating inflammatory condition characterized by irreversible glandular destruction and intractable pain. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated anti-inflammatory properties in preclinical models, yet their impact on clinical outcomes in CP remains unexplored. In this retrospective cohort study, adult patients (≥18 years) with CP were identified from the TriNetX US Collaborative Network. Patients were stratified into the following two cohorts: those prescribed GLP-1 RAs and a control group without such prescriptions. 1:1 propensity score matching was performed to balance cohorts for age, sex, race, and key comorbidities. Primary outcomes were assessed over a 3-year observation period. Hazard ratios (HRs) were estimated using Kaplan-Meier survival analysis. After matching, 10,625 patients were included in each cohort (mean age 59.6 ± 13.1 years; 53.7% female). GLP-1 RA users had a 41% lower hazard of initiating chronic opioids (HR 0.59, 95% confidence interval [CI] 0.52-0.67; P < .001) and a 42% lower hazard of developing opioid use disorder (HR 0.58, 95% CI 0.48-0.69; P < .001). GLP-1 RA therapy was also associated with a marked reduction in the risk of requiring celiac plexus block (HR 0.51, 95% CI 0.34-0.78; P = .001) and endoscopic pancreatic interventions (HR 0.48, 95% CI 0.41-0.56; P < .001). Furthermore, the risk of undergoing major pancreatic surgery was significantly lower in the GLP-1 RA group (HR 0.44, 95% CI 0.33-0.59; P < .001). GLP-1 RA use was associated with a substantial reduction in new opioid prescriptions and invasive pancreatic interventions in CP. These findings suggest that GLP-1 RAs may be helpful in symptom control and multidisciplinary management of selected cases.
Comparative evidence on 24-month clinical outcomes and biomarker trajectories with semaglutide, empagliflozin, and sitagliptin in adults with type 2 diabetes (T2D) and obesity remains limited. To compare 24-month clinical outcomes and longitudinal biomarker trajectories among semaglutide, empagliflozin, and sitagliptin in people with T2D and obesity. Multicenter retrospective cohort study. Using TriNetX, we performed an active-comparator, new-user study with three prespecified 1:1 propensity score-matched contrasts: semaglutide versus empagliflozin, semaglutide versus sitagliptin, and empagliflozin versus sitagliptin. Follow-up was intention-to-treat for 24 months. Multiplicity was addressed with Benjamini-Hochberg false discovery rate correction within two prespecified families: (i) clinical time-to-event endpoints (all-cause mortality, MACE, heart failure, MAKE, MALO, atrial fibrillation, stroke) within each comparator pairing, and (ii) window-level laboratory contrasts within each biomarker at baseline, 6, 12, and 24 months. Versus empagliflozin, semaglutide was associated with lower all-cause mortality (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.51-0.69), major adverse cardiovascular events (MACE; HR 0.76, 95% CI 0.66-0.88), and heart failure (HR 0.62, 95% CI 0.54-0.70). Versus sitagliptin, semaglutide was associated with lower all-cause mortality (HR 0.34, 95% CI 0.27-0.42), MACE (HR 0.64, 95% CI 0.51-0.81), and heart failure (HR 0.54, 95% CI 0.43-0.67). Empagliflozin versus sitagliptin showed lower all-cause mortality (HR 0.48, 95% CI 0.40-0.58) and MACE (HR 0.74, 95% CI 0.59-0.92), whereas heart failure did not differ significantly. In matched cohorts with T2D and obesity, semaglutide was associated with lower 24-month mortality and heart failure risk than empagliflozin, and both semaglutide and empagliflozin were associated with lower mortality and MACE than sitagliptin. Not applicable (retrospective cohort); Institutional Review Board approval CS2-24004, Chung Shan Medical University Hospital. Semaglutide, empagliflozin, and sitagliptin in adults with type 2 diabetes and obesity: 24 month outcomes and biomarker patterns People with type 2 diabetes and obesity often need medicines that address both metabolic control and long term cardiovascular and kidney risks. Comparative evidence from routine care is still limited, especially when clinical outcomes and laboratory patterns are evaluated together. We studied adults who newly started semaglutide, empagliflozin, or sitagliptin to describe how these treatments were associated with outcomes and biomarker changes over time. We used deidentified electronic health records from the TriNetX US Collaborative Network. Among 3,981,497 eligible individuals, we constructed three active comparator cohorts and applied one to one propensity score matching. Patients were followed for up to 24 months using an intention to treat approach. Clinical outcomes included all cause mortality, major adverse cardiovascular events, heart failure, and a kidney composite outcome. Laboratory markers were summarized in prespecified windows around 6, 12, and 24 months, including glycemic measures, lipids, inflammatory markers, cardiac stress markers, and liver and kidney function. Mean corpuscular volume was processed as a negative control laboratory marker to help evaluate residual confounding. Across matched cohorts, semaglutide compared with empagliflozin was associated with lower risks of all cause mortality, major adverse cardiovascular events, and heart failure over 24 months. When compared with sitagliptin, both semaglutide and empagliflozin were associated with lower risks of mortality and major adverse cardiovascular events. The kidney composite outcome showed a different pattern than the cardiovascular outcomes, supporting interpretation in terms of domain specific profiles. This observational study describes associations and may be influenced by unmeasured factors and incomplete laboratory capture.
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[This corrects the article DOI: 10.3389/fimmu.2025.1665716.].
Extended Reality (XR) technologies offer transformative potential for language education, yet current platforms largely neglect the accessibility needs of deaf and hard-of-hearing individuals. Existing solutions typically operate in single-language environments and lack integrated support for sign language and multimodal communication. There is a critical need for inclusive platforms that serve both deaf and hearing learners through cross-modal AI services embedded in immersive environments. This study presents a modular platform integrating six AI services: speech-to-text transcription (OpenAI Whisper), multilingual translation (Meta NLLB), text-to-speech synthesis (AWS Polly), sentiment analysis (RoBERTa), session summarisation (flan-t5-base-samsum), and International Sign (IS) translation via Google MediaPipe. An IS dataset of 750 gesture videos was processed to extract hand landmark coordinates mapped to 3D avatar animations within a Unity-based VR environment on Meta Quest 3 headsets. The system was validated through technical benchmarking of AI service performance, including comparative evaluation of text-to-speech services and multilingual translation models (NLLB-200 and EuroLLM 1.7B variants), load testing to assess platform. scalability, and end-to-end pipeline latency measurement for both the hearing and the deaf user pathways. The educational scenario was additionally evaluated in a companion pilot study, 50 which shares the same underlying AI services and provides complementary user-perception evidence. Technical benchmarking confirmed the platform's viability for real-time XR deployment. TTS benchmarking confirmed AWS Polly's lowest latency (50-100 ms first byte) at competitive cost. The EuroLLM 1.7B Instruct model achieved a BLEU score of 84.34, outperforming NLLB's 79.25. Load testing with 1,000 simulated concurrent users demonstrated average response times under 800 milliseconds with no critical failures. Avatar animation latency for IS sign rendering remained consistently under 300 milliseconds. End-to-end pipeline latency averaged 2.05 ± 0.31 s for the hearing pathway and 2.32 ± 0.34 s for the deaf (IS) pathway, both within accepted thresholds for conversational educational use. The companion pilot (N = 10) reported a mean overall experience rating of 4.6/5.0, 92% user satisfaction and unanimous (100%) demand for expanded language and sign-language support. 50. The results presented in this study focus on the technical feasibility of integrating cross-modal AI services within XR environments for accessible, multilingual language learning. The modular architecture enables independent scaling and adaptation to diverse contexts, laying the groundwork for equitable educational solutions aligned with EU digital accessibility objectives. Learning a new language can be challenging, and it is even more difficult for deaf individuals who rely on sign language. This study addresses the challenge by creating a virtual reality (VR) learning environment where a digital 3D character (avatar) can speak, translate, and perform sign language in real time. The system uses several artificial intelligence tools working together: one that converts speech into text, another that translates text between multiple languages, a third that converts text back into spoken language, and a fourth that translates text into International Sign Language gestures performed by the avatar. Users wear a VR headset and interact with the avatar in a virtual classroom where they can select their preferred language and receive immediate translations in both spoken and signed forms. The system’s technical performance was validated through benchmarking of AI translation models, text-to-speech services, end-to-end pipeline latency measurement, and scalability testing, confirming its suitability for real-time educational applications. Complementary user feedback gathered in a companion pilot study, which uses the same underlying AI services, is cross-referenced where relevant. 50 This research is a step toward creating virtual learning environments where language barriers and hearing limitations no longer prevent people from accessing education.
Patient-partnered basic and translational research is the most productive and meaningful approach to developing informed research questions, generating high-quality data, and producing impactful work. While several organizations have published guidelines for patient-partnered research, few experiential reports in basic science are written from both the patient and researcher perspectives and comment on real-time practical challenges and approaches that ensure the establishment and maintenance of a non-tokenistic, organized, and successful research partnership with patient partners. We describe patient partners' and researchers' experiences working together in a basic science and translational research team studying the drivers of primary sclerosing cholangitis, a rare liver disease for which liver transplantation remains the only treatment to disrupt disease progression. We outline approaches used to support meaningful communication, collaboration, and shared output among project stakeholders, drawing on the perspectives of both basic science researchers and patient representatives involved in long-standing joint research projects. Several practical elements support the success of patient partnership in basic and translational science, including structured communication, clear role definition, mutual respect, sustained engagement, and intentional mechanisms to support patient partners' meaningful contributions. We highlight challenges and strategies used to address them in real time, offering insight into how patient-researcher partnerships can be maintained in an organized, authentic, and non-tokenistic way. This review highlights a patient-partnered research team's experiential insights to bridge the gap between published guidance and real-world practice, reinforcing how authentic patient-researcher partnerships can drive more inclusive and impactful basic and translational science. Involving patients as active partners in research leads to better questions, stronger data, and more meaningful results. While many organizations have created guidelines for including patients in research, there are still very few reports and reviews that describe what this looks like in real time, especially in basic science and translational research in rare liver disease. In this article, we share the experience of both patient partners and researchers working together on a project focused on primary sclerosing cholangitis, a rare liver disease for which liver transplant is the only treatment that can stop progression. We describe how we built and maintained a true partnership by using practical strategies for communication, collaboration, and shared decision making. This work offers lessons learned by both researchers and patient partners and shows how strong patient–researcher relationships can lead to better science and greater impact.
Rett syndrome (RTT) is a rare, X-linked neurodevelopmental disorder that primarily affects females. Trofinetide (TROF) was approved for RTT in individuals aged ≥2 years. Although the DAFFODIL trial examined TROF efficacy in children aged 2-4 years, real-world evidence in this age group remains limited. A retrospective cohort study was conducted using linked medical and pharmacy claims from 01/01/2021-09/30/2024 (study period). Individuals aged 2-4 years with RTT who initiated TROF during 04/01/2023-03/31/2024 (identification period) were included (index date=first TROF RX). Outcomes included baseline characteristics, prescriber specialty, TROF persistence (≤90-day allowable gap), dosing patterns based on shipped/dispensed RXs (BID, mg; % target daily dose [%TDD]), time on treatment, and restarts among non-persistent individuals. Variables were summarized descriptively. Kaplan-Meier analyses assessed the time to treatment non-persistence. Among 159 individuals, 65.4% were persistent and 34.6% were non-persistent; 14.5% of non-persistent individuals restarted TROF. Mean±SD age was 3.2±0.8 vs 3.3±0.7 years in persistent vs non-persistent groups. Females comprised 95.2% vs 87.3%, respectively. Child neurology was the most common prescriber specialty (54.8% vs 63.6%). Non-persistent individuals had higher rates of dysphagia (34.5% vs 16.3%), gastrostomy (20.0% vs 3.8%), and breathing irregularities (16.4% vs 1.9%). Mean BID dose and %TDD were similar between groups across shipments. Median (IQR) time on treatment was 13.3 (6.1-17.2) months in the persistent group vs 4.4 (0.8-12.6) months in the non-persistent group. Kaplan-Meier analysis showed >87.5% remained on TROF beyond 3 months and >65.0% remained on TROF through end of available follow-up. In routine US practice, approximately two-thirds of children aged 2-4 years initiating TROF remained persistent during available follow-up, with sustained use beyond 1 year and a subset (14.5% of non-persistent children) restarting after discontinuation. Non-persistent children had significantly higher baseline rates of dysphagia, gastrostomy, and breathing irregularities, suggesting that early disease-related multisystem complications may be associated with reduced treatment continuity. These findings complement DAFFODIL and provide early real-world evidence on TROF persistence, restarts, and dosing patterns in this young RTT population. Why was the study done? Rett syndrome is a rare genetic disorder that impacts brain development, primarily in young girls. In March 2023, the drug trofinetide became the first approved treatment for this condition in the United States. While clinical trials showed the drug is safe and effective for young children aged 2 to 4, doctors and families need real-world evidence to see how well children stick with the treatment in everyday life outside of strict trial settings. What did the researchers do and find? We analyzed health insurance and pharmacy data for 159 children aged 2 to 4 with Rett syndrome who started trofinetide between April 2023 and March 2024. We looked at how long they stayed on the medication, their daily dosages, and whether those who stopped eventually restarted. Our study revealed that: Two-thirds of the children (65.4%) successfully stayed on their trofinetide treatment continuously for over a year.Children who stopped taking the medication usually did so around the 4-month mark. However, about 14.5% of those children eventually restarted the drug after a break.Children who stopped the medication had higher rates of other health issues before starting, such as stomach problems and seizures, compared to those who stayed on it. What do these results mean? Real-world data shows most young children with Rett syndrome stay on trofinetide long-term. Since those with more pre-existing health issues often stop treatment, doctors can use this information to closely support high-risk patients.
Real-time electrochemical measurements of ionic fluxes and bioelectric signals are set to refine cancer diagnosis and longitudinal follow-ups with the goal of targeting electrophysiological features of clinically useful matrices. Nanoengineered electrodes translate biomolecules and ions into robust electrochemical signals for both laboratory workflows and point-of-care testing. The translational aim is to integrate electrochemical sensing into coherent, physiology-grounded readouts that resolve tumor ion channel dysfunction, membrane depolarization, pericellular acidification, and redox imbalance. Realizing this vision now depends on practical engineering and clinical integration. To advance this ongoing development, researchers are building stable, disposable, portable, and miniaturized electrochemical platforms that couple detection with microfluidics to enrich tumor cells, vesicles, and bio ionic markers for multiplexed cancer measurements. The integration of wearable and implantable systems with machine learning and patient-specific digital twins will enable real-time maps of tumor electrophysiology and model-driven forecasts of treatment response. This perspective outlines a translational roadmap for electrochemical detection of bioelectric biomarkers in cancer, wherein biomarker classes are systematically mapped to corresponding transduction strategies and mechanistic fidelity is reconciled with practical assay design constraints to identify key challenges and opportunities for advancing these technologies from foundational research to validated clinical implementation in precision oncology.
The production of bacterial-based vaccines depends fundamentally on advanced bioreactor technologies, which are continuously evolving to meet rising demands for efficiency, quality, and scalability. In this review, several key challenges that constrain the translational impact of bioreactor technologies for bacterial vaccines were identified. First, there is notable variability in bioreactor performance across different bacterial strains and vaccine targets, which undermines the generalizability of process designs. Second, the understanding of how scale-up affects yield, product quality, immunogenicity, and regulatory readiness remains incomplete. It limits confidence in translating lab-scale results to manufacturing environments. Third, real-time analytics and decision-support tools are not sufficiently integrated into control strategies. This leads to fragmented data-to-decision workflows. The review provides concrete, actionable directions to address these challenges. Emerging trends such as real-time monitoring, simulation tools, data-driven process intensification, and modular, single-use platforms are discussed for their potential to address these limitations. The optimized bioreactor design, precise operational control, and sustainable practices are emphasized. It is also illustrated how multidisciplinary collaborations can tailor bioreactor configurations to specific bacterial strains and vaccine targets that deliver reliable scalability.
Digital and data-driven technologies are increasingly shaping preventive oral healthcare and dental education. While prior studies have explored large language model (LLM) performance in non-English examination settings, their role in benchmarking standardized clinical knowledge against real student performance under identical institutional conditions remains insufficiently examined. This study evaluated GPT-4o, GPT-4.5, and DeepSeek-R1 using 300 standardized dental competency items from institutional examinations (2023-2025). Model performance was benchmarked against data from a real student cohort who completed the same examinations, and intra-model consistency was assessed across multiple independent trials. DeepSeek-R1 achieved the highest overall accuracy (92.33%), significantly outperforming GPT-4.5 and GPT-4o in 2023 and 2024, while showing comparable performance to GPT-4.5 in 2025. Model type was the predominant factor associated with accuracy differences, whereas knowledge domain did not significantly affect results. DeepSeek-R1 and GPT-4.5 also demonstrated greater response consistency than GPT-4o. These findings suggest that optimized LLMs demonstrate strong alignment with standardized examination criteria and student performance patterns, supporting their potential role as supplementary tools for curriculum evaluation in preventive dental education. Caution is warranted in generalizing these results beyond the single-institutional, text-only, Mandarin-language context.