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Large Language Models (LLMs) hold immense potential for transforming education by automating the generation of personalized learning paths. However, traditional LLMs often suffer from hallucinations and content irrelevance. To address these challenges, we propose SKYRAG, a Separated Keyword Retrieval Augmentation Generation system that enhances the learning path generation process by integrating advanced retrieval mechanisms with LLMs. SKYRAG retrieves relevant course materials from Massive Open Online Course (MOOC) platforms, aligning them with individual learner profiles to provide personalized and coherent learning paths. Compared with Naïve RAG, SKYRAG demonstrates superior performance in terms of accuracy, relevance, and user satisfaction, as confirmed by human evaluations across four domains. By improving retrieval precision and addressing the limitations of traditional methods, SKYRAG represents a significant advancement in educational technology. This study contributes to the growing body of research on AI-driven learning systems and highlights SKYRAG’s potential for widespread adoption in dynamic educational environments.

Choosing nutritious foods is essential for daily health, but finding recipes that match available ingredients and dietary preferences can be challenging. Traditional recommendation methods often lack personalization and accurate ingredient recognition. Personalized systems address this by integrating user preferences, dietary needs, and ingredient availability. This study presents Pic2Plate, a framework combining Vision-Language Models (VLMs) and Retrieval-Augmented Generation (RAG) to overcome these challenges. Pic2Plate uses advanced image recognition to extract ingredient lists from user images and RAG to retrieve and personalize recipe recommendations. Leveraging smartphone camera sensors ensures accessibility and portability. Pic2Plate’s performance was evaluated in two areas: ingredient detection accuracy and recipe relevance. The ingredient detection module, powered by GPT-4o, achieved strong results with precision (0.83), recall (0.91), accuracy (0.77), and F1-score (0.86), demonstrating effectiveness in recognizing diverse food items. A survey of 120 participants assessed recipe relevance, with model rankings calculated using the Bradley–Terry method. Pic2Plate’s VLM and RAG integration consistently outperformed other models. These results highlight Pic2Plate’s ability to deliver context-aware, reliable, and diverse recipe suggestions. The study underscores its potential to transform recipe recommendation systems with a scalable, user-centric approach to personalized cooking.

Purpose: Argininosuccinate Synthetase 1 (ASS1) silencing in carcinomas and sarcomas leads to a dependence on extracellular arginine for survival. Arginine deprivation therapies, like PEGylated arginine deiminase (ADI-PEG20), have shown limited effectiveness, which may be due to underlying mechanisms that inhibit apoptosis., Experimental Design: The effects of ADI-PEG20 on cell cycle regulation, apoptosis, and Bcl-xL-mediated survival pathways in ASS1-deficient cancer cells were determined. The mechanism of cell death protection was determined by assessing caspase and PARP cleavage, CDK2 activity, MCL1 expression, and the interactions between Bcl-xL, Bax, and Bak. In vitro synergy was determined, and in vivo efficacy was modeled., Results: Treatment with ADI-PEG20 led to reduced CDK2 activity and inhibited cell cycle progression but did not induce significant cell death. Bcl-xL was found to bind to Bax and Bak, preventing the initiation of apoptosis despite arginine starvation. Inhibition of Bcl-xL allowed proapoptotic Bax and Bak to initiate the intrinsic apoptosis pathway, leading to increased cell death. This was found to be synergistic in vitro and efficacious in combination in vivo., Conclusions: The study identifies Bcl-xL as a key factor limiting the efficacy of arginine starvation therapies. Combining Bcl-xL inhibitors with arginine deprivation strategies may overcome this resistance and enhance therapeutic outcomes. These findings provide a strong preclinical rationale for testing this combination approach in Phase 1 clinical trials for ASS1-deficient cancers.

Objective: To evaluate the impact of a 4-month dietary and lifestyle program co-designed and led by Aboriginal and Torres Strait Islander people on weight and metabolic markers, diet, and physical activity in overweight and obese adults in a remote Indigenous community., Study Design: Single arm, pre-post intervention study., Setting, Participants: Adult residents (18-65 years) of a remote Northern Territory community with body mass index (BMI) values of at least 25 kg/m 2 or waist circumferences exceeding 94 cm (men) or 80 cm (women)., Intervention: Hope for Health, a culturally sensitive 4-month program supporting self-managed health improvement based on dietary and lifestyle change, 1 August to 30 November 2022., Main Outcome Measures: Weight loss of at least 5%; changes in BMI, waist circumference, other metabolic markers (blood pressure, biomarkers of metabolic health and inflammation), diet, and physical activity; participant perceptions of the program., Results: We assessed outcomes for 55 participants who completed weight assessments at both baseline and program end (mean age, 42.5 years [standard deviation, 10.1 years]; 36 women [65%]). Forty participants lost and 15 gained weight; overall mean weight loss was 1.5 kg (95% confidence interval [CI], 0.5-2.4 kg), and ten participants (18%; 95% CI, 9-31%) achieved at least 5% weight reduction. The mean change in BMI (53 participants) was -0.60 kg/m 2 (95% CI, -0.93 to -0.27 kg/m 2 ), in waist circumference (53 participants) -3.2 cm (95% CI, -4.7 to -1.7 cm), and in low-density lipoprotein cholesterol level (37 participants) -0.28 mmol/L (95% CI, -0.47 to -0.08 mmol/L); the relative decline in the HbA 1c level geometric mean (50 participants) was 11% (95% CI, 6-15%). The intake of breads and cereals (median change, -1.5 [95% CI, -2.0 to -1.0] serves/day) and sugar-sweetened beverages (-0.6 [95% CI, -1.4 to -0.1] serves/day) declined; the amount of moderate and vigorous physical activity increased by a median of 103 min/day (95% CI, 74-136 min/day; 19 participants). The program focus on integrating healthy bodies and networks of kin, healthy governance, vibrant language and ceremony, and a healthy environment were seen as central to its value and benefit., Conclusions: Community appreciation of the program and the improvements in cardiometabolic risk factors are encouraging, providing an example of a culturally sensitive, co-designed initiative led by Indigenous people for reducing the prevalence of chronic disease in remote areas., Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN12622000174785; prospective: 2 February 2022)., (© 2025 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Objective: Type1Screen offers islet autoantibody testing to Australians with a family history of type 1 diabetes (T1D) with the dual aims of preventing diabetic ketoacidosis (DKA) and enabling use of disease-modifying therapy. We describe screening and monitoring outcomes 2 years after implementing in-home capillary blood spot sampling., Research Design and Methods: Data from 2,064 participants who registered between July 2022 and June 2024 were analyzed: 1,507 and 557 chose blood spot and venipuncture screening respectively. We compared baseline characteristics and outcomes for 1,243 participants (967 blood spot and 276 venipuncture) whose samples were tested by June 2024., Results: One blood spot and five venous participants reported unsuccessful sample collections. The median (quartile 1, quartile 3) age of blood spot registrants was lower (12.1 [7.1, 27.1] vs. 17.2 [9, 38.4] years; P < 0.0001), and a higher proportion lived in regional Australia (39% vs. 29%; P = 0.0037). Among 72 participants (5.9%) with a positive screening test, 5 screened by blood spot and 2 by venipuncture had no autoantibodies on confirmatory testing. Blood spot screening identified the expected 2.1% prevalence of multiple autoantibodies and a 2.5% prevalence of a single autoantibody compared with 1.5% and 4.1%, respectively, for venipuncture screening. Clinical diabetes developed in 12 participants. All had screened positive and none had DKA., Conclusions: Type1Screen has national reach. In-home blood spot screening is feasible, particularly for younger participants living regionally, and identifies the expected prevalence of preclinical T1D. The lower cost, increased convenience, and greater reach of blood spot screening could help meet increasing demand for early T1D diagnosis., (© 2025 by the American Diabetes Association.)

Objectives: Chlamydia trachomatis (CT) is the most commonly reported bacterial sexually transmitted infection worldwide. Diagnosis relies on nucleic acid amplification techniques, such as PCR, which does not distinguish between viable pathogens and residual bacterial DNA, leading to potential overdiagnosis and overtreatment. PCR with confirmation of pathogen viability has not been widely explored in the sexually transmitted infection field. We aimed to establish a CT viability PCR (V-PCR) and to apply it to anorectal swabs from men who have sex with men (MSM)., Methods: We validated a published V-PCR protocol by preparing artificial samples with known ratios of viable and non-viable CT. Mock samples were treated with propidium monoazide (PMAxx) before DNA extraction and quantitative PCR (qPCR) to detect CT. The V-PCR was then applied to CT PCR-positive anorectal swabs from MSM. Viability was expressed as the difference in CT copies between PMAxx untreated and treated samples (ΔLog10 CT/mL). The anorectal samples were inoculated in cell culture for isolation. Genotyping was performed by examining the ompA gene sequence., Results: Of 236 anorectal swabs, 69 (29.2%) were CT PCR positive, and we obtained V-PCR data from 54. There were 7 of 54 (12.9%), samples with <1% viable CT (>2.52 ΔLog10 CT/mL) 4 of 54 (7.4%) samples with 1% to 10% viable CT (1.59-2.52), 16 of 54 (29.6%) with 10.01% to 50% viable CT (0.86-1.59) and 27 of 54 (50.0%) with 50.01% to 100% viable CT (<0.35-0.86). CT was isolated successfully from 39 of 69 (56.5%) samples in cell culture. Genotypes based on ompA were obtained for 62 of 69 (89.9%) samples: G (n = 15/62), D/Da (n = 15/62), J (n = 15/62), E (n = 11/62), L1 (n = 4/62), and L2 (n = 2)., Discussion: We successfully implemented a viability test based on PCR, which can distinguish, detect and quantify viable CT in anorectal swabs from MSM. Rapid, reliable assessment of CT viability could help to improve antimicrobial stewardship., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The UK has recently established subscription-payment agreements for two antimicrobials: cefiderocol and ceftazidime-avibactam. This article summarises the novel value assessments that informed this process and lessons learned for future pricing and funding decisions., Methods: The evaluations used decision modelling to predict population incremental net health effects (INHEs), informed by systematic reviews, evidence syntheses, national surveillance data and structured expert elicitation., Results: Significant challenges faced during the development of the evaluations led to profound uncertainty in the estimates of INHEs. The value assessment required definition of the population expected to receive the new antimicrobials; estimating value within this heterogenous population; assessing comparative efficacy using antimicrobial susceptibility data due to the absence of relevant clinical data; and predicting population-level benefits despite poor data on current numbers of drug-resistant infections and uncertainties around emerging resistance. Though both antimicrobials offer the potential to treat multi-drug resistant infections, the benefits estimated were modest due to the rarity of true pan-resistance, low life expectancy of the patient population and difficulty of identifying and quantifying additional sources of value., Conclusions: Assessing the population INHEs of new antimicrobials was complex and resource intensive. Future evaluations should continue to assemble evidence relating to areas of expected usage, patient numbers over time and comparative effectiveness and safety. Projections of patient numbers could be greatly enhanced by the development of national level linked clinical, prescribing and laboratory data. A practical approach to synthesising these data would be to combine expert assessments of key parameters with a simple generic decision model., Competing Interests: Declarations. Competing Interests and Disclosures: B.W. sits on the Board of the York Health Economics Consortium, a private sector company (role not remunerated). M.S. has been a paid consultant to various life sciences companies, none relating to antimicrobials. M.W. reports institutional research support and funding from Almirall, Da Volterra, EnteroBiotix, GSK, Merck, MicroPharm, Nabriva, Paratek, Pfizer, Seres, Summit, The European Tissue Symposium and Tillotts, and personal fees from AiCuris, Bayer, Crestone, Da Volterra, Deinove, EnteroBiotix, The European Tissue Symposium, Ferring, GSK, Menarini, Merck, Nestlé, Paion, Paratek, Pfizer, Phico Therapeutics, Qpex Biopharma, Seres, Surface Skins, Summit, Tillotts and Vaxxilon/Idorsia, outside the submitted work. W.H. reports grants and personal fees from F2G, grants and personal fees from Pfizer, grants from Bugworks, grants from Phico Therapeutics, personal fees from GSK, personal fees from Mundipharma, personal fees from Pulmocide and grants from GARDP, outside the submitted work. C.L. reports personal fees from INFEX Therapeutics Ltd, outside the submitted work. P.H. reports that he works for NHS England in the AMR Programme and the UK National Action Plan for AMR has a goal to introduce a delinked payment model. D.Je. reports personal fees from Pfizer and Shionogi, outside the submitted work. B.K., L.S., D.Ja., C.R., S.H., J.H., A.S., S.R., L.B., A.A. and A.B. report no relevant competing interests. Ethics Approval: Ethics approval for the expert elicitation exercise was granted from the University of York Department of Health Sciences Research Governance committee (reference no.: HSRGC/2021/448/G; date of approval: 14 May 2021). No other activities required primary data collection, so no further ethics approval was required. Consent to Participate: The experts included within the expert elicitation exercise received a Participant Information Sheet and completed a Participant Consent Form. These materials were reviewed as part of ethics approval. Consent for Publication (from patients/participants): Consent for publication of results relating to the elicitation exercise was sought as part of the overall consent to participate process. Data Availability: The only primary data collection for this study related to the expert elicitation; ethics approval for this element of the study does not permit data sharing. All queries should be sent to the corresponding author. Code Availability: The code is available from the authors by email request. Funding: This work was funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401. Author Contributions: B.W., B.K., L.S., D.Ja., C.R. and M.S. conceptualised and developed the economic modelling and underlying statistical analyses. B.W., B.K., L.S., D.Ja., C.R., S.H., A.S. and M.S. designed and undertook the review elements and contributed to the design of the evidence synthesis. J.H. and S.R. designed and conducted the evidence synthesis. D.Ja. and L.B. designed and conducted the expert elicitation. M.W., W.H., C.L., P.H., D.Je., A.A. and A.B. contributed to identification of the high-value clinical scenarios and areas of expected usage, contributed to the design of the model including appropriateness of evidence and helped to classify infections sites using specimen data. All authors contributed to the development of the manuscript and reviewed the final version., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The Canadian Stroke Best Practice Recommendations (CSPR) 7th edition includes this new module on the diagnosis and management of vascular cognitive impairment (VCI) with or without neurodegenerative disease. An expert writing group and people with VCI lived experience (PWLE) reviewed current evidence. Existing recommendations were reviewed and revised, and new recommendations added. Sections include definitions, signs and symptoms, screening, assessment, diagnosis, pharmacological and non-pharmacological management, secondary prevention, rehabilitation, and end-of-life care. PWLE were actively involved in all aspects of the development, ensuring their experiences are integrated. A unique VCI journey map, developed by PWLE, is included, and helped to motivate and anchor the recommendations. We encourage it to be displayed across healthcare settings to raise awareness and support persons with VCI. These VCI CSBPRs emphasize the need for integrated multidisciplinary care across the continuum. Evidence for the diagnosis and management of VCI continues to emerge and gaps in knowledge should drive future research. HIGHLIGHTS: This Canadian Stroke Best Practice Recommendations module focuses specifically on VCI using a structured framework and validated methodology. A comprehensive set of evidence-based recommendations is presented that addresses the continuum from symptom onset to diagnosis, management, and end of life. The recommendations consider individuals who experience VCI because of stroke or because of other vascular pathologies such as atrial fibrillation or heart failure. A journey map of an individual's experience with VCI has been developed by individuals with lived experience. It is a valuable guide to inform educational content, approaches to caring for individuals and families with VCI, and systems planning., (© 2025 Heart and Stroke Foundation of Canada. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Noonan syndrome (NS) is a rare, genetic multisystem disorder often presenting with associated craniofacial abnormalities. The authors report an identical twin pair with classical features of NS including short stature, mild ptosis, hypertelorism, down-slanting palpebral fissures, low-set angulated ears, and giant cell tumors in the craniofacial skeleton. Interestingly, these patients also presented with bilateral, symmetric, dystrophic auricular calcifications. Genome sequencing revealed identical germline son of sevenless homolog 1 mutations and inversion of chromosome 2 (p11.2q13). Awareness of the association of auricular calcifications and NS may help guide clinical management for these patients, particularly if auricular procedures are indicated., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Introduction: Few rural hospital medicine programs include workforce development training that provides social and professional support for interdisciplinary teams. Even fewer include training that creates supportive learning environments that result in higher staff satisfaction, lower burnout, and reduced turnover. The Acute Inpatient Medicine-High Reliability, Learning Environment, and Workforce Development Initiative (AIM-HI) aims to create supportive learning environments in Veterans Health Administration (VA) rural hospital medicine teams., Methods: AIM-HI is a type II hybrid implementation study utilizing a convergent mixed methods approach to evaluate the Relational Playbook, a workforce development intervention, and three implementation strategies: behavioral nudges, learning and leadership collaboratives, and leadership coaching. AIM-HI implementation will occur in waves, enrolling additional hospitals every 12 months. In the first wave, AIM-HI will be implemented at three tertiary VA hospitals that treat at least 1000 rural Veterans annually and have an active inpatient hospital medicine program. The primary outcomes in year 1 will be the acceptability, appropriateness, and feasibility of AIM-HI assessed through participant surveys and interviews. In subsequent years, trends in the learning environment, job satisfaction, burnout, and turnover scores will be assessed using a linear mixed-effect model., Discussion: The anticipated impact of AIM-HI is to evaluate the utility of the implementation strategies and assess trends in Playbook intervention outcomes. The Playbook has strong face validity; however, before large-scale adoption across the VA enterprise, it is essential to establish the acceptability, appropriateness, and feasibility of the Playbook and implementation strategies, as well as to gather data on AIM-HI effectiveness., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Journal of Hospital Medicine published by Wiley Periodicals LLC on behalf of Society of Hospital Medicine.)