The interaction of helminth infections with type 2 diabetes (T2D) has been a major area of research in the past few years. This paper, therefore, focuses on the systematic review of the effects of helminthic infections on metabolism and immune regulation related to T2D, with mechanisms through which both direct and indirect effects are mediated. Specifically, the possible therapeutic role of helminths in T2D management, probably mediated through the modulation of host metabolic pathways and immune responses, is of special interest. This paper discusses the current possibilities for translating helminth therapy from basic laboratory research to clinical application, as well as existing and future challenges. Although preliminary studies suggest the potential for helminth therapy for T2D patients, their safety and efficacy still need to be confirmed by larger-scale clinical studies.

Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.

Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.

Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.

Background: The combination of PARP inhibitor and immune checkpoint inhibitors have been proposed as a potentially synergistic combinatorial treatment in IDH mutant glioma, targeting dysregulated homologous recombination repair pathways. This study analyzed the cell-free DNA methylome of patients in a phase 2 trial using the PARP inhibitor Olaparib and the PD-1 inhibitor Durvalumab. Methods: Patients with recurrent high-grade IDH-mutant gliomas were enrolled in a phase II open-label study (NCT03991832). Serum was collected at baseline and monthly and cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) was performed. Binomial GLMnet models were developed and model performance was assessed using validation set data. Results: 29 patients were enrolled between 2020–2023. Patients received olaparib 300mg twice daily and durvalumab 1500mg IV every 4 weeks. The overall response rate was 10% via RANO criteria. 144 plasma samples were profiled with cfMeDIP-seq along with 30 healthy controls. The enriched circulating tumour DNA methylome during response periods exhibited a highly specific signature, accurately discriminating response versus failure (AUC 0.98 ± 0.03). Additionally, samples that were taken while on treatment were able to be discriminated from samples off therapy (AUC 0.74 ± 0.11). Conclusions: The cell-free plasma DNA methylome exhibits highly specific signatures that enable accurate prediction of response to therapy.

Background: Nipocalimab is a human IgG1 monoclonal antibody targeting FcRn that selectively reduces IgG levels without impacting antigen presentation, T- and B-cell functions. This study describes the effect of nipocalimab on vaccine response. Methods: Open-label, parallel, interventional study randomized participants 1:1 to receive intravenous 30mg/kg nipocalimab at Week0 and 15mg/kg at Week2 and Week4 (active) or no drug (control). On Day 3, participants received Tdap and PPSV®23 vaccinations and were followed through Wk16. Results: Twenty-nine participants completed the study and are included (active, n=15; control, n=14). Participants with a positive anti-tetanus IgG response was comparable between groups at Wk2 and Wk16, but lower at Wk4 (nipocalimab 3/15 [20%] vs control 7/14 [50%]; P=0.089). All maintained anti-tetanus IgG above the protective threshold (0.16IU/mL) through Wk16. While anti-pneumococcal-capsular-polysaccharide (PCP) IgG levels were lower during nipocalimab treatment, the percent increase from baseline at Wk2 and Wk16 was comparable between groups. Post-vaccination, anti-PCP IgG remained above 50mg/L and showed a 2-fold increase from baseline throughout the study in both groups. Nipocalimab co-administration with vaccines was safe and well-tolerated. Conclusions: These findings suggest that nipocalimab does not impact the development of an adequate IgG response to T-cell–dependent/independent vaccines and that nipocalimab-treated patients can follow recommended vaccination schedules.

Optimal nutrition supply to the developing foetus is paramount in achieving appropriate foetal growth and development. The Australian dietary guidelines advise about the amounts and types of foods for pregnancy(1). However, previous studies in reproductive aged women(2) and in pregnant women(3) showed suboptimal adherence to dietary recommendations. There is no evidence on the experience of sourcing nor uptake of the dietary guidelines among pregnant women. The aim of this study is to qualitatively explore women’s knowledge and understanding of nutrition information for pregnancy, including the current Australian dietary guidelines for pregnancy. Twelve pregnant women were recruited from a longitudinal study from the first through third trimester of pregnancy. Purposive sampling was adopted with an intention to recruit for diverse health information seeking habits. Semi-structured interviews were conducted with women at different trimesters, transcribed verbatim, and analysed thematically. Three themes were generated regarding information sourcing, uptake and evaluation. (i) Women had limited knowledge about the pregnancy dietary guidelines, leaving them to source pregnancy related nutrition information elsewhere. (ii) Women described other healthy eating advice that contributed to confusion and potential incompatibility with their dietary beliefs and lifestyle practices. (iii) Women shared that they were capable of seeking and evaluating the identified dietary advice, but the inconsistency across information sources contributed to over-cautious behaviour and dietary restrictions. Our findings suggest there is a general lack of awareness of the official dietary guidelines for pregnancy. To optimise pregnancy nutritional intake, efforts should be made to increase utilisation of the Australian dietary guidelines for pregnancy and to support uptake of dietary advice among pregnant women.

Improving neonatal piglet survival is a key driver for improving pig production and enhancing animal welfare. Gestational diabetes is a risk factor for neonatal morbidities in humans, such as hypoglycaemia and respiratory distress(1). There is limited knowledge on the association of gestational diabetes with neonatal survival in commercial pigs. An early study suggested that the diabetic condition of late-gestating sows was positively correlated with the first-week newborn piglet mortality(2). Genetic selection in recent decades for heavier birth weight may have increased the prevalence or severity of gestational diabetes in pigs, considering the positive correlation between gestational diabetes and birth weight. We hypothesised that the diabetic condition of late gestating sows positively correlates with the neonatal piglet mortality rate in sows with modern genetics. Mixed-parity sows (1.5 ± 1.6 parity for mean ± standard deviation (SD); Large White × Landrace) from a commercial piggery in Australia were randomly selected and participated in an oral glucose tolerance test (OGTT) during two seasons (118 sows in winter and 118 sows in summer). On the d109 day of gestation, sows were fed 3.0 g dextrose per kg of metabolic body weight after fasting overnight. Tail blood glucose concentrations were measured using a glucometer (Accu-Chek ®, Roche Diabetes Care Australia Pty) at −10, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120 minutes relative to dextrose feeding. The glucose increment (2.5 ± 1.29 mM for mean ± SD) during OGTT was calculated using the maximum concentration substrating the fasting concentration of blood glucose. The 24-hour piglet mortality rate (5% ± 8.8% for mean ± SD) was calculated as the ratio between piglets that died during the first 24 hours and the total number of born alive on a litter basis. The effect of sow glucose increment, season (winter vs summer), glucose increment × season, number of piglets born alive, and sows parity on the 24-h piglet mortality rate as analysed using a Generalised Linear Model (SPSS 27th Version, IBM SPSS Statistics, Armonk). Results showed that the 24-hour piglet mortality rate was numerically higher in winter than in summer although insignificant (5.7% vs 4.2%, p = 0.41). The glucose increment of gestating sows was positively correlated with the 24-hour piglet mortality rate during winter but not summer, as evidenced by an interaction trend between glucose increment and season (p = 0.059). The regression coefficient suggested that every extra unit (mM) of glucose increment during OGTT corresponded to a 1.4% increase in the 24-hour piglet mortality rate in winter. In conclusion, the diabetic condition of late-gestating sows is a risk factor for neonatal piglet mortality in winter. Developing nutritional strategies to mitigate the diabetic condition of late-gestating sows may benefit neonatal piglet survival.

Objectives/Goals: Our study’s objective is to evaluate RadOnc-GPT, a GPT-4o powered LLM, in generating responses to in-basket messages related to prostate cancer treatment in the Radiation Oncology department. By integrating it with electronic health record (EHR) systems, the goal is to assess its impact on clinician workload, response quality, and efficiency in healthcare communication. Methods/Study Population: RadOnc-GPT was integrated with patient EHRs from both hospital-wide and radiation-oncology-specific databases. The study examined 158 pre-recorded in-basket message interactions from 90 non-metastatic prostate cancer patients. Quantitative natural language processing analysis and two randomized single-blinded grading studies, involving four clinicians and four nurses, were conducted to evaluate RadOnc-GPT’s response quality in completeness, correctness, clarity, empathy, and estimated editing time. Response times were measured to estimate the time saved for clinicians and nurses. The study population included patient messages across all phases of care (pre-, during, and post-treatment) for those undergoing radiotherapy. Results/Anticipated Results: In the single-blinded grader study, clinician graders evaluated 316 responses (158 from human care teams and 158 from RadOnc-GPT). Results showed RadOnc-GPT outperformed human responses in empathy and clarity, while humans excelled in completeness and correctness. Sentiment analyses using TextBlob and VADER revealed RadOnc-GPT responses had a positive mean score of 0.25, whereas human responses clustered around neutral. VADER analysis indicated a high median score for RadOnc-GPT, nearing 1.0, reflecting predominantly positive sentiment, while human responses displayed a broader sentiment range, indicating sensitivity to context. Clinicians averaged 3.60 minutes (SD 1.44) to respond, compared to 6.39 minutes (SD 4.05) for nurses, highlighting RadOnc-GPT’s efficiency in generating timely responses. Discussion/Significance of Impact: RadOnc-GPT effectively generated responses to individualized patient in-basket messages, comparable to those from radiation oncologists and nurses. While human oversight is still necessary to avoid errors, RadOnc-GPT can speed up response times and reduce pressure on care teams, shifting their role from drafting to reviewing responses.

A three-dimensional robust nonlinear cooperative guidance law is proposed to address the challenge of multiple missiles intercepting manoeuvering targets under stringent input constraints and thruster failure. The finite-time convergence theory is used to design a distributed nonlinear sliding mode guidance law, ensuring that the system converges in finite time, with the upper limit of convergence time related to the initial state. A nonlinear sliding surface is adopted to mitigate actuator saturation issues. Then, considering thruster failure, a robust cooperative guidance law is further introduced, ensuring mission completion through the reconstruction of the guidance law. The closed-loop system is proven to be stable using Lyapunov theory, and the influence of hyperparameters on the cooperative guidance law is analysed. Additionally, the results of numerical simulations and hardware-in-the-loop experiments demonstrate the effectiveness and robustness of the proposed algorithm in dealing with stringent input saturation and various disturbances.

Although family factors are considered important for children’s language acquisition, the evidence comes primarily from affluent societies. Thus, this study aimed to examine the relations between family factors (family’s socioeconomic status [SES], home literacy activities, access to print resources, and parental beliefs) and children’s vocabulary knowledge in both urban and rural settings in China. Data from 366 children (urban group: 109, 4.85 years; rural group: 257, 4.89 years) were collected. Results showed that whereas family’s SES significantly predicted access to print resources and children’s vocabulary knowledge in the rural group, parental beliefs directly predicted children’s vocabulary knowledge in the urban group. Multigroup analysis showed that the associations of family’s SES and access to print resources with children’s vocabulary knowledge were stronger in the rural group than in the urban group. Our findings highlight the importance of considering contextual settings when conceptualising the role of family factors in children’s language acquisition.

Persons living with dementia are at risk of becoming lost. While return discussions after missing incidents are common with children, these discussions are seldom done with persons living with dementia. Our objective was to describe the use of return discussions with persons living with dementia according to the literature and practice. We conducted a scoping review using 19 databases to locate scholarly and grey literature on return discussions, followed by 20 semi-structured interviews with first responders and service providers in Canada and the United Kingdom (UK). Eleven scholarly and 94 grey sources were included, most from the UK, related to missing children, none included persons with dementia. According to participants, although there was no standardized procedure, there were themes about conditions that facilitate return discussions. This was the first study to examine return discussion practice in dementia, and results can inform development of evidence-based protocols.

This study presents observations of coherent modes (CMs) in a spherical tokamak using a microwave interferometer near the midplane. The CMs within the 30–60 kHz frequency range were observed during electron cyclotron resonance heating only, and the frequency of the CMs increased proportionally with the square root of the electron temperature near $R = 0.7m$. Generally, these modes displayed bursting and chirping signatures with strong density rise and fall. Their appearance indicated an increase in the intensity of hard x rays, suggesting a deterioration in energetic electron confinement. Furthermore, the effect of CMs on the intensity of energetic electron-driven whistler waves was observed. They decreased when CMs were present and gradually increased with the decrease in CM intensity. The CMs may influence the intensity of whistler waves by affecting the energetic electron confinement.

Background: Hyperacute stroke care demands rapid, coordinated care. Traditional metrics like Door-to-Needle time are pivotal but insufficient for capturing the complexity of endovascular stroke interventions. The SMILES collaboration aims to standardize and optimize protocols for door-to-intervention times, incorporating Crew Resource Management (CRM). Methods: The multidisciplinary initiative integrates both hospitals, ED, neurology, and QI teams. We employed a comprehensive approach: stakeholder engagement, simulation-based learning, process mapping, and literature review. Emphasis was placed on enhancing situational awareness, triage and prioritization, cognitive load management, role clarity, effective communication, and debriefing. Results: The collaboration led to PDSA cycles and development of refined stroke protocols. Interventions included: 1) A ’zero point survey’ for team pre-arrival briefings, enhancing situational awareness and role clarity; 2) Streamlined patient registration to reduce cognitive load and improve triage efficiency; 3) Direct transfer of patients to imaging. Additionally, digital tools were implemented to facilitate communication. Simulation sessions reinforced CRM principles, leading to improved team cohesion and operational performance. Conclusions: The SMILES initiative is grounded in CRM principles by standardizing protocols and emphasizing non-technical skills crucial for high-stakes environments. This improves outcomes but also fosters a culture of safety and efficiency. Future directions include an evaluation of these protocols’ impact on patient factors.