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.

In individuals with irritable bowel syndrome (IBS), eliminating dietary triggers can alleviate symptoms but may lead to nutrient deficiencies and overall health decline. Although various nutritional supplements show promising results in relieving IBS symptoms due to their potential to alter the microbiome, conclusive scientific evidence remains lacking. This exploratory study aims to assess the bifidogenic properties of four nutritional supplement interventions and their impact on IBS-symptoms, faecal microbiota composition, faecal short-chain fatty acid (SCFA) concentrations, stool pattern, and quality of life (QoL), compared to a placebo control. Seventy subjects with IBS, meeting the ROME IV criteria, participated in this randomised, double-blind, placebo-controlled parallel intervention study. Subjects were assigned to one of the four treatment groups, receiving either resistant starch, pea fibre, chondroitin sulfate, protein hydrolysate, or placebo daily for four weeks. Daily reports on stool pattern and gastrointestinal complaints were collected. Stool samples and questionnaires on dietary intake, symptom severity, QoL, and anxiety and depression were collected at baseline and after the 4-week intervention. The results show no significant increase in Bifidobacterium abundance or faecal SCFA levels after the 4-week intervention with any of the four nutritional supplement interventions. While some improvements in symptom severity and QoL were observed within-groups, these were not significantly different from changes observed with placebo. In conclusion, the tested nutritional supplements did not increase Bifidobacterium abundance in subjects with IBS within four weeks. Furthermore, we conclude that future studies should consider a run-in period and a larger sample size to study improvements in IBS symptoms.

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 complement C5 inhibitor (C5IT), ravulizumab, is approved in Canada for the treatment of anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). Updated effectiveness and safety results from the ongoing MG SPOTLIGHT Registry (NCT04202341) are reported. Methods: MGFA classification and MG-ADL total scores were assessed in patients who received ravulizumab only (ravu-only) or transitioned from eculizumab to ravulizumab (ecu-to-ravu), with data available prior to C5IT initiation (“pre-C5IT”) and ≥1 assessment post-initiation (“post-ravu”). Results: Of 52 patients with 2 post-ravu assessments, average treatment duration was 10.4 months at last assessment (LA). Mean±SD MG-ADL scores improved (pre-C5IT: 7.6±3.6; LA: 3.4±3.3), as did the proportions of patients with minimal symptom expression (MSE, MG-ADL≤1) (pre-C5IT: 1/52 [2%]; LA: 17/52 [33%]) and MGFA classification 0-II (pre-C5IT: 18/45 [40%]; LA: 40/45 [89%]). In the ravu-only subgroup, outcomes improved (pre-C5IT vs LA): MG-ADL, 6.3±3.0 vs 4.0±3.4; MGFA 0-II, 9/14 [64%] vs 12/14 [86%]. The ecu-to-ravu subgroup sustained continued gradual improvement from last eculizumab assessment to LA: MG-ADL, 4.4±4.2 vs 3.0±2.8; MGFA 0-II, 19/21 [90%] vs 20/21 [95%]. Ravulizumab was well tolerated; no meningococcal infections were reported. Conclusions: These results demonstrate the long-term effectiveness and safety of ravulizumab in routine clinical practice in patients with gMG.

Background: Ischemic stroke is a major cause of morbidity and mortality in Canada. Since 2015, mechanical thrombectomy has been the standard of care for eligible large vessel occlusions (LVOs), though anesthetic strategies remain variable. Methods: We conducted a single-center retrospective review of patients undergoing mechanical thrombectomy for anterior circulation LVOs between 2021 and 2023. Patients were categorized by anesthetic strategy (general anesthesia vs. conscious sedation), and outcomes, including time to recanalization, angiographic results (mTICI), and 90-day functional status (mRS), were compared. Statistical analyses included Student’s t-test, Mann-Whitney U-test, and Fisher’s exact test. Results: Among 226 patients, 177 (78%) received general anesthesia and 49 (22%) underwent conscious sedation. Baseline characteristics including sex, age, NIHSS, ASPECTS, collaterals, and laterality were similar between groups. Conscious sedation was associated with a statistically significant shorter time from arrival to the angiography suite to groin puncture (p=0.007), but no differences in time to recanalization (p=0.893), angiographic outcomes (p=0.987), or 90-day functional status (p=0.795) were observed. Conclusions: Conscious sedation led to faster procedural initiation, though no difference in clinical or radiographic outcome was observed. Anesthetic choice should be individualized based on patient and physician factors in acute mechanical thrombectomy.

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: 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.

Political scientists regularly rely on a selection-on-observables assumption to identify causal effects of interest. Once a causal effect has been identified in this way, a wide variety of estimators can, in principle, be used to consistently estimate the effect of interest. While these estimators are all justified by appeals to the same causal identification assumptions, they often differ greatly in how they make use of the data at hand. For instance, methods based on regression rely on an explicit model of the outcome variable but do not explicitly model the treatment assignment process, whereas methods based on propensity scores explicitly model the treatment assignment process but do not explicitly model the outcome variable. Understanding the tradeoffs between estimation methods is complicated by these seemingly fundamental differences. In this paper we seek to rectify this problem. We do so by clarifying how most estimators of causal effects that are justified by an appeal to a selection-on-observables assumption are all special cases of a general weighting estimator. We then explain how this commonality provides for diagnostics that allow for meaningful comparisons across estimation methods—even when the methods are seemingly very different. We illustrate these ideas with two applied examples.

Discretionary foods that are energy-dense and nutrient-poor contribute to over one third of total energy intake in Australian children and adults, and the typical portion sizes of many discretionary foods have increased significantly in the last two decades(1). The portion size norms (described as a typical perception of how much of a given food people choose to eat at a single eating occasion) are likely to have increased concurrently, with larger sizes now being considered the new normal(2). Public health interventions are urgently needed to reduce the portion size norms and consumption of discretionary foods(3), but the acceptability of such interventions remains unknown. Therefore, this qualitative study aimed to gain insights into consumers’ attitudes towards potential interventions targeted at promoting portion control of discretionary foods. Four online focus group sessions were conducted via Zoom with healthy Australian adults who regularly consume discretionary foods. A question guide was developed to gather participants’ perspectives around four potential public health interventions; reduction of the default serving sizes, increasing serving size options, changes to package sizes, and improving serving size labelling. A female facilitator moderated all focus groups, with a second moderator present to capture other relevant details. Collected data were analysed using a hybrid approach combining deductive and inductive thematic analyses. A total of 35 participants completed the study (19 females, mean age 38 ± 14 years). Participants identified the current food environment as promoting overconsumption; larger serving sizes were reported to be more ubiquitous and better value for money than smaller size options. An overall positive attitude towards the proposed interventions was noted. Out of the four proposed interventions, participants considered the most acceptable intervention to be providing a wider range of serving size options while maintaining a consistent unit price. Other acceptable interventions included reducing the default serving sizes with concurrent price reduction; education and clear guidance around portion size selection (for example, the involvement of health professionals to promote portion control, along with relevant recommendations of appropriate portion sizes from health authorities); more practical on-pack serving size suggestions; and innovative package designs that enable better portion control without contributing to food and plastic waste. In conclusion, participants identified a need for and were in support of interventions aimed at the portion control of discretionary foods. Further research should focus on examining the feasibility and effectiveness of the potential interventions to reduce the purchasing and consumption of large serving sizes. More efforts from public health authorities are required to develop practical and tailored recommendations for consumers around appropriate portion sizes for discretionary foods. Collaboration with the food industry and policy makers is also necessary for implementing public health interventions to reduce the excessive intake of discretionary foods.

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.

Objectives/Goals: To evaluate equity in utilization of free initial health evaluation (IHE) services among members of a limited health care program, the World Trade Center (WTC) Health Program (Program), to inform intervention development and provide insights for similar healthcare programs. Methods/Study Population: We included Program members who newly enrolled during 2012–2022, and who had an IHE or were alive for ≥ 1 year after enrollment. Program administrative and surveillance data collected from January 2012 to February 2024 were used. We evaluated two outcomes: timely IHE utilization (proportion of members completing an IHE within 6 months of enrollment) and any IHE utilization (proportion completing an IHE by February 2024). We described IHE utilization by enrollment year and various members’ characteristics and conducted multivariable logistic regression models to estimate adjusted odds ratios for IHE utilizations to identify factors related to potential inequities for the two member types: Responders, who performed support services, vs. Survivors, who did not respond but were present in the New York disaster area. Results/Anticipated Results: A total of 27,379 Responders and 30,679 Survivors were included. Responders were 89% male, 70% 45–64 years old at enrollment and 76% White. Survivors were 46% female, 54% 45–64 years old at enrollment, and 57% White. Timely IHE utilizations remained relatively stable (~65%) among Responders across time and increased from 16% among Survivors who enrolled in 2017 to 68% among Survivors who enrolled in 2021. Timely IHE utilization was lower for younger members (enrolled Discussion/Significance of Impact: This study highlights Program achievements and gaps in providing equitable IHE services. Strategies to improve members’ equitable IHE utilization can include: adopt/expand flexible scheduling; increase non-English language capacity and cultural competency; and facilitate transportation/assistance for members with accessibility barriers.

Mapping reviews (MRs) are crucial for identifying research gaps and enhancing evidence utilization. Despite their increasing use in health and social sciences, inconsistencies persist in both their conceptualization and reporting. This study aims to clarify the conceptual framework and gather reporting items from existing guidance and methodological studies. A comprehensive search was conducted across nine databases and 11 institutional websites, including documents up to January 2024. A total of 68 documents were included, addressing 24 MR terms and 55 definitions, with 39 documents discussing distinctions and overlaps among these terms. From the documents included, 28 reporting items were identified, covering all the steps of the process. Seven documents mentioned reporting on the title, four on the abstract, and 14 on the background. Ten methods-related items appeared in 56 documents, with the median number of documents supporting each item being 34 (interquartile range [IQR]: 27, 39). Four results-related items were mentioned in 18 documents (median: 14.5, IQR: 11.5, 16), and four discussion-related items appeared in 25 documents (median: 5.5, IQR: 3, 13). There was very little guidance about reporting conclusions, acknowledgments, author contributions, declarations of interest, and funding sources. This study proposes a draft 28-item reporting checklist for MRs and has identified terminologies and concepts used to describe MRs. These findings will first be used to inform a Delphi consensus process to develop reporting guidelines for MRs. Additionally, the checklist and definitions could be used to guide researchers in reporting high-quality MRs.

Imagine that you are given access to an AI chatbot that compellingly mimics the personality and speech of a deceased loved one. If you start having regular interactions with this “thanabot,” could this new relationship be a continuation of the relationship you had with your loved one? And could a relationship with a thanabot preserve or replicate the value of a close human relationship? To the first question, we argue that a relationship with a thanabot cannot be a true continuation of your relationship with a deceased loved one, though it might support one’s continuing bonds with the dead. To the second question, we argue that, in and of themselves, relationships with thanabots cannot benefit us as much as rewarding and healthy intimate relationships with other humans, though we explain why it is difficult to make reliable comparative generalizations about the instrumental value of these relationships.

Oral supplementation with probiotics, prebiotics, and synbiotics is a novel potential complementary therapy for addressing overweight and obesity through gut microbiota modulation. This systematic review provides a comprehensive summary of the existing evidence to guide future research. Literature searches were conducted in four databases to identify human trials published until May 2024 that examined the impact of probiotic, prebiotic, or synbiotic interventions on faecal microbiota composition changes in overweight and obese participants from Latin American and Caribbean populations (LACPs). Of the 13,090 identified records, five randomised controlled trials (RCTs) from Brazil, Mexico, and Chile met the inclusion criteria for this review. The included RCTs evaluated different forms of therapies over short-term interventions (6 or 8 weeks), with sample sizes ranging from 21 to 39 participants across the studies. Variations in the reported outcomes were observed due to differences in supplement formulation, dosage, population characteristics, and methodological heterogeneity. The findings indicate that the available data are inadequate to establish definitive conclusions regarding the impact of biotic treatments on gut microbiota profiles in LACP. Further research with larger sample sizes and precise microbiota analysis is required to elucidate the implications of dietary interventions on gut microbiota in obesity and related disorders.