Search Results (308)

Despite advances in cancer care, disparities persist. The collection of the social determinants of health (SDOH) is fundamental to addressing disparities. However, SDOH are inconsistently collected in many regions of the world. This two-phase multiple methods study examined patient and community perspectives regarding SDOH data collection in Canada. In phase 1, a survey was administered to patients at a cancer centre (n = 549) to assess perspectives on an SDOH data collection tool. In phase 2, broader perspectives were sought through a community consultation with patient partners experiencing structural inequality (n = 15). Most participants were comfortable with SDOH data collection. Of survey respondents, 95% were comfortable with the collection of language, birthplace, sex, gender, education, and disability, and 82% to 94% were comfortable with SES, sexual orientation, social support, and race/ethnicity. Discomfort levels did not differ across subgroups, except women were more uncomfortable disclosing SES (OR: 2.00; 95%CI: 1.26, 3.19). Most (71%) preferred face-to-face data collection with a healthcare professional and only half were comfortable with storage of SDOH in electronic health records. Open-ended survey responses (n = 1533) and the community consultation revealed concerns about privacy, discrimination, relevance to care, and data accuracy. SDOH data collection efforts should include a clear rationale for patients, training for providers, strong data privacy and security measures, and actionable strategies to address needs. Full article

This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article

As high-CBD cannabis (Cannabis sativa L.) gains legal and commercial relevance in the United States, studies evaluating how external inputs impact critical traits remain limited. This study investigates the effects of methyl jasmonate (MeJA), ammonium bicarbonate (AB), and the genetic source (mother plant identity) on the growth and secondary metabolite traits of indoor cannabis. Plants were treated with 1 mM MeJA and/or AB under controlled conditions, and key traits, such as plant height, chlorophyll content, biomass, trichome density, and cannabinoid concentration, were measured. The MeJA treatment led to a significant 32% increase in trichome density. However, it did not significantly alter CBD or THC concentrations. The AB treatment enhanced vegetative growth, increasing chlorophyll content and plant height while reducing CBD concentrations, but the biomass gains could compensate for the lower cannabinoid in the total production. An interaction between MeJA and AB altered the CBD content, suggesting that MeJA may mitigate AB’s negative effect on cannabinoid synthesis. The genetic source significantly influenced most of the measured traits, highlighting the role of the genotype in trait expression and the importance of clonal consistency. These findings highlight the complex dynamics of external inputs and genetic factors in cannabis production, emphasizing the need for further research to optimize cultivation strategies. Future studies should refine input combinations and doses to improve both yield and cannabinoid profiles. Full article

Neuropeptide FF (NPFF) receptor antagonists prevent morphine-mediated antinociceptive tolerance, and compounds with dual mu opioid receptor (MOR) agonist and NPFF antagonist activity produce antinociception without tolerance. Compounds synthesized showed affinities in radioligand competition binding assays in the nM and µM range at the opioid and NPFF receptors, respectively, and displayed substitution-dependent functional profiles in the [³⁵S]GTPγS functional assay. From six compounds screened in vivo for antinociception and ability to prevent NPFF-induced hyperalgesia in mouse warm water tail withdrawal tests, compound 22b produced dose-dependent MOR-mediated antinociception with an ED₅₀ value (and 95% confidence interval) of 6.88 (4.71–9.47) nmol, i.c.v., and also prevented NPFF-induced hyperalgesia. Meanwhile, 22b did not demonstrate the respiratory depression, hyperlocomotion, or impaired intestinal transit of morphine. Moreover, repeated treatment with 22b produced a 1.6-fold rightward shift in antinociceptive dose response, significantly less acute antinociceptive tolerance than morphine. Evaluated for microsomal stability in vitro and in vivo pharmacokinetic profile, 22b showed suitable microsomal stability paired in vivo with a large apparent volume of distribution and a clearance smaller than the hepatic flow in rats, suggesting no extra-hepatic metabolism. In conclusion, the present study confirms that dual-action opioid–NPFF ligands may offer therapeutic promise as analgesics with fewer liabilities of use. Full article

Background/Objectives: Osteosarcoma is the most common malignant bone tumor in children, characterized by a high degree of genomic instability, resulting in copy number alterations and genomic rearrangements without disease-defining recurrent mutations. Clinical trials based on molecular characterization have failed to find new effective therapies or improve outcomes over the last 40 years. Methods: To better understand the immune microenvironment of osteosarcoma, we performed single-cell RNA sequencing on six tumor biopsy samples, combined with a previously published cohort of six samples. Additional osteosarcoma samples were profiled using spatial transcriptomics for the validation of discovered subtypes and to add spatial context. Results: Analysis revealed immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs), regulatory and exhausted T cells, and LAMP3+ dendritic cells. Conclusions: Using cell–cell communication modeling, we identified robust interactions between MDSCs and other cells, leading to NF-κB upregulation and an immunosuppressive microenvironment, as well as interactions involving regulatory T cells and osteosarcoma cells that promoted tumor progression and a proangiogenic niche. Full article

Background: There is a significant knowledge gap and limited studies have been carried out to evaluate the effect of type 2 diabetes (T2D) on bone quality and skeletal fragility. Previous reviews have tended to focus primarily on bone mineral density (BMD) as a measure of bone quality. However, BMD does not fully reflect the risk of fracture, cannot distinguish between cortical and trabecular bone, and bone fragility in patients with T2D results not only from alterations in bone mineralisation, but also due to changes in bone microarchitecture. In this regard, assessment tools such as trabecular bone score (TBS) and trabecular microarchitectural parameters could be useful and practical tools for examining bone status in people with T2D. Aim: This review aims to examine the effect of type 2 diabetes on bone quality based on a variety of assessment tools. Method: The PRISMA checklist and PICOS framework were relied on for this systematic review and meta-analysis. Two researchers conducted the searches from database inception until 24/02/25. Databases including Academic Search Premier, APA PsycArticles, APA PsycInfo, CINAHL Plus with Full Text, MEDLINE, and the Psychology & Behavioral Sciences Collection were searched for relevant articles. The reference lists of articles were also searched. The Review Manager 5.4.1 software was used to carry out the meta-analysis. Results: Ten studies were included in the systematic review, while nine studies were included in the meta-analysis. Based on the narrative synthesis and meta-analysis, four distinct themes were established: bone mineral density, TBS and trabecular microarchitectural parameters, fracture risk, and body mass index (BMI). The meta-analysis of the effect of T2D on BMD showed that T2D significantly (p < 0.05) increased lumbar spine, total hip, femoral neck, and narrow neck BMD compared with controls. The mean differences (MDs) for the respective parameters were 0.04 (95% CI, 0.03, 0.05, p < 0.0001); 0.05 (95% CI, 0.02, 0.08, p = 0.002); 0.07 (95% CI, 0.04, 0.10, p < 0.0001); and 0.03 (95% CI, 0.01, 0.05, p = 0.0005). While there was a significant reduction (p < 0.0001) in the patients with T2D with respect to volumetric BMD, involving two studies and 1037 participants, with an MD of −12.36 (95% CI,−18.15, −6.57, p < 0.0001), T2D did not appear to have a significant effect (p > 0.05) on total BMD and area BMD compared to controls. In relation to TBS and trabecular microarchitectural parameters, the effect of T2D was not significant (p > 0.05) compared with controls. Furthermore, T2D did not have a significant effect (p > 0.05) on the incidence of hip fracture and non-spine fracture compared to controls. Following meta-analysis, it was found that the T2D significantly (p < 0.05) increased BMI compared to controls with an MD of 0.94 (95% CI, 0.74, 1.14, p < 0.0001). Conclusions: Type 2 diabetes significantly increased (p < 0.05) lumbar spine, total hip, femoral neck, narrow neck BMD, and body mass index compared with controls. However, type 2 diabetes did not appear to have a significant effect (p > 0.05) on TBS, trabecular microarchitectural parameters, and the incidence of hip and non-spine fracture. Full article

Case studies of climate adaptation approaches are needed to inform the broader use of these strategies across longleaf pine (Pinus palustris Mill.) ecosystems in the Southern US. To address this need, we evaluated overstory structure and tree regeneration in longleaf pine-hardwood stands, and a transition approach was implemented to intentionally facilitate change to encourage adaptive responses. Stand density reduction and species selection were prescribed to reduce tree vulnerability to drought stress. Turkey oaks (Quercus laevis W.) were also planted as a part of an assisted population migration strategy. After the treatments, Hurricane Michael impacted the study stands. The percent reduction in large overstory longleaf pines due to the hurricane was 6.3 ± 6.1% (grand mean ± standard deviation, which was derived from the stand means). At least one live planted turkey oak was present in 74 ± 26% of the planted clusters of turkey oaks that could be located six years after planting them. Our findings demonstrate the ability of transition stands to accommodate a large-scale disturbance event and maintain ecosystem functionality, the desired stand structure, and species composition. The relative success of forestry assisted migration plantings of turkey oaks may alleviate some concerns about the risk of maladaptation. Full article

In this work, we address the solvability of a Riemann–Liouville-type fractional-impulsive integral boundary value problem. Under some conditions on the spectral radius corresponding to the related linear operator, we use fixed-point methods to obtain several existence theorems for our problem. In particular, we obtain the existence of multiple positive solutions via the Avery–Peterson fixed-point theorem. Note that our linear operator depends on the impulsive term and the integral boundary condition. Full article

If lettuce is contaminated in the field, Shiga toxin-producing E. coli (STEC) O157:H7 can survive through the distribution chain. Prolonged cold storage during transportation may impact pathogen physiology, affecting subsequent stress survival and virulence. Greenhouse-grown Romaine lettuce, inoculated with three STEC O157:H7 strains, was harvested after 24 h and stored at 2 °C for 5 d following 4 h at harvest temperature (9 °C or 17 °C). Culturable, persister, and viable but non-culturable (VBNC) cells were quantified. Virulence was evaluated using Galleria mellonella and acid tolerance at pH 2.5 and tolerance to 20–25 ppm free chlorine were quantified. Colder harvest temperature (9 °C) before cold storage led to greater transformation of STEC O157:H7 into dormant states and decreased virulence in most cases. Increasing length of cold storage led to decreased virulence and acid tolerance of STEC O157:H7 on lettuce, while having no significant effect on chlorine tolerance. These findings highlight that entry of STEC O157:H7 into dormant states during harvest and transportation at cold temperatures leads to decreased stress tolerance and virulence with increasing cold storage. Changes in STEC O157:H7 physiology on lettuce during cold storage can be integrated into risk assessment tools for producers, which can assist in identifying practices that minimize risk of STEC O157:H7 from consumption of lettuce. Full article

Fear of cancer recurrence (FCR) affects approximately 50% of family caregivers. While FCR in cancer patients has been well-documented, less is known about the experience of FCR in family caregivers. This study aimed to qualitatively explore the distinct characteristics of FCR in family caregivers. A focus group and semi-structured interviews were conducted via videoconferencing with family caregivers of cancer survivors (stages I–III, finished treatment, no recurrence). Participants were recruited through Canadian hospitals, community partners, and social media. The focus group and qualitative interviews explored family caregivers’ experiences of FCR, including its content, frequency, impact, and management. A reflexive thematic analysis was used. In total, twenty family caregivers participated. Six participated in the focus group. Sixteen participated in the interviews. Two participated in both. Family caregivers described their experience of FCR as all-consuming, constant, and marked by a sense of helplessness. Qualitative analysis revealed a major theme of relational aspects of FCR in family caregivers, with the following four inter-related themes: patient-centric hypervigilance, self-silencing, FCR as isolating, and finding support. This qualitative study examined the experiences of family caregivers living with FCR. Our findings highlight that relational factors shape how family caregivers experience and manage their FCR. High-quality survivorship care should be redefined to include FCR interventions tailored to family caregivers. Full article

Background: Lipid nanoparticles (LNPs) have proven effective in delivering RNA-based modalities. Rapid approval of the COVID-19 vaccines highlights the promise of LNPs as a delivery platform for nucleic acid-based therapies and vaccines. Nevertheless, improved LNP designs are needed to advance next-generation vaccines and other gene therapies toward greater clinical success. Lipid components and LNP formulation excipients play a central role in biodistribution, immunogenicity, and stability. Therefore, it is important to understand, identify, and assess the appropriate lipid components for developing a safe and effective formulation. Herein, this study focused on developing a novel Polysorbate-80 (PS-80)-based LNP. We hypothesized that substituting conventional linear PEG-lipids with PS-80, a widely used, biocompatible injectable surfactant featuring a branched PEG-like structure, may change the LNPs biodistribution pattern and enhance long-term stability. By leveraging PS-80’s unique structural properties, this study aimed to develop an mRNA-LNP platform with improved extrahepatic delivery and robust freeze/thaw tolerance. Methods: We employed a stepwise optimization to establish both the lipid composition and formulation buffer to yield a stable, high-performing PS-80-based SARS-CoV-2 mRNA-LNP (SC2-PS80 LNP). We compared phosphate- versus tris-based buffers for long-term stability, examined multiple lipid ratios, and evaluated the impact of incorporating PS-80 (a branched PEG-lipid) on in vivo biodistribution. Various analytical assays were performed to assess particle size, encapsulation efficiency, mRNA purity, and in vitro potency of the developed formulation and a humanized mouse model was used to measure its immunogenicity over six months of storage at −80 °C. Results: Replacing the standard 1,2-dimyristoyl-rac-glycero-3-methoxy polyethylene glycol-2000 (PEG-DMG) lipid with PS-80 increased spleen-specific expression of the mRNA-LNPs after intramuscular injection. Formulating in a tris-sucrose-salt (TSS) buffer preserved the LNP’s physicochemical properties and in vitro potency over six months at −80 °C, whereas a conventional PBS-sucrose (PSS) buffer was less protective under frozen conditions. Notably, TSS-based SC2-PS80 LNPs elicited potent humoral immunity in mice, including high anti-spike IgG titers and robust pseudovirus neutralization, comparable to freshly prepared formulations. Conclusions: A PS-80-based mRNA-LNP platform formulated in TSS buffer confers improved extrahepatic delivery, long-term frozen stability, and strong immunogenicity against SARS-CoV-2 following six months. These findings offer a promising pathway for the design of next-generation mRNA vaccines and therapeutics with enhanced stability and clinical potential. Full article

Background: Adolescent and young adult (AYA) cancer survivors have unique needs, yet few tailored rehabilitation programs exist. CaRE-AYA is an 8-week multidimensional rehabilitation program for AYAs that targets impairments, activity limitations and participation restrictions and comprises an individualized exercise prescription and weekly group-based exercise and self-management education. Methods: We conducted a single-arm multi-method pragmatic feasibility study evaluating CaRE-AYA’s feasibility, acceptability, and safety (primary outcomes) and assessed disability, physical functioning, mental health, and social functioning at baseline (T0), immediately post-intervention (T1), and 3 months post-intervention (T2). Results: Twenty-five participants (median age: 32.8, 76% female) were enrolled. Participation (60%), retention (84% at T1, 72% at T2), and program adherence (76% for education classes, 74% for exercise classes) supported feasibility. Qualitative interviews (n = 9) supported strong perceptions of feasibility and acceptability. No serious adverse events (≥grade 3) attributed to CaRE-AYA occurred. Conclusions: The results suggest CaRE-AYA is feasible, acceptable, and safe. A randomized controlled trial is needed to determine the effectiveness. Full article

It is imperative that researchers include the perspectives from key voices regarding early support practices, yet very few studies have included direct assessment of autistic individuals and parents of young autistic children. Despite emerging evidence of effectiveness of naturalistic developmental behavioral intervention (NDBI) strategies, it is currently unknown whether autistic adults and parents of autistic individuals know about NDBI and if they view NDBI strategies as socially valid practice. We aimed to explore the perceptions of autistic adults and parents of young autistic children regarding the social validity of NDBI strategies implemented in community preschool classrooms and their dissemination potential. We conducted a convergent mixed methods research design to collect quantitative survey data and qualitative semi-structured interview data. We received survey responses from 33 autistic adults and 37 parents of young autistic children and interviewed 12 autistic adults and 12 parents of young autistic children. We conducted a series of paired samples and independent samples t-tests to compare perceptions between groups and thematic analysis to analyze qualitative data. Results indicated high levels of social validity for NDBI across both groups of participants and the need for dissemination of NDBI. Agreement between autistic adults and parents of young autistic children on the social validity of NDBI and recommendations for dissemination are promising preliminary findings that NDBI researchers and practitioners may draw upon when engaging in collaborative support planning and participatory research efforts. Full article

Background/Objectives: To correlate size changes in undifferentiated pleomorphic sarcoma (UPS) on magnetic resonance imaging (MRI) after neoadjuvant chemoradiation therapy (nCRT) with pathological response, risk of local recurrence, and therapeutic regimens. Methods: This retrospective study analyzed clinical, pathological, and imaging data from 39 biopsy-proven UPS subjects. Four readers measured the tumor dimensions before and after nCRT, including two perpendicular axial diameters and the longest coronal/sagittal diameter. Three cross-sectional areas and bounding volume were also calculated. Responders (pR) were defined as having ≤10% viable cells and non-responders (pNR) as having more. Inter-reader agreement was evaluated using Kendall’s concordance coefficient. Changes in tumor size were compared between pR and pNR using one-way ANOVA and Tukey’s HSD test for multiple comparisons of means. Results: pR showed a greater increase in size across all measurements compared to pNR. For the longest axial diameter, the mean increase was 30% ± 35% for pR and 14% ± 31% for pNR, with a mean difference (pR-pNR) of 16% (95% CI: 6–27%, p = 0.003). In tumors treated with radiotherapy alone, pR exhibited larger size increases in all dimensions compared to pNR. In contrast, in the chemoradiation group, pR showed a slight increase, while pNR generally shrank, although these differences did not reach statistical significance. Notably, pNR with local recurrence exhibited a reduction in all tumor dimensions compared to pNR without local recurrence. Conclusions: This exploratory study suggests that tumor size changes may predict pathological response and local recurrence after nCRT in UPS; however, the small sample size limits the generalizability of these findings. Full article

Cardio-Kidney-Metabolic (CKM) Syndrome is a complex systemic disorder characterized by interactions between metabolic risk factors such as obesity, Type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). These interactions contribute to multi-organ dysfunction and a heightened risk of cardiovascular complications. The American Heart Association (AHA) emphasizes the importance of a comprehensive approach to CKM management, incorporating social and environmental determinants of health (SEDH) to better understand disease progression and outcomes. Among these determinants, neighborhood walkability—the extent to which an area supports walking and physical activity—has emerged as a critical yet understudied factor influencing CKM health. This scoping review aims to synthesize the existing evidence on the relationship between neighborhood walkability and CKM outcomes, examining potential pathways, health disparities, and opportunities for targeted interventions. Full article