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Cancer-associated fibroblasts (CAFs) form a dynamic ecosystem that critically influences tumor progression and therapeutic response. Although recent advances in single-cell and spatial omics have uncovered profound stromal diversity, interpreting the mechanistic relevance of this complexity remains a challenge. Here, we propose a more unifying conceptual framework to bridge high-dimensional data with experimental biology. By categorizing CAFs into conserved molecular phenotypes and distinct spatial archetypes, this model illustrates how CAF identities are intimately linked to local tissue contexts. This refined framework brings the complexity of the tumor stroma into greater focus, underscoring the necessary transition from broad stromal targeting toward precision, context-specific modulation. Ultimately, we hope this integrated effort will aid in the collaborative development of next-generation therapies that selectively target pathogenic stroma in cancer to improve patient outcomes.

The American Association of Colleges of Pharmacy (AACP), the national organization representing pharmacy education in the United States, continues to advance strategic engagement with a focus on advocacy. The 2025-2026 AACP Strategic Engagement Committee (SEC) was charged with contributing to the development of an Advocacy WebCenter, now known as the AACP Advocacy Center, to serve as a centralized resource for schools and colleges of pharmacy, providing timely information on legislative, professional, regulatory, and pharmacy education advocacy issues. The 2025-2026 SEC was tasked with establishing a systematic mechanism to enhance communication between AACP leadership and members on advocacy-related priorities and concerns. The SEC also evaluated and refined the definition of advocacy in alignment with AACP's strategic agenda and explored the competencies needed to effectively serve as an Advocacy Champion. These efforts build upon the work of the 2024-2025 SEC, incorporating prior focus group findings and aligning with the updated Accreditation Council for Pharmacy Education (ACPE) Standard 2.f.1 related to advocacy.

The One Big Beautiful Bill Act eliminates the Grad PLUS program and establishes annual and aggregate federal student loan caps beginning July 1, 2026. Physician associate/assistant (PA) programs are currently classified as graduate-level for federal aid purposes, potentially subjecting PA students to lower borrowing limits than other health professions. This study examined perceptions of federal loan caps and anticipated impacts on PA education and workforce. A cross-sectional, anonymous, web-based survey was administered in January 2026 to pre-PAs, PA students, and practicing PAs across the United States. Items assessed demographics, borrowing patterns, perceived affordability, and anticipated behavioral responses under a proposed $20,500 annual federal loan cap. Descriptive statistics, chi-square analyses, independent samples t -tests, and multivariate logistic regression were performed. Among 4,000+ respondents, concern regarding restrictions was high; 72% of PA students and practicing PAs reported being very or extremely concerned. Overall, 90.8% anticipated decreased applicant volume and 89.6% predicted reduced diversity under a $20,500 annual cap. Logistic regression (N = 3,106) indicated that each additional economic disadvantage factor increased odds of reporting discouragement from pursuing PA education by 20% (odds ratio = 1.20; 95% confidence interval: 1.12-1.29). Underrepresented in medicine respondents were disproportionately represented in the highest educational cost and borrowing categories ( p < 0.001). Respondents anticipate negative implications of federal borrowing caps for PA applicant volume, diversity, and service to underserved areas. Financial vulnerability appears central to perceived feasibility of PA education under proposed loan limits, raising equity and workforce sustainability concerns.

Therapeutic cancer vaccines represent a rational immunotherapeutic strategy aimed at inducing tumor-specific adaptive immune responses in patients with established malignancies. In contrast to prophylactic vaccines, these approaches must function within immunosuppressive tumor microenvironments characterized by antigenic heterogeneity, immune dysfunction, and dynamic tumor evolution. Effective vaccine design requires the integration of three essential components: the selection of appropriate tumor-associated or tumor-specific antigens, efficient delivery platforms that enable antigen presentation, and adjuvant systems that promote robust T-cell priming and expansion. Initial clinical investigations in B-cell malignancies and multiple myeloma demonstrated that idiotype-based vaccines can elicit tumor-specific immune responses. However, durable clinical benefit has been inconsistent, reflecting limitations in antigen selection, suboptimal immunogenicity, and tumor-mediated immune evasion. Over the past decade, advances in tumor genomics, next-generation sequencing, and immune monitoring have enabled the development of next-generation vaccine platforms, including dendritic cell-based approaches, personalized neoantigen vaccines, and mRNA-based technologies. Emerging evidence suggests that vaccine efficacy is highly dependent on disease context. Biologically favorable settings such as minimal residual disease (MRD) and post-transplant immune reconstitution provide reduced tumor burden and improved immune competence, thereby enhancing the likelihood of effective immune priming. In parallel, combination strategies incorporating immune checkpoint inhibitors, immunomodulatory agents, and cellular therapies are increasingly being explored to overcome tumor-induced immunosuppression. This review synthesizes current knowledge of therapeutic cancer vaccines in B-cell malignancies and multiple myeloma, with emphasis on immunologic mechanisms, antigen selection, vaccine platforms, and clinical evidence. We further propose a conceptual framework integrating tumor biology, immune context, and combination strategies to guide the rational development of next-generation vaccine therapies.

Fluorescent labeling or tagging of viral proteins is crucial for understanding molecular virology and guiding antiviral interventions. However, traditional methods using large tags are often invasive, impeding visualization of viral proteins in their native states. We detail a methodology combining an amber-free lentiviral packaging system with amber (TAG stop codon) suppression - genetic code expansion and site-specific bioorthogonal click labeling. Amber suppression enables site-specific incorporation of a non-canonical amino acid (ncAA) bearing strained alkynes or alkenes into a target protein. The ncAA-containing viral protein can then be labeled with a fluorophore conjugated with a click-chemistry-reactive functional group via copper-free click chemistry, allowing single-residue fluorescent labeling with minimal impact on protein structure and function. However, amber stop codons that serve as native termination signals in viral genomes can be inadvertently suppressed during genetic code expansion, leading to protein readthrough and unpredictable experimental outcomes. Here, we provide a step-by-step method for constructing a complete amber-free lentivirus, which overcomes this limitation by providing an amber-free viral background. We then describe a stepwise workflow for single ncAA incorporation into the Omicron spike decorated on amber-free lentiviruses, followed by the attachment of organic fluorophores via click chemistry. The methods described here are, in principle, adaptable to other viral surface glycoproteins, non-surface lentiviral proteins, and pseudotyped viral systems, with appropriate optimization and validation as needed.

Precise experimental information on hyperon-nucleon interactions is scarce but of paramount importance to our understanding of the inner structure of compact stars. In this Letter, we report the first experimental results of correlation functions between deuterons (d) and &#x39b; hyperons in Au+Au collisions at sqrt[s_{NN}]=3.0&#x2009;&#x2009;GeV measured by the STAR experiment at the Relativistic Heavy Ion Collider. A clear enhancement at small relative momenta has been observed in the correlation function. Through a Bayesian inference analysis, the source size parameters as a function of collision centrality and the spin-dependent strong interaction parameters (scattering length f_{0} and effective range d_{0}) are extracted using the Lednick&#xfd;-Lyuboshitz formalism. The derived doublet spin state parameters (f_{0}, d_{0}) lead to a novel method to precisely determine &#x39b; separation energy for the weakly bounded hypertriton _{&#x39b;}^{3}H.

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Translation is a fundamental process of life, yet methods to systematically investigate its fidelity have been limited. Most previous estimates of translation-error rates have relied on reporter assays that evaluate only a single codon and fail to capture the full spectrum of translation errors. Here, we present a proteome-wide analysis of mass spectrometry data that directly estimates nearly all pairwise amino-acid substitution rates, revealing mistranslation rates and spectra per amino acid and per codon. Applying this method to ribosomal variants of Escherichia coli reported to differ in translation fidelity, we found no significant differences among their overall error rates, estimated here at 2 per 1000 amino acids. Instead, each variant exhibited unique mistranslation profiles; the putative error-prone variant preferentially misread near-cognate codons at the third position, with a bias that likely led to prior overestimates of its error rate. We also tested the translational-accuracy hypothesis of codon usage, which predicts that codons enriched in highly expressed genes are selected for translational accuracy. Contrary to that prediction, codons favored in highly expressed genes are not translated more accurately. These results underscore the necessity of proteome-wide measures of translation accuracy and highlight the limitations of single-codon approaches for characterizing translation fidelity.

Background: Both neuromodulation and physical therapy have been shown to mitigate motor and non-motor symptoms of Parkinson's disease. To date, no studies have examined the integration of transcutaneous auricular vagus nerve stimulation (taVNS) with physical therapy approaches for improving Parkinsonian symptoms. The purpose of this study was to investigate the safety, tolerability, and feasibility of combining taVNS with physical therapy to enhance the therapeutic benefits of exercise as medicine in a clinical setting. Methods: Participants were randomly assigned to receive active or sham bilateral taVNS in combination with PT for 12 visits over 6 weeks. Safety, tolerability, and feasibility outcomes were primary. Secondly, exploratory analyses of changes in cardiovascular and motor function over time were also performed. Results: Overall, taVNS was safe and well-tolerated prior to PT. Cardiovascular analyses suggest that active taVNS may augment HR response to exercise compared to sham. For motor outcomes, both groups showed significant overall improvements; however, no significant between-group differences were found. Conclusions: The preliminary results obtained in this pilot trial confirm that taVNS combined with physical therapy for individuals with PD is safe and feasible. The exploratory cardiovascular and motor findings support the need for larger, adequately powered clinical trials investigating the integration of taVNS into PT and exercise methods for improving PD symptomology. Trial registration: ClinicalTrials.gov NCT05871151.

Clostridioides difficile (C. difficile) is the leading cause of hospital-acquired life-threatening diarrhea. C. difficile toxins TcdA and TcdB contain a glucosyltransferase domain (GTD) that glucosylates and inactivates host GTPases, disrupting the actin cytoskeleton and compromising epithelial integrity. TcdB, the most potent virulence factor, drives disease progression and is a high-priority target forC. difficiletreatment and prevention. The iminosugar isofagomine has been shown to inhibit the GTD activity of TcdB by an uncompetitive inhibition mechanism, but requires the uridine 5'-diphosphate (UDP) reaction product. Compound classes synthesized here, ranging from isofagomine analogues to acyclic mimics, probe which modifications can tap into UDP-binding energy to enhance inhibition. Structure-activity relationship studies of isofagomine derivatives demonstrate remarkable specificity for isofagomine and limited advantage in accessing the UDP-binding site. Fluorescence and absorbance assays allowed facile inhibition assessment of TcdB's UDP-glucose hydrolysis. The molecules reported here guide scaffolds for future catalytic site inhibitors.

It is well known that healthcare workers experience poor outcomes associated with workplace stress and secondary trauma from on-the-job events. In order to respond, healthcare systems must evolve. Yet it is unknown how trauma-informed approaches (TIAs) may effectively address system-level factors within healthcare settings. The aim of this study was to: (1) map out the existing knowledge about TIAs integrated within healthcare organizations and (2) map out the reported health impact of TIA integration on healthcare workers. A scoping review was conducted using Fink's five-step approach for systematic reviews, with scoping review modifications based on Joanna Briggs Institute guidelines. A total of 6,162 participants from 17 articles published between 2018 and 2024 were included in the retained sample. Key findings indicate: (1) TIA support for healthcare workers is insufficient, necessitating systemic organizational change led by effective leadership, and; (2) TIA integration may protect healthcare workers from trauma and burnout, fostering resilience and well-being. TIAs within healthcare were associated with well-being among healthcare workers. Leadership plays an integral role in establishing trauma-informed organizational climates. Further work must be conducted with a large sample of healthcare workers to explore the perceived impact of trauma-informed system-level efforts aimed at promoting hospital staff's well-being.

The history of Newfoundland, Canada, is told through the cod fishery that led to the development of thousands of outport settlements connected by boat and sea. The collapse of the Northern cod stock and the 1992 fishing moratorium that put 30 000 Newfoundlanders out of work, reshaped the ecological, economical, and social fabric of the island. In the years that followed, fisheries for shellfish became the most important, both in volume and value. I explore the changing landscape of Newfoundland ports and fisheries from 1998 to 2023. The number of fishing ports, vessels, and fishers all declined by more than 70%, while the average number of species fished per port declined by 25%. Fisheries catches dropped by 25% from 1998 to 2023, with shellfish accounting for the greatest share throughout. The total economic value of the fishery was relatively stable from 1998 to 2023.

Racial and ethnic disparities in access to medicines persist across the US. Community pharmacies serve as critical access points for prescription drugs, yet their availability varies widely, potentially contributing to health disparities. We estimated the share of the population living within ten minutes of a community pharmacy across counties, by race and ethnicity, during the period 2010-23. We linked these measures to race and ethnicity-specific, state-level estimates of age- and prevalence-standardized medication use for twenty-seven health condition categories through 2019. A 1&#xa0;percent increase in people living within ten minutes of a community pharmacy at the state level was associated with 0.7&#xa0;percent higher use of medications per prevalent case. This association was strongest for Asian/Pacific Islander, Black, and Hispanic populations. In addition, a 1&#xa0;percent increase in ten-minute community pharmacy access was associated with a 0.52&#xa0;percent decrease in racial and ethnic disparities in medication use. These findings suggest that uneven community pharmacy access may exacerbate racial and ethnic disparities in medication use. Policy makers seeking to improve medication access should consider targeted interventions to preserve or expand pharmacy availability for underserved communities.

Prominent postharvest pathogens of tomato fruit include Alternaria spp. and Botrytis cinerea. While the control of such pathogens typically relies on synthetic chemical fungicides preharvest, microbial biocontrol agents are a sustainable and promising alternative postharvest. Bacillus velezensis SH1 and SH2 and Pseudomonas azotoformans SH3 were previously isolated from disease-suppressive compost tea. To evaluate their effectiveness against tomato pathogens, the bacteria, their cell-free culture filtrates and precipitated subfractions were tested against mycelial growth in vitro. Suppressive effects were also examined against disease development on tomato fruit. From bacterial precipitates, lipopeptides were further identified and quantified. Results showed that all bacteria controlled growth of the three fungi, with P. azotoformans SH3 generally being the most effective. However, in vivo disease lesion suppression varied according to pathogen and tomato cultivar. In cell-free culture filtrate assays, mycelial inhibition was observed from all bacteria against B. cinerea, whereas mainly B. velezensis SH1 inhibited A. solani and A. alternata growth. For bacterial precipitates, B. velezensis SH1 was the best treatment overall, while P. azotoformans SH3 precipitates showed no inhibition. Both B. velezensis strains were confirmed to produce fengycins, iturins and surfactins. Fengycins seemed to play the most important role in the observed activity of the Bacillus lipopeptides. Results suggest that antifungal activity by the bacterial strains is imparted through the release of antifungal compounds, although the role of the produced compounds was variable.

Wearable biosensors enable real-time monitoring of physiological stress. While methadone maintenance treatment (MMT) is effective in opioid use disorder (OUD), inter-dose withdrawal and stress dysregulation remain challenges. We sought to identify wearable-derived digital biomarkers of stress in individuals with OUD receiving MMT. In this cross-sectional, laboratory-based study, 72 adults completed 76 sessions (14 OUD pre-methadone dose, 15 OUD post-dose, 47 healthy controls) of a standardized protocol of calm tasks (e.g., relaxing videos, positive memory recall) followed by stress-inducing tasks (e.g., horror video, mental arithmetic, negative memory recall). Physiological data were continuously recorded using the Empatica E4 wristband (heart rate, heart rate variability [HRV], electrodermal activity [EDA], skin temperature, accelerometry). Features were extracted using open-source toolkits. Linear mixed-effects models tested calm-stress differences and group effects; Random Forest classifiers evaluated calm versus stress classification. Among 340 extracted features, 63 (18.5%) significantly differentiated calm from stress across all groups, with EDA- and accelerometry-derived features showing the most consistent stress sensitivity. Compared with controls, OUD participants demonstrated higher baseline arousal and altered stress reactivity, with the largest responses observed in the pre-dose group. Random Forest models performed best for cognitively demanding tasks (up to 98% accuracy) and more modestly for other tasks. Wearable sensors can detect multidimensional alterations in resting-state physiology and stress reactivity among individuals with OUD on methadone. Future studies should validate these candidate biomarkers and test whether integrating wearable-derived stress detection into treatment improves clinically meaningful outcomes, such as stress management, craving, risk of return to opioid use, and retention.

Since endorsement of the Global Vaccine Action Plan, and continued emphasis under Immunization Agenda 2030, the number of functional National Immunization Technical Advisory Groups (NITAGs) has expanded rapidly, creating increased demand for training in evidence-informed decision making. To support timely national policy decisions relating to immunization, innovative and flexible training approaches are needed. This paper describes and evaluates a novel, webinar-based Evidence-to-Recommendation (EtR) training designed to support NITAGs in developing evidence-based recommendations for transitioning from pentavalent plus inactivated polio vaccine to combined hexavalent vaccines. Between January and June 2025, a five-part EtR webinar series focused on the hexavalent vaccine transition was delivered to countries, primarily within the WHO African Region, who qualify to receive financial and technical support from Gavi, the Vaccine Alliance, to help introduce new vaccines and strengthen their immunization systems. The series emphasized identification of evidence across EtR domains, and a cohort-based model to facilitate regional peer learning. Effectiveness of the webinar series was assessed through electronic post-webinar surveys and virtual key informant interviews. NITAGs from 32 countries participated in one or more webinars, including nine in three or more. Across participating countries, participants consistently rated the webinars as useful, particularly valuing country experiences and practical guidance on EtR domains. Qualitative feedback highlighted peer learning as the most valuable component of the webinar series, alongside practice guidance on EtR domains such as feasibility and resource considerations, and NITAGs showed strong interest in continued technical support, practical, peer-to-peer learning or "twinning", and operational guidance for hexavalent vaccine introduction.

Accurate wetland mapping is essential for monitoring ecosystem health and guiding conservation planning efforts. This study evaluated the effectiveness of deep learning architectures and high-resolution National Agriculture Imagery Program (NAIP) imagery for classifying diverse vegetation cover across five public land holdings in three states with significant seasonally flooded, emergent wetland habitats in the southeastern United States. We built and tested deep learning models in ArcGIS Pro using three architectural encoders (U-Net, PSPNet, and DeepLabV3) with different input combinations, including NAIP natural color (RGB), Near-Infrared bands (NIR), Normalized Difference Vegetation Index (NDVI), Digital Elevation Models (DEM), and Texture metrics derived from NAIP imagery using Gray Level Cooccurrence Matrix (GLCM) features, resulting in eight (8) input combinations and three (3) rotational augmentations (0&#xb0;, 30&#xb0;, and 60&#xb0;). Results revealed differences in classification accuracy ranging from 71 to 90% across sites, with Kappa scores from 0.54 to 0.81. We also found differences in model performance under alternating conditions and in the impact of combinations on performance metrics and computational time. Classification of the forested and scrub-shrub classes was consistent with F1 scores above 0.90 at several sites. However, distinguishing open water, aquatic beds, and emergent marshes became more difficult for some model-training architectures. At Mingo National Wildlife Refuge, clear spectral signatures and high-quality training data yielded the highest accuracy, thereby improving classification performance. In contrast, classification accuracy was lower for Red Slough and Choctaw East Wildlife Management Areas. Across all scenarios, the U-Net and DeepLabV3 models consistently outperformed the PSPNet model, achieving mean F1 scores close to 0.91, whereas PSPNet underperformed, with several configurations falling below 0.80. These results explain that while deep learning methods are effective and adaptable across different wetland types, their success depends on the ecological diversity of these environments. Overall, this research highlights the potential of deep learning for wetland monitoring and its crucial role in supporting conservation and management efforts.

Racial disparities in total joint arthroplasty (TJA) utilization are persistent and well-characterized. Improving surgeon workforce diversity may attract patients from diverse backgrounds. We sought to determine whether the recent hiring of an arthroplasty surgeon of underrepresented minority (URM) background in a predominantly non-URM arthroplasty practice was associated with increased patient diversity. We retrospectively reviewed all primary and revision elective TJAs by six arthroplasty surgeons at our institution from September 2022 to September 2023. Primary outcomes included patient age, sex, and race/ethnicity. Secondary outcomes included patient-reported outcome measures (PROMs) at preoperative and 3-month postoperative follow-up. Comparison cohorts included the following: (1) a recently hired URM attending surgeon; (2) a recently hired non-URM attending surgeon; and (3) four senior non-URM attending surgeons. Unpaired t-tests were used to compare means for continuous variables and chi-squared tests for qualitative variables. Overall, 2,101 patients were included, and 168 patients were included in group 1 (URM surgeon), 75 in group 2 (non-URM surgeon); and 1,858 in group 3 (non-URM senior surgeons). Compared with groups 2 and 3, patients within group 1 comprised a markedly greater proportion of female, Black, and Hispanic/Latino patients (64.8%, 33.3% and 59.7%, respectively, P < 0.01). Racial and ethnic demographic differences persisted when examining patients treated by the non-URM division in the year before the hiring of the URM surgeon. Subgroup analysis of URM patients showed markedly improved SF-12 mental scores for URM patients treated by the URM surgeon compared with those treated by senior surgeons (P < 0.05). Compared with an experience-matched non-URM surgeon and non-URM senior surgeons in the same division, the URM surgeon saw a markedly greater proportion of minority patients in their first year of practice. Hiring diverse orthopaedic faculty may represent a viable strategy for improving health care utilization for minority patients in arthroplasty practices.