Citations

Abstract In many cancers, a major barrier to effective immunotherapy is the dominance of tumor-associated myeloid cells (TAMs), which establish a profoundly immunosuppressive tumor microenvironment (TME). This challenge is particularly pronounced in glioblastoma (GBM), where myeloid cells represent the predominant immune population and actively suppress antitumor immunity. Identifying targets that can reprogram TAMs from an immunosuppressive state toward a pro-inflammatory, antigen-presenting phenotype remains a critical unmet need. Here, we identify the voltage-gated proton channel Hv1 as an immune-restricted regulator of glioma-associated macrophage function. Hv1 is notable not only for its immune-specific expression but also for its established roles in central nervous system (CNS) pathologies, where Hv1 depletion alters microglial and macrophage polarization, reduces myeloid accumulation, dampens inflammatory cytokine production, and limits secondary tissue damage. However, Hv1’s role in shaping the GBM immune landscape—particularly in vivo—has remained poorly understood due to low Hvcn1 transcript abundance and the lack of reliable antibodies and genetic tools. Given the dominance of myeloid cells in GBM and their central role in tumor immune regulation, we sought to define Hv1 function within this highly immunosuppressive brain TME. Analysis of patient datasets revealed that elevated Hv1 expression correlates with poor clinical prognosis. Consistently, Hv1 loss significantly prolonged survival in multiple murine glioma models. Using in vivo two-photon imaging and spectral flow cytometry, we show that Hv1 depletion reprograms TAMs toward an anti-tumor phenotype characterized by enhanced tumor cell phagocytosis, improved antigen presentation, and increased T cell infiltration. By generating new Hv1 reporter and conditional mouse lines, we further demonstrate that tumor-associated microglia and infiltrating macrophages are the principal sources of Hv1 and markedly upregulate its expression in response to glioma. Notably, selective deletion of Hv1 in infiltrating macrophages phenocopied the survival benefit observed with global Hv1 loss. Mechanistically, using mass spectrometry and genetic models, we identify the Stimulator of Interferon Genes (STING) as a previously unrecognized binding partner of Hv1, placing Hv1 within the STING signaling pathway, a central regulator of innate and adaptive immune responses. Together, these findings fill a critical gap in understanding myeloid Hv1 function in GBM and identify Hv1 as a promising target for reprogramming the tumor immune microenvironment. Citation Format: Jiaying Zheng, Lingxiao Wang, Shunyi Zhao, Katayoun Ayasoufi, Meijie Wang, Praveen N. Pallegar, Peter R. Strege, Langni Liu, Yushan Wan, Wenjing Zhang, Emma N. Goddery, Manling Xie, Arthur Beyder, Aaron J. Johnson, Long-Jun Wu. Myeloid Hv1-STING axis tunes glioma immunity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr A016.

The results underscore a multifaceted interaction among cardiopulmonary hemodynamics, right heart pressures, ventilatory response, and autonomic regulation. In particular, altered RV-PA coupling correlated with heightened sympathetic drive, indicating that cardiopulmonary efficiency and hemodynamics may influence central autonomic outputs. This suggests that mechanical stress or overload in the right heart could modulate sympathovagal balance, thereby contributing to altered autonomic responses during exercise in patients with cardiopulmonary disorders.

Abstract Purpose: The Pancreatic Cancer Detection Consortium (PCDC) performed a blinded Early Detection Research Network–defined phase II biomarker bakeoff study of blood-based biomarker panels. The aims were to evaluate panel performance, to compare the panels’ performance with that of cancer antigen 19-9 (CA19-9) alone, and to evaluate the performance of new combinations of the individual biomarkers. Experimental Design: Ten biomarkers representing eight biomarker panels and CA19-9 were evaluated using plasma, serum, and germline DNA from 140 stage I to IV pancreatic ductal adenocarcinoma (PDAC) cases and 140 controls from three tertiary care institutions, with controls frequency matched to cases on age and sex. LASSO regression was employed to explore new biomarker combinations. The primary metric was area under the receiver operating characteristic curve (AUC). Results: The study population was 51% female, with median age 67.3 (minimum: 45, maximum: 90) years. Biomarker panel AUCs ranged from 89.9 to 96.3; the AUC for serum CA19-9 alone was 91.7 [95% confidence interval (CI), 87.8–95.6]. Two panels had significantly higher AUCs than serum CA19-9 alone, the CA19-9/FUT2/3 panel (AUC = 96.3, P = 0.002), and the tissue factor pathway inhibitor/tenascin C (TFPI/TNC-FNIII-C) panel (AUC = 95, P = 0.01). Exploratory models to recombine biomarkers retained all but two biomarkers [optimism-corrected AUC = 96.4 (94–98.9)]. Conclusions: The CA19-9/FUT2/3 panel was the best performing panel in this biomarker bakeoff. Its evaluation in larger studies is warranted. Biomarker bakeoffs are an effective strategy for comparing the performance of promising biomarkers for pancreatic cancer early detection, and the PCDC is well poised to conduct such studies. Recommendations for performing such studies are provided.

OBJECTIVE: Accurate assessment of skin and skin changes across diverse populations is critical for patient health. To promote the knowledge and skills nurses need in practice to identify skin changes, nurse educators must include content on assessment of diverse skin tones in nursing education programs. This study’s objective was to develop and pilot education modules about the assessment of diverse skin tones to be part of an undergraduate nursing course. METHODS: In this quality improvement project, modules highlighted the importance of skin assessment and appropriate techniques for assessing erythema, pallor, cyanosis, and jaundice on diverse skin tones. Undergraduate nursing students completed a questionnaire evaluating the modules and their learning experience. RESULTS: The majority of students (≥70%) agreed or highly agreed that the modules were interesting, informative, engaging, and increased their knowledge. Comments to open-ended questions supported their evaluation ratings. CONCLUSIONS: Undergraduate nursing students positively received education modules on assessing patients with diverse skin tones. Students perceived the modules as having the potential to enhance their learning and assessment skills to prevent and detect skin changes associated with pressure injury. The modules serve as an example of a strategy to integrate education content about diverse skin tones into nursing curricula.

ABSTRACT Predicting delayed graft function (DGF) relies on donor, recipient, and perioperative factors. Despite the growing recognition that DGF duration strongly influences patient outcomes, no models currently address or predict its impact—highlighting an important gap in current research and clinical practice. This study aimed to develop an ensemble‐based machine learning model using perioperative data to predict DGF occurrence and duration. The gradient‐boosted decision trees model was trained and validated on 2725 patients, with k‐fold cross‐validation in an external cohort of 284 patients. Model performance was evaluated based on accuracy, ROC‐AUC, and other metrics using R and Python libraries. The binary DGF prediction model achieved a ROC‐AUC of 0.77, while the DGF duration classification model had an accuracy of 79.2%. DGF duration AUC values by time interval were 0.76 for 0–1 weeks, 0.81 for >1–2 weeks, 0.80 for >2–3 weeks, and 0.87 for >3 weeks; the overall macro‐averaged AUC was 0.81. The mean Brier score for multi‐class predictions was 0.14. External validation showed a 78% accuracy for DGF duration prediction. Acute kidney injury (AKI) and donor donation after circulatory death (DCD) status were key DGF predictors. The use of gradient‐boosted decision trees (GBDT) improves the prediction of both the likelihood and duration of DGF, addressing a current gap in kidney transplant patient care. By facilitating personalized transplant care, this model supports more effective perioperative planning and timely interventions, which may contribute to better patient outcomes.

Abstract Background & Aims Stricturing Crohn’s disease (CD) is a significant problem, and no selective anti-fibrotic therapies are available. Anti-inflammatory approaches are the mainstay of medical treatment. However, data on the efficacy of ustekinumab (USTE) in ileal stricturing CD are lacking. Our aim was to assess its efficacy in this setting. Methods We performed an international multicenter observational cohort study evaluating adult CD patients who received USTE within 6 months of imaging-confirmed symptomatic stricturing small bowel disease. Outcomes were rates of endoscopic balloon dilation (EBD), surgery, intervention (defined as the composite need for EBD or surgery), recurrent obstructive symptoms, and USTE persistence. Results Fifty-seven patients were included (51% female, median age 43 years). Median follow-up was 17 months. Intervention rates were 35%, 45%, and 69% of patients, at 12, 24, and 48 months, respectively. USTE persistence was 78%, 76%, and 52% at 12, 24, and 48 months. Estimated obstructive symptoms rates were 31% and 49% at 12 and 24 months, respectively. EBD within 6 months prior to starting USTE was associated with an increased risk of intervention. Increased bowel wall thickness on imaging, prior biologic use, and obstructive symptom duration were associated with USTE discontinuation. Occurrence of obstructive symptoms during treatment was associated with prior biologic use, EBD within 6 months of starting USTE, and a lower BMI. Conclusions USTE appears to be an appropriate medical option in biologic-experienced CD patients with ileal strictures. Further prospective data are needed to better define outcomes and predictors of response in this setting.

BACKGROUND: Social determinants of health (SDOH) are associated with adverse cancer outcomes, yet the prevalence and impact of SDOH screening across Commission on Cancer (CoC)-accredited programs are unknown. We evaluated national SDOH screening practices and their association with adherence to CoC quality measures. STUDY DESIGN: A cross-sectional survey of 1,445 CoC-accredited programs (October to December 2024) was linked to National Cancer Database data (2020 to 2022). Adult patients treated at 435 responding hospitals (30.1%) were included. Programs were categorized by routine outpatient SDOH screening status. Multivariable logistic regression assessed associations between screening and receipt of quality measure–concordant care, adjusting for screening duration, age, race, ethnicity, Charlson Comorbidity Index, insurance status, rurality, and program type or case count. RESULTS: Of 435 programs, 165 (37.9%) reported routine SDOH screening. Screening programs more frequently treated ≥10% Medicaid or uninsured patients (29.1% vs 19.6%, p = 0.023). Mean performance was higher at screening hospitals for breast radiation within 60 days (66.6% vs 64.6%, p = 0.046), colon adjuvant chemotherapy within 120 days (84.6% vs 81.9%, p = 0.018), and lung systemic therapy within 90 days (77.2% vs 75.4%, p = 0.043). On adjusted analysis, screening for more than 3 years was independently associated with timely colon adjuvant chemotherapy (odds ratio 1.05; 95% CI 1.01 to 1.07; p = 0.033). Findings persisted after excluding safety net hospitals. CONCLUSIONS: Only one-third of responding CoC programs routinely screen for SDOH. Sustained screening was independently associated with improved adherence to time-sensitive colon cancer chemotherapy, supporting integration of patient-level SDOH assessment into oncology care delivery.

ABSTRACT Background and Aims Pruritus is a frequent and debilitating symptom in primary biliary cholangitis (PBC), substantially impairing sleep, mood and quality of life. Peroxisome proliferator‐activated receptor (PPAR) agonists are promising second‐line therapies for patients with an inadequate response to ursodeoxycholic acid (UDCA). We conducted a systematic review and meta‐analysis to evaluate the efficacy of PPAR agonists on pruritus and health‐related quality of life (HRQoL) in PBC. Methods We systematically searched for randomised placebo‐controlled trials (RCTs) of PPAR agonists in PBC through December 2025. Eligible studies reported validated pruritus or HRQoL outcomes. Main outcomes were NRS and PBC‐40 total score. Pooled estimates were calculated using random‐effects models and expressed as mean differences (MD) with 95% confidence intervals (CI). Results Five RCTs evaluating bezafibrate, elafibranor and seladelpar ( n = 660; 390 PPAR agonist; 270 placebo) met the inclusion criteria. For pruritus intensity analyses, data were restricted to participants with moderate‐to‐severe baseline symptoms (NRS ≥ 4) when available. PPAR agonists significantly reduced NRS scores at 3 months (MD, −1.39; 95% CI: −2.49 to −0.29), 6 months (MD, −1.17; 95% CI: −1.96 to −0.38) and 12 months (MD, −1.73; 95% CI, −3.00 to −0.46); in individual agent analyses, bezafibrate and seladelpar reached statistical significance at two or more time points. While improvements were also noted in PBC‐40 itch‐domain and 5D‐itch score, an impact on overall HRQoL as reflected by PBC‐40 total score could not be demonstrated, with a lower level of certainty. Conclusions PPAR agonists, notably bezafibrate and seladelpar, reduce pruritus severity in PBC patients with moderate‐to‐severe symptoms and consistently improve itch‐specific outcomes. However, effects on global HRQoL remain uncertain. These findings underscore the incorporation of validated, symptom‐focused endpoints in future PBC trials.