Citations

Abstract Description CD8 T cell induced blood-brain barrier (BBB) disruption is an established mechanism of neuropathology. The pericyte is a MHC class I expressing neurovascular unit cell type which is critical for maintaining BBB integrity. However, the importance of pericyte antigen-restricted engagement by CD8 T cells is not fully understood. To determine the function of pericyte MHC Class I antigen presentation, we crossed the Pdgfrβ-creERT2 mouse to our novel H-2Db LoxP mouse developed by our laboratory. This transgenic mouse approach enabled us to target pericytes during neuroinflammation. We observed robust knockdown of H-2Db on Pdgfrβ+ pericytes during TMEV infection in these animals. The effect of conditional H-2Db knockdown on this cell type resulted in increased CD4 T cell, CD8 T cell, and B cells infiltration of the brain during TMEV infection, demonstrating an important role of Pdgfrβ+ pericytes for immune cell recruitment into the CNS. To our knowledge, this is the first study demonstrating an important role for MHC class I antigen presentation by pericytes in a murine model of neuroinflammation. Funding Sources Supported by R01NS122174 and R01NS103212 Topic Categories Neuroimmunology (NEUR)

Abstract Description The dura mater of the meninges recruits immune cells for CNS surveillance and response to infections, serving as a critical interface between the brain and the peripheral immune system. Theiler’s murine encephalomyelitis virus (TMEV) infection is a model neurotropic virus for which MHC class I molecules are critical for sterilizing immunity. Using spectral flow cytometry, we profiled the immune response in the dura mater in healthy and TMEV-infected wildtype mice. Acute TMEV infection resulted in the infiltration of diverse immune cell types into the dura mater, including increased cDC1, pDCs, monocytes, NK cells, CD4 T cells, and CD8 T cells. We next examined the importance of MHC class I molecules on diverse immune cell populations in the dura mater during acute TMEV infection. MHC class I deficiency resulted in increased numbers of CD4 T cells with high expression of PD1 in MHC class I-/- (H-2Kb-/-, H-2Db-/-) mice compared to WT mice 7 days post TMEV infection. This demonstrated the importance of MHC class I and CD8 T cells in modulating dura immune cell populations and implies a compensatory shift toward a CD4 T cell response during acute infection. Subsequent studies employing in vivo cell-specific ablation of MHC class I molecules in discrete cell types will further define the impact of antigen presentation on immune regulation and inflammatory outcomes within the dura mater. Topic Categories Neuroimmunology (NEUR)

PURPOSE Neoadjuvant immune checkpoint inhibitors (nICIs) have demonstrated high response rates in deficient mismatch repair/microsatellite instability–high (dMMR/MSI-H) gastroesophageal adenocarcinoma (GEA). The NEONIPIGA and INFINITY trials demonstrated high rates of pathologic complete response (pCR) in this patient population. Furthermore, the INFINITY trial explored the feasibility of managing these patients nonoperatively, demonstrating promising results. This study aimed to evaluate clinical outcomes of nICIs in resectable dMMR/MSI-H GEA, with a focus on the feasibility of nonoperative management (NOM). MATERIALS AND METHODS This retrospective cohort study included patients with resectable dMMR/MSI-H GEA and treated with nICIs ± surgery at the Mayo Clinic. Patients were identified from institutional records, and clinical data were retrospectively reviewed. Primary outcomes were clinical complete response (cCR) and pCR. Secondary outcomes included event-free survival (EFS), radiologic complete response (rCR), and immune-related adverse events (irAEs). RESULTS A total of 26 patients treated between April 1, 2017, and July 30, 2025, were identified. Nine patients (34.6%) underwent surgery, of whom six (66.7%) achieved pCR. Seventeen patients (65.4%) pursued NOM, with 10 (71.4%) of 14 evaluable patients achieving cCR and 14 (82.4%) of 17 evaluable achieving rCR. One patient who initially achieved cCR had a local recurrence on surveillance endoscopy and underwent salvage endoscopic resection. At a median follow-up of 19.3 months, 15 (88.2%) of 17 patients in the NOM cohort were alive and metastasis-free, with EFS rates of 87.3% at 12 and 24 months for all patients. irAEs occurred in nine patients (34.6%), with no grade ≥3 toxicities. CONCLUSION In this retrospective cohort study, nICIs led to high cCR and pCR rates in resectable dMMR/MSI-H GEA, supporting the use of immune checkpoint inhibitors in this setting and the feasibility of NOM in select patients.

After successfully implementing an acute care telemedicine program internally, health care institutions often consider expanding and scaling services externally beyond the initial organizational network. This report outlines important considerations when expanding acute care telemedicine services externally, including cultural alignment and agility, practice context, staffing models, telemedicine technology selection, interrelated services, legal and compliance considerations, quality assurance, risk management, financing, and integration with medical education. These factors may inform program leaders of major planning considerations, potential barriers, and could influence strategic planning. Prospectively identifying and resolving challenges prior to contracting with new external sites will facilitate smooth, successful implementation and high utilization of the acute care telemedicine service.

Abstract Background Dystonia and Parkinson's disease (PD) exhibit clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear. Objective The aim was to assess the frequency of dystonia‐linked pathogenic variants in PD. Methods We screened sequencing data from 15,684 individuals (8272 PD, 3200 atypical parkinsonism, and 4212 unaffected) from the Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership‐Parkinson's Disease (AMP‐PD) for variants in genes linked to isolated dystonia, dystonia‐parkinsonism, and myoclonus‐dystonia. Results Pathogenic variants were identified only in PD patients. Forty‐five PD individuals (0.54%) carried 26 distinct (likely) pathogenic variants in nine dystonia‐linked genes, most frequently in GCH1 , followed by VPS16 . Conclusion Though rare, pathogenic variants in dystonia‐linked genes are present in clinically and pathologically diagnosed PD. Our results reinforce GCH1 as a PD‐relevant gene with clinical implications, whereas variants identified in other genes are rare and of uncertain relation to the PD phenotype. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Variable terminology is used in the literature to describe facial synkinesis and hypertonicity following incomplete recovery from facial paralysis and its associated medical and surgical treatments. Study Objectives: Establish a nomenclature consensus for this condition among a group of facial nerve experts. Design Type: Consensus study. Methods: Using modified Delphi methodology, an international, multidisciplinary group of facial nerve experts reviewed the terminology for the name of the clinical condition and treatments of interest. Online surveys and a virtual discussion were performed to establish consensus, defined a priori as agreement by 80% of the group. Results: Twenty-five facial nerve experts established consensus after three Delphi rounds. Consensus terminology for the condition is “facial synkinesis” with 84% agreement. Medical treatment is termed “chemodenervation” with 100% agreement. Surgical treatments including “selective facial neurectomy,” “selective facial neurotomy,” “selective facial myectomy,” and “selective facial myotomy,” were defined and reached agreement of 100%. Conclusions: This international group of facial nerve experts has recommended standardized nomenclature for the condition of facial synkinesis and its various treatments. While “facial synkinesis” reached consensus as the preferred term, some experts noted it may insufficiently describe the full clinical spectrum, which includes muscle hypertonicity, weakness, and spontaneous twitching.

Abstract With the rapid advancements in large language model technology and the emergence of bioinformatics‐specific language models (BioLMs), there is a growing need for a comprehensive analysis of the current landscape, computational characteristics, and diverse applications. This survey aims to address this need by providing a thorough review of BioLMs, focusing on their evolution, classification, and distinguishing features, alongside a detailed examination of training methodologies, datasets, and evaluation frameworks. We explore the wide‐ranging applications of BioLMs in critical areas such as disease diagnosis, drug discovery, and vaccine development, highlighting their impact and transformative potential in bioinformatics. We identify key challenges and limitations inherent in BioLMs, including data privacy and security concerns, interpretability issues, biases in training data and model outputs, and domain adaptation complexities. Finally, we highlight emerging trends and future directions, offering valuable insights to guide researchers and clinicians toward advancing BioLMs for increasingly sophisticated biological and clinical applications.

Abstract Background Acupuncture, a key modality in traditional Chinese medicine, is gaining global recognition as a complementary therapy and a subject of increasing scientific interest. However, fragmented and unstructured acupuncture knowledge spread across diverse sources poses challenges for semantic retrieval, reasoning, and in-depth analysis. To address this gap, we developed AcuKG, a comprehensive knowledge graph that systematically organizes acupuncture-related knowledge to support sharing, discovery, and artificial intelligence–driven innovation in the field. Methods AcuKG integrates data from multiple sources, including online resources, guidelines, PubMed literature, ClinicalTrials.gov, and multiple ontologies (SNOMED CT, UBERON, and MeSH). We employed entity recognition, relation extraction, and ontology mapping to establish AcuKG, with human-in-the-loop to ensure data quality. Two cases evaluated AcuKG’s usability: (1) how AcuKG advances acupuncture research for obesity and (2) how AcuKG enhances large language model (LLM) application on acupuncture question-answering. Results AcuKG comprises 1839 entities and 11 527 relations, mapped to 1836 standard concepts in 3 ontologies. Two use cases demonstrated AcuKG’s effectiveness and potential in advancing acupuncture research and supporting LLM applications. In the obesity use case, AcuKG identified highly relevant acupoints (eg, ST25, ST36) and uncovered novel research insights based on evidence from clinical trials and literature. When applied to LLMs in answering acupuncture-related questions, integrating AcuKG with GPT-4o and LLaMA 3 significantly improved accuracy (GPT-4o: 46% → 54%, P = .03; LLaMA 3: 17% → 28%, P = .01). Conclusion AcuKG is an open dataset that provides a structured and computational framework for acupuncture applications, bridging traditional practices with acupuncture research and cutting-edge LLM technologies.

Abstract Background Unresectable hepatocellular carcinoma (uHCC) is a leading cause of cancer death. FDA-approved first-line systemic therapies include atezolizumab/bevacizumab (atezo/bev) and durvalumab/tremelimumab (durva/treme); however, there is a lack of comparative data. Methods We reviewed outcomes of patients with uHCC who initiated atezo/bev or durva/treme between 2017 and 2024, across six institutions. Overall survival (OS) and time to treatment discontinuation (TTD) were analyzed using the Kaplan–Meier and Cox models, adjusting for baseline characteristics. Results Four hundred fifty-two uHCC pts were included. Median age: 68 years; 77% male; 81% white. Most common etiologies were viral hepatitis (38.9%) and metabolic dysfunction-associated steatohepatitis (19.5%). Disease progression was the primary reason for treatment discontinuation, atezo/bev (56%) and durva/treme (42%). Outcomes were not statistically significant (median OS [month, m]: 14.0 vs 14.6 [P = .66]; median TTD [m]: 4.9 vs 3.9 [P = .42] for atezo/bev vs durva/treme). Outcomes were significantly different between Child-Pugh classes (CP: A, B7, B8/9, C) respectively, median OS(m): 19.0, 6.1, 5.1, 2.0 (P < .001); median TTD(m): 6.1, 2.3, 3.0, 1.3 (P < .001). Conclusions In this real-world study of uHCC, no significant difference in clinical outcomes was observed between atezo/bev and durva/treme in the first-line setting. CP scores were a key prognostic variable with both regimens.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.