Citations

Background The eccentric stenosis morphology in patients with intracranial atherosclerotic stenosis (ICAS) has a critical impact on the efficacy of endovascular treatment. This study aimed to establish a rabbit model of eccentric carotid atherosclerotic stenosis that mimics the pathophysiological and morphological characteristics of eccentric plaques in humans. Methods Rabbits received localized cryoinjury of the right carotid artery after 2 weeks of a high fat, high cholesterol diet, followed by an additional 8 weeks on the same diet. On the experimental endpoint, comprehensive analyses of the model’s pathological changes were conducted using serum lipid analysis, DSA, optical coherence tomography (OCT), histopathological analysis, and immunohistochemistry. Results The high fat, high cholesterol diet significantly elevated serum lipid levels in rabbits. Hematoxylin and eosin staining results at 24 hours postoperatively revealed focal intimal damage induced by 5 s of cryoinjury. After localized cryoinjury and high fat, high cholesterol diet feeding, DSA results demonstrated significant carotid stenosis, with a stenosis degree of 47±5% and a length of approximately 9 mm. OCT images revealed eccentric fibrous plaque formation at the stenotic site. Morphological analysis of the plaque samples demonstrated a plaque eccentricity index of 0.66±0.05 and a plaque burden of 60.68±7.41%. Histopathological analysis showed that atherosclerotic lesions developed in all rabbits of the model group. Among them, three rabbits had intermediate lesions, one rabbit had atheroma, and eight rabbits had fibroatheroma. Conclusions This study successfully established a rabbit model of eccentric carotid atherosclerotic stenosis, providing a novel experimental platform for transformation research of neurointerventional devices.

Summary Recipients of haploidentical and unrelated haematopoietic cell transplants (HCTs) historically had a higher risk for graft‐versus‐host disease (GvHD). However, with improved GvHD prophylaxis, recent data suggest adult patients undergoing transplantation from unrelated or mismatched donors now experience the rates of GvHD similar to those receiving matched related donor grafts. This finding is not yet explored in paediatric patients. The objectives of this study were to: (1) compare acute and chronic GvHD incidence, mortality and GvHD‐free relapse‐free survival (GRFS) among matched related donor (MRD), matched unrelated donor (MUD) and haploidentical paediatric HCT recipients in the era of enhanced GvHD prophylaxis for high‐risk patients, (2) identify independent risk factors for GvHD and (3) evaluate the efficacy of various GvHD prophylactic regimens in our cohort. We conducted a retrospective, single‐centre medical record abstraction among patients aged 0–25 years who underwent allogeneic HCT for any indication. The results demonstrated that 5‐year cumulative incidence rates of any GvHD, all‐cause mortality and GRFS are similar across the haploidentical, MRD and MUD groups. Tacrolimus‐containing doublet/triplet regimens were associated with decreased GvHD, as compared to ciclosporin. Adding alemtuzumab also decreased risk for GvHD, without increasing relapse rates. Prospective studies with larger cohorts are warranted to further optimize outcomes for paediatric allogeneic HCT patients.

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 Objectives Emotional impairments in people with dementia can be taxing for family caregivers. However, caregivers differ in their resilience to these challenges. We previously found that, compared to healthy controls and people with Alzheimer’s disease, people with frontotemporal lobar degeneration (FTLD) have smaller physiological responses when anticipating upcoming emotional stimuli. This impairment may leave these people with FTLD unprepared for upcoming emotional stimuli because they cannot mount responses needed for appropriate behaviors, which may create stress and difficulties for caregivers. We examined (a) whether smaller preparatory physiological responses in people with dementia are associated with lower emotional well-being and physical functioning in caregivers; and (b) whether these associations are moderated by the dyads’ relationship quality. Methods A total of 158 individuals with FTLD or Alzheimer’s disease and their family caregivers participated. Preparatory physiological responses in people with dementia were quantified as decreases in cardiac interbeat intervals from baseline to an instruction period, during which they were told they would be watching an upcoming emotional film. Caregivers self-reported their emotional well-being, physical functioning, and relationship quality with the people with dementia. Results Smaller preparatory physiological responses in people with dementia were associated with lower emotional well-being (but not physical functioning) in caregivers. This association was moderated by relationship quality (i.e., weakened for caregivers in higher-quality relationships). Discussion Findings advance understanding of risk and resilience factors for negative caregiver outcomes. Positive interpersonal processes in high-quality relationships (e.g., positive appraisal of aberrant behaviors) may buffer caregivers from the impact of emotional impairments in people with dementia.

ABSTRACT Background and Aims Clinically significant portal hypertension (CSPH; hepatic venous pressure gradient (HVPG) ≥ 10 mmHg) is a severe complication of chronic liver disease, with increased risk of variceal bleeding and liver decompensation (at HVPG ≥ 12 mmHg). This study evaluated the performance of multiparametric (mp)MRI for diagnosing CSPH and predicting liver decompensation, compared to ultrasound‐based shear wave elastography (SWE) and blood tests. Methods In this prospective single‐centre study (2018–2022), 59 patients (M 30, mean age 52.7 years) underwent mpMRI and HVPG measurement, with an average interval of 32 ± 31 days. The mpMRI protocol included 2D/3D MR elastography (MRE), T 1 /proprietary iron‐compensated T 1 (cT 1 )/T 1ρ mapping, gadoxetate‐enhanced dynamic contrast‐enhanced MRI (DCE‐MRI) of the liver and spleen, SWE and blood tests. Statistical analyses included Mann–Whitney U tests, ROC analysis, logistic regression and Cox proportional hazards models. Results CSPH was present in 13 patients (22%). Several MRI parameters showed high diagnostic performance for CSPH (AUC ≥ 0.8), with spleen stiffness‐2D MRE (AUC 0.88, 95% confidence interval (CI) 0.78–0.98) and liver uptake on DCE‐MRI (AUC 0.83, 95% CI 0.70–0.96) performing best, while SWE had AUCs of 0.63 (95% CI 0.45–0.81) for liver and 0.67 (95% CI 0.44–0.89) for spleen. Combining spleen stiffness‐2D MRE and liver uptake achieved an AUC of 0.93 (95% CI 0.86–1.00) for diagnosing CSPH. For predicting decompensation, spleen stiffness‐3D MRE and liver uptake rate had AUCs of 0.83 (95% CI 0.68–0.99) and 0.83 (95% CI 0.70–0.95), respectively, outperforming SWE. Conclusions Spleen stiffness measured with MRE combined with gadoxetate liver uptake (measured with DCE‐MRI) can diagnose CSPH and predict liver decompensation, with superior performance compared to SWE. Trial Registration ClinicalTrials.gov identifier: NCT03436550

Abstract Hepatocellular carcinoma (HCC) mortality is increasing globally, partly due to the growing prevalence of nonviral liver diseases. Genome‐wide association studies (GWAS) have identified genetic variants associated with HCC development. Leveraging GWAS summary statistics and linkage disequilibrium score regression (LDSR), we investigated disease co‐development with hepatitis C virus‐negative (HCV‐negative) HCC to provide unique insights into HCC etiology and prioritize relationships for further causal inquiry. We utilized the LDSR statistical framework to estimate the genetic correlation and heritability between HCV‐negative HCC with 901 epidemiologic, behavioral, and clinical traits from the United Kingdom Biobank (UKBB). First, we set the threshold for observed scale heritability of each trait at 0.02 to ensure reliable inferences with adequate study power. Next, we observed significant positive genetic correlations between HCV‐negative HCC and blood‐based biomarkers of liver injury (ALT, GGT) and allostatic load (including glycated hemoglobin, blood pressure, and total albumin). We also identified a positive genetic correlation between HCV‐negative HCC and diseases associated with metabolic dysfunction‐associated steatotic liver disease (MASLD), including diabetes, hypertension, chronic ischemic heart disease, and others. Taken together, our results help to identify polygenic and pleiotropic signals related to different phenotypic traits associated with HCC and support further exploration of the predictive power of blood‐based biomarkers identified in this study for inferring HCC development among HCV‐negative individuals.

Background Sexual and gender diverse (SGD) individuals comprise nearly 10% of the United States’ population but remain underrepresented in cancer research, particularly in intimate partner violence (IPV) studies. Although IPV rates are comparable or higher in SGD individuals than in non-SGD individuals, the literature on IPV in SGD patients with cancer remains sparse. Methods This qualitative study was conducted within a Mayo Clinic IRB-approved parent database on SGD patients with cancer. Eligible patients were adults who self-identified as non-heterosexual or non-cisgender, had an invasive cancer diagnosis, and reported IPV via a four-question screening tool. A detailed medical review was performed to extract qualitative data related to IPV and other violence. Two investigators employed thematic analyses to understand these qualitative data. Results Among 258 SGD patients whose medical records were screened, 13 (5%) reported IPV. Six key themes emerged: (1) IPV co-occurred with other violence (childhood, workplace, sexual violence); (2) IPV was associated with mental health conditions (depression, PTSD, suicidality); (3) Unhealthy coping mechanisms (substance use, risky behaviors) were common; (4) Social isolation and lack of support exacerbated challenges; (5) Internalized stigma influenced self-perception, relationships, healthcare experiences; (6) Chronic stress from cumulative trauma negatively impacted cancer care. Conclusion IPV was reported by a small proportion of SGD cancer patients, and cause and effect associations been IPV and the above themes have not been demonstrated. These findings suggest a need for trauma-informed, culturally competent interventions to address IPV and its broader psychosocial effects in these underserved populations.