Identification of ONECUT3 as a stemness-related transcription factor regulating NK cell-mediated immune evasion in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal response to the current T cell-based immunotherapies, which is attributed to intratumoral heterogeneity caused by PDAC stem cells and lack of major histocompatibility complex class I required for neoantigen presentation. Although this scenario makes natural killer (NK) cells attractive candidates for immunotherapeutic agents targeting MHC-I-deficient cancer stem cells in heterogeneous PDACs, little is known about PDAC stem cell immunology. In our study, PDAC-specific datasets from public databases were collected for in-depth bioinformatic analysis. We found that the abundance of PDAC stemness negatively influenced the infiltration of NK cells and identified the transcription factor ONECUT3 enriched in PDACs with high stemness index scores and Pan-cancer Stemness Signature levels. A series of NK cell-targeted inhibitory immune checkpoints were highly expressed in ONECUT3high PDACs. The patient group with high levels of ONECUT3 expression had a high risk of poor overall survival, even if accompanied by high infiltration of NK cells. Furthermore, the prostanoid metabolic process was enriched in ONECUT3high PDACs with high levels of NK cell-targeted inhibitory immune checkpoints. ONECUT3 enriched in high-stemness PDACs possessed the potential to transcriptionally regulate the prostanoid metabolism-related genes. Our study reveals ONECUT3 as a candidate stemness-related transcription factor regulating NK cell-targeted inhibitory immune checkpoints in PDAC. ONECUT3-mediated prostanoid metabolism may regulate cancer stemness and immune evasion in PDAC. Synergistic inhibition of prostanoid metabolism may improve the efficacy of NK cell-based immunotherapies targeting intratumoral heterogeneity caused by PDAC stem cells.

Association between asthma and headache: Findings from the NHANES 2001-2004.

INTRODUCTION: With the adjustment of sociodemographic factors, our study aimed to explore the association between asthma control and headache using a representative sample in the United States. METHODS: A total of participants aged >20 years from the National Health and Nutrition Examination Survey (NHANES) cycles 2001-2004 were included. The presence of asthma and headache was determined by questionnaires. Multivariate logistic regression was performed. RESULTS: Participants with asthma had higher odds of suffering headaches (odds ratio = 1.62, 95% confidence interval: 1.30-2.02, p < 0.001). Those who had an asthma attack in the past year had higher odds of experiencing headaches than those who did not (odds ratio = 1.94, 95% confidence interval: 1.11-3.39, p = 0.022). No statistically significant association was found between participants who had emergency care visit for asthma in the past year and those who had not. CONCLUSION: Patients with asthma attack in the past year were more likely to have a headache than those who without.

X-linked dystonia parkinsonism: epidemiology, genetics, clinical features, diagnosis, and treatment.

X-linked dystonia parkinsonism (XDP) is a rare X-linked recessive degenerative movement disorder that only affects Filipino descent, predominantly males. Its underlying cause is associated with the genetic alterations in the TAF1/DYT3 multiple transcription system. SINE-VNTR-Alu (SVA) retrotransposon insertion was suggested to be the responsible genetic mutation. Clinically, it initially presents as focal dystonia and generalizes within years. Parkinsonism arises years later and coexists with dystonia. Nonmotor symptoms like cognitive impairment and mood disorders are also common among XDP patients. XDP diagnosis relies on clinical history and physical examination. On imaging, abnormalities of the striatum, such as atrophy, are widely seen and can explain the clinical presentations with a three-model pathway of the striatum. Treatments aim for symptomatic relief of dystonia and parkinsonism and to prevent complications. Oral medications, chemo-denervation, and surgery are used in XDP patients. This review summarizes the currently important information regarding XDP, providing a synoptic overview and understanding of XDP for future studies.