Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells.

CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226.

Design of an equilibrative nucleoside transporter subtype 1 inhibitor for pain relief.

The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A1 receptor (A1R).

A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy.

Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome's influence on ICB efficacy is of particular interest due to its modifiability through various interventions.

Synergistic Effect of Dual-Focus Soft Contact Lenses and 0.05% Atropine on Myopia Control in Children With Rapidly Progressing Myopia.

Objectives: The aim of this study was to evaluate the combined effect of dual-focus soft contact lenses (CLs) and 0.05% atropine in the control of myopia.

Methods: A retrospective study was conducted on 142 myopic children aged 7 to 13 years.

Association of Striatal Dopamine Depletion and Brain Metabolism Changes With Motor and Cognitive Deficits in Patients With Parkinson Disease.

Background And Objectives: Parkinson disease (PD) shows degeneration of dopaminergic neurons in the substantia nigra and characteristic changes in brain metabolism. However, how they correlated and affect motor and cognitive dysfunction in PD has not yet been well elucidated.

Methods: In this single-site cross-sectional study, we enrolled patients with PD who underwent -(3-[F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (F-FP-CIT) PET, F-fluorodeoxyglucose (F-FDG) PET, the Movement Disorder Society-sponsored Unified PD Rating Scale examination, and detailed neuropsychological testing.

Predicting Recurrence after Sublobar Resection in Patients with Lung Adenocarcinoma Using Preoperative Chest CT Scans.

Background Sublobar resection for lung cancer is usually guided by cutoff values for consolidation size (maximal diameter of the solid tumor component) and consolidation-to-tumor ratio (CTR). The effects of these factors as continuous variables and the reason for established cutoffs are, to the knowledge of the authors, unexplored. Purpose To quantitatively assess the predictive value of CTR and consolidation size for cancer recurrence risk after sublobar resection in clinical stage IA lung adenocarcinoma.

Dihydroavenanthramide D Enhances Skin Barrier Function through Upregulation of Epidermal Tight Junction Expression.

Skin barrier dysfunction and thin epidermis are hallmarks of sensitive skin and contribute to premature aging. Avenanthramides are the primary bioactive components of colloidal oatmeal, a commonly used treatment to enhance skin barrier function. This study investigated the relationship between skin barrier function and epidermal characteristics and explored the potential of dihydroavenanthramide D (dhAvD), a synthetic avenanthramide, to improve the skin barrier.

Mechanistic insights into a heterobifunctional degrader-induced PTPN2/N1 complex.

PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 and Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach to drug challenging targets including phosphatases. We developed potent PTPN2/N1 dual heterobifunctional degraders (Cmpd-1 and Cmpd-2) which facilitate efficient complex assembly with E3 ubiquitin ligase CRL4, and mediate potent PTPN2/N1 degradation in cells and mice.

Heterogeneity of claudin 18.2 expression in metastatic gastric cancer.

Claudin 18.2 has emerged as a viable therapeutic target in gastric cancer (GC), but little is known about the heterogeneity of its expression in GC. This study investigated the heterogeneity of claudin 18.

Coenzyme-A-Responsive Nanogel-Coated Electrochemical Sensor for Osteoarthritis-Detection-Based Genetic Models.

An electrochemical sensor sensitive to coenzyme A (CoA) was designed using a CoA-responsive polyallylamine-manganese oxide-polymer dot nanogel coated on the electrode surface to detect various genetic models of osteoarthritis (OA). The CoA-responsive nanogel sensor responded to the abundance of CoA in OA, causing the breakage of MnO in the nanogel, thereby changing the electroconductivity and fluorescence of the sensor. The CoA-responsive nanogel sensor was capable of detecting CoA depending on the treatment time and distinguishing the response towards different OA genetic models that contained different levels of CoA (wild type/WT, NudT7 knockout/N7KO, and Acot12 knockout/A12KO).

Deep Learning Model Using Stool Pictures for Predicting Endoscopic Mucosal Inflammation in Patients With Ulcerative Colitis.

Introduction: Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photographs of patients with UC (DLSUC) to predict endoscopic mucosal inflammation.

Methods: This was a prospective multicenter study conducted in 6 tertiary referral hospitals.

Development of an anti-tauopathy mucosal vaccine specifically targeting pathologic conformers.

Alzheimer's disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Targeted immunotherapy to eliminate pathological tau aggregates is known to improve cognitive deficits in AD animal models. The tau repeat domain (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins.

Application of the Win Ratio Method in the ENGAGE AF-TIMI 48 Trial Comparing Edoxaban With Warfarin in Patients With Atrial Fibrillation.

Background: Cardiovascular trials often use a composite end point and a time-to-first event model. We sought to compare edoxaban versus warfarin using the win ratio, which offers data complementary to time-to-first event analysis, emphasizing the most severe clinical events.

Methods: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind, randomized trial in which patients with atrial fibrillation were assigned 1:1:1 to a higher dose edoxaban regimen (60/30 mg daily), a lower dose edoxaban regimen (30/15 mg daily), or warfarin.

Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups.

Background: Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome-wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics.

Results: Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project.

Validating the Health Benefits of Coffee Berry Pulp Extracts in Mice with High-Fat Diet-Induced Obesity and Diabetes.

The effects of coffee ( L.) berry pulp extracts (CBP extracts) on the improvement of diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD) were evaluated using various in vitro antioxidant activity assays and through a high-fat diet-induced mild diabetic obese mouse model. After an 84-day oral administration of CBP extracts (400-100 mg/kg), bioactivities were evaluated.

Disconnection-Based Prediction of Poststroke Dysphagia.

Background And Purpose: Dysphagia is a common deficit after a stroke and is associated with serious complications. It is not yet fully clear which brain regions are directly related to swallowing. Previous lesion symptom mapping studies may have overlooked structural disconnections that could be responsible for poststroke dysphagia.

Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy.

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy.

Pivotal trial of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from CMERC-HI.

Objective: The potential of using retinal images as a biomarker of cardiovascular disease (CVD) risk has gained significant attention, but regulatory approval of such artificial intelligence (AI) algorithms is lacking. In this regulated pivotal trial, we validated the efficacy of Reti-CVD, an AI-Software as a Medical Device (AI-SaMD), that utilizes retinal images to stratify CVD risk.

Materials And Methods: In this retrospective study, we used data from the Cardiovascular and Metabolic Diseases Etiology Research Center-High Risk (CMERC-HI) Cohort.

Cognition and Cerebral Blood Flow After Extracranial Carotid Revascularization for Carotid Atherosclerosis: A Systematic Review.

Purpose: Extracranial atherosclerotic carotid stenosis is associated with inadequate cerebral blood flow (CBF) and cognitive dysfunction. The impact of extracranial carotid revascularization on cognition and how any cognitive change relates to changes in CBF are less clear. This review examines the effects of revascularization of extracranial carotid disease by carotid endarterectomy (CEA) or carotid stenting (CAS) on cognition, and how this relates to changes in CBF.

Immunogenicity and Safety of a Newly Developed Live Attenuated Varicella Vaccine in Healthy Children: A Multi-National, Randomized, Double-Blinded, Active-Controlled, Phase 3 Study.

Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 in healthy children to those of Varivax (control). Children aged 12 months to 12 years were randomized in a ratio of 1:1 to receive either NBP608 or the control vaccine.

Camel nanobody-based B7-H3 CAR-T cells show high efficacy against large solid tumours.

Rational design of chimeric antigen receptor T (CAR-T) cells based on the recognition of antigenic epitopes capable of evoking the most potent CAR activation is an important objective in optimizing immune therapy. In solid tumors, the B7-H3 transmembrane protein is an emerging target that harbours two distinct epitope motifs, IgC and IgV, in its ectodomain. Here, we generate dromedary camel nanobodies targeting B7-H3 and demonstrate that CAR-T cells, based on the nanobodies recognizing the IgC but not IgV domain, had potent antitumour activity against large tumors in female mice.