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.

Cancer cachexia and weight loss before CAR T-cell therapy for lymphoma are independently associated with poor outcomes.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the care of lymphoma, yet many patients relapse. Several prognostic markers have been associated with CAR T-cell outcomes, such as tumor burden, response to bridging chemotherapy, and laboratory parameters at the time of lymphodepletion or infusion. The effect of cancer cachexia and weight loss before CAR T cells on toxicity and outcomes is not well understood.

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.

Balancing aquaculture and estuarine ecosystems: machine learning-based water quality indices for effective management.

This study delves into the environmental impact of inland aquaculture on estuarine ecosystems by examining the water quality of four estuarine streams within the key inland aquaculture zone of South India. In this region, extensive and intensive aquaculture practices are common, posing potential challenges to estuarine health. The research explores the predictive capabilities of the Gaussian elimination method (GEM) and machine learning techniques, specifically multi-linear regression (MLR) and support vector regressor (SVR), in forecasting the water quality index of these streams.

Ultraviolet light blocking optically clear adhesives for foldable displays via highly efficient visible-light curing.

In developing an organic light-emitting diode (OLED) panel for a foldable smartphone (specifically, a color filter on encapsulation) aimed at reducing power consumption, the use of a new optically clear adhesive (OCA) that blocks UV light was crucial. However, the incorporation of a UV-blocking agent within the OCA presented a challenge, as it restricted the traditional UV-curing methods commonly used in the manufacturing process. Although a visible-light curing technique for producing UV-blocking OCA was proposed, its slow curing speed posed a barrier to commercialization.

High-resolution 3-D scanning electron microscopy (SEM) images of DOT polynucleotides (PN): Unique scaffold characteristics and potential applications in biomedicine.

Introduction: Polynucleotides (PN) are becoming more prominent in aesthetic medicine. However, the structural characteristics of PN have not been published and PN from different companies may have different structural characteristics. This study aimed to elucidate the structural attributes of DOT™ PN and distinguish differences with polydeoxyribonucleotides (PDRN) using high-resolution scanning electron microscopy (SEM) imaging.

Differential response to roflumilast in patients with chronic obstructive pulmonary disease: real-world evidence.

Background: Roflumilast is effective in reducing acute exacerbation in patients with chronic obstructive pulmonary disease (COPD) at high risk of severe exacerbation. Clinical traits related to the benefits of roflumilast need to be evaluated in patients with COPD.

Methods: A longitudinal observational study in patients newly diagnosed with COPD was conducted using claims data from the Health Insurance Review and Assessment Service in South Korea from 2012-2020 after a 2-year washout period.

First in-human evaluation of [1-C]pyruvate in DO for hyperpolarized MRI of the brain: A safety and feasibility study.

Purpose: To investigate the safety and value of hyperpolarized (HP) MRI of [1-C]pyruvate in healthy volunteers using deuterium oxide (DO) as a solvent.

Methods: Healthy volunteers (n = 5), were injected with HP [1-C]pyruvate dissolved in DO and imaged with a metabolite-specific 3D dual-echo dynamic EPI sequence at 3T at one site (Site 1). Volunteers were monitored following the procedure to assess safety.

Clinical Characteristics and Associated Factors to the Development of Glaucoma in Eyes With Myopic Optic Neuropathy.

Purpose: To observe the development of glaucoma in myopic eyes with and without myopic optic neuropathy (MON) and analyze associated factors to the development of typical glaucomatous damage.

Design: A prospective, observational, cohort study.

Methods: A total of 233 myopic eyes with no definite evidence of glaucomatous damage were included.

A murine multiple-injury model for the study of thromboinflammation.

Introduction: Neutrophil extracellular traps (NETs) contribute to trauma-induced coagulopathy. We aimed to develop a murine multiple-injury model that induces thrombo-inflammatory response, that is, NETosis and accelerated thrombin generation.

Methods: Wild-type male mice (n = 10, aged 8-12 weeks) underwent multiple injuries (gastrocnemius crush, femur fracture, and laparotomy) and were compared with an uninjured control group (n = 10).

Stereotactic ablative radiation for pancreatic cancer on a 1.5 Telsa magnetic resonance-linac system.

Purpose: Ablative radiation therapy (A-RT) appears to improve outcomes in locally advanced pancreatic cancer (LAPC) yet requires solutions for respiratory and digestive motion. We report outcomes of A-RT for pancreatic cancer using 1.5 T MR-adaptive treatment delivery.

Can the Virtual Reality-Based Spatial Memory Test Better Discriminate Mild Cognitive Impairment than Neuropsychological Assessment?

Neuropsychological screening tools for mild cognitive impairment (MCI) have been widely used. However, to date, their sensitivity and specificity still remain unsatisfied. This study aims to investigate whether spatial memory can discriminate MCI better than neuropsychological screening tools.

Management of Incidentally Detected Gallbladder Polyps: Society of Radiologists in Ultrasound Consensus Conference Recommendations.

Gallbladder polyps (also known as polypoid lesions of the gallbladder) are a common incidental finding. The vast majority of gallbladder polyps smaller than 10 mm are not true neoplastic polyps but are benign cholesterol polyps with no inherent risk of malignancy. In addition, recent studies have shown that the overall risk of gallbladder cancer is not increased in patients with small gallbladder polyps, calling into question the rationale for frequent and prolonged follow-up of these common lesions.

Deep Learning to Optimize Candidate Selection for Lung Cancer CT Screening: Advancing the 2021 USPSTF Recommendations.

Background A deep learning (DL) model to identify lung cancer screening candidates based on their chest radiographs requires external validation with a recent real-world non-U.S. sample.

Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis.

Background And Objectives: Mitochondrial diseases (MDs) are the commonest group of heritable metabolic disorders. Phenotypic diversity can make molecular diagnosis challenging, and causative genetic variants may reside in either mitochondrial or nuclear DNA. A single comprehensive genetic diagnostic test would be highly useful and transform the field.

Autophagy in PDGFRα+ mesenchymal cells is essential for intestinal stem cell survival.

Autophagy defects are a risk factor for inflammatory bowel diseases (IBDs) through unknown mechanisms. Whole-body conditional deletion of autophagy-related gene (Atg) Atg7 in adult mice (Atg7Δ/Δ) causes tissue damage and death within 3 mo due to neurodegeneration without substantial effect on intestine. In contrast, we report here that whole-body conditional deletion of other essential Atg genes Atg5 or Fip200/Atg17 in adult mice (Atg5Δ/Δ or Fip200Δ/Δ) caused death within 5 d due to rapid autophagy inhibition, elimination of ileum stem cells, and loss of barrier function.

Human pluripotent stem cell-derived myogenic progenitors undergo maturation to quiescent satellite cells upon engraftment.

Human pluripotent stem cell (hPSC)-derived myogenic progenitor cell (MPC) transplantation is a promising therapeutic approach for a variety of degenerative muscle disorders. Here, using an MPC-specific fluorescent reporter system (PAX7::GFP), we demonstrate that hPSC-derived MPCs can contribute to the regeneration of myofibers in mice following local injury and in mice deficient of dystrophin (mdx). We also demonstrate that a subset of PAX7::GFP MPCs engraft within the basal lamina of regenerated myofibers, adopt a quiescent state, and contribute to regeneration upon reinjury and in mdx mouse models.

Neutralizing-antibody-independent SARS-CoV-2 control correlated with intranasal-vaccine-induced CD8 T cell responses.

Effective vaccines are essential for the control of the coronavirus disease 2019 (COVID-19) pandemic. Currently developed vaccines inducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-antigen-specific neutralizing antibodies (NAbs) are effective, but the appearance of NAb-resistant S variant viruses is of great concern. A vaccine inducing S-independent or NAb-independent SARS-CoV-2 control may contribute to containment of these variants.

Development and Validity Assessment of a Self-evaluation Questionnaire for Functional Dyspepsia: A Multicenter Prospective Study in Korea.

Background/aims: Patient-reported outcomes (PROs) are essential for clinical decision making, conduction of clinical research, and drug application acquisition in functional gastrointestinal disorders. The aim of this study is to develop a PRO instrument and to determine the respondents' perception of the efficacy of therapeutic agents for functional dyspepsia (FD).

Methods: A self-evaluation questionnaire for dyspepsia (SEQ-DYSPEPSIA) was developed and validated through a structured process.

Synthetic DNA spike-ins (SDSIs) enable sample tracking and detection of inter-sample contamination in SARS-CoV-2 sequencing workflows.

The global spread and continued evolution of SARS-CoV-2 has driven an unprecedented surge in viral genomic surveillance. Amplicon-based sequencing methods provide a sensitive, low-cost and rapid approach but suffer a high potential for contamination, which can undermine laboratory processes and results. This challenge will increase with the expanding global production of sequences across a variety of laboratories for epidemiological and clinical interpretation, as well as for genomic surveillance of emerging diseases in future outbreaks.

Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease.

Background: Patients with von Hippel-Lindau (VHL) disease have a high incidence of renal cell carcinoma owing to gene inactivation and constitutive activation of the transcription factor hypoxia-inducible factor 2α (HIF-2α).

Methods: In this phase 2, open-label, single-group trial, we investigated the efficacy and safety of the HIF-2α inhibitor belzutifan (MK-6482, previously called PT2977), administered orally at a dose of 120 mg daily, in patients with renal cell carcinoma associated with VHL disease. The primary end point was objective response (complete or partial response) as measured according to the Response Evaluation Criteria in Solid Tumors, version 1.