METTL4-Mediated Mitochondrial DNA N6-Methyldeoxyadenosine Promoting Macrophage Inflammation and Atherosclerosis.

Background: Mitochondrial dysfunction is a key factor in the development of atherogenesis. METTL4 (methyltransferase-like protein 4) mediates N6- methyldeoxyadenosine (6mA) of mammalian mitochondrial DNA (mtDNA). However, the role of METTL4-mediated mitoepigenetic regulation in atherosclerosis is still unknown.

Harmonization of rapid triplet up-conversion and singlet radiation enables efficient and stable white OLEDs.

White organic light-emitting diodes (WOLEDs) hold significant promise in illumination and displays, but achieving high efficiency while maintaining stability is an ongoing challenge. Here, we strategically combine a blue donor-acceptor thermally activated delayed fluorescence (TADF) emitter featuring rapid reverse intersystem crossing rate and a yellow multi-resonance TADF emitter renowned for the fast radiative transition process to achieve warm WOLEDs with exceptional power efficiency exceeding 190 lm W and external quantum efficiency (EQE) of 39%, setting records for WOLEDs. Meanwhile, these devices also exhibit an extended operational lifetime (LT) of 446 h at an initial luminance of 1000 cd m.

Secreted Particle Information Transfer (SPIT) - A Cellular Platform for Genetic Engineering.

A multitude of tools now exist that allow us to precisely manipulate the human genome in a myriad of different ways. However, successful delivery of these tools to the cells of human patients remains a major barrier to their clinical implementation. Here we introduce a new cellular approach for genetic engineering, ecreted article nformation ransfer (SPIT) that utilizes human cells as delivery vectors for genetic engineering.

HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.

HNF4A and HNF1A encode transcription factors that are important for the development and function of the pancreas and liver. Mutations in both genes have been directly linked to Maturity Onset Diabetes of the Young (MODY) and type 2 diabetes (T2D) risk. To better define the pleiotropic gene regulatory roles of HNF4A and HNF1A, we generated a comprehensive genome-wide map of their binding targets in pancreatic and hepatic cells using ChIP-Seq.

Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma.

B-cell maturation antigen (BCMA)-targeting therapeutics have dramatically improved outcomes in relapsed/refractory multiple myeloma (RRMM). However, whether the mechanisms of resistance between these therapies are shared and how the identification of such mechanisms before therapy initiation could refine clinical decision-making remains undefined. We analyzed outcomes for 72 RRMM patients treated with teclistamab, a CD3 × BCMA bispecific antibody, 42% (30/72) of whom had prior BCMA-directed therapy exposure.

Unscheduled health care interactions in patients with multiple myeloma receiving T-cell redirection therapies.

Outcomes for patients with relapsed/refractory multiple myeloma (R/RMM) have dramatically improved after the development and now growing utilization of B-cell maturation antigen-targeted chimeric antigen receptor (CAR) T-cell therapy and bispecific antibody (BsAb) therapy. However, health care utilization as a quality-of-life metric in these growing populations has not been thoroughly evaluated. We performed a retrospective cohort study evaluating the frequency and cause of unscheduled health care interactions (UHIs) among patients with R/RMM responding to B-cell maturation antigen-targeted BsAb and CAR T-cell therapies (N = 46).

Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia.

Background: Chemerin, an inflammatory adipokine, is upregulated in preeclampsia, and its placental overexpression results in preeclampsia-like symptoms in mice. Statins may lower chemerin.

Methods: Chemerin was determined in a prospective cohort study in women suspected of preeclampsia and evaluated as a predictor versus the sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio.

Secreted Particle Information Transfer (SPIT) - A Cellular Platform for Genetic Engineering.

A multitude of tools now exist that allow us to precisely manipulate the human genome in a myriad of different ways. However, successful delivery of these tools to the cells of human patients remains a major barrier to their clinical implementation. Here we introduce a new cellular approach for genetic engineering, ecreted article nformation ransfer (SPIT) that utilizes human cells as delivery vectors for genetic engineering.

HEG1 Protects Against Atherosclerosis by Regulating Stable Flow-Induced KLF2/4 Expression in Endothelial Cells.

Background: Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow, and stable flow (s-flow) protects against atherosclerosis by incompletely understood mechanisms.

Methods: Our single-cell RNA-sequencing data using the mouse partial carotid ligation model was reanalyzed, which identified Heart-of-glass 1 (HEG1) as an s-flow-induced gene. HEG1 expression was studied by immunostaining, quantitive polymerase chain reaction, hybridization chain reaction, and Western blot in mouse arteries, human aortic endothelial cells (HAECs), and human coronary arteries.

lncRNA JPX-Enriched Chromatin Microenvironment Mediates Vascular Smooth Muscle Cell Senescence and Promotes Atherosclerosis.

Background: Senescence is a series of degenerative changes in the structure and physiological function of an organism. Whether JPX (just proximal to XIST)-a newly identified age-related noncoding RNA by us-is associated with atherosclerosis is still unknown. Our study was to investigate the role of JPX and provide insights into potential therapies targeting atherosclerosis.

CD8 effector T cells enhance teclistamab response in BCMA-exposed and -naïve multiple myeloma.

Teclistamab, a B-cell maturation antigen (BCMA)- and CD3-targeting bispecific antibody, is an effective novel treatment for relapsed/refractory multiple myeloma (R/RMM), but efficacy in patients exposed to BCMA-directed therapies and mechanisms of resistance have yet to be fully delineated. We conducted a real-world retrospective study of commercial teclistamab, capturing both clinical outcomes and immune correlates of treatment response in a cohort of patients (n = 52) with advanced R/RMM. Teclistamab was highly effective with an overall response rate (ORR) of 64%, including an ORR of 50% for patients with prior anti-BCMA therapy.

Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups.

Multiple myeloma (MM) is twice as common in Black individuals compared with in White individuals, and diabetes mellitus (DM) disproportionately affects Black patients. Although numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms. We conducted a retrospective clinical study of 5383 patients with MM of which 15% had DM (White, 12% and Black, 25%).

Imaging Findings in Cirrhotic Liver: Pearls and Pitfalls for Diagnosis of Focal Benign and Malignant Lesions.

Cirrhosis is the end stage of chronic liver disease and causes architectural distortion and perfusional anomalies. It is a major risk factor for developing hepatocellular carcinoma (HCC). Common disease entities in noncirrhotic livers, such as hemangiomas, can be rare in cirrhotic livers, and benign entities such as confluent hepatic fibrosis and focal nodular hyperplasia-like lesions may mimic the appearance of malignancies,.

CT Imaging With Machine Learning for Predicting Progression to COPD in Individuals at Risk.

Background: Identifying individuals at risk of progressing to COPD may allow for initiation of treatment to potentially slow the progression of the disease or the selection of subgroups for discovery of novel interventions.

Research Question: Does the addition of CT imaging features, texture-based radiomic features, and established quantitative CT scan to conventional risk factors improve the performance for predicting progression to COPD in individuals who smoke with machine learning?

Study Design And Methods: Participants at risk (individuals who currently or formerly smoked, without COPD) from the Canadian Cohort Obstructive Lung Disease (CanCOLD) population-based study underwent CT imaging at baseline and spirometry at baseline and follow-up. Various combinations of CT scan features, texture-based CT scan radiomics (n = 95), and established quantitative CT scan (n = 8), as well as demographic (n = 5) and spirometry (n = 3) measurements, with machine learning algorithms were evaluated to predict progression to COPD.

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study.

Introduction: Capmatinib, a MET inhibitor, showed substantial antitumour activity with manageable side effects in patients with MET exon 14 (METex14)-mutated advanced non-small cell lung cancer (aNSCLC) in the GEOMETRY mono-1 study. We report patient-reported outcomes (PROs) from this study.

Methods: Enrolled treatment-naïve (1L) or pre-treated (2L) patients with aNSCLC with a METex14-skipping mutation received 400 mg capmatinib twice daily during 21-day treatment cycles.

Arterial Spin-Labeling Parameters and Their Associations with Risk Factors, Cerebral Small-Vessel Disease, and Etiologic Subtypes of Cognitive Impairment and Dementia.

Background And Purpose: Cerebral small-vessel disease may alter cerebral blood flow (CBF) leading to brain changes and, hence, cognitive impairment and dementia. CBF and the spatial coefficient of variation can be measured quantitatively by arterial spin-labeling. We aimed to investigate the associations of demographics, vascular risk factors, location, and severity of cerebral small-vessel disease as well as the etiologic subtypes of cognitive impairment and dementia with CBF and the spatial coefficient of variation.

Outcome of Cataract Surgery in Patients With Retinitis Pigmentosa.

Purpose: To assess the visual outcome of cataract surgery in patients with retinitis pigmentosa (RP).

Design: Retrospective, noncomparative clinical study.

Methods: Preoperative, intraoperative, and postoperative data of patients with RP who were undergoing cataract surgery were collected from several expertise centers across Europe.

Methamphetamine and HIV-1 Tat proteins synergistically induce microglial autophagy via activation of the Nrf2/NQO1/HO-1 signal pathway.

Methamphetamine (METH) is a psychostimulant that is abused throughout the world. METH is a highly addictive drug commonly used by persons living with HIV, and its use can result in cognitive impairment and memory deficits. METH and human immunodeficiency virus-1 transactivator of transcription (HIV-1Tat) have toxic and synergistic effects on the nervous system; however, the mechanism of their synergistic effects has not been clarified.

Association between 24-Hour Movement Behaviors and Smartphone Addiction among Adolescents in Foshan City, Southern China: Compositional Data Analysis.

Smartphone addiction has become a public health issue. To help reduce smartphone addiction, we assessed the combined effect of 24-Hour Movement Behaviors on smartphone addiction during Corona Virus Disease 2019 (COVID-19) home confinement in Foshan, China. Data were collected in a sample of 1323 senior middle school students ((mean age ± standard deviation): 16.