Baseline Smartphone App Survey Return in the Electronic Framingham Heart Study Offspring and Omni 1 Study: eCohort Study.

Background: Smartphone apps can be used to monitor chronic conditions and offer opportunities for self-assessment conveniently at home. However, few digital studies include older adults.

Objective: We aim to describe a new electronic cohort of older adults embedded in the Framingham Heart Study including baseline smartphone survey return rates and survey completion rates by smartphone type (iPhone [Apple Inc] and Android [Google LLC] users).

Development of cerium-doped porous composite aerogel using cellulose nanocrystals for enhanced CO capture and conversion.

Reducing carbon dioxide (CO) levels in the atmosphere is crucial for combating global warming. One effective strategy involves using porous materials for the combined processes of CO capture and catalytic conversion. In this study, we developed composite aerogel materials using cellulose nanocrystals (CNCs) as templates, doped with cerium oxide, to enhance CO capture and conversion.

Associations of plasma extracellular microRNAs with new-onset breast cancer in the Framingham heart study.

Breast cancer is the second leading cause of cancer deaths among women. Multiple microRNAs (miRNAs) have been reported to be associated with breast cancer progression or metastasis. The purpose of the current study was to identify plasma extracellular miRNAs associated with incident breast cancer.

Radiosynthesis and evaluation of a novel F-labeled tracer for PET imaging of glycogen synthase kinase 3.

Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase family that regulates diverse biological processes including glucose metabolism, insulin activity and energy homeostasis. Dysregulation of GSK3 is implicated in the development of several diseases such as type 2 diabetes mellitus, Alzheimer's disease (AD), and various cancer types. In this study, we report the synthesis and evaluation of a novel positron emission tomography (PET) ligand compound 28 (codenamed [F]GSK3-2209).

Radiosynthesis and preclinical evaluation of a carbon-11 labeled PET ligand for imaging metabotropic glutamate receptor 7.

Metabotropic glutamate receptor 7 (mGlu) is a G protein-coupled receptor that is preferentially found in the active zone of neurotransmitter release in the central nervous system (CNS). mGlu plays a vital role in memory, learning, and neuronal development, rendering it a potential target for treating epilepsy, depression, and anxiety. The development of noninvasive imaging ligands targeting mGlu could help elucidate the functional significance of mGlu and accelerate drug discovery for neurological and psychiatric disorders.

Hepatoid adenocarcinoma of the stomach: discrimination from conventional gastric adenocarcinoma with a computed tomography-based radiomics nomogram.

Background: Previous studies found it difficult to differentiate hepatoid adenocarcinoma of the stomach (HAS) from conventional gastric adenocarcinoma (CGA). We aimed to assess the efficacy of a computed tomography (CT)-based radiomics nomogram in identifying HAS.

Methods: Portal phase CT images were collected from 59 patients with HAS and 122 patients with CGA.

Development of a Candidate C-Labeled Selective Phosphodiesterase 1 Radioligand for Positron Emission Tomography.

Phosphodiesterases (PDEs) constitute a superfamily of phosphohydrolytic enzymes that regulate intracellular second messenger signaling by hydrolyzing cyclic adenosine monophosphate and cyclic guanosine monophosphate. Among the 11 subfamilies of PDEs, phosphodiesterase 1 (PDE1) stands out due to its broad implications in central and peripheral pathologies. There are three subtypes of PDE1: PDE1A, PDE1B, and PDE1C.

Expression quantitative trait locus mapping of extracellular microRNAs in human plasma.

MicroRNAs, crucial in regulating protein-coding gene expression, are implicated in various diseases. We performed a genome-wide association study of plasma miRNAs (ex-miRNAs) in 3,743 Framingham Heart Study (FHS) participants and identified 1,027 ex-miRNA-eQTLs (exQTLs) for 37 ex-miRNAs, with 55% replication in an independent study. Colocalization analyses suggested potential genetic coregulation of ex-miRNAs with whole blood mRNAs.

Discovery of F Labeled AZD5213 Derivatives as Novel Positron Emission Tomography (PET) Radioligands Targeting Histamine Subtype-3 Receptor.

The histamine subtype 3 (H) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H receptor. In this study, we synthesized and evaluated the binding effects of [F]H3-2404 and [F]H3-2405 by modifying the structure of AZD5213, a selective H antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum.

Real-world effectiveness and safety of macitentan in patients with pulmonary artery hypertension: a multicenter, retrospective, observational study in China.

Background: Macitentan, either as monotherapy or part of combination therapy, improved clinical outcomes in patients with pulmonary artery hypertension (PAH) in clinical trials. Evidence on the effectiveness and safety of macitentan administered in real-world clinical practice in China is limited.

Methods: This real-world, retrospective, multicenter chart review study was conducted at seven hospitals in China.

Design of Atomically Dispersed CoN Sites and Co Clusters for Synergistically Enhanced Oxygen Reduction Electrocatalysis.

Constructing dual-site catalysts consisting of atomically dispersed metal single atoms and metal atomic clusters (MACs) is a promising approach to further boost the catalytic activity for oxygen reduction reaction (ORR). Herein, a porous Co@SNC featuring the coexistence of Co single-atom sites (CoN) and S-coordinated Co atomic clusters (SCo) in S, N co-doped carbon substrate is successfully synthesized by using porphyrinic metal-organic framework (Co-TPyP MOF) as the precursor. The introduction of the sulfur source creates abundant microstructural defects to anchor Co metal clusters, thus modulating the electronic structure of its surrounding carbon substrate.

PET-based radiomic feature based on the cross-combination method for predicting the mid-term efficacy and prognosis in high-risk diffuse large B-cell lymphoma patients.

Objectives: This study aims to develop 7×7 machine-learning cross-combinatorial methods for selecting and classifying radiomic features used to construct Radiomics Score (RadScore) of predicting the mid-term efficacy and prognosis in high-risk patients with diffuse large B-cell lymphoma (DLBCL).

Methods: Retrospectively, we recruited 177 high-risk DLBCL patients from two medical centers between October 2012 and September 2022 and randomly divided them into a training cohort (n=123) and a validation cohort (n=54). We finally extracted 110 radiomic features along with SUVmax, MTV, and TLG from the baseline PET.

Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle-Aged and Older Adults.

Background: Extracellular microRNAs (miRNAs) are a class of noncoding RNAs that remain stable in the extracellular milieu, where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVDs); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level.

Methods And Results: Plasma miRNA levels were measured in 4440 FHS (Framingham Heart Study) participants.

Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway.

Background: Excessive oxidative stress in the brain is an important pathological factor in neurological diseases. Acetoxypachydiol (APHD) is a lipophilic germacrane-type diterpene extracted as a major component from different species of brown algae within the genus Dictyota. There have been no previous reports on the pharmacological activity of APHD.

Association of Arterial Stiffness With Mid- to Long-Term Home Blood Pressure Variability in the Electronic Framingham Heart Study: Cohort Study.

Background: Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, irrespective of underlying hypertension.

Objective: This study aims to investigate if arterial stiffness traits were associated with subsequent mid- to long-term home BPV in the electronic Framingham Heart Study (eFHS).

High-Density CoSe Sites Embedded within 2D Porous N-Doped Carbon for High-Performance Oxygen Reduction Reaction Electrocatalysis.

Designing and fabricating efficient and stable nonprecious metal-based oxygen reduction reaction (ORR) electrocatalysts is a pressing and challenging task for the pursuit of sustainable new energy devices. Herein, porous P-CoSe@NC electrocatalysts with high-density carbon-coated CoSe sites were successfully fabricated based on a pyridyl-porphyrinic metal-organic framework (Co-TPyP MOF) via a molten salt-assisted synthesis method. The hierarchical pore and N-doping carbon substrate of P-CoSe@NC promotes mass transfer and electron-transfer efficiency, which is beneficial to maximize CoSe site utilization.

NiCoP cocatalyst modified g-CN as ohmic junction photocatalyst for efficient degradation of tetracycline under visible light.

Increasing the electron-hole recombination rate in g-CN can effectively improve its photocatalytic performance. In this work, NiCoP/g-CN (NCP/PCN) composites with ohmic junction were formed by embedding granular NiCoP in irregularly porous g-CN. There was almost no barrier between the metal and the semiconductor in ohmic junction, which made it easier for electrons to slip from PCN to NCP along the curved energy band, and NCP acted as an electron collector to rapidly capture the slipping electrons.

Preclinical Evaluation of Novel Positron Emission Tomography (PET) Probes for Imaging Leucine-Rich Repeat Kinase 2 (LRRK2).

Parkinson's disease (PD) is one of the most highly debilitating neurodegenerative disorders, which affects millions of people worldwide, and leucine-rich repeat kinase 2 (LRRK2) mutations have been involved in the pathogenesis of PD. Developing a potent LRRK2 positron emission tomography (PET) tracer would allow for in vivo visualization of LRRK2 distribution and expression in PD patients. In this work, we present the facile synthesis of two potent and selective LRRK2 radioligands [C] ([C]PF-06447475) and [F] ([F]PF-06455943).

Co-Catalyzed Hydrofluorination of Alkenes: Photocatalytic Method Development and Electroanalytical Mechanistic Investigation.

The hydrofluorination of alkenes represents an attractive strategy for the synthesis of aliphatic fluorides. This approach provides a direct means to form C(sp)-F bonds selectively from readily available alkenes. Nonetheless, conducting hydrofluorination using nucleophilic fluorine sources poses significant challenges due to the low acidity and high toxicity associated with HF and the poor nucleophilicity of fluoride.

Preclinical Evaluation of Azabenzimidazole-Based PET Radioligands for γ-8 Dependent Transmembrane AMPA Receptor Regulatory Protein Imaging.

AMPA glutamate receptors (AMPARs) play a pivotal role in excitatory neurotransmission, particularly in the hippocampus where the TARP γ-8 subunit is enriched and serves as a target for emerging anti-epileptic drugs. To enable in vivo visualization of TARP γ-8 distribution and expression by positron emission tomography (PET), this study focuses on the development of novel F-labeled TARP γ-8 inhibitors and their corresponding precursors, stemming from the azabenzimidazole scaffold. The resulting radioligands [ F]TARP-2204 and [ F]TARP-2205 were successfully synthesized with acceptable radiochemical yield, high molar activity, and excellent radiochemical purity.

Synthesis and Biological Evaluation of Enantiomerically Pure () and ()[18F]OF-NB1 for Imaging the GluN2B Subunit-Containing NMDA Receptors.

GluN2B subunit-containing methyl-d-aspartate (NMDA) receptors have been implicated in various neurological disorders. Nonetheless, a validated fluorine-18 labeled positron emission tomography (PET) ligand for GluN2B imaging in the living human brain is currently lacking. The aim of this study was to develop a novel synthetic approach that allows an enantiomerically pure radiosynthesis of the previously reported PET radioligands ()[F]OF-NB1 and ()[F]OF-NB1 as well as to assess their and performance characteristics for imaging the GluN2B subunit-containing NMDA receptor in rodents.

Circulating metabolites may illustrate relationship of alcohol consumption with cardiovascular disease.

Background: Metabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.

Methods: Cumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women).