Tau-network mapping of domain-specific cognitive impairment in Alzheimer's disease.

Fibrillar tau gradually progresses in the brain during the course of Alzheimer's disease (AD). However, the contribution of tau accumulation in a given brain region to decline in different cognitive domains and thus phenotypic heterogeneity in AD remains unclear. Here, we leveraged the functional connectome to link the locality of tau accumulation to domain-specific cognitive impairment.

SDS-Net: A Synchronized Dual-Stage Network for Predicting Patients Within 4.5-h Thrombolytic Treatment Window Using MRI.

Timely and precise identification of acute ischemic stroke (AIS) within 4.5 h is imperative for effective treatment decision-making. This study aims to construct a novel network that utilizes limited datasets to recognize AIS patients within this critical window.

Nonspecific Signs and/or Symptoms of Cancer: A Retrospective, Observational Analysis from a Secondary Care, US Community Oncology Dataset.

To help determine the unmet need for improved diagnostic tools to evaluate patients with nonspecific signs and/or symptoms (NSSS) and suspicion of cancer, we examined patient characteristics, diagnostic journey, and cancer incidence of patients with NSSS within The US Oncology Network (The Network), a secondary care community oncology setting. This retrospective, observational cohort study included patients aged ≥40 years with ≥1 NSSS in their problem list at their first visit within The Network (the index date) between 1 January 2016 and 31 December 2020. Patients were followed longitudinally with electronic health record data for initial cancer diagnosis, new noncancer diagnosis, death, end of study observation period, or 12 months, whichever occurred first.

The characterization of functional conduction block in patients with multiple types of atrial tachycardia- A discussion on the mechanism of multiple atrial tachycardia.

Background: High-resolution mapping offers superior accuracy in delineating conduction features; however, certain characteristics are still linked to elevated recurrence rates of atrial tachycardia (AT), suggesting the influence of additional mechanisms. This study systematically assessed the substrate of functional conduction block (FCB) regions in relation to the mechanisms of multiple ATs.

Methods: In this study, the Carto system facilitated the mapping of ATs in 13 patients undergoing ablation, each presenting with more than two AT variants.

Broadening Horizons: Exploring mtDAMPs as a Mechanism and Potential Intervention Target in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) have been recognized as the leading cause of premature mortality and morbidity worldwide despite significant advances in therapeutics. Inflammation is a key factor in CVD progression. Once stress stimulates cells, they release cellular compartments known as damage-associated molecular patterns (DAMPs).

Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases.

Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs.

Corrigendum: Alterations via inter-regional connective relationships in Alzheimer's disease.

[This corrects the article DOI: 10.3389/fnhum.2023.

Alterations via inter-regional connective relationships in Alzheimer's disease.

Disruptions in the inter-regional connective correlation within the brain are believed to contribute to memory impairment. To detect these corresponding correlation networks in Alzheimer's disease (AD), we conducted three types of inter-regional correlation analysis, including structural covariance, functional connectivity and group-level independent component analysis (group-ICA). The analyzed data were obtained from the Alzheimer's Disease Neuroimaging Initiative, comprising 52 cognitively normal (CN) participants without subjective memory concerns, 52 individuals with late mild cognitive impairment (LMCI) and 52 patients with AD.

Combined Connectomics, MAPT Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease.

Objective: We aimed to test whether region-specific factors, including spatial expression patterns of the tau-encoding gene MAPT and regional levels of amyloid positron emission tomography (PET), enhance connectivity-based modeling of the spatial variability in tau-PET deposition in the Alzheimer disease (AD) spectrum.

Methods: We included 685 participants (395 amyloid-positive participants within AD spectrum and 290 amyloid-negative controls) with tau-PET and amyloid-PET from 3 studies (Alzheimer's Disease Neuroimaging Initiative, F-AV-1451-A05, and BioFINDER-1). Resting-state functional magnetic resonance imaging was obtained in healthy controls (n = 1,000) from the Human Connectome Project, and MAPT gene expression from the Allen Human Brain Atlas.

Study on the Role of in the Regulation of Plasmid-Mediated -Induced Expression in .

Objective: In this study, we constructed knock-out and knock-in strains from a clinically isolated Kp1strain carrying in its plasmid and compared them with the Kp NTUH-K2044 strain to investigate the relationship between and -induced expression.

Methods: We created the gene deletion mutant strains Kp1-Δ and Kp NTUH-K2044-Δ with pKO3-km plasmid using homologous recombination technology. We constructed the Kp NTUH-K2044-RC and Kp NTUH-K2044-Δ-RC drug resistance model strains with plasmid pACYC184.

Exploring cuproptosis as a mechanism and potential intervention target in cardiovascular diseases.

Copper (Cu) is a vital trace element for maintaining human health. Current evidence suggests that genes responsible for regulating copper influx and detoxification help preserve its homeostasis. Adequate Cu levels sustain normal cardiac and blood vessel activity by maintaining mitochondrial function.

Glucose metabolism disorder: a potential accomplice of SARS-CoV-2.

Globally, 265,713,467 confirmed cases of SARS-CoV-2 (CoV-2), including 5,260,888 deaths, have been reported by the WHO. It is important to study the mechanism of this infectious disease. A variety of evidences show the potential association between CoV-2 and glucose metabolism.

Performance of a Cell-Free DNA-Based Multi-cancer Detection Test in Individuals Presenting With Symptoms Suspicious for Cancers.

Purpose: A multi-cancer detection test using a targeted methylation assay and machine learning classifiers was validated and optimized for screening in prospective, case-controlled Circulating Cell-free Genome Atlas (ClinicalTrials.gov identifier: NCT02889978) substudy 3. Here, we report test performance in a subgroup of participants with symptoms suspicious for cancer to assess the test's ability to potentially facilitate efficient diagnostic evaluation in symptomatic individuals.

Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study.

Background: Analysis of circulating tumour DNA could stratify cancer risk in symptomatic patients. We aimed to evaluate the performance of a methylation-based multicancer early detection (MCED) diagnostic test in symptomatic patients referred from primary care.

Methods: We did a multicentre, prospective, observational study at National Health Service (NHS) hospital sites in England and Wales.

Single-cell transcriptional profiling of hearts during cardiac hypertrophy reveals the role of MAMs in cardiomyocyte subtype switching.

Pathological cardiac hypertrophy is the main predecessor of heart failure. Its pathology is sophisticated, and its progression is associated with multiple cellular processes. To explore new therapeutic approaches, more precise examination of cardiomyocyte subtypes and involved biological processes is required in response to hypertrophic stimuli.

Mitophagy and Traumatic Brain Injury: Regulatory Mechanisms and Therapeutic Potentials.

Traumatic brain injury (TBI), a kind of external trauma-induced brain function alteration, has posed a financial burden on the public health system. TBI pathogenesis involves a complicated set of events, including primary and secondary injuries that can cause mitochondrial damage. Mitophagy, a process in which defective mitochondria are specifically degraded, segregates and degrades defective mitochondria allowing a healthier mitochondrial network.

Functional network segregation is associated with attenuated tau spreading in Alzheimer's disease.

Introduction: Lower network segregation is associated with accelerated cognitive decline in Alzheimer's disease (AD), yet it is unclear whether less segregated brain networks facilitate connectivity-mediated tau spreading.

Methods: We combined resting state functional magnetic resonance imaging (fMRI) with longitudinal tau positron emission tomography (PET) in 42 betamyloid-negative controls and 81 amyloid beta positive individuals across the AD spectrum. Network segregation was determined using resting-state fMRI-assessed connectivity among 400 cortical regions belonging to seven networks.

Combining tau-PET and fMRI meta-analyses for patient-centered prediction of cognitive decline in Alzheimer's disease.

Background: Tau-PET is a prognostic marker for cognitive decline in Alzheimer's disease, and the heterogeneity of tau-PET patterns matches cognitive symptom heterogeneity. Thus, tau-PET may allow precision-medicine prediction of individual tau-related cognitive trajectories, which can be important for determining patient-specific cognitive endpoints in clinical trials. Here, we aimed to examine whether tau-PET in cognitive-domain-specific brain regions, identified via fMRI meta-analyses, allows the prediction of domain-specific cognitive decline.

Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer's disease.

Background: In Alzheimer's disease (AD), fibrillar tau initially occurs locally and progresses preferentially between closely connected regions. However, the underlying sources of regional vulnerability to tau pathology remain unclear. Previous brain-autopsy findings suggest that the myelin levels-which differ substantially between white matter tracts in the brain-are a key modulating factor of region-specific susceptibility to tau deposition.

Hexachloropentadiene in Soil, Air, and Biota Around an Agrochemical Factory: Concentrations, Distribution, and Risk Evaluation.

Hexachloropentadiene (HCPD) is a highly toxic compound that is mainly used for preparation of organochlorine insecticides. To investigate HCPD contamination of the environment during pesticide processing, 153 air, soil, and biota samples were collected around an agrochemical factory in different seasons of 1 year and analyzed for HCPD. The HCPD concentrations were 0.

New Insight in HDACs: Potential Therapeutic Targets for the Treatment of Atherosclerosis.

Atherosclerosis (AS) features include progressive hardening and reduced elasticity of arteries. AS is the leading cause of morbidity and mortality. An increasing amount of evidence showed that epigenetic modifications on genes serve are a main cause of several diseases, including AS.

Epigenetics and Beyond: Targeting Histone Methylation to Treat Type 2 Diabetes Mellitus.

Diabetes mellitus is a global public health challenge with high morbidity. Type 2 diabetes mellitus (T2DM) accounts for 90% of the global prevalence of diabetes. T2DM is featured by a combination of defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin.

Mitochondrial Dynamics: Pathogenesis and Therapeutic Targets of Vascular Diseases.

Vascular diseases, particularly atherosclerosis, are associated with high morbidity and mortality. Endothelial cell (EC) or vascular smooth muscle cell (VSMC) dysfunction leads to blood vessel abnormalities, which cause a series of vascular diseases. The mitochondria are the core sites of cell energy metabolism and function in blood vessel development and vascular disease pathogenesis.

Emerging Role of Mitophagy in the Heart: Therapeutic Potentials to Modulate Mitophagy in Cardiac Diseases.

The normal function of the mitochondria is crucial for most tissues especially for those that demand a high energy supply. Emerging evidence has pointed out that healthy mitochondrial function is closely associated with normal heart function. When these processes fail to repair the damaged mitochondria, cells initiate a removal process referred to as mitophagy to clear away defective mitochondria.