Impacts of EPA's finalized power plant greenhouse gas standards.

Emissions reductions may be met with relatively small costs.

Retrospective study of incidence/prevalence of pigmentary maculopathy and retinopathy in patients receiving pentosan polysulfate sodium.

Purpose: To evaluate prevalence and incidence rates of pigmentary maculopathy and retinopathy (PM/PR), and visual acuity (VA) changes in patients exposed to pentosan polysulfate sodium (PPS) and in patients with interstitial cystitis (IC) not exposed to PPS.

Methods: This is a retrospective cohort study (January 2015-March 2021) which included adult de-identified patients from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) and Komodo Health database. Three patient cohorts were identified: two PPS-exposed patient cohorts, and Non-PPS-exposed IC patient cohort.

TRMT1L-catalyzed mG27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress.

tRNA modifications are critical for several aspects of their functions, including decoding, folding, and stability. Using a multifaceted approach encompassing eCLIP-seq and nanopore tRNA-seq, we show that the human tRNA methyltransferase TRMT1L interacts with the component of the Rix1 ribosome biogenesis complex and binds to the 28S rRNA as well as to a subset of tRNAs. Mechanistically, we demonstrate that TRMT1L is responsible for catalyzing N2,N2-dimethylguanosine (mG) solely at position 27 of tRNA-Tyr-GUA.

Dissociable roles of central striatum and anterior lateral motor area in initiating and sustaining naturalistic behavior.

Understanding how corticostriatal circuits mediate behavioral selection and initiation in a naturalistic setting is critical to understanding behavior choice and execution in unconstrained situations. The central striatum (CS) is well poised to play an important role in these spontaneous processes. Using fiber photometry and optogenetics, we identify a role for CS in grooming initiation.

Restrictive or Liberal Blood Transfusion in Patients with Myocardial Infarction and CKD.

Background: Chronic kidney disease (CKD) is associated with higher risk of myocardial infarction and anemia. Among patients with anemia and CKD who experience myocardial infarction, it remains uncertain if a liberal red blood cell transfusion threshold strategy (hemoglobin cutoff [Hgb] < 10 g/dL) is superior to a restrictive transfusion threshold (Hgb 7-8 g/dL) strategy.

Methods: Among the 3,504 patients enrolled in the Myocardial Ischemia and Transfusion (MINT) trial with non-missing creatinine, we compared baseline characteristics and 30-day and 6-month outcomes of patients without CKD (N = 1279), CKD with eGFR 30-60 mL/min/1.

Children's executive functioning and health behaviors across pediatric life stages and ecological contexts.

Executive functioning (EF) has been linked to chronic disease risk in children. Health behaviors are thought to partially explain this association. The current cross-sectional study evaluated specific domains of EF and varied health behaviors in three pediatric life stages.

Oocyte maturation defect in women undergoing IVF: contributing factors and effects on mature sibling oocyte outcomes.

Purpose: This study aimed to identify demographic and clinical factors associated with low maturation rates and to investigate if the rate of immature oocytes impacts the outcomes of mature sibling oocytes.

Methods: Women undergoing their first IVF-ICSI cycle between 2018 and 2022 at a fertility clinic were included. Cycles were classified into five groups according to the proportion of Metaphase II stage oocytes (MII): Null (0% MII, n = 46), Poor (1-25% MII, n = 44), Low (26-50% MII, n = 453), Acceptable (51-75% MII, n = 1641), and Optimal (76-100% MII, n = 2642).

Immune Checkpoint Blockade Delays Cancer Development and Extends Survival in DNA Polymerase Mutator Syndromes.

Mutations in the exonuclease domains of the replicative nuclear DNA polymerases POLD1 and POLE are associated with increased cancer incidence, elevated tumor mutation burden (TMB), and enhanced response to immune checkpoint blockade (ICB). Although ICB is approved for treatment of several cancers, not all tumors with elevated TMB respond, highlighting the need for a better understanding of how TMB affects tumor biology and subsequently immunotherapy response. To address this, we generated mice with germline and conditional mutations in the exonuclease domains of Pold1 and Pole.

Biomarkers.

Background: Amyloid beta (Aβ) deposition marks an early stage in the progression of Alzheimer's disease (AD), detectable in-vivo years before symptoms emerge and targeted by recently FDA-approved drugs. This has propelled advancements in understanding, measuring, and treating AD, paving the way for disease prevention in those at risk. However, the psychological impact of disclosing Aβ status to cognitively unimpaired individuals remains underexplored.

Biomarkers.

Background: Alzheimer's Disease (AD) is associated with sleep disturbances. Moreover, individuals with sleep disturbances have been reported to have a higher risk for developing AD. The measurement of sleep behavior therefore opens the opportunity for a potential digital biomarker of AD.

Biomarkers.

Background: Recent advances in diagnostics have made it possible to identify early signs of the pathophysiological changes underlying Alzheimer's Disease (AD) via blood tests. However, the use of blood-based biomarkers (BBBMs) for the early detection of AD may be limited in primary care settings despite its potential for wide access and early detection of AD (PMID: 37295421) Therefore, there is a need to understand the barriers and facilitators of BBBM testing for AD in primary care.

Method: We employed a combination of qualitative research, advisory board, and quantitative survey to engage with clinical/scientific advisors and community-based physicians in primary care.

Biomarkers.

Background: Type 2 diabetes (T2D) is a recognized risk factor for dementia. This study aimed to pinpoint blood DNA methylation biomarkers for cognitive decline in older adults with T2D by comparing those who developed dementia with those who remained cognitively normal during follow-up METHOD: Illumina Infinium MethylationEPIC microarray was used for the initial 24 couples and Infinium HumanMethylationEPIC microarray version 2.0 for the subsequent 8 couples.

Biomarkers.

Background: Biomarkers, such as blood p-tau181, p-tau217, and p-tau231, have been created and verified to mirror the pathophysiology of tau and amyloid-β (Aβ) in the brain . Sleep spindles are known to contribute to memory consolidation and generalization and may therefore be a promising biomarker in preclinical Alzheimer's Disease (AD) . The present study investigated the relationship between sleep spindles and p-tau levels in cognitively healthy older African Americans.

Biomarkers.

Background: New innovations take a long time to be utilized into routine healthcare due to intrinsic and practical barriers. Implementation science can identify such barriers and offer potential solutions to speed up this process. Blood-based biomarkers (BBBMs) may enable scalable confirmation of amyloid pathology in the Alzheimer's disease (AD) care pathway with test performance similar to cerebrospinal fluid (CSF) testing and positron emission tomography (PET), so-called confirmatory biomarkers as they can corroborate amyloid pathology with high certainty.

Biomarkers.

Background: Highly specific ATN plasma biomarker assays for neurodegenerative diseases have been developed, but their associations with cognition vary in different populations. Kidney disease, common in diabetes, may decrease the predictive precision of those biomarkers. The aim of this study was to characterize for the first time the relationships between plasma ATN biomarkers and cognitive function in adults with T1D.

Biomarkers.

Background: Cognitive dysfunction is more common in individuals with type 1 diabetes (T1D) compared to the general population. Blood-based biomarkers are accurate in identifying early signs of neurodegeneration. However, studies using these biomarkers in T1D are lacking.

Biomarkers.

Background: South Asian (SA) older adults are one of the fastest growing US populations developing Alzheimer's disease (AD) and related dementias (ADRD). Compared to non-Hispanic white (NHW) Americans, SA are hesitant to enroll in neuropsychological and MRI research. This status complicates accurate assessment and diagnosis.

Use and limitations of clinical data in the identification and classification of low molecular weight chemicals (LMWCs) as respiratory sensitizers: recommendations for improvement.

While progress has been made in recent years, there are still no suitable and accepted , or models that can be used to accurately predict whether a chemical substance has the intrinsic property to cause immune-mediated chemical respiratory allergy, typically manifested as allergic asthma or allergic rhinitis which represents a severe health hazard. Regulatory authorities have relied primarily on clinical evidence (case reports, clinical databases, worker exposure studies) to classify substances as respiratory sensitizers, but this evidence can lack a proven immunological mechanism which is necessary to identify substances which can cause life-long sensitization and clinically relevant allergic symptoms in the respiratory tract in an exposed population (such respiratory allergens may be considered as "true" sensitizers, in analogy to the definition of skin sensitization, and in contrast to respiratory irritants). In light of this, the European Center for Ecotoxicology and Toxicology of Chemicals convened a Task Force to evaluate the types of clinical methods and data sources and the implications of relying on such data for regulatory decision making from a scientific perspective.

Biomarkers.

Background: There is an urgent need for neuropsychological screening tests that are easily deployed and reliable. We have developed a digital neuropsychological screening protocol that is administered on a tablet, automatically scored using artificial intelligence, and requires approximately 10 minutes to administer. This tablet-administered protocol assesses the requisite neurocognitive constructs associated with emergent neurodegenerative illness METHOD: The digital protocol was administered to 77 ambulatory care/ memory clinic patients (Table 1).

Biomarkers.

Background: Studying brain reserve - the brain's resilience to age-related changes or damage - is crucial for understanding protective mechanisms against cognitive decline. The cerebellum may be a key region in brain reserve, but it has been historically understudied. This investigation delves into this critical area within the largest aging multi-cohort to date.

Biomarkers.

Background: To support diagnosis of Alzheimer's disease (AD), concentrations of Aβ, tTau and pTau(181) and the Aβ/Aβ ratio are determined in cerebrospinal fluid (CSF). To increase standardization and comparability between diagnostic laboratories, certified reference material (CRM) is used to evaluate the trueness of novel assays. Due to lack of CRMs for tTau, pTau(181), and Aβ, comparability may be assessed by comparing assays from different manufacturers.

Biomarkers.

Background: It is well known that Alzheimer's disease (AD)-related pathological changes can begin up to a decade before patients experience telltale symptoms, yet presymptomatic detection remains an unmet goal. In the present study, we demonstrate the utility of a panel of autoantibodies capable of detecting AD-related pathological processes at the earliest points along the AD continuum, including presymptomatic AD (up to 10 years before onset of symptoms) and prodromal AD (mild cognitive impairment, MCI).

Method: Utilizing Duritect-AD, a blood-based test employing a customized panel of autoantibody biomarkers and Luminex xMAP® technology, sera from ADNI subjects with confirmed presymptomatic or prodromal AD (MCI) were screened to detect the presence of AD-related pathology.

Biomarkers.

Background: Investigating age-related changes in MEG brain networks offers significant potential for comprehending aging trajectories and unveiling anomalous patterns associated with neurodegenerative disorders, such as Alzheimer's disease. In this study, we extended a deep learning model called Fully Hyperbolic Neural Network (FHNN) to embed MEG brain connectivity graphs into a Lorentz Hyperboloid model for hyperbolic space. Through these embeddings, we then explored the impact of aging on brain functional connectivity across multiple decades.

Biomarkers.

Background: Reductions in medial temporal lobe (MTL) volume, particularly in the amygdala and hippocampus, are present in early Alzheimer's disease (AD). We explore the correlations between hippocampal and amygdalar subfield volumes and brain amyloid-β (Aβ) accumulation using T1-weighted structural MRI and amyloid PET data from ADNI and Eisai clinical trials.

Method: We used FreeSurfer (v7.