APOE loss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer's disease pathology.

The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Knockdown of ε4 may provide a therapeutic strategy for AD, but the effect of APOE loss of function (LoF) on AD pathogenesis is unknown. We searched for APOE LoF variants in a large cohort of controls and patients with AD and identified seven heterozygote carriers of APOE LoF variants.

A familial missense variant in the Alzheimer's disease gene SORL1 impairs its maturation and endosomal sorting.

The SORL1 gene has recently emerged as a strong Alzheimer's Disease (AD) risk gene. Over 500 different variants have been identified in the gene and the contribution of individual variants to AD development and progression is still largely unknown. Here, we describe a family consisting of 2 parents and 5 offspring.

Weight Loss Is a Strong Predictor of Memory Disorder Independent of Genetic Influences.

Background: Past studies identified a link between weight loss and dementia, but lacked consistent conclusions. We sought to establish this link by examining the weight change profiles before and after dementia diagnosis.

Methods: Using data from the Health and Retirement Study (1996-2020), we examined 13,123 participants.

loss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer's Disease pathology.

The ε4 allele of apolipoprotein E () is the strongest genetic risk factor for sporadic Alzheimer's Disease (AD). Knockdown of this allele may provide a therapeutic strategy for AD, but the effect of loss-of-function (LoF) on AD pathogenesis is unknown. We searched for LoF variants in a large cohort of older controls and patients with AD and identified six heterozygote carriers of LoF variants.

A familial missense variant in the Alzheimer's Disease gene impairs its maturation and endosomal sorting.

The gene has recently emerged as a strong Alzheimer's Disease (AD) risk gene. Over 500 different variants have been identified in the gene and the contribution of individual variants to AD development and progression is still largely unknown. Here, we describe a family consisting of 2 parents and 5 offspring.

A Preliminary Comparison of the Methylome and Transcriptome from the Prefrontal Cortex Across Alzheimer's Disease and Lewy Body Dementia.

Background: Pathological amyloid-β and -synuclein are associated with a spectrum of related dementias, ranging from Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) to Parkinson disease dementia (PDD). While these diseases share clinical and pathological features, they also have unique patterns of pathology. However, epigenetic factors that contribute to these pathological differences remain unknown.

Implementation of the I-PASS handoff program in diverse clinical environments: A multicenter prospective effectiveness implementation study.

Background: Handoff miscommunications are a leading source of medical errors. Harmful medical errors decreased in pediatric academic hospitals following implementation of the I-PASS handoff improvement program. However, implementation across specialties has not been assessed.

Patient and Family-Centered I-PASS SCORE Program: Resident and Advanced Care Provider Training Materials.

Introduction: Patient and family-centered rounds (PFCRs) are an important element of family-centered care often used in the inpatient pediatric setting. However, techniques and best practices vary, and faculty, trainees, nurses, and advanced care providers may not receive formal education in strategies that specifically enhance communication on PFCRs.

Methods: Harnessing the use of structured communication, we developed the Patient and Family-Centered I-PASS Safer Communication on Rounds Every Time (SCORE) Program.

TOMM40 genetic variants associated with healthy aging and longevity: a systematic review.

Introduction: Healthy aging relies on mitochondrial functioning because this organelle provides energy and diminishes oxidative stress. Single nucleotide polymorphisms (SNPs) in TOMM40, a critical gene that produces the outer membrane protein TOM40 of mitochondria, have been associated with mitochondrial dysfunction and neurodegenerative processes. Yet it is not clear whether or how the mitochondria may impact human longevity.

ARIMA Model and Few-Shot Learning for Vehicle Speed Time Series Analysis and Prediction.

In the fields of traffic management, traffic health, and vehicle safety, vehicle speed prediction is an important research topic. The greater the difference between vehicle speed and average vehicle speed, or the more discrete the vehicle speed distribution, the higher the accident rate. This paper proposes a vehicle speed prediction method based on adaptive KF (Kalman filtering) in the ARMA (Autoregressive Moving Average) environment to address the problem of high-speed moving vehicle speed prediction.

RNA Transcription in Alzheimer's Disease Brain and Its Implication in Mitochondrial Dysfunction.

Increasing evidence suggests that the Translocase of Outer Mitochondria Membrane 40 () gene may contribute to the risk of Alzheimer's disease (AD). Currently, there is no consensus as to whether expression is up- or down-regulated in AD brains, hindering a clear interpretation of 's role in this disease. The aim of this study was to determine if RNA levels differ between AD and control brains.

Photogenerated charge separation and recombination path modification in monocline LuWO lattice transition and Bi-O antibonding states.

Monoclinic Lu2WO6 undergoes diphase-to-perovskite BiLuWO6 transition via selective occupancy of Bi in three Lu sites. The transformation mechanism, process, and structure stabilities are revealed by variable cell nudged elastic band method, video, and phonon spectrum. Lattice transition brings about photogenerated charge separation in BiLuWO6.

Regulation of circular RNAs act as ceRNA in a hypoxic pulmonary hypertension rat model.

To explore potential critical genes and identify circular RNAs (circRNAs) that act as the competitive endogenous RNA (ceRNA) in a hypoxic pulmonary hypertension (HPH) rat model. Constructed rat model, and a bioinformatics method was used to analyse differentially expressed (DE) genes and construct a circRNA-miRNA-mRNA ceRNA regulatory network. Then, qRT-PCR was used to verify.

Association of Uncommon, Noncoding Variants in the APOE Region With Risk of Alzheimer Disease in Adults of European Ancestry.

Importance: The ε2 and ε4 alleles of the apolipoprotein E (APOE) gene are associated with Alzheimer disease (AD) risk. Although nearby genetic variants have also been shown to be associated with AD, including rs2075650 in the TOMM40 gene and rs4420638 near the APOC1 gene, it is unknown whether these associations are independent of the ε2 and ε4 alleles.

Objective: To assess whether variants near APOE are associated with AD independently of the ε2/ε3/ε4 genotype.

Lack of APOE Christchurch variant in five age of onset outliers with PSEN1, PSEN2 Alzheimer's disease and MAPT frontotemporal dementia.

Introduction: Age of onset modifiers are of considerable importance in Alzheimer's and related dementias. Arboleda-Valesquez et al., reporting on a single PSEN1 subject, suggested that homozygosity for the Christchurch variant of APOE could represent such a modifier.

Receiving sensitivity improvement by wide-spectrum OAM with OTDM and polarization multiplexing in weak atmospheric turbulence.

In this paper, a wide-spectrum orbital angular momentum (OAM) system with a polarization and optical time division multiplexing (OTDM) free-space transmission system is experimentally demonstrated. To enhance the system transmission performance in atmospheric turbulent channel, a wide-spectrum laser and an OAM beam are used. The wide-spectrum laser can be generated by utilizing pumped laser to pump nonlinear fiber, and OAM can be generated with a special light modulator.

I-PASS Mentored Implementation Handoff Curriculum: Frontline Provider Training Materials.

Introduction: The I-PASS Handoff Program is a comprehensive handoff curriculum that has been shown to decrease rates of medical errors and adverse events during patient handoffs. Frontline providers are the key individuals participating in handoffs of patient care. It is important they receive robust handoff training.

Redefining transcriptional regulation of the APOE gene and its association with Alzheimer's disease.

The apolipoprotein E gene (APOE) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), yet the expression of APOE is not clearly understood. For example, it is unclear whether AD patients have elevated or decreased APOE expression or why the correlation levels of APOE RNA and the ApoE protein differ across studies. Likewise, APOE has a single CpG island (CGI) that overlaps with its 3'-exon, and this CGI's effect is unknown.

Teaching at the Bedside: Strategies for Optimizing Education on Patient and Family Centered Rounds.

Resident and attending concern about the potential for decreased teaching has been cited as one of the drawbacks to the adoption of family-centered rounds (FCR). Despite these concerns, FCR can enhance clinical education through direct exposure to multiple patients by all team members, as well as by allowing faculty to teach, model, observe, and assess learners' clinical skills more effectively than in nonbedside settings. This article provides many strategies and approaches to bedside teaching designed to enhance education and communication among care team members as well as patients and their families.

Simulation in Medical Education for the Hospitalist: Moving Beyond the Mock Code.

Simulation in medical education has grown due to an evolution in health care. It uses 4 main modalities to re-create a situation from the clinical environment to allow experiential learning and improve patient care. Simulation must be considered as an educational strategy within a larger curriculum.

Machine Learning for Long Cycle Maintenance Prediction of Wind Turbine.

Within Internet of Things (IoT) sensors, the challenge is how to dig out the potentially valuable information from the collected data to support decision making. This paper proposes a method based on machine learning to predict long cycle maintenance time of wind turbines for efficient management in the power company. Long cycle maintenance time prediction makes the power company operate wind turbines as cost-effectively as possible to maximize the profit.