The Spectrum of Genetic Risk in Alzheimer Disease.

Alzheimer disease (AD), the most common dementing syndrome in the United States, is currently established by the presence of amyloid-β and tau protein biomarkers in the setting of clinical cognitive impairment. These straightforward diagnostic parameters belie an immense complexity of genetic architecture underlying risk and presentation in AD. In this review, we provide a focused overview of the current state of AD genetics.

Transcatheter Management of Tricuspid Regurgitation: A Review of Contemporary Evidence.

Tricuspid regurgitation (TR) is a common valvular heart disease that is associated with increased morbidity and mortality. Traditional surgical interventions, though definitive, carry considerable complexities and risks, especially for high-risk patients, with in-hospital mortality rates of ˜9%. This resulted in the undertreatment of many patients with TR, creating a substantial unmet need.

Impact of using time-averaged exposure metrics on binary endpoints in exposure-response analyses.

Exposure-response (ER) analyses are routinely performed as part of model-informed drug development to evaluate the risk-to-benefit ratio for dose selection, justification, and confirmation. For logistic regression analyses with binary endpoints, several exposure metrics are investigated, based on pharmacological plausibility, including time-averaged concentration to event (C). C is informative because it accounts for dose interruptions, modifications, and reductions and is therefore often compared against ER relationships identified using steady-state exposures.

Development of a portable testing chamber to assess imaging performance of laparoscopes in low- and middle-income countries.

Significance: Laparoscopic surgery is generally unavailable in low- and middle-income countries (LMICs) due to the high cost of installation and lack of qualified personnel to maintain and repair equipment. We developed a low-cost, durable, reusable laparoscopic system, called the KeyScope laparoscope, for use in LMICs. To reliably build and service the KeyScope in LMICs, a portable testing chamber (PTC) is needed to assess image performance.

Classification performance and reproducibility of GPT-4 omni for information extraction from veterinary electronic health records.

Large language models (LLMs) can extract information from veterinary electronic health records (EHRs), but performance differences between models, the effect of hyperparameter settings, and the influence of text ambiguity have not been previously evaluated. This study addresses these gaps by comparing the performance of GPT-4 omni (GPT-4o) and GPT-3.5 Turbo under different conditions and by investigating the relationship between human interobserver agreement and LLM errors.

Temporal trends of liver cancer burden, comparative analysis of risk factors and trend forecasts to 2024 in China, USA, the Republic of Korea, and Mongolia: an analysis based on multiple data sources from Global Burden of Disease 2019, the Global Cancer Observatory, and Cancer Incidence in Five Continents.

Background: Liver cancer represents a significant burden of disease globally, with variations in liver cancer status among countries. In this study, we aimed to evaluate the epidemiological burden of liver cancer in four representative countries - China, the USA, the Republic of Korea, and Mongolia - and cover the highest number of incidence cases, the highest prevalence rates and the burden in developed countries. In addition, we intended to predict the trends in liver cancer in these countries over the next six years.

Organic Micropollutants in Waterways of a Large-Scale Water Diversion Project: Insights from Nontarget Screening and "Community" Analysis.

Large-scale water diversion projects are essential for meeting the needs of water-stressed regions, necessitating an evaluation of their impact on water quality and aquatic ecosystems. This study provides the first snapshots of organic micropollutants (OMPs) along the 1466 km Eastern Route of China's South-to-North Water Diversion Project. Using nontarget analysis with ultrahigh-performance liquid chromatography and high-resolution mass spectrometry, we identified and quantified 357 OMPs from water samples collected during the water diversion period (WDP) and the nonwater diversion period (NWDP).

A Regulatory Roadmap for Repurposing: Comparing Pathways for Making Repurposed Drugs Available In The EU, UK, And US.

To help academic and non-profit investigators interested in drug repurposing navigate regulatory approval processes, we compared pathways for repurposed drugs to obtain approval at EMA, UK MHRA, and the US FDA. Though we found no pathways specifically for repurposed drugs, pathways to market are available in all repurposing scenarios.

The Realization of Portable MRI for Indigenous Communities in the USA and Canada.

The paucity of existing baseline data for understanding neurologic health and the effects of injury on people from Indigenous populations is causally related to the limited representation of communities in neuroimaging research to date. In this paper, we explore ways to change this trend in the context of portable MRI, where portability has opened up imaging to communities that have been neglected or inaccessible in the past. We discuss pathways to engage local leadership, foster the participation of communities for this unprecedented opportunity, and empower field-based researchers to bring the holistic worldview embraced by Indigenous communities to neuroimaging research.

State-Mandated Ethics Oversight Is Inappropriate for Gender-Affirming Care.

A proposed state administrative rule would have required medical ethicists to approve certain aspects of gender-affirming care. The authors argue the proposed rule lacked appropriate justification compared to other instances of state-mandated ethics oversight and would undermine trust, raise practical challenges, and send harmful messages to society, patients, and providers.

How Leaders at High-Performing Healthcare Organizations Think About Organizational Professionalism.

This pilot study is the first formal exploration of the concept of "Organizational Professionalism" (OP) among health system leaders in high-performing healthcare organizations. Semi-structured key informant interviews with 23 leaders from 8 healthcare organizations that were recipients of the Malcolm Baldrige National Quality Award (MBNQA) or Baldrige-based state quality award programs explored conceptualization, operationalization, and measurement of OP. Further exploration and understanding of OP in healthcare organizations has the potential to establish and sustain professional and ethical organizational cultures that bolster trust through the sound implementation of laws, policies, and procedures to support the delivery of high-quality patient care.

Diminution of Public Health Agency Authorities Post-.

In a new era of regulatory oversight, the US Supreme Court upended traditional deference to agency interpretations of ambiguous Congressional provisions in in June 2024. Federal courts were instructed to make their own assessments of statutory authorities amid an onslaught of public health agency challenges surfacing nationally. Even so, SCOTUS may be eyeing further limits on agency powers despite clear and substantial repercussions for the health of the nation.

Detection of Oral Fluid Stains on Fabric via Solution Extraction Combined with Deep Ultraviolet Raman Spectroscopy.

DNA phenotyping plays a central role in modern practical forensics, yet an overwhelming amount of evidence creates significant backlogs in all major crime laboratories. A fast nondestructive test of a potential biological stain prior to DNA phenotyping should reduce the number of irrelevant samples for the analysis and increase the efficiency of the overall process. Evidence items recovered from the crime scene can often include body fluid traces, such as oral fluid (OF).

Transformer Graph Variational Autoencoder for Generative Molecular Design.

In the field of drug discovery, the generation of new molecules with desirable properties remains a critical challenge. Traditional methods often rely on SMILES (Simplified Molecular Input Line Entry System) representations for molecular input data, which can limit the diversity and novelty of generated molecules. To address this, we present the Transformer Graph Variational Autoencoder (TGVAE), an innovative AI model that employs molecular graphs as input data, thus captures the complex structural relationships within molecules more effectively than string models.

The impact of quantitative platform on candidacy for bronchoscopic lung volume reduction: a multi-center retrospective cohort study.

Background: Bronchoscopic lung volume reduction (BLVR) can be an effective treatment for highly selected patients with severe emphysema but only half of carefully selected patients derive clinical benefit. Two commercially available platforms exist to help determine candidacy for BLVR via quantitative analysis of computed tomography (CT) scans.

Objectives: To determine if the two commercially available quantitative platforms identified the same patient population that may benefit from BLVR.

Lipid Curvature and Fluidity Influence Lipid Incorporation Disparities in Nanodiscs.

Nanodiscs have become a popular membrane mimetic system offering a well-defined bilayer environment to stabilize membrane proteins for in vitro analyses using a range of analytical methods; however, lipid compositions common to their deployment are simplistic and often fail to model native membrane complexity. Furthermore, there has been a general lack of rigorous analytical and biophysical characterization of nanodiscs comprising more than one lipid. To address these challenges, we coupled a nanodisc formation and purification workflow with targeted LC-MS/MS analysis to quantify lipids in nanodiscs made with different compositions.

Thermal Gradient-Driven Heterogeneous Actuation of Liquid Crystal Elastomers for a Crawling Robot.

Emerging soft robots based on liquid crystal elastomers (LCEs) exhibit remarkable capabilities for large reversible shape morphing, enabling them to adapt to complex environments and perform diverse tasks such as locomotion and camouflage. Despite extensive studies, current methods for locally controlled actuation of LCE-based soft robots often involve intricate structural design, complex programming of LCEs, incorporation of multiple materials, or complex actuation methods. Here, we present a simple and efficient approach to achieve multiple deformation modes within a simply programmed LCE structure by harnessing Joule heating-induced thermal gradients across the LCE volume.

Improving the Predictive Strength of Better-Ear Four-Frequency Pure-Tone Average With the Addition of the Tinnitus and Hearing Survey-Hearing Subscale.

Objectives: The objective of this project was to quantify the relative efficacy of a four-frequency pure-tone average in the better ear (PTA4), the Hearing subscale of the Tinnitus and Hearing Survey (THS-H), and a combination of the two in predicting speech-in-noise performance, hearing aid recommendation, and hearing aid use among United States service members (SMs).

Design: A two-analysis retrospective study was performed. The first analysis examined the degree to which better-ear PTA4 alone, THS-H alone, and better-ear PTA4 in conjunction with THS-H predicted performance on a speech-in-noise test, the modified rhyme test.

Drug-related macular edema: a real-world FDA Adverse Event Reporting System database study.

Purpose: This study aims to assess the risks associated with drug-induced macular edema and to examine the epidemiological characteristics of this condition.

Methods: This study analyzed data from the U.S.

A qualitative process evaluation of SBIRT implementation in pediatric trauma centers using the Science to Service Laboratory implementation strategy.

Background: Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based practice that can identify adolescents who use alcohol and other drugs and support proper referral to treatment. Despite an American College of Surgeons mandate to deliver SBIRT in pediatric trauma care, trauma centers throughout the United States have faced numerous patient, provider, and organizational level barriers to SBIRT implementation. The Implementing Alcohol Misuse Screening, Brief Intervention, and Referral to Treatment Study (IAMSBIRT) aimed to implement SBIRT across 10 pediatric trauma centers using the Science-to-Service Laboratory (SSL), an empirically supported implementation strategy.

Examining the associations between social support and postpartum depression symptoms among adolescent mothers in Nairobi, Kenya.

Background: Globally, adolescent mothers are at increased risk for postpartum depression (PPD). In Kenya, 15% of adolescent girls become mothers before the age of 18. While social support can buffer a mother's risk of PPD, there are gaps in knowledge as to whether-and which types-of social support are protective for adolescent mothers in Kenya.

Hyperhomocysteinemia-induced VCID results in visual deficits, reduced neuroinflammation and vascular alterations in the retina.

Over recent years, the retina has been increasingly investigated as a potential biomarker for dementia. A number of studies have looked at the effect of Alzheimer's disease (AD) pathology on the retina and the associations of AD with visual deficits. However, while OCT-A has been explored as a biomarker of cerebral small vessel disease (cSVD), studies identifying the specific retinal changes and mechanisms associated with cSVD are lacking.