Advancing Principled Pharmacoepidemiologic Research to Support Regulatory and Healthcare Decision Making: The Era of Real-World Evidence.

A compilation of factors over the past decade-including the availability of increasingly large and rich healthcare datasets, advanced technologies to extract unstructured information from health records and digital sources, advancement of principled study design and analytic methods to emulate clinical trials, and frameworks to support transparent study conduct-has ushered in a new era of real-world evidence (RWE). This review article describes the evolution of the RWE era, including pharmacoepidemiologic methods designed to support causal inferences regarding treatment effects, the role of regulators and other health authorities in establishing distributed real-world data networks enabling analytics at scale, and the many global guidance documents on principled methods of producing RWE. This article also highlights the growing opportunity for RWE to support decision making by regulators, health technology assessment groups, clinicians, patients, and other stakeholders and provides examples of influential RWE studies.

Discovery of Peptidic Siderophore Degradation by Screening Natural Product Profiles in Marine-Derived Bacterial Mono- and Cocultures.

Coral reefs are hotspots of marine biodiversity, which results in the synthesis of a wide variety of compounds with unique molecular scaffolds, and bioactivities, rendering reefs an ecosystem of interest. The chemodiversity stems from the intricate relationships between inhabitants of the reef, as the chemistry produced partakes in intra- and interspecies communication, settlement, nutrient acquisition, and defense. However, the coral reefs are declining at an unprecedented rate due to climate change, pollution, and increased incidence of pathogenic diseases.

Nontarget Analysis and Characterization of a Group of Abundant Polyfluoroalkyl Substances─Fluorinated Benzoylurea Pesticides and Their Analogues and Transformation Products in Fish by LC-HRMS and Chemical Species-Specific Algorithms.

Poly- and perfluoroalkyl substances (PFASs) are a large class of fluorinated chemicals used in various industrial and agrochemical products such as fluorinated benzoylurea (FBU) pesticides. Initiated from an incidental and preliminary finding of three high-abundance FBUs in fish, this study implemented nontarget analysis and characterization for FBUs together with their analogues and transformation products (TPs) in fish using liquid chromatography, high-resolution mass spectrometry, and chemical species-specific algorithms. A total of 23 FBU-relevant compounds were found and tentatively/accurately elucidated with structures, including 18 PFASs and 5 non-PFAS compounds, of which 4 were original FBUs, 8 were FBU analogues, and 11 were FBU-TPs.

Electromyography-Informed Estimates of Joint Contact Forces Within the Lower Back and Knee Joints During a Diverse Set of Industry-Relevant Manual Lifting Tasks.

Repetitive manual labor tasks involving twisting, bending, and lifting commonly lead to lower back and knee injuries in the workplace. To identify tasks with high injury risk, we recruited N = 9 participants to perform industry-relevant, 2-handed lifts with a 11-kg weight. These included symmetrical/asymmetrical, ascending/descending lifts that varied in start-to-end heights (knee-to-waist and waist-to-shoulder).

Neurons as Immunomodulators: From Rapid Neural Activity to Prolonged Regulation of Cytokines and Microglia.

Regulation of the brain's neuroimmune system is central to development, normal function, and disease. Neuronal communication to microglia, the primary immune cells of the brain, is well known to involve purinergic signaling mediated via ATP secretion and the cytokine fractalkine. Recent evidence shows that neurons release multiple cytokines beyond fractalkine, yet these are less studied and poorly understood.

Electrocardiogram-based machine learning for risk stratification of patients with suspected acute coronary syndrome.

Background And Aims: The importance of risk stratification in patients with chest pain extends beyond diagnosis and immediate treatment. This study sought to evaluate the prognostic value of electrocardiogram feature-based machine learning models to risk-stratify all-cause mortality in those with chest pain.

Methods: This was a prospective observational cohort study of consecutive, non-traumatic patients with chest pain.

Regional-specific trends of PM and O temperature sensitivity in the United States.

Climate change poses direct and indirect threats to public health, including exacerbating air pollution. However, the influence of rising temperature on air quality remains highly uncertain in the United States, particularly under rapid reduction in anthropogenic emissions. Here, we examined the sensitivity of surface-level fine particulate matter (PM) and ozone (O) to summer temperature anomalies in the contiguous US as well as their decadal changes using high-resolution datasets generated by machine learning.

Visual image reconstructed without semantics from human brain activity using linear image decoders and nonlinear noise suppression.

In recent years, substantial strides have been made in the field of visual image reconstruction, particularly in its capacity to generate high-quality visual representations from human brain activity while considering semantic information. This advancement not only enables the recreation of visual content but also provides valuable insights into the intricate processes occurring within high-order functional brain regions, contributing to a deeper understanding of brain function. However, considering fusion semantics in reconstructing visual images from brain activity involves semantic-to-image guide reconstruction and may ignore underlying neural computational mechanisms, which does not represent true reconstruction from brain activity.

Elucidating Photochemical Conversion Mechanism of PDMS to Silica under Deep UV Light and Ozone.

Photochemistry-based silica formation offers a pathway toward energy-efficient and controlled fabrication processes. While the transformation of poly(dimethylsiloxane) (PDMS) to silica (often referred to as SiO due to incomplete conversion) under deep ultraviolet (DUV) irradiation in the presence of oxygen/ozone has experimentally been validated, the detailed mechanism remains elusive. This study demonstrates the underlying molecular-level mechanism of PDMS-to-silica conversion using density functional theory (DFT) calculations.

Temperature-dependent pathways in carbon dioxide electroreduction.

Temperature affects both the thermodynamics of intermediate adsorption and the kinetics of elementary reactions. Despite its extensive study in thermocatalysis, temperature effect is typically overlooked in electrocatalysis. This study investigates how electrolyte temperature influences CO electroreduction over Cu catalysts.

Design, optimization, and inference of biphasic decay of infectious virus particles.

Virus population dynamics are driven by counter-balancing forces of production and loss. Whereas viral production arises from complex interactions with susceptible hosts, the loss of infectious virus particles is often approximated as a first-order kinetic process. As such, experimental protocols to measure infectious virus loss are not typically designed to identify non-exponential decay processes.

Identification of cardiac wall motion abnormalities in diverse populations by deep learning of the electrocardiogram.

Cardiac wall motion abnormalities (WMA) are strong predictors of mortality, but current screening methods using Q waves from electrocardiograms (ECGs) have limited accuracy and vary across racial and ethnic groups. This study aimed to identify novel ECG features using deep learning to enhance WMA detection, referencing echocardiography as the gold standard. We collected ECG and echocardiogram data from 35,210 patients in California and labeled WMA using unstructured language parsing of echocardiographic reports.

Self-Contamination Risk and Failure Modes During High-Level PPE Doffing: A Comparison of Two Powered Air Purifying Respirator (PAPR) Hoods: A Pilot Study.

Background: Personal protective equipment (PPE) doffing protocols can reduce risks of pathogen self-contamination. Powered air purifying respirators (PAPRs) may increase these risks. This study compares viral contamination and errors during simulated doffing of single layer vs double layer hood PAPRs.

Default mode network functional connectivity as a transdiagnostic biomarker of cognitive function.

The default mode network (DMN) is intricately linked with processes such as self-referential thinking, episodic memory recall, goal-directed cognition, self-projection, and theory of mind. Over recent years, there has been a surge in examining its functional connectivity, particularly its relationship with frontoparietal networks (FPN) involved in top-down attention, executive function, and cognitive control. The fluidity in switching between these internal and external modes of processing-highlighted by anti-correlated functional connectivity-has been proposed as an indicator of cognitive health.

Automatic medical imaging segmentation via self-supervising large-scale convolutional neural networks.

Purpose: This study aims to develop a robust, large-scale deep learning model for medical image segmentation, leveraging self-supervised learning to overcome the limitations of supervised learning and data variability in clinical settings.

Methods And Materials: We curated a substantial multi-center CT dataset for self-supervised pre-training using masked image modeling with sparse submanifold convolution. We designed a series of Sparse Submanifold U-Nets (SS-UNets) of varying sizes and performed self-supervised pre-training.

Parametric finite element modeling of reinforced polymeric leaflets for improved durability.

Hyaluronic acid-enhanced polyethylene polymeric TAVR shows excellent in vivo anti-calcific, anti-thrombotic, and in vitro hydrodynamic performance. However, during durability testing, impact wear and fatigue cause early valve failure. Heart valve durability can be improved by strengthening the leaflet with fiber reinforcement.

Atomic Gap-State Engineering of MoS for Alkaline Water and Seawater Splitting.

Transition-metal dichalcogenides (TMDs), such as molybdenum disulfide (MoS), have emerged as a generation of nonprecious catalysts for the hydrogen evolution reaction (HER), largely due to their theoretical hydrogen adsorption energy close to that of platinum. However, efforts to activate the basal planes of TMDs have primarily centered around strategies such as introducing numerous atomic vacancies, creating vacancy-heteroatom complexes, or applying significant strain, especially for acidic media. These approaches, while potentially effective, present substantial challenges in practical large-scale deployment.

Endothelial IGFBP6 suppresses vascular inflammation and atherosclerosis.

Beyond dyslipidemia, inflammation contributes to the development of atherosclerosis. However, intrinsic factors that counteract vascular inflammation and atherosclerosis remain scarce. Here we identify insulin-like growth factor binding protein 6 (IGFBP6) as a homeostasis-associated molecule that restrains endothelial inflammation and atherosclerosis.

Location of Primary Tumor Impacts Survival After Pulmonary Metastasectomy for Colorectal Cancer.

Background: The benefit of pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) with isolated lung metastases remains unclear and failure to separate colon from rectal cancer may contribute. Utilizing a large national database, we investigate whether PM is associated with survival benefits in patients presenting with CRC with synchronous lung metastases based upon primary tumor location.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 was queried to identify patients with stage IV CRC with isolated synchronous lung metastases at initial diagnosis.

Selective lead ion sensing via cotton pad-based NaEDTA capped AuNPs: A smartphone-assisted colorimetric method.

Herein, NaEDTA-capped AuNPs specifically designed for selective smartphone-assisted colorimetric detection are synthesized and characterized. NaEDTA-capped AuNPs was synthesized and characterized by UV-Visible spectroscopy, ATR, Raman, XRD, SEM and EDX. The calculated activation energy of the produced nanoparticles was 0.

Evaluation of Multi-Lingual Simplifications of IR Procedural Reports Using GPT-4.

This study assesses the feasibility of Large Language Models like GPT-4 (OpenAI, San Francisco, CA, USA) to summarize interventional radiology (IR) procedural reports to improve layperson understanding and translate medical texts into multiple languages. 200 reports from eight categories were summarized using GPT-4. Readability was assessed with Flesch-Kincaid Reading Level (FKRL) and Flesch Reading Ease Score (FRES).

Amplicon Sequencing Reveals Diversity in Spatially Separated Microbial Communities in the Icelandic Mars Analog Environment Mælifellssandur.

Exploration missions to Mars rely on landers or rovers to perform multiple analyses over geographically small sampling regions, while landing site selection is done using large-scale but low-resolution remote-sensing data. Utilizing Earth analog environments to estimate small-scale spatial and temporal variation in key geochemical signatures and biosignatures will help mission designers ensure future sampling strategies meet mission science goals. Icelandic lava fields can serve as Mars analog sites due to conditions that include low nutrient availability, temperature extremes, desiccation, and isolation from anthropogenic contamination.

Substructure-Specific Antibodies Against Fentanyl Derivatives.

Structural variants of the synthetic opioid fentanyl are a major threat to public health. Following an investigation showing that many derivatives are poorly detected by commercial lateral flow and related assays, we created hapten conjugate vaccines using an immunogenic virus-like particle carrier and eight synthetic fentanyl derivatives designed to mimic the structural features of several of the more dangerous analogues. Immunization of mice elicited strong antihapten humoral responses, allowing the screening of hundreds of hapten-specific hybridomas for binding strength and specificity.