Efficient Generation of Knock-Out Sheep by Electroporation of CRISPR-Cas9 Ribonucleoprotein Complex with Dual-sgRNAs.

In mice, naturally occurring and induced mutations in the suppressor of cytokine signaling-2 () gene are associated with a high growth phenotype characterized by rapid post-weaning weight gain and 30-50% heavier mature body weight. In this work, we demonstrate an electroporation-based method of producing knock-out (KO) sheep. Electroporation of dual-guide CRISPR-Cas9 ribonucleoprotein complexes targeting was performed 6 h post-fertilization in sheep zygotes.

Design and implementation of optics for the experiment for cryogenic large-aperture intensity mapping (EXCLAIM).

This work describes the design and implementation of optics for EXCLAIM, the EXperiment for Cryogenic Large-Aperture Intensity Mapping. EXCLAIM is a balloon-borne telescope that will measure integrated line emission from carbon monoxide at redshifts z < 1 and ionized carbon ([CII]) at redshifts z = 2.5 - 3.

A One-Dimensional Energy Balance Model Parameterization for the Formation of CO Ice on the Surfaces of Eccentric Extrasolar Planets.

Eccentric planets may spend a significant portion of their orbits at large distances from their host stars, where low temperatures can cause atmospheric CO to condense out onto the surface, similar to the polar ice caps on Mars. The radiative effects on the climates of these planets throughout their orbits would depend on the wavelength-dependent albedo of surface CO ice that may accumulate at or near apoastron and vary according to the spectral energy distribution of the host star. To explore these possible effects, we incorporated a CO ice-albedo parameterization into a one-dimensional energy balance climate model.

Optimizing automated photo identification for population assessments.

Several legal acts mandate that management agencies regularly assess biological populations. For species with distinct markings, these assessments can be conducted noninvasively via capture-recapture and photographic identification (photo-ID), which involves processing considerable quantities of photographic data. To ease this burden, agencies increasingly rely on automated identification (ID) algorithms.

Real-World Incidence of Anaplastic Lymphoma Kinase alterations in Hispanics with Non-Small Cell Lung Cancer at a Large Academic Institution in Los Angeles.

Race and ethnicity affect the distribution of molecular alterations seen in patients with non-small cell lung cancer (NSCLC). While anaplastic lymphoma kinase (ALK) alterations are known to occur in 4-5% of the population, data specific to the Hispanic population remains limited. This study describes the real-world incidence of ALK alterations in Hispanic patients with NSCLC treated at a large academic institution in Los Angeles, California, USA to further elucidate the underlying factors that shape differences in mutational profiles.

Electrically Switching Ferroelectric Order in 3R-MoS Layers.

Transition metal dichalcogenides (TMDs) with rhombohedral (3R) stacking order are excellent platforms to realize multiferroelectricity. In this work, we demonstrate the electrical switching of ferroelectric orders in bilayer, trilayer, and tetralayer 3R-MoS dual-gate devices by examining their reflection and photoluminescence (PL) responses under sweeping out-of-plane electric fields. We observe sharp shifts in excitonic spectra at different critical fields with pronounced hysteresis.

Mechanically Robust Bismuth-Embedded Carbon Microspheres for Ultrafast Charging and Ultrastable Sodium-Ion Batteries.

Advancements in the development of fast-charging and long-lasting microstructured alloying anodes with high volumetric capacities are essential for enhancing the operational efficiency of sodium-ion batteries (SIBs). These anodes, however, face challenges such as declined cyclability and rate capability, primarily due to mechanical degradation reduced by significant volumetric changes (over 252%) and slow kinetics of sodium-ion storage. Herein, we introduce a novel anode design featuring densely packed bismuth (Bi) embedded within highly conductive carbon microspheres to overcome the aforementioned challenges.

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.

Molecular H as the Reducing Agent in Low-Temperature Oxide Reduction Using Calcium Hydride.

Low-temperature synthesis is crucial for advancing sustainable manufacturing and accessing novel metastable phases. Metal hydrides have shown great potential in facilitating the reduction of oxides at low temperatures, yet the underlying mechanism─whether driven by H, H, or atomic H─remains unclear. In this study, we employ electrical transport measurements and first-principles calculations to investigate the CaH-driven reduction kinetics in epitaxial α-FeO thin films.

Barriers and Facilitators to Video Telehealth Use in Low-Income Hispanic Patients: A Theory of Planned Behavior Perspective.

Background And Objectives: As telehealth grows in ubiquity, it is important to understand the barriers and facilitators to telehealth utilization in historically marginalized populations. This study utilizes the Theory of Planned Behavior (TPB) to assess correlates of the intention to utilize video consultations among low-income Hispanic patients.

Methods: This cross-sectional observational study included participants (N = 138) recruited from a federally qualified health center affiliated with a large university health system.

Why wasn't mirabegron chosen for the first year of the CMS negotiation program?

Importance: The most used overactive bladder (OAB) medications are anticholinergics, which professional societies recommend avoiding in older patients given dementia risk. Cost prevents patients from switching to preferred beta-3 agonists. Mirabegron was the only beta-3 agonist eligible for the Centers for Medicare/Medicaid Services (CMS) 2023 Drug Negotiation Program (DNP).

Optimizing Exposure Measures in Large-Scale Household Air Pollution Studies: Results from the Multicountry HAPIN Trial.

Repeated measurements of household air pollution may provide better estimates of average exposure but can add to costs and participant burden. In a randomized trial of gas versus biomass cookstoves in four countries, we took supplemental personal 24-h measurements on a 10% subsample for mothers and infants, interspersed between protocol samples. Mothers had up to five postrandomization protocol measurements over 16 months, while infants had three measurements over one year.

Environmental drivers of monomethylmercury photodegradation along the land-to-ocean aquatic continuum.

In surface waters, photodegradation is a major abiotic removal pathway of the neurotoxin monomethylmercury (MMHg), acting as a key control on the amounts of MMHg available for biological uptake. Different environmental factors can alter the rate of MMHg photodegradation. However, our understanding of how MMHg photodegradation pathways in complex matrixes along the land-to-ocean aquatic continuum respond to changes in salinity, dissolved organic carbon (DOC) concentration and dissolved organic matter (DOM) composition is incomplete.

Circadian rhythm of heart rate and activity: A cross-sectional study.

Circadian rhythms are governed by a biological clock, and are known to occur in a variety of physiological processes. We report results on the circadian rhythm of heart rate observed using a wrist-worn wearable device (Fitbit), consisting of over 17,000 individuals over the course of 30 days. We obtain an underlying heart rate circadian rhythm from the time series heart rate by modeling the circadian rhythm as a sum over the first two Fourier harmonics.

Advancing paleoanthropology beyond default nulls.

While we are sympathetic with Stibbard-Hawkes' approach, we disagree with the proposal to switch to a "cognitively modern" null for all species. We argue in favor of a more evidence-driven approach, inspired by recent debates in comparative cognition. Ultimately, parsing the contributions of different genetic and extra-genetic factors in human evolution is more promising than setting a priori nulls.

What would be pre-modern human cognition?

Stibbard-Hawkes's detailed demonstration that in the case of hunter-gatherer artifacts, absence of evidence is not evidence of absence must never be forgotten. The belief that there is a single coherent "human cognitive capacity" difference between modern humans and some unspecified earlier form should be rigorously re-examined.

Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course.

AAPM Truth-based CT (TrueCT) reconstruction grand challenge.

Background: This Special Report summarizes the 2022, AAPM grand challenge on Truth-based CT image reconstruction.

Purpose: To provide an objective framework for evaluating CT reconstruction methods using virtual imaging resources consisting of a library of simulated CT projection images of a population of human models with various diseases.

Methods: Two hundred unique anthropomorphic, computational models were created with varied diseases consisting of 67 emphysema, 67 lung lesions, and 66 liver lesions.

Cognitive aging outcomes are related to both tau pathology and maintenance of cingulate cortex structure.

Introduction: Successful cognitive aging is related to both maintaining brain structure and avoiding Alzheimer's disease (AD) pathology, but how these factors interplay is unclear.

Methods: A total of 109 cognitively normal older adults (70+ years old) underwent amyloid beta (Aβ) and tau positron emission tomography (PET) imaging, structural magnetic resonance imaging (MRI), and cognitive testing. Cognitive aging was quantified using the cognitive age gap (CAG), subtracting chronological age from predicted cognitive age.

Decoding brain structure to stage Alzheimer's disease pathology in Down syndrome.

Introduction: Alzheimer's disease (AD) in Down syndrome (DS) is associated with changes in brain structure. It is unknown if thickness and volumetric changes can identify AD stages and if they are similar to other genetic forms of AD.

Methods: Magnetic resonance imaging scans were collected for 178 DS adults (106 nonclinical, 45 preclinical, and 27 symptomatic).

Increased SOX10, p16, and Cyclin D1 Immunoreactivity Differentiates MAP Kinase-activated Low-grade Gliomas From Piloid Gliosis.

Low-grade gliomas and reactive piloid gliosis can present with overlapping features on conventional histology. Given the large implications for patient treatment, there is a need for effective methods to discriminate these morphologically similar but clinically distinct entities. Using routinely available stains, we hypothesize that a limited panel including SOX10, p16, and cyclin D1 may be useful in differentiating mitogen-activated protein (MAP) kinase-activated low-grade gliomas from piloid gliosis.

Determinants of Racial and Ethnic Differences in Maternal Cardiovascular Health in Early Pregnancy.

Background: Suboptimal cardiovascular health (CVH) in pregnancy is associated with adverse maternal and offspring outcomes. To guide public health efforts to reduce disparities in maternal CVH, we determined the contribution of individual- and neighborhood-level factors to racial and ethnic differences in early pregnancy CVH.

Methods: We included nulliparous individuals with singleton pregnancies who self-identified as Hispanic, non-Hispanic Black (NHB), or non-Hispanic White (NHW) and participated in the nuMoM2b cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be).

Exposure Contrasts of Women Aged 40-79 Years during the Household Air Pollution Intervention Network Randomized Controlled Trial.

Exposure to household air pollution has been linked to adverse health outcomes among women aged 40-79. Little is known about how shifting from biomass cooking to a cleaner fuel like liquefied petroleum gas (LPG) could impact exposures for this population. We report 24-h exposures to particulate matter (PM), black carbon (BC), and carbon monoxide (CO) among women aged 40 to <80 years participating in the Household Air Pollution Intervention Network trial.