X-Chromosome-Linked miRNAs Regulate Sex Differences in Cardiac Physiology.

Background: Males and females exhibit distinct anatomic and functional characteristics of the heart, predisposing them to specific disease states.

Methods: We identified microRNA (miRNAs/miR) with sex-differential expression in mouse hearts.

Results: Four conserved miRNAs are present in a single locus on the X-chromosome and are expressed at higher levels in females than males.

Fully Automated Assessment of Cardiac Chamber Volumes and Myocardial Mass on Non-Contrast Chest CT with a Deep Learning Model: Validation Against Cardiac MR.

: To validate the automated quantification of cardiac chamber volumes and myocardial mass on non-contrast chest CT using cardiac MR (CMR) as a reference. : We retrospectively included 53 consecutive patients who received non-contrast chest CT and CMR within three weeks. A deep learning model created cardiac segmentations on axial soft-tissue reconstructions from CT, covering all four cardiac chambers and the left ventricular myocardium.

Synergistic Antioxidant Effects of Molecular Hydrogen and Cold Atmospheric Plasma in Enhancing Mesenchymal Stem Cell Therapy.

In regenerative medicine, mesenchymal stem cells (MSCs) have shown their importance and potential in tissue reconstruction and immune system modification. However, such cells' potential is often diminished by factors such as oxidative stress, immune rejection, and inadequate engraftment. This review highlights the role of molecular hydrogen (H) and cold atmospheric plasma (CAP) as adjunct therapies to improve the effectiveness of MSC therapy.

Diverging network architecture of the connectome and signaling network.

The connectome describes the complete set of synaptic contacts through which neurons communicate. While the architecture of the connectome has been extensively characterized, much less is known about the organization of causal signaling networks arising from functional interactions between neurons. Understanding how effective communication pathways relate to or diverge from the underlying structure is a central question in neuroscience.

Coancestry superposed on admixed populations yields measures of relatedness at individual-level resolution.

The admixture model is widely applied to estimate and interpret population structure among individuals. Here we consider a "standard admixture" model that assumes the admixed populations are unrelated and also a generalized model, where the admixed populations themselves are related via coancestry (or covariance) of allele frequencies. The generalized model yields a potentially more realistic and substantially more flexible model that we call "super admixture".

Non-Canonical Cytochrome P450 Enzymes in Nature.

Cytochrome P450s (CYPs) are a superfamily of thiolate-ligated heme metalloenzymes principally responsible for the hydroxylation of unactivated C-H bonds. The lower-axial cysteine is an obligatory and universally conserved residue for the CYP enzyme class. Herein, we challenge this paradigm by systematically identifying non-canonical CYPs (ncCYPs) that do not harbor a cysteine ligand.

Aggression experience and observation promote shared behavioral and neural changes.

The ability to observe the social behavior of others and use observed information to bias future action is a fundamental building block of social cognition. A foundational question is whether social observation and experience engage common circuit mechanisms that enable behavioral change. While classic studies on social learning have shown that aggressive behaviors can be learned through observation, it remains unclear whether aggression observation promotes persistent neural changes that generalize to new contexts.

Cysimiditides: RiPPs with a Zn-Tetracysteine Motif and Aspartimidylation.

Aspartimidylation is a post-translational modification found in multiple families of ribosomally synthesized and post-translationally modified peptides (RiPPs). We recently reported on the imiditides, a new RiPP family in which aspartimidylation is the class-defining modification. Imiditide biosynthetic gene clusters encode a precursor protein and a methyltransferase that methylates a specific Asp residue, converting it to aspartimide.

Treatment Patterns and Costs Among Patients With Metastatic Renal Cell Carcinoma in the United States: A Real-World Study Using Integrated Claims and Clinical Data.

Purpose: The treatment landscape for metastatic renal cell carcinoma (mRCC) has evolved in recent years with the use of tyrosine kinase inhibitors (TKIs) and immuno-oncology (IO) therapies. This study examined patient characteristics, treatment patterns, health care resource utilization (HCRU), costs, and survival for individuals with mRCC who received either IO + IO or IO + TKI combinations as first-line (1L) regimens.

Methods: This retrospective cohort study used integrated claims and clinical data from a commercial health plan to study adults with mRCC who began 1L treatment between April 1, 2018, and January 31, 2023.

Completion of lunar magma ocean solidification at 4.43 Ga.

Crystallization of the lunar magma ocean yielded a chemically unique liquid residuum named KREEP. This component is expressed as a large patch on the near side of the Moon and a possible smaller patch in the northwest portion of the Moon's South Pole-Aitken basin on the far side. Thermal models estimate that the crystallization of the lunar magma ocean (LMO) could have spanned from 10 and 200 My, while studies of radioactive decay systems have yielded inconsistent ages for the completion of LMO crystallization covering over 160 My.

Assessment of fit of item response theory models: A critical review of the status quo and some future directions.

This paper provides a literature review of assessment of fit of item response theory models. Various types of fit procedures for item response theory models are reviewed, with a focus on their advantages and disadvantages. Real data examples are used to demonstrate some of the fit procedures.

Dietary or pharmacological inhibition of insulin-like growth factor-1 protects from renal ischemia-reperfusion injury in mice.

One-week protein restriction (PR) limits ischemia-reperfusion (IR) damages and improves metabolic fitness. Similarly, longer-term calory restriction results in increased lifespan, partly via reduced insulin-like growth factor (IGF)-1. However, the influence of short-term PR on IGF-1 and its impact on IR are unknown.

Revisiting the Discrepancy between Experimental and Theoretical Predictions of the Adiabaticity of Ti + CHOH.

We revisit the naked transition metal cation (Ti) and methanol reaction and go beyond the standard Landau-Zener (LZ) picture when modeling the intersystem crossing (ISC) rate between the lowest doublet and quartet states. We use both (i) unconstrained Born-Oppenheimer molecular dynamics (BOMD) calculations with an approximate two-state method to estimate population transfer between spin diabats and (ii) constrained dynamics to explore energetically accessible portions of the - 1 crossing seam, where is the total number of internal degrees of freedom. Whereas previous LZ calculations (that necessarily relied on the Condon approximation to be valid) fell short and predicted much slower crossing probabilities than shown in experiment, we show that ISC can occur rapidly because the spin-orbit coupling (SOC) between the doublet and quartet surfaces can vary by 2 orders of magnitude (depending on where in the seam the crossing occurs during dynamics) and the crossing region is revisited multiple times during a dynamics run of a few hundred femtoseconds.

Humans rationally balance detailed and temporally abstract world models.

How do people model the world's dynamics to guide mental simulation and evaluate choices? One prominent approach, the Successor Representation (SR), takes advantage of temporal abstraction of future states: by aggregating trajectory predictions over multiple timesteps, the brain can avoid the costs of iterative, multi-step mental simulation. Human behavior broadly shows signatures of such temporal abstraction, but finer-grained characterization of individuals' strategies and their dynamic adjustment remains an open question. We developed a task to measure SR usage during dynamic, trial-by-trial learning.

Urinary Kidney Injury Biomarker Profiles in Healthy Individuals and After Nephrotoxic and Ischemic Injury.

Two observational studies were conducted to support an initiative to qualify translational kidney safety biomarkers as clinical drug development tools that identify tubular injury prior to changes in estimated glomerular filtration rate (eGFR). Normal healthy volunteers provided three morning spot urine collections over 4 weeks. Patients undergoing surgical resection and intrathoracic cisplatin for malignant pleural mesothelioma provided urine samples pre- and postoperatively at 4, 8, and 12 hours and daily for 6 days.

The impact of risk compensation adaptive behavior on the final epidemic size.

Public health interventions reduce infection risk, while imposing significant costs on both individuals and the society. Interventions can also lead to behavioral changes, as individuals weigh the cost and benefits of avoiding infection. Aggregate epidemiological models typically focus on the population-level consequences of interventions, often not incorporating the mechanisms driving behavioral adaptations associated with interventions compliance.

Extreme Synergy in the Random-Energy Model.

The random-energy model (REM), a solvable spin-glass model, has impacted an incredibly diverse set of problems, from protein folding to combinatorial optimization, to many-body localization. Here, we explore a new connection to secret sharing. We derive an analytic expression for the mutual information between any two disjoint thermodynamic subsystems of the REM.

Deriving a genetic regulatory network from an optimization principle.

Many biological systems operate near the physical limits to their performance, suggesting that aspects of their behavior and underlying mechanisms could be derived from optimization principles. However, such principles have often been applied only in simplified models. Here, we explore a detailed mechanistic model of the gap gene network in the embryo, optimizing its 50+ parameters to maximize the information that gene expression levels provide about nuclear positions.

Large language models can segment narrative events similarly to humans.

Humans perceive discrete events such as "restaurant visits" and "train rides" in their continuous experience. One important prerequisite for studying human event perception is the ability of researchers to quantify when one event ends and another begins. Typically, this information is derived by aggregating behavioral annotations from several observers.

Emergent Symmetry and Valley Chern Insulator in Twisted Double-Bilayer Graphene.

Theoretical calculations show that twisted double bilayer graphene (TDBG) under a transverse electric field develops a valley Chern number 2 at charge neutrality. Using thermodynamic and thermal activation measurements we report the experimental observation of a universal closing of the charge neutrality gap in the Hofstadter spectrum of TDBG at 1/2 magnetic flux per unit cell, in agreement with theoretical predictions for a valley Chern number 2 gap. Our theoretical analysis of the experimental data shows that the interaction energy, while larger than the flat-band bandwidth in TDBG near 1° does not alter the emergent valley symmetry or the single-particle band topology.

Quantum Turnstiles for Robust Measurement of Full Counting Statistics.

We present a scalable protocol for measuring full counting statistics (FCS) in experiments or tensor-network simulations. In this method, an ancilla in the middle of the system acts as a turnstile, with its phase keeping track of the time-integrated particle flux. Unlike quantum gas microscopy, the turnstile protocol faithfully captures FCS starting from number-indefinite initial states or in the presence of noisy dynamics.

Corner Charge Fluctuation as an Observable for Quantum Geometry and Entanglement in Two-Dimensional Insulators.

Measuring bipartite fluctuations of a conserved charge, such as the particle number, is a powerful approach to understanding quantum systems. When the measured region has sharp corners, the bipartite fluctuation receives an additional contribution known to exhibit a universal angle dependence in 2D isotropic and uniform systems. Here we establish that, for generic lattice systems of interacting particles, the corner charge fluctuation is directly related to quantum geometry.

Effects of brexpiprazole on patient life engagement in schizophrenia: analysis of Positive and Negative Syndrome Scale data.

Objective: Patients with schizophrenia value improved life engagement, a term that describes positive health aspects across emotional, physical, social, and cognitive domains. This analysis of clinical trial data aimed to investigate the effect of brexpiprazole on patient life engagement in schizophrenia over the short and long term.

Methods: Data were pooled from three 6-week, randomized, double-blind, placebo-controlled clinical trials (ClinicalTrials.