Use of patient-derived cell models for characterization of compound heterozygous hypomorphic C2CD3 variants in a patient with isolated nephronophthisis.

Background: Primary ciliopathies are a heterogeneous group of rare disorders predominantly caused by autosomal-recessive genetic variants that disrupt non-motile ciliary function. They often manifest as a syndromic phenotype, frequently involving the kidney. Biallelic pathogenic variants in C2CD3 disrupt ciliogenesis and Sonic Hedgehog (SHH) signaling, resulting in a severe ciliopathy (Orofaciodigital syndrome XIV, OMIM 615948).

Interictal epileptiform discharge-related BOLD responses in the default mode network and subcortical regions.

Objective: To examine the blood oxygen level-dependent (BOLD) responses in the default mode network (DMN) and subcortical regions in relation to epileptic events in scalp EEG and intracranial EEG (iEEG).

Methods: We retrospectively compared BOLD responses in the DMN and subcortical regions to interictal epileptiform discharge (IED) characteristics of the scalp and iEEG in consecutive patients with focal epilepsy. All voxels were used as the denominator to assess the positive and negative BOLD ratios in each region, and the percentage of voxels with significant activation or deactivation was assessed.

The binding of RbgA to a critical 50S assembly intermediate facilitates YphC function in bacterial ribosomal assembly.

The intricate process of 50S ribosomal subunit assembly in Bacillus subtilis involves multiple parallel pathways converging into a crucial intermediate known as the 45S particle. RbgA and YphC, play pivotal roles in completing the maturation of the functional sites in the 45S particle. In this work, we found that RbgA and YphC can independently bind the 45S particle with high affinity, but when RbgA binds first to the particle, it significantly increases the binding affinity of YphC.

The Tolman-Ehrenfest criterion of thermal equilibrium in scalar-tensor gravity.

The Tolman-Ehrenfest criterion for the thermal equilibrium of a fluid at rest in a static general-relativistic geometry is generalized to scalar-tensor gravity. Surprisingly, the gravitational scalar field, which fixes the strength of the effective gravitational coupling, does not play a role in determining thermal equilibrium. As a result, heat does not sink more in a gravitational field where gravity is stronger.

Metrics for evaluation of automatic epileptogenic zone localization in intracranial electrophysiology.

Introduction: Precise localization of the epileptogenic zone is critical for successful epilepsy surgery. However, imbalanced datasets in terms of epileptic vs. normal electrode contacts and a lack of standardized evaluation guidelines hinder the consistent evaluation of automatic machine learning localization models.

An ultra-short-period super-Earth with an extremely high density and an outer companion.

We present the discovery and characterization of a new multi-planetary system around the Sun-like star K2-360 (EPIC 201595106). K2-360 was first identified in K2 photometry as the host of an ultra-short-period (USP) planet candidate with a period of 0.88 d.

Identification of late-stage tau accumulation using plasma phospho-tau217.

Background: Blood-based disease staging across the Alzheimer's disease (AD) continuum holds the promise to identify individuals that profit from disease-modifying therapies. We set out to identify Braak V (Braak V and/or VI) tau PET-positive individuals within amyloid-β (Aβ)-positive individuals using plasma biomarkers.

Methods: In this cross-sectional study, we assessed 289 individuals from the TRIAD cohort and 306 individuals from the WRAP study across the AD continuum.

Sample-to-answer centrifugal microfluidic droplet PCR platform for quantitation of viral load.

Droplet digital polymerase chain reaction (ddPCR) stands out as a highly sensitive diagnostic technique that is gaining traction in infectious disease diagnostics due to its ability to quantitate very low numbers of viral gene copies. By partitioning the sample into thousands of droplets, ddPCR enables precise and absolute quantification without relying on a standard curve. However, current ddPCR systems often exhibit relatively low levels of integration, and the analytical process remains dependent on elaborate workflows for up-front sample preparation.

Self-Interacting Dark Matter Solves the Final Parsec Problem of Supermassive Black Hole Mergers.

Evidence for a stochastic gravitational wave (GW) background, plausibly originating from the merger of supermassive black holes (SMBHs), is accumulating with observations from pulsar timing arrays. An outstanding question is how inspiraling SMBHs get past the "final parsec" of separation, where they have a tendency to stall before GW emission alone can make the binary coalesce. We argue that dynamical friction from the dark matter (DM) spike surrounding the black holes is sufficient to resolve this puzzle, if the DM has a self-interaction cross section of order cm^{2}/g.

Auditory hemispheric asymmetry for actions and objects.

What is the function of auditory hemispheric asymmetry? We propose that the identification of sound sources relies on the asymmetric processing of two complementary and perceptually relevant acoustic invariants: actions and objects. In a large dataset of environmental sounds, we observed that temporal and spectral modulations display only weak covariation. We then synthesized auditory stimuli by simulating various actions (frictions) occurring on different objects (solid surfaces).

scSemiProfiler: Advancing large-scale single-cell studies through semi-profiling with deep generative models and active learning.

Single-cell sequencing is a crucial tool for dissecting the cellular intricacies of complex diseases. Its prohibitive cost, however, hampers its application in expansive biomedical studies. Traditional cellular deconvolution approaches can infer cell type proportions from more affordable bulk sequencing data, yet they fall short in providing the detailed resolution required for single-cell-level analyses.

Composite Hydrogel Sealants for Annulus Fibrosus Repair.

Intervertebral disc (IVD) herniation is a leading cause of disability and lower back pain, causing enormous socioeconomic burdens. The standard of care for disc herniation is nucleotomy, which alleviates pain but does not repair the annulus fibrosus (AF) defect nor recover the biomechanical function of the disc. Existing bioadhesives for AF repair are limited by insufficient adhesion and significant mechanical and geometrical mismatch with the AF tissue, resulting in the recurrence of protrusion or detachment of bioadhesives.

New Probe of the High-z Baryon Acoustic Oscillation Scale: BAO Tomography with CMB×LIM-Nulling Convergence.

Standard rulers such as the baryon acoustic oscillation (BAO) scale serve as workhorses for precision tests of cosmology, enabling distance measurements that probe the geometry and expansion history of our Universe. Aside from BAO measurements from the cosmic microwave background (CMB), most standard ruler techniques operate at relatively low redshifts and depend on biased tracers of the matter density field. In a companion paper [H.

Hyperpolarization-activated currents drive neuronal activation sequences in sleep.

Sequential neuronal patterns are believed to support information processing in the cortex, yet their origin is still a matter of debate. We report that neuronal activity in the mouse postsubiculum (PoSub), where a majority of neurons are modulated by the animal's head direction, was sequentially activated along the dorsoventral axis during sleep at the transition from hyperpolarized "DOWN" to activated "UP" states, while representing a stable direction. Computational modeling suggested that these dynamics could be attributed to a spatial gradient of hyperpolarization-activated currents (I), which we confirmed in ex vivo slice experiments and corroborated in other cortical structures.

The first limit on invisible decays of mesons comes from LEP.

Motivated by the recent evidence for decays at Belle II, we point out that fully invisible and meson decays are strongly constrained by LEP. A reinterpretation of an old inclusive ALEPH search for -hadron decays with large missing energy allows us to place the limits and , both at CL. The limit is only a factor of 6 looser than the world-leading one provided by the BaBar collaboration, while the one is the first limit in the literature on this decay mode.

Upconverting Nanoparticles Coated with Light-Breakable Mesoporous Silica for NIR-Triggered Release of Hydrophobic Molecules.

Upconverting nanoparticles (UCNPs) doped with Yb and Tm are near-infrared (NIR) to ultraviolet (UV) transducers that can be used for NIR-controlled drug delivery. However, due to the low quantum yield of upconversion, high laser powers and long irradiation times are required to trigger this drug release. In this work, we report the one-step synthesis of a nanocomposite consisting of a LiYbF:Tm@LiYF UCNP coated with mesoporous UV-breakable organosilica shells of various thicknesses.

Wave-Function Tomography of Topological Dimer Chains with Long-Range Couplings.

The ability to tailor with a high accuracy the intersite connectivity in a lattice is a crucial tool for realizing novel topological phases of matter. Here, we report the experimental realization of photonic dimer chains with long-range hopping terms of arbitrary strength and phase, providing a rich generalization of the Su-Schrieffer-Heeger model which, in its conventional form, is limited to nearest-neighbor couplings only. Our experiment is based on a synthetic dimension scheme involving the frequency modes of an optical fiber loop platform.

Preventing Preterm Birth: Exploring Innovative Solutions.

This review examines the complexities of preterm birth (PTB), emphasizes the pivotal role of inflammation in the pathogenesis of preterm labor, and assesses current available interventions. Antibiotics, progesterone analogs, mechanical approaches, nonsteroidal anti-inflammatory drugs, and nutritional supplementation demonstrate a limited efficacy. Tocolytic agents, targeting uterine activity and contractility, inadequately prevent PTB by neglecting to act on uteroplacental inflammation.

Tunable nanofluidic device for digital nucleic acid analysis.

Nano/microfluidic-based nucleic acid tests have been proposed as a rapid and reliable diagnostic technology. Two key steps for many of these tests are target nucleic acid (NA) immobilization followed by an enzymatic reaction on the captured NAs to detect the presence of a disease-associated sequence. NA capture within a geometrically confined volume is an attractive alternative to NA surface immobilization that eliminates the need for sample pre-treatment ( label-based methods such as lateral flow assays) or use of external actuators ( dielectrophoresis) that are required for most nano/microfluidic-based NA tests.

Altered Foreign Body Response at the Posterior Surface Compared to the Anterior Surface of Human Silicone Breast Implants.

Soft implantable devices are crucial to optimizing form and function for many patients. However, periprosthetic capsule fibrosis is one of the major challenges limiting the use of implants. Currently, little is understood about how spatial and temporal factors influence capsule physiology and how the local capsule environment affects the implant structure.

Viscoelastic hydrogels regulate adipose-derived mesenchymal stem cells for nucleus pulposus regeneration.

Low back pain is a leading cause of disability worldwide, often attributed to intervertebral disc (IVD) degeneration with loss of the functional nucleus pulposus (NP). Regenerative strategies utilizing biomaterials and stem cells are promising for NP repair. Human NP tissue is highly viscoelastic, relaxing stress rapidly under deformation.