CRISPR/Cas9-mediated editing of COQ4 in induced pluripotent stem cells: A model for investigating COQ4-associated human coenzyme Q deficiency.

Pathogenic variants in the gene COQ4 cause primary coenzyme Q deficiency, which is associated with symptoms ranging from early epileptic encephalopathy up to adult-onset ataxia-spasticity spectrum disease. We genetically modified commercially available wild-type iPS cells by using a CRISPR/Cas9 approach to create heterozygous and homozygous isogenic cell lines carrying the disease-causing COQ4 variants c.458C > T, p.

The Plant of Many Scents: Unraveling the Odorant Composition of Selected CBD Hemp Cultivars.

This study presents the first comprehensive sensory-guided investigation into the odor-active compounds of dried hemp ( L.) flowers. Using gas chromatography-olfactometry (GC-O) in combination with aroma extract dilution analysis (AEDA), 52 odor-active compounds were identified across six cannabidiol-rich cultivars.

Health Inequity in People with Cystic Fibrosis: Can We Close the Gap?

Background Although advances in care have improved cystic fibrosis (CF) outcomes in higher-income countries (HICs), the situation remains alarming in lower-income countries (LICs). Methods People with CF (pwCF) enrolled in the European Cystic Fibrosis Society Patient Registry (ECFSPR) and carrying at least one F508del variant allele were evaluated in 2017 and in 2022 for predicted percent forced expiratory volume (ppFEV1), underweight status, and chronic Pseudomonas aeruginosa (Pa) infection, according to the gross national income (GNI) per capita divided into three terciles (low-income countries, LICs; middle-income countries, MICs; and high-income countries, HICs). Survival was evaluated in the periods 2013-2017 and 2018-2022.

The efficacy, safety and predictability of transepithelial versus mechanical or alcohol-assisted photorefractive keratectomy - a meta-analysis.

Topic: The aim of this study was to assess the meta-analysis of the studies comparing transepithelial photorefractive keratectomy (TransPRK) to classical photorefractive keratectomy (PRK) (mechanical or alcohol-assisted).

Clinical Relevance: While PRK is a well-established procedure, TransPRK, a newer, minimally invasive technique may reduce surgery time and improve patient outcomes. Comparing these techniques helps optimize surgical choices.

Mechanotransduction mechanisms in human erythrocytes: Fundamental physiology and clinical significance.

The hallmarks of mechanosensitive ion channels have been observed for half a century in various cell lines, although their mechanisms and molecular identities remained unknown until recently. Identification of the bona fide mammalian mechanosensory Piezo channels resulted in an explosion of research exploring the translation of mechanical cues into biochemical signals and dynamic cell morphology responses. One of the Piezo isoforms - Piezo1 - is integral in the erythrocyte (red blood cell; RBC) membrane.

Catalytic Asymmetric (-)-Carbonyl-Ene Type Cyclizations.

The carbonyl-ene reaction between aldehydes and olefins constitutes a perfectly atom economic approach to homoallylic alcohols with concomitant C-C bond formation. However, the scope of catalytic asymmetric intermolecular versions is currently limited to activated substrates, while of the two intramolecular types only catalytic asymmetric (-)-carbonyl-ene type cyclizations can be considered mature. The corresponding (-)-cyclizations would arguably find equal utility in chemical synthesis but remain underdeveloped.

Participant Satisfaction, Effectiveness, and Safety With a Novel Dual-Applicator Cryolipolysis System: A Prospective, Multicountry Study.

Background: Cryolipolysis is an effective, well-tolerated noninvasive subcutaneous fat reduction treatment.

Objective: Assess participant satisfaction, effectiveness, and safety of a dual-applicator cryolipolysis system that can deliver simultaneous treatments.

Materials And Methods: Adult participants received treatment to the abdomen/flanks (midsection).

Incretin Signaling Neighborhoods and Adverse Drug Reactions.

In light of the success of blockbuster drugs for type 2 diabetes and obesity based on the GLP-1 hormone, drugmakers have concentrated their efforts on developing new and improved variations that address the route of administration, dosing, pathway selectivity, or polypharmacology. While some of these modifications have demonstrated improved efficacy in clinical studies and offered exciting opportunities for treating other diseases, drug-induced shifts to the conformational landscape of target receptors may have consequences for side effects. Our review summarizes advances in the understanding of the biochemistry, pharmacogenomics, and molecular pharmacology of incretins and their cognate receptors.

The PROtective VEntilation (PROVE) Network - advancing research and collaboration in mechanical ventilation.

The PROtective VEntilation (PROVE) Network is a globally-recognized collaborative research group dedicated to advancing research, education, and collaboration in the field of mechanical ventilation. Established to address critical questions in intraoperative and intensive care ventilation, the network focuses on improving outcomes for patients undergoing mechanical ventilation in diverse settings, including operating rooms, intensive care units, burn units, and resource-limited environments in low- and middle-income countries. The PROVE Network is committed to generating high-quality evidence through a comprehensive portfolio of investigations, including randomized clinical trials, observational research, and meta-analyses.

Should We Always Use a Metaphyseal Cone in Conjunction With Tibial Augments for Uncontained Defects? A Finite-element Biomechanical Analysis.

Background: Choosing the appropriate implants for reconstruction in revision TKA is essential for long-term fixation. While cones and augments are routinely utilized to address tibial defects, the effect of augment location and size on the biomechanical stability of revision TKA constructs and the indications for the use of metaphyseal cones are not known.

Questions/purposes: Is the risk of cement-implant debonding of revision TKA constructs impacted by the thickness and location (medial versus bicompartmental) of tibial augments and the presence of metaphyseal cones during (1) a demanding daily activity like stair ascent and (2) torsional loads?

Methods: Under institutional review board approval, we developed patient-specific finite-element models of revision TKA from four patients (three males and one female, ages 50 to 80 years, BMI 27 to 37 kg/m2) who underwent two-stage revision and had a CT scan with no metal artifact after first-stage implant removal.

Expectation effects on repetition suppression in nociception.

Repetition suppression, the reduced neural response upon repeated presentation of a stimulus, can be explained by models focussing on bottom-up (i.e. adaptation) or top-down (i.

Attosecond All-Optical Retrieval of Valley Polarization via Circular Dichroism in Transient Absorption.

We propose a scheme for retrieving the ultrafast valley polarization (VP) dynamics in two-dimensional hexagonal materials via attosecond circular dichroism (CD) transient absorption spectroscopy. This approach builds on the CD transition between the first and higher conduction bands induced by the circularly polarized probe pulses. The population imbalance at nonequivalent valleys in the first conduction band is proportionally mapped onto the difference in absorption coefficients of two probe pulses with opposite helicities, supporting an unprecedented quantitative retrieval of the corresponding VP dynamics with subfemtosecond time resolution.

Strong Magnon-Phonon Coupling in the Kagome Antiferromagnets.

Magnon-phonon hybridization in ordered materials is a crucial phenomenon with significant implications for spintronics, magnonics, and quantum materials research. We present direct experimental evidence and theoretical insights into magnon-phonon coupling in Mn_{3}Ge, a kagome antiferromagnet with noncollinear spin order. Using inelastic x-ray scattering and ab initio modeling, we uncover strong hybridization between planar spin fluctuations and transverse optical phonons, resulting in a large hybridization gap of ∼2  meV.

Imaging Valence Electron Rearrangement in a Chemical Reaction Using Hard X-Ray Scattering.

We have observed the signatures of valence electron rearrangement in photoexcited ammonia using ultrafast hard x-ray scattering. Time-resolved x-ray scattering is a powerful tool for imaging structural dynamics in molecules because of the strong scattering from the core electrons localized near each nucleus. Such core-electron contributions generally dominate the differential scattering signal, masking any signatures of rearrangement in the chemically important valence electrons.

First Sub-MeV Dark Matter Search with the QROCODILE Experiment Using Superconducting Nanowire Single-Photon Detectors.

We present the first results from the Quantum Resolution-Optimized Cryogenic Observatory for Dark matter Incident at Low Energy (QROCODILE). The QROCODILE experiment uses a microwire-based superconducting nanowire single-photon detector (SNSPD) as a target and sensor for dark matter scattering and absorption, and is sensitive to energy deposits as low as 0.11 eV.

Positive Neutrino Masses with DESI DR2 via Matter Conversion to Dark Energy.

The Dark Energy Spectroscopic Instrument (DESI) is a massively parallel spectroscopic survey on the Mayall telescope at Kitt Peak, which has released measurements of baryon acoustic oscillations determined from over 14 million extragalactic targets. We combine DESI Data Release 2 with CMB datasets to search for evidence of matter conversion to dark energy (DE), focusing on a scenario mediated by stellar collapse to cosmologically coupled black holes (CCBHs). In this physical model, which has the same number of free parameters as ΛCDM, DE production is determined by the cosmic star formation rate density (SFRD), allowing for distinct early- and late-time cosmologies.

Two-Peak Heat Capacity Accounts for Rln(2) Entropy and Ground State Access in the Dipole-Octupole Pyrochlore Ce_{2}Hf_{2}O_{7}.

Magnetic heat capacity measurements of a high-quality single crystal of the dipole-octupole pyrochlore Ce_{2}Hf_{2}O_{7} down to a temperature of T=0.02  K are reported. These show a two-peaked structure, with a Schottky-like peak at T_{1}∼0.

Core-Periphery Detection in Multilayer Networks.

Multilayer networks provide a powerful framework for modeling complex systems that capture different types of interactions between the same set of entities across multiple layers. Core-periphery detection involves partitioning the nodes of a network into core nodes, which are highly connected across the network, and peripheral nodes, which are densely connected to the core but sparsely connected among themselves. In this paper, we propose a new model of core-periphery structure in multilayer networks and a nonlinear spectral method that simultaneously detects the corresponding core and periphery structures of both nodes and layers in weighted and directed multilayer networks.

Multipartite Entanglement Structure of Monitored Quantum Circuits.

Monitored quantum circuits have attracted significant interest as an example of synthetic quantum matter, intrinsically defined by their quantum information content. Here, we propose a multipartite entanglement perspective on monitored phases through the lens of quantum Fisher information. Our findings reveal that unstructured monitored random circuits fail to exhibit divergent multipartite entanglement even at criticality, highlighting their departure from standard quantum critical behavior.

Geospatial patterns in terrestrial organic matter reactivity across four shelf seas spanning the Eurasian Arctic.

Organic matter stored in Arctic permafrost represents a key component of the carbon cycle, yet its reactivity across heterogeneous continent-scale permafrost regions remains poorly understood. Here, we leverage the four shelf seas of the Eurasian Arctic as integrative receptor systems to evaluate terrestrial organic matter reactivity, assessed by examining organic carbon preservation as a function of C-constrained cross-shelf transport time. Our findings reveal higher reactivity of terrestrial organic matter released to the Laptev Sea and the eastern East Siberian Sea, lower reactivity in the western East Siberian Sea, and no deducible degradation in the Kara Sea.

An early surge of norepinephrine along brainstem pathways drives sensory-evoked awakening.

The locus coeruleus-norepinephrine (LC-NE) system regulates arousal and awakening; however, it remains unclear whether the LC does this in a global or circuit-specific manner. We hypothesized that sensory-evoked awakenings are predominantly regulated by specific LC-NE efferent pathways. Anatomical, physiological, and functional modularities of LC-NE pathways involving the mouse basal forebrain (BF) and pontine reticular nucleus (PRN) were tested.

Single-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs of type 1 diabetes progression.

Cell type-specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here, we performed single-nucleus multiomics and spatial transcriptomics in up to 32 nondiabetic (ND), autoantibody-positive (AAB), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine subtypes.

Differential modulation of movement speed with state-dependent deep brain stimulation in Parkinson's disease.

Subthalamic deep brain stimulation (STN-DBS) provides unprecedented spatiotemporal precision for the treatment of Parkinson's disease (PD), allowing for direct real-time state-specific adjustments. Inspired by findings from optogenetic stimulation in mice, we hypothesized that STN-DBS can mimic dopaminergic reinforcement of ongoing movement kinematics during stimulation. To investigate this hypothesis, we delivered DBS bursts during particularly fast and slow movements in 24 patients with PD.

Magnitude uncertainty dominates intermodel spread in zonal-mean precipitation response to anthropogenic aerosol increase.

Anthropogenic aerosols are an important driver of historical climate change but the climate response is not fully understood and the climate model simulations suffer large uncertainties. On the basis of a multimodel ensemble of historical aerosol forcing simulation for a period of global aerosol increase during 1965 to 1989, here, we show that the precipitation response shares a common southward displacement of tropical rain bands but the magnitude differs markedly among models, accounting for 76% of the intermodel uncertainty in zonal-mean precipitation change. Our analysis of atmospheric energetics further reveals key mechanisms for magnitude uncertainty: aerosol radiative forcing drives, cloud radiative feedback amplifies, and ocean circulation damps the intermodel uncertainty in cross-equatorial atmospheric energy transport change and the meridional shift of tropical rain bands.

Universal Effective Charges in the sd and fp Shells.

The 247-keV state in ^{54}Sc, populated in the β decay of ^{54}Ca, is reported here as a nanosecond isomer with a half-life of 26.0(22) ns. The state is interpreted as the 1^{+} member of the πf_{7/2}⊗νf_{5/2} spin-coupled multiplet, which decays to the 3^{+},πf_{7/2}⊗νp_{1/2} ground state.