Human perception of self-motion and orientation during galvanic vestibular stimulation and physical motion.

Galvanic vestibular stimulation (GVS) is an emergent tool for stimulating the vestibular system, offering the potential to manipulate or enhance processes relying on vestibular-mediated central pathways. However, the extent of GVS's influence on the perception of self-orientation pathways is not understood, particularly in the presence of physical motions. Here, we quantify roll tilt perception impacted by GVS during passive whole-body roll tilts in humans (N = 11).

The Next Frontier in Tuberculosis Investigation: Automated Whole Genome Sequencing for Analysis.

A fully automated bacteria whole genome sequencing (WGS) assay was evaluated to characterize (MTB) and non-tuberculosis (NTM) clinical isolates. The results generated were highly reproducible, with 100% concordance in species and sub-lineage classification and 92% concordance between antimicrobial resistance (AMR) genotypic and phenotypic profiles. Using extracted deoxyribonucleic acid (DNA) from MTB clinical isolates as starting material, these findings demonstrate that a fully automated WGS assay, with a short turnaround time of 24.

Galvanic Vestibular Stimulation Advancements for Spatial Disorientation Training.

Spatial disorientation (SD) remains the leading contributor to Class A mishaps in the U.S. Navy, consistent with historical trends.

A computational model of motion sickness dynamics during passive self-motion in the dark.

Predicting the time course of motion sickness symptoms enables the evaluation of provocative stimuli and the development of countermeasures for reducing symptom severity. In pursuit of this goal, we present an Observer-driven model of motion sickness for passive motions in the dark. Constructed in two stages, this model predicts motion sickness symptoms by bridging sensory conflict (i.

Targeted Next-Generation Sequencing Assay for Direct Detection and Serotyping of Salmonella from Enrichment.

In this study, an automated, targeted next-generation sequencing (tNGS) assay to detect and serotype Salmonella from sample enrichments was evaluated. The assay generates millions of reads to detect multiple Salmonella-specific genes and serotype-specific alleles, detecting all Salmonella spp. tested to date, and serotyping 62 common Salmonella serotypes.

An Augmented Reality Hand-Eye Sensorimotor Impairment Assessment for Spaceflight Operations.

Following a transition from microgravity to a gravity-rich environment (e.g., Earth, Moon, or Mars), astronauts experience sensorimotor impairment, primarily from a reinterpretation of vestibular cues, which can impact their ability to perform mission-critical tasks.

Virtual reality as a countermeasure for astronaut motion sickness during simulated post-flight water landings.

Entry motion sickness (EMS) affects crewmembers upon return to Earth following extended adaptation to microgravity. Anticholinergic pharmaceuticals (e.g.

A computational model of motion sickness dynamics during passive self-motion in the dark.

Predicting the time course of motion sickness symptoms enables the evaluation of provocative stimuli and the development of countermeasures for reducing symptom severity. In pursuit of this goal, we present an observer-driven model of motion sickness for passive motions in the dark. Constructed in two stages, this model predicts motion sickness symptoms by bridging sensory conflict (i.

Modeling orientation perception adaptation to altered gravity environments with memory of past sensorimotor states.

Transitioning between gravitational environments results in a central reinterpretation of sensory information, producing an adapted sensorimotor state suitable for motor actions and perceptions in the new environment. Critically, this central adaptation is not instantaneous, and complete adaptation may require weeks of prolonged exposure to novel environments. To mitigate risks associated with the lagging time course of adaptation (e.

Influence of Halides on the Interactions of Ammonium Acids with Metal Halide Perovskites.

Additive engineering is a common strategy to improve the performance and stability of metal halide perovskite through the modulation of crystallization kinetics and passivation of surface defects. However, much of this work has lacked a systematic approach necessary to understand how the functionality and molecular structure of the additives influence perovskite performance and stability. This paper describes the inclusion of low concentrations of 5-aminovaleric acid (5-AVA) and its ammonium acid derivatives, 5-ammoniumvaleric acid iodide (5-AVAI) and 5-ammoniumvaleric acid chloride (5-AVACl), into the precursor inks for methylammonium lead triiodide (MAPbI) perovskite and highlights the important role of halides in affecting the interactions of additives with perovskite and film properties.

Vestibular perceptual thresholds for rotation about the yaw, roll, and pitch axes.

This effort seeks to further assess human perception of self-motion by quantifying and comparing earth-vertical rotational vestibular perceptual thresholds about the yaw, roll, and pitch axes. Early seminal works (Benson Aviat Space Environ Med 60:205-213, 1989) quantified thresholds for yaw, roll, and pitch rotations, using single-cycle sinusoids in angular acceleration with a frequency of 0.3 Hz (3.

Ciltacabtagene Autoleucel, an Anti-B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up.

Purpose: CARTITUDE-1, a phase Ib/II study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel) in heavily pretreated patients with relapsed/refractory multiple myeloma, yielded early, deep, and durable responses at 12 months. Here, we present updated results 2 years after last patient in (median follow-up [MFU] approximately 28 months), including analyses of high-risk patient subgroups.

Methods: Eligible patients had relapsed/refractory multiple myeloma, had received ≥ 3 prior lines of therapy or were double refractory to a proteasome inhibitor and immunomodulatory drug and had received prior proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy.

On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models.

Leigh syndrome (LS) is a neurodegenerative disease characterized by bilaterally symmetric brainstem or basal ganglia lesions. More than 80 genes, largely impacting mitochondrial energy metabolism, can underlie LS, and no approved medicines exist. Described 70 years ago, LS was initially diagnosed by the characteristic, necrotic lesions on autopsy.

JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted -Based Immunotherapy in Patients With NSCLC: Results From Two Phase 1 Studies.

Introduction: JNJ-64041757 (JNJ-757) is a live, attenuated, double-deleted -based immunotherapy expressing human mesothelin. JNJ-757 was evaluated in patients with advanced NSCLC as monotherapy (phase 1) and in combination with nivolumab (phase 1b/2).

Methods: Patients with stage IIIB/IV NSCLC who had received previous therapy were treated with JNJ-757 (1 × 10 or 1 × 10 colony-forming units [CFUs]) alone (NCT02592967) or JNJ-757 (1 × 10 CFU) plus intravenous nivolumab 240 mg (NCT03371381).

Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.

Background: CARTITUDE-1 aimed to assess the safety and clinical activity of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma with poor prognosis.

Methods: This single-arm, open-label, phase 1b/2 study done at 16 centres in the USA enrolled patients aged 18 years or older with a diagnosis of multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. A single cilta-cel infusion (target dose 0·75 × 10 CAR-positive viable T cells per kg) was administered 5-7 days after start of lymphodepletion.

A Targeted Sequencing Assay for Serotyping Using AgriSeq Technology.

The gold standard method for serotyping has relied on antisera-based typing of the O- and H-antigens, which is labor intensive and often unreliable. In the post-genomic era, sequence-based assays are potentially faster to provide results, could combine O-serogrouping and H-typing in a single test, and could simultaneously screen for the presence of other genetic markers of interest such as virulence factors. Whole genome sequencing is one approach; however, this method has limited multiplexing capabilities, and only a small fraction of the sequence is informative for subtyping or identifying virulence potential.

Predicting the rate of oxygen uptake from step counts using ActiGraph waist-worn accelerometers in adults with Down syndrome.

Background: Step rate predicts ambulatory intensity as reflected in the rate of oxygen uptake (VO ) - a measure of energy expenditure. Whether step rate as measured by an accelerometer predicts VO in adults with Down syndrome (DS) is unknown. We examined whether step rate predicts VO in adults with and without DS.

Triaxial accelerometer output predicts oxygen uptake in adults with Down syndrome.

Purpose: This study examined if the relationship between the rate of oxygen uptake (V̇O) and output from hip-and wrist-worn accelerometers differs between adults with and without DS, and evaluated the accuracy of accelerometer output in estimating V̇O.

Materials And Methods: Sixteen adults with DS (10 men) and 19 adults without DS (10 men) performed 12 tasks including physical activities and sedentary behaviors. We measured V̇O with portable spirometry and accelerometer output (vector magnitude [VM]) with hip- and wrist-worn accelerometers.

Dynamic enhancers control skeletal muscle identity and reprogramming.

Skeletal muscles consist of fibers of differing metabolic activities and contractility, which become remodeled in response to chronic exercise, but the epigenomic basis for muscle identity and adaptation remains poorly understood. Here, we used chromatin immunoprecipitation sequencing of dimethylated histone 3 lysine 4 and acetylated histone 3 lysine 27 as well as transposase-accessible chromatin profiling to dissect cis-regulatory networks across muscle groups. We demonstrate that in vivo enhancers specify muscles in accordance with myofiber composition, show little resemblance to cultured myotube enhancers, and identify glycolytic and oxidative muscle-specific regulators.

Systematic review of sedentary behaviour in people with Down syndrome across the lifespan: A clarion call.

Background: Individuals with Down syndrome (DS) experience health disparities possibly associated with high levels of sedentary behaviour (SB). We systematically reviewed SB measurement, levels, patterns, correlates, consequences and interventions in people with DS across the lifespan.

Method: We searched these databases: Embase; PubMed; Web of Science; Scopus; CINAHL; PsycINFO; SPORTDiscus; and Cochrane Library.

Dynamic repression by BCL6 controls the genome-wide liver response to fasting and steatosis.

Transcription is tightly regulated to maintain energy homeostasis during periods of feeding or fasting, but the molecular factors that control these alternating gene programs are incompletely understood. Here, we find that the B cell lymphoma 6 (BCL6) repressor is enriched in the fed state and converges genome-wide with PPARα to potently suppress the induction of fasting transcription. Deletion of hepatocyte enhances lipid catabolism and ameliorates high-fat-diet-induced steatosis.

Loss of Transcriptional Repression by BCL6 Confers Insulin Sensitivity in the Setting of Obesity.

Accumulation of visceral adiposity is directly linked to the morbidity of obesity, while subcutaneous body fat is considered more benign. We have identified an unexpected role for B cell lymphoma 6 (BCL6), a critical regulator of immunity, in the developmental expansion of subcutaneous adipose tissue. In adipocyte-specific knockout mice (Bcl6), we found that Bcl6 deletion results in strikingly increased inguinal, but not perigonadal, adipocyte size and tissue mass in addition to marked insulin sensitivity.

Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs.