Pupil Abnormality Frequency in the First 72 Hours Improves IMPACT score in Traumatic Brain Injury.

Importance: In patients with traumatic brain injury (TBI), baseline pupillary assessment is common. However, the incidence and frequency of pupil abnormalities within the first several days remain poorly characterized.

Objectives: Our aim was to test the association between pupil abnormality frequency over the first 72 hours of admission and clinical outcomes.

Plasma Protein Biomarkers of Spirometry Measures of Impaired Lung Function.

Background: Impaired pulmonary function carries significant risks for lung, cardiovascular, and metabolic disorders.

Research Question: Can circulating protein biomarkers of pulmonary function provide insight into the pathophysiologic features of lung function impairment and links to comorbidities?.

Study Design And Methods: We analyzed plasma levels of 2,922 proteins in 32,493 UK Biobank participants (53% female; mean [SD] age, 57 [8] years) to investigate their associations with spirometry measures of lung function (FEV, FVC, FEV to FVC ratio), and with obstructive (n = 4,713) and restrictive (n = 3,886) spirometry patterns.

Inflammatory Waldenström Macroglobulinemia is associated with clonal hematopoiesis: a multicentric cohort.

Inflammation in Waldenström Macroglobulinemia (iWM) predicts outcomes after immuno-chemotherapy and BTK inhibitors, but its origin is unknown. Here, we unravel increased clonal hematopoiesis in iWM patients (61% versus 23% in non-inflammatory WM), suggesting a contribution of environmental cells to iWM.

Accounting for genetic effect heterogeneity in fine-mapping and improving power to detect gene-environment interactions with SharePro.

Classical gene-by-environment interaction (GxE) analysis can be used to characterize genetic effect heterogeneity but has a high multiple testing burden in the context of genome-wide association studies (GWAS). We adapt a colocalization method, SharePro, to account for effect heterogeneity in fine-mapping and identify candidates for GxE analysis with reduced multiple testing burden. SharePro demonstrates improved power for both fine-mapping and GxE analysis compared to existing methods as well as well-controlled false type I error in simulations.

The Upper Limit of Normal Rate of Lung Function Decline in Healthy Adults in the Framingham Heart Study.

Background: Lung function declines over the course of adulthood; however, a consensus on the normal range of decline in an individual's lung function is lacking.

Research Question: What is the normal range and the upper limit of normal (ULN) decline in lung function in adults without prior tobacco use, occupational dust exposure, or a known diagnosis or symptoms of cardiopulmonary disease?

Study Design And Methods: A retrospective analysis of healthy individuals who have never smoked (N = 1,305) from the Framingham Heart Study with repeated lung function meeting standards for acceptability and reproducibility was conducted. Longitudinal change was derived using a linear mixed effects model and estimated to a 6-year interval.

Exploration of primary care models and timely access to care in New Brunswick (Canada).

Background: This correlative study aimed to examine how the different primary care models (physicians in solo practice, physicians in collaborative practice, physicians and nurse practitioners in collaborative practice, after-hours clinics, community centers, or emergency rooms) were associated with their capability to offer timely access to their patients. The data collected from the primary care provider's perspective was to complete the New Brunswick Health Council results on patients' perspective.

Methods: A convenience sample of 120 primary care providers (33 physicians in solo practice, 33 physicians in collaborative practice, 27 providers in collaborative practice with nurse practitioners, 2 providers working in after-hours clinics, and 10 providers in Emergency departments) responded to an online survey about their primary care models and accessibility.

Loss of heterozygosity of CYP2D6 enhances the sensitivity of hepatocellular carcinomas to talazoparib.

Background: Loss of heterozygosity (LOH) diminishes genetic diversity within cancer genomes. A tumour arising in an individual heterozygous for a functional and a loss-of-function (LoF) allele of a gene occasionally retain only the LoF allele. This can result in deficiency of specific protein activities in cancer cells, creating unique differences between tumour cells and normal cells of the individual.

Soft-Rigid Hybrid Revolute and Prismatic Joints Using Multilayered Bellow-Type Soft Pneumatic Actuators: Design, Characterization, and Its Application as Soft-Rigid Hybrid Gripper.

Despite the exponentially expanding capabilities of robotic systems with the introduction of soft robotics, the lack of practical considerations in designing and integrating soft robotic components hinders the widespread application of newly developed technology in real life. This study investigates the development and performance evaluation of soft-rigid hybrid (SRH) robotic systems employing multilayered bellow-shaped soft pneumatic actuators (MBSPAs) to overcome the common challenges exclusively exhibited in soft robotics. Specifically, we introduce a unique SRH revolute joint enabled by a single thermoplastic polyurethane-MBSPA and rigid components to tackle the limitations of existing soft pneumatic actuators (SPAs), such as restricted payload capacity, vulnerability to external damages, and lack of resilience against outdoor environment.

Synaptic rearrangement of NMDA receptors controls memory engram formation and malleability in the cortex.

Initially hippocampal dependent, memory representations rely on a broadly distributed cortical network as they mature over time. How these cortical engrams acquire stability during systems-level memory consolidation without compromising their dynamic nature remains unclear. We identified a highly responsive "consolidation switch" in the synaptic composition of -methyl-d-aspartate receptors (NMDARs), which dictates the progressive embedding and persistence of enduring memories in the rat cortex.

Au-modified ceria nanozyme prevents and treats hypoxia-induced pulmonary hypertension with greatly improved enzymatic activity and safety.

Background: Despite recent advances the prognosis of pulmonary hypertension remains poor and warrants novel therapeutic options. Extensive studies, including ours, have revealed that hypoxia-induced pulmonary hypertension is associated with high oxidative stress. Cerium oxide nanozyme or nanoparticles (CeNPs) have displayed catalytic activity mimicking both catalase and superoxide dismutase functions and have been widely used as an anti-oxidative stress approach.

Ketamine alleviates NMDA receptor hypofunction through synaptic trapping.

Activity-dependent modulations of N-methyl-D-aspartate glutamate receptor (NMDAR) trapping at synapses regulate excitatory neurotransmission and shape cognitive functions. Although NMDAR synaptic destabilization has been associated with severe neurological and psychiatric conditions, tuning NMDAR synaptic trapping to assess its clinical relevance for the treatment of brain conditions remains a challenge. Here, we report that ketamine (KET) and other clinically relevant NMDAR open channel blockers (OCBs) promote interactions between NMDAR and PDZ-domain-containing scaffolding proteins and enhance NMDAR trapping at synapses.

Identification of Noncoding Functional Regulatory Variants of Gene in Idiopathic Pulmonary Arterial Hypertension.

Background: STIM1 (stromal interaction molecule 1) regulates store-operated calcium entry and is involved in pulmonary artery vasoconstriction and pulmonary artery smooth muscle cell proliferation, leading to pulmonary arterial hypertension (PAH).

Methods: Bioinformatics analysis and a 2-stage matched case-control study were conducted to screen for noncoding variants that may potentially affect transcriptional regulation in 242 patients with idiopathic PAH and 414 healthy controls. Luciferase reporter assay, real-time quantitative polymerase chain reaction, western blot, 5-ethynyl-2'-deoxyuridine (EdU) assay, and intracellular Ca measurement were performed to study the mechanistic roles of those noncoding variants in PAH.

Towards a better future for DNA barcoding: Evaluating monophyly- and distance-based species identification using COI gene fragments of Dacini fruit flies.

The utility of a universal DNA 'barcode' fragment (658 base pairs of the Cytochrome C Oxidase I [COI] gene) has been established as a useful tool for species identification, and widely criticized as one for understanding the evolutionary history of a group. Large amounts of COI sequence data have been produced that hold promise for rapid species identification, for example, for biosecurity. The fruit fly tribe Dacini holds about a thousand species, of which 80 are pests of economic concern.

Association of Dynamic Trajectories of Time-Series Data and Life-Threatening Mass Effect in Large Middle Cerebral Artery Stroke.

Background: Life-threatening, space-occupying mass effect due to cerebral edema and/or hemorrhagic transformation is an early complication of patients with middle cerebral artery stroke. Little is known about longitudinal trajectories of laboratory and vital signs leading up to radiographic and clinical deterioration related to this mass effect.

Methods: We curated a retrospective data set of 635 patients with large middle cerebral artery stroke totaling 95,463 data points for 10 longitudinal covariates and 40 time-independent covariates.

snpAIMeR: R package for evaluating ancestry informative marker contributions in non-model population diagnostics.

Motivation: Single nucleotide polymorphism (SNP) markers are increasingly popular for population genomics and inferring ancestry for individuals of unknown origin. Because large SNP datasets are impractical for rapid and routine analysis, diagnostics rely on panels of highly informative markers. Strategies exist for selecting these markers, however, resources for efficiently evaluating their performance are limited for non-model systems.

APP fragment controls both ionotropic and non-ionotropic signaling of NMDA receptors.

NMDA receptors (NMDARs) are ionotropic receptors crucial for brain information processing. Yet, evidence also supports an ion-flux-independent signaling mode mediating synaptic long-term depression (LTD) and spine shrinkage. Here, we identify AETA (Aη), an amyloid-β precursor protein (APP) cleavage product, as an NMDAR modulator with the unique dual regulatory capacity to impact both signaling modes.