Neonatal systemic gene therapy restores cardiorespiratory function in a rat model of Pompe disease.

Absence of functional acid-α-glucosidase (GAA) leads to early-onset Pompe disease with cardiorespiratory and neuromuscular failure. A novel Pompe rat model ( ) was used to test the hypothesis that neonatal gene therapy with adeno-associated virus serotype 9 (AAV9) restores cardiorespiratory neuromuscular function across the lifespan. Temporal vein administration of AAV9-DES-GAA or sham (saline) injection was done on post-natal day 1; rats were studied at 6-12 months old.

The serotonergic psychedelic N,N-dipropyltryptamine alters information-processing dynamics in in vitro cortical neural circuits.

Most of the recent work in psychedelic neuroscience has been done using noninvasive neuroimaging, with data recorded from the brains of adult volunteers under the influence of a variety of drugs. While these data provide holistic insights into the effects of psychedelics on whole-brain dynamics, the effects of psychedelics on the mesoscale dynamics of neuronal circuits remain much less explored. Here, we report the effects of the serotonergic psychedelic N,N-diproptyltryptamine (DPT) on information-processing dynamics in a sample of in vitro organotypic cultures of cortical tissue from postnatal rats.

Covalent Carbide Interconnects Enable Robust Interfaces and Thin SEI for Graphite Anode Stability under Extreme Fast Charging.

Carbonaceous and carbon-coated electrodes are ubiquitous in electrochemical energy storage and conversion technologies due to their electrochemical stability, lightweight nature, and relatively low cost. However, traditional reliance on conductive additives and binders leads to impermanent electrical pathways. Here, a general approach is presented to fabricate robust electrodes with a progressive failure mechanism by introducing carbide-based interconnects grown via carbothermal conversion of (5 wt%) titanium hydride nanoparticles.

"Real-world" performance of the Confirm Rx™ SharpSense AF detection algorithm: UK Confirm Rx study.

Introduction: The novel Confirm Rx™ implantable cardiac monitor (ICM) with SharpSense™ technology incorporates a new P-wave discriminator designed to improve AF detection. This study aimed to evaluate the diagnostic performance of the Confirm Rx™ ICM in detecting AF episodes of varying durations.

Methods: We conducted a multicenter retrospective analysis of consecutive patients implanted with a Confirm Rx™ ICM (v1.

Long-term outcomes of catheter ablation for atrial fibrillation in octogenarians.

Background And Aims: Catheter ablation is superior to pharmacological therapy in controlling atrial fibrillation (AF). There are few data on the long-term outcome of AF ablation in octogenarian patients. This analysis aims to evaluate the outcome of AF ablation in octogenarians vs.

Role of impedance drop and lesion size index (LSI) to guide catheter ablation for atrial fibrillation.

Background: When using lesion size index (LSI) to guide catheter ablation, it is unclear what combination of power, contact force and time would be preferable to use and what LSI target value to aim for. This study aimed at identifying desirable ablation settings and LSI targets by using tissue impedance drop as indicator of lesion formation.

Methods: Consecutive patients, undergoing their first left atrial (LA) catheter ablation for atrial fibrillation, with radiofrequency energy (RF) powers of 20, 30 and 40 W were enrolled.

Toward Scalable Electrochemical Exfoliation of Molybdenum Disulfide Powder through an Accessible Electrode Design.

Cathodic electrochemical intercalation/exfoliation of transition metal dichalcogenides (TMDs) with bulky tetraalkylammonium-based cations is gaining popularity as it avoids the semiconducting (2H) to metallic (1T) phase transformation in TMDs like molybdenum disulfide (MoS) and, generally, produces sheets with a larger aspect ratio - important for achieving conformal sheet-to-sheet contact in optoelectronic devices. Large single crystals are typically used as the precursor, but these are expensive, often inaccessible, and result in limited quantities of material. In this paper, a 3D-printable electrochemical cell capable of intercalating gram-scale quantities of commercially available TMD powders is presented.

Fluorescence-Based Proteoliposome Methods to Monitor Redox-Active Transition Metal Transmembrane Translocation by Metal Transporters.

Transmembrane transition metal transporter proteins are central gatekeepers in selectively controlling vectorial metal cargo uptake and extrusion across cellular membranes in all living organisms, thus playing key roles in essential and toxic metal homeostasis. Biochemical characterization of transporter-mediated translocation events and transport kinetics of redox-active metals, such as iron and copper, is challenged by the complexity in generating reconstituted systems in which vectorial metal transport can be studied in real time. We present fluorescence-based proteoliposome methods to monitor redox-active metal transmembrane translocation upon reconstitution of purified metal transporters in artificial lipid bilayers.

Acoustic ejection mass spectrometry empowers ultra-fast protein biomarker quantification.

The global scientific response to COVID 19 highlighted the urgent need for increased throughput and capacity in bioanalytical laboratories, especially for the precise quantification of proteins that pertain to health and disease. Acoustic ejection mass spectrometry (AEMS) represents a much-needed paradigm shift for ultra-fast biomarker screening. Here, a quantitative AEMS assays is presented, employing peptide immunocapture to enrich (i) 10 acute phase response (APR) protein markers from plasma, and (ii) SARS-CoV-2 NCAP peptides from nasopharyngeal swabs.

In Silico TRials guide optimal stratification of ATrIal FIbrillation patients to Catheter Ablation and pharmacological medicaTION: the i-STRATIFICATION study.

Aims: Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials.

Methods And Results: A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram.

Metal cation crosslinked, partially reduced graphene oxide membranes with enhanced stability for high salinity, produced water treatment by pervaporative separation.

Graphene oxide (GO)-based membranes hold significant promise for applications ranging from energy storage to protective coatings, to saline water and produced water treatment, owing to their chemical stability and unique barrier properties achieving a high selectivity for water permeation. However, unmodified GO membranes are not stable when submerged in liquid water, creating challenges with their commercial utilization in aqueous filtration and pervaporation applications. To mitigate this, we develop an approach to modify GO membranes through a combination of low temperature thermal reduction and metal cation crosslinking.

Implementing and Evaluating a National Integrated Digital Registry and Clinical Decision Support System in Early Intervention in Psychosis Services (Early Psychosis Informatics Into Care): Co-Designed Protocol.

Background: Early intervention in psychosis (EIP) services are nationally mandated in England to provide multidisciplinary care to people experiencing first-episode psychosis, which disproportionately affects deprived and ethnic minority youth. Quality of service provision varies by region, and people from historically underserved populations have unequal access. In other disease areas, including stroke and dementia, national digital registries coupled with clinical decision support systems (CDSSs) have revolutionized the delivery of equitable, evidence-based interventions to transform patient outcomes and reduce population-level disparities in care.

Entorhinal-based path integration selectively predicts midlife risk of Alzheimer's disease.

Introduction: Entorhinal cortex (EC) is the first cortical region to exhibit neurodegeneration in Alzheimer's disease (AD), associated with EC grid cell dysfunction. Given the role of grid cells in path integration (PI)-based spatial behaviors, we predicted that PI impairment would represent the first behavioral change in adults at risk of AD.

Methods: We compared immersive virtual reality (VR) PI ability to other cognitive domains in 100 asymptomatic midlife adults stratified by hereditary and physiological AD risk factors.

Modular subgraphs in large-scale connectomes underpin spontaneous co-fluctuation events in mouse and human brains.

Previous studies have adopted an edge-centric framework to study fine-scale network dynamics in human fMRI. To date, however, no studies have applied this framework to data collected from model organisms. Here, we analyze structural and functional imaging data from lightly anesthetized mice through an edge-centric lens.

A high throughput immuno-affinity mass spectrometry method for detection and quantitation of SARS-CoV-2 nucleoprotein in human saliva and its comparison with RT-PCR, RT-LAMP, and lateral flow rapid antigen test.

Objectives: Many reverse transcription polymerase chain reaction (RT-PCR) methods exist that can detect SARS-CoV-2 RNA in different matrices. RT-PCR is highly sensitive, although viral RNA may be detected long after active infection has taken place. SARS-CoV-2 proteins have shorter detection windows hence their detection might be more meaningful.

Long Term Survival of Heritable Pulmonary Arterial Hypertension Associated with Hereditary Hemorrhagic Telangiectasia: A Case Series.

Hereditary hemorrhagic telangiectasia (HHT) is a hereditary disease characterized by recurrent epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations. Multiple genetic mutations have been linked to this rare disease, including ENG, ALK1 (ACVRL1), and MADH4. Pulmonary hypertension is a potential complication of HHT, with the most common phenotypes being World Health Organization (WHO) group 1 heritable pulmonary arterial hypertension (PAH), which is typically associated with ALK1 mutation; WHO group 2 pulmonary hypertension due to high output heart failure from hepatic arteriovenous malformations and/or anemia; and WHO group 2 due to high pulmonary artery wedge pressure.

Integrating climate change induced flood risk into future population projections.

Flood exposure has been linked to shifts in population sizes and composition. Traditionally, these changes have been observed at a local level providing insight to local dynamics but not general trends, or at a coarse resolution that does not capture localized shifts. Using historic flood data between 2000-2023 across the Contiguous United States (CONUS), we identify the relationships between flood exposure and population change.

Advertising Exposure From Online and Offline Sources and Youth Tobacco Use: Findings From the Adolescents, Place, and Behavior Study.

Introduction: Tobacco use among adolescents is an ongoing public health concern. Youth tobacco use has been associated with advertising, from both online sources and retail environments.

Aims And Methods: This study examined associations between exposure to tobacco advertisements from tobacco retail outlets (TROs), internet, and social media sources and ever tobacco use among adolescents.

Divergent Temporal Trends of Mercury in Arctic Char from Paired Lakes Influenced by Climate-Related Drivers.

Climate-driven changes including rising air temperatures, enhanced permafrost degradation, and altered precipitation patterns can have profound effects on contaminants, such as mercury (Hg), in High Arctic lakes. Two physically similar lakes, East Lake and West Lake at the Cape Bounty Arctic Watershed Observatory on Melville Island, Nunavut, Canada are being affected by climate change differently. Both lakes have experienced permafrost degradation in their catchments; however, West Lake has also undergone multiple underwater Mass Movement Events (MMEs; beginning in fall 2008), leading to a sustained 50-fold increase in turbidity.

'Pill-in-the-pocket' Oral Anticoagulation Guided by Daily Rhythm Monitoring for Stroke Prevention in Patients with AF: A Systematic Review and Meta-analysis.

Aims: In patients with a low AF burden and long periods of sinus rhythm, 'pill-in-the-pocket' oral anticoagulation (OAC) may, taken as needed in response to AF episodes, offer the same thromboembolic protection as continuous, life-long OAC, while reducing bleeding complications at the same time. The purpose of this study is to systematically summarise available evidence pertaining to the feasibility, safety and efficacy of pill-in-the-pocket OAC.

Methods: Medline and Embase were searched from inception to July 2022 for studies adopting a pill-in-the-pocket OAC strategy in AF patients guided by daily rhythm monitoring (PROSPERO/CRD42020209564).

What determines the optimal pharmacological treatment of atrial fibrillation? Insights from in silico trials in 800 virtual atria.

The best pharmacological treatment for each atrial fibrillation (AF) patient is unclear. We aim to exploit AF simulations in 800 virtual atria to identify key patient characteristics that guide the optimal selection of anti-arrhythmic drugs. The virtual cohort considered variability in electrophysiology and low voltage areas (LVA) and was developed and validated against experimental and clinical data from ionic currents to ECG.

Partial entropy decomposition reveals higher-order information structures in human brain activity.

The standard approach to modeling the human brain as a complex system is with a network, where the basic unit of interaction is a pairwise link between two brain regions. While powerful, this approach is limited by the inability to assess higher-order interactions involving three or more elements directly. In this work, we explore a method for capturing higher-order dependencies in multivariate data: the partial entropy decomposition (PED).

Defibrillation Threshold Testing for Right-sided Device Implants: A Review to Inform Shared Decision-making, in Association with the British Heart Rhythm Society.

Prevention of sudden death using ICDs requires the reliable delivery of a high-energy shock to successfully terminate VF. Until more recently, the device implant procedure included conducting defibrillation threshold (DFT) testing involving VF induction and shock delivery to ensure efficacy. Large clinical trials, including SIMPLE and NORDIC ICD, have subsequently demonstrated that this is unnecessary, with a practice of omitting DFT testing having no impact on subsequent clinical outcomes.

Co-evolving dynamics and topology in a coupled oscillator model of resting brain function.

Dynamic models of ongoing BOLD fMRI brain dynamics and models of communication strategies have been two important approaches to understanding how brain network structure constrains function. However, dynamic models have yet to widely incorporate one of the most important insights from communication models: the brain may not use all of its connections in the same way or at the same time. Here we present a variation of a phase delayed Kuramoto coupled oscillator model that dynamically limits communication between nodes on each time step.