Preferential adsorption of noble gases in zeolitic tuff with variable saturation: A modeling study of counter-intuitive diffusive-adsorptive behavior.

Noble gas transport through geologic media has important applications in the prediction and characterization of measured gas signatures related to underground nuclear explosions (UNEs). Retarding processes such as adsorption can cause significant species fractionation of radionuclide gases, which has implications for measured and predicted signatures used to distinguish radioxenon originating from civilian nuclear facilities or from UNEs. Accounting for the effects of variable water saturation in geologic media on tracer transport is one of the most challenging aspects of modeling gas transport because there is no unifying relationship for the associated tortuosity changes between different rock types, and reactive transport processes such as adsorption that are affected by the presence of water likewise behave differently between gas species.

The pseudoknot region and poly-(C) tract comprise an essential RNA packaging signal for assembly of foot-and-mouth disease virus.

Virus assembly is a crucial step for the completion of the viral replication cycle. In addition to ensuring efficient incorporation of viral genomes into nascent virions, high specificity is required to prevent incorporation of host nucleic acids. For picornaviruses, including FMDV, the mechanisms required to fulfil these requirements are not well understood.

One-Size-Fits-Many: Antisense oligonucleotides for rescuing splicing mutations in hotspot exons.

Mutations that impact splicing play a significant role in disease etiology but are not fully understood. To characterize the impact of exonic variants on splicing in 71 clinically-actionable disease genes in asymptomatic people, we analyzed 32,112 exonic mutations from ClinVar and Geisinger MyCode using a minigene reporter assay. We identify 1,733 splice-disrupting mutations, of which the most extreme 1-2% of variants are likely to be deleterious.

Carbon Mineralization in Fractured Mafic and Ultramafic Rocks: A Review.

Mineral carbon storage in mafic and ultramafic rock masses has the potential to be an effective and permanent mechanism to reduce anthropogenic CO. Several successful pilot-scale projects have been carried out in basaltic rock (e.g.

Rethinking Porosity-Based Diffusivity Estimates for Sorptive Gas Transport at Variable Temperatures.

The detection of noble gas radioisotopes following a suspected underground nuclear explosion is the surest indicator that nuclear detonation has occurred. However, the accurate interpretation and attribution of radioisotopic signatures is only possible with a complete understanding of transport processes occurring between the nuclear cavity and surface. In the far-field, diffusive forces contributing to gas transport are impacted by temperature gradients and subsurface lithology.

A novel in-situ Raman spectroscopic cell for aqueous geochemistry at the solid-liquid interface.

In-situ Raman spectroscopy has the potential to be a powerful technique for monitoring geochemical reactions at a solid-liquid interface in real time. In this article, we present the development and testing of an in-situ Raman spectroscopic cell, which can be used for reaction systems at moderate temperatures and pressure [<1000 psi (6.89 MPa), <100 °C, relevant to subsurface geologic systems] and can hold samples large enough for chemical mapping of heterogeneous rock surfaces.

'Spikeopathy': COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA.

The COVID-19 pandemic caused much illness, many deaths, and profound disruption to society. The production of 'safe and effective' vaccines was a key public health target. Sadly, unprecedented high rates of adverse events have overshadowed the benefits.

Large-scale functional screen identifies genetic variants with splicing effects in modern and archaic humans.

Humans coexisted and interbred with other hominins which later became extinct. These archaic hominins are known to us only through fossil records and for two cases, genome sequences. Here, we engineer Neanderthal and Denisovan sequences into thousands of artificial genes to reconstruct the pre-mRNA processing patterns of these extinct populations.

The labels and models used to describe problematic substance use impact discrete elements of stigma: A registered report.

Objectives: Problematic substance use is one of the most stigmatized health conditions leading research to examine how the labels and models used to describe it influence public stigma. Two recent studies examine whether beliefs in a disease model of addiction influence public stigma but result in equivocal findings-in line with the mixed-blessings model, Kelly et al. (2021) found that while the label "chronically relapsing brain disease" reduced blame attribution, it decreased prognostic optimism and increased perceived danger and need for continued care; however, Rundle et al.

Perspectives on user engagement of satellite Earth observation for water quality management.

The management and governance of our surface waters is core to life and prosperity on our planet. However, monitoring data are not available to many potential users and the disparate nature of water bodies makes consistent monitoring across so many systems difficult. While satellite Earth observation (EO) offers solutions, there are numerous challenges that limit the use of satellite EO for water monitoring.

Correction: King et al. Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus. 2022, , 1820.

In the original publication [...

UpStreAm doxycycline in ST-eLeVation myocArdial infarction: targetinG infarct hEaling and ModulatIon (SALVAGE-MI trial).

Aims: Experimental studies demonstrate protective effects of doxycycline on myocardial ischaemia-reperfusion injury. The trial investigated whether doxycycline administered prior to reperfusion in patients presenting with ST-elevation myocardial infarction (STEMI) reduces infarct size (IS) and ameliorates adverse left ventricular (LV) remodelling.

Methods And Results: In this randomized, double-blind, placebo-controlled trial, patients presenting with STEMI undergoing primary percutaneous coronary intervention (PPCI) were randomized to either intravenous doxycycline or placebo prior to reperfusion followed by 7 days of oral doxycycline or placebo.

Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus.

Viruses can evolve to respond to immune pressures conferred by specific antibodies generated after vaccination and/or infection. In this study, an in vitro system was developed to investigate the impact of serum-neutralising antibodies upon the evolution of a foot-and-mouth disease virus (FMDV) isolate. The presence of sub-neutralising dilutions of specific antisera delayed the onset of virus-induced cytopathic effect (CPE) by up to 44 h compared to the untreated control cultures.

The RNA pseudoknots in foot-and-mouth disease virus are dispensable for genome replication, but essential for the production of infectious virus.

Non-coding regions of viral RNA (vRNA) genomes are critically important in the regulation of gene expression. In particular, pseudoknot (PK) structures, which are present in a wide range of RNA molecules, have a variety of roles. The 5' untranslated region (5' UTR) of foot-and-mouth disease virus (FMDV) vRNA is considerably longer than in other viruses from the picornavirus family and consists of a number of distinctive structural motifs that includes multiple (2, 3 or 4 depending on the virus strain) putative PKs linked in tandem.

Gas diffusion through variably-water-saturated zeolitic tuff: Implications for transport following a subsurface nuclear event.

Noble gas transport through geologic media has important applications in the characterization of underground nuclear explosions (UNEs). Without accurate transport models, it is nearly impossible to distinguish between xenon signatures originating from civilian nuclear facilities and UNEs. Understanding xenon transport time through the earth is a key parameter for interpreting measured xenon isotopic ratios.

Arrhythmias and Their Electrophysiological Mechanisms in Takotsubo Syndrome: A Narrative Review.

Background: Takotsubo syndrome (TTS), an acute and usually reversible condition, is associated with both tachy- and bradyarrhythmias. Such arrhythmias can be life-threatening, e.g.

Reprogramming RNA processing: an emerging therapeutic landscape.

The production of a mature mRNA requires coordination of multiple processing steps, which ultimately control its content, localization, and stability. These steps include some of the largest macromolecular machines in the cell, which were, until recently, considered undruggable due to their biological complexity. Building from an expanded understanding of the underlying mechanisms that drive these processes, a new wave of therapeutics is seeking to target RNA processing.

Predictors of Referral to Cardiac Rehabilitation in Patients following Hospitalisation with Heart Failure: A Multivariate Regression Analysis.

Background: This exploratory observational case−control study investigated the rate of referral to cardiac rehabilitation (CR) among patients hospitalised with heart failure (HF) and identified factors associated with referral. Methods: Patients hospitalised with HF as identified by the Victorian Cardiac Outcomes Registry HF study were included. Factors found to be univariately associated with referral were selected for multivariate logistic regression.

Using electronic medical record data to assess chronic kidney disease, type 2 diabetes and cardiovascular disease testing, recognition and management as documented in Australian general practice: a cross-sectional analysis.

Objectives: To evaluate the capacity of general practice (GP) electronic medical record (EMR) data to assess risk factor detection, disease diagnostic testing, diagnosis, monitoring and pharmacotherapy for the interrelated chronic vascular diseases-chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease.

Design: Cross-sectional analysis of data extracted on a single date for each practice between 12 April 2017 and 18 April 2017 incorporating data from any time on or before data extraction, using baseline data from the Chronic Disease early detection and Improved Management in PrimAry Care ProjecT. Deidentified data were extracted from GP EMRs using the Pen Computer Systems Clinical Audit Tool and descriptive statistics used to describe the study population.

Massively parallel reporter assays discover de novo exonic splicing mutants in paralogs of Autism genes.

To determine the contribution of defective splicing in Autism Spectrum Disorders (ASD), the most common neurodevelopmental disorder, a high throughput Massively Parallel Splicing Assay (MaPSY) was employed and identified 42 exonic splicing mutants out of 725 coding de novo variants discovered in the sequencing of ASD families. A redesign of the minigene constructs in MaPSY revealed that upstream exons with strong 5' splice sites increase the magnitude of skipping phenotypes observed in downstream exons. Select hits were validated by RT-PCR and amplicon sequencing in patient cell lines.

Clinical risk prediction model for 30-day all-cause re-hospitalisation or mortality in patients hospitalised with heart failure.

Background: This study aimed to develop a risk prediction model (AUS-HF model) for 30-day all-cause re-hospitalisation or death among patients admitted with acute heart failure (HF) to inform follow-up after hospitalisation. The model uses routinely collected measures at point of care.

Methods: We analyzed pooled individual-level data from two cohort studies on acute HF patients followed for 30-days after discharge in 17 hospitals in Victoria, Australia (2014-2017).

Disparities in Care and Outcome of Stroke Patients from Culturally and Linguistically Diverse Communities in Metropolitan Australia.

Acute stroke is a time-critical emergency where diagnosis and acute management are highly dependent upon the accuracy of the patient's history. We hypothesised that the language barrier is associated with delayed onset time to thrombolysis and poor clinical outcomes. This study aims to evaluate the effect of language barriers on time to thrombolysis and clinical outcomes in acute ischemic stroke.