Perceived acceptability and appropriateness of a web-based program targeting risk for anxiety in young children and their parents.

Objective: This mixed-methods study examined perceived acceptability and appropriateness of a novel digital mental health program targeting anxiety risk (i.e., perfectionism or error sensitivity) in 5-to-7-year-old children and their parents.

Correlates of alcohol use and alcohol use disorder among individuals with DSM-5 social anxiety disorder: A population based study.

Alcohol use disorder (AUD) commonly cooccurs with social anxiety disorder (SAD). With changes to diagnostic criteria of psychiatric disorders in the DSM-5, the present study sought to observe the associations between daily alcohol use, AUD, and social anxiety in a large sample of individuals with lifetime (N = 1255) and past-year (N = 908) SAD. The sample was derived from a large nationally representative study of adults in the United States.

Relational victimization prospectively predicts increases in error-related brain activity and social anxiety in children and adolescents across two years.

Recent research has focused on identifying neural markers associated with risk for anxiety, including the error-related negativity (ERN). An elevated ERN amplitude has been observed in anxious individuals from middle childhood onward and has been shown to predict risk for future increases in anxiety development. The ERN is sensitive to environmental influences during development, including interpersonal stressors.

Prefrontal transcranial magnetic stimulation boosts response vigour during reinforcement learning in healthy adults.

A 10-Hz repetitive transcranial magnetic stimulation to the left dorsal lateral prefrontal cortex has been shown to increase dopaminergic activity in the dorsal striatum, a region strongly implicated in reinforcement learning. However, the behavioural influence of this effect remains largely unknown. We tested the causal effects of 10-Hz stimulation on behavioural and computational characteristics of reinforcement learning.

The impact of punishment on error-related brain activity in children.

The error-related negativity (ERN) is sensitive to individual differences relating to anxiety and is modulated by manipulations that increase the threat-value of committing errors. In adults, the ERN magnitude is enhanced when errors are followed by punishment, especially among anxious individuals. Punitive parenting is related to an elevated ERN in children; however, the effects of task-based punishment on the ERN in children have yet to be understood.

Megakaryopoiesis impairment through acute innate immune signaling activation by azacitidine.

Thrombocytopenia, prevalent in the majority of patients with myeloid malignancies, such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), is an independent adverse prognostic factor. Azacitidine (AZA), a mainstay therapeutic agent for stem cell transplant-ineligible patients with MDS/AML, often transiently induces or further aggravates disease-associated thrombocytopenia by an unknown mechanism. Here, we uncover the critical role of an acute type-I interferon (IFN-I) signaling activation in suppressing megakaryopoiesis in AZA-mediated thrombocytopenia.

Neurophysiological predictors of gaze-contingent music reward therapy among adults with social anxiety disorder.

Social anxiety disorder (SAD) is associated with fear of negative evaluation and heightened performance monitoring. The best-established treatments help only a subset of patients, and there are no well-established predictors of treatment response. The current study investigated whether individual differences in processing errors might predict response to gaze-contingent music reward therapy (GC-MRT).

Resting posterior alpha power and adolescent major depressive disorder.

For several decades, resting electroencephalogram (EEG) alpha oscillations have been used to characterize neurophysiological alterations related to major depressive disorder. Prior research has generally focused on frontal alpha power and asymmetry despite resting alpha being maximal over posterior electrode sites. Research in depressed adults has shown evidence of hemispheric asymmetry for posterior alpha power, however, the resting posterior alpha-depression link among adolescents remains unclear.

The genomes of precision edited cloned calves show no evidence for off-target events or increased de novo mutagenesis.

Background: Animal health and welfare are at the forefront of public concern and the agricultural sector is responding by prioritising the selection of welfare-relevant traits in their breeding schemes. In some cases, welfare-enhancing traits such as horn-status (i.e.

Long-Term Evaluation of Women Referred to a Breast Cancer Family History Clinic (Manchester UK 1987-2020).

Clinics for women concerned about their family history of breast cancer are widely established. A Family History Clinic was set-up in Manchester, UK, in 1987 in a Breast Unit serving a population of 1.8 million.

Transgenic goats producing an improved version of cetuximab in milk.

Therapeutic monoclonal antibodies (mAbs) represent one of the most important classes of pharmaceutical proteins to treat human diseases. Most are produced in cultured mammalian cells which is expensive, limiting their availability. Goats, striking a good balance between a relatively short generation time and copious milk yield, present an alternative platform for the cost-effective, flexible, large-scale production of therapeutic mAbs.

Cognitive resources are distributed among the entire auditory landscape in auditory scene analysis.

Although attention has been shown to enhance neural representations of selected inputs, the fate of unselected background sounds is still debated. The goal of the current study was to understand how processing resources are distributed among attended and unattended sounds during auditory scene analysis. We used a three-stream paradigm with four acoustic features uniquely defining each sound stream (frequency, envelope shape, spatial location, tone quality).

Antisense STAT3 inhibitor decreases viability of myelodysplastic and leukemic stem cells.

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Transcriptomic analysis of stem and progenitor populations in MDS and AML demonstrated overexpression of STAT3 that was validated in an independent cohort. STAT3 overexpression was predictive of a shorter survival and worse clinical features in a large MDS cohort.

Cattle with a precise, zygote-mediated deletion safely eliminate the major milk allergen beta-lactoglobulin.

We applied precise  zygote-mediated genome editing to eliminate beta-lactoglobulin (BLG), a major allergen in cows' milk. To efficiently generate LGB knockout cows, biopsied embryos were screened to transfer only appropriately modified embryos. Transfer of 13 pre-selected embryos into surrogate cows resulted in the birth of three calves, one dying shortly after birth.

Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice.

In this study we identified and characterized a novel cyclic peptide that facilitates the rapid transportation of conjugated molecules across the epithelial layer of the small intestine. The peptide was initially selected from phage display libraries using a large animal experimental model, which employed consecutive in vitro and in vivo panning. The procedure was designed to enrich for peptides that facilitated transcytosis across the intestinal epithelium into the intestinal afferent lymphatic system.

Primary transgenic bovine cells and their rejuvenated cloned equivalents show transgene-specific epigenetic differences.

Cell-mediated transgenesis, based on somatic cell nuclear transfer (SCNT), provides the opportunity to shape the genetic make-up of cattle. Bovine primary fetal fibroblasts, commonly used cells for SCNT, have a limited lifespan, and complex genetic modifications that require sequential transfections can be challenging time and cost-wise. To overcome these limitations, SCNT is frequently used to rejuvenate the cell lines and restore exhausted growth potential.

DNA oligonucleotides and plasmids perform equally as donors for targeted gene conversion.

Site-specific gene modifications in cells are initiated by the introduction of exogenous DNA. We used a recently established cell assay to compare the ability of DNA donors to induce a single point mutation that converts a target gene encoding blue fluorescent protein (BFP) into expressing green fluorescent protein (GFP). In a chromosomal assay with cells stably expressing BFP, we showed that fluorescently labeled single-stranded oligonucleotides and a donor plasmid cotranscribing a red fluorescent protein provide similar efficiencies in triggering BFP-GFP conversions.

Site-specific modification of the bovine genome using Cre recombinase-mediated gene targeting.

Cre recombinase (Cre)-mediated targeted insertion of a transgene is a powerful technique that can be used to tailor genomes. When combined with somatic cell nuclear transfer it could offer an efficient way to generate transgenic livestock with site-specific genetic modifications that are free of antibiotic selection markers. We have engineered primary bovine fibroblasts to contain a chromosomal acceptor site with incompatible loxP/lox2272 sites for Cre-mediated cassette exchange and show for the first time that Cre-mediated targeting can be applied in these acceptor cells.

A randomized clinical trial comparing two physiotherapy interventions for chronic low back pain.

Study Design: A randomized clinical trial with blinded assessment.

Objectives: To investigate the clinical efficacy of 2 active interventions for patients with chronic low back pain.

Summary Of Background Data: Manual therapy and exercise prescription are treatments frequently prescribed for patients with chronic low back pain.