SenPred: a single-cell RNA sequencing-based machine learning pipeline to classify deeply senescent dermal fibroblast cells for the detection of an in vivo senescent cell burden.

Background: Senescence classification is an acknowledged challenge within the field, as markers are cell-type and context dependent. Currently, multiple morphological and immunofluorescence markers are required. However, emerging scRNA-seq datasets have enabled an increased understanding of senescent cell heterogeneity.

Loss-of-function of RNA-binding protein PRRC2B causes translational defects and congenital cardiovascular malformation.

Alternative splicing generates variant forms of proteins for a given gene and accounts for functional redundancy or diversification. A novel RNA-binding protein, Pro-rich Coiled-coil Containing Protein 2B (PRRC2B), has been reported by multiple laboratories to mediate uORF-dependent and independent regulation of translation initiation required for cell cycle progression and proliferation. We identified two alternative spliced isoforms in human and mouse hearts and HEK293T cells, full-length (FL) and exon 16-excluded isoform ΔE16.

Ultraviolet radiation thin film dosimetry: A review of properties and applications.

Spectroradiometry, radiometry, and dosimetry are employed for the measurement of ultraviolet radiation (UVR) irradiance and non-ionizing exposure. Different types of UVR dosimeter have been developed for measuring personal and environmental UVR exposures since film dosimetry was pioneered in the 1970s. An important type of dosimeter is the thin film variant, which contains materials that undergo changes in optical absorbance when exposed to UVR.

Consistency in the Assessment of Dried Blood Spot Specimen Size and Quality in U.K. Newborn Screening Laboratories.

In 2015, U.K. newborn screening (NBS) laboratory guidelines were introduced to standardize dried blood spot (DBS) specimen quality acceptance and specify a minimum acceptable DBS diameter of ≥7 mm.

A Novel Case of IFNAR1 Deficiency Identified a Common Canonical Splice Site Variant in DOCK8 in Western Polynesia: The Importance of Validating Variants of Unknown Significance in Under-Represented Ancestries.

Advanced genomic technologies such as whole exome or whole genome sequencing have improved diagnoses and disease outcomes for individuals with genetic diseases. Yet, variants of unknown significance (VUS) require rigorous validation to establish disease causality or modification, or to exclude them from further analysis. Here, we describe a young individual of Polynesian ancestry who in the first 13 mo of life presented with SARS-CoV-2 pneumonia, severe enterovirus meningitis and adenovirus gastroenteritis, and severe adverse reaction to MMR vaccination.

TRP-2 / gp100 DNA vaccine and PD-1 checkpoint blockade combination for the treatment of intracranial tumors.

Intracranial tumors present a significant therapeutic challenge due to their physiological location. Immunotherapy presents an attractive method for targeting these intracranial tumors due to relatively low toxicity and tumor specificity. Here we show that SCIB1, a TRP-2 and gp100 directed ImmunoBody® DNA vaccine, generates a strong TRP-2 specific immune response, as demonstrated by the high number of TRP2-specific IFNγ spots produced and the detection of a significant number of pentamer positive T cells in the spleen of vaccinated mice.

Looking at the fringes of MedTech innovation: a mapping review of horizon scanning and foresight methods.

Objectives: Horizon scanning (HS) is a method used to examine signs of change and may be used in foresight practice. HS methods used for the identification of innovative medicinal products cannot be applied in medical technologies (MedTech) due to differences in development and regulatory processes. The aim of this study is to identify HS and other methodologies used for MedTech foresight in support to healthcare decision-making.

Safety and usability of proning pillows in intensive care: A scoping review.

Objectives: Proning is an established technique for the care of intubated patients with severe respiratory failure. Positioning devices used to support the head and body of patients placed in the prone position are often associated with the formation of pressure injuries. Despite robust literature on the prevention and monitoring of pressure injuries, little is described about the role of proning pillows on pressure injuries.

"It was really poor prior to the pandemic. It got really bad after": A qualitative study of the impact of COVID-19 on prison healthcare in England.

Background: The impact of COVID-19 has been exceptional, particularly on the National Health Service which has juggled COVID affected patients alongside related staff shortages and the existing (and growing) health needs of the population. In prisons too, healthcare teams have been balancing patient needs against staffing shortfalls, but with additional strains unique to the prison population. Such strains include drastic lockdown regimes and prolonged isolation, the need to consider health alongside security, known health inequalities within prisoner groups, and an ageing and ethnically diverse population (both groups disproportionately affected by COVID).

Establishing therapeutic and supportive relationships throughout delivery of a school-based group parenting program via telehealth: Exploring causal pathways.

Background: Access to specialised early intervention mental health services for children, including group counselling for parents/carers, is still a challenge in non-metropolitan areas of Australia.

Aim: To gain understanding of the acceptability of a school-based targeted parenting group program delivered via telehealth by exploring the experiences of parents/carers, clinicians and school staff, and asking what works, how, why and in what circumstances.

Methods: Caregivers, clinicians and school staff involved in the delivery of a mental health program via telehealth into primary schools in two rural Local Health Districts (LHDs) in southern New South Wales (NSW) were invited to participate in interviews and/or focus group discussions.

GuitarPD: A Randomized Pilot Study on the Impact of Nontraditional Guitar Instruction on Functional Movement and Well-Being in Parkinson's Disease.

Playing musical instruments may have positive effects on motor, emotional, and cognitive deficits in patients with Parkinson's disease (PD). This pilot study examined the feasibility of a six-week nontraditional guitar instruction program for individuals with PD. Twenty-six participants with idiopathic PD (Age: 67.

Vitruvian plot: a visualisation tool for multiple outcomes in network meta-analysis.

Objective: A network meta-analysis (NMA) usually assesses multiple outcomes across several treatment comparisons. The aims to facilitate communication of multiple outcomes from NMAs to patients and clinicians.

Methods: We developed this tool following the recommendations on the communication of benefit-risk information from the available literature.

Lower polyunsaturated fatty acid levels and FADS2 expression in adult compared to neonatal keratinocytes are associated with FADS2 promotor hypermethylation.

Keratinocytes produce lipids that are critical for the skin barrier, however, little is known about the impact of age on fatty acid (FA) biosynthesis in these cells. We have examined the relationship between keratinocyte FA composition, lipid biosynthetic gene expression, gene promoter methylation and age. Expression of elongase (ELOVL6 and 7) and desaturase (FADS1 and 2) genes was lower in adult versus neonatal keratinocytes, and was associated with lower concentrations of n-7, n-9 and n-10 polyunsaturated FA in adult cells.

A Diverse Range of Hemozoin Inhibiting Scaffolds Act on as Heme Complexes.

A diverse series of hemozoin-inhibiting quinolines, benzamides, triarylimidazoles, quinazolines, benzimidazoles, benzoxazoles, and benzothiazoles have been found to lead to exchangeable heme levels in cultured (NF54) that ranged over an order of magnitude at the IC. Surprisingly, less active compounds often exhibited higher levels of exchangeable heme than more active ones. Quantities of intracellular inhibitor measured using the inoculum effect exhibited a linear correlation with exchangeable heme, suggesting formation of heme-inhibitor complexes in the parasite.

Genomic characterization of a PPP1CB-ALK fusion with fusion gene amplification in a congenital glioblastoma.

ALK (Anaplastic lymphoma kinase) fusion proteins are oncogenic and have been seen in various tumors. PPP1CB-ALK fusions are rare but have been reported in a few patients with low- or high-grade gliomas. However, little is known regarding the mechanism of fusion formation and genomic break points of this fusion.

CoQ Deficient Endothelial Cell Culture Model for the Investigation of CoQ Blood-Brain Barrier Transport.

Primary coenzyme Q (CoQ) deficiency is unique among mitochondrial respiratory chain disorders in that it is potentially treatable if high-dose CoQ supplements are given in the early stages of the disease. While supplements improve peripheral abnormalities, neurological symptoms are only partially or temporarily ameliorated. The reasons for this refractory response to CoQ supplementation are unclear, however, a contributory factor may be the poor transfer of CoQ across the blood-brain barrier (BBB).

A review on the ability of smartphones to detect ultraviolet (UV) radiation and their potential to be used in UV research and for public education purposes.

The effects of ultraviolet (UV) radiation on life on Earth have continuously been the subject of research. Over-exposure to UV radiation is harmful, but small amounts of exposure are required for good health. It is, therefore, crucial for humans to optimise their own UV exposure and not exceed UV levels that are sufficient for essential biological functions.

A 20-Year Retrospective Review of Retinoblastoma at Two Tertiary Academic Hospitals in Johannesburg, South Africa.

Aim: This paper presents a 20-year review of retinoblastoma in Johannesburg, South Africa, aiming to better characterize the disease in this sub-Saharan setting.

Methods: The study represents a retrospective case series of retinoblastoma patients presenting to Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital between January 1, 1992, and December 31, 2011.

Results: The total number of cases identified was 282, with 245 meeting the study inclusion criteria.

Copy number alterations determined by single nucleotide polymorphism array testing in the clinical laboratory are indicative of gene fusions in pediatric cancer patients.

Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients.

Web-based integrated bipolar parenting intervention for parents with bipolar disorder: a randomised controlled pilot trial.

Background: People with bipolar disorder (BD) experience additional parenting challenges associated with mood driven fluctuations in communication, impulse control and motivation. This paper describes a novel web-based self-management approach (Integrated Bipolar Parenting Intervention; IBPI) to support parents with BD.

Method: Parents with BD with children aged 3-10 years randomised to IBPI plus treatment as usual (TAU) or waitlist control (WL).