Genomic variations associated with risk and protection against vincristine-induced peripheral neuropathy in pediatric cancer patients.

Vincristine-induced peripheral neuropathy is a common and highly debilitating toxicity from vincristine treatment that affects quality of life and often requires dose reduction, potentially affecting survival. Although previous studies demonstrated genetic factors are associated with vincristine neuropathy risk, the clinical relevance of most identified variants is limited by small sample sizes and unclear clinical phenotypes. A genome-wide association study was conducted in 1100 cases and controls matched by vincristine dose and genetic ancestry, uncovering a statistically significant (p < 5.

Machine learning model identifies genetic predictors of cisplatin-induced ototoxicity in CERS6 and TLR4.

Background: Cisplatin-induced ototoxicity remains a significant concern in pediatric cancer treatment due to its permanent impact on quality of life. Previously, genetic association analyses have been performed to detect genetic variants associated with this adverse reaction.

Methods: In this study, a combination of interpretable neural networks and Generative Adversarial Networks (GANs) was employed to identify genetic markers associated with cisplatin-induced ototoxicity.

Dried blood spots are a valid alternative to venipuncture for COVID-19 antibody testing.

Background: Serologic analysis is an important tool towards assessing the humoral response to COVID-19 infection and vaccination. Numerous serologic tests and platforms are currently available to support this line of testing. Two broad antibody testing categories are point-of-care lateral flow immunoassays and semi-quantitative immunoassays performed in clinical laboratories, which typically require blood collected from a finger-stick and a standard venipuncture blood draw, respectively.

Clinical and analytical evaluation of the Abbott AdviseDx quantitative SARS-CoV-2 IgG assay and comparison with two other serological tests.

Introduction: Serological testing is an important tool to assist with assessing the immune response to SARS-CoV-2 infections, the causative agent of COVID-19. A quantitative assay was recently developed by Abbott Laboratories to measures antibodies against the receptor binding domain of the spike protein. In addition to assessing disease prevalence, this assay is useful towards determining the scale and duration of the humoral response to infection and vaccination.

A pharmacogenomic investigation of the cardiac safety profile of ondansetron in children and pregnant women.

Background: Ondansetron is a highly effective antiemetic for the treatment of nausea and vomiting. However, this medication has also been associated with QT prolongation. Pharmacogenomic information on therapeutic response to ondansetron exists, but no investigation has been performed on genetic factors that influence the cardiac safety of this medication.

Patient-specific genetic factors predict treatment failure in sofosbuvir-treated patients with chronic hepatitis C.

Background & Aims: According to pivotal clinical trials, cure rates for sofosbuvir-based antiviral therapy exceed 96%. Treatment failure is usually assumed to be because of virological resistance-associated substitutions or clinical risk factors, yet the role of patient-specific genetic factors has not been well explored. We determined if patient-specific genetic factors help predict patients likely to fail sofosbuvir treatment in real-world treatment situations.

Novel variant in glycophorin c gene protects against ribavirin-induced anemia during chronic hepatitis C treatment.

Background: The current use of ribavirin in difficult-to-cure chronic hepatitis C patients (HCV) and patients with severe respiratory infections is constrained by the issue of ribavirin-induced hemolytic anemia that affects 30% of treated patients, requiring dosage modification or discontinuation. Though some genetic variants have been identified predicting this adverse effect, known clinical and genetic factors do not entirely explain the risk of ribavirin-induced anemia.

Methods: We assessed the associations of previously identified variants in inosine triphosphatase (ITPA), solute carrier 28A2 (SLC28A2) and vitamin D receptor (VDR) genes with ribavirin-induced anemia defined as hemoglobin decline of ≥30 g/L on treatment, followed by a staged discovery (n = 114), replication (n = 74), and combined (n = 188) genome-wide association study to uncover potential new predictive variants.

Analyses of Adverse Drug Reactions-Nationwide Active Surveillance Network: Canadian Pharmacogenomics Network for Drug Safety Database.

Adverse drug reactions (ADRs) are a major problem in modern medicine, representing up to the fourth-highest cause of mortality. Pharmacogenomic tests are 1 of the most promising methods to tackle the challenge of ADRs. The objective of this study was to analyze the clinical and demographic information of the pan-Canadian active surveillance network, Canadian Pharmacogenomics Network for Drug Safety (CPNDS).

High Prevalence of Abandoned Needlesticks from Injecting Drug Users in Milton Keynes, UK: Analysing Access to Needle Exchange Centres and Drug Dependency Services.

Background: In 2015, Milton Keynes (MK) Council waste management team shows an increase in the numbers of abandoned used needles being found across MK. MK is an area of high Human Immunodeficiency Virus (HIV) prevalence and high Hepatitis C (HCV) in People Who Inject Drugs (PWID), the overriding concern was for the safety of the public.

Methods: Analysis of data collection to understand the scale and spread of the problem, preventing/ reducing the incidence of abandoned needles and looking at access to the designated Drug Dependency Unit (DDU) and the Blood Borne Virus (BBV) service.

Avoiding hospital admission in COPD: impact of a specialist nursing team.

Chronic obstructive pulmonary disease (COPD) is a common, preventable and incurable disease. The costs of caring for patients with COPD is estimated to be more than £800 million a year for acute hospital admissions alone ( Department of Health, 2012 ). The hospital-at-home model is increasingly being adopted for COPD patients following British Thoracic Society (BTS) guidelines for the delivery of hospital admission-avoidance schemes ( BTS, 2007 ).

Randomized clinical trial of a handheld cooling device (Menopod®) for relief of menopausal vasomotor symptoms.

Objective: Anecdotal reports suggest that application of a cool device to the back of the neck at the onset of a hot flush can afford symptomatic relief. The effects of a novel handheld mechanical cooling device in a population of perimenopausal women with moderate-to-severe vasomotor symptoms were evaluated.

Methods: In this randomized, double-blind, sham-controlled pilot study, 40 perimenopausal women experiencing ≥ 7 moderate-to-severe hot flushes per day were recruited at a single university site.

Can whole-drawer images measure up? A reply to Johnson et al. (2013)?

Johnson et al. (2013) found that morphometric measurements of dragonfly wings taken from actual specimens and measurements taken from whole-drawer images of those specimens were equally accurate. We do not believe that their conclusions are justified by their data and analysis.

Relaxed phylogenetics and the palaeoptera problem: resolving deep ancestral splits in the insect phylogeny.

The order in which the 3 groups of winged insects (the Pterygota) diverged from their common ancestor has important implications for understanding the origin of insect flight. But despite this importance, the split between the Odonata (dragonflies and damselflies), Ephemeroptera (mayflies), and Neoptera (the other winged orders) remains very much unresolved. Indeed, previous studies have obtained strong apparent support for each of the 3 possible branching patterns.

COPD: criteria to assist in the identification of the palliative phase.

For people with chronic obstructive pulmonary disease (COPD), hospital admission can be associated with a poor prognosis. Consequently, the end stage of the illness needs to be recognized for timely palliative care to be initiated. Tools to enhance the palliative phase such as the Gold Standards Framework and the Liverpool Care Pathway rely on the recognition of the final phase of a person's life.

Developing criteria to assist in the palliative phase of COPD.

For people with chronic obstructive pulmonary disease (COPD), hospital admission can be associated with a poor prognosis. Consequently, the end-stage of the illness needs to be recognized for timely palliative care to be initiated. Tools to enhance the palliative phase, such as the Gold Standards Framework and the Liverpool Care Pathway, rely on the recognition of the final phase of a person's life.

Molecular genetic analysis and ecological evidence reveals multiple cryptic species among thynnine wasp pollinators of sexually deceptive orchids.

Sexually deceptive Chiloglottis orchids lure their male thynnine wasp pollinators to the flower by emitting semiochemicals that mimic the specific sex pheromone of the wasp. Sexual deception is possible because chemical rather than visual cues play the key role in wasp mate search, suggesting that cryptic wasp species may be frequent. We investigated this prospect among Neozeleboria wasp pollinators of Chiloglottis orchids, drawing on evidence from molecular phylogenetic analysis at three genes (CO1, rhodopsin and wingless), population genetic and statistical parsimony analysis at CO1, orchid associations and their semiochemicals, and geographic ranges.

Phylogeny and evolution of the Meliphagoidea, the largest radiation of Australasian songbirds.

The Meliphagoidea comprises the largest radiation of Australasian passerines. Here we present the first detailed molecular phylogenetic analysis of its families and genera, particularly the Acanthizidae, using sequences from nine gene regions including both mitochondrial and nuclear DNA. Our results support some suggested relationships but challenge other groupings, particularly in Meliphagidae and Acanthizidae.

The bean common mosaic virus lineage of potyviruses: where did it arise and when?

There are more than 30 species in the bean common mosaic virus lineage of the genus Potyvirus. We have used their partial coat protein gene sequences to infer their phylogenies and have compared these with host and provenance information. Members of six species of the lineage have been isolated from crops distributed around the world, but three of these show clear links with South and East Asia.

Conservation of essential design features in coiled coil silks.

Silks are strong protein fibers produced by a broad array of spiders and insects. The vast majority of known silks are large, repetitive proteins assembled into extended beta-sheet structures. Honeybees, however, have found a radically different evolutionary solution to the need for a building material.

The relationship between nocturnal urinary leptin and gonadotrophins as children progress towards puberty.

Background/aims: Leptin is necessary for normal human pubertal development but its exact role in the period leading up to the onset of puberty has not been defined. This study has assessed the relationship between leptin and gonadotrophin secretion over time as children progress into puberty.

Subjects And Methods: Twenty children (13 boys and 7 girls) judged to be close to the initiation of puberty were recruited.

Evolution of larval host plant associations and adaptive radiation in pierid butterflies.

Butterflies in the family Pieridae (Lepidoptera: Papilionoidea) feed as larvae on plants belonging primarily to three distantly related angiosperm orders: Fabales (legumes and allied plants), Brassicales (crucifers and related plants containing mustard oil glucosides), and Santalales ('mistletoes'). However, some utilize plants from 13 other families in a further eight orders. We investigated the evolutionary history of host plant use of the Pieridae in the context of a recent phylogenetic hypothesis of the family, using simple character optimization.

The acceptance of medical students by women with gynaecology appointments.

Objectives: To determine the proportion of women unwilling to see medical students for their upcoming gynaecologic appointments and to determine whether information about medical student training could influence their decisions.

Methods: Questionnaires were mailed to 1230 women with outpatient gynaecology specialist appointments. The women were asked if they would be willing to see a medical student at their upcoming appointment.

Phenotypic variation in constitutional delay of growth and puberty: relationship to specific leptin and leptin receptor gene polymorphisms.

Objectives: Constitutional delay of growth and puberty (CDGP) is a variant of normal pubertal timing and progress, often with dominant inheritance. It is likely that one or more genes will be associated with CDGP. Possible candidates are the leptin (L) and the leptin receptor (LR) genes, as the leptin axis links nutritional status to pubertal development.