Publications by authors named "Hall P"

TASK-1 and TASK-3 are pH-sensitive two-pore domain (K2P/KCNK) K channels. Their functional roles make them promising targets for treatment of multiple disorders including sleep apnea, pain, and atrial fibrillation. Mutations in these channels are also associated with neurodevelopmental and hypertensive disorders.

View Article and Find Full Text PDF

Sandhoff Disease (SD), a fatal neurodegenerative disorder, is caused by the absence of ß-hexosaminidase (Hex) and subsequent accumulation of GM2 ganglioside in lysosomes. Previous studies have led to adeno-associated virus (AAV) gene therapy for children with GM2 gangliosidosis in both expanded access and Phase I/II clinical trials via intracranial and/or cerebrospinal fluid-based delivery. The current study investigated intravenous (IV) gene therapy of SD cats, treated at one month of age with a bicistronic AAV vector.

View Article and Find Full Text PDF

Background: Tissue stiffness, dictated by organisation of interstitial fibrillar collagens, increases breast cancer risk and contributes to cancer progression. Tamoxifen is a standard treatment for receptor-positive breast cancer and is also aproved for primary prevention. We investigated the effect of tamoxifen and its main metabolites on the breast tissue collagen organisation as a proxy for stiffness and explored the relationship between mammographic density (MD) and collagen organisation.

View Article and Find Full Text PDF

Human astroviruses (HAstV) are major causes of gastroenteritis, especially in children, and there are no vaccines or antivirals currently available. Little is known about host factors required for their cellular entry. Here we utilized complementary CRISPR-Cas9-based knockout and activation screens to identify neonatal Fc receptor (FcRn) and dipeptidyl-peptidase IV (DPP4) as entry factors for HAstV infection in vitro.

View Article and Find Full Text PDF

The NHGRI-EBI GWAS Catalog serves as a vital resource for the genetic research community, providing access to the most comprehensive database of human GWAS results. Currently, it contains close to 7 000 publications for >15 000 traits, from which more than 625 000 lead associations have been curated. Additionally, 85 000 full genome-wide summary statistics datasets-containing association data for all variants in the analysis-are available for downstream analyses such as meta-analysis, fine-mapping, Mendelian randomisation or development of polygenic risk scores.

View Article and Find Full Text PDF

Background: Exercise (EX) or cognitive and social enrichment (ENRICH) are 2 strategies for promoting cognition poststroke. Whether sleep moderates the effects of EX or ENRICH on cognition in adults with chronic stroke is unknown.

Methods: A 3-arm parallel randomized clinical trial among community-dwelling adults aged 55+ years with chronic stroke (ie, ≥12 months since stroke).

View Article and Find Full Text PDF
Article Synopsis
  • * In the KARISMA trial, 824 women were analyzed, finding that a decrease in MBD was linked to endoxifen levels of 2-3 ng/mL, particularly in those taking 5-10 mg doses of tamoxifen.
  • * The research suggests a potential range of effective endoxifen levels for improving MBD in premenopausal women, but emphasizes the need for studies using established clinical outcomes for confirmation.
View Article and Find Full Text PDF

Measurement of lysosomal disease (LD) biomarkers can reveal valuable information about disease status. Lyso-globotriaosylceramide (lyso-Gb), glucosylsphingosine (lyso-Gb), galactosylsphingosine (psychosine), and glucose tetrasaccharide (Glca1-6Glca1-4Glca1-4Glc, Glc) are biomarkers associated with Fabry, Gaucher, Krabbe, and Pompe disease, respectively. Clinical biomarker testing is performed to guide patient management, including monitoring disease progression and initiating treatment, and in diagnostic evaluations of either symptomatic patients or asymptomatic individuals with a positive family history or abnormal newborn screen.

View Article and Find Full Text PDF

The NHGRI-EBI GWAS Catalog serves as a vital resource for the genetic research community, providing access to the most comprehensive database of human GWAS results. Currently, it contains close to 7,000 publications for more than 15,000 traits, from which more than 625,000 lead associations have been curated. Additionally, 85,000 full genome-wide summary statistics datasets - containing association data for all variants in the analysis - are available for downstream analyses such as meta-analysis, fine-mapping, Mendelian randomisation or development of polygenic risk scores.

View Article and Find Full Text PDF

Metachromatic leukodystrophy (MLD) is a rare neurodegenerative lysosomal storage disease resulting from bi-allelic pathogenic variants in the ARSA gene. MLD is distinguished clinically based on the age of onset into late-infantile, juvenile, and adult. The late-infantile type is the most severe phenotype presenting with hypotonia, weakness, gait abnormalities, which progresses to mental and physical decline leading to early death.

View Article and Find Full Text PDF

Purpose: To characterize real-world attrition rates across first-line (1L) to third-line (3L) therapies in patients with HER2-positive (HER2 +) metastatic breast cancer (mBC) receiving routine care in seven hospital systems across Europe (France, Germany, Italy, Spain, and the UK).

Methods: This retrospective, observational, multi-country, cohort study collected electronic medical record data from women aged ≥ 18 years diagnosed with HER2 + mBC from 2017-2021. The primary endpoint was attrition rate (the proportion of patients receiving a line of therapy [LOT] with no further evidence of subsequent LOTs).

View Article and Find Full Text PDF
Article Synopsis
  • * Accurately mapping torsion in chromatin is difficult due to the challenge of establishing a zero-torsion baseline signal influenced by chromatin accessibility.
  • * A new high-resolution method using trimethylpsoralen (TMP) allows researchers to measure torsional stress while maintaining chromatin state, revealing insights about transcription and its effects on genome architecture.
View Article and Find Full Text PDF
Article Synopsis
  • DNA replication and transcription happen at the same time on the same DNA, which can create conflicts between the replisome and RNA polymerase, potentially causing genome instability.
  • Research shows that collisions between RNA polymerase and the replication fork are more harmful when they come from opposite directions (head-on) compared to when they run in the same direction (co-directional), but the exact reasons behind this aren't fully understood.
  • The study found that RNA polymerase binds more stably in head-on conflicts, especially with longer RNA transcripts, which enhances its ability to block replication; an RNA-DNA hybrid forms during this process, creating additional complications for the replication fork but could also help initiate replication on the lagging strand.
View Article and Find Full Text PDF

Purpose: Variants in result in a rare neurodevelopmental disorder characterized by a variable clinical presentation of symptoms including developmental delay, epilepsy, motor dysfunction, and autism spectrum disorder. haploinsufficiency has been confirmed as the predominant pathway of related neurodevelopmental disorders (NDDs), however, the molecular mechanism underlying the variable clinical presentation remains unclear.

Methods: Here, through work of the Undiagnosed Diseases Network, we identify an undiagnosed individual with an inherited p.

View Article and Find Full Text PDF

Background: People with stroke and their families face numerous challenges as they leave hospital to return home, often experiencing multifaceted unmet needs and feelings of abandonment. The essential elements of an intervention intended to support transition-to-home after stroke are unclear.

Objective: The aim of the project was to engage in a co-design process to identify the key components of a pragmatic intervention to inform a transition-to-home support pathway following stroke.

View Article and Find Full Text PDF

Study Question: How do surrogates think, feel, and reflect on their experiences of being a surrogate over time?

Summary Answer: Despite continuing to require physical, emotional, and interpersonal labour, surrogates in this study reflected positively on their experiences of being a surrogate decades later.

What Is Known Already: Research on families created through surrogacy shows that it can be a positive experience for both the intended parents and the surrogate. No existing research has examined the experiences of surrogacy for surrogates beyond 10 years post-birth.

View Article and Find Full Text PDF

Background: Despite known benefits of physical activity in reducing breast cancer risk, its impact on mammographic characteristics remain unclear and understudied. This study aimed to investigate associations between pre-diagnostic physical activity and mammographic features at breast cancer diagnosis, specifically mammographic breast density (MBD) and mammographic tumor appearance (MA), as well as mode of cancer detection (MoD).

Methods: Physical activity levels from study baseline (1991-1996) and mammographic information from the time of invasive breast cancer diagnosis (1991-2014) of 1116 women enrolled in the Malmö Diet and Cancer Study cohort were used.

View Article and Find Full Text PDF

Molecular details of genome packaging are little understood for the majority of viruses. In enteroviruses (EVs), cleavage of the structural protein VP0 into VP4 and VP2 is initiated by the incorporation of RNA into the assembling virion and is essential for infectivity. We have applied a combination of bioinformatic, molecular and structural approaches to generate the first high-resolution structure of an intermediate in the assembly pathway, termed a provirion, which contains RNA and intact VP0.

View Article and Find Full Text PDF

Melanoma of the skin is the 17th most common cancer worldwide. Early detection of suspicious skin lesions (melanoma) can increase 5-year survival rates by 20%. The 7-point checklist (7PCL) has been extensively used to suggest urgent referrals for patients with a possible melanoma.

View Article and Find Full Text PDF

Transferrin isoform analysis is an established laboratory test for congenital disorders of glycosylation (CDG). Despite its long history of clinical use, little has been published about its empirical sensitivity for specific conditions. We conducted a retrospective analysis of ten years of testing data and report our experience with transferrin testing for type I profiles and its sensitivity for the most common congenital disorder of glycosylation, PMM2-CDG.

View Article and Find Full Text PDF

Thiopurine 6-mercaptopurine (6-MP) is metabolized by thiopurine methyl transferase (TPMT). TPMT genetic variation results in some individuals having reduced or absent TPMT enzyme activity. If these individuals take a full thiopurine dose, life-threatening adverse events can occur.

View Article and Find Full Text PDF

Background: Mitigating attrition is a key component to reduce selection bias in longitudinal randomized controlled trials (RCTs). Few studies of electronic nicotine delivery systems (ENDS) allow for the examination of long-term retention. This analysis explores the relationship between attrition, baseline measures, and condition assigned for a RCT involving ENDS differing in nicotine delivery over a 24-week intervention period.

View Article and Find Full Text PDF

Monocyte patrolling of the vasculature has been ascribed primarily to the non-classical monocyte subset. However, a recent study of the glomerular microvasculature provided evidence that both classical and non-classical monocytes undergo periods of intravascular retention and migration. Despite this, whether these subsets contribute differentially to acute glomerular inflammation is unknown.

View Article and Find Full Text PDF
Article Synopsis
  • * Analysis of data from over 55,000 breast cancer patients showed that co-observation of variants in BRCA1, BRCA2, and PALB2 with other breast cancer genes occurred less frequently than expected, suggesting a potential correlation with pathogenicity.
  • * The findings indicate that identifying a variant of uncertain significance alongside a known pathogenic variant supports evidence against the variant's pathogenicity, which could improve variant classification in clinical settings and for other genetic conditions.
View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: A non-numeric value encountered

Filename: controllers/Author.php

Line Number: 219

Backtrace:

File: /var/www/html/application/controllers/Author.php
Line: 219
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: A non-numeric value encountered

Filename: libraries/Pagination.php

Line Number: 413

Backtrace:

File: /var/www/html/application/controllers/Author.php
Line: 274
Function: create_links

File: /var/www/html/index.php
Line: 316
Function: require_once