Publications by authors named "Watkins W"

Article Synopsis
  • - This study investigates how heritability affects hearing acuity across different frequencies by analyzing 34 family pedigrees from the Utah CEPH, using genomic sequencing and audiometric tests.
  • - Results show that heritability decreases as frequency increases, with estimates going from 51% at 250Hz to 30% at 8000Hz, indicating stronger genetic influence at lower frequencies.
  • - The genetic correlation between hearing acuity at similar frequencies is high (e.g., 0.80 between 250Hz and 500Hz), while correlations drop significantly between distant frequencies (0.21 between 250Hz and 8000Hz), highlighting the nuanced genetic factors affecting hearing abilities.
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  • Researchers discovered a strong and selective antagonist for the lysophosphatidic acid receptor 1 (LPAR1), which has antifibrotic properties, initially validated through a specific assay involving MRTF-A.* -
  • Structural modifications improved the compound's stability and pharmacokinetics, leading to a promising candidate for oral dosing that effectively blocked LPA-induced histamine release and showed efficacy against lung fibrosis in preclinical tests.* -
  • Despite its potential, the development of the LPAR1 antagonist was discontinued due to observed CNS toxicity in dog models, raising safety concerns for clinical use in idiopathic pulmonary fibrosis (IPF).*
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We describe a new type of spectropolarimeter in which light is separated to simultaneously measure six spectra carrying polarimetric information on a 2D CMOS camera. The polarization separation along one of the camera axes was obtained using a novel prism, and the spectral dispersion along the other camera axis was obtained using an imaging spectrometer. An ideal version of the six-fold separating prism is first described, in which polarimetric separation is performed along the canonical polarization states used to define the Stokes vector, and it can be explained without any math.

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Purpose/objectives: Bridging radiation therapy (bRT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). It is unknown how the extent of cytoreduction during bRT impacts outcomes.

Materials/methods: We retrospectively reviewed patients with LBCL treated with bRT followed by CAR T-cell therapy.

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Prematurity-associated lung disease (PLD) is a long-term consequence of preterm-birth. Since the underlying mechanisms of PLD remain poorly characterised, we compared the urinary metabolome between recently described spirometry phenotypes of PLD. Preterm- and term-born children aged 7-12 years, from the Respiratory Health Outcomes in Neonates (RHiNO) cohort, underwent spirometry and urine collection.

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  • Burns are common childhood injuries that can have serious effects, making timely first aid information crucial for parents, who often turn to social media for support and advice.
  • The study investigates how feasible it is to find and analyze conversations among parents about burn first aid on various social media platforms to inform intervention strategies.
  • While platforms like Facebook and Reddit had limited or inaccessible data, useful discussions around burn first aid were found on Mumsnet, Netmums, YouTube, and Twitter, particularly regarding sunburn, with a majority of conversations initiated by parents seeking advice.
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Using five complementary short- and long-read sequencing technologies, we phased and assembled >95% of each diploid human genome in a four-generation, 28-member family (CEPH 1463) allowing us to systematically assess mutations (DNMs) and recombination. From this family, we estimate an average of 192 DNMs per generation, including 75.5 single-nucleotide variants (SNVs), 7.

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This project introduces an innovative virtual reality (VR) training program for student Nurse Practitioners, incorporating advanced 3D modeling, animation, and Large Language Models (LLMs). Designed to simulate realistic patient interactions, the program aims to improve communication, history taking, and clinical decision-making skills in a controlled, authentic setting. This abstract outlines the methods, results, and potential impact of this cutting-edge educational tool on nursing education.

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  • Genome sequencing has improved our understanding of genetic factors in complex disorders but is still underexplored for predicting clinical outcomes, particularly after surgery for congenital heart defects (CHD).
  • Using AI, researchers analyzed data from 2,253 CHD patients, linking harmful genotypes in specific genes to a higher risk of severe post-operative complications.
  • The findings suggest that both the presence and absence of damaging genotypes can significantly inform predictions about patient outcomes following congenital cardiac surgery.
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Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum β-lactamases (bla) and carbapenemases (bla, bla-like and bla), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates.

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The farnesoid X receptor (FXR) is a nuclear receptor that controls bile acid, lipid, and cholesterol metabolism. FXR-targeted drugs have shown promise in late-stage clinical trials for non-alcoholic steatohepatitis. Herein, we used clinical results from our first non-steroidal FXR agonist, Px-102 (4-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methoxy]phenyl]cyclopropyl] benzoic acid), to develop cilofexor, a potent, non-steroidal FXR agonist with a more manageable safety profile.

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  • Establishing effective biomarkers for diagnosing and predicting multiple sclerosis (MS) is difficult when relying on single biomarkers, leading researchers to explore multi-biomarker combinations.
  • In a study involving 77 MS patients and 80 with other neurological disorders, 24 fluid biomarkers were examined, showing that combination models significantly outperformed single biomarker predictions.
  • The best diagnostic combination achieved an area under the curve of 0.97, while optimal predictions for relapse timing and disability milestones greatly improved, indicating the potential of multi-biomarker approaches in MS management.
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Rationale: Increased outdoor air pollution worsens lung function in children. However, these associations are less well studied in preterm-born individuals.

Objectives: We assessed associations between ambient air pollutants and spirometry measures in preterm-born children.

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Background/objectives: A national study was undertaken through the British ophthalmology surveillance unit (BOSU) to determine the incidence, presenting features and management of essential infantile esotropia (EIE) in the UK.

Methods: Data from a prospective national observational study of newly diagnosed EIE presenting to clinicians in the United Kingdom over a 12-month period were collected. Cases with a confirmed diagnosis by a clinician of a constant, non-accommodative esotropia ≥20 prism dioptres (PD), presenting at ≤12 months, with no neurological or ocular abnormalities were identified through BOSU.

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  • This systematic review investigates the link between cholesterol metabolism and mortality in critically ill patients, focusing on how cholesterol levels at ICU admission relate to outcomes.
  • The analysis included 24 studies, revealing that non-survivors had significantly lower levels of HDL-C, total cholesterol, and LDL-C compared to survivors, indicating a potential marker for predicting severity in critical illness.
  • The findings suggest that cholesterol levels are connected to inflammatory processes, highlighting the importance of HDL biomarkers as early indicators of health status and the need for more research on HDL's varying functions.
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Preterm-born children are at risk of long-term pulmonary deficits, including those who developed bronchopulmonary dysplasia (BPD) in infancy, however the underlying mechanisms remain poorly understood. We characterised the exhaled breath condensate (EBC) metabolome from preterm-born children, both with and without BPD. Following spirometry, EBC from children aged 7-12 years, from the Respiratory Health Outcomes in Neonates study, were analysed using Time-of-Flight Mass Spectrometry.

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Background: Telomeres shorten after each cell division. Since preterm-born babies are delivered early and often suffer from inflammatory conditions such as bronchopulmonary dysplasia (BPD), their telomere length may be altered.

Objectives: We assessed associations of early and current life factors with telomere length in saliva samples obtained from 7-12-year-old children born at ≤34 weeks' gestation and term-born controls.

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Introduction: Although different phenotypes of lung disease after preterm birth have recently been described, the underlying mechanisms associated with each phenotype are poorly understood. We, therefore, compared the urinary proteome for different spirometry phenotypes in preterm-born children with preterm- and term-born controls.

Methods: Preterm and term-born children aged 7-12 years, from the Respiratory Health Outcomes in Neonates (RHiNO) cohort, underwent spirometry and urine collection.

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  • Anastomotic stricture is a common complication after oesophageal atresia and tracheoesophageal fistula repair, with acid gastro-oesophageal reflux disease (GORD) thought to contribute to this issue, leading to recommendations for acid suppression post-surgery.
  • A systematic review and meta-analysis were conducted, analyzing data from 12 observational studies; however, no randomized studies were found, and many studies showed a high risk of bias.
  • The analysis indicated a potential slight increase in stricture odds for patients taking acid suppression medication, but the results were not statistically significant, suggesting no clear link between this medication and anastomotic stricture formation after surgery.
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Despite evidence demonstrating persistent lung function deficits in preterm-born children, especially in those who had bronchopulmonary dysplasia (BPD) in infancy, the underlying biological mechanisms explaining these lung function deficits remain poorly understood. We characterised the exhaled breath condensate (EBC) proteome in preterm-born children, with and without BPD; and before and after inhaler treatment. EBC from children aged 7-12 years, from the Respiratory Health Outcomes in Neonates (RHiNO) study, were analysed by Nano-LC Mass Spectrometry with Tandem Mass Tag labelling.

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Machine learning (ML) algorithms are powerful tools that are increasingly being used for sepsis biomarker discovery in RNA-Seq data. RNA-Seq datasets contain multiple sources and types of noise (operator, technical and non-systematic) that may bias ML classification. Normalisation and independent gene filtering approaches described in RNA-Seq workflows account for some of this variability and are typically only targeted at differential expression analysis rather than ML applications.

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Introduction: Early recognition and appropriate management of paediatric sepsis are known to improve outcomes. A previous system's biology investigation of the systemic immune response in neonates to sepsis identified immune and metabolic markers that showed high accuracy for detecting bacterial infection. Further gene expression markers have also been reported previously in the paediatric age group for discriminating sepsis from control cases.

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Quantum machine learning (QML) can complement the growing trend of using learned models for a myriad of classification tasks, from image recognition to natural speech processing. There exists the potential for a quantum advantage due to the intractability of quantum operations on a classical computer. Many datasets used in machine learning are crowd sourced or contain some private information, but to the best of our knowledge, no current QML models are equipped with privacy-preserving features.

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Background: Number of metastatic sites can identify patient populations with non-small cell lung cancer (NSCLC) that benefit from aggressive therapy. Total volume of disease is also relevant. We evaluated the prognostic impact of biologically active volume of disease (BaVD) on patients with metastatic lung adenocarcinoma.

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