Publications by authors named "Tomlinson C"
This study explores digital inclusion for youth in out-of-home placement within the child welfare system, a group impacted by significant social determinants affecting health. Recognized as a "super social determinant of health," digital inclusion holds promise in addressing key health factors, such as social relationships, support systems, and information access. The study surveyed 131 foster parents and 152 kinship providers across varied U.
View Article and Find Full Text PDFObjectives: To investigate healthcare utilisation and cost in individuals with long COVID (LC) at population level.
Design: Case-control cohort analysis with multiple age-, sex-, ethnicity-, deprivation-, region- and comorbidity-matched control groups: (1) COVID only, no LC; (2) pre-pandemic; (3) contemporary non-COVID; and (4) pre-LC (self-controlled, pre-COVID pandemic).
Setting: National, population-based, linked UK electronic health records (British Heart Foundation/NHS England Secure Data Environment).
Background: This study estimated to what extent the number of measurements of cardiometabolic risk factors (e.g., blood pressure, cholesterol, glycated haemoglobin) were impacted by the COVID-19 pandemic and whether these have recovered to expected levels.
View Article and Find Full Text PDFRecent successes in developing small molecule degraders that act through the ubiquitin system have spurred efforts to extend this technology to other mechanisms, including the autophagosomal-lysosomal pathway. Therefore, reports of autophagosome tethering compounds (ATTECs) have received considerable attention from the drug development community. ATTECs are based on the recruitment of targets to LC3/GABARAP, a family of ubiquitin-like proteins that presumably bind to the autophagosome membrane and tether cargo-loaded autophagy receptors into the autophagosome.
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- Recent research on mRNA therapeutics has increased due to COVID-19, with applications in vaccination, cancer therapy, and immune modulation, but they face challenges like instability and degradation.
- Traditional agarose gel electrophoresis has been the standard for analyzing RNA, but newer methods, like those using the Agilent 2100 Bioanalyzer, offer better quality assessment despite being more expensive and less accessible.
- The proposed full-lane quantification (FLQ) method integrates ImageJ with programming in Python and R to provide a quick and affordable way to evaluate mRNA degradation, yielding results comparable to those from more sophisticated systems.
The neonatal liver may be affected by a variety of congenital and acquired diseases. Imaging has an important role in the workup and management of many neonatal hepatic abnormalities. Some aspects of imaging the liver and imaging findings are specific to neonatal patients when compared with those in older children.
View Article and Find Full Text PDFBackground: Heart failure is common, complex, and often associated with coexisting chronic medical conditions and a high mortality. We aimed to assess the epidemiology of people admitted to hospital with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), including the period covering the COVID-19 pandemic, which was previously not well characterised.
Methods: In this retrospective, cohort study, we used whole-population electronic health records with 57 million individuals in England to identify patients hospitalised with heart failure as the primary diagnosis in any consultant episode of an in-patient admission to a National Health Service (NHS) hospital.
Objective: To investigate the changing characteristics of SARS-CoV-2-related pediatric hospital admissions over time.
Study Design: This was a national, observational cohort study from July 1, 2020, to August 31, 2023, using English population-linked electronic health records. We identified 45 203 children younger than 18 years old in whom SARS-CoV-2 either caused or contributed to hospitalization, excluding those admitted with "incidental" infection.
Article Synopsis
- CRABP2 is a protein that transports retinoic acid to the nucleus, where it activates gene transcription by interacting with retinoic acid receptors.
- CRABP2 also binds specifically to cyclin D3, and the binding sites for cyclin D3 and retinoic acid overlap within a specific region of the protein.
- Mutations that disrupt the binding of both cyclin D3 and retinoic acid alter the structure of CRABP2, revealing insights into its function and interaction with cyclin D3 in the context of the CDK4/6 complex.
Article Synopsis
- Solid organ transplantation is critical for saving lives in children, but the rate of pediatric organ donations is still low in Canada.
- A survey of Canadian organ donation organizations and pediatric transplant programs revealed considerable discrepancies in policies regarding organ allocation and acceptance criteria.
- There is a need for improved standardization in training, policies, and guidelines for pediatric organ donation and transplantation to enhance the process across the country.
Background: Despite the growing interest in the use of human genomic data for drug target identification and validation, the extent to which the spectrum of human disease has been addressed by genome-wide association studies (GWAS), or by drug development, and the degree to which these efforts overlap remain unclear.
Methods: In this study we harmonize and integrate different data sources to create a sample space of all the human drug targets and diseases and identify points of convergence or divergence of GWAS and drug development efforts.
Results: We show that only 612 of 11,158 diseases listed in Human Disease Ontology have an approved drug treatment in at least one region of the world.
The incidence of injuries reported in artistic gymnastics varies greatly. This is partly due to inconsistencies in defining and reporting injuries in artistic gymnastics. The objective was to develop consistent definitions and methodology for reporting injuries in artistic gymnastics.
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- Prenatal detection of copy number variants (CNVs) aids in diagnosing fetal genetic abnormalities and enhances early intervention in prenatal care.
- * Various techniques such as SNP arrays, CGH arrays, NIPT, WES, and WGS are used for CNV detection, each with unique advantages and limitations.
- * Accurate classification and interpretation of CNVs are critical for effective clinical management and addressing genetic counseling challenges, especially for variants with uncertain clinical significance.
Article Synopsis
- - Mother's milk has diverse bacterial communities, and this study investigates how these bacteria affect the gut microbiota of very-low-birth-weight (VLBW) infants during hospitalization, analyzing 94 mother-infant pairs and 422 milk-stool samples.
- - Approximately 30%-40% of the bacterial types found in the infants' guts are also present in the mother's milk, showing a direct link between milk consumption and gut microbiota development in VLBW infants, influenced by feeding practices and antibiotic use.
- - The findings suggest that the microbiota in mother's milk plays a significant role in shaping the gut bacteria of VLBW infants, indicating that specific milk bacteria and their interactions are important for gut colonization.
Article Synopsis
- - Chikungunya virus (CHIKV) causes severe symptoms like fever, rash, and joint pain, with millions infected, primarily in low and middle-income regions, due to its mosquito carriers spreading into new areas.
- - The virus has a macrodomain in its genome that interferes with the immune response, making it essential for viral replication, which positions it as a potential target for antiviral drug development.
- - A high-throughput crystallographic fragment screen identified 109 fragments that bind to the CHIKV nsP3 macrodomain, leading to the design of three fragments aimed at trapping the active sites, and this data is publicly available for future research.
A strategy for pandemic preparedness is the development of antivirals against a wide set of viral targets with complementary mechanisms of action. SARS-CoV-2 nsp3-mac1 is a viral macrodomain with ADP-ribosylhydrolase activity, which counteracts host immune response. Targeting the virus' immunomodulatory functionality offers a differentiated strategy to inhibit SARS-CoV-2 compared to approved therapeutics, which target viral replication directly.
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- - Previous research suggested leucine needs for adults might range from 25 to 40 mg⋅kg⋅d, with new data indicating a potential requirement of up to 55 mg⋅kg⋅d, but this study specifically focused on young adult males using a method called indicator amino acid oxidation (IAAO).
- - The study involved ten healthy young males who were given varying amounts of leucine (from 10 to 75 mg⋅kg⋅d) over a three-day period to assess their leucine requirements while monitoring biochemical responses.
- - Results indicated that the average leucine requirement for these males was approximately 33.6 mg⋅kg⋅d, which supports prior findings and
For many diseases there are delays in diagnosis due to a lack of objective biomarkers for disease onset. Here, in 41,931 individuals from the United Kingdom Biobank Pharma Proteomics Project, we integrated measurements of ~3,000 plasma proteins with clinical information to derive sparse prediction models for the 10-year incidence of 218 common and rare diseases (81-6,038 cases). We then compared prediction models developed using proteomic data with models developed using either basic clinical information alone or clinical information combined with data from 37 clinical assays.
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- Early-life nutrition, particularly the intake of mother's milk, plays a significant role in the brain development of preterm-born children, specifically in areas related to processing speed.
- A study involving 40 five-year-old children who were born preterm showed that while general macronutrient intake had no impact, higher consumption of mother's milk was linked to increased volumes in critical brain regions.
- The findings suggest that mother's milk may support better processing speed by enhancing brain structure in these vulnerable children, highlighting the need for further research on nutritional strategies to improve outcomes for preterm infants.
Declining physical function with aging is associated with structural and functional brain network organization. Gaining a greater understanding of network associations may be useful for targeting interventions that are designed to slow or prevent such decline. Our previous work demonstrated that the Short Physical Performance Battery (eSPPB) score and body mass index (BMI) exhibited a statistical interaction in their associations with connectivity in the sensorimotor cortex (SMN) and the dorsal attention network (DAN).
View Article and Find Full Text PDFObjective: To identify highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in contexts of influenza and cardiovascular disease(CVD).
Methods: Using national, linked electronic health records for England (NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals (of all ages) with COVID-19 and LC (2020-2023). We compared all-cause hospitalization and mortality by prior CVD, high CV risk, vaccination status (COVID-19/influenza), and CVD drugs, investigating impact of vaccination and CVD prevention using population preventable fractions.
Clinical Management of Patients With Relapsed/Refractory Multiple Myeloma Treated With Talquetamab.
Clin Lymphoma Myeloma Leuk
October 2024
Article Synopsis
- Talquetamab is a bispecific antibody that targets the GPRC5D antigen in patients with relapsed/refractory multiple myeloma, showing over 71% overall response rates in clinical trials.
- Adverse events (AEs) associated with talquetamab mainly included dermatologic and oral issues, although the majority were low grade and manageable through various treatment strategies.
- Effective management of more serious AEs, like cytokine release syndrome and neurotoxicity, along with proper education for healthcare providers, can help maintain the quality of life for patients undergoing treatment.
Article Synopsis
- - The 2A protease of enterovirus species, responsible for critical steps in viral replication, is a key target for combating pediatric hand-foot-and-mouth disease and preparing for potential outbreaks.
- - Inhibiting the 2A protease can disrupt the folding and assembly of viral capsid proteins, preventing the production of mature viral particles and presenting a strategy for antiviral treatment.
- - A crystallographic fragment screening campaign successfully identified 75 compounds that bind to the 2A protease, with 38 unique ones targeting the active site, paving the way for the creation of broad-spectrum anti-enteroviral drugs.
Article Synopsis
- - Zika virus (ZIKV) infections are linked to serious health issues like microcephaly in newborns and Guillain-Barre syndrome in adults, with no current vaccines or antiviral treatments available.
- - The NS3 protease and its co-factor NS2B play a crucial role in processing viral proteins, making them a key target for drug development.
- - A successful crystallographic study identified 48 compounds that bind to the NS2B-NS3 protease, along with 6 additional fragments targeting a possible allosteric site, paving the way for new inhibitors to be developed.