Publications by authors named "Samuel Thompson"

The efficacy of radiation treatment (RT) of head and neck squamous cell carcinoma (HNSCC) is limited by radioresistance and the toxicity of FDA approved radiosensitizers. In extension to our previous research where we demonstrated that telaglenastat (CB839) increased efficacy of RT in in vitro and in vivo HNSCC models, here, we examine the radiosensitizing effects of telaglenastat in comparison to cisplatin's, as cisplatin is currently the standard of care for concurrent therapy. Combination of telaglenastat with RT reduced tumor volume in a HNSCC patient derived xenograft mouse model.

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Retinoic acid receptor beta () is a transcriptional regulator crucial for coordinating retinoic acid- (RA-) mediated morphogenic movements, cell growth, and differentiation during eye development. Loss- or gain-of-function coding variants have been associated with microphthalmia, coloboma, and anterior segment defects. We identified a variant c.

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Introduction Delays in theatre start times are expensive and associated with poor outcomes. To reduce these delays, a Golden Patient (GP) protocol was used at one of Britain's major trauma centres, the Queen Elizabeth University Hospital, Glasgow. We sought to clarify how often Golden Patients (GPs) were stepped down from being first on the day's trauma list and to identify significant contributing factors.

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While much prior work has explored the constraints on protein sequence and evolution induced by physical protein-protein interactions, the sequence-level constraints emerging from non-binding functional interactions in metabolism remain unclear. To quantify how variation in the activity of one enzyme constrains the biochemical parameters and sequence of another, we focus on dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS), a pair of enzymes catalyzing consecutive reactions in folate metabolism. We use deep mutational scanning to quantify the growth rate effect of 2696 DHFR single mutations in 3 TYMS backgrounds under conditions selected to emphasize biochemical epistasis.

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Enzyme abundance, catalytic activity, and ultimately sequence are all shaped by the need of growing cells to maintain metabolic flux while minimizing accumulation of deleterious intermediates. While much prior work has explored the constraints on protein sequence and evolution induced by physical protein-protein interactions, the sequence-level constraints emerging from non-binding functional interactions in metabolism remain unclear. To quantify how variation in the activity of one enzyme constrains the biochemical parameters and sequence of another, we focused on dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS), a pair of enzymes catalyzing consecutive reactions in folate metabolism.

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Estimates of deep-time biodiversity typically rely on statistical methods to mitigate the impacts of sampling biases in the fossil record. However, these methods are limited by the spatial and temporal scale of the underlying data. Here we use a spatially explicit mechanistic model, based on neutral theory, to test hypotheses of early tetrapod diversity change during the late Carboniferous and early Permian, critical intervals for the diversification of vertebrate life on land.

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Article Synopsis
  • Histone lysine methyltransferases (KMTs) and demethylases (KDMs) are key enzymes that regulate gene expression and chromatin structure, and their malfunction is linked to congenital regulopathies.
  • The study found damaging genetic variants in KMTs and KDMs in families with developmental eye diseases, indicating a connection to structural eye defects along with other abnormalities.
  • Genetic testing is crucial for accurate diagnosis in affected individuals, as the research identified nine novel variants, many of which may be pathogenic, expanding the understanding of KMT and KDM roles in ocular developmental disorders.
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Article Synopsis
  • - ARHGAP35 is important for various cellular processes and has been linked to cancer and developmental issues in both humans and mice, particularly in eye and neural structures.
  • - Researchers found harmful genetic variants of ARHGAP35 in five people from four families with eye disorders such as anophthalmia and microphthalmia, along with other health problems.
  • - The identified genetic variants mainly affected the protein's C-terminus and suggest that ARHGAP35 may play a significant role in eye development, hinting at a shared mechanism for related ocular diseases, but more research is needed.
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FOXC1 encodes a forkhead-domain transcription factor associated with several ocular disorders. Correct FOXC1 dosage is critical to normal development, yet the mechanisms controlling its expression remain unknown. Together with FOXQ1 and FOXF2, FOXC1 is part of a cluster of FOX genes conserved in vertebrates.

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Article Synopsis
  • Axenfeld-Rieger syndrome (ARS) is a rare genetic disorder characterized by eye anomalies and potential systemic features, with varying subtypes linked to specific genes that influence the severity and type of symptoms.
  • A study examined 128 individuals with genetic variants related to ARS, revealing a range of ocular anomalies and distinct systemic features for different gene types, including high rates of dental and heart defects.
  • The findings emphasize the importance of gene-specific diagnoses for ARS, as clinical features can significantly differ based on the affected gene, and suggest that the De Hauwere syndrome may be related to the FOXC1 gene.
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Melting experiments on FeS were conducted to 75 GPa and 2800 K in laser-heated and internally resistive-heated diamond anvil cells withx-ray diffraction and/or post-mortem textural observation. From the constrained melting curve, we assessed the thermal equation of state for FeS liquid. Then we constructed a thermodynamic model of melting of the system Fe-FeS including the eutectic relation under high pressures based on our new experimental data.

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Members of the bacterial 6SS midase ffector (Tae) superfamily of toxins are delivered between competing bacteria to degrade cell wall peptidoglycan. Although Taes share a common substrate, they exhibit distinct antimicrobial potency across different competitor species. To investigate the molecular basis governing these differences, we quantitatively defined the functional determinants of Tae1 from PAO1 using a combination of nuclear magnetic resonance and a high-throughput in vivo genetic approach called deep mutational scanning (DMS).

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Background: The optimal treatment of Gartland type IIa supracondylar humerus fractures remains controversial. We report the results of a series of patients with type IIa fractures who underwent closed reduction and immobilization using conscious sedation in the emergency department. Our goal was to identify variables associated with fractures that were successfully managed nonoperatively.

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Objectives: Financial toxicity due to cancer treatment is a significant concern for patients. To increase transparency related to treatment costs, the Hospital Price Transparency Final Rule (HPTFR) was passed on January 1, 2021. We used hospital pricing documentation to explore the costs of head and neck cancer (HNC) radiotherapy in Ohio, hypothesizing a large variance in cost based on geography.

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Missense variants located in the N-terminal region of WDR37 were recently identified to cause a multisystemic syndrome affecting neurological, ocular, gastrointestinal, genitourinary, and cardiac development. WDR37 encodes a WD40 repeat-containing protein of unknown function. We identified three novel WDR37 variants, two likely pathogenic de novo alleles and one inherited variant of uncertain significance, in individuals with phenotypes overlapping those previously reported but clustering in a different region of the protein.

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Folding a linear chain of amino acids into a three-dimensional protein is a complex physical process that ultimately confers an impressive range of diverse functions. Although recent advances have driven significant progress in predicting three-dimensional protein structures from sequence, proteins are not static molecules. Rather, they exist as complex conformational ensembles defined by energy landscapes spanning the space of sequence and conditions.

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Our ability to rationally optimize allosteric regulation is limited by incomplete knowledge of the mutations that tune allostery. Are these mutations few or abundant, structurally localized or distributed? To examine this, we conducted saturation mutagenesis of a synthetic allosteric switch in which Dihydrofolate reductase (DHFR) is regulated by a blue-light sensitive LOV2 domain. Using a high-throughput assay wherein DHFR catalytic activity is coupled to growth, we assessed the impact of 1548 viable DHFR single mutations on allostery.

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The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles.

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Background: Voluntary turnover (VTO) of nursing employees is expensive for hospital systems and is often associated with lower levels of patient satisfaction, as well as adverse patient outcomes such as falls and medication errors.

Purpose: The aim of this study was to establish nurses' electronic medical record (EMR) use patterns and test if they can be used to predict VTO.

Methodology/approach: The study followed 1,836 hospital nurses via the collection of EMR metadata through two 1-month time periods that were 1 year apart.

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Pore functionalized membranes with appropriate ion exchange/chelate groups allow toxic metal sorption under convective flow conditions. This study explores the sorption capacity of ionic mercury in a polyvinylidene fluoride-poly(acrylic acid) (PVDFs-PAA) functionalized membrane immobilized with cysteamine (MEA). Two methods of MEA immobilization to the PVDF-PAA membrane have been assessed: (i) ion exchange (IE) and (ii) carbodiimide cross-linker chemistry using 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDC) and -hydroxysuccinimide (NHS), known as EDC/NHS coupling.

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The Ni-Fe-S-containing A-cluster of acetyl-coenzyme A (CoA) synthase (ACS) assembles acetyl-CoA from carbon monoxide (CO), a methyl group (CH), and CoA. To accomplish this feat, ACS must bind CoA and interact with two other proteins that contribute the CO and CH, respectively: CO dehydrogenase (CODH) and corrinoid Fe-S protein (CFeSP). Previous structural data show that, in the model acetogen Moorella thermoacetica, domain 1 of ACS binds to CODH such that a 70-Å-long internal channel is created that allows CO to travel from CODH to the A-cluster.

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Traumatic lower-extremity amputations often result in complications and surgical revisions. The authors report the in-hospital morbidity and mortality of traumatic lower-extremity amputations at a metropolitan level I trauma center for a large rural region and compare below-knee (BK) vs higher-level amputation complications. They retrospectively reviewed 168 adult patients during a 10-year period (2005 to 2015) who had a traumatic injury to the lower extremity that required an amputation.

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The Forkhead Box C1 (FOXC1) gene encodes a forkhead/winged helix transcription factor involved in embryonic development. Mutations in this gene cause dysgenesis of the anterior segment of the eye, most commonly Axenfeld-Rieger syndrome (ARS), often with other systemic features. The developmental mechanisms and pathways regulated by FOXC1 remain largely unknown.

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