Publications by authors named "Alan Wong"

Absolute pitch (AP) refers to the ability to identify the pitch of a tone without external references. It is commonly believed that only individuals with special genetic makeup and early musical training within the critical period can develop AP. Recent studies have begun to challenge the critical period notion by showing the possibility of AP acquisition in adults.

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Background: GLP-1 receptor agonists have neurotrophic properties in in-vitro and in-vivo models of Parkinson's disease and results of epidemiological studies and small randomised trials have suggested possible benefits for risk and progression of Parkinson's disease. We aimed to establish whether the GLP-1 receptor agonist, exenatide, could slow the rate of progression of Parkinson's disease.

Methods: We did a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial at six research hospitals in the UK.

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Introduction: Asthma attacks are set off by triggers such as pollutants from the environment, respiratory viruses, physical activity and allergens. The aim of this research is to create a machine learning model using data from mobile health technology to predict and appropriately warn a patient to avoid such triggers.

Methods: Lightweight machine learning models, XGBoost, Random Forest, and LightGBM were trained and tested on cleaned asthma data with a 70-30 train-test split.

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Numerous high-specificity Cas9 variants have been engineered for precision genome editing. These variants typically harbor multiple mutations designed to alter the Cas9-single guide RNA (sgRNA)-DNA complex interactions for reduced off-target cleavage. By dissecting the contributions of individual mutations, we attempt to derive principles for designing high-specificity Cas9 variants.

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Cancer cells metastatic to the leptomeninges encounter a metabolically-challenging extreme microenvironment. To understand adaptations to this space, we subjected leptomeningeal-metastatic (LeptoM) mouse breast and lung cancers isolated from either the leptomeninges or orthotopic primary sites to ATAC-and RNA-sequencing. When inhabiting the leptomeninges, the LeptoM cells demonstrated transcription downstream of retinoid-X-receptors (RXRs).

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A case report of a severely dyspnoeic kyphoscoliotic patient intended for an elective major thoracic surgery for suspected lung malignancy. With baseline near maximal breathing frequency and shallow breaths and poor lung mechanics, the first encountered anaesthetist considered this patient too high risk for lobectomy. This case illustrated the application of cardiopulmonary exercise testing to provide an objective assessment of the patient's functional capacity, ventilatory efficiency and delineation of modifiable respiratory components that guide the formulation of individualized prehabilitation programme.

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Autophagy is a conserved catabolic process where double membrane-bound structures form around macromolecules or organelles targeted for degradation. Autophagosomes fuse with lysosomes to facilitate degradation and macromolecule recycling for homeostasis or growth in a cell autonomous manner. In cancer cells, autophagy is often up-regulated and helps cancer cells survive nutrient deprivation and stressful growth conditions.

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Correction for 'High-resolution magic-angle spinning NMR metabolic profiling with spatially localized spectroscopy under slow sample spinning' by Alan Wong, , 2023, , 6302-6308, https://doi.org/10.1039/D3AY01812A.

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Article Synopsis
  • * Cardiovascular involvement occurs in up to 70% of patients, with symptoms ranging from asymptomatic to severe issues like cardiac tamponade and heart failure, often identified through imaging.
  • * More research is needed on the long-term outcomes and treatment responses for ECD patients with cardiovascular manifestations, as recent literature has started to highlight these cases.
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A strategy to obtain the greatest number of best-performing variants with least amount of experimental effort over the vast combinatorial mutational landscape would have enormous utility in boosting resource producibility for protein engineering. Toward this goal, we present a simple and effective machine learning-based strategy that outperforms other state-of-the-art methods. Our strategy integrates zero-shot prediction and multi-round sampling to direct active learning via experimenting with only a few predicted top variants.

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Folate, an essential vitamin, is a one-carbon acceptor and donor in key metabolic reactions. Erythroid cells harbor a unique sensitivity to folate deprivation, as revealed by the primary pathological manifestation of nutritional folate deprivation: megaloblastic anemia. To study this metabolic sensitivity, we applied mild folate depletion to human and mouse erythroid cell lines and primary murine erythroid progenitors.

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Background: Sialic acid-binding immunoglobulin-like lectin (Siglec)-6 and Siglec-8 are closely related mast cell (MC) receptors with broad inhibitory activity, but whose functional differences are incompletely understood.

Methods: Proteomic profiling using quantitative mass spectrometry was performed on primary mouse MCs to identify proteins associated with Siglec-6 and Siglec-8. For functional characterization, each receptor was evaluated biochemically and in ex vivo and in vivo inhibition models of IgE and non-IgE-mediated MC activation in Siglec-6- or Siglec-8-expressing transgenic mice.

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The sequence in the 5' untranslated regions (UTRs) is known to affect mRNA translation rates. However, the underlying regulatory grammar remains elusive. Here, we propose MTtrans, a multi-task translation rate predictor capable of learning common sequence patterns from datasets across various experimental techniques.

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Mapping mutations and discovering cellular determinants that cause the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to induce infected cells to form syncytia would facilitate the development of strategies for blocking the formation of such cell-cell fusion. Here we describe high-throughput screening methods based on droplet microfluidics and the size-exclusion selection of syncytia, coupled with large-scale mutagenesis and genome-wide knockout screening via clustered regularly interspaced short palindromic repeats (CRISPR), for the large-scale identification of determinants of cell-cell fusion. We used the methods to perform deep mutational scans in spike-presenting cells to pinpoint mutable syncytium-enhancing substitutions in two regions of the spike protein (the fusion peptide proximal region and the furin-cleavage site).

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Owing to its feasibility and versatility, High-Resolution Magic-Angle Spinning (HRMAS) NMR spectroscopy is considered an essential analytical technique in metabolomics for assessing the biochemical composition of tissue samples. Localized profiling with HRMAS has recently emerged and shown promise for spatial resolution of metabolic profiles within the sampling tissues. However, the requisite sample spinning in a few kHz can perturb the tissues spatially and morphologically.

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Objectives: To examine whether a fluid resuscitation strategy based on guidelines (at least 30 mL/kg IV crystalloids) vs. a restrictive approach with <30 mL/kg within three hours affects in-hospital mortality in patients with sepsis and a history of heart failure (HF).

Data Sources: On 03/07/2023, we searched Embase, PubMed, and Scopus for peer-reviewed papers and abstracts using the PRISMA guidelines.

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Aqueous solutions are crucial to most domains in biology and chemistry, including in energy fields such as catalysis and batteries. Water-in-salt electrolytes (WISEs), which extend the stability of aqueous electrolytes in rechargeable batteries, are one example. While the hype for WISEs is huge, commercial WISE-based rechargeable batteries are still far from reality, and there remain several fundamental knowledge gaps such as those related to their long-term reactivity and stability.

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Selecting the most suitable existing base editors and engineering new variants for installing specific base conversions with maximal efficiency and minimal undesired edits are pivotal for precise genome editing applications. Here, we present a platform for creating and analyzing a library of engineered base editor variants to enable head-to-head evaluation of their editing performance at scale. Our comprehensive comparison provides quantitative measures on each variant's editing efficiency, purity, motif preference, and bias in generating single and multiple base conversions, while uncovering undesired higher indel generation rate and noncanonical base conversion for some of the existing base editors.

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Individuals with schizophrenia show impairments in a variety of selective attention tasks. Research on the negative priming (NP) effect in schizophrenia has yielded mixed evidence. This meta-analysis aimed to examine the NP effect exhibited by patients with schizophrenia and the impact of study methodology on findings.

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Dihydrofolate reductase (DHFR) is an established anti-cancer drug target whose inhibition disrupts folate metabolism and STAT3-dependent gene expression. Cycloguanil was proposed as a DHFR inhibitor in the 1950s and is the active metabolite of clinically approved DHFR inhibitor Proguanil. The Cycloguanil scaffold was explored to generate potential cancer therapies in the 1970s.

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Synopsis of recent research by authors named "Alan Wong"

  • - Alan Wong's recent research spans various fields, focusing on cancer biology, highlighting mechanisms of lipid metabolism mediated by retinoid X receptor signaling in metastatic cancer cells, particularly within the leptomeninges microenvironment.
  • - His work also addresses clinical challenges, exemplified in a case report demonstrating a tailored prehabilitation approach using cardiopulmonary exercise testing for a high-risk surgical patient, showcasing the potential to improve patient outcomes through individualized interventions.
  • - Additionally, Wong has made significant strides in protein engineering and genetics, developing machine learning strategies to optimize protein variant discovery, which could vastly enhance resource efficiency in protein engineering efforts.

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