Publications by authors named "Lok S"

It is now possible to generate large volumes of high-quality images of biomolecules at near-atomic resolution and in near-native states using cryogenic electron microscopy/electron tomography (Cryo-EM/ET). However, the precise annotation of structures like filaments and membranes remains a major barrier towards applying these methods in high-throughput. To address this, we present TARDIS (ransformer-bsed apid imensionless nstance egmentation), a machine-learning framework for fast and accurate annotation of micrographs and tomograms.

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  • The study investigates the role of the transcription factor Foxp2 in kidney fibrosis, a key process leading to chronic kidney disease (CKD) and kidney failure, highlighting its correlation with epithelial-to-mesenchymal transition (EMT).
  • Analysis of human kidney biopsies and experiments in genetically modified mice demonstrate that increased Foxp2 expression is associated with various forms of CKD, and its deletion reduces inflammation and fibrosis in kidney tissue.
  • Findings reveal that Foxp2 influences key cellular mechanisms, including the regulation of TGF-β signaling and cell cycle, ultimately affecting the progression of kidney fibrosis through the modulation of target genes related to cell growth and ECM production.
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  • The study investigates the relationship between surface characteristics like wetting and topography and their impact on ice adhesion strength (IAS), highlighting inconsistencies in previous research efforts.
  • It summarizes various wetting and topography parameters linked to IAS and evaluates a broad range of surfaces using advanced measurement techniques.
  • Findings reveal significant errors in past assumptions about IAS correlations, particularly challenging the notion of practical work of adhesion, and identify a promising wetting parameter that could effectively correlate with shear IAS on certain smooth surfaces.
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Background: Obturator hernia is a rare type of pelvic hernia that often presents with vague symptoms that can easily be confused with other conditions. Delayed diagnosis can lead to increased morbidity and complications.

Case Presentation: A 67-year-old female with a history of rheumatoid arthritis presented with escalating right knee pain, unresponsive to increasing doses of opioids.

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Structural studies on purified virus have revealed intricate architectures, but there is little structural information on how viruses interact with host cells . Cryo-focused ion beam (FIB) milling and cryo-electron tomography (cryo-ET) have emerged as revolutionary tools in structural biology to visualize the dynamic conformational of viral particles and their interactions with host factors within infected cells. Here, we review the state-of-the-art cryo-ET technique for viral structure studies and highlight exemplary studies that showcase the remarkable capabilities of cryo-ET in capturing the dynamic virus-host interaction, advancing our understanding of viral infection and pathogenesis.

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This study evaluated patient-reported outcomes (PROs) of Medicine Access Programmes (MAPs) for Australian metastatic breast cancer patients on ribociclib. Limited patient awareness of MAP enrolment was identified, emphasising the need for improved education and consent processes. Most patients expressed gratitude for accessing non-funded medications and perceived enhanced medication adherence as a key benefit.

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The aim of this randomized controlled trial was to examine the effect of Physical Activity Program applied to patients with schizophrenia on subjective well-being, happiness and problem-solving skills levels. This study was conducted with a total of 86 individuals diagnosed with schizophrenia (43 intervention and 43 control) registered in a family health center. Subjective Well-Being Scale, the Short Form of the Oxford Happiness Questionnaire and Problem-Solving Inventory were used to collect the data at baseline and, post-intervention.

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The muskox (Ovibos moschatus), an integral component and iconic symbol of arctic biocultural diversity, is under threat by rapid environmental disruptions from climate change. We report a chromosomal-level haploid genome assembly of a muskox from Banks Island in the Canadian Arctic Archipelago. The assembly has a contig N50 of 44.

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Background: BAL cellular analysis is often recommended during the initial diagnostic evaluation of fibrotic interstitial lung disease (ILD). Despite recommendation for its use, between-center heterogeneity exists and supportive data concerning the clinical utility and correlation of BAL findings with radiologic features or patterns remain sparse.

Research Question: In patients with fibrotic ILD, are BAL findings associated with radiologic features, patterns, and clinical diagnoses?

Study Design And Methods: Patients with fibrotic ILD who underwent BAL for diagnostic evaluation and who were enrolled in the prospective Canadian Registry for Pulmonary Fibrosis were re-reviewed in a standardized multidisciplinary discussion (MDD).

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Synthetic data generation in omics mimics real-world biological data, providing alternatives for training and evaluation of genomic analysis tools, controlling differential expression, and exploring data architecture. We previously developed Precious1GPT, a multimodal transformer trained on transcriptomic and methylation data, along with metadata, for predicting biological age and identifying dual-purpose therapeutic targets potentially implicated in aging and age-associated diseases. In this study, we introduce Precious2GPT, a multimodal architecture that integrates Conditional Diffusion (CDiffusion) and decoder-only Multi-omics Pretrained Transformer (MoPT) models trained on gene expression and DNA methylation data.

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Background: Digital cognitive behavioral therapy for insomnia (dCBTi) is an effective intervention for treating insomnia. The findings regarding its efficacy compared to face-to-face cognitive behavioral therapy for insomnia are inconclusive but suggest that dCBTi might be inferior. The lack of human support and low treatment adherence are believed to be barriers to dCBTi achieving its optimal efficacy.

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Key Points: Long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 () was upregulated in human and murine AKI. It returned to baseline after recovery in humans. Its knockdown preserved kidney function in animals.

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Traf2- and Nck-interacting kinase (TNIK) has emerged as a key regulator of pathological metabolic signaling in several diseases and is a promising drug target. Originally studied for its role in cell migration and proliferation, TNIK possesses several newly identified functions that drive the pathogenesis of multiple diseases. Specifically, we evaluate TNIK's newfound roles in cancer, metabolic disorders, and neuronal function.

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Background: Fibrotic interstitial lung disease (ILD) is frequently associated with abnormal oxygenation; however, little is known about the accuracy of oxygen saturation by pulse oximetry (SpO) compared with arterial blood gas (ABG) saturation (SaO), the factors that influence the partial pressure of carbon dioxide (PaCO) and the impact of PaCO on outcomes in patients with fibrotic ILD.

Study Design And Methods: Patients with fibrotic ILD enrolled in a large prospective registry with a room air ABG were included. Prespecified analyses included testing the correlation between SaO and SpO, the difference between SaO and SpO, the association of baseline characteristics with both the difference between SaO and SpO and the PaCO, the association of baseline characteristics with acid-base category, and the association of PaCO and acid-base category with time to death or transplant.

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Background And Objective: Establishing an accurate and timely diagnosis of idiopathic pulmonary fibrosis (IPF) is essential for appropriate management and prognostication. In some cases, surgical lung biopsy (SLB) is performed but carries non-negligible risk. The objective of this retrospective study was to determine if SLB is associated with accelerated lung function decline in patients with IPF using the Canadian Registry for Pulmonary Fibrosis.

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Background: Previous studies have shown the importance of frailty in patients with fibrotic interstitial lung disease (ILD).

Research Question: Is the Clinical Frailty Scale (CFS) a valid tool to improve risk stratification in patients with fibrotic ILD?

Study Design And Methods: Patients with fibrotic ILD were included from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. The CFS was assessed using available information from initial ILD clinic visits.

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Article Synopsis
  • In January 2020, a workshop at EMBL-EBI focused on data needs for cryoEM structure deposition and validation, specifically in single-particle analysis.
  • The workshop gathered 47 experts to discuss data processing, model building, validation, and archiving, leading to consensus recommendations.
  • The report outlines the workshop's goals, key discussions, challenges for future methods, and the progress made on implementing the recommendations.
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Objectives: Interstitial lung disease (ILD) in CTDs has highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality, and immunosuppression response.

Methods: Patients with CTD-ILD had high-resolution chest CT (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern [usual interstitial pneumonia (UIP); non-specific interstitial pneumonia (NSIP); organizing pneumonia (OP); fibrotic hypersensitivity pneumonitis (fHP); and other].

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Background And Aims: Drug-induced liver injury (DILI) is one of the most frequent reasons for failure of drugs in clinical trials or market withdrawal. Early assessment of DILI risk remains a major challenge during drug development. Here, we present a mechanism-based weight-of-evidence approach able to identify certain candidate compounds with DILI liabilities due to mitochondrial toxicity.

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  • Interstitial pneumonia with autoimmune features (IPAF) shares similarities with connective tissue disease-associated interstitial lung disease (CTD-ILD) but does not fully meet the criteria for a specific connective tissue disease.
  • A study compared the characteristics and survival of IPAF with CTD-ILD and unclassifiable ILD, revealing that IPAF patients are older and have a greater smoking history compared to CTD-ILD, while having worse lung function than unclassifiable ILD.
  • The findings suggest that while patients with IPAF experience worse survival rates compared to CTD-ILD, they have similar mortality to those with unclassifiable ILD, raising questions about whether IPAF should be viewed as a separate category of interstitial lung disease
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Article Synopsis
  • - A workshop at EMBL-EBI in January 2020 brought together 47 experts to discuss data needs for cryoEM structures, focusing particularly on single-particle analysis.
  • - The report outlines the workshop's purpose, the discussions held, and the consensus recommendations made by the attendees.
  • - It also highlights future challenges in method development and notes the progress made on implementing some of the recommendations discussed.
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Aim: We investigated the prevalence of incidental coronary artery calcifications (CAC) from non-electrocardiogram (ECG)-gated computed tomography (CT) chest (both contrast and non-contrast) for inpatients. We also assessed for downstream investigation and statin prescription from the inpatient teams. Incidental CAC are frequent findings on non-ECG-gated CT chest.

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  • Hypoxemia in fibrotic interstitial lung disease (ILD) signals disease progression and can predict patient mortality.
  • A risk prediction tool was created to identify new-onset exertional and resting hypoxemia using data from ILD registries in Canada, Australia, and the U.S.
  • The model's effectiveness was assessed, showing good performance based on factors like age, body mass index, and specific lung function measures, although the validation cohort showed some issues with calibration for resting hypoxemia.
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Background: The study aimed to investigate the efficacy of a 12-week physical activity intervention for caregivers of patients with schizophrenia.

Method: Family caregivers of patients with schizophrenia were recruited and randomized into either a physical activity group (n = 31) or a control group (n = 31). The 12-week "Physical Activity Program" consisted of 10 minutes of warm-up activities as the initial segment, 20 minutes of rhythmic exercises as the activity segment, 10 minutes of cool-down exercises as the final segment, and 40 minutes of free walking.

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