Publications by authors named "Simon K Chan"

Human papillomavirus (HPV) integration has been implicated in transforming HPV infection into cancer. To resolve genome dysregulation associated with HPV integration, we performed Oxford Nanopore long-read sequencing on 72 cervical cancer genomes from an Ugandan dataset that was previously characterized using short-read sequencing. We found recurrent structural rearrangement patterns at HPV integration events, which we categorized as: del(etion)-like, dup(lication)-like, translocation, multibreakpoint, or repeat region integrations.

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Article Synopsis
  • HPV integration may transform an infection into cancer, and studying its effects has been challenging with traditional sequencing methods.
  • Using long-read sequencing on 63 cervical cancer genomes, researchers identified six types of HPV integration events and discovered a phenomenon called heterologous integration, where 24% of integrants had variable HPV copies.
  • The study also revealed that the methylation status of HPV integrations affects gene expression and the surrounding human epigenome, offering insights into how integrated HPV contributes to cervical cancer development.
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As more clinically-relevant genomic features of myeloid malignancies are revealed, it has become clear that targeted clinical genetic testing is inadequate for risk stratification. Here, we develop and validate a clinical transcriptome-based assay for stratification of acute myeloid leukemia (AML). Comparison of ribonucleic acid sequencing (RNA-Seq) to whole genome and exome sequencing reveals that a standalone RNA-Seq assay offers the greatest diagnostic return, enabling identification of expressed gene fusions, single nucleotide and short insertion/deletion variants, and whole-transcriptome expression information.

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To facilitate the understanding of pregabalin and optimize its clinical usage in Hong Kong, an expert panel (11 psychiatrists, one family physician and one anesthesiologist) experienced in treating anxiety and somatic symptoms was invited to establish a set of consensus statements based on several discussion areas. A non-systematic literature search for relevant articles was conducted. The panelists addressed the discussion areas by sharing their clinical experience and available literature in a couple of meetings.

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Cervical cancer is the most common cancer affecting sub-Saharan African women and is prevalent among HIV-positive (HIV) individuals. No comprehensive profiling of cancer genomes, transcriptomes or epigenomes has been performed in this population thus far. We characterized 118 tumors from Ugandan patients, of whom 72 were HIV, and performed extended mutation analysis on an additional 89 tumors.

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Article Synopsis
  • * Previous treatments, particularly DNA-damaging chemotherapy and mutations in DNA repair genes, were linked to increased mutations across the genome, indicating therapy-related changes.
  • * Findings reveal that specific genetic alterations and mutation patterns can predict responses to treatments and overall patient survival, emphasizing the potential of this dataset for future cancer research and clinical applications.
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The threespine stickleback is a geographically widespread and ecologically highly diverse fish that has emerged as a powerful model system for evolutionary genomics and developmental biology. Investigations in this species currently rely on a single high-quality reference genome, but would benefit from the availability of additional, independently sequenced and assembled genomes. We present here the assembly of four new stickleback genomes, based on the sequencing of microfluidic partitioned DNA libraries.

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Objectives: To examine the feasibility and potential efficacy of 5% lidocaine medicated plaster for acute postoperative pain in a parallel, blinded, randomized controlled pilot trial.

Methods: Twenty-eight women undergoing elective gynecological surgery with midline incisions were randomly allocated 5% lidocaine medicated patch (Lignopad) or placebo plasters. Postoperative pain at rest and on movement at 24 hours were the primary study endpoints, with secondary endpoints of postoperative pain within the first 48 hours, cumulative morphine consumption (mg), predicted peak flow rate (PFR) (%) and adverse effects.

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Background: We examined the effectiveness and tolerability of transdermal buprenorphine (TDB) treatment in real-world setting in Asian patients with musculoskeletal pain.

Methods: This was an open-label study conducted in Hong Kong, Korea, and the Philippines between June 2013 and April 2015. Eligible patients fulfilled the following criteria: 18 to 80 years of age; clinical diagnosis of osteoarthritis, rheumatoid arthritis, low back pain, or joint/muscle pain; chronic non-malignant pain of moderate to severe intensity (Box-Scale-11 [BS-11] pain score ≥ 4), not adequately controlled with non-opioid analgesics and requiring an opioid for adequate analgesia; and no prior history of opioid treatment.

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Large-scale multiplexed identification of somatic alterations in cancer has become feasible with next generation sequencing (NGS). However, calibration of NGS somatic analysis tools has been hampered by a lack of tumor/normal reference standards. We thus performed paired PCR-free whole genome sequencing of a matched metastatic melanoma cell line (COLO829) and normal across three lineages and across separate institutions, with independent library preparations, sequencing, and analysis.

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Background: Hypovitaminosis D is associated with adverse surgical outcomes. We quantified the environmental, demographic, and modifiable determinants of serum 25-hydroxyvitamin D (25-OHD) concentration and assessed the potential impact of a preoperative screening questionnaire for moderate-to-severe hypovitaminosis D (25-OHD <30 nmol/L).

Methods: In a retrospective cohort study of 227 Chinese patients (69 males and 158 females) undergoing 261 joint arthroplasty, we collected information on recent sun exposure, dietary vitamin D intake, vitamin D supplementation, and Western Ontario and McMaster Universities osteoarthritis index using a questionnaire and measured a fasting 25-OHD concentration using a liquid chromatography-tandem mass spectrometry before surgery.

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The purpose of this study was to evaluate the dosimetric profiles and delivery accuracy of running-start-stop (RSS) delivery in tomotherapy and to present initial quality assurance (QA) results on the accuracy of the dynamic jaw motion, dosimetric penumbrae of the RSS dynamic jaw and the static jaw were measured by radiographic films. Delivery accuracy of the RSS was evaluated by gamma analysis on film measurements of 12 phantom plans. Consistency in the performance of RSS was evaluated by QA procedures over the first nine months after the installation of the feature.

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Background: Postoperative nausea and vomiting (PONV) are common complications following surgery and anaesthesia. Antiemetic drugs are only partially effective in preventing PONV. An alternative approach is to stimulate the PC6 acupoint on the wrist.

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Problem: The availability of less expensive and smaller ultrasound machines has enabled the use of ultrasound in virtually all major medical/surgical disciplines. Some medical schools have incorporated point-of-care ultrasound training into their undergraduate curriculum, whereas many postgraduate programs have made ultrasound training a standard. The Chinese University of Hong Kong has charged its Department of Anaesthesia and Intensive Care to spearhead the introduction of ultrasound into the final-year medical curriculum by introducing handheld transthoracic echocardiography as part of perioperative assessment.

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Background: Autocrine motility factor receptor (AMFR) has been linked to metastasis and tumorigenicity. The aim of this study was to evaluate expression and prognostic significance of AMFR in colorectal carcinoma.

Methods: AMFR expression was evaluated in 127 colon cancer specimens, 131 rectal cancer specimens, and 47 colonic and 25 rectal corresponding lymph node metastases.

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Purpose: To describe the use of cerebral oximetry to detect a lack of right cerebral perfusion resulting from a malpositioned catheter used for antegrade cerebral perfusion during deep hypothermic circulatory arrest (DHCA). The simple corrective surgical adjustment that followed averted a potentially serious complication.

Clinical Features: A 57-yr-old male with a type-A aortic dissection undergoing DHCA required antegrade cerebral perfusion for cerebral protection.

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Background: Cyclo-oxygenase-2 (COX-2), an inducible enzyme expressed in areas of inflammation, is a target of interest for colorectal cancer therapy. Currently, the predictive significance of COX-2 in colorectal cancer remains unclear.

Methods: Tissue microarrays were constructed using 118 colon cancer and 85 rectal cancer specimens; 44 synchronous metastatic colon cancer and 22 rectal cancer lymph nodes were also evaluated.

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Background: Despite the different preoperative imaging modalities available for parathyroid adenoma localization, there is currently no uniform consensus on the most appropriate preoperative imaging algorithm that should be routinely followed prior to the surgical management of primary hyperparathyroidism (PHPT). We sought to determine the incremental value of adding neck ultrasonography to scintigraphy-based imaging tests.

Methods: In a single institution, surgically naive patients with PHPT underwent the following localization studies before parathyroidectomy: 1) Tc-99m sestamibi imaging with single photon emission computed tomography/computed tomography (SPECT/CT) or Tc-99m sestamibi imaging with SPECT alone, or 2) ultrasonography in addition to those tests.

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Background: The mountain pine beetle (MPB, Dendroctonus ponderosae) epidemic has affected lodgepole pine (Pinus contorta) across an area of more than 18 million hectares of pine forests in western Canada, and is a threat to the boreal jack pine (Pinus banksiana) forest. Defence of pines against MPB and associated fungal pathogens, as well as other pests, involves oleoresin monoterpenes, which are biosynthesized by families of terpene synthases (TPSs). Volatile monoterpenes also serve as host recognition cues for MPB and as precursors for MPB pheromones.

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Background: The mountain pine beetle, Dendroctonus ponderosae Hopkins, is the most serious insect pest of western North American pine forests. A recent outbreak destroyed more than 15 million hectares of pine forests, with major environmental effects on forest health, and economic effects on the forest industry. The outbreak has in part been driven by climate change, and will contribute to increased carbon emissions through decaying forests.

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Dysregulation of nucleophosmin 1 (NPM1) has been found in numerous solid and hematological malignancies. Our previous meta-analysis of colorectal cancer (CRC) high throughput gene expression profiling studies identified it as a consistently reported up-regulated gene in the malignant state. Our aims were to compare NPM1 expression in normal colon, adenoma and CRC, to correlate their expressions with clinico-pathological parameters, and to assess the biological role of aberrant NPM1 expression in CRC cells.

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Higher cyclooxygenase 2 (COX-2) expression is often observed in aggressive colorectal cancers (CRCs). Here, we attempt to examine the association between COX-2 expression in therapy-refractory CRC, how it affects chemosensitivity, and whether, in primary tumors, it is predictive of clinical outcomes. Our results revealed higher COX-2 expression in chemoresistant CRC cells and tumor xenografts.

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Background: Fine needle aspiration biopsy represents the critical initial diagnostic test used for evaluation of thyroid nodules. Our objectives were to determine the cytological distribution, the utility of clinicopathologic characteristics for predicting malignancy and the true proportion of cancer among individuals who presented with indeterminate cytology and had undergone thyroid surgery for suspicion of cancer.

Methods: We retrospectively reviewed 1040 consecutive primary thyroid operations carried out over an 8-year period at a tertiary care endocrine referral centre.

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Article Synopsis
  • * There is a lack of genomic resources available for bark beetles, limiting effective monitoring and management of their spread.
  • * Research generated extensive transcriptome data through advanced sequencing techniques, creating a valuable genomic resource for gene discovery and studying the beetle's biology at the molecular level.
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Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed.

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