Publications by authors named "L C Wong"

3,718 Publications

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SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters.

Nature 2022 Jan 21. Epub 2022 Jan 21.

Colombia/Wisconsin One-Health Consortium and One-Health Genomic Laboratory, Universidad Nacional de Colombia, Medellín, Colombia.

The recent emergence of B.1.1.529, the Omicron variant has raised concerns for escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in pre-clinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of multiple B.1.1.529 Omicron isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2) expressing mice and hamsters. Despite modeling data suggesting that B.1.1.529 spike can bind more avidly to murine ACE2, we observed less infection in 129, C57BL/6, BALB/c, and K18-hACE2 transgenic mice as compared with previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease, and pathology with B.1.1.529 also were milder compared to historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.
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http://dx.doi.org/10.1038/s41586-022-04441-6DOI Listing
January 2022

Speech Perception in Noise Is Associated With Different Cognitive Abilities in Chinese-Speaking Older Adults With and Without Hearing Aids.

Front Psychol 2021 4;12:640300. Epub 2022 Jan 4.

Audiology Centre, Union Hospital, Tai Wai, Hong Kong SAR, China.

Chinese-speaking older adults usually do not perceive a hearing problem until audiometric thresholds exceed 45 dB HL, and the audiometric thresholds of the average hearing-aid (HA) user often exceed 60 dB HL. The purpose of this study was to examine the relationships between cognitive and hearing functions (measured as audiometric or speech reception thresholds) in older Chinese adults with HAs and with untreated hearing loss (HL). Participants were 49 Chinese older adults who used HAs and had moderate to severe HL (HA group), and 46 older Chinese who had mild to moderately severe HL but did not use HAs (untreated; or UT group). Multiple linear regression analysis was employed to evaluate how well age, education level, audiometric thresholds, and speech perception in noise were related to performance on general cognitive function, working memory, executive function, attention, and verbal learning tests. Results showed that speech perception in noise alone accounted for 13-25% of the variance in general cognitive function, working memory, and executive function in the UT group, and 9-21% of the variance in general cognitive function and verbal learning in the HA group (i.e., medium effect sizes). Audiometric thresholds did not explain any proportion of the variance in cognitive functioning in the HA or UT group. Thus, speech perception in noise accounts for more variance in cognitive performance than audiometric thresholds, and is significantly associated with different cognitive functions in older Chinese adults with HAs and with untreated HL.
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http://dx.doi.org/10.3389/fpsyg.2021.640300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764161PMC
January 2022

The change in management by F-DCFPyL PSMA PET scanning in patients undergoing post-prostatectomy radiotherapy, with early biochemical response outcomes.

J Nucl Med 2022 Jan 20. Epub 2022 Jan 20.

GenesisCare Ringwood, Australia.

Prostate specific membrane antigen (PSMA) tracers have increased sensitivity in detection of prostate cancer compared to conventional imaging. We assessed the management impact of F-DCFPyL PET/CT in patients with PSA recurrence post radical prostatectomy (RP) and report early biochemical response in patients who underwent radiation treatment. One-hundred patients were enrolled into a prospective study, with a prior RP for prostate cancer, PSA 0.2-2.0ng/mL and no prior treatment. All patients underwent a diagnostic CT and F-DCFPyL PSMA PET/CT, and management intent was completed at 3 times points (original, post-CT and post-PSMA) and compared. Patients who underwent radiotherapy with 6-month PSA response data are presented. Ninety-eight patients are reported with a median PSA 0.32 ng/mL (95% CI 0.28-0.36), with 71.4% pT3a/b disease and International Society of Urological Pathology (ISUP) grade group ≥3 in 59.2%. F-DCFPyL PET/CT detected disease in 46.9% of patients compared to 15.5% using diagnostic CT (PSMA PET 29.2% local recurrence and 29.6% pelvic nodal disease). Major change in management intent was higher post-PSMA vs post-CT (12.5% vs 3.2%, = 0.010) and similarly, moderate change in intent (31.3% vs 13.7%, = 0.001). The most common change was an increase recommendation of elective pelvic radiation (15.6% to 33.3%), nodal boost (0% to 22.9%) and concurrent androgen deprivation therapy (ADT) use (22.9% to 41.7%) from original to post-PSMA intent due to detection of nodal disease. 86 patients underwent F-DCFPyl guided radiotherapy. 55/86 patients did not receive ADT or ADT recovered with 18 month PSA response from 0.32 ng/mL to 0.02 ng/mL, 94.5% of patients with PSA ≤0.20ng/mL and 74.5% with PSA ≤0.03 ng/mL. F-DCFPyL PET/CT has significant impact to management intent in patients being considered for salvage radiotherapy post-RP with PSA recurrence. Increased detection of disease, particularly in the pelvic lymph nodes resulted in increased pelvic irradiation and concurrent ADT use. Early results in patients who are staged with F-DCFPyL PET/CT-staged show favourable PSA response.
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http://dx.doi.org/10.2967/jnumed.121.263521DOI Listing
January 2022

Fading memories in aging and neurodegeneration: Is p75 neurotrophin receptor a culprit?

Ageing Res Rev 2022 Jan 17;75:101567. Epub 2022 Jan 17.

Department of Physiology, National University of Singapore, Singapore; Life Sciences Institute Neurobiology Programme, National University of Singapore, Singapore; Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Aging and age-related neurodegenerative diseases have become one of the major concerns in modern times as cognitive abilities tend to decline when we get older. It is well known that the main cause of this age-related cognitive deficit is due to aberrant changes in cellular, molecular circuitry and signaling pathways underlying synaptic plasticity and neuronal connections. The p75 neurotrophin receptor (p75) is one of the important mediators regulating the fate of the neurons in the nervous system. Its importance in neuronal apoptosis is well documented. However, the mechanisms involving the regulation of p75 in synaptic plasticity and cognitive function remain obscure, although cognitive impairment has been associated with a higher expression of p75 in neurons. In this review, we discuss the current understanding of how neurons are influenced by p75 function to maintain normal neuronal synaptic strength and connectivity, particularly to support learning and memory in the hippocampus. We then discuss the age-associated alterations in neurophysiological mechanisms of synaptic plasticity and cognitive function. Furthermore, we also describe current evidence that has begun to elucidate how p75 regulates synaptic changes in aging and age-related neurodegenerative diseases, focusing on the hippocampus. Elucidating the role that p75 signaling plays in regulating synaptic plasticity will contribute to a better understanding of cognitive processes and pathological conditions. This will in turn provide novel approaches to improve therapies for the treatment of neurological diseases in which p75 dysfunction has been demonstrated.
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http://dx.doi.org/10.1016/j.arr.2022.101567DOI Listing
January 2022

Automatic detection and segmentation of morphological changes of the maxillary sinus mucosa on cone-beam computed tomography images using a three-dimensional convolutional neural network.

Clin Oral Investig 2022 Jan 15. Epub 2022 Jan 15.

Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, China.

Objectives: To propose and evaluate a convolutional neural network (CNN) algorithm for automatic detection and segmentation of mucosal thickening (MT) and mucosal retention cysts (MRCs) in the maxillary sinus on low-dose and full-dose cone-beam computed tomography (CBCT).

Materials And Methods: A total of 890 maxillary sinuses on 445 CBCT scans were analyzed. The air space, MT, and MRCs in each sinus were manually segmented. Low-dose CBCTs were divided into training, training-monitoring, and testing datasets at a 7:1:2 ratio. Full-dose CBCTs were used as a testing dataset. A three-step CNN algorithm built based on V-Net and support vector regression was trained on low-dose CBCTs and tested on the low-dose and full-dose datasets. Performance for detection of MT and MRCs using area under the curves (AUCs) and for segmentation using Dice similarity coefficient (DSC) was evaluated.

Results: For the detection of MT and MRCs, the algorithm achieved AUCs of 0.91 and 0.84 on low-dose scans and of 0.89 and 0.93 on full-dose scans, respectively. The median DSCs for segmenting the air space, MT, and MRCs were 0.972, 0.729, and 0.678 on low-dose scans and 0.968, 0.663, and 0.787 on full-dose scans, respectively. There were no significant differences in the algorithm performance between low-dose and full-dose CBCTs.

Conclusions: The proposed CNN algorithm has the potential to accurately detect and segment MT and MRCs in maxillary sinus on CBCT scans with low-dose and full-dose protocols.

Clinical Relevance: An implementation of this artificial intelligence application in daily practice as an automated diagnostic and reporting system seems possible.
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http://dx.doi.org/10.1007/s00784-021-04365-xDOI Listing
January 2022
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