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Biomedical subjects

Tih-Shih Lee

Publications and source records attributed to Tih-Shih Lee.

4 recordsLinked to original sources

Development and Validation of Machine Learning Models for Predicting Early Cognitive Decline Using Home Sensor-Derived Behavioral Data: Sensors in-Home for Elder Wellbeing (SINEW) Cohort Study.

BACKGROUND: As the global population continues to age, the prevalence of geriatric conditions, including dementia and frailty, is also increasing. Early identification of individuals at an elevated risk of these conditions, such as those presenting with mild cognitive impairment (MCI) or prefrailty, can provide a critical window for prompt intervention aimed at preventing or reversing disease progression. To promote such early identification, there is a burgeoning interest in the use of digital sensor technology and predictive modeling. OBJECTIVE: This study aimed to use a continuous, home-based monitoring sensor system for older adults to distinguish those exhibiting normal aging from those with MCI, early dementia, prefrailty, or frailty, and to predict their transition from normal aging to one of these conditions. METHODS: This longitudinal cohort study will recruit 200 community-dwelling adults aged ≥65 years with normal cognition or MCI at baseline. A multi-sensor system will be installed in participants' homes, including passive infrared motion sensors, door contact sensors, bed sensors, medication box sensors, wearable activity bands, and Bluetooth proximity beacons. These devices will continuously capture spatiotemporal activity patterns, mobility indicators, sleep behaviors, and medication-taking routines. Annual assessments will include standardized cognitive tests (eg, Montreal Cognitive Assessment, Mini-Mental State Examination, Rey Auditory-Verbal Learning Test, digit span, Color Trails Test, semantic fluency, Stroop), frailty measures (modified Fried phenotype, gait speed, grip strength), mental health scales, sleep quality, and psychosocial indicators. Sensor-derived features-such as gait variability, activity regularity, sleep fragmentation, and medication adherence patterns-will be integrated with clinical data to develop supervised machine learning models. Planned approaches include logistic regression, random forests, gradient boosting, and deep learning. Model performance will be evaluated using cross-validation and independent test sets. Primary metrics will include area under the receiver operating characteristic curve, sensitivity, specificity, precision, recall, and F1-score. Models will be benchmarked against gold-standard clinical diagnoses and validated using temporal subsets of the dataset. RESULTS: Enrollment for this study started in November 2019 and will continue until March 2030. As of June 2025, we have enrolled 138 participants. Full data analysis has yet to begin. CONCLUSIONS: We aim to develop a reliable and effective sensor system for in-home use that will facilitate the early detection of cognitive and physical decline. In so doing, it will add to our current understanding of digital biomarkers. It is common for older adults to seek clinical intervention only when their cognitive impairment has already reached an advanced stage. The implementation of readily deployable sensor systems within community settings presents us with opportunities for prompt intervention, which holds the potential for delaying or reversing disease progression and allowing for a greater number of functional and meaningful years.

Humans↗

GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus.

The gamma amino butyric acid (GABA) transporters GAT-1 and GAT-3 were localized by immunohistochemistry in hippocampi removed for the control of medically intractable temporal lobe epilepsy (TLE). The study aimed to determine the relationship of GABA transporter expression to known patterns of hippocampal hyperexcitability and extracellular GABA levels. GAT-1 was localized in axon terminals and small neuronal cell bodies, and in non-sclerotic hippocampi was strongly expressed throughout all regions of the hippocampal formation. In the epileptogenic hippocampus exhibiting Ammon's horn sclerosis, immunoreactivity was reduced in the sclerotic regions CA3 and CA1, and around the cell bodies of dentate granule cells, but was increased along granule cell dendrites. GAT-3 was weakly expressed, if at all, in non-sclerotic hippocampi, but more prominently expressed in sclerotic hippocampi. GAT-3 expression was confined to cells resembling protoplasmic astrocytes, which were located in regions of relative neuronal sparing such as the dentate gyrus and hilus of the sclerotic hippocampus. The reduction in GAT-1 around granule cells in the sclerotic hippocampus could explain the prolonged GABA responses in this region. The loss of GAT-1 (a marker of GABAergic terminals) would also suggest a reduced GABAergic input to the granule cells, thus facilitating hyperexcitability. The increased GAT-3 expression in astrocytes in regions of relative neuronal sparing in the sclerotic hippocampus may be related to the overall low levels of extracellular GABA observed in the sclerotic hippocampus and their increased excitability.

Adolescent↗

Abuse of prescription buprenorphine, regulatory controls and the role of the primary physician.

INTRODUCTION: Buprenorphine is an opioid partial agonist approved in several countries for the treatment of opioid dependence. It was approved in Singapore in 2002 for this indication, and is more widely available in the primary care setting and can be prescribed by all licensed physicians who have undergone designated training. There is limited literature addressing the risk of its illicit abuse via intravenous self-administration. CLINICAL PICTURE: We report 2 such cases of the abuse of prescription buprenorphine in the psychiatric consultation-liaison service of a general teaching hospital, the treatment approaches and outcomes. CONCLUSION: We also briefly review the indications, uses and abuses of buprenorphine in Singapore, and as reported in other countries, and the roles of primary care physicians, in order to stimulate greater awareness and understanding among specialists and general practitioners, who would encounter these patients in various settings.

Adult↗

New facets of the neuropathology and molecular profile of human temporal lobe epilepsy.

This review summarizes the salient features of the anatomical and molecular neuropathology of the hippocampus from patients with intractable temporal lobe epilepsy (TLE). It argues that sclerotic hippocampus is essential for seizure expression and that sclerosis is not a consequence of seizures, but is related to the epileptogenicity of the seizure focus. While neurons in sclerotic hippocampus may contribute to hippocampal hyperexcitability, this role is perhaps less important than that of the astrocytes. The astrocytes in sclerotic hippocampus may directly influence excitability through altered water homeostasis and K+ buffering by redistribution of AQP4 transporters on their plasma membrane. It is proposed that they contribute to a high extracellular glutamate level through reduced glutamine synthetase, and activation through pro-inflammatory factors that release chemokines and cytokines, which enhance calcium-dependent glutamate release. Such a focal pool of glutamate may diffuse to surrounding neuron-rich areas to generate seizure activity in TLE.

Animals↗