INTRODUCTION: An interdisciplinary panel, comprising professionals from medicine, AI and data science, law and ethics, and patient advocacy, convened to discuss key principles on regulation, implementation and evaluation of AI models in healthcare for Singapore. METHOD: The panel considered 14 statements split across 4 themes: "The Role and Scope of Regulatory Entities," "Regulatory Processes," "Pre-Approval Evaluation of AI Models" and "Medical AI in Practice". Moderated by a thematic representative, the panel deliberated on each statement and modified it until a majority agreement threshold is met. The roundtable meeting was convened in Singapore on 1 July 2024. While the statements reflect local perspectives, they may serve as a reference for other countries navigating similar challenges in AI governance in healthcare. RESULTS: Balanced testing approaches, differentiated regulatory standards for autonomous and assistive AI, and context-sensitive requirements are essential in regulating AI models in healthcare. A hybrid approach-integrating global standards with local needs to ensure AI comple-ments human decision-making and enhances clinical expertise-was recommended. Additionally, the need for patient involvement at multiple levels was underscored. There are active ongoing efforts towards development and refinement of AI governance guidelines and frameworks balancing between regulation and freedom. The statements defined therein provide guidance on how prevailing values and viewpoints can streamline AI implementation into healthcare. CONCLUSION This roundtable discussion is among the first in Singapore to develop a structured set of state-ments tailored for the regulation, implementation and evaluation of AI models in healthcare, drawing on interdisciplinary expertise from medicine, AI, data science, law, ethics and patient advocacy.
Singapore ; Humans ; Artificial Intelligence/standards* ; Delivery of Health Care/organization & administration*

Positional information plays a crucial role in embryonic pattern formation, yet its role in tooth development remains unexplored. In this study, we investigated the regional specification of lingual and buccal dental mesenchyme during tooth development. Tooth germs at the cap stage were dissected from mouse mandibles, and their lingual and buccal mesenchymal regions were separated for bulk RNA sequencing. Gene ontology analysis revealed that odontogenesis, pattern specification, and proliferation-related genes were enriched in the lingual mesenchyme, whereas stem cell development, mesenchymal differentiation, neural crest differentiation, and regeneration-related genes were predominant in the buccal mesenchyme. Reaggregation experiments using Wnt1^creERT/+; R26R^tdT/+ and WT mouse models demonstrated that lingual mesenchyme contributes to tooth formation, while buccal mesenchyme primarily supports surrounding tissues. Furthermore, only the lingual part of tooth germs exhibited odontogenic potential when cultured in vitro and transplanted under the kidney capsule. Bulk RNA transcriptomic analysis further validated the regional specification of the lingual and buccal mesenchyme. These findings provide novel insights into the molecular basis of positional information in tooth development and pattern formation.
Animals ; Mice ; Odontogenesis/genetics* ; Tooth Germ/cytology* ; Mesoderm/cytology* ; Cell Differentiation ; Mesenchymal Stem Cells ; Tooth/embryology*

Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Background: The effectiveness of intravenous tissue plasminogen activator (IV tPA) in patients with large-vessel occlusion (LVO) receiving endovascular treatment (EVT) for acute ischemic stroke (AIS) has been questioned. We investigated IV tPA effectiveness in real-world AIS patients, including those with intracranial LVO receiving EVT. Methods: We identified patients with AIS who presented to hospital with National Institutes of Health Stroke Scale ≥4 within 8 hours of symptom onset from the institutional stroke registry. The association of IV tPA use with effectiveness and safety outcomes was analyzed in overall enrolled AIS patients; LVO patients; and patients treated with EVT. The effect of IV tPA was assessed using multiple logistic regression. Results: Among the 654 patients meeting study entry criteria, 238 (36.4%) received IV tPA and 416 (63.6%) did not. Multiple logistic regression analysis and shift analysis revealed IV tPA was associated with improved outcomes in overall enrolled AIS population, LVO, and EVT-treated subgroups. Among EVT-treated patients, IV tPA was associated with higher likelihood of ambulatory or better outcome (modified Rankin Scale 0–3) with odds ratio of 1.95 (P=0.03). Conclusions In this real-world study, IV tPA use was associated with improved outcomes for patients with AIS, including among LVO patients treated and not treated with EVT, in the contemporary mechanical thrombectomy era.

Background: As the global population ages, medical professionals are also aging. This study investigates the status of Korean anesthesiologists over the age of 60. Methods: Anesthesiologists aged 60 and older, residing and working in Korea, were invited to participate in this study via e-mail from February to March 2021 and by mail from June to August 2021. The survey consisted of 40 questions covering 10 topics, including health status, residence, work style, and economic status. Depending on the type of question, answers were ranked on a scale of 1, 2, and 3, with the most preferred response being selected. Results: A total of 63 responses were received, resulting in a response rate of 26.5%. Among the respondents, 56 were currently practicing as anesthesiologists and reported satisfaction with their clinical practice and life status. On average, they treated 24 patients per day without experiencing significant discomfort or inconvenience in their roles as senior physicians. Twenty-four respondents acknowledged physical discomfort related to aging, and nine expressed cautions regarding age-related changes. Fifty-two respondents indicated that reeducation for advanced medical practice as anesthesiologists was necessary. Conclusions Senior anesthesiologists in Korea are primarily working in secondary and tertiary hospitals and are satisfied with their current life status. A comprehensive evaluation of reeducation programs for advanced clinical practice and retirement strategies for senior anesthesiologists is needed to address the growing number of aging physicians in the workforce.

Background: Bronchospasm is a rare but potentially life-threatening complication during anesthesia that requires prompt recognition and management. Traditional auscultation plays a key role but is limited in objective interpretation and continuous monitoring. Case: We report a case of intraoperative bronchospasm during laparoscopic surgery, detected early through real-time acoustic visualization using a digitalized esophageal stethoscope. The visualization of lung sounds facilitated the rapid identification of expiratory wheezing and abnormal spectrogram patterns characteristic of bronchospasm. Immediate intervention with a bronchodilator resolved the condition without further complications. Conclusions This case demonstrates the utility of visual stethoscopes in enhancing perioperative respiratory management. Real-time visualization and quantification of lung sounds offer anesthesiologists a valuable tool for early diagnosis and collaborative decision-making during critical respiratory events.

Background: The clinical manifestations of metastatic brachial plexopathy include pain, sensory loss, paresthesia, weakness, and reduced range of motion. These symptoms closely resemble those of shoulder disorders and peripheral nerve entrapment, which are commonly diagnosed in pain clinics, increasing the risk of misdiagnosis or delayed diagnosis, particularly in patients with a history of malignancy.Case: A 51-year-old woman with a history of breast cancer in complete remission for 19 years presented with shoulder pain, arm weakness, and tingling in the fingers. Initial treatments for suspected cervical radiculopathy, shoulder disorders, and nerve entrapment were ineffective. Electromyography and nerve conduction studies revealed electrophysiological abnormalities consistent with left brachial plexopathy. Magnetic resonance imaging of the brachial plexus confirmed metastatic involvement. The patient is currently undergoing chemotherapy. Conclusions Clinicians must be vigilant of the possibility of malignancy in patients with a history of cancer and should pursue comprehensive diagnostic evaluations to exclude cancer recurrence.

Traditionally, anesthesiologists have recommended performing auscultation of breath and heart sounds with a precordial or esophageal stethoscope during anesthesia. The stethoscope is generally considered the most important single device used for monitoring. Unfortunately, many anesthesiologists neglect the perioperative use of a stethoscope, even though it provides a wealth of information about the circulatory system, heart, and lungs. Although point-of-care ultrasound appears to offer greater diagnostic value in some situations, it is premature to dismiss the stethoscope, and its diminished perioperative role should be reconsidered. Recent technological advances have allowed changes in the roles of these modalities to help attending anesthesiologists perform easy assessments using clinically meaningful information from auscultation. The phonocardiopulmogram (PCPG), a real-time visual acoustic monitor, is a rediscovered and renovated technique that allows non-invasive continuous heart-lung function monitoring. However, the novel role of the PCPG as a continuous acoustic monitor, particularly for S1 and S2 heart sounds and their respiratory variations, remains relatively unexplored. This device may convey information about cardiac contractility, cardiac output, and fluid responsiveness. Furthermore, continuous lung sound visualization has potential as a monitoring modality during anesthesia, including during bronchospasm and endobronchial intubation. With its ease of use and intuitive mechanism, the PCPG can be applied during general anesthesia and follow-up in both post-anesthesia and intensive care unit settings, particularly for the detection of acute adverse events during the perioperative period.

Background: Bullous pemphigoid (BP) is an autoimmune blistering disease driven by autoantibodies against BP180 and BP230. While type 2 inflammation plays a key role, the precise immune cell alterations and transcriptomic changes remain unclear. Objective: To characterize immune cell composition and transcriptomic changes in BP patients using fluorescence-activated cell sorting (FACS)-based immunophenotyping and RNA sequencing. Methods: A case-control study was conducted on 10 newly diagnosed, treatment-naive BP patients and six healthy controls. Disease activity was assessed using the Bullous Pemphigoid Disease Area Index (BPDAI). Peripheral blood mononuclear cells were isolated for FACS analysis to determine immune cell subsets. RNA sequencing was performed to identify differentially expressed genes (DEGs) and enriched pathways. Statistical analyses included t-tests, Mann-Whitney U tests, and correlation analysis. Results: FACS analysis revealed a reduction in CD4 + T cells, T helper 2 (Th2), and B cells in BP patients (p<0.05), alongside an increase in M2a-like monocytes (p<0.001). RNA sequencing identified 262 DEGs, with secretory leukocyte peptidase inhibitor (SLPI) and transmembrane protein 237 being the most significantly upregulated. Proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) and SAM domain, SH3 domain, and nuclear localization signals 1 (SAMSN1) positively correlated with BPDAI (p<0.001). Gene ontology analysis highlighted enrichment in inflammatory responses and neutrophil degranulation pathways. Conclusion BP patients show distinct immune dysregulation, including decreased CD4 + T cells, Th2, and B cells, increased M2a-like monocytes, altered gene expression profiles, and correlations between PSTPIP2, SAMSN1 and disease activity. These findings provide insights into pathogenesis and potential therapeutic targets of BP.