Faculty Bibliography

Despite extensive research on hemispheric asymmetries, the mechanisms regulating lateralized brain functions are incompletely understood. Growing evidence suggests that lateralized neural circuits are side-specifically controlled, in part, by neuropeptides acting as neuromodulators, paracrine factors, and neurohormones. This review highlights evidence supporting this concept in the contexts of lateralized pain processing in the amygdala, control of auditory signaling, lateralized interoceptive signaling, and side-specific endocrine regulation. Our focus is primarily on rodent studies, with supporting data from humans and nonmammalian species, including turtles and nematodes. Left-right side-specific control may be rooted in a bipartite, lateralized organization of neuropeptide systems. Neuropeptides with asymmetric actions may act locally within specific brain regions or be coordinated across the neuraxis. These findings converge on a model in which neuropeptides enable lateralized control through interconnected mechanisms spanning gene expression, neural circuits, and behavioral outcomes.

Early identification of high-risk trauma patients in the prehospital setting is crucial for optimizing resource allocation and improving survival. We developed and externally validated a real-time AI model predicting emergency room mortality using 21 prehospital variables. Model development and internal validation utilized the Korean Trauma Data Bank (KTDB; 204,189 patients), and external validation included four South Korean trauma centers (8,358 patients) and one Australian Level 1 center (3,578 patients). Our Prehospital-AI model, an ensemble of XGBoost, LightGBM, and random forest, achieved an AUROC of 0.923 (sensitivity: 0.780, specificity: 0.880) on the test set, outperforming the shock index (AUROC: 0.712). External validation yielded AUROCs of 0.925-0.956 across South Korean centers and 0.895 in the Australian center. Here we show that the Prehospital-AI model enables accurate, real-time risk assessment in the prehospital setting, outperforming traditional triage tools and improving trauma system efficiency. Nonetheless, additional multinational studies are warranted to further evaluate its generalizability across diverse trauma care systems.

Pyramidal cells (PCs) of hippocampal area CA2 exhibit increased excitability in temporal lobe epilepsy (TLE) and in mouse models of TLE. In epileptic mice, selective inhibition of CA2 PCs reduces chronic seizures. Here we asked if activating CA2 PCs increases seizures. Mice expressing Cre recombinase in CA2 PCs (Amigo2-Cre mice) were injected with the convulsant pilocarpine to induce a period of severe seizures (status epilepticus, SE), which leads to chronic seizures after 3-4 weeks (epilepsy). Epileptic mice were injected with a Cre-dependent adeno-associated virus (AAV) to express an excitatory designer receptor exclusively activated by designer drug (eDREADD; hM3Dq) in dorsal CA2 bilaterally and implanted with subdural EEG electrodes. After recovery, mice were recorded continuously using video and EEG for 6 weeks, 3 weeks with drinking water containing the eDREADD activator clozapine-N-oxide (CNO) and 3 weeks without CNO. CA2 activation with CNO caused a significant increase in seizure frequency and duration. Seizures occurred in clusters (many seizures per day over several consecutive days) and mice given water with CNO had a greater maximum number of seizures per day during a cluster compared to water without CNO. CNO had no significant effect in control mice. In naïve Amigo2-Cre mice expressing hM3Dq, pre-treatment with CNO before pilocarpine administration shortened the latency to SE and increased EEG power at the start of SE. Taken together with prior findings, the results suggest that CA2 is a control point for regulating seizures in the pilocarpine mouse model of TLE.

The cardiac conduction system (CCS) has a vital role in initiating and coordinating nearly 3 billion heartbeats throughout a person's lifetime. The CCS comprises two primary tissue types: the impulse-generating, slow-conducting nodes and the fast-conducting components of the ventricular conduction system. Dysfunction in this system can give rise to a spectrum of clinical symptoms, including palpitations, syncope, heart failure and even sudden cardiac death. Owing to the limited therapeutic options other than electronic pacemakers, substantial research efforts have been aimed at uncovering the root causes of conduction system disorders. A comprehensive investigative approach integrating genetics, transcriptomics and proteomics has been used to unravel the complex biology of these diseases. Advances in single-cell genomic and transcriptomic technologies, together with spatial transcriptomics, are offering new insights into the cellular microenvironments that govern conduction system function. In this Review, we examine the latest progress in understanding the biology of the CCS, situating new findings within both established and emerging scientific paradigms. Additionally, we discuss how these insights can be leveraged to improve clinical risk assessment, expand drug discovery efforts, accelerate technology aimed at promoting CCS regeneration and foster the development of innovative therapies, including biological pacemakers.

Acute rheumatic fever (ARF) is an immune-mediated nonsuppurative complication of group A streptococcal (GAS) pharyngitis. Approximately 470,000 new cases of ARF occur annually, with a more significant disease burden in developing countries with higher rates of untreated or inadequately treated GAS infections. Globally, over 275,000 deaths yearly are attributed to rheumatic heart disease (RHD). The most significant contributors to the spread of GAS pharyngitis are household overcrowding, poor sanitation, and inadequate access to healthcare. The pathophysiology of ARF is characterized by an aberrant immune response to GAS infection triggered by molecular mimicry between GAS antigens and self-antigens. This immune response typically manifests 2 to 4 weeks after the initial GAS infection and may lead to the development of carditis, valvulitis, Sydenham chorea, subcutaneous nodules, erythema marginatum, and polyarthritis that is usually migratory. The severity and distribution of these manifestations vary significantly between individuals making the diagnosis of ARF challenging. Early recognition of ARF using the modified Jones criteria is essential in treating acute infection and preventing complications. A major long-term consequence is RHD, which carries significant morbidity and mortality.

Monitoring intracellular calcium is central to understanding cell signaling across nearly all cell types and organisms. Fluorescent genetically encoded calcium indicators (GECIs) remain the standard tools for in vivo calcium imaging, but require intense excitation light, leading to photobleaching, background autofluorescence and phototoxicity. Bioluminescent GECIs, which generate light enzymatically, eliminate these artifacts but have been constrained by low dynamic range and suboptimal calcium affinities. Here we show that CaBLAM ('calcium bioluminescence activity monitor'), an engineered bioluminescent calcium indicator, achieves an order-of-magnitude improvement in signal contrast and a tunable affinity matched to physiological cytosolic calcium. CaBLAM enables single-cell and subcellular activity imaging at video frame rates in cultured neurons and sustained imaging over hours in awake, behaving animals. These capabilities establish CaBLAM as a robust and general alternative to fluorescent GECIs, extending calcium imaging to regimes where excitation light is undesirable or infeasible.

AIM/OBJECTIVE:Postoperative delirium (POD) is a frequent neurological complication following surgery, often leading to poor prognoses. The red blood cell distribution width (RDW) to albumin ratio (RAR), an emerging indicator of inflammation and nutrition, was extensively utilized for prognostic evaluation of neurological disorders in elderly patients. However, the relationship between RAR and POD was not evaluated. This study aimed to investigate the independent risk factors for POD and assess the predictive value of preoperative RAR among elderly patients who had gastrointestinal tumors. METHODS:We conducted a retrospective analysis to collect perioperative data on 203 patients aged 65 years or older undergoing gastrointestinal tumor surgery from November 2023 to August 2024. The risk factors for POD were detected through univariate and multivariate logistic regression analyses. Propensity score matching (PSM) was employed to make their clinical characteristics balanced. RESULTS:Out of 203 patients, 30 (14.8%) experienced POD, with a median age of 70 (range 67-76). Hypertension, creatinine, MCH, and RAR were determined as independent risk factors for POD through multivariate logistic regression analysis. In the post-PSM cohort, RAR was still verified as a factor influencing POD. CONCLUSIONS:Hypertension, creatinine, MCH, and RAR were recognized as independent risk factors for postoperative delirium in patients following gastrointestinal tumor surgery. Particularly, the preoperative RAR served as a more efficient index for predicting POD. TRIAL REGISTRATION/BACKGROUND:Chinese Clinical Trial Center: ChiCTR2400094315.