Faculty Bibliography

Intercompartmental water exchange in brain and other biological tissue can be probed in vivo with diffusion MRI (dMRI). We assess the accuracy of a recently proposed method for estimating a mean exchange rate by performing Monte Carlo simulations of random walkers through a packing of permeable, randomly placed, parallel cylinders to model water exchange within axonal fiber bundles. The diffusivity and kurtosis of the full system are calculated for a broad range of diffusion times and model parameters. The mean exchange rate is estimated from the logarithmic derivative of the kurtosis with respect to the diffusion time and compared with the exchange rate predicted by the Kärger model (KM), which is exact in certain limits. The mean exchange rate is also compared with the reciprocal exchange time obtained by conventional fitting of the kurtosis time dependence to a two-compartment KM, with a high correlation being found between the two quantities. The estimates from the logarithmic derivative are in good agreement with the KM predictions when the exchange time is long in comparison to the compartment traversal times, which corresponds to barrier-limited exchange. Compared to the standard procedure of fitting the kurtosis to the KM over a broad range of diffusion times, using the logarithmic derivative reduces the data acquisition burden by only requiring a narrow range of times and increases generality in that number of compartments need not be specified. This method may be useful for estimating the mean exchange rate from the kurtosis time dependence measured with dMRI.

OBJECTIVE:To validate the carotid web (CW) risk stratification assessment described in previous works within a larger cohort of patients with symptomatic and incidentally found asymptomatic CWs. METHODS:A retrospective analysis of our institution's electronic medical records identified all patients with a diagnosis of CW from 2017 to 2024. We included symptomatic patients and those with asymptomatic CWs, that is, incidentally found webs without history of stroke or transient ischemic attack. Patient charts were reviewed for demographics, imaging, comorbidities, and a diagnosis of stroke after diagnosis of asymptomatic CW. All angles were measured as described in previous work on a sagittal reconstruction of neck CT angiography in which the common carotid artery (CCA), external carotid artery, and internal carotid artery (ICA) were well visualized, together with the CW itself. Principal component analysis and logistic regression were performed to evaluate the association between high-risk angles and stroke risk.  RESULTS: Twenty-six symptomatic and 26 asymptomatic patients were identified. Of note, the number of patients with hypertension, hyperlipidemia, and smoking history was 17 (65.0%), 16 (62.0%), and 8 (31.0%) for symptomatic patients and 18 (69.0%), 17 (65.0%), and 15 (58.0%) for asymptomatic patients. All angular measurements showed statistically significant associations with stroke status. The CCA-web-pouch angle showed the strongest association (p=2.07×10⁻⁴), followed by the CCA-pouch-tip angle (p=3.23×10⁻⁴), ICA-web-pouch angle (p=0.004), and ICA-pouch-tip angle (p=0.005). Each additional high-risk angle increased the odds of stroke by 9.47-fold (p<0.0001). The associated probability of stroke increased from 6.3% with no high-risk angles to 39.1% with one high-risk angle and further to 85.9% with two high-risk angles. The model demonstrated high sensitivity, correctly identifying 84.6% of positive cases, and high specificity, correctly identifying 88.5% of negative cases. The F1 score was 0.863, indicating good overall model performance.  CONCLUSION: Given this successful stratification of CWs into high- and low-risk groups, the utilization of geometric CW parameters may play a role in improving patient selection for intervention in the setting of incidentally diagnosed CW. .

Individuals with Down syndrome (DS) are at risk for early-onset Alzheimer's disease (AD), marked by neurodegeneration in hippocampal and basal forebrain circuits. Early-life interventions offer therapeutic potential, including maternal choline supplementation (MCS). MCS improves cognitive outcomes and neuroplasticity in rodent models of neurodevelopmental and neurodegenerative disorders, yet cell-type specific molecular effects remain unknown. We investigated the effect of MCS upon the onset of septohippocampal degeneration at 6 months of age in the Ts65Dn mouse model of DS/AD. Using laser capture microdissection and single population RNA-sequencing, transcriptomic changes were profiled within hippocampal CA1 and CA3 pyramidal neurons and dentate gyrus granule cells comparing trisomic and disomic offspring. Bioinformatic analysis revealed MCS-mediated downregulation of apoptotic pathways and upregulation of cognition-related functions across all populations, alongside cell-specific responses. These findings highlight MCS as a promising strategy for modulating disease-relevant pathways in a hippocampal cell-type-specific manner during early neurodegeneration in DS/AD.

We report a 71-year-old woman who developed disabling orthostatic tremor and severe orthostatic hypertension following cosmetic neck lift surgery. Autonomic testing demonstrated exaggerated pressor responses and excessive orthostatic catecholamine release, consistent with sympathoadrenal overactivation due to impaired carotid baroreflex function. This case highlights a potential autonomic complication of aesthetic neck surgery.

As vertebrates transitioned from water to land, locomotion shifted from undulatory swimming to limb-based movement. How spinal circuits and their cell types evolved to support this transition remains unclear. We leverage frog metamorphosis, which recapitulates this transition within a single organism, to define how spinal circuits generate aquatic versus terrestrial motor patterns. At swim stages, spinal architecture is uniform, with a transcriptionally and anatomically homogeneous motor and interneurons. As limbs develop and their movement complexifies, spinal circuits expand in neuron number and subtype diversity. This expansion is most pronounced for V1 inhibitory neurons, which increase ∼70-fold and diversify into transcriptionally distinct subtypes. Disrupting transcription factors defining emerging motor and V1 populations reveals molecular segregation between swim and limb circuits, highlighting the role of subtype diversity in motor coordination. A multifold increase in inhibitory neuron diversity thus underlies the tail-to-limb locomotor transition, providing a framework for spinal circuit adaptation during vertebrate evolution.

In mice and many other species, aggression levels are low in virgin females but increase dramatically during lactation to protect vulnerable offspring. This aggression, aimed at protecting the young, is known as maternal aggression. It emerges abruptly after parturition, peaks during early lactation, and declines after weaning. Given its stereotyped temporal profile, hormones associated with pregnancy and lactation are believed to play critical roles in its rise and fall. In addition, maternal aggression diminishes within hours of pup separation and rapidly recovers upon pup reunion, indicating a secondary, pup-dependent regulation of its expression. Here, we review current knowledge of the female aggression circuit and the hormonal and neural mechanisms that reshape it during pregnancy and lactation. We propose a two-step model in which pregnancy-associated sex hormone surges refine the aggression circuit, while lactation-associated neuropeptide signals gate circuit output in response to the need to protect offspring.

Ion channels are the second most common clinical drug target besides G protein-coupled receptors. Aneurysmal diseases pose a significant threat to human life. Novel drug targets for its treatment remain to be explored. We investigated the role of an ion channel, calcium homeostasis modulators 5 (CALHM5), on the development of aortic aneurysms. We characterized CALHM5 as a plasma membrane ion channel abundant in smooth muscle cells of both humans and mice, playing a pivotal role in regulating calcium homeostasis. Notably, CALHM5 deficiency suppressed the transcription of the L-type calcium channel (LTCC) pore-forming subunit by downregulating cAMP-response element binding proteins. This in turn diminished blood vessel contractility and decreased blood flow. Intriguingly, CALHM5 expression is downregulated in smooth muscle tissues of aortic aneurysm patients. Furthermore, CALHM5 deficiency was observed to ameliorate the development of abdominal aortic aneurysms in mice, partly by stimulating smooth muscle cell proliferation. CALHM5 emerges as an ion channel prominently expressed in arterial smooth muscles, serving as a physiological regulator of smooth muscle contraction and presenting itself as a promising therapeutic target for aortic aneurysms.

UNLABELLED:= 123), we found that people’s willingness to exert effort is positively associated with outcome expected value under both risk and ambiguity. Additionally, people exert more effort when outcome distribution uncertainty increases in risky situations, but are insensitive to ambiguity, except when facing extreme ambiguity. Our results demonstrate an unexpected dissociation. Humans will engage in effort-based information-seeking, even for non-instrumental information, when facing risk. In contrast, they show a much lower willingness to expend effort to resolve non-instrumental ambiguity. SUPPLEMENTARY INFORMATION:The online version contains supplementary material available at 10.1038/s41598-026-43803-2.

BACKGROUND:Accurate and equitable prediction of trauma-related in-hospital mortality is critical for guiding clinical decisions and optimising trauma care resources. Traditional severity scoring systems like the Injury Severity Score (ISS) do not account for demographic factors, potentially limiting their fairness and generalisability across diverse populations. METHODS:We developed and externally validated an artificial intelligence (AI) model based on ISS and integrated demographic features (age and sex) to predict in-hospital mortality after trauma. Data from the Korean Trauma Data Bank were used for model development and internal validation, comprising 121,418 patients with trauma aged ≥15 years treated at 19 trauma centres in South Korea (2017-2022). External validation was performed on an independent cohort of 7458 patients from five trauma centres (four in South Korea and one in Australia, 2022-2024). The primary outcome was trauma-related in-hospital mortality. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, accuracy, and balanced accuracy. Fairness was evaluated by comparing AUROC differences across age (<65 vs ≥65 years) and sex (female vs male) subgroups. FINDINGS/RESULTS:The ISS-based AI model incorporating age and sex achieved high predictive performance (internal validation AUROC, 0.934; external validation AUROC range, 0.901-0.920), outperforming conventional ISS-based methods. The model also demonstrated improved fairness, showing reduced AUROC differences across subgroups (age: 0.068 vs 0.091; sex: 0.021 vs 0.046 for AI model vs ISS, respectively). INTERPRETATION/CONCLUSIONS:Scaling an ISS-based AI model through demographic integration yielded accurate, fair, and generalisable predictions of trauma-related in-hospital mortality. This approach may enhance trauma care decision-making and enable more equitable resource allocation across diverse clinical settings. FUNDING/BACKGROUND:This research was supported by the MSIT (Ministry of Science and ICT), Korea, under the ITRC (Information Technology Research Center) support program (IITP-2025-RS-2024-00438239) and the Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT) (RS-2024-00509257, Global AI Frontier Lab). In addition, this research was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (RS-2025-02220492).

Ultrasound is the imaging study of choice for the initial diagnosis of autosomal dominant polycystic kidney disease (ADPKD) due to its high diagnostic accuracy and ability to detect kidney cysts as small as 2 to 3 mm. MRI of the kidneys is also highly sensitive at detecting small cysts and is an alternative to US. MRI is the preferred modality for determining total kidney volume (TKV). TKV can be used as an imaging biomarker to predict kidney function decline, track disease progression, and evaluate the effectiveness of treatment. CT abdomen and pelvis with contrast is the test of choice for detecting suspected complications such as renal cyst hemorrhage, rupture, or infection. MRI of the abdomen without and with contrast can also be used for diagnosing complications of ADPKD and is usually appropriate regardless of kidney function. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.