A fluorescent sensor for real-time measurement of extracellular oxytocin dynamics in the brain.

Oxytocin (OT), a hypothalamic neuropeptide that acts as a neuromodulator in the brain, orchestrates a variety of animal behaviors. However, the relationship between brain OT dynamics and complex animal behaviors remains largely elusive, partly because of the lack of a suitable technique for its real-time recording in vivo. Here, we describe MTRIAOT, a G-protein-coupled receptor-based green fluorescent OT sensor that has a large dynamic range, suitable affinity, ligand specificity for OT orthologs, minimal effects on downstream signaling and long-term fluorescence stability. By combining viral gene delivery and fiber photometry-mediated fluorescence measurements, we demonstrate the utility of MTRIAOT for real-time detection of brain OT dynamics in living mice. MTRIAOT-mediated measurements indicate variability of OT dynamics depending on the behavioral context and physical condition of an animal. MTRIAOT will likely enable the analysis of OT dynamics in a variety of physiological and pathological processes.

Tribo-Chemical Reactions in DLC-Zirconia Sliding under Ethanol Gas Environment.

A reactive force field (ReaxFF) molecular dynamics simulation is performed for the sliding of diamond-like carbon (DLC) and yttria-stabilized zirconia (YSZ) under an ethanol gas environment, motivated by the previous experiment of ultralow friction phenomenon (friction fade-out). We observe (i) dissociation of ethanol into ethoxy and hydrogen, both of which simultaneously adsorb on the YSZ surface, and (ii) dissociation of ethanol into ethyl and hydroxy, the former of which forms a bond with another ethanol molecule and the latter of which adsorbs on the DLC surface. Reaction (i) is enhanced by the sliding motion, but occurs even without it, while reaction (ii) only occurs during sliding with a sufficiently high load pressure. The potentials of mean force for the two reactions are also calculated combining the steered MD and Jarzynski equality. It is shown that the activation energies of reactions (i) and (ii) are significantly lowered by the YSZ and DLC surfaces, respectively, as compared to those in a vacuum. The resultant activation energy is higher for reaction (ii) than for reaction (i).

Association between aortic thrombi detected using non-obstructive general angioscopy and atrial fibrillation.

Atrial fibrillation (AF) is an independent risk factor for stroke and systemic embolism. Cardiogenic and aortogenic emboli are causes of stroke or systemic embolism. Non-obstructive general angioscopy (NOGA) can be used to diagnose aortic intimal findings, including thrombi and atherosclerotic plaques, but little is known about NOGA-derived aortic intimal findings in patients with AF. This study focused on aortic intimal findings in patients with AF and evaluated the association between AF and aortic thrombi detected using NOGA. We enrolled 283 consecutive patients with coronary artery disease who underwent NOGA of the aorta between January 2017 and August 2022. Aortic intimal findings were screened using NOGA after coronary arteriography. The patients were divided into two groups according to their AF history (AF, n = 50 and non-AF, n = 233). Patients in the AF group were older than those in the non-AF group. Sex, body mass index, and coronary risk factors were not significantly different between the two groups. In the NOGA findings, the presence of intense yellow plaques and ruptured plaques was not significantly different between the two groups. Aortic thrombi were more frequent in the AF group than in the non-AF group (92.0 vs. 71.6%, p < 0.001). Multivariate logistic regression found that AF was independently associated with aortic thrombi (odds ratio 3.87 [95% CI 1.28-11.6], p = 0.016). The presence of aortic thrombi observed using NOGA was associated with AF in patients with coronary artery disease. The roles of aortic thrombi as well as cardiogenic embolism may require clarification.

Dynamics of the suprapatellar bursa during knee joint extension.

PURPOSE: The suprapatellar bursa is located in the proximal deep layer of the patella and is thought to reduce tissue friction by changing from a single-membrane structure to a double-membrane structure during knee joint motion. However, the dynamics of the suprapatellar bursa have only been inferred from positional relationships, and the actual dynamics have not been confirmed. METHODS: Dynamics of the suprapatellar bursa during knee joint motion were observed in eight knees of four Thiel-fixed cadavers and the angle at which the bursa begins to show a double membrane was revealed. The flexion angles of knee joints were measured when the double-membrane structure of the suprapatellar bursa began to appear during knee joint extension. RESULTS: The suprapatellar bursa changes from a single membrane to a double-membrane structure at 91 ± 4° of flexion, when the knee joint is moved from a flexed position to an extended position. CONCLUSION: The suprapatellar bursa may be involved in limitations to knee joint range of motion and pain at an angle of approximately 90°. Further studies are needed to verify whether the same dynamics are observed in living subjects.

Asymmetric Strecker reaction at the solid/solid interface.

Related to absolute asymmetric synthesis, a stereospecific reaction at the solid/solid interface arising from crystal chirality of the achiral or racemic substrates has not yet been reported. Here, we demonstrate the asymmetric Strecker-type solid/solid reaction between the chiral crystal of a racemic cyanohydrin (kryptoracemate) and the achiral crystal of an ammonium salt to afford highly enantioenriched α-aminonitrile in combination with amplification of chirality. rac-Cyanohydrin provides its chiral surface as a reactive site and the reaction proceeds with dissociation of cyanohydrin; thus, an asymmetric Strecker-type reaction takes place at the interface of the substrate crystals. Strecker synthesis coupled with cyanohydrin synthesis offers a credible abiotic synthesis mechanism of α-amino acids and α-hydroxy acids. For the first time, stereochemical relationship has been found between the two chiral intermediates, aminonitrile and cyanohydrin, which are in equilibrium in the synthesis mechanism.

Prognostic risk stratification based on left ventricular mechanical dyssynchrony in patients at low or intermediate risk of major cardiac events using the J-ACCESS risk model.

There have been no reports on prognostic prediction and risk stratification based on stress phase bandwidth (SPBW), or a left ventricular (LV) mechanical dyssynchrony index, in patients with known or suspected stable coronary artery disease (CAD) at low or intermediate risk of major cardiac events (MCEs) using the J-ACCESS risk model. We retrospectively investigated 4,996 consecutive patients with known or suspected CAD who underwent rest 201Tl and stress 99mTc-tetrofosmin electrocardiogram (ECG)-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) and followed up for 3 years to confirm their prognosis. MCE risk over 3 years was estimated using an equation based on that used in the J-ACCESS study. The composite endpoint was the onset of MCEs consisting of cardiac death, non-fatal myocardial infarction (MI), and severe heart failure requiring hospitalization. SPBW was calculated by phase analysis with the Heart Risk View-F software and its normal upper limit was set to 38°. Based on the estimated 3-year incidence of MCEs obtained from the J-ACCESS risk model, 4,123 of the 4,996 consecutive patients were classified as low (n = 2,653) or intermediate risk (n = 1,470) and they were analyzed for follow-up. During the follow-up, 153 patients experienced MCEs: cardiac death (n = 38), non-fatal MI (n = 45), and severe heart failure (n = 70). The results of the multivariate analysis showed age, estimated glomerular filtration rate (eGFR), stress LV ejection fraction, and stress SPBW to be independent predictors of MCEs. The actual 3-year MCE rate in patients at intermediate risk was significantly higher than in those at low risk (6.7% vs. 2.1%, P < 0.0001). However, the actual 3-year MCE rate in patients with abnormal SPBW (> 38°) was 4.0% and 9.2% in low- and intermediate-risk patients, respectively, which corresponded to intermediate and high risk. Kaplan-Meier analysis also showed significant risk stratification by normal SPBW values for both low- and intermediate-risk patients. LV mechanical dyssynchrony assessed with ECG-gated SPECT MPI is useful for risk stratification of known or suspected stable CAD patients at low or intermediate risk of MCEs and may help identify higher risk patients who could not be identified as being at risk based on J-ACCESS risk assessment.

Square-Planar Anionic Pt0 Complexes.

A T-shaped Pt0 complex with a diphosphine-borane (DPB) ligand was prepared. The Pt→B interaction enhances the electrophilicity of the metal and triggers the addition of Lewis bases to give the corresponding tetracoordinate complexes. For the first time, anionic Pt0 complexes are isolated and structurally authenticated. X-ray diffraction analyses show the anionic complexes [(DPB)PtX]- (X=CN, Cl, Br, I) to be square-planar. The d10 configuration and Pt0 oxidation state of the metal were unambiguously established by X-ray photoelectron spectroscopy and DFT calculations. The coordination of Lewis acids as Z-type ligands is a powerful mean to stabilize elusive electron-rich metal complexes and achieve uncommon geometry.

Association between the Angle of the Left Subclavian Artery and Procedural Time for Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome.

Background: The effect of left subclavian artery tortuosity during percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) remains unclear. Methods: Of 245 ACS patients (from November 2019 and May 2021), 79 who underwent PCI via a left radial approach (LRA) were included. We measured the angle of the left subclavian artery in the coronal view on CT imaging as an indicator of the tortuosity and investigated the association between that angle and the clinical variables and procedural time. Results: Patients with a left subclavian artery angle of a median of <70 degrees (severe tortuosity) were older (75.4 ± 11.7 vs. 62.9 ± 12.3 years, P < 0.001) and had a higher prevalence of female sex (42.1% vs. 14.6%, P=0.007), hypertension (94.7% vs. 75.6%, P=0.02), and subclavian artery calcification (73.7% vs. 34.2%, P < 0.001) than those with that ≥70 degrees. The left subclavian artery angle correlated negatively with the sheath cannulation to the first balloon time (ρ = -0.51, P < 0.001) and total procedural time (ρ = -0.32, P=0.004). A multiple linear regression analysis revealed that the natural log transformation of the sheath insertion to first balloon time was associated with a subclavian artery angle of <70 degrees (ß = 0.45, P < 0.001). Conclusion: Our study showed that lower left subclavian artery angles as a marker of the tortuosity via the LRA were strongly associated with a longer sheath insertion to balloon time and subsequent entire procedure time during the PCI.

High-accuracy determination of trace elements by total reflection X-ray fluorescence spectrometry using freeze-dried specimens.

Total reflection X-ray fluorescence (TXRF) analysis is conducted to determine trace elements in a sample solution, which is dropped onto a substrate and dried. Therefore, the form of the residue affects the quantitative results. The absorption of X-ray fluorescence (XRF) follows the Lambert-Beer law; the absorption effect of XRF in a thick residue (dotted-type residue) is stronger than that in a thin residue (film-type residue). The absorption effect is particularly remarkable during the determination of low-Z elements in a high-elemental concentration solution. In this study, we propose a new film-like-residue preparation process based on the freeze-drying method to obtain accurate TXRF results. The sample solution is dropped onto the substrate and inserted into a chamber. The chamber is cooled using liquid nitrogen; resultantly, an aliquot of the sample is frozen. The chamber is depressurized using a vacuum pump, and the freeze-dried residue is prepared by maintaining the chamber at room temperature. To evaluate the efficiency of the freeze-drying-based method for sample preparation for TXRF analysis, we prepare a multi-element solution containing high-elemental concentration components. For the residue prepared using the freeze-drying method, the relative standard deviations of the quantitative values and the minimum detection limits are improved because the absorption effect is weakened. The sample preparation process based on the freeze-drying method facilitates accurate TXRF analysis of high-elemental concentration solutions and can be applied for the analysis of trace elements in different types of solutions such as environmental water and wastewater.

Prognostic value of the normalization of left ventricular mechanical dyssynchrony after revascularization in patients with coronary artery disease.

There are no reports indicating a prognostic difference based on normalization of left ventricular (LV) mechanical dyssynchrony after revascularization in patients with coronary artery disease (CAD). We retrospectively investigated 596 patients who underwent rest 201Tl and stress 99mTc-tetrofosmin electrocardiogram-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging. All patients had significant stenosis with ≥ 75% narrowing of the coronary arterial diameter detected by coronary angiography performed after confirmation of ≥ 5% ischemia by the SPECT. Patients underwent revascularization and thereafter were re-evaluated by the SPECT during a chronic phase, and followed-up to confirm their prognosis for ≥ 1 year. The composite endpoint was the onset of major cardiac events (MCEs) consisting of cardiac death, non-fatal myocardial infarction (MI), unstable angina pectoris (UAP), and severe heart failure requiring hospitalization. The stress phase bandwidth (SPBW) was calculated by phase analysis with the Heart Risk View-F software and its normal upper limit was set to 38°. During the follow-up, 64 patients experienced MCEs: Cardiac death (n = 11), non-fatal MI (n = 5), UAP (n = 26), and severe heart failure (n = 22). The results of the multivariate analysis showed the ∆summed difference score %, ∆stress LV ejection fraction, and stress SPBW after revascularization to be independent predictors of MCEs. Additionally, the results of the multivariate logistic regression analysis showed the summed rest score%, summed difference score%, stress LV ejection fraction, and perfusion defects in the left circumflex artery region before revascularization to be independent predictors for normalized SPBW after revascularization. The prognosis of patients who normalized SPBW after revascularization was similar to that of patients with a normal SPBW before revascularization, while patients who did not normalize after revascularization had the worst prognosis. In conclusion, normalization of LV dyssynchrony after revascularization assessed with nuclear cardiology may help predict future MCEs and thus a useful indicator for predicting improved prognosis in patients with CAD.

In situ study of sensor behavior of MoS2 field effect transistor for methyl orange molecule in ultra high vacuum condition.

We investigate the sensor behavior of the MoS2 field effect transistor (FET) device with the deposition of methyl orange (MO) molecule which is widely used as a chemical probe. The channel of the FET is made of the single layer of MoS2 which makes it highly sensitive to the molecule adsorption, but at the same time the behavior depends much on the surface conditions of the MoS2 channel. In order to make the channel-surface conditions more defined, we prepare an in situ experimental system in which the molecule deposition and the surface- and electrical-characterization of the MoS2 FET are executed in a single ultra-high vacuum chamber. This system makes it possible to examine the change of the FET properties with precise control of the molecule coverage in the sub-monolayer region without the effect of the atmosphere. We detected the shift of the I d-V g curve of the MoS2-FET device with the increase of the molecule coverage (θ) of the MO molecule, which is quantitatively analyzed by plotting the threshold voltage (V th) of the I d-V g curve as a function of θ. The V th shifts towards the negative direction and the initial change with θ can be expressed with an exponential function of θ, which can be accounted for with the Langmuir type adsorption of the molecule for the first layer and the charge transfer from the molecule to the substrate. The V th versus θ curve shows a kink at a certain θ, which is conserved as the starting of the second layer growth. We detected the adsorption of MO far less than monolayer and the phase change from the first layer to the second layer growth, which is realized by the benefit of the in situ UHV experimental condition.

Use of a Novel Fluorescent Catheter to Locate the Ureters during Total Laparoscopic Hysterectomy.

Ureteral injury can occur during total laparoscopic hysterectomy. This report documents our experience in using the near-infrared ray catheter (NIRC), a newly developed fluorescent ureteral catheter made of material that contains a fluorescent dye to improve visualization of the ureters. We have used the device in 3 patients between 40 and 50 years of age (mean, 46.3 ± 4.5 years) undergoing total laparoscopic hysterectomy and bilateral salpingectomy for uterine myomas. The time of catheter insertion ranged from 4 minutes and 9 seconds to 10 minutes and 57 seconds. A number of intraoperative procedures were performed near the ureters, namely, identification and ligation of the uterine arteries, dissection of the cardinal ligament, incision of the vaginal canal, and suturing of the vaginal stump. The abovementioned fluorescent ureteral catheter appears green on a monitor when illuminated by near-infrared light, and this facilitated real-time confirmation of the ureter positions, increasing surgical safety. The patients were followed up for 6 months postoperatively, and no urinary tract infection or injury was found. Prophylactic use of the fluorescent ureteral catheter may improve visualization of the ureters in patients considered to be at high risk of ureteral injury, such as those expected to exhibit ureteral deviation due to severe adhesions or an enlarged uterus and when the surgeon has little experience in laparoscopic surgery.

Synthesis and Guest-Binding Properties of pH/Reduction Dual-Responsive Cyclophane Dimer.

A water-soluble cyclophane dimer having two disulfide groups as a reduction-responsive cleavable bond as well as several acidic and basic functional groups as a pH-responsive ionizable group 1 was successfully synthesized. It was found that 1 showed pH-dependent guest-binding behavior. That is, 1 strongly bound an anionic guest, 6-p-toluidinonaphthalene-2-sulfonate (TNS) with binding constant (K/M-1) for 1:1 host-guest complexes of 9.6 × 104 M-1 at pH 3.8, which was larger than those at pH 7.4 and 10.7 (6.0 × 104 and 2.4 × 104 M-1, respectively), indicating a favorable electrostatic interaction between anionic guest and net cationic 1. What is more, release of the entrapped guest molecules by 1 was easily controlled by pH stimulus. Large favorable enthalpies (ΔH) for formation of host-guest complexes were obtained under the pH conditions employed, suggesting that electrostatic interaction between anionic TNS and 1 was the most important driving force for host-guest complexation. Such contributions of ΔH for formation of host-guest complexes decreased along with increased pH values from acidic to basic solutions. Upon addition of dithiothreitol (DTT) as a reducing reagent to an aqueous PBS buffer (pH 7.4) containing 1 and TNS, the fluorescence intensity originating from the bound guest molecules decreased gradually. A treatment of 1 with DTT gave 2, having less guest-binding affinity by the cleavage of disulfide bonds of 1. Consequently, almost all entrapped guest molecules by 1 were released from the host. Moreover, such reduction-responsive cleavage of 1 and release of bound guest molecules was performed more rapidly in aqueous buffer at pH 10.7.

Experimental and Theoretical Investigation of an SN2-type Pathway for Borate-Fluorine Bond Cleavage by Electron-Rich Late-Transition Metal Complexes.

B-F σ-bond activation of a fluoroborate has been experimentally achieved through reactions with electron-rich iridium(I) and palladium(0) complexes. The selectivity of B-F σ-bond cleavage by iridium complexes was improved through the high nucleophilicity of the iridium center, implying that a different pathway from that of well-accepted F- abstraction was in effect. The palladium(0) complex was found to promote exclusive B-F σ-bond cleavage even at ambient temperature. Density functional theory (DFT) calculations suggested that B-F σ-bond activation occurred through an SN2-type pathway, which is, to our knowledge, the first proposal of SN2-type borate-fluorine σ-bond cleavage mediated by a transition metal complex. The high feasibility of the SN2-type pathway appears to be attributed to the relatively low deformation energy of the transition state. It was also found that countercation Cs+ effectively stabilized the transition state and product by serving as a F- acceptor.

Microfluidic tank assisted nicotine sensing property of field effect transistor composed of an atomically thin MoS2 channel.

We investigated the sensor behavior of a field effect transistor, the channel of which is made of atomically thin MoS2 layers, focusing on the interaction of the MoS2 channel with the solution containing target molecules. For this purpose, we made a newly designed device in which the mask covered the electrodes of the source and the drain in order to make the solution contact only with the channel. In addition, a micro-fluid tank was fabricated above the channel as a solution reservoir. We examined the FET properties of this device for the sensing of the nicotine molecule for the development of a detection system for this molecule in the human body under in vivo conditions. We detected the sensor behavior both for the drop-cast process and for the condition where the channel contacts with the solution. The drain-current vs. gate-voltage variation of the MoS2-FET with the attachment of the nicotine molecule was clearly observed for both cases. For the latter case, the threshold voltage shifted in the negative gate-voltage direction with the increase of the concentration of the nicotine in the solution. This can be explained by the electron transfer from the molecule to the MoS2 channel, which was further confirmed by analyzing the X-ray photoemission spectroscopy and Raman spectroscopy together with the DFT calculation. The sensor can detect the variation of the nicotine concentration in the IPA solution by detecting the Vth change of the MoS2-FET.

Phase III trial comparing the efficacy and safety of recombinant- or urine-derived human chorionic gonadotropin for ovulation triggering in Japanese women diagnosed with anovulation or oligo-ovulation and undergoing ovulation induction with follitropin-alfa.

Aim: Outside of Japan, recombinant-human chorionic gonadotropin (r-hCG) is widely used for the induction of final follicular maturation and early luteinization in women undergoing ovulation induction; whereas in Japan, urine-derived hCG (u-hCG) is predominantly used. The primary objective of this study was to demonstrate the non-inferiority of r-hCG to u-hCG for ovulation induction, as assessed by the ovulation rate. Methods: This was an open-label, parallel-group, randomized, multicenter, phase III trial in Japanese women with anovulation or oligo-ovulation secondary to hypothalamic-pituitary dysfunction or polycystic ovary syndrome, undergoing ovulation induction with recombinant-human follicle-stimulating hormone. The women were randomized (2:1) to receive either a single 250 µg s.c. dose of r-hCG or a single 5000 IU i.m. dose of u-hCG for ovulation triggering. Results: Eighty-one women were randomized to either r-hCG (n=54) or u-hCG (n=27). Ovulation occurred in 100% of the participants and treatment with r-hCG was observed to be non-inferior to u-hCG for ovulation induction. Overall, the type and severity of adverse events were as expected for women receiving fertility treatment. Conclusion: This study demonstrated that r-hCG was non-inferior to u-hCG for inducing ovulation. Furthermore, r-hCG demonstrated an expected safety profile, with no new safety concerns identified.

Association between an early revascularization strategy and major cardiac events based on left ventricular dyssynchrony in patients at intermediate risk of major cardiac events using the J-ACCESS risk model.

Objective This retrospective study aimed to investigate the association between therapeutic strategies and the development of major cardiac events (MCEs) in intermediate-risk patients by using the J-ACCESS risk model in combination with the stress phase bandwidth (SPBW), an index of left ventricular dyssynchrony. Methods Patients were followed-up for three years to confirm their prognosis. Based on the estimated propensity scores, the patients who underwent revascularization within the first 60 days after SPECT and those who did not were matched 1:1 (n = 367 per group). The composite endpoint was the occurrence of MCEs, consisting of cardiac death, non-fatal myocardial infarction, and severe heart failure. SPBW was calculated by a phase analysis using the Heart Risk View-F software program, and the MCE rate was compared between the two groups by applying the normal value of SPBW (38°). Patients The study included 2,053 patients with either known or suspected CAD who underwent electrocardiogram-gated single-photon emission computed tomography myocardial perfusion imaging and were at intermediate risk of MCE according to the J-ACCESS risk model. Results During follow-up, 54 of the 734 patients (7.4%) experienced MCEs. The overall incidence of MCE in intermediate-risk patients was not significantly different between the two groups. However, the incidence of MCE in patients with an abnormal SPBW was significantly lower in those who underwent early revascularization (4.8% vs. 11.9%, P = 0.0407). Conclusion The combination of the J-ACCESS risk model and the SPBW is thus considered to be an optimal treatment strategy for patients at intermediate risk of MCE, and early revascularization may lead to an improved prognosis in intermediate-risk patients with an abnormal SPBW.

A case of repeated stent fracture.

Stent fracture is one of the complications of drug-eluting stent implantation. An 84-year-old man underwent coronary angiography for unstable angina. He had diffuse severe stenosis and calcified plaque in the left anterior descending artery and underwent percutaneous coronary intervention (PCI) in the left anterior descending artery for severe stenosis with chest pain. Thereafter, two subsequent stent fractures occurred, so the patient underwent another PCI to cover them. However, a stent fracture was found again one year later. The patient was asymptomatic and PCI was avoided due to the risk of further stent fracture. When a stent fracture occurs, it is important to provide appropriate treatment according to the anatomical findings of the vessel, symptoms and the presence of ischemia.

Performance of Generative Pretrained Transformer on the National Medical Licensing Examination in Japan.

The remarkable performance of ChatGPT, launched in November 2022, has significantly impacted the field of natural language processing, inspiring the application of large language models as supportive tools in clinical practice and research worldwide. Although GPT-3.5 recently scored high on the United States Medical Licensing Examination, its performance on medical licensing examinations of other nations, especially non-English speaking nations, has not been sufficiently evaluated. This study assessed GPT's performance on the National Medical Licensing Examination (NMLE) in Japan and compared it with the actual minimal passing rate for this exam. In particular, the performances of both the GPT-3.5 and GPT-4 models were considered for the comparative analysis. We initially used the GPT models and several prompts for 290 questions without image data from the 116th NMLE (held in February 2022 in Japan) to maximize the performance for delivering correct answers and explanations of the questions. Thereafter, we tested the performance of the best GPT model (GPT-4) with optimized prompts on a dataset of 262 questions without images from the latest 117th NMLE (held in February 2023). The best model with the optimized prompts scored 82.7% for the essential questions and 77.2% for the basic and clinical questions, both of which sufficed the minimum passing scoring rates of 80.0% and 74.6%, respectively. After an exploratory analysis of 56 incorrect answers from the model, we identified the three major factors contributing to the generation of the incorrect answers-insufficient medical knowledge, information on Japan-specific medical system and guidelines, and mathematical errors. In conclusion, GPT-4 with our optimized prompts achieved a minimum passing scoring rate in the latest 117th NMLE in Japan. Beyond its original design of answering examination questions for humans, these artificial intelligence (AI) models can serve as one of the best "sidekicks" for solving problems and addressing the unmet needs in the medical and healthcare fields.

Association Between Aortic Wall Parameters on Multidetector Computed Tomography and Ruptured Plaques By Nonobstructive General Angioscopy.

BACKGROUND: Nonobstructive general angioscopy (NOGA) can identify vulnerable plaques in the aortic lumen that serve as potential risk factors for cardiovascular events such as embolism. However, the association between computed tomography (CT) images and vulnerable plaques detected on NOGA remains unknown. METHODS AND RESULTS: We investigated 101 patients (67±11 years; women, 13.8%) who underwent NOGA and contrast-enhanced CT before or after 90 days in our hospital. On CT images, the aortic wall thickness, aortic wall area (AWA), and AWA in the vascular area were measured at the thickest point from the 6th to the 12th thoracic vertebral levels. Furthermore, the association between these measurements and the presence or absence of NOGA-derived aortic plaque ruptures (PRs) at the same vertebral level was assessed. NOGA detected aortic PRs in the aortic lumens at 145 (22.1%) of the 656 vertebral levels. The presence of PRs was significantly associated with greater aortic wall thickness (3.3±1.7 mm versus 2.1±1.2 mm), AWA (1.33±0.68 cm2 versus 0.89±0.49 cm2), and AWA in the vascular area (23.2%±9.3% versus 17.2%±7.6%) (P<0.001 for all) on the CT scans compared with the absence of PRs. The frequency of PRs significantly increased as the aortic wall thickness increased. Notably, a few NOGA-derived PRs were detected on CT in near-normal intima. CONCLUSIONS: The presence of NOGA-derived PRs was strongly associated with increased aortic wall thickness, AWA, and AWA in the vascular area, measured using CT. NOGA can detect PRs in the intima that appear almost normal on CT scans.