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Aims: To investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BPL-003, a novel intranasal benzoate salt formulation of 5-methoxy- N,N -dimethyltryptamine (5-MeO-DMT), in healthy participants. Methods: In all, 44 psychedelic-naïve participants enrolled in the double-blind, placebo-controlled single ascending dose study (1–12 mg BPL-003). Concentrations of 5-MeO-DMT and its pharmacologically active metabolite, bufotenine, were determined in plasma and urine. PD endpoints included subjective drug intensity (SDI) rating, the Mystical Experience Questionnaire (MEQ-30) and the Ego Dissolution Inventory (EDI). Results: BPL-003 was well tolerated at doses up to 12 mg. There were no serious adverse events (AEs), and most AEs were mild; the most common being nasal discomfort, nausea, headache and vomiting. 5-MeO-DMT was rapidly absorbed and eliminated; the median time to peak plasma concentration was approximately 8–10 min and the mean terminal elimination half-life was <27 min. 5-MeO-DMT systemic exposure increased approximately dose-proportionally, while plasma bufotenine concentrations and urinary excretion of 5-MeO-DMT and bufotenine were negligible. The intensity of the SDI ratings was associated with plasma 5-MeO-DMT concentrations. MEQ-30 and EDI scores generally increased with the BPL-003 dose; 60% of participants had a 'complete mystical experience' at 10 and 12 mg doses. Profound and highly emotional consciousness-altering effects were observed with BPL-003, with a rapid onset and short-lasting duration. Conclusion: The novel intranasal formulation of BPL-003 was well tolerated with dose-proportional increases in PK and PD effects. The short duration of action and induction of mystical experiences suggest clinical potential, warranting further trials. Clinical trial registration: NCT05347849. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the improvement in gait velocity variability after cerebrospinal fluid (CSF) elimination, and the association between gait velocity variability and gait and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. Methods: The gait velocity of 44 patients with idiopathic normal pressure hydrocephalus was measured using the Timed Up and Go Test (TUG) for a total of 10 times over 3 days each before and after CSF elimination. The coefficient of variation (CV) in the time required for the sequence of actions in TUG (TUG‐CV) was calculated using 10 TUG data, and used for measuring intraindividual gait velocity variability. Gait quality was evaluated with the Gait Status Scale Revised (GSSR), and cognitive function was evaluated with the Mini‐Mental State Examination and the Frontal Assessment Battery. Results: The TUG, TUG‐CV, GSSR and Frontal Assessment Battery results improved significantly after CSF elimination. The analyses using pre‐CSF elimination results showed that the TUG‐CV significantly and positively correlated with the TUG and GSSR results, and negatively with Mini‐Mental State Examination results, but not with age and the Frontal Assessment Battery results. The stepwise multiple regression analysis indicates that the TUG, GSSR and Mini‐Mental State Examination results were significant predictors of the TUG‐CV. The analysis using data of change after CSF elimination showed that ΔTUG and ΔGSSR were significant predictors of ΔTUG‐CV. Conclusions: Gait velocity variability improved after CSF elimination, and gait velocity variability was associated with gait disturbances and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. Geriatr Gerontol Int 2024; 24: 693–699. [ABSTRACT FROM AUTHOR]

Sparse connectivity of a superconducting quantum computer results in large experimental overheads of SWAP gates. In this study, we consider employing a virtual two-qubit gate (VTQG) as an error suppression technique. The VTQG enables a non-local operation between a pair of distant qubits using only single qubit gates and projective measurements. Here, we apply the VTQG to the digital quantum simulation of the transverse-field Ising model on an IBM quantum computer to suppress the errors due to the noisy two-qubit operations. We present an effective use of VTQG, where the reduction in multiple SWAP gates results in increasing the fidelity of output states. The obtained results indicate that the VTQG can be useful for suppressing the errors due to additional SWAP gates. In our experiments, we have observed one order of magnitude improvement in accuracy for the quantum simulation of the transverse-field Ising model with 8 qubits. Finally, we have demonstrated an efficient implementation of the VTQG by utilizing dynamic circuits. This scheme reduces experimental overheads for implementing m VTQGs from O (10 m) to O (6 m). [ABSTRACT FROM AUTHOR]

Transient noise appearing in the data from gravitational‐wave detectors frequently causes problems, such as instability of the detectors and overlapping or mimicking gravitational‐wave signals. Because transient noise is considered to be associated with the environment and instrument, its classification would help to understand its origin and improve the detector's performance. In a previous study, an architecture for classifying transient noise using a time–frequency 2D image (spectrogram) is proposed, which uses unsupervised deep learning combined with variational autoencoder and invariant information clustering. The proposed unsupervised‐learning architecture is applied to the Gravity Spy dataset, which consists of Advanced Laser Interferometer Gravitational‐Wave Observatory (Advanced LIGO) transient noises with their associated metadata to discuss the potential for online or offline data analysis. In this study, focused on the Gravity Spy dataset, the training process of unsupervised‐learning architecture of the previous study is examined and reported. [ABSTRACT FROM AUTHOR]

Background: The thromboxane receptor (TP) antagonist NTP42 is in clinical development for treatment of cardiopulmonary diseases, such as pulmonary arterial hypertension. In this randomized, placebo-controlled Phase I clinical trial, NTP42, administered as the oral formulation NTP42:KVA4, was evaluated for safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in healthy males. Methods: The first-in-human trial had three Parts: A, single ascending dose (SAD) study with seven groups given 0.25–243 mg NTP42:KVA4 or placebo; B, food effect study where one SAD group (9 mg) was also given NTP42:KVA4 or placebo after a high-fat breakfast; C, multiple ascending dose study with three groups given 15–135 mg NTP42:KVA4 or placebo once-daily for 7 days. Results: Seventy-nine volunteers participated. No serious adverse events occurred, where any drug- or placebo-related adverse events were mild to moderate, with no correlation to NTP42:KVA4 dose. NTP42 was rapidly absorbed, yielding dose proportional increases in exposure after single and repeat dosing. PK confirmed that, with a clearance (T1/2) of 18.7 h, NTP42:KVA4 is suited to once-daily dosing, can be taken with or without food, and does not accumulate on repeat dosing. At doses ≥1 mg, NTP42 led to complete and sustained inhibition of thromboxane-, but not ADP-, induced platelet aggregation ex vivo, with direct correlation between NTP42 exposure and duration of PD effects. Conclusion: Orally administered NTP42:KVA4 was well tolerated, with favorable PK/PD profiles and evidence of specific TP target engagement. These findings support continued clinical development of NTP42:KVA4 for cardiopulmonary or other relevant diseases with unmet needs. [ABSTRACT FROM AUTHOR]

Background: The assessment of small metastatic liver tumours using dual-energy computed tomography (DECT) has not been fully established. Purpose: To assess the effect of low-keV virtual monochromatic imaging (VMI) with non-contrast and contrast-enhanced DECT on the qualitative and quantitative image parameters of small liver metastases. Material and methods: Two radiologists retrospectively evaluated 92 metastatic liver tumours (5–20 mm) in 32 patients. Non-contrast and contrast-enhanced VMI were reconstructed at seven energy levels (40–100 keV) with 10-keV intervals. Lesion boundary, lesion delineation, image noise, and overall image quality were evaluated using the visual analogue scale. A high subjective score indicates good overall image quality, clear nodal boundaries and delineation, and less noticeable image noise. Subjective scores were compared using the Kruskal–Wallis test. A quantitative analysis involving the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) was performed. Results: The lesion boundary was highest at 40 keV and significantly improved during the non-contrast portal venous phase compared to that at higher keV (p <.005). The lesion delineation score was significantly higher at 40 keV and tended to decrease at higher keV. Image noise and overall image quality were rated low at low keV; however, those at 80, 90, and 100 keV were rated the highest (p <.005). The CNR and SNR were highest for non-contrast CT at 100 keV. During the portal venous phase, no significant differences were observed in CNR and SNR at each keV. Conclusion: Low-keV imaging using non-contrast and contrast-enhanced DECT is useful for delineating small hepatic metastatic tumours. Graphical Abstract [ABSTRACT FROM AUTHOR]