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Background: Pulmonary artery involvement (PAI) is not rare in Takayasu arteritis (TA). Persistently elevated pulmonary arterial pressure in TA‐PAI patients leads to pulmonary hypertension (PH), and eventually cardiac death. Thus, the early detection of right ventricular dysfunction before the onset of PH is important. Purpose: To explore the potential of right ventricular global peak longitudinal and circumferential strain (RVGLS and RVGCS, respectively) in detecting right ventricular myocardial damage in TA‐PAI patients without PH. Study Type: Retrospective. Population: One hundred and six TA patients (39.6 ± 13.9 years), of whom 52 were non‐PAI and 54 were PAI patients (36 without PH and 18 with PH), along with 58 sex‐ and age‐matched healthy volunteers (HVs) (36.7 ± 13.2 years). The involved arteries were validated by aorta magnetic resonance (MR) angiography and pulmonary artery computed tomography angiography. Field Strength/Sequence: 3 T/Cine imaging sequence with a steady‐state free precession readout. Assessment: Cardiac MRI‐derived parameters measured by two radiologists independently were compared among HVs, and TA patients with and without PAI. In addition, these indices were further compared among HVs, and TA‐PAI patients with and without PH. Statistical Tests: Student's t test, one‐way ANOVA analysis, Pearson and Spearman correlation analysis, and reproducibility analysis. A P‐value of <0.05 was considered statistically significant. Results: Although the TA‐PAI patients without PH had a similar RV ejection fraction (RVEF) with HV (P = 0.348), RVGLS (non‐PH 20.6 ± 3.7% vs. HV 24.0 ± 3.1%) was significantly lower and RVGCS (non‐PH 14.8 ± 3.9% vs. HV 13.0 ± 2.7%) higher. The TA‐PAI patients with PH had significantly poorer RVGLS (PH 13.5 ± 3.8% vs. non‐PH 20.6 ± 3.7%) and RVGCS (PH 10.9 ± 3.2% vs. non‐PH 14.8 ± 3.9%) than those without PH. Data Conclusion: Right ventricular dysfunction was detected in the TA‐PAI patients without PH. MR‐feature tracking may be an effective method for detecting early cardiac damage in the TA‐PAI patients without PH. Level of Evidence: 3 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Targeting receptor‐interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [11C]CNY‐10 is reported, which may enable brain RIPK1 imaging. [11C]CNY‐10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [11C]CNY‐10 is characterized by PET imaging in rodents and a non‐human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [11C]CNY‐10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [11C]CNY‐10‐based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [11C]CNY‐10 for AD and potentially other RIPK1‐related human studies. [ABSTRACT FROM AUTHOR]

On August 11, 2022, FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd, ENHERTU, Daiichi Sankyo) for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. The approval was based on a prespecified interim analysis of DESTINY-Lung02 (Study U206), a multi-center, randomized, dose-optimization trial in patients with NSCLC harboring activating HER2 -mutations. At the approved dose of 5.4 mg/kg given intravenously every 3 weeks, the overall response rate (ORR) was 58% (95% confidence interval [CI]: 43, 71). The median duration of response was 8.7 months (95% CI: 7.1, not estimable). These results were consistent with response rates observed at the 6.4 mg/kg dose level. The most common (≥ 20%) adverse reactions were nausea, constipation, decreased appetite, vomiting, fatigue, and alopecia. The rate of interstitial lung disease (ILD) or pneumonitis was 6% at the 5.4 mg/kg dose level and 14% at the 6.4 mg/kg dose level. In the setting of similar efficacy and reduced toxicity, approval was granted for the 5.4 mg/kg dose level. The applicant conducted a randomized, dose-optimization study with guidance from the FDA Oncology Center of Excellence's Project Optimus. This is the first approval of a targeted therapy for HER2 -mutated NSCLC. [ABSTRACT FROM AUTHOR]

The coupling effects between the stage house and the auditorium in opera houses make the sound field very complex. In the present study, the effects of stage absorption on the primary monaural objective room acoustic parameters in the seating area of an opera house in China were investigated by means of computer simulation and scaled model measurement. In computer simulations, the absorption coefficient of the ceiling and walls of the stage house was changed across several steps, and then a series of experiments were conducted in a 1:20 scaled hall with and without curtains and wall absorption on the stage to verify the simulation results. It was found that stage absorption has a significant influence on early decay time (EDT), reverberation time (RT) and clarity (C80) in the seating area, while the effect on sound strength (G) is much smaller. The values of EDT and RT decrease with an increase in sound absorption on the stage, while C80 displays an opposite trend. In addition, when the average absorption coefficient of the stage walls and ceiling is over 0.5, the variations in these four parameters due to the increase in stage absorption can be constrained within an acceptable range. [ABSTRACT FROM AUTHOR]

Elsinochrome A (EA) is a naturally occurring photosensitizer with potential applications in photodynamic therapy (PDT) for various malignancies. Despite its promising therapeutic properties, the poor solubility of EA hampers its effective utilization in clinical settings. To circumvent this limitation, we engineered four distinct nano-formulations: PLGA/EA nanoparticles (NPs), CMC-PLGA/EA NPs, mPEG-PCL/EA nanomicelles (NMs), and LHP-CHOL/EA nanoliposomes (NLs), all designed to enhance the solubility of EA. A comparative evaluation of these formulations, based on metrics such as particle size, Zeta potential, drug loading efficiency, and encapsulation efficiency, identified PLGA/EA NPs and mPEG-PCL/EA NMs as the most efficacious candidates. Subsequent in vitro investigations into the drug release kinetics under varying pH conditions and the impact on cell viability and apoptosis in A549 and MCF-7 cell lines were conducted. Remarkably, the maximum drug release for PLGA/EA NPs and mPEG-PCL/EA NMs was recorded at 62.5% and 70.8% in an acidic environment (pH 5.7), respectively. Upon exposure to 460 nm light, PLGA/EA NPs induced a significant reduction in A549 cell viability to 13.8% and an apoptosis rate of 93.8%, whereas mPEG-PCL/EA NMs elicited a decrease in MCF-7 cell viability to 12.8% and an apoptosis rate of 73.0%. [ABSTRACT FROM AUTHOR]