In-silico simultaneous respiratory and circulatory measurement during voluntary breathing, exercise, and mental stress: A computational approach.

Voluntary breathing (VB), short-term exercise (STE), and mental stress (MS) can modulate breathing rate (BR), heart rate (HR), and blood pressure (BP), thereby affecting human physical and mental state. While existing experimental studies have explored the relationship between VB, STE, or MS and BR, HR, and BP changes, their findings remain fragmented due to individual differences and challenges in simultaneous, BR, HR, and BP measurements. We propose a computational approach for in-silico simultaneous measurements of the physiological values by comprehensive prediction of the respiratory and circulatory system responses to VB, STE, or MS.

Prognostic factors and treatment choice for stage IV, low-volume metastasis hormone-sensitive prostate cancer: cross-sectional study of real-world data.

Background: Many metastatic prostate cancer prognostics have been suggested, but few are validated. Nodal metastasis burden and baseline biochemical characteristics are overlooked in the currently accepted stratifications for metastatic hormone-sensitive prostate cancer (mHSPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is likely to increase the incidence of pelvic nodal and mHSPC undetected by conventional scans.

Antagonistic Feedback Control of Muscle Length Changes for Efficient Involuntary Posture Stabilization.

Simultaneous and cooperative muscle activation results in involuntary posture stabilization in vertebrates. However, the mechanism through which more muscles than joints contribute to this stabilization remains unclear. We developed a computational human body model with 949 muscle action lines and 22 joints and examined muscle activation patterns for stabilizing right upper or lower extremity motions at a neutral body posture (NBP) under gravity using actor-critic reinforcement learning (ACRL).

Structure-Activity Relationship Study of CYM51010, an agonist for the µ-δ Opioid Receptor Heterodimer.

Although opioid analgesics are indispensable in treating pain, these drugs are accompanied by life-threatening side effects. While clinically relevant opioid drugs target the µ opioid receptor (MOR), a heterodimer between the MOR and the δ opioid receptor (DOR) has emerged as another target to develop safer analgesics. Although some heterodimer-preferring agonists have been reported so far, it is still difficult to activate the MOR/DOR heterodimer selectively in the presence of MOR or DOR monomers/homodimers.

Impact of LAG-3/FGL1 pathway on immune evasive contexture and clinical outcomes in advanced urothelial carcinoma.

Background: Anti-programmed death-1 (PD-1)/anti-PD-ligand-1 (PD-L1) pathway inhibition is a standard regimen for advanced urothelial carcinoma (UC); however, its limited efficacy has been reflected in reported medium response rates. This study explored the role of next-generation coinhibitory receptors (IRs; lymphocyte activation gene 3 (LAG-3), T-cell immunoglobulin and mucin domain 3 (TIM-3), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT)) and their ligands (LGs) in the response to PD-(L)1 blockade therapy and the oncological outcomes in patients with UC.

Methods: We investigated metastatic UC cases who underwent PD-(L)1 therapy (cohort 1: n=348, cohort 2: n=89, and cohort 4: n=29) or advanced UC cases involving surgery (cohort 3: n=293 and cohort 5: n=90).