Concerted or Stepwise? An Experimental and Computational Study to Reveal the Mechanistic Change as a Result of the Substituent Effects.

This study investigates the Cope elimination reaction, focusing on the mechanistic shift between concerted and stepwise pathways influenced by substituent effects. Experimental approaches, including kinetic isotope effects (KIEs) and linear free energy relationships (LFERs), alongside density functional theory (DFT) computations, were employed to explore the influence of substituents on the reaction kinetics and pathways. Our findings reveal temperature- and substituent-dependent partitioning between the concerted syn-β elimination and the stepwise E1cB mechanism, providing deeper insights into the mechanistic diversity of elimination reactions.

Safety and tolerability of the M2 muscarinic acetylcholine receptor modulator BAY 2413555 in heart failure with reduced ejection fraction in the REMOTE-HF study.

BAY 2413555 is a novel selective and reversible positive allosteric modulator of the type 2 muscarinic acetylcholine (M2) receptor, aimed at enhancing parasympathetic signaling and restoring cardiac autonomic balance for the treatment of heart failure (HF). This study tested the safety, tolerability and pharmacokinetics of this novel therapeutic option. REMOTE-HF was a multicenter, double-blind, randomized, placebo-controlled, phase Ib dose-titration study with two active arms.

Disentangling the Impact of Forest Management Intensity Components on Soil Biological Processes.

Temperate forests cover 25% of the world's forest area and most of them are managed for timber production. To increase yields, native deciduous trees have been commonly replaced by fast-growing conifers, especially in Western and Central Europe. Despite the importance of forest soils for a variety of ecosystem functions, the effects of forest management intensity on soil biological processes have not yet been sufficiently understood.

Investigating context-specific sedentary behaviours and cardiometabolic health in college-based young adults (CONTEXT-SB): a protocol for a longitudinal observational study.

Background: Sedentary behaviour (SB) is detrimental to cardiometabolic disease (CMD) risk, which can begin in young adulthood. To devise effective SB-CMD interventions in young adults, it is important to understand which context-specific SB (CS-SB) are most detrimental for CMD risk, the lifestyle behaviours that cluster with CS-SBs and the socioecological predictors of CS-SB.

Methods And Analysis: This longitudinal observational study will recruit 500 college-aged (18-24 years) individuals.

ADNI Private Partners Scientific Board (PPSB) Diversity, Equity, and Inclusion (DE&I) Working Group: A new collaboration that crosses boundaries for industry, academia, and under-represented patients.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partners Scientific Board (PPSB) Diversity, Equity, and Inclusion Working Group (DE&I WG) was established to work with the ADNI3 Diversity Task Force to provide an industry perspective on increasing the representation of diverse participants in ADNI3 and to build precompetitive cross-industry knowledge in engagement and recruitment of under-represented participants (URPs). In this article, we review and highlight the role and ongoing activities within the ADNI PPSB DE&I WG and provide a cross-industry perspective on areas where precompetitive collaboration can improve the inclusiveness in clinical trials, drawing on examples from ADNI4. HIGHLIGHTS: New collaboration crosses boundaries to allow PPSB DE&I WG members to work together in a preproprietary way.