Introspection about forced and free choice: Accurate subjective time estimation for externally as well as self-determined actions.

Free-choice behavior is unique in that actions are internally self-determined, unlike forced-choice behavior, which is externally specified. Several studies suggest these two action modes can lead to different behavioral, affective, and motivational outcomes. We examined whether people estimate free-choice differently from forced-choice processing time due to possible introspective biases associated with these modes.

3-Dimensional morphological characterization of neuroretinal microglia in Alzheimer's disease via machine learning.

Alzheimer's Disease (AD) is a debilitating neurodegenerative disease that affects 47.5 million people worldwide. AD is characterised by the formation of plaques containing extracellular amyloid-β (Aβ) and neurofibrillary tangles composed of hyper-phosphorylated tau proteins (pTau).

Psychotropic medication usage in sporadic versus genetic behavioral-variant frontotemporal dementia.

Introduction: Psychotropic medication (PM) use in behavioral-variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD.

Methods: We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study.

Vascular and inflammatory biomarkers of cardiovascular events in non-steroidal anti-inflammatory drug users.

Aims: The Standard care vs. Celecoxib Outcome Trial (SCOT) found similar risk of cardiovascular events with traditional non-steroidal anti-inflammatory drugs (NSAIDs) and the cyclooxygenase-2-selective drug celecoxib. While pre-clinical work has suggested roles for vascular and renal dysfunction in NSAID cardiovascular toxicity, our understanding of these mechanisms remains incomplete.

Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA).

The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014-2019; 2019-2024) have occurred following peer review, and a third cycle (Phase 3) has just begun. A unique construct was mandated, consisting of 20 national teams in Phase I and 19 teams in Phase II (with research topics spanning from basic to clinical science to health resource systems) along with cross-cutting programs to support them.

Towards Designer Photocatalysts: Structure-Property Relationships in 2,6-Diaryl-pyryliums.

Fully organic photocatalyst systems are highly attractive, not merely because they are transition-metal free, but more importantly due to their unique and often potent reactivity. A detailed understanding of the various redox states, both ground and excited state, and specifically what structural parameters control them is therefore crucial for harnessing the full potential of these systems in organic synthesis. However, unlike their organometallic counterparts, detailed structure-property relationships for organic photocatalysts are largely absent from the literature.

A comment on the Revised Diffusion Model for Conflict tasks (RDMC).

In conflict tasks, such as the Simon, Eriksen flanker, or Stroop task, a relevant and an irrelevant feature indicate the same or different responses in congruent and incongruent trials, respectively. The congruency effect refers to faster and less error-prone responses in congruent relative to incongruent trials. Distributional analyses reveal that the congruency effect in the Simon task becomes smaller with increasing RTs, reflected by a negative-going delta function.

Escape rooms in pharmacy education: More than just a game.

Unlabelled: An educational escape room is a form of game-based learning that has been shown to improve students' learning experience. A cardiovascular escape room was designed to promote the development of transversal skills and help students retain learned content knowledge in an integrated pharmacology and therapeutic unit in a Pharmacy course.

Objective: This study aims to design, pilot, and evaluate the students' self-perceived transversal skills, learning experience and knowledge acquisition from a cardiovascular educational escape room.

The Digital Platform and Its Emerging Role in Decentralized Clinical Trials.

Decentralized clinical trials (DCTs) are becoming increasingly popular. Digital clinical trial platforms are software environments where users complete designated clinical trial tasks, providing investigators and trial participants with efficient tools to support trial activities and streamline trial processes. In particular, digital platforms with a modular architecture lend themselves to DCTs, where individual trial activities can correspond to specific platform modules.

Photomediated Hexafluoroisopropoxylation of Unactivated Aryl Halides.

The use of fluoroalkoxy groups, such as trifluoromethoxy and 2,2,2-trifluoroethoxy groups, in pharmaceutical and agrochemical development has increased dramatically in recent years. However, hexafluoroisopropoxy groups have remained significantly under-represented, presumably due to limited synthetic methods for accessing this substituent in good yields. Herein, we report a mild, photochemical nucleophilic aromatic substitution (SAr) approach for the synthesis of hexafluoroisopropyl aryl ethers from unactivated and abundant aryl halides.

The influence of reward and loss outcomes after free- and forced-tasks on voluntary task choice.

In four experiments, we investigated the impact of outcomes and processing mode (free versus forced) on subsequent voluntary task-switching behavior. Participants freely chose between two tasks or were forced to perform one, and the feedback they received randomly varied after correct performance (reward or no-reward; loss or no-loss). In general, we reasoned that the most recently applied task goal is usually the most valued one, leading people to prefer task repetitions over switches.

Genotype-Blinded Trial of Ambulatory Blood Pressure Response to Torasemide.

Background: UMOD (uromodulin) has been linked to hypertension through potential activation of Na-K-2Cl cotransporter (NKCC2), a target of loop diuretics. We posited that hypertensive patients carrying the rs13333226-AA genotype would demonstrate greater blood pressure responses to loop diuretics, potentially mediated by this UMOD/NKCC2 interaction.

Methods: This prospective, multicenter, genotype-blinded trial evaluated torasemide (torsemide) efficacy on systolic blood pressure (SBP) reduction over 16 weeks in nondiabetic, hypertensive participants uncontrolled on ≥1 nondiuretic antihypertensive for >3 months.

Use of heart failure medical therapy before and after a cancer diagnosis: A longitudinal study.

Aims: We aim to evaluate change in the use of prognostic guideline-directed medical therapies (GDMTs) for heart failure (HF) before and after a cancer diagnosis as well as the matched non-cancer controls, including renin-angiotensin-system inhibitors (RASIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs).

Methods And Results: We conducted a longitudinal study in patients with HF in the UK Clinical Practice Research Datalink between 2005 and 2021. We selected patients with probable HF with reduced ejection fraction (HFrEF) based on diagnostic and prescription records.

Deciphering Distinct Genetic Risk Factors for FTLD-TDP Pathological Subtypes via Whole-Genome Sequencing.

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 cases and 3,153 controls, and meta-analysis with the Dementia-seq cohort, compiled from 26 institutions/brain banks in the United States, Europe and Australia. We confirm as the strongest overall FTLD-TDP risk factor and identify as a novel FTLD-TDP risk factor.

Examining Associations Between Smartphone Use and Clinical Severity in Frontotemporal Dementia: Proof-of-Concept Study.

Background: Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown.

Proactive reward in conflict tasks: Does it only enhance general performance or also modulate conflict effects?

In the present study, we investigated the influence of performance-contingent reward prospects on task performance across three visual conflict tasks with manual responses (Experiments 1 & 2: Simon and Stroop tasks; Experiment 3: Simon and Eriksen flanker task) using block-wise (Experiment 1) and trial-wise (Experiments 2 & 3) manipulations to signal the possibility of reward. Across all experiments, task performance (in reaction time and/or error rates) generally improved in reward compared with no-reward conditions in each conflict task. However, there was, if any, little evidence that the reward manipulation modulated the size of the mean conflict effects, and there was also no evidence for conflict-specific effects of reward when controlling for time-varying fluctuations in conflict processing via distributional analyses (delta plots).

Perceptual target discriminability modulates the Simon effect beyond the fading of distractor-based activation: Insights from delta plots and diffusion model analyses.

The visual Simon task is widely employed to explore the underlying mechanisms of sensorimotor processing in the presence of task-relevant (targets) and task-irrelevant (distracting) location information. Critically, the Simon effect is considered as an indicator of action-related interference resulting from distractor-based activation, which fades out over time. In this study, we tested whether attenuated Simon effects with slower task processing may be fully explained by the fading of distractor-based response activation.

Seeding activity of human superoxide dismutase 1 aggregates in familial and sporadic amyotrophic lateral sclerosis postmortem neural tissues by real-time quaking-induced conversion.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with average lifespan of 2-5 years after diagnosis. The identification of novel prognostic and pharmacodynamic biomarkers are needed to facilitate therapeutic development. Metalloprotein human superoxide dismutase 1 (SOD1) is known to accumulate and form aggregates in patient neural tissue with familial ALS linked to mutations in their SOD1 gene.

A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults.

Background: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available.

Methods: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults.

Impact of Post Manufacturing Handling of Protein-Based Biologic Drugs on Product Quality and User Centricity.

This article evaluates the current gaps around the impact of post-manufacturing processes on the product qualities of protein-based biologics, with a focus on user centricity. It includes the evaluation of the regulatory guidance available, describes a collection of scientific literature and case studies to showcase the impact of post-manufacturing stresses on product and dosing solution quality. It also outlines the complexity of clinical handling and the need for communication, and alignment between drug providers, healthcare professionals, users, and patients.