Movement Sensing Opportunities for Monitoring Dynamic Cognitive States.

In occupational domains such as sports, healthcare, driving, and military, both individuals and small groups are expected to perform challenging tasks under adverse conditions that induce transient cognitive states such as stress, workload, and uncertainty. Wearable and standoff 6DOF sensing technologies are advancing rapidly, including increasingly miniaturized yet robust inertial measurement units (IMUs) and portable marker-less infrared optical motion tracking. These sensing technologies may offer opportunities to track overt physical behavior and classify cognitive states relevant to human performance in diverse human-machine domains.

Heart Failure Part 3: Diuretic Management in Older People.

Heart failure is a common condition in the older population. As severity progresses, fluid accumulates resulting in congestive symptoms. Loop diuretics are the cornerstone of managing fluid overload and dosing should target euvolemia and congestive symptoms.

Expanding the inhibitor space of the WWP1 and WWP2 HECT E3 ligases.

The HECT E3 ubiquitin ligases 1 (WWP1) and 2 (WWP2) are responsible for the ubiquitin-mediated degradation of key tumour suppressor proteins and are dysregulated in various cancers and diseases. Here we expand their limited inhibitor space by identification of NSC-217913 displaying a WWP1 IC of 158.3 µM (95% CI = 128.

Algorithmic Spaced Retrieval Enhances Long-Term Memory in Alzheimer Disease: Case-Control Pilot Study.

Background: Spaced retrieval is a learning technique that involves engaging in repeated memory testing after increasingly lengthy intervals of time. Spaced retrieval has been shown to improve long-term memory in Alzheimer disease (AD), but it has historically been difficult to implement in the everyday lives of individuals with AD.

Objective: This research aims to determine, in people with mild cognitive impairment (MCI) due to AD, the efficacy and feasibility of a mobile app that combines spaced retrieval with a machine learning algorithm to enhance memory retention.

Enzymatic Fluoromethylation as a Tool for ATP-Independent Ligation.

-adenosylmethionine-dependent methyltransferases are involved in countless biological processes, including signal transduction, epigenetics, natural product biosynthesis, and detoxification. Only a handful of carboxylate methyltransferases have evolved to participate in amide bond formation. In this report we show that enzyme-catalyzed F-methylation of carboxylate substrates produces F-methyl esters that readily react with - or -nucleophiles under physiological conditions.

CropLife Europe Crop Development Database: An open-source, pan-European, harmonized crop development database for use in regulatory pesticide exposure modeling and risk assessment.

There is a regulatory need for crop development dates to assess current default values used within chemical exposure assessments as well as to justify refinements within risk assessments. However, a readily available pan-European crop phenology database covering key FOrum for the Co-ordination of pesticide fate models and their USe (FOCUS) crops and scenarios to meet this need is not currently available. Therefore, we describe the development of a harmonized, pan-European, CropLife Europe Crop Development Database (C2D2), that is fully aligned with this regulatory requirement utilizing efficacy trials data generated for regulatory submissions when registering plant protection products under Regulation (EU)1107/2009.

Enzymatic Fluoromethylation as a Tool for ATP-Independent Ligation.

S-adenosylmethionine-dependent methyltransferases are involved in countless biological processes, including signal transduction, epigenetics, natural product biosynthesis, and detoxification. Only a handful of carboxylate methyltransferases have evolved to participate in amide bond formation. In this report we show that enzyme-catalyzed F-methylation of carboxylate substrates produces F-methyl esters that readily react with N- or S-nucleophiles under physiological conditions.

When Memory and Metamemory Align: How Processes at Encoding Influence Delayed Judgment-of-Learning Accuracy.

Judgments of learning are most accurate when made at a delay from the initial encoding of the assessed material. A wealth of evidence suggests that this is because a delay encourages participants to base their predictions on cues retrieved from long-term memory, which are generally the most diagnostic of later memory performance. We investigated the hypothesis that different types of study techniques affect delayed JOL accuracy by influencing the accessibility of cues stored in long-term memory.

Targeting mitochondrial dysfunction with elamipretide.

Although currently employed therapies for heart failure decrease overall mortality and improve patient quality of life temporarily, the disease is known to progress even for patients who receive all guideline-recommended therapies. This indicates that our concise understanding of heart failure and of disease progression is incomplete, and there is a need for new interventions that may augment, or even supplant, currently available options. A literature review reveals that an exciting, novel area of current research is focused on mitochondria, which are uniquely juxtaposed at the sites of both generation of high-energy molecules and initiation of programmed cell death.

Are witnesses able to avoid highly accessible misinformation? Examining the efficacy of different warnings for high and low accessibility postevent misinformation.

The reliability of eyewitness memory continues to be an area of concern, particularly in situations that involve conflicting sources of information (e.g., the misinformation effect; Loftus et al.

Angiotensin II: A Review of Current Literature.

Up to one-third of all patients admitted to intensive care units carry a diagnosis of shock. The use of angiotensin II is becoming widespread in all forms of shock, including cardiogenic, after the U.S.

Frontiers in PROTACs.

Targeting protein-protein interactions (PPI) is a key focus in the development of new and emerging small-molecule therapeutics. Shallow interacting surfaces can render PPI targeting notoriously difficult. This leaves many therapeutically captivating targets 'undruggable'.

Visual category learning: Navigating the intersection of rules and similarity.

Visual categorization is fundamental to expertise in a wide variety of disparate domains, such as radiology, art history, and quality control. The pervasive need to master visual categories has served as the impetus for a vast body of research dedicated to exploring how to enhance the learning process. The literature is clear on one point: no category learning technique is always superior to another.

Site-selective redox isomerizations of furanosides using a combined arylboronic acid/photoredox catalyst system.

In the presence of an arylboronic acid and a hydrogen atom transfer mediator under photoredox conditions, furanoside derivatives undergo site-selective redox isomerizations to 2-keto-3-deoxyfuranosides. Experimental evidence and computational modeling suggest that the transformation takes place by abstraction of the hydrogen atom from the 2-position of the furanoside-derived arylboronic ester, followed by C3-O bond cleavage spin-center shift. This mechanism is reminiscent of the currently accepted pathway for the formation of 3'-ketodeoxynucleotides by ribonucleotide reductase enzymes.

Design of an in vitro biocatalytic cascade for the manufacture of islatravir.

Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates.

Andexanet Alfa (Andexxa) for the Reversal of Direct Oral Anticoagulants.

Andexanet alfa (Andexxa) for the reversal of direct oral anticoagulants.

Acute stress enhances general-knowledge semantic memory.

Acute psychological stress consistently impairs episodic memory, which consists of memory for events that are associated with a specific context. However, researchers have not yet established how stress influences semantic memory, which consists of general knowledge that is devoid of context. In the present study, participants either underwent stress induction or a control task prior to taking a trivia test that was designed to measure semantic memory.

Design and Delivery of Clinical Pharmacokinetics in Colleges and Schools of Pharmacy.

To describe how clinical pharmacokinetics is being delivered across curricula in pharmacy programs, including the curricular position of clinical pharmacokinetic topics, topics currently taught, and instructional methods used in delivering the course content. A survey was distributed to one representative faculty member from each pharmacy college who was most able to answer questions about their institution's delivery of clinical pharmacokinetic material. Responses were collected from 82 out of the 108 pharmacy colleges who participated in the study.

Discovery of Small Molecule WWP2 Ubiquitin Ligase Inhibitors.

We have screened small molecule libraries specifically for inhibitors that target WWP2, an E3 ubiquitin ligase associated with tumour outgrowth and spread. Selected hits demonstrated dose-dependent WWP2 inhibition, low micromolar IC50 values, and inhibition of PTEN substrate-specific ubiquitination. Binding to WWP2 was confirmed by ligand-based NMR spectroscopy.

Ledipasvir/Sofosbuvir (harvoni): improving options for hepatitis C virus infection.

Ledipasvir/sofosbuvir (Harvoni): improving options for hepatitis C virus infection.