Addressing the challenges of integrating digital health technologies to measure patient-centred outcomes in clinical registries.

Longitudinal patient registries generate important evidence for advancing clinical care and the regulatory evaluation of health-care products. Most national registries rely on data collected as part of routine clinical encounters, an approach that does not capture real-world, patient-centred outcomes, such as physical activity, fatigue, ability to do daily tasks, and other indicators of quality of life. Digital health technologies that obtain such real-world data could greatly enhance patient registries but unresolved challenges have so far prevented their broad adoption.

Solvent-mediated oxide hydrogenation in layered cathodes.

Self-discharge and chemically induced mechanical effects degrade calendar and cycle life in intercalation-based electrochromic and electrochemical energy storage devices. In rechargeable lithium-ion batteries, self-discharge in cathodes causes voltage and capacity loss over time. The prevailing self-discharge model centers on the diffusion of lithium ions from the electrolyte into the cathode.

Mechanistic Insights from the Crystal Structure and Computational Analysis of the Radical SAM Deaminase DesII.

Radical S-adenosyl-L-methionine (SAM) enzymes couple the reductive cleavage of SAM to radical-mediated transformations that have proven to be quite broad in scope. DesII is one such enzyme from the biosynthetic pathway of TDP-desosamine where it catalyzes a radical-mediated deamination. Previous studies have suggested that this reaction proceeds via direct elimination of ammonia from an α-hydroxyalkyl radical or its conjugate base (i.

Profiling cells with DELs: Small molecule fingerprinting of cell surfaces.

DNA-encoded small molecule library technology has recently emerged as a new paradigm for identifying ligands against drug targets. To date, it has been used to identify ligands against targets that are soluble or overexpressed on cell surfaces. Here, we report applying cell-based selection methods to profile surfaces of mouse C2C12 myoblasts and myotube cells in an unbiased, target agnostic manner.

Mobilizing data during a crisis: Building rapid evidence pipelines using multi-institutional real world data.

The COVID-19 pandemic generated tremendous interest in using real world data (RWD). Many consortia across the public and private sectors formed in 2020 with the goal of rapidly producing high-quality evidence from RWD to guide medical decision-making, public health priorities, and more. Experiences were gathered from five large consortia on rapid multi-institutional evidence generation during the COVID-19 pandemic.

Diversity, Equity, and Inclusion in Clinical Research: A Path Toward Precision Health for Everyone.

Healthcare disparities are a persistent societal problem. One of the contributing factors to this status quo is the lack of diversity and representativeness of research efforts, which result in nongeneralizable evidence that, in turn, provides suboptimal means to enable the best possible outcomes at the individual level. There are several strategies that research teams can adopt to improve the diversity, equity, and inclusion (DEI) of their efforts; these strategies span the totality of the research path, from initial design to the shepherding of clinical data through a potential regulatory process.

Byproduct formation during the biosynthesis of spinosyn A and evidence for an enzymatic interplay to prevent its formation.

Biosynthesis of spinosyn A in involves a 1,4-dehydration followed by an intramolecular [4 + 2]-cycloaddition catalyzed by SpnM and SpnF, respectively. The cycloaddition also takes place in the absence of SpnF leading to questions regarding its mechanism of catalysis and biosynthetic role. Substrate analogs were prepared with an unactivated dienophile or an acyclic structure and found to be unreactive consistent with the importance of these features for cyclization.

DNA-Encoded Library Hit Confirmation: Bridging the Gap Between On-DNA and Off-DNA Chemistry.

DNA-encoded library (DEL) technology is a powerful platform for hit identification in academia and the pharmaceutical industry. When conducting off-DNA resynthesis hit confirmation after affinity selection, PCR/sequencing, and data analysis, one typically assumes a "one-to-one" relationship between the DNA tag and the chemical structure of the attached small-molecule it encodes. Because library synthesis often yields a mixture, this approximation increases the risk of overlooking positive discoveries and valuable information.

Relations between implicit attitudes towards eating disorder stimuli and disordered eating symptoms among at-risk college women.

This study examined implicit attitudes towards different eating disorder (ED) relevant stimuli- emaciation, hard-exercise, the self, and eating related stimuli-and their relationship with explicit ED symptoms in two symptomatic samples of college-aged women. Study 1 found that positive implicit attitudes towards eating and self-relevant images were associated with greater state body image satisfaction and self-esteem and with less ED-related intentions. Study 2 found that positive implicit attitudes towards eating and self-relevant images were associated with less trait global ED psychopathology and distress and greater self-esteem.

The Impact of Variable Selection Coverage on Detection of Ligands from a DNA-Encoded Library Screen.

DNA-encoded library (DEL) technology has become a prominent screening platform in drug discovery owing to the capacity to screen billions or trillions of compounds in a single experiment. Although numerous successes with DEL technology have been reported, we are unaware of a rigorous examination of the many different variables that can influence a screen's success. Herein, we explore the impact of variable sample sequencing depth on the detection of tool compounds with known affinities toward a given target while simultaneously probing the effect of initial compound input.

Brain Differences Associated with Self-Injurious Thoughts and Behaviors: A Meta-Analysis of Neuroimaging Studies.

This meta-analysis aims to evaluate whether the extant literature justifies any definitive conclusions about whether and how SITBs may be associated with brain differences. A total of 77 papers (N = 4,903) published through January 1, 2019 that compared individuals with and without SITBs were included, resulting in 882 coordinates. A pooled meta-analysis assessing for general risk for SITBs indicated a lack of convergence on structural differences.

Water adsorption on vanadium oxide thin films in ambient relative humidity.

In this work, ambient pressure x-ray photoelectron spectroscopy (APXPS) is used to study the initial stages of water adsorption on vanadium oxide surfaces. V 2p, O 1s, C 1s, and valence band XPS spectra were collected as a function of relative humidity in a series of isotherm and isobar experiments. Experiments were carried out on two VO thin films on TiO (100) substrates, prepared with different surface cleaning procedures.

Synthesis of Multifunctional 2-Aminobenzimidazoles on DNA via Iodine-Promoted Cyclization.

2-Aminobenzimidazole cores are among the most common structural components in medicinal chemistry and can be found in many biologically active molecules. Herein, we report a mild protocol for the synthesis of multifunctional 2-aminobenzimidazoles on-DNA with broad substrate scopes. The reaction conditions expand our ability to design and synthesize 2-aminobenzimidazole core-focused DNA-encoded libraries.

Psychological primitives can make sense of biopsychosocial factor complexity in psychopathology.

Background: Many agree that the biopsychosocial contributions to psychopathology are complex, yet it is unclear how we can make sense of this complexity. One approach is to reduce this complexity to a few necessary and sufficient biopsychosocial factors; although this approach is easy to understand, it has little explanatory power. Another approach is to fully embrace complexity, proposing that each instance of psychopathology is caused by a partially unique set of biopsychosocial factors; this approach has high explanatory power, but is impossible to comprehend.