Conformational transitions of Streptococcus pyogenes Cas9 induced by salt and single-guide RNA binding.

Streptococcus pyogenes (Sp) Cas9 has been widely utilized to edit genomes across diverse species. To achieve high efficiency and specificity as a gene editing enzyme, Sp Cas9 undergoes a series of sequential conformational changes during substrate binding and catalysis. Here, we employed single molecule FRET techniques to investigate the effect of different KCl concentrations on conformational dynamics of Sp Cas9 in the presence or absence of a single-guide RNA (sgRNA).

The effectiveness of digital tools to maintain physical activity among people with a long-term condition(s): A systematic review and meta-analysis.

Objective: Given the well-accepted health benefits, it is important to identify scalable ways to support people with long-term conditions (LTCs) to remain physically active. This systematic review aimed to evaluate the effect of digital tools on the maintenance of physical activity (PA) amongst this population.

Methods: Electronic databases were searched for randomised controlled trials investigating the effect of digital tools on PA maintenance at least three months post-intervention compared with a non-digital control in participants with long-term conditions.

A metric of team multitasking throughput.

We developed a novel, unobtrusive estimate of team multitasking throughput (tMT). We demonstrate it through the quantitative assessment of tMT in distributed dyads when objective performance and purported reliability are manipulated among teammates. In a within-subjects experiment, we investigated the effects of teammates' performance and purported reliability on tMT.

The Use of Extrinsic Performance Feedback and Reward to Enhance Upper Limb Motor Behavior and Recovery Post-Stroke: A Scoping Review.

Background: During post-stroke motor rehabilitation, patients often receive feedback from therapists or via rehabilitation technologies. Research suggests that feedback may benefit motor performance, skill acquisition, and action selection. However, there is no consensus on how extrinsic feedback should be implemented during stroke rehabilitation to best leverage specific neurobehavioral mechanisms to optimize recovery.

Pure open versus robotic radical cystectomy with intracorporeal urinary diversion: a propensity matched analysis.

Objective: To compare surgical parameters and short-term outcomes between open radical cystectomy (ORC) and robotic radical cystectomy with total intracorporeal urinary diversion (icRARC).

Methods: Among the study period, 133 patients who underwent ORC and pelvic node dissection for bladder cancer (group 1) were matched and compared to 61 patients who underwent icRARC during the same period (group 2). The groups were matched 1:1 according to their propensity scores adjusted on their baseline demographics and disease characteristics.

MrgprA3 neurons drive cutaneous immunity against helminths through selective control of myeloid-derived IL-33.

Skin uses interdependent cellular networks for barrier integrity and host immunity, but most underlying mechanisms remain obscure. Herein, we demonstrate that the human parasitic helminth Schistosoma mansoni inhibited pruritus evoked by itch-sensing afferents bearing the Mas-related G-protein-coupled receptor A3 (MrgprA3) in mice. MrgprA3 neurons controlled interleukin (IL)-17 γδ T cell expansion, epidermal hyperplasia and host resistance against S.

Longitudinal changes in BMD in adults with cystic fibrosis.

Improved survival in people with cystic fibrosis (pwCF) presents new complexities of care, including CF-related bone disease, a common complication in older pwCF. The trajectory of bone loss with age in this population remains unclear. The objective of this study was to estimate the average rate of change in BMD in adults with CF.

Impact of COVID-19 infection on lung function and nutritional status amongst individuals with cystic fibrosis: A global cohort study.

Background: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF).

Methods: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021.

Higher inflammatory proteins predict future depressive symptom severity among adolescents with lower emotional clarity.

Background: A growing body of work has implicated inflammation in the pathogenesis of depression. As not all individuals with heightened levels of peripheral inflammation develop symptoms of depression, additional work is needed to identify other factors that catalyze the relationship between inflammation and depressive symptoms. Given that elevated levels of inflammatory activity can induce a variety of emotional changes, the present study examined whether emotional clarity, the trait-like ability to identify, discern, and express one's emotions, influences the strength of the association between inflammatory signaling and concurrent and prospective symptoms of depression.

Comparative Safety Analysis of Nabilone Versus Opioids: A Population-Based Cohort Study.

Background: Some have advocated that nabilone be used rather than opioids to manage chronic, noncancer pain, since the former drug may have a better safety profile.

Objective: We compared the safety of incident nabilone use relative to incident opioid use with respect to multiple clinically important outcomes.

Design: A population-based, retrospective cohort study.

Socioeconomic burden of cystic fibrosis in Canada.

Background: Cost of illness studies are important tools to summarise the burden of disease for individuals, the healthcare system and society. The lack of standardised methods for reporting costs for cystic fibrosis (CF) makes it difficult to quantify the total socioeconomic burden. In this study, we aimed to comprehensively report the socioeconomic burden of CF in Canada.

Clinical outcomes after liver transplant in people with cystic fibrosis: A systematic review and meta-analysis.

Background: Data on the impact of liver transplantation (LT) in cystic fibrosis (CF) on lung function and exacerbations are limited. The objective of this study was to summarize the literature on lung function, nutritional status, survival, and complications following LT in people with CF.

Methods: Three databases were searched until September 2023, to identify the impact of LT in CF.

Cytokine/Antibody Fusion Protein Design and Evaluation.

Cytokines constitute a class of secreted proteins that activate transmembrane receptors to coordinate a vast array of physiological processes, particularly those related to immune activity. Due to their vital role in immune regulation, cytokines have garnered great interest as potential therapeutic agents. Unfortunately, the clinical success of cytokine drugs has been limited by their multifunctional activities, which hinder therapeutic performance and lead to harmful toxicities.

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19.

Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 ("vax-plasma").