Branching Ionizable Lipids Can Enhance the Stability, Fusogenicity, and Functional Delivery of mRNA

Ionizable lipids with branched tails have been used in lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics like COVID-19 vaccines. However, due to the limited commercial availability of branched ingredients, a systematic analysis of how the branched tails affect LNP quality has been lacking to date. Herein, a-branched tail lipids are focused, as they can be synthesized from simple commercially available chemicals, and the length of each chain can be independently controlled. Furthermore, symmetry and total carbon number can be used to describe a-branched tails, facilitating the design of a systematic lipid library to elucidate "structure-property-function" relationships. Consequently, a lipid library is developed containing 32 different types of a-branched tails. This library is used to demonstrate that branched chains increase LNP microviscosity and headgroup ionization ability in an acidic environment, which in turn enhances the stability and in vivo efficacy of mRNA-LNPs. Of the branched lipids, CL4F 8-6 LNPs carrying Cas9 mRNA and sgRNA could achieve 54% genome editing and 77% protein reduction with a single dose of 2.5 mg kg(-1). This mechanism-based data on branched lipids is expected to provide insights into rational lipid design and effective gene therapy in the future.

The Role of Prior Online Learning Experience on Student Community of Inquiry, Engagement, and Satisfaction Scores

The increase in online education creates a need to explore how learning outcomes, student satisfaction, and student perceptions about online courses are affected by prior online learning experiences. This study examined the role of prior online learning experience on students' perceived cognitive presence, social presence, teaching presence, engagement, and satisfaction. The archival data of online learners at a large midwestern university (a total n=878), including survey responses related to Community of Inquiry (CoI), engagement, and satisfaction, were utilized to conduct statistical analyses to determine whether student responses differed by the number of online courses taken previously. We found that only social presence scores (CoI sub-scale) and emotional engagement scores (engagement sub-scale) differed by the number of the online courses taken. However, the effect size was small. We concluded that student satisfaction, engagement, and perceptions of cognitive and teaching presence are not related to prior online course experiences. Implications are discussed.

Efficiency & Patient Satisfaction of Colorectal Telephone Consultation during the Covid-19 Pandemic

Aim: COVID-19 has necessitated a new approach to consult patients due to requirement for social distancing and avoiding unnecessary contact. This study aimed to assess the feasibility and patients' satisfaction of virtual clinic (VC) appointment compared to face-to- face (F2F) appointment. This study aimed to assess the feasibility and patients' satisfaction of virtual clinic (VC) appointment compared to face-to- face (F2F) appointment. Method(s): Patients referred under routine referral to the service between 09/10/2019 and 31/12/2019 and waiting for an appointment for more than one year were screened and allocated to VC or F2F according to set criteria based on symptoms and pathology. Demographic data, symptoms, pathology and waiting time were collected retrospectively. Structured telephone interviews were conducted to evaluate patients' satisfaction. Result(s): 559 patients were referred in the study period. Of this, 33.6% and 49.4% were triaged to attend a VC, or F2F clinic, respectively. Of the VC patients, 53.9% patients were discharged after an initial appointment, whereas 37.3% patients required a follow-up F2F appointment due to persistent symptoms or patient preference. Of the F2F patients, 82.8% were from the initial triage due to requirement for clinical examination or patients' preference. 90.5% of patients who underwent VC reported being either satisfied or very satisfied with their experience, in contrast to 86.0% of patients who underwent a F2F appointment (P < 0.05). Conclusion(s): VC appointments significantly reduced waiting times and only 1/3 of VC patients required a further F2F appointment. Patient were more satisfied with VC than an F2F appointment, and it may be a useful approach for service efficiency, particularly during ongoing COVID pandemic.

World robot summit 2020 assembly challenge - summary of the competition and its outcomes*

The World Robot Summit (WRS) is a robotic 'challenge and exposition' organized by the Japanese government to accelerate social implementation, research and development of robots working in realistic daily life, society, and industrial fields. In this paper, we introduce a robot competition of the Industrial Robotics Category of the WRS, called 'Assembly Challenge', which is organized by the WRS Industrial Robotics Competition Committee in order to promote the development of the next-generation production systems that can respond to new production demands in agile and lean manners. After the pre-competition held in Tokyo in October 2018, the main competition, the WRS 2020, was originally scheduled to be held in Aichi (partly in Fukushima) in 2020, which was also the Olympic year. However, due to the pandemic of COVID-19, the event was postponed, and the competition was actually held in Aichi in September 2021. In this paper, we introduce the contents and results of the WRS 2020 and analyze the results. We would also like to summarize the 5-year project since 2017 and discuss the outcomes of the WRS.

The effect of relational mobility on the early and late stages of the COVID-19 outbreak: Discussion from the socioecological perspective

In the first year of the pandemic, the number of COVID-19 cases per 100,000 population in Japan is not as high as in other countries. Among the factors that may be related to infection rates, we focus on a socioecological factor called relational mobility. In this article, we argue that while low relational mobility in Japan suppressed the spread of COVID-19 at the beginning of the outbreak, it could actually prevent the full containment of the virus. In low relational mobility societies (e.g., Japan), people can engage in physical distancing relatively easily and tend to “monitor” others' compliance. These behaviors helped suppress the spread of COVID-19 in Japan during the outbreak. On the flip side, the emphasis on relationship harmony could prevent the virus from being fully contained in low relational mobility societies as people fear being identified and avoid taking a PCR test or cooperating in contact tracing. Thus, monitoring the behaviors of nonconformists by the public in low relational mobility societies could actually work against controlling the virus. © 2021 Japanese Psychological Association. All rights reserved.

Risk of missing colorectal cancer with a COVID-adapted diagnostic pathway using quantitative faecal immunochemical testing.

BACKGROUND: COVID-19 has brought an unprecedented challenge to healthcare services. The authors' COVID-adapted pathway for suspected bowel cancer combines two quantitative faecal immunochemical tests (qFITs) with a standard CT scan with oral preparation (CT mini-prep). The aim of this study was to estimate the degree of risk mitigation and residual risk of undiagnosed colorectal cancer. METHOD: Decision-tree models were developed using a combination of data from the COVID-adapted pathway (April-May 2020), a local audit of qFIT for symptomatic patients performed since 2018, relevant data (prevalence of colorectal cancer and sensitivity and specificity of diagnostic tools) obtained from literature and a local cancer data set, and expert opinion for any missing data. The considered diagnostic scenarios included: single qFIT; two qFITs; single qFIT and CT mini-prep; two qFITs and CT mini-prep (enriched pathway). These were compared to the standard diagnostic pathway (colonoscopy or CT virtual colonoscopy (CTVC)). RESULTS: The COVID-adapted pathway included 422 patients, whereas the audit of qFIT included more than 5000 patients. The risk of missing a colorectal cancer, if present, was estimated as high as 20.2 per cent with use of a single qFIT as a triage test. Using both a second qFIT and a CT mini-prep as add-on tests reduced the risk of missed cancer to 6.49 per cent. The trade-off was an increased rate of colonoscopy or CTVC, from 287 for a single qFIT to 418 for the double qFIT and CT mini-prep combination, per 1000 patients. CONCLUSION: Triage using qFIT alone could lead to a high rate of missed cancers. This may be reduced using CT mini-prep as an add-on test for triage to colonoscopy or CTVC.

The COVID-19 pandemic: considerations for resuming normal colorectal services.

This European Society of Coloproctology guidance focuses on a proposed conceptual framework to resume standard service in colorectal surgery. The proposed conceptual framework is a schematic and stepwise approach including: in-depth assessment of damage to non-COVID-19-related colorectal service; the return of service (integration with the COVID-19-specific service and the existing operational continuity planning); safety arrangements in parallel with minimizing downtime; the required support for staff and patients; the aftermath of the pandemic and continued strategic planning. This will be dynamic guidance with ongoing updates using critical appraisal of emerging evidence. We will welcome input from all stakeholders (statutory organizations, healthcare professionals, public and patients). Any new questions, new data and discussion are welcome via https://www.escp.eu.com/guidelines.