An optimized prime editing system for efficient modification of the pig genome.

Prime editing (PE) is a recent gene editing technology that can mediate insertions or deletions and all twelve types of base-to-base conversions. However, its low efficiency hampers the application in creating novel breeds and biomedical models, especially in pigs and other important farm animals. Here, we demonstrate that the pig genome is editable using the PE system, but the editing efficiency was quite low as expected. Therefore, we aimed to enhance PE efficiency by modulating both exogenous PE tools and endogenous pathways in porcine embryonic fibroblasts (PEFs). First, we modified the pegRNA by extending the duplex length and mutating the fourth thymine in a continuous sequence of thymine bases to cytosine, which significantly enhanced PE efficiency by improving the expression of pegRNA and targeted cleavage. Then, we targeted SAMHD1, a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) that impedes the reverse transcription process in retroviruses, and found that treatment with its inhibitor, cephalosporin C zinc salt (CPC), increased PE efficiency up to 29-fold (4-fold on average), presumably by improving the reverse transcription process of Moloney murine leukemia virus reverse transcriptase (M-MLV RT) in the PE system. Moreover, PE efficiency was obviously improved by treatment with a panel of histone deacetylase inhibitors (HDACis). Among the four HDACis tested, panobinostat was the most efficient, with an efficiency up to 122-fold (7-fold on average), partly due to the considerable HDACi-mediated increase in transgene expression. In addition, the synergistic use of the three strategies further enhanced PE efficiency in PEFs. Our study provides novel approaches for optimization of the PE system and broadens the application scope of PE in agriculture and biomedicine.

Identifying Design Opportunities for Adaptive mHealth Interventions That Target General Well-Being: Interview Study With Informal Care Partners.

BACKGROUND: Mobile health (mHealth) interventions can deliver personalized behavioral support to users in daily contexts. These interventions have been increasingly adopted to support individuals who require low-cost and low-burden support. Prior research has demonstrated the feasibility and acceptability of an mHealth intervention app (CareQOL) designed for use with informal care partners. To further optimize the intervention delivery, we need to investigate how care partners, many of whom lack the time for self-care, react and act in response to different behavioral messages. OBJECTIVE: The goal of this study was to understand the factors that impact care partners' decision-making and actions in response to different behavioral messages. Insights from this study will help optimize future tailored and personalized behavioral interventions. METHODS: We conducted semistructured interviews with participants who had recently completed a 3-month randomized controlled feasibility trial of the CareQOL mHealth intervention app. Of the 36 participants from the treatment group of the randomized controlled trial, 23 (64%) participated in these interviews. To prepare for each interview, the team first selected representative behavioral messages (eg, targeting different health dimensions) and presented them to participants during the interview to probe their influence on participants' thoughts and actions. The time of delivery, self-reported perceptions of the day, and user ratings of a message were presented to the participants during the interviews to assist with recall. RESULTS: The interview data showed that after receiving a message, participants took various actions in response to different messages. Participants performed suggested behaviors or adjusted them either immediately or in a delayed manner (eg, sometimes up to a month later). We identified 4 factors that shape the variations in user actions in response to different behavioral messages: uncertainties about the workload required to perform suggested behaviors, concerns about one's ability to routinize suggested behaviors, in-the-moment willingness and ability to plan for suggested behaviors, and overall capability to engage with the intervention. CONCLUSIONS: Our study showed that care partners use mHealth behavioral messages differently regarding the immediacy of actions and the adaptation to suggested behaviors. Multiple factors influence people's perceptions and decisions regarding when and how to take actions. Future systems should consider these factors to tailor behavioral support for individuals and design system features to support the delay or adaptation of the suggested behaviors. The findings also suggest extending the assessment of user adherence by considering the variations in user actions on behavioral support (ie, performing suggested or adjusted behaviors immediately or in a delayed manner). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/32842.

The Dosing of Mobile-Based Just-in-Time Adaptive Self-Management Prompts for Caregivers: Preliminary Findings From a Pilot Microrandomized Study.

BACKGROUND: Caregivers of people with chronic illnesses often face negative stress-related health outcomes and are unavailable for traditional face-to-face interventions due to the intensity and constraints of their caregiver role. Just-in-time adaptive interventions (JITAIs) have emerged as a design framework that is particularly suited for interventional mobile health studies that deliver in-the-moment prompts that aim to promote healthy behavioral and psychological changes while minimizing user burden and expense. While JITAIs have the potential to improve caregivers' health-related quality of life (HRQOL), their effectiveness for caregivers remains poorly understood. OBJECTIVE: The primary objective of this study is to evaluate the dose-response relationship of a fully automated JITAI-based self-management intervention involving personalized mobile app notifications targeted at decreasing the level of caregiver strain, anxiety, and depression. The secondary objective is to investigate whether the effectiveness of this mobile health intervention was moderated by the caregiver group. We also explored whether the effectiveness of this intervention was moderated by (1) previous HRQOL measures, (2) the number of weeks in the study, (3) step count, and (4) minutes of sleep. METHODS: We examined 36 caregivers from 3 disease groups (10 from spinal cord injury, 11 from Huntington disease, and 25 from allogeneic hematopoietic cell transplantation) in the intervention arm of a larger randomized controlled trial (subjects in the other arm received no prompts from the mobile app) designed to examine the acceptability and feasibility of this intensive type of trial design. A series of multivariate linear models implementing a weighted and centered least squares estimator were used to assess the JITAI efficacy and effect. RESULTS: We found preliminary support for a positive dose-response relationship between the number of administered JITAI messages and JITAI efficacy in improving caregiver strain, anxiety, and depression; while most of these associations did not meet conventional levels of significance, there was a significant association between high-frequency JITAI and caregiver strain. Specifically, administering 5-6 messages per week as opposed to no messages resulted in a significant decrease in the HRQOL score of caregiver strain with an estimate of -6.31 (95% CI -11.76 to -0.12; P=.046). In addition, we found that the caregiver groups and the participants' levels of depression in the previous week moderated JITAI efficacy. CONCLUSIONS: This study provides preliminary evidence to support the effectiveness of the self-management JITAI and offers practical guidance for designing future personalized JITAI strategies for diverse caregiver groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT04556591; https://clinicaltrials.gov/ct2/show/NCT04556591.

Investigating walking speed variability of young adults in the real world.

BACKGROUND: Walking speed strongly correlates with health outcomes, making accurate assessment essential for clinical evaluations. However, assessments tend to be conducted over short distances, often in a laboratory or clinical setting, and may not capture natural walking behavior. To address this gap, the following questions are investigated in this work: Is walking speed significantly influenced by the continuity and duration of a walking bout? Can preferred walking speed be inferred by grouping walking bouts using duration and continuity? METHODS: We collected two weeks of continuous data from fifteen healthy young adults using a thigh-worn accelerometer and a heart rate monitor. Walking strides were identified and grouped into walking periods. We quantified the duration and the continuity of each walking period. Continuity is used to parameterize changes in stepping rate related to pauses during a bout of walking. Finally, we analyzed the influence of duration and continuity on estimates of stride speed, and examined how the distribution of walking speed varies depending on different walking modes (defined by duration and continuity). RESULTS: We found that continuity and duration can be used to explain some of the variability in real-world walking speed (p<0.001). Speeds estimated from long continuous walks with many strides (42% of all recorded strides) had the lowest standard deviation. Walking speed during these bouts was 1.41ms-1 (SD = 0.26ms-1). SIGNIFICANCE: Walking behavior in the real world is largely variable. Features of real-world walks, like duration and continuity, can be used to explain some of the variability observed in walking speed. As such, we recommend using long continuous walks to confidently isolate the preferred walking behavior of an individual.

An app-based just-in-time-adaptive self-management intervention for care partners: The CareQOL feasibility pilot study.

PURPOSE/OBJECTIVE: The primary objective of this study was to establish the feasibility and acceptability of an intensive data collection protocol that involves the delivery of a personalized just-in-time adaptive intervention (JITAI) in three distinct groups of care partners (care partners of persons with spinal cord injury [SCI], Huntington's disease [HD], or hematopoietic cell transplantation [HCT]). RESEARCH METHOD/DESIGN: Seventy care partners were enrolled in this study (n = 19 SCI; n = 21 HD, n = 30 HCT). This three-month (90 day) randomized control trial involved wearing a Fitbit to track sleep and steps, providing daily reports of health-related quality of life (HRQOL), and completing end of month HRQOL surveys. Care partners in the JITAI group also received personalized pushes (i.e., text-based phone notifications that include brief tips or suggestions for improving self-care). At the end of three-months, care partners in both groups completed a feasibility and acceptability questionnaire. RESULTS: Most (98.6%) care partners completed the study, average compliance was 88% for daily HRQOL surveys, 96% for daily steps, and 85% for daily sleep (from wearing the Fitbit), and all monthly surveys were completed with the exception of one missed 3-month assessment. The acceptability of the protocol was high; ratings exceeded 80% agreement for the different elements of the study. Improvements were seen for the majority of the HRQOL measures. There was no evidence of measurement reactivity. CONCLUSIONS/IMPLICATIONS: Findings provide strong support for the acceptability and feasibility of an intensive data collection protocol that involved the administration of a JITAI. Although this trial was not powered to establish efficacy, findings indicated improvements across a variety of different HRQOL measures (~1/3 of which were statistically significant). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Evaluation of eight-style Tai chi on cognitive function in patients with cognitive impairment of cerebral small vessel disease: study protocol for a randomised controlled trial.

INTRODUCTION: Cerebral small vessel disease (CSVD) is a critical factor that causes cognitive decline and progresses to vascular dementia and acute cerebrovascular events. Tai chi has been proven to improve nerve plasticity formation and directly improve cognitive function compared with other sports therapy, which has shown its unique advantages. However, more medical evidence needs to be collected in order to verify that Tai chi exercises can improve cognitive impairment due to CSVD. The main purposes of this study are to investigate the effect of Tai chi exercise on neuropsychological outcomes of patients with cognitive impairment related to CSVD and to explore its mechanism of action with neuroimaging, including functional MRI (fMRI) and event-related potential (P300). METHODS AND ANALYSIS: The design of this study is a randomised controlled trial with two parallel groups in a 1:1 allocation ratio with allocation concealment and assessor blinding. A total of 106 participants will be enrolled and randomised to the 24-week Tai chi exercise intervention group and 24-week health education control group. Global cognitive function and the specific domains of cognition (memory, processing speed, executive function, attention and verbal learning and memory) will be assessed at baseline and 12 and 24 weeks after randomisation. At the same time, fMRI and P300 will be measured the structure and function of brain regions related to cognitive function at baseline and 24 weeks after randomisation. Recruitment is currently ongoing (recruitment began on 9 November 2020). The approximate completion date for recruitment is in April 2021, and we anticipate to complete the study by December 2021. ETHICS AND DISSEMINATION: Ethics approval was given by the Medical Ethics Committee of the Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine (approval number: 2019-058-04). The findings will be disseminated through peer-reviewed publications and at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000033176; Pre-results.

Leveraging Walking Performance to Understand Work Fatigue Among Young Adults: Mixed-Methods Study.

BACKGROUND: Work fatigue negatively impacts personal health in the long term. Prior research has indicated the possibility of leveraging both walking parameters and perceptual measures to assess a person's fatigue status. However, an effective and ubiquitous approach to assessing work fatigue in young adults remains unexplored. OBJECTIVE: The goals of this paper were to (1) explore how walking rhythms and multiple streams of data, including reaction time, self-reports, and an activity diary, reflect work-induced fatigue in the lab setting; (2) identify the relationship between objective performance and subjective perception in indicating fatigue status and fatigability; and (3) propose a mobile-based assessment for work-induced fatigue that uses multiple measurements. METHODS: We conducted a 2-day in-lab study to measure participants' fatigue status using multiple measurements, including the stair climb test (SCT), the 6-minute walk test (6MWT), and the reaction time test. Both the SCT and the 6MWT were conducted at different points in time and under 2 conditions (measurement time, including prior to and after work, and pace, including normal and fast). Participants reported their fatigue perception through questionnaires completed before conducting walking tests and in an activity diary recorded over a week. Walking performance data were collected by a smartphone with a built-in 3-axis accelerometer. To examine the effect of fatigability on walking performance, we first clustered participants into 2 groups based on their reported mental fatigue level in the entry surveys and then compared their walking performance using a generalized linear model (GLM). The reaction time was examined using a 2-way repeated-measures GLM. We conducted semistructured interviews to understand participants' fatigue perception after each day's walking tests. RESULTS: All participants (N=26; mean age 24.68 years) were divided into 2 groups-the fatigue-sensitive group (11/26, 42%) and the fatigue-nonsensitive group (15/26, 58%)-based on their mental subscores from 3 entry surveys: Fatigue Scale-14, Three-Dimensional Work Fatigue Inventory, and Fatigue Self-Assessment Scale (FSAS). The fatigue-sensitive group reported a significantly higher FSAS score in the before-work setting (t50=-3.361; P=.001). The fatigue-sensitive group covered fewer steps than the fatigue-nonsensitive group (ß1=-0.099; SE 0.019; t1=-5.323; P<.001) and had a higher step-to-step time variability in the 6MWT (ß1=9.61 × 10-4; t1=2.329; P=.02). No strong correlation between subjective and objective measurements was observed in the study. CONCLUSIONS: Walking parameters, including step counts and step-to-step time variability, and some selected scales (eg, FSAS) were found to reflect participants' work-induced fatigue. Overall, our work suggests the opportunity of employing mobile-based walking measurements to indicate work fatigue among young adults.

Introducing Temperature-Controlled Phase Transition Elastin-like Polypeptides to Transient Electronics: Realization of Proactive Biotriggered Electronics with Local Transience.

Transient electronics have dramatically changed inner-body therapy in health care. They stand out because of their harmless dissolution in the human body with no lingering electronic trash. However, high-precision biomedical implants require programmable and serial remedy operations, and controlling the whole-device destruction is not proactive and precise. Thus, a novel biotriggered and temperature-controlled transient electronics fabrication method using elastin-like polypeptides (ELPs) as triggers is proposed. Biocompatible ELPs simply mixed with trace silver nanowire (AgNW) can serve as the "switch" for the electronics to respond to local temperature changes in deionized water, exhibiting an agile response time. A ratio gradient experiment of the ELPs and AgNW shows that more programmable and precise transience properties (initial resistance, ready time, response time, and stable resistance) can be achieved by using a designated proportion. Further, we validated that the 3D-printing-based ELP-triggering transient electronics fabrication method is very simple yet effective for preparing transient wireless charging LEDs. Transient devices comprising ELPs-AgNW and PLGA-Ag respond within 160 s below 10 °C and degrade within a certain period.

Application of smart bracelet to monitor frailty-related gait parameters of older Chinese adults: A preliminary study.

AIM: Smart bracelets are popular today. Based on their built-in motion sensors, they can serve as a cost-effective method of gait assessment in home-based care. Few studies have applied smart bracelets in the gait assessment of older Chinese adults. The present study aimed to: (i) establish reference gait parameters of older Chinese adults using smart bracelets under single and dual task; and (ii) explore the differences in gait parameters among non-frail and pre-frail Chinese older adults. METHODS: A total of 50 community-dwelling older Chinese adults aged ≥50 years wore a smart bracelet sensor in the L3 region of the back and underwent a 10-m walking test under single- and dual-task conditions. Participants were preliminarily classified into non-frail and pre-frail groups based on the Fatigue, Resistance, Ambulation, Illnesses and Loss of Weight scale. Gait parameters including average walking speed, step frequency, root mean square (RMS), acceleration amplitude variability, step variability, step regularity and step symmetry were calculated based on the data exported from the bracelet. RESULTS: Multivariate analysis of covariance (mancova) analysis showed that older adults had significantly decreased speed and step frequency (P < 0.05) under the dual cognitive task condition. Pre-frail older adults showed significantly decreased speed, mediolateral RMS, vertical RMS, anteroposterior RMS, vertical amplitude variability and vertical step regularity compared with non-frail older adults (P < 0.05). CONCLUSIONS: The present study suggested that the decline in gait parameters as a result of frailty could be detected by the smart bracelet sensor. Geriatr Gerontol Int 2018; 18: 1366-1371.

The Effect of Chinese Traditional Exercise-Baduanjin on Physical and Psychological Well-Being of College Students: A Randomized Controlled Trial.

BACKGROUND: The physical and mental health of college students tends to continuously decline around the world, therefore, it is important to improve their health during college period. Baduanjin, a traditional Chinese exercise which combines movements with breath and mind, may be one of the selectable effective exercises. However, the effect of Baduanjin exercise on college students has not been established. In this study, we systematically assessed the effectiveness and safety of Baduanjin exercise on physical and mental health of college students by a rigorous randomized, parallel-controlled design. METHODS: A total of 222 college students from Fujian University of Traditional Chinese Medicine were recruited and randomly allocated at an equal ratio into control or Baduanjin training. Participants in control group were informed to maintain their original activity habit, and those in Baduanjin exercise group received a 12-week Baduanjin exercise training with a frequency of 1 hour per day and 5 days per week on the basis of their original activity habit. The physical and psychological outcomes, including lumbar muscle strength, lower limb proprioception function, physical fitness, as well as self-reported symptom intensity, stress, self-esteem, mood, quality of life, quality of sleep, and adverse events, were evaluated at baseline, 13 weeks (at the end of 12-week intervention), and 25 weeks (after the 12-week follow-up period). Intention-to-treat analysis was performed for the above outcomes. RESULTS: Compared with controls, significant improvements in Baduanjin exercise group at the end of 12-week intervention period were found on lower limb proprioception function (the rate of average trace error on right lower limb (%): control 23.50±5.50, Baduanjin 21.92±6.54, P=0.004; the rate of average trace error on left lower limb (%): control 22.32±6.62, Baduanjin 20.63±4.62, P=0.046), cardiorespiratory endurance (step test index: control 47.66±5.94, Baduanjin 50.07±9.30, P=0.025), flexibility (control 14.35±7.26cm, Baduanjin 15.39±6.43cm, P=0.009) and explosive force of lower limb (standing long jump test (m): control 1.77±0.24, Baduanjin 1.79±0.22, P=0.005 for adjustment baseline) in physical outcomes, and attention (Schulte Grid test (second): control 210.4±51.15, Baduanjin 192.4±47.14, P=0.034) in mental outcome. Lumbar muscle strength in Baduanjin group had been moderately enhanced but no significant difference compared to controls. No significant changes in other physical and mental outcomes, including vital capacity, blood pressure, heart rate, hand grip force, self-symptom intensity, stress, self-efficacy, quality of life, and quality of sleep, were found between groups. No adverse event was reported during the study period. CONCLUSION: Regular Baduanjin exercise had an advantage for college students on improvement of lower limb proprioception, enhance of cardiorespiratory endurance, flexibility, explosive force of lower limb and attention, compared with usual exercise. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-13003329 http://www.chictr.org.

The effect of Baduanjin exercise for physical and psychological wellbeing of college students: study protocol for a randomized controlled trial.

BACKGROUND: The physical and mental health of college students tends to continuously decline around the world. Since they are in a significant transition period which presents opportunities and challenges in health promotion, it is important to improve their health in this period. As a traditional Chinese exercise form which combines movements with breath and mind, Baduanjin may be one of the selectable effective exercises. However, evidence of Baduanjin exercise for college students has not been completely established. The primary aim of this trial is to evaluate the effectiveness and safety of Baduanjin exercise for physical and mental health of college students through a rigorous randomization, parallel-controlled design. METHOD/DESIGN: We will conduct a randomized, single-blind, parallel-controlled trial. A total of 222 college students from Fujian University of Traditional Chinese Medicine who meet the eligibility criteria will be recruited and randomly allocated into Baduanjin training or usual exercise control group. Baduanjin training will last 12 weeks (1 h per day, 5 days per week). The physical and psychological outcomes, including lumbar muscle strength, lumbar proprioception function, physical fitness, as well as self-reported symptom intensity, stress, self-esteem, mood, quality of life, quality of sleep, and adverse events, will be evaluated by blinded outcome assessors at baseline, 13 weeks (at the end of intervention), and 25 weeks (after the 12-week follow-up period). DISCUSSION: This protocol presents an objective design of a randomized, single-blind trial that aims to evaluate the effectiveness and safety of Baduanjin exercise for physical and mental health of college students. If the outcome is positive, the results will provide higher-quality evidence to better inform the college students regarding their selection about whether to receive such exercise. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-13003329. Registration date: 18 July, 2013.