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Abstract Background Alcohol screening and brief intervention (SBI) is an evidence-based intervention recommended by the World Health Organization. This study applied the Consolidated Framework for Implementation Research (CFIR) to understand facilitators and barriers of SBI implementation in primary care settings in Hong Kong, China. Methods This was a sequential mixed-method study. In-depth interviews of 21 physicians and 20 nurses working in the primary care settings from the public and private sectors were first conducted to identify CFIR constructs that were relevant to SBI implementation in the Chinese context and potential factors not covered by the CFIR. A questionnaire was then developed based on the qualitative findings to investigate factors associated with SBI implementation among 282 physicians and 295 nurses. Results The in-depth interviews identified 22 CFIR constructs that were facilitators or barriers of SBI implementation in Hong Kong. In addition, the stigmatization of alcohol dependence was a barrier and the belief that it was important for people to control the amount of alcohol intake in any situation was mentioned as a facilitator to implement SBI. In the survey, 22% of the participants implemented SBI in the past year. Factors associated with the SBI implementation echoed most of the qualitative findings. Among physicians and nurses in both sectors, they were more likely to implement SBI when perceiving stronger evidence supporting SBI, better knowledge and self-efficacy to implement SBI, more available resources, and clearer planning for SBI implementation in the clinics but less likely to do so when perceiving SBI implementation to be complicated and of higher cost, and drinking approved by the Chinese culture. Participants were more likely to implement SBI when perceiving SBI fit better with the existing practice and better leadership engagement in the public sector, but not in the private sector. Perceiving a stronger need and greater importance to implement SBI were associated with higher likelihood of SBI implementation among physicians, but not among nurses. Perceiving better organizational culture supporting SBI was positively associated with SBI implementation among nurses, but not among physicians. Conclusions There was a significant gap between SBI evidence and its implementation. Some strategies to improve SBI implementation may be different between physicians and nurses and between those in the public and private sectors. The CFIR is a useful framework for understanding facilitators and barriers of SBI implementation in primary care settings.

Abstract Background Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology of Alzheimer’s disease (AD). The natural psychedelic N, N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti-AD potential through protecting neuronal ER-mitochondrial interplay. Methods 3×TG-AD transgenic mice were administered with chronic DMT (2 mg/kg) for 3 weeks and then performed water maze test. The Aβ accumulation in the mice brain were determined. The Sig-1r level upon DMT treatment was tested. The effect of DMT on the ER-mitochondrial contacts site and multiple mitochondria-associated membrane (MAM)-associated proteins were examined. The effect of DMT on calcium transport between ER and mitochondria and the mitochondrial function were also evaluated. Results chronic DMT (2 mg/kg) markedly alleviated cognitive impairment of 3×TG-AD mice. In parallel, it largely diminished Aβ accumulation in the hippocampus and prefrontal cortex. DMT restored the decreased Sig-1r levels of 3×TG-AD transgenic mice. The hallucinogen reinstated the expression of multiple MAM-associated proteins in the brain of 3×TG-AD mice. DMT also prevented physical contact and calcium dynamic between the two organelles in in vitro and in vivo pathological circumstances. DMT modulated oxidative phosphorylation (OXPHOS) and ATP synthase in the in vitro model of AD. Conclusion The anti-AD effects of DMT are associated with its protection of neuronal ER-mitochondria crosstalk via the activation of Sig-1r. DMT has the potential to serve as a novel preventive and therapeutic agent against AD.

Traditional metrology has been unable to adequately address the needs of the emerging integrated circuits (ICs) at the nano scale; thus, new metrology and techniques are needed. For example, the reliability challenges in fabrication need to be well understood and controlled to facilitate mass production of through-substrate-via (TSV) enabled three-dimensional integrated circuits (3D-ICs). This requires new approaches to the metrology. In this paper, we use the microwave propagation characteristics to study the reliability issues that precede the physical damage caused by electromigration in the Cu-filled TSVs. The pre-failure microwave insertion losses and group delay are dependent on both the device temperature and the amount of current forced through the devices-under- test. The microwave insertion losses increase with the increase in the test temperature, while the group delay increases with the increase in the forced direct current magnitude. The microwave insertion losses are attributed to the defect mobility at the Cu-TiN interface, and the group delay changes are due to resistive heating in the interconnects, which perturbs the dielectric properties of the cladding dielectrics of the copper fill in the TSVs. [ABSTRACT FROM AUTHOR]

Lycium ruthenicum Murray (LR), known as “black goji berry” or “black wolfberry”, is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the H2O2-challenged immortalized microglial (IMG) cell line in vitro. LRE oral feeding (2 g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further in vitro study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina.

BackgroundCommunity engagement plays a vital role in global immunization strategies, offering the potential to overcome vaccination hesitancy and enhance vaccination confidence. Although there is significant backing for community engagement in health promotion, the evidence supporting its effectiveness in vaccination promotion is fragmented and of uncertain quality. ObjectiveThis review aims to systematically examine the effectiveness of different contents and extent of community engagement for promoting vaccination rates. MethodsThis study was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive and exhaustive literature search was performed in 4 English databases (PubMed, Embase, Web of Science, and Cochrane Library) and 2 Chinese databases (CNKI and Wan Fang) to identify all possible articles. Original research articles applying an experimental study design that investigated the effectiveness of community engagement in vaccination promotion were eligible for inclusion. Two reviewers independently performed the literature search, study selection, quality assessment, and data extraction. Discrepancies were resolved through discussion, with the arbitration of a third reviewer where necessary. ResultsA total of 20 articles out of 11,404 records from 2006 to 2021 were retrieved. The studies used various designs: 12 applied single-group pre-post study designs, 5 were cluster randomized controlled trials (RCTs), and 3 were non-RCTs. These studies targeted multiple vaccines, with 8 focusing on children’s immunization, 8 on human papillomavirus vaccine, 3 on hepatitis B virus vaccine, and 1 on COVID-19 vaccine. The meta-analysis revealed significant increases in vaccination rates both in pre-post comparison (rate difference [RD] 0.34, 95% CI 0.21-0.47, I2=99.9%, P

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation, differentiation, migration, and survival, as well as angiogenesis, in the context of brain injury. However, whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown. In this study, we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats. The gel slowly released basic fibroblast growth factor, which improved the local microenvironment, activated endogenous neural stem/progenitor cells, and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons, while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery. This study revealed the mechanism by which bioactive materials repair ischemic strokes, thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Abstract College transfer students are those who follow a different trajectory in their higher education journeys than traditional students, completing a sub-degree before pursuing a bachelor’s degree at a university. While the possibility of transferring makes higher education accessible to these students, previous studies have found that they face various challenges, from issues with course load to language challenges. This study aims to examine (1) the critical factors contributing to the success of transfer students in a language course; and (2) how transfer students perform better or worse than those who enter university directly. This study conducted learning analytics with 700 college transfer students in Hong Kong, retrieving their demographic and learning data from the learning management system and the university academic registry. The results suggest that English exam scores, current semester GPA, graduating GPA at community college and current course load are important predictors of transfer students’ success in language courses. This study also finds that transfer students have lower levels of language proficiency than direct entrants. It concludes with specific recommendations to make higher education more accessible to transfer students and suggestions on how to use learning analytics to track students with different trajectories.

Objectives: This study aimed to tailor and pilot a health education program using the PRECEDE-PROCEED model to promote vaccination and enhance self-protective behaviors against COVID-19 in Hong Kong populations. Study design: Quasi-experimental study. Methods: Phases 1–4 of the PRECEDE-PROCEED model were used to identify the needs for COVID-19 prevention. Strategies to address predisposing, reinforcing, and enabling factors in the PRECEDE-PROCEED model were developed, and an intervention package was generated thereafter. A pre–post experimental study was conducted among 50 participants to preliminarily assess the effects of the intervention based on Phases 5 and 8 of the PRECEDE-PROCEED model. Results: The 3-month intervention package contained 16 health education videos, 36 health tips, individual consultations, regular reminders of vaccination, incentive of anti-epidemic packages, and vaccine booking services. By the third month, 33 participants took a new dose of COVID-19 vaccine, and 5 participants withdrew. The vaccination rate for new dose achieved 73.3% (95% CI: 58.06–85.40%). Compared with the Hong Kong population in the same period, our study demonstrated higher increase in vaccination rate (9.97 vs. 1.36 doses per 1000 person-days). The percentage of early testing in personal and family level increased to 86.7% and 84.4%, respectively (both p < 0.05). For correct mask wearing and hand washing, the scores increased from a baseline score of 9.1 ± 1.6 and 4.9 ± 1.3 to 9.5 ± 1.0 and 5.3 ± 1.2, respectively (both p < 0.05). Conclusions: The application of the PRECEDE-PROCEED model effectively facilitated the stepwise development, implementation, and evaluation of a health education program for improving vaccination rates and fostering self-protective behaviors against infections.

Cytokine hormones have a short plasma half-life and require frequent administration. For example, growth hormone replacement involves daily injections. In common with other cytokines, the extracellular domain of the growth hormone receptor circulates as a binding protein, which naturally prolongs the biological half-life of growth hormone. Here we have studied the biological actions of a ligand-receptor fusion of growth hormone and the extracellular domain of its receptor. The genetically engineered ligand-receptor fusion protein was purified from mammalian cell culture. In rats, the ligand-receptor fusion had a 300-times reduced clearance as compared to native growth hormone, and a single injection promoted growth for 10 d, far exceeding the growth seen after administration of native growth hormone. The ligand-receptor fusion forms a reciprocal, head-to-tail dimer that provides a reservoir of inactive hormone similar to the natural reservoir of growth hormone and its binding protein. In conclusion, a ligand-receptor fusion of cytokine to its extracellular receptor generates a potent, long-acting agonist with exceptionally slow absorption and elimination. This approach could be easily applied to other cytokines., Author(s): Ian R Wilkinson [1, 7]; Eric Ferrandis [2, 7]; Peter J Artymiuk [3, 7]; Marc Teillot [2]; Chantal Soulard [2]; Caroline Touvay [2]; Sarbendra L Pradhananga [1]; Sue Justice [...]

BackgroundImmersive virtual reality (IVR)–assisted experiential learning has the potential to foster empathy among undergraduate health care students toward older adults with cognitive impairment by facilitating a sense of embodiment. However, the extent of its effectiveness, including enhancing students’ learning experiences and achieving intended learning outcomes, remains underexplored. ObjectiveThis study aims to evaluate the impacts of IVR-assisted experiential learning on the empathy of undergraduate health care students toward older people with cognitive impairment as the primary outcome (objective 1) and on their learning experience (objective 2) and their attainment of learning outcomes as the secondary outcomes (objective 3). MethodsA multiple-methods design was used, which included surveys, focus groups, and a review of the students’ group assignments. Survey data were summarized using descriptive statistics, whereas paired 2-tailed t tests were used to evaluate differences in empathy scores before and after the 2-hour IVR tutorial (objective 1). Focus groups were conducted to evaluate the impacts of IVR-assisted experiential learning on the empathy of undergraduate health care students toward older people with cognitive impairment (objective 1). Descriptive statistics obtained from surveys and thematic analyses of focus groups were used to explore the students’ learning experiences (objective 2). Thematic analysis of group assignments was conducted to identify learning outcomes (objective 3). ResultsA total of 367 undergraduate nursing and occupational therapy students were recruited via convenience sampling. There was a significant increase in the students’ empathy scores, measured using the Kiersma-Chen Empathy Scale, from 78.06 (SD 7.72) before to 81.17 (SD 8.93) after (P

Summary: Purpose: Controlling blood pressure minimizes the risk of cardiovascular events among patients with hypertension. Despite regular follow-ups, the hypertension management for patients aged ≥45 years is limited as evidenced from a decreased control rate. This pilot study aimed to test a theory-guided educational program for community-dwelling patients with hypertension. Methods: Sixty-nine patients with hypertension aged ≥45 years and having high blood pressure (>130/80 mmHg) were recruited in this two-arm pilot randomized controlled trial. Participants in the intervention group underwent a program guided by the Health Promotion Model, whereas those in the control group received usual care. Data were collected at baseline, week 8, and week 12 and used to assess the blood pressure, pulse pressure, self-efficacy, and adherence to hypertension management. Data were analyzed using a generalized estimating equation based on the intention-to-treat principle. Process evaluation was conducted to assess the feasibility and acceptability of the educational program. Results: The results obtained using the generalized estimating equation revealed that the educational program led to reduction in the systolic blood pressure (β = −7.12, p = .086) and pulse pressure (β = −8.20, p = .007) and to improve self-efficacy (β = 2.61, p = .269) at week 12. The program had a small-to-moderate effect on the reduction of systolic blood pressure (effect size = −0.45) and pulse pressure (effect size = −0.66) and self-efficacy (effect size = 0.23). The participants were highly satisfied with the educational program. Conclusions: The educational program was found to be feasible and acceptable and may be incorporated into current hypertension management practices at the community level. Trial registration: ClinicalTrials.gov with identifier: NCT04565548.

Microglia, as resident macrophages in the central nervous system, play a multifunctional role in the pathogenesis of Alzheimer’s disease (AD). Their clustering around amyloid-β (Aβ) deposits is a core pathological feature of AD. Recent advances in single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) have revealed dynamic changes in microglial phenotypes over time and across different brain regions during aging and AD progression. As AD advances, microglia primarily exhibit impaired phagocytosis of Aβ and tau, along with the release of pro-inflammatory cytokines that damage synapses and neurons. Targeting microglia has emerged as a potential therapeutic approach for AD. Treatment strategies involving microglia can be broadly categorized into two aspects: (1) enhancing microglial function: This involves augmenting their phagocytic ability against Aβ and cellular debris and (2) mitigating neuroinflammation: Strategies include inhibiting TNF-α signaling to reduce the neuroinflammatory response triggered by microglia. Clinical trials exploring microglia-related approaches for AD treatment have garnered attention. Additionally, natural products show promise in enhancing beneficial effects and suppressing inflammatory responses. Clarifying microglial dynamics, understanding their roles, and exploring novel therapeutic approaches will advance our fight against AD.

Background: Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment, this versatile, economical treatment option is attractive in the ophthalmic field. The safety and toxicity profile of ART intravitreal application are in utmost need. Methods: In this study, immortalized microglial (IMG) cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions. Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation. Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice. Retinal function was tested by electroretinogram, and retinal ganglion cell (RGC) survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection. Results: ART below 5μM was safe for IMG cells in vitro. Both 2.5 and 5 ​μM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1β, IL-6, TNF-α, and Arg-1. In the in vivo study, intravitreal injection of ART below 100 ​μM did not cause deterioration in the retinal function and RGC survival of the mouse eyes, while 1 ​mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival. In addition, treatment with ART of 25, 50, and 100 ​μM significantly decreased TNF-α gene expression while ART of 100 ​μM significantly increased IL-10 in the mouse retina. Conclusions: Intravitreal injection of 100 ​μM ART could downregulate TNF-α while upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss. ART might be used as anti-inflammatory agent for retinal disorders.

Single Rhodamine 6G (R6G) molecules in levitated glycerol microdroplets have been detected with signal-to-noise ratios of >40 using CW laser-induced fluorescence. The fluorescence signal from single R6G molecules was identified by the magnitude of the fluorescence signal and by the unique time dependence of the fluorescence count rate before photobleaching. This high sensitivity allows single molecules to be counted by use of a digital detection approach offering significantly lower detection limits than those possible with conventional detection methods.

BackgroundComplete documentation of critical care events in the accident and emergency department (AED) is essential. Due to the fast-paced and complex nature of resuscitation cases, missing data is a common issue during emergency situations. ObjectiveThis study aimed to evaluate the impact of a tablet-based resuscitation record on documentation completeness during medical resuscitations and nurses’ perceptions of the use of the tablet app. MethodsA mixed methods approach was adopted. To collect quantitative data, randomized retrospective reviews of paper-based resuscitation records before implementation of the tablet (Pre-App Paper; n=176), paper-based resuscitation records after implementation of the tablet (Post-App Paper; n=176), and electronic tablet-based resuscitation records (Post-App Electronic; n=176) using a documentation completeness checklist were conducted. The checklist was validated by 4 experts in the emergency medicine field. The content validity index (CVI) was calculated using the scale CVI (S-CVI). The universal agreement S-CVI was 0.822, and the average S-CVI was 0.939. The checklist consisted of the following 5 domains: basic information, vital signs, procedures, investigations, and medications. To collect qualitative data, nurses’ perceptions of the app for electronic resuscitation documentation were obtained using individual interviews. Reporting of the qualitative data was guided by Consolidated Criteria for Reporting Qualitative Studies (COREQ) to enhance rigor. ResultsA significantly higher documentation rate in all 5 domains (ie, basic information, vital signs, procedures, investigations, and medications) was present with Post-App Electronic than with Post-App Paper, but there were no significant differences in the 5 domains between Pre-App Paper and Post-App Paper. The qualitative analysis resulted in main categories of “advantages of tablet-based documentation of resuscitation records,” “challenges with tablet-based documentation of resuscitation records,” and “areas for improvement of tablet-based resuscitation records.” ConclusionsThis study demonstrated that higher documentation completion rates are achieved with electronic tablet-based resuscitation records than with traditional paper records. During the transition period, the nurse documenters faced general problems with resuscitation documentation such as multitasking and unique challenges such as software updates and a need to familiarize themselves with the app’s layout. Automation should be considered during future app development to improve documentation and redistribute more time for patient care. Nurses should continue to provide feedback on the app’s usability and functionality during app refinement to ensure a successful transition and future development of electronic documentation records.

Introduction KEYNOTE-394 showed pembrolizumab significantly improved overall survival, progression-free survival, and objective response rate with manageable safety versus placebo for patients from Asia with previously treated advanced hepatocellular carcinoma. We present results on health-related quality of life (HRQoL). Methods HRQoL was evaluated using the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EuroQol-5D-3L (EQ-5D-3L) questionnaires. Key HRQoL endpoints were least squares mean (LSM) score changes from baseline to week 12 and time to deterioration (TTD) for EORTC QLQ-C30 global health status (GHS)/QoL. p values were one-sided and nominal without adjustment for multiplicity. Results The HRQoL population included patients randomly assigned to pembrolizumab (n = 298) and placebo (n = 152). From baseline to week 12, a greater decline in EORTC QLQ-C30 GHS/QoL score was observed with placebo (LSM, −8.4; 95% CI: −11.7 to −5.1) versus pembrolizumab (−4.0; 95% CI: −6.4 to −1.6; difference vs placebo: 4.4; 95% CI: 0.5–8.4; nominal p = 0.0142). Similarly, a greater decline in EQ-5D-3L visual analog scale score was observed with placebo (−6.9; 95% CI: −9.4 to −4.5) versus pembrolizumab (−2.7; 95% CI: −4.5 to −1.0; difference vs placebo: 4.2; 95% CI: 1.2–7.2; nominal p = 0.0030). TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (hazard ratio, 0.85; 95% CI: 0.58–1.25; nominal p = 0.1993). Conclusion Patients receiving placebo showed greater decline in HRQoL than those receiving pembrolizumab. Combined with efficacy and safety data from KEYNOTE-394 and the global KEYNOTE-240 and KEYNOTE-224 trials, our data support the clinically meaningful benefit and manageable tolerability of pembrolizumab as second-line therapy for patients with advanced hepatocellular carcinoma.

Background The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance. Methods Therefore, an inventory surveillance of the ESBL-Escherichia coli (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted. Additionally, the in vitro efficacy of flomoxef and other established antibiotics against ESBL-EC was evaluated. Results A total of 127 non-repetitive ESBL-EC strains isolated from clinical samples were collected during a multicentre study performed in five representative Malaysian hospitals. Of all the isolates, 33.9% were isolated from surgical site infections and 85.8% were hospital-acquired infections. High rates of resistance to cefotaxime (100%), cefepime (100%), aztreonam (100%) and trimethoprim-sulfamethoxazole (100%) were observed based on the broth microdilution test. Carbapenems remained the most effective antibiotics against the ESBL-EC, followed by flomoxef. Antibiotic resistance genes were identified by PCR. The blaCTX-M-1 was the most prevalent ESBL gene, with 28 isolates (22%) harbouring blaCTX-M-1 only, 27 isolates (21.3%) co-harbouring blaCTX-M-1 and blaTEM, and ten isolates (7.9%) co-harbouring blaCTX-M-1, blaTEM and blaSHV. A generalised linear model showed significant antibacterial activity of imipenem against different types of infection. Besides carbapenems, this study also demonstrated a satisfactory antibacterial activity of flomoxef (81.9%) on ESBL-EC, regardless of the types of ESBL genes.

BackgroundN95 respirators are used to limit the transmission of respiratory viruses in clinical settings. There are two to three major types of N95 available for all healthcare workers in Hong Kong. However, after the coronavirus outbreak and the consequent shortage of many commonly used respirators, several new N95 respirators were adopted temporarily in clinical settings without evaluation. Prior literature indicates that traditional N95 respirators used in hospitals in Hong Kong are not fit for Chinese people and have fit rates ranging from 50 to 60%. This study aims to investigate and compare the fit rate, real-time leakage, and mask usability of traditional and new N95 respirators among Chinese healthcare workers.MethodsThis study will employ two sequential phases. Phase 1 has a cross-sectional exploratory design used to investigate the fit rate and mask usability of three types of respirators. Phase 2 will examine the effectiveness of respiratory protection by comparing traditional and new N95 respirators by a randomized crossover trial. Eligible participants will be randomly allocated through a controlled crossover experiment to either a traditional or new respirator group (n = 100 in each arm) for performing standard clinical procedures. The primary outcome (real-time leakage) will be recorded at 30 s intervals during nasopharyngeal suctioning and cardiopulmonary resuscitation. The secondary outcomes are the fit rate and mask usability. After a 2 min suctioning (15 s twice) and 4 min one-person CPR, the fit rate (assessed by standard N95 fit testing) and mask usability (measured by self-reported mask usability scale) will be recorded as data of post-procedure. After 10 min rest, measurement of real-time leakage (i.e., crossover), fit test, and usability will be repeated.DiscussionThe result of real-time leakage will be a vital indicator of the respiratory protection of Chinese healthcare workers while performing prevalent clinical procedures, such as resuscitation. The fit rate and usability result will serve as an essential reference for consumable purchase policy in clinical settings.Trial registration: ISRCTN registry: ISRCTN40115047. Retrospectively registered on May 9, 2023. https://www.isrctn.com/ISRCTN40115047.

The ability to count individual molecules or the concept of digital molecular detection and the mathematical framework for defining detection limits under various experimental constraints are presented and discussed. It was found that significant advantages accrue when using a digital detection strategy against a conventional approach with modest signal-to-noise ratio for detection of single molecules. The feasibility of implementing a digital detection strategy for highly fluorescing molecules are shown by these experiments.

Abstract Image-guided drawing can compensate for a lack of skill but often requires a significant number of repetitive strokes to create textures. Existing automatic stroke synthesis methods are usually limited to predefined styles or require indirect manipulation that may break the spontaneous flow of drawing. We present an assisted drawing system to autocomplete repetitive short strokes during a user’s normal drawing process. Users draw over a reference image as usual; at the same time, our system silently analyzes the input strokes and the reference to infer strokes that follow the user’s input style when certain repetition is detected. Users can accept, modify, or ignore the system’s predictions and continue drawing, thus maintaining fluid control over drawing. Our key idea is to jointly analyze image regions and user input history to detect and predict repetition. The proposed system can effectively reduce the user’s workload when drawing repetitive short strokes, helping users to create results with rich patterns.

Retinal structural and functional changes in humans can be manifestations of different physiological or pathological conditions. Retinal imaging is the only way to directly inspect blood vessels and their pathological changes throughout the whole body non-invasively. Various quantitative analysis metrics have been used to measure the abnormalities of retinal microvasculature in the context of different retinal, cerebral and systemic disorders. Recently developed optical coherence tomography angiography (OCTA) is a non-invasive imaging tool that allows high-resolution three-dimensional mapping of the retinal microvasculature. The identification of retinal biomarkers from OCTA images could facilitate clinical investigation in various scenarios. We provide a framework for extracting computational retinal microvasculature biomarkers (CRMBs) from OCTA images through a knowledge-driven computerized automatic analytical system. Our method allows for improved identification of the foveal avascular zone (FAZ) and introduces a novel definition of vessel dispersion in the macular region. Furthermore, retinal large vessels and capillaries of the superficial and deep plexus can be differentiated, correlating with retinal pathology. The diagnostic value of OCTA CRMBs was demonstrated by a cross-sectional study with 30 healthy subjects and 43 retinal vein occlusion (RVO) patients, which identified strong correlations between OCTA CRMBs and retinal function in RVO patients. These OCTA CRMBs generated through this “all-in-one” pipeline may provide clinicians with insights about disease severity, treatment response and prognosis, aiding in the management and early detection of various disorders.

The 3′,5′-dimethoxybenzoin (DMB) system has been widely investigated as a photoremovable protecting group (PRPG) for the elimination of various functional groups and has been applied in many fields. The photolysis of DMB fluoride leads to a highly efficient photocyclization–deprotection reaction, resulting in a high yield of 3′,5′-dimethoxybenzofuran (DMBF) in a MeCN solution, while there is a competitive reaction that produces DMB in an aqueous solution. The yield of DMB increased as the volume ratio of water increased. To understand the solvent effect of the photolysis of selected DMB-based compounds, a combination of femtosecond to nanosecond transient absorption spectroscopies (fs-TA and ns-TA), nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) and quantum chemical calculation was employed to study the photophysical and photochemical reaction mechanisms of DMB fluoride in different solutions. Facilitated by the bichromophoric nature of DMB fluoride with electron-donating and -withdrawing chromophores, the cyclized intermediates could be found in a pure MeCN solution. The deprotection of a cyclic biradical intermediate results in the simultaneous formation of DMBF and a cyclic cation species. On the other hand, in aqueous solution, fs-TA experiments revealed that α-keto cations could be observed after excitation directly, which could easily produce the DMB through the addition of a hydroxyl within 8.7 ps. This work provides comprehensive photo-deactivation mechanisms of DMB fluoride in MeCN and aqueous conditions and provides critical insights regarding the biomedical application of DMB-based PRPG compounds.

Abstract Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder involving skeletal dysplasia and heterotopic ossification (HO) of muscle and connective tissue. We aimed to define a novel biomarker in FOP that enables reliable assessment of musculoskeletal tissue integrity. Considering logistical difficulties that FOP patients often face, our goal was to identify an at-home biomarker technique. Electrical impedance myography (EIM) is a non-invasive, portable method that can inform on muscle health. 15 FOP patients (age 10–52) and 13 healthy controls were assessed. Using EIM, multiple muscle groups were characterized per participant in a 45-min period. The Cumulative Analogue Joint Involvement Scale (CAJIS) was implemented to determine mobility burden severity. We additionally evaluated physical activity levels via a Patient-Reported Outcomes Measurement Information System (PROMIS)-based questionnaire. Relative to controls, FOP patients demonstrated significantly lower regional and whole-body phase values at 50 kHz and 100 kHz, indicating more diseased muscle tissue. Lower whole-body phase and reactance values, and higher resistance values, were associated with greater FOP burden (CAJIS score range: 4–30) and lower physical activity levels at 50 kHz and 100 kHz. This study points to the potential utility of EIM as a clinical biomarker tool capable of characterizing muscle integrity in FOP.

Clinical manifestations of tuberculosis range from asymptomatic infection to a life-threatening disease such as tuberculous meningitis (TBM). Recent studies showed that the spectrum of disease severity could be related to genetic diversity among clinical strains of Mycobacterium tuberculosis (Mtb). Certain strains are reported to preferentially invade the central nervous system, thus earning the label “hypervirulent strains”.However, specific genetic mutations that accounted for enhanced mycobacterial virulence are still unknown. We previously identified a set of 17 mutations in a hypervirulent Mtb strain that was from TBM patient and exhibited significantly better intracellular survivability. These mutations were also commonly shared by a cluster of globally circulating hyper-virulent strains. Here, we aimed to validate the impact of these hypervirulent-specific mutations on the dysregulation of gene networks associated with virulence in Mtb via multi-omic analysis. We surveyed transcriptomic and proteomic differences between the hyper-virulent and low-virulent strains using RNA-sequencing and label-free quantitative LC-MS/MS approach, respectively. We identified 25 genes consistently differentially expressed between the strains at both transcript and protein level, regardless the strains were growing in a nutrient-rich or a physiologically relevant multi-stress condition (acidic pH, limited nutrients, nitrosative stress, and hypoxia). Based on integrated genomic-transcriptomic and proteomic comparisons, the hypervirulent-specific mutations in FadE5 (g. 295,746 C >T), Rv0178 (p. asp150glu), higB (p. asp30glu), and pip (IS6110-insertion) were linked to deregulated expression of the respective genes and their functionally downstream regulons. The result validated the connections between mutations, gene expression, and mycobacterial pathogenicity, and identified new possible virulence-associated pathways in Mtb.

Aim: Patients with inflammatory bowel disease (IBD) are diagnosed with anxiety/depression at higher rates than the general population. We aimed to determine the frequency of anxiety/depression among IBD patients and the temporal association with abdominal surgery and stoma formation. Method: We conducted a retrospective cohort study in adult patients with IBD using difference‐in‐difference methodology and a large commercial claims database (2003–2016). Outcomes were anxiety/depression diagnoses before and after major abdominal surgery or stoma formation. Results: We identified 10 481 IBD patients who underwent major abdominal surgery, 18.8% of whom underwent stoma formation, and 41 924 nonsurgical age‐ and sex‐matched IBD controls who were assigned random index dates. Rates of anxiety and depression increased among all cohorts (P < 0.001). Surgical patients had higher odds of anxiety [one surgery, adjusted OR 6.90 (95% CI 6.11–7.79), P < 0.001; two or more surgeries, 7.53 (5.99–9.46), P < 0.001] and depression [one surgery, 6.15 (5.57–6.80), P < 0.001; two or more surgeries, 6.88 (5.66–8.36), P < 0.001] than nonsurgical controls. Undergoing multiple surgeries was associated with a significant increase in depression from 'pre' to 'post' time periods [1.43 (1.18–1.73), P < 0.001]. Amongst surgical patients, stoma formation was independently associated with anxiety [1.40 (1.17–1.68), P < 0.001] and depression [1.23 (1.05–1.45), P = 0.01]. New ostomates experienced a greater increase in postoperative anxiety [1.24 (1.05–1.47), P = 0.01] and depression [1.19 (1.03–1.45), P = 0.01] than other surgical patients. Conclusion: IBD patients who undergo surgery have higher rates of anxiety and depression than nonsurgical patients. Rates of anxiety and depression increase following surgery. Stoma formation represents an additional risk factor. These findings suggest the need for perioperative psychosocial support services. [ABSTRACT FROM AUTHOR]

IntroductionLycium barbarum glycopeptide (LbGp) is the main bioactive compound extracted from the traditional Chinese medicine. L. barbarum berries and has been proven to have numerous health benefits, including antioxidative, anti-inflammatory, anticancer, and cytoprotective activities. However, the antiaging effect of LbGp remains unknown.MethodsThe lifespan and body movement of C. elegans were used to evaluate the effect of LbGp on lifespan and health span. The thrashing assay was used to determine the role of LbGp in Parkinson’s disease. To investigate the mechanisms of LbGp-induced antiaging effects, we analyzed changes in lifespan, movement, and the expression of longevity-related genes in a series of worm mutants after LbGp treatment.ResultsWe found that LbGp treatment prolonged the lifespan and health span of C. elegans. Mechanistically, we found that LbGp could activate the transcription factors DAF-16/FOXO, SKN-1/Nrf2, and HSF-1, as well as the nuclear receptor DAF-12, thereby upregulating longevity-related genes to achieve lifespan extension. In addition, we found that the lifespan extension induced by LbGp partially depends on mitochondrial function. Intriguingly, LbGp also ameliorated neurodegenerative diseases such as Parkinson’s disease in a DAF-16-, SKN-1-, and HSF-1-dependent manner.ConclusionOur work suggests that LbGp might be a viable candidate for the treatment and prevention of aging and age-related diseases.

BackgroundUniversity students are identified as a high-risk group for mental health problems. Artworks have been found effective in enhancing individuals’ mental well-being in different populations, but none have been conducted on university students. This study was to address this research gap to determine the feasibility and estimate the preliminary effects of Zentangle and Pastel Nagomi on the mental well-being of undergraduate students during the COVID-19 pandemic.MethodThis was a 3-arm randomized controlled trial, with 33 undergraduates allocated to two 8-week artworks (Zentangle or Pastel Nagomi Art group) and a control group. Data were collected at baseline, and weeks 4, 6, 8, and 12. Focus group interviews were conducted at the 12-week follow-up.ResultsThe consent and attrition rates were 80.5 and 6.06%, respectively. The attendance rate ranged from 83.3 to 100%. Compared with the control group, the Pastel Nagomi art group had a significant improvement in retaining positive affect at week 6. This retention could be further observed at week 12. Moreover, the Zentangle group had a significant increase in positive affect at week 4, with better retention at week 12. In addition, the within-group analyses showed that the Pastel Nagomi art group had significantly decreased negative affect at weeks 6 and week 12; and the Zentangle group had significantly decreased depression at week 8. The qualitative findings suggested that the intervention resulted in the participants enjoying the artwork process, and being proud of their artwork and personal growth.LimitationThe study included an imbalance number of online vs. face-to-face sessions, and repeated measures may have affected the results.ConclusionThe study suggests that both artworks are effective in improving undergraduates’ mental well-being and that it is feasible to conduct future large-scale studies (263 words).

Aging often leads to awareness decline and psychological stress. Meditation, a method of modulating consciousness, may help individuals improve overall awareness and increase emotional resilience toward stress. This study explored the potential influence of the Awareness Training Program (ATP), a form of consciousness modulation, on age-related brain wave changes and psychological stress in middle-aged adults. Eighty-five participants with mild stress were recruited and randomly assigned to ATP (45.00 ± 8.00 yr) or control (46.67 ± 7.80 yr) groups, matched by age and gender. Ten-minute resting-state EEG data, obtained while the participants’ eyes were closed, were collected using a 128-channel EEG system (EGI). A strong positive Pearson correlation was found between fast-wave (beta wave, 12–25 Hz; gamma wave, 25–40 Hz) EEG and age. However, after the 7-week ATP intervention, this correlation became insignificant in the ATP group. Furthermore, there was a significant reduction in stress levels, as measured by the Chinese version of the 10 item Perceived Stress Scale (PSS-10), in the ATP group. These results suggest that ATP may help modulate age-related effects on fast brain waves, as evidenced by the reduced correlation magnitude between age and gamma waves, and lower psychological stress. This suggests that ATP, as a form of consciousness modulation, may improve stress resilience and modulate age-related gamma wave changes.