Applying the Consolidated Framework for Implementation Research to investigate factors of implementing alcohol screening and brief intervention among primary care physicians and nurses in Hong Kong, China: an exploratory sequential mixed-method study.

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.

Death education interventions for people with advanced diseases and/or their family caregivers: A scoping review.

BACKGROUND: People with life-threatening diseases and their family caregivers confront psychosocial and spiritual issues caused by the persons' impending death. Reviews of death education interventions in the context of life-threatening diseases are scarce and limited to certain intervention types. AIMS: This study aims to ascertain existing evidence on death education interventions for the population of adults with advanced diseases and/or their family caregivers and identify gaps for future research. DESIGN: A scoping review guided by Arksey and O'Malley's framework. DATA SOURCES: Thirteen electronic databases were searched for experimental and qualitative studies on death education interventions for the advanced disease population and/or their family caregivers between 1 January 1960 and 25 October 2023. RESULTS: Nine types of interventions were identified in 47 studies, which included 5 qualitative and 42 experimental designs, half of which were pilot and feasibility trials. Most of the studies focused on people with advanced cancer, and only seven investigated caregivers or families/couples. Death-related outcomes were less likely to be assessed relative to psychological outcomes, spiritual well-being, and quality of life. Life review interventions, cognitive-behavior therapy, narrative therapy, and general psychosocial interventions decreased depression and anxiety, but evidence was limited. Factors contributing to the interventions' success included intervention content, which enabled the disclosure of personal experience and death concerns comfortably, trained professionals, and connection to family caregivers. CONCLUSIONS: This work identified a few potentially effective death education interventions for psychological outcomes for people with advanced cancer or their caregivers. Additional trials are needed to confirm the effectiveness of these interventions.

Community Engagement in Vaccination Promotion: Systematic Review and Meta-Analysis.

BACKGROUND: Community 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. OBJECTIVE: This review aims to systematically examine the effectiveness of different contents and extent of community engagement for promoting vaccination rates. METHODS: This 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. RESULTS: A 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<.001) and between-group comparison (RD 0.18, 95% CI 0.07-0.29, I2=98.4%, P<.001). The meta-analysis revealed that participant recruitment had the largest effect size (RD 0.51, 95% CI 0.36-0.67, I2=99.9%, P<.001), followed by intervention development (RD 0.36, 95% CI 0.23-0.50, I2=100.0%, P<.001), intervention implementation (RD 0.35, 95% CI 0.22-0.47, I2=99.8%, P<.001), and data collection (RD 0.34, 95% CI 0.19-0.50, I2=99.8%, P<.001). The meta-analysis indicated that high community engagement extent yielded the largest effect size (RD 0.49, 95% CI 0.17-0.82, I2=100.0%, P<.001), followed by moderate community engagement extent (RD 0.45, 95% CI 0.33-0.58, I2=99.6%, P<.001) and low community engagement extent (RD 0.15, 95% CI 0.05-0.25, I2=99.2%, P<.001). The meta-analysis revealed that "health service support" demonstrated the largest effect sizes (RD 0.45, 95% CI 0.25-0.65, I2=99.9%, P<.001), followed by "health education and discussion" (RD 0.39, 95% CI 0.20-0.58, I2=99.7%, P<.001), "follow-up and reminder" (RD 0.33, 95% CI 0.23-0.42, I2=99.3%, P<.001), and "social marketing campaigns and community mobilization" (RD 0.24, 95% CI 0.06-0.41, I2=99.9%, P<.001). CONCLUSIONS: The results of this meta-analysis supported the effectiveness of community engagement in vaccination promotion with variations in terms of engagement contents and extent. Community engagement required a "fit-for-purpose" approach rather than a "one-size-fits-all" approach to maximize the effectiveness of vaccine promotion. TRIAL REGISTRATION: PROSPERO CRD42022339081; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=339081.

A phase 1 study of the irreversible FLT3 inhibitor FF-10101 in relapsed or refractory acute myeloid leukemia.

ABSTRACT: FLT3 tyrosine kinase inhibitors (TKIs) have clinical efficacy for patients with FLT3-mutated AML (acute myeloid leukemia), but their impact is limited by resistance in the setting of monotherapy and by tolerability problems when used in combination therapies. FF-10101 is a novel compound that covalently binds to a cysteine residue near the active site of FLT3, irreversibly inhibiting receptor signaling. It is effective against most FLT3 activating mutations, and, unlike other inhibitors, is minimally vulnerable to resistance induced by FLT3 ligand. We conducted a phase 1 dose escalation study of oral FF-10101 in patients with relapsed and/or refractory AML, the majority of whom harbored FLT3-activating mutations and/or had prior exposure to FLT3 inhibitors. Fifty-four participants enrolled in cohorts receiving doses ranging from 10 to 225 mg per day and 50 to 100 mg twice daily (BID). The dose limiting toxicities were diarrhea and QT prolongation. Among 40 response-evaluable participants, the composite complete response rate was 10%, and the overall response rate (including partial responses) was 12.5%, including patients who had progressed on gilteritinib. Overall, 56% of participants had prior exposure to FLT3 inhibitors. The recommended phase 2 dose was 75 mg BID. FF-10101 potentially represents a next-generation advance in the management of FLT3-mutated AML. This trial was registered at www.ClinicalTrials.gov as #NCT03194685.

Prostate diffusion-weighted imaging (DWI) in MR-guided radiotherapy: Reproducibility assessment on 1.5 T MR-Linac and 1.5 T MR-simulator.

PURPOSE: Diffusion-weighted imaging (DWI) holds promise for image-guided radiotherapy (MRgRT) in prostate cancer. However, challenges persist due to image distortion, artifacts, and apparent diffusion coefficient (ADC) reproducibility issues. This study aimed to assess DWI image quality and ADC reproducibility on both a 1.5 T MR-simulator and a 1.5 T MR-Linac, employing measurements from both an ACR MRI phantom and prostate cancer patients undergoing MRgRT. METHODS: DW-MRI scans were conducted on 19 patients (mean age = 69 ± 8 years, with 23 MR-visible intra-prostatic lesions) and an ACR MRI phantom using a 1.5 T MR-simulator (b-values = 0, 800, 1400s/mm2) and a 1.5 T MR-Linac (b-values = 50, 500, 800 s/mm2). ADC homogeneity in the phantom was evaluated via 1D profile flatness (FL) in three directions. Image quality was assessed through qualitative 5-point Likert scale ratings and quantitative ADC and signal-to-noise ratio (SNR) measurements. Intra-observer reproducibility of image quality scores was evaluated using ICC(1, 2). Geometric distortion was measured by comparing landmark sizes on the ACR phantom against the ground truth. Mean ADC and reproducibility were assessed using Bland-Altman plots. RESULTS: Both MR-simulator and MR-Linac demonstrated high ADC homogeneity (FL > 87.5% - MR-simulator: 97.23 ± 0.62%, MR-Linac: 94.75 ± 0.62%, p < 0.05) in the phantom. Image quality scores revealed acceptable ratings (≥3) for capsule demarcation, image artifacts, and geometric distortion in patients. However, intra-prostatic lesions were barely discernible in b800 images for both MR-simulator (average score = 2.37 ± 1.33) and MR-Linac (average score = 2.16 ± 1.28). While MR-Linac DWI scans exhibited significantly more severe geometric distortion than MR-simulator scans (p < 0.01), most phantom measurements fell within the image in-plane resolution of 3 mm. Significant differences were noted in MR-simulator ADC (CTV: 1.20 ± 0.14 × 10-3 mm2/s (MR-simulator) vs 1.06 ± 0.10 × 10-3 mm2/s (MR-Linac); GTV: 1.05 ± 0.21 × 10-3 mm2/s vs 0.91 ± 0.16 × 10 mm2/s, all p < 0.05), with a small non-zero bias observed in the Bland-Altman analysis (CTV: 12.3%; GTV: 14.5%). CONCLUSION: The significantly larger MR-simulator ADC and the small non-zero bias hint at potential systematic differences in ADC values acquired from an MR-simulator and an MR-Linac, both at 1.5 T. Although acceptable ADC homogeneity was noted, caution is warranted in interpreting MR-Linac DWI images due to occasional severe artifacts. Further studies are essential to validate DWI and ADC as reliable imaging markers in prostate cancer MRgRT.

Corrigendum: Evaluation of N95 respirators on fit rate, real-time leakage, and usability among Chinese healthcare workers: study protocol of a randomized crossover trial.

[This corrects the article DOI: 10.3389/fpubh.2023.1266607.].

One-year clinical outcomes of MR-guided stereotactic body radiation therapy with rectal spacer for patients with localized prostate cancer.

BACKGROUND AND PURPOSE: This prospective study aimed to investigate adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (MRgSBRT) with rectal spacer for localized prostate cancer (PC) and report 1-year clinical outcomes. MATERIALS AND METHODS: Thirty-four consecutive patients with low- to high-risk localized PC that underwent 5-fraction adaptive MRgSBRT with rectal spacer were enrolled. The dosimetric comparison was performed on a risk- and age-matched cohort treated with MRgSBRT but without a spacer at a similar timepoint. Clinician-reported outcomes were based on Common Terminology Criteria for Adverse Events. Patient-reported outcomes were based on the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline, acute (1-3 months), subacute (4-12 months), and late (> 12 months) phases. RESULTS: The median follow-up was 390 days (range 28-823) and the median age was 70 years (range 58-82). One patient experienced rectal bleeding soon after spacer insertion that subsided before MRgSBRT. The median distance between the midline of the prostate midgland and the rectum after spacer insertion measured 7.8 mm (range 2.6-15.3), and the median length of the spacer was 45.9 mm (range 16.8-62.9) based on T2-weighted MR imaging. The use of spacer resulted in significant improvements in target coverage (V100% > 95% = 98.6% [range 93.4-99.8] for spacer vs. 97.8% [range 69.6-99.7] for non-spacer) and rectal sparing (V95% < 3 cc = 0.7 cc [range 0-4.6] for spacer vs. 4.9 cc [range 0-12.5] for non-spacer). Nine patients (26.5%) experienced grade 1 gastrointestinal toxicities, and no grade ≥ 2 toxicities were observed. During the 1-year follow-up period, EPIC scores for the bowel domain remained stable and were the highest among all other domains. CONCLUSIONS: MRgSBRT with rectal spacer for localized PC showed exceptional tolerability with minimal gastrointestinal toxicities and satisfactory patient-reported outcomes. Improvements in dosimetry, rectal sparing, and target coverage were achieved with a rectal spacer. Randomized trials are warranted for further validation.

The Effects of Immersive Virtual Reality-Assisted Experiential Learning on Enhancing Empathy in Undergraduate Health Care Students Toward Older Adults With Cognitive Impairment: Multiple-Methods Study.

BACKGROUND: Immersive 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. OBJECTIVE: This 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). METHODS: A 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). RESULTS: A 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<.001). Students expressed high satisfaction with the IVR learning innovation, with a high satisfaction mean score of 20.68 (SD 2.55) and a high self-confidence mean score of 32.04 (SD 3.52) on the Student Satisfaction and Self-Confidence scale. Students exhibited a good sense of presence in the IVR learning environment, as reflected in the scores for adaptation (41.30, SD 6.03), interface quality (11.36, SD 3.70), involvement (62.00, SD 9.47), and sensory fidelity (31.47, SD 5.23) on the Presence Questionnaire version 2.0. In total, 3 major themes were identified from the focus groups, which involved 23 nursing students: enhanced sympathy toward older adults with cognitive impairment, improved engagement in IVR learning, and confidence in understanding the key concepts through the learning process. These themes supplement and align with the survey results. The analysis of the written assignments revealed that students attained the learning outcomes of understanding the challenges faced by older adults with cognitive impairment, the importance of providing person-centered care, and the need for an age-friendly society. CONCLUSIONS: IVR-assisted experiential learning enhances students' knowledge and empathy in caring for older adults with cognitive impairment. These findings suggest that IVR can be a valuable tool in professional health care education.

Documentation Completeness and Nurses' Perceptions of a Novel Electronic App for Medical Resuscitation in the Emergency Room: Mixed Methods Approach.

BACKGROUND: Complete 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. OBJECTIVE: This 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. METHODS: A 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. RESULTS: A 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." CONCLUSIONS: This 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.

A study of Bayesian deep network uncertainty and its application to synthetic CT generation for MR-only radiotherapy treatment planning.

BACKGROUND: The use of synthetic computed tomography (CT) for radiotherapy treatment planning has received considerable attention because of the absence of ionizing radiation and close spatial correspondence to source magnetic resonance (MR) images, which have excellent tissue contrast. However, in an MR-only environment, little effort has been made to examine the quality of synthetic CT images without using the original CT images. PURPOSE: To estimate synthetic CT quality without referring to original CT images, this study established the relationship between synthetic CT uncertainty and Bayesian uncertainty, and proposed a new Bayesian deep network for generating synthetic CT images and estimating synthetic CT uncertainty for MR-only radiotherapy treatment planning. METHODS AND MATERIALS: A novel deep Bayesian network was formulated using probabilistic network weights. Two mathematical expressions were proposed to quantify the Bayesian uncertainty of the network and synthetic CT uncertainty, which was closely related to the mean absolute error (MAE) in Hounsfield Unit (HU) of synthetic CT. These uncertainties were examined to demonstrate the accuracy of representing the synthetic CT uncertainty using a Bayesian counterpart. We developed a hybrid Bayesian architecture and a new data normalization scheme, enabling the Bayesian network to generate both accurate synthetic CT and reliable uncertainty information when probabilistic weights were applied. The proposed method was evaluated in 59 patients (13/12/32/2 for training/validation/testing/uncertainty visualization) diagnosed with prostate cancer, who underwent same-day pelvic CT- and MR-acquisitions. To assess the relationship between Bayesian and synthetic CT uncertainties, linear and non-linear correlation coefficients were calculated on per-voxel, per-tissue, and per-patient bases. For accessing the accuracy of the CT number and dosimetric accuracy, the proposed method was compared with a commercially available atlas-based method (MRCAT) and a U-Net conditional-generative adversarial network (UcGAN). RESULTS: The proposed model exhibited 44.33 MAE, outperforming UcGAN 52.51 and MRCAT 54.87. The gamma rate (2%/2 mm dose difference/distance to agreement) of the proposed model was 98.68%, comparable to that of UcGAN (98.60%) and MRCAT (98.56%). The per-patient and per-tissue linear correlation coefficients between the Bayesian and synthetic CT uncertainties ranged from 0.53 to 0.83, implying a moderate to strong linear correlation. Per-voxel correlation coefficients varied from -0.13 to 0.67 depending on the regions-of-interest evaluated, indicating tissue-dependent correlation. The R2 value for estimating MAE solely using Bayesian uncertainty was 0.98, suggesting that the uncertainty of the proposed model was an ideal candidate for predicting synthetic CT error, without referring to the original CT. CONCLUSION: This study established a relationship between the Bayesian model uncertainty and synthetic CT uncertainty. A novel Bayesian deep network was proposed to generate a synthetic CT and estimate its uncertainty. Various metrics were used to thoroughly examine the relationship between the uncertainties of the proposed Bayesian model and the generated synthetic CT. Compared with existing approaches, the proposed model showed comparable CT number and dosimetric accuracies. The experiments showed that the proposed Bayesian model was capable of producing accurate synthetic CT, and was an effective indicator of the uncertainty and error associated with synthetic CT in MR-only workflows.

Evaluation of N95 respirators on fit rate, real-time leakage, and usability among Chinese healthcare workers: study protocol of a randomized crossover trial.

Background: N95 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. Methods: This 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. Discussion: The 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.

A non-defect precursor gate oxide breakdown model.

Understanding defect creation is central to efforts to comprehend gate dielectric breakdown in metal-oxide-semiconductor-field-effect-transistors (MOSFETs). While gate dielectrics other than SiO2 are now popular, models develop for SiO2 breakdown are used for these dielectrics too. Considering that the Si-O bond is very strong, modeling efforts have focused in ways to weaken it so that defect creation (bond-breaking) is commensurate with experimental observations. So far, bond-breaking models rely on defect-precursors to make the energetics manageable. Here it is argued that the success of the percolation model for gate oxide breakdown precludes the role of defect precursors in gate oxide breakdown. It is proposed that defect creation involves "normal" Si-O bonds. This new model relies on the fact that hole transport in SiO2 is in the form of a small polaron - meaning that it creates a transient local distortion as it travels. It is this transient distortion that enables normal Si-O bonds to be weakened (albeit transiently) enough that breaking the bonds at a rate commensurate with measurements becomes possible without the help of the externally applied field.

Effects of Bis(imino)acenaphthene (Bian)-Derived Ligands on the Cytotoxicity, DNA Interactions, and Redox Activity of Palladium(II) Bipyridine Complexes.

A series of heteroleptic bipyridine Pd(II) complexes based on 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene (dpp-Bian) or 1,2-bis[(2,4,6-trimethylphenyl)imino]acenaphthene (tmp-Bian) were prepared. All complexes were fully characterized by spectrochemical methods, and their crystal structures were confirmed by X-ray diffraction analysis. The 72 h stability of heteroleptic bipyridine Pd(II) complexes with Bian ligands under physiological conditions was investigated using 1H NMR spectroscopy. The anticancer activity of all complexes was assessed in a panel of cancer cell lines in comparison with uncoordinated ligands and clinically used drugs cisplatin and doxorubicin. The ability of the complexes to bind DNA was investigated using several methods, including EtBr replacement assay, density functional theory calculations, circular dichroism spectroscopy, DNA gel electrophoresis, and TUNEL assay. The electrochemical activity of all complexes and the uncoordinated ligands was studied using cyclic voltammetry, and reactive oxygen species production in cancer cells was investigated using confocal microscopy. Heteroleptic bipyridine PdII-Bian complexes were cytotoxic in a low micromolar concentration range and showed some selectivity toward cancer cells in comparison with noncancerous MRC-5 lung fibroblasts.

Educational Program with Text Messaging for Community-Dwelling Patients with Hypertension: A Pilot Randomized Controlled Trial.

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 (ß = -7.12, p = .086) and pulse pressure (ß = -8.20, p = .007) and to improve self-efficacy (ß = 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.

Mixed-mode Zentangle and Pastel Nagomi artwork for improving mental well-being in university students during COVID-19 pandemic - a randomized controlled feasibility trial.

Background: University 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. Method: This 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. Results: The 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. Limitation: The study included an imbalance number of online vs. face-to-face sessions, and repeated measures may have affected the results. Conclusion: The 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).

A phase 1/2a safety, pharmacokinetics, and efficacy study of the novel nucleoside analog FF-10502-01 for the treatment of advanced solid tumors.

BACKGROUND: The nucleoside FF-10502-01, structurally similar to but with different biologic effects than gemcitabine, shows promising activity both alone and combined with cisplatin in preclinical gemcitabine-resistant tumor models. We conducted an open-label, single-arm, 3 + 3 first-in-human trial to explore the safety, tolerability, and antitumor activity of FF-10502-01 in patients with solid tumors. METHODS: Patients with inoperable metastatic tumors refractory to standard therapies were enrolled. Escalating intravenous FF-10502-01 doses (8-135 mg/m2 ) were administered weekly for 3 weeks in 28-day cycles until progressive disease or unacceptable toxicity was observed. Three expansion cohorts were subsequently evaluated. RESULTS: A phase 2 dose of 90 mg/m2 was determined after evaluating 40 patients. Dose-limiting toxicities included hypotension and nausea. Phase 2a enrolled patients with cholangiocarcinoma (36), gallbladder cancer (10), and pancreatic/other tumors (20). Common adverse events were grade 1-2 rash, pruritus, fever, and fatigue. Grade 3 or 4 hematologic toxicities were observed at low incidences, including thrombocytopenia (5.1%) and neutropenia (2%). Confirmed partial responses (PRs) occurred in five patients with gemcitabine-refractory tumors, including three with cholangiocarcinoma and one each with gallbladder and urothelial cancer. Median progression-free and overall survival rates in patients with cholangiocarcinoma were 24.7 and 39.1 weeks, respectively. Prolonged progression-free survival in patients with cholangiocarcinoma was associated with BAP1 and PBRM1 mutations. CONCLUSION: FF-10502-01 was well tolerated with manageable side effects and limited hematologic toxicity. Durable PRs and disease stabilizations were observed in heavily pretreated biliary tract patients who had received prior gemcitabine. FF-10502-01 is distinct from gemcitabine and may represent an effective therapy.

Magnetic field induced dose effects in radiation therapy using MR-linacs.

MR-guided radiotherapy (MRgRT) is one of the most significant advances in radiotherapy in recent years. The hybrid systems were designed to visualize patient anatomical and physiological changes during the course of radiotherapy, enabling more precise treatment. However, before MR-linacs reach their full potential in delivering safe and accurate treatments to patients, the radiotherapy team must understand how a magnetic field alters the dosimetric properties of the radiation beam and its potential impact on treatment quality and clinical outcomes. This review aims to provide an in-depth description of the magnetic field induced dose effects for the two widely available systems, the 0.35 T and the 1.5 T MR-linacs. In MR-linac treatments, the primary photon beam passes through MR components that never exist in conventional linacs, which alter both in-field and out-of-field doses. More importantly, the interplay between the always-on magnetic field and the secondary electrons is not negligible. This interplay affects dose deposition in the patient, resulting in reduced in-field skin dose due to purged-out contaminant electrons, shortened build-up distance and a shifted crossline profile owing to asymmetric dose kernel. Especially two effects, namely, electron return effect (ERE) and electron stream effect (ESE), are not seen in conventional radiotherapy. This review also summarizes the clinical observations on the site-specific treatments influenced mostly by the magnetic field. In MR-linac treatment, the head and neck region is one of the most challenging sites as ERE occurs at low and high density tissue interfaces and around air cavities, generating hot and cold spots. In breast cancer treatment, consideration should be given to the increased in-field skin dose induced by ERE and the increased out-of-field dose caused by ESE for regions such as the ears, chin, and neck. In lung cancer treatments, tissue inhomogeneity combined with ERE will exacerbate target dose heterogeneity and increase or decrease interface dose. Lastly, treatment in the abdomen and pelvic region will be affected by the presence of gas pockets near the target. The review provides practical recommendations to mitigate these effects.

Thick gate oxide extrinsic breakdown - the potential role of neutral hydrogen atom.

Power electronics is currently a hot topic due to its important role in fighting climate change. Gate oxide breakdown is the Achilles heel of power devices, and it is well known that extrinsic breakdown is the chief concern. However, the root cause of extrinsic breakdown is poorly understood. Recently, a "lucky defect" model was introduced to explain extrinsic breakdown beyond the traditional "local thinning" model. In this work, the "lucky defect" model is further developed to allow it to examine the responsible defect's energy distribution. It is found that only defects with energy 1.5 eV ± 0.3 eV above the substrate conduction band can produce the breakdown distributions commonly reported. Few studied defects can satisfy this requirement. An exception is the neutral hydrogen atom, and its known properties are consistent with experimental results in the literature. If confirmed, this has important implication on how to remedy extrinsic breakdown.

ACVR1-activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans.

ABSTRACT: Altered bone morphogenetic protein (BMP) signaling is associated with many musculoskeletal diseases. However, it remains unknown whether BMP dysfunction has direct contribution to debilitating pain reported in many of these disorders. Here, we identified a novel neuropathic pain phenotype in patients with fibrodysplasia ossificans progressiva (FOP), a rare autosomal-dominant musculoskeletal disorder characterized by progressive heterotopic ossification. Ninety-seven percent of these patients carry an R206H gain-of-function point mutation in the BMP type I receptor ACVR1 (ACVR1 R206H ), which causes neofunction to Activin A and constitutively activates signaling through phosphorylated SMAD1/5/8. Although patients with FOP can harbor pathological lesions in the peripheral and central nervous system, their etiology and clinical impact are unclear. Quantitative sensory testing of patients with FOP revealed significant heat and mechanical pain hypersensitivity. Although there was no major effect of ACVR1 R206H on differentiation and maturation of nociceptive sensory neurons (iSNs) derived from FOP induced pluripotent stem cells, both intracellular and extracellular electrophysiology analyses of the ACVR1 R206H iSNs displayed ACVR1-dependent hyperexcitability, a hallmark of neuropathic pain. Consistent with this phenotype, we recorded enhanced responses of ACVR1 R206H iSNs to TRPV1 and TRPA1 agonists. Thus, activated ACVR1 signaling can modulate pain processing in humans and may represent a potential target for pain management in FOP and related BMP pathway diseases.

Determining the reliable feature change in longitudinal radiomics studies: A methodological approach using the reliable change index.

PURPOSE: Determination of reliable change of radiomics feature over time is essential and vital in delta-radiomics, but has not yet been rigorously examined. This study attempts to propose a methodological approach using reliable change index (RCI), a statistical metric to determine the reliability of quantitative biomarker changes by accounting for the baseline measurement standard error, in delta-radiomics. The use of RCI was demonstrated with the MRI data acquired from a group of prostate cancer (PCa) patients treated by 1.5 T MRI-guided radiotherapy (MRgRT). METHODS: Fifty consecutive PCa patients who underwent five-fractionated MRgRT were retrospectively included, and 1023 radiomics features were extracted from the clinical target volume (CTV) and planning target volume (PTV). The two MRI datasets acquired at the first fraction (MRI11 and MRI21) were used to calculate the baseline feature reliability against image acquisition using intraclass correlation coefficient (ICC). The RCI was constructed based on the baseline feature measurement standard deviation, ICC, and feature value differences at two time points between the fifth (MRI51) and the first fraction MRI (MRI11). The reliable change of features was determined in each patient only if the calculated RCI was over 1.96 or smaller than -1.96. The feature changes between MRI51 and MRI11 were correlated to two patient-reported quality-of-life clinical endpoints of urinary domain summary score (UDSS) and bowel domain summary score (BDSS) in 35 patients using the Spearman correlation test. Only the significant correlations between a feature that was reliably changed in ≥7 patients (20%) by RCI and an endpoint were considered as true significant correlations. RESULTS: The 352 (34.4%) and 386 (37.7%) features among all 1023 features were determined by RCI to be reliably changed in more than five (10%) patients in the CTV and PTV, respectively. Nineteen features were found reliably changed in the CTV and 31 features in the PTV, respectively, in 10 (20%) or more patients. These features were not necessarily associated with significantly different longitudinal feature values (group p-value < 0.05). Most reliably changed features in more than 10 patients had excellent or good baseline test-retest reliability ICC, while none showed poor reliability. The RCI method ruled out the features to be reliably changed when substantial feature measurement bias was presented. After applying the RCI criterion, only four and five true significant correlations were confirmed with UDSS and BDSS in the CTV, respectively, with low true significance correlation rates of 10.8% (4/37) and 17.9% (5/28). No true significant correlations were found in the PTV. CONCLUSIONS: The RCI method was proposed for delta-radiomics and demonstrated using PCa MRgRT data. The RCI has advantages over some other statistical metrics commonly used in the previous delta-radiomics studies, and is useful to reliably identify the longitudinal radiomics feature change on an individual basis. This proposed RCI method should be helpful for the development of essential feature selection methodology in delta-radiomics.