Glutathione Consumptive Dual-Sensitive Lipid-Composite Nanoparticles Induce Immunogenic Cell Death for Enhanced Breast Tumor Therapy.

Although chemotherapy remains the standard therapy for tumor treatment, serious side effects can occur because of nontargeted distribution and damage to healthy tissues. Hollow mesoporous silica nanoparticles (HMSNs) modified with lipids offer potential as delivery systems to improve therapeutic outcomes and reduce adverse effects. Herein, we synthesized HMSNs with integrated disulfide bonds (HMSN) for loading with the chemotherapeutic agent oxaliplatin (OXP) which were then covered with the synthesized hypoxia-sensitive lipid (Lip) on the surface to prepare the dual-sensitive lipid-composite nanoparticles (HMSN-OXP-Lip). The empty lipid-composite nanoparticles (HMSN-Lip) would consume glutathione (GSH) in cells because of the reduction of disulfide bonds in HMSN and would also inhibit GSH production because of NADPH depletion driven by Lip cleavage. These actions contribute to increased levels of ROS that induce the immunogenic cell death (ICD) effect. Simultaneously, HMSN-Lip would disintegrate in the presence of high concentrations of GSH. The lipid in HMSN-OXP-Lip could evade payload leakage during blood circulation and accelerate the release of the OXP in the tumor region in the hypoxic microenvironment, which could significantly induce the ICD effect to activate an immune response for an enhanced therapeutic effect. The tumor inhibitory rate of HMSN-OXP-Lip was almost twice that of free OXP, and no apparent side effects were observed. This design provides a dual-sensitive and efficient strategy for tumor therapy by using lipid-composite nanoparticles that can undergo sensitive drug release and biodegradation.

NIR-Triggered Thermosensitive Nanoreactors for Dual-Guard Mechanism-Mediated Precise and Controllable Cancer Chemo-Phototherapy.

Thermosensitive nanoparticles can be activated by externally applying heat, either through laser irradiation or magnetic fields, to trigger the release of drug payloads. This controlled release mechanism ensures that drugs are specifically released at the tumor site, maximizing their effectiveness while minimizing systemic toxicity and adverse effects. However, its efficacy is limited by the low concentration of drugs at action sites, which is caused by no specific target to tumor sties. Herein, hyaluronic acid (HA), a gooey, slippery substance with CD44-targeting ability, was conjugated with a thermosensitive polymer poly(acrylamide-co-acrylonitrile) to produce tumor-targeting and thermosensitive polymeric nanocarrier (HA-P) with an upper critical solution temperature (UCST) at 45 °C, which further coloaded chemo-drug doxorubicin (DOX) and photosensitizer Indocyanine green (ICG) to prepare thermosensitive nanoreactors HA-P/DOX&ICG. With photosensitizer ICG acting as the "temperature control element", HA-P/DOX&ICG nanoparticles can respond to temperature changes when receiving near-infrared irradiation and realize subsequent structure depolymerization for burst drug release when the ambient temperature was above 45 °C, achieving programmable and on-demand drug release for effective antitumor therapy. Tumor inhibition rate increased from 61.8 to 95.9% after laser irradiation. Furthermore, the prepared HA-P/DOX&ICG nanoparticles possess imaging properties, with ICG acting as a probe, enabling real-time monitoring of drug distribution and therapeutic response, facilitating precise treatment evaluation. These results provide enlightenment for the design of active tumor targeting and NIR-triggered programmable and on-demand drug release of thermosensitive nanoreactors for tumor therapy.

Visual deterioration outcomes following optic pathway glioma treatment: a 12-year single institution retrospective study.

OBJECTIVE: The surgical treatment of optic pathway gliomas (OPG) remains controversial, with visual outcomes often unpredictable. The present study explored surgical and clinical factors influencing visual acuity (VA) after OPG treatment and developed anatomical subtypes correlated with clinical symptoms. METHODS: Children with OPG who underwent initial partial tumor resection at Beijing Tiantan Hospital from January 2011 to December 2022 were retrospectively analyzed. Multivariate logistic regression and random forest analyses were performed to identify risk factors for post-treatment VA deterioration and a decision tree model was created based on significant factors. RESULTS: A total of 140 patients were enrolled. Multivariate logistic regression analysis identified surgical approach and initial VA as independent predictors of post-treatment VA deterioration (P < 0.05). Surgical approach, initial VA, and extent of tumor resection were the most significant factors for risk assessment and were included in the decision tree model, with surgical approach as the most important "root" node. The model demonstrated good predictive performance, with area under the curve values of 0.75 and 0.66 for the training and test datasets, respectively. A simple anatomical classification was developed, which revealed clinical characteristic differences among OPG types. Meanwhile, a correlation analysis of post-treatment visual deterioration was performed for each of the three anatomical types. CONCLUSION: This study offers a predictive model for visual outcomes following initial tumor-reduction surgery in OPG patients, which may help in visual outcomes risk stratification. Additionally, the anatomical classification effectively indicates OPG growth direction, offering potential insights into clinical symptoms.

First-principles molecular dynamics study on the behaviors of Cs in a mixed system of liquid metal and LiCl-KCl molten salt.

The structure and dynamic properties of Cs in the mixed system of LiCl-KCl molten salt and a liquid metal (Bi and Pb) electrode are investigated through first-principles molecular dynamics simulation. It is found that the dynamic properties of different ions in molten salt could be significantly affected when the liquid metal electrode is coupled and this influence varies with the type of liquid metal applied. The microstructures of the mixed systems of molten salt and liquid metal electrode: MS-Cs-Bi, MS-CsCl-Bi, MS-Cs-Pb, and MS-CsCl-Pb, are also investigated by the bond angle distribution function, Voronoi tessellation analysis, five-fold symmetry parameter, and bond-orientational order parameter. The comparison study of the microstructures of the mixed systems when different liquid metal electrodes are applied provides information on the liquid metal electrode selection when conducting electrolysis. The present study represents the first demonstration of the study of a mixed system of salt and liquid electrode for practical applications and would be greatly beneficial to the development of pyroprocessing of spent nuclear fuel.

Practice patterns, role and impact of advanced practice nurses in stroke care: A mixed-methods systematic review.

AIM(S): To undertake a systematic review of the practice patterns and roles of advanced practice nurses (APNs) in inpatient and outpatient stroke-care services; and to evaluate the impact of APN-led inpatient and outpatient stroke-care services on clinical and patient-reported outcomes. DESIGN: A mixed-methods systematic review. METHODS: A systematic search was conducted across six electronic databases for primary studies. Data were synthesised using a convergent integrated approach. DATA SOURCES (INCLUDE SEARCH DATES) *FOR REVIEWS ONLY: A systematic search was conducted across PubMed, CINAHL, Cochrane Library, Embase, PsycInfo and ProQuest Dissertations & Theses Global, for primary studies published between the inception of the databases and 3 November 2022. RESULTS: Findings based on the 18 included primary studies indicate that the APNs' roles have been implemented across the continuum of stroke care, including pre-intervention care, inpatient care and post-discharge care. Practicing at an advanced level, the APNs engaged in clinical, operational and educational undertakings across services and disciplines. Positive clinical and patient-reported outcomes have been attributed to their practice. CONCLUSION: The review highlights the critical role of APNs in improving stroke care, especially in the pre-intervention phase. Their clinical expertise, patient-centered approach and collaboration can transform stroke care. Integrating APNs into stroke care teams is essential for better management and outcomes in light of the increasing stroke burden. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Healthcare institutions should integrate APNs to enhance pre-intervention stroke care, improve diagnostic accuracy and expedite treatment. APNs can prioritise patient-centric care, including assessments, coordination and education. Medication reconciliation, timely rehabilitation referrals and lifestyle modifications for secondary stroke prevention are crucial. Implementing advanced practice nursing frameworks ensures successful APN integration, leading to improved stroke care and better patient outcomes in response to the growing stroke burden. IMPACT (ADDRESSING): What problem did the study address? Poor clarity of the role of advanced practice nurses among patients, physicians, healthcare professionals, health policymakers and nurses. What were the main findings? Advanced practice nurses practise across the continuum of stroke care, mainly in pre-intervention care which takes place before initiating treatment, inpatient care and post-discharge care. The implementation of the advanced practice nurse role in stroke care has contributed positively to clinical and patient-reported outcomes. Where and on whom will the research have an impact? Insights from the review are envisioned to inform healthcare policymakers and leaders in the implementation and evaluation of the APN role in stroke care. REPORTING METHOD: Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution. TRIAL AND PROTOCOL REGISTRATION: https://figshare.com/ndownloader/files/41606781; Registered on Open Science Framework osf.io/dav8j.

pH- and temperature-responsive supramolecular assemblies with highly adjustable viscoelasticity: a multi-stimuli binary system.

Stimuli-responsive materials are increasingly needed for the development of smart electronic, mechanical, and biological devices and systems relying on switchable, tunable, and adaptable properties. Herein, we report a novel pH- and temperature-responsive binary supramolecular assembly involving a long-chain hydroxyamino amide (HAA) and an inorganic hydrotrope, boric acid, with highly tunable viscous and viscoelastic properties. The system under investigation demonstrates a high degree of control over its viscosity, with the capacity to achieve over four orders of magnitude of control through the concomitant manipulation of pH and temperature. In addition, the transformation from non-Maxwellian to Maxwellian fluid behavior could also be induced by changing the pH and temperature. Switchable rheological properties were ascribed to the morphological transformation between spherical vesicles, aggregated/fused spherical vesicles, and bicontinuous gyroid structures revealed by cryo-TEM studies. The observed transitions are attributed to the modulation of the head group spacing between HAA molecules under different pH conditions. Specifically, acidic conditions induce electrostatic repulsion between the protonated amino head groups, leading to an increased spacing. Conversely, under basic conditions, the HAA head group spacing is reduced due to the intercalation of tetrahydroxyborate, facilitated by hydrogen bonding.

A nomogram for predicting post-operative hydrocephalus in children with medulloblastoma.

Post-operative hydrocephalus is common among children with medulloblastoma after initial tumor resection. This study aimed to establish a novel model for predicting the development of post-operative hydrocephalus in children with medulloblastoma. Only pediatric patients who received initial medulloblastoma resection at Beijing Tiantan Hospital between January 2018 and May 2021 were included in this study. The potential risk factors associated with post-operative hydrocephalus were identified based on multivariate logistic regression and the nomogram. Receiver operating characteristic (ROC) curve were used to evaluate the performance of the nomogram model based on an independent cohort of medulloblastoma patients who underwent surgery from June 2021 to March 2022. A total of 105 patients were included in the primary cohort. Superior invasion (P = 0.007), caudal invasion (P = 0.025), and intraventricular blood ≥ 5 mm (P = 0.045) were significantly related to the development of post-operative hydrocephalus and thus were assembled into the nomogram model. The model accurately predicted post-operative hydrocephalus based on the calibration curve. The area under the ROC curves for the primary and validation cohorts was 0.849 and 0.855, respectively. In total, the nomogram we developed may aid clinicians in assessing the potential risk of pediatric patients with MB developing post-operative hydrocephalus, especially those who would otherwise not have received a diversionary procedure at presentation.

Artificial Intelligence Versus Human-Controlled Doctor in Virtual Reality Simulation for Sepsis Team Training: Randomized Controlled Study.

BACKGROUND: Interprofessional communication is needed to enhance the early recognition and management of patients with sepsis. Preparing medical and nursing students using virtual reality simulation has been shown to be an effective learning approach for sepsis team training. However, its scalability is constrained by unequal cohort sizes between medical and nursing students. An artificial intelligence (AI) medical team member can be implemented in a virtual reality simulation to engage nursing students in sepsis team training. OBJECTIVE: This study aimed to evaluate the effectiveness of an AI-powered doctor versus a human-controlled doctor in training nursing students for sepsis care and interprofessional communication. METHODS: A randomized controlled trial study was conducted with 64 nursing students who were randomly assigned to undertake sepsis team training with an AI-powered doctor (AI-powered group) or with medical students using virtual reality simulation (human-controlled group). Participants from both groups were tested on their sepsis and communication performance through simulation-based assessments (posttest). Participants' sepsis knowledge and self-efficacy in interprofessional communication were also evaluated before and after the study interventions. RESULTS: A total of 32 nursing students from each group completed the simulation-based assessment, sepsis and communication knowledge test, and self-efficacy questionnaire. Compared with the baseline scores, both the AI-powered and human-controlled groups demonstrated significant improvements in communication knowledge (P=.001) and self-efficacy in interprofessional communication (P<.001) in posttest scores. For sepsis care knowledge, a significant improvement in sepsis care knowledge from the baseline was observed in the AI-powered group (P<.001) but not in the human-controlled group (P=.16). Although no significant differences were found in sepsis care performance between the groups (AI-powered group: mean 13.63, SD 4.23, vs human-controlled group: mean 12.75, SD 3.85, P=.39), the AI-powered group (mean 9.06, SD 1.78) had statistically significantly higher sepsis posttest knowledge scores (P=.009) than the human-controlled group (mean 7.75, SD 2.08). No significant differences were found in interprofessional communication performance between the 2 groups (AI-powered group: mean 29.34, SD 8.37, vs human-controlled group: mean 27.06, SD 5.69, P=.21). However, the human-controlled group (mean 69.6, SD 14.4) reported a significantly higher level of self-efficacy in interprofessional communication (P=.008) than the AI-powered group (mean 60.1, SD 13.3). CONCLUSIONS: Our study suggested that AI-powered doctors are not inferior to human-controlled virtual reality simulations with respect to sepsis care and interprofessional communication performance, which supports the viability of implementing AI-powered doctors to achieve scalability in sepsis team training. Our findings also suggested that future innovations should focus on the sociability of AI-powered doctors to enhance users' interprofessional communication training. Perhaps in the nearer term, future studies should examine how to best blend AI-powered training with human-controlled virtual reality simulation to optimize clinical performance in sepsis care and interprofessional communication. TRIAL REGISTRATION: ClinicalTrials.gov NCT05953441; https://clinicaltrials.gov/study/NCT05953441.

Deep learning classification of capnography waveforms: secondary analysis of the PRODIGY study.

Capnography monitors trigger high priority 'no breath' alarms when CO2 measurements do not exceed a given threshold over a specified time-period. False alarms occur when the underlying breathing pattern is stable, but the alarm is triggered when the CO2 value reduces even slightly below the threshold. True 'no breath' events can be falsely classified as breathing if waveform artifact causes an aberrant spike in CO2 values above the threshold. The aim of this study was to determine the accuracy of a deep learning approach to classifying segments of capnography waveforms as either 'breath' or 'no breath'. A post hoc secondary analysis of data from 9 North American sites included in the PRediction of Opioid-induced Respiratory Depression In Patients Monitored by capnoGraphY (PRODIGY) study was conducted. We used a convolutional neural network to classify 15 s capnography waveform segments drawn from a random sample of 400 participants. Loss was calculated over batches of 32 using the binary cross-entropy loss function with weights updated using the Adam optimizer. Internal-external validation was performed by iteratively fitting the model using data from all but one hospital and then assessing its performance in the remaining hospital. The labelled dataset consisted of 10,391 capnography waveform segments. The neural network's accuracy was 0.97, precision was 0.97 and recall was 0.96. Performance was consistent across hospitals in internal-external validation. The neural network could reduce false capnography alarms. Further research is needed to compare the frequency of alarms derived from the neural network with the standard approach.

Factors associated with registered nurses' academic performance in advanced practice nursing preparatory education: A retrospective cohort study.

AIM: To explore factors associated with academic performance in the Master of Nursing programme. BACKGROUND: Advanced practice nursing preparatory education generally involves completion of the Master of Nursing programme. While prior clinical experiences and on-the-job training are believed to underpin the preparation for such education, studies have suggested only weak or no associations between nurses' academic success in graduate schools and their clinical experiences. METHODS: A retrospective cohort study was conducted in the nursing department of a university in Singapore. Academic and demographic data were extracted in February 2020 from a shared repository of anonymised teaching and learning data. R was used to select and merge data tables into a usable format for subsequent analysis. Students enrolled between 2010 and 2017 were included for the analysis (n = 246). RESULTS: Age was statistically significantly associated with overall cumulative academic performance (p < 0.001). Younger students on average academically outperformed older students. Unmarried students were associated with better cumulative academic performance in the Clinical Practicum 2 module (p = 0.018). CONCLUSION: Younger students have historically outperformed their older counterparts in the Master of Nursing programme. There is a need to reassess the requirement of five years of clinical experience as an admission criterion for the Master of Nursing programme in Singapore. IMPLICATIONS FOR NURSING POLICY: There is a need to re-evaluate the admission criteria to better engage and retain younger nurses interested in advanced nursing practice. Nursing educators and leaders can partner with academics to develop advanced practice-specific education for pre-master nurses with the aptitude and interest in pursuing this track.

Tungstate-mediated In-situ Passivation of Grain Boundary Grooves in Perovskite Solar Cells.

Possessed with advantageous optoelectronic properties, perovskites have boosted the rapid development of solution-processed solar cells. The performance of perovskite solar cells (PSCs) is significantly weakened by the carrier loss at grain boundary grooves (GBGs); however, it receives limited attention and there lacks effective approach to solve this issue. Herein, for the first time, we constructed the tungstate/perovskite heterointerface via a "two step" in situ reaction approach that provides effective defect passivation and ensures efficient carrier dynamics at the GBGs. The exposed perovskite at grain boundaries is converted to wide-band-gap PbWO4 via an in-situ reaction between Pb2+ and tungstate ions, which passivate defects due to the strong ionic bonding. Moreover, recombination loss is further suppressed via the heterointerface energetics modification based on an additional transformation from PbWO4 to CaWO4 . PSCs based on this groove modification strategy showed good universality in both normal and inverted structure, with an improved efficiency of 23.25 % in the n-i-p device and 23.33 % in the p-i-n device. Stable power output of the modified device could maintain 91.7 % after around 1100 h, and the device efficiency could retain 92.5 % after aging in air for around 2110 h, and 93.1 % after aging at 85 °C in N2 for 972 h.

The role of imaging features and resection status in the survival outcome of sporadic optic pathway glioma children receiving different adjuvant treatments.

Optic pathway glioma (OPG) is a rare brain tumor affecting children, with no standard treatment strategy. This study described the sporadic OPG survival outcomes after surgical treatment and analyzed the role of imaging features and resection status in children receiving different adjuvant treatments. This retrospective study included 165 OPG patients whose clinical information were obtained from the hospital record system. Tumor volume and residual tumor volume were calculated by delineating the lesion area. Kaplan-Meier method and Cox proportional hazards model were conducted to analyze the independent prognosis factor. A total of 165 patients were included in this study. Respectively, the 5-year overall survival (OS) and progression-free survival (PFS) were 87.58% and 77.87%. Residual tumor size and first adjuvant treatment (AT) after surgery were both associated with PFS. In patients with small-size residual tumors, there was no significant difference in PFS between the AT treatment groups. Moreover, age, exophytic cystic components, leptomeningeal metastases, and AT were associated with OS. In patients with exophytic cystic components and those with leptomeningeal metastases, there was no significant difference in OS. Our results revealed that OPG patients could avoid or defer AT by maximized resection. Age ≤ 2 years was a disadvantageous factor for OS. Patients with exophytic cystic components were more likely to benefit from primary surgery, and CT or RT was not beneficial for these patients. Patients with leptomeningeal metastases had a poor prognosis regardless of the treatment they received. Future prospective clinical studies are needed to develop more effective treatment regimens.

The subjective experience of family caregivers of people living with Parkinson's disease: a meta-ethnography of qualitative literature.

BACKGROUND AND AIMS: Parkinson's disease patients (PwPD) rely heavily on their family caregivers. However, there remains uncertainty regarding the subjective experience of the family caregivers of PwPD. This study aims to provide an in-depth summary of the current knowledge about the subjective experiences of family caregivers caring for PwPD, to understand the factors that influence this experience and to provide the evidence for healthcare services. METHODS: We conducted a systematic review and meta-ethnography using Noblit and Hare's approach. The search strategy used MeSH terms in combination with free-text searching of 10 databases (from their inception until July 2021). Titles and abstracts were reviewed by two reviewers and, for the studies that met the eligibility criteria, full-text articles were obtained. The Critical Appraisal Skills Program (CASP) checklist was employed to assess the quality of studies. RESULTS: A total of 3318 studies were screened and 29 qualitative studies were included in this review. These studies recorded the experience of 399 participants across 12 countries, most were females. Five themes emerged: (a) feelings related to PD; (b) challenges to family life; (c) external challenges; (d) adjustment and adaptation; (e) external support. We propose a new conceptual model that highlights that the experiences of caregivers for PwPD are dynamic and influenced by a variety of internal and external factors. CONCLUSION: Our findings illustrate the complex and dynamic experiences of family caregivers for PwPD. It is necessary to explore how the influencing factors can be modified to improve the lived experience of family caregivers.

Evaluation of the Transverse Crack Depth of Rail Bottoms Based on the Ultrasonic Guided Waves of Piezoelectric Sensor Arrays.

A method based on the high-frequency ultrasonic guided waves (UGWs) of a piezoelectric sensor array is proposed to monitor the depth of transverse cracks in rail bottoms. Selecting high-frequency UGWs with a center frequency of 350 kHz can enable the monitoring of cracks with a depth of 3.3 mm. The method of arranging piezoelectric sensor arrays on the upper surface and side of the rail bottom is simulated and analyzed, which allows the comprehensive monitoring of transverse cracks at different depths in the rail bottom. The multi-value domain features of the UGW signals are further extracted, and a back propagation neural network (BPNN) is used to establish the evaluation model of the transverse crack depth for the rail bottom. The optimal evaluation model of multi-path combination is reconstructed with the minimum value of the root mean square error (RMSE) as the evaluation standard. After testing and comparison, it was found that each metric of the reconstructed model is significantly better than each individual path; the RMSE is reduced to 0.3762; the coefficient of determination R2 reached 0.9932; the number of individual evaluation values with a relative error of less than 10% and 5% accounted for 100% and 87.50% of the total number of evaluations, respectively.

Understanding the gender gap in advanced practice nursing: A qualitative study.

AIMS: We aim to explore the perceptions of registered nurses undergoing the advanced practice nurse preparatory programme and of advanced practice nurses towards the recruitment of men into the advanced practice nursing workforce. BACKGROUND: Given the need to expand and diversify the advanced practice nursing workforce, it is important to recognize the potential implications of gender disparity. It is critical to understand why few males are recruited into the advanced practice nursing preparatory programme and to determine whether gender-related bias is present in the professional development of nurses. METHOD: We use a descriptive qualitative design. Semi-structured interviews were conducted via Zoom (April to August 2021). RESULTS: Three themes were generated: 'The odds are eventually in the favour of men', 'The APN career-track is unpopular among men', and 'Balancing the gender gap in the APN workforce'. All themes are supported by three subthemes. CONCLUSIONS: Although males in nursing enjoy opportunistic advantages in entering the advanced practice nursing workforce, they are not interested in the role and not staying long enough in the nursing profession to become advanced practice nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should be more cognizant of the different social stereotypes faced by males and females in nursing. With such awareness, they can be more supportive and less biased in career counselling and job appraisals.

The development of advanced practice nurses in Singapore.

The development of advanced practice nursing has evolved globally over the past decades and has become an important component in the contemporary healthcare system. The term 'advanced practice nurse' is used to refer to nurses practising at a higher level than traditional nurses and is defined as a registered nurse who has acquired the expert knowledge base, complex decision-making skills and clinical competencies for expanded practice. In 2003, Singapore embarked on the development of advanced practice nurses as an initiative to improve the nursing professional image, retain excellent clinical nurses and fill the gaps in the provision of healthcare services for the ageing population. This paper documents Singapore's journey of advanced practice nursing development and shares our unique learning experience in the aspects of education, certification, registration and scope of practice.

The impact of COVID19 on advanced practice nursing education and practice: A qualitative study.

AIM: To explore Master of Nursing students' perspectives toward the impact of coronavirus disease 2019 (COVID-19) on the advanced practice nurse preparatory education and practice. BACKGROUND: Like many nursing education programmes, the advanced practice nurse preparatory training was greatly affected and had to radically change to adapt to the disruptions caused by the pandemic. The COVID-19 pandemic has created a strain on the healthcare system and advanced practice nurses have been expected to modify their normal practice to provide care in unprecedented ways. METHODS: The study used a descriptive qualitative design. Semi-structured video-conference interviews were conducted in an autonomous university (June-July 2020). The recruitment of participants (n = 14) concluded upon data saturation. A thematic analysis was conducted. The COnsolidated criteria for REporting Qualitative research (COREQ) guidelines were used. FINDINGS: Three main themes were identified: (1) overcome adversity through innovation, (2) acceptance of remote learning and (3) versatility of advanced practice nurses in an ongoing pandemic. Each theme was further explained by two subthemes to further elucidate the impact of COVID-19 on the advanced practice nurse preparatory training and practice. DISCUSSION: The evolution of the advanced practice nurse preparatory education catalysed by the COVID-19 pandemic brought on innovation. The ability of advanced practice nurses to adapt to evolving healthcare needs was also highlighted. CONCLUSION: Although face-to-face teaching and services are gradually returning, some innovations that arose during the pandemic may be worth keeping. IMPLICATIONS FOR NURSING: Nursing educators in higher education institutions can benefit from adopting technology to mitigate the challenges posed by the ongoing pandemic IMPLICATIONS FOR NURSING POLICY: Nurse leaders should review the role of advanced practice nurses to determine how best to capitalise on their practice to meet rising healthcare needs.

Association of novel rare coding variants with juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common type of arthritis among children, but a few studies have investigated the contribution of rare variants to JIA. In this study, we aimed to identify rare coding variants associated with JIA for the genome-wide landscape. METHODS: We established a rare variant calling and filtering pipeline and performed rare coding variant and gene-based association analyses on three RNA-seq datasets composed of 228 JIA patients in the Gene Expression Omnibus against different sets of controls, and further conducted replication in our whole-exome sequencing (WES) data of 56 JIA patients. Then we conducted differential gene expression analysis and assessed the impact of recurrent functional coding variants on gene expression and signalling pathway. RESULTS: By the RNA-seq data, we identified variants in two genes reported in literature as JIA causal variants, as well as additional 63 recurrent rare coding variants seen only in JIA patients. Among the 44 recurrent rare variants found in polyarticular patients, 10 were replicated by our WES of patients with the same JIA subtype. Several genes with recurrent functional rare coding variants have also common variants associated with autoimmune diseases. We observed immune pathways enriched for the genes with rare coding variants and differentially expressed genes. CONCLUSION: This study elucidated a novel landscape of recurrent rare coding variants in JIA patients and uncovered significant associations with JIA at the gene pathway level. The convergence of common variants and rare variants for autoimmune diseases is also highlighted in this study.

Carbon Monoxide-Saturated Polymerized Placenta Hemoglobin Optimizes Mitochondrial Function and Protects Heart Against Ischemia-Reperfusion Injury.

ABSTRACT: Ischemia-reperfusion (I-R) injury is detrimental to cardiovascular system. This study was designed to investigate whether carbon monoxide-saturated polymerized human placenta hemoglobin (CO-PolyPHb) attenuates cardiac I-R injury and to elucidate the underlying mechanism(s). Sixty male adult Sprague-Dawley rats were randomly divided into 6 groups: saline + sham group, PolyPHb + sham group, CO-PolyPHb + sham group, saline + I-R group, PolyPHb + I-R group, and CO-PolyPHb + I-R group. Rats were pretreated with injection of PolyPHb, CO-PolyPHb (0.5 g Hb/kg/d), or an equivalent volume of saline via caudal vein for 3 days. After pretreatment, hearts were isolated Langendorff perfused and subjected to 30-minute no-flow ischemia and 120-minute reperfusion. As compared with the saline + I-R group, pretreatment with CO-PolyPHb greatly improved the recovery of cardiac function, reduced infarct size, and suppressed the release of cardiac enzyme. Importantly, CO-PolyPHb showed more prominent cardioprotective effect than PolyPHb, exhibiting a promising therapeutic potential in cardiac I-R injury. Further study demonstrated that CO-PolyPHb activated molecular signaling toward mitophagy and significantly elevated the mitochondrial respiratory function in the heart. In addition, CO-PolyPHb upregulated the phosphorylation of the proteins in insulin signaling pathway and increased the glucose uptake rate in cardiomyocytes. Pharmacological inhibition of this pathway by wortmannin abrogated the anti-I-R effect of CO-PolyPHb. In conclusion, using an isolated rat heart model, we have demonstrated that pretreatment with CO-PolyPHb provided protective effect against cardiac I-R injury, and this protection was mediated by the improvement of mitochondrial function and activation of insulin signaling pathway in the heart.

Wildfire Risk Assessment of Transmission-Line Corridors Based on Naïve Bayes Network and Remote Sensing Data.

Considering the complexity of the physical model of wildfire occurrence, this paper develops a method to evaluate the wildfire risk of transmission-line corridors based on Naïve Bayes Network (NBN). First, the data of 14 wildfire-related factors including anthropogenic, physiographic, and meteorologic factors, were collected and analyzed. Then, the relief algorithm is used to rank the importance of factors according to their impacts on wildfire occurrence. After eliminating the least important factors in turn, an optimal wildfire risk assessment model for transmission-line corridors was constructed based on the NBN. Finally, this model was carried out and visualized in Guangxi province in southern China. Then a cost function was proposed to further verify the applicability of the wildfire risk distribution map. The fire events monitored by satellites during the first season in 2020 shows that 81.8% of fires fall in high- and very-high-risk regions.