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Large Language Models (LLMs) have the potential to improve education by personalizing learning. However, ChatGPT-generated content has been criticized for sometimes producing false, biased, and/or hallucinatory information. To evaluate AI's ability to return clear and accurate anatomy information, this study generated a custom interactive and intelligent chatbot (Anatbuddy) through an Open AI Application Programming Interface (API) that enables seamless AI-driven interactions within a secured cloud infrastructure. Anatbuddy was programmed through a Retrieval Augmented Generation (RAG) method to provide context-aware responses to user queries based on a predetermined knowledge base. To compare their outputs, various queries (i.e., prompts) on thoracic anatomy (n = 18) were fed into Anatbuddy and ChatGPT 3.5. A panel comprising three experienced anatomists evaluated both tools' responses for factual accuracy, relevance, completeness, coherence, and fluency on a 5-point Likert scale. These ratings were reviewed by a third party blinded to the study, who revised and finalized scores as needed. Anatbuddy's factual accuracy (mean ± SD = 4.78/5.00 ± 0.43; median = 5.00) was rated significantly higher (U = 84, p = 0.01) than ChatGPT's accuracy (4.11 ± 0.83; median = 4.00). No statistically significant differences were detected between the chatbots for the other variables. Given ChatGPT's current content knowledge limitations, we strongly recommend the anatomy profession develop a custom AI chatbot for anatomy education utilizing a carefully curated knowledge base to ensure accuracy. Further research is needed to determine students' acceptance of custom chatbots for anatomy education and their influence on learning experiences and outcomes., (© 2024 American Association for Anatomy.)

There is a long-standing lack of learner satisfaction with quality and quantity of feedback in health professions education (HPE) and training. To address this, university and training programmes are increasingly using technological advancements and data analytic tools to provide feedback. One such educational technology is the Learning Analytic Dashboard (LAD), which holds the promise of a comprehensive view of student performance via partial or fully automated feedback delivered to learners in real time. The possibility of displaying performance data visually, on a single platform, so users can access and process feedback efficiently and constantly, and use this to improve their performance, is very attractive to users, educators and institutions. However, the mainstream literature tends to take an atheoretical and instrumentalist view of LADs, a view that uncritically celebrates the promise of LAD's capacity to provide a 'technical fix' to the 'wicked problem' of feedback in health professions education. This paper seeks to recast the discussion of LADs as something other than a benign material technology using the lenses of Miller and Rose's technologies of government and Barry's theory of Technological Societies, where such technical devices are also inherently agentic and political. An examination of the purpose, design and deployment of LADs from these theoretical perspectives can reveal how these educational devices shape and govern the HPE learner body in different ways, which in turn, may produce a myriad of unintended- and ironic- effects on the feedback process. In this Reflections article we wish to encourage health professions education scholars to examine the practices and consequences thereof of the ever-expanding use of LADs more deeply and with a sense of urgency., (© 2024. The Author(s).)

Purpose: In the context of developmental trajectories, the association between adaptive functioning and core autism symptomatology remains unclear. The current study examines the associations of adaptive behavior with autism symptom sub-domains and with different facets of symptom expression., Methods: Participants include 36 children with a recent diagnosis of autism (33 males; mean age = 56.4 months; SD = 9 months). Families were recruited in the context of the Pediatric Autism Research Cohort (PARC) project. Parents filled out questionnaires at two time points, six months apart, regarding their child's autism symptoms and adaptive functioning. The longitudinal relationship between adaptive functioning and autism symptoms was investigated using Mixed Linear Model analyses: one assessing the relationship between general symptom levels and adaptive functioning, and another examining the associations between symptom frequency and impact with adaptive functioning. We conducted Pearson correlation tests at both time points to assess the associations between symptom sub-domains and adaptive functioning., Results: Findings showed that higher autism symptoms associated with lower adaptive behavior skills, and that this association remained stable over time. Autism impact scores did not significantly relate to adaptive skills, as opposed to frequency scores. Associations between adaptive functioning and autism symptom sub-domains strengthened over time., Conclusion: These findings suggest that adaptive functioning is associated with parent-report autism symptomatology, and that this association changes and, on average, becomes stronger over time. Findings may indicate that frequency and impact of symptoms have differential roles in the development of adaptive skills and are worthy of further exploration., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Arteriovenous fistula (AVF) is the optimal form of vascular access for most haemodialysis dependant patients; however, it is prone to the formation of stenoses that compromise utility and longevity. Whilst there are many factors influencing the development of these stenoses, pathological flow-related phenomena may also incite the formation of intimal hyperplasia, and hence a stenosis. Repeated CFD-derived resistance was calculated for six patient who had a radiocephalic AVF, treated with an interwoven nitinol stent around the juxta-anastomotic region to address access dysfunction. A three-dimensional freehand ultrasound system was used to obtain patient-specific flow profiles and geometries, before performing CFD simulations to replicate the flow phenomena in the AVF, which enabled the calculation of CFD-derived resistance. We presented six patient cases who were examined before and after treatment and our results showed a 77% decrease in resistance, recorded after a surgical intervention to address access dysfunction. Problematic AVFs were found to have high resistance, particularly in the venous segment. AVFs with no reported clinical problems, and clinical patency, had low resistance in the venous segment. There did not appear to be any relationship with clinical problems/patency and resistance values in the arterial segment. Identifying changes in resistance along the circuit allowed stenoses to be identified, independent to that determined using standard sonographic criteria. Our exploratory study reveals thatCFD-derived resistance is a promising metric that allows for non-invasive identification of diseased AVFs. The pipeline analysis enabled regular surveillance of AVF to be studied to aid with surgical planning and outcome, further exhibiting its clinical utility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The developmentally variable nature of autism poses challenges in providing timely services tailored to a child's needs. Despite a recent focus on longitudinal research, priority-setting initiatives with stakeholders highlighted the importance of studying a child's day-to-day functioning and social determinants of health to inform clinical care. To address this, we are conducting a pragmatic multi-site, patient-oriented longitudinal investigation: the Pediatric Autism Research Cohort ( PARC) Study . In young children (<7 years of age) newly diagnosed with autism, we will: (1) examine variability in trajectories of adaptive functioning from the point of diagnosis into transition to school; and (2) identify factors associated with trajectories of adaptive functioning., Methods and Analysis: We aim to recruit 1300 children under 7 years of age with a recent (within 12 months) diagnosis of autism from seven sites: six in Canada; one in Israel. Participants will be followed prospectively from diagnosis to age 8 years, with assessments at 6-month intervals. Parents/caregivers will complete questionnaires administered via a customized online research portal. Following each assessment timepoint, families will receive a research summary report describing their child's progress on adaptive functioning and related domains. Analysis of the longitudinal data will map trajectories and examine child, family and service characteristics associated with chronogeneity (interindividual and intraindividual heterogeneity over time) and possible trajectory turning points around sensitive periods like the transition to school., Ethics and Dissemination: Ethics approvals have been received by all sites. All parents/respondents will provide informed consent when enrolling in the study. Using an integrated knowledge translation approach, where stakeholders are directly engaged in the research process, the PARC Study will identify factors associated with trajectories of functioning in children with autism. Resulting evidence will be shared with government policy makers to inform provincial and national programs. Findings will be disseminated at conferences and published in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The arteriovenous fistula (AVF) is commonly faced with stenosis at the juxta-anastomotic (JXA) region of the vein. Implantation of a flexible nitinol stent across the stenosed JXA has led to the retention of functioning AVFs leading to the resulting AVF geometry being distinctly altered, thereby affecting the haemodynamic environment within it. In this study, large eddy simulations of the flow field within a patient-specific AVF geometry before and after stent implantation were conducted to detail the change in flow features. Although the diseased AVF had much lower flow rates, adverse flow features, such as recirculation zones and swirling flow at the anastomosis, and jet flow at the stenosis site were present. Larger velocity fluctuations (leading to higher turbulent kinetic energy) stemming from these flow features were apparent in the diseased AVF compared to the stented AVF. The unsteadiness at the stenosis created large regions of wall shear stress (WSS) fluctuations downstream of the stenosis site that were not as apparent in the stented AVF geometry. The larger pressure drop across the diseased vein, compared to the stented vein, was primarily caused by the constriction at the stenosis, potentially causing the lower flow rate. Furthermore, the WSS fluctuations in the diseased AVF could lead to further disease progression downstream of the stenosis. The change in bulk flow unsteadiness, pressure drop, and WSS behaviour confirms that the haemodynamic environment of the diseased AVF has substantially improved following the flexible stent implantation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mesenchymal stromal cells (MSCs) ameliorate pre-clinical sepsis and sepsis-associated acute kidney injury (SA-AKI) but clinical trials of single-dose MSCs have not indicated robust efficacy. This study investigated immunomodulatory effects of a novel MSC product (CD362-selected human umbilical cord-derived MSCs [hUC-MSCs]) in mouse endotoxemia and polymicrobial sepsis models. Initially, mice received intra-peritoneal (i.p.) lipopolysaccharide (LPS) followed by single i.p. doses of hUC-MSCs or vehicle. Next, mice underwent cecal ligation and puncture (CLP) followed by intravenous (i.v.) doses of hUC-MSCs at 4 h or 4 and 28 h. Analyses included serum/plasma assays of biochemical indices, inflammatory mediators and the AKI biomarker NGAL; multi-color flow cytometry of peritoneal macrophages (LPS) and intra-renal immune cell subpopulations (CLP) and histology/immunohistochemistry of kidney (CLP). At 72 h post-LPS injections, hUC-MSCs reduced serum inflammatory mediators and peritoneal macrophage M1/M2 ratio. Repeated, but not single, hUC-MSC doses administered at 48 h post-CLP resulted in lower serum concentrations of inflammatory mediators, lower plasma NGAL and reversal of sepsis-associated depletion of intra-renal T cell and myeloid cell subpopulations. Hierarchical clustering analysis of all 48-h serum/plasma analytes demonstrated partial co-clustering of repeated-dose hUC-MSC CLP animals with a Sham group but did not reveal a distinct signature of response to therapy. It was concluded that repeated doses of CD362-selected hUC-MSCs are required to modulate systemic and local immune/inflammatory events in polymicrobial sepsis and SA-AKI. Inter-individual variability and lack of effect of single dose MSC administration in the CLP model are consistent with observations to date from early-phase clinical trials., (© 2022. The Author(s).)

Mesembryanthemum crystallinum L. is a nutritious edible facultative halophyte. This study aimed to investigate the physiology and quality of M. crystallinum L. grown under different salinities and salt-priming conditions. All plants were first grown in 10% artificial seawater (ASW) for 10 days. After that, some plants remained in 10% ASW while the others were transferred to 20%, 30%, 40%, or 50% ASW for another 10 days. Some plants also underwent a salt priming by transferring them gradually from 10% to 100% ASW over a span of 10 days (defined as salt primed). All plants were green and healthy. However, there were reductions in shoot and root productivity, leaf growth, and water content, but also an increase in leaf succulence after transferring plants to higher salinities. The salt-primed plants showed higher photosynthetic light use efficiency with higher chlorophyll concentration compared to other plants. The concentrations of proline, ascorbic acid (ASC), and total phenolic compounds (TPC) increased as percentages of ASW increased. The salt-primed plants switched from C 3 to crassulacean acid metabolism photosynthesis and accumulated the greatest amounts of proline, ASC, and TPC. In conclusion, higher salinities and salt priming enhance the nutritional quality of M. crystallinum L. but compromises productivity.

Objective: The day-to-day experience of families with an Autistic child may be shaped by both, child characteristics and available resources, which often are influenced by the socioeconomic context of the family. Using a socioecological approach, this study explored the quantitative associations between child autistic symptoms, family socioeconomic status, and family life. Methods: Data came from the Pediatric Autism Research Cohort-PARC Study (pilot). Parents of children with a recent diagnosis of autism completed a set of assessments, including the Autism Family Experience Questionnaire, Autism Impact Measure, and a Sociodemographic Questionnaire. A series of multiple, iterative linear regression models were constructed to ascertain quantitative associations between child autistic symptoms, socioeconomic context, and family life. Results: A total of 50 children (mean age: 76 months; SD: 9.5 months; and 84% male) with data on the variables of interest were included in the analysis. The frequency of child autistic symptoms was associated with family life outcomes ( p = 0.02 and R 2 = 24%). Once autistic symptom frequency, symptom impact, and sociodemographic variables were considered, parents of higher educational attainment reported worse family life outcomes compared to their lesser-educated counterparts. This cumulative regression model had considerable explanatory capability ( p = 0.01, R 2 = 40%). Conclusion: This study demonstrates the utility of using a socioecological approach to examine the dynamic interplay between child characteristics and family circumstances. Our findings suggest that family life for parents (of an autistic child) who have obtained higher education is reported (by the parents themselves) as less satisfactory compared to that of parents without higher education, once adjusted for the autistic symptom frequency of child, symptom impact, and income. These findings can inform the design and delivery of more family-centered care pathways during the years following a diagnosis of autism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Koziarz, Roncadin, Kata, Duku, Cauwenbergs, Mahoney, Di Rezze, Anderson, Drmic, Eerkes, Dekker, Georgiades, Hoult, Kraus de Camargo, Ng, Rosenbaum, Mesterman, Gentles, Robertson, Bennett and Georgiades.)

Aim: To investigate whether a digital sleep intervention improves child and care giver sleep and psychosocial outcomes., Methods: A total of 120 families with children aged 2-13 years, reporting moderate to severe child behavioural sleep problems, were recruited from a hospital sleep clinic waitlist or the community. Children from non-English speaking families, with known intellectual disability (IQ < 70) or severe medical problems excluded. Tailored behavioural sleep strategies were delivered to primary care givers via a smart phone app and complementary website. Eligible families completed a baseline questionnaire and child 'sleep check' then received the digital sleep intervention for 5 weeks, and then completed a post questionnaire., Outcomes: care giver report of child sleep as no/mild versus moderate/severe problem over past month (primary outcome); problem child sleep patterns (Brief Infant Sleep Questionnaire or Child Sleep Habits Questionnaire), child temperament, care giver mental health (Kessler 6), care giver sleep, health service use for their child's sleep and time off work/activities to access services., Results: At follow up, care givers reported fewer moderate/severe child sleep problems (84.6-40.7%), improved problem child sleep patterns, better temperament and improved care giver mental health. Care giver sleep quality and quantity remained unchanged. Health service use (averaged over a 6-month period pre- and post-intervention) fell from 18.9% pre- to 14.1% post-intervention., Conclusion: A digital sleep intervention appears promising in improving sleep in children with moderate/severe behavioural sleep problems, and care giver mental health. It may be a useful alternative to face-to-face management of behavioural sleep problems., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Objective: The aim of this study is to assess the feasibility (uptake, retention and adherence) and acceptability of a combination of smartphone apps to deliver a digitized safety plan, BeyondNow, and personalized management strategies, BlueIce , with adolescents discharged from a mental health inpatient ward following self-harm, suicidal ideation and/or behavior., Methods: Participants in this pre-post pilot study included 20 adolescents between 13-18 years, presenting with self-harming or suicidal behaviors in an inpatient psychiatric ward at a tertiary pediatric hospital. Participants were familiarized with the apps and completed baseline measures prior to discharge. They used the apps for six weeks before completing the follow-up survey, which measured feasibility and acceptability of the apps, as well as suicide resilience., Results: Seventeen participants completed the pilot. Most of the sample accessed both apps at least once, three accessed the BeyondNow safety plan five times or more, and six used the BlueIce toolbox five times or more. A total of 73.5% of the sample that experienced a crisis used at least one of the apps at least once. Forty seven percent felt that the apps would not keep them safe when in crisis, although almost all of the sample rated both apps as easy to use (94% for BeyondNow, and 82% for BlueIce). Medium to large effect sizes were also found with regard to improvements in suicide resilience., Conclusion: Both apps were found to be feasible and acceptable in this population, and easy to use, although no conclusions can be drawn regarding the clinical efficacy of the apps., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics approval and standards: The study was approved by the Royal Children’s Hospital Human Research Ethics Committee (HREC: 38,169 A). The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and international committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. No professional writers were involved in writing this manuscript., (© The Author(s) 2020.)

Propofol and dexmedetomidine are commonly used in clinical situations where neuroinflammation may be imminent or even established but comparative data on their effects on neuroinflammatory and cognitive parameters are lacking. Using a murine model of neuroinflammation induced by systemic lipopolysaccharide (LPS), this study compared the effects of these two agents on cognitive function, neuroinflammatory parameters, oxidative stress and neurotransmission. Male adult C57BL/6 N mice were anaesthetised with propofol or dexmedetomidine prior to intraperitoneal injection of LPS. Cognitive and motor function were assessed by the Y-maze and Rotarod tests respectively. Inflammatory responses were evaluated by relative levels of cytokine mRNA and immunoreactivity of glia cells. LPS caused a marked elevation in IL-1β and TNF-α levels both peripherally and in the brain, together with microglia activation (p <  0.05) and cognitive impairment. These changes were accompanied by an increase in 8-hydroxy-2'-deoxyguanosine (8-OHdG) (p <  0.05). Dexmedetomidine attenuated microglia activation (p <  0.05) and the elevation in 8-OHdG level (p <  0.05). Propofol did not affect cognition. However, both drugs lowered the number of vesicular glutamate transporter 1 (VGLUT 1), but was associated with higher levels of apoptosis and 8-OHdG (p <  0.05). Data from this study suggest dexmedetomidine and propofol have different anti-neuroinflammatory and neuroprotective profiles. However, neither drug can fully attenuate the effects of LPS induced cognitive impairment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is the most prevalent but still incurable neurodegenerative form of dementia. Early diagnosis and intervention are crucial for delaying the onset and progression of the disease. We herein report a novel fluoro-substituted cyanine, F-SLOH, which exhibits good Aβ oligomer selectivity with a high binding affinity, attributed to the synergistic effect of strong π-π stacking and intermolecular CH···O and CH···F interactions. The selectivity towards the Aβ oligomers in the brain was ascertained by in vitro labelling on tissue sections and in vivo labelling through the systemic administration of F-SLOH in 7 month APP/PS1 double transgenic (Tg) and APP/PS1/Tau triple Tg mouse models. F-SLOH also shows remarkably effective inhibition on Aβ aggregation and highly desirable neuroprotective effects against Aβ-induced toxicities, including the inhibition of ROS production and Ca 2+ influx. Its excellent blood-brain barrier (BBB) penetrability and low bio-toxicity further support its tremendous potential as a novel theranostic agent for both early diagnosis and therapy of AD.

Competing Interests: The authors have declared no potential conflicts of interest.

Several studies suggest a relationship between anesthesia-induced tau hyperphosphorylation and the development of postoperative cognitive dysfunction. This study further characterized the effects of continuous propofol infusion on tau protein phosphorylation in rats, with or without temperature control. Propofol was administered intravenously to 8-10-week-old male Sprague-Dawley rats and infused to the loss of the righting reflex for 2 h continuously. Proteins from cortex and hippocampus were examined by western blot and immunohistochemistry. Rectal temperature was significantly decreased during propofol infusion. Propofol with hypothermia significantly increased phosphorylation of tau at AT8, AT180, Thr205, and Ser199 in cortex and hippocampus except Ser396. With temperature maintenance, propofol still induced significant elevation of AT8, Thr205, and Ser199 in cortex and hippocampus; however, increase of AT180 and Ser396 was only found in hippocampus and cortex, respectively. Differential effects of propofol with or without hypothermia on multiple tau related kinases, such as Akt/GSK3β, MAPK pathways, or phosphatase (PP2A), were demonstrated in region-specific manner. These findings indicated that propofol increased tau phosphorylation under both normothermic and hypothermic conditions, and temperature control could partially attenuate the hyperphosphorylation of tau. Further studies are warranted to determine the long-term impact of propofol on the tau pathology and cognitive functions.

Exposure to anesthetic agents has been linked to abnormal tau protein phosphorylation, an antecedent to the development of neurofibrillary tangles. This study evaluates the direct and indirect effects of dexmedetomidine. Primary culture of cortical neurons established from Sprague-Dawley (SD) rat embryos were exposed to dexmedetomidine for 1 or 6 hours, and the degree of tau phosphorylation at the AT8, AT180, and S396 sites was assessed by western blot analysis. To assess and compare their relative in vivo effects, the same agent was administered intravenously to 8 to 10 week old male SD rats and titrated to the loss of the righting reflex for 2 hours. After 1 hour of recovery, the rats were sacrificed and samples taken from the cortex and hippocampus were subjected to western blot and immunohistochemical analysis. The in vitro studies reviewed significant hyperphosphorylation only at the S396 site, and these changes have largely disappeared at 6 hours. With temperature maintenance, dexmedetomidine induced significant changes in hyperphosphorylation at the AT8 site in the cortex and hippocampus and at the AT180 in the hippocampus. The direct effect of anesthetic agents on fully differentiated cortical neurons is epitope-specific and short-lived. The in vivo effects are comparatively more complicated and depend not only on the phosphorylation site but the regions of the brain examined. These findings suggest that dexmedetomidine increases tau phosphorylation both in vitro and in vivo under normothermic conditions, and further studies are warranted to determine the long-term impact of this anesthetic on the tau pathology and even cognitive function.

This is the first work that revealed the neuro-protective effect of functionalized quantum dots against the cytotoxicity induced by beta-amyloid peptides. This study gives insight into the future treatment of Alzheimer's disease. It opens many avenues for the development of the next generation nanotechnology for biomedical and therapeutic applications.

In the present study, N-methyl-D-aspartate receptor 2B (NR2B)-specific siRNA was applied in parkinsonian models. Our previous results showed that reduction in expression of N-methyl-D-aspartate receptor 1 (NR1), the key subunit of N-methyl-D-aspartate receptors, by antisense oligos ameliorated the motor symptoms in the 6-hydroxydopamine (6-OHDA)-lesioned rat, an animal model of Parkinson's disease (PD).

Errorless academic compliance training is a graduated, noncoercive approach to treating oppositional behavior in children. In the present study, three teaching staff in a special education classroom were trained to conduct this intervention with three male students diagnosed with autism spectrum disorders. During baseline, staff delivered a range of academic and other classroom requests and recorded student compliance. A hierarchy of compliance probabilities was then calculated, ranging from Level 1 (requests yielding high levels of compliance) to Level 4 (those typically yielding noncompliance). At treatment initiation, teaching staff delivered high densities of Level 1 requests and provided reinforcement for compliance. Subsequent request levels were faded in over time, at a slow enough rate to ensure continued high compliance. By intervention end, all three students demonstrated substantially improved compliance to classroom requests that had commonly yielded noncompliance before intervention. Covariant improvement in on-task skills was also evident.

Confocal fluorescence demonstrates that single molecules of dye-labelled Cytochrome C or B5 containing paramagnetic Fe(III) can be magnetically placed into the interstices of super-crystal which is composed of three dimensional regular arrays of Fe(3)O(4) nanoparticles.