Research Advances of Lipid Nanoparticles in the Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is a common type of gastrointestinal tract (GIT) cancer and poses an enormous threat to human health. Current strategies for metastatic colorectal cancer (mCRC) therapy primarily focus on chemotherapy, targeted therapy, immunotherapy, and radiotherapy; however, their adverse reactions and drug resistance limit their clinical application. Advances in nanotechnology have rendered lipid nanoparticles (LNPs) a promising nanomaterial-based drug delivery system for CRC therapy. LNPs can adapt to the biological characteristics of CRC by modifying their formulation, enabling the selective delivery of drugs to cancer tissues. They overcome the limitations of traditional therapies, such as poor water solubility, nonspecific biodistribution, and limited bioavailability. Herein, we review the composition and targeting strategies of LNPs for CRC therapy. Subsequently, the applications of these nanoparticles in CRC treatment including drug delivery, thermal therapy, and nucleic acid-based gene therapy are summarized with examples provided. The last section provides a glimpse into the advantages, current limitations, and prospects of LNPs in the treatment of CRC.

Using AI-Based Virtual Companions to Assist Adolescents with Autism in Recognizing and Addressing Cyberbullying.

Social media platforms and online gaming sites play a pervasive role in facilitating peer interaction and social development for adolescents, but they also pose potential threats to health and safety. It is crucial to tackle cyberbullying issues within these platforms to ensure the healthy social development of adolescents. Cyberbullying has been linked to adverse mental health outcomes among adolescents, including anxiety, depression, academic underperformance, and an increased risk of suicide. While cyberbullying is a concern for all adolescents, those with disabilities are particularly susceptible and face a higher risk of being targets of cyberbullying. Our research addresses these challenges by introducing a personalized online virtual companion guided by artificial intelligence (AI). The web-based virtual companion's interactions aim to assist adolescents in detecting cyberbullying. More specifically, an adolescent with ASD watches a cyberbullying scenario in a virtual environment, and the AI virtual companion then asks the adolescent if he/she detected cyberbullying. To inform the virtual companion in real time to know if the adolescent has learned about detecting cyberbullying, we have implemented fast and lightweight cyberbullying detection models employing the T5-small and MobileBERT networks. Our experimental results show that we obtain comparable results to the state-of-the-art methods despite having a compact architecture.

Effectiveness of H-files and Pro-Taper universal systems in removing Gutta-percha during endodontic retreatment: A comparative study.

Objective: This research was aimed at assessing the effectiveness of manual H-files versus a combination of a Pro-Taper universal rotary canal preparation system and retreatment system in removing gutta-percha (GP) during endodontic retreatment, by using a digital radiography technique. Methods: This ex vivo study used a non-probability consecutive sampling technique. The study sample comprised 60 extracted anterior permanent teeth, each with one root with a straight root canal (RC). After preparation, RCs were obturated with GP and sealer. Subsequently, teeth were stored for 2 weeks in a humid environment at 37 °C. Thirty teeth each were randomly assigned to the control (group I), and experimental (group II) groups. GP removal was performed with H-files {group I) or a combination of a Pro-Taper universal rotary canal preparation system and retreatment system (group 2). Digital radiographs were acquired with Carestream digital radiovisiography software (Kodak; version-VER.6.10.8.3-A), and the presence of residual GP was analyzed. AutoCAD (2006) software was used to demarcate the RC and residual root filling. The residual GP in both groups was compared with independent sample t-tests. Results: The remaining root filling did not significantly differ when GP was removed with conventional Hedstrom files versus a combination of Pro-Taper Universal preparation and retreatment file systems. The residual GP was confined to the apical third of the canals in both groups. Conclusions: Pro-Taper Universal preparation and retreatment file systems have similar effectiveness to manual H-files in GP removal in straight canals.

Taxonomic discordance of immersive realities in dentistry: A systematic scoping review.

OBJECTIVES: This review aimed to map taxonomy frameworks, descriptions, and applications of immersive technologies in the dental literature. DATA: The Preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) guidelines was followed, and the protocol was registered at open science framework platform (https://doi.org/10.17605/OSF.IO/H6N8M). SOURCES: Systematic search was conducted in MEDLINE (via PubMed), Scopus, and Cochrane Library databases, and complemented by manual search. STUDY SELECTION: A total of 84 articles were included, with 81 % between 2019 and 2023. Most studies were experimental (62 %), including education (25 %), protocol feasibility (20 %), in vitro (11 %), and cadaver (6 %). Other study types included clinical report/technique article (24 %), clinical study (9 %), technical note/tip to reader (4 %), and randomized controlled trial (1 %). Three-quarters of the included studies were published in oral and maxillofacial surgery (38 %), dental education (26 %), and implant (12 %) disciplines. Methods of display included head mounted display device (HMD) (55 %), see through screen (32 %), 2D screen display (11 %), and projector display (2 %). Descriptions of immersive realities were fragmented and inconsistent with lack of clear taxonomy framework for the umbrella and the subset terms including virtual reality (VR), augmented reality (AR), mixed reality (MR), augmented virtuality (AV), extended reality, and X reality. CONCLUSIONS: Immersive reality applications in dentistry are gaining popularity with a notable surge in the number of publications in the last 5 years. Ambiguities are apparent in the descriptions of immersive realities. A taxonomy framework based on method of display (full or partial) and reality class (VR, AR, or MR) is proposed. CLINICAL SIGNIFICANCE: Understanding different reality classes can be perplexing due to their blurred boundaries and conceptual overlapping. Immersive technologies offer novel educational and clinical applications. This domain is fast developing. With the current fragmented and inconsistent terminologies, a comprehensive taxonomy framework is necessary.

Predictive Value of Impulse Oscillometry Combined with Fractional Expiratory Nitric Oxide Test for Asthma in Preschool Children.

Objective: Prediction of asthma in preschool children is challenging and lacks objective indicators. The aim is to observe and analyze the variances between impulse oscillometry (IOS) and fractional expiratory nitric oxide (FeNO) in preschool children with wheezing, establish a joint prediction model, and explore the diagnostic value of combining IOS with FeNO in diagnosing asthma among preschool children. Patients and methods: This study enrolled children aged 3-6 years with wheezing between June 2021 and June 2022. They were categorized as asthmatic (n=104) or non-asthmatic (n=109) after a 1-year follow-up. Clinical data, along with IOS and FeNO measurements from both groups, underwent univariate regression and multiple regression analyses to identify predictive factors and develop the most accurate model. The prediction model was built using the stepwise (stepAIC) method. The receiver operating characteristic curve (ROC), calibration curve, Hosmer-Lemeshow test, and decision curve analysis (DCA) were employed to validate and assess the model. Results: During univariate analysis, a history of allergic rhinitis, a history of eczema or atopic dermatitis, and measures including FeNO, R5, X5, R20, Fres, and R5-R20 were found to be associated with asthma diagnosis. Subsequent multivariate analysis revealed elevated FeNO, R5, and X5 as independent risk factors. The stepAIC method selected five factors (history of allergic rhinitis, history of eczema or atopic dermatitis, FeNO, R5, X5) and established a prediction model. The combined model achieved an AUROC of 0.94, with a sensitivity of 0.89 and specificity of 0.88, surpassing that of individual factors. Calibration plots and the HL test confirmed satisfactory accuracy. Conclusion: This study has developed a prediction model based on five factors, potentially aiding clinicians in early identification of asthma risk among preschool children.

Energy Efficiency Optimisation of Joint Computational Task Offloading and Resource Allocation Using Particle Swarm Optimisation Approach in Vehicular Edge Networks.

With the progression of smart vehicles, i.e., connected autonomous vehicles (CAVs), and wireless technologies, there has been an increased need for substantial computational operations for tasks such as path planning, scene recognition, and vision-based object detection. Managing these intensive computational applications is concerned with significant energy consumption. Hence, for this article, a low-cost and sustainable solution using computational offloading and efficient resource allocation at edge devices within the Internet of Vehicles (IoV) framework has been utilised. To address the quality of service (QoS) among vehicles, a trade-off between energy consumption and computational time has been taken into consideration while deciding on the offloading process and resource allocation. The offloading process has been assigned at a minimum wireless resource block level to adapt to the beyond 5G (B5G) network. The novel approach of joint optimisation of computational resources and task offloading decisions uses the meta-heuristic particle swarm optimisation (PSO) algorithm and decision analysis (DA) to find the near-optimal solution. Subsequently, a comparison is made with other proposed algorithms, namely CTORA, CODO, and Heuristics, in terms of computational efficiency and latency. The performance analysis reveals that the numerical results outperform existing algorithms, demonstrating an 8% and a 5% increase in energy efficiency.

Emerging Trends in Virtual Surgical Planning for Orthognathic Surgery: A Global Overview of Research and Publication Patterns.

PURPOSE: Anticipating trends and pursuing innovative ideas are imperative for the advancement of science. The objective of this study was to conduct a bibliometric analysis of 3-dimensional virtual simulation in orthognathic surgery, explore its implications for clinical practice, and identify future publication trends through digital tools. METHODS: This study employed a retrospective bibliometric analysis using data obtained from the Web of Science database. The search strategy focused on articles related to orthognathic surgery and virtual simulation techniques. RStudio and bibliometrix tools were used to data mining. The independent variables retrieved from digital analysis were the emerging themes related to virtual planning in orthognathic surgery. The trends that we identified were facial esthetics, digital workflow, personalized treatments, and complex cases. The primary outcome variable was the number of publications dedicated to virtual simulation in orthognathic surgery, along with secondary outcomes such as citation rates, language of publication, country of origin, institutional affiliations, and emerging research themes. Covariates included variables related to publication characteristics, author affiliations, and geographic distribution of publications. Publication analyses over time involved descriptive statistics, regression analysis, Pearson correlation tests, and graphical representation techniques. Statistical significance was set at a 95% confidence interval (P value < .05). RESULTS: A comprehensive analysis of 987 articles reveals the impact of included authors, with a mean h-index of 62 (SD = 18.4). The analysis further illuminates a discernible upward trend in publications on this subject, showcasing a linear pattern with a notable R2 value of 0.88 (P = .021). English remains the predominant language of publication, accounting for 97.97% of articles, while contributions hailed from a diverse spectrum of 56 countries. Interestingly, a moderate correlation emerges between publication numbers and gross domestic product per capita (r = 0.30, P = .044) and total area (r = 0.30, P = .032), whereas a more substantial correlation is evident with total population (r = 0.61, P = .034). Notably, the most cited article amassed 254 citations. Furthermore, a Pearson correlation coefficient of 0.97 underscores the correlation between citation density and the year of publication. CONCLUSION: The bibliometric indicators provided insights for evaluating research productivity and the quality of research output. Emerging themes included facial esthetics, 3-dimensional printing, and the utilization of custom-made templates and implants. This study holds relevance for maxillofacial surgeons, academics, and researchers alike.

Effects of e-cigarette smoking on periodontal health: A scoping review.

OBJECTIVES: Use of electronic cigarettes (ECs), also known as vaping, has gained remarkable popularity globally during the last decade especially among young people. Current evidence suggests that vaping may be associated with health risks. The aim of this study is to evaluate whether vaping increases the risk for initiation and progression of periodontal disease; and to appraise the clinical changes seen in patients using e-cigarettes, and how these changes impact the management of periodontal disease. STUDY SELECTION, DATA AND SOURCES: A comprehensive electronic search was conducted on the PubMed, Scopus and Embase databases using the following search terms: Electronic Cigarettes OR vaping OR electronic nicotine delivery systems OR e-cigarettes AND Periodontitis. The search was limited to studies published from 1st January 2012 to 31st December 2022. RESULTS: A total of 23 clinical studies focusing on the effect of e-cigarette smoking on the periodontal clinical parameters, levels of inflammatory mediators, alteration in periodontal microflora, and response to periodontal treatment were found to be eligible for inclusion in the review. Vaping may be associated with greater clinical attachment loss (CAL) compared to non-smokers. Moreover, ECs are also associated with unfavorable effects on periodontal microbial counts, biomarkers of inflammation and oxidative stress. CONCLUSIONS: Vaping may play a role in the initiation and progression of periodontal disease by altering the host response resulting in the release of inflammatory cytokines and periodontal microflora. Clinical studies show deleterious effects of vaping on periodontal health as well as less favourable response to periodontal treatment is observed in e-cigarette users compared to non-smokers. However, compared to cigarette smoking, the effects of vaping are less remarkable.

Self-reported preparedness of final year undergraduate dental students and interns in Saudi Arabia: a multi-institutional study.

BACKGROUND: Contemporary undergraduate dental education aims to equip the dental students with clinical competence, empathy, and professionalism to enable them to deliver safe and effective dental care to the communities. The purpose of this study was to assess the self-reported preparedness of final year dental students and interns at three Saudi dental institutions, using the pre-validated Dental Undergraduates Preparedness Assessment Scale (DU-PAS). METHODS: A cross-sectional study design was employed to assess the self-reported preparedness of the participants using the DU-PAS. Following ethics approval, a probability sampling technique was used to recruit undergraduate dental students and interns from three dental institutions in Saudi Arabia. The data was collected online on Google Forms and all participants provided their consent to participate in the study prior to providing their responses to DU-PAS. RESULTS: Responses were received from 397 participants including 171 males and 226 females yielding a response rate of 60.3%. The total mean score of the participants was 81.85 ± 13.11. Although higher scores were reported in males, the interaction between gender and DU-PAS scores were not significant. Interaction between DU-PAS scores and stage of education showed significant effect of the stage of education with interns reporting higher overall scores. The participants reported that they were able to perform most clinical procedures independently. However, low confidence was reported in performing multi-rooted endodontics, fabrication of removable dentures and orthodontic assessment. The participants also expressed their confidence in a wide range of behavioural attributes related to communication, teamworking and professionalism. However, lack of experience was noted in referral for oral cancer, interpreting research, and evaluation of new dental products using an evidence-based approach. CONCLUSION: The study provides useful insights into the self-reported preparedness of undergraduate dental students and interns in three dental institutions. While the overall preparedness of the participants was comparable to their international peers, the findings underscore the need for further enhancements to the teaching and training of undergraduate students particularly in multirooted endodontics, removable prosthodontics and orthodontics.

Facile synthesis of manganese-hafnium nanocomposites for multimodal MRI/CT imaging and in vitro photodynamic therapy of colon cancer.

Precise diagnosis of complex and soft tumors is challenging, which limits appropriate treatment options to achieve desired therapeutic outcomes. However, multifunctional nano-sized contrast enhancement agents based on nanoparticles improve the diagnosis accuracy of various diseases such as cancer. Herein, a facile manganese-hafnium nanocomposites (Mn3O4-HfO2 NCs) system was designed for bimodal magnetic resonance imaging (MRI)/computed tomography (CT) contrast enhancement with a complimentary function of photodynamic therapy. The solvothermal method was used to fabricate NCs, and the average size of Mn3O4 NPs and Mn3O4-HfO2 NCs was about 7 nm and 15 nm, respectively, as estimated by TEM. Dynamic light scattering results showed good dispersion and high negative (-33 eV) zeta potential, indicating excellent stability in an aqueous medium. Mn3O4-HfO2 NCs revealed negligible toxic effects on the NCTC clone 929 (L929) and mouse colon cancer cell line (CT26), demonstrating promising biocompatibility. The synthesized Mn3O4-HfO2 NCs exhibit significant enhancement in T1-weighted magnetic resonance imaging (MRI) and X-ray computed tomography (CT), indicating the appropriateness for dual-modal MRI/CT molecular imaging probes. Moreover, ultra-small Mn3O4-HfO2 NCs show good relaxivities for MRI/CT. These nanoprobes Mn3O4-HfO2 NCs further possessed outstanding reactive oxygen species (ROS) generation ability under minute ultraviolet light (6 mW·cm-2) to ablate the colon cancer cells in vitro. Therefore, the designed multifunctional Mn3O4-HfO2 NCs were ideal candidates for cancer diagnosis and photodynamic therapy.

Synthesis and characterizations of conocarpus- and azadirachta-derived activated carbons as wastewater recycling material.

Water being the most important fluid supporting the life as well as industry is getting sparse and polluted day by day. Activated carbon (AC) can be utilized in various applications of significant environmental impact and sustainable living such as carbon dioxide sensing and capturing, air purification, and water recycling. However, in the wake of the recent corona pandemic which resulted in global lockdown and took the entire world by shock, a cost-effective and simple synthesis of such a useful material remains dire need of time. Therefore, this paper describes a simple and cost-effective synthesis of activated carbon (AC) of high porosity and surface area derived from the pruning of conocarpus and azadirachta trees. In reference to the study under consideration, alongside numerous others, a furnace was employed to synthesize activated carbon. However, our approach utilized a more conventional methodology wherein the environmental parameters were not optimized. In furnace-based procedures, factors such as temperature, pressure, and humidity are meticulously regulated, contrasting with the conventional methodologies where such parameters lack optimal control. Consequently, employing a furnace does not constitute a cost-effective approach for the physical activation of organic samples thus proving a furnace is not imperative for physical activation. The synthesis was carried out by physical activation in the form of carbonization followed by chemical activation with potassium hydroxide (KOH). The influence of activated carbon from each pruning over filtration of water containing industrial dye was investigated. Activation temperature and impregnation ratio of 600-800 °C and 1:5 were selected respectively. X-ray diffraction patterns (XRD) for all AC samples indicted the appearance of broad peaks at 2θ value of 20-30° which confirms the presence of carbon in the sample. The physical morphology arrangement by SEM analysis showed uneven arrangement of pores of conocarpus which indicated higher iodine number and hence higher adsorption capacity of 442.13 mg/g.

Successful Treatment of Chronic Actinic Dermatitis with Tofacitinib.

We present the case of a 58-year-old male patient who presented with pruritic skin plaques and papules on the scalp, face, back, and back of the hands for over a year. The symptoms worsened upon exposure to sunlight and improved on cloudy days. Despite previous attempts at treatment with glucocorticoid ointment and antihistamine drugs, the patient experienced progressive aggravation of symptoms. Physical examination revealed hypertrophic and infiltrating nodules, with significant scratches and local exudation. Skin biopsy confirmed the diagnosis of sun-induced dermatosis. The patient was initiated on tofacitinib, an oral Janus Kinase inhibitor, along with a halometasone ointment, oral ebastine tablets, and strict sun protection. Over the course of four revisits spanning four months, the patient experienced a significant improvement in symptoms, with the rash almost disappearing and pruritus subsiding. The treatment was well tolerated and no adverse effects were observed. Follow-up for six months post-treatment showed no recurrence of symptoms. This case highlights the efficacy of tofacitinib in managing sun-induced pruritic plaques and suggests it as a potential therapeutic option in similar cases.

Ten tips for effective use and quality assurance of multiple-choice questions in knowledge-based assessments.

Multiple-choice questions (MCQs) are the most popular type of items used in knowledge-based assessments in undergraduate and postgraduate healthcare education. MCQs allow assessment of candidates' knowledge on a broad range of knowledge-based learning outcomes in a single assessment. Single-best-answer (SBA) MCQs are the most versatile and commonly used format. Although writing MCQs may seem straight-forward, producing decent-quality MCQs is challenging and warrants a range of quality checks before an item is deemed suitable for inclusion in an assessment. Like all assessments, MCQ-based examinations must be aligned with the learning outcomes and learning opportunities provided to the students. This paper provides evidence-based guidance on the effective use of MCQs in student assessments, not only to make decisions regarding student progression but also to build an academic environment that promotes assessment as a driver for learning. Practical tips are provided to the readers to produce authentic MCQ items, along with appropriate pre- and post-assessment reviews, the use of standard setting and psychometric evaluation of assessments based on MCQs. Institutions need to develop an academic culture that fosters transparency, openness, equality and inclusivity. In line with contemporary educational principles, teamwork amongst teaching faculty, administrators and students is essential to establish effective learning and assessment practices.

ChatGPT-A double-edged sword for healthcare education? Implications for assessments of dental students.

INTRODUCTION: Open-source generative artificial intelligence (AI) applications are fast-transforming access to information and allow students to prepare assignments and offer quite accurate responses to a wide range of exam questions which are routinely used in assessments of students across the board including undergraduate dental students. This study aims to evaluate the performance of Chat Generative Pre-trained Transformer (ChatGPT), a generative AI-based application, on a wide range of assessments used in contemporary healthcare education and discusses the implications for undergraduate dental education. MATERIALS AND METHODS: This was an exploratory study investigating the accuracy of ChatGPT to attempt a range of recognised assessments in healthcare education curricula. A total of 50 independent items encompassing 50 different learning outcomes (n = 10 per item) were developed by the research team. These included 10 separate items based on each of the five commonly used question formats including multiple-choice questions (MCQs); short-answer questions (SAQs); short essay questions (SEQs); single true/false questions; and fill in the blanks items. Chat GPT was used to attempt each of these 50 questions. In addition, ChatGPT was used to generate reflective reports based on multisource feedback; research methodology; and critical appraisal of the literature. RESULTS: ChatGPT application provided accurate responses to majority of knowledge-based assessments based on MCQs, SAQs, SEQs, true/false and fill in the blanks items. However, it was only able to answer text-based questions and did not allow processing of questions based on images. Responses generated to written assignments were also satisfactory apart from those for critical appraisal of literature. Word count was the key limitation observed in outputs generated by the free version of ChatGPT. CONCLUSION: Notwithstanding their current limitations, generative AI-based applications have the potential to revolutionise virtual learning. Instead of treating it as a threat, healthcare educators need to adapt teaching and assessments in medical and dental education to the benefits of the learners while mitigating against dishonest use of AI-based technology.

Perceived confidence of dental students and new graduates in performing tooth extractions-An exploratory study.

INTRODUCTION: The ability to perform uncomplicated tooth extractions is a core clinical skill in undergraduate dental education. The aim of this study was to evaluate pre-extraction assessment skills of dental students and interns and explore their self-perceived confidence in performing these tooth extractions. MATERIALS AND METHODS: A cross-sectional survey investigated the self-perceived confidence to perform the extraction for a set of eight expert-rated cases. The participants were dental students at three different stages, that is, in Years 4 and 5 of the Bachelor of Dental Surgery (BDS) programme and interns. The participants were asked to rate the difficulty level of each of the eight tooth extraction cases. The self-perceived confidence of the participants to perform extraction of each was also explored. Finally, the participants were asked to identify the main reason for the perceived lack of confidence. RESULTS: A total of 199 responded to the survey, yielding a response rate of 94.7%. The effect of grade of extraction (the expert rating of cases) and stage of education on difficulty ratings was assessed using a mixed three stage of education × 4-grade ANOVA, with response (Difficult = 1, Easy = 0) as the dependent variable. The results showed that there was a correlation between the stage of education and grade of extraction and affected the self-perceived confidence of the participants. Gender showed a significant impact with females categorizing significantly more cases as difficult. A three-way contingency table (counts of each confidence-level response by stage of education by expert rating of cases) suggests a statistically significant association between the three factors. Most participants identified limited clinical exposure as the main reason for their perceived lack of confidence. CONCLUSION: The findings of this study show that a majority of the participants were able to recognize tooth extraction cases which were beyond the scope of their training stage with females reporting a lower confidence. Increased clinical exposure to a wider range of tooth extraction cases with varying levels of difficulty may contribute to improving the self-confidence of undergraduate dental students and interns.

Self-perceived preparedness of new dental graduates from a Middle Eastern university.

INTRODUCTION: Preparedness for independent clinical practice is a core goal of undergraduate dental education. The aim of this study was to evaluate the self-reported preparedness for the dental practice among new dental graduates from a University in the Middle East. METHODS: Following ethics approval, a purposive sampling techniques were used to invite newly qualified dental graduates at a Middle Eastern University. A validated research instrument, namely the Dental Undergraduate Preparedness Assessment Scale (DU-PAS), was used to evaluate the self-perceived preparedness of the participants. Data collection was undertaken online using Google Forms and data were analysed to compute the descriptive statistics, reliability and demographic differences among the participants. RESULTS: A total of 82 participants provided their response yielding a response rate of 68%. The participants included 49 males and 33 females. The overall reliability of DU-PAS was excellent. (α = 0.93). The participants included less than 40% of participants were able independently to prescribe medications, assess orthodontics needs and perform endodontic treatment on multirooted teeth. In addition, more than 65% indicated low confidence in evaluating new dental materials and products, interpreting new research findings and behavioural management of children. CONCLUSION: The present findings identified strengths and weaknesses of new dental graduates from a Middle Eastern university. The participants were confident in basic clinical skills but lower confidence was reported for complex dental procedures. The findings highlight the learning needs of new dental graduates and can serve to inform the undergraduate curriculum to enhance the preparedness of future cohorts of dental graduates.

Angiotensin-Neprilysin inhibition in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.

BACKGROUND: The effect of sacubitril/valsartan on patients with heart failure (HF) with preserved ejection fraction (HFpEF) is a topic of ongoing debate. METHODS: Medline was queried from inception through the last week of May 2023 for randomized studies assessing the effects of sacubitril/valsartan in patients with HFpEF. For continuous outcomes, we pooled either the geometric mean ratios (gMR) or weighted mean difference (WMD) with 95% confidence intervals (CI). For dichotomous outcomes, we pooled Risk ratios (RR) with 95% CI. RESULTS: Four trials were included (N=8,129). Compared to the control, sacubitril/valsartan was associated with a reduction in NT-proBNP levels (gMR: 0.84, 95% CI 0.80, 0.88) and improvement in KCCQ score (WMD: 0.85, 95% CI: 0.02, 1.67). We observed no differences for HF hospitalization (RR: 0.90, 95% CI: 0.79, 1.01), cardiovascular mortality (RR: 0.83, 95% CI: 0.52, 1.32), all-cause mortality (RR: 0.99, 95% CI: 0.86-1.13) and improvement (RR: 1.15, 95% CI: 0.93, 1.42) or worsening (RR: 0.92, 95% CI: 0.78, 1.09) of NYHA class between the sacubitril/valsartan and comparator group. Sacubitril/valsartan was generally safe, and patients were less likely to have a ≥50% decline in eGFR compared to control (RR: 0.60, 95% CI: 0.39, 0.92). CONCLUSION: Pooled analysis suggests that sacubitril/valsartan reduces natriuretic peptide levels and improves the quality of life in patients with HFpEF, which may translate into better clinical outcomes as observed by a numerical trend towards improvement in major HF outcomes with sacubitril/valsartan therapy.

Ex vivo discovery of synergistic drug combinations for hematologic malignancies.

Combination therapies have improved outcomes for patients with acute myeloid leukemia (AML). However, these patients still have poor overall survival. Although many combination therapies are identified with high-throughput screening (HTS), these approaches are constrained to disease models that can be grown in large volumes (e.g., immortalized cell lines), which have limited translational utility. To identify more effective and personalized treatments, we need better strategies for screening and exploring potential combination therapies. Our objective was to develop an HTS platform for identifying effective combination therapies with highly translatable ex vivo disease models that use size-limited, primary samples from patients with leukemia (AML and myelodysplastic syndrome). We developed a system, ComboFlow, that comprises three main components: MiniFlow, ComboPooler, and AutoGater. MiniFlow conducts ex vivo drug screening with a miniaturized flow-cytometry assay that uses minimal amounts of patient sample to maximize throughput. ComboPooler incorporates computational methods to design efficient screens of pooled drug combinations. AutoGater is an automated gating classifier for flow cytometry that uses machine learning to rapidly analyze the large datasets generated by the assay. We used ComboFlow to efficiently screen more than 3000 drug combinations across 20 patient samples using only 6 million cells per patient sample. In this screen, ComboFlow identified the known synergistic combination of bortezomib and panobinostat. ComboFlow also identified a novel drug combination, dactinomycin and fludarabine, that synergistically killed leukemic cells in 35 % of AML samples. This combination also had limited effects in normal, hematopoietic progenitors. In conclusion, ComboFlow enables exploration of massive landscapes of drug combinations that were previously inaccessible in ex vivo models. We envision that ComboFlow can be used to discover more effective and personalized combination therapies for cancers amenable to ex vivo models.

Enhancing learning experiences in pre-clinical restorative dentistry: the impact of virtual reality haptic simulators.

BACKGROUND: Utilization of Virtual Reality haptic simulation (VRHS) to aid in the training of various pre-clinical skills is of recent interest. The aim of this study was to evaluate the impact of VRHS in restorative dentistry on the learning experiences and perceptions of dental students. METHODS: An interventional study design was utilized to recruit third year students. All participants provided informed consents and were randomly divided into two groups. Group 1: Initially performed a Class I cavity preparation with the VRHS, followed by the same exercise using the phantom head/ acrylic typodont teeth in a conventional simulation environment (CSE). Group 2: Initially performed Class I preparations in a CSE, followed by the same exercise using VRHS. Both groups performed the exercises on a lower right first molar. To understand students' perception, an online questionnaire was circulated. Data analysis involved Chi-square tests, independent t-tests and Mann-Whitney U-tests using the R statistical environment package. RESULTS: A total of 23 dental students participated in this study. Although student's perceptions were similar in both groups, a strong agreement that VRHS training might be used to supplement standard pre-clinical training was noted. Advancements to the VRHS hardware and software are required to bridge the gap and provide a smooth transition to clinics. CONCLUSION: Novice dental students generally perceived VRHS as a useful tool for enhancing their manual dexterity. Dental institutions should endorse virtual reality technology with caution, ensuring a planned integration into the curriculum to optimize benefit. Feedback is pivotal to effective learning in simulation-based education, and the triangulation of feedback could serve as a powerful aid to maximize the learning experience.