Broad Implementation Research Articles

Knowledge and practice of dental professionals regarding vertical teeth preparation techniques

BackgroundVertical preparation techniques (VPTs), particularly the biologically oriented preparation technique (BOPT), have gained prominence in restorative dentistry due to their conservative approach to tooth structure preservation and improved aesthetic outcomes. This study aims to assess the knowledge and clinical practices of VPTs, including BOPT, among dental professionals in Sanaa, Yemen, and explore the barriers to their widespread use.Materials and methodsAn online cross-sectional survey was conducted among general practitioners and specialists in Sanaa, Yemen using a structured, self-administered questionnaire. The survey explored the participants’ knowledge, familiarity, and clinical use of VPTs and their perceptions of its advantages and challenges. Data were analyzed using descriptive statistics and Chi-square tests to evaluate associations between professional roles and VPT knowledge and practice. P values < 0.05 indicated statistical significance.ResultsOut of 285 participants, 76.8% were familiar with VPTs but only 11.6% reported using these approaches in clinical practice. The primary source of knowledge acquisition was informal, with 26.3% of the participants citing social media as their main resource. Specialists demonstrated significantly higher proficiency and confidence in applying VPTs compared with general practitioners (p < 0.05). Key challenges identified in clinical adoption were controlling gingival bleeding (32.28%) and achieving precise margins during tooth preparation (34.74%). The majority (55.8%) of participants acknowledged the potential of VPTs as the future of restorative dentistry. Despite these benefits, 36.1% of the respondents emphasized the need for further training and educational programs to enhance proficiency and overcome the perceived complexity of these techniques.ConclusionThis study highlights significant gaps in the knowledge and practice of VPTs, particularly BOPT, among the participants. While these techniques offer promising clinical and aesthetic benefits, their adoption is hindered by inadequate training and perceived complexity. Targeted educational interventions and further research are needed to support the broad implementation of VPTs in clinical practice.Clinical trial numberNot applicable.

Effectiveness of an Internet-Based Acceptance and Commitment Therapy Intervention for Reducing Psychological Distress in Health Care Professionals: Randomized Controlled Trial.

Psychological distress is prevalent among health care professionals and can lead to poor-quality patient care. Internet-based acceptance and commitment therapy (iACT) is a promising intervention for improving mental health due to its low cost and easy access. However, there is limited evidence of its effectiveness in reducing health care professionals' psychological distress. This study aims to examine the effects of iACT on psychological distress (stress, anxiety, and depression) among health care professionals in China. From October 2022 to February 2023, a total of 108 health care professionals were recruited via WeChat and randomized into a 6-week iACT intervention program with therapist support (n=54) or waitlist control group (n=54). The intervention included 21 self-guided sessions combining teaching videos, mindfulness practices, and journal writing, followed by 7 live conferences to share experiences and discuss questions, all conducted via WeChat. Primary outcomes (stress, anxiety, and depression) and secondary outcomes (burnout and psychological flexibility) were collected using the Sojump platform, the most popular web-based survey platform in China. Generalized estimating equations were used to compare the outcomes between groups and assess the effects of group, time, and group-by-time interaction. Subgroup and sensitive analyses were performed to test the robustness of our findings across various groups. Among the 108 health care professionals, 68 (63%) completed the follow-up assessment at week 10, including 35 (64.8%) in the iACT group and 33 (61.1%) in the waitlist control group. Of the 54 participants in the iACT group, all attended at least 2 sessions, and 25 attended all 28 sessions. On average, participants attended 20 (71%) sessions. The iACT group showed significant improvement in the Depression Anxiety and Stress Scales-21 total score (d=0.82, 95% CI 0.39-1.26), and the effects were sustained for 4 weeks after the intervention (d=1.08, 95% CI 0.57-1.59). Compared to the control group, the iACT group showed significantly lower scores in burnout at week 6 (d=1.42, 95% CI 0.95-1.89) and week 10 (d=1.52, 95% CI 0.98-2.06). The iACT group showed significantly higher psychological flexibility at week 6 (d=1.23, 95% CI 0.77-1.69) and week 10 (d=1.15, 95% CI 0.64-1.66). The iACT effectively decreased health care professionals' psychological distress and burnout and improved their psychological flexibility. Our findings provide implications and guidance for the development and broad implementation of iACT in health care settings to improve the mental health of health care professionals. Chinese Clinical Trial Register ChiCTR2400093584; https://tinyurl.com/38werwsk.

Recent advancements in aquaponics with special emphasis on its sustainability

AbstractAn aquaponic system which is an integration of hydroponics with aquaculture is sustainable, ecologically friendly, and uses non‐renewable resources with very high efficacy. The increasing trend in aquaponics research demonstrates a growing recognition of its potential to address critical global issues such as food security, water conservation, and sustainable agriculture, particularly in regions vulnerable to climate change and resource limitations. It has witnessed remarkable advancements in recent years, with various methods and variations emerging to enhance its functionality and productivity. The purpose of this review is to unify fragmented research on aquaponics and provide a comprehensive resource that emphasizes its potential for broad adoption and successful implementation in varied environments. This review focuses on recent innovations in aquaponic system designs for various climates and examines key advancements in critical areas, including microbial communities, biofiltration, feed management, water quality, and nutrient cycling, emphasizing the interdisciplinary nature of aquaponics. Coupled systems suit moderate climates with high resource efficiency, while decoupled systems offer flexibility across diverse climates by allowing independent control of each component. Innovations such as sandponics, algaeponics, and saline aquaponics address challenges like water scarcity and nutrient efficiency. Smart technologies like IoT and AI are integrated into aquaponics, automating monitoring and nutrient management for better productivity. Emerging areas, including vermi‐aquaponics and flocponics, offer new solutions for nutrient cycling, making aquaponics more efficient, adaptable, and resource‐conserving globally. This paper also examines the sustainability aspects of aquaponics, emphasizing its economic, social, and environmental dimensions. Despite high setup costs and nutrient complexities, aquaponics offers significant potential for sustainable food production by minimizing water use and reducing synthetic fertilizers. Its scalability in both urban and rural areas, along with innovations like vertical systems, presents promising solutions for enhancing agriculture and food security across diverse environments.

Constructing positively charged hollow fiber nanofiltration membranes with high performance for the treatment of wastewater containing heavy metal ions

The presence of heavy metal ions in wastewater has been identified as a significant environmental and human health concern. Positively charged hollow fiber (HF) Nanofiltration (NF) membranes show great promise and excellent potential for the removal of heavy metal ions due to Donnan exclusion effect. Nevertheless, the current limitations of positively charged HF NF membranes, including complex preparation process, low flux and poor selectivity, continue to impede their broader implementation. In this work, a high flux HF NF membrane with positively charged surface was fabricated via doping piperazine in the aqueous-phase solution of polyethyleneimine to modulate the interfacial polymerization and to adjust the structure of the subsequent polyamide skin layer. Subsequently, the surface of this nascent skin layer was modified with diethylenetriamine/ethanol solution to increase its positive charge density, and thus to improve the rejection of multivalent cations. The optimal HF NF membrane shows a pure water permeability of 160 LMH/MPa and a MgCl2 rejection of higher than 97 %. In addition, it shows a rejection of higher than 95 % for heavy metal salts such as CoCl2, MnCl2, NiCl2, CuCl2 and Cr2(SO4)3, and a rejection of more than 98 % for antibiotics such as tetracycline hydrochloride, oxytetracycline and levofloxacin. It also possesses good resistance to acid and contamination. In addition, the optimal HF NF membrane has been successfully scaled up to a module of 20 filaments and still shows excellent separation performance, suggesting its vast potential for industrial application.

ABOUT THE USE OF DIGITAL HYDRAULIC VALVES IN INDUSTRY

The article discusses digital hydraulic valves, which are an innovative alternative to traditional proportional analog valves. Digital hydraulics utilize a combination of simple, reliable, and inexpensive ON/OFF type valves, offering high precision in flow and pressure control through programmable logic controllers. The main advantage of such systems is the reduction in energy consumption, as they eliminate the need for constant pump operation and have no internal leakage. The article highlights the economic benefits of digital valves, including lower initial investments due to their lower cost compared to proportional counterparts. Importantly, if one valve fails, the system remains operational, as the failure of individual components does not critically affect overall performance. Special attention is given to coding schemes and control methods, particularly binary coding and pulse number modulation. Binary coding allows for significantly improved regulation accuracy with a minimal number of valves and ensures system fault tolerance. The use of parallel-connected valves, which offer a wide range of states, allows precise control of flows and pressures without the need for switching after the desired positions are set. Additionally, digital hydraulic systems provide fast response times and precise control, making them effective for various industrial applications. Further research in this area could lead to the development of new technological solutions and broader implementation in the industry. The article also covers the technical aspects of such systems, particularly pulse-width modulation, the most common approach to controlling two-way valves. PWM achieves high regulation accuracy through frequency modulation, although low switching frequencies may cause pressure pulsations, which must be compensated through specialized system design or damping devices. In conclusion, digital hydraulic valves represent a promising solution for increasing the efficiency and reliability of hydraulic systems in modern industries, with the potential for significant reductions in energy consumption and operational costs.

Performance Enhancement of EEG Signatures for Person Authentication Using CNN BiLSTM Method

&amp;nbsp;Despite their vulnerability to competent forgers, signatures are one of the most widely used user verification methods. Recent research has revealed that EEG signals are harder to reproduce and give superior biometric information. This study aims to improve the effectiveness of person authentication by using deep learning techniques on electroencephalogram (EEG) signals. The broad implementation of EEG-based authentication systems has been hindered by problems such as noise, variability, and inter-subject variances despite the potential distinctiveness of EEG signals. We propose a multiscale convolutional neural network (CNN) and a Bidirectional LSTM (BiLSTM) model called CNN-BiLSTM to extract features and classify raw EEG data. This methodology involves acquiring raw EEG data, preprocessing for noise reduction, standardization, normalization, and employing deep learning techniques for feature extraction and classification. Experimental results exhibit a notable improvement in accuracy and reliability compared to existing EEG authentication methods such as LOF, CNN, FCN, EfficientNet-B0, and BiLSTM. The results showcase the performance of the proposed deep learning model utilizing established metrics such as precision, sensitivity, specificity, and accuracy. The proposed methodology outperforms existing methods and achieves a training and validation accuracy of 98.9% and 92.2%, respectively. The findings of the research demonstrate that the proposed approach has been successful in achieving highly effective results by using EEG signals for the purpose of resolving issues related to person identification.&amp;nbsp;

Optimising the treatment of chronic ischemic heart disease by training general practitioners to deliver very brief advice on physical activity (OptiCor): protocol of the systematic development and evaluation of a complex intervention

BackgroundChronic ischemic heart disease (IHD) is one of the leading causes of morbidity and mortality. Physical activity (PA) is an effective secondary preventive strategy in IHD management. The German treatment guideline recommends that general practitioners (GPs) deliver PA advice to patients. This recommendation seems inadequately implemented, often due to GP’s insufficient specific training. International guidelines recommend training GPs in how to deliver such advice effectively and efficiently. Evidence is lacking on whether such training can enhance the frequency and quality of PA advice in routine care. The OptiCor project aims to develop and evaluate a GP training in the delivery of very brief PA advice to optimise the treatment of patients with IHD in general practice.MethodsOptiCor comprises three study phases according to the Medical Research Council recommendations for developing and evaluating complex interventions.Phase 1 (needs analysis): A nationwide representative household survey will be conducted to collect data on the receipt of GP-delivered PA advice in people with IHD. Qualitative interviews and group discussions with GPs and people with IHD will help to explore, e.g., attitudes, experiences with, and barriers and facilitators of PA advice implementation or reception, respectively. Findings will inform the training development.Phase 2 (pilot): A pragmatic cluster randomised controlled trial (cRCT) on the effectiveness of the developed training on proportions of GP-delivered PA advice during routine care of IHD patients will be piloted.Phase 3 (evaluation): A full pragmatic cRCT will be conducted with patient-reported proportions of GP-delivered PA advice as primary endpoint. Collection of health economic and process-related data will facilitate a potential future broad implementation and health economic evaluation of the training.DiscussionIf the developed training successfully improves proportions and quality of GP delivered PA advice to patients with IHD, it could serve as a low-threshold and sustainable strategy for implementing PA recommendations in the secondary prevention of IHD in routine GP practice.Trial registrationWork package (WP) 1, WP5, and WP6 have been prospectively registered at German Clinical Trials Register (WP1: DRKS00031304, 19/06/2023; WP5: DRKS00034641, 10/07/2024; WP6: DRKS00034642; 10/07/2024).

A Comparative Analysis between Islamic Economics and Environmental Economics: Historical Development and its Significance for Contemporary Challenges

This article investigates the possible relationship between Islamic and Environmental Economics to address environmental concerns. Comparative analysis shows that Environmental Economics has been more successful in addressing environmental challenges, even though both frameworks approach the economic activity with different concepts. Environmental Economics has been successful because of its all-encompassing focus on environmental factors, acceptance on a worldwide scale, relevance of policies, and individual-centered methodology. On the other hand, Islamic economics, which functions mainly at the community level, needs more clarity with broader implementation. The strengths of each strategy are examined in this research, which concludes that environmental economics provides a more flexible and universally applicable framework for promoting economic activity by environmental preservation. The results add to the current discussion on sustainable development by highlighting the significance of combining realistic, internationally recognized strategies with moral principles to create a sustainable future.

Uncovering the toll of the first three COVID-19 waves: excess mortality and social patterns in Belgium

BackgroundThis study aims to assess which population groups experienced the heaviest mortality burden during the first three COVID-19 waves in Belgium; and investigate potential changes in social differences in all-cause mortality during the epidemic and compared to the pre-COVID period.MethodsExhaustive all-cause mortality information (2015–2021) from the Belgian population register was linked to demographic and socioeconomic census and register data. Annual cohorts consisting of 6.5 million to 6.8 million persons were created selecting persons aged 35 and older. Excess mortality was investigated comparing the 137,354 deaths observed during the first three COVID-19 waves with mortality in the reference period 2015–2019. Methods of analysis include direct standardization and Poisson regression analyses.ResultsElderly men experienced the highest absolute mortality burden during all three COVID-waves, followed by elderly women, middle-aged men, and middle-aged women. Care home residents consistently experienced higher mortality rates during the first and second wave compared to peers living in other living arrangements. In wave 3, care home residents showed significant absolute mortality deficits compared to the reference period. When adjusting for all demographic and socioeconomic factors, the traditional pattern of educational and income mortality inequalities was found among the elderly population during the COVID-waves. In contrast, the educational mortality gap among middle-aged persons deepened during COVID-waves 2 and 3 with excess mortality between 19 and 30% observed among mainly lower-educated persons. Income mortality inequalities among middle-aged women and men remained stable or even diminished for some specific groups in some waves.ConclusionThe widening educational mortality gap among middle-aged persons in successive waves suggest an important role of knowledge and associated educational resources during the COVID-19 epidemic. Belgium’s broad implementation of public health control and prevention measures may have successfully averted a further widening of social mortality inequality between income groups and among the elderly population.

Economic Evidence on Cost Sharing and Alternative Insurance Designs to Address Moral and Behavioral Hazards in High-Income Health Care Systems: A Systematic Review.

In health insurance, "moral hazard" describes the concept that coverage without an out-of-pocket cost to consumers could result in health care utilization beyond economically efficient levels. In response, payers in the United States (US) have designed pharmaceutical benefit plans with significant cost exposure (e.g., co-pays, co-insurance, or deductibles). While substantial evidence links patient cost exposure to reduced drug spending, it remains unclear to what degree this translates into greater efficiency or an indiscriminate drop in overall consumption also reducing needed utilization. We conducted a systematic literature review to understand whether commonly implemented utilization management (UM) strategies and insurance designs with a behavioral or value-based (BID/VBID) component have been explored as tools to mitigate moral hazard and to assess how cost-sharing policies and innovative insurance designs impact consumer spending. Eligible studies compared conventional cost-exposure policies to BID/VBID, including tiered cost-sharing and other UM strategies. We found that broad implementation of patient cost exposure is not well supported by empirical evidence assessing efficiency-defined as the use of clinically appropriate services with value at or above the marginal cost of health care utilization in the contemporary US setting. As a result, payers and policy makers alike ought to explore insurance alternatives that more closely align health care consumption incentives to value of care.

Screening and referral programs for diabetes and cardiovascular disease: Can community pharmacists bridge the care gap?

Background and ObjectivesHeart disease and diabetes are leading causes of death in the U.S., with timely screening, referrals, and education being critical for effective treatment. The Community-based Valued-driven Care Initiative (CVCI) aimed to develop, implement, and evaluate the feasibility of delivering patient-centered care interventions for high priority disease states in community pharmacies. This article focuses specifically on two of the selected interventions, both of which were screening and referral (S&R) programs for the prevention and treatment of cardiovascular disease (CVD) and diabetes (DM) respectively. This exploratory evaluation was designed as an effectiveness-implementation hybrid Type II study. Its objectives were to assess both implementation and preliminary program effectiveness using mixed data. MethodsFifteen community pharmacies opted to implement one of the two programs over a 12-month period. Implementation feasibility involved examining program adoption rates by sites and patients; acceptability, appropriateness, feasibility, and intent to sustain use survey scores; and pharmacists' interviews. Program effectiveness was based on patient referral rates, physician follow-up communication rates, and perceived outcomes, collected via patient logs, surveys, and interviews. ResultsTwo of the 15 sites discontinued participation, yielding an 87 % adoption rate. Patient adoption varied based on contact and screening rates, due to differences in patient recruitment, staffing, and workflow. Pharmacist acceptability, compatibility, and feasibility remained high throughout implementation; however, only three pharmacy sites planned on continuing offering the programs. All at-risk patients were appropriately referred based on screening results, with 65 % having their screening results communicated to their primary healthcare providers. The programs were perceived as beneficial, increasing pharmacists' knowledge and motivation, enhancing relationships with patients, and producing an impact on patients'' health. DiscussionResults highlight the implementation feasibility and preliminary outcomes of delivering DM and CVD S&R programs in community pharmacies. However, despite these positive results, most pharmacies did not intend to continue the programs, underscoring the continued need for sustainable clinical services models in non-traditional settings. Success with broader implementation will require a paradigm shift in support of community pharmacists as clinical care extenders.

Clinical trial of arthroscopic debridement combined with functional exercise in the treatment of advanced knee osteoarthritis: A retrospective observational study.

Advanced knee osteoarthritis (KOA) impacts both knees, resulting in pain, deformity, and substantial restrictions in joint mobility. This study aims to examine the effectiveness of combining arthroscopic debridement with functional exercise in treating advanced KOA. A total of 296patients diagnosed with advanced KOA were divided into two groups: the observation group (n= 152) received arthroscopic debridement combined with functional exercise, while the control group (n= 144) underwent arthroscopic debridement only. The study compared and observed the outcomes between the two groups. There were no significant differences in knee joint function, inflammation level, and oxidative stress between the two groups before treatment (P> 0.05). Following treatment for six months, the observation group exhibited significantly lower visual analog scale (VAS) score, tissue inhibitors of metalloproteinase-1 (TIMP-1), tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), matrix metalloproteinase-3 (MMP-3), and malondialdehyde (MDA) levels compared to the control group (P< 0.05). Meanwhile, the observation group showed significantly higher levels of Lysholm score, hospital for special surgery (HSS) score, range of motion (ROM) of knee, peak torque (PT) and total work (TW) for knee extension and flexion, superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione (GSH) compared to the control group (P< 0.05). Besides, the effective treatment rate in the observation group was notably higher than that in the control group (80.92% vs. 69.44%, P< 0.05). The combination of arthroscopic debridement with functional exercise is an effective treatment for advanced KOA. This approach not only enhances the function and strength of knee joint and reduces inflammatory response but also boosts the body's antioxidant capacity. The treatment exhibits encouraging outcomes and warrants broad implementation.

A Modular Approach for Accessing 3D Heterocycles via 1,2‐Dicyanation of Planar N‐Heteroarenes

AbstractThe rapid construction of three‐dimensional (3D) heterocyclic frameworks is a key challenge in contemporary medicinal chemistry. The molecules with three‐dimensional complexity hold a greater probability to improve clinical outcomes, solubility, selectivity for target proteins, and metabolic stability. However, the prevalence of flat molecules persists among new drug candidates, primarily owing to the multitude of chemical methods available for their synthesis. In principle, the dearomative functionalization of N‐heteroarene allows for the conversion of readily available planar molecules into partially or fully saturated nitrogen heterocycles, which are most significant structural motifs of pharmaceuticals and natural products. Unfortunately, these reactions are very rare because of the inherent challenge imposed by heteroarenes’ poor reactivity, rendering the process thermodynamically unfavorable. Herein, we report a modular approach for accessing 3D chemical space in translating planar heteroarenes into valuable 3D heterocycles via the installation of a highly versatile cyano group as a new vector. This approach is enabled by the in situ generation of reactive, non‐symmetric iodane by combining cyanide anion and bench‐stable PhI(OAc)2. This reaction represents a rare example of 1,2‐dicyanation of N‐heteroarenes that meets the numerous requirements for broad implementation in drug and agrochemical discovery. The transformation is highly selective and amenable to a wide range of N‐heteroarenes and late‐stage partial saturation of drugs and agrochemicals.

A Modular Approach for Accessing 3D Heterocycles via 1,2-Dicyanation of Planar N-Heteroarenes.

The rapid construction of three-dimensional (3D) heterocyclic frameworks is a key challenge in contemporary medicinal chemistry. The molecules with three-dimensional complexity hold a greater probability to improve clinical outcomes, solubility, selectivity for target proteins, and metabolic stability. However, the prevalence of flat molecules persists among new drug candidates, primarily owing to the multitude of chemical methods available for their synthesis. In principle, the dearomative functionalization of N-heteroarene allows for the conversion of readily available planar molecules into partially or fully saturated nitrogen heterocycles, which are most significant structural motifs of pharmaceuticals and natural products. Unfortunately, these reactions are very rare because of the inherent challenge imposed by heteroarenes' poor reactivity, rendering the process thermodynamically unfavorable. Herein, we report a modular approach for accessing 3D chemical space in translating planar heteroarenes into valuable 3D heterocycles via the installation of a highly versatile cyano group as a new vector. This approach is enabled by the in situ generation of reactive, non-symmetric iodane by combining cyanide anion and bench-stable PhI(OAc)2. This reaction represents a rare example of 1,2-dicyanation of N-heteroarenes that meets the numerous requirements for broad implementation in drug and agrochemical discovery. The transformation is highly selective and amenable to a wide range of N-heteroarenes and late-stage partial saturation of drugs and agrochemicals.

Conductive hydrogels: Intelligent dressings for monitoring and healing chronic wounds

Abstract Conductive hydrogels (CHs) represent a burgeoning class of intelligent wound dressings, providing innovative strategies for chronic wound repair and monitoring. Notably, CHs excel in promoting cell migration and proliferation, exhibit powerful antibacterial and anti-inflammatory properties, and enhance collagen deposition and angiogenesis. These capabilities, combined with real-time monitoring functions, play a pivotal role in accelerating collagen synthesis, angiogenesis, and continuous wound surveillance. This review delves into the preparation, mechanisms, and applications of CHs in wound management, highlighting their diverse and significant advantages. It emphasizes the effectiveness of CHs in treating various chronic wounds, such as diabetic ulcers, infected wounds, temperature-related injuries, and athletic joint wounds. Additionally, it explores the diverse applications of multifunctional intelligent CHs in advanced wound care technologies, encompassing self-powered dressings, electrically-triggered drug delivery, comprehensive diagnostics and therapeutics, and scar-free healing. Furthermore, the review highlights the challenges to their broader implementation, explores the future of intelligent wound dressings, and discusses the transformative role of CHs in chronic wound management, particularly in the context of the anticipated integration of artificial intelligence (AI). Additionally, this review underscores the challenges hindering the widespread adoption of CHs, delves into the prospects of intelligent wound dressings, and elucidates the transformative impact of CHs in managing chronic wounds, especially with the forthcoming integration of artificial intelligence (AI). This integration promises to facilitate predictive analytics and tailor personalized treatment plans, thereby further refining the healing process and elevating patient satisfaction. Addressing these challenges and harnessing emerging technologies, we postulate, will establish CHs as a cornerstone in revolutionizing chronic wound care, significantly improving patient outcomes.

The Unveiled Novel regulator of Adeno-associated virus production in HEK293 cells

The field of gene therapy using Adeno-associated viral (AAV) vector delivery is rapidly advancing in the biotherapeutics industry. Despite its successes, AAV manufacturing remains a challenge due to limited production yields. The triple plasmid transfection of HEK293 cells represents the most extensively utilized system for AAV production. The regulatory factors and mechanisms underlying viral production in HEK293 cells are largely unknown. In this study, we isolated high-titer AAV production clones from a parental HEK293 population using a single limiting dilution step, and subsequently elucidating their underlying molecular mechanisms through whole transcriptome analysis. LncRNA TCONS_00160397 was upregulated in clones and shown to promoted HEK293 cells proliferation and improved the titer of AAV production. Mechanistically, results from proteomics and metabolomics indicated that TCONS_00160397 regulated the ABC transporters pathway. These findings furnish a rich repository of knowledge and actionable targets for the rational optimization of HEK293-based producer lines, thereby paving the way for tangible improvements in AAV vector output and expediting the broad implementation of gene therapies.

Application of spatial-omics to the classification of kidney biopsy samples in transplantation.

Improvement of long-term outcomes through targeted treatment is a primary concern in kidney transplant medicine. Currently, the validation of a rejection diagnosis and subsequent treatment depends on the histological assessment of allograft biopsy samples, according to the Banff classification system. However, the lack of (early) disease-specific tissue markers hinders accurate diagnosis and thus timely intervention. This challenge mainly results from an incomplete understanding of the pathophysiological processes underlying late allograft failure. Integration of large-scale multimodal approaches for investigating allograft biopsy samples might offer new insights into this pathophysiology, which are necessary for the identification of novel therapeutic targets and the development of tailored immunotherapeutic interventions. Several omics technologies - including transcriptomic, proteomic, lipidomic and metabolomic tools (and multimodal data analysis strategies) - can be applied to allograft biopsy investigation. However, despite their successful application in research settings and their potential clinical value, several barriers limit the broad implementation of many of these tools into clinical practice. Among spatial-omics technologies, mass spectrometry imaging, which is under-represented in the transplant field, has the potential to enable multi-omics investigations that might expand the insights gained with current clinical analysis technologies.

Chamilo LMS for web-based e-learning development in a vocational high school

The development of a web-based e-learning at SMK Negeri 4 Padang was initiated by the absence of a structured e-learning system at the school. This study aims to design and implement e-learning using the Chamilo Learning Management System (LMS) platform, ensuring its validity and practicality. The study employs Research and Development (R&amp;D), adapting 3 stages of the ADDIE model, including analyzing, designing, and developing. The results of the validity test, assessed by three lecturers as media validators, show a score of 91.84%, categorized as very valid. The practicality test results show that 92.31% of teachers and 82.34% of students rated the system on the very practical category. Based on this data, the developed e-learning system at SMK Negeri 4 Padang is considered valid and practical. However, this study has not been through the broader implementation and evaluation. Therefore, it is suggested for further researchers conducting the similar studies to get it come to the whole stages of ADDIE model, confirming its effectiveness.

Analyzing the economic ramifications of the broad implementation of generic prasugrel

Abstract Introduction The 2023 European Acute Coronary Syndrome (ACS) guidelines state that prasugrel (PRG) should be considered in preference to ticagrelor (TCG) in patients (pts) who proceed to percutaneous coronary angioplasty (PCI). In Portugal, PRG is less available due to earlier evidence considering pretreatment and contraindications for each drug. PRG (10mg) is currently a generic drug, while TCG is not. We aimed to evaluate the proportion of pts that could be switched from TCG to PRG, and the economic impact of a widespread national adoption. Methods To determine eligibility for generic PRG 10mg, we examined a single center prospective database of consecutive ACS pts undergoing PCI in a full year. Eligibility for TCG and PRG was based on drug specific contraindications, previous stroke for PRG and chronic liver disease (CLD) for TCG, and indication for PRG dose reduction (≤60 kg and ≥75 years). To estimate hospital costs we used the price per pill indicated by the pharmacy (0.98€ TCG, 0.67€ PRG). To obtain post-discharge and NHS savings we used the INFARMED public information. We estimated 3500 PCIs per year on a national level, based on published data. Results A total of 780 pts were included, median age 68±10.4years, 523 (67.1%) were male, 51.9% (n=406) had non-ST elevation ACS. Mean admission time was 8.36 days. Considering PRG and TCG contraindications, 157 pts (20.3%) had a previous history of stroke and 20pts (2.6%) had CLD. 150 pts (19.2%) had PRG dose reduction criteria. Eligible for PRG 10mg and TCG 90mg were 434 pts (57.8% of total PCI pts). Cost per admission would be 33 697.35€ for TCG and 17 617.28€ for PRG. At a national level, hospital costs can be reduced by 16080.07€. Considering the 1-year outpatient setting and a widespread generic PRG 10mg adoption, NHS savings are estimated in 898 323.59€, and patient savings in 401248.25€ (198.38€ per patient). Conclusions ACS pts in real-world scenarios exhibit both eligibility for PRG and TCG. Considering the lower cost, the NHS can potentially save 914 403,66€ (figure 1) annually through the widespread adoption of generic PRG 10mg.

Self-Guided Blood Pressure Screening in the Community: Opportunities, and Challenges.

Community-based health check kiosks provide opportunities to improve the detection and long-term monitoring of hypertension. We describe the sociodemographic and cardiovascular characteristics of first-time and repeat users of these kiosks. This was an observational study. Deidentified data collected from 430 SiSU Health consumer-facing health check stations in pharmacies across Australia between January 2018 and November 2020 were analyzed. Using a logistic regression, we identified factors associated with repeat checks in the overall cohort and in those with possible hypertension presented as adjusted odds ratios (aOR) and 95% CIs. A total of 982 122 unique checks were conducted; 54% (n=530 139) of the health check users were female, and the average age of all users was 38.2 (SD 16.0) years. Of those that used the kiosks, 13% used them more than once. Overall, 22% met the definition of possible hypertension, 16% (n=136 345) had blood pressure (BP) ≥140/90 mm Hg, 4% (n=34 349) had BP >160/100 mm Hg, and 13% (121 282) reported taking BP medicines. In the adjusted analysis, first-time users who were aged 50 to 69 years (aOR 0.91 [95% CI 0.87-0.96]) or ≥70 years (aOR 0.68 [95% CI 0.62-0.74]) were less likely than young users (18-29 years) to return for a second health check. Those in very remote areas were 61% (aOR 0.39 [95% CI 0.19-0.72]), and smokers were 13% less likely to return (aOR 0.87 [95% CI 0.83-0.91]). People taking BP medications were more likely to return (aOR 1.16 [95% CI 1.09-1.22]). Community-based health checks may identify people with high BP and could provide an option for self-monitoring. Broader implementation is needed to increase the reach in rural areas and among the elderly population.