Evidence-based Principles Research Articles

Power, data and social accountability: defining a community-led monitoring model for strengthened health service delivery.

Despite international commitment to achieving the end of HIV as a public health threat, progress is off-track and existing gaps have been exacerbated by COVID-19's collision with existing pandemics. Born out of models of political accountability and historical healthcare advocacy led by people living with HIV, community-led monitoring (CLM) of health service delivery holds potential as a social accountability model to increase the accessibility and quality of health systems. However, the effectiveness of the CLM model in strengthening accountability and improving service delivery relies on its alignment with evidence-based principles for social accountability mechanisms. We propose a set of unifying principles for CLM to support the impact on the quality and availability of health services. Building on the social accountability literature, core CLM implementation principles are defined. CLM programmes include a community-led and independent data collection effort, in which the data tools and methodology are designed by service users and communities most vulnerable to, and most impacted by, service quality. Data are collected routinely, with an emphasis on prioritizing and protecting respondents, and are then be used to conduct routine and community-led advocacy, with the aim of increasing duty-bearer accountability to service users. CLM efforts should represent a broad and collective community response, led independently by impacted communities, incorporating both data collection and advocacy, and should be understood as a long-term approach to building meaningful engagement in systems-wide improvements rather than discrete interventions. The CLM model is an important social accountability mechanism for improving the responsiveness of critical health services and systems to communities. By establishing a collective understanding of CLM principles, this model paves the way for improved proliferation of CLM with fidelity of implementation approaches to core principles, rigorous examinations of CLM implementation approaches, impact assessments and evaluations of CLM's influence on service quality improvement.

Aligning Greece’s Regulatory Governance With International Transformative Principles and Objectives: The Case of the UN 2030 Agenda for Sustainable Development

Abstract The article highlights the importance that the international dimension of the regulatory context of draft legislation acquires for the drafting of effective regulation. It attempts to demonstrate the added value that the integrated incorporation of fundamental regulatory principles and objectives derived from influential global regulatory texts enjoying full acceptance, like the UN Resolution on the 2030 Agenda for Sustainable Development, brings to a country’s regulatory governance. From an empirical perspective, the article focuses on a thorough analysis of the degree to which Greece’s law-making process is interconnected and aligned with core regulatory principles of the 2030 Agenda, such as the principle of policy coherence, the evidence-based principle, and the principle of inclusion. It examines the key instruments, procedures, and ways in which these principles are appropriately mainstreamed into the Greek legislative process and the institutional and policy framework of the Government on which its legislative interventions are founded. As a case study, the alignment and coherence of the provisions of a specific law pertaining to tourism development with the overarching regulatory principles of the UN 2030 Agenda are examined. Τhe concluding part presents some proposals that could contribute to improving the way the SDGs are effectively mainstreamed into Greece’s legislative process.

Bridging the knowledge gap: educational needs of Iranian women for virtual breast cancer prevention: a qualitative study

BackgroundBreast cancer prevention is a globally significant and cost-effective public health priority, particularly in low- and middle-income countries. Empowering women through improved health literacy is a key strategy for reducing the disease burden. However, effective educational programs must be tailored to the specific cultural context and needs of the target community. This study explored the educational needs of Iranian women for a virtual breast cancer prevention program.MethodsA descriptive qualitative design was used from January to July 2022. Purposive sampling with maximum variation was utilized to recruit a sample of 28 participants. Data collection was conducted through semi-structured interviews. Following the method outlined by Graneheim and Lundman, qualitative content analysis was employed to analyze the interview data. MAXQDA 2020 software was used for data analysis. Components of trustworthiness, including credibility, dependability, confirmability, and transferability, were considered.ResultsOur findings identified three primary categories: “developing women’s scientific, practical, and attitudinal capabilities”; “features of program content”; and “principles of electronic content design”. These results offer valuable insights into the educational needs of Iranian women for virtual breast cancer prevention programs.ConclusionsTo design an effective virtual program, it is crucial to address all three domains: cognitive, emotional, and psychomotor. Program content should be organized and presented using methods that sensitize women to the importance of breast cancer prevention and motivate them to participate. Furthermore, the program’s design should be grounded in evidence-based practices and principles of electronic content design, ensuring cultural sensitivity to the needs of Iranian women.

Healing Havens: How Evidence-Based Design is Transforming Medical Spaces Into Therapeutic Environments.

To explore how evidence-based design is transforming healthcare environments into transforming spaces that improve patient outcomes and staff experiences. Traditional hospital designs often prioritize functionality over patient and staff well-being. This editorial examines the shift toward evidence-based design in healthcare facilities. We review recent studies and case examples demonstrating the impact of thoughtful healthcare design on infection rates, patient recovery, and staff performance. Evidence shows that elements such as private rooms, access to nature, and improved lighting can significantly reduce infections, accelerate healing, and enhance staff satisfaction. Implementing evidence-based design principles in healthcare environments can lead to measurable improvements in patient outcomes, staff performance, and overall healthcare quality.

Individual placement and support (IPS) – a time-out from modernity: an investigation on the relationship between IPS specialists and clients

ABSTRACT This study examines how evidence-based individual placement and support (IPS) interventions can be perceived to go beyond their constituent principles and fidelity scale to foster a relationship between IPS specialists and clients guided by three principles that promote deceleration and resonance, concepts put forward by Hartmut Rosa. This article is based on a case-study involving two municipalities in Denmark where the IPS method was implemented, resulting in high fidelity and good job outcomes. This study shows that when IPS specialists adhere to the IPS model, their relationship with their clients was seemingly guided by three values, namely, patience in securing sustainable employment, persistence in experimenting with employment and accepting and dealing with barriers to employment. These values originate from the evidence-based IPS approach and principles, but they can be interpreted to supplement the IPS model and form a professional practice. This practice promotes deceleration of social life as well as the immersion of clients in a resonant relationship with job opportunities, with their own mental health and with IPS specialists. The IPS intervention is in sharp contrast to the regular employment service wherein clients are pressured into taking jobs they do not want before they are ready to work. In this sense, the relationship IPS clients establish with IPS specialists is a time-out from modernity.

Provinols™, a Polyphenolic Extract of Red Wine, Inhibits In-Stent Neointimal Growth in Cholesterol-Fed Rabbit.

Background/Objectives: Epidemiological studies indicate a potential correlation between the consumption of polyphenols and a reduced risk of developing cardiovascular disorders. The present study investigates the potential of a red wine polyphenol oral extract, Provinols™, to reduce neointimal hyperplasia following angioplasty in a hypercholesterolemic rabbit model. Methods: New Zealand white rabbits were fed 1% cholesterol-enriched chow for a period of eight weeks prior to the induction of iliac balloon injury and subsequent stent placement. Following the implantation of the stent, Provinols™ (20 mg/kg/day) or an identical placebo was administered orally for a period of four weeks in a randomized manner. Twenty-eight days following the stenting procedure, the arteries were harvested after euthanasia and subjected to histology assignment analysis. Results: The administration of Provinols™ did not result in a statistically significant change in either blood pressure or plasma cholesterol levels. However, Provinols™ treatment led to a notable reduction in the growth of the intima within the stented area, as well as a reduction in the thickness and surface area of the intima. It is of note that treatment with Provinols™ was associated with a reduction in the accumulation of fat within the arteries and a diminished inflammatory response to injury. Conclusions: The findings demonstrate that oral administration of Provinols™ has the potential to reduce in-stent neointimal growth and lipid deposition, likely due to its anti-inflammatory properties in iliac arteries from hypercholesterolemic rabbits. Additionally, these findings provide an evidence-based rationale for the potential therapeutic benefits of plant-derived polyphenols in the prevention of restenosis associated with stent placement.

Empowering Neurodiverse Voices in Research Ethics through a Playful Card-Based Approach

Whenever carrying out research, all participants must know their rights, especially when those participants are perceived as being part of a vulnerable group; however, discussing ethics in investigation can be difficult. To solve this challenge, a playful approach was taken, as playfulness can make dull tasks – especially those that can cause discomfort and difficulties – more entertaining and help people approach them with an open mind. This study reports on four empirical approaches that used a playful process to raise awareness about ethical concerns when doing research with neurodiverse people. For this activity, 39 cards describing and illustrating several relevant and evidence-based ethical principles were created. Then, three case studies were developed, each based on a different focus group composed of ten neurodivergent self-advocates and one with professors and students from Brazil. Each neurodivergent group was also accompanied by three support workers from the partner associations (two of the groups were accompanied by the same individuals). In total, 56 participants engaged in a playful activity that consisted of a game of ‘broken telephone’ where the title of a card (representing an ethical principle) is read to one of the players who then has to whisper it to the next person in line, repeating this process until reaching the last person. The last person then says what they heard out loud, with the original message being revealed for contrast. The title of the cards was discussed by the groups to understand if it was clear and understandable or difficult and confusing. Although not all the cards were validated through the activity, 14 were flagged by neurodivergent people as "needing changes". The feedback was recorded and is presented here. This study set out to validate a set of cards in easy-to-read language that could introduce ethical concepts to participants in research projects through a playful activity. Future study will see the cards iterated upon through the feedback gathered along with the creation of a small guide on how they may be used in playful activities.

Crispr-mediated genome editing reveals a preponderance of non-oncogene addictions as targetable vulnerabilities in pleural mesothelioma

Pleural mesothelioma (PM) is an aggressive cancer with limited treatment options. In particular, the frequent loss of tumor suppressors, a key oncogenic driver of the disease that is therapeutically intractable, has hampered the development of targeted cancer therapies. Here, we interrogate the PM genome using CRISPR-mediated gene editing to systematically uncover PM cell susceptibilities and provide an evidence-based rationale for targeted cancer drug discovery. This analysis has allowed us to identify with high confidence numerous known and novel gene dependencies that are surprisingly highly enriched for non-oncogenic pathways involved in response to various stress stimuli, in particular DNA damage and transcriptional dysregulation. By integrating genomic analysis with a series of in vitro and in vivo functional studies, we validate and prioritize several non-oncogene addictions conferred by CDK7, CHK1, HDAC3, RAD51, TPX2, and UBA1 as targetable vulnerabilities, revealing previously unappreciated aspects of PM biology. Our findings support the growing consensus that stress-responsive non-oncogenic signaling plays a key role in the initiation and progression of PM and provide a functional blueprint for the development of unprecedented targeted therapies to combat this formidable disease.

Effect of Language Learning Apps on Vocabulary Acquisition in South Africa

Purpose: The aim of the study was to analyze the effect of language learning apps on vocabulary acquisition in South Africa. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: The effect of language learning apps on vocabulary acquisition in South Africa indicate that these digital tools significantly enhance learners' vocabulary skills. Research shows that students who regularly used language learning apps demonstrated a notable improvement in their vocabulary acquisition compared to those who relied on traditional methods. The interactive features of these apps, such as gamified learning and spaced repetition, contributed to increased engagement and retention of new words. Additionally, learners reported higher motivation levels and a greater sense of autonomy in their language studies. Unique Contribution to Theory, Practice and Policy: Constructivist learning theory, cognitive load theory & second language acquisition (SLA) theory may be used to anchor future studies on the effect of language learning apps on vocabulary acquisition in South Africa. Educational institutions should collaborate with app developers to ensure that language learning apps incorporate these theories. Policymakers should encourage the adoption of evidence-based design principles in the development of educational technology by providing funding and resources for research in this area.

Using Geovisualizations to Educate the Public About Environmental Health Hazards: What Works and Why.

Informing the public about environmental risks to health is crucial for raising awareness around hazards, and promoting actions that minimize exposures. Geographic visualizations-geovisualizations-have become an increasingly common way to disseminate web-based information about environmental hazards, displaying spatial variations in exposures and health outcomes using a map. Unfortunately, ineffective geovisualizations can result in inaccurate inferences about a hazard, leading to misguided actions or policies. In this narrative review, we discuss key considerations for the use of geovisualizations to promote environmental health literacy. Many conventional geovisualizations used for hazard education and risk communication fail to consider how people process visual information. Design choices that prompt viewers to think and feel, leveraging processes such as individual attention, memory, and emotion, could promote improved comprehension and decision making around environmental health risks using geovisualizations. Based on the studies reviewed, we recommend six strategies for designing effective, evidence-based geovisualizations, synthesizing evidence from the cognitive sciences, cartography, and environmental health. These strategies include: Displaying only key data, tailoring and testing geovisualizations with the desired audience, using salient cues, leveraging emotion, aiding pattern recognition, and limiting visual distractions. Geovisualizations offer a promising avenue for advancing public awareness and fostering proactive measures in addressing complex environmental health challenges. This review highlights how incorporating evidence-based design principles into geovisualizations could promote environmental health literacy. More experimental research evaluating geovisualizations, using interdisciplinary approaches, is needed.

A Practical Approach for Developing Shared Decision-Making Knowledge, Skills, and Capability for Busy Health Care Practitioners.

There has been substantial development of shared decision-making (SDM) methods and approaches in the past few decades, but despite this, building capability and scaling application of SDM in clinical practice remains a challenge. Here the authors describe the development and initial experience with a new virtual Practical Approach continuing education program for busy practicing clinicians who care for people with complex, chronic, and costly conditions who are frequently faced with preference-sensitive decisions. This program was designed to provide plain language training in SDM for real-world clinical practice using an easy 4-step approach that does not require prior training or formal education in SDM theory or methods. The authors describe the development of the Practical Approach program using established evidence-based principles. The program was piloted in 4 different settings across 2 chronic conditions. Qualitative interviews of program participants were conducted to observe SDM attitudes and observed performance in repeated case-based simulation role-play exercises to assess knowledge and skills performance. The authors observed improved and more realistic SDM attitudes in qualitative interviews with program participants after exposure to the program compared to baseline, and they similarly observed improved knowledge and skills demonstrated in sequential simulations conducted as participants were exposed to the program. Post-program focus groups revealed that participants perceived the program to be feasible, acceptable, and useful. Initial experience with the Practical Approach program suggests that it may beneficially affect basic SDM knowledge, skills, and attitudes in busy practicing clinicians who are novices in SDM. It also has demonstrated initial feasibility, utility, and acceptability.

Mavacamten for Obstructive Hypertrophic Cardiomyopathy: Rationale for Clinically Guided Dose Titration to Optimize Individual Response.

Mavacamten is the first and only cardiac myosin inhibitor approved in 5 continents for the treatment of adults with symptomatic New York Heart Association class II and III obstructive hypertrophic cardiomyopathy. An evidence-based rationale was used to develop individualized mavacamten dosing, guided by commonly used clinical parameters. Echocardiography is recommended as part of routine clinical assessment of patients with hypertrophic cardiomyopathy, and left ventricular (LV) outflow tract gradient and LV ejection fraction are parameters that can be readily assessed and monitored by echocardiography. Therefore, an echocardiography-based, clinically guided dose-titration strategy was developed to optimize patient benefit from mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy while minimizing the risk of LV ejection fraction reduction. Results from clinical trials paired with extensive modeling and simulation analyses support a dose-titration and monitoring strategy based on serial echocardiographic measures of Valsalva LV outflow tract gradient and LV ejection fraction. This dosing approach allows for the identification of the lowest individualized mavacamten dose and exposure required to provide improvements in LV outflow tract obstruction, functional capacity, and symptoms. Mavacamten is primarily metabolized by CYP2C19 (cytochrome P450 2C19), and CYP2C19 metabolizer phenotype has an effect on mavacamten exposure. Therefore, this approach has also been demonstrated to provide a favorable safety profile irrespective of patients' CYP2C19 metabolizer status. The dose-titration strategy includes additional considerations for the potential onset of systolic dysfunction in the context of intercurrent illness, and for the potential of drug-drug interactions with inhibitors and substrates of cytochrome P450 enzymes. This posology is reflected in the mavacamten US prescribing information.

Metabolic Syndrome Drug Therapy: The Potential Interplay of Pharmacogenetics and Pharmacokinetic Interactions in Clinical Practice: A Narrative Review

Metabolic syndrome (MetS) presents a significant global health challenge, characterized by a cluster of metabolic alterations including obesity, hypertension, insulin resistance/dysglycemia, and atherogenic dyslipidemia. Advances in understanding and pharmacotherapy have added complexity to MetS management, particularly concerning drug interactions and pharmacogenetic variations. Limited literature exists on drug–drug–gene interactions (DDGIs) and drug–drug–transporter gene interactions (DDTGIs), which can significantly impact pharmacokinetics and pharmacodynamics, affecting treatment outcomes. This narrative review aims to address the following three key objectives: firstly, shedding a light on the PK metabolism, transport, and the pharmacogenetics (PGx) of medicines most commonly used in the MetS setting (relevant lipid-lowering drugs, antihypertensives and antihyperglycemics agents); secondly, exemplifying potential clinically relevant pharmacokinetic drug interactions, including drug–drug interactions, DDGIs, and DDTGIs; and, thirdly, describing and discussing their potential roles in clinical practice. This narrative review includes relevant information found with the use of interaction checkers, pharmacogenetic databases, clinical pharmacogenetic practice guidelines, and literature sources, guided by evidence-based medicine principles.

Understanding Self-medication Trends in First-year Medical Students: A Cross-sectional Study

Abstract Objectives: The objective is to explore self-medication perceptions and practices among 1st year undergraduate medical students. Materials and Methods: This cross-sectional study was conducted among 1st-year medical students in a private college in North Karnataka. A prevalidated questionnaire assessing self-medication perceptions and practices was administered to 176 participants through Google Forms. Descriptive statistics were used to analyze the data. Results: Nearly half of our study participants (52.3%) reported engaging in self-medication. The common sources of information included previous experience/prescriptions (43.8%) and advice from parents/friends (41.5%). Reasons for self-medication included perceiving the illness as nonsevere (82.4%) and time-saving (10.8%). The most common conditions prompting self-medication were the common cold (29%), fever (25.6%), and pain (18.8%). Analgesics (28.4%) and antipyretics (27.3%) were the most commonly used drug classes. Conclusion: The relatively lower prevalence of self-medication among 1st-year medical students in this study may be attributed to factors such as the targeted focus on this specific demographic, limited availability of self-medication resources in hostels, and foundational training emphasizing evidence-based medicine principles. However, concerns arise regarding the use of alternative medicine systems like Ayurveda, potentially leading to herb–drug interactions. To address these issues, structured educational initiatives, regulatory enforcement, and improved access to health-care consultations are crucial for promoting rational medication use and mitigating self-medication risks among medical students.

Forecasting Informal care needs of the urban-rural older adults in China based on microsimulation model

BackgroundForecasting the intensity, source, and cost of informal care for older adults in China is essential to establish and enhance policy support systems for informal care within the context of East Asian traditional culture that emphasizes filial piety. This study aims to analyze the current situation and influencing factors for the informal care needs and predict the trends of informal care needs for older adults in China from 2020 to 2040.MethodsUsing the CHARLS database from 2015 to 2018, this study first combined a two-part model and a multinomial logit to analyze the influencing factors for the informal care needs of urban-rural older adults in China. Secondly, a multi-state Markov model was constructed to forecast the number of urban-rural older populations in each health state from 2020 to 2040. Finally, based on a microsimulation model, this study predicted the trends of informal care intensity, source, and cost for older adults in urban and rural areas from 2020 to 2040.ResultsIn 2040, the size of the disabled older population in China will expand further. In rural areas, the total number of disabled people in 2040 (39.77 million) is 1.50 times higher than that in 2020; In urban areas, the total number of disabled people in 2040 (56.01 million) is 2.51 times higher than that in 2020. Compared with 2020, older adults population with mild, moderate and severe disability in 2040 would increase by 87.60%, 101.70%, and 115.08%, respectively. In 2040, the number of older adults receiving low-, medium-, and high-intensity care in China will be 38.60 million, 22.89 million, and 41.69 million, respectively, and older people will still rely on informal care provided by spouses and children (from spouses only: 39.26 million, from children only: 36.74 million, from spouses and children only: 16.79 million, other: 10.39 million). The total cost of informal care in 2040 will be 1,086.65 billion yuan, 2.22 times that of 2020 (490.31 billion yuan), which grows faster than the economic growth rate.ConclusionFrom 2020 to 2040, the informal care needs of older people in rural areas will increase first and then decrease due to the demographic structure and rapid urbanization. In contrast, the informal care needs of older people in urban areas will continuously increase from 2020 to 2040, with the growth rate gradually slowing down. This study provides an evidence-based rationale for scientifically measuring the economic value of informal care and reasonably allocating care resources.

Evidence-based research of the indicator system for evaluating the application effect of TCM standards

The traditional Chinese medicine evaluation indicator system can effectively identify and recognize deficiencies in the implementation of standards and provide a rationale for improving the technical content, enhancing the effectiveness of implementation and promoting the dissemination of traditional Chinese medicine culture and technology globally. Evidence-based principles can be an important method to guide the development of traditional Chinese medicine indicators and to promote the application of standards. This paper introduces the development status of NICE indicators and provides reference ideas for constructing evaluation indicator for traditional Chinese medicine standards application based on evidence-based principles. The specific steps for constructing an evaluation indicator system for traditional Chinese medicine standard application include identifying indicator domains, evidence synthesis, developing indicators, constructing an indicator system, cost- effectiveness and resource impact analyses, and finalizing indicators for training and promotion. In order to promote the further development of traditional Chinese medicine, it is necessary to strengthen the integrated construction of “guidelines-standards-indicators”, accelerate the establishment of a coordination mechanism between domestic and international organizations, and pay attention to the characteristics of traditional Chinese medicine and focusing on implications for practice and policy.

Incorporating Parents' Lived Experiences Into the Pediatric Audiology Course: A Qualitative Analysis of Student Reflections.

This study explores the underutilized pedagogical approach of incorporating lived experiences of parents with children possessing diverse hearing profiles and their family characteristics into the audiology curriculum for students. The aim was to investigate the impact of integrating such experiences into the classroom as an andragogical learning experience through the qualitative analysis of written student reflections. Twelve (N = 12) third-year female audiology students enrolled in a pediatric auditory (re)habilitation course attended a parent panel presentation during their regularly scheduled face-to-face class. Five parents of children with diverse hearing differences and diverse technology, communication, and educational choices participated on the panel as guest speakers via the Zoom platform. Students completed written reflections based on Rolfe's reflective framework. Written reflections were downloaded from Canvas and de-identified prior to uploading to NVivo software for coding, utilizing an inductive grounded theory coding strategy coupled with content analysis. This study underscores the effectiveness of written reflections as an effective andragogical learning model. Through reflective practice, students gained a deeper understanding of their experiences, values, and learning journeys, enhancing their competency in pediatric audiology and auditory (re)habilitation. Students articulated previous knowledge and learning experiences, utilized newfound insights from exposure to the parent panel of shared lived experiences, and connected this knowledge with future clinical applications. Key findings underscore the effectiveness of reflective practice as an andragogical learning model, facilitating the integration of prior experiences with new knowledge. Moreover, it aids the transition of the professional journey from the familiar to the unfamiliar, demonstrating the impact of combining real-world lived experiences to reinforce and highlight classroom topics. Additionally, reflective practice enhances professional efficacy by valuing patient/parent perspectives regarding clinical care and aligning with evidence-based principles.

Dendrobium nobile alkaloids modulate calcium dysregulation and neuroinflammation in Alzheimer's disease: A bioinformatic analysis

IntroductionDendrobium nobile Lindl alkaloids, or DNLA for short, are the most active ingredients found in D.nobile, a top grade plant in Shen Nong Ben Cao Jing, with an extensive history of medicinal use in Chinese traditional medicine (TCM) as a multifunctional therapeutic agent. Recent evidence has emerged linking the neuroprotective and anti-aging effects of DNLA to their involvement in promoting autophagy of toxic amyloid-β (Aβ) plaques and modulation of key enzymes involved in the hyperphosphorylation of Tau proteins. Although amyloid buildup and the aggregation of Tau proteins are central to the onset of Alzheimer's disease (AD), evidence on how DNLA relate to other overlooked dysregulated AD-associated pathways is still lacking. MethodsWe intend on deciphering the underlying mechanisms driving the anti-AD effect of DNLA, using a combination of network analysis based on differentially expressed genes found in AD patients, target fishing, centrality analysis, enrichment analysis and hub genes identification. ResultsIn total, 2069 genes were found differentially expressed in SRP181886 and a PPI network constructed with common targets between DNLA and AD. Five hub genes were identified having a discriminatory power greater than 0.7; HTR2A, GRIN2B, GABRA1, HTR2C, GRIN2A, with the former being the top bottleneck node in the network. Enrichment analysis found that DNLA exert an anti-AD effect through the regulation of the calcium signaling pathway and the serotonergic system, by modulating key receptors implicated in excitatory/inhibitory neurotransmission. Additionally, DNLA were found to modulate two subunits of NMDA receptor involved in the release of pro-inflammatory cytokines, underlying the possible involvement of DNLA in neuroinflammation. DiscussionThis further emphasizes the therapeutic value of D.nobile and the multi-target, multi-pathway potential of DNLA to counteract the deleterious effects of calcium dysregulation and excitatory toxicity in AD, while providing evidence-based rationale behind the traditional use of D. nobile in TCM.

An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab.

Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase. We propose two alternative dosing regimens for subcutaneous atezolizumab to reduce drug expenses while ensuring effective exposure; one may be directly implemented in the clinic. We developed two alternative dose interval prolongation strategies based on pharmacokinetic modeling and simulation. The first dosing regimen was based on patients' weight while maintaining equivalent systemic drug exposure by adhering to Food and Drug Administration (FDA) guidelines for in silico dose adjustments. The second dosing regimen aimed to have a minimum atezolizumab concentration above the 6 µg/mL threshold, associated with 95% intratumoral PD-L1 receptor saturation for at least 95% of all patients. We found that, for the weight-based dosing regimen, the approved 3-week dosing interval could be extended to 5 weeks for patients < 50 kg and 4 weeks for patients weighing 50-65 kg. Besides improving patient convenience, these alternative dosing intervals led to a predicted 7% and 12% cost reduction for either the USA or European population. For the second dosing regimen, we predicted that a 6-week dosing interval would result in 95% of the patients above the 6 µg/mL threshold while reducing costs by 50%. We have developed and evaluated two alternative dosing regimens that resulted in a cost reduction. Our weight-based dosing regimen can be directly implemented and complies with FDA guidelines for alternative dosing regimens of PD-L1 inhibitors. For the more progressive alternative dosing regimen aimed at the intratumoral PD-L1 receptor threshold, further evidence on efficacy and safety is needed before implementation.

Immediate Versus Delayed Low-Stakes Questioning: Encouraging the Testing Effect Through Embedded Video Questions to Support Students’ Knowledge Outcomes, Self-Regulation, and Critical Thinking

AbstractIn light of the educational challenges brought about by the COVID-19 pandemic, there is a growing need to bolster online science teaching and learning by incorporating evidence-based pedagogical principles of Learning Experience Design (LXD). As a response to this, we conducted a quasi-experimental, design-based research study involving nN = 183 undergraduate students enrolled across two online classes in an upper-division course on Ecology and Evolutionary Biology at a large R1 public university. The study extended over a period of 10 weeks, during which half of the students encountered low-stakes questions immediately embedded within the video player, while the remaining half received the same low-stakes questions after viewing all the instructional videos within the unit. Consequently, this study experimentally manipulated the timing of the questions across the two class conditions. These questions functioned as opportunities for low-stakes content practice and retention, designed to encourage learners to experience testing effect and augment the formation of their conceptual understanding. Across both conditions, we assessed potential differences in total weekly quiz grades, page views, and course participation among students who encountered embedded video questions. We also assessed students’ self-report engagement, self-regulation, and critical thinking. On average, the outcomes indicated that learners exposed to immediate low-stakes questioning exhibited notably superior summative quiz scores, increased page views, and enhanced participation in the course. Additionally, those who experienced immediate questioning demonstrated heightened levels of online engagement, self-regulation, and critical thinking. Moreover, our analysis delved into the intricate interplay between treatment conditions, learners’ self-regulation, critical thinking, and quiz grades through a multiple regression model. Notably, the interaction between those in the immediate questioning condition and self-regulation emerged as a significant factor, suggesting that the influence of immediate questioning on quiz grades varies based on learners’ self-regulation abilities. Collectively, these findings highlight the substantial positive effects of immediate questioning of online video lectures on both academic performance and cognitive skills within an online learning context. This discussion delves into the potential implications for institutions to continually refine their approach in order to effectively promote successful online science teaching and learning, drawing from the foundations of pedagogical learning experience design paradigms and the testing effect model.