Individual Trials Research Articles

Absolute treatment effects of novel antidiabetic drugs on a composite renal outcome: meta-analysis of digitalized individual patient data

BackgroundAbsolute treatment benefits—expressed as numbers needed to treat—of the glucose lowering and cardiovascular drugs, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT2) inhibitors on renal outcomes remain uncertain. With the present meta-analysis of digitalized individual patient data, we aimed to display and compare numbers needed to treat of both drugs on a composite renal outcome.MethodsFrom Kaplan–Meier plots of major cardiovascular outcome trials of GLP-1 receptor agonists and SGLT2 inhibitors vs. placebo, we digitalized individual patient time-to-event information on composite renal outcomes with WebPlotDigitizer 4.2; numbers needed to treat from individual cardiovascular outcome trials were estimated using parametric Weibull regression models and compared to original data. Random-effects meta-analysis generated meta-numbers needed to treat with 95% confidence intervals (CI).ResultsTwelve cardiovascular outcome trials (three for GLP-1 receptor agonists, nine for SGLT2 inhibitors) comprising 90,865 participants were included. Eight trials were conducted in primary type 2 diabetes populations, two in a primary heart failure and two in a primary chronic kidney disease population. Mean estimated glomerular filtration rate at baseline ranged between 37.3 and 85.3 ml/min/1.73 m2. Meta-analyses estimated meta-numbers needed to treat of 85 (95% CI 60; 145) for GLP-1 receptor agonists and 104 (95% CI 81; 147) for SGLT2 inhibitors for the composite renal outcome at the overall median follow-up time of 36 months.ConclusionThe present meta-analysis of digitalized individual patient data revealed moderate and similar absolute treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors compared to placebo for a composite renal outcome.Graphical

A short history of the phosphorus index and Andrew Sharpley's contributions from inception through development and implementation.

In the 1980s, growing recognition of agricultural phosphorus (P) sources to surface water eutrophication led to scrutiny of animal feeding operations. In 1990, the USDA-Natural Resources Conservation Service (NRCS) invited prominent scientists to find a solution. It was at an initial meeting that Dr. Andrew Sharpley suggested that P assessment could be modeled after the Universal Soil Loss Equation, where a matrix of factors influencing P loss would be associated with farm nutrient management recommendations. After codifying the P assessment into the USDA-NRCS 590 Nutrient Management Standard some 10years later, 48 states chose to develop their own P Index. Sharpley, working with many others, helped develop several state P Indices. In 2000, Sharpley secured funding from the USDA-Agricultural Research Service to support the National P Research Project, which conducted in-field P runoff assessments using standardized rainfall simulated studies across 20 states; this allowed individual trials to be aggregated for agroecological regions that were then incorporated into specific state P Indices. Eventually, comparison of P Indices across state boundaries led to a white paper at the behest of USDA-NRCS that resulted in three regional projects evaluating modeling approaches to support or replace P Indices. Sharpley's national umbrella project pointed to shortcomings in water quality models, such as APEX or TBET, as a replacement for state P Indices, which remain a key part of the USDA-590 standard. As a selfless leader, capable of attracting and assembling diverse, productive interdisciplinary teams, Sharpley was essential to the inception, development, and implementation of the P Index.

Both stimulus-specific and configurational features of multiple visual stimuli shape the spatial ventriloquism effect.

Studies on multisensory perception often focus on simplistic conditions in which one single stimulus is presented per modality. Yet, in everyday life, we usually encounter multiple signals per modality. To understand how multiple signals within and across the senses are combined, we extended the classical audio-visual spatial ventriloquism paradigm to combine two visual stimuli with one sound. The individual visual stimuli presented in the same trial differed in their relative timing and spatial offsets to the sound, allowing us to contrast their individual and combined influence on sound localization judgements. We find that the ventriloquism bias is not dominated by a single visual stimulus but rather is shaped by the collective multisensory evidence. In particular, the contribution of an individual visual stimulus to the ventriloquism bias depends not only on its own relative spatio-temporal alignment to the sound but also the spatio-temporal alignment of the other visual stimulus. We propose that this pattern of multi-stimulus multisensory integration reflects the evolution of evidence for sensory causal relations during individual trials, calling for the need to extend established models of multisensory causal inference to more naturalistic conditions. Our data also suggest that this pattern of multisensory interactions extends to the ventriloquism aftereffect, a bias in sound localization observed in unisensory judgements following a multisensory stimulus.

Expression of Concern: Trait variation across biological scales shapes community structure and ecosystem function.

Start, D. and Gilbert, B., Trait variation across biological scales shapes community structure and ecosystem function. Ecology, 2019, (https://doi.org/10.1002/ecy.2769). This Expression of Concern is for the above article, published online on 3 September 2019 in Wiley Online Library (wileyonlinelibrary.com), and has been published by agreement between the journal Editor in Chief, Ecological Society of America, Benjamin Gilbert and John Wiley & Sons Ltd. The decision to express concern involves Figure S10, for which the Editor in Chief and co-author have been unable to reconcile the description in the Methods (which suggests a integer response variable for the number of Daphnia eaten in an individual trial) with the decimal values that appear in this supplemental figure. We therefore cannot be certain in the finding reported in the first paragraph of the Results of a concave-down relationship between Daphnia consumption and Epitheca activity. Our attempts to seek clarification from the author (Dr. Start) went unanswered.

A generative model of electrophysiological brain responses to stimulation.

Each brain response to a stimulus is, to a large extent, unique. However this variability, our perceptual experience feels stable. Standard decoding models, which utilise information across several areas to tap into stimuli representation and processing, are fundamentally based on averages. Therefore, they can focus precisely on the features that are most stable across stimulus presentations. But which are these features exactly is difficult to address in the absence of a generative model of the signal. Here, I introduce genephys, a generative model of brain responses to stimulation publicly available as a Python package that, when confronted with a decoding algorithm, can reproduce the structured patterns of decoding accuracy that we observe in real data. Using this approach, I characterise how these patterns may be brought about by the different aspects of the signal, which in turn may translate into distinct putative neural mechanisms. In particular, the model shows that the features in the data that support successful decoding-and, therefore, likely reflect stable mechanisms of stimulus representation-have an oscillatory component that spans multiple channels, frequencies, and latencies of response; and an additive, slower response with a specific (cross-frequency) relation to the phase of the oscillatory component. At the individual trial level, still, responses are found to be highly variable, which can be due to various factors including phase noise and probabilistic activations.

A generative model of electrophysiological brain responses to stimulation

Each brain response to a stimulus is, to a large extent, unique. However this variability, our perceptual experience feels stable. Standard decoding models, which utilise information across several areas to tap into stimuli representation and processing, are fundamentally based on averages. Therefore, they can focus precisely on the features that are most stable across stimulus presentations. But which are these features exactly is difficult to address in the absence of a generative model of the signal. Here, I introduce genephys, a generative model of brain responses to stimulation publicly available as a Python package that, when confronted with a decoding algorithm, can reproduce the structured patterns of decoding accuracy that we observe in real data. Using this approach, I characterise how these patterns may be brought about by the different aspects of the signal, which in turn may translate into distinct putative neural mechanisms. In particular, the model shows that the features in the data that support successful decoding—and, therefore, likely reflect stable mechanisms of stimulus representation—have an oscillatory component that spans multiple channels, frequencies, and latencies of response; and an additive, slower response with a specific (cross-frequency) relation to the phase of the oscillatory component. At the individual trial level, still, responses are found to be highly variable, which can be due to various factors including phase noise and probabilistic activations.

Probiotics for adults with major depressive disorder compared with antidepressants: a systematic review and network meta-analysis.

Despite recent advances in antidepressants in treating major depression (MDD), their usage is marred by adverse effects and social stigmas. Probiotics may be an efficacious adjunct or standalone treatment, potentially circumventing the aforementioned issues with antidepressants. However, there is a lack of head-to-head clinical trials between these 2 interventions. A systematic review and network meta-analysis was conducted to compare the efficacy and acceptability of these 2 interventions in treating MDD. Six databases and registry platforms for the clinical trial were systematically searched to identify the eligible double-blinded, randomized controlled trials published between 2015 and 2022. Two authors selected independently the placebo-controlled trials of antidepressants and microbiota-targeted interventions (prebiotics, probiotics, and synbiotics) used for the treatment of MDD in adults (≥18 years old). Standardized mean differences (SMDs) of depressive symptom scores from individual trials were pooled for network meta-analysis (PROSPERO no. CRD42020222305). Forty-two eligible trials covering 22 interventions were identified, of which 16 were found to be effective in MDD treatment and the certainty of evidence was moderate to very low. When all trials were considered, compared with placebo, SMDs of interventions ranged from -0.16 (95% credible interval: -0.30, -0.04) for venlafaxine to -0.81 (-1.06, -0.52) for escitalopram. Probiotics were superior to brexpiprazole (SMD [95% credible interval]: -0.42 [-0.68, -0.17]), cariprazine (-0.44 [-0.69, -0.24]), citalopram (-0.37 [-0.66, -0.07]), duloxetine (-0.26, [-0.51, -0.04]), desvenlafaxine (-0.38 [-0.63, -0.14]), ketamine (-0.32 [-0.66, -0.01]), venlafaxine (-0.47 [-0.73, -0.23]), vilazodone (-0.37 [-0.61, -0.12]), vortioxetine (-0.39 [-0.63, -0.15]), and placebo (-0.62 [-0.86, -0.42]), and were noninferior to other antidepressants. In addition, probiotics ranked the second highest in the treatment hierarchy after escitalopram. Long-term treatment (≥8 weeks) using probiotics showed the same tolerability as antidepressants. Probiotics, compared with antidepressants and placebo, may be efficacious as an adjunct or standalone therapy for treating MDD. PROSPERO registration no. CRD42020222305.

Molecular Markers Help with Breeding for Agronomic Traits of Spring Wheat in Kazakhstan and Siberia.

The Kazakhstan-Siberia Network for Spring Wheat Improvement (KASIB) was established in 2000, forming a collaboration between breeding and research programs through biannual yield trials. A core set of 142 genotypes from 15 breeding programs was selected, genotyped for 81 DNA functional markers and phenotyped for 10 agronomic traits at three sites in Kazakhstan (Karabalyk, Shortandy and Shagalaly) and one site in Russia (Omsk) in 2020-2022. The study aim was to identify markers demonstrating significant effects on agronomic traits. The average grain yield of individual trials varied from 118 to 569 g/m2. Grain yield was positively associated with the number of days to heading, plant height, number of grains per spike and 1000-kernel weight. Eight DNA markers demonstrated significant effects. The spring-type allele of the Vrn-A1 gene accelerated heading by two days (5.6%) and was present in 80% of the germplasm. The winter allele of the Vrn-A1 gene significantly increased grain yield by 2.7%. The late allele of the earliness marker per se, TaMOT1-D1, delayed development by 1.9% and increased yield by 4.5%. Translocation of 1B.1R was present in 21.8% of the material, which resulted in a 6.2% yield advantage compared to 1B.1B germplasm and a reduction in stem rust severity from 27.6 to 6.6%. The favorable allele of TaGS-D1 increased both kernel weight and yield by 2-3%. Four markers identified in ICARDA germplasm, ISBW2-GY (Kukri_c3243_1065, 3B), ISBW3-BM (TA004946-0577, 1B), ISBW10-SM2 (BS00076246_51, 5A), ISBW11-GY (wsnp_Ex_c12812_20324622, 4A), showed an improved yield in this study of 3-4%. The study recommends simultaneous validation and use of selected markers in KASIB's network.

DESAIN MODUL MATEMATIKA BILINGUAL (INDONESIA-ARAB): PENGEMBANGAN MODUL KOMPETISI SAINS MADRASAH (KSM) MATEMATIKA TERINTEGRASI

This research aims to develop a bilingual mathematics module for KSM in the field of integrated mathematics. The research method uses the Research and Development (RnD) method of the Borg and Gall model which is simplified in 4 stages, namely introduction, development, testing and dissemination. The results of the development of a bilingual (Indonesian-Arabic) mathematics module at KSM are suitable for use. The validation results from media experts have an average value of 3.69 and are in the suitable category for use. Media expert validation has an average value of 3.70 and is in the category suitable for use. The validation results by practitioners have an average value of 3.62 and are in the suitable category for use. Trials by subject teachers had an average score of 3.71 and were in the very interesting category. The individual trials had an average score of 3.61 and were in the very interesting category. Small group trials in each madrasah had an average score of 3.83 and were in the very interesting category and large group trials had an average score of 3.74 and were in the very interesting category. The final stage is dissemination carried out by distributing bilingual mathematics module books.

Validation and Development of Dragonflies Book Species in Barambai to Increase Science Process Skills

The biodiversity and diverse habitat of dragonflies in Kalimantan have an enormous potential that can be utilized in various fields, one of which is the field of education. Utilizing local potential as teaching materials, one of which is the Guidebook, is considered capable of supporting learning. Several skills are trained in learning activities, including science process skills. This study aims to describe the Identification Handbook's validity, practicality, and effectiveness. The stages of development conducted are self-evaluation, expert test by three lecturers of Master of Biology Education at Hull Mangkurat University, individual trial of three students, small group test of five students, and significant group test of twenty undergraduate Biology Education students who have passed the Invertebrate Zoology course. The research results of the Dragonfly Identification Guidebook are the validity of the Dragonfly Identification Guidebook score of 3.57 with a very decent category and the effectiveness of the overall N-Gain average of 0.6 with a medium category that can be implemented in learning.

Patient engagement in clinical trial design for rare neuromuscular disorders: impact on the DELIVER and ACHIEVE clinical trials

BackgroundEngaging individuals living with disease in drug development and regulatory processes leads to more thoughtful and sensitive trial designs, drives more informative and meaningful outcomes from clinical studies, and builds trust between the public, government, and industry stakeholders. This engagement is especially important in the case of rare diseases, where affected individuals and their families face many difficulties getting information, treatment, and support. Dyne Therapeutics is developing therapeutics for people with genetically-driven muscle diseases. During the development of potential treatments for Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1), Dyne sought the opinions of individuals living with these diseases to inform its clinical trial design and to decrease the difficulties that participants and families might experience participating in them.MethodsDyne engaged individuals and families living with DMD and DM1 as expert partners in its clinical development programs. Dyne convened panels of affected individuals and care partners/parents of individuals living with DMD (n = 8) or DM1 (n = 18). Workshops focused on how affected individuals and their families evaluate and select clinical trials for participation, the importance, quality, and burden associated with individual trial design elements, participation considerations such as site location and the study visit design, patient privacy, the suitability and scope of travel and participant support programs, and the accessibility of content in the informed consent (or assent) forms. Dyne also engaged the DMD Community Advisory Board (CAB) to collect feedback and advice on designing optimal and meaningful clinical trials and measuring relevant outcomes.ResultsThe issues most important to individuals living with DM1 and DMD regarding clinical trials were the ability to participate/access to the trial, perceptions of benefit and risk of trials and potential treatments, the flexibility of participation, clear communication from the sponsor, availability of information from trusted sources, and patient enrollment. In response to the patient advisory workshops and CAB feedback, Dyne refined clinical trial inclusion/exclusion criteria and clinic visit design, developed a travel service program to address the burden of clinical trial travel and enable long-distance and cross-border participation, planned for home visits when feasible, and allowed for adequate rest before clinic visit initiation and between assessments. Additionally, Dyne developed and implemented a transparent and consistent communications plan (including age-appropriate content) for trial participants and community members, and assessed and adjusted procedures to provide maximum participant comfort and lower anxiety, particularly with younger participants.ConclusionsOngoing communication with the Duchenne CAB and with DMD and DM1 patient advisory committee members allows Dyne to stay current with disease community perspectives and feedback on the needs and preferences of those affected and has provided valuable insights into the participant experience thereby helping Dyne initiate clinical trials that better meet the needs of affected individuals and their families.

Navigating the outcome maze: a scoping review of outcomes and instruments in clinical trials in genetic neurodevelopmental disorders and intellectual disability.

Individuals with genetic neurodevelopmental disorders (GNDs) or intellectual disability (ID) are often affected by complex neuropsychiatric comorbidities. Targeted treatments are increasingly available, but due to the heterogeneity of these patient populations, choosing a key outcome and corresponding outcome measurement instrument remains challenging. The aim of this scoping review was to describe the research on outcomes and instruments used in clinical trials in GNDs and ID. Clinical trials in individuals with GNDs and ID for any intervention over the past 10 years were included in the review. MEDLINE, PsycINFO, and Cochrane CENTRAL were searched. Titles and abstracts were independently screened for eligibility with a subsample of 10% double-screening for interrater reliability. Data from full texts were independently reviewed. Discrepancies were discussed until consensus was reached. Information was recorded on patient populations, interventions, designs, outcomes, measurement instruments, and type of reporter when applicable. Qualitative and descriptive analyses were performed. We included 312 studies reporting 91 different outcomes, with cognitive function most frequently measured (28%). Various outcome measurement instruments (n = 457) were used, with 288 in only a single clinical trial. There were 18 genetic condition-specific instruments and 16 measures were designed ad-hoc for one particular trial. Types of report included proxy-report (39%), self-report (22%), clinician-report (16%), observer-report (6%), self-assisted report (1%), or unknown (16%). This scoping review of current practice reveals a myriad of outcomes and outcome measurement instruments for clinical trials in GNDs and ID. This complicates generalization, evidence synthesis, and evaluation. It underlines the need for consensus on suitability, validity, and relevancy of instruments, ultimately resulting in a core outcome set. A series of steps is proposed to move from the myriad of measures to a more unified approach.

E-Modules with A Contextual Approach to Natural Science Content Improve Student Learning Outcomes

The learning process for science content is still teacher-centred; students tend to accept what the teacher explains, but it needs to provide opportunities for students to develop independently. So, if learning is left like that, student learning outcomes will stay the same. This research aims to develop e-module media with a contextual approach to class V elementary school science content. This research is development research using the ADDIE model. The subjects of this research consisted of learning content experts, learning design experts, learning media experts, 3 individual trial students, 6 small group trial students and 37 field trial students. The data collection methods used were questionnaire, pre-test and post-test methods. Data analysis techniques use qualitative, quantitative analysis and inferential statistics. The research results show that the e-module developed is valid based on learning content experts, learning design experts, and learning media experts; the results obtained are in the very good category, and individual trials and small group tests are in the very good category. Testing the effectiveness of e-modules using a contextual approach, there was a significant difference in learning outcomes for science content before and after using e-module learning media with a contextual approach. The research conclusion is that the e-module is feasible and valid to use.

A Conceptual Design of a Generative Artificial Intelligence System for Education

Artificial Intelligence (AI) and, more specifically, Generative Artificial Intelligence (GenAI) are among the most trending disruptive technologies, offering unprecedented possibilities for innovation in education by customising learning paths, fostering creativity, and bridging knowledge gaps. Gen AI is a subfield of AI which generates content (text, image, audio or video) that is comparable to human-generated content. It uses complex Machine Learning (ML) models and Neural Networks (NN) trained on large datasets. The launch of ChatGPT in November 2022 has significantly raised the standards for generative artificial intelligence capabilities. Since then, researchers and practitioners have extensively investigated the potential applications of this technology. Consequently, GenAI has been applied in various sectors, including business and marketing, media and entertainment, arts and design, research and innovation, and education. While it is evident that GenAI has a high potential transformative power on education, its actual application in classical educational settings such as schools and universities remains limited to individual (student or teacher) trials without institutional guidance and support. The aim of this is expressed in two points: (1) to explore the advances in GenAI and provide guidelines on leveraging the technology in the context of learning and teaching. (2) to identify the main barriers to adopting GenAI in education and how to address them when building a Gen AI application for education. The paper’s main contribution is conceptualising a Gen AI system for learning and teaching. Such a system produces course content, exercises, and supplementary materials tailored to the curriculum and each student’s learning pace and style. This system will enhance comprehension and retention, making education more accessible and effective. Secondarily, the research addresses the ethical issues and other barriers to adopting GenAI in education.

The effect of normobaric hypoxia on acute exercise-induced changes in blood sphingoid base-1-phosphates metabolism in cyclists.

Extracellular sphingosine-1-phosphate (S1P) emerged as an important regulator of muscle function. We previously found that plasma S1P concentration is elevated in response to acute exercise and training. Interestingly, hypoxia, which is commonly utilized in training programs, induces a similar effect. Therefore, the aim of the current study was to determine the effect of normobaric hypoxia on exercise-induced changes in blood sphingolipid metabolism. Fifteen male competitive cyclists performed a graded cycling exercise until exhaustion (GE) and a simulated 30 km individual time trial (TT) in either normoxic or hypoxic (FiO2 = 16.5%) conditions. Blood samples were taken before the exercise, following its cessation, and after 30 min of recovery. We found that TT increased dihydrosphingosine-1-phosphate (dhS1P) concentration in plasma (both HDL- and albumin-bound) and blood cells, as well as the rate of dhS1P release from erythrocytes, regardless of oxygen availability. Plasma concentration of S1P was, however, reduced during the recovery phase, and this trend was augmented by hypoxia. On the other hand, GE in normoxia induced a selective increase in HDL-bound S1P. This effect disappeared when the exercise was performed in hypoxia, and it was associated with reduced S1P level in platelets and erythrocytes. We conclude that submaximal exercise elevates total plasma dhS1P concentration via increased availability of dihydrosphingosine resulting in enhanced dhS1P synthesis and release by blood cells. Maximal exercise, on the other hand, induces a selective increase in HDL-bound S1P, which is a consequence of mechanisms not related to blood cells. We also conclude that hypoxia reduces post-exercise plasma S1P concentration.

The Moderating Effects of Cognitive Processes on Pain-related Outcomes

Although evidence supports the importance of pain-related thoughts (ie, cognitive content, or what people think) as predictors of pain and pain-related function, evidence regarding the role of cognitive processes (ie, how people think about pain, eg, by accepting pain, not making judgments about pain, or being absorbed by the pain experience) in adjustment to chronic pain is in its early stages. Using baseline data from a clinical trial of individuals with chronic low back pain (N = 327), the study aimed to increase knowledge regarding the associations between cognitive processes, pain intensity, pain interference, and depression. The results indicate that a number of cognitive processes are significantly related to pain intensity when controlling for catastrophizing, although the pattern of associations found was opposite to those anticipated. One cognitive process (pain absorption) was found to be significantly associated with pain interference, and 9 of 10 cognitive processes were significantly associated with depression when controlling for catastrophizing. In each case, the processes thought to be adaptive were negatively associated with pain interference and depression, and processes thought to be maladaptive evidenced the opposite pattern. The findings are consistent with—but do not prove, given the cross-sectional nature of the data—the possibility that cognitive processes play an important role in adjustment to chronic pain. The potential role these variables play in depression was particularly noteworthy. Longitudinal and experimental studies to evaluate the causal nature of the associations identified are warranted. PerspectiveThe study findings highlight the potential importance of cognitive process variables (ie, how people think) in adjustment to chronic pain. Research to evaluate cognitive processes as potential mechanism variables in pain treatment is warranted.

Availability of evidence and comparative effectiveness for surgical versus drug interventions: an overview of systematic reviews and meta-analyses

ObjectivesThis study aims to examine the prevalence of comparisons of surgery to drug regimens, the strength of evidence of such comparisons and whether surgery or the drug intervention was favoured.DesignSystematic...

Development of project-based interactive e-modules in accordance with the IQF integrated curriculum concept in learning organic chemical reactions to improve student chemistry learning outcomes

Project-based interactive learning is the right choice to encourage students to learn actively and effectively to improve their learning outcomes. The aim of the research is to find project-based interactive e-Module teaching materials that are valid, effective, standard, suitable for use. Research stages: Needs analysis; e-Module development; standardization validation; individual, small and large group trials; effectiveness test, and test students' perception of satisfaction. The research uses the ADDIE method. Sample: Curriculum, teaching materials from publishers A and B, expert validators and 45 students. Test the feasibility and effectiveness of the e-Module, measuring the increase in learning outcomes and student satisfaction using test instruments. Data were processed and analyzed descriptively using SPSS. Research findings: the interactive e-Module teaching materials developed are valid, effective and standard, suitable for use. The product was effective in small group trials with student learning outcomes of (M 79.35%), large group (M= 79.85%), high and effective category. Respondents' assessment of the product was very valid, suitable for use (M = 3.81). The student satisfaction index is very satisfied (M = 88.80%). Hypothesis testing with paired ttest obtained sig. 0.011. Because sig < α (0.011 < 0.05), there are differences in post-test and pre-test learning outcomes. In conclusion, the project-based interactive e-Module teaching materials developed are valid, effective, standard, and suitable for use to improve student chemistry learning outcomes.

Individual Treatment Trial of PIGV-Associated Mabry Syndrome with D-Mannose in a Young Child

We describe the first individual treatment trial with D-mannose in a young girl with PIGV-CDG. PIGV-CDG belongs to the GPI anchor deficiencies leading to intellectual disability, dysmorphic features, epilepsy, and, less frequently, organ malformations. A hallmark of the GPI anchor deficiencies is the elevated serum alkaline phosphatase (AP). Our patient carried the germline homozygous PIGV variant c.1022C>A, p. (Ala341Glu), the most commonly reported pathogenic variant leading to PIGV-CDG so far. We aimed to improve the impaired enzymatic function of PIGV through elevated substrate levels by giving D-mannose orally. We monitored the clinical status, developmental progress as well as serum AP levels. Our patient experienced no side effects. Standardized developmental testing showed better developmental progress during the 21-month treatment period with D-mannose than in the 12 months following the discontinuation of treatment. The D-Mannose treatment might have had a positive effect on the development of our patient with PIGV-CDG.

Problem Based Learning (PBL) Video Learning Based on Energy Source Material Videoscribe

Learning media plays a vital role in learning activities to achieve the goals of learning activities. However, most teachers still need to use media more, causing low student learning outcomes. Thus, supporting media is necessary for learning. This research aims to create learning videos for the Problem-Based Learning model based on VideoScribe for science content. The type of study used is development research with the ADDIE model. Product trials were conducted to test product validity by material and media experts, teachers conducted practicality tests, and effectiveness tests were given to students using a one-group pretest-posttest design. Data collection methods are questionnaires and tests. The data analysis technique used is qualitative and quantitative descriptive analysis. The study results obtained validity according to media experts at 4.70, learning design experts at 4.75, practicality of practitioner responses at 4.80, individual trials at 4.60, and small group trials at 4.62 in the outstanding category. Effectiveness testing found that the media was significantly effective. These results align with the study's aim to obtain valid and effective learning videos. The research concludes that PBL model learning videos based on VideoScribe with science content are declared valid and effective in learning activities to improve science learning outcomes for third-grade elementary school students.