Trial Phase Research Articles

Targeted delivery of the domestic anticancer drug from the group of aziridine triazines (literature review)

Currently, the targeted delivery of anticancer drugs can significantly increase the effectiveness of therapy, reduce the side effects of systemic chemotherapy, and improve the quality of patients with cancer. This review aimed to summarize data about the domestic antitumor drug 2,4-bis(1-aziridinyl)-6-(2,2-dimethyl-5-hydroxymethyl-1,3-dioxan-5-yl)amino-1,3,5-thriazine (dioxadet), its nanoforms, possibilities of its use in the clinic, and main antitumor nanodrugs clinically introduced in recent years. Library databases (eLibrary, PubMed, CyberLeninka, ResearchGate, Springer, Wiley Online Library, and Elsevier) were searched for relevant information. The literature review summarizes data on the preclinical trials of dioxadet and provides information on its nanoforms, such as nanogels, nanodiamonds, silica particles, and copolymers with lactic and caproic acids. New drug nanoforms open up opportunities to reduce drug side effects and systemic toxicity, maintain optimal therapeutic concentrations, increase the drug circulation time in the blood, and control its release. The possibility of using chemopreparation cytotoxic doses is the main advantage of new nanodrugs. To date, approximately 20 antitumor nanodrugs have been introduced in clinical practice, and some nanodrugs are undergoing preclinical trials or are in various phases of clinical trials. Thus, the development of a new effective nanoform, i.e., dioxadet, makes it possible to ensure targeted drug delivery in higher cytotoxic doses to target cells, increase selective action, and reduce cytostatic toxicity to normal cells.

IMPACT OF COVID VACCINATION IN INDIA: A STUDY OF MEERUT DISTRICT

Early in December 2019, the COVID-19 pandemic broke out in Wuhan, China, and quickly spread throughout the world, devastating human health. To combat the COVID-19 pandemic, quick work was needed to develop and test vaccines for safety and efficacy due to the public health emergency. COVID-19 vaccines were approved for emergency use before the conclusion of traditional clinical trial phases, but there isn't a thorough analysis of the safety information provided by the vaccination trials. There is no data on vaccination effects on the Indian population that are gender-specific. This study aims to evaluate the adverse effects of different vaccines for COVID-19, particularly in young adults based on health issues they encountered, and to determine the factors linked to experiencing adverse events after vaccination, also focusing on gender-specific side effects of vaccine (if there are any). Furthermore, there was a noticeable increase in the number of individuals reporting mental illness. Therefore, this study also attempts to understand the impact of the COVID-19 vaccination on the mental health of people in India with a particular focus on the Meerut district. A structured Google questionnaire will be utilized to collect the required data for the study through a random sampling technique from 200 young adults in the Meerut district who have received at least one dose of the COVID-19 vaccine. Descriptive statistics were used to examine the frequency and length of systemic and generalized symptoms. KEYWORDS: Covid-19, Health issues, vaccination,

Experiences With Unionization Among General Surgery Resident Physicians, Faculty, and Staff

Labor unions are a mechanism for employee advocacy, but their role in surgery resident wellness is poorly characterized. To understand experiences with unionization among general surgery residents and residency program faculty and staff. This exploratory qualitative study included data from the Surgical Education Culture Optimization Through Targeted Interventions Based on National Comparative Data (SECOND) trial. In the exploratory phase of the SECOND trial (from March 6, 2019, to March 12, 2020), semistructured interviews about wellness were conducted with residents, faculty (attending physicians), and staff (program administrators) at 15 general surgery residency programs. Unionization was identified as an emergent theme in the interviews. Data analysis was performed from March 2019 to May 2023. The main outcome was resident and faculty experience with resident labor unions. In the qualitative analysis, lexical searches of interview transcripts identified content regarding resident labor unions. A codebook was developed inductively. Transcripts were coded by dyads, using a constant comparative approach, with differences reconciled by consensus. A total of 22 interview transcripts were identified with relevant content. Of these, 19 were individual interviews conducted with residents (n = 10), faculty (n = 4), administrative staff (n = 1), a program director (n = 1), a department chair (n = 1), and designated institutional officials (n = 2), and 3 were from resident focus groups. Residents from all postgraduate year levels, including professional development (ie, research) years, were represented. Interviewees discussed resident unions at 2 programs (1 recently unionized and 1 with a decades-long history). Interviewees described the lack of voice and the lack of agency as drivers of unionization ("Residents…are trying to take control of their well-being"). Increased salary stipends and/or housing stipends were the most concretely identified union benefits. Unanticipated consequences of unionization were described by both residents and faculty, including (1) irrelevance of union-negotiated benefits to surgical residents, (2) paradoxical losses of surgery department-provided benefits, and (3) framing of resident-faculty relationships as adversarial. Union executives were noted to be nonphysician administrators whose participation in discussions about clinical education progression may increase the time and effort to remediate a resident and/or reduce educators' will to meaningfully intervene. Active surgical resident participation within the union allows for an understanding of surgical trainees' unique needs and reduced conflict. In this qualitative study, unionization was a mechanism for resident voice and agency; the desire to unionize likely highlighted the lack of other such mechanisms in the training environment. However, these findings suggest that unionization may have had unintended consequences on benefits, flexibility, and teaching. Effective advocacy, whether within or outside the context of a union, was facilitated by participation from surgical residents. Future research should expand on this exploratory study by including a greater number of institutions and investigating the evolution of themes over time.

Production of an introperative safety list in interventional cardiology. From pilot project to clinical practice guidelines hospital

Abstract Introduction The safety list was created to respond to two complexities: the first is the fallibility of human memory and attention; The second is the tendency to skip some operations even when remembering that they should be performed: not all operations in the supply chain of a process are always considered important so the shortcut is taken, motivated by the fact that nothing has ever happened so far. Safety in Interventional Cardiology laboratories is characterized by the intrinsic complexity that characterizes all interventional procedures, even the simplest ones: complexity due to the number of people and professionals involved, the acute and/or serious conditions of the patients, the amount of information required, the urgency with which the processes must be performed, the high technological and high level of specialization and the multiplicity of critical points of the processes that can cause serious harm to patients. For this reason, an intraoperative safety list for interventional cardiology has been designed and drawn up. Aim In view of Law no. 24 of 8 March 2017, a provision on the safety of care and the assisted person, it was necessary to have a document aimed at: improving the quality and safety of surgical interventions and interventional/structural procedures, dissemination of recommendations and safety standards aimed at strengthening pre- intra and post-operative processes, Implementation of safety standards through the application of the safety list, adapting it to the characteristics of your organization. Materials and methods The trial phase began in 2021 and was tested on about 800 patients, in 2022 on about 900 patients. The safety list has been designed to combine an intraoperative "check list" with a "nursing card", collecting information relating to the individual people assisted, in order to promote continuity and personalization of care, represents a resource for research on nursing care, for the analysis of care complexity and allows the traceability of the actions carried out. Results and conclusions After years of constant reviews and updates with the collaboration of the Risk Management and Quality staff, the safety list has become a fundamental part of the work of the operating room, supporting both system and individual changes, strengthening standards for safety and communication processes, counteracting possible failure factors, having been included in the hospital Guidelines on the management of patients undergoing surgery.

Oral Anti-Diabetic Semaglutide: A GLP-1 RA Peptide

T2DM has emerged as a global disorder. Although there are many treatment options available for T2DM patients, still several patients complaint about inadequate blood sugar levels. Diabetes management is not limited to just lowering of blood glucose level, it needs a multifactorial approach in treatment. Glucagon- like peptide-1 receptor agonists (GLP-1RA) are a new category of T2DM drugs that acts on various targets such as body weight reduction, renal and cardiovascular benefits. Despite of being so beneficial the major drawback of semaglutide has been its subcutaneous route of administration. Majority of the patients are unable to continue semaglutide for long because of their reluctance towards daily injectable. To avoid this oral semaglutide is introduced. Oral semaglutide is a GLP- 1RA which is displays high glycaemic control. However, in order to increase its bioavailability, it needs to be co formulated with sodium N-(8-[2-hydroxybenzyol] amino) caprylate (SNAC). Oral semaglutide has gone through a very intense series of clinical trials known as, Peptide Innovation for Early Diabetes Treatment (PIONEER). These trials have established benefits of oral semaglutide regarding reduction in glycaemic levels and body weight. It is deemed to be fit for regular consumption. In this review we discuss many aspects of oral semaglutide such as, its chemical structure, route of administration, challenges associated with the oral form of semaglutide, dosage, mechanism of oral bioavailability, robust indications, its placement in the line of defence, drug- drug interaction, various clinical trials (Phase trials and PIONEER studies) including their results. It also summarizes the benefits of oral semaglutide beyond glycaemic control and some future scope of research in the field.

Small molecule inhibitors of the VEGF and tyrosine kinase for the treatment of cervical cancer.

Cervical cancer accounts for most deaths due to cancer in women, majorly in developing nations. The culprit behind this disease is the human papillomavirus(HPV) which accounts for more than 90% of cervical cancer cases. The viral strains produce proteins that favor the knocking down of the apoptosis process and continuous growth of cells in the cervix leading to tumor growth. Proangiogenic growth factors, such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), angiopoietins, and other endothelial growth factors (EGF), are secreted by tumor cells and the surrounding microenvironment, which further advances the development of cancer. The extracellular domain of receptor tyrosine kinases is employed by ligands (like VEGF and EGF) to engage and activate them by inducing receptor dimerization, which facilitates the cascade impact of these factors. The tyrosine kinase domains of each receptor autophosphorylate each other, activating the receptor and initiating signaling cascades that promote angiogenesis, migration, proliferation, and survival of endothelial cells. Cancer cells benefit from its modified signaling pathways, which cause oncogenic activation. Upon early cervical cancer detection, the second-line therapy strategy involves blocking the signaling pathways with VEGF and small molecule tyrosine kinase inhibitors (TKIs). This review paper highlights the genesis of cervical cancer and combating it using VEGF and tyrosine kinase inhibitors by delving into the details of the currently available inhibitors. Further, we have discussed the inhibitor molecules that are currently in various phases of clinical trials. This paper will surely enhance the understanding of cervical cancer and its treatment approaches and what further interventions can be done to alleviate the disease currently serving as a major health burden in the developing world.

The Effect of Priority Assignment the Role of Evaluator and Executive in Collaborative Training on the Acquisition of Kinematic and Accuracy of Dart Throwing Skill

Background: Collaborative training can enhance individual learning, but the effect of role assignment on skill acquisition is unclear. Objectives: Therefore, this study aims to explore the influence of the evaluator and executor roles on the accuracy and kinematic indicators of dart throwing skill. Methods: Forty-eight female university students (mean age = 21.71 ± 1.14 years) participated in the study. Following dart throwing familiarization, participants were randomly assigned to individual group (IG), first-performer (FPG), and first-evaluator groups (FEG) (as a dyad condition) with alternating role orders. All groups completed a pre-test of 10 dart throws while kinematics was recorded via video camera. Practice consisted of 20 blocks of 6 trials (n = 120 physical trials for IG; n = 60 evaluation and n = 60 physical trials for FPG and FEG). Post-tests 1 and 2 directly followed after role reversals for dyads after each 60 trials in the acquisition phase. Accuracy was assessed via mean radial and variable errors. Kinematics (elbow release angle, average angular velocity, elbow range of motion) were analyzed using Kinovea software. Results: A two-way ANOVA revealed the FPG exhibited a significantly smaller release angle compared to IG. However, no significantly differences observed between FEG and IG for kinematic variables. Accuracy improved significantly from pre-to post-test at the three groups. Individual group led to higher accuracy than FPG, and frist-performer group had higher RE than the first-evaluator. Conclusions: The findings of this study support the benefits of observational learning in the early stages of learning. Also, priority assignment the role of evaluator and executive can influences motor performance in a dyadic approach.

Influence of reinforcement learning on the inhibitory control of Internet gaming disorder.

Reward processing dysfunction and inhibition control deficiency have been observed in Internet gaming disorder (IGD). However, it is still unclear whether the previous reinforcement learning depends on reward/punishment feedback influences on the cognitive inhibitory control of IGD. This study compared the differences between an IGD group and healthy people without game experiences in the probability selection task and the subsequent stop signal task by the method of behavioral experiments, in order to explore whether the reward learning ability is impaired in the IGD group. We also discuss the influence of previous reward learning on subsequent inhibition control. The results showed that (1) during the reward learning phase, the IGD group's accuracy was significantly lower than that of the control group; (2) compared with the control group, the IGD group's reaction times were longer in the transfer phase; (3) for no-go trials of the inhibitory control phase after reward learning, the accuracy of the reward-related stimulation in the IGD group was lower than that of punishment-related or neutral stimulation, but there was no significant difference among the three conditions in the control group. These findings indicated that the reinforcement learning ability of the IGD group was impaired, which further caused the abnormal response to reinforcement stimuli.

Glucosinolate Hydrolytic Products-A Multi-Arm Warrior.

Glucosinolates are the most controversial yet ignored class of phytochemicals. These are the middleman phytochemicals which have low bioactivity. But once there is any injury in the plant-manmade, insect caused, or natural-a magic happens. The compound is broken down into smaller phytochemicals referred to as glucosinolate hydrolytic products (nitriles, isothiocyanates, and thiocyanates). These hydrolytic products are like show stopper of fashion industry. These compounds have one of the highest bioactivity in the nature. These have been associated with a varied range of bioactivities (anticancer, antioxidant, insecticidal, weedicide, etc) by researchers across the globe. The objective of the current article is to provide a critical review to highlight some of the important bioactivities of these ignored compounds and for promoting researchers to atleast give these compounds a chance-to glow in the dark. This review has been written from analysis of accessible literature mostly from the last 5 years (2018-2023), with some critically essential exceptions. The review highlighted brief background of glucosinolates and its hydrolysis. Effort were made to include most of the biological properties of the compound. Special emphasis has been given to the anticancer activities of the compound with details of involved mechanism. Considering the wide array of bioactivities of glucosinolate hydrolytic products, it is essential to consider it as a prospective medicinal compound. More glucosinolate hydrolytic products-in similar manner as sulforaphane-can be proceeded to phase trials. The mechanistic pathway for production of glucosinolate hydrolytic products and related biological activities have been discussed in details. The bioactivities have been further explained using the involved mechanism.

Molecular Targets of Plant-based Alkaloids and Polyphenolics in Liver and Breast Cancer- An Insight into Anticancer Drug Development.

Liver and Breast cancer are ranked as the most prevailing cancers that cause high cancer-related mortality. As cancer is a life-threatening disease that affects the human population globally, there is a need to develop novel therapies. Among the available treatment options include radiotherapy, chemotherapy, surgery, and immunotherapy. The most superlative modern method is the use of plant-derived anticancer drugs that target the cancerous cells and inhibit their proliferation. Plant-derived compounds are generally considered safer than synthetic drugs/traditional therapies and could serve as potential novel targets to treat liver and breast cancer to revolutionize cancer treatment. Alkaloids and Polyphenols have been shown to act as anticancer agents through molecular approaches. They disrupt various cellular mechanisms, inhibit the production of cyclins and CDKs to arrest the cell cycle, and activate the DNA repairing mechanism by upregulating p53, p21, and p38 expression. In severe cases, when no repair is possible, they induce apoptosis in liver and breast cancer cells by activating caspase-3, 8, and 9 and increasing the Bax/Bcl-2 ratio. They also deactivate several signaling pathways, such as PI3K/AKT/mTOR, STAT3, NF-kB, Shh, MAPK/ERK, and Wnt/β-catenin pathways, to control cancer cell progression and metastasis. The highlights of this review are the regulation of specific protein expressions that are crucial in cancer, such as in HER2 over-expressing breast cancer cells; alkaloids and polyphenols have been reported to reduce HER2 as well as MMP expression. This study reviewed more than 40 of the plant-based alkaloids and polyphenols with specific molecular targets against liver and breast cancer. Among them, Oxymatrine, Hirsutine, Piperine, Solamargine, and Brucine are currently under clinical trials by qualifying as potent anticancer agents due to lesser side effects. As a lot of research is there on anticancer compounds, there is a desideratum to compile data to move towards clinical trials phase 4 and control the prevalence of liver and breast cancer.

Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression

BackgroundMajor depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin’s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression.MethodsFifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures.DiscussionThis study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin’s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response.Trial registrationClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

The contribution of auditory imagery and visual rhythm perception to sensorimotor synchronization with external and imagined rhythm.

Sensorimotor synchronization (SMS) refers to the temporal coordination of an external stimulus with movement. Our previous work revealed that while SMS with visual flashing patterns was less consistent than with auditory or tactile patterns, it was still evident in a sample of nonmusicians. Although previous studies have speculated the potential role of auditory imagery, its contribution to visual SMS performance is not well quantified. Utilizing a synchronization-continuation finger-tapping task with a visual stimulus that included implied motion, we aimed to examine how participants' imagery ability, musicality, and rhythm perception affected SMS performance. We quantified participants' SMS consistency in synchronization (with visual cues) and continuation (without visual cues) phases. Participants also performed a perception task assessing their ability to detect temporal perturbations in the visual rhythm and completed musical ability and imagery questionnaires. Our linear regression model for SMS consistency included the trial phase, self-reported auditory imagery control and musicality, and visual rhythm perception as predictors. Significant effects of trial phase and auditory imagery scores on SMS consistency suggested that participants performed SMS more consistently while the guiding visual stimulus was present and that the higher one's self-reported auditory imagery ability, the better their SMS when continuing with unguided rhythm. One's visual rhythm perception accuracy significantly correlated with SMS consistency during the synchronization phase, and there was no correlation between rhythm perception and auditory imagery control. Overall, our results suggested relatively independent contributions of auditory imagery and visual rhythm perception to SMS with visual rhythm. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effects of gamma-ray irradiation dose and dose rates on the growth and radiosensitivity of soybean varieties Grobogan and Mutiara 1

Abstract Enhancing soybean production can be achieved through plant breeding, utilizing gamma ray radiation mutation techniques to develop superior varieties. Understanding radiosensitivity is crucial for comprehending the impact of radiation on plant morphology and physiology. This study aims to investigate the impacts of varying doses and dose rates of Cobalt-60 gamma radiation on the growth and development of two soybean varieties, Grobogan and Mutiara 1. This study was conducted to understand how varied radiation doses influence growth parameters and to determine the radiosensitivity, LD50 value, in mutants of the Grobogan and Mutiara 1 soybean varieties. The study employed a randomized complete design with two factors. The first factor was radiation dose ranging from 0 to 1000 Gy. The second factor was dose rate, categorized into low dose rate (219.5 Gy/hour) and high dose rate (4470.2 Gy/hour). The results revealed that the LD50 value of Grobogan variety was estimated at 588.56 Gy at a low dose rate and 657.17 Gy at a high dose rate, while the Mutiara 1 variety had an LD50 value estimate of 512.36 Gy at a low dose rate and 514.30 Gy at a high dose rate. The study also found that the gamma ray radiation dose in the seedling phase trial influenced several growth parameters, including germination percentage, seedling height, development of stem nodes, and formation of leaves. Furthermore, field phase trial showed that a range of radiation dose at 100-300 Gy led to an increase in the number of branches in both soybean varieties and plant height in the Grobogan variety. It also resulted in an increase in the production of pods and total weight of seeds in the Mutiara 1 variety. These findings offer valuable insights into optimizing radiation doses for increasing genetic diversity in soybean.

A Review on Indole as a Cardinal Scaffold for Anticancer Drugs Development

Abstract: Chemotherapy is the mainstay of therapeutic cancer therapy; however, the development of resistance typically makes it less effective. There are continuous efforts by researchers to find novel lead compounds with potent anti-cancer activity. Generally, synthetic or natural heterocyclic compounds have been investigated in detail as a scaffold for cancer therapeutics. Among them, indole, owing to its unique physiochemical and biological properties, provides a promising platform for the development of pharmacophores for drug development against cancer, acting via various mechanisms. Till now, several indole-based derivatives have been identified as anti-cancer agents, which are either being used in clinics or are in various phases of clinical trials, suggesting their importance in anti-cancer drug development. These anti-cancer drugs have been classified into different classes depending on their mechanism of action. For example, histone deacetylase inhibitors (HDAC inhibitors), silent mating type information regulation 2 homolog (SIRT) inhibitors, tubulin inhibitors, proviral insertion site in Moloney murine leukemia virus (Pim) inhibitors, DNA Topoisomerase inhibitors, and kinase inhibitors. In this review, the author's approach is to compile the recent developments on indole-based anti-cancer drugs and provide insight into the respective structureactivity relationships (SARs) of the compounds. We hope the review will provide a thorough understanding to the reader and guide to developing novel and potent indole-based anticancer agents against drug-sensitive and drug-resistant cancer in the future.

Oxidative Stress and Dopaminergic Metabolism: A Major PD Pathogenic Mechanism and Basis of Potential Antioxidant Therapies

Reactive oxygen species (ROS)-induced oxidative stress triggers the vicious cycle leading to the degeneration of dopaminergic neurons in the nigra pars compacta. ROS produced during the metabolism of dopamine is immediately neutralized by the endogenous antioxidant defense system (EADS) under physiological conditions. Aging decreases the vigilance of EADS and makes the dopaminergic neurons more vulnerable to oxidative stress. As a result, ROS left over by EADS oxidize the dopamine-derived catechols and produces a number of reactive dopamine quinones, which are precursors to endogenous neurotoxins. In addition, ROS causes lipid peroxidation, uncoupling of the electron transport chain, and DNA damage, which lead to mitochondrial dysfunction, lysosomal dysfunction, and synaptic dysfunction. The mutations in genes such as DNAJC6, SYNJ1, SH3GL2, LRRK2, PRKN, and VPS35 caused by ROS have been associated with synaptic dysfunction and the pathogenesis of Parkinson’s disease (PD). The available drugs that are used against PD can only delay the progression of the disease, but they produce various side effects. Through their antioxidant activity, flavonoids can substantiate the EADS of dopaminergic neurons and disrupt the vicious cycle incepted by oxidative stress. In this review, we show how the oxidative metabolism of dopamine generates ROS and dopamine-quinones, which then exert unrestrained OS, causing mutations in several genes involved in the proper functioning of mitochondrion, synapse, and lysosome. Besides, we also present some examples of approved drugs used for the treatment of PD, therapies in the clinical trial phase, and an update on the flavonoids that have been tested to boost the EADS of dopaminergic neurons.

How Valid is the Development of the E-Module for AR-enabled Cube Surface Area Material in The Context of The Palembang Wardrobe?

This research aims to produce an e-module of cube surface area material using the context of a typical Palembang cupboard with the help of valid augmented reality (AR) technology. The type of research used is Research and Development (R&D) or research and development with the ADDIE (Analyze, Design, Development, Implementation, and Evaluation) development model research procedure, but this article does not discuss the implementation phase, only the development part. The subjects used in this research were class VIII students at SMP Negeri 50 Palembang. Data collection was carried out using questionnaires and interviews. The results of the e-module development were validated by experts and an average score of 0.8 was obtained in the high category. Then a small group trial phase of 6 students was carried out to see the feasibility of the e-module. So it can be concluded that the e-module on the surface area of ??a cube using the context of a typical Palembang cupboard with the help of augmented reality technology is valid based on expert assessments and student comments.

Independent Curriculum Management Through Developing Teaching Modules on Style Materials

Educational achievement in Education for Sustainable Development (hereafter, EfSD) demands fair and equitable education. This condition gives rise to various preparations that must be taken into account by teaching staff through program plans and strategies designed to achieve the quality of education as regulated in the curriculum. The aim of the research is to examine the conditions for implementing EfSD in elementary schools through the management of learning modules. The research uses the Research and Development or RD method with the ADDIE model. The research begins with an analysis stage consisting of analysis of problems, needs and curriculum, teachers and students. The design stage takes the form of resource management and management of material aspects through the development of independent curriculum teaching modules. At this stage, a validation test was carried out by material experts and practitioners which resulted in an average of 94.48%. Then the implementation or trial phase was limited to 10 students, the test was extensive on 22 grade 4 students. The evaluation stage aims to determine the suitability of the independent curriculum teaching module product for use in schools. The test results showed that student responses were limited to 87.87% and broadly 93.24%. It can be concluded that the development of teaching modules attracts students to learn according to their characteristics, skills and interests.

Design and Build a KIT Humoris (Ohm's Law for Dynamic Electricity) for Science Learning in Junior High School

The role of tools as educational media is crucial in facilitating the learning of scientific concepts, allowing students to master science materials and develop their skills effectively. This research aims to develop a KIT as an experimental approach to learning focused on investigating the relationships among voltage, current, resistance, and power. This study employs a research and development (R&D) approach to design and implement an impactful science learning tool for science experiments. The envisioned impact of this learning tool is to captivate students' interest and concept understanding in science education, especially in Ohm's law for the dynamic electricity topic. The design of the KIT Humoris is specifically structured to establish and illustrate the relationships between voltage, current, and resistance, as well as to calculate power based on voltage and current values. The user-friendly design and visually appealing features of the KIT Humoris make it a practical tool that enhances the tangible understanding of science concepts. Integrating this tool with the Merdeka Curriculum allows teachers to customize lessons according to the unique needs of their students. The design process involves meticulous planning, prototype development, and continuous evaluation to ensure the tool's effectiveness. Results from the trial phase indicate heightened student engagement, improved conceptual understanding, and a profound practical learning experience. KIT Humoris is a valuable science learning tool, providing an engaging and practical approach aligned with the Merdeka Curriculum. Its successful implementation increases student enthusiasm and a deeper comprehension of scientific principles. The implications are contributing to the innovation of teaching methods, especially in the context of the Merdeka Curriculum. From a practical standpoint, the tool has a positive impact on students and their understanding of science concepts.

Biomarker Driven Antifungal Stewardship (BioDriveAFS) in acute leukaemia—a multi-centre randomised controlled trial to assess clinical and cost effectiveness: a study protocol for a randomised controlled trial

BackgroundAcute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing).MethodsBioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC).The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking.The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed.DiscussionThe BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship.Trial registrationISRCTN11633399. Registered 24/06/2022.

Alcohol-associated liver disease: Emerging therapeutic strategies.

The large and growing burden of alcohol-associated liver disease-and the considerable burden of morbidity and mortality associated with it-has been a drive toward ongoing research into novel strategies for its treatment, with a particular focus upon alcohol-associated hepatitis (AH). Management of alcohol-use disorder forms the central pillar of alcohol-associated liver disease care, with evidence-based psychological and pharmacological approaches being well established, and certain models demonstrating improved clinical outcomes when hepatology and addiction services are co-located. Corticosteroids have previously been used somewhat indiscriminately in patients with severe AH, but effective tools now exist to assess early response (and limit futile ongoing exposure). Techniques to predict risk of corticosteroid-related infection are also available, although current clinical strategies to mitigate this risk are limited. A variety of novel therapeutic approaches to AH are at different phases of trials and evidence gathering, with some of the most promising signals related to cytokine manipulation, epigenetic modulation, and targeting of the gut microbiota (ie, by means of fecal microbiota transplant). While remaining an ongoing source of debate, early liver transplant in severe AH has grown in interest and acceptability over the past decade as evidence supporting its efficacy builds, in the process challenging paradigms about mandatory pretransplant sobriety periods. However, uncertainty remains regarding the optimal selection criteria, and whether liver transplant has a role for only a highly limited proportion of patients with AH or more widespread application. This review aims to provide an overview of this fast-moving field.