Stages Of Trials Research Articles

Prevalence of substance and hazardous alcohol use and their association with risky sexual behaviour among youth: findings from a population-based survey in Zimbabwe

ObjectivesHazardous drinking (HD) and substance use (SU) can lead to disinhibited behaviour and are both growing public health problems among Southern African youths. We investigated the prevalence of SU and...

Phase 1b trial of IFx-Hu2.0, a novel in situ cancer vaccine, in checkpoint inhibitor-resistant Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (cSCC).

9592 Background: MCC and cSCC have limited treatment options when refractory to immune checkpoint inhibitor (ICI) therapy. IFx-Hu2.0 (IFx) is a plasmid DNA encoding for an immunogenic bacterial protein, Emm55, formulated with a transfection agent for direct intra-tumoral (IT) injection. In this Phase 1b study, we evaluated the safety and efficacy of different schedules of IT IFx in patients (pts) with advanced MCC or cSCC. Methods: In the first trial stage (n=9), IT IFx was administered in up to 3 lesions on 3 schedules following a 3+3 exposure escalation schema; weekly x 1, 2, or 3. In the second trial expansion stage (n=11), IT IFx was administered weekly x 3. The primary objective of the study was to establish safety and feasibility of repeated IT administrations of the investigational agent. ≥80% completion of planned study therapy was predefined as a successful feasibility outcome. Given the proposed potential for immune priming effects of IFx, we performed an unplanned exploratory analysis of post-protocol treatment efficacy to evaluate response to ICI rechallenge. Results: We treated 22 pts (MCC, 13; cSCC, 9). All pts had received prior anti-PD(L)1 based treatment with disease progression being the reason for ICI discontinuation in all patients but one. Two pts did not complete planned study therapy due to rapid clinical progression and were replaced but included in the safety analysis. IT IFx was well tolerated at all dose schedules evaluated with 1 high-grade toxicity deemed possibly treatment related (G3 hepatitis in a patient recently treated with ICI). The study therefore met predefined study endpoints for safety and efficacy. After protocol specified IT therapy, 11 MCC pts and 6 cSCC pts were treated with anti-PD(L)1 based therapy as the immediate post-protocol treatment. Five of 9 (56%) evaluable MCC patients and 1 of 7 (14%) cSCC patients experienced an objective response to this ICI rechallenge, with duration of response ongoing in 4 patients (6+, 19+, 21+, 23+ months) and the two other responses lasting 23 and 33 months. The two remaining MCC patients were not evaluable for response from IO rechallenge due to radiation administered to the only measurable disease site(s), but both remain progression free at 11+ and 13+ months with previously progressive disease. Conclusions: IT IFx-Hu2.0 is safe and feasible to administer at weekly dosing repeated up to 3 weeks. An unplanned exploratory analysis revealed frequent (56%) and durable responses in advanced MCC to ICI re-challenge despite prior resistance to this class of drug, suggesting that IFx induced an immune priming effect. Preliminary biomarker analyses to investigate this phenomenon are ongoing and will be presented. Clinical trial information: NCT04160065 .

Use of gene expression patterns to identify unique molecular subtypes in muscle invasive bladder cancer: GUSTO.

TPS4621 Background: Muscle invasive bladder cancer (MIBC) is an aggressive disease with poor survival rates that are not improving. Curative treatment includes systemic neoadjuvant chemotherapy prior to radical cystectomy and adjuvant immunotherapy. However, many patients do not respond to chemotherapy or immunotherapy. Histologically similar MIBCs can be classified using gene expression patterns into unique molecular subtypes. Retrospective studies have shown that molecular subtypes each have unique biology and consequently respond differently to treatment. The GUSTO trial tests the hypothesis that outcomes can be optimized through subtype-guided allocation. Methods: Eligible participants are those with confirmed non-metastatic MIBC, an ECOG performance status 0-1, being considered for cisplatin-based neoadjuvant chemotherapy and radical cystectomy. Formalin-fixed diagnostic (TURBT) tumor samples undergo gene expression microarray analysis and characterization using the GUSTO Classifier (consisting of the Veracyte Decipher assay and TCGA_2017 classification system) to determine the molecular subtype: basal, neuronal, luminal infiltrated, luminal or luminal papillary. A total of 320 eligible patients (T2-4a N0 M0 or T(any) N1 M0 MIBC) will be randomized 1:1 to either standard of care treatment (neoadjuvant cisplatin and gemcitabine) or subtype-guided treatment (basal and neuronal subtypes - neoadjuvant cisplatin, gemcitabine, durvalumab and tremelimumab and adjuvant durvalumab; luminal infiltrated - neoadjuvant durvalumab and tremelimumab and adjuvant durvalumab; luminal and luminal papillary - proceeding directly to radical cystectomy). Sites are notified when a patient has been assigned a molecular subtype. Patients and sites in the standard of care arm remain blind to the genomic subtype. The trial has three stages: Stage 1 (after 6 months of recruitment) will assess feasibility of recruitment and molecular subtyping in clinical timelines. Outcomes include recruitment rate, time to, and success of subtype allocation. Stage 2 (after 24 months of recruitment) will confirm recruitment feasibility and assess sample size assumptions. Outcomes are recruitment numbers, distributions of subtypes, and pathological complete response (pCR) in the standard of care arm. A re-estimation of the sample size for stage 3 will be considered. Stage 3 (after 12 months post-cystectomy for the last participant randomized) will assess treatment outcomes using this stratified approach. The primary outcome for Stage 3 is the rate of pCR in each molecular subtype within the experimental arm. Progression between trial stages will be dependent upon achieving pre-defined criteria. Recruitment began in September 2023. The study will open the first 20 sites ready to proceed and is accepting expressions of interest. Clinical trial information: 17378733.

Design and characterization of 3D-printed hollow microneedle arrays for transdermal insulin delivery

The delivery of insulin to diabetic patients remains a challenge due to the limitations of current insulin delivery paradigms, including painful cannula insertion, potential infections, interference with activity, embarrassment, and sometimes cost. To address this problem, we designed and fabricated nine prototypes of stereolithographic 3D-printed microneedle arrays (MNAs) appropriate for the minimally invasive delivery of insulin. We characterized their transdermal penetration performance by delivering fluid at a constant rate to porcine skin through these MNAs. Moreover, we characterized the force required for these MNAs to puncture porcine skin using a mechanical testing apparatus. We developed an improved method of mechanical testing for the MNAs against porcine skin by incorporating an imitation soft tissue layer under the skin and compared the MNA results with those using a single microneedle and a hypodermic needle. In addition, we investigated the mechanical flexural strength of the MNAs by performing a flexural failure load test on them. We confirmed that the prototype MNAs are mechanically robust and do not fracture during skin penetration, setting the stage for future trials in vitro and in vivo. The final, optimized designs are freely available in stereolithography (STL) file format.

Effect of a 12-week remote exercising program (ExIOnc) on quality of life and symptoms of older patients with cancer in Brazil.

1623 Background: Leading organizations, including ASCO, recommend physical activity for patients with cancer. However, numerous barriers hinder patients from maintaining regular physical activity, particularly among older adults, who have lower participation in exercise programs. This study aims to evaluate the effects of a 12-week supervised remote exercise program on the health-related quality of life (HRQOL) of older patients with cancer (aged ≥65) undergoing treatment in Brazil. Methods: This was a single-arm pilot study evaluating a remote physical activity program which combined supervised and remote exercise. Eligible patients were contacted through WhatsApp for the initial assessment and received guidance on weekly exercises. The Vedius platform was employed to demonstrate proper home exercise techniques. The prescribed regimen consisted of 3-5 hours per week (4-6 days a week), encompassing both resistance and aerobic exercise. Outcome measures included overall HRQOL (FACT-G, scale 0-108) and symptom assessment (ESAS). Assessments were conducted at baseline and after 12 weeks. Descriptive statistics were calculated, and linear mixed models were employed to analyze changes from before to after the intervention. Results: Out of 46 approached patients, 41 patients were enrolled, with a median age of 70 years (range 65-88). Of the participants, 56.1% were female, 70.7% were white, and 58.2% were married, with 53.5% holding a college degree. The most common cancer types were breast (26.8%), genitourinary (22.0%), and lung (17.1%), all diagnosed at advanced stages. A significant improvement was observed in overall HRQOL (MT1=83.2 to MT2=94.4, P=0.001). Improvements were also seen in the severity of various symptoms, including pain (MT1=1.6 to MT2=0.7, P=0.001), fatigue (MT1=3.8 to MT2=1.3, P=0.001), nausea (MT1=0.8 to MT2=0.2, P=0.01), depression (MT1=2.6 to MT2=0.8, P=0.001), anxiety (MT1=3.2 to MT2=1.2, P=0.001), drowsiness (MT1=1.8 to MT2=0.4, P=0.001), and appetite (MT1=2.2 to MT2=0.6, P=0.001). Conclusions: This study demonstrates a positive impact of a 12-week remote physical activity program on HRQOL and symptom management for older patients with cancer, and set the stage for future randomized trials. Despite the challenges posed by cancer treatment, incorporating such programs into patient care could be an effective strategy to enhance overall well-being and mitigate treatment-related symptoms.

Development and Challenges of Cyclic Peptides for Immunomodulation.

Cyclic peptides are polypeptide chains formed by cyclic sequences of amide bonds between protein-derived or non-protein-derived amino acids. Compared to linear peptides, cyclic peptides offer several unique advantages, such as increased stability, stronger affinity, improved selectivity, and reduced toxicity. Cyclic peptide has been proved to have a promising application prospect in the medical field. In addition, this paper mainly describes that cyclic peptides play an important role in anti-cancer, anti-inflammatory, anti-virus, treatment of multiple sclerosis and membranous nephropathy through immunomodulation. In order to know more useful information about cyclic peptides in clinical research and drug application, this paper also summarizes cyclic peptides currently in the clinical trial stage and cyclic peptide drugs approved for marketing in the recent five years. Cyclic peptides have many advantages and great potential in treating various diseases, but there are still many challenges to be solved in the development process of cyclic peptides.

Novel Treatment Options for Knee Cartilage Defects in 2023.

Articular cartilage lesions are a common injury that have become increasingly treatable with joint preservation procedures. Well-documented allograft and cellular treatments for these lesions are detailed elsewhere in this volume. This article discusses three new unique options for addressing these defects taking three different paths to address these complex injuries. Agili-C is an existing FDA- and EMEA-approved option using an acellular aragonite-based scaffold to treat both chondral and osteochondral lesions, with or without concurrent arthritis. Cartistem is a stem-cell-based product composed of culture-expanded allogeneic human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel, which is in its final clinical trial stages in the United States, but already has regulatory approval in Korea. IMPACT and RECLAIM studies have shown the safety and efficacy of a new one-stage procedure utilizing autologous chondrons combined with allogeneic mesenchymal stem cells (MSCs) that can provide another effective single-stage treatment option.

An ancillary care policy in a vaccine trial conducted in a resource-constrained setting: evaluation and policy recommendations

IntroductionClear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for a vaccine trial in the Democratic...

The Accessibility, Affordability, and Early Detection of Tuberculosis

Tuberculosis (TB) stands as the leading cause of death from an infectious agent worldwide, with a high fatality rate. It is primarily transmitted through the airborne Mycobacterium tuberculosis (M. tb) from an infected patient to a healthy individual. Annually, millions of people go undiagnosed for TB at an early stage and lose the opportunity for timely treatment, making early TB diagnosis a high priority. Prevalence surveys also have shown that many individuals with lab-confirmed TB disease lack symptoms and do not seek diagnosis or care. Moreover, delays in initiating treatment are commonly observed even after TB diagnosis, heightening the risk of disease transmission in the community. This research paper aims to address these challenges by analyzing the impact of various socioeconomic, policy, and healthcare factors on the accessibility of TB diagnosis. Furthermore, it aims to analyze current effective tuberculosis diagnosis techniques, assessing their strengths and weaknesses. Despite the presence of promising new drugs in the clinical trial stage offering hope for patients with extensively drug-resistant tuberculosis (XDR-TB) or very drug-resistant TB, the primary challenge remains the timely and species-specific detection of Tuberculosis. In addition to the detection of disease, identifying its drug resistance patterns and ensuring the availability of highly active short-course drug treatments are imperative, ideally lasting just a few weeks. This is essential to support the World Health Organization’s (WHO) Global efforts to “END TB” by 2030, to reach 90% of people primarily through early diagnosis, innovative treatments, and vaccine development.

Reformulation of Regulations Regarding Restorative Justice in Cases of Criminal Acts of Bullying Against Children at Investigation Level

Children as the most vulnerable and weak social creatures are often placed in the weakest position, do not have the right to speak, and often experience violations of their rights. One of them is the limitation of diversion obligations for law enforcers which is only limited to criminal acts with a threat of under 7 (seven) years, which is contrary to the intention of the legislators in providing age limits for children and is contrary to the psychological nature of children. If investigators have applied diversion consistently in cases where only children who are bullied are under 7 (seven) years of age, it is not certain that the investigator's objectivity according to law is directly proportional to the objectivity according to community justice. This research is aimed at finding out the regulations related to restorative justice in cases of criminal acts of bullying against children at the investigation level as well as formulating a reformulation of regulations related to restorative justice in cases of criminal acts of bullying against children at the investigation level in the future. The type of research in this research is normative juridical. This research aims to understand and interpret legal norms and analyze their consequences or implications. It is still found that there is still a lot of restorative justice that is not applied to children who are bullied at the investigation stage, so that children have to face the next stage of justice, even up to the trial stage. Concrete steps are needed by Indonesian National Police investigators to ensure that restorative justice is applied consistently at the investigation stage of criminal acts of child bullying. The government together with the Police of the Republic of Indonesia through the legislative body should reformulate regulations related to restorative justice in cases of criminal acts of bullying against children at the investigation level in the future which can be carried out through reformulation regarding material requirements as intended in Article 5 of the Republic of Indonesia State Police Regulation Number 8 of 2021 concerning the Handling of Criminal Offenses Based on Restorative Justice, namely points a and f as well as the rules regarding the requirements for implementing Diversion in Article 7 of Law (UU) Number 11 of 2012 concerning the Juvenile Criminal Justice System by taking into account the main interests of the child.

Green Logistics Sustainable and Eco- friendly Transportation Practices

The goal of this study is to better understand the factors implementing eco-friendly practices in transportation to reduce environmental impact. Well, understanding of factors may not lead to the implementation of eco-friendly practices. The COP26 resolution to achieve carbon neutrality till 2050. The logistics and transportation industry contributes more to global greenhouse gas emission. Government and organization strategies analyze if the problem is genuine or not for the public. This study finds and investigates some elements that have a substantial impact on the green logistics and eco-friendly business practices. Making aware to the public as well as logistics industry about green logistics and eco-friendly technology is the future. Electric vehicles and other fuels option should be the problemsolving of logistics industry as well as for the people which they are facing. Make electric vehicles and other green packing method or fuels on the trial stage and gather feedback from the pilot audience that the green logistics is solving the problem you identified. Data was collected through the customer survey. Using technology that is easily operated and that focuses on environmental impact of logistics transportation. green and sustainable eco-friendly transports help reducing cost and dependency on fuels like petrol diesel etc. green logistics helps in the economic growth that will help the logistics provider and people of that area to be developed. it presents the split routing optimization problem of lowcarbon distribution with the optimization goal of reducing carbon emissions. The study shows how to tackle the problem, and end with a conclusion to appeal the industry to start the green journey now.

Virulent Attack: Role-Playing Learning Media to Enhance Student’s Cognitive Learning Outcomes

The cognitive learning outcomes of 10th-grade students at SMA Islam Malang regarding the concept of viruses are low. This is due to the perception among students that the virus concept is difficult to grasp, and the learning methods employed tend to be monotonous. Consequently, the aim of this study is to develop and assess the effectiveness of 'Virulent Attack' - a role-playing learning media adapted from the popular game Werewolf - in improving the cognitive learning outcomes of high school students in understanding the virus concept. Following the ADDIE development model, the study involved 29 X-D students from SMA Islam Malang who had no prior knowledge of the virus concept. The validation test was conducted by three experts (one material expert, one media expert, and one biology teacher) using a validation sheet questionnaire. The practicality test was carried out by students during the trial stages, and one educational practitioner provided feedback through a response questionnaire. The effectiveness test was evaluated by comparing students' pretest and posttest scores on cognitive learning outcomes, which were analyzed using the N-Gain score criteria. The findings indicate that 'Virulent Attack' is highly valid (material expert: 100%, media expert: 94.64%, biology teacher: 96.68%), practical (average score: 90.58%), and moderately effective in improving cognitive outcomes (N-Gain score: 0.66, effectiveness: 66.55%). Importantly, the game provided a positive learning experience, increased motivation, and facilitated a deeper conceptual understanding, suggesting its potential application in real-world educational contexts. These findings not only highlight the value of role-playing games in educational settings but also have practical implications for incorporating such media into biology curricula to enhance engagement and understanding.

Abstract B027: The MAT2A inhibitor IDE397: a novel combination backbone for urothelial cancer subjects with MTAP deficiency

Abstract Methylthioadenosine phosphorylase (MTAP) loss, due to focal homozygous deletions in chromosome 9 (9p21.3), occurs in over 25% of urothelial carcinoma and is an adverse prognostic factor for overall survival. Furthermore, MTAP-deleted tumors are associated with a “cold” tumor immune microenvironment and are resistant to immune checkpoint inhibitor therapy. Loss of MTAP confers a dependency on methionine adenosyltransferase 2A (MAT2A), which catalyzes the production of the primary methyl donor for all cellular methyltransferase reactions, S-adenosyl methionine (SAM). IDE397, a potent small molecule inhibitor of MAT2A, was developed to selectively exploit this synthetic lethal vulnerability in MTAP −/− tumors. The accumulation of the metabolite MTA in MTAP −/− tumors combined with a reduction of SAM by MAT2A inhibition results in selective inhibition of PRMT5, a methyltransferase that governs spliceosome fidelity. This triggers pre-mRNA splicing defects that may induce RNA polymerase stalling and can cause R-loop accumulation. Furthermore, due to essential roles in 1-carbon metabolism, MAT2A inhibition together with MTAP loss leads to depletion of metabolites required for both de novo and salvage nucleotide biosynthesis, thus preventing effective management of DNA replication and DNA damage repair. Notably, R-loops must be resolved by topoisomerase activity (TOP1) to prevent replication conflict and mitotic catastrophe. These combinatorial mechanistic relationships underpin a hypothesis that dual inhibition of MAT2A and TOP1 will fully capitalize on the synthetic lethal vulnerabilities associated with MTAP loss in urothelial cancers (replication stress, genomic instability). Consistent with this, IDE397 in combination with TOP1 inhibitors demonstrated synergistic combination benefit in MTAP −/− bladder cancer cell lines in vitro and in cell-line derived xenograft (CDX) models in vivo. IDE397 exposure was associated with heavily disordered methionine metabolism and accumulation of DNA damage response intermediates. In the ongoing Phase 1 dose escalation/expansion study of IDE397 in MTAP −/− solid tumors (NCT04794699), measurable tumor shrinkage has been observed in urothelial cancers (including a CR per RECIST 1.1) along with molecular responses on serial ctDNA measurements. Supported by our preclinical data, and the clinical observation that MTAP −/− urothelial cancers may be more sensitive to sacituzumab govitecan (SG); a TROP-2-targeting TOP1 ADC (UNITE study; JCO.2023.41.16_suppl.4572), a combination of SG+IDE397 could represent a novel early-line therapy for these patients with high unmet need. We plan to evaluate the combination of SG+IDE397 in MTAP-/- urothelial cancers in the next stage of the ongoing IDE397 trial (NCT04794699). Citation Format: Claire L. Neilan, Marcus M. Fischer, Damien Garbett, Arjun A. Rao, Mili Mandal, Michael A. White, Jasgit C. Sachdev. The MAT2A inhibitor IDE397: a novel combination backbone for urothelial cancer subjects with MTAP deficiency [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B027.

On the functions of the prosecutor in criminal proceedings

The article is devoted to the study of the functions of the prosecutor in the judicial stages of criminal proceedings, and provides an analysis of statistical data from the General Prosecutor’s Office of the Russian Federation on the participation of prosecutors in criminal proceedings. The results obtained allow us to assert that the prosecutor performs two functions during criminal proceedings: the criminal procedural function of prosecution and the constitutional and legal function of supervision over compliance with the Constitution of the Russian Federation and the execution of laws. At the same time, at the stages of trial (in the court of first instance) and appeal proceedings, when the principle of adversarial parties is fully implemented, the prosecutor supports the state prosecution, thereby performing the procedural function of the prosecution. In the remaining stages of judicial proceedings, the prosecutor exercises the function of supervising compliance with the law. The conclusion is formulated that the proposed approach requires a rethinking of the role of the prosecutor in criminal proceedings from the position of the constitutional and legal status of the Russian prosecutor’s office, as well as amendments to the norms of criminal procedure law.

Study on Start-up Success Factors on Rural Area: - A Case Study of FoodVastu Online Delivery

The goal of this study is to better understand the factors of start-ups in rural areas. Well, understanding of factors may not lead to the failure of the start-up. Small business owners are worried about the startup strategies because about 50% of new small startups fail during their first 5 years of operation. When starting a business in rural areas people are not aware of the technology and concept of time saving. Market entry strategies analyze if the problem is genuine or not for the public. This study finds and investigates some elements that have a substantial impact on the success or failure of start-ups. Making aware to the public aware of rural areas' technology is the future. Start-up should be the problem-solving of people which they are facing. Make a start-up on the trial stage and gather feedback from the pilot audience that the start-up is solving the problem you identified. Data was collected through the customer survey. Using technology that is easily adapted by the population of rural areas (WordPress, Wix, Shopify, etc.). Start-ups help to generate employment in the rural area. Helps in the economic growth that will help the area to be developed. UI of any start-up based on tech in rural areas should be very user friendly which will help to learn quicker to any user. Make your product or service that fits the market or not.

Sinefungin analogs targeting VP39 methyltransferase as potential anti-monkeypox therapeutics: a multi-step computational approach.

The increasing spread of the Monkeypox virus (MPXV) presents a significant public health challenge, emphasising the urgent requirement for effective treatments. Our study focuses on the VP39 Methyltransferase enzyme of MPXV as a critical target for therapy. By utilising virtual screening, we investigated natural compounds with structural similarities to sinefungin, a broad-acting MTase inhibitor. From an initial set of 177 compounds, we identified three promising compounds-CNP0346326, CNP0343532, and CNP008361, whose binding scores were notably close to that of sinefungin. These candidates bonded strongly to the VP39 enzyme, hinting at a notable potential to impede the virus. Our rigorous computational assays, including re-docking, extended molecular dynamics simulations, and energetics analyses, validate the robustness of these interactions. The data paint a promising picture of these natural compounds as front-runners in the ongoing race to develop MPXV therapeutics and set the stage for subsequent empirical trials to refine these discoveries into actionable medical interventions.

Application of nanoparticles in breast cancer treatment: a systematic review.

It is estimated that cancer is the second leading cause of death worldwide. The primary or secondary cause of cancer-related mortality for women is breast cancer. The main treatment method for different types of cancer is chemotherapy with drugs. Because of less water solubility of chemotherapy drugs or their inability to pass through membranes, their body absorbs them inadequately, which lowers the treatment's effectiveness. Drug specificity and pharmacokinetics can be changed by nanotechnology using nanoparticles. Instead, targeted drug delivery allows medications to be delivered to the targeted sites. In this review, we focused on nanoparticles as carriers in targeted drug delivery, their characteristics, structure, and the previous studies related to breast cancer. It was shown that nanoparticles could reduce the negative effects of chemotherapy drugs while increasing their effectiveness. Lipid-based nanocarriers demonstrated notable results in this instance, and some products that are undergoing various stages of clinical trials are among the examples. Nanoparticles based on metal or polymers demonstrated a comparable level of efficacy. With the number of cancer cases rising globally, many researchers are now looking into novel treatment approaches, particularly the use of nanotechnology and nanoparticles in the treatment of cancer. In order to help clinicians, this article aimed to gather more information about various areas of nanoparticle application in breast cancer therapy, such as modifying their synthesis and physicochemical characterization. It also sought to gain a deeper understanding of the mechanisms underlying the interactions between nanoparticles and biologically normal or infected tissues.

Development of Vaccine Candidates Against Mycobacterium Tuberculosis in 2019-2023

ABSTRACT With extensive use of the Bacillus Calmette–Guérin (BCG) vaccine, the global prevalence of Mycobacterium tuberculosis (MTB) remains. A number of vaccines proposed to cure and prevent tuberculosis (TB) infection are undergoing various stages of clinical trials. Although vaccine production is progressing, more attention is needed. A number of TB vaccines are currently undergoing clinical trials, most of which rely on a combination of proteins and/or adjuvants or recombinant viral vectors specific for MTB antigens. We tried to cover the range of TB vaccines in this study by analyzing their composition, the immunological responses they elicit, and the stages of clinical trials. To find out the Development Of Prospective Vaccines Against Mycobacterium Tuberculosis. This research uses a literature review, between August 2023 and November 2023, the authors of this literature review checked PubMed, Science Direct, Google Scholar, and other databases containing research findings or scientific articles. Only studies that met the above search criteria were included in the systematic review. Many recently developed tuberculosis vaccines are reportedly in the final stages of clinical trials, where they have significantly strengthened the immune system and even produced protection against the host. Immunization produced by vaccines that have successfully passed the initial stages of clinical trials is safe and effective, and can even surpass BCG in terms of immunity. Based on the description above, it can be concluded that many recently developed tuberculosis vaccines are reported to be in the final stages of clinical trials, where they have significantly strengthened the immune system and even produced protection against the host. Immunization produced by vaccines that have successfully passed the initial stages of clinical trials is safe and effective, and can even surpass BCG in terms of immunity. With the development of new TB vaccines that strengthen the body's immunity and create effective delivery mechanisms, hopes for TB treatment and prevention are increasing. The development of vaccine effects can be facilitated, in part, through the use of effective delivery mechanisms, which have also been used in TB vaccines. Keywords: Tuberculosis, Vaccine, Bacteria, Mycobacterium Tuberculosis, BCG

CREATION OF GOOGLE SITES-BASED E-MODULES FOR DIGITAL DOCUMENT ELEMENTS AT HIGH VOCATIONAL SCHOOLS

This research aims to evaluate the feasibility and practicality of developing an e-module based on Google Sites for digital document elements. The study was conducted at SMK Negeri 40 Jakarta in class X Office Management with 36 participating students. The method used is Research and Development (R&D) with the ADDIE development model (Analyze, Design, Development, Implementation, and Evaluation). The research subjects consisted of 9 validators (three subject matter experts, three instructional design experts, and three media experts) and 36 class X MP students. The data analysis techniques included validation tests and practicality tests. The validation test was conducted by subject matter experts with a result of 88%, categorized as highly feasible; instructional design experts with a result of 97%, categorized as highly feasible; and media experts with a result of 90%, categorized as feasible. The practicality test was conducted by 36 class X MP students through three stages of trials: one-to-one evaluation with a result of 93%, considered highly practical; small group trials with a result of 92%, considered highly practical; and large group trials with a result of 91%, considered highly practical. The results of the research and development indicate that the e-module based on Google Sites for digital document elements at SMK Negeri 40 Jakarta is deemed highly feasible and highly practical for use in learning activities.

Punishing the Innocent: An Insight into Wrongly Convicted Individuals

Wrongful convictions have increasingly plagued the Indian criminal justice system. Instances of innocent individuals being wrongfully prosecuted suggest that some states witness convictions at trial stages, only for the accused to be acquitted upon appeal. However, there is no established system for identifying or tracking individuals wrongfully convicted, as state officials do not maintain records of acquittals or discharges. This lack of oversight perpetuates erroneous miscarriages of justice, resulting in innocent individuals not only losing their rights but also facing social alienation. This study examines the phenomenon of wrongful convictions in India, exploring its causes, consequences, and potential solutions. Drawing upon legal analysis and case laws, this study identifies various factors contributing to wrongful convictions, including flawed investigation procedures, police misconduct, inadequate legal representation, and systemic issues within the criminal justice system. Furthermore, it highlights the social, psychological, and economic tolls experienced by wrongfully convicted individuals and their families. The study also discusses the challenges faced in rectifying wrongful convictions and proposes a range of reforms aimed at preventing future injustices, such as improving investigation techniques, enhancing legal aid services, strengthening judicial oversight, and promoting public awareness and advocacy. By addressing the root causes of wrongful convictions and implementing systemic reforms, India can strive towards a more equitable and just legal system that upholds the rights and dignity of all individuals. In addition the purpose of this study to find out what approaches the state utilizes to resolve this issue of wrongful conviction and also aims to emphasize what are the remedies already available under existing laws and also to underline the need of standard legal framework for looking compensations to victims of wrongful convictions.