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Background: The Foods with Function Claim was introduced in Japan in April 2015 to make more products available that are labeled with health functions. A product's functionality of function claims must be explained by the scientific evidence presented in clinical trials (CTs) or systematic reviews, but the quality of recent CTs is unclear. The purpose of this study was to evaluate the risk of bias (RoB) using "a revised tool to assess risk (RoB 2)" published in 2018 for notifications based on all recent CTs published on the Consumer Affairs Agency website. Methods: A total of 38 submitted papers based on CTs that were published on the Consumer Affairs Agency website during the period from 1 January 2023 to 30 June 2024 were eligible. The RoB 2 tool provides a framework for considering the risk of bias in the findings of any type of randomized trial. This tool with five domains was used to evaluate the quality of research methods. Results: Eligible CTs were assessed as "low risk" (11%, n = 4), "medium risk" (13%, n = 5), and "high risk" (76%, n = 29). A number of highly biased papers were published. Bias occurred in all five domains, especially "bias in selection of the reported result (Domain 5)", which was the most serious ("high risk"; 75%). For elements correlated with RoB, there was no significant difference (p = 0.785) in the RoB 2 score between for-profit and academic research in the author's affiliated organization. There was no significant difference (p = 0.498) in the RoB score between the published year categories of 2000–2019 and 2020–2024, and no significant difference (p = 0.643) in the RoB score between English and Japanese language publications. Conclusion: Overall, the quality of the latest CTs submitted after 2023 was very low, occurring in all five domains, and was most serious for "bias in selection of the reported result (Domain 5)". [ABSTRACT FROM AUTHOR]

Gastric cancer, which is considered a major health concern, is the sixth most frequent cancer and the second leading cause of cancer-related mortality across the globe. The present survey aimed to systematically review the anti-gastric cancer effect of all organic and inorganic nanoparticles (NPs) in in vitro, in vivo, and clinical trials. The investigation followed the PRISMA guidelines, and the findings were recorded in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-Analysis Facility database. A detailed search was conducted on various English databases, such as Scopus, Web of Science, EMBASE, PubMed, and Google Scholar, with no specified publication time frame to obtain papers regarding the anti-gastric cancer properties of nanoparticles. The search process was performed using the following terms: "Nanoparticles," "Gastric cancer," "Antigastric cancer," "Metal nanoparticles," "Organic nanoparticles," "Inorganic nanoparticles, "in vitro," "Clinical," and "in vivo,". Out of 11,189 papers, 31 articles, including 19 (45.5%) in vitro, 3 (13.6%) in vivo, 3 (13.6%) clinical trials, and 6 (27.3%) in vitro/in vivo, up to 2023, met the inclusion criteria for discussion in this systematic review. The most widely used NPs were found to be organic nanoparticles, such as polylactic acid and poly lactic-co-glycolic acid (16, 80.0%), followed by inorganic nanoparticles, such as silver NPs (13, 41.9.0%). This review study highlighted the high anti-gastric cancer potential of a wide range of organic and non-organic NPs through their activity via some mechanisms, such as the induction of apoptosis, gene therapy, and drug delivery. Nonetheless, further studies, especially in clinical settings, are needed to confirm their anti-gastric effects and accurate mechanisms. [ABSTRACT FROM AUTHOR]

Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell‐ and platelet‐rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in‐human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2‐year follow‐up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell‐ and PRP‐treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost‐effectiveness assessments to determine the benefits of cell/PRP treatments. [ABSTRACT FROM AUTHOR]

Background: Fibroblast cells have the ability to improve skin conditions through regenerative medicine and cell-based therapies. The purpose of this scoping review is to assess the contribution of fibroblast cells to skin homeostasis and extracellular matrix deposition in clinical trials involving skin disorders and cosmetic applications. Methods: Using targeted search terms, published publications from January 2000 to August 2023 that addressed fibroblast uses in clinical trials of skin conditions were obtained from bibliographic databases like PubMed, Scopus, and Web of Science (WoS). Precise inclusion and exclusion criteria were used during the screening process. The potential benefits of induction treatment with fibroblasts lead to the choosing of clinical trials for this kind of treatment. Results: Out of the 820 published ppapers initially identified, only 35 studies fulfilled our meticulous eligibility criteria after careful screening. To ensure clarity, we methodically eliminated any duplicate or irrelevant published papers, thereby offering a transparent account of our selection process. Conclusion: This study highlights the advantages of fibroblast therapy in treating skin conditions such as diabetic foot, venous leg ulcers, and cosmetic reasons. Fibroblasts possess remarkable regenerating capabilities, making dermal fibroblast therapy crucial in cell-based and skin regenerative treatments. Nevertheless, additional research is required for more disorders and cosmetic applications. [ABSTRACT FROM AUTHOR]

Telemedicine is now being used more frequently to evaluate patients with myasthenia gravis (MG). Assessing this condition involves clinical outcome measures, such as the standardized MG-ADL scale or the more complex MG-CE score obtained during clinical exams. However, human subjectivity limits the reliability of these examinations. We propose a set of AI-powered digital tools to improve scoring efficiency and quality using computer vision, deep learning, and natural language processing. This paper focuses on automating a standard telemedicine video by segmenting it into clips corresponding to the MG-CE assessment. This AI-powered solution offers a quantitative assessment of neurological deficits, improving upon subjective evaluations prone to examiner variability. It has the potential to enhance efficiency, patient participation in MG clinical trials, and broader applicability to various neurological diseases. [ABSTRACT FROM AUTHOR]

Leonurine is an alkaloid unique to the Leonurus genus, which has many biological activities, such as uterine contraction, anti-inflammation, anti-oxidation, regulation of cell apoptosis, anti-tumor, angiogenesis, anti-platelet aggregation, and inhibition of vasoconstriction. This paper summarizes the extraction methods, synthetic pathways, biosynthetic mechanisms, pharmacokinetic properties, pharmacological effects in various diseases, toxicology, and clinical trials of leonurine. To facilitate a successful transition into clinical application, intensified efforts are required in several key areas: structural modifications of leonurine to optimize its properties, comprehensive pharmacokinetic assessments to understand its behavior within the body, thorough mechanistic studies to elucidate how it works at the molecular level, rigorous safety evaluations and toxicological investigations to ensure patient wellbeing, and meticulously conducted clinical trials to validate its efficacy and safety profile. [ABSTRACT FROM AUTHOR]

All disease, but especially non-communicable diseases, are related to dysfunction of one or more regulatory systems. In developing countries, long-term management of patients with chronic diseases has many challenges and is generally not financially viable, but Africa in particular, which is rich in diverse ethnomedicines presents a more feasible long-term therapeutic approach in this niche. However, despite comprehensive preclinical investigations on numerous plant-derived candidate medicines, only a small portion of these reach the patient as recognised medicines. In this review, we use the example of rooibos (Aspalathus linearis (Burm.f.) R. Dahlgren)-which is globally consumed as aromatic, caffeine-free tea-to illustrate the hurdles that need to be overcome in the low-to middle-income countries, before progression of ethnomedicines to official treatment regimens can be achieved. In terms of methodology, regulatory system focused rooibos papers indexed on PubMed for the past three decades (n = 112) were accessed. Papers reporting duplication of previous results were excluded, as well as review papers. Topics covered includes the high standard of ethnomedicine drug discovery and efficacy testing research performed in Africa (and South Africa in particular in the case of rooibos), the potential bias in terms of preclinical research focus, ethnomedicine ownership and the requirement for independent clinical trial coordination and/or management. [ABSTRACT FROM AUTHOR]

Background: Engagement and partnership with consumers and communities throughout research processes produces high quality research meeting community needs and promoting translation of research into improved policy and practice. Partnership is critical in research involving Aboriginal and/or Torres Strait Islander people (First Nations Peoples) to ensure cultural safety. We present lessons from the design, implementation and progress of the National Health and Medical Research Council funded INtravenous iron polymaltose for First Nations Australian patients with high FERRitin levels on hemodialysis (INFERR) clinical trial. Main body: The trial was designed to understand the benefits and harms of iron therapy in First Nations Australians on haemodialysis with anaemia and hyperferritinaemia. The lack of evidence for treatment was discussed with patients who were potential participants. A key element ensuring safe conduct of the INFERR trial was the establishment of the Indigenous Reference Groups (IRGs) comprising of dialysis patients based in the Top End of Australia and Central Australia. Two IRGs were needed based on advice from First Nations communities and researchers/academics on the project regarding local cultural differences and approaches to trial conduct. The IRGs underpin culturally safe trial conduct by providing input into study materials and translating study findings into effective messages and policies for First Nations dialysis patients. Throughout the trial conduct, the IRGs' role has developed to provide key mechanisms for advice and guidance regarding research conduct both in this study and more broadly. Support provided to the IRGs by trial First Nations Research Officers and independent First Nations researchers/academics who simplify research concepts is critical. The IRGs have developed feedback documents and processes to participants, stakeholders, and the renal units. They guarantee culturally safe advice for embedding findings from the trial into clinical practice guidelines ensuring evidence-based approaches in managing anaemia in haemodialysis patients with hyperferritinaemia. Conclusion: Active consumer and community partnership is critical in research conduct to ensure research impact. Strong partnership with consumers in the INFERR clinical trial has demonstrated that First Nations Consumers will engage in research they understand, that addresses health priorities for them and where they feel respected, listened to, and empowered to achieve change. Plain English summary: In this paper, we present the importance of actively involving consumers in the planning, implementation and conduct of research using the example of a clinical trial among Aboriginal and/or Torres Strait Australians (First Nations Australians) who have kidney disease and are currently receiving haemodialysis. The study assesses how safe and effective it is for people on dialysis to receive iron given through the vein during dialysis when they have anaemia and high levels of a blood test called ferritin, a test used routinely to measure iron levels. Two consumer reference groups of First Nations patients on dialysis, one based in the Top End of Australia and the other based in Central Australia, are supported by First Nations Research Officers and Research Academics to make sure that the research is performed in a way that involves, respects and values First Nations participation, culture, and knowledge. Active consumer and community partnership in this study has supported robust research governance processes which we believe are crucial for knowledge translation to have a positive impact for patients. [ABSTRACT FROM AUTHOR]

Mucosal melanoma (MM) is a rare and aggressive form of melanoma with a poorer prognosis compared to other subtypes. Recent large-scale next-generation sequencing studies, including our own research, have demonstrated that the molecular characteristics and potential oncogenic drivers of MM differ significantly from those of cutaneous melanoma. The emergence of selective CDK4/6 inhibitors, already approved for use in breast cancer and undergoing phase III clinical trials for other solid tumors, represents a promising development in the treatment of MM. Recent studies have shown that CDK4/6 inhibitors not only induce cell cycle arrest but also play a crucial role in facilitating the interaction between tumor cells and the host immune system. Moreover, our findings indicate that dysregulation of cell cycle progression due to cyclin‐dependent kinase 4 (CDK4) amplification is a significant genetic characteristic in a substantial portion of MM cases. Targeting CDK4 in specific MM patients shows promise for precision cancer therapy, utilizing molecularly characterized MM patient-derived xenograft (PDX) models and clinical trials. This paper provides an overview of existing literature on CDK4/6 dysregulation in MM, as well as preclinical and clinical investigations on CDK4/6 inhibitors and potential combination therapies for MM treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Ultrasonography is a basic tool used in the evaluation of thyroid nodules, but there is no single feature of this method which predicts malignancy with statistical significance. The aim of the study is to assess the usefulness of contrast enhanced-ultrasound (CEUS) in the differential diagnosis of thyroid nodules. The highest value of the study results from the multiparameter approach to the evaluation of thyroid lesions in the light of new diagnostics methods and assessment of the unique combinations of both B-mode and CEUS features as predictors of thyroid cancers. Moreover, several qualitative contrast features predicting benign lesions were evaluated. The preliminary results indicate that CEUS is a useful tool in assessing the risk of malignancy of thyroid lesions. The combination of the qualitative enhancement parameters and B-mode sonographic features significantly increases the method's usefulness. Further studies should be performed to introduce CEUS patterns in the diagnostic algorithm of thyroid nodules. Background: Ultrasonography is a primary method used in the evaluation of thyroid nodules, but no single feature of this method predicts malignancy with high accuracy. Therefore, this paper aims to assess the utility of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of thyroid nodules. Methods: The study group comprised 188 adult patients (155 women and 33 men) who preoperatively underwent CEUS of a thyroid nodule classified as Bethesda categories II–VI after fine-needle aspiration biopsy. During the CEUS examination, 1.5 mL of SonoVue contrast was injected intravenously, after which 15 qualitative CEUS enhancement patterns were analysed. Results: The histopathologic results comprised 65 benign thyroid nodules and 123 thyroid carcinomas. The dominant malignant CEUS features, such as hypo- and heterogeneous enhancement and slow wash-in phase, were evaluated, whereas high enhancement, ring enhancement, and a slow wash-out phase were assessed as predictors of benign lesions. Two significant combinations of B-mode and CEUS patterns were noted, namely, hypoechogenicity with heterogeneous enhancement and non-smooth margins with hypo- or iso-enhancement. Conclusions: The preliminary results indicate that CEUS is a useful tool in assessing the risk of malignancy of thyroid lesions. The combination of the qualitative enhancement parameters and B-mode sonographic features significantly increases the method's usefulness. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is a common clinical disorder, ranks as the second most disabling disease worldwide, and often manifests with unilateral onset. Contralateral acupuncture (CAT), as a classical acupuncture method, has been proven to be effective in the treatment of migraine without aura (MWoA). However, its neural mechanisms have not been investigated using multimodal magnetic resonance imaging (MRI). Methods and analysis: In this multimodal neuroimaging randomized trial, a total of 96 female MWoA participants and 30 female healthy controls (HCs) will be recruited. The 96 female MWoA participants will be randomized into three groups: Group A (CAT group), Group B [ipsilateral acupuncture (IAT) group], and Group C (sham CAT group) in a 1:1:1 allocation ratio. Each group will receive 30 min of treatment every other day, three times a week, for 8 weeks, followed by an 8-week follow-up period. The primary outcome is the intensity of the migraine attack. Data will be collected at baseline (week 0), at the end of the 8-week treatment period (weeks 1-8), and during the 8-week follow-up (weeks 9-16). Adverse events will be recorded. Multimodal MRI scans will be conducted at baseline and after 8-week treatment. Discussion: This study hypothesized that CAT may treat MWoA by restoring pathological alterations in brain neural activity, particularly by restoring crossintegrated functional connectivity with periaqueductal gray (PAG) as the core pathological brain region. The findings will provide scientific evidence for CAT in the treatment of MWoA. Ethics and dissemination: The Medical Ethics Committee of the Second Affiliated Hospital of Yunnan University of Chinese Medicine has given study approval (approval no. 2022-006). This trial has been registered with the Chinese Clinical Trials Registry (registration no. ChiCTR2300069456). Peer-reviewed papers will be used to publicize the trial's findings. [ABSTRACT FROM AUTHOR]

Clinical trials have evolved with digital technologies and tend towards patient-centricity. A multi-stakeholder approach is needed to address the emerging complexities in clinical trials. In particular, the introduction of digital technologies and an emphasis on patientcentricity are the major trends in clinical trials. In response, we established a public-private partnership-based organization named Advanced Regulatory Innovation for Clinical Trials Transformation (ARICTT). Eleven organizations in total, from academia, industry, and regulatory agencies, participate in ARICTT. Based on multi-stakeholder collaboration from academia, industry, and government/regulatory bodies, we collected and prioritized current topics in clinical trials based on an internal survey. We established a three-year roadmap with axes that were termed trend, goal, structure, theme, topic, and method. In addition, we planned the development of recommendations based on real-world cases with feasibility studies. We developed appropriate organizational structure to fulfill the roadmap of ARICTT. The selected topics were decentralized clinical trials during the first year, followed by the three topics that were awarded the highest priority according to the internal survey: advances in the informed consent process, supporting sites using digital technology, and an effective recruitment strategy. We developed a case-based recommendation paper presenting an overview of the regulatory landscape and practical considerations with explanatory cases. We also designed and conducted fully decentralized trials to evaluate considerations in real-world settings for the selected topics. Overall engagement and communication were supported by the online platform and annual symposiums. In conclusion, we established a multi-stakeholder, public-private partnership-based organization to accelerate the transformation of clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: This article summarises the international Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial for patients with rhabdomyosarcoma. The trial has multiple research questions relating to chemotherapy and radiotherapy and biological and imaging studies as well as to the introduction of novel drugs for patients with very high-risk disease. The rationale, background, and international collaboration of the trial are explained, and how the data will be used to inform future studies is outlined. The Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial is an overarching, multinational study for children and adults with rhabdomyosarcoma (RMS). The trial, developed by the European Soft Tissue Sarcoma Study Group (EpSSG), incorporates multiple different research questions within a multistage design with a focus on (i) novel regimens for poor prognostic subgroups, (ii) optimal duration of maintenance chemotherapy, and (iii) optimal use of radiotherapy for local control and widespread metastatic disease. Additional sub-studies focusing on biological risk stratification, use of imaging modalities, including [18F]FDG PET-CT and diffusion-weighted MRI imaging (DWI) as prognostic markers, and impact of therapy on quality of life are described. This paper forms part of a Special Issue on rhabdomyosarcoma and outlines the study background, rationale for randomisations and sub-studies, design, and plans for utilisation and dissemination of results. [ABSTRACT FROM AUTHOR]

Gut microbiota, regarded as the second genome of the human body, has become a key modulator of cancer treatment. It is an emerging topic in precision medicine, and many studies have reported that the variability in most diseases and individuals is related to gut microbiota characteristics. Numerous clinical studies on cancer treatment have demonstrated a correlation between therapeutic responses to immunotherapeutic cancer drugs and gut immunity or the microbiome. In this paper, we present the current clinical research on herbal medicines and gut microbiota and explore the possibility of integrative cancer treatment with herbal medicines and immunotherapeutic cancer drugs. We identified six clinical trials enrolled in the Clinical Research Information Service and five clinical studies on gut microbiota and herbal medicines in MEDLINE via PubMed. Generally, clinical studies have used 16S rRNA sequencing to analyze the gut microbiota. Study findings have suggested that the gut microbiota can be used as a biomarker to predict the pharmacological effects of herbal medicines. Gut microbiota modifications by herbal medicines may inhibit tumor progression. Herbal medicines are metabolized to active substances through interactions with the microbiome and control the dysbiosis of the gut microbiome. Further research on the possibility of individualized precision medicine by analyzing the gut microbiota after administering herbal medicine is needed. [ABSTRACT FROM AUTHOR]

Eating disorders (EDs) are serious, deadly disorders that emerge in adolescence and early adulthood. Further, reported incidences of EDs are increasing worldwide. As such, accessible, affordable, and effective early intervention and prevention efforts are critical. The Body Project is a well-established ED prevention program with demonstrated success at reducing ED symptom severity and the risk of onset of EDs in young females. However, it has not yet been formally evaluated in an Australian population, nor have the benefits of the treatment for young people of all genders been thoroughly investigated. This protocol paper outlines the design for a study which aims to investigate the outcomes and feasibility of the Body Project as a brief ED prevention program within an Australian youth mental health service: headspace Camperdown. This pragmatic trial will compare outcomes between a Body Project treatment group and a Treatment-as-usual control group. Primary outcomes include body image concerns, ED symptomatology and general psychological distress, measured pre- and post-treatment, and at one-month follow-up. All young people attending headspace Camperdown for care are eligible for participation in the trial. The Body Project program is comprised of four group-based 1.5 h sessions run over 4 consecutive weeks. Overall, a trial of the Body Project as an ED prevention program is warranted to investigate the outcomes of the intervention in this sample and will provide valuable information about the feasibility for widespread implementation of the treatment as part of a stepped-care approach to intervention for EDs at youth mental health service locations across Australia. ANZCTR Trial Registration Number: ACTRN12623000695606 (registered 29 June 2023). [ABSTRACT FROM AUTHOR]

Background: The new European Medicines Agency (EMA) Clinical Trials Information System (CTIS), based on the Clinical Trials Regulation (CTR EU 536/2014), came into full effect on 31 January 2022 and was intended to provide an easier, more streamlined approach to the registration of clinical trials taking place in Europe. Using the experience gained on the new regulatory framework from three multi-national European clinical research studies of outbreak-prone infectious diseases, this article describes the advantages and shortcomings of the new clinical trial submission procedure. Methods: We report the time to approval, size of the application dossier, and number of requests for information (RFIs) for each study. We also explore the experience of each study within the regulatory framework and its use of CTIS to document the real-world, practical consequences of the system on individual studies. The study assesses the experience of three multi-country studies conducted in Europe working within the EU and non-EU regulatory environments. Results: While the time to regulatory and ethical approval has improved since the implementation of the new regulation, the timelines for approvals are still unacceptably slow, particularly for studies being conducted in the context of an evolving outbreak. Within the new regulatory approval procedure, there is evidence of conflicting application requirements, increased document burden, barriers to submitting important modifications, and debilitating technical hurdles. Conclusions: CTIS promised to lower the administrative bar, but unfortunately this has not been achieved. There are challenges that need to be urgently confronted and addressed for international research collaborators to effectively manage health crises in the future. While the value of multi-national outbreak research is clear, the limitations and delays imposed by the system, which raise challenging ethical questions about the regulation, are prejudicial to all clinical research, especially publicly funded academic studies. This report is relevant to both regulators and clinical researchers. It is hoped that these findings can help improve pan-European clinical trials, especially for the purpose of epidemic preparedness and response. Trial registration: This paper references experiences gained during management of three pan-European trials: EU-SolidAct's Bari-SolidAct (CT No. 2022-500385-99-00 - 15 March 2022) and AXL-SolidAct (CT No. 2022-500363-12-00 - 19 April 2022), and MOSAIC (CT No. 2022-501132-42-00 - 22 June 2022). [ABSTRACT FROM AUTHOR]

In this paper, we discuss challenges associated with implementing a policy for Ancillary Care (AC) for related and unrelated (serious) adverse events during an Ebola vaccine trial conducted in a remote area of the Democratic Republic of the Congo. Conducting clinical trials in resourceconstrained settings can raise context-related challenges that have implications for study participants' health and wellbeing. During the Ebola vaccine study, three participants were injured in road traffic accidents, but there were unexpected difficulties when trying to apply the AC policy. First, because of the nature of the adverse events, the insurer refused to cover the costs. Second, the AC policy did not address treatments by traditional medicine, even though traditional medicines are frequently used and highly trusted in the study community. This highlighted a contrast between the researchers' well-intentioned AC approach and the participants' legitimate preferences. The way in which researchers should address their responsibility to provide AC is not straightforward; it requires contextualization. Our experience highlights the importance of involving community representatives and the local ethics committee to ensure development of an AC policy that is culturally and ethically appropriate. Additionally, the insurance contract should clearly stipulate which adverse events are linked to the trial participation, and thus eligible for coverage, to avoid controversies when claims are made. [ABSTRACT FROM AUTHOR]

We have developed Convacell®—a COVID-19 vaccine based on the recombinant nucleocapsid (N) protein of SARS-CoV-2. This paper details Convacell's® combined phase I/II and IIb randomized, double-blind, interventional clinical trials. The primary endpoints were the frequency of adverse effects (AEs) and the titers of specific anti-N IgGs induced by the vaccination; secondary endpoints included the nature of the immune response. Convacell® demonstrated high safety in phase I with no severe AEs detected, 100% seroconversion by day 42 and high and sustained for 350 days anti-N IgG levels in phase II. Convacell® also demonstrated a fused cellular and humoral immune response. Phase IIb results showed significant post-vaccination increases in circulating anti-N IgG and N protein-specific IFNγ+-producing PBMC quantities among 438 volunteers. Convacell® showed same level of immunological efficacy for single and double dose vaccination regimens, including for elderly patients. The clinical studies indicate that Convacell® is safe and highly immunogenic. [ABSTRACT FROM AUTHOR]

Objective·To analyze the development trend and current situation of high-level clinical research at Shanghai Jiao Tong University School of Medicine (SJTUSM) from 2015 to 2023, and to summarize the strategies for improving clinical research capability of SJTUSM, aiming to provide reference and inspiration for medical universities to promote high-level clinical research.Methods·Papers published by first authors from SJTUSM or its affiliated hospitals during this period were retrieved in the Web of Science core collection database. General descriptive methods were used to quantify the number of clinical research papers, registered clinical trials, clinical research talent teams, and the current status of clinical research cooperation. Bibliometric methods were used to visualize the international collaboration and topic distribution of retrieved clinical research papers. The differences in the number of clinical research publications, Q1 publications, publications in top clinical medical journals, and full-time researchers between the periods of 2015‒2018 and 2019‒2023 were compared and analyzed.Results·From 2015 to 2023, a total of 9 468 clinical research papers were published by SJTUSM or its affiliated hospitals as the first author′s institution, showing an increasing trend year by year. During this period, the number of Q1 publications of SJTUSM′s clinical research, publications in top clinical medical journals, clinical studies registered on the United States Clinical Trial Registry website, clinical studies registered on the Chinese Clinical Trial Registry website, clinical guidelines and expert consensus publications, full-time research team members, and newly added national-level talents all showed an overall upward trend. Tumors, cardiovascular and cerebrovascular diseases, major chronic diseases, and mental illnesses were the main research hotspots. A total of 1 308 papers (13.82%) were international collaborative papers. Developed countries/regions such as the United States (733 papers), Australia (137 papers), and the United Kingdom (99 papers) were closely cooperating with SJTUSM. From 2019 to 2023, there was a significant increase in the number of clinical research papers, Q1 publications, publications in top clinical medical journals, and newly added full-time research team members in affiliated hospitals compared to the period from 2015 to 2018 (all P

Magnetic induction hyperthermia (MIH), is a technique that has developed rapidly in recent years in the field of tumor thermotherapy. It implants a magnetic heating medium (millimeter-sized heat seeds, micron-sized magnetic particles and nanometer-sized magnetic fluids, etc.) inside the tumor. The material heats up under the induction of an external alternating magnetic field (100–500 kHz), which causes a high temperature zone to rapidly form in the local biological tissues and induces apoptosis in tumor cells. Magnetic induction hyperthermia has the advantages of high safety, strong targeting, repeatable treatment, and the size of the incision during treatment is negligible compared to surgical resection, and is currently used in clinical treatment. However, the millimeter-scale heat seed heating that is typically used in treatments can result in uneven temperatures within the tissue. Common MIH heating devices are bulky and complex in design, and are not easy for medical staff to get their hands on, which are issues that limit the diffusion of MIH. In this view, this paper will discuss the basic theoretical research on MIH and the progress of MIH-related technologies, with a focus on the latest research and development results and research hotspots of nanoscale ferromagnetic media and magnetic heat therapy devices, as well as the validation results and therapeutic efficacy of the new MIH technology on animal experiments and clinical trials. In this paper, it is found that induction heating using magnetic nanoparticles improves the uniformity of the temperature field, and the magneto-thermal properties of nanoscale ferromagnetic materials are significantly improved. The heating device was miniaturized to simplify the operation steps, while the focusing of the magnetic field was locally enhanced. However, there are fewer studies on the biotoxicity aspects of nanomedicines, and the localized alternating magnetic field uniformity used for heating and the safety of the alternating magnetic field after irradiation of the human body have not been sufficiently discussed. Ultimately, the purpose of this paper is to advance research related to magnetic induction thermotherapy that can be applied in clinical treatment.

• CAM offers a potentially effective treatment for CIPN patients. • CAM is now considered safe and feasible under the guidance of clinicians. • More rigorous protocols should be considered in future clinical trials of CAM. • Focus on emotional processing in cancer survivors when applying CAM therapy. To summarizes the available evidence on the effectiveness, safety, and feasibility of complementary and alternative medicine (CAM) in the management of chemotherapy-induced peripheral neuropathy (CIPN). We searched for systematic reviews, and meta-analyzes published up to April 2023 in the Pubmed and Web of Science databases. The latest original research on related topics was also reviewed. The search was restricted to English-language papers. Two independent reviewers performed a quality assessment of the identified literature. The results of 35 systematic reviews and meta-analyzes were included in this study. Preliminary evidence suggests that CAM, including acupuncture, physical activity (PA), herbal and nutritional supplements, mind-body therapies, touch therapy, and non-invasive neuromodulation techniques, have shown tremendous potential for the prevention and treatment of CIPN. Of these, there is strong evidence supporting acupuncture, PA, and herbal medicine. However, existing clinical studies are also limited by the heterogeneity of study methods, insufficient sample size, and poor study design. Further studies are needed to validate the efficacy of CAM in patients with CIPN and to elucidate potential therapeutic mechanisms. Current research has reached a preliminary conclusion suggesting the potential efficacy of certain CAMs in the management of CIPN. Future clinical trials should incorporate more robust study design protocols and larger sample sizes to enhance the validity of findings. [ABSTRACT FROM AUTHOR]

Abstract Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell‐ and platelet‐rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in‐human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2‐year follow‐up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell‐ and PRP‐treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost‐effectiveness assessments to determine the benefits of cell/PRP treatments.

Background: The Foods with Function Claim was introduced in Japan in April 2015 to make more products available that are labeled with health functions. A product’s functionality of function claims must be explained by the scientific evidence presented in clinical trials (CTs) or systematic reviews, but the quality of recent CTs is unclear. The purpose of this study was to evaluate the risk of bias (RoB) using “a revised tool to assess risk (RoB 2)” published in 2018 for notifications based on all recent CTs published on the Consumer Affairs Agency website. Methods: A total of 38 submitted papers based on CTs that were published on the Consumer Affairs Agency website during the period from 1 January 2023 to 30 June 2024 were eligible. The RoB 2 tool provides a framework for considering the risk of bias in the findings of any type of randomized trial. This tool with five domains was used to evaluate the quality of research methods. Results: Eligible CTs were assessed as “low risk” (11%, n = 4), “medium risk” (13%, n = 5), and “high risk” (76%, n = 29). A number of highly biased papers were published. Bias occurred in all five domains, especially “bias in selection of the reported result (Domain 5)”, which was the most serious (“high risk”; 75%). For elements correlated with RoB, there was no significant difference (p = 0.785) in the RoB 2 score between for-profit and academic research in the author’s affiliated organization. There was no significant difference (p = 0.498) in the RoB score between the published year categories of 2000–2019 and 2020–2024, and no significant difference (p = 0.643) in the RoB score between English and Japanese language publications. Conclusion: Overall, the quality of the latest CTs submitted after 2023 was very low, occurring in all five domains, and was most serious for “bias in selection of the reported result (Domain 5)”.

Background : Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival. Methods: CompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention. Eligible OPC patients include those with human papillomavirus (HPV) negative, T1–T4, N1–N3 or T3–4, N0, or HPV positive N3, T4, or current smokers (or ≥ 10 pack years previous smoking history) with T1–T4, N2b–N3. CompARE was originally designed with four arms (one control [arm 1] and three experimental: arm 2—induction chemotherapy followed by arm 1; arm 3—dose-escalated radiotherapy plus concomitant cisplatin; and arm 4—resection of primary followed by arm 1). The three original experimental arms have been closed to recruitment and a further experimental arm opened (arm 5—induction durvalumab followed by arm 1 and then adjuvant durvalumab). Currently recruiting are arm 1 (control): standard treatment of 3-weekly cisplatin 100 mg/m2 or weekly 40 mg/m2 with intensity-modulated radiotherapy using 70 Gy in 35 fractions ± neck dissection determined by clinical and radiological assessment 3 months post-treatment, and arm 5 (intervention): one cycle of induction durvalumab 1500 mg followed by standard treatment then durvalumab 1500 mg every 4 weeks for a total of 6 months. The definitive and interim primary outcome measures are overall survival time and event-free survival (EFS) time, respectively. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complication rates, and cost-effectiveness. The design anticipates that after approximately 7 years, 84 required events will have occurred to enable analysis of the definitive primary outcome measure for this comparison. Planned interim futility analyses using EFS will also be performed. Discussion: CompARE is designed to be efficient and cost-effective in response to new data, emerging new treatments or difficulties, with the aim of bringing new treatment options for these patients. Trial registration: ISRCTN ISRCTN41478539. Registered on 29 April 2015 [ABSTRACT FROM AUTHOR]

Background Lewy body dementia (LBD) is a prevalent yet frequently underdiagnosed form of dementia, accounting for up to 15% of all dementia cases. Aims This study aims to increase awareness and advocacy for LBD by gathering and critically assessing the economic evidence, including the cost of illness and cost-effectiveness of interventions for managing LBD. Method A systematic literature review was undertaken with EMBASE, Medline, CINAHL, PsycINFO, NHS Economic Evaluation Database and EconLit. This search was supplemented by grey literature on Google Scholar and reviewing the reference lists of identified studies. The papers included in the review were published between 2008 and 2023, and involved participants with LBD (dementia with Lewy bodies or Parkinson's disease dementia), which either addressed the cost of illness or conducted an economic evaluation. Results Thirteen papers were included, comprising ten cost-of-illness studies and three economic evaluations. The cost of LBD tends to be higher than that of other forms of dementia, such as Alzheimer's disease, and these costs escalate more steeply as the disease progresses. These cost differences may not be solely influenced by the subtype of dementia, but possibly also by patient characteristics like physical and cognitive abilities. Cost-effectiveness of potential interventions for LBD is limited. Conclusions Despite numerous drug trials and other interventions for dementia, very few have targeted LBD, let alone explored the cost-effectiveness of such therapies for LBD. This disparity highlights the urgent need for cost-effective strategies and interventions targeting LBD. We propose the establishment of universally accepted standards for LBD research.

Background: This review aims to perform a complete evaluation of the impact of photobiomodulation (PMB) on postoperative endodontic pain. Materials and Methods: The PRISMA checklist was used to perform this systematic review. The electronic databases were searched, including Google Scholar, PubMed, and Embase. Sixty-three papers were obtained through a main electronic search and a hand search. Nine trials met the criteria after screening the titles, abstracts, and/or full texts. Results: Seven out of nine studies showed that PMB has a significant impact on relieving postoperative endodontic pain, with no statistically significant difference in the severity of pain between the laser and control groups in the two remaining studies. In addition, eight studies showed no adverse effects, indicating that we can remove the adverse effects of drugs such as nonsteroidal anti-inflammatory drugs. However, one study showed evidence of the consequences of PMB application on teeth with symptomatic irreversible pulpitis. Therefore, it can be concluded that PMB should not be used in teeth with pain because of irreversible pulpitis. Conclusion: Although there is some understanding from a cellular viewpoint of the effects of PMB, there is still some uncertainty about whether these cell-level modifications impact reducing the postendodontic pain. [ABSTRACT FROM AUTHOR]

BACKGROUND: It remains uncertain which endothelial keratoplasty (EK) technique yields the best outcomes while maintaining safety, particularly in eyes with coexisting ocular conditions. Moreover, the impact of endothelial cell loss (ECL) on long-term graft survival requires further investigation. Adjuvant ripasudil, a rho kinase inhibitor, may address the challenge of ECL in corneal transplantation. This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1), a multicentre, outcome-masked, randomised, placebo-controlled, four-arm clinical trial. METHODS: A total of 160 eligible patients with endothelial dysfunction will be enrolled from five participating sites in the USA. The patients will be randomly assigned in a 2×2 factorial design to one of the following treatment groups: group 1-ultrathin Descemet stripping endothelial keratoplasty (UT-DSAEK) plus topical ripasudil 0.4%; group 2-UT-DSAEK plus topical placebo; group 3-Descemet membrane endothelial keratoplasty (DMEK) plus topical ripasudil 0.4% and group 4-DMEK plus topical placebo. Primary outcomes include the best spectacle-corrected visual acuity at 12 months and ECL at 12 months. Secondary outcomes include visual acuity at different time points, vision-related quality of life, endothelial cell morphology and cost-effectiveness. RESULTS: The study outcomes will be analysed using mixed effects linear regression models, taking into account the treatment arms and relevant covariates. Adverse events, including rebubble procedures, graft failure and graft rejection, will be documented and analysed using appropriate statistical methods. CONCLUSION: DETECT I aims to provide evidence on the comparative effectiveness of UT-DSAEK and DMEK, as well as the potential benefits of adjuvant topical ripasudil in reducing ECL. The results of this trial will contribute to optimising corneal transplantation techniques and improving long-term graft survival, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation. ETHICS AND DISSEMINATION: A data and safety monitoring committee (DSMC) has been empaneled by the NEI.All study protocols will be subject to review and approval by WCG IRB as the single IRB of record.This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request.

Background: The Otago Exercise Programme is an effective intervention for falls prevention. However, there is limited evidence in relation to studies that compare efficacy for falls prevention when delivered Otago Exercise Programme in a group or individual format in a primary care context. Objective: To compare the Otago Exercise Programme delivered as a group vs. individual format for community dwelling older adults, over a one year period. The hypothesis was that neither format would be inferior to the other. Methods: Design: A four-year multicentre, randomized, non-inferiority clinical trial, with two arms— Otago Exercise Programme group training and individual Otago exercise training. Setting(s): 21 primary healthcare centers. Participants: A sample size of 728 participants was established. Participants were aged between 65 and 80 years; living in the community; able to walk independently; and agreed to take part in the study and provided signed informed consent. Intervention: The Otago Exercise Programme was delivered mainly by nurses in primary care, with five face to face sessions, and a reinforcement 6 months later. Participants were encouraged to exercise at home between face to face sessions. Data collection: at baseline and after 6 and 12 months from October 2017 to 2020. Primary outcome: people who reported at least one fall. Secondary outcomes: number of falls, cause of falls, consequences and assistance, adherence and satisfaction. Group allocation was blinded to the researchers involved in analysis. Reporting: Consolidated Standards of Reporting Trials recommendations for the Statement for Randomized Trials of Nonpharmacologic Treatments. Results: Eight hundred twenty-seven participants were randomized (226 were allocated in group training and 272 in individual training). The analysis of the proportion of people who reported at least one fall and number of falls showed no differences between individual and group training. Assessment of the equivalence between the interventions at 12 months showed that the confidence interval for the difference of people who reported at least one fall was found to be within the equivalence limit of 10% considered. However, in those participants with a previous history of falls, group format showed potentially greater benefit. The participants in individual training presented higher scores on the Exercise Adherence Rating Scale test. No differences were found in satisfaction between the groups. Conclusions: The group Otago Exercise Programme is equivalent to individually delivered Otago Exercise Programme in terms of prevention of falls over a 12-month follow up. Adherence was higher in individual training. Implications: Healthcare professionals could offer either Otago Exercise Programme format dependent on patient preference and be confident that that standardized intervention provides patient benefit. Trial Registration: ClinicalTrials.gov (NCT03320668). Data registration 31/10/2017. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced cancer and family caregivers often use avoidant coping strategies, such as delaying advance care planning discussions, which contribute to deterioration in their quality of life. Mindfulness-based interventions have shown promise in improving quality of life in this population but have rarely been applied to advance care planning. This pilot trial examined the preliminary efficacy of a group-based Mindfulness to Enhance Quality of Life and Support Advance Care Planning (MEANING) intervention for patient-caregiver dyads coping with advanced cancer. Primary outcomes were patient and caregiver quality of life or well-being, and secondary outcomes included patient advanced care planning engagement (self-efficacy and readiness) and other psychological and symptom outcomes. Methods: In this pilot trial, dyads coping with advanced cancer were recruited from five oncology clinics in the midwestern U.S. and randomized to six weekly group sessions of a mindfulness intervention (n = 33 dyads) or usual care (n = 22 dyads). Outcomes were assessed via surveys at baseline, post-intervention, and 1 month post-intervention. All available data were included in the multilevel models assessing intervention efficacy. Results: Patients in the MEANING condition experienced significant increases in existential well-being and self-efficacy for advance care planning across follow-ups, whereas usual care patients did not. Other group differences in outcomes were not statistically significant. These outcomes included other facets of patient well-being, caregiver quality of life, patient readiness for advance care planning, caregiver burden, and patient and caregiver depressive symptoms, anxiety, sleep disturbance, cognitive avoidance, and peaceful acceptance of cancer. However, only MEANING patients showed moderate increases in psychological well-being across follow-ups, and MEANING caregivers showed moderate increases in quality of life at 1-month follow-up. Certain psychological outcomes, such as caregiver burden at 1-month follow-up, also showed moderate improvement in the MEANING condition. Patients in both conditions reported small to moderate increases in readiness to engage in advance care planning. Conclusions: A mindfulness-based intervention showed promise in improving quality-of-life and advance care planning outcomes in patients and caregivers coping with advanced cancer and warrants further testing. Trial Registration: ClinicalTrials.gov NCT03257007. Registered 22 August 2017, https://clinicaltrials.gov/ct2/show/NCT03257007. [ABSTRACT FROM AUTHOR]

The use of digital health technologies to measure outcomes in clinical trials opens new opportunities as well as methodological challenges. Digital outcome measures may provide more sensitive and higher-frequency measurements but pose vital statistical challenges around how such outcomes should be defined and validated and how trials incorporating digital outcome measures should be designed and analysed. This article presents eight methodological questions, exploring issues such as the length of measurement period, choice of summary statistic and definition and handling of missing data as well as the potential for new estimands and new analyses to leverage the time series data from digital devices. The impact of key issues highlighted by the eight questions on a primary analysis of a trial are illustrated through a simulation study based on the 2019 Bellerophon INOPulse trial which had time spent in MVPA as a digital outcome measure. These eight questions present broad areas where methodological guidance is needed to enable wider uptake of digital outcome measures in trials. [ABSTRACT FROM AUTHOR]

Background: Thalassemia is one of the most common genetic disorders. Patients with beta-thalassemia major confront serious clinical and psychosocial challenges in their all lives, which require coping strategies. It appears that psychological interventions are necessary to improve their coping skills. The aim of this study was to determine the effect of applying emotional intelligence components on coping strategies in adolescents with beta- thalassemia major. Methods: This randomized clinical trial study involved 60 teenagers with beta- thalassemia major who were divided equally into intervention and control groups. The experimental group participated in 9 sessions of an emotional intelligence program consisting of 90 min, held both virtually and in person, two sessions per week. We investigated problem-focused and emotion-focused (including positive emotion-focused and negative emotion-focused) coping strategies of both groups of adolescents using the Billings and Moos questionnaire before the intervention, immediately after the intervention, and one month after the intervention. Data were analyzed using SPSS 21. Then, according to the research objectives, independent t-tests, Chi-square, Mann–Whitney, repeated measures Analysis of Variance (ANOVA) and Bonferroni test were used. Results: In experimental group, the mean score of problem-focused (problem-solving, cognitive evaluation) and positive emotion-focused (social support) coping increased from (14.2 ± 2.6) and (5.0 ± 0.5) before the intervention to (29.6 ± 3.1) and (10.9 ± 1.3) one month after the intervention, respectively (P < 0.001). However, the mean score of emotional inhibition and somatic inhibition (negative emotion-focused) decreased from (13.8 ± 1.7) and (6.7 ± 1.5) before the intervention to (8.6 ± 2.0) and (3.8 ± 1.8) one month after the intervention, respectively (P < 0.001). While the mean score of problem-focused and emotion-focused coping strategies before and one month after the intervention remained stable in the control group. Conclusions: Adolescents with beta-thalassemia suffer from psychosocial disorders and they also cope maladaptive with their illness. Applying emotional intelligence has improved their coping strategies. Caregivers should be encouraged to assess coping skills in teenagers with beta-thalassemia major and use methods such as emotional intelligence to improve them. Therefore, it can help these adolescents to deal effectively with stress and complications of the disease. Trial registration number: IRCT20210521051356N1 (17/06/2021). [ABSTRACT FROM AUTHOR]

Cognitive decline, a common consequence of aging, detrimentally affects independence, physical activity, and social interactions. This decline encompasses various cognitive functions, including processing speed, memory, language, and executive functioning. This trial aimed to investigate, with a double-blind, placebo-controlled clinical trial on 96 healthy older adults, the efficacy of once-daily 250 mg of a standardized grape (Vitis vinifera L.) juice extract (Cognigrape®) in improving short- and long-term cognitive functions. The results revealed significant improvements across multiple cognitive domains, notably immediate and delayed memory, visuospatial abilities, language, and attention, with improvements occurring within just 14 days, which continued to improve after 84 days of supplementation. The extract exhibited statistically significant enhancements in the Mini-Mental State Evaluation (MMSE), assessment of neuropsychological status (RBANS), "Esame Neuropsicologico Breve 2 (ENB-2), and Modified Bells Test (MBT) scores, with the latter test revealing a significant improvement in selective attention within just 90 min of the first dose. These positive results highlight the potential this natural grape extract has on improving cognitive function both acutely and chronically in a healthy aging population, which in turn supports a longer health span, at least cognitively. [ABSTRACT FROM AUTHOR]

Background: Gingival diseases, encompassing a spectrum of oral health concerns, represent a prevalent issue within the global population. Despite their widespread occurrence, the research landscape concerning effective interventions, particularly those rooted in herbal products, remains somewhat limited. Addressing this knowledge gap, the current study undertook a comprehensive evaluation aimed at assessing the clinical efficacy of a novel intervention: a 5% thymoquinone (TQ) gel. This investigation specifically focused on the application of TQ gel as an adjunctive measure to the standard protocol of scaling (SC) in individuals afflicted with plaque-induced gingivitis. Through rigorous examination and analysis, this study seeks to provide valuable insights into the potential utility and therapeutic benefits of this herbal-based intervention in managing gingival diseases. Objective: To evaluate the efficacy of 5% TQ gel using a novel liposome drug delivery as a topical application following SC in gingivitis patients. Methods: A double-blinded, parallel, randomized controlled clinical trial. The study was performed at the Faculty of Dentistry, King Abdulaziz University, and Qassim University, Saudi Arabia. This trial enrolled 63 participants in an age group between 18 and 40 years attending the outpatient clinics of the Faculty of Dentistry, Qassim University, Saudi Arabia, and a clinical diagnosis of gingivitis was made. The enrolled subjects were categorized into three groups: Group I—TQ gel with SC, Group II—Placebo with SC, and Group III—SC alone, and clinical outcomes were measured at baseline and two-week follow-up visits. Plaque index (PI), papillary bleeding index (PBI), and any adverse events with TQ gel are categorized as mild, moderate, and severe. 63 patients. Group I (n = 21); Group II (n = 21); Group III (n = 21). Results: The paired t-test compared the mean differences in PI and PBI at two time points and it was observed that there were significant differences in Group I with p-values of 0.04 and 0.05, respectively. A one-way ANOVA test was performed and it showed significant differences in the mean scores between the three groups for PI (p-value—0.01) and PBI (p-value—0.05). The post hoc Tukey's test compared the mean differences in PI and PBI between the groups and the results were in favor of Group I which used TQ gel with SC. Conclusions: The clinical trial concluded that the plaque and gingival bleeding scores were significantly reduced in the group of patients who intervened with TQ gel following SC when compared to SC-alone and placebo groups. Also, there were significant reductions in the scores from the baseline to the two-week follow-up visit in patients treated with TQ gel and SC. [ABSTRACT FROM AUTHOR]

The future directions in leveraging real-world evidence (RWE) and real-world data (RWD) in the field of lymphoma, as compared to traditional experimental clinical trials, are poised to significantly impact research methodologies, treatment strategies, and patient care. Current methods of clinical trials involve a well-controlled design and patient selection bias. Integrating RWE and RWD with experimental clinical trials offers a multifaceted approach to understanding lymphoma and enhancing patient outcomes. In this review, we discuss how RWE has helped shape lymphoma clinical trials, and we compare and evaluate evidence obtained from real-world lymphoma studies/databases with that obtained from clinical trials. We also discuss methods for utilizing surrogate endpoints to facilitate clinical trials and expedite drug development. RWE can be leveraged to bridge the gap between data obtained from clinical trial populations and the broader patient population encountered in clinical practice, by highlighting differences in outcomes and the need for effective treatment strategies across diverse patient groups. [ABSTRACT FROM AUTHOR]

As obesity evolves as a global pandemic, the use of drugs to treat it is booming. The latest among these are Glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Along with their use, the incidence of adverse events has become more common. Although severe effects have been mentioned, details and associations are unclear regarding some of them. We performed a systematic review of studies related to GLP-1 RA drugs. Drugs that have been the subject of at least three studies meeting all our criteria were included. Analysis of GLP-1 RA therapies across eight studies, involving 4422 subjects, indicated varying rates of Serious Adverse Events (SAEs). Semaglutide demonstrated an SAE incidence of 8.9%, compared to 6.2% for Liraglutide. These results were not statistically significant. For both drugs, no clear association with pancreatitis or neoplasm was established. Discontinuation rates due to adverse effects were 10.3% for Semaglutide and 8.3% for Liraglutide. Severe adverse effects with GLP-1 RA use are not uncommon, and warrant further close monitoring when patients are started on treatment. Further studies are required to analyze the difference between the adverse effect profiles of each drug and to assess whether or not each of these severe adverse effects is dose dependent. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking has major detrimental effects on oral health. Tobacco interventions in dental settings are effective, but rarely delivered. The American Dental Hygienists Association recommends that oral health providers: Ask patients about tobacco use, Advise quitting tobacco use, and Refer to state quitlines (Ask-Advise-Refer; AAR). While AAR connects patients to counseling, it does not directly connect patients to medication. Nicotine replacement therapy sampling (NRTS) is an empirically supported intervention to provide starter packs of nicotine replacement therapy (NRT) to people who smoke. NRTS combined with AAR could be an effective tobacco treatment intervention for dental settings. Methods: This manuscript describes the study protocol for the Free Samples for Health (FreSH) study, a group randomized clinical trial testing the effectiveness of NRTS + AAR vs. AAR alone on long-term smoking abstinence. Fifty dental practices in the Midwest and Northeast nodes of the National Dental Practice-Based Research Network are randomly assigned to provide AAR and either a 2-week supply of 14-mg nicotine patches and 4-mg nicotine lozenges (NRTS condition) or an electric toothbrush (ET condition). Approximately 1,200 patients who currently smoke—regardless of interest in quitting— are recruited during dental visits. Participants complete a baseline survey in-person, then after visit, 1-, 3-, and 6-month follow-up surveys remotely. The primary outcome is carbon monoxide-confirmed 7-day point prevalence abstinence from combustible tobacco measured at 6 months post-enrollment. Secondary outcomes include: 24-h intentional quit attempts, change in cigarettes smoked per day, NRT utilization, attitudes toward NRT, intention to use NRT, and intention to quit smoking. A key informant process evaluation and cost effectiveness analysis will provide information for future implementation of NRTS. Discussion: This is the first clinical trial to assess the effectiveness of NRTS on promoting smoking cessation in dental settings. If effective, this treatment could be implemented to increase the provision of smoking cessation interventions in dental settings to provide an additional treatment access point for people who smoke. Trial Registration. Registered at ClincalTrials.gov (NCT05627596) on 11/25/2022. [ABSTRACT FROM AUTHOR]

The most prevalent cause of dementia is Alzheimer's disease. Cognitive decline and accelerating memory loss characterize it. Alzheimer's disease advances sequentially, starting with preclinical stages, followed by mild cognitive and/or behavioral impairment, and ultimately leading to Alzheimer's disease dementia. In recent years, healthcare providers have been advised to make an earlier diagnosis of Alzheimer's, prior to individuals developing Alzheimer's disease dementia. Regrettably, the identification of early-stage Alzheimer's disease in clinical settings can be arduous due to the tendency of patients and healthcare providers to disregard symptoms as typical signs of aging. Therefore, accurate and prompt diagnosis of Alzheimer's disease is essential in order to facilitate the development of disease-modifying and secondary preventive therapies prior to the onset of symptoms. There has been a notable shift in the goal of the diagnosis process, transitioning from merely confirming the presence of symptomatic AD to recognizing the illness in its early, asymptomatic phases. Understanding the evolution of disease-modifying therapies and putting effective diagnostic and therapeutic management into practice requires an understanding of this concept. The outcomes of this study will enhance indepth knowledge of the current status of Alzheimer's disease's diagnosis and treatment, justifying the necessity for the quest for potential novel biomarkers that can contribute to determining the stage of the disease, particularly in its earliest stages. Interestingly, latest clinical trial status on pharmacological agents, the nonpharmacological treatments such as behavior modification, exercise, and cognitive training as well as alternative approach on phytochemicals as neuroprotective agents have been covered in detailed. [ABSTRACT FROM AUTHOR]

Invariant natural killer T (iNKT) cells are immune cells that harness properties of both the innate and adaptive immune system and exert multiple functions critical for the control of various diseases. Prevention of graft-versus-host disease (GVHD) by iNKT cells has been demonstrated in mouse models and in correlative human studies in which high iNKT cell content in the donor graft is associated with reduced GVHD in the setting of allogeneic hematopoietic stem cell transplants. This suggests that approaches to increase the number of iNKT cells in the setting of an allogeneic transplant may reduce GVHD. iNKT cells can also induce cytolysis of tumor cells, and murine experiments demonstrate that activating iNKT cells in vivo or treating mice with ex vivo expanded iNKT cells can reduce tumor burden. More recently, research has focused on testing anti-tumor efficacy of iNKT cells genetically modified to express a chimeric antigen receptor (CAR) protein (CAR-iNKT) cells to enhance iNKT cell tumor killing. Further, several of these approaches are now being tested in clinical trials, with strong safety signals demonstrated, though efficacy remains to be established following these early phase clinical trials. Here we review the progress in the field relating to role of iNKT cells in GVHD prevention and anti- cancer efficacy. Although the iNKT field is progressing at an exciting rate, there is much to learn regarding iNKT cell subset immunophenotype and functional relationships, optimal ex vivo expansion approaches, ideal treatment protocols, need for cytokine support, and rejection risk of iNKT cells in the allogeneic setting. [ABSTRACT FROM AUTHOR]

Our prototype system designed for clinical data acquisition and recording of studies is a novel electronic data capture (EDC) software for simple and lightweight data capture in clinical research. Existing software tools are either costly or suffer from very limited features. To overcome these shortcomings, we designed an EDC software together with a mobile client. We aimed at making it easy to set-up, modifiable, scalable and thereby facilitating research. We wrote the software in R using a modular approach and implemented existing data standards along with a meta data driven interface and database structure. The prototype is an adaptable open-source software, which can be installed locally or in the cloud without advanced IT-knowledge. A mobile web interface and progressive web app for mobile use and desktop computers is added. We show the software's capability, by demonstrating four clinical studies with over 1600 participants and 679 variables per participant. We delineate a simple deployment approach for a server-installation and indicate further use-cases. The software is available under the MIT open-source license. Conclusively the software is versatile, easily deployable, highly modifiable, and extremely scalable for clinical studies. As an open-source R-software it is accessible, open to community-driven development and improvement in the future. [ABSTRACT FROM AUTHOR]

Background: Non-invasive neuroregulation techniques have been demonstrated to improve certain motor symptoms in Parkinson's disease (PD). However, the currently employed regulatory techniques primarily concentrate on stimulating single target points, neglecting the functional regulation of networks and circuits. The supplementary motor area (SMA) has a significant value in motor control, and its functionality is often impaired in patients with PD. The matching SMA-primary motor cortex (M1) paired transcranial magnetic stimulation (TMS) treatment protocol, which benefits patients by modulating the sequential and functional connections between the SMA and M1, was elucidated in this study. Methods: This was a single-center, double-blind, randomized controlled clinical trial. We recruited 78 subjects and allocated them in a 1:1 ratio by stratified randomization into the paired stimulation (n = 39) and conventional stimulation groups (n = 39). Each patient underwent 3 weeks of matching SMA-M1 paired TMS or sham-paired stimulation. The subjects were evaluated before treatment initiation, 3 weeks into the intervention, and 3 months after the cessation of therapy. The primary outcome measure in this study was the Unified Parkinson's Disease Rating Scale III, and the secondary outcome measures included non-motor functional assessment, quality of life (Parkinson's Disease Questionnaire-39), and objective assessments (electromyography and functional near-infrared spectroscopy). Discussion: Clinical protocols aimed at single targets using non-invasive neuroregulation techniques often improve only one function. Emphasizing the circuit and network regulation in PD is important for enhancing the effectiveness of TMS rehabilitation. Pairing the regulation of cortical circuits may be a potential treatment method for PD. As a crucial node in motor control, the SMA has direct fiber connections with basal ganglia circuits and complex fiber connections with M1, which are responsible for motor execution. SMA regulation may indirectly regulate the function of basal ganglia circuits. Therefore, the developed cortical pairing stimulation pattern can reshape the control of information flow from the SMA to M1. The novel neuroregulation model designed for this study is based on the circuit mechanisms of PD and previous research results, with a scientific foundation and the potential to be a means of neuroregulation for PD. [ABSTRACT FROM AUTHOR]

Background: Use of Continuous Subcutaneous Insulin Infusion (CSII) has been shown to improve glycemic outcomes in Type 1 Diabetes (T1D), but high costs limit accessibility. To address this issue, an inter-operable, open-source Ultra-Low-Cost Insulin Pump (ULCIP) was developed and previously shown to demonstrate comparable delivery accuracy to commercial models in standardised laboratory tests. This study aims to evaluate the updated ULCIP in-vivo, assessing its viability as an affordable alternative for those who cannot afford commercially available devices. Methods: This first-in-human feasibility study recruited six participants with T1D. During a nine-hour inpatient stay, participants used the ULCIP under clinical supervision. Venous glucose, insulin, and β-Hydroxybutyrate were monitored to assess device performance. Results: Participants displayed expected blood glucose and blood insulin levels in response to programmed basal and bolus insulin dosing. One participant developed mild ketosis, which was treated and did not recur when a new pump reservoir was placed. All other participants maintained β-Hydroxybutyrate < 0.6 mmol/L throughout. Conclusion: The ULCIP safely delivered insulin therapy to users in a supervised inpatient environment. Future work should focus on correcting a pump hardware issue identified in this trial and extending device capabilities for use in closed loop control. Longer-term outpatient studies are warranted. Trial Registration: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623001288617) on the 11 December 2023. [ABSTRACT FROM AUTHOR]

This study, conducted between 4 October 2013, and 30 November 2018, tested the hypothesis that triple antimicrobial therapy, targeting Mycobacterium avium subspecies paratuberculosis (MAP), long considered a putative cause, would favorably affect Crohn's disease. A double-blind multicenter study of adults with active Crohn's disease, (i.e., Crohn's Disease Activity Index [CDAI] 220–450 plus C-reactive protein ≥ 1.0 mg/dL, fecal calprotectin (FCP) >162.9 µg/g stool, or recent endoscopic or radiographic confirmation of active disease) receiving concomitant standard-of-care Crohn's disease treatment (Clinicaltrials.gov: NCT01951326) were stratified by anti-tumor necrosis factor use and randomized (1:1) to anti-MAP RHB-104 (clarithromycin 95 mg, rifabutin 45 mg, and clofazimine 10 mg per capsule) (n = 166), resulting in clarithromycin 950 mg/day, rifabutin 450 mg/day, and clofazimine 100 mg/day, or placebo (n = 165) for up to 52 weeks. A greater proportion of RHB-104 versus placebo-treated patients met the primary endpoint—remission (i.e., CDAI < 150)—at week 26 (36.7% [61/166] vs. 22.4% [37/165], respectively; 95% CI for difference: 4.6, 24.0, p = 0.0048; chi-square test). Clinical response (reduction of CDAI by ≥100 points from baseline) at week 26 (first secondary endpoint) was also higher among the patients treated with RHB-104 (73/166 [44.0%]) compared with placebo (50/165 [30.3%]; 95% CI for difference: 3.4, 24.0, p = 0.0116), and it remained higher at week 52 among the patients treated with RHB-104 (59/166 [35.5%] vs. (35/165 [21.2%] for placebo; 95% CI for difference: 4.7, 23.9, p = 0.0042). A statistically significantly greater decline in FCP (another prospective efficacy endpoint) was also observed in RHB-104-treated patients, compared with placebo, at weeks 12, 26, and 52. The rates of serious adverse events were similar between groups (RHB-104: 18.7%; placebo: 18.8%). No patient died during the study. Antimicrobial therapy directed against MAP resulted in significantly greater improvement in clinical and laboratory (FCP) measures of active Crohn's disease. [ABSTRACT FROM AUTHOR]

AuroLase® Therapy—a nanoparticle-enabled focal therapy—has the potential to safely and effectively treat localized prostate cancer (PCa), preserving baseline functionality. This article presents a detailed case of localized PCa treated with AuroLase, providing insight on expectations from the diagnosis of PCa to one year post-treatment. AuroLase Therapy is a two-day treatment consisting of a systemic infusion of gold nanoshells (~150-nm hydrodynamic diameter) on Day 1, and sub-ablative laser treatment on Day 2. Multiparametric MRI (mpMRI) was used for tumor visualization, treatment planning, and therapy response assessment. The PCa was targeted with a MR/Ultrasound-fusion (MR/US) transperineal approach. Successful treatment was confirmed at 6 and 12 months post-treatment by the absence of disease in MR/US targeted biopsies. On the mpMRI, confined void space was evident, an indication of necrotic tissues encompassing the treated lesion, which was completely resolved at 12 months, forming a band-like scar with no evidence of recurrent tumor. The patient's urinary and sexual functions were unchanged. During the one-year follow-up, changes on the DCE sequence and in the Ktrans and ADC values assist in qualitatively and quantitatively evaluating tissue changes. The results highlight the potential of gold-nanoparticle-enabled sub-ablative laser treatment to target and control localized PCa, maintain quality of life, and preserve baseline functionality. [ABSTRACT FROM AUTHOR]

We assessed the glucometabolic effects of oligomalt, a novel fully slowly digestible carbohydrate, compared with maltodextrin, in cross-over randomized controlled trials (NCT05058144; NCT05963594) involving healthy volunteers (HV), people with overweight or obesity (PwO), and people with type 2 diabetes (T2D). We tested 33 g and/or 50 g of oligomalt/maltodextrin, which were dissolved in 300 mL of water and consumed after fasting in the morning. The primary exploratory endpoint was the incremental area under the curve (iAUC) for postprandial glucose, assessed by frequent blood sampling over 3 h. Insulin levels were also assessed. In the HV cohort, a 4 h hydrogen breath test was performed with 15 g of inulin as a positive control. Analysis was performed by a mixed model. Oligomalt elicited a lower post-prandial glucose response compared to maltodextrin in HV (50 g, n = 15 [7 women], mean age/BMI 31 years/22.6 kg/m2), in PwO (33 g and 50 g, n = 26 [10 women], age/BMI 44 years/29.9 kg/m2, mean HbA1c 5.3%), and in people with T2D (50 g, n = 22 [13 women], age/BMI 61 years/31.8 kg/m2, HbA1c 7.4%), with significant reductions observed in PwO and T2D for the 0–1 h window (HV: −19% [p = 0.149]/PwO33g-38% [p = 0.0002]/PwO50g-28% [p = 0.0027]/T2D-38% [p < 0.0001]; the 0–2 h window (HV: −17% [p = 0.311]/PwO33g-34% [p = 0.0057]/PwO50g-21% [p = 0.0415]/T2D-37% [p < 0.0001]), and the 0–3 h window (HV: −15% [p = 0.386]/PwO33g-30% [p = 0.0213]/PwO50g0−19% [p = 0.0686]/T2D−37% [p = 0.0001]). The post-prandial insulin response was significantly lower, by 38–60%, across all populations, dose, and time points, with oligomalt. In HV, the breath-hydrogen pattern was comparable between oligomalt and maltodextrin, but increased significantly with inulin. These data support the glucometabolic advantages of oligomalt over maltodextrin, hence confirming it as a healthier carbohydrate, and underscoring its full digestibility. This therefore opens up the possibility for the incorporation of oligomalt in relevant food products/matrices. [ABSTRACT FROM AUTHOR]

Abstract Background Fibroblast cells have the ability to improve skin conditions through regenerative medicine and cell-based therapies. The purpose of this scoping review is to assess the contribution of fibroblast cells to skin homeostasis and extracellular matrix deposition in clinical trials involving skin disorders and cosmetic applications. Methods Using targeted search terms, published publications from January 2000 to August 2023 that addressed fibroblast uses in clinical trials of skin conditions were obtained from bibliographic databases like PubMed, Scopus, and Web of Science (WoS). Precise inclusion and exclusion criteria were used during the screening process. The potential benefits of induction treatment with fibroblasts lead to the choosing of clinical trials for this kind of treatment. Results Out of the 820 published ppapers initially identified, only 35 studies fulfilled our meticulous eligibility criteria after careful screening. To ensure clarity, we methodically eliminated any duplicate or irrelevant published papers, thereby offering a transparent account of our selection process. Conclusion This study highlights the advantages of fibroblast therapy in treating skin conditions such as diabetic foot, venous leg ulcers, and cosmetic reasons. Fibroblasts possess remarkable regenerating capabilities, making dermal fibroblast therapy crucial in cell-based and skin regenerative treatments. Nevertheless, additional research is required for more disorders and cosmetic applications.