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Background: Women in Africa are experiencing a rising burden of endometrial cancer. Research and investment to improve treatment and outcomes are critically needed. We systematically reviewed and characterized endometrial cancer-related research within a clinically relevant context to help organize and assess existing endometrial cancer research in Africa. Methods: According to PRISMA guidelines, we searched online databases for published endometrial cancer articles from African countries from January 1, 2011, to July 20, 2021. Based on our inclusion and exclusion criteria, independent reviewers documented the study design, country/region, human development index, focus of research, type of interventions performed, and histologic and molecular type to illustrate the breadth of research coverage in each region. Results: A total of 18 research articles were included. With an average Human Development Index (HDI) in Africa of 0.536, the average HDI of the represented countries in this study was 0.709. The majority (88.9%) of prospective endometrial cancer research articles in Africa were from North Africa, with Egypt encompassing 83.3% of the papers. Most of these studies focused on endometrial cancer diagnosis. Research on the treatment of endometrial cancer is still emerging (33% of papers). Of all included articles, only 11.1% represented Sub-Saharan Africa, where the majority population of black Africans reside. Conclusions: Endometrial cancer research in Africa is extremely limited, with the majority being concentrated in African countries with higher HDIs. As the incidence of endometrial cancer rises in Sub-Saharan Africa, there is a pressing need for more prospective clinical research to tackle the growing disease burden and improve outcomes. [ABSTRACT FROM AUTHOR]

[Objective] Globally, biobanks have become an essential tool for the protection and development of human genetic resources, and their development has played a very pivotal role in promoting basic research in life sciences and clinical diagnosis and treatment of major diseases. High-quality and standardized biobanks have become essential for basic research, translational clinical medicine research, and the implementation of precision medicine strategies. Recently, China has established some national or regional alliance-level biobanks; however, the issue of sharing mechanisms has always been a long-term factor restricting the full utilization of biological resources. There are a few examples of colleges and universities coordinating resources to promote the construction of school-level biobanks. [Methods] Herein, the focus is on constructing biobanks in medical colleges and universities in China, analyzing the difficulties and bottlenecks in sharing, and corresponding optimization policy references are proposed. The research methods employed are literature review, typical case analysis, survey questionnaire, and in-depth interviews, among others, to conduct multichannel and all-around research on the problem. [Results] Based on the literature survey, this paper summarizes the problems hindering biobank sharing into internal construction systems, external institutional management, and ethical issues, such as imperfect sample quality standardization and information access, informed consent, benefit sharing, and other specific issues. Through questionnaires, semi-structured interviews, and in-depth interviews, the results reveal that insufficient willingness to share, incomplete information disclosure, unclear benefit-sharing mechanism, lack of standardization of sample and information quality, and ethical concerns are the prominent problems hindering sharing. The relatively successful mechanism of the international and domestic representative biobanks in promoting sharing includes the formulation and implementation of unified biobank construction standards and norms, establishment of public and open information platforms, standardization of sharing rules and processes, benefit-sharing and distribution mechanism, and full implementation of scientific and reasonable ethical principles. [Conclusion] By referring to international and domestic successful cases while considering the advantages and foundations of medical colleges and universities, this paper proposes the following suggestions for biobank construction in medical colleges and universities. First, it is crucial to strengthen the top-level design and to create a "centralized and disaggregated" biological sample storage platform and network-sharing platform. Second, it is necessary to continuously strengthen the scientific construction of biological sample banks, promote the standardization of biological sample bank technology, boost the strength of professional management teams, and pay great attention to the disciplinary construction of biobanks. Third, strengthening the construction of the ethical governance system and ensuring reasonable informed consent and data security are important measures to promote effective data sharing while ensuring data privacy. Last, drawing on agreements signed by both parties for sample and data sharing, it is essential to establish the life cycle of research result data, constantly improve the sharing management mechanism, and innovate the benefit-sharing model. [ABSTRACT FROM AUTHOR]

This paper examines the ethical and legal challenges encountered during the GATEKEEPER Project and how these challenges informed the development of a comprehensive framework for future Large-Scale Pilot (LSP) projects. GATEKEEPER is a LSP Project with 48 partners conducting 30 implementation studies across Europe with 50,000 target participants grouped into 9 Reference Use Cases. The project underscored the complexity of obtaining ethical approval across various jurisdictions with divergent regulations and procedures. Through a detailed analysis of the issues faced and the strategies employed to navigate these challenges, this study proposes an ethical and legal framework. This framework, derived from a comparative analysis of ethical application forms and regulations, aims to streamline the ethical approval process for future LSP research projects. By addressing the hurdles encountered in GATEKEEPER, the proposed framework offers a roadmap for more efficient and effective project management, ensuring smoother implementation of similar projects in the future. [ABSTRACT FROM AUTHOR]

The prevalence of cerebral palsy (CP) varies globally, with higher rates and burden of disease in low- and middle-income countries. CP is a lifelong condition with no cure, presenting diverse challenges such as motor impairment, epilepsy, and mental health disorders. Research progress has been made but more is needed, especially given consumer demands for faster advancements and improvements in the scientific evidence base for interventions. This paper explores three strategies to accelerate CP research: consumer engagement, global clinical trial networks, and adaptive designs. Consumer engagement involving individuals with lived experience enhances research outcomes. Global clinical trial networks provide efficiency through larger and more diverse participant pools. Adaptive designs, unlike traditional randomized controlled trials, allow real-time modifications based on interim analyses, potentially answering complex questions more efficiently. The establishment of a CP Global Clinical Trials Network, integrating consumer engagement, global collaboration, and adaptive designs, marks a paradigm shift. The Network aims to address consumer-set research priorities. While challenges like ethical considerations and capacity building exist, the potential benefits for consumers, clinicians, researchers, and funding bodies are substantial. This paper underscores the urgency of transforming CP research methodologies for quicker translation of novel treatments into clinical practice to improve quality of life for those with CP. [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]

Simple Summary: This paper provides a review of statistical methods for tumor-agnostic clinical trials. In particular, the review focuses on basket trials and provides methodological insights into various Bayesian approaches. The key concept of borrowing information through Bayesian hierarchical models is emphasized, and some novel trial designs are introduced. The review is expected to provide oncology and biostatistics researchers with more exposure to powerful Bayesian methods for the design and analysis of tumor-agnostic clinical trials. Basket trials allow simultaneous evaluation of a single therapy across multiple cancer types or subtypes of the same cancer. Since the same treatment is tested across all baskets, it may be desirable to borrow information across them to improve the statistical precision and power in estimating and detecting the treatment effects in different baskets. We review recent developments in Bayesian methods for the design and analysis of basket trials, focusing on the mechanism of information borrowing. We explain the common components of these methods, such as a prior model for the treatment effects that embodies an assumption of exchangeability. We also discuss the distinct features of these methods that lead to different degrees of borrowing. Through simulation studies, we demonstrate the impact of information borrowing on the operating characteristics of these methods and discuss its broader implications for drug development. Examples of basket trials are presented in both phase I and phase II settings. [ABSTRACT FROM AUTHOR]

Based on fieldwork carried out at the Early Drug Development Service of a world‐leading cancer institution, our study sheds lights on decision‐making processes at the stage where decisions are made about which clinical trial to pursue and thus which experimental drugs will feed the growing pipeline of molecularly guided therapies and therapeutic strategies available to treating physicians. The paper shows how such collective decision‐making practices by a translational research unit employ formal tools and ad hoc valuation strategies that interweave technical‐scientific matters of concern with patient‐oriented clinical ones, as part of the institutional assetization of biomedical knowledge production. In the process, decision‐making practices in part define the conditions of possibility for the provision of care in what is increasingly becoming a 'clinic of variants.' They do so by reconfiguring on an evolving basis the socio‐material ecosystem through which precision oncology is enacted as a rapidly evolving assemblage of patients, physicians, research and support staff, protocols, molecular markers, drugs and administrative components. [ABSTRACT FROM AUTHOR]

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use's (ICH) renovation of Good Clinical Practice (GCP) represents a philosophical shift in the conduct of clinical research away from a one-size-fits-all application to promoting a proactive, risk-based approach. The aim of this paper is to enhance the understanding of specific topics detailed in ICH E8 based on direct feedback from TransCelerate member companies who identified Quality by Design (QbD), Critical to Quality (CtQ), Fit for Purpose, and Stakeholder Engagement, as most changed and open to interpretation. The TransCelerate framework seeks to highlight and expand each of these central topics to support utilization and implementation of a strong foundation for quality in clinical development. [ABSTRACT FROM AUTHOR]

This is the fourth in a series of papers that provides an historical record in this journal of contributions made by the most influential figures in the field of stuttering. Ann Packman is an Australian researcher who will retire shortly. This paper reflects on her long and productive career, and her contributions to the field. With a background in literature, linguistics, philosophy, psychology, and the brain and language, she became well equipped to contribute to understanding stuttering causality. That work, and an accompanying collection of basic and applied clinical research, was constantly grounded with the thoughts and feelings of those who stutter in the community. • Ann Packman is an Australian researcher who will retire shortly. • This paper reflects on her career and her contributions to the field. • Her work was grounded with the thoughts and feelings of those who stutter. [ABSTRACT FROM AUTHOR]

The co-medication strategy of Chinese Materia Medica (CMM) and western medicines under the holistic integrative medicine (HIM) model offers the advantages of increased efficacy and reduced toxicity, particularly in clinical practice for treating complex and challenging diseases. However, due to the mutual fragmentation of basic theories and principles of medication decision-making between traditional Chinese medicine (TCM) and western medicine, research on the mechanisms for the combined use of CMM and western medicines has become a challenging problem in modern clinical medicine research. Traditional drug combination mining models encounter numerous bottlenecks when dealing with this complex decision-making problem with multi-source information characteristics. This paper aims to mine the optimal drug combination strategy from a real-life decision-making scenario of co-medication between CMM and western medicines. It abstracts this realistic problem as a class of complex network optimal overlapping community detection problem, focusing on solving key difficulties such as the inability of existing drug complex network models to handle the multi-source information of drugs and the randomness in the community detection process. We integrate co-medication prescription information with attribute information to construct the speaker-listener label propagation algorithm based on semantic attribute features (SA-SLPA) and develop a new medicine combination identification strategy based on weighted complex networks. Using 6671 clinically real prescriptions, we conclude that the detection quality of the SA-SLPA method proposed in this paper is improved by up to 78% compared to existing methods. This improvement illustrates the scientificity and effectiveness of the model in this paper and provides new ideas for the application of theoretical models and methods of interdisciplinary disciplines such as decision science, data science, and computational science in the field of modern medicine. • A speaker-listener label propagation algorithm based on semantic attribute features is proposed. • A medicine complex network is constructed to fuse multi-source information. • A new drug combination identification strategy is proposed. [ABSTRACT FROM AUTHOR]

Background: Orally administered second-generation gepants are effective for the treatment of migraine. The intranasal administration of the third-generation gepant zavegepant might have additional benefits including a rapid onset of action, but it is not clear yet to which extent this has clinical relevance. Methods: We examined the effect of zavegepant on the relaxations induced by calcitonin gene-related peptide (CGRP) in human isolated middle meningeal arteries. Furthermore, we connected the pharmacodynamics and pharmacokinetics of gepants by combining data from clinical and basic research. Results: We showed that 10 nM zavegepant potently antagonized the functional response to CGRP. We also showed that all gepants are effective at inhibiting functional responses to CGRP at their therapeutic plasma concentrations. Conclusions: The relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients. [ABSTRACT FROM AUTHOR]

Background: Qingfei Paidu Decoction (QFPDD) has played an important role in the prevention and treatment of COVID-19 infection in China. The present study aims to perform an econometric analysis and visualization of the literature on the treatment of COVID-19 with QFPDD in the Chinese databases and English databases. Methods: Six databases including such as Chinese databases CNKI, VIP, CBM, WANFANG as well as English databases PubMed, Web of Science were searched for publications related to the prevention and treatment of COVID-19 with QFPDD. The institutions, authors, keywords of each publication were cisualized using the software of CiteSpace. Results: A total of 187 literature on the prevention and treatment of novel coronavirus infection with QFPDD were included, of which 145 (77.5%) were in Chinese and 42 (22.5%) were in English. Those publications were written by 926 authors from 383 institutions. There were 78 theoretical studies (41.7%), 63 clinical studies (33.7%), and 46 basic studies (24.6%). The cooperative institutions with the core of "Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences" and "Shanghai University of Chinese Medicine Cross Academy of Science" have been formed, and two core teams with "Wang Yanping" and "Zhang Weidong" have been formed. The keyword analysis showed that the research mainly focuses on pathologic pathogenesis, clinical efficacy, adverse reactions, integrated Chinese and western medicine therapy, network pharmacology research. Conclusion: QFPDD has attracted worldwide attention, mechanism research and clinical research may become a future development trend. Therefore, in-depth basic research and clinical studies with large samples and multi-center cooperation should be carried out to provide high-level evidence-based evidence for the prevention and treatment of COVID-19 with QFPDD. [ABSTRACT FROM AUTHOR]

Engaging in clinical trials in Africa not only enhances researchers' comprehension of local health concerns but also plays a crucial role in tackling global health challenges. In Tanzania, there has been a surge of clinical research for the past 10 years indicating a need to improve ethical and clinical trial regulatory capacity. Several initiatives to address the clinical trial regulatory and ethics challenges have been done. Lessons from such initiatives are important to inform evidence-based decision-making for sustainability. The ASCEND project with the theme of "Moving Tanzania's Clinical Research Ethics and Medicines Regulatory Capacity to the Next Level: Fostering Medicine Quality, Safety and Good Clinical Practice (GCP) on Clinical Trials" was implemented in Tanzania Mainland and Zanzibar from November 2020 to December 2023. A thorough review of the project implementation reports and on deliverables was conducted to identify the lessons learned. Inductive content analysis was used to analyze the information. A total of seven lessons were deduced from the reviewed documents. These include capacity building through training on clinical trials review and approval process, research ethics and GCP inspection which cannot be overlooked; engaging the community in reporting adverse drug events is worth considering; digitalization of electronic systems enhances clinical trial control and creates a dynamic regulatory ecosystem; compliance to requirements for clinical trials conduct is enhanced by training of early and mid-career researchers; networking and broad stakeholders' engagement and participation in ethics and regulations governing clinical trials is a cornerstone for strengthening collaboration between researchers and regulators; the need for electronic systems for monitoring and evaluation of the project is inevitable and the need for adhering to project timelines is crucial for successful implementation of the project. Sustainability is the take-home message from the ASCEND project and should inform stakeholders for future improvement. Continuous investment and advancement in research ethics and regulatory oversight across Africa should be prioritized. [ABSTRACT FROM AUTHOR]

This perspective article explores the challenges and potential of using speech as a biomarker in clinical settings, particularly when constrained by the small clinical datasets typically available in such contexts. We contend that by integrating insights from speech science and clinical research, we can reduce sample complexity in clinical speech AI models with the potential to decrease timelines to translation. Most existing models are based on high-dimensional feature representations trained with limited sample sizes and often do not leverage insights from speech science and clinical research. This approach can lead to overfitting, where the models perform exceptionally well on training data but fail to generalize to new, unseen data. Additionally, without incorporating theoretical knowledge, these models may lack interpretability and robustness, making them challenging to troubleshoot or improve post-deployment. We propose a framework for organizing health conditions based on their impact on speech and promote the use of speech analytics in diverse clinical contexts beyond cross-sectional classification. For high-stakes clinical use cases, we advocate for a focus on explainable and individually-validated measures and stress the importance of rigorous validation frameworks and ethical considerations for responsible deployment. Bridging the gap between AI research and clinical speech research presents new opportunities for more efficient translation of speech-based AI tools and advancement of scientific discoveries in this interdisciplinary space, particularly if limited to small or retrospective datasets. [ABSTRACT FROM AUTHOR]

Simple Summary: Bone metastases represent a serious and common challenge in advanced cancer patients, making early detection crucial. The growing implementation of artificial intelligence (AI) in various medical fields is revolutionizing healthcare by enhancing diagnostic accuracy. This systematic review includes 59 articles and sought to assess the potential of machine learning models in the fields of nuclear medicine, clinical research, radiology, and molecular biology. The review provides a comprehensive analysis of AI's effectiveness in detecting bone metastases, which had not yet been thoroughly conducted. The findings highlight the benefits of integrating AI technologies in the inspected fields, encouraging further advancements and adoption of AI to ultimately improve patient care and treatment planning. This study provides invaluable perceptions into the promising application of computational intelligence in the detection of bone metastases, demonstrating its superiority over standard tests. However, further research is necessary to substantiate these findings with the aim of developing better-trained data-driven models soon. Background: Metastasis commonly occur in the bone tissue. Artificial intelligence (AI) has become increasingly prevalent in the medical sector as support in decision-making, diagnosis, and treatment processes. The objective of this systematic review was to assess the reliability of AI systems in clinical, radiological, and pathological aspects of bone metastases. Methods: We included studies that evaluated the use of AI applications in patients affected by bone metastases. Two reviewers performed a digital search on 31 December 2023 on PubMed, Scopus, and Cochrane library and extracted authors, AI method, interest area, main modalities used, and main objectives from the included studies. Results: We included 59 studies that analyzed the contribution of computational intelligence in diagnosing or forecasting outcomes in patients with bone metastasis. Six studies were specific for spine metastasis. The study involved nuclear medicine (44.1%), clinical research (28.8%), radiology (20.4%), or molecular biology (6.8%). When a primary tumor was reported, prostate cancer was the most common, followed by lung, breast, and kidney. Conclusions: Appropriately trained AI models may be very useful in merging information to achieve an overall improved diagnostic accuracy and treatment for metastasis in the bone. Nevertheless, there are still concerns with the use of AI systems in medical settings. Ethical considerations and legal issues must be addressed to facilitate the safe and regulated adoption of AI technologies. The limitations of the study comprise a stronger emphasis on early detection rather than tumor management and prognosis as well as a high heterogeneity for type of tumor, AI technology and radiological techniques, pathology, or laboratory samples involved. [ABSTRACT FROM AUTHOR]

Background: Treatment of chronic inflammatory bowel disease (IBD) aims to improve patients' quality of life and the extent of treatment success is measured via patient reported outcomes (PROs). However, questionnaires used to collect PROs often include scales that are not specific to IBDs. Improving these scales requires a deeper understanding of patients' lived experience. With this study we give first insights and develop hypotheses on how patients with IBDs experience their body and self and how they adjust their life plans in the context of precision medicine (PM). The guiding question is to understand what they need to achieve a good life, while facing their disease. Methods: We developed a conception of the "good life" that draws on Philippa Foot's "naturalized" approach and distinguishes six different dimensions that are relevant for a good life. This conception guided us as we conducted 10 qualitative interviews with patients suffering from IBD who were in precision medicine clinical research settings. The interviews aimed to gain insights for answering our research question: How do body experiences affect the good life of patients with IBD? We analyzed the interviews with interpretative phenomenological analysis (IPA). Results: Five group experiential themes emerged: (i) Life options and plans, (ii) other people's responses, (iii) strategies to deal with others' responses, (iv) perception of the body and self, and (v) perception of life as good despite suffering. We report here on three of them (i, iv and v), which are primarily relevant for evaluating the outcomes of PM care. Whereas with "life options and plans (i)," our study predominantly confirmed previous research, with "perception of the body and self (iv)," we found that some of the patients changed their relationship to their body and themselves. They perceived the body or the disease as the "other" and their self appears divorced from their own body. Although this might be an avoidance strategy patients use to assign responsibility for their condition and its "disgusting" symptoms to the "other," it is important to include it in patient reported outcome (PRO) assessments. Conclusions: We conclude with the insight that the multi-dimensional approach based on Foot's concept of a good life is well-suited as a basis for investigating the quality of life of people with IBD. Interviews based on this concept produced results that go beyond the understanding of health-related quality of life (HRQoL). Additionally, we offer some considerations about patients' opportunities for achieving a good life and suggestions for further developing patient reported outcome scales. [ABSTRACT FROM AUTHOR]

Simple Summary: The high-level aims of the Advocate-BREAST initiative are to study and improve the overall experience of patients with breast cancer (BC) through education, shared decision making, and patient-centered clinical trials. Advocate-BREAST80+ is a survey substudy that specifically focused on the unique needs and perspectives of BC patients aged ≥80 years. Although patients aged ≥80 years experienced less anxiety and symptom-related distress compared with younger patients, they were significantly less satisfied with information regarding short and long term side effects of BC therapies, as well as the management of same. Older patients were significantly less likely to have participated in a clinical trial or be open to considering this option in future. Future research should address unique educational needs and barriers to research participation in older BC patients. Focused interviews could assist with better comprehension of the lived experience of these patients, given the smaller number of BC patients ≥80 years in many available databases. Background: There are limited evidence-based data to guide treatment recommendations for breast cancer (BC) patients ≥80 years (P80+). Identifying and addressing unmet needs are critical. Aims: Advocate-BREAST80+ compared the needs of P80+ vs. patients < 80 years (P80−). Methods: In 12/2021, a REDCap survey was electronically circulated to 6918 persons enrolled in the Mayo Clinic Breast Disease Registry. The survey asked about concerns and satisfaction with multiple aspects of BC care. Results: Overall, 2437 participants responded (35% response rate); 202 (8.3%) were P80+. P80+ were less likely to undergo local regional and systemic therapies vs. P80− (p < 0.01). Notably, P80+ were significantly less satisfied with information about the short and long-term side effects of BC therapies and managing toxicities. P80+ were also less likely to have participated in a clinical trial (p < 0.001) or to want to do so in the future (p = 0.0001). Conclusions: Although P80+ experienced less anxiety and symptom-related distress compared with P80−, they were significantly less satisfied with information regarding the side effects of BC therapies and their management. P80+ were significantly less likely to have participated in a clinical trial or be open to considering this option. Future studies should address educational needs pertaining to side effects and barriers to research participation in P80+. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the discoverability of supporting research materials, including supporting documents, individual participant data (IPD), and associated publications, in US federally funded COVID-19 clinical study records in ClinicalTrials.gov (CTG). Methods: Study registration records were evaluated for (1) links to supporting documents, including protocols, informed consent forms, and statistical analysis plans; (2) information on how unaffiliated researchers may access IPD and, when applicable, the linking of the IPD record back to the CTG record; and (3) links to associated publications and, when applicable, the linking of the publication record back to the CTG record. Results: 206 CTG study records were included in the analysis. Few records shared supporting documents, with only 4% of records sharing all 3 document types. 27% of records indicated they intended to share IPD, with 45% of these providing sufficient information to request access to the IPD. Only 1 dataset record was located, which linked back to its corresponding CTG record. The majority of CTG records did not have links to publications (61%), and only 21% linked out to at least 1 results publication. All publication records linked back to their corresponding CTG records. Conclusion: With only 4% of records sharing all supporting document types, 12% sufficient information to access IPD, and 21% results publications, improvements can be made to the discoverability of research materials in federally funded, COVID-19 CTG records. Sharing these materials on CTG can increase their discoverability, therefore increasing the validity, transparency, and reusability of clinical research. [ABSTRACT FROM AUTHOR]

Melanoma, a highly prevalent cancer worldwide, exhibits remarkable diversity and plasticity, with the adverse prognosis of advanced melanoma remaining a focal point of investigation. Despite the emergence of novel drugs and combination therapies improving patient outcomes, challenges such as drug resistance and incomplete mechanistic understanding persist. Transcriptional programs play a pivotal role in determining the characteristics of both normal and tumour cells, with their dysregulation of these programs being a hallmark of melanoma. Abnormalities in transcription regulation not only impact the characteristics of melanoma cells but also influence the tumor's metabolism and immune microenvironment, forming a complex network in tumours. Thus, understanding these changes comprehensively is crucial for unravelling the mechanisms underlying melanoma initiation, progression, response to targeted and immune therapies, and treatment resistance. This review primarily explores the transcriptional features in normal melanocytes and melanoma cells, emphasizing their profound impact on cell metabolism and immune evasion. Furthermore, the plasticity of melanoma cells and its relationship with treatment resistance and metastasis are highlighted, emphasizing the importance of targeting dysregulated transcriptional factors and pathways. Finally, potential clinical implications in targeting transcriptional abnormalities are highlighted, particularly in metastatic or treatment-resistant melanomas. This comprehensive overview aims to contribute to the advancement of melanoma research and the development of precise and effective treatments. [ABSTRACT FROM AUTHOR]

Effective integration of research within healthcare organisations is recognised to improve outcomes. A research strategy within a hospital Trust in South West England was revised, following the launch of a national Chief Nursing Officer (CNO) strategy that promotes research engagement and activity. The aim was to develop, implement and evaluate this revised strategic plan for research. High-level engagement within the organisation was established and previous initiatives evaluated. A 6-year plan with 2-year targets was defined and evaluated at year end. The four pillars of the CNO strategy were central to the revised strategy, underpinned by digital innovation. Evaluation of the earlier strategy indicated excellent engagement with the Chief Nurse Research Fellow initiative and the Clinical Academic Network. The 'Embedding Research In Care' (ERIC) unit was reconfigured to an ERIC model, which aided question generation and project development. Year one objectives were achieved within the revised plan. Implementing a research strategy within an organisation requires a cultural shift and a long-term vision is required with measurable objectives. The team demonstrated significant progress through high-level leadership, mentoring and cross-professional collaboration. [ABSTRACT FROM AUTHOR]

Background: While healthcare policy has fostered implementation strategies to improve inclusion and access of under-served groups to clinical care, systemic and structural elements still disproportionately prevent service users from accessing research opportunities embedded within clinical settings. This contributes to the widening of health inequalities, as the absence of representativeness prevents the applicability and effectiveness of evidence-based interventions in under-served clinical populations. The present study aims to identify the individual (micro), organisational (meso) and structural (macro) barriers to clinical research access in patients with comorbid alcohol use disorder and alcohol-related liver disease. Methods: A focused ethnography approach was employed to explore the challenges experienced by patients in the access to and implementation of research processes within clinical settings. Data were collected through an iterative-inductive approach, using field notes and patient interview transcripts. The framework method was utilised for data analysis, and themes were identified at the micro, meso and macro levels. Results: At the micro-level, alcohol-related barriers included encephalopathy and acute withdrawal symptoms. Alcohol-unrelated barriers also shaped the engagement of service users in research. At the meso-level, staff and resource pressures, as well as familiarity with clinical and research facilities were noted as influencing intervention delivery and study retention. At the wider, macro-level, circumstances including the 'cost of living crisis' and national industrial action within healthcare settings had an impact on research processes. The findings emphasise a 'domino effect' across all levels, demonstrating an interplay between individual, organisational and structural elements influencing access to clinical research. Conclusions: A combination of individual, organisational and structural barriers, exacerbated by the COVID-19 pandemic, and the socioeconomic landscape in which the study was conducted further contributed to the unequal access of under-served groups to clinical research participation. For patients with comorbid alcohol use disorder and alcohol-related liver disease, limited access to research further contributes towards a gap in effective evidence-based treatment, exacerbating health inequalities in this clinical population. [ABSTRACT FROM AUTHOR]

Although Chronic Obstructive Pulmonary Disease (COPD) is highly prevalent, it is often underdiagnosed. One of the main characteristics of this heterogeneous disease is the presence of periods of acute clinical impairment (exacerbations). Obtaining blood biomarkers for either COPD as a chronic entity or its exacerbations (AECOPD) will be particularly useful for the clinical management of patients. However, most of the earlier studies have been characterized by potential biases derived from pre-existing hypotheses in one or more of their analysis steps: some studies have only targeted molecules already suggested by pre-existing knowledge, and others had initially carried out a blind search but later compared the detected biomarkers among well-predefined clinical groups. We hypothesized that a clinically blind cluster analysis on the results of a non-hypothesis-driven wide proteomic search would determine an unbiased grouping of patients, potentially reflecting their endotypes and/or clinical characteristics. To check this hypothesis, we included the plasma samples from 24 clinically stable COPD patients, 10 additional patients with AECOPD, and 10 healthy controls. The samples were analyzed through label-free liquid chromatography/tandem mass spectrometry. Subsequently, the Scikit-learn machine learning module and K-means were used for clustering the individuals based solely on their proteomic profiles. The obtained clusters were confronted with clinical groups only at the end of the entire procedure. Although our clusters were unable to differentiate stable COPD patients from healthy individuals, they segregated those patients with AECOPD from the patients in stable conditions (sensitivity 80%, specificity 79%, and global accuracy, 79.4%). Moreover, the proteins involved in the blind grouping process to identify AECOPD were associated with five biological processes: inflammation, humoral immune response, blood coagulation, modulation of lipid metabolism, and complement system pathways. Even though the present results merit an external validation, our results suggest that the present blinded approach may be useful to segregate AECOPD from stability in both the clinical setting and trials, favoring more personalized medicine and clinical research. [ABSTRACT FROM AUTHOR]

Objective: Psychiatric patients in general, and elderly psychiatric patients in particular, are at risk of adverse drug reactions due to comorbidities and inappropriate polypharmacy. Interdisciplinary and clinical-pharmacologist-led medication reviews may contribute to medication safety in the field of psychiatry. In this study, we reported the frequency and characteristics of clinical-pharmacological recommendations in psychiatry, with a particular focus on geriatric psychiatry. Method: A clinical pharmacologist, in collaboration with the attending psychiatrists and a consulting neurologist, conducted interdisciplinary medication reviews in a general psychiatric ward with a geropsychiatric focus at a university hospital over a 25- week period. All clinical and pharmacological recommendations were recorded and evaluated. Results: A total of 316 recommendations were made during 374 medication reviews. Indications/contraindications of drugs were the most frequently discussed topics (59/316; 18.7 %), followed by dose reductions (37/316; 11.7 %), and temporary or permanent discontinuation of medications (36/316; 11.4 %). The most frequent recommendations for dose reduction involved benzodiazepines (9/37; 24.3 %). An unclear or absent indication was the most common reason for recommending temporary or permanent discontinuation of the medication (6/36; 16.7 %). Conclusion: Interdisciplinary clinical pharmacologist-led medication reviews represented a valuable contribution to medication management in psychiatric patients, particularly the elderly ones. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer remains one of the leading causes of death worldwide due to widespread metastasis. Circulating tumor cells (CTCs) were first detected in 1886 and have been thought of as seeds of metastasis. However, emerging evidence has shown that CTCs can be used for early disease detection and as predictors of disease prognosis and treatment response. This review discusses recent findings regarding the detection and characterization of CTCs. Integrating these findings into routine clinical workflows promises to revolutionize the diagnosis and treatment of cancer. Circulating tumor cells (CTCs) are cells released from the primary and metastatic tumor and intravasate into the blood or lymphatic vessels, where they are transported to distant sites and act as seeds that initiate cancer metastases or the development of further lesions. Recent advances in CTC research have shown their relevance as prognostic markers for early and metastatic disease detection, predictive biomarkers for relapse, and response to medical intervention or therapy. The rapidly evolving landscape of CTC biology has opened new avenues for understanding cancer progression, metastasis, and treatment response. Additionally, translating these findings into clinical applications holds promise for improving cancer diagnostics, prognosis, and personalized therapeutic strategies. This review discusses the significance of CTCs in cancer research and their associated challenges. We explore recent developments in the detection and characterization of CTCs and their implications in cancer research and clinical practice. [ABSTRACT FROM AUTHOR]

Background: Cerebral palsy (CP) is characterized by abnormal pronunciation, posture, and movement. Spastic CP accounts for more than 70% of all CP. To date, there has been no bibliometric analysis to summarize study on spastic CP. Here, we aim to conduct a bibliometric analysis of spastic CP to summarize this field's knowledge structure, research hotspots, and frontiers. Method: Publications about spastic CP were searched utilizing the Web of Science Core Collection (WoSCC) database from 1 January 2000 to 30 November 2022, the WoSCC literature analysis wire, VOSviewer 1.6.18, CiteSpace 6.1.R4 and Online analysis platform for bibliometrics were used to conduct the analysis. Results: A total of 3988 publications, consisting of 3699 articles and 289 reviews, were included in our study. The United States emerged as the most productive country, while Kathleen Univ Leuven was the most productive institution. The leading author was Desloovere K. A total of 238 journals contributed to this field, with Developmental medicine and child neurology being the leading journal. Important keywords and keyword clusters included Spastic cerebral palsy, Reliability, and Gross motor function. Keywords identified through burst detection indicated that hotspots in this field were management, randomized controlled trials, and definition. Conclusion: Based on the analysis of bibliometric on spastic CP over the past 20 years, the trends and the knowledge graph of the countries, institutions, authors, references, and the keywords have been identified, providing accurate and expedited insights into critical information and potentially new directions in the study of spastic CP. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of proprietary drugs targeting KRAS-mutant tumors has historically been a formidable challenge. This difficulty stems from the high affinity of RAS proteins for GTP and the lack of a hydrophobic "pocket" conducive to drug binding. However, the emergence of CRISPR technology, a groundbreaking gene-editing tool, has revolutionized tumor studies, particularly those focusing on KRAS mutations. This article offers a review of both fundamental and translational research leveraging the CRISPR system in the context of KRAS-mutant cancer. It encapsulates recent strides made in understanding KRAS biology's mechanistic nuances, shedding light on pivotal themes such as drug resistance, anti-tumor immune responses, epigenetic regulation, and the exploitation of synthetic lethality by mutant KRAS. In conclusion, the article touches upon the current limitations of employing CRISPR technology in KRAS-related research, while also suggesting avenues for future refinement and optimization in this dynamic field. Once considered "undruggable" due to the strong affinity of RAS proteins for GTP and the structural lack of a hydrophobic "pocket" for drug binding, the development of proprietary therapies for KRAS-mutant tumors has long been a challenging area of research. CRISPR technology, the most successful gene-editing tool to date, is increasingly being utilized in cancer research. Here, we provide a comprehensive review of the application of the CRISPR system in basic and translational research in KRAS-mutant cancer, summarizing recent advances in the mechanistic understanding of KRAS biology and the underlying principles of drug resistance, anti-tumor immunity, epigenetic regulatory networks, and synthetic lethality co-opted by mutant KRAS. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses articles in the issue on topics including paediatric discharge medicines service, enhancing drug therapy in ostomy patients, and opioid therapy communication risks.