Intervertebral disc (IVD) degeneration is a common phenomenon that affects patients with increasing prevalence with increasing age. Both conservative treatments, such as the use of pain medication or physical therapy, and surgical treatments, such as fusion or disc replacement therapies, are offered to patients. Both non-invasive and invasive treatments have been shown to improve pain and quality of life for patients. This review explores the role of regenerative medicine techniques as a promising therapeutic intervention that can be used before or in combination with conservative therapy and surgery to enhance the treatment process in patients with IVD degeneration or disc pathology. Currently, there are four major modules of regenerative medicine: genetic therapy, platelet-rich plasma therapy, stem cell transplantation and tissue engineering. Several research studies have shown promising outcomes of stem cell transplantation and tissue engineering when combined with either surgical or conservative treatment, resulting in improved pain outcomes. The additional benefit of regenerative medicine techniques, specifically stem cell transplantation, is the potential for treating the root pathology of degeneration. Regenerative medicine techniques also have the potential to either halt or reverse degeneration as opposed to current standards of care for managing symptoms. There is a plethora of current research highlighting the benefits of regenerative medicine techniques; however, there remains clinical concerns and ethical concerns regarding the use of regenerative therapy techniques such as stem cell transplantation in the context of IVD degeneration.
Genome-wide association studies (GWAS) have been instrumental in elucidating the genetic architecture of various traits and diseases. Despite the success of GWAS, inherent limitations such as identifying rare and ultra-rare variants, the potential for spurious associations and pinpointing causative agents can undermine diagnostic capabilities. This review provides an overview of GWAS and highlights recent advances in genetics that employ a range of methodologies, including whole-genome sequencing (WGS), Mendelian randomisation (MR), the Pangenome's high-quality Telomere-to-Telomere (T2T)-CHM13 panel and the Human BioMolecular Atlas Program (HuBMAP), as potential enablers of current and future GWAS research. The state of the literature demonstrates the capabilities of these techniques to enhance the statistical power of GWAS. WGS, with its comprehensive approach, captures the entire genome, surpassing the capabilities of the traditional GWAS technique focused on predefined single nucleotide polymorphism sites. The Pangenome's T2T-CHM13 panel, with its holistic approach, aids in the analysis of regions with high sequence identity, such as segmental duplications. MR has advanced causative inference, improving clinical diagnostics and facilitating definitive conclusions. Furthermore, spatial biology techniques such as HuBMAP enable 3D molecular mapping of tissues at single-cell resolution, offering insights into pathology of complex traits. This study aimed to elucidate and advocate for the increased application of these technologies, highlighting their potential to shape the future of GWAS research.
Meningitis, which is defined by inflammation of the meninges, is a major cause of death and morbidity worldwide. Traditional diagnostic approaches, such as imaging procedures and the study of cerebrospinal fluid, are intrusive, time consuming and sometimes non-specific. The suggested approach entails creating a biosensor based on microneedles that can detect in real time without the requirement for labels. The biosensor uses highly sensitive detection techniques to detect changes in ionic current and modulation of impedance in response to biomolecules that are of interest, such as proteins and nucleic acids, which are linked to meningitis infections. Initial studies have shown that the microneedle-based biosensor for meningitis diagnosis is both feasible and effective. When it comes to identifying bacterial and aseptic meningitis biomarkers from blood and cerebrospinal fluid (CSF) samples, the biosensor showed excellent sensitivity and specificity. This novel technique has the potential to enhance patient outcomes by facilitating prompt intervention and tailored therapy by offering a quick, safe and accurate way to distinguish between bacterial and aseptic meningitis. To maximise the biosensor's performance and confirm its therapeutic usefulness in various contexts, more investigations and advancements are necessary.
The spatiotemporal heterogeneity of neurons, circuits and regulators is being uncovered at a single-cell level, from the single-cell gene expression to functional regulations. The classifications, architectonics and functional communications amongst neural cells and circuits within the brain can be clearly delineated using single-cell multiomics and transomics. This Editorial highlights the spatiotemporal heterogeneity of neurons and circuits as well as regulators, initiates the translation of neuronal diversity and spatial organisation at single-cell levels into clinical considerations, and enables the discovery and development of new therapies for neurological diseases. It is predicted that single-cell and spatial multiomics will be integrated with metabolomic profiles and corresponding gene epigenetic modifications. The interactions amongst DNAs, RNAs and proteins in a cell provide details of intracellular functional regulations and new opportunities for the translation of temporospatial diversity of neural cell subtypes/states into clinical practice. The application of single-cell multiomics with four-dimensional genome to the human pathological brain will lead us to a new milestone of the diagnosis and treatment.
The persistent threat of tuberculosis (TB) on a global scale hasprompted a reevaluation of preventive strategies, with a particular focus onthe Bacille Calmette-Guérin (BCG) vaccine's role in revaccination. Theresurgence underscores an urgent need for enhanced measures, prompting acritical examination of BCG revaccination strategies. Drawing from the researchof Paulo Cesar Pereira dos Santos and a synthesis of randomized controlledtrials (RCTs), this review identifies key considerations for refining BCGrevaccination's efficacy against Mycobacterium tuberculosis (MTB) andTB. The main body of this review integrates four principal domains essentialfor optimizing BCG revaccination: the timing of revaccination, the assessmentof various BCG strains, the evaluation of the vaccine's effectiveness on MTBand non-tuberculous mycobacteria (NTM) strains, and the enhancement of RCTmethodologies. Determining the optimal revaccination timing is paramount forbolstering immunity, especially in regions with high TB prevalence. Theanalysis of different BCG strains provides insights into strain-specificimmunogenicity, informing vaccine deployment strategies. Additionally, understanding the vaccine's impact on a range of mycobacterial infections iscrucial for its broader application in various microbial contexts. The reviewemphasizes the refinement of RCT designs to ensure robust and consistentoutcomes, facilitating the reproducibility of results in diverse settings. Itproposes a strategy that not only suggests modifications to revaccinationpractices to increase global TB prevention effectiveness but also calls forcontinuous research to improve BCG revaccination methodologies. The paperadvocates for a standardized, evidence-driven approach to global TB preventionthat takes into account regional epidemiological differences. In conclusion, this review significantly contributes to the discourse on TB prevention, advocating for evidence-based, standardized approaches that could potentiallytransform the role of BCG revaccination in global TB prevention efforts. Thefindings support current initiatives aimed at developing policies based onsolid evidence, ensuring the scientific integrity and practical relevance ofBCG revaccination strategies.
Background: The creation of breast cancer practice guidelines requires proper management of financial relationships with drug companies, as they can introduce conflicts of interest (COIs) among guideline authors. However, little is known about the specific landscape and fraction of financial interactions between the authors of the Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, edition 2022 (JBCS2022) and drug companies.
Methods: Using payment data publicly disclosed by major drug companies in Japan, this study analysed the personal payments made to the authors of JBCS2022 between 2016 and 2020. We performed descriptive analyses on the payment data.
Results: Of the 149 JBCS2022 authors, 115 (77.2%) received at least one personal payment totaling $3 828 455 from drug companies between 2016 and 2020. The average and median payment amounts per author were $25 772 (standard deviation: $58 197) and $2761 (interquartile range: $322‒$15 828), respectively. The total annual payments per JBCS2022 authors between 2016 and 2019 increased from $588 054 in 2016 to $967 802 in 2019. The JBCS2022 chairperson and vice-chairperson received $246 936 (fourth highest) and $216 744 (fifth highest) over the 5 years. More than 60% of personal payments to the JBCS2022 authors were not declared by the authors as they were below the declaration threshold set by the Japanese Breast Cancer Society. However, nine authors undeclared personal payments summing $594 615 even though these payments were higher than the thresholds.
Conclusion: This study demonstrated that the majority of the breast cancer guideline authors received personal payments from drug companies in Japan. Furthermore, the majority of payments were not declared because of the less transparent COI policy.
Cancers that can manifest in the oral cavity, nasal cavity, larynx, pharynx, sinuses, and other head and neck areas are collectively called “head and neck cancers” (HNC). HNC can be broadly classified into five types: salivary gland; oral and oropharyngeal; nasal cavity and paranasal sinus; nasopharyngeal, and laryngeal and hypopharyngeal cancers. HNC accounts for one million new diagnoses annually, making it the seventh most common form of the disease globally. Among all HNCs, 90% are head and neck squamous cell carcinoma (HNSCC) which is highly heterogenous, relapsing, and metastatic with poor survival. Despite the availability of new treatments, the five-year survival rate for HNSCC patients has been reported to be approximately 50%. An early diagnosis may increase the disease management and outcomes, but it is challenging to detect smaller-sized lesions and differentiate malignant and non-malignant lesions with the available tools. Current circumstances demand an improvement in existing diagnostic strategies and the advent of novel diagnostic tools.
Background: Molecular diagnostic technology is the foundation of precision medicine, which has the advantages of good specificity, high sensitivity, strong targeting, rapiddiagnosis, etc. It has a wide range of applications in the field of pediatrics. However, molecular diagnostic technology is characterized by complicated experimental operation, high difficulty in data analysis and interpretation, in consistent standards among laboratories, and difficult standardization of technical processes. Enhancing the application value of molecular diagnostic technology in pediatrics and promoting the high-quality development of the discipline requires careful consideration by relevant management and professionals.
Methods: This study firstly outlines the development history of molecular diagnostic technology. Then, it analyzes the application of molecular diagnostic technology in the field of pediatrics. Finally, it explores the countermeasures for the management of molecular diagnostic laboratories.
Results: This study highlights the importance of molecular diagnostic technology in providing information and decision-making basis for disease prevention, prediction, diagnosis, treatment and regression. It has a wide range of applications in the molecular diagnosis of pediatric hereditary diseases, malignant tumors and infectious diseases. In addition, the countermeasures for the management of molecular diagnostic laboratories are proposed from the five aspects of laboratory, personnel team construction, standardized management, multidisciplinary cross-discipline, research and translation, safety managementand ethical supervision, and management upgrading and modernization.
Conclusions: Molecular diagnostic technology, as the basis of precision medicine, has become one of the important frontier fields in the development of contemporary pediatric medicine. Enhanced laboratory capacity in molecular diagnostic techniques can improve outcomes in the prevention, prediction, diagnosis, treatment, prognosis and research of pediatricdiseases, and lay the groundwork for child healthcare.
Background: The use of cervical collars in the management of acute cervical spine injuries has been part of standard practice in the trauma setting for decades, aimed at preventing secondary injuries.
Objectives: To review the recent evidence challenging the routine use of cervical collars, addressing the limited scientific support, associated risks, and guidelines for their use.
Methods: A comprehensive literature review was conducted, analyzing recent studies and guidelines from authoritative bodies such as the American Association for Neurological Surgeons and the Congress of Neurological Surgeons. The review focused on the efficacy, risks, and recommendations regarding cervical collar use in acute cervical spine injuries.
Results: Recent evidence questions the routine use of cervical collars, highlighting limited scientific support and several associated risks, including pressure ulcers and decreased venous return. Cervical collars may also be contraindicated in individuals with abnormal spinal structures, such as those with Ankylosing Spondylitis. The efficacy of cervical collars is debated, particularly concerning undiagnosed spinal fractures, where delayed diagnosis can result in permanent injuries. Despite these risks, cervical collars may be beneficial in low-resource areas and when used effectively with early clearance post-injury. Current guidelines recommend immobilizing patients suspected of cervical spine injury but stress the importance of proper evaluation of the need for immobilization. Recent guidelines advocate for spinal motion restriction over traditional immobilization, emphasizing the need for better risk assessment and implementation strategies.
Conclusions/Clinical Importance: Re-evaluating the routine use of cervical collars is crucial due to potential risks and limited supporting evidence, with a focus on individualized assessment and adherence to updated guidelines favoring spinal motion restriction.
Combination therapy has emerged as an efficacy strategy for treating complex diseases. Its potential to overcome drug resistance and minimize toxicity makes it highly desirable. However, the vast number of potential drug pairs presents a significant challenge, rendering exhaustive clinical testing impractical. In recent years, deep learning-based methods have emerged as promising tools for predicting synergistic drug combinations. This review aims to provide a comprehensive overview of applying diverse deep-learning architectures for drug combination prediction. This review commences by elucidating the quantitative measures employed to assess drug combination synergy. Subsequently, we delve into the various deep-learning methods currently employed for drug combination prediction. Finally, the review concludes by outlining the key challenges facing deep learning approaches and proposes potential challenges for future research.
Extracellular vesicles (EVs), including exosomes, ectosomes, and apoptotic bodies, play crucial roles in cellular communication and disease processes. Among these, exosomes are particularly significant for diagnosing, and cancer (which remains a leading cause of death worldwide). Exosomes offer cutting-edge approaches in cancer nanomedicine, cancer biomarkers investigation (diagnosis and prognosis), and therapeutic. Exosomes are found in several body fluids (Blood, plasma, serum, urine, saliva, sweat, CSF, tear). It transforms the liquid biopsy method with more specificity. Exosome-based sensor (electrochemical and aptamer-based) developers were more effective and sensitive for cancer scanning. Therapeutic prospect stem cell-derived exosomes, and plant-derived exosomes become more promising. Due to its non-toxicity (depending on the source), non-immunogenic, biocompatibility and ability to cross biological membranes. Exosomes are an exciting nano-drug transporter with specificity. Current time-modified exosomes support to development of effective, efficient, and cost-effective nanomedicine against cancer. Advanced nanotechnology and exosome combining (single exosome profiling, exosome barcoding)transform cancer theranostics approaches. Exosomes introduce a new horizon of cancer nanomedicine.
Cancer therapeutic development is the most challenging domain in cancer. Cell-based cancer therapeutics come up with promising effectiveness. This approach was also cell-modified for better targeting efficiency development. Cell engineering-based cancer therapeutic is a cutting-edge method in cancer therapy. Due to complications of this process, cost and post-treatment side effects, this phenomenon came into the question mark. In this scenario, extracellular vesicle (EVs) research introduces a cell-free cancer therapeutic approach. In the therapeutic aspect most used EVs, come from stem cells, plants, and engineered cells. Among several EVs populations, Exosomes are the most used worldwide cell-free therapeutic tool for ageing cancer. The most interesting facts about exosomes are the biocompatible, non-immunoreactive, cross-biological barrier, and non-toxic (depending on the parental cell's nature). In this article, we are exploring modified exosomes (biological or chemical) that create a remarkable outcome in cancer therapeutic development compared to engineered cell-based therapeutics. Hope, in the future, modified exosomes become an effective, affordable, and specific cancer-targeting precision medicine.