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Intrinsic biological clocks drive the circadian rhythm, which coordinates the physiological and pathophysiological processes in the body. Recently, a bidirectional relationship between circadian rhythms and several neurological diseases has been reported. Neurological diseases can lead to the disruption of circadian homeostasis, thereby increasing disease severity. Therefore, optimizing the current treatments through circadian-based approaches, including adjusted dosing, changing lifestyle, and targeted interventions, offer a promising opportunity for better clinical outcomes and precision medicine. In this review, we provide detailed implications of the circadian rhythm in neurological diseases through bench-to-bedside approaches. Furthermore, based on the unsatisfactory clinical outcomes, we critically discuss the potential of circadian-based interventions, which may encourage more studies in this discipline, with the hope of improving treatment efficacy in neurological diseases. [ABSTRACT FROM AUTHOR]

• Advancements in ischemic stroke research introduce new treatment challenges. • This narrative review selectively highlights advances with clinical impact using a fictional case. • Outstanding questions are addressed that can benefit from experimental-clinical research collaborations. Ischemic stroke research has enabled significant advancements in diagnosis, treatment, and management of this debilitating disease, yet challenges remain standing in the way of better patient prognoses. In this narrative review, a fictional case illustrates challenges and uncertainties that medical professionals still face – penumbra identification, lack of neuroprotective agents, side-effects of tissue plasminogen activator, dearth of molecular biomarkers, incomplete microvascular reperfusion or no-reflow, post-recanalization hyperperfusion, blood pressure management and procedural anesthetic effects. The current state of the field is broadly reviewed per topic, with the aim to introduce a broad audience (scientist and clinician alike) to recent successes in translational stroke research and pending scientific queries that are tractable for preclinical assessment. Opportunities for co-operation between clinical and experimental stroke experts are highlighted to increase the size and frequency of strides the field makes to improve our understanding of this disease and ways of treating it. [ABSTRACT FROM AUTHOR]

The ion channels Piezo 1 and Piezo 2 have been identified as membrane mechano-proteins. Studying mechanosensitive channels in chemosensory organs could help in understanding the mechanisms by which these channels operate, offering new therapeutic targets for various disorders. This study investigates the expression patterns of Piezo proteins in zebrafish chemosensory organs. For the first time, Piezo protein expression in adult zebrafish chemosensory organs is reported. In the olfactory epithelium, Piezo 1 immunolabels kappe neurons, microvillous cells, and crypt neurons, while Calretinin is expressed in ciliated sensory cells. The lack of overlap between Piezo 1 and Calretinin confirms Piezo 1's specificity for kappe neurons, microvillous cells, and crypt neurons. Piezo 2 shows intense immunoreactivity in kappe neurons, one-ciliated sensory cells, and multi-ciliated sensory cells, with overlapping Calretinin expression, indicating its olfactory neuron nature. In taste buds, Piezo 1 immunolabels Merkel-like cells at the bases of cutaneous and pharyngeal taste buds and the light and dark cells of cutaneous and oral taste buds. It also marks the dark cells of pharyngeal taste buds and support cells in oral taste buds. Piezo 2 is found in the light and dark cells of cutaneous and oral taste buds and isolated chemosensory cells. These findings provide new insights into the distribution of Piezo channels in zebrafish chemosensory organs, enhancing our understanding of their sensory processing and potential therapeutic applications. [ABSTRACT FROM AUTHOR]

The article discusses the field of translational pathology in drug discovery, which aims to combine disciplines and techniques to enhance prevention, diagnosis, and therapies. Translational pathology involves translating clinical data into basic research and applying knowledge gained from basic science research to clinical practice. The authors argue that translational pathology can improve the drug discovery process by helping to overcome obstacles and bridge the gap between basic research and clinical trials. They highlight the potential use of pathohistological evaluation in target validation, in vitro and in vivo screening, pharmacokinetic studies, and clinical trials. The article emphasizes the need to understand the limitations of animal models in relation to human disease and the importance of investigating the expression and function of target-expressing cell types in both naive tissue and disease models. The article also highlights the heterogeneity of tissue composition and cell types within tumor samples, which has implications for treatment outcomes. Pathological evaluation is suggested as a valuable tool for assessing drug distribution and understanding disease pathophysiology. The article concludes by discussing the role of translational pathology in personalized medicine and the identification of drug targets. The document provides a list of references from various scientific articles related to topics such as transgenic and gene knockout mouse models, integrins in cancer progression, personalized therapy selection, drug discovery and development, and the challenges of translational pathology. [Extracted from the article]

Background: Fundamentally defined by an imbalance in energy consumption and energy expenditure, obesity is a significant risk factor of several musculoskeletal conditions including osteoarthritis (OA). High-fat diets and sedentary lifestyle leads to increased adiposity resulting in systemic inflammation due to the endocrine properties of adipose tissue producing inflammatory cytokines and adipokines. We previously showed serum levels of specific adipokines are associated with biomarkers of bone remodelling and cartilage volume loss in knee OA patients. Whilst more recently we find the metabolic consequence of obesity drives the enrichment of pro-inflammatory fibroblast subsets within joint synovial tissues in obese individuals compared to those of BMI defined 'health weight'. As such this present study identifies obesity-associated genes in OA joint tissues which are conserved across species and conditions. Methods: The study utilised 6 publicly available bulk and single-cell transcriptomic datasets from human and mice studies downloaded from Gene Expression Omnibus (GEO). Machine learning models were employed to model and statistically test datasets for conserved gene expression profiles. Identified genes were validated in OA tissues from obese and healthy weight individuals using quantitative PCR method (N = 38). Obese and healthy-weight patients were categorised by BMI > 30 and BMI between 18 and 24.9 respectively. Informed consent was obtained from all study participants who were scheduled to undergo elective arthroplasty. Results: Principal component analysis (PCA) was used to investigate the variations between classes of mouse and human data which confirmed variation between obese and healthy populations. Differential gene expression analysis filtered on adjusted p-values of p < 0.05, identified differentially expressed genes (DEGs) in mouse and human datasets. DEGs were analysed further using area under curve (AUC) which identified 12 genes. Pathway enrichment analysis suggests these genes were involved in the biosynthesis and elongation of fatty acids and the transport, oxidation, and catabolic processing of lipids. qPCR validation found the majority of genes showed a tendency to be upregulated in joint tissues from obese participants. Three validated genes, IGFBP2 (p = 0.0363), DOK6 (0.0451) and CASP1 (0.0412) were found to be significantly different in obese joint tissues compared to lean-weight joint tissues. Conclusions: The present study has employed machine learning models across several published obesity datasets to identify obesity-associated genes which are validated in joint tissues from OA. These results suggest obesity-associated genes are conserved across conditions and may be fundamental in accelerating disease in obese individuals. Whilst further validations and additional conditions remain to be tested in this model, identifying obesity-associated genes in this way may serve as a global aid for patient stratification giving rise to the potential of targeted therapeutic interventions in such patient subpopulations. [ABSTRACT FROM AUTHOR]

Background: Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies. Target product profile: Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings. Conclusion: Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease. [ABSTRACT FROM AUTHOR]

Purpose: Artificial intelligence (AI) has emerged as a transformative force in medical research and is garnering increased attention in the public consciousness. This represents a critical time period in which medical researchers, healthcare providers, insurers, regulatory agencies, and patients are all developing and shaping their beliefs and policies regarding the use of AI in the healthcare sector. The successful deployment of AI will require support from all these groups. This commentary proposes that widespread support for medical AI must be driven by clear and transparent scientific reporting, beginning at the earliest stages of scientific research. Methods: A review of relevant guidelines and literature describing how scientific reporting plays a central role at key stages in the life cycle of an AI software product was conducted. To contextualize this principle within a specific medical domain, we discuss the current state of predictive tissue outcome modeling in acute ischemic stroke and the unique challenges presented therein. Results and Conclusion: Translating AI methods from the research to the clinical domain is complicated by challenges related to model design and validation studies, medical product regulations, and healthcare providers' reservations regarding AI's efficacy and affordability. However, each of these limitations is also an opportunity for high-impact research that will help to accelerate the clinical adoption of state-of-the-art medical AI. In all cases, establishing and adhering to appropriate reporting standards is an important responsibility that is shared by all of the parties involved in the life cycle of a prospective AI software product. [ABSTRACT FROM AUTHOR]

BackgroundSepsis is a life-threatening condition that causes millions of deaths globally each year. The need for biomarkers to predict the progression of sepsis to septic shock remains critical, with rapid, reliable methods still lacking. Transcriptomics data has recently emerged as a valuable resource for disease phenotyping and endotyping, making it a promising tool for predicting disease stages. Therefore, we aimed to establish an advanced machine learning framework to predict sepsis and septic shock using transcriptomics datasets with rapid turnaround methods.MethodsWe retrieved four NCBI GEO transcriptomics datasets previously generated from peripheral blood samples of healthy individuals and patients with sepsis and septic shock. The datasets were processed for bioinformatic analysis and supplemented with a series of bench experiments, leading to the identification of a hub gene panel relevant to sepsis and septic shock. The hub gene panel was used to establish a novel prediction model to distinguish sepsis from septic shock through a multistage machine learning pipeline, incorporating linear discriminant analysis, risk score analysis, and ensemble method combined with Least Absolute Shrinkage and Selection Operator analysis. Finally, we validated the prediction model with the hub gene dataset generated by RT-qPCR using peripheral blood samples from newly recruited patients.ResultsOur analysis led to identify six hub genes (GZMB, PRF1, KLRD1, SH2D1A, LCK, and CD247) which are related to NK cell cytotoxicity and septic shock, collectively termed 6-HubGss. Using this panel, we created SepxFindeR, a machine learning model that demonstrated high accuracy in predicting sepsis and septic shock and distinguishing septic shock from sepsis in a cross-database context. Remarkably, the SepxFindeR model proved compatible with RT-qPCR datasets based on the 6-HubGss panel, facilitating the identification of newly recruited patients with sepsis and septic shock.ConclusionsOur bioinformatic approach led to the discovery of the 6-HubGss biomarker panel and the development of the SepxFindeR machine learning model, enabling accurate prediction of septic shock and distinction from sepsis with rapid processing capabilities.

Summary: Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. Findings: The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019). Interpretation: The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).

Digital twins enable simulation, comprehensive analysis and predictions, as virtual representations of physical systems. They are also finding increasing interest and application in the healthcare sector, with a particular focus on digital twins of the brain. We discuss how digital twins in neuroscience enable the modeling of brain functions and pathology as they offer an in-silico approach to studying the brain and illustrating the complex relationships between brain network dynamics and related functions. To showcase the capabilities of digital twinning in neuroscience we demonstrate how the impact of brain tumors on the brain’s physical structures and functioning can be modeled in relation to the philosophical concept of plasticity. Against this technically derived backdrop, which assumes that the brain’s nonlinear behavior toward improvement and repair can be modeled and predicted based on MRI data, we further explore the philosophical insights of Catherine Malabou. Malabou emphasizes the brain’s dual capacity for adaptive and destructive plasticity. We will discuss in how far Malabou’s ideas provide a more holistic theoretical framework for understanding how digital twins can model the brain’s response to injury and pathology, embracing Malabou’s concept of both adaptive and destructive plasticity which provides a framework to address such yet incomputable aspects of neuroscience and the sometimes seemingly unfavorable dynamics of neuroplasticity helping to bridge the gap between theoretical research and clinical practice.

The article "Bridging Clinical Practice and Research: The Importance of Translational Medicine" discusses the concept of translational medicine, which aims to connect basic scientific discoveries with clinical applications. It highlights the significance of translational medicine in advancing patient care by accelerating the development of new therapies and improving outcomes. The article also addresses the challenges faced in translational medicine, such as the complexity of human diseases and the high cost of research, while emphasizing the role of regulatory agencies in ensuring the safety and efficacy of new treatments. [Extracted from the article]

Background: The differences between existing preclinical models and the tumor microenvironment in vivo are one of the significant challenges hindering cancer therapy development. Patient‐derived tumor organoids (PDTO) can highly retain tumor heterogeneity. Thus, it provides a more reliable platform for research in tumor biology, new drug screening, and precision medicine. Methods: We conducted a systematic review to summarise the characteristics of the existing preclinical models, the advantages of patient‐derived tumor organoids in reconstructing the tumor microenvironment, and the latest research progress. Moreover, this study deciphers organoid culture technology in the clinical precision treatment of head and neck cancer to achieve better transformation. Studies were identified through a comprehensive search of Ovid MEDLINE (Wolters Kluwer), PubMed (National Library of Medicine), web of Science (Thomson Reuters) and, Scopus (Elsevier) databases, without publication date or language restrictions. Results: In tumor development, the interaction between cellular and non‐cellular components in the tumor microenvironment (TME) has a crucial role. Co‐culture, Air‐liquid interface culture, microfluidics, and decellularized matrix have depicted great potential in reconstructing the tumor microenvironment and simulating tumor genesis, development, and metastasis. Conclusion: An accurate determination of stromal cells, immune cells, and extracellular matrix can be achieved by reconstructing the head and neck cancer tumor microenvironment using the PDTO model. Moreover, the interaction between head and neck cancer cells can also play an essential role in implementing the individualized precision treatment of head and neck cancer. [ABSTRACT FROM AUTHOR]

Aim: Peripheral nerve injury regeneration studies using animal models are crucial to different pre-clinical therapeutic approaches efficacy evaluation whatever the surgical technique explored. Materials & methods: A 944 articles systematic review on 'peripheral nerve injury in animal models' over the last 9 years was carried out. Results: It was found that 91% used rodents, and only 9% employed large animals. Different nerves are studied, with generated gaps (10,78 mm) and methods applied for regeneration evaluation uniformed. Sciatic nerve was the most used (88%), followed by median and facial nerves (2.6%), significantly different. Conclusion: There has not been a significant scale-up of the in vivo testing to large animal models (anatomically/physiologically closer to humans), allowing an improvement in translational medicine for clinical cases. [ABSTRACT FROM AUTHOR]

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The concept of "translational bioethics" has received considerable attention in recent years. Most publications draw an analogy to translational medicine and describe bioethical research that aims at implementing and evaluating ethical interventions. However, current accounts of translational bioethics are often rather vague and seem to differ with regard to conceptual and methodological assumptions. It is not clear and scarcely analyzed what exactly "translation" in the field of bioethics means, in particular regarding goals and processes so that it is justified to appeal to translational medicine. In this article, we thus explore possible analogies and disanalogies between translational medicine and translational bioethics to establish whether the often occurring reference to concepts of translational medicine in the field of bioethics can be justified by substantial analogies. We will first provide an account of different models of translational medicine. In a second step, we will propose an analytic definition that explicitly articulates the essential characteristics of "translational research" irrespective of the research field (i.e., biomedicine, bioethics). Subsequently, we will explore whether and in how far general characteristics and phases of translational research in medicine can be applied to translational research in bioethics. Based on our analyses, we will come to the skeptical conclusion that at present there are considerable conceptual disanalogies and unsolved conceptual problems that disallow using "translational bioethics" in a meaningful analogy to respective accounts in biomedicine. Nevertheless, we will demonstrate that some insights gained by the conceptual accounts of translational medicine can contribute to advance current research activities in bioethics. [ABSTRACT FROM AUTHOR]

Specific subpopulations of neurons in nerve and sensory systems must be developed and maintained, and this is accomplished in significant part by neurotrophins (NTs) and the signaling receptors on which they act, called tyrosine protein kinase receptors (Trks). The neurotrophins–tyrosine protein kinase receptors (NTs/Trks) system is involved in sensory organ regulation, including the visual system. An NTs/Trks system alteration is associated with neurodegeneration related to aging and diseases, including retinal pathologies. An emergent model in the field of translational medicine, for instance, in aging study, is the annual killifish belonging to the Nothobranchius genus, thanks to its short lifespan. Members of this genus, such as Nothobranchius guentheri, and humans share a similar retinal stratigraphy. Nevertheless, according to the authors' knowledge, the occurrence and distribution of the NTs/Trks system in the retina of N. guentheri has never been investigated before. Therefore, the present study aimed to localize neurotrophin BDNF, NGF, and NT-3 and TrkA, TrkB, and TrkC receptors in the N. guentheri retina using the immunofluorescence method. The present investigation demonstrates, for the first time, the occurrence of the NTs/Trks system in N. guentheri retina and, consequently, the potential key role of these proteins in the biology and survival of the retinal cells. [ABSTRACT FROM AUTHOR]

Nursing translational research (TR) begins with clinical discovery and medical research and leads to clinical application in patients. TR is key to improving nursing quality and developing the nursing profession. However, its development in China remains limited, and the reasons for this are unclear. We aim to enhance the recognition of nursing TR among nursing practitioners in China by exploring their cognition about nursing TR and associated influences. We distributed an internet-based questionnaire to 683 nursing practitioners between February 13 and March 15, 2023. We analyzed the characteristics and cognition of nursing TR using descriptive statistics, the chi-squared test, Fisher's exact test, the Wilcoxon rank-sum test, Kruskal–Wallis H test, and stepwise logistic regression analysis. The majority (79.65%) of nursing practitioners who responded to the questionnaire were willing to participate in nursing TR. Nursing practitioners with a higher educational level, stronger recognition of the importance of nursing TR, and stronger recognition of transdisciplinary nursing TR were more willing to participate in nursing TR. The results of this study can accelerate nursing practitioners' willingness to participate in nursing TR. We identified strategies to promote TR: provide further education, optimize courses in higher education, disseminate information, provide guidance on the importance of nursing TR, and establish a nursing TR platform with appropriate potential collaborators. • Participation in translational medical research (TMR) depends on education. • Nurses' willingness to practice TMR increases due to collaborative benefits. • Accelerating willingness to participate depends on opportunities to improve education. • Opportunities should include platform with transdisciplinary collaborators. [ABSTRACT FROM AUTHOR]

Background: Obesity is a complex metabolic disorder that is associated with several diseases. Recently, precision nutrition (PN) has emerged as a tailored approach to provide individualised dietary recommendations. Aim: This review discusses the major intrinsic and extrinsic components considered when applying PN during the management of obesity and common associated chronic conditions. Results: The review identified three main PN components: gene–nutrient interactions, intestinal microbiota, and lifestyle factors. Genetic makeup significantly contributes to inter-individual variations in dietary behaviours, with advanced genome sequencing and population genetics aiding in detecting gene variants associated with obesity. Additionally, PN-based host-microbiota evaluation emerges as an advanced therapeutic tool, impacting disease control and prevention. The gut microbiome's composition regulates diverse responses to nutritional recommendations. Several studies highlight PN's effectiveness in improving diet quality and enhancing adherence to physical activity among obese patients. PN is a key strategy for addressing obesity-related risk factors, encompassing dietary patterns, body weight, fat, blood lipids, glucose levels, and insulin resistance. Conclusion: PN stands out as a feasible tool for effectively managing obesity, considering its ability to integrate genetic and lifestyle factors. The application of PN-based approaches not only improves current obesity conditions but also holds promise for preventing obesity and its associated complications in the long term. [ABSTRACT FROM AUTHOR]

The expansion applications of semiconducting polymer dots (Pdots) among optical nanomaterial field have long posed a challenge for researchers, promoting their intelligent application in multifunctional nano-imaging systems and integrated nanomedicine carriers for diagnosis and treatment. Despite notable progress, several inadequacies still persist in the field of Pdots, including the development of simplified near-infrared (NIR) optical nanoprobes, elucidation of their inherent biological behavior, and integration of information processing and nanotechnology into biomedical applications. This review aims to comprehensively elucidate the current status of Pdots as a classical nanophotonic material by discussing its advantages and limitations in terms of biocompatibility, adaptability to microenvironments in vivo, etc. Multifunctional integration and surface chemistry play crucial roles in realizing the intelligent application of Pdots. Information visualization based on their optical and physicochemical properties is pivotal for achieving detection, sensing, and labeling probes. Therefore, we have refined the underlying mechanisms and constructed multiple comprehensive original mechanism summaries to establish a benchmark. Additionally, we have explored the cross-linking interactions between Pdots and nanomedicine, potential yet complete biological metabolic pathways, future research directions, and innovative solutions for integrating diagnosis and treatment strategies. This review presents the possible expectations and valuable insights for advancing Pdots, specifically from chemical, medical, and photophysical practitioners’ standpoints.

Lung cancer is one of the leading causes of death among all cancer deaths. This cancer is classified into two different histological subtypes: non-small cell lung cancer (NSCLC), which is the most common subtype, and small cell lung cancer (SCLC), which is the most aggressive subtype. Understanding the molecular characteristics of lung cancer has expanded our knowledge of the cellular origins and molecular pathways affected by each of these subtypes and has contributed to the development of new therapies. Traditional treatments for lung cancer include surgery, chemotherapy, and radiotherapy. Advances in understanding the nature and specificity of lung cancer have led to the development of immunotherapy, which is the newest and most specialized treatment in the treatment of lung cancer. Each of these treatments has advantages and disadvantages and causes side effects. Today, combination therapy for lung cancer reduces side effects and increases the speed of recovery. Despite the significant progress that has been made in the treatment of lung cancer in the last decade, further research into new drugs and combination therapies is needed to extend the clinical benefits and improve outcomes in lung cancer. In this review article, we discussed common lung cancer treatments and their combinations from the most advanced to the newest.

Companion animals, such as dogs and cats, have gained considerable attention in translational medicine due to their potential as models for human diseases. The use of these animals in research has opened new avenues for developing treatments that can benefit both human and veterinary patients, aligning with the One Health approach. Unlike traditional laboratory models like mice, rats, and rabbits, companion animals naturally develop diseases that closely mirror those in humans, including but not limited to diabetes, aging, cancer, and neurological disorders, making them particularly valuable in translational research. Recent advances have highlighted the role of companion animals in enhancing the effectiveness of novel therapies during clinical trials, as they are exposed to diverse environmental and lifestyle factors similar to those experienced by humans. However, the integration of companion animals into translational medicine presents challenges, particularly in terms of collaboration between veterinary and human medicine, where terminology differences in anatomy, clinical terminology, and animal classification can lead to miscommunication. In conclusion, these findings underscore the need for better implementation of the One Health approach by uniting the fragmented collaboration between veterinarians and doctors through interdisciplinary training and fostering unified efforts across both fields, with experts from various disciplines contributing their specialized knowledge in clinical practice and research.

Prostate cancer is one of the leading causes of cancer-related deaths worldwide, even when diagnosed at an early stage in humans and dogs. Dogs have a significant incidence of spontaneous prostate cancer, which is highly similar to human androgen-independent prostate cancer and represents a valuable model for comparative studies. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two main cannabinoids extracted from Cannabis sativa and have demonstrated antiproliferative and anti-invasive properties in different tumor types. In this study, CBD or THC-rich extracts inhibited the proliferation of two canine prostatic carcinoma cell lines, PC1 and PC2, showing an IC50 of 3.43 and 3.57 μM for CBD rich extracts, and 4.90 and 4.48 μM THC rich extracts, respectively. Cell death was also observed with both Annexin V and Propidium iodide staining for the canine cell lines. These results provide new information concerning the use of rich oil in canine PC and open a promising opportunity for further in vitro and in vivo studies to establish the mechanisms of action of these compounds using dogs as a natural model for prostatic carcinoma.

This article discusses the use of naturalistic, field assays with free-ranging animals as alternatives to laboratory models in scientific research. The authors highlight the differences between field and laboratory research, noting that while laboratory studies provide control and standardization, field studies offer important contextual factors. The article presents several examples of field assays that have replaced or supplemented laboratory tests, including studies on European catfish, rhesus macaques, wild mice, Tanimbar corellas, and prairie voles. The authors emphasize the strengths and weaknesses of these assays and argue for the importance of incorporating more naturalistic approaches in research. [Extracted from the article]

Rapid screening of tuberculosis by evaluation of associated volatile organic biomarkers in breath is a promising technology that is significantly faster and more convenient than traditional sputum culture tests. Methyl nicotinate (MN) and methyl p-anisate (MPA) have been isolated as potential biomarkers for mycobacterium tuberculosis and have been found in the breath of patients with active pulmonary tuberculosis. A novel approach to detection of these biomarkers in liquid droplets (e.g. from breath condensate) using inexpensive screen-printed electrodes is presented. Previous modelling studies suggest that these biomarkers complex with certain transition metals of particular valence state. This interaction can be exploited by mixing the biomarker sample into an electroactive solution (EAS) containing the functional metal ion and observing the change electrochemically. The study focuses on low biomarker concentrations, determined to be clinically relevant based on preliminary GC-MS studies of the levels found in patient breath. It was found that both the cyclic voltammogram and square wave voltammogram of copper(II) change significantly when as little as 0.1 mM MN is added to the solution, with analysis times of less than 2 min. Copper(II) exhibits three separate peaks during square wave voltammetry. The location and area of each peak are affected differently as the concentration of MN increases, suggesting a reaction with specific oxidation states of the metal. In this way, a "fingerprint" method can be used to identify biomarkers once their known interaction is established.

Abstract Background Resistance training is commonly recommended as part of secondary prevention for post-coronary artery bypass graft (CABG) patients in conjunction with aerobic exercise. Despite its potential benefits, there is currently a lack of studies investigating the impact of resistance training on proprotein convertase subtilisin kexin 9 (PCSK9). Aim To evaluate the effect of intensive resistance training on proprotein convertase subtilisin kexin 9 (PCSK9) levels among post-CABG patients undergoing cardiac rehabilitation (CR). Methods In this prospective, open-label, randomized trial, 87 post-coronary artery bypass graft (CABG) patients were randomly assigned into two groups: moderate to high intensity resistance training and aerobic training (n = 44) or aerobic training alone (n = 43) for a total of 12 sessions. Changes in PCSK9 levels was determined as a primary endpoint, while secondary endpoints included changes in the six-minute walk test (6-MWT) results, aerobic capacity, WHO-5 well-being index, fasting blood glucose, and lipid profile. Both groups underwent intention-to-treat analysis. Results Following completion of cardiac rehabilitation program, the intervention group demonstrated a significant decrease in mean PCSK9 levels when compared to the control group (β = -55 ng/ml, 95% CI -6.7 to -103.3, p = 0.026), as well as significant improvements in the 6-MWT result (β = 28.2 m, 95% CI 2.4–53.9, p = 0.033), aerobic capacity (β = 0.9 Mets, 95% CI 0.1–1.7, p = 0.021), and WHO-5 well-being index (β = 8.1, 95% CI 2.0–14.4, p = 0.011) in patients who received resistance and aerobic training. No statistically significant changes were observed in fasting blood glucose, cholesterol, LDL-C, HDL-C, and triglyceride levels. Conclusion Resistance training in CR significantly reduced PCSK­9 levels and increases patient’s functional capacity and quality of life. (NCT02674659 04/02/2016).

In recent years, artificial intelligence (AI) technology has gradually penetrated into many medical specialties, bringing unprecedented changes to the medical field. At present, with the application of AI technology in the field of ophthalmology developing rapidly, AI diagnosis is rapid, highly accurate and objective, which can optimise the diagnosis and treatment mode of ophthalmology patients and greatly improve the efficiency of clinical diagnosis. Some AI ophthalmic imaging research has been translated into products, and therefore both domestic and international AI retinal imaging products are now available. However, due to various factors such as training data, R&D capability, clinical validation and market adaptation, many research outcomes still wait to to be translated. Therefore, we propose new therapeutic regimens of retinal diseases and analyze the underlying constraints to technology translation in AI research, with the hope of improving the use of AI technology in the diagnosis and treatment of fundus diseases.

This comprehensive review explores two antiretroviral drugs, Etravirine (ETV) and Darunavir (DRV), a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor, that are commonly used in human immunodeficiency virus (HIV) infection treatment, often in combination with each other. The pharmacokinetic properties of these drugs are covered as well as the clinical trials of these two drugs combined. This paper also delves into the possible repurposing of these two drugs for other diseases, with drug repurposing being a significant factor in addressing global health challenges. DRV was extensively studied for treating COVID-19, as well as other infections, such as candidiasis and cryptococcosis, while ETV proved to be efficient in hampering Zika virus brain infection. The focus on cancer repurposing is also explored, with the results revealing that ETV has a particular inhibitory effect on ovarian cancer in vitro and on cancer molecules, such as anterior gradient protein 2 homolog (AGR2) and casein kinase 1 (CK1ε), and that DRV has an in silico inhibitory effect on human lactate dehydrogenase A (LDHA) and induces the in vitro and in vivo inhibition of pepsin, consequent laryngopharyngeal reflux, and possible laryngeal and hypopharyngeal carcinomas. The significance of fresh methods of drug development is emphasized in this work, as is the enormous potential for new therapeutic uses of the antiretroviral drugs ETV and DRV in viral and non-viral disorders.

Abstract Background Germany faces a lack of clinician scientists. This problem is widely acknowledged, not just in Germany, as clinician scientists are crucial for medical translation and innovation: trained in medical practice and research they are capable of translating scientific problems into clinical application and vice versa, clinical problems into research. The implementation of nationwide clinician scientist programs (CSPs) in Germany is supposed to solve the lack of trained clinician scientists and, as consequence, to improve the translational relationship between biomedical research and clinical practice. Against the backdrop of an increasing number of CSPs, our study provides early insights into their effectiveness with a focus on what it means to become a clinician scientist and to establish a subsequent career path as a clinician scientist in Germany. Methods During a research project that was conducted from 2020 to 2023 and funded by the German Federal Ministry of Education and Research, we studied thirteen CSPs. We developed a qualitative questionnaire and interviewed 36 clinician scientists in training, their program supervisors, as well as policy stakeholders. The goal of the interviews was to identify the key obstacles in establishing a career path for clinician scientists in Germany. Results We found three types of challenges for establishing and ensuring long term career paths for clinician scientists: First, local working conditions need to allow for clinician scientists to create and perform tasks that combine research, teaching, patient care and translation synergistically. Protection from the urgency of patient care and from metrics-based performance measures both in the clinic and in research seem key here. Second, a stable career path requires new target positions besides clinic management and senior residency. Third, there is a need for cultural change within university medicine that recognizes and rewards new translation-focused practices. Conclusion We find that CSPs improve working conditions for the duration of the program and provide protected time for doing research. After the programs, however, the career paths remain unstable, mainly due to a lack of target positions for clinician scientists. CSPs support the initial development of the clinician scientist’ role, but not in a sustainable way, because the separation of research and patient care is stabilized on an institutional and systemic level. The tasks clinician scientists perform in research remain separate from patient care and teaching, thus, limiting their translational potential. In order to remain a clinician scientist within this differentiated system of university medicine, clinician scientists have to do a significant amount of extra work.

Access to the molecular culprits of allergic reactions allows for the leveraging of molecular allergology as a new precision medicine approach—one built on interdisciplinary, basic, and clinical knowledge. Molecular allergology relies on the use of allergen molecules as in vitro tools for the diagnosis and management of allergic patients. It complements the conventional approach based on skin and in vitro allergen extract testing. Major applications of molecular allergology comprise accurate identification of the offending allergen thanks to discrimination between genuine sensitization and allergen cross-reactivity, evaluation of potential severity, patient-tailored choice of the adequate allergen immunotherapy, and prediction of its expected efficacy and safety. Allergen cross-reactivity, defined as the recognition of 2 or more allergen molecules by antibodies or T cells of the same specificity, frequently interferes with allergen extract testing. At the mechanistic level, allergen cross-reactivity depends on the allergen, the host’s immune response, and the context of their interaction. The multiplicity of allergen molecules and families adds further difficulty. Understanding allergen cross-reactivity at the immunologic level and translating it into a daily tool for the management of allergic patients is further complicated by the ever-increasing number of characterized allergenic molecules, the lack of dedicated resources, and the need for a personalized, patient-centered approach. Conversely, knowledge sharing paves the way for improved clinical use, innovative diagnostic tools, and further interdisciplinary research. Here, we aimed to provide a comprehensive and unbiased state-of-the art systematic review on allergen cross-reactivity. To optimize learning, we enhanced the review with basic, translational, and clinical definitions, clinical vignettes, and an overview of online allergen databases.

Until now, significant healthcare challenges and growing urgent clinical requirements remain incompletely addressed by presently available biomedical materials. This is due to their inadequate mechanical compatibility, suboptimal physical and chemical properties, susceptibility to immune rejection, and concerns about long-term biological safety. As an alternative, liquid metal (LM) opens up a promising class of biomaterials with unique advantages like biocompatibility, flexibility, excellent electrical conductivity, and ease of functionalization. However, despite the unique advantages and successful explorations of LM in biomedical fields, widespread clinical translations and applications of LM-based medical products remain limited. This article summarizes the current status and future prospects of LM biomaterials, interprets their applications in healthcare, medical imaging, bone repair, nerve interface, and tumor therapy, etc. Opportunities to translate LM materials into medicine and obstacles encountered in practices are discussed. Following that, we outline a blueprint for LM clinics, emphasizing their potential in making new-generation artificial organs. Last, the core challenges of LM biomaterials in clinical translation, including bio-safety, material stability, and ethical concerns are also discussed. Overall, the current progress, translational medicine bottlenecks, and perspectives of LM biomaterials signify their immense potential to drive future medical breakthroughs and thus open up novel avenues for upcoming clinical practices. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the leading causes of death among all cancer deaths. This cancer is classified into two different histological subtypes: non-small cell lung cancer (NSCLC), which is the most common subtype, and small cell lung cancer (SCLC), which is the most aggressive subtype. Understanding the molecular characteristics of lung cancer has expanded our knowledge of the cellular origins and molecular pathways affected by each of these subtypes and has contributed to the development of new therapies. Traditional treatments for lung cancer include surgery, chemotherapy, and radiotherapy. Advances in understanding the nature and specificity of lung cancer have led to the development of immunotherapy, which is the newest and most specialized treatment in the treatment of lung cancer. Each of these treatments has advantages and disadvantages and causes side effects. Today, combination therapy for lung cancer reduces side effects and increases the speed of recovery. Despite the significant progress that has been made in the treatment of lung cancer in the last decade, further research into new drugs and combination therapies is needed to extend the clinical benefits and improve outcomes in lung cancer. In this review article, we discussed common lung cancer treatments and their combinations from the most advanced to the newest. [ABSTRACT FROM AUTHOR]

Bioelectricity is the electrical activity that occurs within living cells and tissues. This activity is critical for regulating homeostatic cellular function and communication, and disruptions of the same can lead to a variety of conditions, including cancer. Cancer cells are known to exhibit abnormal electrical properties compared to their healthy counterparts, and this has driven researchers to investigate the potential of harnessing bioelectricity as a tool in cancer diagnosis, prognosis, and treatment. In parallel, bioelectricity represents one of the means to gain fundamental insights on how electrical signals and charges play a role in cancer insurgence, growth, and progression. This review provides a comprehensive analysis of the literature in this field, addressing the fundamentals of bioelectricity in single cancer cells, cancer cell cohorts, and cancerous tissues. The emerging role of bioelectricity in cancer proliferation and metastasis is introduced. Based on the acknowledgement that this biological information is still hard to access due to the existing gap between biological findings and translational medicine, the latest advancements in the field of nanotechnologies for cellular electrophysiology are examined, as well as the most recent developments in micro‐ and nano‐devices for cancer diagnostics and therapy targeting bioelectricity. [ABSTRACT FROM AUTHOR]