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The accurate identification of the primary tumor origin in metastatic cancer cases is crucial for guiding treatment decisions and improving patient outcomes. Copy number alterations (CNAs) and copy number variation (CNV) have emerged as valuable genomic markers for predicting the origin of metastases. However, current models that predict cancer type based on CNV or CNA suffer from low AUC values. To address this challenge, we employed a cutting-edge neural network approach utilizing a dataset comprising CNA profiles from twenty different cancer types. We developed two workflows: the first evaluated the performance of two deep neural networks-one ReLU-based and the other a 2D convolutional network. In the second workflow, we stratified cancer types based on anatomical and physiological classifications, constructing shallow neural networks to differentiate between cancer types within the same cluster. Both approaches demonstrated high AUC values, with deep neural networks achieving a precision of 60%, suggesting a mathematical relationship between CNV type, location, and cancer type. Our findings highlight the potential of using CNA/CNV to aid pathologists in accurately identifying cancer origins with accessible clinical tests.

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Diabetes mellitus (DM) is a prevalent metabolic disease. The clinical impact of sustained hyperglycemia on ligament healing has not been well characterized. Diabetes is a known cause of macro-, microvascular, and diabetic ulcer healing difficulties among tissues. Therefore, we aimed to investigate the healing potential occurring in injured and healthy ligaments among diabetic and healthy individuals using a rat model. We hypothesize that DM may contribute to altering the knee medial collateral ligament (MCL), thus its morphology, biochemical fitness, and functionality. The study cohort consisted of 40 rats. The animals were randomized into four equal groups. Groups I and II (20 rats) received saline subcutaneously and served as controls. Groups III and IV (20 rats) were injected with a single dose of streptozotocin (STZ). All animals underwent surgery to cut the left tibial collateral ligament in the hind limb and suture it. The access site was sutured to create inflammation and study the regenerative capacities of animals with normal carbohydrate metabolism and pharmacologically induced diabetes. Each animal then underwent sham surgery to access and suture the right tibial collateral ligament in the hind limb without ligament intervention. After the animals had undergone surgeries, groups II and IV were given melatonin supplementation for 4 weeks. Rats with DM presented with more fibrosis and calcification of the MCL and decreased healing potential. Treatment with melatonin in diabetic rats mitigated alterations and improved the antioxidant status of ligaments from the diabetic group.

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Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.

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Amyotrophic Lateral Sclerosis (ALS) is a poorly understood and fatal disease. It has a low prevalence and a 2-4 year survival period. Various theories and hypotheses relating to its development process have been proposed, albeit with no breakthrough in its treatment. Recently, the role of the adaptive immune system in ALS, particularly CD4+ T cells, has begun to be investigated. CD4+ T cells are a heterogeneous group of immune cells. They include highly pro-inflammatory types such as Th1 and Th17, as well as highly anti-inflammatory cells such as Tregs. However, the landscape of the role of CD4+ T cells in ALS is still not clearly understood. This review covers current hypotheses that elucidate how various CD4+ T cells can contribute to ALS development. These hypotheses include the SWITCH model, which suggests that, in the early stages of the disease, Tregs are highly capable of regulating the immune response. However, in the later stages of the disease, it seems that pro-inflammatory cells such as Th1 and Th17 are capable of overwhelming Treg function. The reason why this occurs is not known. Several research groups have proposed that CD4+ T cells as a whole might experience aging. Others have proposed that gamma delta T cells might directly target Tregs. Additionally, other research groups have argued that less well-known CD4+ T cells, such as Emoes+ CD4+ T cells, may be directly responsible for neuron death by producing granzyme B. We propose that the ALS landscape is highly complicated and that there is more than one feasible hypothesis. However, it is critical to take into consideration the differences in the ability of different populations of CD4+ T cells to infiltrate the blood-brain barrier, taking into account the brain region and the time of infiltration. Shedding more light on these still obscure factors can help to create a personalized therapy capable of regaining the balance of power in the battle between the anti-inflammatory and pro-inflammatory cells in the central nervous system of ALS patients.

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Ginger (Zingiber officinale Roscoe) is broadly used as a traditional remedy and food ingredient, and numerous preclinical and clinical studies have demonstrated health benefits in a range of age-related disorders. Moreover, longevity-promoting effects have been demonstrated in several (preclinical) research models. With this work, we aimed to comprehensively review the reported effects of ginger and its bioactive constituents on the twelve established hallmarks of aging, with the ultimate goal of gaining a deeper understanding of the potential for future interventions in the area of longevity-extension and counteracting of aging-related diseases. The reviewed literature supports the favorable effects of ginger and some of its constituents on all twelve hallmarks of aging, with a particularly high number of animal research studies indicating counteraction of nutrient-sensing dysregulations, mitochondrial dysfunction, chronic inflammation, and dysbiosis. On this background, validation in human clinical trials is still insufficient or is entirely missing, with the exception of some studies indicating positive effects on deregulated nutrient-sensing, chronic inflammation, and dysbiosis. Thus, the existing body of literature clearly supports the potential of ginger to be further studied in clinical trials as a supplement for the promotion of both lifespan and health span.

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Ginger (Zingiber officinale) has a rich history of traditional medicinal use and has attracted a global interest in its health benefits. This study aims to provide insights into the clinical research landscape on ginger, focusing on its pharmacological effects and studied health-related outcomes. The study design involves systematic analysis of data from clinical trials available on ClinicalTrials.gov and discussion of findings in the context of the existing scientific knowledge. A comprehensive analysis of clinical trials registered on ClinicalTrials.gov related to ginger was first conducted, and the scientific background related to specific ginger clinical research avenues was further evaluated through PubMed searches. A variety of trial designs were identified, including treatment, prevention, and supportive care objectives. A total of 188 studies were identified on ClinicalTrials.gov, of which 89 met the inclusion criteria. Among the 89 trials, treatment objectives were predominant (47.2%), and dietary supplements (40.4%) and drugs (27%) were the most prevalent intervention types. These trials covered various health outcomes, such as antiemetic activity, analgesic function, effects on health-related quality of life, blood pressure variation, energy expenditure, and reduction in xerostomia. This study analysis provides a comprehensive overview of the clinical trials landscape on ginger, focusing on its broad spectrum of potential health benefits. While individual trials show promising results, a significant gap in the available data with a low reporting rate of final results is identified, underscoring the need for further research to establish conclusive evidence of ginger's therapeutic potentials.

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Introduction: Family-centered care (FCC) is a model of care provision that sees a patient's loved ones as essential partners to the health care team and positively influences the psychological safety of patients and loved ones. Objectives: This review aims to present an overview of impactful publications, authors, institutions, journals, countries, fields of application and trends of FCC in the 21st century as well as suggestions on further research. Methods: The Web of Science Database was searched for publications on FCC between January 2000 and Dezember 2023. After screening for duplicates, VOS Viewer and CiteSpace were used to analyze and visualize the data. Results: Scientific interest in FCC has grown and resulted in the scientific output of 4,836 publications originating from 103 different countries. Based on the frequent author keywords, FCC was of greatest interest in neonatology and pediatrics, nursing, critical and intensive care, end-of-life and palliative care, and patient-related outcomes. The recent research hotspots are "patient engagement," "qualitative study," and "health literacy." Conclusion: FCC has gained recognition and spread from the pediatric to the adult palliative, intensive, end-of-life and geriatric care settings. This is a very reassuring development since adults, especially when older, want and need the assistance of their social support systems. Recent research directions include the involvement of patients in the development of FCC strategies, health literacy interventions and the uptake of telemedicine solutions.

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Objectives: Telemedical applications are solutions to challenges in the healthcare system. However, it is unclear what intensive care unit healthcare professionals expect from such solutions. This study investigated the expectations and concerns of nurses and physicians when implementing telemedicine tools in intensive care units (tele-ICU). Methods: The study was conducted in intensive care units in 2020 during the second wave of the COVID-19 pandemic. It used a mixed-methods approach targeted at physicians and nurses and involved 14 qualitative interviews and 63 quantitative questionnaires. Results: The qualitative and quantitative data showed that both nurses and physicians were willing to use tele-ICU. Nurses recognised the advantages of real-time access to expertise offered by tele-ICU, but feared this would reduce physicians' on-site patient time. Physicians, in turn, were concerned that they would be expected to be continuously on call. The majority in both groups agreed that any tele-ICU solution must be simple to use and integrate easily into existing organisational structures, networks, and work routines. Additionally, COVID-19 significantly influenced expectations: those who reported having more personal health concerns during the pandemic were more predisposed to favour the use of tele-ICU. Conclusions: Overall, tele-ICU supports better care, but a successful implementation depends on its ease of use and context-sensitive approaches. Effectively integrating tele-ICU solutions into daily clinical routines requires input from nurses and physicians and their involvement in the implementation process from the outset, as well as consideration of existing organisational structures. Such measures will vastly increase the chance of acceptance and successful adoption of telemedical solutions in clinical practice.

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Alzheimer's disease (AD) is a chronic neurodegenerative disorder with a global impact. The past few decades have witnessed significant strides in comprehending the underlying pathophysiological mechanisms and developing diagnostic methodologies for AD, such as neuroimaging approaches. Neuroimaging techniques, including positron emission tomography and magnetic resonance imaging, have revolutionized the field by providing valuable insights into the structural and functional alterations in the brains of individuals with AD. These imaging modalities enable the detection of early biomarkers such as amyloid-ß plaques and tau protein tangles, facilitating early and precise diagnosis. Furthermore, the emerging technologies encompassing blood-based biomarkers and neurochemical profiling exhibit promising results in the identification of specific molecular signatures for AD. The integration of machine learning algorithms and artificial intelligence has enhanced the predictive capacity of these diagnostic tools when analyzing complex datasets. In this review article, we will highlight not only some of the most used diagnostic imaging approaches in neurodegeneration research but focus much more on new tools like artificial intelligence, emphasizing their application in the realm of AD. These advancements hold immense potential for early detection and intervention, thereby paving the way for personalized therapeutic strategies and ultimately augmenting the quality of life for individuals affected by AD.

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As one of the leading causes of global mortality and morbidity, various neurological diseases cause social and economic burdens. Despite significant advances in the treatment of neurological diseases, establishing a proper disease model, especially for degenerative and infectious diseases, remains a major challenging issue. For long, mice were the model of choice but suffered from serious drawbacks of differences in anatomical and functional aspects of the nervous system. Furthermore, the collection of post-mortem brain tissues limits their usage in cultured cell lines. Overcoming such limitations has prompted the usage of stem cells derived from the peripheral nervous system, such as the cells of the olfactory mucosa as a preferred choice. These cells can be easily cultured in vitro and retain the receptors of neuronal cells life-long. Such cells have various advantages over embryonic or induced stem cells, including homology, and ease of culture and can be conveniently obtained from diseased individuals through either biopsies or exfoliation. They have continuously helped in understanding the genetic and developmental mechanisms of degenerative diseases like Alzheimer's and Parkinson's disease. Moreover, the mode of infection of various viruses that can lead to post-viral olfactory dysfunction, such as the Zika virus can be monitored through these cells in vitro and their therapeutic development can be fastened.

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Adverse drug reactions continue to be not only one of the most urgent problems in clinical medicine, but also a social problem. The aim of this study was a bibliometric analysis of the use of digital technologies to prevent adverse drug reactions and an overview of their main applications to improve the safety of pharmacotherapy. The search was conducted using the Web of Science database for the period 1991-2023. A positive trend in publications in the field of using digital technologies in the management of adverse drug reactions was revealed. A total of 72% of all relevant publications come from the following countries: the USA, China, England, India, and Germany. Among the organizations most active in the field of drug side effect management using digital technologies, American and Chinese universities dominate. Visualization of publication keywords using VOSviewer software 1.6.18 revealed four clusters: "preclinical studies", "clinical trials", "pharmacovigilance", and "reduction of adverse drug reactions in order to improve the patient's quality of life". Molecular design technologies, virtual models for toxicity modeling, data integration, and drug repurposing are among the key digital tools used in the preclinical research phase. Integrating the application of machine learning algorithms for data analysis, monitoring of electronic databases of spontaneous messages, electronic medical records, scientific databases, social networks, and analysis of digital device data into clinical trials and pharmacovigilance systems, can significantly improve the efficiency and safety of drug development, implementation, and monitoring processes. The result of combining all these technologies is a huge synergistic provision of up-to-date and valuable information to healthcare professionals, patients, and health authorities.

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Autoimmune Regulator 1 (AIRE1) and Forebrain Embryonic Zinc Finger-Like Protein 2 (FEZF2) play pivotal roles in orchestrating the expression of tissue-restricted antigens (TRA) to facilitate the elimination of autoreactive T cells. AIRE1's presence in the gonads of various vertebrates has raised questions about its potential involvement in gene expression control for germline cell selection. Nevertheless, the evolutionary history of these genes has remained enigmatic, as has the rationale behind their apparent redundancy in vertebrates. Furthermore, the origin of the elimination process itself has remained elusive. To shed light on these mysteries, we conducted a comprehensive evolutionary analysis employing a range of tools, including multiple sequence alignment, phylogenetic tree construction, ancestral sequence reconstruction, and positive selection assessment. Our investigations revealed intriguing insights. AIRE1 homologs emerged during the divergence of T cells in higher vertebrates, signifying its role in this context. Conversely, FEZF2 exhibited multiple homologs spanning invertebrates, lampreys, and higher vertebrates. Ancestral sequence reconstruction demonstrated distinct origins for AIRE1 and FEZF2, underscoring that their roles in regulating TRA have evolved through disparate pathways. Furthermore, it became evident that both FEZF2 and AIRE1 govern a diverse repertoire of genes, encompassing ancient and more recently diverged targets. Notably, FEZF2 demonstrates expression in both vertebrate and invertebrate embryos and germlines, accentuating its widespread role. Intriguingly, FEZF2 harbors motifs associated with autophagy, such as DKFPHP, SYSELWKSSL, and SYSEL, a process integral to cell selection in invertebrates. Our findings suggest that FEZF2 initially emerged to regulate self-elimination in the gonads of invertebrates. As organisms evolved toward greater complexity, AIRE1 likely emerged to complement FEZF2's role, participating in the regulation of cell selection for elimination in both gonads and the thymus. This dynamic interplay between AIRE1 and FEZF2 underscores their multifaceted contributions to TRA expression regulation across diverse evolutionary contexts.

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BACKGROUND AND OBJECTIVE: To improve the currently low conviction rate in cases of child abuse a forensic examination center for children and adolescents (FOKUS) was established in Vienna, Austria. Besides a state of the art treatment combined with forensic documentation, one of FOKUS' key goals is to identify potential areas for improvements within the process legal proceedings in cases of child abuse through constant scientific monitoring. The accompanying study at hand includes all patients referred to FOKUS within a two year timeframe (n = 233), monitoring their progression from first contact with the medical professionals from FOKUS to the end of criminal proceedings. A detailed analysis of case files was performed in those cases that were reported to the legal authorities by the clinicians of FOKUS (n = 87). Aim of the study is to investigate which factors contribute to the initiation of legal proceedings and a successful conviction. RESULTS: Multivariate logistic regression analyses showed that main proceedings were opened more often in cases where the offender was an adult (p < 0.001) or admitted his guilt (p < 0.001) and if digital traces were available (p = 0.001) or trial support (p = 0.024) present. Furthermore, the combined occurrence of medical documentation and victim disclosure was related to a higher probability of opening main trials. CONCLUSION: These findings underline how challenging the successful persecution of an offender in cases of child abuse is.

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Nutrition is a key determinant of health, and the dissemination of reliable nutrition information to consumers is of great importance for public health. Especially with the rise of digital communication technologies and the wide-spread online misinformation, the provision of qualitative science-based information related to diet is of great importance. The NutritionFacts.org has been established as a prominent online source of evidence-based nutrition information. In this work we aimed to investigate the use of the associated hashtag #NutritionFacts on X (formerly Twitter) over a 5 years period, from 10th of April 2018 to 10th of April 2023. The conducted analysis with the use of Symplur Signals revealed that 18,998 tweets mentioning #NutritionFacts were posted by 6,136 X users, generating a total of 50,348,223 impressions (views). Both institutional and individual accounts were broadly participating in the dissemination of #NutritionFacts tweets, and the user location profiling indicated wide international engagement with the hashtag. This work indicates that #NutritionFacts has been established as an important hashtag utilized on X for the dissemination of evidence-based information related to nutrition.

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This study conducted a comprehensive patent and bibliometric analysis to elucidate the evolving scientific landscape surrounding the development and application of pulse oximeters, including in the field of digital medicine. Utilizing data from the Lens database for the period of 2000-2023, we identified the United States, China, the Republic of Korea, Japan, Canada, Australia, Taiwan, and the United Kingdom as the predominant countries in patent issuance for pulse oximeter technology. Our bibliometric analysis revealed a consistent temporal trend in both the volume of publications and citations, underscoring the growing importance of pulse oximeters in digitally-enabled medical practice. Using the VOSviewer software(version 1.6.18), we discerned six primary research clusters: (1) measurement accuracy; (2) integration with the Internet of Things; (3) applicability across diverse pathologies; (4) telemedicine and mobile applications; (5) artificial intelligence and deep learning; and (6) utilization in anesthesiology, resuscitation, and intensive care departments. The findings of this study indicate the prospects for leveraging digital technologies in the use of pulse oximetry in various fields of medicine, with implications for advancing the understanding, diagnosis, prevention, and treatment of cardio-respiratory pathologies. The conducted patent and bibliometric analysis allowed the identification of technical solutions to reduce the risks associated with pulse oximetry: improving precision and validity, technically improved clinical diagnostic use, and the use of machine learning.

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Background: The digitalization of medicine is becoming a transformative force in modern healthcare systems. This study aims to investigate discussions regarding patient safety, as well as summarize perceived approaches to mitigating risks of adverse events expressed through the #PatientSafety Twitter hashtag during the COVID-19 pandemic. Methods: This research is grounded in the analysis of data extracted from Twitter under the hashtag #PatientSafety between December 1, 2019 and February 1, 2023. Symplur Signals, which represents a tool offering a method to monitor tweets containing hashtags registered with the Symplur Healthcare Hashtag Project, was used for analyzing the tweets shared in the study period. For text analytics of the relevant data, we further used the word cloud generator MonkeyLearn, and VOSviewer. Results: The analysis encompasses 358'809 tweets that were shared by 90'079 Twitter users, generating a total of 1'183'384'757 impressions. Physicians contributed to 18.65% of all tweets, followed by other healthcare professionals (14.31%), and health-focused individuals (10.91%). Geographically, more than a third of tweets (60.90%) were published in the United States. Canada and India followed in second and third positions, respectively. Blocks of trending terms of greater interest to the global Twitter community within the hashtag #PatientSafety were determined to be: "Patient," "Practical doctors," and "Health Care Safety Management." The findings demonstrate the engagement of the Twitter community with COVID-19 and problems related to the training, experience of doctors and patients during a pandemic, communication, the vaccine safety and effectiveness, and potential use of off-label drugs. Noteworthy, in the field of pharmacovigilance, Twitter has the possibility of identifying adverse reactions associated with the use of drugs, including vaccines. The issue of medical errors has been also discussed by Twitter users using the hashtag #PatientSafety. Conclusion: It is clear that various stakeholders, including students, medical practitioners, health organizations, pharmaceutical companies, and regulatory bodies, leverage Twitter to rapidly exchange medical information, data on the disease symptoms, and the drug effects. Consequently, there is a need to further integrate Twitter-derived data into the operational routines of healthcare organizations.

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Individuals with spinal cord injury (SCI) have higher infection rates compared to those without SCI. In this review, the immune status difference between individuals with and without traumatic SCI is investigated by examining their peripheral immune cells and markers. PubMed, Cochrane, EMBASE, and Ovid MEDLINE were searched without language or date restrictions. Studies reporting peripheral immune markers' concentration and changes in functional capabilities of immune cells that compared individuals with and without SCI were included. Studies with participants with active infection, immune disease, and central nervous system (CNS) immune markers were excluded. The review followed the PRISMA guidelines. Effect estimates were measured by Weighted Mean Difference (WMD) using a random-effects model. Study quality was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool. Fifty-four studies (1813 with SCI and 1378 without SCI) contributed to the meta-analysis. Leukocytes (n = 23, WMD 0.78, 95% CI 0.17; 1.38, I2 83%), neutrophils (n = 11, WMD 0.76, 95% CI 0.09; 1.42, I2 89%), C-reactive protein (CRP) (n = 12, WMD 2.25, 95% CI 1.14; 3.56, I2 95%), and IL6 (n = 13, WMD 2.33, 95% CI 1.20; 3.49, I2 97%) were higher in individuals with SCI vs. without SCI. Clinical factors (phase of injury, completeness of injury, sympathetic innervation impairment, age, sex) and study-related factors (sample size, study design, and serum vs. plasma) partially explained heterogeneity. Immune cells exhibited lower functional capability in individuals with SCI vs. those without SCI. Most studies (75.6%) had a moderate risk of bias. The immune status of individuals with SCI differs from those without SCI and is clinically influenced by the phase of injury, completeness of injury, sympathetic innervation impairment, age, and sex. These results provide information that is vital for monitoring and management strategies to effectively improve the immune status of individuals with SCI.

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Digital health technologies have been in use for many years in a wide spectrum of healthcare scenarios. This narrative review outlines the current use and the future strategies and significance of digital health technologies in modern healthcare applications. It covers the current state of the scientific field (delineating major strengths, limitations, and applications) and envisions the future impact of relevant emerging key technologies. Furthermore, we attempt to provide recommendations for innovative approaches that would accelerate and benefit the research, translation and utilization of digital health technologies.

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