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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.

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.

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.

IntroductionFamily-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.ObjectivesThis 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.MethodsThe 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.ResultsScientific 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.”ConclusionFCC 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.

Algae, both micro- and macroalgae, are recognized for their rich repository of bioactive compounds with potential therapeutic applications. These marine organisms produce a variety of secondary metabolites that exhibit significant anti-inflammatory, antioxidant, and antimicrobial properties, offering promising avenues for the development of new drugs and nutraceuticals. Algae-derived compounds, including polyphenols, carotenoids, lipids, and polysaccharides, have demonstrated efficacy in modulating key inflammatory pathways, reducing oxidative stress, and inhibiting microbial growth. At the molecular level, these compounds influence macrophage activity, suppress the production of pro-inflammatory cytokines, and regulate apoptotic processes. Studies have shown that algae extracts can inhibit inflammatory signaling pathways such as NF-κB and MAPK, reduce oxidative damage by activating Nrf2, and offer an alternative to traditional antibiotics by combatting bacterial infections. Furthermore, algae’s therapeutic potential extends to addressing diseases such as cardiovascular disorders, neurodegenerative conditions, and cancer, with ongoing research exploring their efficacy in preclinical animal models. The pig model, due to its physiological similarities to humans, is highlighted as particularly suitable for validating the bioactivities of algal compounds in vivo. This review underscores the need for further investigation into the specific mechanisms of action and clinical applications of algae-derived biomolecules.

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.

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.

The aim of this study was to perform a bibliometric analysis to discover what topics of dental YouTube videos have been investigated by the scientific literature, and evaluate how video characteristics were related to citation count. The Scopus electronic literature database was accessed to identify relevant papers. After screening, a total of 128 papers entered the analysis. The bibliographic data were provided by Scopus, whereas content evaluations were manually performed. Most papers evaluated videos recorded in English (85.9%). Each of the 128 papers analyzed a mean (±SD) of 79.2 ± 61.6 videos. Mean journal impact factor was 1.8 ± 1.4, and mean citation count was 13.0 ± 22.4. The preference for publication of papers was inclined towards dental journals (80.5%), with the majority (54.7%) being published without open access. Papers dealing with videos targeting patients/public had higher citations than those targeting dental professionals only (14.1 ± 23.4 vs. 4.0 ± 6.3, p < 0.001). The most represented as well as the most highly cited specialty of the dental YouTube publications was oral and maxillofacial surgery/oral medicine. Some twin or triplet studies published in the same year covering the same topic were identified, but they often covered a different number of videos.

Implementing global strategies for sustainable poultry production is imperative, considering the continuous growth of the human population and the subsequent rise in demand for poultry products, which must be fully safe for future consumers. Identifying and implementing safe, environmentally friendly, and cost-effective alternatives such as postbiotics have become imperative in sustainable poultry farming. This is primarily due to the increasing apprehensions surrounding antimicrobial resistance, the need to minimise or eliminate the use of antibiotic growth promoters, and the growing consumer preference for products that are free from chemicals and antibiotics. Postbiotics refer to bioactive compounds that are synthesised by lactic acid bacteria during the process of metabolising prebiotics. These compounds, also known as biogenics or metabolites, are soluble factors that offer notable health benefits. This concept is a recent development in the field of animal nutrition. Postbiotics possess modes of action and capabilities similar to probiotics, albeit lacking live cells, owing to the presence of probiotic secondary metabolites. These encompass several pharmacologically active compounds that positively influence the performance and quality of poultry products. This article examines the concept, impact and approaches associated with using an innovative solution such as postbiotics in the context of sustainable poultry production.

Background: Studies show that malnutrition is common among cancer patients, ranging from about 20% to more than 70%. It is known that malnutrition that is not managed properly worsens the course of the disease, prolongs the hospital stay, and impacts the quality of life and treatment toxicities. Malnutrition has many negative effects, therefore individualization and optimization of nutritional support is crucial for the patient's health. This study aimed to assess the impact of home enteral nutrition (HEN) planned with the use of indirect calorimetry on the nutritional status and body composition of cancer patients. Methods: This prospective, observational study included 28 patients with cancer recruited at the Nutrition Clinic of Department of General, Gastroenterologic and Oncologic Surgery, of the Medical University of Warsaw from December 2021 to December 2022. All patients were supported with HEN setup based on individual caloric needs for 3 months. We evaluated nutritional status, body composition, and biochemical markers of malnutrition. Results: For 67.9 % of patients, using the equations rather than indirect calorimetry would underestimate energy needs. Individualized HEN resulted in weight loss stops in 46.4 % of patients. The average change in body mass in the study group was positive and was equal to 0.46 ± 6.73 kg. No significant differences were found when comparing the mid-arm circumference (MAC) and triceps skinfold thickness (SFT) before and after inclusion in HEN, although, as in the case of body mass SFT showed an upward trend. Moreover, the percentage of patients with insufficient total protein (TP) and serum albumin concentrations decreased. This difference was statistically significant for albumin. The Nutritional Risk Index (NRI) was also significantly higher. The analysis of body composition also showed a decrease in the percentage of patients with reduced fat-free mass (FFM), body cell mass (BCM), and phase angle (PhA) value. Conclusions: The results of our research highlight the significance of well-planned nutritional care for cancer patients. Utilizing HEN and individualized approaches can effectively preserve body mass, composition, and nutritional status while minimizing safety risks, ultimately improving quality of life. Indirect calorimetry if available can be helpful to optimize nutrition care for patients with cancer in HEN.

Coronavirus disease 2019 (COVID-19) still remains the most disastrous infection continuously affecting millions of people worldwide. Herein, we performed a comparative study between the anti-influenza drug favipiravir (FAV) and the anti-thalassemia drug deferiprone (DFP) in order to examine their potential as basic scaffolds for the generation of most effective and structurally novel antivirals. To conduct the initial molecular modelling and virtual screening steps, our recently proposed single crystal X-ray diffraction (SCXRD)/HYdrogen DEssolvation (HYDE) technology platform has been used. This platform allows molecular design, interactive prioritization and virtual evaluation of newly designed molecules, simultaneously affecting two COVID-related targets, including angiotensin-converting enzyme 2 (ACE2) as a host-cellular receptor (host-based approach) and the main protease (Mpro) enzyme of the spike glycoprotein of SARS-Cov-2 (virus-based approach). Based on the molecular docking results, DFP has shown higher binding affinity (Ki HYDE values) over FAV towards both biological targets. The tautomeric, physicochemical, and biological properties of FAV and DFP have been studied both experimentally and theoretically using molecular spectroscopy (UV–VIS absorption), parallel artificial membrane permeability assay, and cell biology (PAMPA and MTT assay), as well as DFT quantum chemical calculations. According to the obtained results, the enol tautomers of both compounds are considerably more stable in different organic solvents. However, the keto tautomer of FAV was estimated to be most preferable under physiological conditions, which is in good agreement with the molecular docking studies. The isolated crystal structure of DFP is in an excellent agreement with the computation in respect of the most stable tautomer. Combined single X-ray/molecular modeling studies including HYDE analyses provided not only insights into the protein–ligand interactions within the binding site of SARS-Cov-2-ACE2 and SARS-Cov-2-Mpro, but also a valuable information regarding the most stable enol tautomeric form of DFP that contributes to its estimated higher potency against these targets.

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.

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.

7-ketocholesterol is a cytotoxic oxysterol which is frequently increased in many chronic inflammatory and age-related diseases. Thus, the inhibition of the toxicity of 7-ketocholesterol is a major challenge to treat these diseases. 158N oligodendrocytes were used to evaluate the cytoprotective effects of lipids: ω-3 and ω-9 fatty acids (α-linolenic acid (C18:3n-3), eicosapentaenoic acid (C20:5n-3), docosahexaenoic acid (C22:6n-3), erucic acid (C22:1n-9) and oleic acid (C18:1n-9)), Lorenzo's oil (a mixture of oleic and erucic acid, 4:1) and sulfo-N-succinimidyl oleate (SSO, a synthetic derivative of oleic acid). On 158N cells, the ability of these molecules to inhibit 7KC-induced oxiapoptophagy (plasma membrane alteration, loss of ΔΨm, peroxisomal dysfunction, reactive oxygen species overproduction, induction of apoptosis and autophagy) were determined. ARPE-19 epithelial retinal cells were also used to evaluate the cytoprotective effect of SSO on 7KC-induced cell death. Unlike ω-3 and ω-9 fatty acids and Lorenzo's oil, sulfo-N-succinimidyl oleate had no cytotoxic effects over a wide range of concentrations. Noteworthy, unlike fatty acids and Lorenzo's oil, the cytoprotective effects of sulfo-N-succinimidyl oleate on 7KC-induced oxiapoptophagy, a caspase-dependent mode of cell death on 158N cells, were not associated with an accumulation of lipid droplets. In addition, on ARPE-19 cells, sulfo-N-succinimidyl oleate prevented 7KC-induced oxidative stress and cell death. These different characteristics of SSO make it possible to envisage its use for therapeutic purposes in diseases where 7-ketocholesterol levels are increased without eventual secondary side effects due to lipid droplets formation.