Search Results (637)

Background: Cuproptosis is a copper-induced mitochondrial cell death, and regulating cuproptosis is becoming a rising cancer treatment modality. Here, we attempted to establish a cuproptosis-associated lncRNAs (CRLs) signature (CRlncSig) to predict the survival, immune landscape, and treatment response in ovarian cancer (OC) patients. Methods: A series of statistical analyses were used to identify the key CRLs that are closely related to the prognosis, and a prognostic CRlncSig was constructed. The predictive accuracy of the CRlncSig was further validated in an independent Gene Expression Omnibus (GEO) set. Then, we compared the immune cell infiltration, immune checkpoints, tumor microenvironment (TME), tumor mutational burden (TMB), drug sensitivity, and efficacy of immunotherapy between the two subgroups. We further built a nomogram integrating the CRlncSig and different clinical traits to enhance the clinical application of the CRlncSig. Results: Nine hub CRLs, namely RGMB-AS1, TYMSOS, DANCR, LINC00702, LINC00240, LINC00996, DNM1P35, LINC00892, and TMEM254-AS1, were correlated with the overall survival (OS) of OC and a prognostic CRlncSig was established. The CRlncSig classified OC patients into two risk groups with strikingly different survival probabilities. The time-dependent ROC (tdROC) curves demonstrated good predictive ability in both the training cohort and an independent validation cohort. Multivariate analysis confirmed the independent predictive performance of the CRlncSig. We constructed a nomogram based on the CRlncSig, which can predict the prognosis of OC patients. The high-risk score was characterized by decreased immune cell infiltration and activation of stroma, while activation of immunity was observed in the low-risk subgroup. Moreover, patients in low-risk subgroups had more Immunophenoscore (IPS) and fewer immune escapes compared to high-risk subgroups. Finally, an immunotherapeutic cohort confirmed the value of the CRlncSig in predicting immunotherapy outcomes. Conclusions: The developed CRlncSig may be promising for the clinical prediction of OC patient outcomes and immunotherapeutic responses. Full article

Lumpy skin disease (LSD), caused by the LSD virus (LSDV), a dsDNA virus of the genus Capripoxvirus, represents a significant cross-border infectious threat, particularly impacting cattle and water buffaloes through transmission by blood-feeding insects. Traditionally endemic to Southern Africa, LSD has rapidly spread over the past decade through the Middle East to Eastern Europe and China, reaching Korea in October 2023. This outbreak prompted a nationwide vaccination campaign, addressing both the disease’s severe economic impact and its status as a notifiable disease under the World Organisation for Animal Health. This study assesses the seropositivity of the LSD vaccine in cattle across four Korean provinces 2–3 months post-vaccination, aiming to inform improvements in biosecurity and vaccination strategies. Overall, 30.59% of the cattle tested (1196 out of 3910) exhibited positive antibody responses, comparable to international post-vaccination findings. Analysis further revealed differences in the antibody positivity between farm types and management practices. Specifically, farms where vaccines were administered by veterinarians showed no significant difference in antibody positivity between Korean native cattle and dairy cattle, regardless of the presence of restraint facilities. However, on farms where vaccinations were conducted by the owners, dairy cattle demonstrated a higher seropositivity (43.30 ± 33.39%) compared to Korean native cattle (21.97 ± 20.79%) in the absence of restraint facilities. Further comparisons underscored the impact of restraint facilities on vaccination efficacy, with dairy farms generally achieving higher antibody positivity (29.43 ± 30.61%) than farms with Korean native cattle (23.02 ± 23.33%) (p < 0.05), suggesting that consistent vaccine delivery methods enhance immunogenic responses. Contrarily, no significant difference was noted in antibody positivity between large- and small-scale farms, indicating that farm size did not notably impact the effectiveness of the vaccinator. These findings emphasize that while current vaccines are sufficiently inducing immunity, enhancing vaccination strategies, particularly through trained personnel and improved restraint facilities, is crucial. This study’s insights into the impact of vaccination and farm management practices provide valuable guidance for refining LSD control measures in Korea and potentially other affected regions. Full article

Background: Multiple sclerosis (MS) is an immune-mediated inflammatory disease that primarily targets the myelin of axons. Extremities are frequently affected, resulting in a negative impact on both activities of daily living (ADL) and quality of life. In recent years, there has been increasing interest in the potential benefits of exercise and blood flow restriction training (BFRT) programs as a therapeutic tool in people with neurological disorders. The aim of the present systematic review was to know the clinical effects of BFRT programs in people with MS. Methods: A systematically comprehensive literature search was conducted and registered in PROSPERO prior to its execution under the reference number CRD42024588963. The following data sources were used: Pubmed, Scopus, Web of Science (WOS) and the Cochrane Library. The following data were extracted from the papers: study design, sample, interventions, dosage, outcome measures and results. To assess the methodological quality of the papers included, the Quality Index of Downs and Black was used. Additionally, the articles were classified according to the levels of evidence and grades of recommendation for diagnosis studies established by the Oxford Center for Evidence-Based Medicine. Also, the Cochrane Handbook for Systematic Reviews of Interventions was used by two independent reviewers to assess risk of bias, assessing the six different domains. Results: Seven articles with a total of 71 participants were included in the review. Of the seven articles, five papers studied the effectiveness of BFRT combined with strengthening exercises and two papers studied the effect of BFRT combined with aerobic exercise. Of the five articles that analyzed BFRT combined with strengthening exercises, only two presented a control group. Both performed a low-load resistance training in combination with BFRT with four series, 30/15/15/15 repetitions and a rest of 1 min between the series and 3 min between the exercises. The control groups to which they were compared performed a high intensity strengthening exercise protocol which had the same exercises, sets, rests and duration of the protocol as the experimental groups. For those two papers which investigated the effects of BFRT combined with aerobic training, exercise was performed in two sessions per week for a period of 8 and 6 weeks, respectively. In both studies, the experimental protocol began with a warm-up phase and ended with a cool-down phase, and there were differences in cuff management. All these investigations found positive effects in the interventions that combined exercise with BFRT. The characteristics, outcome measures, effects of the interventions and the assessment of the methodological quality of the included studies and risk of bias are shown in the tables. Conclusions: BFRT in people with MS appears to be effective and safe for people with MS. BFRT might show positive clinical effects on strength, hypertrophy and balance outcomes. Nevertheless, future research should be conducted with better methodological quality to ensure the potential benefits of BFRT in people with MS since the studies analyzed present a high risk of bias and methodological limitations. Full article

Background: The Measles–Rubella Microarray Patch (MR-MAP) is an important technology that is expected to reduce coverage and equity gaps for measles-containing vaccines (MCVs), reach zero-dose children, and contribute to elimination of measles and rubella. MR-MAPs are anticipated to be easier to deploy programmatically and could be delivered by lesser-trained health workers, thereby increasing immunization coverage. The most advanced MR-MAP has reached clinical proof-of-concept through a Phase I/II trial in the target population of infants and young children. The World Health Organization (WHO) and partners have developed the Phase III clinical trial framework for MR-MAPs presented in this article. Objectives and Methods: The purpose of such framework is to inform the considerations, design and approach for the pivotal clinical trial design, while considering the anticipated data requirements to inform regulatory approval, WHO prequalification, and policy decision. Results: The proposed Phase III trial would compare the immunogenicity and safety of an MR-MAP with MR vaccine delivered subcutaneously in 9- to 10-month-old infants. An analysis of non-inferiority (NI) of immunogenicity would occur six weeks after the first dose. Should regulatory agencies or policy makers require, a proportion of infants could receive a second dose of either the same or alternate MR vaccine presentation six months after the first dose, with those children returning six weeks after the second dose for a descriptive assessment of immunogenicity, and then followed up six months after the second dose for evaluation of safety and immunogenicity. It is anticipated that this proposed pivotal Phase III trial framework would generate the required clinical data for regulatory licensure and WHO prequalification (PQ) of MR-MAPs. However, the trial design would need to be reviewed and confirmed by a national regulatory authority (NRA) that will assess the product for regulatory licensure and the WHO PQ team. Additional research will likely be required to generate data on concomitant vaccine delivery, the safety and immunogenicity of MR-MAPs in other age groups such as children 1–5 years and infants younger than 9 months of age, and the impact of MR-MAPs on coverage and equity. Such studies could be conducted during or after clinical MR-MAP development. Full article

Omics approaches were extensively applied during the coronavirus disease 2019 (COVID-19) pandemic to understand the disease, identify biomarkers with diagnostic and prognostic value, and discover new molecular targets for medications. COVID-19 continues to challenge the healthcare system as the virus mutates, becoming more transmissible or adept at evading the immune system, causing resurgent epidemic waves over the last few years. In this study, we used saliva from volunteers who were negative and positive for COVID-19 when Omicron and its variants became dominant. We applied a direct solid-phase extraction approach followed by non-target metabolomics analysis to identify potential salivary signatures of hospital-recruited volunteers to establish a model for COVID-19 screening. Our model, which aimed to differentiate COVID-19-positive individuals from controls in a hospital setting, was based on 39 compounds and achieved high sensitivity (85%/100%), specificity (82%/84%), and accuracy (84%/92%) in training and validation sets, respectively. The salivary diagnostic signatures were mainly composed of amino acids and lipids and were related to a heightened innate immune antiviral response and an attenuated inflammatory profile. The higher abundance of thyrotropin-releasing hormone in the COVID-19 positive group highlighted the endocrine imbalance in low-severity disease, as first reported here, underscoring the need for further studies in this area. Full article

Background: The cortisol awakening response (CAR) is a pivotal component of the body’s stress response, yet its dynamics under repeated acute stress and its interplay with immune biomarkers remain inadequately understood. Methods: This study examined 80 second-year military medical students undergoing a 5-day intensive surgical simulation designed to elicit stress responses. Salivary samples were collected daily upon waking and 30 min thereafter to measure cortisol and a panel of cytokines using bead-based multiplex ELISA. Results: Analysis revealed a significant blunting of the CAR on the third day of training (p = 0.00006), followed by a recovery on the fourth day (p = 0.0005). Concurrently, specific cytokines such as CXCL1 (r = 0.2, p = 0.0005), IL-6 (r = 0.13, p = 0.02), IL-10 (r = 0.14, p = 0.02), and VEGF-A (r = 0.17, p = 0.003) displayed patterns correlating with the CAR, with increased strength of associations observed when assessing cytokine levels against the CAR of the preceding day (CXCL1 r = 0.41, p = 0.0002. IL-6 r = 0.38, p = 0.0006. IL-10 r = 0.3, p = 0.008. VEGF-A r = 0.41, p = 0.0002). Conclusions: These results suggest a temporal relationship between stress-induced cortisol dynamics and immune regulation. The CAR pattern demonstrated in this study may represent induction of and recovery from psychological burnout. Moreover, the observed cytokine associations provide insight into the mechanisms by which stress can influence immune function. The results may have broader implications for managing stress in high-performance environments, such as military and medical professions, and for identifying individuals at risk of stress-related immune suppression. Full article

For several years, the determination of a differential cell count of a raw milk sample has been proposed as a more accurate tool for monitoring the udder health of dairy cows compared with using the absolute somatic cell count. However, the required sample preparation and staining process can be labor- and cost-intensive. Therefore, the aim of our study was to demonstrate the feasibility of analyzing unlabeled blood and milk leukocytes from dairy cows by means of digital holographic microscopy (DHM). For this, we trained three different machine learning methods, i.e., k-Nearest Neighbor, Random Forests, and Support Vector Machine, on sorted leukocyte populations (granulocytes, lymphocytes, and monocytes/macrophages) isolated from blood and milk samples of three dairy cows by using fluorescence-activated cell sorting. Afterward, those classifiers were applied to differentiate unlabeled blood and milk samples analyzed by DHM. A total of 70 blood and 70 milk samples were used. Those samples were collected from five clinically healthy cows at 14-time points within a study period of 26 days. The outcome was compared with the results of the same samples analyzed by flow cytometry and (in the case of blood samples) also to routine analysis in an external laboratory. Moreover, a standard vaccination was used as an immune stimulus during the study to check for changes in cell morphology or cell counts. When applied to isolated leukocytes, Random Forests performed best, with a specificity of 0.93 for blood and 0.84 for milk cells and a sensitivity of 0.90 and 0.81, respectively. Although the results of the three analytical methods differed, it could be demonstrated that a DHM analysis is applicable for blood and milk leukocyte samples with high reliability. Compared with the flow cytometric results, Random Forests showed an MAE of 0.11 (SD = 0.04), an RMSE of 0.13 (SD = 0.14), and an MRE of 1.00 (SD = 1.11) for all blood leukocyte counts and an MAE of 0.20 (SD = 0.11), an RMSE of 0.21 (SD = 0.11) and an MRE of 1.95 (SD = 2.17) for all milk cell populations. Further studies with larger sample sizes and varying immune cell compositions are required to establish method-specific reference ranges. Full article

Background/Objectives: Inborn errors of immunity (IEI) encompass various congenital disorders, resulting in immunity defects and recurrent infections. Home-based subcutaneous immunoglobulin replacement therapy (scIgRT) is the best treatment option for those with primary antibody deficiency (PAD). However, the lack of standardized procedures in patient training remains a challenge. Our study investigates nurses’ practice and perspectives, aiming to identify areas for improvement in at-home scIgRT practice. Methods: We prepared a structured survey regarding scIgRT, including needle choice experience and perception of adverse events, and distributed it among qualified nurses involved in patient training and scIgRT supervising. Results: We included 56 nurses with a median age of 50 years. Among them, 67.9% represented adult care providers, while 32.1% supervised IgRT in children. Most respondents (83.9%) used the classic or assisted with hyaluronidase scIgRT preparations. Single-channel needles were administered most commonly (85.7%). The needle length was mostly chosen solely by a nurse (57.1%) or in cooperation with the patient (23.2%). Next, 9 mm and 12 mm needles were used most often (92.9% and 78.6%, respectively). As expected, the 6 mm needle was more frequently applied for children compared to adults (n = 16, 88.9% vs. n = 11, 28.9%, p < 0.001), while 12 mm was primarily used in adults (n = 35, 92.1% vs. n = 9, 50.0%, p < 0.001). Visual skin fold assessment was the basis for the needle selection (58.9%), followed by the injection site rule (26.8%) or a choice between two available needle types for thinner or thicker patients (25.0%). Results of this survey indicate that, according to nurses’ opinions presented in this survey, the needle length could be associated with local scIgRT adverse events, such as side needle leakage or local burning. Yet, it was likely unrelated to general adverse signs, such as headaches or dizziness. Most respondents (66.1%) indicated that, even if local adverse events occur, patients are reluctant to change scIgRT preparation or needle length. Most participants (69.6%) reported that the optimal administration technique needs to be discussed with the patient before and during scIgRT. Conclusions: This study sheds light on scIgRT practice in Poland, emphasizing deficiency in needle selection technique. Future research should focus on standardized training and advanced needle selection procedures on patient outcomes, investigating the correlation between needle strategies and adverse events, as well as the effectiveness of scIgRT. Full article

Background/Objectives: The human gut microbiome is a complex ecosystem of microorganisms that can influence our health and exercise habits. On the other hand, physical exercise can also impact our microbiome, affecting our health. Our narrative review examines the bidirectional relationship between physical activity and the gut microbiome, as well as the potential for targeted probiotic regimens to enhance sports performance. Methods: We conducted a comprehensive literature review to select articles published up till January 2024 on the topics of physical exercise, sports, probiotics, and gut microbiota from major scientific databases, incorporating over 100 studies. Results: We found that the impact of physical activity on the gut microbiome varies with the type and intensity of exercise. Moderate exercise promotes a healthy immune system, while high-intensity exercise for a long duration can cause a leaky gut and consequent systemic inflammation, which may disrupt the microbial balance. Combining aerobic and resistance training significantly affects bacterial diversity, linked to a lower prevalence of chronic metabolic disorders. Furthermore, exercise enhances gut microbiome diversity, increases SCFA production, improves nutrient utilization, and modulates neural and hormonal pathways, improving gut barrier integrity. Our findings also showed probiotic supplementation is associated with decreased inflammation, enhanced sports performance, and fewer gastrointestinal disturbances, suggesting that the relationship between the gut microbiome and physical activity is mutually influential. Conclusions: The bidirectional relationship between physical activity and the gut microbiome is exemplified by how exercise can promote beneficial bacteria while a healthy gut microbiome can potentially enhance exercise ability through various mechanisms. These findings underscore the importance of adding potential tailored exercise regimens and probiotic supplementation that consider individual microbiome profiles into exercise programs. Full article

This systematic review synthesizes evidence on biomarker responses to physiological loads in professional male team sport athletes, providing insights into induced fatigue states. Structured searches across major databases yielded 28 studies examining various biomarkers in elite team sport players. Studies evaluated muscle damage markers, anabolic/catabolic hormones reflecting metabolic strain, inflammatory markers indicating immune activity and tissue damage, immunological markers tied to infection risk, and oxidative stress markers showing redox imbalances from excessive physiological load. Responses were examined in official matches and training across competitive seasons. The evidence shows that professional team sports induce significant alterations in all studied biomarkers, reflecting measurable physiological strain, muscle damage, oxidative stress, inflammation, and immunosuppression during intensive exercise. These effects tend to be larger and more prolonged after official matches compared to training. Reported recovery time courses range from 24-h to several days post-exercise. Monitoring biomarkers enables quantifying cumulative fatigue and physiological adaptations to training/competition loads, helping to optimize performance while mitigating injury and overtraining. Key biomarkers include creatine kinase, testosterone, cortisol, testosterone/cortisol ratio, salivary immunoglobulin-A, and markers of inflammation and oxidative stress. Further research should extend biomarker monitoring to cover psychological stress and affective states alongside physiological metrics for deeper insight into athlete wellness and readiness. Full article

Introduction: Sepsis remains a major contributor to critical care mortality and morbidity worldwide. Despite advances in understanding its complex immunopathology, the compartmentalized nature of immune responses across different organs has yet to be fully translated into targeted therapies. This review explores the burden of sepsis on organ-specific immune dysregulation, immune resilience, and epigenetic reprogramming, emphasizing translational challenges and opportunities. Methods: We implemented a systematic literature search strategy, incorporating data from studies published between 2010 and 2024, to evaluate the role of molecular profiling techniques, including transcriptomics and epigenetic markers, in assessing the feasibility of targeted therapies. Results: Sepsis-induced immune dysregulation manifests differently in various organs, with lung, heart, liver, and kidney responses driven by unique local immune environments. Organ-specific biomarkers, such as the Spns2/S1P axis in lung macrophages, mitochondrial dysfunction in the heart, proenkephalin for early acute kidney injury (AKI), and adrenomedullin for predicting multi-organ failure, offer promising avenues for timely intervention. Furthermore, immune resilience, particularly through regulatory T-cell modulation and cytokine targeting (e.g., IL-18), is crucial for long-term recovery. Epigenetic mechanisms, including histone modification and trained immunity, present opportunities for reprogramming immune responses but require more precision to avoid unintended inflammatory sequelae. Conclusions: A deeper understanding of compartmentalized immune responses and the dynamic immune landscape in sepsis is critical for developing precision therapies. Real-time immune monitoring and organ-targeted interventions could revolutionize sepsis management, although significant barriers remain in clinical translation. Further research is required to establish biomarkers and treatment timing that optimize therapeutic efficacy while minimizing systemic risks. Full article

A high-altitude, low-pressure hypoxic environment has severe effects on the health and work efficiency of its residents, and inadequate preventive measures and adaptive training may lead to the occurrence of AMS. Acute exposure to hypoxia conditions can have a less-favorable physiological effect on the human immune system. However, the regulation of the immune system in high-altitude environments is extremely complex and remains elusive. This study integrated system bioinformatics methods to screen for changes in immune cell subtypes and their associated targets. It also sought potential therapeutically effective natural compound candidates. The present study observed that monocytes, M1 macrophages and NK cells play a crucial role in the inflammatory response in AMS. IL15RA, CD5, TNFSF13B, IL21R, JAK2 and CXCR3 were identified as hub genes, and JAK2 was positively correlated with monocytes; TNFSF13B was positively correlated with NK cells. The natural compound monomers of jasminoidin and isoliquiritigenin exhibited good binding affinity with JAK2, while dicumarol and artemotil exhibited good binding affinity with TNFSF13B, and all are expected to become a potential therapeutic agents. Full article

Background/Objectives: High-grade gliomas are the most common primary malignant brain tumors in adults. These neoplasms remain predominantly incurable due to the genetic diversity within each tumor, leading to varied responses to specific drug therapies. With the advent of new targeted and immune therapies, which have demonstrated promising outcomes in clinical trials, there is a growing need for image-based techniques to enable early prediction of treatment response. This study aimed to evaluate the potential of radiomics and artificial intelligence implementation in predicting progression-free survival (PFS) in patients with highest-grade glioma (CNS WHO 4) undergoing a standard treatment plan. Methods: In this retrospective study, prediction models were developed in a cohort of 51 patients with pathologically confirmed highest-grade glioma (CNS WHO 4) from the authors’ institution and the repository of the Cancer Imaging Archive (TCIA). Only patients with confirmed recurrence after complete tumor resection with adjuvant radiotherapy and chemotherapy with temozolomide were included. For each patient, 109 radiomic features of the tumor were obtained from a preoperative magnetic resonance imaging (MRI) examination. Four clinical features were added manually—sex, weight, age at the time of diagnosis, and the lobe of the brain where the tumor was located. The data label was the time to recurrence, which was determined based on follow-up MRI scans. Artificial intelligence algorithms were built to predict PFS in the training set (n = 75%) and then validate it in the test set (n = 25%). The performance of each model in both the training and test datasets was assessed using mean absolute percentage error (MAPE). Results: In the test set, the random forest model showed the highest predictive performance with 1-MAPE = 92.27% and a C-index of 0.9544. The decision tree, gradient booster, and artificial neural network models showed slightly lower effectiveness with 1-MAPE of 88.31%, 80.21%, and 91.29%, respectively. Conclusions: Four of the six models built gave satisfactory results. These results show that artificial intelligence models combined with radiomic features could be useful for predicting the progression-free survival of high-grade glioma patients. This could be beneficial for risk stratification of patients, enhancing the potential for personalized treatment plans and improving overall survival. Further investigation is necessary with an expanded sample size and external multicenter validation. Full article

Aloe vera is one of the most significant therapeutical plant species that belongs to the family Liliaceae. Aloe vera is composed of a high amount of water, with the remainder being dry matter. The dry matter contains a lot of bioactive compounds like carbohydrates, fats, and enzymes, with various therapeutic and antimicrobial properties. It can enhance the proliferation of cells and prevent cell damage by anti-oxidative properties (stimulating the secretion of superoxide dismutase and peroxidase). Human skin is colonized by microbes like fungi (Candida albicans), bacteria (Propionibacterium acnes, Staphylococcus aureus), and mites. These commensals are responsible for skin characteristics such as acidic pH, the pungent smell of sweat, etc. Human fetuses lack skin microbiota, and their skin is colonized after birth. Commensals present on the skin have a crucial role in training the human immune system against other pathogenic microbes. Propionibacterium acnes act as an opportunistic pathogen when the balance between the commensals is disturbed. We also emphasize the recent progress in identifying the aloe metabolite biosynthesis pathways and the associated enzyme machinery. The hyperproliferation of Propionibacterium acnes causes acne, and acemannan plays a significant role in its cure. Hence, we need to consider a new treatment approach based on the root cause of this dysbiosis. Full article

Background: Identifying factors affecting heart health in amateur athletes can significantly impact their health and help them achieve high performance. The current knowledge of these predictors is insufficient. The purpose of this study was to identify the biochemical determinants of maximal oxygen uptake (VO2 max) in male amateur long-distance cross-country skiers (37.9 ± 6.58 years, 51.08 ± 4.61 VO2 max ml/kg/min) in the preparation period. Methods: In this cross-sectional study, a time trial test was used to determine VO2 max and venous blood via biochemical markers. Descriptive statistics and Pearson correlation were used to analyze the data. The regression model determined the predictors. Results: VO2 max was significantly correlated with nine moderate or weak variables. Two regression models (R² = 0.94 and R² = 0.9) each identified two determinants of VO2 max, hemoglobin (p < 0.001) and C-reactive protein (p < 0.001), as well as erythrocyte sedimentation (p < 0.001) and platelets (p = 0.03). Only hemoglobin positive affected VO2 max. Conclusions: The results may indicate, in addition to results regarding hemoglobin concentration and its changes, the necessity to monitor the immune system, which may affect the capacity for amateur exercise. Biochemical monitoring is an essential tool for evaluating the individual adaptation to exercise and developing an effective training plan. The application of this knowledge can facilitate the achievement of optimal individual performance capabilities among cross-country skiing amateurs. Full article