Increasing evidence suggests the role of reactive oxygen and nitrogen species (RONS) in regulating antitumor immune effects and immunosuppression. RONS modify biomolecules and induce oxidative post-translational modifications (oxPTM) on proteins that can alarm phagocytes. However, it is unclear if and how protein oxidation by technical means could be a strategy to foster antitumor immunity and therapy. To this end, cold gas plasma technology producing various RONS simultaneously to oxidize the two melanoma-associated antigens MART and PMEL is utilized. Cold plasma-oxidized MART (oxMART) and PMEL (oxPMEL) are heavily decorated with oxPTMs as determined by mass spectrometry. Immunization with oxidized MART or PMEL vaccines prior to challenge with viable melanoma cells correlated with significant changes in cytokine secretion and altered T-cell differentiation of tumor-infiltrated leukocytes (TILs). oxMART promoted the activity of cytotoxic central memory T-cells, while oxPMEL led to increased proliferation of cytotoxic effector T-cells. Similar T-cell results are observed after incubating splenocytes of tumor-bearing mice with B16F10 melanoma cells. This study, for the first time, provides evidence of the importance of oxidative modifications of two melanoma-associated antigens in eliciting anticancer immunity.

OBJECTIVE: Cold physical plasma (CPP) has emerged as an effective therapy in oncology by inducing cytotoxic effects in various cancer cells, including chondrosarcoma (CS), Ewing\'s sarcoma (ES), and osteosarcoma (OS). The current study investigated the impact of CPP on cell motility in CS (CAL-78), ES (A673), and OS (U2-OS) cell lines, focusing on the actin cytoskeleton.
METHODS: The CASY Cell Counter and Analyzer was used to study cell proliferation and determine the optimal concentrations of fetal calf serum to maintain viability without stimulation of cell proliferation. CellTiter-BlueCell viability assay was used to determine the effects of CPP on the viability of bone sarcoma cells. The Radius assay was used to determine cell migration. Staining for Deoxyribonuclease I, G-actin, and F-actin was used to assay for the effects on the cytoskeleton.
RESULTS: Reductions in cell viability and motility were observed across all cell lines following CPP treatment. CPP induced changes in the actin cytoskeleton, leading to decreased cell motility.
CONCLUSIONS: CPP effectively reduces the motility of bone sarcoma cells by altering the actin cytoskeleton. These findings underscore CPP\'s potential as a therapeutic tool for bone sarcomas and highlight the need for further research in this area.

BACKGROUND: The role of prostate-specific antigen (PSA) testing in prostate cancer (PCa) screening has evolved over recent decades with multiple randomized controlled trials (RCTs) spurring guideline changes. At present, controversy exists due to the indolent nature of many prostate cancers and associated risks of overdiagnosis and overtreatment. This review examines major RCTs evaluating PSA screening to inform clinical practices.
METHODS: We summarize findings from primary RCTs investigating PSA screening\'s impact on PCa mortality and incidence: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, the European Randomized Study of Screening for Prostate Cancer (ERSPC), and the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP).
RESULTS: The PLCO Trial randomized men to annual PSA and DRE screening or usual care, reporting no significant difference in PCa mortality between groups at 17 years (RR 0.93, [95% CI: 0.81-1.08]), yet significantly increased detection and concomitant decreased detection in Gleason 6 (RR 1.17, [95% CI: 1.11-1.23]) and 8-10 disease (RR 0.89, [95% CI: 0.80-0.99]) in the screening group, respectively. The ESPRC Trial randomized men across seven European countries to PSA screening every 2-4 years or usual care, noting a 20% reduction in PCa mortality at 9 years (RR 0.81, [95% CI: 0.65-0.98]) and significant decrease in metastatic disease at 12 years (RR 0.70, [95% CI: 0.60-0.82]). The CAP Trial assessed a single PSA screening test\'s impact on PCa mortality yielding no significant difference in PCa mortality at 10 years (RR 0.96, [95% CI: 0.85-1.08]). Limitations amongst studies included high contamination between study arms and low compliance with study protocols.
CONCLUSIONS: While the CAP and initial PLCO trials showed no significant reduction in PCa mortality, the ERSPC demonstrated a 21% reduction at 13 years, with further benefits at extended follow-up. Differences in outcomes are attributed to variations in trial design, contamination, adherence rates, and PSA thresholds. Future studies are needed focus on optimizing screening intervals, targeting high-risk populations, and incorporating non-invasive diagnostic tools to improve screening efficacy and reduce associated harms.

Clinical therapies, including dermatology and oncology, require safe application. In vitro experiments allow only limited conclusions about in vivo effects, while animal studies in, e.g., rodents have ethical constraints at a large scale. Chicken embryos lack pain reception until day 15 postfertilization, making the in ovo model a suitable alternative to in vivo safety assessment. In addition, the hen\'s egg test on chorioallantoic membrane assay allows irritation potential analysis for topical treatments, but standardized analysis has been limited so far. Medical gas plasma is a topical, routine, approved dermatology treatment. Recent work suggests the potential of this technology in oncology. Its main mode of action is the release of various reactive species simultaneously. Intriguingly, varying plasma feed gas compositions generates customized reactive species profiles previously shown to be optimized for specific applications, such as skin cancer treatment. To support clinical implications, we developed a novel chicken embryo CAM scoring and study scheme and employed the model to analyze 16 different plasma feed gas settings generated by the atmospheric pressure plasmajet kINPen, along with common anticancer drugs (e.g., cisplatin) and physiological mediators (e.g., VEGF). Extensive gas- and liquid-phase plasma reactive species profiling was done and was found to have a surprisingly low correlation with irritation potential parameters. Despite markedly different reactive species patterns, feed gas-modulated kINPen plasma was equally tolerated compared to standard argon plasma. CAM irritation with gas plasmas but not anticancer agents was reversed 48 h after treatment, underlining the only temporary tissue effects of medical gas plasma. Our results indicate a safe therapeutic application of reactive species.

Our previous studies have revealed that L. acidophilus possesses inhibitory effects on PCV2 proliferation in vivo, although the underlying mechanisms remain elusive. Probiotics like L. acidophilus are known to exert antiviral through their metabolites. Therefore, in this study, non-targeted metabolomics was used to detect the changes in metabolites of L. acidophilus after 24 h of proliferation. Subsequently, high-throughput molecular docking was utilized to analyze the docking scores of these metabolites with PCV2 Cap and Rep, aiming to identify compounds with potential anti-PCV2 effects. The results demonstrated that 128 compounds such as Dl-lactate were significantly increased. The results of high-throughput molecular docking indicated that compounds such as ergocristine, and telmisartan formed complexes with Cap and Rep, suggesting their potential anti-PCV2 properties. Furthermore, compounds like vitamin C, exhibit pharmacological effects consistent with L. acidophilus adding credence to the idea that L. acidophilus may exert pharmacological effects through its metabolites. These results will provide a foundation for the study of L. acidophilus.

Schistosomiasis is one of the most common causes of morbidity and mortality from parasitic diseases. Mass treatment has proven to be insufficient because of repeated infection after treatment and the appearance of strains resistant to drug therapy. Hence, immunization is a new approach to control the disease and limit the pathological consequences of schistosomiasis. To evaluate the prophylactic effect of Cercarial antigen (CAP) loaded on chitosan nanoparticles (CSNPs) as a potential vaccine against Schistosoma mansoni-infected mice. 130 mice divided into 2 groups were used: Group I: Control groups (50 mice) subdivided into subgroup Ia (10 mice): Non-infected mice (normal control), subgroup Ib (20 mice): Schistosoma infected mice (infected control) and subgroup Ic (20 mice): Non-infected mice receiving NPs only. Group II: Vaccinated group (80 mice) subdivided equally into subgroup IIa (CAP): Received cercarial antigen and subgroup IIb (CAP + CSNP): Received cercarial antigen loaded on chitosan NPs then both vaccinated groups were infected with S. mansoni 3 weeks following the initial vaccination dose. CAP + CSNP and CAP groups showed significant reduction in adult worms count, hepatic egg count, hepatic granulomas number and size in comparison to the infected control group. Elevation of serum IgG and IgM levels, CD4+ and CD8+ T cell frequencies, IL-4, IL-10 and INF-γ levels was more significant in CAP + CSNP group than CAP group. CAP + CSNP is a promising new preparation of Schistosomal antigens that gave better results than immunization with CAP alone. CSNPs enhanced the immune and protective effect of CAP as validated by parasitological, histopathological and immunohistochemical studies.

Auditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r = -0.407), but noise exposure effects are weak (r = -0.152). We conclude that noise exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem.

OBJECTIVE: Controlled attenuation parameter (CAP) is a noninvasive and quantitative method to evaluate hepatic steatosis, which is not well evaluated in children. The aim of this study was to examine the diagnostic value of CAP for hepatic steatosis in children with obesity based on MR proton density fat fraction (PDFF).
METHODS: About 108 pediatric patients with nonalcoholic fatty liver disease (NAFLD) who were assessed for PDFF, CAP, and other laboratory results were enrolled. In this study, pediatric patients were separated for the obese group (n=80) and the severe obese group (n=28). Hepatic steatosis grades (0-3) were classified according to PDFF using cutoff values of 6.4 , 17.4, and 22.1 %.
RESULTS: There are significant differences in CAP between the obese and severe obese groups (p<0.05). CAP showed a good correlation with PDFF in pediatric patients with NAFLD for diagnosing hepatic steatosis using a cutoff value of 265 dB/m (p<0.001). Meanwhile, ALT significantly outperforms CAP in receiver-operating curve (ROC) analysis for diagnosing hepatic steatosis grades. The diagnostic accuracy of CAP for steatosis is 77.8 %, and the diagnostic accuracy of ALT for steatosis is 83.3 %.
CONCLUSIONS: While CAP holds promise as a diagnostic tool for pediatric NAFLD, its diagnostic performance warrants some caution. The potential of CAP is evident; however, ALT emerges as a simpler and more accurate measure for detecting hepatic steatosis in children. Further research is essential to determine the optimal role of CAP in pediatric NAFLD diagnosis and management.

The initial objective of this study was to shed light on the evolution of small DNA tumor viruses by analyzing de novo assemblies of publicly available deep sequencing datasets. The survey generated a searchable database of contig snapshots representing more than 100,000 Sequence Read Archive records. Using modern structure-aware search tools, we iteratively broadened the search to include an increasingly wide range of other virus families. The analysis revealed a surprisingly diverse range of chimeras involving different virus groups. In some instances, genes resembling known DNA-replication modules or known virion protein operons were paired with unrecognizable sequences that structural predictions suggest may represent previously unknown replicases and novel virion architectures. Discrete clades of an emerging group called adintoviruses were discovered in datasets representing humans and other primates. As a proof of concept, we show that the contig database is also useful for discovering RNA viruses and candidate archaeal phages. The ancillary searches revealed additional examples of chimerization between different virus groups. The observations support a gene-centric taxonomic framework that should be useful for future virus-hunting efforts.

OBJECTIVE: Patients hospitalized for community-acquired pneumonia (CAP) may have a higher risk of new-onset atrial fibrillation (NOAF). The C2HEST score was developed to evaluate the NOAF risk in the general population. Data on the value of the C2HEST score in acute patients admitted with CAP are lacking. We want to establish the predictive value of C2HEST score for NOAF in patients with CAP.
METHODS: Patients with CAP enrolled in the SIXTUS cohort were enrolled. C2HEST score was calculated at baseline. In-hospital NOAF was recorded. Receiver-operating Characteristic (ROC) curve and multivariable Cox proportional hazard regression analysis were performed.
RESULTS: We enrolled 473 patients (36% women, mean age 70.6 ± 16.5 years), and 54 NOAF occurred. Patients with NOAF were elderly, more frequently affected by hypertension, heart failure, previous stroke/transient ischemic attack, peripheral artery disease and hyperthyroidism. NOAF patients had also higher CURB-65, PSI class and CHA2DS2-VASc score. The C-index of C2HEST score for NOAF was 0.747 (95% confidence interval [95%CI] 0.705-0.786), higher compared to CURB-65 (0.611, 95%CI 0.566-0.655, p = 0.0016), PSI (0.665, 95%CI 0.621-0.708, p = 0.0199) and CHA2DS2-VASc score (0.696, 95%CI 0.652-0.737, p = 0.0762). The best combination of sensitivity (67%) and specificity (70%) was observed with a C2HEST score ≥ 4. This result was confirmed by the multivariable Cox analysis (Hazard Ratio [HR] for C2HEST score ≥ 4 was 10.7, 95%CI 2.0-57.9; p = 0.006), independently from the severity of pneumonia.
CONCLUSIONS: The C2HEST score was a useful predictive tool to identify patients at higher risk for NOAF during hospitalization for CAP.
BACKGROUND: www.
RESULTS: gov (NCT01773863).