Multiple pathogens are competing against the human immune response, leading to outbreaks that are increasingly difficult to control. For example, the SARS-CoV-2 virus continually evolves, giving rise to new variants. The ability to evade the immune system is a crucial factor contributing to the spread of these variants within the human population. With the continuous emergence of new variants, it is challenging to comprehend all the possible combinations of previous infections, various vaccination types, and potential exposure to new variants in an individual patient. Rather than conducting variant-to-variant comparisons, an efficient approach could involve identifying key protein regions associated with the immune evasion of existing immunity against the virus. In this study, we propose a new biotechnological application of bacteriophages, the phage display platform for experimental identification of regions (linear epitopes) that may function as cross-reacting IgG hotspots in SARS-CoV-2 structural proteins. A total of 34,949 epitopes derived from genomes of all SARS-CoV-2 variants deposited prior to our library design were tested in a single assay. Cross-reacting IgG hotspots are protein regions frequently recognized by cross-reacting antibodies in many variants. The assay facilitated the one-step identification of immunogenic regions of proteins that effectively induced specific IgG in SARS-CoV-2-infected patients. We identified four regions demonstrating both significant immunogenicity and the activity of a cross-reacting IgG hotspot in protein S (located at NTD, RBD, HR1, and HR2/TM domains) and two such regions in protein N (at 197–280 and 358–419 aa positions). This novel method for identifying cross-reacting IgG hotspots holds promise for informing vaccine design and serological diagnostics for COVID-19 and other infectious diseases.

Calprotectin is a calcium-binding protein involved in inflammatory processes. In the context of abdominal aortic aneurysm (AAA), elevated levels of calprotectin may indicate immune system activation and chronic inflammation, which are among the mechanisms contributing to the development and progression of AAA. The receptor for advanced glycation end-products (RAGE) is a receptor that binds various ligands, including advanced glycation end-products formed during the glycation of proteins and lipids under oxidative stress conditions. Activation of RAGE is associated with inflammatory processes, oxidative stress, and tissue remodeling, which may contribute to the weakening of the aortic wall and aneurysm formation. The main objective of this study was to evaluate the effectiveness of both biomarkers in distinguishing patients with abdominal aortic aneurysm. A total of 27 patients with diagnosed AAA were included in the study. The control group consisted of 27 patients without AAA. Plasma levels of calprotectin and sRAGE were measured in both groups. Statistical analysis included the Shapiro–Wilk test, Mann–Whitney U test, and the Hosmer-Lemeshow (H-L) test. The likelihood of having AAA was found to be over one hundred times greater in individuals classified into the AAA group based on a decision tree model using calprotectin and sRAGE levels, compared to those classified into the no-AAA group. Calprotectin concentration was identified as a stronger predictor of AAA than sRAGE. The optimal cut-off value for plasma calprotectin was determined as ≥1136 ng/mL, yielding a sensitivity of 81.5% and a specificity of 100.0% for discriminating AAA patients from controls. It may be beneficial in future studies to explore non-invasive approaches, such as measuring calprotectin levels in stool and sRAGE in urine, as a potential screening method for AAA. Monitoring the concentrations of these biomarkers in bodily fluids, as a non-invasive method, could support screening efforts for AAA.

Recurrent respiratory papillomatosis (RRP), caused mainly by human papillomavirus types 6 and 11 (HPV6/11), can persist despite the absence of recognized systemic immunodeficiency. We reanalyzed three transcriptomic datasets using the same predefined immune-gene programs: paired papilloma and autologous laryngeal mucosa from 12 patients, single-cell RNA sequencing from papillomas of four RRP donors and pharyngopalatine mucosa from three controls, and paired papilloma samples from 17 patients before and after INO-3107, a DNA immunotherapy encoding HPV6/11 antigens and interleukin-12. In untreated tissue, cluster of differentiation 8 (CD8)- and natural killer (NK)-associated cytotoxic program scores were lower and the transforming growth factor beta (TGF-β) suppressive program score was higher, reproducing findings from the same cohort. The lower cytotoxic pattern was not reproduced within the recovered combined T-cell and NK-cell population, although no single-cell comparison remained significant after correction for multiple testing. After INO-3107, CD8- and NK-associated cytotoxic, T helper 1 (Th1)/interferon gamma (IFN-γ), and C-X-C motif chemokine receptor 3 (CXCR3)-associated trafficking program scores increased significantly, whereas TGF-β and M2-like suppressive programs showed no comparable statistically supported change. Together, these findings show that different components of the local immune response do not change in parallel and support a model of selective treatment-associated immune remodeling. This pattern may inform future biomarker and combination-treatment studies.

Background: Prolonged hospitalization, postoperative complications, and unplanned readmission remain major problems after major surgery. RESET evaluates a continuous perioperative pathway integrating individualized prehabilitation, coordinated inpatient care, enhanced-recovery principles, discharge planning, and transitional care in adults undergoing oncological surgery and patients aged 70 years or older undergoing non-oncological surgery. Methods: RESET is a prospective, two-center, two-arm randomized controlled study (NCT07727876). Up to 12,800 patients will be screened and approximately 8960 randomized 9:1 to RESET or standard care, including about 5740 oncological and 3220 non-oncological participants. The three primary outcomes are prolonged index hospitalization (≥14 days), unplanned readmission within 30 days after discharge, and postoperative complications within 30 days after surgery. Each outcome is evaluated separately in both clinical populations, yielding six primary hypothesis tests. Holm’s procedure will control the family-wise error rate at α = 0.01 across all six tests, with endpoint- and population-specific confirmatory conclusions. Secondary outcomes include length of stay, multidomain health status, satisfaction, adherence, organizational effectiveness, and direct healthcare costs. Conclusions: RESET will evaluate the clinical and implementation effects of an integrated perioperative pathway across two surgical populations.

Background/Objectives: Maximum aortic diameter remains central to abdominal aortic aneurysm (AAA) surveillance and decisions about repair, but it does not capture the full biological and mechanical state of the aneurysm wall. We explored diameter-associated transcriptomic patterns across human AAA datasets and compared responses associated with rupture and regional high wall stress. Methods: Six public human AAA transcriptomic datasets were reanalyzed using the same fixed 30-component biological-program panel while preserving the design and participant structure of each source study. Cross-dataset comparisons were performed on continuous custom-module effects. Uncertainty in the diameter comparison was assessed by resampling participants within both cohorts in 50,000 bootstrap replicates. Results: The diameter analyses showed a positive observed effect pattern (component Pearson r = 0.660; family Pearson r = 0.701), although no custom module reached nominal significance in both. The bootstrap median family correlation was lower (r = 0.306; 95% interval, −0.427 to 0.775), and the interval included zero. Rupture and high wall stress showed little overall molecular correlation (component r = 0.004; family r = 0.070), despite shared directions of selected hypoxia- and inflammation-related responses. Wall-layer, thrombus, and single-cell analyses revealed spatial and cellular heterogeneity. Conclusions: The observed diameter-associated molecular pattern remains exploratory rather than an established cross-dataset association. Aneurysm size, regional mechanical loading, and rupture appear to involve related but partly distinct aspects of AAA biology.