Antigenic Changes Research Articles

Transcriptomic profiles of monocyte-derived macrophages exposed to SARS-CoV-2 VOCs reveal immune-evasion escape driven by delta.

Since the breakout of COVID-19, the mutated forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown enhanced rates of transmission and adaptation to humans. The variants of concern (VOC), designated Alpha, Beta, Gamma, Delta, and Omicron emerged independent of one another, and in turn rapidly became dominant. The success of each VOC, as well as the virus fitness, were enabled by altered intrinsic functional properties and, reasonably, to virus antigenicity changes, conferring the ability to evade a primed immune response. We analysed the gene expression profiles of monocyte-derived macrophages (MDM) isolated from whole blood of healthy participants exposed to the 5 different SARS-CoV-2 VOC: D614G, Alpha (B.1.1.7), Gamma (P1), Delta (B.1.617.2), and Omicron BA.1 (B.1.1.529), and to the HCoV-OC43 strain, a coronavirus already present in the population before the SARS-CoV-2 pandemic. Whole transcriptome RNA-Seq, for both coding and non-coding RNAs, was then made. After exposure to the 5 VOC of MDM, we initially assessed the presence of the viral SARS-CoV-2 transcripts to confirm viral entry. We then analysed the RNA-Seq data and observed a significant deregulation of both coding and non-coding RNAs. In particular, our RNA-Seq analysis showed a significant up-regulation of several genes involved in different immunological processes, such as PARP9/PARP14 axes, in macrophages exposed to D614G, Alpha, and Gamma variants. Surprisingly, our data showed that macrophages exposed to the Delta variant exhibited a transcriptional profile more similar to the naïve control group, while macrophages exposed to the Omicron variant showed intermediate differentially expressed genes (DEGs) between the two groups. By checking the canonical markers for M1/M2 differentiation states, we did not observe any expression in macrophages exposed to the Delta variant, suggesting an M0 status, comparable to the naïve control group. Finally, we observed a significant deregulation of 3 main types of non-coding RNAs (ncRNAs): long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small nucleolar RNAs (snoRNAs), some of which are common to coronaviruses, and some specific to SARS-CoV-2. The SARS-CoV-2-dependent alteration of the transcriptome of monocyte-derived macrophage (MDM)-infected cells can be linked to the chronological order of the variants' appearance in the human population. Our data suggest an evolution of VOC in modulating the host immune response, with a strong change in pace beginning with the advent of the Delta variant. MDMs exposed to Delta showed a failure in the activation of the adaptive immune response, and this correlates with the more severe symptoms developed by people affected with this SARS-CoV-2 variant.

Changes in prostate specific antigen value in patients with COVID-19.

To evaluate changes in prostate-specific antigen (PSA) values in patients with coronavirus disease 2019 (COVID-19). Male patients who were admitted to our flu outpatient clinic with cough, fever, weakness, and bone and joint pain were evaluated. The acute phase reactants of erythrocyte sedimentation rate, C-reactive protein, ferritin, and fibrinogen were measured both at the time the patients first presented at the clinic and 1 month after recovery from COVID-19 infection. PSA and free PSA were also measured at the same time. The difference in acute phase reactants and PSA values during active COVID-19 infection and after recovery was assessed using the paired samples t-test. The mean PSA values of the patients were 2.73 ± 3.7 μg/L in the period of active infection, and 2.04 ± 2.32 μg/L 1 month later (p = 0.12). In the 29 patients with PSA values in the gray zone, the PSA values were determined as 6.6 ± 4.4 μg/L during infection and 4.1 ± 2.9 μg/L after treatment (p = 0.001). The results of this study showed that PSA values in the gray zone during COVID-19 infection decreased after treatment when the patient recovered.

Prognostic significance of CEA reduction rate in patients with abnormally high preoperative CEA levels who underwent surgery for lung cancer

BackgroundThe aim of this research was to investigates the prognostic importance of change in carcinoembryonic antigen (CEA) levels (particularly abnormal high concentration) in patients with non-small cell lung cancer (NSCLC) between before and after surgery.MethodsThe study involved 68 patients with NSCLC ( preoperative CEA value ≥ 10 ng/ml) who received curative operation from 2012 to 2020. Preoperative and postoperative serum CEA levels, CEA reduction, and other clinicopathological factors were determined on medical records. Receiver operating characteristic curves were used to calculate cut-off levels for prognostic markers. Multivariate analyses with a Cox proportional hazards regression model were performed to identify Independent prognostic variables.ResultsThe optimal cut-off was value for the CEA reduction rate was 77.3%. The area under the curve for the CEA reduction rate was greater compared with those for preoperative and postoperative CEA levels. The Kaplan–Meier method revealed a significantly worse prognosis in the low CEA reduction rate group versus the high CEA reduction rate group regarding overall survival (OS) (p = 0.002). In the multivariate analysis, the CEA reduction rate (hazard ratio: 3.36, 95% confidence interval: 1.32–8.51, p = 0.011) was identified as an independent and exclusive prognostic marker for OS.ConclusionsIn NSCLC, which is characterized by high preoperative CEA levels, the CEA reduction rate after surgery is a useful prognostic factor. Importantly, it is a more powerful indicator for OS compared with postoperative CEA levels. Further, large-sample-size cohort studies focusing on this issue are warranted.

Antigenic changes in influenza A(H3N2) driven by genetic evolution: Insights from virological surveillance, EU/EEA, week 40/2023 to week 9/2024.

BackgroundDuring the 2023/24 influenza season in the European Union/European Economic Area (EU/EEA), influenza viruses A(H1N1)pdm09, A(H3N2) and B/Victoria viruses were co-circulating.AimWe aimed to describe the circulating influenza viruses by (sub)type, genetic clade, antigenic group and antiviral susceptibility in that season in the EU/EEA.MethodsWe collected surveillance data from EU/EEA countries through weekly submissions to The European Surveillance System (TESSy). Data were submitted in strain-based format for weeks 40/2023 to 9/2024.ResultsTwenty-nine EU/EEA countries reported 154,718 influenza virus detections (primary care sentinel and non-sentinel combined), of which 97% (150,692) were type A and 3% (4,026) were type B. Of the subtyped influenza A viruses, 30,463 (75%) were influenza A(H1)pdm09 and 10,174 (25%) were influenza A(H3). For 809 (20%) of the type B viruses, the lineage was determined; all were B/Victoria/2/87 lineage, and none were B/Yamagata/16/88 lineage. Genetic diversification of seasonal influenza viruses continued, and clade 5a.2a of A(H1N1)pdm09, 2a.3a.1 of A(H3N2) and V1A.3a.2 of B/Victoria-lineage viruses dominated. Of the A(H3N2) 2a.3a.1 viruses, 23% were antigenically distinct from the 2023/24 vaccine virus.ConclusionThe 2023/24 influenza season was characterised by co-circulation of different influenza (sub)types, antigenically similar to the components recommended for the 2023/24 northern hemisphere vaccine, A/Victoria/4897/2022 (egg-based) and A/Wisconsin/67/2022 (cell culture- or recombinant-based). However, genetic diversification of the viruses continued. The World Health Organization's vaccine recommendations for the northern hemisphere 2024/25 season were updated to include a new A(H3N2) component, while maintaining the current A(H1N1)pdm09 and B/Victoria components.

Virus neutralization test for confirmation of ELISA-positive SARS-CoV-2 antibodies in dogs.

Constant antigenic changes, new variants and easy transmission of SARS-CoV-2 virus should acquire greater zoonotic attention and need to remain alert. In this retrospective study the aim was to analyze seropositivity to SARS-CoV-2 in dogs by commercial ELISA. The Virus neutralization test (VNT) was modified for the purpose of confirmation of SARS-CoV-2 antibodies in ELISA-positive dog sera. The sera were collected from 204 dogs from different veterinary clinics across Vojvodina Province, Serbia, during COVID-19 pandemic. For the screening of antibodies a commercial double multi-species antigen ELISA was used, followed by the VNT modified with SARS-CoV-2 as a confirmatory test. VNT was modified as "one step" test using local isolate of SARS-CoV-2 and the results were checked by cytopathic effect in cell culture on the 96-well microtiter plate. Obtained data have shown that 9 out of 204 dogs were positive by ELISA (4.4%), while 2 (0.97%) sera were doubtful. VNT confirmed 9 positive dogs, but 2 doubtful samples were negative, exhibiting the seroconversion to SARS-CoV-2 in 4.4% dogs from Vojvodina region during pandemic of COVID-19. VNT with SARS-CoV-2 helped to elucidate ELISA ambiguous results. The occurrence of antibodies to SARS-CoV-2 in dogs in this study during COVID-19 pandemic suggested the possibility of viral transmission to dogs, implicating the potential for zoonotic transmission. This was the first research on seroconversion to SARS-CoV-2 in dogs from the Province of Vojvodina, the northernmost part of Serbia.

SpliceMutr Enables Pan-Cancer Analysis of Splicing-Derived Neoantigen Burden in Tumors.

SpliceMutr shows that splicing antigenicity changes in response to ICI therapies and that native modulation of the splicing machinery through mutations increases the contribution of splicing to the neoantigen load of some The Cancer Genome Atlas cancer subtypes. Future studies of the relationship between splicing antigenicity and immune checkpoint inhibitor response pan-cancer are essential to establish the interplay between antigen heterogeneity and immunotherapy regimen on patient response.

Behavioral and Health Outcomes of mRNA COVID-19 Vaccination: A Case-Control Study in Japanese Small and Medium-Sized Enterprises.

Background Despite ongoing waves of Coronavirus disease 2019 (COVID-19) infections, including significant surges such as the 10th wave, understanding the impact of messenger RNA (mRNA) COVID-19 vaccination on infection risk and associated behavioral changes remains crucial. This study aims to urgently evaluate the effects of mRNA COVID-19 vaccination on COVID-19 infection rates and related behaviors among participants of the Yamato Project, which includes employees of Japanese small and medium-sized enterprises (SMEs). Methods A case-control study was conducted using data collected from a survey administered by the Japan Small and Medium Enterprise Management Council in December 2023. Participants included individuals who were part of the Yamato Project, not necessarily limited to SME employees. The survey gathered information on demographic characteristics, COVID-19 infection status, vaccination history, health status before January 2020, and various preventive behaviors. The primary outcome was the presence or absence of COVID-19 infection. Data were analyzed using univariate and multivariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between vaccination status and COVID-19 infection. Results A total of 913 participants were included in the final analysis. The adjusted ORs for COVID-19 infection among vaccinated individuals compared to unvaccinated individuals were 1.85 (95% CI: 1.33-2.57, p < 0.001). The odds of contracting COVID-19 increased with the number of vaccine doses: one to two doses (OR: 1.63, 95% CI: 1.08-2.46, p = 0.020), three to four doses (OR: 2.04, 95% CI: 1.35-3.08, p = 0.001), and five to seven doses (OR: 2.21, 95% CI: 1.07-4.56, p = 0.033). Behavioral analysis indicated that a reduced frequency of bathing and exercising was significantly associated with higher COVID-19 infection rates (p < 0.05). Conclusions The study observed a higher reported incidence of COVID-19 infection among vaccinated individuals during the pandemic period, which increased with the number of vaccine doses received. This paradoxical finding may be influenced by various factors, including immune response mechanisms, such as antibody-dependent enhancement (ADE) or original antigenic sin, behavioral changes, and exposure risk. Understanding these factors is crucial for urgently enhancing public health strategies and vaccination programs.

A Modified Novel Validated High-Throughput Hemagglutinin Inhibition Assay Using Recombinant Virus-like Particles and Human Red Blood Cells for the Objective Evaluation of Recombinant Hemagglutinin Nanoparticle Seasonal Influenza Vaccine.

Currently available seasonal influenza vaccines confer variable protection due to antigenic changes resulting from the accumulation of diverse mutations. The analysis of new seasonal influenza vaccines is challenging in part due to the limitations of the traditional hemagglutination inhibition (HAI) assay with A/H3N2 strains. An improved and objective novel HAI assay was developed with recombinant virus-like particles (VLPs) and an egg-derived virus as agglutinins, the oseltamivir treatment of VLPs, human red blood cells, and using an automated image reader-based analysis of hemagglutination. HAI validation was demonstrated using four VLPs and egg-derived strains, with 46-56 serum samples tested 12 times in duplicate per strain. The validated HAI assay was precise as indicated by the percent geometric coefficient of variation for intra-, inter-, and total assay precision, as well as accurate as evidenced by percent bias measurements. The assay exhibited linearity, specificity for homologous type/subtype strains, and sensitivity with a starting dilution of 1:10. Assay robustness and sample stability were demonstrated as a percentage difference compared to reference condition. Validated HAI results were equivalent for the single and duplicate sample testing and correlated well with a qualified live wild-type influenza microneutralization assay. These findings demonstrate the suitability of this high-throughput novel modified validated HAI assay for evaluating vaccine immunogenicity and efficacy.

Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance.

H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple nonhuman mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here, we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine virus, and we show that a mutation present in some recent H5 HAs causes a large antigenic change. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.

Efficacy of an Inactivated Whole-Virus A/Victoria/361/2011 (IVR-165) (H3N2) Influenza Vaccine in Ferrets.

It has been reported that the high-growth reassortant (HGR) A(H3N2) influenza viruses used for split influenza vaccine (SV) production have some amino acid substitutions in hemagglutinin due to egg adaptation during virus propagation, causing antigenic differences between HGR and epidemic viruses. To clarify whether inactivated whole-virus vaccine (WV) derived from the A(H3N2) HGR virus possessing egg adaptation could induce cross-protective immune responses against epidemic A(H3N2) viruses, the efficacy of WV was compared with that of SV in a ferret model. When the ferrets immunized with WV or SV derived from HGR A/Victoria/361/2011 (IVR-165) virus were challenged with the homologous virus A/Victoria/361/2011 (IVR-165) or its original cell-propagated A/Victoria/361/2011 virus, respectively, WV successfully shortened the duration of virus shedding of both challenge viruses, whereas SV shortened only that of the homologous virus, A/Victoria/361/2011 (IVR-165). When WV-immunized ferrets were challenged with A/Fukushima/69/2015 virus, which is an epidemic virus antigenically different from the A/Victoria/361/2011 virus, WV could shorten the duration of shedding of this virus. In addition, we found that early induction of nasal IgG and IgA antibodies by vaccines helped shorten the virus-shedding period, although this was dependent on the degree of difference in antigenicity of the challenge virus. These results indicate that vaccination with WV, not with SV, would be a solution to avoid decreased vaccine effectiveness due to the antigenic change of HGR virus by egg adaptation during virus propagation.

Exploring B-cell epitope conservation and antigenicity shift in current COVID-19 variants: Analyzing spike-antibody interactions for therapeutic uses

SARS-CoV-2, responsible for the global COVID-19 pandemic, has undergone significant genetic changes, leading to various variants impacting transmissibility, severity, and vaccine efficacy. The methodology involved evaluating SARS-CoV-2 variants designated by WHO as Variants of Interest (VOIs) and Variants Under Monitoring (VUMs). Several noteworthy mutations including G446S, K417N, T478K, E484A, N501Y, and Y505H exhibit a strong pattern of convergent evolution across all these variants, particularly at antigenic sites within the spike protein. Conformational epitopes mapping and antigenicity shift analyses implicated epitope changes which were compared for therapeutic purposes. VUMs BA.2.86 and XBB.2.3 show significant antigenicity changes and epitope dynamics, correlating with high root mean square deviation values and epitope expansions or contractions. Nonsynonymous mutations are predominant in all variants, suggesting functional changes affecting transmissibility and immune evasion. VOIs XBB.1.5, BA.2.86, and CH.1.1 show high solvent-accessible surface area and radius of gyration, indicating structural expansion and increased epitope availability. In contrast, stable VOI EG.5.1 displays minimal structural changes and moderate epitope expansions. We evaluated two classes of antibodies for their effectiveness in neutralizing SARS-CoV-2 variants. Antibodies CC12.1 and P4A1 from Class I, alongside CV07-250, P5A-2G9, and MW05 from Class II, display strong binding across multiple variants, indicating broad neutralizing capabilities. Specifically, P4A1 shows the highest affinity for EG.5 and EG.5.1, while MW05 exhibits the strongest binding to XBB.1.5, CH.1.1, and XBB.2.3, highlighting their potent neutralization potential. This study aims to elucidate epitope variations in evolving SARS-CoV-2 strains, offering critical insights for developing targeted interventions against current challenges posed by the virus.

Contribution of immunoglobulin products in influencing seasonal influenza infection and severity in antibody immune deficiency patients receiving immunoglobulin replacement therapy.

Seasonal and pandemic influenza infection present a potential threat to patients with antibody deficiency. The acceptance and effect of the current recommendation for annual vaccination against influenza for patients with antibody deficiency is not well investigated and due to antigenic drift or shift the protective capacity of regular IgG replacement therapy (IgRT) is considered low. This narrative review considers the effect of influenza vaccination in immunodeficient patients and discusses available information on the effect of immunoglobulin products on seasonal influenza infectivity and severity in antibody deficiency patients receiving IgRT. The humoral immune response to seasonal influenza vaccination is reduced in patients with antibody immune deficiency. However, there is no evidence that the proportion of patients with primary antibody deficiency who develop influenza illness, and the severity of such illness, is increased when compared with the general population. The IgRT that patients receive has been shown to contain neutralizing antibodies as a consequence of past flu infections against both the hemagglutinin and neuraminidase surface proteins and other viral internal proteins of different influenza A virus strains. Studies have demonstrated not only significant levels of specific but also cross-reactive antibodies against seasonal influenza virus strains. Thus, despite the yearly changes in influenza viral antigenicity that occur, IgRT could potentially contribute to the protection of patients against seasonal influenza. Currently, only limited clinical data are available confirming a preventative effect of IgRT with respect to seasonal influenza infection. In conclusion, there is some evidence that IgRT could contribute to protection against seasonal influenza in patients with antibody-related immunodeficiency. However, additional clinical data are needed to confirm the extent and relevance of this protection and identify the main responsible virus targets of that protection.

Insights into Genetic and Antigenic Characteristics of Influenza A(H1N1)pdm09 Viruses Circulating in Sicily During the Surveillance Season 2023-2024: The Potential Effect on the Seasonal Vaccine Effectiveness.

After disruption in the influenza circulation due to the emergence of SARS-CoV-2, the intensity of seasonal outbreaks has returned to the pre-pandemic levels. This study aimed to evaluate the evolution and variability of whole-genome sequences of A(H1N1)pdm09, the predominant influenza virus in Sicily (Italy) during the season 2023-2024. The potential vaccine efficacy was calculated using the pepitope model based on amino acid changes in the dominant epitope of hemagglutinin. The HA gene sequences showed several amino acid substitutions, some of which were within the major antigenic sites. The phylogenetic analysis showed that Sicilian strains grouped into two main genetic clades (6B.1A.5a.2a.1 and 6B.1A.5a.2a) and several subclades. Notably, about 40% of sequences partially drifted from the WHO-recommended vaccine strain A/Victoria/4897/2022 for the Northern Hemisphere. These sequences mostly belonged to the subclades C.1.8 and C.1.9 and harboured the amino acid mutations responsible for the modest predicted vaccine efficacy (E = 38.12% of 53%, pepitope = 0) against these viruses. Amino acid substitutions in other gene segments were also found. Since influenza viruses are constantly evolving, genomic surveillance is crucial in monitoring their molecular evolution and the occurrence of genetic and antigenic changes, and, thus, their potential impact on vaccine efficacy.

Real-World Clinical Outcomes of Low Dose versus Standard Dose Abiraterone in Patients with Metastatic Castration-Resistant Prostate Cancer: A Prospective Pragmatic Study

Introduction: Abiraterone is a standard treatment for metastatic castration-resistant prostate cancer (mCRPC). Food intake has shown significant effect on its pharmacokinetics. The aim of this study was to evaluate the efficacy and safety of standard dose abiraterone under fasting conditions versus low dose abiraterone with a low-fat meal in patients with mCRPC. Methods: In this prospective real world study 32 patients with mCRPC were treated in two groups of 16 cases by routine clinical practice of their treating physician with low-dose abiraterone (250 mg with a low fat breakfast) or standard-dose abiraterone (1000 mg in fasting state). The changes in serum prostate specific antigen (PSA) level and PSA response rate (≥50% reduction after 12 weeks) were the primary end points. Results: The median changes of serum PSA before and after treatment, as well as the PSA nadir were not significantly different between the two groups (P = 0.128 and P = 0.051, respectively). Despite a trend toward higher PSA response rate in the low-dose group, the difference was not statistically significant (75.0% vs. 62.5%; P = 0.704). Median serologic progression free survival (PFS) was significantly higher in the low-dose group (15 vs. 8 months; Log-rank P = 0.031). There was a trend toward lower adverse events in the low-dose group, but this difference was not statistically significant (37.5% vs. 62.5%; P = 0.289). Conclusion: Low-dose abiraterone seems to be comparable to standard-dose abiraterone in mCRPC with 75% lower financial cost; however, this conclusion needs to be proved by further well designed and large scale studies.

Randomized trial of low intensity shockwave therapy for erectile dysfunction utilizing grayscale ultrasound for analysis of erectile tissue homogeneity/inhomogeneity.

Electrohydraulic shockwave devices have been Food and Drug Administration-cleared for improved blood flow and connective tissue activation and have been used to treat erectile dysfunction (ED). In this study, the main focus was to evaluate improvement in erectile tissue quality after low intensity shockwave therapy (LiSWT). A single-blind, sham-controlled, randomized, prospective study, was performed in men with ED naïve to shockwave or radial ballistic pressure wave therapy. Participants were randomized 1:2 to simulated (sham) or active LiSWT treatment. After simulated treatments, participants in the Sham Arm were converted to active LiSWT, while participants initially in the Active Treatment Arm received no further treatment. Assessments were performed at baseline and two follow-up visits. Subjective parameters of erectile function (EF) were assessed by total and EF domain scores of the International Index of Erectile Function (IIEF) and sexual encounter profile (SEP). Objective parameters of penile erection were measurements of hypoechoic areas in images obtained by grayscale ultrasound (GUS) with high resolution 15.4 MHz probe and cavernosal artery peak systolic velocity (PSV) and end diastolic velocity (EDV) by color duplex Doppler ultrasound (DUS). Outcome measures for erectile and urinary function were also obtained. Simulated LiSWT did not significantly change any assessment parameter. Sham Arm participants who converted to active LiSWT had significantly increased mean IIEF total (P=0.02) and IIEF-EF scores that approached statistical significance (P=0.06), relative to baseline. Similarly, at the end of the study, Active Treatment Arm participants had significantly increased mean IIEF total (P=0.02) and IIEF-EF scores that approached statistical significance (P=0.07), relative to baseline. Additionally, at the end of the study, SEP3 success rates (erection lasting long enough for successful intercourse) approached statistical significance when Sham Arm participants were converted to active LiSWT (P=0.08) and reached statistical significance in the Active Treatment Arm (P=0.049). GUS assessments by visual grading were significantly correlated to IIEF-EF score (P=0.002) and were significantly increased relative to baseline in the Active Treatment Arm at follow-up Assessment 1 (P=0.03) and Assessment 2 (P=0.04). The greatest reduction in hypoechoic area after LiSWT occurred in the proximal penile shaft. EDV was also significantly reduced in the Active Treatment Arm at follow-up Assessment 1 (P=0.04) and Assessment 2 (P=0.04). LiSWT also resulted in improved prostate symptom scores, approaching significance in the Active Treatment Arm (P=0.055) with no changes in prostate-specific antigen. Treatment-related adverse events were limited and transient. In this prospective trial, LiSWT was safe and efficacious for erectile symptoms using GUS imaging as a novel, non-invasive method to assess improvements in corporal veno-occlusive function. Improved veno-occlusion and reduced hypoechoic area demonstrated by GUS imaging suggest that LiSWT decreases connective tissue content in penile erectile tissue. Lower urinary tract symptoms also improved with LiSWT. NCT06600893 on clinicaltrials.gov.

Drugs causing prostate-specific antigen changes: the food and drug administration adverse event reporting system combined with Mendelian randomization analysis

ABSTRACT Background Prostate cancer is one of the most common malignancies in men worldwide, and prostate-specific antigen (PSA) screening is widely used for its early detection. Drug use may affect PSA levels, but the effect for most drugs is currently unknown. Methods This study first investigated drugs related to PSA changes through the Food and Drug Administration Adverse Event Reporting System (FAERs) database, and then used a Mendelian randomization (MR) method to explore the causal relationship between specific drugs and PSA changes using a genome-wide association study (GWAS) data. The statistical analysis software SAS and R were used in the study. Results Through analysis of the FAERs database, 22 drugs were found to be associated with an increase in PSA, and 14 drugs were associated with a decrease in PSA. MR analysis showed that the use of tamsulosin may lead to an increase in PSA. Heterogeneity test, horizontal pleiotropy test and leave-one-out Analysis verified the stability of the results. MR analyses for other drugs did not show statistical significance. Conclusion This study provided a basis for better understanding the impact of medications on prostate health, helping to avoid overdiagnosis or underdiagnosis of high-risk patients. However, research still requires larger-scale validation and in-depth exploration.

Predicting Regression of Barrett's Esophagus-Can All the King's Men Put It Together Again?

The primary pre-neoplastic lesion of the lower esophagus in the vicinity of the gastroesophageal junction (GEJ) is any Barrett's esophageal lesions (BE), and esophageal neoplasia has increased in the US population with predispositions (Caucasian males, truncal obesity, age, and GERD). The responses to BE are endoscopic and screening cytologic programs with endoscopic ablation of various forms. The former have not been proven to be cost-effective and there are mixed results for eradication. A fresh approach is sorely needed. We prospectively followed 2229 mostly male veterans at high risk for colorectal cancer in a 27-year longitudinal long-term study, collecting data on colorectal neoplasia development and other preneoplastic lesions, including BE and spontaneous regression (SR). Another cross-sectional BE study at a similar time period investigated antigenic changes at the GEJ in both BE glandular and squamous mucosa immunohistochemistry and the role of inflammation. Ten of the prospective cohort (21.7%) experienced SR out of a total of forty-six BE patients. Significant differences between SR and stable BE were younger age (p < 0.007); lower platelet levels (p < 0.02); rectal p87 elevation in SR (p < 0.049); a reduced innate immune system (InImS) FEREFF ratio (ferritin: p87 colonic washings) (p < 0.04). Ancillary testing showed a broad range of neoplasia biomarkers. InImS markers may be susceptible to intervention using commonplace and safe medical interventions and encourage SR.

Isolation and characterization of porcine epidemic diarrhea virus with mutations in the spike gene in China

Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV) has caused enormous economic losses to the global swine industry. Due to frequent mutations in the spike (S) gene of PEDV, commercial vaccines used today are gradually losing their protective efficacy against variants. It's significant to monitor the S gene of PEDV variants and understand its evolutionary trend. In this study, we report four novel PEDV strains isolated from Sichuan, Guangdong and Shanxi Provinces and determined their S gene sequences. Phylogenetic analysis showed that they all belong to GII genotype. Amino acid alignment revealed a unique mutation pattern. We also predicted their three-dimensional structures and continuous B-cell epitopes and compared them to those of the vaccine strain. Our study provides references for understanding the evolution of S gene and antigenic change of S protein, which are of great significance for formulating the prevention and control of PEDV.

A multi-center, randomized, open label, two-arm study to evaluate safety & efficacy of nutraceutical tablet as adjuvant when compared with standard of care in patients with benign prostatic hyperplasia

BackgroundBenign Prostrate Hyperplasia (BPH) is a progressive disease of ageing men that may be associated with enlargement of the prostate and lower urinary tract symptoms (LUTS). Herbal/Nutraceutical formulations in addition to standard of care (SOC) could alleviate the symptoms, and thus improve the quality of life of patients. ObjectivesTo evaluate safety & efficacy of nutraceutical tablet as an adjuvant with SOC. Materials and MethodsThis was a prospective, randomized two-arm study aimed to assess the safety and efficacy of Herbal/Nutraceutical Formulation (IP) + SOC versus only SOC, in BPH patients. The primary efficacy endpoint was the change in international prostate symptom score (IPSS) within and between two arms. The safety was evaluated in terms of adverse events and change in prostate specific antigen (PSA) levels. Results140 eligible patients (70 / arm) were evaluated for efficacy and safety endpoints. The baseline characteristics of patients in two arms differed nonsignificantly. The change in IPSS-storage, voiding and QoL scores, from day 1 to 90 were statistically significant in both the arms (p < 0.0001). However, by day 90, the change in these scores in SOC+IP arm were significantly higher than that of SOC arm. Further, the change in International Index of Erectile Function (IIEF) scores was significant in SOC+IP arm (p < 0.05), while non-significant in SOC arm. The adverse events non-significantly differed between two arms. ConclusionThe herbal/nutraceutical formulation combined with SOC are safe and effective for the treatment of BPH. The combination therapy was effective in reducing urine-related symptoms and improving the QoL of BPH patients.

Ascites and Serum Interleukin-10 Levels as a Prognostic Tool for Ovarian Cancer Outcomes.

Interleukin-10 (IL-10) has been shown to be present at high levels in the ascites of ovarian cancer (OC) patients; however, little is known about its prognostic value. We sought to correlate IL-10 levels in ascites and sera of OC patients with clinicopathologic characteristics and oncologic outcomes. IL-10 levels and clinical data from biobanked ascites and serum samples of OC patients were evaluated. Receiver operating characteristic curves were used to quantify marker performance and identify IL-10-high and IL-10-low groups. Correlations between IL-10 levels and clinicopathologic data were performed. Survival outcomes were calculated, while the factors affecting them were also investigated. A total of 106 patients had ascites samples, of which 44 serum samples were also available. Mean ascites IL-10 levels were significantly higher in patients with serous histology compared to endometrioid histology (p = 0.024). Fold-change in ascites IL-10 during treatment positively correlated with clinical response, as determined by a change in serum cancer antigen (CA)-125 levels (p = 0.0126). Median progression-free survival (PFS) and overall survival (OS) were shorter in patients with high compared with low ascites IL-10 levels (PFS: 18 versus 60 months; p = 0.007, OS: 42 versus 85 months; p = 0.029). A significant positive correlation was seen between ascites and sera IL-10 levels (p = 0.019). In multivariable analyses, a high ascites IL-10 level was associated with a significantly worse prognosis (PFS hazard ratio (HR) = 1.93; p = 0.02). Patients with high ascites levels of IL-10 have worse outcomes, which are likely reflective of the immunosuppressive effect of IL-10. This highlights its potential role as an immunomodulator in the tumor microenvironment, leading to OC immune evasion.