Virus Infection Research Articles

Impact of universal masking in reducing the risk of nosocomial respiratory viruses among people with cancer.

Universal masking within healthcare settings was adopted to combat the spread of coronavirus disease 2019 (COVID-19). In addition to mitigating the risk for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, it also had an added benefit of preventing the nosocomial transmission of other respiratory viral diseases. This study examines the impact of the masking intervention on nosocomial respiratory viral infections (RVI) in vulnerable sub-populations of people with cancer at a tertiary care hospital. Interrupted time series analysis. We reviewed non-SARS-CoV-2 nosocomial RVI between January 1, 2017 and December 31, 2023 and compared its quarterly trends before (January 2017 to March 2020) and after (April 2020 to December 2023) the universal masking intervention was implemented. Prior to the masking policy, there was no significant change in the quarterly rate of non-SARS-CoV-2 nosocomial RVI (baseline trend: P = 0.662). Crude infection rates decreased from 5.6% preintervention to 4.3% after the masking policy was implemented (P < 0.001). Quarterly trends continued to steadily decline post-intervention (β = -0.10, SE = 0.04, P < 0.007). Our results suggest that universal face masking is associated with reduced non-SARS-CoV-2 nosocomial RVI, providing further evidence to support the continued use of face masks in healthcare settings to protect the health of immunocompromised patients.

SMC5/6-Mediated Transcriptional Regulation of Hepatitis B Virus and Its Therapeutic Potential

Cells have developed various mechanisms to counteract viral infections. In an evolutionary arms race, cells mobilize cellular restriction factors to fight off viruses, targeted by viral factors to facilitate their own replication. The hepatitis B virus (HBV) is a small dsDNA virus that causes acute and chronic infections of the liver. Its genome persists in the nuclei of infected hepatocytes as a covalently closed circular DNA (cccDNA) minichromosome, thus building up an episomal persistence reservoir. The chromosomal maintenance complex SMC5/6 acts as a restriction factor hindering cccDNA transcription, whereas the viral regulatory protein HBx targets SMC5/6 for proteasomal degradation, thus relieving transcriptional suppression of the HBV minichromosome. To date, no curative therapies are available for chronic HBV carriers. Knowledge of the factors regulating the cccDNA and the development of therapies involving silencing the minichromosome or specifically interfering with the HBx-SMC5/6 axis holds promise in achieving sustained viral control. Here, we summarize the current knowledge of the mechanism of SMC5/6-mediated HBV restriction. We also give an overview of SMC5/6 cellular functions and how this compares to the restriction of other DNA viruses. We further discuss the therapeutic potential of available and investigational drugs interfering with the HBx-SMC5/6 axis.

Immunogenicity and Safety of the Recombinant Adjuvanted Herpes Zoster Vaccine in Patients with Chronic Lymphocytic Leukemia and Multiple Myeloma

Background/objectives: Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are susceptible to viral infections, including varicella-zoster virus (VZV) reactivation due to both disease-related and treatment-induced immunosuppression. The recombinant adjuvanted herpes zoster vaccine (RZV) has shown high efficacy in immunocompetent adults, but immunogenicity data in CLL and MM patients are limited. This study evaluates the immunogenicity and safety of RZV in this population. Methods: Patients with CLL and MM vaccinated with RZV (administered in two doses at least one month apart) were included in the study. Pre- and post-vaccination anti-VZV IgM and IgG antibody levels were measured to assess immunogenicity, and adverse events (AEs) were captured for safety evaluation. Results: Seventy-eight patients received both vaccine doses, and 71 had post-vaccination samples. Most of the patients were IgM seronegative and IgG seropositive before vaccination. Pre-vaccination IgG levels were higher in CLL patients compared to MM patients (p = 0.001), while post-vaccination IgG levels significantly increased in both CLL (p &lt; 0.0001) and MM (p &lt; 0.0001) patients. In actively treated CLL patients, pre-vaccination IgG levels were significantly lower than in not actively treated patients (p = 0.002). Post-vaccination IgG levels were lower in MM patients receiving antiviral prophylaxis concurrently with the vaccination (p = 0.013). AEs were reported in 49.4% of patients after the first dose and 48.7% after the second dose, mostly mild (local or low-grade systemic). One case of immune thrombocytopenia was noted. Conclusions: RZV demonstrated strong immunogenicity and acceptable safety in CLL and MM patients, significantly boosting IgG levels, even in actively treated or heavily pretreated patients.

The Role of Viral Infections in the Development and Progression of COPD.

Chronic obstructive pulmonary disease (COPD) is a common chronic disease seen in smokers associated with poor functional status, quality of life, and morbidity and mortality from acute worsening of chronic symptoms, also called exacerbations. As a disease, the risk factors for COPD are well defined; however, there is room for innovation in identifying underlying biological processes, or "endotypes," that lead to the emergence and/or progression of COPD. Identifying endotypes allows for more thorough understanding of the disease, may reveal the means of disease prevention, and may be leveraged in novel therapeutic approaches. In this review, we discuss the interface of viral infections with both cellular and epithelial immunity as a potential endotype of interest in COPD.

Knowledge, Attitude and Practice of Nurses and Midwives towards Hepatitis B Infection and Control Measures in Alban Gaded Hospital, Khartoum, Sudan

Purpose: Infection with the hepatitis B virus (HBV) causes severe morbidity and death, burdening world health. Nurses and midwives, among other healthcare professionals, are more likely to contract the illness. Few studies have looked at the knowledge, attitude, and practices (KAP) of healthcare professionals in Sudan with regard to HBV infection, despite the fact that diverse components of KAP have an impact on health-related behaviors. This study's objective was to assess the knowledge, attitude, and practice (KAP) level of nurses and midwives concerning HBV viral infection in, Khartoum, Sudan.  Methods: In the Sudanese state of Khartoum, a public hospital (Alban Gaded Hospital) underwent a cross-sectional descriptive hospital-based study. To assess KAP's understanding of nurses and midwives about HBV infection. Self-administered questionnaires were used and approved by the supervisor for distribution to the population chosen for the study. The data was handed over to the Medical Director whom personally ensured the questionnaires were signed and filled by the Healthcare workers (HCWs) of the chosen criteria at the field. A member of group (23:B) took care of the supervision aside with the medical director, and made sure the data was collected as needed. The data at hand were subjected to statistical analysis using SPSS version 24.0 (Statistical Package for Social Sciences).  Results: 95 samples out of 99 were collected. According to participants’ knowledge: 67.95% have good knowledge about HBV, while 32.05% lack basic knowledge about it. The participants’ attitude towards HBV is above average showing 60.3% safe attitude. Lastly, the study shows excellent practice of the participants’ behavior towards HBV safety measures with a score of 92.3% safe practice. From the hospital, a total of 95 out of 99 nurses and midwives took part in the study. Two thirds of the respondents practiced safety, and the majority of respondents had a positive attitude about HBV preventative measures. More than half of the respondents (58.2%) had an average level of understanding. A minor but serious score of (12.6%) was noticed of the individuals, dealing with patients without wearing gloves. More over half of the nurses and midwives were not vaccinated against HBV; more than 50% of participants had incorrect ideas regarding the symptoms and route of HBV infection and all 95 participants voted (NO) for ever being infected by HBV.  Conclusion: In Alban Gaded hospital, the majority of the nurses and midwives were aware of HBV infection. But a sizeable majority of the participants lacked the necessary understanding of early immunization after birth. The study found a probability of high risk infection due to exposure under the poor level of HBV vaccine coverage rate. Moreover a clear point of limitation was noticed in Table 4 third question, where it asks whether you are or ever was infected by HBV. All the participants denied, showing a sense of partiality. Further occupational exposure prevention measures, training programs on HBV infection, including post-exposure prophylaxis, and increasing the vaccination rate of all HCWS are also strongly encouraged.

Structure-based identification of small-molecule inhibitors that target the DIII domain of the Dengue virus glycoprotein E pan-serotypically.

Dengue viral infection is caused by the Dengue virus, which spreads to humans through the bite of infected mosquitos. Dengue affects over half of the global population, with an estimated 500 million infections per year. Despite this, no effective treatment is currently available, however, several promising candidates are undergoing pre-clinical/clinical testing. The existence of four major serotypes is an important challenge in the development of drugs and vaccines to combat Dengue virus infection. Hence, the drug/vaccine thereby developed should neutralize all the four serotypes equally. However, there is no pan-serotype specific treatment for Dengue virus, thereby emphasizing the need for the identification of novel drug-like compounds that can target all serotypes of the Dengue virus equally. To this end, we employed virtual screening methodologies to find drug-like compounds that target the domain III of glycoprotein E. Most importantly, domain III of E protein is involved in viral fusion with the host membrane and is also targeted by neutralizing antibodies. Our study found two small molecule drug-like compounds (out of the 3 million compounds screened) having similar binding affinity with all four serotypes. The compounds thereby identified exhibit favourable drug like properties and can be developed as a treatment for Dengue virus.

New concept for the prevention of acute respiratory infections

Medical personnel and family members of patients with acute respiratory diseases (ARD) are at increased risk of infection during epidemics or pandemics. In this regard, it is necessary to develop and implement accessible preventive measures. The aim of the study was to evaluate the effectiveness of the use of IFNα-2b for the prevention of acute respiratory viral infections in persons located at the source of infection (medical personnel and members of their families). Patients (n = 31) with acute respiratory infections and 117 people from their environment (family members in constant contact with patients) were examined. The subjects underwent a clinical examination and laboratory tests a clinical blood test and a study of the content of the main populations and subpopulations of lymphocytes in the blood. Persons in contact with ARD patients were divided into three groups: persons who received the drug “Grippferon” for 7 days; persons who received the drug “Grippferon” in a prophylactic dose for 7 days; persons in contact with patients with ARD but who have not received the drug “Grippferon”. When assessing the state of the immune system, it was found that the most common type of immune reaction in patients and their people around was activation of innate immunity (48.39% and 66.67%, respectively). At the same time, immunodeficiency in the group of patients with ARD was detected much more often than in persons in contact with them. In addition, patients were more likely to have monocytosis (1.4 times), T lymphocytopenia (2.1 times) and an increase in the number of regulatory T lymphocytes (7.6 times). More than 50% of those examined in both groups showed an increase in the number of NK cells in the blood. An examination of persons in contact with patients with ARD after 7 days of using the “Grippferon” in different doses revealed that the lowest frequency of acute respiratory viral infections symptoms was found in the group receiving IFN at a therapeutic dose. In the group receiving IFN in a prophylactic dose, the frequency of acute respiratory viral infection (ARVI) symptoms was detected in almost 40% of those examined. More than 80% of people from the group who did not receive the “Grippferon” had symptoms of ARVI after a week of contact with patients with ARD. Thus, the use of IFN in therapeutic doses during the epidemic for persons in contact with patients is proposed as a new concept for the prevention of ARD.

Pulmonary arterial hypertension in human immunodeficiency virus infections

Pulmonary arterial hypertension (PAH) is an important health issue in the twenty-first century. The introduction of highly active retroviral therapy has prolonged survival in patients infected with the human immunodeficiency virus (HIV), and this has led to the emergence of new health issues, including PAH, in those patients. This review considers the advances in understanding the pathophysiology of PAH in HIV infections and the approaches to the treatment of these patients. Keywords: Pulmonary arterial hypertension, HIV, pathophysiology, treatment

An In Silico Approach to Discover Efficient Natural Inhibitors to Tie Up Epstein–Barr Virus Infection

Epstein–Barr virus (EBV), also known as human herpesvirus 4, is a member of the herpes virus family. EBV is a widespread virus and causes infectious mononucleosis, which manifests with symptoms such as fever, fatigue, lymphadenopathy, splenomegaly, and hepatomegaly. Additionally, EBV is associated with different lymphocyte-associated non-malignant, premalignant, and malignant diseases. So far, no effective treatment or therapeutic drug is known for EBV-induced infections and diseases. This study investigated natural compounds that inhibit EBV glycoprotein L (gL) and block EBV fusion in host cells. We utilised computational approaches, including molecular docking, in silico ADMET analysis, and molecular dynamics simulation. We docked 628 natural compounds against gL and identified the four best compounds based on binding scores and pharmacokinetic properties. These four compounds, with PubChem CIDs 4835509 (CHx-HHPD-Ac), 2870247 (Cyh-GlcNAc), 21206004 (Hep-HHPD-Ac), and 51066638 (Und-GlcNAc), showed several interactions with EBV gL. However, molecular dynamics simulations indicated that the protein–ligand complexes of CID: 4835509 (CHx-HHPD-Ac) and CID: 2870247 (Cyh-GlcNAc) are more stable than those of the other two compounds. Therefore, CIDs 4835509 and 2870247 (Cyh-GlcNAc) may be potent natural inhibitors of EBV infection. These findings can open a new way for effective drug design against EBV and its associated infections and diseases.

Evaluation of the performance and stability of early maturing orange-fleshed sweetpotato genotypes in selected areas in Ethiopia.

Orange-fleshed sweetpotato varieties that mature and harvest sooner play an important role in addressing food and nutrition demands in areas where irregular rainfall makes sustainable production challenging. A national variety trial was conducted in 2021 and 2022 during the main cropping season using ten OFSP genotypes in three locations in Sidama, South, and Oromia regions of Ethiopia, namely Hawassa, Arbaminch, and Koka, respectively. The objective of this study was to develop and select early-maturing and high-yielding OFSP genotypes for short-term harvesting (3-4 months). The field trial was conducted in a randomized complete block design with three replications. Data were collected on root yield and yield-related traits, sweetpotato virus disease reactions (SPVD), root dry matter (DMC), and beta-carotene contents (BCC) and were subjected to analysis of variance. A genotype plus genotype by environment interaction (GGE) bi-plot was also used to determine genotype stability. The results showed the presence of highly significant (p<0.001) differences among locations and genotypes, reflecting the existence of differential responses among genotypes in varied locations. Based on combined analysis, G3 (13NC9350A-9-3) outperformed the other genotypes for most of the traits considered, except for DMC, i.e., which has an equivalent to the check variety (Alamura) and showed a yield advantage of 41.4% over it. The GGE biplot also revealed that the G3 was the vertex genotype with the consistent performance in all environments. It had a low score of 1.39 on the 1-9 scoring scale, indicating that it falls within the resistant range, with adequate levels of BCC (5.5 mg/100 g) and DMC (30.0%). Furthermore, G3 is an early-maturing variety, which allows other crops to be grown in double and relay cropping systems. Therefore, based on its outstanding performance, G3 is recommended for verification and release for cultivation in mid- to low-land areas in Ethiopia.

Viral Infections and the Glutathione Peroxidase Family: Mechanisms of Disease Development.

Significance: The glutathione peroxidase (GPx) family is recognized for its essential function in maintaining cellular redox balance and countering the overproduction of reactive oxygen species (ROS), a process intricately linked to the progression of various diseases including those spurred by viral infections. The modulation of GPx activity by viruses presents a critical juncture in disease pathogenesis, influencing cellular responses and the trajectory of infection-induced diseases. Recent Advances: Cutting-edge research has unveiled the GPx family's dynamic role in modulating viral pathogenesis. Notably, GPX4's pivotal function in regulating ferroptosis presents a novel avenue for the antiviral therapy. The discovery that selenium, an essential micronutrient for GPx activity, possesses antiviral properties has propelled us toward rethinking traditional treatment modalities. Critical Issues: Deciphering the intricate relationship between viral infections and GPx family members is paramount. Viral invasion can precipitate significant alterations in GPx function, influencing disease outcomes. The multifaceted nature of GPx activity during viral infections suggests that a deeper understanding of these interactions could yield novel insights into disease mechanisms, diagnostics, prognostics, and even chemotherapeutic resistance. Future Directions: This review aims to synthesize current knowledge on the impact of viral infections on GPx activity and expression and identify key advances. By elucidating the mechanisms through which GPx family members intersect with viral pathogenesis, we propose to uncover innovative therapeutic strategies that leverage the antioxidant properties of GPx to combat viral infections. The exploration of GPx as a therapeutic target and biomarker holds promise for the development of next-generation antiviral therapies. Antioxid. Redox Signal. 00, 000-000.

Evaluation of oxidative stress biomarkers for differentiating bacterial and viral infections: a comparative study of glutathione disulfide (GSSG) and reduced glutathione (GSH)

Background and aims. This study evaluates the potential of oxidative stress biomarkers, specifically glutathione disulfide (GSSG) and reduced glutathione (GSH), for differentiating bacterial and viral infections. Oxidative stress plays a crucial role in the immune response, and glutathione is a key regulator of cellular redox balance. The aim was to assess whether differences in GSH and GSSG levels could be used as diagnostic markers for infection type. Methods. A chemiluminescence-based method evaluated GSH and GSSG as potential biomarkers for distinguishing between bacterial and viral infections. The GSH and GSSG concentrations were analyzed across bacterial, viral, and control groups. Results. Our data revealed significant differences in the GSH/GSSG ratio between the analyzed groups, with bacterial infections showing higher oxidative stress markers compared to viral infections. A combined analysis of GSH and GSSG concentrations, visualized through heatmaps and ROC curves, improved diagnostic accuracy, with clustering patterns distinguishing infection types. Conclusions. These findings suggest that the GSH/GSSG ratio could be used as a biomarker in distinguishing between bacterial and viral infections, offering potential clinical applications for more accurate diagnosis. Further research is required to validate these results in larger cohorts and to explore the underlying mechanisms of oxidative stress in pathogen-specific immune responses.

Hepatitis B viral infection and its common genotype circulation: A molecular approach

Hepatitis B virus (HBV) is the causes of liver infection and associated with cirrhosis, carcinoma, and fibrosis of liver. In this research study, we conducted an observational study to evaluate the distribution of HBV infection and its genotypes in selected cities of Khyber Pakhtunkhwa, Pakistan. A total of 426 samples were collected from selected cities of Khyber Pakhtunkhwa. Mardan (n = 163), Dir (Lower) (n = 116), Malakand (n = 53), Miran Shah (n = 29), Dera Ismail Khan (n = 28), Swat (n = 22), and Hangu (n = 15). For molecular identification of hepatitis B virus infection, the ICT (Immunochromatographic techniques) kits were used for the Screening of Hepatitis B virus infection among general population. The positive samples of ICT test were further subjected to Real-time Polymerase chain reaction (PCR), of which 282 (66.2 %) were males, and 144 (33.8 %) were females. Out of 426 ICT kit positive samples, 218 (51.18 %) were found PCR positive. The maximum number of positive cases, 157 (36.86 %), was found between 15 and 34 years. Sixty samples were further processed for HBV genotyping. A mixed genotype was detected in 29 (48.3 %) individuals, followed by genotype D in 23 (38.3 %) and untypable in 8 (13.3 %). The positivity rate of HBV was recorded high among males compared to females. Most patients who reported positive for HBV were co-infected with two genotypes. This research will help to provide background information to government and health authorities to raise public awareness and improve the capacity of the healthcare delivery system for hepatitis B virus infection.

Recent Advances in Designing Adeno-Associated Virus-Based Vaccines Against Viral Infections

Over 80% of the world’s deadliest pandemics are caused by viral infections, and vaccination remains the most effective way to prevent these infections from spreading. Since the discovery of the first vaccine over two centuries ago, several vaccine design technologies have been developed. Next-generation vaccines, based on mRNA and viral vector technologies, have recently emerged as alternatives to traditional vaccines. Adenoviral vector-based vaccines against coronavirus disease 2019 have demonstrated a more sustained antibody response as compared to mRNA vaccines. However, this has not been without complications, with a few cases of severe adverse events identified in vaccinated individuals, and the underlying mechanism is the subject of intense investigation. Adeno-associated viral vectors induce a weaker cellular immune response compared to adenoviral vectors, and it is mainly for this reason that there has been a diminished interest in exploring them as a vaccine platform until recently. This review will discuss recent developments and the potential of adeno-associated viral vectors as anti-viral vaccines.

Hepatitis B Virus-Associated Liver Carcinoma: The Role of Iron Metabolism and Its Modulation.

Hepatitis B virus (HBV) infection is a significant contributor to the development of hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality worldwide. Iron, a central co-factor in various metabolic pathways, plays an essential role in liver function, but its dysregulation can lead to severe health consequences. Accumulation of iron within hepatic cells over time is linked to increased liver injury and is strongly associated with sensitive exposure to a range of conditions, including cirrhosis, fibrosis and ultimately, HCC. This review explores the intricate interplay between iron metabolism and HCC within the context of HBV infection. Hepatic iron overload can arise from liver injury and disruptions in iron homeostasis, causing hepatic necrosis, inflammation, and fibrosis, ultimately culminating in carcinogenesis. Moreover, alterations in serum iron components in HBV-related scenarios have been observed to impact the persistence of HBV infection. Notably, the progression of HBV-associated liver damage exhibits distinct characteristics at various stages of liver disease. In addition to elucidating the complex relationship between iron metabolism and HCC in the context of HBV infection, this review also investigates the prognostic implications of systemic iron levels for HCC. Furthermore, it aims to provide a comprehensive understanding of the intricate interplay between iron metabolism and HCC, extending the discussion to the context of hepatitis C virus (HCV) infection. By shedding light on these multifaceted connections, this review aims to contribute to our understanding of the pathogenesis of HBV-associated HCC and potentially identify novel therapeutic avenues for intervention.

Nitric Oxide-Photodelivering Materials with Multiple Functionalities: From Rational Design to Therapeutic Applications.

The achievement of materials that are able to release therapeutic agents under the control of light stimuli to improve therapeutic efficacy is a significant challenge in health care. Nitric oxide (NO) is one of the most studied molecules in the fascinating realm of biomedical sciences, not only for its crucial role as a gaseous signaling molecule in the human body but also for its great potential as an unconventional therapeutic in a variety of diseases including cancer, bacterial and viral infections, and neurodegeneration. Handling difficulties due to its gaseous nature, reduced region of action due to its short half-life, and strict dependence of the biological effects on its concentration and generation site are critical questions to be solved for appropriate therapeutic uses of NO. Light-activatable NO precursors, namely, NO photodonors (NOPDs), address the above issues since they are stable in the dark and permit in a noninvasive fashion the remote-controlled delivery of NO on demand with great spatiotemporal precision. Engineering biocompatible materials with NOPDs and their combination with additional imaging, therapeutic, and phototherapeutic components leads to intriguing light-responsive multifunctional constructs exhibiting promising potential for biomedical applications. This contribution illustrates the most significant progress made over the last five years in achieving engineered materials including nanoparticles, gels, and thin films, sharing the common feature to deliver NO under the exclusive control of the biocompatible visible/near infrared light inputs. We will highlight the logical design behind the fabrication of these systems, illustrating the potential therapeutic applications with particular emphasis on cancer and bacterial infections.

Antiviral Effects of Avian Interferon-Stimulated Genes

Interferons (IFNs) stimulate the expression of numerous IFN-stimulating genes via the Janus kinase-signal transducers and activators of the transcription (JAK-STAT) signaling pathway, which plays an important role in the host defense against viral infections. In mammals, including humans and mice, a substantial number of IFN-stimulated genes (ISGs) have been identified, and their molecular mechanisms have been elucidated. It is important to note that avian species are phylogenetically distant from mammals, resulting in distinct IFN-induced ISGs that may have different functions. At present, only a limited number of avian ISGs have been identified. In this review, we summarized the identified avian ISGs and their antiviral activities. As gene-editing technology is widely used in avian breeding, the identification of avian ISGs and the elucidation of their molecular mechanism may provide important support for the breeding of avians for disease resistance.

Influenza Vaccine Effectiveness Against Illness and Asymptomatic Infection in 2022-2023: A Prospective Cohort Study.

Previous estimates of vaccine effectiveness (VE) against asymptomatic influenza virus infection based on seroconversion have varied widely and may be biased. We estimated 2022-2023 influenza VE against illness and asymptomatic infection in a prospective cohort. In the HEROES-RECOVER cohort, adults at increased occupational risk of influenza exposure across 7 US sites provided weekly symptom reports and nasal swabs for reverse transcription-polymerase chain reaction (RT-PCR) influenza testing. Laboratory-confirmed influenza virus infections were classified as symptomatic (≥1 symptom) or asymptomatic during the week of testing. Participants reported demographic information and vaccination through surveys; most sites verified vaccination through medical record and immunization registry review. Person-time was calculated as days from the site-specific influenza season start (September-October 2022) through date of infection, study withdrawal, or season end (May 2023). We compared influenza incidence among vaccinated versus unvaccinated participants overall, by symptom status, and by influenza A subtype, using Cox proportional hazards regression adjusted for site and occupation. We estimated VE as (1 - adjusted hazard ratio) × 100%. In total, 269 of 3785 (7.1%) participants had laboratory-confirmed influenza, including 263 (98%) influenza A virus infections and 201 (75%) symptomatic illnesses. Incidence of laboratory-confirmed influenza illness among vaccinated versus unvaccinated participants was 23.7 and 33.2 episodes per 100 000 person-days, respectively (VE: 38%; 95% CI: 15%-55%). Incidence of asymptomatic influenza virus infection was 8.0 versus 11.6 per 100 000 (VE: 13%; 95% CI: -47%, 49%). Vaccination reduced incidence of symptomatic but not asymptomatic influenza virus infection, suggesting that influenza vaccination attenuates progression from infection to illness.

Spatial transcriptomics analysis identifies therapeutic targets in diffuse high-grade gliomas

IntroductionDiffuse high-grade gliomas are the most common malignant adult neuroepithelial tumors in humans and a leading cause of cancer-related death worldwide. The advancement of high throughput transcriptome sequencing technology enables rapid and comprehensive acquisition of transcriptome data from target cells or tissues. This technology aids researchers in understanding and identifying critical therapeutic targets for the prognosis and treatment of diffuse high-grade glioma.MethodsSpatial transcriptomics was conducted on two cases of isocitrate dehydrogenase (IDH) wild-type diffuse high-grade glioma (Glio-IDH-wt) and two cases of IDH-mutant diffuse high-grade glioma (Glio-IDH-mut). Gene set enrichment analysis and clustering analysis were employed to pinpoint differentially expressed genes (DEGs) involved in the progression of diffuse high-grade gliomas. The spatial distribution of DEGs in the spatially defined regions of human glioma tissues was overlaid in the t-distributed stochastic neighbor embedding (t-SNE) plots.ResultsWe identified a total of 10,693 DEGs, with 5,677 upregulated and 5,016 downregulated, in spatially defined regions of diffuse high-grade gliomas. Specifically, SPP1, IGFBP2, CALD1, and TMSB4X exhibited high expression in carcinoma regions of both Glio-IDH-wt and Glio-IDH-mut, and 3 upregulated DEGs (SMOC1, APOE, and HIPK2) and 4 upregulated DEGs (PPP1CB, UBA52, S100A6, and CTSB) were only identified in tumor regions of Glio-IDH-wt and Glio-IDH-mut, respectively. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses revealed that upregulated DEGs were closely related to PI3K/Akt signaling pathway, virus infection, and cytokine-cytokine receptor interaction. Importantly, the expression of these DEGs was validated using GEPIA databases. Furthermore, the study identified spatial expression patterns of key regulatory genes, including those involved in protein post-translational modification and RNA binding protein-encoding genes, with spatially defined regions of diffuse high-grade glioma.DiscussionSpatial transcriptome analysis is one of the breakthroughs in the field of medical biotechnology as this can map the analytes such as RNA information in their physical location in tissue sections. Our findings illuminate previously unexplored spatial expression profiles of key biomarkers in diffuse high-grade glioma, offering novel insight for the development of therapeutic strategies in glioma.

Neutrophil count predicts the complete response after transarterial chemoembolization related to favorable outcome in hepatocellular carcinoma.

Systemic inflammatory markers have emerged as novel prognostic biomarkers associated with prognosis for tumors. This study aims to investigate the predictive value of systemic inflammatory markers for complete response (CR) in patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE). This retrospective study enrolled 575 HCC patients undergoing TACE. Survival outcomes were evaluated based on tumor response, and the analysis was conducted using a Kaplan-Meier curve. Predictive factors for achieving a CR after the initial TACE were analyzed by univariate and multivariate analyses in a Cox regression model. After the initial TACE, 246 of 575 (42.8%) patients achieved a CR. During a median of 60 months follow-up, the CR group had better overall survival than non-CR group (median: 82.3 vs. 51.6 months, P < 0.001). Pre-TACE neutrophil count was associated with tumor response (P = 0.06). Multivariate analysis showed that hepatitis B virus infection [hazard ratio (HR) = 0.585, 95% confidence interval (CI) = 0.360-0.952, P = 0.031] and pre-TACE neutrophil count (HR = 2.854, 95% CI = 1.115-7.307, P = 0.029) were independent predictive factors for CR after the initial TACE. Additionally, a high pre-TACE neutrophil count was associated with male gender (P < 0.001), large tumor size (P < 0.001), advanced Barcelona Clinic Liver Cancer stage (P = 0.003), and high protein induced by vitamin K absence or antagonist-II level (P < 0.001). Patients who achieved CR after the initial TACE showed a favorable prognosis. Pre-TACE neutrophil count was found to be an independent predictor of CR. These findings offer valuable insights for identifying patients who would derive the greatest benefit from TACE and for distinguishing those who may require alternative treatment approaches for HCC.