High Fatality Rate Research Articles

Structure of the Nipah virus polymerase phosphoprotein complex

The Nipah virus (NiV), a member of the Paramyxoviridae family, is notorious for its high fatality rate in humans. The RNA polymerase machinery of NiV, comprising the large protein L and the phosphoprotein P, is essential for viral replication. This study presents the 2.9-Å cryo-electron microscopy structure of the NiV L-P complex, shedding light on its assembly and functionality. The structure not only demonstrates the molecular details of the conserved N-terminal domain, RNA-dependent RNA polymerase (RdRp), and GDP polyribonucleotidyltransferase of the L protein, but also the intact central oligomerization domain and the C-terminal X domain of the P protein. The P protein interacts extensively with the L protein, forming an antiparallel β-sheet among the P protomers and with the fingers subdomain of RdRp. The flexible linker domain of one P promoter extends its contact with the fingers subdomain to reach near the nascent RNA exit, highlighting the distinct characteristic of the NiV L-P interface. This distinctive tetrameric organization of the P protein and its interaction with the L protein provide crucial molecular insights into the replication and transcription mechanisms of NiV polymerase, ultimately contributing to the development of effective treatments and preventive measures against this Paramyxoviridae family deadly pathogen.

A dual-targeted small-molecule photosensitizer with enhanced dual antitumor and anti-vascular effect for metastatic advanced prostate cancer photodynamic therapy

Advanced prostate cancer is regarded as a fatal disease, characterized by limited treatment options, poor prognosis and considerable tumor metastasis closely related to angiogenesis. Photodynamic therapy emerges as a promising and safe therapeutic modality for advanced prostate cancer with high metastasis and high fatality rate due to its focal damage to tumor cells, as well as its anti-angiogenesis and antitumor immunity capabilities. Herein, a tumor-targeting vascular disrupting agent ASA-404 was introduced to conjugate with a photosensitizer ZnPc for targeted prostate cancer treatment and enhanced vascular-disrupting efficiency. Notably, this novel organic small-molecule photosensitizer Pc-ASA possess a well-defined chemical structure and purity, as well as good photophysical and photochemical properties, which are of benefit for clinical approval and application. Pc-ASA prefers to accumulate in both prostate cancer cells and vascular endothelial cells. Moreover, the conjugation of ASA-404 boosts the photodynamic anticancer effect of Pc-ASA towards both prostate cancer cells and vascular endothelial cells. Ultimately, PC-ASA can successfully inhibit the migration and metastasis of prostate cancer cells, offering significant advantages in advanced prostate cancer management. Our study might open a window in the development of the tumor and vascular dual-targeted small-molecule photosensitizers, with the potential to achieve safe and efficient treatment of metastatic advanced prostate cancer through dual mode of antitumor and anti-vascular action.

A critical review on phytochemicals as antiviral medications for SARS-CoV-2 virus infection.

A pandemic of acute respiratory infection, which was specified as coronavirus disease 2019, was instigated by a different strain of the virulent coronavirus SARS-CoV-2 that first appeared in late 2019. Since viral infections spread fast and there is presently no effective treatment, the use of plants with a long history of use in treating these infections has been explored regularly. The pandemic of coronavirus disease 2019 (COVID-19) has brought to light the dearth of medications with approval to treat acute viral illnesses. Because of this, the illness had a high fatality rate. The mortality rate was initially quite high and varied according to the patient's geographic location. For instance, among Chinese patients, the rate was 3·6%, whereas 1·5% of COVID-19-related deaths were documented outside of China. As of 2020, India has a 1.4% case fatality rate (CFR) of COVID-19 mortality, compared to 2.8% in Brazil and 1.8% in the USA. Many studies are being conducted to create pharmaceutical compounds specifically targeting important SARS-CoV-2 proteins. Several drug discovery initiatives are being undertaken to find powerful inhibitors by combining biochemical assay and computer-aided drug design techniques. Although plant-derived compounds have not had much success in the dominion of antivirals, plants are, however, believed to be a limitless supply of medications for a variety of diseases and clinical conditions. The scientific foundation required for developing novel natural source medications is provided by the chemical characterization and analysis of plant components. Most viral infections treated by ethnobotanical applications and historical literature on ayurveda, and traditional medicine are generally attributed to phytochemicals, which are compounds derived from medicinal plants. In this review, we have described the application of vascular plant-derived chemicals, such as tannins, polyphenols, alkaloids, and flavonoids, as antivirals, especially for managing COVID-19. This article discusses novel bioactive compounds and their molecular structures that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as prospective candidates for anti-coronavirus disease drugs. Moreover, to confirm the effectiveness of the phytochemicals that have demonstrated antiviral activity, clinical trials would need to be conducted in addition to the preclinical research that has already been done. To ensure spectacular findings, more applications of the compound would need to be studied to fully understand the effects of those phytochemicals whose clinical usefulness has already been established.

Acute bacterial meningitis without cerebrospinal fluid pleocytosis in children: results from a nationwide prospective surveillance system between 2001 and 2022

ObjectivesWe aimed to describe cases of acute bacterial meningitis (ABM) without cerebrospinal fluid (CSF) pleocytosis and the clinical and biological characteristics of affected children. MethodsWe analyzed results of a nation-wide population-based prospective surveillance study of acute ABM in children aged 3 months to 15 years in France. Absence of CSF pleocytosis was defined as CSF leukocyte count ≤5/mm3. ResultsWe included 4754 cases of acute ABM from 2001 to 2022: 173 patients (3.6%) did not have CSF pleocytosis. ABM cases without CSF pleocytosis were mainly related to meningococcus (70% vs 44% with CSF pleocytosis, P <0.001). When performed in CSF with normal leukocyte count, Gram staining results were positive for 33%, culture for 80%, polymerase chain reaction results for 41%, and antigen detection for 20% of cases. Case fatality rate was higher for cases without than those with CSF pleocytosis (18% vs 6%, P <0.001). On multivariate analysis, absence of CSF pleocytosis was associated only with seizures before hospital arrival (adjusted odds ratio 2.3, 95% confidence interval 1.2-4.6, P <0.01). ConclusionsABM without CSF pleocytosis is infrequent but not exceptional, particularly in children with seizures before hospital arrival. Extended vaccination against meningococcus could prevent this clinical form with a high case fatality rate.

A case of visual impairment due to HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation in childhood acute myeloid leukemia-M2 subtype.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a crucial treatment option for children with M2 subtype acute myeloid leukemia (AML). Human herpesvirus 6 (HHV-6) encephalitis following transplantation is a rare postoperative complication, with a poor prognosis and a high fatality rate in allo-HSCT recipients. In this report, a juvenile patient with AMLwas successfully treated after developing visual impairment as a result of HHV-6B encephalitis during allo-HSCT therapy. HHV-6 encephalitis-associated visual impairment after transplantation is rare, and clinical diagnosis and treatment are challenging, requiring more attention in the future.

Mortality predictors in emergency department adult patients with sepsis: A systematic review

Background: Sepsis was regarded as a major global public health concern; it continues to be associated with a high death rate despite advancements in contemporary treatment. This research aims to evaluate the predictive effect of clinical scoring systems and biomarkers for sepsis patients in ED. Method: In accordance with PRISMA principles, we carried out this systematic review. We used the internet databases MEDLINE, Google Scholar, and EMBASE to conduct a thorough search of the literature. Articles written in English and released between 2015 and 2023 were involved in the search. Using predictors and ED, we first conducted a comprehensive search that included sepsis and infectious illnesses. Result: A total of 3029 patients from 7 publications—3 cohort, 2 observational, and 2 case control studies—were included in this study. The study by Song et al. in 2019 had the highest fatality rate (46.6%), while the study by Duplessis et al. in 2018 had the lowest mortality rate (6.4%). SIRS criteria, qSOFA score, International Sepsis Conference 2001, and American College of Chest Physicians Guidelines are the diagnostic criteria that are employed. AUC varied from 33.7 (MMP9) to 0.89 (IL-6). Conclusion: AUC was increased significantly when CSSs were combined with IgE, presepsin, IL-6 and PCT.

Ebola Virus Matrix Protein VP40 Single Mutations G198R and G201R Significantly Enhance Plasma Membrane Localization.

Viral proteins frequently undergo single or multiple amino acid mutations during replication, which can significantly alter their functionality. The Ebola virus matrix protein VP40 is multifunctional but primarily responsible for creating the viral envelope by binding to the inner leaflet of the host cell plasma membrane (PM). Changes to the VP40 surface cationic charge via mutations can influence PM interactions, resulting in altered viral assembly and budding. A recent mutagenesis study evaluated the effects of several mutations and found that mutations G198R and G201R enhanced VP40 assembly at the PM and virus-like particle budding. These two mutations lie in the loop region of the C-terminal domain (CTD), which directly interacts with the PM. To understand the role of these mutations in PM localization at the molecular level, we performed both all-atom and coarse-grained molecular dynamics simulations using a dimer-dimer configuration of VP40, which contains the CTD-CTD interface. Our studies indicate that the location of mutations on the outer surface of the CTD regions can lead to changes in membrane binding orientation and degree of membrane penetration. Direct PI(4,5)P2 interactions with the mutated residues seem to further stabilize and pull VP40 into the PM, thereby enhancing interactions with numerous amino acids that were otherwise infrequently or completely inaccessible. These multiscale computational studies provide new insights at the atomic and molecular level as to how VP40-PM interactions are altered through single amino acid mutations. Given the high case fatality rates associated with Ebola virus disease in humans, it is essential to explore the mechanisms of viral assembly in the presence of mutations to mitigate the severity of the disease and understand the potential of future outbreaks.

Optimization study of tail-lateral occupant injury and restraint system for an off-road vehicle ramp rollover

The process of rollover accidents involving specialized vehicles is characterized by intense motion and long duration. Although these accidents are infrequent, they often lead to a high fatality rate. In this study, we utilized LS-Dyna software to simulate the rollover of a vehicle on a side ramp. This simulation aimed to verify the reliability of our model establishment by comparing the vehicle’s motion attitude and center-of-mass acceleration with experimental results. Additionally, we sought to investigate the lateral occupant injuries that occur in the tail section of a certain type of specialized vehicle during a rollover. Initially, we obtained the vehicle’s motion trajectory and the dummy’s motion state through simulation. Subsequently, we extracted the injury response of each part of the dummy. We then simplified the entire vehicle model and made improvements to the occupant restraint system, ultimately designing an enhanced system. Finally, we approximated and replaced the entire vehicle model by establishing an approximation model. We combined this with an optimization algorithm to optimize the occupant restraint system. The simulation results demonstrate that the improved occupant restraint system significantly reduces the axial force on the neck of the occupant and the comprehensive evaluation index of injury. Furthermore, the simulation results for each component fall below the injury limit value specified in the FMVSS208 crash occupant protection standard. Therefore, the improved occupant restraint system proposed in this study effectively mitigates lateral occupant injury during rollover accidents.

Soluplus-TPGS Mixed Micelles as a Delivery System for Brigatinib: Characterization and In Vitro Evaluation.

Lung cancer is a major public health concern, with a high incidence and fatality rate. Its treatment is very difficult, as it is mostly diagnosed in advanced stages. Non-small cell lung carcinoma (NSCLC) is the major form of lung carcinoma that persists. Brigatinib (BGT), a powerful small-molecule tyrosine kinase inhibitor, has demonstrated significant therapeutic potential in the treatment of NSCLC with anaplastic lymphoma kinase (ALK) mutations. However, the therapeutic applicability of BGT is hampered by its low solubility and bioavailability. In this study, we developed a mixed micelle system comprising Soluplus and TPGS loaded with BGT. BGT was encapsulated into the mixed micelles using various combinations of Soluplus and TPGS, with encapsulation efficiency (EE%) ranging from 52.43 ± 1.07 to 97.88 ± 2.25%. The dynamic light scattering data showed that the mixed micelles ranged in size from 75.7 ± 0.46 to 204.3 ± 5.40 nm. The selected mixed micelles (F6) showed approximately 38% BGT release in the first 2 h, and subsequently, within 72 h, the release was 94.50 ± 5.90%. The NMR experiment confirmed the formation of micelles. Additionally, the mixed micelles showed significantly higher cellular uptake (p < 0.05) and increased cytotoxicity (p < 0.05) as compared to the free BGT. Specifically, the obtained IC50 values for BGT-loaded Soluplus-TPGS mixed micelles and free BGT were 22.59 ± 6.07 and 61.45 ± 6.35 μg/mL, respectively. The results of the in vitro stability experiment showed that the selected mixed micelle (F6) was stable at both room temperature and 4 °C, with only minor changes in size and PDI. Our results indicate great potential for the developed Soluplus-TPGS mixed micelles as a delivery system for BGT.

Treatment outcomes in retinoblastoma and the effect of tumor topography.

Retinoblastoma, the most common intraocular malignancy in children, has high fatality rates if untreated. It is crucial to monitor treatment effectiveness and explore factors influencing favorable outcomes. Our study aims to examine how tumor location impacts the response to standard treatments and the achievement of favorable outcomes among retinoblastoma patients, while controlling for other tumor-related factors. This retrospective study analyzed medical records of retinoblastoma patients from November 2012 to December 2022 enrolled in the retinoblastoma program at the Children's Cancer Center of Lebanon (established in collaboration with St.yJude Children's Research Hospital, Memphis, TN). Data were extracted from the electronic chart reviews and operative reports of examinations under anesthesia (EUAs), and included patient's demographics, tumor characteristics (size, location), and treatment parameters (treatment type, resolution, recurrence). The study included 42 patients with retinoblastoma, with a total of 57 eyes and 115 tumors/lesions. The median age at diagnosis was 12months (range: 2-36months). Among the patients, 26 (61.9%) were males and 16 (38.1%) were females. A minority of patients (21.4%) presented with unilateral involvement, whereas the majority (78.6%) had bilateral involvement. The locations of retinoblastoma lesions were distributed as follows: optic nerve (4.4%), macula (19.1%), superior (16.5%), inferior (17.4%), nasal (27.8%), and temporal (14.8%). Resolution rate tended to be highest for tumors close to optic nerve and temporal lesions, but no statistical significance was attained (p=.45). Macular lesions tended to have the fastest resolution, but again not significantly (p=.5). Multiple logistic regression revealed that the odds for resolution of tumor was not significantly associated with tumor size (p=.57) or location (p=.52). Location of retinoblastoma lesions was not directly associated with recurrence-free resolution in our cohort. Further research in large retinoblastoma databases is needed to explore the association of tumor characteristics with recurrence and the need for secondary therapeutic interventions.

Establishment and validation of a clinical risk scoring model to predict fatal risk in SFTS hospitalized patients

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high case fatality rate. Significant gaps remain in studies analyzing the clinical characteristics of fatal cases.MethodsFrom January 2017 to June 2023, 427 SFTS cases were included in this study. A total of 67 variables about their demographic, clinical, and laboratory data were collected. Univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) method was used to screen predictors from the cohort. Multivariate logistic regression was used to identify independent predictors and nomograms were developed. Calibration, decision curves and area under the curve (AUC) were used to assess model performance.ResultsThe multivariate logistic regression analysis screened out the four most significant factors, including age > 70 years (p = 0.001, OR = 2.516, 95% CI 1.452–4.360), elevated serum PT (p < 0.001, OR = 1.383, 95% CI 1.143–1.673), high viral load (p < 0. 001, OR = 1.496, 95% CI 1.290–1.735) and high level of serum urea (> 8.0 μmol/L) (p < 0.001, OR = 4.433, 95% CI 1.888–10.409). The AUC of the nomogram based on these four factors was 0.813 (95% CI, 0.758–0.868). The bootstrap resampling internal validation model performed well, and decision curve analysis indicated a high net benefit.ConclusionsThe nomogram based on age, elevated PT, high serum urea level, and high viral load can be used to help early identification of SFTS patients at risk of fatality.

Long-term persistence of diverse clones shapes the transmission landscape of invasive Listeria monocytogenes

BackgroundThe foodborne bacterium Listeria monocytogenes (Lm) causes a range of diseases, from mild gastroenteritis to invasive infections that have high fatality rate in vulnerable individuals. Understanding the population genomic structure of invasive Lm is critical to informing public health interventions and infection control policies that will be most effective especially in local and regional communities.MethodsWe sequenced the whole draft genomes of 936 Lm isolates from human clinical samples obtained in a two-decade active surveillance program across 58 counties in New York State, USA. Samples came mostly from blood and cerebrospinal fluid. We characterized the phylogenetic relationships, population structure, antimicrobial resistance genes, virulence genes, and mobile genetic elements.ResultsThe population is genetically heterogenous, consisting of lineages I–IV, 89 clonal complexes, 200 sequence types, and six known serogroups. In addition to intrinsic antimicrobial resistance genes (fosX, lin, norB, and sul), other resistance genes tetM, tetS, ermG, msrD, and mefA were sparsely distributed in the population. Within each lineage, we identified clusters of isolates with ≤ 20 single nucleotide polymorphisms in the core genome alignment. These clusters may represent isolates that share a most recent common ancestor, e.g., they are derived from the same contamination source or demonstrate evidence of transmission or outbreak. We identified 38 epidemiologically linked clusters of isolates, confirming eight previously reported disease outbreaks and the discovery of cryptic outbreaks and undetected chains of transmission, even in the rarely reported Lm lineage III (ST3171). The presence of animal-associated lineages III and IV may suggest a possible spillover of animal-restricted strains to humans. Many transmissible clones persisted over several years and traversed distant sites across the state.ConclusionsOur findings revealed the bacterial determinants of invasive listeriosis, driven mainly by the diversity of locally circulating lineages, intrinsic and mobile antimicrobial resistance and virulence genes, and persistence across geographical and temporal scales. Our findings will inform public health efforts to reduce the burden of invasive listeriosis, including the design of food safety measures, source traceback, and outbreak detection.

Severe Fever with Thrombocytopenia Syndrome in South Korea, 2016-2021: Clinical Features of Severe Progression and Complications.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection with a high case fatality rate. The serious clinical features need to be further defined. We performed a retrospective analysis among SFTS patients in South Korea during 2016-2021 to update the current status. The basic epidemiology of all reported cases was analyzed, and the detailed clinical data of the subjects were further collected from study hospitals selected in terms of their geographic location and capability of SFTS care. Cases of SFTS were reported across the country and were greatly increased since the initial endemic phase, even under the passive surveillance system. The case fatality rate remained at approximately 16.8%. Coinfections at admission were present in 7.8% of the patients. Major complications included bleeding (15.2%), hemophagocytic lymphohistiocytosis (6.7%), bacteremia or candidemia (4.0%), and invasive pulmonary aspergillosis (1.7%). It took a median 4 days from the onset of illness to hospital admission. Rapid clinical deterioration was observed with a median 1 day for intensive care unit admission, 3 days for mechanical ventilation, 4 days for renal replacement therapy, and 5 days for death, all after the hospitalization. Multivariate analysis showed that the fatality was associated with older age, bacteremia, or candidemia during hospitalization, and the presence of several variables at admission such as fever, altered mentality, aspartate aminotransferase >200 IU/L, serum creatinine level >1.2 mg/dL, and prolonged prothrombin time and activated partial thromboplastin time. Treatment options to improve clinical outcomes are limited, despite best supportive care. Specific treatment is urgently needed to change the fatal course.

Sociopolitical context and COVID-19 fatality rates in OECD countries: a configurational approach

BackgroundThe effectiveness of crisis response can be influenced by various structural, cultural, and functional aspects within a social system. This study uses a configurational approach to identify combinations of sociopolitical conditions that lead to a high case fatality rate (CFR) of COVID-19 in OECD countries.MethodsA Fuzzy set qualitative comparative analysis (QCA) is conducted on a sample of 38 OECD countries. The outcome to be explained is high COVID-19 CFR. The five potentially causal conditions are level of democracy, state capacity, trust in government, health expenditure per capita, and the median age of population. A comprehensive QCA robustness test protocol is applied, which includes sensitivity ranges, fit-oriented robustness, and case-oriented robustness tests.ResultsNone of the causal conditions in both the presence and negation form were found to be necessary for high or low levels of COVID-19 CFR. Two different combinations of sociopolitical conditions were usually sufficient for the occurrence of a high CFR of COVID-19 in OECD countries. Low state capacity and low trust in government are part of both recipes. The entire solution formula covers 84 percent of the outcome. Some countries have been identified as contradictory cases. The explanations for their COVID-19 CFR require more in-depth case studies.ConclusionsFrom a governance perspective, the weakness of government in effectively implementing policies, and the citizens’ lack of confidence in their government, combined with other structural conditions, serve as barriers to mounting an effective response to COVID-19. These findings can support the idea that the effects of social determinants of COVID-19 outcomes are interconnected and reinforcing.

A Critical Assessment of Remdesivir

Abstract: The COVID-19 pandemic that originated in Wuhan city, China, has affected every village in India. This has killed millions of people. This disease involves symptomatic and asymptomatic mutations. The purpose of this review was to assess the effectiveness of remdesivir particularly against SAR-CoV-2 (Coronaviridae family). The relevant works have been studied with respect to the drug's chemistry, mechanism of action, pharmacokinetics, pharmacodynamics, clinical data, and side effects. Remdesivir has been used in many cases of coronavirus-infected patients because it has been proven to possess beneficial effects; however, significant adverse effects have also been reported. Remdesivir has been reported to help in lowering the disease's high fatality rate. However, the WHO has warned against using the medicine because there is no clinical data to support its therapeutic efficacy.

Role of C-reactive Protein and Procalcitonin in Early Diagnostic Accuracy and Their Prognostic Significance in Sepsis.

Sepsis is a serious condition that often results in high fatality rates, particularly in intensive care units (ICUs). Its nonspecific clinical characteristics makes early diagnosis and therapy difficult, despite how critical they are. The use of biomarkers like procalcitonin (PCT) and C-reactive protein (CRP) in the diagnosis and prognosis of sepsis has demonstrated encouraging results. In contrast to PCT, which is highly selective for bacterial infections, CRP is an acute-phase protein that reflects systemic inflammation. This study aimed to assess the diagnostic accuracy and prognostic significance of CRP and PCT in early sepsis detection and outcome prediction. This study was a retrospective cohort study that involved 90 patients in the ICU who met the criteria for sepsis-3. CRP and PCT levels, clinical data, and outcomes were obtained from electronic medical records. The diagnostic accuracy was tested using receiver operating characteristic (ROC) curves, while the prognostic relevance was analyzed by Kaplan-Meier survival analysis and Cox proportional hazards regression. The mean CRP level was 102.3 mg/L and PCT level was 5.4 ng/mL. ROC analysis revealed an area under the curve (AUC) of 0.78 for CRP and 0.82 for PCT, indicating better diagnostic performance for PCT. High levels of CRP and PCT were associated with poorer survival, with median survival times of 18 and 15 days, respectively, for high-level groups. Cox regression identified CRP and PCT as significant predictors of mortality, with hazard ratios of 1.50 and 1.68, respectively. Both CRP and PCT are valuable biomarkers for diagnosing and prognosticating sepsis. PCT, with its higher specificity for bacterial infections, demonstrates superior diagnostic accuracy compared to CRP. Elevated levels of both biomarkers are associated with increased mortality risk, highlighting their potential role in early sepsis management and outcome prediction.

Torsemide as a Primary Choice in Edema Associated with Heart Failure.

Heart failure (HF) is the fastest-growing disease with a higher fatality rate. The most differentiating feature of HF is pulmonary or peripheral edema, which is characterized by a gradient between intravascular and extravascular pressure. Loop diuretics were chosen as the primary treatment for edema associated with HF due to their efficacy and early onset of action. If an oral dose had not been provided, intravenous (IV) administration of torsemide, or equal doses of furosemide and bumetanide, was preferred. However, the key variables for selecting and administering loop diuretics are their pharmacological qualities as well as their clinical efficacy. Torsemide has greater bioavailability, a higher rate of absorption, a longer duration of action, and lesser ototoxicity, making it the primary choice in the management of edematous HF.

An attachment glycoprotein nanoparticle elicits broadly neutralizing antibodies and protects against lethal Nipah virus infection

Nipah virus (NiV) is a zoonotic emergent paramyxovirus that can cause severe encephalitis and respiratory infections in humans, with a high fatality rate ranging from 40% to 75%. Currently, there are no approved human vaccines or antiviral drugs against NiV. Here, we designed a ferritin-based self-assembling nanoparticle displaying the NiV G head domain on the surface (NiV G-ferritin) and assessed immune responses elicited by the soluble NiV G head domain (NiV sG) or NiV G-ferritin. Immunization with NiV G-ferritin or NiV sG conferred complete protection against lethal NiV challenge without detection of viral RNA in Syrian golden hamsters. Compared to NiV sG, NiV G-ferritin induced significantly faster, broader, and higher serum neutralizing responses against three pathogenic henipaviruses (NiV-Malaysia, NiV-Bangladesh, and Hendra virus). Moreover, NiV G-ferritin induced a durable neutralizing immunity in mice as antisera potently inhibited NiV infection even after six months of the third immunization. Additionally, we isolated a panel of 27 NiV G-binding monoclonal antibodies (mAbs) from NiV G-ferritin immunized mice and found that these mAbs targeted four distinct antigenic sites on NiV G head domain with two sites that have not been defined previously. Notably, 25 isolated mAbs have potent neutralizing activity with 50% inhibitory concentrations less than 10 ng/mL against NiV pseudovirus. Collectively, these findings provide new insights into the immunogenicity of NiV G protein and reveal that NiV G-ferritin is a safe and highly effective vaccine candidate against Nipah virus infection.

A Review of Social Issues in Relation to the Rabies Outbreak in Sarawak, Malaysia

This article aims to review studies on social issues, patient management, and preventive behaviors related to the human rabies outbreak in Sarawak. The review analysed 19 documents from databases and 6 newspaper reports. Studies highlighted factors such as population density, seasonal patterns, and contact with dogs as contributing to the risk of rabies. Control efforts focused on dog vaccination and public education. Key epidemiological studies revealed a high case fatality rate and low rates of immediate medical treatment post-exposure. Social issues such as mishandling of patients, lack of federal support, and low public awareness were significant obstacles. Community engagement and interventions, including educational tools and behavioral assessments, were essential for improving rabies control. Health-seeking behavior patterns showed a general lack of prompt action post-exposure, with many patients seeking treatment too late. Prevention strategies emphasized the “One Health” approach, integrating human and animal health surveillance to enhance rabies control. Comprehensive public education, community involvement, and resource allocation are critical to addressing the ongoing challenges of rabies prevention in Sarawak.

The effects of GCRV on various tissues of grass carp (Ctenopharyngodon idella) and identification of differential interferon-stimulating genes (ISGs) through muscle transcriptome analysis

Grass carp hemorrhagic disease is caused by the grass carp reovirus (GCRV). The disease spreads rapidly and has a high fatality rate, which seriously affects grass carp culture. Moreover, the molecular mechanisms underlying grass carp hemorrhagic disease remain unclear. To decipher the effects of GCRV on grass carp tissues, resistant grass carp A (GA) and susceptible grass carp B (GB) were selected through GCRV treatment, and control grass carp C (GC) was also established. The gill, liver, and muscle tissues exhibited different onset symptoms under the influence of GCRV by histological observation. We selected muscle samples with significant differences in symptoms for Illumina RNA sequencing. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed 3512, 3074, and 1853 differentially expressed genes between "GC vs. GB," "GC vs. GA," and "GA vs. GB," respectively. Additionally, 40 differential immune-related genes and 28 differential interferon-stimulating genes (ISGs) related to the interferon (IFN) pathway were identified. The expression of immunogene-related genes of GB and GA, such as MDA5, IL-34, NF-KB, TRIM25, SOCS3, CEBPB, and BCL2, and genes associated with the JAK-STAT signaling pathway, such as IRF4, STAT1, STAT3, JAK 1, and JAK 2, was significantly upregulated. The IFN and JAK-STAT signaling pathways were closely related to anti-GCRV infection. The transcriptome data and predicted immune genes and ISGs in this study provide novel insights into the treatment of GCRV.