Integrating immunoinformatics and computational epitope prediction for a vaccine candidate against respiratory syncytial virus.

Respiratory syncytial virus (RSV) poses a significant global health threat, especially affecting infants and the elderly. Addressing this, the present study proposes an innovative approach to vaccine design, utilizing immunoinformatics and computational strategies. We analyzed RSV's structural proteins across both subtypes A and B, identifying potential helper T lymphocyte, cytotoxic T lymphocyte, and linear B lymphocyte epitopes. Criteria such as antigenicity, allergenicity, toxicity, and cytokine-inducing potential were rigorously examined. Additionally, we evaluated the conservancy of these epitopes and their population coverage across various RSV strains. The comprehensive analysis identified six major histocompatibility complex class I (MHC-I) binding, five MHC-II binding, and three B-cell epitopes. These were integrated with suitable linkers and adjuvants to form the vaccine. Further, molecular docking and molecular dynamics simulations demonstrated stable interactions between the vaccine candidate and human Toll-like receptors (TLR4 and TLR5), with a notable preference for TLR4. Immune simulation analysis underscored the vaccine's potential to elicit a strong immune response. This study presents a promising RSV vaccine candidate and offers theoretical support, marking a significant advancement in vaccine development efforts. However, the promising in silico findings need to be further validated through additional in vivo studies.

Optoelectronic Properties of Nitrogen-Doped Hexagonal Graphene Quantum Dots: A First-Principles Study.

Graphene quantum dots have been widely studied owing to their unique optical, electrical, and optoelectrical properties for various applications in solar devices. Here, we investigate the optoelectronic properties of hexagonal and nitrogen-doped graphene quantum dots using the first-principles method. We find that doping nitrogen atoms to hexagonal graphene quantum dots results in a significant red shift toward the visible light range as compared to that of the pristine graphene quantum dots, and the doped nitrogen atoms also induce a clear signature of anisotropy of the frontier orbitals induced by the electron correlation between the doped nitrogen atoms and their adjacent carbon atoms. Moreover, time-dependent density functional theory calculations with the M06-2X functional and 6-311++G(d,p) basis set reproduce well the experimental absorption spectra reported recently. These results provide us with a novel approach for more systematic investigations on next-generation solar devices with assembled quantum dots to improve their light selectivity as well as efficiency.

Prognostic values of serum lactate-to-bicarbonate ratio and lactate for predicting 28-day in-hospital mortality in children with dengue shock syndrome.

This study aimed to assess the clinical utility of blood lactate-to-bicarbonate (L/B) ratio, as a prognostic factor for 28-day in-hospital mortality in children with dengue shock syndrome (DSS), admitted to the pediatric intensive care unit (PICU). This single-center retrospective study was conducted at a tertiary children hospital in southern Vietnam from 2013 to mid-2022. Prognostic models for DSS mortality were developed, using a predefined set of covariates in the first 24 hours of PICU admission. Area under the curves (AUCs), multivariable logistic and Least Absolute Shrinkage and Selection Operator (LASSO) regressions, bootstrapping and calibration slope were performed. A total of 492 children with DSS and complete clinical and biomarker data were included in the analysis, and 26 (5.3%) patients died. The predictive values for DSS mortality, regarding lactate showing AUC 0.876 (95% CI, 0.807-0.944), and that of L/B ratio 0.867 (95% CI, 0.80-0.934) (P values of both biomarkers < .001). The optimal cutoff point of the L/B ratio was 0.25, while that of lactate was 4.2 mmol/L. The multivariable model showed significant clinical predictors of DSS fatality including severe bleeding, cumulative amount of fluid infused and vasoactive-inotropic score (>30) in the first 24 hours of PICU admission. Combined with the identified clinical predictors, the L/B ratio yielded higher prognostic values (odds ratio [OR] = 8.66, 95% confidence interval [CI], 1.96-38.3; P < .01) than the lactate-based model (OR = 1.35, 95% CI, 1.15-1.58; P < .001). Both the L/B and lactate models showed similarly good performances. Considering that the L/B ratio has a better prognostic value than the lactate model, it may be considered a potential prognostic biomarker in clinical use for predicting 28-day mortality in PICU-admitted children with DSS.

Discovering peptides and computational investigations of a multiepitope vaccine target Mycobacterium tuberculosis.

Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis (TB), a prevalent airborne infectious disease. Despite the availability of the Bacille Calmette-Guerin vaccine, its global efficacy remains modest, and tuberculosis persists as a significant global public health threat. Addressing this challenge and advancing towards the End MTB Strategy, we developed a multiepitope vaccine (MEV) based on immunoinformatics and computational approaches. Immunoinformatics screening of MBT protein identified immune-dominant epitopes based on Major Histocompatibility Complex (MHC) allele binding, immunogenicity, antigenicity, allergenicity, toxicity, and cytokine inducibility. Selected epitopes were integrated into an MEV construct with adjuvant and linkers, forming a fully immunogenic vaccine candidate. Comprehensive analyses encompassed the evaluation of immunological and physicochemical properties, determination of tertiary structure, molecular docking with Toll-Like Receptors (TLR), molecular dynamics (MD) simulations for all atoms, and immune simulations. Our MEV comprises 534 amino acids, featuring 6 cytotoxic T lymphocyte, 8 helper T lymphocyte, and 7 linear B lymphocyte epitopes, demonstrating high antigenicity and stability. Notably, molecular docking studies and triplicate MD simulations revealed enhanced interactions and stability of MEV with the TLR4 complex compared to TLR2. In addition, the immune simulation indicated the capacity to effectively induce elevated levels of antibodies and cytokines, emphasizing the vaccine's robust immunogenic response. This study presents a promising MEV against TB, exhibiting favorable immunological and physicochemical attributes. The findings provide theoretical support for TB vaccine development. Our study aligns with the global initiative of the End MTB Strategy, emphasizing its potential impact on addressing persistent challenges in TB control.

A Retrospective Study Evaluating Guideline Adherence of Neonatal Parenteral Nutrition in a Belgian Neonatal Intensive Care Unit.

Introduction Clinical nutrition for preterm and critically ill neonates remains a challenge. Preterms are often hemodynamically and metabolically compromised, which limits infusion volumes of nutrients and hinders achieving recommended nutrient intakes. While guidelines provide recommended ranges for parenteral nutrition (PN) intakes, they generally recommend enteral nutrition as soon as possible. Thus, in clinical practice, gradually increasing EN intakes complicates assessments of PN guideline adherence. Via a pragmatic approach, we assessed adherence to PN recommendations for macronutrients and energy as stated in the 2018 guidelines of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Methods In this retrospective study, we assessed the nutrition of preterm and critically ill term neonates from the neonatal intensive care unit of the University Hospital Brussels. We analyzed intakes for the first week of life, in which critically ill neonates at our center usually receive the majority of nutrients via PN. The PN-based provision of macronutrients and energy was analyzed descriptively in relation to the ESPGHAN 2018 recommendations. Results Macronutrients and energy provision gradually increased until they reached recommended or targeted values. Compared to term neonates, energy and lipid provision for preterms increased faster, while amino acid provision exceeded the ESPGHAN 2018 recommendations. Conclusions This study adds clinical practice data to the severely understudied field of the ESPGHAN 2018 PN guideline compliance. Using a pragmatic assessment of our nutrition protocols, we found the need to reduce the amount of amino acids per kg body weight per day to meet guideline recommendations.

Immunoinformatics and computational approaches driven designing a novel vaccine candidate against Powassan virus.

Powassan virus (POWV) is an arthropod-borne virus (arbovirus) capable of causing severe illness in humans for severe neurological complications, and its incidence has been on the rise in recent years due to climate change, posing a growing public health concern. Currently, no vaccines to prevent or medicines to treat POWV disease, emphasizing the urgent need for effective countermeasures. In this study, we utilize bioinformatics approaches to target proteins of POWV, including the capsid, envelope, and membrane proteins, to predict diverse B-cell and T-cell epitopes. These epitopes underwent screening for critical properties such as antigenicity, allergenicity, toxicity, and cytokine induction potential. Eight selected epitopes were then conjugated with adjuvants using various linkers, resulting in designing of a potentially stable and immunogenic vaccine candidate against POWV. Moreover, molecular docking, molecular dynamics simulations, and immune simulations revealed a stable interaction pattern with the immune receptor, suggesting the vaccine's potential to induce robust immune responses. In conclusion, our study provided a set of derived epitopes from POWV's proteins, demonstrating the potential for a novel vaccine candidate against POWV. Further in vitro and in vivo studies are warranted to advance our efforts and move closer to the goal of combatting POWV and related arbovirus infections.

Age-time-specific transmission of hand-foot-and-mouth disease enterovirus serotypes in Vietnam: A catalytic model with maternal immunity.

Hand, foot and mouth disease (HFMD) is highly prevalent in the Asia Pacific region, particularly in Vietnam. To develop effective interventions and efficient vaccination programs, we inferred the age-time-specific transmission patterns of HFMD serotypes enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) in Ho Chi Minh City, Vietnam from a case data collected during 2013-2018 and a serological survey data collected in 2015 and 2017. We proposed a catalytic model framework with good adaptability to incorporate maternal immunity using various mathematical functions. Our results indicate the high-level transmission of CV-A6 and CV-A10 which is not obvious in the case data, due to the variation of disease severity across serotypes. Our results provide statistical evidence supporting the strong association between severe illness and CV-A6 and EV-A71 infections. The HFMD dynamic pattern presents a cyclical pattern with large outbreaks followed by a decline in subsequent years. Additionally, we identify the age group with highest risk of infection as 1-2 years and emphasise the risk of future outbreaks as over 50% of children aged 6-7 years were estimated to be susceptible to CV-A16 and EV-A71. Our study highlights the importance of multivalent vaccines and active surveillance for different serotypes, supports early vaccination prior to 1 year old, and points out the potential utility for vaccinating children older than 5 years old in Vietnam.

High-density stable glasses formed on soft substrates.

Enabled by surface-mediated equilibration, physical vapour deposition can create high-density stable glasses comparable with liquid-quenched glasses aged for millions of years. Deposition is often performed at various rates and temperatures on rigid substrates to control the glass properties. Here we demonstrate that on soft, rubbery substrates, surface-mediated equilibration is enhanced up to 170 nm away from the interface, forming stable glasses with densities up to 2.5% higher than liquid-quenched glasses within 2.5 h of deposition. Gaining similar properties on rigid substrates would require 10 million times slower deposition, taking ~3,000 years. Controlling the modulus of the rubbery substrate provides control over the glass structure and density at constant deposition conditions. These results underscore the significance of substrate elasticity in manipulating the properties of the mobile surface layer and thus the glass structure and properties, allowing access to deeper states of the energy landscape without prohibitively slow deposition rates.

Feasibility of wearable monitors to detect heart rate variability in children with hand, foot and mouth disease.

Hand foot and mouth disease (HFMD) is caused by a variety of enteroviruses, and occurs in large outbreaks in which a small proportion of children deteriorate rapidly with cardiopulmonary failure. Determining which children are likely to deteriorate is difficult and health systems may become overloaded during outbreaks as many children require hospitalization for monitoring. Heart rate variability (HRV) may help distinguish those with more severe diseases but requires simple scalable methods to collect ECG data.We carried out a prospective observational study to examine the feasibility of using wearable devices to measure HRV in 142 children admitted with HFMD at a children's hospital in Vietnam. ECG data were collected in all children. HRV indices calculated were lower in those with enterovirus A71 associated HFMD compared to those with other viral pathogens.HRV analysis collected from wearable devices is feasible in a low and middle income country (LMIC) and may help classify disease severity in HFMD.

Designing a Multiepitope Vaccine against Eastern Equine Encephalitis Virus: Immunoinformatics and Computational Approaches.

Eastern equine encephalitis virus (EEEV) is a significant threat to human and animal populations, causing severe encephalitis, often leading to long-term neurological complications and even mortality. Despite this, no approved antiviral treatments or EEEV human vaccines currently exist. In response, we utilized immunoinformatics and computational approaches to design a multiepitope vaccine candidate for EEEV. By screening the structural polyprotein of EEEV, we predicted both T-cell and linear B-cell epitopes. These epitopes underwent comprehensive evaluations for their antigenicity, toxicity, and allergenicity. From these evaluations, we selected ten epitopes highly suitable for vaccine design, which were connected with adjuvants using a stable linker. The resulting vaccine construct demonstrated exceptional antigenic, nontoxic, nonallergenic, and physicochemical properties. Subsequently, we employed molecular docking and molecular dynamics simulations to reveal a stable interaction pattern between the vaccine candidate and Toll-like receptor 5. Besides, computational immune simulations predicted the vaccine's capability to induce robust immune responses. Our study addresses the urgent need for effective EEEV preventive strategies and offers valuable insights for EEEV vaccine development. As EEEV poses a severe threat with potential spread due to climate change, our research provides a crucial step in enhancing public health defenses against this menacing zoonotic disease.

Emerging Enterovirus A71 Subgenogroup B5 Causing Severe Hand, Foot, and Mouth Disease, Vietnam, 2023.

We report on a 2023 outbreak of severe hand, foot, and mouth disease in southern Vietnam caused by an emerging lineage of enterovirus A71 subgenogroup B5. Affected children were significantly older than those reported during previous outbreaks. The virus should be closely monitored to assess its potential for global dispersal.

Associations of obesity and dengue-associated mortality, acute liver failure and mechanical ventilation in children with dengue shock syndrome.

Dengue-associated complications, including dengue shock syndrome, severe respiratory distress, and pediatric acute liver failure (PALF), are associated with high mortality rates in patients with dengue. There is increasing prevalence of overweight and obesity among children worldwide. Obesity may activate inflammatory mediators, leading to increased capillary permeability and plasma leakage in patients with dengue. Several studies have shown a correlation between obesity and DSS, but did not include dengue fatality or PALF. Therefore, we hypothesized possible associations between obesity and critical dengue-associated clinical outcomes among PICU-admitted children with DSS, including dengue-related mortality, mechanical ventilation (MV) requirements, and dengue-associated PALF. The nutritional status of the participants was assessed using World Health Organization growth charts. A total of 858 participants with complete nutritional data were enrolled in this study. Obesity was significantly associated with risk of severe respiratory failure and MV support (odds ratio = 2.3, 95% CI: 1.31-4.06, P < .01); however, it was not associated with dengue-associated mortality or acute liver failure. Obese pediatric patients with DSS should be closely monitored for severe respiratory distress and the need for high-flow oxygenation support, particularly MV, soon after hospitalization.

Heterogeneity of Alzheimer's disease identified by neuropsychological test profiling.

Alzheimer's disease (AD) is a highly heterogeneous disorder. Untangling this variability could lead to personalized treatments and improve participant recruitment for clinical trials. We investigated the cognitive subgroups by using a data-driven clustering technique in an AD cohort. People with mild-moderate probable AD from Taiwan was included. Neuropsychological test results from the Cognitive Abilities Screening Instrument were clustered using nonnegative matrix factorization. We identified two clusters in 112 patients with predominant deficits in memory (62.5%) and non-memory (37.5%) cognitive domains, respectively. The memory group performed worse in short-term memory and orientation and better in attention than the non-memory group. At baseline, patients in the memory group had worse global cognitive status and dementia severity. Linear mixed effect model did not reveal difference in disease trajectory within 3 years of follow-up between the two clusters. Our results provide insights into the cognitive heterogeneity in probable AD in an Asian population.

Non-coding RNAs versus protein biomarkers to diagnose and differentiate acute stroke: Systematic review and meta-analysis.

BACKGROUND: Stroke diagnosis is dependent on lengthy clinical and neuroimaging assessments, while rapid treatment initiation improves clinical outcome. Currently, more sensitive biomarker assays of both non-coding RNA- and protein biomarkers have improved their detectability, which could accelerate stroke diagnosis. This systematic review and meta-analysis compares non-coding RNA- with protein biomarkers for their potential to diagnose and differentiate acute stroke (subtypes) in (pre-)hospital settings. METHODS: We performed a systematic review and meta-analysis of studies evaluating diagnostic performance of non-coding RNA- and protein biomarkers to differentiate acute ischemic and hemorrhagic stroke, stroke mimics, and (healthy) controls. Quality appraisal of individual studies was assessed using the QUADAS-2 tool while the meta-analysis was performed with the sROC approach and by assessing pooled sensitivity and specificity, diagnostic odds ratios, positive- and negative likelihood ratios, and the Youden Index. SUMMARY OF REVIEW: 112 studies were included in the systematic review and 42 studies in the meta-analysis containing 11627 patients with ischemic strokes, 2110 patients with hemorrhagic strokes, 1393 patients with a stroke mimic, and 5548 healthy controls. Proteins (IL-6 and S100 calcium-binding protein B (S100B)) and microRNAs (miR-30a) have similar performance in ischemic stroke diagnosis. To differentiate between ischemic- or hemorrhagic strokes, glial fibrillary acidic protein (GFAP) levels and autoantibodies to the NR2 peptide (NR2aAb, a cleavage product of NMDA neuroreceptors) were best performing whereas no investigated protein or non-coding RNA biomarkers differentiated stroke from stroke mimics with high diagnostic potential. CONCLUSIONS: Despite sampling time differences, circulating microRNAs (< 24 h) and proteins (< 4,5 h) perform equally well in ischemic stroke diagnosis. GFAP differentiates stroke subtypes, while a biomarker panel of GFAP and UCH-L1 improved the sensitivity and specificity of UCH-L1 alone to differentiate stroke.

Remote Real-Time Training for Sustainable Cleft Operation in Rural Region of West Africa: Effective Webinar in the COVID-19 Pandemic.

INTRODUCTION: The surgical requirement for cleft lip and palate repair remains unmet in many developing areas of the world, including remote regions of Ghana. This article reviews the utilization of Internet education and online consultation for cleft lip and palate surgical training in Sunyani Regional Hospital (SRH), Ghana. METHODS: The cleft lip and palate treatment was promoted to patients in remote areas of Sunyani, Ghana region, through a charitable outreach program. These basic designs and settings were managed by local participants such as doctors, residents, nurses, and staff in SRH, Ghana. RESULTS: From November 2014 to December 2020, the authors collaborated in surgical treatment for 84 cases that were diagnosed with unilateral cleft lip, bilateral cleft lip, hard and soft palate cleft, and microstomia. The type of surgery has varied and has included cheiloplasty, palatoplasty, and others. The average scores of esthetic outcome evaluation were nasal form=2.4, symmetry of the nose=2.9, and vermillion border=2.9. Through the program, the surgeons and residents became significantly more proficient at cleft lip and palate surgery. The seminar topics have covered essential and sustainable topics based on SRH's current needs and showed the effectiveness in the current coronavirus disease-19 pandemic situation. CONCLUSIONS: The shortage of orofacial cleft surgeons working in rural areas like Sunyani, Ghana, remains an obstacle that poses a challenge to any effort to improve health care quality in these rural communities. Sustainable remote education is essential for the training of local cleft surgeons to fill this local need; our collaborative and charitable program could be a recommended education design for cleft surgeons and institutes for their sustainable education.

Endovascular treatment for life-threatening hemoptysis due to rupture of descending thoracic aortic aneurysm: A case series.

INTRODUCTION AND IMPORTANCE: Aortic aneurysm is an uncommon but life-threatening cause of hemoptysis. Treatments include surgery and/or endovascular intervention, each with its own advantages and disadvantages. Endovascular intervention is associated with good early and medium-term outcomes. CASE PRESENTATIONS: We report three cases of hemoptysis due to ruptured thoracic aortic aneurysm who underwent endovascular intervention. In all three cases, endovascular grafts were placed in the descending thoracic aorta, the number of grafts used was 1, the average time to stop hemoptysis was 4 to 5 days, and the length of hospital stay was between 6 and 8 days. No intravascular fistula, renal failure, prolonged mechanical ventilation and other major cardiovascular events were reported. CLINICAL DISCUSSION: Endovascular treatment for descending TAA has been demonstrated to be safe and effective, particularly in emergencies in which patients presented with life-threatening hemoptysis, due to its rapid access to the aorta. In our experience at a tertiary hospital in southern Vietnam, the procedural time for a thoracic endovascular aortic repair is relatively brief and can last between 15 and 30 min. Thus, endovascular treatment for ruptured TAA can substantially improve patient prognosis, reduce mortality and complications. CONCLUSION: The implementation of endovascular intervention can help improve prognosis, reduce mortality and complications in patients with hemoptysis due to ruptured thoracic aortic aneurysm.

Preoperative magnetic resonance imaging of anal fistulas with scrotal extension: a retrospective study.

Introduction: This study aimed to elucidate the magnetic resonance (MR) characteristics of anal fistulas extending to the scrotum, and the applicable rules, and to correlate MR features with surgical findings. Methods: We conducted a retrospective study in 150 consecutive patients with anal fistulas extending into the scrotum, who were diagnosed and underwent surgery at University Medical Center Ho Chi Minh City between January 2017 and April 2022. MR findings were evaluated and compared with surgical findings using Cohens kappa coefficient (k) with a 95% confidence interval. Results: 150 patients (mean age 37.6 ± 10.9 years) with 166 fistulas, including 150 anal fistulas with scrotal extension. Most fistulas were low transsphincteric (80.0%, 120/150 patients). There was a strong agreement for primary tract classification and detecting the location of internal openings between MRI and surgical findings with k = 0.83 (0.780.87) and k = 0.89 (0.85 0.93) (p<0.001), respectively. There is a significant correlation between the location of internal openings and the type of fistula (p<0.05). Low transsphincteric fistulas were predominant in the anterior group (103/122 patients vs. 10/19 patients), while in the posterior group, it was more common in the high transsphincteric fistulas (7/19 patients vs. 14/122 patients), and the intersphincteric fistulas (1/19 patients vs. 5/122 patients); and the suprasphincteric fistulas were only seen in the posterior group (1 patient). Conclusion: Anal fistulas with scrotal extension are exceptions to Goodsalls rule. Albeit long-tract fistulas, most are low transsphincteric and have anterior internal openings.

Identification of a Novel Eight-Gene Risk Model for Predicting Survival in Glioblastoma: A Comprehensive Bioinformatic Analysis.

Glioblastoma (GBM) is one of the most progressive and prevalent cancers of the central nervous system. Identifying genetic markers is therefore crucial to predict prognosis and enhance treatment effectiveness in GBM. To this end, we obtained gene expression data of GBM from TCGA and GEO datasets and identified differentially expressed genes (DEGs), which were overlapped and used for survival analysis with univariate Cox regression. Next, the genes' biological significance and potential as immunotherapy candidates were examined using functional enrichment and immune infiltration analysis. Eight prognostic-related DEGs in GBM were identified, namely CRNDE, NRXN3, POPDC3, PTPRN, PTPRN2, SLC46A2, TIMP1, and TNFSF9. The derived risk model showed robustness in identifying patient subgroups with significantly poorer overall survival, as well as those with distinct GBM molecular subtypes and MGMT status. Furthermore, several correlations between the expression of the prognostic genes and immune infiltration cells were discovered. Overall, we propose a survival-derived risk score that can provide prognostic significance and guide therapeutic strategies for patients with GBM.

Reduced Sensitivity to Background Reward Underlies Apathy After Traumatic Brain Injury: Insights From an Ecological Foraging Framework.

BACKGROUND: Altered reward processing is increasingly recognised as a crucial mechanism underpinning apathy in many brain disorders. However despite its clinical relevance, little is known about the mechanisms of apathy following moderate-to-severe traumatic brain injury (TBI). In real-life situations, reward representations encompass both foreground (gains from current activity) and background (potential gains from the broader environment) elements. This latter variable provides a crucial set-point for switching behaviour in many naturalistic settings. We hypothesised apathy post-TBI would be associated with disrupted background reward sensitivity. METHODS: We administered a computer-based foraging task to 45 people with moderate-to-severe TBI (20 with apathy, 39 males) and 37 matched controls. Participants decided when to leave locations (patches) where foreground reward rates depleted at differing rates, to pursue greater rewards from other patches in the environment, which had either a high or low background reward rate. Primary analysis was performed using linear mixed effects models, with patch leaving time the dependent variable. RESULTS: Findings showed a significant interaction between apathy and background reward sensitivity, driven by apathetic TBI participants not altering patch-leaving decisions as environmental reward rate changed. In contrast, although TBI was associated with reduced sensitivity to changing foreground rewards, this did not vary as a function of apathy. CONCLUSIONS: These results provide the first evidence directly linking disrupted background reward processing to apathy in any brain disorder. They identify a novel mechanism for apathy following moderate-to-severe TBI, and point towards novel interventions to improve this debilitating complication of head injury.