Reduced durability of hybrid immunity to SARS-CoV-2 in immunocompromised children.

Background: In endemic COVID-19, immunocompromised children are vulnerable until vaccinated but the optimal primary vaccination regime and need for booster doses remains uncertain.

Methods: We recruited 19 immunocompromised children (post-solid organ transplantation, have autoimmune disease or were on current or recent chemotherapy for acute lymphoblastic leukemia), and followed them from the start of primary vaccination with BNT162b2 mRNA SARS-CoV-2 until 1-year post-vaccination. We investigated the quality of vaccine immunogenicity, and longevity of hybrid immunity, in comparison to healthy children.

Clinical Implementation of Nephrologist-Led Genomic Testing for Glomerular Diseases in Singapore: Rationale and Protocol.

Introduction: The early diagnosis and appropriate treatment of monogenic glomerular diseases can reduce kidney failure, avoid unnecessary investigations such as kidney biopsies and ineffective treatment with immunosuppressants, guide transplant decisions, and inform the genetic risks of their family members. Yet, genetic testing for kidney disease is underutilized in Singapore. We aimed to implement a nephrologist-led genetic service and evaluate the acceptance, adoption, utility, and cost-effectiveness of genetic testing for monogenic glomerular disease in Singapore.

Recurrent Hospitalizations for Fluid Overload in Diabetes with Kidney Failure Treated with Dialysis.

Introduction: Diabetes mellitus is the most common cause of end-stage kidney disease (ESKD) in Singapore. ESKD patients have high disease burden and are at increased risk of recurrent hospitalizations, including fluid overload. This study aimed to characterize the risk factors associated with readmissions for fluid overload that will identify high-risk hospitalizations for interventions to reduce readmissions.

Re-programming by a six-factor-secretome in the patient tumor ecosystem during nutrient stress and drug response.

Cancer cells need nutrients to grow and proliferate. During nutrient stress in the microenvironment, it is unclear or cancer cells can adopt alternative resources to re-wire and survive in patients. We discovered a 6-factor-secretome remarkably sustains a critical cell mass during nutrient stress in a pediatric embryonal brain tumor, atypical teratoid rhabdoid tumor (ATRT).

CD57 defines a novel cancer stem cell that drive invasion of diffuse pediatric-type high grade gliomas.

Background: Diffuse invasion remains a primary cause of treatment failure in pediatric high-grade glioma (pHGG). Identifying cellular driver(s) of pHGG invasion is needed for anti-invasion therapies.

Methods: Ten highly invasive patient-derived orthotopic xenograft (PDOX) models of pHGG were subjected to isolation of matching pairs of invasive (HGG) and tumor core (HGG) cells.

Fractionated radiation therapy alters energy metabolism and induces cellular quiescence exit in patient-derived orthotopic xenograft models of high-grade glioma.

Radiation is one of the standard therapies for pediatric high-grade glioma (pHGG), of which the prognosis remains poor. To gain an in-depth understanding of biological consequences beyond the classic DNA damage, we treated 9 patient-derived orthotopic xenograft (PDOX) models, including one with DNA mismatch repair (MMR) deficiency, with fractionated radiations (2 Gy/day x 5 days). Extension of survival time was noted in 5 PDOX models (P < 0.

Direct Implantation of Patient Brain Tumor Cells into Matching Locations in Mouse Brains for Patient-Derived Orthotopic Xenograft Model Development.

Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice.

Secondary Intention Healing for Fingertip Amputations in a Tropical Climate.

Various studies have examined occlusive dressings in fingertip amputations and reported good outcomes. Occlusive dressing preserves appropriate pH, cell accumulation and moisture for healing, thereby limiting scar formation and deformity. To our knowledge, no study was performed in tropical Asia.

Trade-Offs between Vaccine Effectiveness and Vaccine Safety: Personal versus Policy Decisions.

Objective: We aimed to investigate whether individuals' trade-offs between vaccine effectiveness and vaccine safety vary if they are asked to consider the perspective of a policymaker making decisions for others compared with the decisions they would make for themselves.

Method: A web-enabled discrete choice experiment survey was administered between 1 April and 1 May 2022 to participants recruited from the general population of two Southeast Asian countries (Indonesia and Vietnam). In each country, 500 participants were randomly assigned to make decisions regarding coronavirus disease 2019 (COVID-19) vaccines for others as a policymaker or in a personal capacity for their own use.

Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models.

Background: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM.

Susceptibilities of CNS Cells towards Rabies Virus Infection Is Linked to Cellular Innate Immune Responses.

Rabies is caused by neurotropic rabies virus (RABV), contributing to 60,000 human deaths annually. Even though rabies leads to major public health concerns worldwide, we still do not fully understand factors determining RABV tropism and why glial cells are unable to clear RABV from the infected brain. Here, we compare susceptibilities and immune responses of CNS cell types to infection with two RABV strains, Tha and its attenuated variant Th2P-4M, mutated on phospho- (P-protein) and matrix protein (M-protein).

Outcome of childhood epistaxis with treatment of allergic rhinitis: a randomized controlled study.

Unlabelled: The purpose of this study is to (1) to determine if treatment of underlying allergic rhinitis (AR) in children will affect epistaxis outcome, (2) to compare efficacy of three outpatient AR treatment regimens in epistaxis outcomes, and (3) to investigate potential factors in the pathogenesis of epistaxis with underlying AR. A single-blind randomized-controlled study was conducted in the Otolaryngology clinic in KK Women's and Children's Hospital. Sixty children aged below 18 years with underlying untreated AR, with first presentation of epistaxis, were randomized to three different AR treatments: treatment 1, antihistamine (20 patients); treatment 2, nasal steroid spray (20 patients); and treatment 3, both antihistamine and nasal steroid spray (20 patients).

Current status of silica-based nanoparticles as therapeutics and its potential as therapies against viruses.

In the past decade, interest in nanoparticles for clinical indications has been steadily gaining traction. Most recently, Lipid Nanoparticles (LNP) have been used successfully to construct the SARS-CoV-2 mRNA vaccines for rapid pandemic response. Similarly, silica is another nanomaterial which holds much potential to create nanomedicines against pathogens of interest.

A fast-growing dengue virus mutant reveals a dual role of STING in response to infection.

The four dengue viruses (DENVs) have evolved multiple mechanisms to ensure its survival. Among these mechanisms is the ability to regulate its replication rate, which may contribute to avoiding premature immune activation that limit infection dissemination: DENVs associated with dengue epidemics have shown slower replication rate than pre-epidemic strains. Correspondingly, wild-type DENVs replicate more slowly than their clinically attenuated derivatives.

A phase I/II randomized, double-blinded, placebo-controlled trial of a self-amplifying Covid-19 mRNA vaccine.

Coronavirus disease-19 (Covid-19) pandemic have demonstrated the importantance of vaccines in disease prevention. Self-amplifying mRNA vaccines could be another option for disease prevention if demonstrated to be safe and immunogenic. Phase 1 of this randomized, double-blinded, placebo-controlled trial (N = 42) assessed the safety, tolerability, and immunogenicity in healthy young and older adults of ascending levels of one-dose ARCT-021, a self-amplifying mRNA vaccine against Covid-19.

RNA Viruses, Pandemics and Anticipatory Preparedness.

RNA viruses are likely to cause future pandemics and therefore we must create and organize a deep knowledge of these viruses to prevent and manage this risk. Assuming prevention will fail, at least once, we must be prepared to manage a future pandemic using all resources available. We emphasize the importance of having safe vaccine candidates and safe broad-spectrum antivirals ready for rapid clinical translation.

Hypoxia-driven immunosuppression by Treg and type-2 conventional dendritic cells in HCC.

Background And Aims: Hypoxia is one of the central players in shaping the immune context of the tumor microenvironment (TME). However, the complex interplay between immune cell infiltrates within the hypoxic TME of HCC remains to be elucidated.

Approach And Results: We analyzed the immune landscapes of hypoxia-low and hypoxia-high tumor regions using cytometry by time of light, immunohistochemistry, and transcriptomic analyses.

High-throughput single-cell quantification of hundreds of proteins using conventional flow cytometry and machine learning.

Modern immunologic research increasingly requires high-dimensional analyses to understand the complex milieu of cell types that comprise the tissue microenvironments of disease. To achieve this, we developed Infinity Flow combining hundreds of overlapping flow cytometry panels using machine learning to enable the simultaneous analysis of the coexpression patterns of hundreds of surface-expressed proteins across millions of individual cells. In this study, we demonstrate that this approach allows the comprehensive analysis of the cellular constituency of the steady-state murine lung and the identification of previously unknown cellular heterogeneity in the lungs of melanoma metastasis–bearing mice.

Efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy in Japanese participants of HAWK.

Purpose: To compare the efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy (PCV) over 96 weeks in the HAWK study.

Design: HAWK was a global, 2-year, randomised, double-masked, multicentre phase III trial in participants with neovascular age-related macular degeneration.

Methods: Of the Japanese participants with PCV, 39 received brolucizumab 6 mg and 30 received aflibercept 2 mg.

Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis.

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme BFasL, EomesTCF-1, PD-1CD8 Tc1 cells.

Maximizing the potential of aggressive mouse tumor models in preclinical drug testing.

Atypical teratoid rhabdoid tumor (ATRT) is an aggressive embryonal brain tumor among infants and young children. Two challenges exist for preclinical testing in ATRT. First, genetically quiet, ATRT is a difficult tumor to target molecularly.

A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice.

A self-transcribing and replicating RNA (STARR)-based vaccine (LUNAR-COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full-length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolongs SARS-CoV-2 spike glycoprotein expression.