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.

Preserving positivity in density-explicit field-theoretic simulations.

Field-theoretic simulations are numerical methods for polymer field theory, which include fluctuation corrections beyond the mean-field level, successfully capturing various mesoscopic phenomena. Most field-theoretic simulations of polymeric fluids use the auxiliary field (AF) theory framework, which employs Hubbard-Stratonovich transformations for the particle-to-field conversion. Nonetheless, the Hubbard-Stratonovich transformation imposes significant limitations on the functional form of the non-bonded potentials.

Model predictive control of non-interacting active Brownian particles.

Active matter systems are strongly driven to assume non-equilibrium distributions owing to their self-propulsion, , flocking and clustering. Controlling the active matter systems' spatiotemporal distributions offers exciting applications such as directed assembly, programmable materials, and microfluidic actuation. However, these applications involve environments with coupled dynamics and complex tasks, making intuitive control strategies insufficient.

Assessment of the partial saddle point approximation in field-theoretic polymer simulations.

Field-theoretic simulations are numerical treatments of polymer field theory models that go beyond the mean-field self-consistent field theory level and have successfully captured a range of mesoscopic phenomena. Inherent in molecularly-based field theories is a "sign problem" associated with complex-valued Hamiltonian functionals. One route to field-theoretic simulations utilizes the complex Langevin (CL) method to importance sample complex-valued field configurations to bypass the sign problem.

Improved Elastic Recovery from ABC Triblock Terpolymers.

The promise of ABC triblock terpolymers for improving the mechanical properties of thermoplastic elastomers is demonstrated by comparison with symmetric ABA/CBC analogs having similar molecular weights and volume fraction of B and A/C domains. The ABC architecture enhances elasticity (up to 98% recovery over 10 cycles) in part through essentially full chain bridging between discrete hard domains leading to the minimization of mechanically unproductive loops. In addition, the unique phase space of ABC triblocks also enables the fraction of hard-block domains to be higher ( ≈ 0.

Anthracycline-Free Protocol for Favorable-Risk Childhood ALL: A Noninferiority Comparison Between Malaysia-Singapore ALL 2003 and ALL 2010 Studies.

Purpose: To investigate whether, for children with favorable-risk B-cell precursor ALL (BCP-ALL), an anthracycline-free protocol is noninferior to a modified Berlin-Frankfurt-Muenster ALL-IC2002 protocol, which includes 120 mg/m of anthracyclines.

Patients And Methods: Three hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (≤0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials.

Life-threatening infections during treatment for acute lymphoblastic leukemia on the Malaysia-Singapore 2003 and 2010 clinical trials: A risk prediction model.

Aim: Life-threatening infections significantly impact the care of children undergoing therapy for acute lymphoblastic leukemia (ALL) who are at risk of severe sepsis due to both host and treatment factors. Our aim was to develop a life-threatening infection risk prediction model that would allow remote rapid triage of patients to reduce time to first dose of antibiotics and sepsis-related mortality.

Methods: A retrospective analysis of 2068 fever episodes during ALL therapy was used for model building and subsequent internal validation.

Distinct clinical characteristics of DUX4- and PAX5-altered childhood B-lymphoblastic leukemia.

Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44).

Delayed immune-related adverse events with anti-PD-1-based immunotherapy in melanoma.

Background: Immune-related adverse events (irAEs) typically occur within 4 months of starting anti-programmed cell death protein 1 (PD-1)-based therapy [anti-PD-1 ± anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4)], but delayed irAEs (onset >12 months after commencement) can also occur. This study describes the incidence, nature and management of delayed irAEs in patients receiving anti-PD-1-based immunotherapy.

Patients And Methods: Patients with delayed irAEs from 20 centres were studied.

Successful toxicity reduction during delayed intensification in the non-high-risk arm of Malaysia-Singapore Acute Lymphoblastic Leukaemia 2010 study.

Unlabelled: In non-high-risk (non-HR) patients, the Malaysia-Singapore Acute Lymphoblastic Leukaemia 2003 (MS2003) study achieved good outcomes. However, its delayed-intensification (DI) phase, comprising repeated blocks of protocol III (2003-PIII), was toxic and caused significant treatment delays. The successor MS2010 study attempted to lower DI toxicity by replacing myelosuppressive drugs (doxorubicin, cytarabine) with vincristine and asparaginase.

Intracellular vincristine levels in lymphoblasts affect treatment outcome in childhood B-lymphoblastic leukaemia: Ma-Spore ALL 2010 study.

Aims: Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up-front window of Ma-Spore ALL 2010 (MS2010) study.

A "Wait-and-See" Approach to Quiescent Single-System Langerhans Cell Histiocytosis to Spare Children From Chemotherapy.

Langerhans Cell Histiocytosis (LCH) is a childhood disorder of histiocytes that is generally treated with systemic chemotherapy. Spontaneous resolution has been previously reported in Single System LCH (SS-LCH), which is less aggressive than multisystem disease. However, there are no clear guidelines on which patients can be safely spared from systemic chemotherapy.

Long-term calibration models to estimate ozone concentrations with a metal oxide sensor.

Ozone (O) is a potent oxidant associated with adverse health effects. Low-cost O sensors, such as metal oxide (MO) sensors, can complement regulatory O measurements and enhance the spatiotemporal resolution of measurements. However, the quality of MO sensor data remains a challenge.

Complete Photonic Band Gaps with Nonfrustrated ABC Bottlebrush Block Polymers.

Bottlebrush block polymers are a promising platform for self-assembled photonic materials, yet most work has been limited to one-dimensional photonic crystals based on the lamellar phase. Here we demonstrate with simulation that nonfrustrated ABC bottlebrush block polymers can be used to self-assemble three-dimensional photonic crystals with complete photonic band gaps. To show this, we have developed a computational approach that couples self-consistent field theory (SCFT) simulations to Maxwell's equations, thereby permitting a direct link between molecular design, self-assembly, and photonic band structures.

Epidemiology of childhood malignant mediastinal masses and clinical factors associated with intensive care unit admission: A Singapore experience.

Aim: Majority of mediastinal masses in children are malignant. These masses are complex to manage as they have a risk of compression to surrounding structures. Many of these children have to be managed in the intensive care unit (ICU).

Identifying IGH disease clones for MRD monitoring in childhood B-cell acute lymphoblastic leukemia using RNA-Seq.

Identifying patient-specific clonal IGH/TCR junctional sequences is critical for minimal residual disease (MRD) monitoring. Conventionally these junctional sequences are identified using laborious Sanger sequencing of excised heteroduplex bands. We found that the IGH is highly expressed in our diagnostic B-cell acute lymphoblastic leukemia (B-ALL) samples using RNA-Seq.

Health-Related Quality of Life in Pediatric Patients with Leukemia in Singapore: A Cross-Sectional Pilot Study.

There has been a paradigm shift in health service delivery to a more holistic approach, which considers Quality of Life (QoL) and overall functioning. Health-Related Quality of Life (HRQoL) is a multidimensional construct that encompasses physical functioning as well as psychosocial aspects of emotional and social functioning. This study explored factors related to HRQoL in Asian pediatric patients with leukemia in Singapore.

Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With IKZF1 Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study.

Purpose Although IKZF1 deletion ( IKZF1) confers a higher risk of relapse in childhood B-cell acute lymphoblastic leukemia (B-ALL), it is uncertain whether treatment intensification will reverse this risk and improve outcomes. The Malaysia-Singapore ALL 2010 study (MS2010) prospectively upgraded the risk assignment of patients with IKZF1 to the next highest level and added imatinib to the treatment of all patients with BCR- ABL1 fusion. Patients and Methods In total, 823 patients with B-ALL treated in the Malyasia-Singapore ALL 2003 study (MS2003; n = 507) and MS2010 (n = 316) were screened for IKZF1 using the multiplex ligation-dependent probe amplification assay.

Effective Response Metric: a novel tool to predict relapse in childhood acute lymphoblastic leukaemia using time-series gene expression profiling.

Accurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under- or over-treatment. We hypothesized that time-series gene expression profiles (GEPs) of bone marrow samples during remission-induction therapy can measure the response and be used for relapse prediction. We computed the time-series changes from diagnosis to Day 8 of remission-induction, termed Effective Response Metric (ERM-D8) and tested its ability to predict relapse against contemporary risk assignment methods, including National Cancer Institutes (NCI) criteria, genetics and minimal residual disease (MRD).

Bioelectrocatalytic NAD/NADH inter-conversion: transformation of an enzymatic fuel cell into an enzymatic redox flow battery.

Diaphorase and a benzylpropylviologen redox polymer were combined to create a bioelectrode that can both oxidize NADH and reduce NAD. We demonstrate how bioelectrocatalytic NAD/NADH inter-conversion can transform a glucose/O enzymatic fuel cell (EFC) with an open circuit potential (OCP) of 1.1 V into an enzymatic redox flow battery (ERFB), which can be rapidly recharged by operation as an EFC.

Mutation spectrum of RB1 mutations in retinoblastoma cases from Singapore with implications for genetic management and counselling.

Retinoblastoma (RB) is a rare childhood malignant disorder caused by the biallelic inactivation of RB1 gene. Early diagnosis and identification of carriers of heritable RB1 mutations can improve disease outcome and management. In this study, mutational analysis was conducted on fifty-nine matched tumor and peripheral blood samples from 18 bilateral and 41 unilateral unrelated RB cases by a combinatorial approach of Multiplex Ligation-dependent Probe Amplification (MLPA) assay, deletion screening, direct sequencing, copy number gene dosage analysis and methylation assays.

Whole-genome noncoding sequence analysis in T-cell acute lymphoblastic leukemia identifies oncogene enhancer mutations.

There is an Inside Commentary on this article in this issue.