Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children.

Background: B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes.

ZMIZ1::ABL1 Fusion: An Uncommon Molecular Event With Clinical Implications in Pediatric Cancer.

Context.—: Pediatric B-cell acute lymphoblastic leukemia is genetically and phenotypically heterogeneous, with a genetic landscape including chromosomal translocations that disrupt ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1).

Objective.

Mono-allelic KCNB2 variants lead to a neurodevelopmental syndrome caused by altered channel inactivation.

Ion channels mediate voltage fluxes or action potentials that are central to the functioning of excitable cells such as neurons. The KCNB family of voltage-gated potassium channels (Kv) consists of two members (KCNB1 and KCNB2) encoded by KCNB1 and KCNB2, respectively. These channels are major contributors to delayed rectifier potassium currents arising from the neuronal soma which modulate overall excitability of neurons.

Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group.

Purpose: Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019.

Methods: We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials.

Expanding the Clinical Utility of Targeted RNA Sequencing Panels beyond Gene Fusions to Complex, Intragenic Structural Rearrangements.

Gene fusions are a form of structural rearrangement well established as driver events in pediatric and adult cancers. The identification of such events holds clinical significance in the refinement, prognostication, and provision of treatment in cancer. Structural rearrangements also extend beyond fusions to include intragenic rearrangements, such as internal tandem duplications (ITDs) or exon-level deletions.

Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial.

Background: The outcome of children with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia significantly improved with the combination of imatinib and intensive chemotherapy. We aimed to investigate the efficacy of dasatinib, a second-generation ABL-class inhibitor, with intensive chemotherapy in children with newly diagnosed Ph-positive acute lymphoblastic leukaemia.

Methods: CA180-372/COG AALL1122 was a joint Children's Oncology Group (COG) and European intergroup study of post-induction treatment of Ph-positive acute lymphoblastic leukaemia (EsPhALL) open-label, single-arm, phase 2 study.

Childhood Early T Cell Precursor Acute Lymphoblastic Leukaemia with t(12;17) (p13;q21) Translocation - A Rare Entity or Part of ETP/Myeloid Mixed Phenotype Acute Leukaemia.

The translocation t (12;17) (p13; q21) is a rare cytogenetic event most commonly described in pre-B- acute lymphoblastic leukaemia and acute myeloid leukaemia. We identified a child with an immunophenotype of Early T Cell Precursor Acute Lymphoblastic Leukaemia ETP- ALL having t (12;17) (p13; q21) translocation as the primary karyotypic anomaly. The association of t (12;17) (p13; q21) with ETP-ALL has not been described previously in literature.

Effect of Nutritional Supplementation on Illness Outcome in Adolescents with HIV on HAART: A Randomized, Double-Blind Clinical Trial.

Objective: To assess the effect of macronutrient and micronutrient supplementation on body mass index (BMI), hemoglobin (Hb), CD4 count, triglyceride levels, and morbidity among adolescents with human immunodeficiency virus (HIV) living in India.

Methods: A prospective, randomized, double-blinded, placebo-controlled trial was conducted among 80 adolescents (10-19 y) with HIV on highly active antiretroviral therapy (HAART) for a minimum of 6 mo using simple randomization. Participants in the intervention arm received 400 kcal and 15 g protein as a powder daily and multivitamin tablets thrice weekly for 3 mo.

A Decade's Experience in Pediatric Chromosomal Microarray Reveals Distinct Characteristics Across Ordering Specialties.

Chromosomal microarray (CMA) is a testing modality frequently used in pediatric patients; however, published data on its utilization are limited to the genetic setting. We performed a database search for all CMA testing performed from 2010 to 2020, and delineated the diagnostic yield based on patient characteristics, including sex, age, clinical specialty of providers, indication of testing, and pathogenic finding. The indications for testing were further categorized into Human Phenotype Ontology categories for analysis.

Noncoding genetic variation in GATA3 increases acute lymphoblastic leukemia risk through local and global changes in chromatin conformation.

Inherited noncoding genetic variants confer significant disease susceptibility to childhood acute lymphoblastic leukemia (ALL) but the molecular processes linking germline polymorphisms with somatic lesions in this cancer are poorly understood. Through targeted sequencing in 5,008 patients, we identified a key regulatory germline variant in GATA3 associated with Philadelphia chromosome-like ALL (Ph-like ALL). Using CRISPR-Cas9 editing and samples from patients with Ph-like ALL, we showed that this variant activated a strong enhancer that upregulated GATA3 transcription.

Inherited and de novo variants extend the etiology of -associated neurodevelopmental disorder.

Alterations in the gene have recently emerged as the cause of developmental delay with or without intellectual impairment or behavioral abnormalities (MIM # 619575). The 32 cases currently described in the literature have predominantly de novo alterations in and a wide spectrum of neurodevelopmental abnormalities. Here, we report four patients with novel pathogenic variants identified by research genome sequencing, clinical exome sequencing, and international matchmaking.

Emergence of carbon nanoscrolls from single walled carbon nanotubes: an oxidative route.

Carbon nanoscrolls (CNS), a one dimensional (1D) helical form of carbon, have received enormous attention recently due to their unique structure, superior properties and potential applications. In this work, radial merging of HiPCO single walled nanotube (SWNT) bundles and emergence of CNS are reported following a reflux action involving wet oxidation, HCl washing and annealing at 900 °C. We observe macroscopic quantities of graphene sheets (GS) in the post-treated sample and beautiful manifestation of curling and folding of the GS into CNS.

Revised Neuroblastoma Risk Classification System: A Report From the Children's Oncology Group.

Purpose: Treatment planning for children with neuroblastoma requires accurate assessment of prognosis. The most recent Children's Oncology Group (COG) risk classification system used tumor stage as defined by the International Neuroblastoma Staging System. Here, we validate a revised classifier using the International Neuroblastoma Risk Group Staging System (INRGSS) and incorporate segmental chromosome aberrations (SCA) as an additional genomic biomarker.

Oxidative stress responses of a freshwater fish, Labeo rohita, to a xenobiotic, bisphenol S.

Bisphenol S (BPS) is an organic chemical that has been used as a substitute for bisphenol A (BPA) in making polycarbonate plastics, epoxy resins, thermal receipt papers, and currency bills, as BPA has been reported to have dreadful effects on the living system. From this view point, the present study investigates whether BPS has the same or rather more toxic effects like BPA or not. Limited studies were carried out on the effect of BPS on fish.

5' Amplification in Neuroblastoma: A Case Report.

Neuroblastoma is the most common cancer in infants younger than 12 months of age, occurring with an incidence of 1 in 100,000 children. The clinical outcome of neuroblastoma ranges from spontaneous regression to treatment-resistant progression and/or metastasis, and accounts for 8-10% of childhood cancer deaths. Segmental chromosomal aberrations, as well as and amplification, are among factors contributing to an unfavorable genomic profile and high-risk disease classification.

Low reflectance of carbon nanotube and nanoscroll-based thin film coatings: a case study.

Research on carbon material-based thin films with low light reflectance has received significant attention for the development of high absorber coatings for stray light control applications. Herein, we report a method for the successful fabrication of stable thin films comprised of carbon nanotubes (CNTs) and nanoscrolls (CNS) on an aluminium (Al) substrate, which exhibited low reflectance of the order of 2-3% in the visible and near-infrared (NIR) spectral bands. Changes in the structural and chemical composition of pristine single-walled carbon nanotube (SWCNT) samples were analyzed after each processing step.

Enhanced MAPK1 Function Causes a Neurodevelopmental Disorder within the RASopathy Clinical Spectrum.

Signal transduction through the RAF-MEK-ERK pathway, the first described mitogen-associated protein kinase (MAPK) cascade, mediates multiple cellular processes and participates in early and late developmental programs. Aberrant signaling through this cascade contributes to oncogenesis and underlies the RASopathies, a family of cancer-prone disorders. Here, we report that de novo missense variants in MAPK1, encoding the mitogen-activated protein kinase 1 (i.

Disease-associated mosaic variation in clinical exome sequencing: a two-year pediatric tertiary care experience.

Exome sequencing (ES) has become an important tool in pediatric genomic medicine, improving identification of disease-associated variation due to assay breadth. Depth is also afforded by ES, enabling detection of lower-frequency mosaic variation compared to Sanger sequencing in the studied tissue, thus enhancing diagnostic yield. Within a pediatric tertiary-care hospital, we report two years of clinical ES data from probands evaluated for genetic disease to assess diagnostic yield, characteristics of causal variants, and prevalence of mosaicism among disease-causing variants.

Correction: Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Reclassification of Variants of Uncertain Significance in Children with Inherited Arrhythmia Syndromes is Predicted by Clinical Factors.

Genetic testing is important to augment clinical diagnosis and inform management of inherited arrhythmias syndromes (IAS), but variants of uncertain significance (VUS) are common and remain a challenge in clinical practice. In 2015, American College of Medical Genetics (ACMG) published updated guidelines for interpretation of genetic results. Despite increasing understanding of human genomic variation, there are no guidelines for reinterpretation of prior genetic test results.

Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1.

Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear. This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation.