KMT2A-MAML2 rearrangement emerged and regressed during neuroblastoma therapy without leukemia after 12.8-year follow-up.

Twelvepatients without therapy-related leukemia were studied after completing TOP2 poison chemotherapy in a high-risk neuroblastoma regimen. One patient harbored an inv(11) that was a KMT2A rearrangement. The KMT2A-MAML2 transcript was expressed at low level.

Long-term exposures to air pollutants affect in children: a longitudinal study.

Annual average PM and NO were associated with airway inflammation as measured by FeNO in schoolchildren, adding new evidence that long-term exposure affects FeNO beyond the well-documented short-term effects.

Patterns and determinants of exhaled nitric oxide trajectories in schoolchildren over a 7-year period.

Fractional exhaled nitric oxide ( ), a marker of allergic airway inflammation, is used in respiratory research and asthma clinical care; however, its trajectory with increasing age during childhood has not been well characterised. We examined longitudinally during a period of important somatic growth to describe trajectories across childhood and adolescence in healthy participants and evaluate clinical factors as potential determinants of trajectories. was collected at six visits over 8 years in a population-based cohort of 1791 schoolchildren without asthma (median age at entry 8.

Impact of different fixed flow sampling protocols on flow-independent exhaled nitric oxide parameter estimates using the Bayesian dynamic two-compartment model.

Exhaled nitric oxide (FeNO) is an established respiratory biomarker with clinical applications in the diagnosis and management of asthma. Because FeNO depends strongly on the flow (exhalation) rate, early protocols specified that measurements should be taken when subjects exhaled at a fixed rate of 50 ml/s. Subsequently, multiple flow (or "extended") protocols were introduced which measure FeNO across a range of fixed flow rates, allowing estimation of parameters including C NO and C NO which partition the physiological sources of NO into proximal airway wall tissue and distal alveolar regions (respectively).

Identification and characterization of a novel heparan sulfate-binding domain in Activin A longest variants and implications for function.

Activins regulate numerous processes including inflammation and are synthesized as precursors consisting of a long N-terminal pro-region and a mature protein. Genomic human databases currently list three activin A (Act A) variants termed X1, X2 and X3. The X3 variant is the shortest, lacks N-terminal segments present in X1 and X2, and has been the focus of most past literature.

Correction to: HnRNPA2 is a novel histone acetyltransferase that mediates mitochondrial stress-induced nuclear gene expression.

[This corrects the article DOI: 10.1038/celldisc.2016.

Cluster-based bagging of constrained mixed-effects models for high spatiotemporal resolution nitrogen oxides prediction over large regions.

Background: Accurate estimation of nitrogen dioxide (NO) and nitrogen oxide (NO) concentrations at high spatiotemporal resolutions is crucial for improving evaluation of their health effects, particularly with respect to short-term exposures and acute health outcomes. For estimation over large regions like California, high spatial density field campaign measurements can be combined with more sparse routine monitoring network measurements to capture spatiotemporal variability of NO and NO concentrations. However, monitors in spatially dense field sampling are often highly clustered and their uneven distribution creates a challenge for such combined use.

Exposure measurement error in air pollution studies: A framework for assessing shared, multiplicative measurement error in ensemble learning estimates of nitrogen oxides.

Background: Increasingly ensemble learning-based spatiotemporal models are being used to estimate residential air pollution exposures in epidemiological studies. While these machine learning models typically have improved performance, they suffer from exposure measurement error that is inherent in all models. Our objective is to develop a framework to formally assess shared, multiplicative measurement error (SMME) in our previously published three-stage, ensemble learning-based nitrogen oxides (NO) model to identify its spatial and temporal patterns and predictors.

Longitudinal associations of in utero and early life near-roadway air pollution with trajectories of childhood body mass index.

Background: Evidence suggests that childhood near-roadway air pollution (NRAP) exposures contribute to increased body mass index (BMI); however, effects of NRAP exposure during the vulnerable periods including in utero and first year of life have yet to be established. In this study, we examined whether exposure to elevated concentrations of NRAP during in utero and/or first year of life increase childhood BMI growth.

Methods: Participants in the Children's Health Study enrolled from 2002 to 2003 with annual visits over a four-year period and who changed residences before study entry were included (n = 2318).

Short-term effects of airport-associated ultrafine particle exposure on lung function and inflammation in adults with asthma.

Background: Exposure to ultrafine particles (UFP, particles with aerodynamic diameter < 100 nm) is associated with reduced lung function and airway inflammation in individuals with asthma. Recently, elevated UFP number concentrations (PN) from aircraft landing and takeoff activity were identified downwind of the Los Angeles International Airport (LAX) but little is known about the health impacts of airport-related UFP exposure.

Methods: We conducted a randomized crossover study of 22 non-smoking adults with mild to moderate asthma in Nov-Dec 2014 and May-Jul 2015 to investigate short-term effects of exposure to LAX airport-related UFPs.

Significance of green granules in neutrophils and monocytes.

Intracytoplasmic green granules in neutrophils have been the subject of conjecture and discussion. Sometimes nicknamed "death cells," these granules are often associated with severe liver disease and have been said to predict acute bad outcomes in severely ill patients. Some recommend that the laboratory community report these granules to treating clinicians as an indication of poor prognosis.

Genetic and epigenetic susceptibility of airway inflammation to PM in school children: new insights from quantile regression.

Background: The fractional concentration of exhaled nitric oxide (FeNO) is a biomarker of airway inflammation that has proved to be useful in investigations of genetic and epigenetic airway susceptibility to ambient air pollutants. For example, susceptibility to airway inflammation from exposure to particulate matter with aerodynamic diameter < =2.5 μm (PM) varies by haplotypes and promoter region methylation in inducible nitric oxide synthase (iNOS encoded by NOS2).

Bayesian estimation of physiological parameters governing a dynamic two-compartment model of exhaled nitric oxide.

The fractional concentration of nitric oxide in exhaled breath (fe) is a biomarker of airway inflammation with applications in clinical asthma management and environmental epidemiology. fe concentration depends on the expiratory flow rate. Standard fe is assessed at 50 mL/sec, but "extended NO analysis" uses fe measured at multiple different flow rates to estimate parameters quantifying proximal and distal sources of NO in the lower respiratory tract.

Constrained Mixed-Effect Models with Ensemble Learning for Prediction of Nitrogen Oxides Concentrations at High Spatiotemporal Resolution.

Spatiotemporal models to estimate ambient exposures at high spatiotemporal resolutions are crucial in large-scale air pollution epidemiological studies that follow participants over extended periods. Previous models typically rely on central-site monitoring data and/or covered short periods, limiting their applications to long-term cohort studies. Here we developed a spatiotemporal model that can reliably predict nitrogen oxide concentrations with a high spatiotemporal resolution over a long time span (>20 years).

Telehealth Support of Managed Care for a Correctional System: The Open Architecture Telehealth Model.

Introduction: The intent was to evaluate time to match initial investment of a new, statewide correctional system telehealth program based upon cumulative savings by avoidance of transportation and custody-related costs.

Materials And Methods: The setting was a statewide correctional system where prisoners received medical care through enhanced telemedicine technology supported by newly recruited specialty providers delivered through an open architecture system. The patients were incarcerated persons requiring nonemergent consultations in 10 specialties.

Genome-wide TOP2A DNA cleavage is biased toward translocated and highly transcribed loci.

Type II topoisomerases orchestrate proper DNA topology, and they are the targets of anti-cancer drugs that cause treatment-related leukemias with balanced translocations. Here, we develop a high-throughput sequencing technology to define TOP2 cleavage sites at single-base precision, and use the technology to characterize TOP2A cleavage genome-wide in the human K562 leukemia cell line. We find that TOP2A cleavage has functionally conserved local sequence preferences, occurs in cleavage cluster regions (CCRs), and is enriched in introns and lincRNA loci.

The Effects of Policy-Driven Air Quality Improvements on Children's Respiratory Health.

Introduction: Ambient air pollution causes substantial morbidity and mortality in the United States and worldwide. To reduce this burden of adverse health effects, a broad array of strategies to reduce ambient air pollution has been developed and applied over past decades to achieve substantial reductions in ambient air pollution levels. This has been especially true in California, where the improvement of air quality has been a major focus for more than 50 years.

HnRNPA2 is a novel histone acetyltransferase that mediates mitochondrial stress-induced nuclear gene expression.

Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2).

The next generation of target capture technologies - large DNA fragment enrichment and sequencing determines regional genomic variation of high complexity.

Background: The ability to capture and sequence large contiguous DNA fragments represents a significant advancement towards the comprehensive characterization of complex genomic regions. While emerging sequencing platforms are capable of producing several kilobases-long reads, the fragment sizes generated by current DNA target enrichment technologies remain a limiting factor, producing DNA fragments generally shorter than 1 kbp. The DNA enrichment methodology described herein, Region-Specific Extraction (RSE), produces DNA segments in excess of 20 kbp in length.

Unique Familial MLL(KMT2A)-Rearranged Precursor B-Cell Infant Acute Lymphoblastic Leukemia in Non-twin Siblings.

Background: Infant acute lymphoblastic leukemia (ALL) has never occurred in families except for the ∼100% concordant cases in monozygous twins attributed to twin-to-twin metastases. We report the first kindred with infant ALL in non-twin siblings. The siblings were diagnosed with MLL-rearranged (MLL-R) ALL 26 months apart.

Traffic-related air pollution and alveolar nitric oxide in southern California children.

Mechanisms for the adverse respiratory effects of traffic-related air pollution (TRAP) have yet to be established. We evaluated the acute effects of TRAP exposure on proximal and distal airway inflammation by relating indoor nitric oxide (NO), a marker of TRAP exposure in the indoor microenvironment, to airway and alveolar sources of exhaled nitric oxide (FeNO).FeNO was collected online at four flow rates in 1635 schoolchildren (aged 12-15 years) in southern California (USA) breathing NO-free air.