Preserved Edge Convolutional Neural Network for Sensitivity Enhancement of Deuterium Metabolic Imaging (DMI)

Purpose: Common to most MRSI techniques, the spatial resolution and the minimal scan duration of Deuterium Metabolic Imaging (DMI) are limited by the achievable SNR. This work presents a deep learning method for sensitivity enhancement of DMI. Methods: A convolutional neural network (CNN) was designed to estimate the 2H-labeled metabolite concentrations from low SNR and distorted DMI FIDs. The CNN was trained with synthetic data that represent a range of SNR levels typically encountered in vivo. The estimation precision was further improved by fine-tuning the CNN with MRI-based edge-preserving regularization for each DMI dataset. The proposed processing method, PReserved Edge ConvolutIonal neural network for Sensitivity Enhanced DMI (PRECISE-DMI), was applied to simulation studies and in vivo experiments to evaluate the anticipated improvements in SNR and investigate the potential for inaccuracies. Results: PRECISE-DMI visually improved the metabolic maps of low SNR datasets, and quantitatively provided higher precision than the standard Fourier reconstruction. Processing of DMI data acquired in rat brain tumor models resulted in more precise determination of 2H-labeled lactate and glutamate + glutamine levels, at increased spatial resolution (from >8 to 2 $\mu$L) or shortened scan time (from 32 to 4 min) compared to standard acquisitions. However, rigorous SD-bias analyses showed that overuse of the edge-preserving regularization can compromise the accuracy of the results. Conclusion: PRECISE-DMI allows a flexible trade-off between enhancing the sensitivity of DMI and minimizing the inaccuracies. With typical settings, the DMI sensitivity can be improved by 3-fold while retaining the capability to detect local signal variations

Screening for pineal trilateral retinoblastoma revisited: a meta-analysis

Topic To determine until what age children are at risk for pineal trilateral retinoblastoma (TRb), whether its onset is linked to the age at which intraocular retinoblastomas develop, and the lead time from a detectable pineal TRb to symptoms. Clinical relevance About 45% of patients with retinoblastoma – those with a germline RB1 pathogenic variant – are at risk for pineal TRb. Early detection and treatment is essential for survival. Current evidence is unclear on the usefulness of screening for pineal TRb and, if useful, until what age screening should be continued. Methods We conducted a study according to the MOOSE guideline for reporting meta-analyses of observational studies. We searched PubMed and Embase between January 1, 1966, and February 27, 2019, for published literature. We considered articles reporting patients with TRb with survival and follow-up data. Inclusion of articles was performed separately and independently by two authors, and two authors also independently extracted the relevant data. They resolved discrepancies by consensus. Results One hundred thirty-eight patients with pineal TRb were included. Of 22 asymptomatic patients, 21 (95%) were diagnosed before the age of 40 months (median 16, interquartile range 9–29). Age at diagnosis of pineal TRb in patients diagnosed with retinoblastoma at ≤6 months versus >6 months of age were comparable (P=0.44), suggesting independency between the ages at diagnosis of intraocular retinoblastoma and pineal TRb. The laterality of intraocular retinoblastoma and its treatment were unassociated with the age when the pineal TRb was diagnosed. The lead time from an asymptomatic to a symptomatic pineal TRb was approximately 1 year. By performing a screening magnetic resonance imaging scan every 6 months after the diagnosis of heritable retinoblastoma (median age 6 months) until the age of 36 months, at least 311 and 776 scans would be required to detect one asymptomatic pineal TRb and to save one life, respectively. Conclusion Patients with retinoblastoma are at risk for pineal trilateral retinoblastoma for a shorter period than previously assumed and the age at diagnosis of pineal trilateral retinoblastoma is independent of the age at diagnosis of retinoblastoma. The GRADE level of evidence for these conclusions remains low.Peer reviewe

Maternal urinary iodine concentration in pregnancy and children's cognition: Results from a population-based birth cohort in an iodine-sufficient area

OBJECTIVE: Reports from populations with an insufficient iodine intake suggest that children of mothers with mild iodine deficiency during pregnancy are at risk for cognitive impairments. However, it is unknown whether, even in iodine-sufficient areas, low levels of iodine intake occur that influence cognitive development in the offspring. This study investigated the association between maternal low urinary iodine concentration (UIC) in pregnancy and children's cognition in a population-based sample from a country with an optimal iodine status (the Netherlands). SETTING AND PARTICIPANTS: In 1525 mother–child pairs in a Dutch multiethnic birth cohort, we investigated the relation between maternal UIC<150 μg/g creatinine, assessed <18 weeks gestation and children's cognition. OUTCOMES MEASURES: Non-verbal IQ and language comprehension were assessed during a visit to the research centre using Dutch test batteries when the children were 6 years. RESULTS: In total, 188 (12.3%) pregnant women had UIC<150 μg/g creatinine, with a median UIC equal to 119.3 μg/g creatinine. The median UIC in the group with UIC>150 μg/g creatinine was 322.9 μg/g and in the whole sample 296.5 μg/g creatinine. There was a univariate association between maternal low UIC and children's suboptimum non-verbal IQ (unadjusted OR=1.44, 95% CI 1.02 to 2.02). However, after adjustment for confounders, maternal low UIC was not associated with children's non-verbal IQ (adjusted OR=1.33, 95% CI 0.92 to 1.93). There was no relation between maternal UIC in early pregnancy and children's language comprehension at 6 years. CONCLUSIONS: The lack of a clear association between maternal low UIC and children's cognition probably reflects that low levels of iodine were not frequent and severe enough to affect neurodevelopment. This may result from the Dutch iodine fortification policy, which allows iodised salt to be added to almost all processed food and emphasises the monitoring of iodine intake in the population

Asynchronous pineoblastoma is more likely after early diagnosis of retinoblastoma : a meta-analysis

Purpose To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its effect on screening. Methods We updated the search (PubMed and Embase) for published literature as performed by our research group in 2014 and 2019. Trilateral retinoblastoma (TRb) patients were eligible for inclusion if identifiable as unique and the age at which TRb was diagnosed was available. The search yielded 97 new studies. Three new studies and eight new patients were included. Combined with 189 patients from the previous meta-analysis, the database included 197 patients. The main outcome was the percentage of asynchronous TRb in patients diagnosed before and after preset age thresholds of 6 and 12 months of age at retinoblastoma diagnosis. Results Seventy-nine per cent of patients with pineoblastoma are diagnosed with retinoblastoma before the age of 12 months. However, baseline MRI screening at time of retinoblastoma diagnosis fails to detect the later diagnosed pineal TRb in 89% of patients. We modelled that an additional MRI performed at the age of 29 months picks up 53% of pineoblastomas in an asymptomatic phase. The detection rate increased to 72%, 87% and 92%, respectively, with 2, 3 and 4 additional MRIs. Conclusions An MRI of the brain in heritable retinoblastoma before the age of 12 months misses most pineoblastomas, while retinoblastomas are diagnosed most often before the age of 12 months. Optimally timed additional MRI scans of the brain can increase the asymptomatic detection rate of pineoblastoma.Peer reviewe

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Finding the missing honey bee genes: lessons learned from a genome upgrade

BACKGROUND: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes. RESULTS: Here, we report an improved honey bee genome assembly (Amel_4.5) with a new gene annotation set (OGSv3.2), and show that the honey bee genome contains a number of genes similar to that of other insect genomes, contrary to what was suggested in OGSv1.0. The new genome assembly is more contiguous and complete and the new gene set includes ~5000 more protein-coding genes, 50% more than previously reported. About 1/6 of the additional genes were due to improvements to the assembly, and the remaining were inferred based on new RNAseq and protein data. CONCLUSIONS: Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.Funding for the project was provided by a grant to RG from the National Human Genome Research Institute, National Institutes of Health (NHGRI, NIH) U54 HG003273. Contributions from members of the CGE lab were supported by Agriculture and Food Research Initiative Competitive grant no. 2010- 65205-20407 from the USDA National Institute of Food Agriculture. AKB was supported by a Clare Luce Booth Fellowship at Georgetown University

Bone sarcomas: ESMO–EURACAN–GENTURIS–ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up

Production costs have been covered by ESMO from central funds

Temporal Analysis of the Honey Bee Microbiome Reveals Four Novel Viruses and Seasonal Prevalence of Known Viruses, Nosema, and Crithidia

Honey bees (Apis mellifera) play a critical role in global food production as pollinators of numerous crops. Recently, honey bee populations in the United States, Canada, and Europe have suffered an unexplained increase in annual losses due to a phenomenon known as Colony Collapse Disorder (CCD). Epidemiological analysis of CCD is confounded by a relative dearth of bee pathogen field studies. To identify what constitutes an abnormal pathophysiological condition in a honey bee colony, it is critical to have characterized the spectrum of exogenous infectious agents in healthy hives over time. We conducted a prospective study of a large scale migratory bee keeping operation using high-frequency sampling paired with comprehensive molecular detection methods, including a custom microarray, qPCR, and ultra deep sequencing. We established seasonal incidence and abundance of known viruses, Nosema sp., Crithidia mellificae, and bacteria. Ultra deep sequence analysis further identified four novel RNA viruses, two of which were the most abundant observed components of the honey bee microbiome (∼1011 viruses per honey bee). Our results demonstrate episodic viral incidence and distinct pathogen patterns between summer and winter time-points. Peak infection of common honey bee viruses and Nosema occurred in the summer, whereas levels of the trypanosomatid Crithidia mellificae and Lake Sinai virus 2, a novel virus, peaked in January

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)

Background: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design. Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma 3 cm, located between 115 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane i