Tumour subregion analysis of colorectal liver metastases using semi-automated clustering based on DCE-MRI: Comparison with histological subregions and impact on pharmacokinetic parameter analysis.

PURPOSE: To use a novel segmentation methodology based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to define tumour subregions of liver metastases from colorectal cancer (CRC), to compare these with histology, and to use these to compare extracted pharmacokinetic (PK) parameters between tumour subregions. MATERIALS AND METHODS: This ethically-approved prospective study recruited patients with CRC and ≥1 hepatic metastases scheduled for hepatic resection. Patients underwent DCE-MRI pre-metastasectomy. Histological sections of resection specimens were spatially matched to DCE-MRI acquisitions and used to define histological subregions of viable and non-viable tumour. A semi-automated voxel-wise image segmentation algorithm based on the DCE-MRI contrast-uptake curves was used to define imaging subregions of viable and non-viable tumour. Overlap of histologically-defined and imaging subregions was compared using the Dice similarity coefficient (DSC). DCE-MRI PK parameters were compared for the whole tumour and histology-defined and imaging-derived subregions. RESULTS: Fourteen patients were included in the analysis. Direct histological comparison with imaging was possible in nine patients. Mean DSC for viable tumour subregions defined by imaging and histology was 0.738 (range 0.540-0.930). There were significant differences between Ktrans and kep for viable and non-viable subregions (p < 0.001) and between whole lesions and viable subregions (p < 0.001). CONCLUSION: We demonstrate good concordance of viable tumour segmentation based on pre-operative DCE-MRI with a post-operative histological gold-standard. This can be used to extract viable tumour-specific values from quantitative image analysis, and could improve treatment response assessment in clinical practice

First record of Rhabdoceras suessi (Ammonoidea, Late Triassic) from the Transylvanian Triassic Series of the Eastern Carpathians (Romania) and a review of its biochronology, paleobiogeography and paleoecology

Abstract The occurrence of the heteromorphic ammonoid Rhabdoceras suessi Hauer, 1860, is recorded for the first time in the Upper Triassic limestone of the Timon-Ciungi olistolith in the Rarău Syncline, Eastern Carpathians. A single specimen of Rhabdoceras suessi co-occurs with Monotis (Monotis) salinaria that constrains its occurrence here to the Upper Norian (Sevatian 1). It is the only known heteromorphic ammonoid in the Upper Triassic of the Romanian Carpathians. Rhabdoceras suessi is a cosmopolitan species widely recorded in low and mid-paleolatitude faunas. It ranges from the Late Norian to the Rhaetian and is suitable for high-resolution worldwide correlations only when it co-occurs with shorter-ranging choristoceratids, monotid bivalves, or the hydrozoan Heterastridium. Formerly considered as the index fossil for the Upper Norian (Sevatian) Suessi Zone, by the latest 1970s this species lost its key biochronologic status among Late Triassic ammonoids, and it generated a controversy in the 1980s concerning the status of the Rhaetian stage. New stratigraphic data from North America and Europe in the subsequent decades resulted in a revised ammonoid biostratigraphy for the uppermost Triassic, the Rhaetian being reinstalled as the topmost stage in the current standard timescale of the Triassic. The geographic distribution of Rhabdoceras is compiled from published worldwide records, and its paleobiogeography and paleoecology are discussed

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Alk (en) ylresorcinol concentrations in'Kensington Pride'mango peel and antifungal activity against Colletotrichum gloeosporioides

Two preformed alk(en)ylresorcinols, 5-n-heptadecenylresorcinol and 5-n-pentadecylresorcinol, were identified in ‘Kensington Pride’ mango fruit peel. The alk(en)ylresorcinols had antifungal activity against C. gloeosporioides, as determined from thin layer chromatography bioassays. Soil-applied activators of plant defence (Acibenzolar at 150 mg L-1, and soluble potassium silicate at 200 and 1000 mg L-1) did not influence concentrations of 5-n-heptadecenylresorcinol or 5-n-pentadecyl¬resorcinol in mango peel when applied 2 months after fruit set and one month later. Concentrations of both alk(en)ylresorcinols were high 2 months after fruit set but levels declined by 50% within 1 month (2 months before commercial harvest) and did not change significantly from commercial harvest until eating-ripe