Potassium Silicate as Low-Temperature Binder in 3D-Printed Porous Structures for CO Separation.

Activated carbon sorbents were directly 3D-printed into highly adaptable monolithic/multi-channel systems by using potassium silicate as a low-temperature binder. By employing emerging 3D-printing technologies, monolithic structured sorbents were printed and fully characterized using N, Ar, and CO-sorption and Hg-intrusion porosimetry. The CO-capture performance and the required temperature for active-site regeneration were evaluated by thermogravimetric analysis-looping experiments.

Uncombable hair syndrome due to maternal uniparental disomy of chromosome 1.

Uncombable hair syndrome is a hair shaft condition in which the hair is frizzy, light in color (silver to light brown), and cannot be combed flat. Autosomal dominant (with complete or incomplete penetrance), autosomal recessive, and sporadic cases have been reported. In 2016 causative mutations in three genes were identified for uncombable hair syndrome, all with an autosomal recessive inheritance pattern: PADI3, TGM3, and TCHH.

Electron-beam patterned calibration structures for structured illumination microscopy.

Super-resolution fluorescence microscopy can be achieved by image reconstruction after spatially patterned illumination or sequential photo-switching and read-out. Reconstruction algorithms and microscope performance are typically tested using simulated image data, due to a lack of strategies to pattern complex fluorescent patterns with nanoscale dimension control. Here, we report direct electron-beam patterning of fluorescence nanopatterns as calibration standards for super-resolution fluorescence.

Phenotypic expansion of EGP5-related Vici syndrome: 15 Dutch patients carrying a founder variant.

Vici syndrome (OMIM 242840) is a very rare autosomal recessive multisystem disorder first described in 1988. In 2013, bi-allelic loss-of-function mutations in EPG5 were reported to cause Vici syndrome. Five principal diagnostic features of Vici syndrome have been proposed: agenesis of the corpus callosum, cataracts, cardiomyopathy, hypopigmentation, and combined immunodeficiency.

SEPT-GD: A decision tree to prioritise potential RNA splice variants in cardiomyopathy genes for functional splicing assays in diagnostics.

Background: Splice prediction algorithms currently used in routine DNA diagnostics have limited sensitivity and specificity, therefore many potential splice variants are classified as variants of uncertain significance (VUSs). However, functional assessment of VUSs to test splicing is labour-intensive and time-consuming. We developed a decision tree to prioritise potential splice variants for functional studies and functionally verified the outcome of the decision tree.

Chemically modified dsRNA induces RNAi effects in insects in vitro and in vivo: A potential new tool for improving RNA-based plant protection.

Global agriculture loses over $100 billion of produce annually to crop pests such as insects. Many of these crop pests either are not currently controlled by artificial means or have developed resistance against chemical pesticides. Long dsRNAs are capable of inducing RNAi in insects and are emerging as novel, highly selective alternatives for sustainable insect management strategies.

Expanding the clinical spectrum of primary coenzyme Q10 deficiency type 6: The first case with cardiomyopathy.

We report a 19-month-old patient with cardiomyopathy as the first presenting feature of primary COQ10 deficiency-6. This case expands the phenotypic spectrum of this disorder. Furthermore, it shows that genetic testing for primary COQ10 deficiency should be considered in patients with pediatric-onset cardiomyopathy as it can guide treatment options.

Validation of New Gene Variant Classification Methods: a Field-Test in Diagnostic Cardiogenetics.

In the molecular genetic diagnostics of Mendelian disorders, solutions are needed for the major challenge of dealing with the large number of variants of uncertain significance (VUSs) identified using next-generation sequencing (NGS). Recently, promising approaches using constraint metrics to calculate case excess scores (CE), etiological fractions (EF), and gnomAD-derived constraint scores have been reported that estimate the likelihood of rare variants in specific genes or regions that are pathogenic. Our objective is to study the usability of these constraint data into variant interpretation in a diagnostic setting, using our cardiomyopathy cohort.

Case series, chemotherapy-induced cardiomyopathy: mind the family history!

Background: Cardiotoxicity presenting as cardiomyopathy is a common side effect in cancer treatment especially with anthracyclines. The role of genetic predisposition is still being investigated.

Case Summary: Four unrelated patients with a familial burden for cardiac disease, who developed cardiomyopathy after anthracycline treatment are presented.

TAB2 deletions and variants cause a highly recognisable syndrome with mitral valve disease, cardiomyopathy, short stature and hypermobility.

Deletions that include the gene TAB2 and TAB2 loss-of-function variants have previously been associated with congenital heart defects and cardiomyopathy. However, other features, including short stature, facial dysmorphisms, connective tissue abnormalities and a variable degree of developmental delay, have only been mentioned occasionally in literature and thus far not linked to TAB2. In a large-scale, social media-based chromosome 6 study, we observed a shared phenotype in patients with a 6q25.

Structured illumination microscopy with noise-controlled image reconstructions.

Super-resolution structured illumination microscopy (SIM) has become a widely used method for biological imaging. Standard reconstruction algorithms, however, are prone to generate noise-specific artifacts that limit their applicability for lower signal-to-noise data. Here we present a physically realistic noise model that explains the structured noise artifact, which we then use to motivate new complementary reconstruction approaches.

Optimization of negative stage bias potential for faster imaging in large-scale electron microscopy.

Large-scale electron microscopy (EM) allows analysis of both tissues and macromolecules in a semi-automated manner, but acquisition rate forms a bottleneck. We reasoned that a negative bias potential may be used to enhance signal collection, allowing shorter dwell times and thus increasing imaging speed. Negative bias potential has previously been used to tune penetration depth in block-face imaging.

Retarding Field Integrated Fluorescence and Electron Microscope.

The authors present the application of a retarding field between the electron objective lens and sample in an integrated fluorescence and electron microscope. The retarding field enhances signal collection and signal strength in the electron microscope. This is beneficial for samples prepared for integrated fluorescence and electron microscopy as the amount of staining material added to enhance electron microscopy signal is typically lower compared to conventional samples in order to preserve fluorescence.

A homozygous variant in growth and differentiation factor 2 (GDF2) may cause lymphatic dysplasia with hydrothorax and nonimmune hydrops fetalis.

The etiology of nonimmune hydrops fetalis is extensive and includes genetic disorders. We describe a term-born female neonate with late onset extensive nonimmune hydrops, that is, polyhydramnios, edema, and congenital bilateral chylothorax. This newborn was successfully treated with repetitive thoracocentesis, total parenteral feeding, octreotide intravenously and finally surgical pleurodesis and corticosteroids.

De novo variants in CAMTA1 cause a syndrome variably associated with spasticity, ataxia, and intellectual disability.

Previously, intragenic CAMTA1 copy number variants (CNVs) have been shown to cause non-progressive, congenital ataxia with or without intellectual disability (OMIM#614756). However, ataxia, intellectual disability, and dysmorphic features were all incompletely penetrant, even within families. Here, we describe four patients with de novo nonsense, frameshift or missense CAMTA1 variants.

Declining detection rates for APC and biallelic MUTYH variants in polyposis patients, implications for DNA testing policy.

This study aimed to determine the prevalence of APC-associated familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) in a large cohort, taking into account factors as adenoma count and year of diagnosis. All application forms used to send patients in for APC and MUTYH variant analysis between 1992 and 2017 were collected (n = 2082). Using the data provided on the application form, the APC and biallelic MUTYH prevalence was determined and possible predictive factors were examined using multivariate multinomial logistic regression analysis in SPSS.

An alternative approach to establishing unbiased colorectal cancer risk estimation in Lynch syndrome.

Purpose: Biallelic pathogenic variants in the mismatch repair (MMR) genes cause a recessive childhood cancer predisposition syndrome known as constitutional mismatch repair deficiency (CMMRD). Family members with a heterozygous MMR variant have Lynch syndrome. We aimed at estimating cancer risk in these heterozygous carriers as a novel approach to avoid complicated statistical methods to correct for ascertainment bias.

Cancer Risks for PMS2-Associated Lynch Syndrome.

Purpose: Lynch syndrome due to pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, and MSH6 is predominantly associated with colorectal and endometrial cancer, although extracolonic cancers have been described within the Lynch tumor spectrum. However, the age-specific cumulative risk (penetrance) of these cancers is still poorly defined for PMS2-associated Lynch syndrome. Using a large data set from a worldwide collaboration, our aim was to determine accurate penetrance measures of cancers for carriers of heterozygous pathogenic PMS2 variants.

PRRT2-related phenotypes in patients with a 16p11.2 deletion.

We studied the presence of benign infantile epilepsy (BIE), paroxysmal kinesigenic dyskinesia (PKD), and PKD with infantile convulsions (PKD/IC) in patients with a 16p11.2 deletion including PRRT2 or with a PRRT2 loss-of-function sequence variant. Index patients were recruited from seven Dutch university hospitals.

Toward an effective exome-based genetic testing strategy in pediatric dilated cardiomyopathy.

Purpose: We evaluated the diagnostic yield in pediatric dilated cardiomyopathy (DCM) of combining exome sequencing (ES)-based targeted analysis and genome-wide copy-number variation (CNV) analysis. Based on our findings, we retrospectively designed an effective approach for genetic testing in pediatric DCM.

Methods: We identified 95 patients (in 85 families) with pediatric onset of DCM.