Clinical development of WEE1 inhibitors in gynecological cancers: A systematic review.

Introduction: The anti-tumor activity of WEE1 inhibitors (WEE1i) in gynecological malignancies has recently been demonstrated in clinical trials and its rationale is based on biological/molecular features of gynecological cancers. With this systematic review, we aim to outline the clinical development and current evidence regarding the efficacy and safety of these targeted agents in in this patient group.

Methods: Systematic literature review of trials including patients with gynecological cancers treated with a WEE1i.

Sequential Defects in Cardiac Lineage Commitment and Maturation Cause Hypoplastic Left Heart Syndrome.

Background: Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most common and severe manifestation within the spectrum of left ventricular outflow tract obstruction defects occurring in association with ventricular hypoplasia. The pathogenesis of HLHS is unknown, but hemodynamic disturbances are assumed to play a prominent role.

Comparing genome-scale DNA methylation and CNV marks between adult human cultured ITGA6+ testicular cells and seminomas to assess in vitro genomic stability.

Autologous transplantation of spermatogonial stem cells is a promising new avenue to restore fertility in infertile recipients. Expansion of the initial spermatogonial stem cell pool through cell culturing is a necessary step to obtain enough cells for effective repopulation of the testis after transplantation. Since in vitro propagation can lead to (epi-)genetic mutations and possibly malignant transformation of the starting cell population, we set out to investigate genome-wide DNA methylation status in uncultured and cultured primary testicular ITGA6+ sorted cells and compare them with germ cell tumor samples of the seminoma subtype.

Pregnancy complications in singleton pregnancies with isolated fetal heart defects.

Introduction: As the prenatal detection rates of congenital heart defects (CHDs) increase, obstetricians are more frequently faced with pregnancies complicated by a fetal CHD. Congenital anomalies in general are associated with preterm birth and fetal demise. The aim of this study was to gain insight into the prevalence of preterm birth and fetal demise in singleton pregnancies with fetuses with isolated CHDs.

Fluorinated steroids do not improve outcome of isolated atrioventricular block.

Introduction: Congenital atrioventricular block (CAVB) is a rare disorder with a significant morbidity and mortality. Consensus regarding the prescription and efficacy of prenatal corticosteroids is lacking. This nationwide study was initiated to evaluate the effects of prenatal treatment with corticosteroids on the outcome of CAVB in The Netherlands.

Right ventricular outflow tract obstruction in complicated monochorionic twin pregnancy.

Objectives: Severe right ventricular outflow tract obstruction (RVOTO) is a potential complication in recipient twins of twin-to-twin transfusion syndrome (TTTS) that requires postnatal follow-up or treatment. We aimed to evaluate pregnancy characteristics of neonates with RVOTO from complicated monochorionic twin pregnancies, determine the incidence of RVOTO in TTTS cases and construct a prediction model for its development.

Methods: This was an observational cohort study of all complicated monochorionic twin pregnancies with a postnatal diagnosis of RVOTO examined at our center.

Head growth in fetuses with isolated congenital heart defects: lack of influence of aortic arch flow and ascending aorta oxygen saturation.

Objectives: Congenital heart defects (CHDs) are reported to be associated with a smaller fetal head circumference (HC) and neurodevelopmental delay. Recent studies suggest that altered intrauterine brain hemodynamics may explain these findings. Our objectives were to evaluate the pattern of head growth in a large cohort of fetuses with various types of CHD, analyze these patterns according to the type of CHD and estimate the effect of cerebral hemodynamics with advancing gestation in the second and third trimesters.

Chromosomal abnormalities and copy number variations in fetal left-sided congenital heart defects.

Objectives: To demonstrate the spectrum of copy number variants (CNVs) in fetuses with isolated left-sided congenital heart defects (CHDs), and analyse genetic content.

Methods: Between 2003 and 2012, 200 fetuses were identified with left-sided CHD. Exclusion criteria were chromosomal rearrangements, 22q11.

A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours.

Background: The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and some of these miRNAs show elevated serum levels at diagnosis. Here, we developed a robust technical pipeline to quantify these miRNAs in the serum and cerebrospinal fluid (CSF).

Prenatal diagnosis of congenital heart defects: accuracy and discrepancies in a multicenter cohort.

Objective: To examine the accuracy of fetal echocardiography in diagnosing congenital heart disease (CHD) at the fetal medicine units of three tertiary care centers.

Methods: This was a multicenter cohort study of tertiary echocardiography referrals between 2002 and 2012. Prenatal and postnatal diagnoses were compared and the degree of agreement was classified as 'correct' (anatomy correct and the postnatal diagnosis led to a similar outcome as expected), 'discrepant' (anatomical discrepancies present but the severity and prognosis of the defect were diagnosed correctly) or 'no similarity' (the pre- and postnatal diagnoses differed completely).

Genome wide DNA methylation profiles provide clues to the origin and pathogenesis of germ cell tumors.

The cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are assumed to be germ cells from different maturation stages. This is (potentially) reflected in their methylation status as fetal maturing primordial germ cells are globally demethylated during migration from the yolk sac to the gonad. Imprinted regions are erased in the gonad and later become uniparentally imprinted according to fetal sex.

Characterization and quantification of dynamic eccentric regurgitation of the left atrioventricular valve after atrioventricular septal defect correction with 4D Flow cardiovascular magnetic resonance and retrospective valve tracking.

Background: To characterize and directly quantify regurgitant jets of left atrioventricular valve (LAVV) in patients with corrected atrioventricular septal defect (AVSD) by four-dimensional (4D)Flow Cardiovascular Magnetic Resonance (CMR), streamline visualization and retrospective valve tracking.

Methods: Medical ethical committee approval and informed consent from all patients or their parents were obtained. In 32 corrected AVSD patients (age 26 ± 12 years), echocardiography and whole-heart 4DFlow CMR were performed.

Prenatal detection of congenital heart disease--results of a national screening programme.

Objective: Congenital heart disease (CHD) is the most common congenital malformation and causes major morbidity and mortality. Prenatal detection improves the neonatal condition before surgery, resulting in less morbidity and mortality. In the Netherlands a national prenatal screening programme was introduced in 2007.

Pediatric germ cell tumors presenting beyond childhood?

Four cases are reported meeting the criteria of a pediatric (i.e., Type I) testicular germ cell tumor (TGCT), apart from the age of presentation, which is beyond childhood.

Identification of known and novel germ cell cancer-specific (embryonic) miRs in serum by high-throughput profiling.

microRNAs (miRs) are short non-coding RNA molecules (≈21 nucleotides) involved in regulation of translation. As such they are crucial for normal cell development and differentiation as well as cellular maintenance. Dysregulation of miRs has been reported in various diseases, including cancer.

Prenatal detection of transposition of the great arteries reduces mortality and morbidity.

Objectives: To evaluate the prenatal detection of transposition of the great arteries (TGA), after the introduction of a Dutch screening program in 2007, as well as the effect of prenatal detection on pre- and postsurgical mortality and morbidity.

Methods: In a geographical cohort study, all infants with TGA who were born between 1 January 2002 and 1 January 2012 were included. The cases were divided into two groups: those with and those without a prenatal diagnosis.

An oncofetal and developmental perspective on testicular germ cell cancer.

Germ cell tumors (GCTs) represent a diverse group of tumors presumably originating from (early fetal) developing germ cells. Most frequent are the testicular germ cell cancers (TGCC). Overall, TGCC is the most frequent malignancy in Caucasian males (20-40 years) and remains an important cause of (treatment related) mortality in these young men.

DMRforPairs: identifying differentially methylated regions between unique samples using array based methylation profiles.

Background: Array based methylation profiling is a cost-effective solution to study the association between genome methylation and human disease & development. Available tools to analyze the Illumina Infinium HumanMethylation450 BeadChip focus on comparing methylation levels per locus. Other tools combine multiple probes into a range, identifying differential methylated regions (DMRs).

Forty-Five Years of Duchenne Muscular Dystrophy in The Netherlands.

Background: Duchenne muscular dystrophy (DMD) is a progressive muscle disease. No curative therapy is currently available, but in recent decades standards of care have improved. These improvements include the use of corticosteroids and mechanical ventilation.

Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular) germ cell cancer patients: a proof of principle.

Germ cell cancers (GCC) are the most frequent malignancy in young Caucasian males. GCC can consist of seminomas (SE) and non-seminomas (malignant NS: embryonal carcinoma (EC), yolk sac tumor (YS), choriocarcinoma (CH) and teratoma (TE)). Current serum-markers used for diagnosis and follow-up (AFP, hCG) are predominantly related to YS and CH and marker positivity can vary during disease.

miMsg: a target enrichment algorithm for predicted miR-mRNA interactions based on relative ranking of matched expression data.

Motivation: Algorithms predicting microRNA (miR)-mRNA interactions generate high numbers of possible interactions, many of which might be non-existent or irrelevant in a certain biological context. It is desirable to develop a transparent, user-friendly, unbiased tool to enrich miR-mRNA predictions.

Results: The miMsg algorithm uses matched miR/mRNA expression data to enrich miR-mRNA predictions.

Volumetric Computed Tomography Angiography in the Evaluation of Mediastinal Fluid Collections following Congenital Cardiac Surgery.

We present 3 patients with 4 causes of mediastinal fluid collection after congenital cardiac surgery in this extended case report. Volumetric computed tomography played an essential role in diagnosing causes and extent, relevant to subsequent management. Recent advances in volumetric computed tomography allow fast and accurate imaging of cardiovascular and extravascular structures in children with acceptable radiation dose, providing a powerful imaging tool for the evaluation of complications after congenital cardiac surgery.

Right ventricular outflow tract obstruction in monochorionic twins with selective intrauterine growth restriction.

Monochorionic twin pregnancies are at increased risk of perinatal mortality and morbidity due to twin-twin transfusion syndrome (TTTS), selective intrauterine growth restriction (sIUGR), and higher incidence of congenital heart malformations. The incidence of right ventricular outflow tract obstruction (RVOTO) in recipients with TTTS is known to be higher than in the general population. There is limited data on the risk of RVOTO in monochorionic twins with sIUGR.