DGRPool, a web tool leveraging harmonized Genetic Reference Panel phenotyping data for the study of complex traits.

Genome-wide association studies have advanced our understanding of complex traits, but studying how a GWAS variant can affect a specific trait in the human population remains challenging due to environmental variability. is in this regard an excellent model organism for studying the relationship between genetic and phenotypic variation due to its simple handling, standardized growth conditions, low cost, and short lifespan. The Genetic Reference Panel (DGRP) in particular has been a valuable tool for studying complex traits, but proper harmonization and indexing of DGRP phenotyping data is necessary to fully capitalize on this resource.

Quantitative ultrasound of the calcaneus (QUS): A valuable tool in the identification of patients with non-metastatic prostate cancer requiring screening for osteoporosis.

Unlabelled: Non-metastatic prostate cancer (PCa) patients are at increased risk for osteoporosis and fractures mainly due to androgen deprivation therapy (ADT)-associated hypogonadism, but this remains largely underdiagnosed and untreated. In this study, we examine the value of pre-screening calcaneal QUS in identifying patients who should be referred for screening for osteoporosis using dual-energy X-Ray absorptiometry (DXA). In a single-center retrospective cross-sectional cohort study, we analysed data on DXA and calcaneal QUS measurements systematically collected between 2011 and 2013 in all non-metastatic PCa patients attending our Uro-Oncological Clinic at the Leiden University Medical Center.

Uncovering the burden of hidden ciliopathies in the 100 000 Genomes Project: a reverse phenotyping approach.

Background: The 100 000 Genomes Project (100K) recruited National Health Service patients with eligible rare diseases and cancer between 2016 and 2018. PanelApp virtual gene panels were applied to whole genome sequencing data according to Human Phenotyping Ontology (HPO) terms entered by recruiting clinicians to guide focused analysis.

Methods: We developed a reverse phenotyping strategy to identify 100K participants with pathogenic variants in nine prioritised disease genes (), representative of the full phenotypic spectrum of multisystemic primary ciliopathies.

Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis.

Background: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments.

Local bone metabolism during the consolidation process of spinal interbody fusion.

Introduction: Although computed tomography (CT) can identify the presence of eventual bony bridges following lumbar interbody fusion (LIF) surgery, it does not provide information on the ongoing formation process of new bony structures. F sodium fluoride (F-NaF) positron emission tomography (PET) could be used as complementary modality to add information on the bone metabolism at the fusion site. However, it remains unknown how bone metabolism in the operated segment changes early after surgery in uncompromised situations.

Molecular diagnoses in the congenital malformations caused by ciliopathies cohort of the 100,000 Genomes Project.

Background: Primary ciliopathies represent a group of inherited disorders due to defects in the primary cilium, the 'cell's antenna'. The 100,000 Genomes Project was launched in 2012 by Genomics England (GEL), recruiting National Health Service (NHS) patients with eligible rare diseases and cancer. Sequence data were linked to Human Phenotype Ontology (HPO) terms entered by recruiting clinicians.

Early bone ingrowth and segmental stability of a trussed titanium cage versus a polyether ether ketone cage in an ovine lumbar interbody fusion model.

Background Context: Lumbar interbody fusion is an effective treatment for unstable spinal segments. However, the time needed to establish a solid bony interbody fusion between the two vertebrae may be longer than twelve months after surgery. During this time window, the instrumented spinal segment is assumed to be at increased risk for instability related complications such as cage migration or subsidence.

Extensive tissue-specific expression variation and novel regulators underlying circadian behavior.

Natural genetic variation affects circadian rhythms across the evolutionary tree, but the underlying molecular mechanisms are poorly understood. We investigated population-level, molecular circadian clock variation by generating >700 tissue-specific transcriptomes of ( ) and 141 Genetic Reference Panel (DGRP) lines. This comprehensive circadian gene expression atlas contains >1700 cycling genes including previously unknown central circadian clock components and tissue-specific regulators.

Dissecting the eQTL Micro-Architecture in .

The study of expression quantitative trait loci (eQTL) using natural variation in inbred populations has yielded detailed information about the transcriptional regulation of complex traits. Studies on eQTL using recombinant inbred lines (RILs) led to insights on and regulatory loci of transcript abundance. However, determining the underlying causal polymorphic genes or variants is difficult, but ultimately essential for the understanding of regulatory networks of complex traits.

Deep neuromuscular block does not improve surgical conditions in patients receiving sevoflurane anaesthesia for laparoscopic renal surgery.

Background: Deep neuromuscular block is associated with improved working conditions during laparoscopic surgery when propofol is used as a general anaesthetic. However, whether deep neuromuscular block yields similar beneficial effects when anaesthesia is maintained using volatile inhalation anaesthesia has not been systematically investigated. Volatile anaesthetics, as opposed to intravenous agents, potentiate muscle relaxation, which potentially reduces the need for deep neuromuscular block to obtain optimal surgical conditions.

Assessment of Growth Reduction of Five Clinical Pathogens by Injectable S53P4 Bioactive Glass Material Formulations.

The one-stage treatment of chronic osteomyelitis with S53P4 bioactive glass (BAG) granules has shown excellent results. However, these granules possess suboptimal handling properties. Therefore, new injectable S53P4 putty materials have been developed by the incorporation of a synthetic binder to contain glass granules.

Impact of high- versus low-dose neuromuscular blocking agent administration on unplanned 30-day readmission rates in retroperitoneal laparoscopic surgery.

Recent data shows that a neuromuscular block (NMB) induced by administration of high doses of rocuronium improves surgical conditions in certain procedures. However, there are limited data on the effect such practices on postoperative outcomes. We performed a retrospective analysis to compare unplanned 30-day readmissions in patients that received high-dose versus low-dose rocuronium administration during general anesthesia for laparoscopic retroperitoneal surgery.

Temporal dynamics of gene expression in heat-stressed Caenorhabditis elegans.

There is considerable insight into pathways and genes associated with heat-stress conditions. Most genes involved in stress response have been identified using mutant screens or gene knockdowns. Yet, there is limited understanding of the temporal dynamics of global gene expression in stressful environments.

Bayesian association scan reveals loci associated with human lifespan and linked biomarkers.

The enormous variation in human lifespan is in part due to a myriad of sequence variants, only a few of which have been revealed to date. Since many life-shortening events are related to diseases, we developed a Mendelian randomization-based method combining 58 disease-related GWA studies to derive longevity priors for all HapMap SNPs. A Bayesian association scan, informed by these priors, for parental age of death in the UK Biobank study (n=116,279) revealed 16 independent SNPs with significant Bayes factor at a 5% false discovery rate (FDR).

Contribution of trans regulatory eQTL to cryptic genetic variation in C. elegans.

Background: Cryptic genetic variation (CGV) is the hidden genetic variation that can be unlocked by perturbing normal conditions. CGV can drive the emergence of novel complex phenotypes through changes in gene expression. Although our theoretical understanding of CGV has thoroughly increased over the past decade, insight into polymorphic gene expression regulation underlying CGV is scarce.

Beyond penile cancer, is there a role for sentinel node biopsy in urological malignancies?

This review aims to discuss the current state-of-the-art of sentinel node (SN) mapping in urological malignancies. The principles and methodological aspects of lymphatic mapping and SN biopsy in urological malignancies are reviewed. Literature search was restricted to English language.

Influence of variations in arterial PCO2 on surgical conditions during laparoscopic retroperitoneal surgery.

Background: Although deep neuromuscular block (post-tetanic-count 1-2 twitches) improves surgical conditions during laparoscopic retroperitoneal surgery compared with standard block (train-of-four 1-2 twitches), the quality of surgical conditions varies widely, often related to diaphragmatic contractions. Hypocapnia may improve surgical conditions. Therefore we studied the effect of changes in arterial carbon dioxide concentrations on surgical conditions in patients undergoing laparoscopic surgery under general anaesthesia and deep neuromuscular block.