Publications by authors named "Beek R"

Article Synopsis
  • Clinical exome sequencing (ES) aids in diagnosing rare genetic disorders by analyzing protein-coding sequences, but 40-60% of patients still lack a conclusive diagnosis, with some revealing monoallelic variants in recessive disorders.* -
  • The study explored short-read genome sequencing (GS) on 174 individuals with identified monoallelic variants, successfully uncovering additional pathogenic variants in five patients and rare non-coding variants in 24 others, with three variants confirmed to affect splicing.* -
  • Overall, GS increased the diagnostic yield, identifying a likely second pathogenic variant in 4.6% of the cohort and providing a possible diagnosis for 12.1%, suggesting it could be a valuable first-tier
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In mammals, early embryonic development exhibits highly unusual spatial positioning of genomic regions at the nuclear lamina, but the mechanisms underpinning this atypical genome organization remain elusive. Here, we generated single-cell profiles of lamina-associated domains (LADs) coupled with transcriptomics, which revealed a striking overlap between preimplantation-specific LAD dissociation and noncanonical broad domains of H3K27me3. Loss of H3K27me3 resulted in a restoration of canonical LAD profiles, suggesting an antagonistic relationship between lamina association and H3K27me3.

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Microbiology education has a serious handicap - the lack of visibility of the players of the subject and their interactions - which engenders a disproportionate reliance upon multimedia teaching aids (MTAs). The International Microbiology Literacy Initiative (IMiLI) is creating educational resources in societally-relevant microbiology complemented by appropriate MTAs. However, proper guidance supporting microbiology educators in locating and selecting, or commissioning the creation of, adequate MTAs for different target audiences and learning objectives is lacking.

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Wastewater-based surveillance (WBS) has become a widespread method to monitor transmission of SARS-CoV-2 and other human pathogens in Europe. We conducted a survey about WBS systems' objectives, approaches, representativeness and usefulness in 10 invited European countries in 2023, i.e.

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Management of suspected early-onset sepsis (EOS) is undergoing continuous evolution aiming to limit antibiotic overtreatment, yet current data on the level of overtreatment are only available for a select number of countries. This study aimed to determine antibiotic initiation and continuation rates for suspected EOS, along with the incidence of culture-proven EOS in The Netherlands. In this retrospective study from 2019 to 2021, data were collected from 15 Dutch hospitals, comprising 13 regional hospitals equipped with Level I-II facilities and 2 academic hospitals equipped with Level IV facilities.

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INPP5E encodes inositol polyphosphate-5-phosphatase E, an enzyme involved in regulating the phosphatidylinositol (PIP) makeup of the primary cilium membrane. Pathogenic variants in INPP5E hence cause a variety of ciliopathies: genetic disorders caused by dysfunctional cilia. While the majority of these disorders are syndromic, such as the neuronal ciliopathy Joubert syndrome, in some cases patients will present with an isolated phenotype-most commonly non-syndromic retinitis pigmentosa (RP).

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Wastewater-based epidemiological surveillance at municipal wastewater treatment plants has proven to play an important role in COVID-19 surveillance. Considering international passenger hubs contribute extensively to global transmission of viruses, wastewater surveillance at this type of location may be of added value as well. The aim of this study is to explore the potential of long-term wastewater surveillance at a large passenger hub as an additional tool for public health surveillance during different stages of a pandemic.

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Opportunistic sensors are increasingly used for rainfall measurement. However, their raw data are collected by a variety of systems that are often not primarily intended for rainfall monitoring, resulting in a plethora of different data formats and a lack of common standards. This hinders the sharing of opportunistic sensing (OS) data, their automated processing, and, at the end, their practical usage and integration into standard observation systems.

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Background: Delayed cord clamping has significant beneficial effects on the neonate and its transition to extrauterine life and, therefore, is common practice at vaginal births in the Netherlands. In 2015, 16% of neonates were born via cesarean delivery; moreover, in 81% of these cases, the umbilical cord was clamped and cut immediately. Neonatal benefits of delayed cord clamping are an increased circulating volume of 25 to 30 mL/kg, leading to a higher preload of both the right and left ventricles during the transition from umbilical circulation to pulmonary circulation, thus maintaining a stable left ventricle output, and to higher neonatal hemoglobin and hematocrit levels 24 to 48 hours after birth.

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Introduction: Polydrug use patterns among young adults using ecstasy vary, as well as their willingness to change them. Polydrug use patterns are likely associated with different adverse health outcomes. It is unknown whether polydrug use patterns of young adults who use ecstasy are similar in different countries.

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Gene expression programs result from the collective activity of numerous regulatory factors. Studying their cooperative mode of action is imperative to understand gene regulation, but simultaneously measuring these factors within one sample has been challenging. Here we introduce Multiplexing Antibodies by barcode Identification (MAbID), a method for combinatorial genomic profiling of histone modifications and chromatin-binding proteins.

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Since the start of the COVID-19 pandemic in 2020, wastewater surveillance programs were established, or upscaled, in many countries around the world and have proven to be a cost-effective way of monitoring infectious disease pathogens. Many of these programs use RT-qPCR, and quantify the viral concentrations in samples based on standard curves, by including preparations of a reference material with known nucleic acid or virus concentrations in the RT-qPCR analyses. In high-throughput monitoring programs it is possible to combine data from multiple previous runs, circumventing the need for duplication and resulting in decreased costs and prolonged periods during which the reference material is obtained from the same batch.

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Wastewater-based surveillance enables tracking of SARS-CoV-2 circulation at a local scale in near-real time. Here we investigate the relation between virus loads and the number of hospital admissions in the Netherlands. Inferred virus loads from August 2020 until February 2022 in each of the 344 Dutch municipalities are analysed in a Bayesian multilevel Poisson regression to relate virus loads to daily age-stratified (in groups of 20 years) hospital admissions.

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Background: Human milk comprises large fat globules enveloped by a native phospholipid membrane, whereas infant formulas contain small, protein-coated lipid droplets. Previous experimental studies indicated that mimicking the architecture of human milk lipid droplets in infant milk formula (IMF) alters lipid metabolism with lasting beneficial impact on later metabolic health.

Objectives: To evaluate in a follow-up (FU) study of a randomized, controlled trial whether a Concept IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids beneficially impacts long-term body mass index (BMI in kg/m) trajectories and blood pressure at school age.

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This study evaluated the effect of adductor canal block (ACB) versus femoral nerve block (FNB) on readiness for discharge in patients undergoing outpatient anterior cruciate ligament (ACL) reconstruction. We hypothesized that ACB would provide sufficient pain relief while maintaining motor strength and safety, thus allowing for earlier discharge. This was a randomized, multi-center, superiority trial.

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Introduction: Shoulder arthroplasty is mostly performed as an inpatient procedure. Same-day discharge arthroplasty has shown positive results in hip and knee surgery. Primary objective of this study was to investigate whether a safe and satisfactory same-day discharge (SDD) can be predicted with a set of easy to use predefined criteria, without increasing complications and re-admissions.

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The Dutch national open database on COVID-19 has been incrementally expanded since its start on 30 April 2020 and now includes datasets on symptoms, tests performed, individual-level positive cases and deaths, cases and deaths among vulnerable populations, settings of transmission, hospital and ICU admissions, SARS-CoV-2 variants, viral loads in sewage, vaccinations and the effective reproduction number. This data is collected by municipal health services, laboratories, hospitals, sewage treatment plants, vaccination providers and citizens and is cleaned, analysed and published, mostly daily, by the National Institute for Public Health and the Environment (RIVM) in the Netherlands, using automated scripts. Because these datasets cover the key aspects of the pandemic and are available at detailed geographical level, they are essential to gain a thorough understanding of the past and current COVID-19 epidemiology in the Netherlands.

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Article Synopsis
  • Surveillance of SARS-CoV-2 in wastewater can track the virus's spread in real-time across local areas, but individual sewage measurements can fluctuate significantly and may not always capture the complete picture.
  • A study in the Netherlands implemented a sophisticated model to analyze sewage data from over 300 treatment plants, covering nearly all of the population, allowing for accurate estimation of virus loads over time.
  • The approach successfully monitored variations in local virus loads during the pandemic, showing significant differences between locations and providing insight into epidemic trends despite daily data variability.
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Background: Switching from intravenous antibiotic therapy to oral antibiotic therapy among neonates is not yet practised in high-income settings due to uncertainties about exposure and safety. We aimed to assess the efficacy and safety of early intravenous-to-oral antibiotic switch therapy compared with a full course of intravenous antibiotics among neonates with probable bacterial infection.

Methods: In this multicentre, randomised, open-label, non-inferiority trial, patients were recruited at 17 hospitals in the Netherlands.

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Ciliopathies are rare congenital disorders, caused by defects in the cilium, that cover a broad clinical spectrum. A subgroup of ciliopathies showing significant phenotypic overlap are known as skeletal ciliopathies and include Jeune asphyxiating thoracic dysplasia (JATD), Mainzer-Saldino syndrome (MZSDS), cranioectodermal dysplasia (CED), and short-rib polydactyly (SRP). Ciliopathies are heterogeneous disorders with >187 associated genes, of which some genes are described to cause more than one ciliopathy phenotype.

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We describe the development of two methods for obtaining confluent monolayers of polarized, differentiated equine oviduct epithelial cells (EOEC) in Transwell inserts and microfluidic chips. EOECs from the ampulla were isolated post-mortem and seeded either (1) directly onto a microporous membrane as differentiated EOECs (direct seeding protocol) or (2) first cultured to a confluent de-differentiated monolayer in conventional wells, then trypsinized and seeded onto a microporous membrane (re-differentiation protocol). Maintenance or induction of EOEC differentiation in these systems was achieved by air-liquid interface introduction.

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Background: Monitoring emerging trends in the increasingly dynamic European drug market is vital; however, information on change at the individual level is scarce. In the current study, we investigated changes in drug use over 12 months in European nightlife attendees.

Method: In this longitudinal online survey, changes in substances used, use frequency in continued users, and relative initiation of use at follow-up were assessed for 20 different substances.

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During circulation in humans and natural selection to escape antibody recognition for decades, A/H3N2 influenza viruses emerged with altered receptor specificities. These viruses lost the ability to agglutinate erythrocytes critical for antigenic characterization and give low yields and acquire adaptive mutations when cultured in eggs and cells, contributing to recent vaccine challenges. Examination of receptor specificities of A/H3N2 viruses reveals that recent viruses compensated for decreased binding of the prototypic human receptor by recognizing α2,6-sialosides on extended LacNAc moieties.

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In this retrospective cohort study, the response to routinely administered Haemophilus influenzae type B vaccine, pneumococcal and pertussis vaccinations in 27 children exposed to antitumor necrosis factor alpha (anti-TNFα) during pregnancy was measured. The overall vaccination response seems comparable for children exposed to anti-TNFα and healthy infants. After primary vaccination series, inadequate response was present in some patients and might be related to exposure to anti-TNFα.

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