Leiden University Scholarly Publications

Thomaidou, S.; Slieker, R.C.; Slik, A.R. van der; Boom, J.; Mulder, F.; Munoz-Garcia, A.; ... ; Zaldumbide, A. 2021

Long RNA sequencing and ribosome profiling of inflamed beta-cells reveal an extensive translatome landscape

Article / Letter to editor

open access

2022-04-01T00:00:00Z

Type 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell-mediated destruction of the insulin-producing pancreatic beta -cells. Increasing evidence suggest that the beta ... Show moreType 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell-mediated destruction of the insulin-producing pancreatic beta -cells. Increasing evidence suggest that the beta -cells themselves contribute to their own destruction by generating neoantigens through the production of aberrant or modified proteins that escape central tolerance. We recently demonstrated that ribosomal infidelity amplified by stress could lead to the generation of neoantigens in human beta -cells, emphasizing the participation of nonconventional translation events in autoimmunity, as occurring in cancer or virus-infected tissues. Using a transcriptome-wide profiling approach to map translation initiation start sites in human beta -cells under standard and inflammatory conditions, we identify a completely new set of polypeptides derived from noncanonical start sites and translation initiation within long noncoding RNA. Our data underline the extreme diversity of the beta -cell translatome and may reveal new functional biomarkers for beta -cell distress, disease prediction and progression, and therapeutic intervention in T1D. Show less

Bakker, T.; Abu-Hanna, A.; Dongelmans, D.A.; Vermeijden, W.J.; Bosman, R.J.; Lange, D.W. de; ... ; SIMPLIFY Study Grp 2021

Clinically relevant potential drug-drug interactions in intensive care patients: a large retrospective observational multicenter study

Article / Letter to editor

open access

Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all... Show morePurpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when con -sidering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients. ? 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less

Boersma, F.K.; Ferguson, J.; Groenewegen, P.; Mulder, F.; Schmidt, A.; Wolbers, J. 2018

Platformsturing van zelforganisatie tijdens rampen

Article / Letter to editor

open access

2018-12-31T00:00:00Z

During a disaster or crisis, the response capacity of the government is put under extreme pressure. At the same time, citizens are often resilient in times of crisis and are increasingly capable of...

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During a disaster or crisis, the response capacity of the government is put under extreme pressure. At the same time, citizens are often resilient in times of crisis and are increasingly capable of organizing themselves. Social media and online platforms have increased the possibilities for self-organization through improved connectivity. In practice, we see that governments struggle to deal with this form of self-organization, while it also offers a unique opportunity to increase the response capacity. The smart use of citizens’ initiatives offers opportunities and can increase the effectiveness of the government’s action. This article focuses on the following question: what role do online platforms play in smartly guiding the self-organization of citizens during crises and disasters? We answer the question on the basis of two examples: the role of online platforms in the aftermath of the earthquakes in Nepal in 2015, and the coordination of the reception of refugees during the crisis in the Netherlands in the winter of 2015-2016.

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