Biologically relevant integration of transcriptomics profiles from cancer cell lines, patient-derived xenografts, and clinical tumors using deep learning.

Cell lines and patient-derived xenografts are essential to cancer research; however, the results derived from such models often lack clinical translatability, as they do not fully recapitulate the complex cancer biology. Identifying preclinical models that sufficiently resemble the biological characteristics of clinical tumors across different cancers is critically important. Here, we developed MOBER, Multi-Origin Batch Effect Remover method, to simultaneously extract biologically meaningful embeddings while removing confounder information.

Information Service "My Cancer Navigator" to Support Shared Decision-Making: An Online Survey Among Patients with Cancer and Their Caregivers.

The personalized information service My Cancer Navigator (MCN) answers therapy-related questions of patients with cancer and their caregivers, to address information needs and contribute to shared decision-making (SDM). An explorative and descriptive cross-sectional study using online surveys was conducted to assess whether users perceived a change in factors contributing to SDM after using the service. Of 253 invited MCN users, 109 (43.

Evolution of Eligibility Criteria in Inflammatory Bowel Disease Clinical Trials: A Clinical Trial Databank Analysis.

Background: Eligibility criteria in clinical trials have been criticised for being overly restrictive without clinical justification.

Objective: We aimed to investigate the types, evolution, and current status of eligibility criteria in clinical trials for inflammatory bowel diseases (IBD).

Methods: We performed a clinical trial databank search on clinicaltrials.

STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment.

Transcription-coupled nucleotide excision repair (TC-NER) efficiently eliminates DNA damage that impedes gene transcription by RNA polymerase II (RNA Pol II). TC-NER is initiated by the recognition of lesion-stalled RNA Pol II by CSB, which recruits the CRL4 ubiquitin ligase and UVSSA. RNA Pol II ubiquitylation at RPB1-K1268 by CRL4 serves as a critical TC-NER checkpoint, governing RNA Pol II stability and initiating DNA damage excision by TFIIH recruitment.

Patient preferences for inflammatory bowel disease treatments: protocol development of a global preference survey using a discrete choice experiment.

Background: As the therapeutic landscape for inflammatory bowel disease (IBD) continues to expand, a need exists to understand how patients perceive and value different attributes associated with their disease as well as with current and emerging treatments. These insights can inform the development and regulation of effective interventions for IBD, benefiting various stakeholders including healthcare professionals, drug developers, regulators, Health Technology Assessment bodies, payers, and ultimately patients suffering from IBD. In response to this, the present patient preference study was developed with the aim to (1) determine the relative preference weights for IBD treatment and disease related attributes, and (2) explain how preferences may differ across patients with different characteristics (preference heterogeneity).

A survey of the representativeness and usefulness of wastewater-based surveillance systems in 10 countries across Europe in 2023.

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.

Heart failure patients' perspectives on treatment outcomes and unmet medical needs: A qualitative preference study.

Aims: Decision-makers still predominantly focus on the perspective of non-patient stakeholders, which may deviate from the unique perspective of heart failure (HF) patients. To enhance patient-centred decision-making, there is a need for more patient-based evidence derived directly from the patients themselves. Hence, this study aimed to understand (i) HF patients' unmet medical needs and preferred treatment outcomes; (ii) patients' risk tolerance; and (iii) their information needs, uncertainties and satisfaction towards HF treatment.

Transcription-coupled DNA-protein crosslink repair by CSB and CRL4-mediated degradation.

DNA-protein crosslinks (DPCs) arise from enzymatic intermediates, metabolism or chemicals like chemotherapeutics. DPCs are highly cytotoxic as they impede DNA-based processes such as replication, which is counteracted through proteolysis-mediated DPC removal by spartan (SPRTN) or the proteasome. However, whether DPCs affect transcription and how transcription-blocking DPCs are repaired remains largely unknown.

Development of a reverse transcriptase digital droplet polymerase chain reaction-based approach for SARS-CoV-2 variant surveillance in wastewater.

An urgent need for effective surveillance strategies arose due to the global emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although vaccines and antivirals are available, concerns persist about the evolution of new variants with potentially increased infectivity, transmissibility, and immune evasion. Therefore, variant monitoring is crucial for public health decision-making.

Comparing Discrete Choice Experiment with Swing Weighting to Estimate Attribute Relative Importance: A Case Study in Lung Cancer Patient Preferences.

Introduction: Discrete choice experiments (DCE) are commonly used to elicit patient preferences and to determine the relative importance of attributes but can be complex and costly to administer. Simpler methods that measure relative importance exist, such as swing weighting with direct rating (SW-DR), but there is little empirical evidence comparing the two. This study aimed to directly compare attribute relative importance rankings and weights elicited using a DCE and SW-DR.

Live-cell imaging of endogenous CSB-mScarletI as a sensitive marker for DNA-damage-induced transcription stress.

Transcription by RNA polymerase II (RNA Pol II) is crucial for cellular function, but DNA damage severely impedes this process. Thus far, transcription-blocking DNA lesions (TBLs) and their repair have been difficult to quantify in living cells. To overcome this, we generated, using CRISPR-Cas9-mediated gene editing, mScarletI-tagged Cockayne syndrome group B protein (CSB) and UV-stimulated scaffold protein A (UVSSA) knockin cells.

How can patient preferences be used and communicated in the regulatory evaluation of medicinal products? Findings and recommendations from IMI PREFER and call to action.

Patients have unique insights and are (in-)directly affected by each decision taken throughout the life cycle of medicinal products. Patient preference studies (PPS) assess what matters most to patients, how much, and what trade-offs patients are willing to make. IMI PREFER was a six-year European public-private partnership under the Innovative Medicines Initiative that developed recommendations on how to assess and use PPS in medical product decision-making, including in the regulatory evaluation of medicinal products.

Time series modelling for wastewater-based epidemiology of COVID-19: A nationwide study in 40 wastewater treatment plants of Belgium, February 2021 to June 2022.

Background: Wastewater-based epidemiology (WBE) has been implemented to monitor surges of COVID-19. Yet, multiple factors impede the usefulness of WBE and quantitative adjustment may be required.

Aim: We aimed to model the relationship between WBE data and incident COVID-19 cases, while adjusting for confounders and autocorrelation.

Balancing benefits and risks in lung cancer therapies: patient preferences for lung cancer treatment alternatives.

Background: In the treatment of Non-Small Cell Lung Cancer (NSCLC) the combination of Immuno- Oncotherapy (IO) and chemotherapy (CT) has been found to be superior to IO or CT alone for patients' survival. Patients and clinicians are confronted with a preference sensitive choice between a more aggressive treatment with a greater negative effect on quality of life versus alternatives that are less effective but have fewer side effects.

Objectives: The aims of this study were to: (a) quantify patients' preferences for relevant attributes related to Immuno-Oncotherapy treatment alternatives, and (b) evaluate the maximum acceptable risk (MAR)/Minimum acceptable benefit (MAB) that patients would accept for treatment alternatives.

Uncertainty management in regulatory and health technology assessment decision-making on drugs: guidance of the HTAi-DIA Working Group.

Objectives: Uncertainty is a fundamental component of decision making regarding access to and pricing and reimbursement of drugs. The context-specific interpretation and mitigation of uncertainty remain major challenges for decision makers. Following the 2021 HTAi Global Policy Forum, a cross-sectoral, interdisciplinary HTAi-DIA Working Group (WG) was initiated to develop guidance to support stakeholder deliberation on the systematic identification and mitigation of uncertainties in the regulatory-HTA interface.

Real-time image and time-lapse technology to select the single blastocyst to transfer in assisted reproductive cycles.

The success of an assisted reproduction cycle should be the achievement of a healthy singleton live birth following the replacement of one embryo. Therefore, one of the most critical points for embryologists has been the selection criteria and how to choose the best embryo to transfer with high implantation potential. In this vein, morphological evaluation has been historically the method applied.

Patients as research partners in preference studies: learnings from IMI-PREFER.

Background: There is growing recognition of the importance of patient and public stakeholder involvement (PPI) in patient preference research. However, limited evidence exists regarding the impact, barriers and enablers of PPI in preference studies. The Innovative Medicines Initiative (IMI)-PREFER project conducted a series of preference case studies which incorporated PPI.

ATXN3 controls DNA replication and transcription by regulating chromatin structure.

The deubiquitinating enzyme Ataxin-3 (ATXN3) contains a polyglutamine (PolyQ) region, the expansion of which causes spinocerebellar ataxia type-3 (SCA3). ATXN3 has multiple functions, such as regulating transcription or controlling genomic stability after DNA damage. Here we report the role of ATXN3 in chromatin organization during unperturbed conditions, in a catalytic-independent manner.

Avidity engineering of human heavy-chain-only antibodies mitigates neutralization resistance of SARS-CoV-2 variants.

Emerging SARS-CoV-2 variants have accrued mutations within the spike protein rendering most therapeutic monoclonal antibodies against COVID-19 ineffective. Hence there is an unmet need for broad-spectrum mAb treatments for COVID-19 that are more resistant to antigenically drifted SARS-CoV-2 variants. Here we describe the design of a biparatopic heavy-chain-only antibody consisting of six antigen binding sites recognizing two distinct epitopes in the spike protein NTD and RBD.

Tiered dietary exposure assessment of steviol glycosides in the Belgian population.

The objective of the present study was to assess the dietary intake of steviol glycosides in the Belgian population and to conduct a risk assessment by comparing the estimated intakes to the acceptable daily intake (ADI). A tiered approach was adopted in this study. First, a Tier 2 assessment was performed using maximum permitted levels.

What matters most to patients with multiple myeloma? A Pan-European patient preference study.

Introduction: Given the rapid increase in novel treatments for patients with multiple myeloma (MM), this patient preference study aimed to establish which treatment attributes matter most to MM patients and evaluate discrete choice experiment (DCE) and swing weighting (SW) as two elicitation methods for quantifying patients' preferences.

Methods: A survey incorporating DCE and SW was disseminated among European MM patients. The survey included attributes and levels informed by a previous qualitative study with 24 MM patients.

Considerations on staffing levels for a modern assisted reproductive laboratory.

The duties recently performed in the embryology laboratory have deeply increased compared to those realized a couple of decades ago. Currently, procedures include conventional in vitro fertilization (IVF) and ICSI techniques, or processing of surgically retrieved sperm, embryo culture and time-lapse monitoring, blastocyst culture, as well as trophectoderm biopsy for preimplantation genetic testing and cryopreservation. These techniques require not only time, but also high knowledge level and acutely concentration by the embryologist team.

How to balance valuable innovation with affordable access to medicines in Belgium?

Countries are struggling to provide affordable access to medicines while supporting the market entry of innovative, expensive products. This aims to discuss challenges and avenues for balancing health care system objectives of access, affordability and innovation related to medicines in Belgium (and in other countries). This focuses on the R&D, regulatory approval and market access phases, with particular attention to oncology medicines, precision medicines, orphan medicines, advanced therapies, repurposed medicines, generics and biosimilars.