Incorporation of ionizable lipids into the outer shell of lipid-coated calcium phosphate nanoparticles boosts cellular mRNA delivery.

Messenger RNA is a highly promising biotherapeutic modality with great potential in preventive and therapeutic vaccination, and in the modulation of cellular function through transient expression of therapeutic proteins. However, for cellular delivery, mRNA requires packaging into delivery vehicles that mediate uptake and also shield the mRNA against degradation. Lipid-coated calcium phosphate (LCP) nanoparticles encapsulate the mRNA in a calcium phosphate core, which is coated by a bilayer of structural lipids, positively charged lipids and pegylated lipid to mediate cellular uptake and achieve colloidal stabilization.

Guselkumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients: results of the phase 3, randomized, placebo-controlled PROTOSTAR study.

Background: No currently approved treatment for pediatric plaque psoriasis selectively targets interleukin (IL)-23. In adults, guselkumab (a selective IL-23 inhibitor targeting the p19 subunit) demonstrated substantial efficacy with a favorable safety profile in treating moderate-to-severe plaque psoriasis.

Objective: PROTOSTAR (NCT03451851) evaluated the efficacy and safety of guselkumab in pediatric patients with moderate-to-severe plaque psoriasis.

Development and alpha-testing of a patient decision aid for patients with chronic myeloid leukemia regarding dose reduction.

Background: Dose reduction of tyrosine kinase inhibitors (TKIs) is an option for some chronic myeloid leukemia (CML) patients to minimize side effects while maintaining efficacy. Shared decision-making (SDM) and patient decision aids (PDAs) are advocated to make informed choices such as reducing the dose of TKIs. This paper describes the development and alpha-testing of a PDA for patients with CML receiving TKI dose reduction.

A rare homozygous variant causes adult-onset diabetes.

Introduction: Maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM) are the most prevalent causes of monogenic diabetes. MODY is an autosomal dominant condition with onset in childhood and young adulthood, while NDM is defined with diabetes onset within 6 months of age and can be caused by dominant, recessive, X-linked genes or by chromosomal abnormalities. Here, we describe a rare case of monogenic diabetes in a patient who is homozygous for an gene variant.

Uncomplicated Type B Aortic Dissection - A European Multicentre Cross-Sectional Evaluation.

Objectives: A multicentre European randomized control trial - European Uncomplicated Type B Aortic Repair (EU-TBAR) is being developed to compare pre-emptive TEVAR with custom-made devices vs conventional OMT. The pre-trial set-up is confluent on different pillars, including evaluation of 1) European activity, trends, and governance, 2) outcome reporting, and 3) cost evaluation. This article aimed to demonstrate the observational cross-sectional survey results from participating centres and highlight the risk assessment, activity, practices, and governance of uncomplicated type B aortic dissection (uTBAD).

Trends in the Incidence, Organization of Care, and Surgical Treatment of Medullary Thyroid Cancer: A Population-Based Study.

Medullary thyroid cancer (MTC) is a rare cancer with variable disease course. To enable optimal care, centralization and consensus guidelines are essential. This study describes trends in the incidence, organization of care, surgical treatment, and outcomes of MTC over 30 years in the Netherlands.

Role of ZFHX4 in orofacial clefting based on human genetic data and zebrafish models.

Orofacial clefting (OFC) is a frequent congenital anomaly and can occur either in the context of underlying syndromes or in isolation (nonsyndromic). The two common OFC phenotypes are cleft lip with/without cleft palate (CL/P) and cleft palate only (CPO). In this study, we searched for penetrant CL/P genes, by evaluating de novo copy number variants (CNV) from an exome sequencing dataset of 50 nonsyndromic patient-parent trios.

Geometric deep learning improves generalizability of MHC-bound peptide predictions.

The interaction between peptides and major histocompatibility complex (MHC) molecules is pivotal in autoimmunity, pathogen recognition and tumor immunity. Recent advances in cancer immunotherapies demand for more accurate computational prediction of MHC-bound peptides. We address the generalizability challenge of MHC-bound peptide predictions, revealing limitations in current sequence-based approaches.

Use of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Nodal Staging in Prostate Cancer and Tailoring of Treatment: A Continuing Conundrum.

Trials have shown that prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) is more accurate than conventional imaging for staging of nodal status in prostate cancer. We discuss the advantages of PSMA PET/CT over current options for nodal staging and highlight the issues that need to be resolved for implementation of this modality in routine practice.

Artemether-lumefantrine-amodiaquine or artesunate-amodiaquine combined with single low-dose primaquine to reduce Plasmodium falciparum malaria transmission in Ouélessébougou, Mali: a five-arm, phase 2, single-blind, randomised controlled trial.

Background: Triple artemisinin-based combination therapies (TACTs) can delay the spread of antimalarial drug resistance. Artesunate-amodiaquine is widely used for uncomplicated Plasmodium falciparum malaria. We therefore aimed to determine the safety and efficacy of artemether-lumefantrine-amodiaquine and artesunate-amodiaquine with and without single low-dose primaquine for reducing gametocyte carriage and transmission to mosquitoes.

Negative memory bias predicts change in psychiatric problems in a naturalistic psychiatric patient sample.

Self-referential negative memory bias contributes to depression and other psychiatric disorders. Co-morbidity between these disorders is highly common in clinical practice, but transdiagnostic predictors like negative memory bias are not well understood yet. Therefore, the present study aimed to investigate the predictive value of negative memory bias for long-term change in broad psychiatric problems.

Parameter map guided explainable segmentation framework for breast cancer using amide proton transfer weighted imaging.

Background: Amide proton transfer weighted (APTw) imaging has demonstrated extensive clinical applications in diagnosing, treating evaluating, and prognosis prediction of breast cancer. There is a pressing need to automatically segment breast lesions on APTw original images to facilitate downstream quantification, which is however challenging.

Purpose: To build a segmentation model on the original images of APTw imaging sequence by leveraging the varying contrasts between breast lesions and their surrounding glandular and fat tissues displayed on the original images of APTw imaging at different frequency offsets.

The Political Economy of Priority Setting and Resource Allocation in European Oral Health Policy.

Aim: Pressing oral health care challenges pose prioritization dilemmas for governments. This study aimed to identify key determinants of prioritization in oral health policy in Denmark, Germany, the Netherlands, and the United Kingdom, as part of a series of the DELIVER project.

Methods: A literature review based on a search of PubMed and Google Scholar articles related to these countries from January 1, 2000, to October 17, 2023, and key informant interviews with policy makers were conducted to identify key trends in oral health policy choices and determinants of priority setting and resource allocation processes.

Genetic variation on dolutegravir pharmacokinetics and relation to safety and efficacy outcomes: a systematic review.

Background: Dolutegravir (DTG) is an antiviral agent used for the treatment of HIV, however, there is uncertainty over the influence of genetic variation on DTG exposure, and whether it has clinical implications for the efficacy or toxicity in different populations. This systematic review aims to create an overview of the impact of pharmacogenomics (PGx) on DTG exposure, efficacy, and toxicity.

Methods: Publications up to 14 November 2023 were searched and articles were selected on the following criteria: original research articles providing data on people with HIV, data on PGx and either PK or PD or both PD and PGx.

Cancer-associated fibroblasts, tumor and radiotherapy: interactions in the tumor micro-environment.

Cancer-associated fibroblasts (CAFs) represent a group of genotypically non-malignant stromal cells in the tumor micro-environment (TME) of solid tumors that encompasses up to 80% of the tumor volume. Even though the phenotypic diversity and plasticity of CAFs complicates research, it is well-established that CAFs can affect many aspects of tumor progression, including growth, invasion and therapy resistance. Although anti-tumorigenic properties of CAFs have been reported, the majority of research demonstrates a pro-tumorigenic role for CAFs via (in)direct signaling to cancer cells, immunomodulation and extracellular matrix (ECM) remodeling.

Cumulative incidence of chronic pain after visiting a Dutch emergency department with acute pain.

Background: Chronic pain is a substantial problem in modern healthcare resulting in health care overutilization. The cumulative incidence of developing chronic pain after visiting the emergency department with acute pain has been determined for specific patient groups only. If the cumulative incidence of chronic pain in emergency department patients with acute pain is high, more proactive measures are justified to limit development of chronic pain.

Soft tissue tumor imaging in adults: European Society of Musculoskeletal Radiology-Guidelines 2024: imaging immediately after neoadjuvant therapy in soft tissue sarcoma, soft tissue tumor surveillance, and the role of interventional radiology.

Objectives: An update of the first European Society of Musculoskeletal Radiology (ESSR) consensus on soft tissue tumor imaging in 2015 became necessary due to technical advancements, further insights into specific entities, and the revised WHO classification (2020) and AJCC staging system (2017). The third part of the revised guidelines covers algorithms and techniques beyond initial imaging: (1) Imaging after neoadjuvant therapy in soft tissue sarcoma, (2) sarcoma surveillance, and (3) special aspects, including surveillance of non-malignant entities and the role of interventional radiology.

Materials And Methods: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries.

Hypercoagulation after Hospital Discharge in Acute Severe Ulcerative Colitis: A Prospective Study.

Background & Aims: Venous thromboembolism is a serious complication during and following hospitalization with acute severe ulcerative colitis (ASUC). We evaluated serial thrombotic profiles of patients with ASUC from the point of hospitalization up to 12 weeks post-discharge and compared these with control patients with quiescent UC.

Methods: Twenty-seven patients with ASUC and 25 control patients with quiescent ulcerative colitis (UC) were recruited.

Distinct impact modes of polygenic disposition to dyslexia in the adult brain.

Dyslexia is a common and partially heritable condition that affects reading ability. In a study of up to 35,231 adults, we explored the structural brain correlates of genetic disposition to dyslexia. Individual dyslexia-disposing genetic variants showed distinct patterns of association with brain structure.

Continuous Biosensing to Monitor Acute Systemic Inflammation, a Diagnostic Need for Therapeutic Guidance.

Continuous monitoring of acute inflammation can become a very important next step for guiding therapeutic interventions in severely ill patients. This Perspective discusses the current medical need for patients with acute inflammatory diseases and the potential of continuous biosensing technologies. First, we discuss biomarkers that could help to monitor the state of a patient with acute systemic inflammation based on theoretical studies and empirical data.

Magnetic resonance-guided stereotactic body radiation therapy for pancreatic oligometastases from renal cell carcinoma.

Stereotactic body radiation therapy (SBRT) may be a non-invasive strategy to treat patients with pancreatic oligometastases from renal cell carcinoma (RCC). We analyzed 11 patients treated with MR-guided SBRT to 31 pancreatic oligometastases. At a median follow-up of 31.

Unravelling the art of developing skilled communication: a longitudinal qualitative research study in general practice training.

Doctor-patient communication is a core competency in medical education, which requires learners to adapt their communication flexibly to each clinical encounter. Although conceptual learning models exist, information about how skilled communication develops over time is scant. This study aims to unpack this process of communication learning and to identify its facilitators.

Brain change trajectories in healthy adults correlate with Alzheimer's related genetic variation and memory decline across life.

Throughout adulthood and ageing our brains undergo structural loss in an average pattern resembling faster atrophy in Alzheimer's disease (AD). Using a longitudinal adult lifespan sample (aged 30-89; 2-7 timepoints) and four polygenic scores for AD, we show that change in AD-sensitive brain features correlates with genetic AD-risk and memory decline in healthy adults. We first show genetic risk links with more brain loss than expected for age in early Braak regions, and find this extends beyond APOE genotype.