Insight into distribution and composition of nonhuman N-Glycans in mammalian organs via MALDI-TOF and MALDI-MSI.

The major hurdle of xenotransplantation is the immune response triggered by human natural antibodies interacting with carbohydrate antigens on the transplanted animal organ. Specifically, terminal glycoprotein motifs such as galactose-α1,3-galactose (α-Gal) and N-glycolylneuraminic acid (Neu5Gc) are significant obstacles. Little is known about the abundance and compositions of asparagine-linked complex carbohydrates (N-glycans) carrying these motifs in mammalian organs.

Feasibility of digital phenotyping based on continuous glucose monitoring to support personalized lifestyle medicine in type 2 diabetes.

Objectives: Type 2 diabetes is a highly prevalent age-related chronic condition, with complex and heterogeneous pathogenesis. A 5-point oral glucose tolerance test can identify type 2 diabetes subtypes or "diabetypes" based on the degree of insulin resistance in muscle and/or liver, and beta-cell dysfunction. Due to its costly and invasive nature, the oral glucose tolerance test is not scalable.

Priority Setting Partnership on Placental Pathology: Consensus recommendations for placental research.

Introduction: The placenta supports the metabolic and respiratory requirements of the fetus. Placental disorders, caused by various pathophysiological mechanisms, may result in adverse pregnancy and neonatal outcomes. Knowledge gaps remain in the understanding, reporting and interpretation of placental pathology relating to clinical conditions.

The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).

Background: Many patients with cancer exhibit primary or rapid secondary resistance to targeted therapy (TT). We hypothesized that a higher number of altered oncogenic signaling pathways [pathway alteration load (PAL)] would reduce the benefit of TT which only intervenes in one pathway. This hypothesis was tested in the Drug Rediscovery Protocol (DRUP).

Deintensification of Radiotherapy Use in Treatment of Ductal Carcinoma In Situ in the Netherlands-A Nationwide Overview From 2008 Until 2022.

Aims: Ductal Carcinoma In Situ (DCIS) treated by breast-conserving surgery followed by radiotherapy aims to decrease the probability of locally recurrent disease. The role of whole breast irradiation, specifically in DCIS having low recurrence risk and low risk of becoming invasive, is increasingly debated. Also, the added value of applying boost irradiation in DCIS has been questioned.

Multiple Perspectives on the Need for Real-World Evidence to Inform Regulatory and Health Technology Assessment Decision-Making: Scoping Review and Stakeholder Interviews.

Purpose: Real-world evidence (RWE) is increasingly considered in regulatory and health technology assessment (HTA) decision-making, though perspectives on its relevance may vary. Expanding on a recent review regarding regulatory decisions, this study aimed to identify factors influencing the need for RWE in HTA decision-making, confirm and enrich factors with stakeholder views, and evaluate similarities and differences between regulatory and HTA needs.

Methods: Previous scoping review methodology was used to identify factors influencing the need for RWE in HTA decision-making.

Noninvasive blood-brain barrier integrity mapping in patients with high-grade glioma and metastasis by multi-echo time-encoded arterial spin labeling.

Purpose: In brain tumors, disruption of the blood-brain barrier (BBB) indicates malignancy. Clinical assessment is qualitative; quantitative evaluation is feasible using the K leakage parameter from dynamic susceptibility contrast MRI. However, contrast agent-based techniques are limited in patients with renal dysfunction and insensitive to subtle impairments.

Establishing reference curves for vital tissue perfusion using quantitative near-infrared fluorescence imaging with indocyanine green.

Purpose: Assessment of tissue perfusion using near-infrared fluorescence (NIR) with indocyanine green (ICG) is gaining popularity, however reliable and objective interpretation remains a challenge. Therefore, this study aimed to establish reference curves for vital tissue perfusion across target tissues using this imaging modality.

Methods: Data from five prospective study cohorts conducted in three Dutch academic medical centres between December 2018 and June 2023 was included.

Longitudinal association between nailfold capillaroscopy and incident interstitial lung disease: A EUSTAR database analysis.

Objectives: To evaluate (1) the association between nailfold capillaroscopy pattern and 5-year risk for incident interstitial lung disease and (2) the association between transition in nailfold capillaroscopy pattern and risk of incident interstitial lung disease.

Methods: Data of adult patients from the EUSTAR database fulfilling the ACR-EULAR criteria with a disease duration ⩽5 years, having a scleroderma pattern at nailfold capillaroscopy with high-resolution computed tomography confirmed absence of interstitial lung disease (i.e.

Generation of effective and specific human TCRs against tumor/testis antigen NY-ESO-1 in mice with humanized T cell recognition system.

Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1 restricted to HLA-A*02:01.

A Bibliometric Analysis of the 100 Top-Cited Articles on Vertical Root Fractures.

The aim of this study was to perform a meticulous analysis and bibliometric evaluation of the top 100 most cited articles in vertical root fractures (VRFs). The bibliometric research method included 100 top-cited articles on VRFs retrieved from the Web of Science database. The key terms "vertical root fracture" OR "vertical root fractures" were used to retrieve the required dataset.

Symptom management in isocitrate dehydrogenase mutant glioma.

According to the 2021 World Health Organization classification of CNS tumors, gliomas harboring a mutation in isocitrate dehydrogenase (mIDH) are considered a distinct disease entity, typically presenting in adult patients before the age of 50 years. Given their multiyear survival, patients with mIDH glioma are affected by tumor and treatment-related symptoms that can have a large impact on the daily life of both patients and their caregivers for an extended period of time. Selective oral inhibitors of mIDH enzymes have recently joined existing anticancer treatments, including resection, radiotherapy, and chemotherapy, as an additional targeted treatment modality.

Exploring the potential of the ketogenic diet in autism spectrum disorder: metabolic, genetic, and therapeutic insights.

Current treatment approaches for Autism spectrum disorder (ASD) primarily focus on symptom management rather than addressing underlying dysfunctions. The ketogenic diet (KD), a high-fat, low-carbohydrate diet inducing nutritional ketosis, has shown promise in treating epilepsy and may offer therapeutic benefits for ASD by modulating metabolic and neuroprotective pathways. This review examined the potential impact of KD on underlying mechanisms in ASD.

Evaluation and refinement of thresholds for early migration of total knee replacements as an estimator of late aseptic loosening: an updated systematic review of RSA and survival studies.

Background And Purpose:  This study updates 2 parallel systematic reviews and meta-analyses from 2012, which established the 1-year radiostereometric (RSA) migration thresholds for tibial components of total knee replacements (TKR) based on the risk of late revision for aseptic loosening from survival studies. The primary aim of this study was to determine the (mis)categorization rate of the 2012 thresholds using the updated review as a validation dataset. Secondary aims were evaluation of 6-month migration, mean continuous (1- to 2-year) migration, and fixation-specific thresholds for tibial component migration.

Do P-glycoprotein-mediated drug-drug interactions at the blood-brain barrier impact morphine brain distribution?

P-glycoprotein (P-gp) is a key efflux transporter and may be involved in drug-drug interactions (DDIs) at the blood-brain barrier (BBB), which could lead to changes in central nervous system (CNS) drug exposure. Morphine is a P-gp substrate and therefore a potential victim drug for P-gp mediated DDIs. It is however unclear if P-gp inhibitors can induce clinically relevant changes in morphine CNS exposure.

Gastroesophageal reflux disease is associated with a more severe interstitial lung disease in systemic sclerosis in the EUSTAR cohort.

Objectives: Gastroesophageal reflux disease (GERD) is frequent in systemic sclerosis (SSc) and could predict progression of interstitial lung disease (ILD). We aimed to analyse (1) the prevalence of GERD among SSc-ILD patients, (2) its association with disease characteristics and (3) predictive factors for ILD progression in SSc-ILD patients with GERD.

Methods: SSc patients from the EUSTAR database with ILD were included.

Long-term mortality of Dutch COVID-19 patients admitted to the intensive care medicine: a retrospective analysis from a national quality registry.

Objective: To describe the 12-month mortality of Dutch COVID-19 intensive care unit patients, the total COVID-19 population and various subgroups on the basis of the number of comorbidities, age, sex, mechanical ventilation, and vasoactive medication use.

Methods: We included all patients admitted with COVID-19 between March 1, 2020, and March 29, 2022, from the Dutch National Intensive Care (NICE) database. The crude 12-month mortality rate is presented via Kaplan-Meier survival curves for each patient subgroup.

Double trouble: a comprehensive study into unrelated genetic comorbidities in adult patients with Facioscapulohumeral Muscular Dystrophy Type I.

Facioscapulohumeral dystrophy type 1 (FSHD1) displays prominent intra- and interfamilial variability, which complicates the phenotype-genotype correlation. In this retrospective study, we investigated FSHD1 patients classified as category D according to the Comprehensive Clinical Evaluation Form (CCEF), a category defined by FSHD patients showing uncommon clinical features, to identify genetic causes explaining these uncommon phenotypes. Demographics, clinical data and clinical scales of FSHD1 patients were retrospectively evaluated.

Dielectric profile at the Pt(111)/water interface.

The dielectric constant, although a simplified concept when considering atomic scales, enters many mean-field, electrochemical interface models and constant potential models as an important parameter. Here, we use ab initio and machine-learned molecular dynamics to scrutinize the behavior of the electronic contribution to ɛr(z) as a function of distance z from a Pt(111) surface. We show that the resulting dielectric profile can largely be explained as a sum of the metallic response and the density-scaled water response at the interface.

Maximizing expectancy violation and exposure outcomes in patients with PTSD.

It has been proposed that maximizing expectancy violation enhances the efficacy of exposure therapy. The clinical utility of expectancy violation remains unclear and it has not yet been studied in PTSD. We aimed to test whether explicitly focusing on expectancy violation leads to superior exposure outcomes.

A case of developmental topographical disorientation: impact on diagnostic trajectory and everyday life.

Developmental Topographical Disorientation (DTD) refers to impaired ability to create and consult mental maps in the absence of neurological abnormalities. We present the case study of I.S.