Perfusion Pressures and Weight Loss During Normothermic Machine Perfusion of Human Donor Livers.

Background: Normothermic machine perfusion (NMP) is increasingly used to preserve and assess donor livers prior to transplantation. Due to its success, it is expected that more centers will start using this technology. However, NMP may also cause adverse effects.

Genome-wide meta-analysis associates donor-recipient non-HLA genetic mismatch with acute cellular rejection post-liver transplantation.

Background: Acute cellular rejection (ACR) remains a common complication causing significant morbidity post-liver transplantation. Non-human leukocyte antigen (non-HLA) mismatches were associated with an increased risk of ACR in kidney transplantation. Therefore, we hypothesized that donor-recipient non-HLA genetic mismatch is associated with increased ACR incidence post-liver transplantation.

Brain magnetic resonance imaging of patients with spinal muscular atrophy type 2 and 3.

Background And Objective: Proximal spinal muscular atrophy (SMA) is caused by deficiency of the ubiquitously expressed survival motor neuron protein. Although primarily a hereditary lower motor neuron disease, it is probably also characterized by abnormalities in other organs. Brain abnormalities and cognitive impairment have been reported in severe SMA.

Divergent WNT signaling and drug sensitivity profiles within hepatoblastoma tumors and organoids.

Hepatoblastoma, the most prevalent pediatric liver cancer, almost always carries a WNT-activating CTNNB1 mutation, yet exhibits notable molecular heterogeneity. To characterize this heterogeneity and identify novel targeted therapies, we perform comprehensive analysis of hepatoblastomas and tumor-derived organoids using single-cell RNA-seq/ATAC-seq, spatial transcriptomics, and high-throughput drug profiling. We identify two distinct tumor epithelial signatures: hepatic 'fetal' and WNT-high 'embryonal', displaying divergent WNT signaling patterns.

Polyradiculitis as a Neurological Complication Associated with Adagrasib: A Case Report.

Introduction: Adagrasib is an upcoming anticancer treatment for KRAS G12C-mutated non-small-cell lung carcinoma, colorectal cancer and potentially other solid tumors harboring this mutation. It is generally well-tolerated and reports of neurological adverse events so far have been limited.

Case Presentation: We present to our best knowledge the first case of a 70-year-old woman who was admitted with polyradiculitis as a treatment-related complication of adagrasib.

Improving Infant Mental Health: A Pilot Study on the Effectiveness, Acceptability and Feasibility of Eye Movement Desensitization and Reprocessing (EMDR) Storytelling in Infants With Post-traumatic Distress After Medical Procedures.

Although the prevalence of symptoms of post-traumatic stress disorder (PTSD) in infants and young children is similar as in older age groups, and PTSD intervention is as important in this age group, research on PTSD-treatment in infants is very scarce. Eye Movement Desensitization and Reprocessing (EMDR) Storytelling is a trauma-focused treatment that is being used by clinicians for infants with PTSD-symptoms. The aim was to assess the feasibility, acceptability and initial indications of effectiveness of EMDR Storytelling for infants aged 3-24 months with PTSD-symptoms after medical procedures.

Polyconnectomic Scoring of Functional Connectivity Patterns Across Eight Neuropsychiatric and Three Neurodegenerative Disorders.

Background: Neuropsychiatric and neurodegenerative disorders involve diverse changes in brain functional connectivity. As an alternative to approaches that search for specific mosaic patterns of affected connections and networks, we used polyconnectomic scoring to quantify disorder-related whole-brain connectivity signatures into interpretable, personalized scores.

Methods: The polyconnectomic score (PCS) measures the extent to which an individual's functional connectivity mirrors the whole-brain circuitry characteristics of a trait.

Associations between white matter microstructure and cognitive decline in major depressive disorder versus controls in Germany: a prospective case-control cohort study.

Background: Cognitive deficits are a key source of disability in individuals with major depressive disorder (MDD) and worsen with disease progression. Despite their clinical relevance, the underlying mechanisms of cognitive deficits remain poorly elucidated, hampering effective treatment strategies. Emerging evidence suggests that alterations in white matter microstructure might contribute to cognitive dysfunction in MDD.

A comparison of the renal function biomarkers serum creatinine, pro-enkephalin and cystatin C to predict clearance of pemetrexed.

Introduction: For drugs with a narrow therapeutic window, there is a delicate balance between efficacy and toxicity, thus it is pivotal to administer the right dose from the first administration onwards. Exposure of pemetrexed, a cytotoxic drug used in lung cancer treatment, is dictated by kidney function. To facilitate optimized dosing of pemetrexed, accurate prediction of drug clearance is pivotal.

Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET-Mutated Non-Small Cell Lung Cancer-Results from the Drug Rediscovery Protocol.

Purpose: To provide patients with MET-mutated advanced non-small cell lung cancer (METmut aNSCLC) access to crizotinib, further substantiate evidence of its efficacy and safety in this setting, and find potential biomarkers for nonresponse.

Patients And Methods: In the Drug Rediscovery Protocol (NCT0295234), patients with an actionable molecular profile are treated with off-label registered drugs. Both treated and untreated patients with aNSCLC harboring MET exon 14 skipping or other MET mutations received crizotinib 250 mg BID until disease progression or intolerable toxicity.

Smart, sustainable, and circular port maintenance: A comprehensive framework and multi-stakeholder approach.

Ports and waterways are key in supporting the waterborne supply chains that form the backbone of global trade. Maintaining adequate water depth is vital for accessibility and safe navigation. Port authorities and contractors are the key players in developing maintenance strategies, and they strive for a mutually beneficial compromise.

Cost-effectiveness analysis of a lung cancer screening program in the netherlands: a simulation based on NELSON and NLST study outcomes.

Background: In the Netherlands, lung cancer is the leading cause of cancer-related death, accounting for more than 10,000 annual deaths. Lung cancer screening (LCS) studies using low-dose computed tomography (LDCT) have demonstrated that early detection reduces lung cancer mortality. However, no LCS program has been implemented yet in the Netherlands.

Development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry method to quantify the small molecule inhibitors adagrasib, alectinib, brigatinib, capmatinib, crizotinib, lorlatinib, selpercatinib, and sotorasib in human plasma.

Small molecule inhibitors (SMIs) are increasingly being used in the treatment of non-small cell lung cancer. To support pharmacokinetic research and clinical treatment monitoring, our aim was to develop and validate an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay for quantification of eight SMIs: adagrasib, alectinib, brigatinib, capmatinib, crizotinib, lorlatinib, selpercatinib, and sotorasib. Development of the UPLC-MS/MS assay was done by trying different columns and eluents to optimize peak shape.

Trait mindfulness during pregnancy and maternal-infant bonding: Longitudinal associations with infant temperament and social-emotional development.

Maternal love and caregiving are pillars for optimal child development and may affect infant outcomes from pregnancy onwards. The present study aimed to examine whether maternal trait mindfulness during pregnancy and pre- and postnatal maternal-infant bonding were associated with maternal perceptions of infant temperament and social-emotional development. In total, 408 Dutch women (M = 31.

An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab.

Background: Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase.

Head-to-head comparison of composite and individual biomarkers to predict clinical benefit to PD-1 blockade in non-small cell lung cancer.

Background: The efficacy of PD-1 blocking agents in advanced NSCLC has shown prolonged effectiveness, but only in a minority of patients. Multiple biomarkers have been explored to predict treatment benefit, yet their combined performance remains inadequately examined. In this study, we assessed the combined predictive performance of multiple biomarkers in NSCLC patients treated with nivolumab.

Optimising primary molecular profiling in non-small cell lung cancer.

Introduction: Molecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting.

Age Trajectories of the Structural Connectome in Child and Adolescent Offspring of Individuals With Bipolar Disorder or Schizophrenia.

Background: Offspring of parents with severe mental illness (e.g., bipolar disorder or schizophrenia) are at elevated risk of developing psychiatric illness owing to both genetic predisposition and increased burden of environmental stress.

Insomnia Subtypes Have Differentiating Deviations in Brain Structural Connectivity.

Background: Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within the insomnia population could obscure detection of involved brain circuits.

Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan.

Background: The antibody-drug conjugate sacituzumab govitecan is approved for metastatic triple-negative breast cancer and has shown promising results in various other types of cancer. Its costs may limit patient access to this novel effective treatment modality.

Objective: The purpose of this study was to develop an evidence-based rational dosing regimen that results in targeted drug exposure within the therapeutic range while minimizing financial toxicity, to improve treatment access.

Proactive monitoring of drug-drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer.

Background: Small-molecule inhibitors (SMIs) have revolutionised the treatment of non-small cell lung cancer (NSCLC). However, SMI-induced drug-drug interactions (DDIs) with frequently co-administered direct oral anticoagulants (DOACs), increase thromboembolic and bleeding risks. This study investigated and proactively managed the consequences of DOAC-SMI DDIs.