From promise to practice: CAR T and Treg cell therapies in autoimmunity and other immune-mediated diseases.

Autoimmune diseases, characterized by the immune system's attack on the body's own tissues, affect millions of people worldwide. Current treatments, which primarily rely on broad immunosuppression and symptom management, are often associated with significant adverse effects and necessitate lifelong therapy. This review explores the next generation of therapies for immune-mediated diseases, including chimeric antigen receptor (CAR) T cell and regulatory T cell (Treg)-based approaches, which offer the prospect of targeted, durable disease remission.

Developing a European framework for the prevention of communicable diseases: three points for attention.

The capacity to deliver programmes that prevent and control infectious diseases is a key public health function. The European Centre for Disease Prevention and Control (ECDC) aims to support and strengthen this capacity in European Union/ European Economic Area (EU/EEA) countries as part of its 2021-27 strategy which includes explicit attention to social and behavioural aspects of disease prevention. To achieve its strategic goals, it is important that ECDC improves its knowledge of prevention strategies, actors and activities in EU/EEA countries.

Treatment of Renal Artery Aneurysm by ex situ Repair and Autotransplantation: A Nationwide Cohort Study.

Introduction: Renal artery aneurysm (RAA) is a rare vascular disease with a mortality rate of up to 80% upon rupture. This study aimed to investigate the safety and efficacy of ex situ repair and autotransplantation for endovascularly untreatable RAA.

Methods: A retrospective nationwide cohort study was conducted in RAA patients undergoing ex situ repair and autotransplantation in the Netherlands.

Modeling the atrioventricular conduction axis using human pluripotent stem cell-derived cardiac assembloids.

The atrioventricular (AV) conduction axis provides electrical continuity between the atrial and ventricular chambers. The "nodal" cardiomyocytes populating this region (AV canal in the embryo, AV node from fetal stages onward) propagate impulses slowly, ensuring sequential contraction of the chambers. Dysfunction of AV nodal tissue causes severe disturbances in rhythm and contraction, and human models that capture its salient features are limited.

Impact of device variability and protocol differences on kidney function during normothermic machine perfusion: A comparative study using porcine and human kidneys.

Introduction: A growing interest in renal normothermic machine perfusion (NMP) has resulted in more clinically available perfusion devices. While all perfusion systems have the same aim, there are significant differences in their circuits, pumps, sensors, and software. Therefore, our objective was to assess the impact of different perfusion protocols and devices on kidney function and perfusion parameters during NMP.

Dental topography of prosimian premolars predicts diet: A comparison in premolar and molar dietary classification accuracies.

Objectives: This study tests whether (1) premolar topography of extant "prosimians" (strepsirrhines and tarsiers) successfully predicts diet and (2) whether the combination of molar and premolar topography yields higher classification accuracy than using either tooth position in isolation.

Materials And Methods: Dental topographic metrics (ariaDNE, relief index, and orientation patch count rotated) were calculated for 118 individual matched-pairs of mandibular fourth premolars (P) and second molars (M). The sample represents 7 families and 22 genera.

Prediction of Disease Progression and Clinical Response in Systemic Sclerosis: Experience From a Proof-of-Concept Trial.

Objective: Using the modified Rodnan skin score (mRSS) as a surrogate for disease activity, a phase 2a study in patients with systemic sclerosis (SSc) measured efficacy of the autotaxin inhibitor ziritaxestat. Mathematical modeling of mRSS was used to predict disease progression, examine candidate trial designs, and predict the probability of successfully discriminating treatment effect.

Methods: Patients with SSc receiving 600 mg of ziritaxestat or placebo for 24 weeks were included, in addition to data up to week 52 of the open-label extension (OLE).

Effective and safe implementation of robot-assisted donor nephrectomy by experienced laparoscopic surgeons.

Background: In June 2021, the first robot-assisted donor nephrectomy (RADN) was performed at the Leiden University Medical Center (LUMC), the Netherlands. The goal of this study was to investigate whether this procedure has been implemented safely and efficiently.

Methods: RADN was retrospectively compared to laparoscopic donor nephrectomy (LDN) performed during the same time period (June 2021 until November 2022).

A cell-free nutrient-supplemented perfusate allows four-day ex vivo metabolic preservation of human kidneys.

The growing disparity between the demand for transplants and the available donor supply, coupled with an aging donor population and increasing prevalence of chronic diseases, highlights the urgent need for the development of platforms enabling reconditioning, repair, and regeneration of deceased donor organs. This necessitates the ability to preserve metabolically active kidneys ex vivo for days. However, current kidney normothermic machine perfusion (NMP) approaches allow metabolic preservation only for hours.

Red blood cells as oxygen carrier during normothermic machine perfusion of kidney grafts: Friend or foe?

Renal ex vivo normothermic machine perfusion (NMP) is under development as an assessment tool for high-risk kidney grafts and as a means of achieving more physiologically accurate organ preservation. On-going hemolysis has been reported during NMP, as this technique relies on red blood cells for oxygen delivery. In this study, we confirm the occurrence of progressive hemolysis during 6-hour kidney NMP.

COVID-19 in a Dutch Nursing Home: A Longitudinal Retrospective Care-Home-Level Case Study on Infection Rate, Survival Rate, and Daily Functioning.

During the pandemic, nursing homes in the Netherlands were heavily affected by COVID-19. This study assesses the impact of COVID-19 on infection rate, survival rate, and daily functioning over the course of two years among residents of a nursing home in the Netherlands that was amongst the first nursing homes to be affected by the pandemic. This retrospective study followed 70 residents during a two-year period, starting in March 2020.

Complex Evolutionary History With Extensive Ancestral Gene Flow in an African Primate Radiation.

Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants.

Endothelial to mesenchymal transition in kidney fibrosis.

Fibrotic diseases are characterized by the uncontrolled accumulation of extracellular matrix (ECM) components leading to disruption of tissue homeostasis. Myofibroblasts as the main ECM-producing cells can originate from various differentiated cell types after injury. Particularly, the process of endothelial-to-mesenchymal transition (endMT), describing phenotypic shifts of endothelial cells to adopt a fully mesenchymal identity, may contribute to the pool of myofibroblasts in fibrosis, while leading to capillary rarefaction and exacerbation of tissue hypoxia.

Retention of military combat lifesaving skills during six months following classroom-style and individualized-style initial training.

The current study was performed to obtain insight into the retention of combat lifesaving (CLS) skills after initial training and to compare a more individualized-style training with a more classroom-style training. We measured performance at 0 month, 2 months, and 6 months after initial training in 40 CLSers (17 individualized, 23 classroom). Each test consisted of two 20-minute scenarios with a medical mannequin to simulate combat injuries.

Sexual Distancing During 5 Periods Around and During the COVID-19 Pandemic, Amsterdam, the Netherlands.

Background: Social and sexual distancing (ie, abstaining from sex with persons outside one's household) was important in the control of the COVID-19 pandemic. Compliance to distancing measures can change over time. We assessed changes in compliance to the sexual distancing measures during five periods of the COVID-19 pandemic in the Netherlands.

The Integration of Social Science for Community Engagement in the Humanitarian Fields of Conflicts and Disasters: A Scoping Review.

Community engagement (CE) is essential to humanitarian assistance, and the social sciences have been credited in recent epidemics and disease outbreaks as having played a crucial, supportive role. Broadening this attention to other humanitarian fields, this scoping review asks what lessons learned can be found in grey and peer-reviewed literature on the integration of the social sciences in CE for conflicts and disasters. Using an analytical framework developed through a UNICEF-led project called Social Science for Community Engagement (SS4CE) in Humanitarian Action, we identified 1093 peer reviewed publications and 315 grey literature reports of possible relevance.

Comparison of 2 Immunosuppression Minimization Strategies in Kidney Transplantation: The ALLEGRO Trial.

Background: Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited.

Methods: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation.

A global catalog of whole-genome diversity from 233 primate species.

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families.

The landscape of tolerated genetic variation in humans and primates.

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans.

The landscape of tolerated genetic variation in humans and primates.

Unlabelled: Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human.

Identification of genetic variants that impact gene co-expression relationships using large-scale single-cell data.

Background: Expression quantitative trait loci (eQTL) studies show how genetic variants affect downstream gene expression. Single-cell data allows reconstruction of personalized co-expression networks and therefore the identification of SNPs altering co-expression patterns (co-expression QTLs, co-eQTLs) and the affected upstream regulatory processes using a limited number of individuals.

Results: We conduct a co-eQTL meta-analysis across four scRNA-seq peripheral blood mononuclear cell datasets using a novel filtering strategy followed by a permutation-based multiple testing approach.

A comparison of myocardial magnetic resonance extracellular volume mapping at 3 T against histology of tissue collagen in severe aortic valve stenosis and obstructive hypertrophic cardiomyopathy.

Objective: Quantitative extracellular volume fraction (ECV) mapping with MRI is commonly used to investigate in vivo diffuse myocardial fibrosis. This study aimed to validate ECV measurements against ex vivo histology of myocardial tissue samples from patients with aortic valve stenosis or hypertrophic cardiomyopathy.

Materials And Methods: Sixteen patients underwent MRI examination at 3 T to acquire native T maps and post-contrast T maps after gadobutrol administration, from which hematocrit-corrected ECV maps were estimated.