Proximity adjusted centroid mapping for accurate detection of nuclei in dense 3D cell systems.

In the past decade, deep learning algorithms have surpassed the performance of many conventional image segmentation pipelines. Powerful models are now available for segmenting cells and nuclei in diverse 2D image types, but segmentation in 3D cell systems remains challenging due to the high cell density, the heterogenous resolution and contrast across the image volume, and the difficulty in generating reliable and sufficient ground truth data for model training. Reasoning that most image processing applications rely on nuclear segmentation but do not necessarily require an accurate delineation of their shapes, we implemented Proximity Adjusted Centroid MAPping (PAC-MAP), a 3D U-net based method that predicts the position of nuclear centroids and their proximity to other nuclei.

An agarose fluidic chip for high-throughput organoid imaging.

Modern cell and developmental biology increasingly relies on 3D cell culture systems such as organoids. However, routine interrogation with microscopy is often hindered by tedious, non-standardized sample mounting, limiting throughput. To address these bottlenecks, we have developed a pipeline for imaging intact organoids in flow, utilizing a transparent agarose fluidic chip that enables efficient and consistent recordings with theoretically unlimited throughput.

International consensus statement on microbiome testing in clinical practice.

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value.

Non-utopian optical properties computed of a tomographically reconstructed real photonic nanostructure.

State-of-the-art computational methods combined with common idealized structural models provide an incomplete understanding of experimental observations on real nanostructures, since manufacturing introduces unavoidable deviations from the design. We propose to close this knowledge gap by using the real structure of a manufactured nanostructure as input in computations to obtain a realistic comparison with measurements on the same nanostructure. We demonstrate this approach on the structure of a real inverse woodpile photonic bandgap crystal made from silicon, as previously obtained by synchrotron X-ray imaging.

Single-cell analysis of osmoregulation reveals heterogeneity of aquaporin 4 functionality in human astrocytes.

The water channel aquaporin 4 (AQP4) contributes to water flow and waste removal across the blood-brain barrier and its levels, organization and localization are perturbed in various neurological diseases, including Alzheimer's Disease. This renders AQP4 a potentially valuable therapeutic target. However, most functional assays aimed at identifying modulators of AQP4 function are performed with primary rodent cells and do not consider inter-cellular variations in AQP4 abundance and presentation.

Nanocomposite membrane for simultaneous removal of dye and heavy metal ions from wastewater.

A catalytic 2D nanocomposite membrane (CNC) was fabricated and used for the simultaneous removal of methylene blue (MB) and heavy metal ions in aqueous solution. Both molybdenum disulfide (MoS) and graphene oxide (GO) were incorporated in a chitosan polymer matrix, and the fabricated CNC membrane exhibited performance as a nanofiltration membrane. Here MoS activated HO to generate very reactive oxygen species (ROS), such as hydroxyl radicals, allowing the catalytic breakdown of the organic dye contaminants and reducing heavy metal ions.

Mental health and its consequences in people living with HIV: A network approach.

Objectives: Psychiatric symptoms occur frequently in people living with human immunodeficiency virus (PLWH), which may affect quality of life, sexual risk behavior, and adherence to antiretroviral therapy (ART). Data from large cohorts are limited, and symptoms are often analyzed in isolation. Therefore, we applied a network analysis to assess the interrelatedness of mental health indicators in a large cohort of PLWH.

Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study.

Background: Insights into the mechanisms driving metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLHIV) remain limited. Plasma proteomics holds promise for biomarker discovery and the elucidation of biological mechanisms.

Methods: We performed cross-sectional analyses on data from 1036 virally suppressed PLHIV using antiretroviral treatment (ART) from the Dutch multi-centre 2000HIV cohort.

Evolution of aberrant brain-wide spatiotemporal dynamics of resting-state networks in a Huntington's disease mouse model.

Background: Huntington's disease (HD) is marked by irreversible loss of neuronal function for which currently no availability for disease-modifying treatment exists. Advances in the understanding of disease progression can aid biomarker development, which in turn can accelerate therapeutic discovery.

Methods: We characterised the progression of altered dynamics of whole-brain network states in the zQ175DN mouse model of HD using a dynamic functional connectivity (FC) approach to resting-state fMRI and identified quasi-periodic patterns (QPPs) of brain activity constituting the most prominent resting-state networks.

Omics-based analysis of cultivation in food-grade media.

Over the past years, the gut microbiota and its correlation to health and disease has been studied extensively. In terms of beneficial microbes, an increased interest in () has been observed since its discovery. Direct evidence for the role of in host health has been provided in both mice and human studies.

Analysis of the fermentation kinetics and gut microbiota modulatory effect of dried chicory root reveals the impact of the plant-cell matrix rationalizing its conversion in the distal colon.

The cell matrix of plant foods has received little attention in prebiotic fiber research. We aimed to understand the impact of the plant cell matrix in dried chicory root on its breakdown in the human gut to explain its reported beneficial effects on gut and metabolic health. We applied digestion and fermentation models together with an gut barrier integrity model.

Calciprotein particles induce arterial stiffening ex vivo and impair vascular cell function.

Calciprotein particles (CPPs) are an endogenous buffering system, clearing excessive amounts of Ca and PO from the circulation and thereby preventing ectopic mineralization. CPPs circulate as primary CPPs (CPP1), which are small spherical colloidal particles, and can aggregate to form large, crystalline, secondary CPPs (CPP2). Even though it has been reported that CPPs are toxic to vascular smooth muscle cells (VSMC) in vitro, their effect(s) on the vasculature remain unclear.

Gut microbiota wellbeing index predicts overall health in a cohort of 1000 infants.

The human gut microbiota is central in regulating all facets of host physiology, and in early life it is thought to influence the host's immune system and metabolism, affecting long-term health. However, longitudinally monitored cohorts with parallel analysis of faecal samples and health data are scarce. In our observational study we describe the gut microbiota development in the first 2 years of life and create a gut microbiota wellbeing index based on the microbiota development and health data in a cohort of nearly 1000 infants using clustering and trajectory modelling.

Enhancing the Separation Performance of Cellulose Membranes Fabricated from 1-Ethyl-3-methylimidazolium Acetate by Introducing Acetone as a Co-Solvent.

Cellulose, a sustainable raw material, holds great promise as an ideal candidate for membrane materials. In this work, we focused on establishing a low-cost route for producing cellulose microfiltration membranes by adopting a co-solvent system comprising the ionic liquid 1-ethyl-3-methylimidazolium acetate ([EMIM]OAc) and acetone. The introduction of acetone as a co-solvent into the casting solution allowed control over the viscosity, thereby significantly enhancing the morphologies and filtration performances of the resulting cellulose membranes.

The risk of non-AIDS defining events is lower in ART-naive HIV controllers than in normal progressors on suppressive ART.

Background: We aimed to compare the non-AIDS events (nADE) risk between normal progressors using ART (NP-ART) and people with HIV (PWH) that naturally control HIV infection (HIV controllers), as well as the outcomes after ART in HIV controllers on nADE.

Methods: The primary endpoint was major nADE defined as the composite of cardiovascular disease, non-AIDS malignancy or all-cause mortality, whichever came first..

From SPECT/CT towards absolute quantification? - the case of unilateral condylar hyperplasia of the mandible.

Background: Unilateral condylar hyperplasia (UCH) of the mandible is a rare condition characterized by asymmetric growth of the mandibular condyles. Bone scintigraphy with SPECT(/CT) is commonly used to diagnose UCH and guide treatment. Still, varying results have been reported using the traditional threshold of 55%:45% in relative tracer uptake.

Ferroptosis is a targetable detrimental factor in metabolic dysfunction-associated steatotic liver disease.

There is an unmet clinical need for pharmacologic treatment for metabolic dysfunction-associated steatotic liver disease (MASLD). Hepatocyte cell death is a hallmark of this highly prevalent chronic liver disease, but the dominant type of cell death remains uncertain. Here we report that ferroptosis, an iron-catalyzed mode of regulated cell death, contributes to MASLD.

Inhibition of hepatic bile salt uptake by Bulevirtide reduces atherosclerosis in Oatp1a1Ldlr mice.

Bile salts can strongly influence energy metabolism through systemic signaling, which can be enhanced by inhibiting the hepatic bile salt transporter Na taurocholate cotransporting polypeptide (NTCP), thereby delaying hepatic reuptake of bile salts to increase systemic bile salt levels. Bulevirtide is an NTCP inhibitor and was originally developed to prevent NTCP-mediated entry of Hepatitis B and D into hepatocytes. We previously demonstrated that NTCP inhibition lowers body weight, induces glucagon-like peptide-1 (GLP1) secretion, and lowers plasma cholesterol levels in murine obesity models.

Transcriptomic and proteomic profiling of bi-partite and tri-partite murine iPSC-derived neurospheroids under steady-state and inflammatory condition.

induced-pluripotent stem cell (iPSC)-derived neurospheroid (NSPH) models are an emerging in vitro toolkit to study the influence of inflammatory triggers on neurodegeneration and repair in a 3D neural environment. In contrast to their human counterpart, the absence of murine iPSC-derived NSPHs for profound characterisation and validation studies is a major experimental research gap, even though they offer the only possibility to truly compare or validate in vitro NSPH responses with in vivo brain responses. To contribute to these developments, we here describe the generation and characterisation of 5-week-old CXCR1 CCR2 murine (m)iPSC-derived bi-partite (neurons + astrocytes) and tri-partite (neurons + astrocytes + microglia) NSPH models that can be subjected to cellular activation following pro-inflammatory stimulation.