Clinical Outcomes in Pediatric Patients With Type 1 Diabetes With Early Versus Late Diagnosis: Analysis From the DPV Registry.

Objective: This study was conducted to evaluate the effects of early clinical diagnosis of type 1 diabetes by comparison of clinical parameters at diagnosis and during follow-up in patients with pediatric type 1 diabetes with early, intermediate, and late diagnosis.

Research Design And Methods: In a population-based analysis, data on 14,292 pediatric patients with type 1 diabetes diagnosed between 2015 and 2019 were retrieved from the Diabetes Prospective Documentation (DPV) registry in March 2023. Patients were divided into four groups: one with diabetic ketoacidosis (DKA) at diagnosis and three with early, intermediate, or late diagnosis based on age-dependent HbA1c terciles.

Identification of circulating miRNAs as fracture-related biomarkers.

Fracture non-unions affect many patients worldwide, however, known risk factors alone do not predict individual risk. The identification of novel biomarkers is crucial for early diagnosis and timely patient treatment. This study focused on the identification of microRNA (miRNA) related to the process of fracture healing.

Metabolic control during the first two years of the COVID-19 pandemic in pediatric patients with type 1 diabetes: results from the German DPV initiative.

Aim: To assess effects of the SARS-CoV2 pandemic on metabolic control in youth with type 1 diabetes (T1D) in Germany in a population-based analysis.

Methods: Data from 33,372 pediatric T1D patients from the Diabetes Prospective Follow-up (DPV) registry, with face-to-face visits or telemedicine contacts in the years 2019-2021, were available. Datasets from eight time periods between March 15, 2020, and December 31, 2021, according to SARS-CoV2 incidence waves, were compared to those from five control time periods.

Prevalence of type 1 and type 2 diabetes in children and adolescents in Germany from 2002 to 2020: A study based on electronic health record data from the DPV registry.

Background: To provide estimates of the nationwide prevalence of type 1 diabetes (T1D) and type 2 diabetes (T2D) in individuals younger than 20 years of age in Germany from 2002 to 2020 and to identify trends.

Methods: Data were obtained from the electronic health record "Diabetes Prospective Follow-up Registry (DPV)" specific to diabetes care. Prevalence was estimated based on prevalent cases at the end of each year for the years 2002, 2008, 2014, and 2020 per 100 000 persons assuming a Poisson distribution and directly age- and/or sex-standardized to the population in 2020.

Spatio-temporal predictions of COVID-19 test positivity in Uppsala County, Sweden: a comparative approach.

Previous spatio-temporal COVID-19 prediction models have focused on the prediction of subsequent number of cases, and have shown varying accuracy and lack of high geographical resolution. We aimed to predict trends in COVID-19 test positivity, an important marker for planning local testing capacity and accessibility. We included a full year of information (June 29, 2020-July 4, 2021) with both direct and indirect indicators of transmission, e.

Venous injection of a triphasic calcium-based implant in a sheep model of pulmonary embolism demonstrates minimal acute systemic effects.

Purpose: Implant leakage is the most common complication of vertebral augmentation. Alternative injectable materials must demonstrate intravascular safety comparable to or better than polymethyl methacrylate (PMMA). This study assessed the systemic effects of a triphasic calcium-based implant or PMMA injected directly into the femoral vein in a large animal model designed to mimic severe intravascular implant leakage.

scAmpi-A versatile pipeline for single-cell RNA-seq analysis from basics to clinics.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful technique to decipher tissue composition at the single-cell level and to inform on disease mechanisms, tumor heterogeneity, and the state of the immune microenvironment. Although multiple methods for the computational analysis of scRNA-seq data exist, their application in a clinical setting demands standardized and reproducible workflows, targeted to extract, condense, and display the clinically relevant information. To this end, we designed scAmpi (Single Cell Analysis mRNA pipeline), a workflow that facilitates scRNA-seq analysis from raw read processing to informing on sample composition, clinically relevant gene and pathway alterations, and in silico identification of personalized candidate drug treatments.

In Vitro Evaluation of a Nanoparticle-Based mRNA Delivery System for Cells in the Joint.

Biodegradable and bioresponsive polymer-based nanoparticles (NPs) can be used for oligonucleotide delivery, making them a promising candidate for mRNA-based therapeutics. In this study, we evaluated and optimized the efficiency of a cationic, hyperbranched poly(amidoamine)s-based nanoparticle system to deliver tdTomato mRNA to primary human bone marrow stromal cells (hBMSC), human synovial derived stem cells (hSDSC), bovine chondrocytes (bCH), and rat tendon derived stem/progenitor cells (rTDSPC). Transfection efficiencies varied among the cell types tested (bCH 28.

[Corona and globalization: Arrested developmentCorona et la mondialisation enchaînée].

The term "globalization" doesn't refer to a current epoch of world history, but to an undulated process interrupted by harsh setbacks. Its phases of upswing are characterized by exponential growth. They end when tipping points arrive.

Collection and preprocessing of fine needle aspirate patient samples for single cell profiling and data analysis.

High cell viability and recovered cell concentration are typical quality control requirements for single-cell processing and quality data. This protocol describes procedures for sampling, live-cell biobanking, preprocessing for single-cell RNA sequencing, and analysis of fine-needle aspiration (FNA) samples of the skin. The minimally invasive nature of FNA collection is more accepted by patients and allows for frequent longitudinal sampling, resulting in high-quality single-cell sequencing data that capture cellular heterogeneity in clinical samples.

Oncolytic virotherapy-mediated anti-tumor response: a single-cell perspective.

Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex 1 virus (HSV-1) approved for cancer therapy. We investigate its effect on the clinical, histological, single-cell transcriptomic, and immune repertoire level using repeated fine-needle aspirates (FNAs) of injected and noninjected lesions in primary cutaneous B cell lymphoma (pCBCL). Thirteen patients received intralesional T-VEC, 11 of which demonstrate tumor response in the injected lesions.

The Tumor Profiler Study: integrated, multi-omic, functional tumor profiling for clinical decision support.

The application and integration of molecular profiling technologies create novel opportunities for personalized medicine. Here, we introduce the Tumor Profiler Study, an observational trial combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making with an exploratory approach to improve the biological understanding of the disease.

Early versus delayed insulin pump therapy in children with newly diagnosed type 1 diabetes: results from the multicentre, prospective diabetes follow-up DPV registry.

Background: Although continuous subcutaneous insulin infusion therapy (ie, insulin pump therapy) is associated with improved metabolic control compared with multiple daily insulin injections in children with type 1 diabetes, it is unclear when it is best to start it after diagnosis. In this study, we aimed to compare the outcomes between early and delayed start of insulin pump therapy in young patients with type 1 diabetes.

Methods: We based the current study on data from the multicentre, prospective diabetes follow-up registry (ie, Diabetes-Patienten-Verlaufsdokumentation [DPV]).

IgM Antibody Repertoire Fingerprints in Mice Are Personalized but Robust to Viral Infection Status.

Antibody repertoire sequencing provides a molecular fingerprint of current and past pathogens encountered by the immune system. Most repertoire studies in humans require measuring the B cell response in the blood, resulting in a large bias to the IgM isotype. The extent to which the circulating IgM antibody repertoire correlates to lymphoid tissue-resident B cells in the setting of viral infection remains largely uncharacterized.

Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow.

At present, it is not clear how memory B lymphocytes are maintained over time, and whether only as circulating cells or also residing in particular tissues. Here we describe distinct populations of isotype-switched memory B lymphocytes (Bsm) of murine spleen and bone marrow, identified according to individual transcriptional signature and B cell receptor repertoire. A population of marginal zone-like cells is located exclusively in the spleen, while a population of quiescent Bsm is found only in the bone marrow.

Differential Regulation of circRNA, miRNA, and piRNA during Early Osteogenic and Chondrogenic Differentiation of Human Mesenchymal Stromal Cells.

The goal of the present study is to identify the differential expression of circular RNA (circRNA), miRNA, and piwi-interacting RNA (piRNA) after lineage commitment towards osteo- and chondrogenesis of human bone marrow mesenchymal stromal cells (hMSCs). The cells were maintained for 7 days in either osteogenic or chondrogenic medium. RNA sequencing was performed to assess the expression of miRNA and piRNA, while RNA hybridization arrays were used to identify which circRNA were differentially expressed.

Quantitative and Qualitative Analysis of Humoral Immunity Reveals Continued and Personalized Evolution in Chronic Viral Infection.

Control of established chronic lymphocytic choriomeningitis virus (LCMV) infection requires the production of neutralizing antibodies, but it remains unknown how the ensemble of antibodies evolves during ongoing infection. Here, we analyze the evolution of antibody responses during acute or chronic LCMV infection, combining quantitative functional assays and time-resolved antibody repertoire sequencing. We establish that antibody responses initially converge in both infection types on a functional and repertoire level, but diverge later during chronic infection, showing increased clonal diversity, the appearance of mouse-specific persistent clones, and distinct phylogenetic signatures.

Chronic Viral Infection Promotes Efficient Germinal Center B Cell Responses.

Persistent viral infections subvert key elements of adaptive immunity. To compare germinal center (GC) B cell responses in chronic and acute lymphocytic choriomeningitis virus infection, we exploit activation-induced deaminase (AID) fate-reporter mice and perform adoptive B cell transfer experiments. Chronic infection yields GC B cell responses of higher cellularity than acute infections do, higher memory B cell and antibody secreting cell output for longer periods of time, a better representation of the late B cell repertoire in serum immunoglobulin, and higher titers of protective neutralizing antibodies.

Phenotypic Characterization of Bone Marrow Mononuclear Cells and Derived Stromal Cell Populations from Human Iliac Crest, Vertebral Body and Femoral Head.

(1) In vitro, bone marrow-derived stromal cells (BMSCs) demonstrate inter-donor phenotypic variability, which presents challenges for the development of regenerative therapies. Here, we investigated whether the frequency of putative BMSC sub-populations within the freshly isolated mononuclear cell fraction of bone marrow is phenotypically predictive for the in vitro derived stromal cell culture. (2) Vertebral body, iliac crest, and femoral head bone marrow were acquired from 33 patients (10 female and 23 male, age range 14-91).

Publisher Correction: Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.

The original version of this Article contained an error in the spelling of the author Jule Müller, which was incorrectly given as Julia Müller. Additionally, in Fig. 4a, the blue-red colour scale for fold change in ageing/disease regulation included a blue stripe in place of a red stripe at the right-hand end of the scale.

CD146/MCAM distinguishes stem cell subpopulations with distinct migration and regenerative potential in degenerative intervertebral discs.

Objective: This study aimed to characterize the mesenchymal stem cell (MSC) subpopulation migrating towards a degenerated intervertebral disc (IVD) and to assess its regenerative potential.

Design: Based on initial screening for migration towards C-C motif chemokine ligand 5 (CCL5), the migration potential of CD146+ and CD146- mesenchymal stem cells (MSCs) was evaluated in vitro and in a degenerated organ culture model (degeneration by high-frequency loading in a bioreactor). Discogenic differentiation potential of CD146+ and CD146- MSCs was investigated by in vitro pellet culture assay with supplementation of growth and differentiation factor-6 (GDF6).

Programmed Cell Death Ligand 1 Immunohistochemistry: A Concordance Study Between Surgical Specimen, Biopsy, and Tissue Microarray.

Background: The immunohistochemical analysis of programmed cell death ligand 1 (PD-L1) expression in tumor tissue of non-small-cell lung cancer patients has now been integrated in the diagnostic workup. Analysis is commonly done on small tissue biopsy samples representing a minimal fraction of the whole tumor. The aim of the study was to evaluate the correlation of PD-L1 expression on biopsy specimens with corresponding resection specimens.

Shear and Dynamic Compression Modulates the Inflammatory Phenotype of Human Monocytes .

Monocytes and their derived macrophages are found at the site of remodeling tissue, such as fracture hematoma, that is exposed to mechanical forces and have been previously implicated in the reparative response. However, the mechanoresponsive of monocytes and macrophages to skeletal tissue-associated mechanical forces and their subsequent contribution to skeletal repair remains unclear. The aim of this study was to investigate the potential of skeletal tissue-associated loading conditions to modulate human monocyte activation and phenotype.