TrAGEDy-trajectory alignment of gene expression dynamics.

Motivation: Single-cell transcriptomics sequencing is used to compare different biological processes. However, often, those processes are asymmetric which are difficult to integrate. Current approaches often rely on integrating samples from each condition before either cluster-based comparisons or analysis of an inferred shared trajectory.

paraCell: a novel software tool for the interactive analysis and visualization of standard and dual host-parasite single-cell RNA-seq data.

Advances in sequencing technology have led to a dramatic increase in the number of single-cell transcriptomic datasets. In the field of parasitology, these datasets typically describe the gene expression patterns of a given parasite species at the single-cell level under experimental conditions, in specific hosts or tissues, or at different life cycle stages. However, while this wealth of available data represents a significant resource, analysing these datasets often requires expert computational skills, preventing a considerable proportion of the parasitology community from meaningfully integrating existing single-cell data into their work.

Supersaturation mutagenesis reveals adaptive rewiring of essential genes among malaria parasites.

Malaria parasites are highly divergent from model eukaryotes. Large-scale genome engineering methods effective in model organisms are frequently inapplicable, and systematic studies of gene function are few. We generated more than 175,000 transposon insertions in the genome, averaging an insertion every 138 base pairs, and used this "supersaturation" mutagenesis to score essentiality for 98% of genes.

scRNA-seq reveals elevated interferon responses and TNF-α signaling via NFkB in monocytes in children with uncomplicated malaria.

Malaria causes significant morbidity and mortality worldwide, disproportionately impacting sub-Saharan Africa. Disease phenotypes associated with infection can vary widely, from asymptomatic to life-threatening. To date, prevention efforts, particularly those related to vaccine development, have been hindered by an incomplete understanding of which factors impact host immune responses resulting in these divergent outcomes.

Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a diverse family of variant surface antigens, encoded by var genes, that mediates binding of infected erythrocytes to human cells and plays a key role in parasite immune evasion and malaria pathology. The increased availability of parasite genome sequence data has revolutionised the study of PfEMP1 diversity across multiple P. falciparum isolates.

Genetic factors regulating Plasmodium falciparum gametocytogenesis identified by phenotypic screens.

Successful transmission of Plasmodium falciparum from one person to another relies on the complete intraerythrocytic development of non-pathogenic sexual gametocytes infectious for anopheline mosquitoes. Understanding the genetic factors that regulate gametocyte development is vital for identifying transmission-blocking targets in the malaria parasite life cycle. Toward this end, we conducted a forward genetic study to characterize the development of gametocytes from sexual commitment to mature stage V.

Performance of Urinary Markers in Patients With Suspicious Cystoscopy During Follow-up of Recurrent Non-muscle Invasive Bladder Cancer: BTA Stat, NMP22 BladderChek, UBC Rapid Test, CancerCheck UBC Rapid VISUAL, and Uromonitor in Comparison to Cytology.

Objective: To compare all available rapid tests on a large cohort of recurrent bladder cancer during follow-up in this multicentre-study is the first study. BTA stat, NMP22 BladderChek, UBC Rapid Test CancerCheck UBC rapid VISUAL, and uromonitor are urinary-based rapid tests for bladder cancer detection.

Methods: In total, 187 urine samples were analyzed from patients with suspected recurrent non-muscle invasive urothelial bladder cancer on cystoscopy during follow-up in a real-world assessment.

Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis.

Current rheumatoid arthritis (RA) treatments do not restore immune tolerance. Investigating dendritic cell (DC) populations in human synovial tissue (ST) may reveal pathways to reinstate tolerance in RA. Using single-cell and spatial transcriptomics of ST biopsies, as well as co-culture systems, we identified condition- and niche-specific DC clusters with distinct functions.

Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population.

Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTDs), including coronavirus disease 2019 (COVID-19), but there are minimal data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. In this study, we used histology and high-dimensional imaging to characterize fatal lung disease in Malawian adults with (n = 9) and without (n = 7) COVID-19, and we generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved COVID-19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in US, European and Asian cohorts, by type I/III interferon (IFN) responses, particularly in blood-derived monocytes, and in the Malawian cohort, by response to IFN-γ in lung-resident macrophages.

Real-world performance of Uromonitor® in urothelial bladder cancer detection: a multicentric trial.

Objectives: To compare Uromonitor® (U-Monitor Lda, Porto, Portugal), a multitarget DNA assay that detects mutated proto-oncogenes (telomerase reverse transcriptase [TERT], fibroblast growth factor receptor 3 [FGFR-3], Kirsten rat sarcoma viral oncogene homologue [KRAS]), with urine cytology in the urine-based diagnosis of urothelial carcinoma of the bladder (UCB) within a multicentre real-world setting.

Patients And Methods: This multicentre, prospective, double-blind study was conducted across four German urological centres from 2019 to 2024. We evaluated the diagnostic performance of Uromonitor compared to urine cytology in a cohort of patients with UCB and in healthy controls within a real-world setting.

Annotation and visualization of parasite, fungi and arthropod genomes with Companion.

As sequencing genomes has become increasingly popular, the need for annotation of the resulting assemblies is growing. Structural and functional annotation is still challenging as it includes finding the correct gene sequences, annotating other elements such as RNA and being able to submit those data to databases to share it with the community. Compared to de novo assembly where contiguous chromosomes are a sign of high quality, it is difficult to visualize and assess the quality of annotation.

A novel computational pipeline for gene expression augments the discovery of changes in the transcriptome during transition from in vivo to short-term in vitro culture.

The pathogenesis of severe malaria involves cytoadhesive microvascular sequestration of infected erythrocytes, mediated by erythrocyte membrane protein 1 (PfEMP1). PfEMP1 variants are encoded by the highly polymorphic family of genes, the sequences of which are largely unknown in clinical samples. Previously, we published new approaches for gene profiling and classification of predicted binding phenotypes in clinical isolates (Wichers et al.

Semantic congruency modulates the speed-up of multisensory responses.

Responses to multisensory signals are often faster compared to their unisensory components. This speed-up is typically attributed to target redundancy in that a correct response can be triggered by one or the other signal. In addition, semantic congruency of signals can also modulate multisensory responses; however, the contribution of semantic content is difficult to isolate as its manipulation commonly changes signal redundancy as well.

Sterile protection against malaria by repeated blood stage infection in the monkey model.

The malaria parasite remains a major global public health challenge, and no vaccine is approved for use in humans. Here, we assessed whether strain-transcendent immunity can be achieved by repeated infection in monkeys. Sterile immunity was achieved after two homologous infections, whereas subsequent heterologous challenge provided only partial protection.

Doping of porous carbons with sulfur and nitrogen markedly enhances their surface activity for formaldehyde removal.

The surfaces of phosphoric acid activated carbon, referred to as CG, and steam activated one, referred to as SX, were modified through an introduction of S- and N- groups originated from thiourea. The prepared samples were used for formaldehyde removal at room temperature. Heating at 450, 600 and 950 °C altered both surface chemistry and porosity.

Bladder cancer course, four genetic high-risk variants, and histopathological findings.

Urinary bladder cancer, a smoking and occupation related disease, was subject of several genome-wide association studies (GWAS). However, studies on the course of the disease based on GWAS findings differentiating between muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC) are rare. Thus we investigated 4 single nucleotide polymorphisms (SNPs) detected in GWAS, related to the genes coding for TACC3 (transforming, acidic coiled-coil containing protein 3), for FGFR3 (fibroblast growth factor receptor 3), for PSCA (prostate stem cell antigen) and the genes coding for CBX6 (chromobox homolog 6) and APOBEC3A (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A).

Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis.

B cells are key pathogenic drivers of chronic inflammation in rheumatoid arthritis (RA). There is limited understanding of the relationship between synovial B cell subsets and pathogenic antibody secreting cells (ASCs). This knowledge is crucial for the development of more targeted B-cell depleting therapies.

Functional Recovery after the Application of Amniotic Tissues and Methylene Blue during Radical Prostatectomy-A Pilot Study.

Amniotic tissues and methylene blue (MB) provide the ability for neuroregeneration, and MB enables intraoperative neurostaining. We first combined the techniques to explore a neuroprotective effect on early functional outcomes in a retrospective proof-of-concept trial of 14 patients undergoing radical prostatectomy (RP). The patients were followed up at a median of 13 months, and the continence and potency rates were reported.

BTA stat®, NMP22® BladderChek®, UBC® Rapid Test, and CancerCheck® UBC® rapid VISUAL as urinary marker for bladder cancer: Final results of a German multicenter study.

Introduction And Objective: BTA stat®, NMP22® BladderChek®, UBC® Rapid Test, and CancerCheck® UBC® rapid VISUAL are urinary-based rapid tests. This multicenter study is the first study comparing all available rapid tests on a large cohort of bladder cancer patients and healthy controls in one setting.

Methods: In total 732 urine samples (second morning urine) in a real-world assessment have been analyzed.

From contigs towards chromosomes: automatic improvement of long read assemblies (ILRA).

Recent advances in long read technologies not only enable large consortia to aim to sequence all eukaryotes on Earth, but they also allow individual laboratories to sequence their species of interest with relatively low investment. Long read technologies embody the promise of overcoming scaffolding problems associated with repeats and low complexity sequences, but the number of contigs often far exceeds the number of chromosomes and they may contain many insertion and deletion errors around homopolymer tracts. To overcome these issues, we have implemented the ILRA pipeline to correct long read-based assemblies.

The exception that proves the rule: Virulence gene expression at the onset of Plasmodium falciparum blood stage infections.

Controlled human malaria infections (CHMI) are a valuable tool to study parasite gene expression in vivo under defined conditions. In previous studies, virulence gene expression was analyzed in samples from volunteers infected with the Plasmodium falciparum (Pf) NF54 isolate, which is of African origin. Here, we provide an in-depth investigation of parasite virulence gene expression in malaria-naïve European volunteers undergoing CHMI with the genetically distinct Pf 7G8 clone, originating in Brazil.

A novel Modulator of Ring Stage Translation (MRST) gene alters artemisinin sensitivity in .

The implementation of artemisinin (ART) combination therapies (ACTs) has greatly decreased deaths caused by malaria, but increasing ACT resistance in Southeast Asia and Africa could reverse this progress. Parasite population genetic studies have identified numerous genes, single-nucleotide polymorphisms (SNPs), and transcriptional signatures associated with altered artemisinin activity with SNPs in the Kelch13 (K13) gene being the most well-characterized artemisinin resistance marker. However, there is an increasing evidence that resistance to artemisinin in is not related only to K13 SNPs, prompting the need to characterize other novel genes that can alter ART responses in .