These data suggest that RTx in low-weight children is a feasible option, at least in selected centers with appropriate surgical and medical expertise.

Ureteropelvic junction obstruction (UPJO) is the most common obstructive uropathy and its optimal management remains controversial. However, there is a current trend towards non-surgical management. We aimed to determine the effects of the non-surgical management in children with unilateral UPJO. For a systematic review, we searched MEDLINE, EMBASE, CENTRAL, clinical trials registries, and selected conference proceedings for eligible studies. Any type of study reporting the outcomes renal function, secondary surgical intervention, drainage pattern or hydronephrosis of non-surgical management in children with unilateral UPJO was included. Data from 20 studies were extracted and evaluated by two independent authors. The pooled prevalence was 21% for split renal function deterioration, 27.9% for secondary surgical intervention, 3.2% for progressive hydronephrosis, and 82.2% for improved drainage pattern. Not all patients with surgical intervention regained split renal function from enrolment. Renal imaging methods did not strongly correlate with each other. Many studies had to be excluded because of a lack of detection of an obstruction or mixed populations with bilateral UPJO or other uropathies. The variable definitions of UPJO, different criteria for surgical intervention, incongruity of management protocols, and the imprecise reporting of outcomes were limiting factors in the comparability of the results, leading to heterogeneity in meta-analyses. Although the available evidence cannot recommend or refute the current non-surgical management, the systematic review clarifies aspects of the ongoing controversy by providing realistic estimates for non-surgical management in children with unilateral UPJO. Additionally, it reveals unclear potential risks, particularly for long-term outcomes, which were rarely reported.

Background: The blood transcriptome is expected to provide a detailed picture of an organism's physiological state with potential outcomes for applications in medical diagnostics and molecular and epidemiological research. We here present the analysis of blood specimens of 3,388 adult individuals, together with phenotype characteristics such as disease history, medication status, lifestyle factors, and body mass index (BMI). The size and heterogeneity of this data challenges analytics in terms of dimension reduction, knowledge mining, feature extraction, and data integration. Methods: Self-organizing maps (SOM)-machine learning was applied to study transcriptional states on a population-wide scale. This method permits a detailed description and visualization of the molecular heterogeneity of transcriptomes and of their association with different phenotypic features. Results: The diversity of transcriptomes is described by personalized SOM-portraits, which specify the samples in terms of modules of co-expressed genes of different functional context. We identified two major blood transcriptome types where type 1 was found more in men, the elderly, and overweight people and it upregulated genes associated with inflammation and increased heme metabolism, while type 2 was predominantly found in women, younger, and normal weight participants and it was associated with activated immune responses, transcriptional, ribosomal, mitochondrial, and telomere-maintenance cell-functions. We find a striking overlap of signatures shared by multiple diseases, aging, and obesity driven by an underlying common pattern, which was associated with the immune response and the increase of inflammatory processes. Conclusions: Machine learning applications for large and heterogeneous omics data provide a holistic view on the diversity of the human blood transcriptome. It provides a tool for comparative analyses of transcriptional signatures and of associated phenotypes in population studies and medical applications.

Objective: Cellular heterogeneity is regarded as a major factor affecting treatment response and resistance in malignant melanoma. Recent developments in single-cell sequencing technology have provided deeper insights into these mechanisms. Methods: Here, we analyzed a BRAF V600E -mutant melanoma cell line by single-cell RNA-seq under various conditions: cells sensitive to BRAF inhibition with BRAF inhibitor vemurafenib and cells resistant to BRAF inhibition with vemurafenib alone or vemurafenib in combination with the MEK1/2 inhibitors cobimetinib or trametinib. Dimensionality reduction by t-distributed stochastic neighbor embedding and self-organizing maps identified distinct trajectories of resistance development clearly separating the 4 treatment conditions in cell and gene state space. Results: Trajectories associated with resistance to single-agent treatment involved cell cycle, extracellular matrix, and de-differentiation programs. In contrast, shifts detected in double-resistant cells primarily affected translation and mitogen-activated protein kinase pathway reactivation, with a small subpopulation showing markers of pluripotency. These findings were validated in pseudotime analyses and RNA velocity measurements. Conclusions: The single-cell transcriptomic analyses reported here employed a spectrum of bioinformatics methods to identify mechanisms of melanoma resistance to single-and double-agent treatments. This study deepens our understanding of treatmentinduced cellular reprogramming and plasticity in melanoma cells and identifies targets of potential relevance to the management of treatment resistance.

Against this background, screening for VUR needs to be scrutinized and restricted to selected risk groups. What is known: • Screening of patients with ureteropelvic junction obstruction (UPJO) for vesicoureteral reflux (VUR) is recommended based on a small number of repeatedly cited studies. • The lack of conclusive evidence results in different treatment strategies and leads to difficulties when communicating diagnoses and treatment options to parents. What is new: • A robust prevalence for VUR in children with UPJO based on all published evidence and the resulting number needed to screen are given for decision-making in daily clinical practice. • The results may be a precursor for implementation into guidelines.