Search Results (2,662)

Background: Antimicrobial resistance mediated by ESBL-producing Klebsiella pneumoniae is an emerging concern in both human and veterinary medicine, with companion animals increasingly considered relevant within the One Health framework. This study aimed to investigate the fecal carriage of ESBL-producing K. pneumoniae complex in cats from Italy and to characterize the strains by the phenotypic and genetic profile of ESBL production, virulent pathotypes, antibiotic resistance profile and biofilm production. Methods: Fecal samples collected from cats admitted to the Veterinary Teaching Hospital of Milan (Italy) in 2020–2026 were bacteriologically and genetically analyzed. Results: All the Klebsiella pneumoniae strains isolated [4/200 (2%, 95% CI: 0.06–3.94%)] were ESBL-producing K. pneumoniae complex isolates harboring bla_CTX-M-15, bla_SHV, and bla_TEM genes. The isolates were detected with higher presence in cats with diarrhea and were found only in cats treated with antibiotics and hospitalized. All four ESBL-producing isolates were classified as the classical K. pneumoniae pathotype based on the negative string test results, the absence of reliable virulence genes used for pathotype identification (peg-344, iucA, rmpA and rmpA2), and the lack of K1 and K2 serotypes, despite the detection of terB and irp2 virulence genes in one and two isolates, respectively. All four ESBL-producing K. pneumoniae complexes were classified as multidrug-resistant, with resistance mainly observed to β-lactams, fluoroquinolones, quinolones and folate antagonists. All four ESBL-producing K. pneumoniae complexes demonstrated biofilm-forming abilities, with two isolates showing weak adhesion, one moderate adhesion, and one strong adhesion. Conclusions: The detection of ESBL genes together with the MDR pattern, biofilm-forming capacity and selected virulence determinants suggests the potential epidemiological relevance of cats in the dissemination of antimicrobial-resistant K. pneumoniae complexes, underscoring the need for strengthened surveillance and prevention strategies in veterinary settings to provide information to pet cat owners and children who may interact with stray cats, in full implementation of the One Health approach. Full article

Background: Pediatric idiopathic nephrotic syndrome (INS) is classified primarily by corticosteroid response, delaying identification of steroid-resistant disease and exposing children to unnecessary treatment toxicity. Novel biomarkers could enable earlier biological stratification and treatment guidance. Objectives: The study aimed to map available evidence on candidate biomarkers in pediatric INS published since 2020, with emphasis on anti-nephrin autoantibodies and their potential for clinical translation. Data Sources: PubMed/MEDLINE and Web of Science Core Collection (January 2020–October 2025), with a supplementary verification search in Scopus and Embase and manual reference screening. Eligibility Criteria: Original studies reporting circulating, urinary, or tissue-based biomarkers in children aged 0–18 years with idiopathic NS, with outcomes related to diagnosis, treatment response, relapse prediction, or monitoring. Studies in adults only, secondary NS, or animal models were excluded. Results: After screening, 34 studies met the eligibility criteria and were included, grouped into five categories: autoantibodies, urinary markers, immune cell signatures, cytokines/chemokines, and exploratory markers (metabolomics, extracellular vesicles, lipid profiles, microRNAs). Anti-nephrin IgG emerged as the most mechanistically informative marker, with seroprevalence declining across phenotypes (SSNS 68%, SDNS 28%, non-genetic SRNS 14%, genetic SRNS 2%) and positivity predicting response to intensified immunosuppression. Of the candidates reviewed, urinary NGAL and peripheral B-cell subset monitoring are the most readily implementable with existing laboratory infrastructure. Conclusions: Pediatric INS encompasses a spectrum of immune-mediated podocytopathies that may soon be distinguishable by emerging biomarker profiles. Anti-nephrin autoantibodies provide the strongest mechanistic evidence for an autoimmune podocytopathy. Full article

The genus Vibrio contains over 150 species of aquatic origin, some of which are important foodborne pathogens, while others cause diseases in finfish, shellfish and/or coral. Accurate identification of these bacteria is important, but highly challenging given their taxonomic diversity. Here we used a range of methods to identify strains from New Zealand oysters initially identified as Vibrio vulnificus. The API20E kit either misidentified, or failed to identify the strains depending on the database used; comparisons of the 16S rRNA gene sequences could not distinguish them from over 50 exemplars of other Vibrio spp. or Allocatenococcus thiocycli. Elastic light scatter analysis showed clear differences between each of the novel isolates and reference strains of Vibrio parahaemolyticus and V. vulnificus, but limits of the in-house database precluded identification. Our whole-genome sequencing (WGS) pipeline allowed genomes and plasmids to be effectively sequenced to completion, enabling in silico DNA-DNA hybridization analysis with 162 Vibrio spp., which identified the strains as either V. campbellii, or one that may represent a novel species closely related to V. rotiferianus. Genome analysis also revealed a variety of genes found in aquacultural and human pathogens, including V. cholerae. Furthermore, resistance to multiple antibiotic classes was indicated both genetically and phenotypically. The implications for New Zealand aquaculture and public health are discussed. WGS is an effective identification strategy for taxonomically complex bacteria such as Vibrio spp. Full article

Background: Wheat (Triticum aestivum L.) seedling performance under heat and drought stress is critical for crop establishment. Identifying cultivars with superior seedling vigor under stress conditions helps breeding programs and seed production systems. Methods: We aimed to evaluate the early growth performance of wheat seedlings from 28 Brazilian commercial cultivars under heat and osmotic stress. Seedlings were assessed through shoot and root lengths and dry weight and analyzed using Scott–Knott grouping, heritability estimates, PCA and stress tolerance index. Results: Osmotic stress affected a wider range of traits than heat stress and revealed phenotypic and genetic variability among cultivars. Root length and root dry weight exhibited high broad-sense heritability, indicating a substantial genotypic contribution under the tested conditions and supporting their use for early-stage screening. Multivariate analyses revealed contrasting adaptation strategies, including root elongation and preferential allocation of biomass to roots under stress conditions. Through uni- and multivariate analyses, we suggested cultivars are potentially tolerant to heat and osmotic stresses. Conclusions: Root-related traits proved to be the most informative indicators of adaptation to stress, and the integration of stress tolerance indices and multivariate analyses enabled the identification of promising cultivars for further validation under greenhouse and field conditions. Full article

Background/Objectives: Antimicrobial resistance (AMR) in poultry-production environments is an important One Health concern. This phenotypic baseline study investigated the detection and antimicrobial-resistance profiles of Escherichia coli and Salmonella spp. recovered from broiler-farm environmental matrices in the Rabat–Salé–Kénitra region of Morocco. Methods: A cross-sectional field study was conducted in 13 broiler farms on 35 sampling dates between 24 November 2023 and 28 April 2025. A total of 543 samples were collected from poultry manure, drinking troughs, farm soil, soils approximately 200 and 500 m from the poultry houses, and well water. Isolates were identified by culture and API 20E; Salmonella spp. identification was additionally confirmed by real-time PCR. Disk-diffusion results were interpreted using applicable CLSI M100, 31st edition, criteria, and colistin was tested by the colistin broth disk elution MIC method. Multidrug resistance (MDR) was defined as resistance to at least one agent in three or more antimicrobial classes. Results: Escherichia coli and Salmonella spp. were detected in 190/543 (35.0%) and 127/543 (23.4%) samples, respectively. Among E. coli isolates, 115/190 (60.5%) were MDR; the highest matrix-specific proportions occurred in farm soil (85.7%), drinking troughs (83.3%), and poultry manure (75.7%). Among Salmonella spp. isolates, 82/127 (64.6%) were MDR, with the highest proportions in poultry manure (92.9%) and drinking troughs (78.3%). The predominant resistance rates were ampicillin (84.7%), tetracycline (61.6%), and chloramphenicol (55.8%) in E. coli, and nalidixic acid (73.2%), ampicillin (61.4%), and tetracycline (55.9%) in Salmonella spp. Resistant isolates were also detected in surrounding soils and well water; however, the study design did not permit source attribution or inference of transmission direction. Conclusions: Broiler-farm environmental matrices in the study area may represent reservoirs of phenotypically antimicrobial-resistant E. coli and Salmonella spp. The findings provide baseline evidence supporting integrated One Health surveillance, improved biosecurity, manure and litter management, water-system sanitation, and responsible veterinary antimicrobial use. Genomic typing and environmental source-tracking are required to determine persistence and transmission pathways. Full article

Background: Founder mutations in MYBPC3 may contribute substantially to the genetic burden of hypertrophic cardiomyopathy (HCM) and provide important insights into genotype–phenotype correlations and population-specific disease mechanisms. In this study, we investigated two recurrent canonical splice-site variants, MYBPC3 c.1458-1G>A and c.3331-1G>A, identified in patients with HCM from the Emilia-Romagna region of Northern Italy. Methods: Ninety-one unrelated patients with HCM carrying either MYBPC3c.1458-1G>A or c.3331-1G>A were analyzed. Haplotype reconstruction was performed to assess a possible founder effect and estimate the approximate age of the shared ancestral allele. Functional characterization was carried out by RNA sequencing of myocardial tissue to evaluate the impact of the variants on splicing. Clinical and phenotypic data were compared with those of carriers of other truncating MYBPC3 variants or pathogenic variants in other sarcomeric genes. Results: Both variants, classified as pathogenic according to ACMG criteria, shared a conserved variant-specific core haplotype. Founder age was estimated at approximately 10.5 generations (~262 years), consistent with a regional founder effect. RNA sequencing demonstrated aberrant splicing for both variants, resulting in premature termination codons and presumably subsequent nonsense-mediated mRNA decay. Clinically, carriers showed delayed disease onset, with a mean onset in the fifth decade of life, and a comparatively milder phenotype, including a lower incidence of sudden cardiac death, than patients carrying other truncating MYBPC3 variants or pathogenic variants in other sarcomeric genes. Both variants exhibited partial penetrance (approximately 63–67%) and age-dependent variable expressivity. Conclusions:MYBPC3 c.1458-1G>A and c.3331-1G>A represent novel founder alleles associated with HCM in Northern Italy. Identification of these locally prevalent variants improves molecular diagnosis, family screening, and supports the development of variant-targeted therapeutic approaches. Full article

Attention-deficit/hyperactivity disorder (ADHD) is traditionally defined by symptoms of inattention, hyperactivity, and impulsivity. However, growing evidence suggests that this framework incompletely reflects the underlying neurobiology and clinical heterogeneity of the disorder, particularly in females. Current models of dopaminergic neurotransmission propose that ADHD is characterized not by simple dopamine deficiency but by dysregulation of tonic and phasic dopamine signaling. Theoretical models propose that reduced tonic dopamine activity may coexist with enhanced stimulus-dependent phasic responses in ADHD. Whether such signaling differences produce alternating states of underactivation and hyperactivation within the same individual has not been directly demonstrated and constitutes a central hypothesis of the present framework. In this narrative hypothesis paper, I examine evidence linking dopaminergic dysregulation to a broader ADHD phenotype encompassing four functional domains: energy regulation, attention allocation, behavioral activation, and emotional reactivity and awareness. Within these domains, hyperactivity and hypoactivity, inattention and hyperfocus, impulsive responding and difficulty initiating action, and emotional hyperreactivity and alexithymia are treated as potentially related manifestations rather than established psychometric opposites. Neuroimaging studies report alterations in dopamine transporter and receptor availability, while clinical and behavioral studies document associations between ADHD and different, sometimes contrasting manifestations within the proposed domains. Importantly, internally experienced manifestations such as emotional dysregulation, hypoactivity, procrastination, and hyperfocus appear particularly relevant to female presentations of ADHD. I propose that ADHD should be conceptualized as a multidimensional disorder of dopaminergic regulation. This framework may better explain phenotypic diversity, improve identification of underrecognized presentations, and guide future biomarker-driven and precision-medicine approaches to ADHD. Full article

Despite the success of modern antiretroviral therapy in achieving virological suppression, people living with HIV face an elevated risk of cardiovascular diseases, particularly heart failure with preserved ejection fraction. This study evaluates the cardiometabolic phenotype and functional capacity in a Romanian HIV cohort to delineate the metabolic footprint of chronic infection. In this cross-sectional study based on prospectively collected, protocol-driven phenotyping, we evaluated 50 consecutive outpatients from a university-affiliated infectious diseases clinic in Timisoara. Eligibility strictly required clinical stability and sustained virological suppression (plasma HIV-RNA < 50 copies/mL for ≥12 months). The analysis revealed widespread metabolic dysregulation, with 52% exhibiting excess weight and 64% showing atherogenic dyslipidemia. Integrase strand transfer inhibitor-based regimens were significantly correlated with an increased body mass index (p = 0.034) and elevated LDL cholesterol (aOR = 2.4, 95% CI [1.18–4.95], p = 0.022). Furthermore, we observed a pronounced metabolic age gap (+4.5 ± 2.8 years), defined as the deviation of bioimpedance-estimated metabolic age from the patients’ chronological age. This gap (p = 0.028), alongside historical immunodeficiency indicated by a low nadir CD4+ count (aOR = 0.998, 95% CI [0.991–0.999], p = 0.021), strongly predicted exercise intolerance, independent of current immune reconstruction. Sarcopenic obesity (present in 18% of the cohort) and an elevated triglycerides-to-HDL ratio (aOR = 2.14, 95% CI [1.15–3.98], p = 0.016) emerged as robust independent negative predictors of functional capacity. Additionally, subclinical myocardial remodeling, evidenced by impaired Global Longitudinal Strain, significantly predicted reduced aerobic capacity (aOR = 0.72, 95% CI [0.58–0.89], p = 0.003). Consequently, contemporary HIV management must transition beyond virological control to integrated cardiometabolic screening. Utilizing cardiopulmonary exercise testing, echocardiography, and metabolic biomarkers is critical for the early identification of subclinical “functional HIV-associated frailty” and mitigating the trajectory toward overt cardiovascular diseases. Full article

The adoption of artificial intelligence (AI) has been steadily growing across various fields in recent years. AI can have significant advantages for industries, including automation, reliable prediction, enhanced process control, and improved efficiency. Particularly, the field of academic research has embraced AI as a tool to address global challenges. Yeast strains, especially Saccharomyces cerevisiae, serve as key model organisms and industrial cell factories, enabling fundamental biological discoveries and advanced biotechnological applications through conserved eukaryotic pathways and modern metabolic engineering tools. Yeast cell biology can benefit from AI through its optimization of the fermentation process via an advanced control system, accelerated identification and classification of yeast strains through deep learning, predictive analysis of multi-omics biological data, strain engineering, and as a powerful approach in the evolution of the yeast genotype–phenotype map to explore novel biology. This review evaluates the benefits of using AI in biological studies leveraging yeast strains, discusses the challenges and limitations, and outlines the prospects. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), a leading cause of chronic liver disease, encompasses a continuum from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. This review aimed to synthesize current evidence on how metabolomic, lipidomic, and spatial multi-omic approaches illuminate MASLD pathogenesis and support precision hepatology. Methods: A structured narrative review was conducted through searches of PubMed, Scopus, and Web of Science, complemented by manual screening of key references. Studies were prioritized when they addressed MASLD biology, metabolic rewiring, lipid remodeling, mitochondrial dysfunction, inflammatory and fibrogenic pathways, gut–liver–adipose crosstalk, biomarker development, or therapeutic monitoring. Results: The reviewed evidence identifies MASLD as a systemic metabolic disorder shaped by excess lipid flux, enhanced de novo lipogenesis, impaired mitochondrial adaptation, oxidative and endoplasmic reticulum stress, sterile inflammation, and hepatic stellate-cell activation. Recurrent metabolomic signatures include altered amino acid, fatty acids, bile acid, and microbial co-metabolite pathways. Lipidomic studies consistently implicate depletion of protective polyunsaturated fatty acids, lysophosphatidylcholines, and phosphatidylcholines, in association with accumulation of diacylglycerols and ceramides, in the transition from steatosis to MASH and fibrosis. Emerging spatial and multi-omic analyses further resolve cell-specific metabolic niches involving hepatocytes, macrophages, endothelial cells, and stellate cells. Conclusions: Metabolomics provides a mechanistic and translational bridge between molecular injury, histological progression, and non-invasive risk stratification in MASLD. Future progress requires standardized analytical workflows, longitudinal validation, causal pathway interrogation, and integration with imaging, genetics, microbiome profiling, and treatment-response phenotyping. Clinical implementation will require standardized platforms, transparent metabolite identification, external validation across diverse populations, cost-effectiveness analyses, and regulatory-grade evidence of clinical utility. Full article

Functional near-infrared spectroscopy (fNIRS) is a portable, non-invasive tool for studying cortical function in children with neurodevelopmental and neurological disorders. Although fNIRS use is increasing, heterogeneous study paradigms and cortical targets have limited cross-condition comparisons and the identification of shared research priorities. This systematic review maps cortical regions and reporting patterns in five key conditions—autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), cerebral palsy (CP), hypoxic–ischemic encephalopathy (HIE), and epilepsy (Ep)—from January 2015 to December 2025. A systematic search across five databases identified 72 relevant studies meeting PRISMA 2020 criteria, revealing both similarities and differences across disorders. The prefrontal cortex (PFC) was studied in all five conditions (5/5: 100%), making it the most consistently investigated cortical region. The parietal and temporal cortices were studied in 4 of 5 conditions (80%). The frontal cortex had the most regions investigated, while the temporal cortex showed the most consistent coverage across conditions (2.25 conditions per region). Beyond regional preferences, condition-specific patterns were aligned with their disorder phenotypes: social brain networks in ASD, prefrontal executive systems in ADHD, sensorimotor changes in CP, cerebrovascular monitoring in HIE, and state-dependent changes in Ep. Across conditions, researchers found altered prefrontal activity, disrupted connectivity, and compensatory brain responses, supporting broader frameworks. Collectively, these findings identify the PFC as a shared target for transdiagnostic fNIRS investigations while highlighting important gaps in regional coverage and methodological consistency. Despite methodological differences, fNIRS shows promise for identifying both shared and unique brain patterns in pediatric neurodevelopmental and neurological disorders. This review provides a framework for prioritizing cortical targets and guiding future standardized fNIRS research in pediatric populations. Full article

Maize is a staple crop supporting global food security. Comprehensive evaluation of its phenotypic variation and environmental adaptability is urgently needed. In this study, three mutually independent maize germplasm panels with a total of 1197 hybrids were characterized using 39 standardized DUS traits: Panel A (783 hybrids, single location, 2023), Panel B (129 hybrids, two locations in the same year), and Panel C (285 hybrids, single location across two consecutive years). Tassel- and anthocyanin-related traits exhibited wide phenotypic variation and strong germplasm discrimination ability, while leaf margin anthocyanin (Char. 8) displayed rare genotypes with unique identification values. Hierarchical clustering divided all materials into eight distinct groups. PCA revealed weak overall phenotypic differentiation, which is likely driven by long-term directional selection in modern maize breeding. AMMI-based stability evaluation demonstrated that grain morphological traits (Char. 33, Char. 35) maintained stable performance across locations and years, whereas anthocyanin-related descriptors (Char. 8, Char. 14) showed severe environmental plasticity. Using the classic Multi-Trait Stability Index (MTSI), we screened top stable genotypes: 77, 69 and 52 for cross-location trials, and N90, N85 and N107 for multi-year trials. BLUP five-fold cross-validation revealed that grain morphological traits achieved high cross-location predictive correlation (r² > 0.80), whereas cross-year predictability was notably lower, reflecting greater influence of annual climatic fluctuations. Collectively, this study constructs a standardized analytical pipeline to mine routine multi-environment DUS records, identifies stable elite germplasm, and provides data-driven references for optimizing maize breeding and improving official DUS testing efficiency. Full article

Progressive Familial Intrahepatic Cholestasis (PFIC) is a rare liver disorder that, although typically present in childhood, can also occur in adulthood. Early diagnosis is crucial for appropriate clinical management, prognostic assessment, and therapeutic decision-making; however, it remains challenging due to phenotypic variability and the frequent identification of genetic variants of uncertain significance (VUS). Advances in next-generation sequencing (NGS) and whole-exome sequencing (WES) have improved the detection of disease-associated variants, revealing that the same genetic variants—often in a heterozygous state—may lead to adult-onset cholestatic disease, with milder or atypical presentations, while still conferring a significant risk of progressive liver injury and related complications. To assess the diagnostic yield and clinical utility of NGS panels and WES in adults with suspected PFIC or unexplained cholestatic liver disease, focusing on variant interpretation, emerging disease-associated genes, and clinical significance of VUS. A literature review was conducted to assess molecular diagnostics in adult cryptogenic cholestasis, with a focus on studies employing targeted NGS panels and WES. Selected studies were examined for diagnostic yield, variant classification, interpretive challenges, including VUS, and integration with clinical data. Data on patient demographics, sequencing techniques, and variant interpretation strategies were extracted to evaluate the current capabilities and limitations of genomic testing. From an initial search of 211 publications, 15 studies met the inclusion criteria, comprising five large adult cohorts and ten single-patient or trio-based reports. Across 72 patients, sequencing technologies identified 75 pathogenic or likely pathogenic variants, predominantly missense mutations, demonstrating high genetic heterogeneity. The most implicated genes included ABCB4, ABCB11, ATP8B1, TJP2, and USP53, with diagnostic yields ranging from 13.2% in large heterogeneous cohorts to substantially higher rates in carefully selected individual cases. VUS were identified in up to 67% of cases, highlighting the need for multidisciplinary interpretation integrating clinical, biochemical, and genetic data. Emerging evidence also implicated ciliopathy-associated genes such as DCDC2, NPHP3, PKHD1, TULP3, and TTC21B, expanding the genetic spectrum of adult cholestasis. Clinically, presentations ranged from mild biochemical abnormalities to progressive cholestasis, with pruritus being a common feature across studies. Comprehensive genetic testing significantly enhances diagnostic accuracy, informs prognosis, and guides individualized management in adults with cryptogenic cholestasis. Emerging evidence suggests that ciliopathy-associated genes may contribute to the genetic architecture of adult cholestatic disorders, further expanding the spectrum of disease-associated genes. However, the high prevalence of VUS remains a major challenge, highlighting the need for functional studies, longitudinal follow-up, and improved variant interpretation frameworks. As genomic technologies and analytical approaches continue to evolve, genetic testing is expected to play an increasingly central role in precision hepatology. Full article

Research over the last decades have demonstrated that macrophages, considered canonical players of the immune system, also perform many other important biological functions in adult organisms. These properties have stimulated extensive research, particularly given their importance in human pathologies, including cancer. However, despite significant advances in our understanding of macrophage functions in adult organisms and diseases, their roles in embryonic systems remain comparatively underexplored. Owing to their complex developmental origin and the lack of pronounced phenotypes in embryos subjected to either spontaneous or experimentally induced macrophage ablation, macrophages have often been considered as a largely passive scavenger population associated with programmed cell death during organ and tissue remodeling. Here, we highlight key findings regarding macrophage functions during vertebrate morphogenesis. We emphasize the differences in phenotypic outcomes following macrophage ablation in adult organisms, embryos, and models of organ regeneration. Currently, the remarkable plasticity of the macrophage lineage complicates the identification of specific trophic functions involved in organ morphogenesis. Developing new approaches that improve the efficiency of macrophage ablation models, along with implementing complementary gain-of-function strategies, will contribute to a deeper understanding of the role of macrophages during embryonic development. Full article

Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of pediatric chronic kidney disease (CKD) and comprise a heterogeneous group of developmental disorders with a substantial genetic contribution. Advances in next-generation sequencing have facilitated the identification of numerous candidate genes and rare variants associated with CAKUT. However, establishing causality and defining the biological functions of implicated genes remain major challenges. Functional validation is therefore essential to bridge the gap between gene discovery and mechanistic understanding, enabling the interpretation of genetic variation within the context of kidney development and disease. The zebrafish (Danio rerio) has emerged as a powerful in vivo model for studying renal development and interrogating the function of CAKUT-associated genes. Its utility stems from a high degree of genetic and developmental conservation with humans, conserved nephrogenic pathways, optical transparency during embryogenesis, and the relative ease of genetic manipulation. In this review, we provide an overview of zebrafish kidney development within the broader context of vertebrate nephrogenesis, highlighting the key genetic programs governing intermediate mesoderm specification, nephron segmentation, and pronephric morphogenesis. We then systematically examine CAKUT-associated genes that have been modeled in zebrafish, focusing on studies that have linked genetic perturbations to renal development and structural phenotypes. Finally, we discuss the strengths and limitations of zebrafish models for functional genomics and variant interpretation and consider their emerging role in bridging genetic discovery with mechanistic insights into CAKUT pathogenesis. Full article