Search Results (2,818)

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

Nutritional deterioration in adults with acute myeloid leukemia (AML) may be present at diagnosis and may evolve rapidly during intensive chemotherapy, lower-intensity treatment, and allogeneic hematopoietic cell transplantation (allo-HCT). This structured narrative review critically examines nutritional screening and diagnostic instruments, anthropometry and body composition, laboratory-derived composite indices, and objective physical-function measures. PubMed was searched for publications from 1 January 2015 through 13 July 2026; Google Scholar and reference lists were used foradditional citation searching. Of 292 records screened, 52 full-text reports were assessed and 34 empirical studies were included. Methodological limitations were appraised with the 2018 Mixed Methods Appraisal Tool. Evidence was heterogeneous and predominantly observational. PG-SGA and NRS-2002 identified nutritional risk and nutrition-impact symptoms, but their classifications were not interchangeable with GLIM diagnosis, body-composition phenotyping, or prognostic indices. BMI alone did not capture muscle depletion. CT, quantitative CT, BIA-derived phase angle, skeletal muscle indices, and repeated anthropometry detected clinically relevant changes, although thresholds varied and fluid shifts may bias BIA. Albumin-based indices, including CONUT, sCONUT, NRI, GNRI, PNI, and the C-reactive protein/albumin ratio, were associated with outcomes in several retrospective cohorts, but largely reflect inflammation, disease burden, and treatment effects as well as nutrition; no head-to-head evidence establishes superiority. SPPB, gait speed, walking tests, chair stands, and grip strength provided prognostic information in selected older and transplant cohorts, including patients treated with hypomethylating agents plus venetoclax. The evidence supports repeated, multimodal assessment, while remaining insufficient to prove that any single tool or tool-guided intervention improves survival. Future studies require standardized definitions, sex-stratified validation, contemporary treatment cohorts, and trials integrating nutrition, symptom control, and exercise. Full article

Long QT Syndrome type 2 (LQT2) and Brugada syndrome are inherited cardiac channelopathies that predispose affected individuals to ventricular arrhythmias and sudden cardiac death. We report the case of a 15-year-old male carrying two pathogenic variants: one in SCN5A and one in KCNH2, genes classically associated with Brugada syndrome and LQT2, respectively. The patient presented with an atypical phenotype characterized predominantly by atrial arrhythmias, atrioventricular (AV) conduction abnormalities, and wide complex tachycardia and sinus node disease without the characteristic electrocardiographic features of either syndrome. The phenotype was most likely driven predominantly by the SCN5A variant. Given his unpredictable episodes of high-grade conduction block and potential risk of ventricular arrhythmias, a transvenous implantable cardioverter-defibrillator (ICD) was implanted. Family screening revealed segregation of SCN5A and KCNH2 variants in different relatives, each with mild or absent phenotype. This case highlights the complexity of genotype–phenotype correlations in inherited arrhythmia syndromes and the importance of individualized genetics-informed management. Full article

Krabbe disease is an autosomal recessive leukodystrophy caused by a deficiency of the lysosomal enzyme galactosylceramidase (GALC), responsible for the degradation of galactolipids, resulting in toxic psychosine accumulation and progressive demyelination of the central and peripheral nervous systems. Newborn screening (NBS) has increased recognition of later-onset Krabbe disease, although interpretation of complex GALC genotypes remains challenging, particularly in the presence of “pseudodeficiency” and modifier alleles. In this case report, we describe a child with late-infantile Krabbe disease identified through NBS with markedly reduced GALC activity and a homozygous GALC haplotype containing c.956A>G (p.Tyr319Cys; Y319C) and c.1685T>C (p.Ile562Thr; I562T), in addition to other benign variants. Retrospective analysis of the newborn screening specimen demonstrated mild psychosine elevation. Despite preserved neurodevelopment, longitudinal surveillance demonstrated progressive cerebral white matter abnormalities by 3 years and 9 months of age and psychosine elevation in erythrocytes (14 pmol/g Hb; controls < 5), prompting umbilical cord blood transplantation (UCBT). Following transplantation, GALC enzyme activity normalized, psychosine levels decreased, and serial neuroimaging demonstrated radiographic stability without neurologic regression at last follow-up (9 years old). This case expands the phenotypic spectrum associated with homozygosity for the p.Tyr319Cys variant and highlights the role of p.Ile562Thr in amplifying the pathogenic potential when in cis with p.Tyr319Cys. This GALC haplotype illustrates how “pseudodeficiency” and modifier alleles may collectively influence biochemical, radiologic, and clinical disease expression. These findings emphasize the importance of integrating genotype, psychosine, enzyme activity, and longitudinal neuroimaging when evaluating infants with NBS results positive for Krabbe disease. Full article

Here we report the draft genome sequences of three Enterococcus faecalis strains, LAB1, LAB10, and LAB11, isolated from the pond water of a tilapia (Oreochromis niloticus) aquaculture farm at the University Nangui Abrogoua, Abidjan, Ivory Coast. These strains were previously characterised for their probiotic, plant growth-promoting (PGP), and nitrifying properties. All three strains were assigned to sequence type ST19 by multilocus sequence typing (MLST). The draft genomes of LAB1, LAB10, and LAB11 consist of 34, 35, and 34 contigs, totalling 2.94 Mb each (GC content 37.40%). Prokka annotation predicted 2872, 2873, and 2875 protein-coding sequences (CDS) for LAB1, LAB10, and LAB11, respectively. Genomic screening revealed no vancomycin resistance genes; however, tet(M) and lsa(A) resistance determinants were identified in all three strains, located on a repUS43-type plasmid replicon. Fourteen virulence factor homologs conserved in the E. faecalis reference strain V583 were detected, including Ebp pili, gelatinase (gelE), Fsr quorum-sensing system, and capsule biosynthesis genes, but no cytolysin operon was identified. Genes associated with stress tolerance (katA, sodA), bile salt hydrolysis (cbh), siderophore transport (fepC, fhuD), and ethanolamine nitrogen metabolism (eutB/eutC) were identified in all three genomes. Pan-genome analysis with the E. faecalis reference strain revealed 551 core gene clusters and 279 gene clusters exclusive to the three aquaculture isolates. Despite their high genomic similarity, we report the three genomes as distinct isolates due to observed differences in their expressed phenotypic properties. These sequences provide a genomic resource supporting the development of multifunctional probiotic consortia for integrated aquaponic systems. 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: 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

Background: The directional relationship between epigenetic age acceleration (EAA) and musculoskeletal disease remains unresolved. This study integrated bidirectional Mendelian randomization (MR) with multi-layer genomic evidence to evaluate directionality, shared genetic architecture, and robustness to instrument definition. Methods: Four EAA clocks (IEAA, PhenoAA, HannumAA, and GrimAA) and ten musculoskeletal phenotypes were analyzed in a 10 × 4 bidirectional two-sample MR design. EAA instruments underwent GRCh37 functional annotation, genome-wide-significant external-association screening for the index variants and European linkage-disequilibrium proxies, pair-specific Steiger filtering, and conservative Set A/B/C sensitivity analyses. The juvenile-arthritis reverse models underwent instrument-flow reconstruction, strength assessment, liability-scale directionality testing, and minimum-detectable-effect analysis. Additional analyses comprised LD score regression (LDSC), PLACO+ cross-trait locus mapping, Bayesian colocalization, multivariable MR (MVMR) with exact-SNP matched univariable comparators, and integrated evidence synthesis. Results: Forward MR yielded two nominal HannumAA associations. The inverse HannumAA–spondyloarthritis estimate remained directionally consistent across the original, Steiger-filtered, and conservative external-association-filtered sets, whereas the HannumAA–pain-in-thoracic-spine estimate lost nominal significance in the conservative set; no forward result survived correction across 40 tests. GrimAA forward estimates were sensitive to use of the fallback instrument threshold. Reverse MR identified ten nominal associations. For juvenile arthritis, three harmonized instruments had F statistics of 51.25–102.35; liability-scale Steiger comparisons supported the tested direction under all 16 outcome-by-prevalence combinations, although the 788-case discovery GWAS and possible winner’s curse remained important limitations. LDSC identified FDR-significant positive genetic correlations of GrimAA with hip osteoarthritis (r_g = 0.267, p = 8.49 × 10⁻⁵, q = 0.0019) and knee osteoarthritis (r_g = 0.269, p = 9.52 × 10⁻⁵, q = 0.0019). PLACO+ identified 738 genome-wide-significant cross-trait variants and 65 independent loci; six of 37 evaluable loci showed strong colocalization. Of 96 MVMR models, 43 had primary-exposure conditional F ≥ 10, and 32 also had candidate-trait conditional F ≥ 10. After exact-SNP matching, the 43 primary-strength models were operationally classified as 35 partially attenuated and eight independent-signal models, with no fully attenuated model; no adjusted association survived multiplicity correction. Conclusions: The results support a prioritized genomic map with substantial instrument- and model-specific uncertainty. Disease-to-clock signals were richer than clock-to-disease signals, GrimAA shared polygenic architecture with osteoarthritis, and selected loci showed strong shared-variant evidence, while the MR and MVMR findings remained unsuitable for definitive causal or mediation claims. Full article

Background/Objectives: Cognitive impairment can weaken self-management competency in heart failure (HF) patients. This study estimated domain-specific cognitive impairment prevalence using actuarial criteria and identified latent cognitive profiles among Korean HF outpatients. Methods: Using a previously collected cross-sectional dataset of 106 HF outpatients, cognitive function was assessed with the Seoul Neuropsychological Screening Battery-II. Actuarial criteria determined domain-specific impairment, and latent profile analysis (LPA) derived cognitive profiles based on domain composite z-scores. Results: Any cognitive impairment (≥1 impaired domain) was present in 32.1% (95% confidence interval [CI], 24.0–41.5%), most frequently affecting executive function (17.9%) and memory (15.1%). LPA identified three exploratory profiles: relatively preserved (30.2%), memory-vulnerable (45.3%), and globally vulnerable (24.5%). In exploratory models, anxiety symptoms were associated with higher odds of memory-vulnerable profile membership (odds ratio [OR] = 2.81, 95% CI, 1.03–7.64) and overall vulnerability in a Firth penalized analysis (OR = 3.39, 95% CI, 1.46–8.11), whereas depressive symptoms showed no significant association. No associations remained statistically significant after false discovery rate correction. Conclusions: Cognitive vulnerability in HF outpatients is phenotypically heterogeneous and showed a possible, unconfirmed association with anxiety symptoms that did not remain statistically significant after correction for multiple comparisons. Outpatient HF care planning may benefit from considering both domain-specific deficits and latent cognitive profile patterns; however, these exploratory findings require validation in larger cohorts. 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

γ-Aminobutyric acid (GABA) is a non-proteinogenic amino acid that acts as a major signaling molecule across the nervous, cardiovascular, and immune systems. While GABA has historically been produced via chemical synthesis or plant extraction, microbial fermentation using lactic acid bacteria (LAB) provides a safe, sustainable, and food-grade alternative. This review details the recent progress of LAB-derived GABA, covering the workflow from strain selection to functional food applications. We discuss how modern screening methods combine high-throughput phenotypic testing with genomic mining of the gad operon to efficiently identify high-yielding strains. The biochemical mechanisms of the GABA shunt are also explained, alongside recent CRISPR-based metabolic engineering efforts designed to bypass natural yield limits. Furthermore, we address practical industrial challenges—such as the poor proteolytic ability of key producers like Levilactobacillus brevis—and evaluate viable solutions, including symbiotic co-cultures and optimized downstream purification steps. The review then summarizes the specific health benefits of dietary LAB-derived GABA, focusing on its ability to relieve anxiety via the microbiota-gut–brain axis, control blood pressure, and regulate immunity. Finally, we analyze the current regulatory and sensory hurdles, highlighting how integrating multi-omics data can help establish LAB-derived GABA as a reliable ingredient for functional foods and personalized nutrition. Full article

Single-replicate field trials are common in early-stage maize hybrid screening, but raw plot observations contain field noise that can weaken genomic prediction. We evaluated whether pedigree and spatial adjustment improve the predictability of phenotypic targets and Top-N recovery, whether joint pedigree-spatial adjustment provides complementary gains, and whether target construction has a larger influence than baseline model choice. Across four sites, five agronomic traits, four phenotypic inputs, and six genomic prediction models, pedigree-corrected phenotypes (Ped) increased mean predictive ability from 0.465 ± 0.157 for raw observations (Raw) to 0.573 ± 0.131 and increased upper-tail Top-20 recall from 0.558 ± 0.146 to 0.656 ± 0.146 under a 20% predicted retention window. Spatial correction alone (Spa) was less predictable than Raw, whereas joint pedigree-spatial correction (Ped+Spa) improved over Raw but did not exceed Ped. Phenotypic input explained substantially more variation in predictive ability than model choice, whose main effect was not significant (F5428 = 1.59, p = 0.161). These results support pedigree correction as a useful target-construction strategy in the evaluated single-replicate trials while showing that spatial adjustment is conditional on model adequacy and trial structure. Top-N recall directly represents favorable direction recovery for grain yield; for grain moisture, plant height, ear height, and silking date, the archived upper-tail metric is interpreted as rank consistency because the favorable direction or ideotype is breeding-program-dependent. Full article

Rice is highly vulnerable to concurrent drought-heat stress, which intensifies the disruption of plant growth and can cause high seedling mortality. Limited genetic diversity further constrains breeding for combined stress adaptation. Thus, mutation breeding has emerged as a solution for inducing beneficial variability in rice genomes. Based on this solution, this study aimed to identify rice mutants tolerant to drought and heat through artificial screening combined with multi-trait index analysis. Experiments were conducted from April to August 2025 at Hasanuddin University in two sequential phases: seedling screening in a controlled stress chamber and pot evaluation under semi-controlled conditions. Mutants were derived from the seeds of the double haploid (DH) rice line HS1-28-1-5, which was previously developed through anther culture and exhibited potential abiotic stress adaptability. DH seeds were exposed to gamma irradiation (200–1000 Gy) as the M1 population. Based on radiosensitivity evaluation, 200 and 400 Gy were selected and used in the present study as the M2 populations. Rice M2 evaluation results indicated that 200 Gy irradiation enhanced phenotypic variability with improved performance, whereas M2 400 Gy resulted in broader but less stable variation. Yield components were strongly associated with weight per clump, with panicle length being the primary direct contributor and weight per panicle mediating indirect effects. Principal component analysis accounted for 89.13% of the total variation, which was predominantly driven by yield traits. Integrated weighted average absolute score–tolerance score analysis classified genotypes into tolerance groups, identifying 33 putative tolerant mutants, with M2 200 Gy mutants demonstrating superior adaptability to drought-heat stress. These findings suggest that moderate irradiation coupled with multi-trait index selection provides a reproducible framework for identifying putative drought-heat-tolerant rice candidates at early stages while retaining relevance to subsequent yield recovery. Full article

Arterial hypertension in adolescents is increasingly a lifestyle-driven disorder, and a growing share of cardiovascular risk in this age group is hidden from conventional office measurement. Intensive nighttime screen use, together with the chronic sleep loss that accompanies it, may disrupt circadian control of the cardiovascular system, an effect we designate, as a proposed integrative concept, digital chronotoxicity. Through melatonin suppression, sustained sympathetic and neuroendocrine activation, oxidative stress, and metabolic dysregulation, this exposure is hypothesized to attenuate the physiological nocturnal fall in blood pressure and to contribute to the non-dipper phenotype, a predictor of early vascular aging that remains invisible to office readings. This narrative review traces the mechanistic pathway from screen exposure to the loss of nocturnal dipping and reframes the problem as a diagnostic one. Twenty-four-hour ambulatory blood pressure monitoring is positioned as the reference standard for detecting the at-risk phenotype and masked hypertension; the cardiac, vascular, renal, autonomic, and neurocognitive biomarkers of early hypertension-mediated organ damage are reviewed; and emerging wearable and artificial-intelligence tools for continuous, preventive screening are examined. An integrated screening pathway is proposed, on the premise that the evaluation of a hypertensive adolescent is incomplete without a digital and sleep history alongside ambulatory monitoring. Reframed in this way, pediatric hypertension becomes a detectable chronobiological disease. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options. Depression and anxiety are common comorbidities in patients with IPF, and emerging evidence suggests that neuroactive pathways may also influence fibrotic remodeling. On this basis, we investigated desipramine, a tricyclic antidepressant, as a potential modulator of fibroblast state in lung fibrosis. Desipramine was identified in an FDA-approved compound screen as a pro-lipogenic hit in TGF-β-stimulated fibroblasts and was subsequently evaluated across a stepwise validation pipeline of increasing biological complexity. In WI-38 fibroblasts, desipramine was well tolerated at 10 μM and reduced myofibroblast-associated features while increasing lipid-associated staining. In a fibroblast-supported alveolosphere assay, desipramine altered qualitative organoid clustering and changed the transcript levels of specific mesenchymal markers under profibrotic stimulation, whereas direct treatment of MLE-12 epithelial cells did not elicit a consistent response. While desipramine demonstrated pro-lipogenic and anti-myofibroblastic phenotypic shifts in reductionist 2D cultures, these effects failed to translate robustly into complex 3D human lung tissue slices or in vivo disease models. Ultimately, our findings highlight the critical necessity of utilizing complex translational pipelines to rigorously validate early screening hits before therapeutic efficacy is assumed. Full article