👤 Richa Bajpai

Dyslipidemia is a universal finding in nephrotic syndrome with relapse, but there are limited data on its prevalence in disease remission. Primary objectives of the study were to identify dyslipidemia and analyze the profile of serum apolipoproteins and lipoprotein(a) in children with nephrotic syndrome in disease remission. This cross-sectional study included children (2-18 years) with nephrotic syndrome. A detailed history was elicited, and an examination was performed; blood investigations included glycosylated hemoglobin, serum albumin, kidney function tests (KFT), fasting lipid profile, serum apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB), and lipoprotein(a), and a spot urine for urine protein-to-creatinine ratio. The median age (IQR) of 92 enrolled children (male 65; female 27) was 8 (6-11) years. Forty-seven had steroid-sensitive nephrotic syndrome (SSNS), 29 had steroid-resistant nephrotic syndrome (SRNS) in disease remission, and 16 were in relapse and included for comparison. Dyslipidemia was seen in 39.5%, with a prevalence of 32% in SSNS, 51.7% in SRNS during remission, and 100% in children in relapse, using conventional markers. ApoB/ApoA-1 ratio ≥0.6 was seen in 14.2% and 29.6% of children with SSNS and SRNS, respectively, while a ratio ≥0.8 was seen in only 5.2% of those in remission. The median values of the ApoB/ApoA-1 ratio in remission and relapse were 0.5 (0.4-0.6) and 0.85 (0.62-1.33), respectively. ApoB, ApoA-1, and ApoB/ApoA-1 showed sensitivities of 63.3%, 40%, and 13.3%, and specificities of 82.6%, 80.4%, and 100%, respectively, for the diagnosis of dyslipidemia, and receiver operator characteristic analysis showed area under the curve of 0.704, 056, and 0.65, respectively. Identification of dyslipidemia using conventional parameters may lead to overdiagnosis in nephrotic syndrome during disease remission; the ApoB/ApoA-1 ratio appears to be a better marker. Show less

Cognitive dysfunction affects over 50 million individuals worldwide, with Alzheimer's disease (AD) representing two-thirds of cases. We identified Human proteomic analysis revealed eQTL mapping identified Show less

Solid-tubulocystic variant of intrahepatic cholangiocarcinoma (ST-iCCA) is newly described entity characterized by two distinct histologic growth patterns: (1) solid sheets of tumor cells with focal necrosis giving pseudopapillary appearance and (2) tubular or pseudoglandular structures containing pink, colloid-like material. Tumor cells are inhibin-positive and harbor NIPBL::NACC1 fusion gene. To date, only 28 cases of ST-iCCA have been documented. While prior molecular studies provided insights into ST-iCCA, genetic profiles of individual histologic components have not been explored. This study presents first transcriptomic analysis comparing the solid/pseudopapillary and pseudoglandular components of ST-iCCA. Two cases of histologically confirmed ST-iCCA were identified for RNA sequencing which was performed on solid/pseudopapillary component, pseudoglandular component, and normal tissue. Analysis revealed distinct gene expression profiles for each pattern. Solid/pseudopapillary component uniquely overexpressed DMRTA1, NEXMIF, PRDM6, SORCS3, and NALF, while pseudoglandular component exhibited unique overexpression of HRG, ITIH3, TAT, APOA2, CP, ALDOB, CPS1, F2, KHG1, SERPINC1, HPX, C9, ADGRF1, MUC21, SAA2, SPRR2A, SAA1, FGL1, CFHR1, and LBP. These findings establish unique gene signatures for these variants of ST-iCCA, providing potential biomarkers for differential diagnosis, prognosis and targeted therapy. The distinct genetic profiles may also uncover novel therapeutic targets to address the aggressive nature of ST-iCCA. Show less

The purpose of the study was to examine the urinary levels of kidney injury molecule-1 (KIM-1) and angiopoietin-like protein-4 (ANGPTL-4) in individuals with diabetic kidney disease (DKD) and their association with established DKD diagnostic markers such as albuminuria and estimated glomerular filtration rate (eGFR). Levels of ANGPTL-4 and KIM-1 were estimated in urine samples. A total of 135 participants were recruited into three groups: 45 diabetes type 2 patients in the control group and 90 DKD patients in two disease groups. Concentrations of ANGPTL-4 and KIM-1 were conclusively related to the urinary albumin-creatinine ratio (UACR). Also, the levels of both ANGPTL-4 and KIM-1 were negatively associated with the eGFR. Multivariable Poisson regression analysis showed that urinary ANGPTL-4 (PR: 3.40; 95% CI: 2.32 to 4.98; Show less

Oncogenic fusions formed through chromosomal rearrangements are hallmarks of childhood cancer that define cancer subtype, predict outcome, persist through treatment, and can be ideal therapeutic targets. However, mechanistic understanding of the etiology of oncogenic fusions remains elusive. Here we report a comprehensive detection of 272 oncogenic fusion gene pairs by using tumor transcriptome sequencing data from 5190 childhood cancer patients. We identify diverse factors, including translation frame, protein domain, splicing, and gene length, that shape the formation of oncogenic fusions. Our mathematical modeling reveals a strong link between differential selection pressure and clinical outcome in CBFB-MYH11. We discover 4 oncogenic fusions, including RUNX1-RUNX1T1, TCF3-PBX1, CBFA2T3-GLIS2, and KMT2A-AFDN, with promoter-hijacking-like features that may offer alternative strategies for therapeutic targeting. We uncover extensive alternative splicing in oncogenic fusions including KMT2A-MLLT3, KMT2A-MLLT10, C11orf95-RELA, NUP98-NSD1, KMT2A-AFDN and ETV6-RUNX1. We discover neo splice sites in 18 oncogenic fusion gene pairs and demonstrate that such splice sites confer therapeutic vulnerability for etiology-based genome editing. Our study reveals general principles on the etiology of oncogenic fusions in childhood cancer and suggests profound clinical implications including etiology-based risk stratification and genome-editing-based therapeutics. Show less