Institute of Chartered Accountants of Nigeria

About: Institute of Chartered Accountants of Nigeria is a based out in . It is known for research contribution in the topics: Population & Adipose tissue. The organization has 528 authors who have published 579 publications receiving 18688 citations.

Genome-scale screens identify factors regulating tumor cell responses to natural killer cells

Abstract: To systematically define molecular features in human tumor cells that determine their degree of sensitivity to human allogeneic natural killer (NK) cells, we quantified the NK cell responsiveness of hundreds of molecularly annotated ‘DNA-barcoded’ solid tumor cell lines in multiplexed format and applied genome-scale CRISPR-based gene-editing screens in several solid tumor cell lines, to functionally interrogate which genes in tumor cells regulate the response to NK cells. In these orthogonal studies, NK cell–sensitive tumor cells tend to exhibit ‘mesenchymal-like’ transcriptional programs; high transcriptional signature for chromatin remodeling complexes; high levels of B7-H6 (NCR3LG1); and low levels of HLA-E/antigen presentation genes. Importantly, transcriptional signatures of NK cell–sensitive tumor cells correlate with immune checkpoint inhibitor (ICI) resistance in clinical samples. This study provides a comprehensive map of mechanisms regulating tumor cell responses to NK cells, with implications for future biomarker-driven applications of NK cell immunotherapies. The use of natural killer (NK) cells in immunotherapy as an alternative to allogeneic T cells is gaining ground. Here, two genome-scale high-throughput platforms are used to identify genes that modulate the sensitivity of multiple solid tumor cell lines to NK-mediated killing.

Effect of maternal obesity on birthweight and neonatal fat mass: A prospective clinical trial.

Abstract: Objective: To discriminate the effect of maternal obesity and gestational diabetes on birth weight and adipose tissue of the newborn. Methods: Normal BMI women (group N, n = 243; 18.5≤ BMI<25 kg/m2) and obese women (group Ob, n = 253; BMI≥30 kg/m2) were recruited in a prospective study between 15 and 18 weeks of gestation. All women were submitted to a 75g oral glucose tolerance test in the second and third trimester. First trimester fasting blood glucose was also obtained from Ob women. All women with one measurement above normal values were considered positive for gestational diabetes and first treated by dietary intervention. When dietary measures were not efficient, they were treated by insulin. Neonatal anthropometrics, sum of skinfolds and cord serum hormones were measured. Results: 222 N and 226 Ob mothers and their newborns were included in the analysis. Diabetes was diagnosed in 20% and 45.2% of N and Ob women, respectively. Birth weight was not statistically different between groups (boys: 3456g±433 and 3392g±463; girls: 3316g±402 and 3391g±408 for N and Ob, respectively). Multivariate analysis demonstrated that skinfold thickness and serum leptin concentrations were significantly increased in girls born to women with obesity (18.0mm±0.6 versus 19.7mm±0.5, p = 0.004 and 11.3ng/mL±1.0 versus 15.3ng/mL±1.0, p = 0.02), but not in boys (18.4mm±0.6 versus 18.5mm±0.5, p = 0.9 and 9.3ng/mL±1.0 versus 9.0ng/mL±1.0, p = 0.9). Based on data from 136 N and 124 Ob women, maternal insulin resistance at 37 weeks was also positively related to skinfold in girls, only, with a 1-point increase in HOMA-IR corresponding to a 0.33mm±0.08 increase in skinfold (p<0.0001). Conclusions: Regardless of gestational diabetes, maternal obesity and insulin resistance were associated with increased adiposity in girls only. Persistence of this sexual dimorphism remains to be explored during infancy.

Prospective assessment and histological analysis of adherent perinephric fat in partial nephrectomies.

Abstract: Objectives The complexity of partial nephrectomy (PN) is partly anticipated by morphometric tumor-based scores that do not consider patient-related issues such as adherent perinephric fat (APF) Also, the objective is to prospectively assess the predictive factors of APF during PN, its effect on complications, and to correlate it to the histological reality Methods A total of 125 consecutive patients undergoing robotic or open PN were prospectively included The Mayo adhesive probability score (MAP score) was compared to the peroperative presence of APF defined by a score≥2 Adipose tissue was analyzed histologically for fibrosis and inflammatory infiltrate of CD68+macrophages Univariate and multivariate logistic regression analyses were performed to evaluate predictive factors of APF, and outcomes were compared using chi-square and Kruskal-Wallis tests Results APF was present in 51 patients (408%) and associated with slight longer operating time and increased blood loss Warm ischemia time, margins, transfusion, and the Clavien-Dindo score were not different In multivariate analysis, only male sex, age, waist circumference, fat density on computed tomography, and MAP score were significant predictors of APF A radioclinical score was more predictive of APF than MAP score alone Histologically, there was no macrophage infiltration but larger adipocytes in APF without significant differences in fibrosis Conclusions APF can be accurately predicted using radioclinical data as the MAP score, combined with sex, age, and waist circumference APF is associated with increased operative time and blood loss without postoperative complications Histological analysis finds larger adipocytes in APF without inflammatory infiltrate, and no difference in fibrosis

Prediction of Long-Term Diabetes Remission After RYGB, Sleeve Gastrectomy, and Adjustable Gastric Banding Using DiaRem and Advanced-DiaRem Scores.

Abstract: DiaRem is a clinical scoring system designed to predict diabetes remission (DR) 1-year post-Roux-en-Y gastric bypass (RYGB). We examined long-term (2- and 5-year) postoperative DR prediction by DiaRem and an advanced-DiaRem (Ad-DiaRem) score following RYGB, sleeve gastrectomy (SG), and gastric banding (GB). We accessed data from a computerized database of persons with type 2 diabetes and BMI ≥ 30 kg/m2 who underwent RYGB, SG, or GB, and determined DR status 2- and 5-year postoperative according to preoperative DiaRem and the Ad-DiaRem calculated scores. Among 1459 patients with 5-year postoperative diabetes status data, 53.6% exhibited DR. For RYGB, Ad-DiaRem trended to exhibit mildly improved predictive capacity 5-year postoperatively compared to DiaRem: Areas under receiver operating characteristic [AUROC] curves were 0.85 (0.76–0.93) and 0.78 (0.69–0.88), respectively. The positive predictive values (PPVs) detecting > 80% of those achieving DR (i.e., sensitivity ≥ 0.8) were 78.2% and 73.2%, respectively, and higher Ad-DiaRem scores more consistently associated with decreased DR rates. Following SG, both scores had an AUROC of 0.82, but Ad-DiaRem still had a higher PPV for predicting > 80% of those with 5-year postoperative DR (76.2% and 71.0%). Predictive capacity parameters were comparatively lower, for both scores, when considering DR 5-year post-GB (AUROC: 0.73 for both scores, PPV: 66.3% and 64.3%, respectively). Ad-DiaRem provides modest improvement compared to DiaRem in predicting long-term DR 5-years post-RYGB. Both scores similarly provide fair predictive capacity for 5-year postoperative DR after SG.