Bulletin of Computer Science and Electrical Engineering (BCSEE)
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Prognostic Value of 18 F-FDG PET/CT in Diffuse Large B-Cell Lymphoma Treated with a Risk-Adapted Immunochemotherapy Regimen
No full textEarly identification of patients with diffuse large B-cell lymphoma (DLBCL) who are likely to experience disease recurrence or refractory disease after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) would be useful for improving risk-adapted treatment strategies. We aimed to assess the prognostic value of
F-FDG PET/CT parameters at baseline, interim, and end of treatment (EOT).
We analyzed the prognostic impact of
F-FDG PET/CT in 166 patients with DLBCL treated with a risk-adapted immunochemotherapy regimen. Scans were obtained at baseline, after 4 cycles of R-CHOP or 3 cycles of RR-CHOP (double dose of R) and 1 cycle of CHOP alone (interim) and 6 wk after completing therapy (EOT). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier and the impact of clinical/PET factors assessed with Cox models. We also assessed the predictive ability of the recently proposed International Metabolic Prognostic Index (IMPI).
The median follow-up was 7.9 y. International Prognostic Index (IPI), baseline metabolic tumor volume (MTV), and change in maximum SUV (ΔSUV
) at interim scans were statistically significant predictors for OS. Baseline MTV, interim ΔSUV
, and EOT Deauville score were statistically significant predictors of PFS. Combining interim PET parameters demonstrated that patients with Deauville 4-5 and positive ΔSUV
≤ 70% at restaging (∼10% of the cohort) had extremely poor prognosis. The IMPI had limited discrimination and slightly overestimated the event rate in our cohort.
Baseline MTV and interim ΔSUV
predicted both PFS and OS with this sequential immunochemotherapy program. Combining interim Deauville score with interim ΔSUV
may identify an extremely high-risk DLBCL population
Geographic disparities in utilization of living donor liver transplants for racial and ethnic minorities in the united states
No full textA note on null distance and causality encoding
No full textUnder natural conditions, the null distance introduced by Sormani and Vega[10] is a metric space distance function on spacetime, which, in a certainprecise sense, can encode the causality of spacetime. The null distancefunction requires the choice of a time function. The purpose of this note is toobserve that the causality assumptions related to such a choice in results usedto establish global encoding of causality, due to Sakovich and Sormani [9] andto Burtscher and Garc\'ia-Heveling [2], can be weakened
Abstract 5972: CDK1 bridges NF-kB and b-catenin signaling in response to H. pylori infection in gastric tumorigenesis
No full textAbstract Background: Cell cycle dysregulation is a hallmark of cancer, resulting in unregulated cell proliferation and, eventually, tumor development. Cyclin-dependent kinase 1 (CDK1) is a cell cycle regulatory protein that is involved in cell cycle maintenance. CDK1 has been discovered to be substantially elevated in a several tumors and is linked to poor overall and relapse-free survival. The aim of this study is to understand the regulation role of Helicobacter Pylori infection and inflammation on CDK1 expression in gastric cancer. Methods: Using TCGA data and our integrated comprehensive gene expression analysis, we found a significant overexpression of CDK1 in gastric cancer human and mouse tissues. We detected overexpression of CDK1 in human and mouse gastric glands in response to H. pylori infection. Our data demonstrated that H. pylori infection induced phosphorylation (S536) and activation of NF-kB in vitro and in vivo. Furthermore, H. pylori infection and TNF-α treatment increased the CDK1 mRNA and protein levels in gastric cancer cell lines. Using the ChIP assay, we detected direct biding of NF-κB on the CDK1 promoter regulating its transcription. CDK1 promoted activation of the β-catenin signaling pathway. Using the pTOP/pFOP luciferase reporter assays, as a measure of β-catenin/TCF transcription activity, we confirmed CDK1-dependent activation of β-catenin in response to H. pylori infection. Pharmacologic and genetic inhibition of CDK1 reversed these effects and decreased number and size of gastric tumors organoid from mouse and human. Conclusion: Our findings demonstrate NF-kB-mediated induction of CDK1 expression in response to H. pylori infection with subsequent activation of tumorigenic β-catenin signaling. This novel regulatory link between infection, CDK1, and β-catenin suggests the importance of considering CDK1 inhibitors in gastric cancer. Citation Format: Marwah M. Al-Mathkour, Shoumin Zhu, Longlong Cao, Shayan Khalafi, Zheng Chen, Julio Poveda, Dunfa Peng, Heng Lu, Mohammed Soutto, Tianling Hu, Oliver McDonalnd, Alexander Zaika, Wael El-Rifai. CDK1 bridges NF-kB and b-catenin signaling in response to H. pylori infection in gastric tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5972
Cutaneous changes in diabetic patients: primed for aberrant healing?
No full textCutaneous manifestations affect most patients with diabetes mellitus, clinically presenting with numerous dermatologic diseases from xerosis to diabetic foot ulcers (DFUs). Skin conditions not only impose a significant quality of life impairment on individuals with diabetes but also predispose patients to further complications. Knowledge of cutaneous biology and the wound healing process under diabetic conditions is largely limited to animal models, and studies focusing on biology of the human condition of DFUs remain limited. In this review, we discuss the critical molecular, cellular, and structural changes to the skin in the hyperglycemic and insulin-resistant environment of diabetes with a focus specifically on human-derived data. Elucidating the breadth of the cutaneous manifestations coupled with effective diabetes management is important for improving patient quality of life and averting future complications including wound healing disorders. This article is protected by copyright. All rights reserved
Genomic assessment of early‐onset AD identifies novel risk loci and an incomplete genetic overlap with late‐onset AD
No full textBackground
Early Onset Alzheimer Disease (EOAD, age at onset [AAO] 65). To address this, we present a genome‐wide association study of non‐Mendelian EOAD and compare it to LOAD GWAS.
Methods
Primary single‐variant analyses were performed using two additive logistic regression for case‐control models (full: SNPs, PCs, sex and APOE‐ɛ4 dosage as covariates; reduced: SNPs and PCs); secondary models included PCs+sex and PCs+APOE. Models were applied on data derived from the Alzheimer Disease Genetics Consortium (ADGC), composed by unrelated individuals. Samples varied from 1293‐1459 cases and 8894‐9366 controls for EOAD, and 8795‐9508 cases and 9702‐10273 controls for LOAD, depending on the considered model. The SNP heritability (h2) and genetic correlation (rg) were estimated using LD score regression. Gene‐based and pathway analysis (gene sets from Msigdb‐v7.0) were performed using FUMA/MAGMA‐v1.6.
Results
We identified two novel loci associated with EOAD: Chromosome 4 (full model: chr4:102027610, P = 2.98×10−08, near PPP3CA gene) and Chromosome 12 (PCs+sex model: rs117001070, P = 2.11×10−08, intergenic between LINC02444 and LINC02882). We additionally confirmed BIN1 and APOE in the EOAD subset. Several known genes also showed a significant association with LOAD. Heritability analyses showed higher h2 values for EOAD (h2 = 0.29, 0.29, 0.29 and 0.27) than LOAD (h2 = 0.19, 0.16, 0.19, and 0.15), for full, reduced, PCs+sex and PCs+APOE models respectively. Genetic correlation showed moderate but incomplete genetic correlation between EOAD and LOAD. Other than APOE (p = 3.89×10−12), gene‐based tests showed nominal association for EOAD C8orf44‐SGK3 (p = 9.95×10−06), SGK3 (p = 2.01×10−05) and HIST1H2AC (p = 3.04×10−05), and plausible pathways such as HDL remodeling (p = 5.50×10−05) and positive regulation of cholesterol efflux (p = 9.79×10−05). These pathways were nominally associated with LOAD (p = 0.04 and p = 4.05×10−03).
Conclusions
We identified two novel loci associated to EOAD not previously reported by LOAD studies. Heritability and genetic correlation results suggest that the genetic etiology of EOAD has an incomplete genetic overlap with LOAD
A genomic data archive from the Network for Pancreatic Organ donors with Diabetes
No full textThe Network for Pancreatic Organ donors with Diabetes (nPOD) is the largest biorepository of human pancreata and associated immune organs from donors with type 1 diabetes (T1D), maturity-onset diabetes of the young (MODY), cystic fibrosis-related diabetes (CFRD), type 2 diabetes (T2D), gestational diabetes, islet autoantibody positivity (AAb+), and without diabetes. nPOD recovers, processes, analyzes, and distributes high-quality biospecimens, collected using optimized standard operating procedures, and associated de-identified data/metadata to researchers around the world. Herein describes the release of high-parameter genotyping data from this collection. 372 donors were genotyped using a custom precision medicine single nucleotide polymorphism (SNP) microarray. Data were technically validated using published algorithms to evaluate donor relatedness, ancestry, imputed HLA, and T1D genetic risk score. Additionally, 207 donors were assessed for rare known and novel coding region variants via whole exome sequencing (WES). These data are publicly-available to enable genotype-specific sample requests and the study of novel genotype:phenotype associations, aiding in the mission of nPOD to enhance understanding of diabetes pathogenesis to promote the development of novel therapies
Social motivation predicts gaze following between 6 and 14 months
No full textInfants vary in their ability to follow others' gazes, but it is unclear how these individual differences emerge. We tested whether social motivation levels in early infancy predict later gaze following skills. We longitudinally tracked infants' (N = 82) gazes and pupil dilation while they observed videos of a woman looking into the camera simulating eye contact (i.e., mutual gaze) and then gazing toward one of two objects, at 2, 4, 6, 8, and 14 months of age. To improve measurement validity, we used confirmatory factor analysis to combine multiple observed measures to index the underlying constructs of social motivation and gaze following. Infants' social motivation-indexed by their speed of social orienting, duration of mutual gaze, and degree of pupil dilation during mutual gaze-was developmentally stable and positively predicted the development of gaze following-indexed by their proportion of time looking to the target object, first object look difference scores, and first face-to-object saccade difference scores-from 6 to 14 months of age. These findings suggest that infants' social motivation likely plays a role in the development of gaze following and highlight the use of a multi-measure approach to improve measurement sensitivity and validity in infancy research
Obesity among Latinx people in the United States: A review
No full textObesity is a serious, chronic disease that is associated with a range of adiposity-based comorbidities, including cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver disease. In the United States, obesity is a public health crisis, affecting more than 40% of the population. Obesity disproportionately affects Latinx people, who have a higher prevalence of obesity and related comorbidities (such as cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver disease) compared with the general population. Many factors, including genetic predisposition, environmental factors, traditional calorie-dense Latinx diets, family dynamics, and differences in socioeconomic status, contribute to the increased prevalence and complexity of treating obesity in the Latinx population. Additionally, significant heterogeneity within the Latinx population and disparities in health care access and utilization between Latinx people and the general population add to the challenge of obesity management. Culturally tailored interventions have been successful for managing obesity and related comorbidities in Latinx people. Antiobesity medications and bariatric surgery are also important options for obesity treatment in Latinx people. As highlighted in this review, when managing obesity in the Latinx population, it is critical to consider the impact of genetic, dietary, cultural, and socioeconomic factors, in order to implement an individualized treatment strategy
Use of the Decipher genomic classifier among men with prostate cancer in the United States
No full textRecords of prostate cancer cases from participating SEER program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the Decipher 22-gene genomic classifier (GC) prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy tested cohort, and post-operative radiotherapy in the GC tested cohort as well as adverse pathology after prostatectomy.A total of 572,545 patients were included in the analysis, of which 8,927 patients underwent GC testing. GC biopsy tested patients were more likely to undergo active surveillance/watchful waiting (AS/WW) compared to untested patients (OR [95% CI] 2.21 [2.04 to 2.38], p < 0.001). AS/WW was highest for those with GC low risk classification (41%) as compared to those with intermediate (27%) or high (11%) GC risk (p < 0.001). Among NCCN low- and favorable-intermediate patients, higher GC risk was associated with greater use of local therapy (OR 4.79 [3.51 to 6.55], p < 0.001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathology (OR 2.94 [1.38 to 6.27], p = 0.005). Use of radiation after prostatectomy was significantly associated with higher GC risk group (OR 2.69 [1.89 - 3.84]).There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of post-operative radiotherapy. PATIENT SUMMARYThis study linked the use of the Decipher Genomic Classifier (GC) to a US national database of men with prostate cancer. Use of GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a three-fold higher chance of having worrisome findings in surgical specimens