Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.
Patient-level predictors of enrollment in pediatric biorepositories are poorly described. Especially in pandemic settings, understanding who is likely to enroll in a biorepository is critical to interpreting analyses conducted on biospecimens. We describe predictors of pediatric COVID-19 biorepository enrollment and biospecimen donation to identify gaps in COVID-19 research on pediatric biospecimens.We compared data from enrollees and non-enrollees aged 0-25 years with suspected or confirmed COVID-19 infection who were approached for enrollment in the Massachusetts General Hospital pediatric COVID-19 biorepository between April 12, 2020, and May 28, 2020, from community or academic outpatient or inpatient settings. Demographic and clinical data at presentation to care were from automatic and manual chart extractions. Predictors of enrollment and biospecimen donation were assessed with Poisson regression models.Among 457 individuals approached, 214 (47%) enrolled in the biorepository. A COVID-19 epidemiologic risk factor was recorded for 53%, and 15% lived in a US Centers for Disease Control and Prevention-defined COVID-19 hotspot. Individuals living in a COVID-19 hotspot (relative risk (RR) 2.4 [95% confidence interval (CI): 1.8-3.2]), with symptoms at presentation (RR 1.8 [95% CI: 1.2-2.7]), or admitted to hospital (RR 1.8 [95% CI: 1.2-2.8]) were more likely to enroll. Seventy-nine percent of enrollees donated any biospecimen, including 97 nasopharyngeal swabs, 119 oropharyngeal swabs, and 105 blood, 16 urine, and 16 stool specimens, respectively. Age, sex, race, ethnicity, and neighborhood-level socioeconomic status based on zip code did not predict enrollment or biospecimen donation.While fewer than half of individuals approached consented to participate in the pediatric biorepository, enrollment appeared to be representative of children affected by the pandemic. Living in a COVID-19 hotspot, symptoms at presentation to care and hospital admission predicted biorepository enrollment. Once enrolled, most individuals donated a biospecimen.
To characterize the antiinflammatory function of high-density lipoprotein (HDL) in patients with rheumatoid arthritis (RA) and to identify specific differences in HDL-associated proteins and enzymes that distinguish proinflammatory HDL from normal, antiinflammatory HDL.We studied 132 RA patients. The antiinflammatory function of HDL was assessed by a cell-free assay, and proinflammatory HDL was defined by an HDL inflammatory index > or =1. Plasma and HDL-associated protein levels of apolipoprotein A-I (Apo A-I), haptoglobin, hemopexin, hemoglobin, and myeloperoxidase (MPO) were measured by direct and sandwich enzyme-linked immunosorbent assays, respectively. Lecithin:cholesterol acyltransferase (LCAT) activity was measured by a commercially available assay.Age, disease activity, the presence of erosive disease, non-Caucasian race, and smoking were significantly associated with proinflammatory HDL on multivariate analysis. Patients with proinflammatory HDL had higher measures of systemic inflammation, and a significant correlation was observed between RA disease activity (using the Disease Activity Score in 28 joints) and the HDL inflammatory index (r = 0.54, P < 0.0001). Compared with patients with antiinflammatory HDL, patients with proinflammatory HDL had significantly higher levels of haptoglobin, hemoglobin, Apo A-I, and MPO associated with HDL (P < 0.05 for all comparisons except MPO, which was P = 0.05). LCAT activity was lowest in patients with proinflammatory HDL, but was also significantly reduced in RA patients with antiinflammatory HDL as compared with healthy controls (P = 0.001).Proinflammatory HDL in this RA patient cohort was associated with active disease and an altered protein cargo as compared with antiinflammatory HDL in RA patients and in healthy controls. The antiinflammatory function of HDL was inversely correlated with systemic inflammation in RA patients and may warrant further investigation as a mechanism by which active RA increases cardiovascular morbidity and mortality.
Many software systems are being developed to help with business processes, which typically involve a number of (human) tasks in achieving organizational goals. However, aligning a software system well with its intended business process has been challenging, since the tasks in a business process usually lacks formal definitions and can be performed via multiple different allocations of resources. In this paper, we propose a goal-oriented transformational approach to deriving use cases, as requirements on the software system, from a business process which is modeled in BPMN (Business Process Model and Notation). In this approach, a business process is modeled not only in terms of the functionally-oriented BPMN but also non-functional business goals, and the target software requirements are also modeled in terms of functionally-oriented use cases together with non-functional requirements. Those tasks to be performed by a software system are transformed into use cases, in consideration of multiple alternative interpretations of business tasks, different allocations of software functionality and the granularity of the target requirements guided via similarity and granularity. Additionally, an intermediate model is utilized in the 2-step transformation process to deal with the ontological gap and the many-to-many relationships between the source and the target. This process is facilitated by context-aware transformation rules and a supporting tool. A study of a quote flow business process shows that our goal-oriented transformational approach helps produce more cohesive, correct and comprehensive use cases.
Abstract Integrated hepatitis B virus (HBV) DNA detected in more than 85% of HBV-infected hepatocellular carcinoma (HBV-HCC) can cause insertional mutagenesis, chromosomal instability, sustained viral protein expression, and/or immune-mediated inflammation leading to HCC carcinogenesis. An opportunistic outcome of HBV DNA integration events, which occur randomly into the host genome, is the creation of a unique HBV-host junction sequence (HBV-JS) in individually infected hepatocytes representing a specific molecular signature of that cell. A noninvasive approach to detect HBV-JS's will enable frequent monitoring and aid in assessing HBV treatment efficacy and HCC disease progression. Here, we assessed the feasibility of detecting HBV-JS's in urine of HBV-infected patients as a proof-of-concept for utilizing urine as a noninvasive HBV-JS liquid biopsy for HBV-related disease monitoring. Utilizing an in-house developed HBV primer extension capture (PEC) NGS assay, we assessed early-stage HBV-patient tumor tissue and matched urine (n=8). Five of 8 urine samples contained detectable HCC tissue-derived HBV-JS's, including a TERT junction sequence. Next, we assessed 32 urine specimens collected from 28 HBV-infected patients including hepatitis (n=5), cirrhosis (n=11), HCC (n=4), and post-HCC (n=8). Interestingly, all urine samples contained HBV-JS sequences with 30 of 32 urines containing integrations in gene-coding regions. Of 351 unique HBV-JS in gene-coding regions identified in urine, 11 HBV-JS's have also been previously reported in tissue of HCC patients, including TERT. All eleven HBV-JS's were identified in cirrhosis or HCC patient cohorts. Furthermore, the distribution of urinary integrated HBV DNA in the HBV genome in all disease categories was found predominantly clustered in HBV DR1-2 (>70%), an integration hotspot, consistent with findings in tissue. Altogether this support the potential of urine as a noninvasive HBV-JS liquid biopsy to monitor HBV-infected patients for disease progression and treatment efficacy. Citation Format: Selena Lin, Yu-lan Kao, Robin Su, Ting-Tsung Chang, Yih-Jyh Lin, Yixiao Cui, Hie-Won Hann, Grace Park, Wei Song, Ying-Hsiu Su. Detection of liver-derived hepatitis B virus-host junction sequences in urine of hepatitis B infected patients for noninvasive disease monitoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 545.
Objective To evaluate factors that influence the responses defined by the American College of Rheumatology (ACR) 20% criteria for improvement in rheumatoid arthritis (RA). Methods ACR 20% and 50% response rates were calculated from data collected for the intervals 0–6, 0–12, and 0–24 months for 180 RA patients participating in the Western Consortium of Practicing Rheumatologists long-term observational study of early seropositive RA (mean ± SD duration of RA at study entry 6.0 ± 3.4 months). Analyzable cases were patients with paired data for tender and swollen joint counts plus at least 3 of the following criteria: physician's and patient's global assessments of disease activity and patient's score for pain (by visual analog scale), physical function score on the Health Assessment Questionnaire (HAQ), and levels of an acute-phase reactant. Response rates were then recalculated by 3 different methods: 1) using only cases with complete paired data for all criteria, 2) sequentially assuming no improvement in each of the 5 secondary criteria, and 3) substituting grip strength for HAQ scores. Results Using 464 paired observations for all analyzable cases, ACR 20% (50%) improvement rates were 52.6% (33.0%), compared with 55.6% (34.8%) for 365 paired observations from the cases with complete data. Decreases in ACR response rates when secondary criteria were sequentially set at “no improvement” ranged from 11.7% (pain at 0–6 months) to 1.2% (C-reactive protein at 0–12 months), but these were not statistically different by the kappa statistic. Overall numerical rankings of the relative contributions of the secondary criteria to the ACR 20% or 50% response rates were physician's global assessment, pain, HAQ, patient's global assessment, and acute-phase reactant. Only 7.8% of paired grip strength observations showed ≥20% improvement, compared with 71% of paired HAQ observations. Conclusion The use of all “analyzable” cases (paired data for tender and swollen joint counts plus ≥3 of the 5 secondary criteria) increases the number of subjects and only slightly decreases the ACR response rate compared with analyses limited to cases with complete data. The contributions of the secondary criteria are not statistically different, supporting their equal weighting in the ACR definition of improvement. The ACR 20% response rates are higher when the HAQ, rather than grip strength, is used to measure physical function.
The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on the role of essential amino acids. Mice were fed diets depleted of specific essential amino acids and their behavioral rhythms were monitored and tryptophan was selected for downstream analyses. The role of tryptophan metabolism in modulating circadian homeostasis was studied using isotope tracing as well as transcriptomic- and metabolomic- analyses. Dietary tryptophan depletion alters behavioral rhythms in mice. Furthermore, tryptophan metabolism was shown to be regulated in a time- and light- dependent manner. A multi-omics approach and combinatory diet/light interventions demonstrated that tryptophan metabolism modulates temporal regulation of metabolism and transcription programs by buffering photic cues. Specifically, tryptophan metabolites regulate central circadian functions of the suprachiasmatic nucleus and the core clock machinery in the liver. Tryptophan metabolism is a modulator of circadian homeostasis by integrating environmental cues. Our findings propose tryptophan metabolism as a potential point for pharmacologic intervention to modulate phenotypes associated with disrupted circadian rhythms.
