An agent-based model of COVID-19 dynamics during enhanced community quarantine: Exploring the role of food relief system in the presence of two SARS-CoV-2 variants

Introduction: The onset of the SARS-CoV-2 pandemic alerted the Philippine government to impose the enhanced community quarantine (ECQ) as a means to hamper human mobility and interaction and eventually diminish transmission. Due to severe limitations in accessibility to basic needs due to ECQ, the government devised amelioration programs. A year after the declaration of the SARS-CoV-2 pandemic, variants of concern were detected locally. Consequently, there is a necessity to prepare reinstatement of strict non-pharmaceutical interventions while meeting the food-related basic needs of the population. Studies related to food distribution during a strict community quarantine have been lacking. The importance of allocating provisions during extreme pandemic measures should be properly analyzed, especially when attempts had been made by local government units. Methods: This study devised an agent-based model (ABM) to observe the effects of the food relief system in mitigating the disease during Davao City ECQ when two variants are present in two adjacent villages. These relief distribution types are as follows: “regular and sufficient,” “regular but insufficient,” and “irregular” relief type. In total, three barangay scenarios were considered. Results and discussion: For the worst-case scenario, wherein a lot of infections are anticipated, the results show that the “irregular” relief type peaked at the highest number of cases, while the “regular and sufficient” relief type showed little to almost no new cases. The compromise-case scenario showed almost no difference between “regular but insufficient” and “regular and sufficient.” For the best-case scenario, the three relief types showed low average infected cases with almost small variance. The model was then compared, situationally, with Davao City barangays during ECQ and recommended which food relief type applies to the barangays. This could serve as a baseline on how food reliefs could be optimally distributed in cases where barangay conditions differently affect and transmit the SARS-CoV-2 virus of different variants with varying transmission rates within a community. Further development of the model should potentially be useful for decision support not only during pandemics but also in contexts where resource allocation to a community is involved

Conditioning intensity and peritransplant flow cytometric MRD dynamics in adult AML

In acute myeloid leukemia (AML), measurable residual disease (MRD) before or after allogeneic hematopoietic cell transplantation (HCT) is an established independent indicator of poor outcome. To address how peri-HCT MRD dynamics could refine risk assessment across different conditioning intensities, we analyzed 810 adults transplanted in first or second remission after myeloablative conditioning (MAC; n = 515) or non-MAC (n = 295) who underwent multiparameter flow cytometry–based MRD testing before as well as 20 to 40 days after allografting. Patients without pre- and post-HCT MRD (MRDneg/MRDneg) had the lowest risks of relapse and highest relapse-free survival (RFS) and overall survival (OS). Relative to those patients, outcomes for MRDpos/MRDpos and MRDneg/MRDpos patients were poor regardless of conditioning intensity. Outcomes for MRDpos/MRDneg patients were intermediate. Among 161 patients with MRD before HCT, MRD was cleared more commonly with a MAC (85 of 104; 81.7%) than non-MAC (33 of 57; 57.9%) regimen (P = .002). Although non-MAC regimens were less likely to clear MRD, if they did, the impact on outcome was greater. Thus, there was a significant interaction between conditioning intensity and “MRD conversion” for relapse (P = .020), RFS (P = .002), and OS (P = .001). Similar findings were obtained in the subset of 590 patients receiving HLA-matched allografts. C-statistic values were higher (indicating higher predictive accuracy) for peri-HCT MRD dynamics compared with the isolated use of pre-HCT MRD status or post-HCT MRD status for prediction of relapse, RFS, and OS. Across conditioning intensities, peri-HCT MRD dynamics improve risk assessment over isolated pre- or post-HCT MRD assessments in patients with AML

SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation.

Dysregulation of tissue development pathways can contribute to cancer initiation and progression. In murine embryonic prostate epithelia, the transcription factor SOX9 is required for proper prostate development. In this study, we examined a role for SOX9 in prostate cancer in mouse and human. In Pten and Nkx3.1 mutant mice, cells with increased levels of SOX9 appeared within prostate epithelia at early stages of neoplasia, and higher expression correlated with progression at all stages of disease. In transgenic mice, SOX9 overexpression in prostate epithelia increased cell proliferation without inducing hyperplasia. In transgenic mice that were also heterozygous for mutant Pten, SOX9 overexpression quickened the induction of high-grade prostate intraepithelial neoplasia. In contrast, Sox9 attenuation led to a decrease proliferating prostate epithelia cells in normal and homozygous Pten mutant mice with prostate neoplasia. Analysis of a cohort of 880 human prostate cancer samples showed that SOX9 expression was associated with increasing Gleason grades and higher Ki67 staining. Our findings identify SOX9 as part of a developmental pathway that is reactivated in prostate neoplasia where it promotes tumor cell proliferation