Bulletin of Computer Science and Electrical Engineering (BCSEE)
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Abstract 3627: Inhibition of tumor cell-autonomous p38 MAPK suppresses IL1α-mediated inflammatory tumor-stromal crosstalk in pancreatic adenocarcinoma
No full textAbstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) continues to face major therapeutic challenges due to its innate and acquired chemoresistance. Oncogenic, activating KRAS mutations facilitate extensive cytokine-mediated crosstalk between tumor cells and the fibrotic stroma, producing a pro-inflammatory and immunosuppressive tumor microenvironment (TME). We have identified interleukin-1α (IL1α), downstream of KRAS, as a critical mediator of the inflammatory response due to its pleiotropic effects on cancer-associated fibroblast (CAF) activation and immune evasion. However, the regulatory mechanisms of IL1α expression remain incompletely understood. We identified p38 stress-associated MAPK α (p38α) as a central, KRAS-driven regulatory pathway involved in IL1α production within PDAC tumor cells. Methods: Differential gene expression analyses were performed on patient data from The Cancer Genome Atlas (TCGA) was queried for overactive pathways downstream KRAS in “high-IL1A” PDAC cases. Inhibition of p38α was achieved pharmacologically with pexmetinib and genetically with an shRNA lentiviral system in human and murine PDAC cell lines. ChIP-qPCR and co-immunoprecipitation were performed on a human PDAC cell line with and without p38α inhibition. Single-cell RNA sequencing (scRNA-seq) and flow cytometry were performed on tumors from a PDAC murine model, Ptf1aCre/+; LSL-KrasG12D/+; Tgfbr2flox/flox (PKT), treated with or without pexmetinib. PKT mice were treated daily with pexmetinib, gemcitabine and paclitaxel chemotherapy, or combination therapy for downstream analysis and survival studies. Results: Both pharmacologic and genetic inhibition of p38α significantly reduced IL1A transcription and protein levels in human and murine PDAC tumor cell lines. Furthermore, p38α inhibition reduced binding of Sp1 and NF-κB to the IL1A promoter and prevented IL1α-mediated polarization of inflammatory CAFs in vitro. In PKT mice, p38α inhibition reduced tumor cell-specific Il1a and inflammatory CAF gene signatures by scRNA-seq, and favorably altered the infiltrating immune populations by flow cytometry. Lastly, pexmetinib with chemotherapy significantly reduced tumor burden and improved overall survival in a PDAC murine model. Conclusions: These findings provide a new therapeutic opportunity to target the p38α MAPK pathway for suppression of IL1α-mediated stromal activation and combination with chemotherapy to overcome therapeutic resistance by modulating the stromal and immune microenvironment in PDAC. Citation Format: Samara Singh, Austin R. Dosch, Siddharth Mehra, Iago de Castro Silva, Anna Bianchi, Vanessa Tonin Garrido, Zhiqun Zhou, Haleh Amirian, Edmond W. Box, Jashodeep Datta, Nagaraj Nagathihalli, Nipun B. Merchant. Inhibition of tumor cell-autonomous p38 MAPK suppresses IL1α-mediated inflammatory tumor-stromal crosstalk in pancreatic adenocarcinoma. [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 3627
Genetic structure of common bottlenose dolphins (Tursiops truncatus) inhabiting adjacent South Florida estuaries – Biscayne Bay and Florida Bay
No full textCoastal common bottlenose dolphins show a variety of migration and residency patterns adding to the difficulty of defining stocks for management purposes. Genetic structure plays an important role in identifying population stocks of dolphins. This study examines genetic differentiation in common bottlenose dolphins both between two social groups occurring in Biscayne Bay, Florida and between Biscayne Bay and an adjacent group of dolphins in Florida Bay. Skin biopsy samples were sequenced at the mitochondrial DNA (mtDNA) control region and genotyped at microsatellite loci. Significant genetic differentiation was found between bottlenose dolphins in Biscayne Bay and Florida Bay (mtDNA FST = 0.139, p ≤ 0.001; microsatellite FST = 0.042, p ≤ 0.001) supporting independent management stock status for these two populations. Within Biscayne Bay, evidence of weak but significant population differentiation was found between the two social groups using microsatellite markers (FST = 0.0149, p ≤ 0.009); however, differentiation was not evident from the mtDNA-based estimates of FST and φST. The lack of differentiation at mtDNA coupled with field observations indicating overlapping home ranges for these two groups suggests ongoing, though perhaps low, levels of interbreeding. These data are insufficient to warrant splitting the Biscayne Bay management stock at this time
COVID-19 Vaccine Confidence Mediates the Relationship between Health Literacy and Vaccination in a Diverse Sample of Urban Adults
No full textWe sought to analyze the relationship between health literacy, confidence in COVID-19 vaccines, and self-reported vaccination. We hypothesized that the relationship between health literacy and vaccination would be mediated by vaccine confidence. We recruited (N = 271) English- and Spanish-speaking adults in Boston and Chicago from September 2018 to September 2021. We performed a probit mediation analysis to determine if confidence in COVID-19 vaccines and health literacy predicted self-reported vaccination. We hypothesized that the relationship between health literacy and vaccination would be mediated by vaccine confidence. Participants were on average 50 years old, 65% female, 40% non-Hispanic Black, 25% Hispanic, and 30% non-Hispanic White; 231 (85%) reported at least one COVID-19 vaccination. A higher mean vaccine confidence score (
= -7.9,
< 0.001) and higher health literacy (
= -2.2,
= 0.03) were associated with vaccination, but only vaccine confidence predicted vaccination in a multivariate model. Vaccine confidence mediated the relationship between health literacy and COVID-19 vaccination (mediated effects: 0.04; 95% CI [0.02, 0.08]). We found that using a simple tool to measure vaccine confidence identified people who declined or delayed COVID-19 vaccination in a diverse sample of adults with varying levels of health literacy. Simple short survey tools can be useful to identify people who may benefit from vaccine promotion efforts and evidence-based communication strategies
Living with water: Evolving adaptation preferences under increasing sea-level rise in Miami-Dade County, FL, USA
No full textGreat uncertainty exists about household responses to intensifying sea-level rise and related flooding, especially about when residents may consider relocation. Understanding how preferences for in-situ adaptation versus climate mobility evolve through time across communities with varying capacities can help identify policy solutions suited to a range of community needs. We present an analysis of 40 interviews and 597 survey responses from residents of Miami-Dade County, FL, USA—an area of substantial and increasing flood-related risk where concerns related to climate mobilities are emerging. We integrate new flood hazard models depicting chronic inundation and 1%-annual-chance flooding with street-level detail under increasing sea-level rise, which when combined with the interview and survey data reveal the multiplicities of spatiotemporal risk. Overall, we find that up to 75% of all participating respondents have experienced precipitation-based flooding in recent years, and “new normal” experiences of inundation are already reshaping current decisions to move. However, up to 57% of survey respondents preferred in-situ adaptations over moving away, highlighting a need for society-wide commitments to long-term adaptation. Socioeconomic pressures dominated climate mobility considerations among interview and survey respondents, raising climate justice concerns over socially inequitable mobility outcomes. Examinations of differential climate mobility pressures and preferences for adaptation increase understanding of the transformations reshaping coastal communities today to guide more equitable societal adaptations in the future
Nurse Care Management for Opioid Use Disorder Treatment The PROUD Cluster Randomized Clinical Trial
No full textImportance Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments. Objective To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization. Design, Setting, and Participants The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system’s randomization date through 2 years after. Intervention The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine. Main Outcomes and Measures The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up. Results During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics ( P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70). Conclusions and Relevance The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD. Trial Registration ClinicalTrials.gov Identifier: NCT0340763
Red Blood Cell Microparticles Limit Hemorrhage Following Intracerebral Hemorrhage in Spontaneously Hypertensive Rats
No full textPushing AI to wireless network edge: an overview on integrated sensing, communication, and computation towards 6G
No full textPushing artificial intelligence (AI) from central cloud to network edge has reached board consensus in both industry and academia for materializing the vision of artificial intelligence of things (AIoT) in the sixth-generation (6G) era. This gives rise to an emerging research area known as edge intelligence, which concerns the distillation of human-like intelligence from the vast amount of data scattered at the wireless network edge. Typically, realizing edge intelligence corresponds to the processes of sensing, communication, and computation, which are coupled ingredients for data generation, exchanging, and processing, respectively. However, conventional wireless networks design the three mentioned ingredients separately in a task-agnostic manner, which leads to difficulties in accommodating the stringent demands of ultra-low latency, ultra-high reliability, and high capacity in emerging AI applications like auto-driving and metaverse. This thus prompts a new design paradigm of seamlessly integrated sensing, communication, and computation (ISCC) in a task-oriented manner, which comprehensively accounts for the use of the data in downstream AI tasks. In view of its growing interest, this study provides a timely overview of ISCC for edge intelligence by introducing its basic concept, design challenges, and enabling techniques, surveying the state-of-the-art advancements, and shedding light on the road ahead
Prevalence of Low Testosterone in Men with Cystic Fibrosis and CBAVD: a cross-sectional study using a large, multi-institutional database
No full textOBJECTIVETo investigate the prevalence and treatment rates of low testosterone (T) in men with Cystic Fibrosis (CF). CF is a genetic disease with highly variable presentation that results from a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Phenotypic manifestations of CF include alterations in function of the lungs, liver, pancreas, and reproductive system. Despite the well-described association between CF and infertility secondary to congenital bilateral absence of the vas deferens (CBAVD), men with CF report further sexual and reproductive health concerns, many of which are often associated with low testosterone. METHODSWe queried the TrinetX database for men over 18 years old with CF or CBAVD to assess what percentage of men had a T level measured, and if hypogonadal (below 300 ng/dL), what percentage received T therapy (TT). We hypothesized that low T would be under-evaluated in the CF population. RESULTSSerum T levels were measured in 10.1% of men with CF and 8.9% of men with CBAVD. Within each group, 464 men with CF (32.7%) and 132 with CBAVD (43.0%) demonstrated low T. The majority of men with T<300 ng/dL went on to appropriately receive TT: 59.3% of men with CF and 78% with CBAVD. CONCLUSIONOur data suggests that hypogonadism is highly prevalent in men with CF and CBAVD. Investigation and appropriate treatment of testosterone deficiency may significantly improve quality of life
