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At least 199 records · Page 11

Genetically engineered mouse models of esophageal cancer

Esophageal cancer is the most common cause of cancer-related death worldwide with a diverse geographical distribution, poor prognosis, and diagnosis in advanced stages of the disease. Identification of the mechanisms involved in esophageal cancer development is evaluative to improve outcomes for patients. Genetically engineered mouse models (GEMMs) of cancer provide the physiologic, molecular, and histologic features of the human tumors to determine the pathogenesis and treatments for cancer, hence exhibiting a source of tremendous potential for oncology research. The advancement of cancer modeling in mice has improved to the extent that researchers can observe and manipulate the disease process in a specific manner. Despite the significant differences between mice and humans, mice can be great models for human oncology researches due to similarities between them at the molecular and physiological levels. Due to most of the existing esophageal cancer GEMMs do not propose an ideal system for pathogenesis of the disease, genetic risks, and microenvironment exposure, so identification of challenges in GEM modeling and well-developed technologies are required to obtain the most value for patients. In this review, we describe the biology of human and mouse, followed by the exciting esophageal cancer mouse models with a discussion of applicability and challenges of these models for generating new GEMMs in future studies.

60 APPLIED LIFE SCIENCES↗

Implementation of Monte Carlo Transport in the General Relativistic SpEC Code

Neutrino transport and neutrino-matter interactions are known to play an important role in the evolution of neutron star mergers and of their post-merger remnants. Neutrinos cool remnants, drive post-merger winds, and deposit energy in the low-density polar regions where relativistic jets may eventually form. Neutrinos also modify the composition of the ejected material, impacting the outcome of nucleosynthesis in merger outflows and the properties of the optical/infrared transients that they power (kilonovae). So far, merger simulations have largely relied on approximate treatments of the neutrinos (leakage, moments) that simplify the equations of radiation transport in a way that makes simulations more affordable but also introduces unquantifiable errors in the results. To improve on these methods, we recently published a first simulation of neutron star mergers using a low-cost Monte Carlo algorithm for neutrino radiation transport. Our transport code limits costs in optically thick regions by placing a hard ceiling on the value of the absorption opacity of the fluid, yet all approximations made within the code are designed to vanish in the limit of infinite numerical resolution. We provide here an in-depth description of this algorithm, of its implementation in the SpEC merger code, and of the expected impact of our approximations in optically thick regions. We argue that the last is a subdominant source of error at the accuracy reached by current simulations and for the interactions currently included in our code. We also provide tests of the most important features of this code.

79 ASTRONOMY AND ASTROPHYSICS↗

Quantum critical collapse abhors a naked singularity

Classical critical collapse yields naked singularities from smooth initial data, challenging cosmic censorship, and shaping the spectrum of primordial black holes. We show that one-loop vacuum polarization near the threshold qualitatively changes this outcome by dressing the singularity with a horizon within a controlled semiclassical regime. In analytically tractable Einstein-scalar critical spacetimes, a one-loop $s$-wave treatment linearized around self-similar backgrounds shows that regularity uniquely selects an asymptotically Minkowskian, vacuum-polarization state. Its renormalized stress tensor carries a universal quantum growing mode that competes with the classical unstable mode, shifts the critical point, and generates a trapped surface along with a finite mass gap at the new threshold, thereby enforcing horizon formation even under arbitrary fine-tuning. In primordial collapse, the threshold shift enters exponentially into the formation fraction, while the mass gap truncates the low-mass tail, suggesting potentially important consequences for the predicted mass spectrum. Furthermore, these results provide a self-consistent semiclassical treatment of critical collapse and yield sharp predictions within the one-loop, near-critical, linearized regime.

Anomalies↗

Updates to the MSFC Meteoroid Stream Model

The Marshall Space Flight Center (MSFC) Meteoroid Stream Model simulates particle ejection and subsequent evolution from comets in order to provide meteor shower forecasts to spacecraft operators for hazard mitigation and planning purposes. The model, previously detailed, has recently been updated; the changes include the implementation of the RADAU integrator, an improved planetary treatment, and the inclusion of general relativistic effects in the force function. The results of these updates are investigated with respect to various meteoroid streams and the outcome presented.

Moser, D. E.↗

Impaired cardiac glycolysis and glycogen depletion are linked to poor myocardial outcomes in juvenile male swine with metabolic syndrome and ischemia

Abstract Obesity continues to rise in the juveniles and obese children are more likely to develop metabolic syndrome (MetS) and related cardiovascular disease. Unfortunately, effective prevention and long‐term treatment options remain limited. We determined the juvenile cardiac response to MetS in a swine model. Juvenile male swine were fed either an obesogenic diet, to induce MetS, or a lean diet, as a control (LD). Myocardial ischemia was induced with surgically placed ameroid constrictor on the left circumflex artery. Physiological data were recorded and at 22 weeks of age the animals underwent a terminal harvest procedure and myocardial tissue was extracted for total metabolic and proteomic LC/MS–MS, RNA‐seq analysis, and data underwent nonnegative matrix factorization for metabolic signatures. Significantly altered in MetS versus. LD were the glycolysis‐related metabolites and enzymes. In MetS compared with LD Glycogen synthase 1 (GYS1)‐glycogen phosphorylases (PYGM/PYGL) expression disbalance resulted in a loss of myocardial glycogen. Our findings are consistent with the concept that transcriptionally driven myocardial changes in glycogen and glucose metabolism‐related enzymes lead to a deficiency of their metabolite products in MetS. This abnormal energy metabolism provides insight into the pathogenesis of the juvenile heart in MetS. This study reveals that MetS and ischemia diminishes ATP availability in the myocardium via altering the glucose‐G6P‐pyruvate axis at the level of metabolites and gene expression of related enzymes. The observed severe glycogen depletion in MetS coincides with disbalance in expression of GYS1 and both PYGM and PYGL. This altered energy substrate metabolism is a potential target of pharmacological agents for improving juvenile myocardial function in MetS and ischemia.

Broadwin, Mark↗

Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery

OBJECTIVES: This study was conducted to evaluate follow-up results in patients with hypertrophic obstructive cardiomyopathy (HOCM) who underwent either percutaneous transluminal septal myocardial ablation (PTSMA) or septal myectomy. BACKGROUND: Controversy exists with regard to these two forms of treatment for patients with HOCM. METHODS: Of 51 patients with HOCM treated, 25 were treated by PTSMA and 26 patients via myectomy. Two-dimensional echocardiograms were performed before both procedures, immediately afterwards and at a three-month follow-up. The New York Heart Association (NYHA) functional class was obtained before the procedures and at follow-up. RESULTS: Interventricular septal thickness was significantly reduced at follow-up in both groups (2.3 +/- 0.4 cm vs. 1.9 +/- 0.4 cm for septal ablation and 2.4 +/- 0.6 cm vs. 1.7 +/- 0.2 cm for myectomy, both p < 0.001). Estimated by continuous-wave Doppler, the resting pressure gradient (PG) across the left ventricular outflow tract (LVOT) significantly decreased immediately after the procedures in both groups (64 +/- 39 mm Hg vs. 28 +/- 29 mm Hg for PTSMA, 62 +/- 43 mm Hg vs. 7 +/- 7 mm Hg for myectomy, both p < 0.0001). At three-month follow-up, the resting PG remained lower in the PTSMA and myectomy groups (24 +/- 19 mm Hg and 11 +/- 6 mm Hg, respectively, vs. those before procedures, both p < 0.0001). The NYHA functional class was also significantly improved in both groups (3.5 +/- 0.5 vs. 1.9 +/- 0.7 for PTSMA, 3.3 +/- 0.5 vs. 1.5 +/- 0.7 for myectomy, both p < 0.0001). CONCLUSIONS: Both myectomy and PTSMA reduce LVOT obstruction and significantly improve NYHA functional class in patients with HOCM. However, there are benefits and drawbacks for each therapeutic method that must be counterbalanced when deciding on treatment for LVOT obstruction.

Non-NASA Center↗

Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions: ExMC Pharmacy Research Plan

The Exploration Medical Capabilities (ExMC) Element of NASA's Human Research Program is charged with identifying medical capabilities that can address the challenges of prevention, diagnosis, and treatment of disease and injuries that could occur during exploration missions beyond Earth's orbit. Faced with the obstacle of access to in-flight medical care, and limitations of vehicle space, time, and communications; it is necessary to prioritize what medical consumables are manifested for the flight, and which medical conditions are addressed. Studies of astronaut health establish the incidence of common and high risk medical conditions that require medical intervention during long-duration exploration missions. In 2000, the Institute of Medicine (IOM) convened a committee of experts, Committee on Creating a Vision for Space Medicine during Travel beyond Earth Orbit, to examine the issues surrounding astronaut health and safety for long duration space missions. Two themes run throughout the committee's final report: (1) that not enough is known about the risks to human health during long-duration missions beyond Earth's orbit or about what can effectively mitigate those risks to enable humans to travel and work safely in the environment of deep space and (2) that everything reasonable should be done to gain the necessary information before humans are sent on missions of space exploration (IOM, 2001). Although several spaceflight focused pharmaceutical research studies have been conducted, few have provided sufficient data regarding medication usage or potency changes during spaceflight. The Du pharmaceutical stability study assessed medications flown on space shuttles to and from the International Space Station (ISS) from 2006 until 2008; of which some medications were still viable beyond their expiration dates (Du et al, 2011). However, as with many spaceflight studies, the small 'n' associated with this study limits the ability to draw strong conclusions from it. Dr. Wotring and others have recently published articles containing information regarding medication usage, indications, and efficacy gleaned from spaceflight records (Wotring et al, 2015, 2016; Barger et al, 2014; Basner and Dinges, 2014). Although some conclusions can be drawn from these studies, the inability to fully quantify medication usage, indications, side effects, and effectiveness, limits insight as to which medications should be prioritized for further research.

Antonsen, Erik↗

Safety and efficacy of peripheral nerve blocks to treat refractory headaches after aneurysmal subarachnoid hemorrhage – A pilot observational study

Objectives: Headache after aneurysmal subarachnoid hemorrhage (HASH) is common, severe, and often refractory to conventional treatments. Current treatment standards include medications including opioids, until the pain is mitigated. Peripheral nerve blocks (PNBs) may be an effective therapeutic option for HASH. We conducted a small before-and-after study of PNBs to determine safety, feasibility, and efficacy in treatment of HASH. Methods: We conducted a pilot before-and-after observational study and collected data for 5 patients in a retrospective control group and 5 patients in a prospective intervention PNB group over a 12-month period. All patients received a standard treatment of medications including acetaminophen, magnesium, gabapentin, dexamethasone and anti-spasmodics or anti-emetics as needed. Patients in the intervention group received bilateral greater occipital, lesser occipital, and supraorbital PNBs in addition to medications. The primary outcome was pain severity, measured by Numeric pain rating scale (NPRS). All patients were followed for 1 week following enrollment. Results: The mean ages in the PNB group and control group were 58.6 and 57.4, respectively. One patient in the control group developed radiographic vasospasm. Three patients in both groups had radiographic hydrocephalus and IVH, requiring external ventricular drain (EVD) placement. The PNB group had an average reduction in mean raw pain score of 2.76 (4.68, 1.92 p = 0.024), and relative pain score by 0.26 (0.48, 0.22 p = 0.026), compared to the control group. The reduction occurred immediately after PNB administration. Conclusion: PNB can be a safe, feasible and effective treatment modality for HASH. Further investigations with a larger sample size are warranted.

60 APPLIED LIFE SCIENCES↗

Application of Peracetic Acid in Poultry Processing: Effects of Treatment Dynamics and Emerging Risk of Resistance Development in Salmonella spp.

Nontyphoidal Salmonella is a leading cause of foodborne illness, with poultry representing a major source. Peracetic acid (PAA), a widely adopted antimicrobial in poultry processing, offers advantages over traditional disinfectants but has sparked interest in its combined use with other antimicrobials and potential resistance. This review evaluates the efficacy of PAA in mitigating Salmonella in combination with other food-grade antimicrobials, explores possible synergism, efficacy under varying treatment parameters, resistance development against PAA, and its role in resistance evolution. While PAA demonstrates broad-spectrum efficacy, its performance varies with environmental parameters; higher temperatures generally enhance antimicrobial action but also accelerate PAA degradation. Organic matter diminishes PAA efficacy by reactive quenching. Variability in concentration and contact time further influences outcomes. Despite its oxidative mode of action and presumed low risk for resistance, emerging studies indicate that Salmonella can develop adaptive tolerance and potential cross/coresistance following repeated or sublethal exposure to PAA. These adaptations may involve genetic upregulation of oxidative stress response pathways, efflux systems, and modifications in cell membrane integrity, raising concerns about the long-term sustainability of PAA use. Additionally, combinatorial treatments (e.g., PAA with UV-C, enzymes, or organic acids) show promise in enhancing efficacy while mitigating resistance risks. Despite recognition of PAA's safety and effectiveness, knowledge gaps remain regarding standardized resistance definitions, serotype-specific tolerance, and optimal intervention strategies in commercial settings. Therefore, there is a need for standardized testing protocols, robust studies on potential resistance, and further exploration of synergistic PAA applications to ensure sustained poultry product safety and public health protection.

37 - INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL C↗

Understanding Competing Risks

Highlights: • Clinicians and researchers need to be cognizant of competing risks (ie, the occurrence of an event that precludes future development of the outcome of interest). • Censoring is appropriate when a patient being censored at a particular time (eg, owing to loss to follow-up) is deemed to have approximately the same future risk of developing the outcome of interest as patients still being followed, and when the reason for censoring is not related to events of interest. • Censoring is not appropriate in many scenarios; for example, a dead patient can never develop a future cancer recurrence or late effect. • Kaplan-Meier (KM) analysis is commonly used for a time-to-event analysis when the primary outcome (eg, overall survival) has no meaningful competing risk and censoring is appropriate. Cox proportional hazards modeling can be used for multivariable analysis to examine the association between covariates and the primary outcome. • In the presence of competing events, incorrect use of the KM analysis will likely lead to an overestimation of the risk of the outcome of interest and biased estimates from both univariable and multivariable analyses. Therefore, KM usually should not be used to determine local recurrence risk because humanity is always at risk for dying, which is a competing risk. • A competing risk analysis is therefore most appropriate when there are competing events to the primary outcome of interest. The most commonly used multivariable model in these situations is the Fine-Gray model. • Many fundamental questions in radiation oncology—local and regional recurrence, treatment-related toxicity—are best addressed using competing risk methodologies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Lycorine targets multiple myeloma stem cell‐like cells by inhibition of Wnt/β‐catenin pathway

Summary Multiple myeloma (MM) is characterised by the proliferation and accumulation of malignant plasma cells in the bone marrow. Despite the progress in treatment over the last few years, MM remains incurable and the majority of patients relapse. MM stem‐like cells (MMSCs) have been considered as the main reason for drug resistance and eventual relapse. Currently, therapeutic agents are not enough to eradicate MMSCs, and finding effective strategies to eradicate MMSCs may improve the outcome of patients. Here we showed that lycorine, a natural compound from the Amaryllidaceae species, effectively inhibits the proliferation of myeloma cells from cell lines or patients, mainly through decreasing ALDH1 + cells. Mechanistically, lycorine decreases the MMSC population through inhibition of the Wnt/β‐catenin pathway by reducing the β‐catenin protein level. Moreover, lycorine could overcome the increasing proportion of ALDH1 + cells caused by bortezomib (BTZ) treatment, and a combination BTZ and lycorine have a synergistic effect on anti‐myeloma cells. Furthermore, we found a similar reduction of MMSC characteristics by lycorine in BTZ‐resistant MM cells and primary CD138 + plasma cells. Collectively, our findings indicate lycorine as a promising agent to target MMSCs to overcome the drug resistance of BTZ, and that, alone or in combination with BTZ, lycorine is a potential therapeutic strategy for MM treatments.

Wang, Haiqin↗

Women in Data Science Livermore Datathon 2024

The WiDS Datathon 2024 focuses on a prediction task using a roughly 39k record dataset (split into training and test sets) representing patients and their characteristics (age, race, BMI, zip code), their diagnosis and treatment information (breast cancer diagnosis code, metastatic cancer diagnosis code, metastatic cancer treatments, … etc.), their geo (zip-code level) demographic data (income, education, rent, race, poverty, …etc), as well as toxic air quality data (Ozone, PM25 and NO2) that tie health outcomes to environmental conditions. Each row in the data corresponds a single patient and her Diagnosis Period.

59 BASIC BIOLOGICAL SCIENCES↗

Novel Modular Treatment System for Distributed Energy Recovery and Water Reclamation from Industrial Wastewaters

The overarching goal of this work was to accelerate the commercialization of a distributed, modular, agile treatment technology - the Modular Encapsulated Two-stage Anaerobic Biological (METAB) system - by advancing it to pilot-scale. Specifically, the METAB system was developed to treat high strength wastewater (5,000-35,000 mg/L chemical oxygen demand (COD)), produce hydrogen (H2) and methane (CH4), and achieve these outcomes without a membrane for retention of microorganisms.

42 ENGINEERING↗

A 2D/3D Heterostructure Perovskite Solar Cell with a Phase‐Pure and Pristine 2D Layer

Abstract Interface engineering plays a critical role in advancing the performance of perovskite solar cells. As such, 2D/3D perovskite heterostructures are of particular interest due to their optoelectrical properties and their further potential improvements. However, for conventional solution‐processed 2D perovskites grown on an underlying 3D perovskite, the reaction stoichiometry is normally unbalanced with excess precursors. Moreover, the formed 2D perovskite is impure, leading to unfavorable energy band alignment at the interface. Here a simple method is presented that solves both issues simultaneously. The 2D formation reaction is taken first to completion, fully consuming excess PbI 2 . Then, isopropanol is utilized to remove excess organic ligands, control the 2D perovskite thickness, and obtain a phase‐pure, n = 2, 2D perovskite. The outcome is a pristine (without residual 2D precursors) and phase‐pure 2D perovskite heterostructure with improved surface passivation and charge carrier extraction compared to the conventional solution process. PSCs incorporating this treatment demonstrate a notable improvement in both stability and power conversion efficiency, with negligible hysteresis, compared to the conventional process.

14 SOLAR ENERGY↗

Zeolite‐Based Catalysts for Conversion of Oxygenated Polymer Waste by Positron Annihilation

Positron Annihilation Lifetime Spectroscopy (PALS) has been employed to investigate the catalysts HZSM-5 and MESO−Y, which play a pivotal role in catalyzing and upgrading plastics, with a primary focus on oxygenated polymers, thereby transforming existing plastic materials into simpler, higher-quality value-added products. Here, in this study, PALS was systematically compared with other complementary analytical techniques. The research outcomes have successfully demonstrated the efficacy of PALS in elucidating the morphology and topology of zeolites at micro/meso-meter scales. The first experiment focuses on H-ZSM-5 zeolite subjected to treatments involving polyurethane and polypropylene. The second experiment delves into H-ZSM-5 zeolites with varying Si/Al ratios, both before and after conversion. The third experiment investigates Y zeolites that are surfactant templated to induce meso-porosity, examining their fresh state as well as their post-conversion condition. The PALS analysis was supplemented by BET (Brunauer-Emmett-Teller) analysis and NMR (Nuclear Magnetic Resonance) spectroscopies. Notably, PALS exhibits superior sensitivity, at the sub-nanometer scale, suggesting its potential as a preferred complementary method for catalysis studies. In conclusion, the integration of PALS into the repertoire of analytical tools enhances our understanding of catalyst behavior and catalytic processes, offering valuable insights for the advancement of plastic recycling and catalysis research.

32 - ENERGY CONSERVATION, CONSUMPTION, AND UTILIZA↗

Analysis of Multi-Output Hybrid Energy Systems Interacting with the Grid: Application of Improved Price-Taker and Price-Maker Approaches to Nuclear-Hydrogen Systems

The growing recognition of the value of hydrogen as an energy intermediate in supporting future power systems with high shares of variable renewable energy has prompted many studies to quantify the economic potential of multi-output hybrid systems, which are one type of integrated energy systems (IES). Because of the complexity of modeling multiple sectors, these studies typically use simplified modeling approaches to capture the interactions between sectors. In this study, we explore the implications of alternative modeling approaches for nuclear-hydrogen IES focusing on a power system in the Midwest United States. We combine highly resolved capacity expansion and production cost modeling tools of the power system with a detailed hydrogen system optimization tool to determine the optimal electrolyzer and storage sizing and optimal operations of the nuclear-hydrogen hybrid resource across three future study years. We compare economic and operational outcomes across a spectrum of modeling approaches, including a non-hybridized base approach; a traditional price-taker approach that does not include the impact of hydrogen production on the electricity system; a power-system-focused price-maker approach that does not account for temporal hydrogen constraints; and two improved price-taker and price-maker approaches that each address the impact of revenue-optimal levels of electricity production on the resulting power system and temporal hydrogen constraints on the overall feasible solution. Results show how a traditional price-taker approach can overestimate the economic benefits of multi-output nuclear-hydrogen IES compared to our two improved approaches that estimate both hydrogen system constraints and power system interaction. We find that hydrogen output requirements and storage size limits are key drivers to overall operations and some economic outcomes. Under our assumed constant hydrogen output requirement, storage costs, test system, and modeling approaches, our results indicate that hybridization can provide a net benefit, but results are sensitive to the treatment of hydrogen revenues and electricity prices as impacted by the power system evolution.

capacity expansion modeling↗

Integrating microbial communities into algal biotechnology: a pathway to enhanced commercialization

Microalgae are increasingly recognized for their potential in wastewater treatment and the sustainable production of feedstock for fuel, feed, food, and other bioproducts. Like conventional agricultural systems, algal cultivation involves complex microbial communities. However, despite their pivotal role in cultivation outcomes, especially at the commodity-scale, the critical interactions between microalgae and their microbiomes are often overlooked. Here we synthesize current knowledge on the taxonomic diversity, ecological roles, and biotechnological potential of algal microbiomes, with a focus on their interactions with algal hosts through nutrient exchange, growth modulation, pathogen defense, and environmental conditioning. We also examine how environmental factors such as nutrient availability, salinity, and temperature influence these interactions. Advances in microbiome engineering, including synthetic biology and ecological approaches, offer opportunities to enhance beneficial algal-microbiome interactions, thereby improving growth, resilience, and yield. These advancements could lead to more sustainable and economically viable microalgae cultivation, with far-reaching implications for environmental management and biotechnological innovation. By addressing key economic and environmental barriers, microbiome engineering holds transformative potential to revolutionize large-scale algae cultivation and provide sustainable solutions to global challenges.

Microbiology↗

Predicting the impact of particle-particle collisions on turbophoresis with a reduced number of computational particles

A common feature of wall-bounded turbulent particle-laden flows is enhanced particle concentrations in a thin layer near the wall due to a phenomenon known as turbophoresis. Even at relatively low bulk volume fractions, particle-particle collisions regulate turbophoresis in a critical way, making simulations sensitive to collisional effects. Lagrangian tracking of every particle in the flow can become computationally expensive when the physical number of particles in the system is large. Artificially reducing the number of particles in the simulation can mitigate the computational cost. When particle-particle collisions are an important aspect determining the simulation outcome, as in the case when turbophoresis plays an active role, simply reducing the number of particles in the simulation significantly alters the computed particle statistics. This paper introduces a computational particle treatment for particle-particle collisions which reproduces the results of a full simulation with a reduced number of particles. This is accomplished by artificially enhancing the particle collision radius based on scaling laws for the collision rates. The proposed method retains the use of deterministic collision models and is applicable for both low and high Stokes number regimes.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗