Toward real-time, volumetric dosimetry for FLASH-capable clinical synchrocyclotrons using protoacoustic imaging.

Background: Radiation delivery with ultra-high dose rate (FLASH) radiotherapy (RT) holds promise for improving treatment outcomes and reducing side effects but poses challenges in radiation delivery accuracy due to its ultra-high dose rates. This necessitates the development of novel imaging and verification technologies tailored to these conditions.

Purpose: Our study explores the effectiveness of proton-induced acoustic imaging (PAI) in tracking the Bragg peak in three dimensions and in real time during FLASH proton irradiations, offering a method for volumetric beam imaging at both conventional and FLASH dose rates.

Shrinkage priors for isotonic probability vectors and binary data modeling, with applications to dose-response modeling.

Motivated by the need to model dose-response or dose-toxicity curves in clinical trials, we develop a new horseshoe-based prior for Bayesian isotonic regression modeling a binary outcome against an ordered categorical predictor, where the probability of the outcome is assumed to be monotonically non-decreasing with the predictor. The set of differences between outcome probabilities in consecutive categories of the predictor is equipped with a multivariate prior having support over simplex. The Dirichlet distribution, which can be derived from a normalized sum of independent gamma-distributed random variables, is a natural choice of prior, but using mathematical and simulation-based arguments, we show that the resulting posterior is prone to underflow and other numerical instabilities, even under simple data configurations.

Identifying employee, workplace and population characteristics associated with COVID-19 outbreaks in the workplace: a population-based study.

Objectives: To identify risk factors that contribute to outbreaks of COVID-19 in the workplace and quantify their effect on outbreak risk.

Methods: We identified outbreaks of COVID-19 cases in the workplace and investigated the characteristics of the individuals, the workplaces, the areas they work and the mode of commute to work, through data linkages based on Middle Layer Super Output Areas in England between 20 June 2021 and 20 February 2022. We estimated population-level associations between potential risk factors and workplace outbreaks, adjusting for plausible confounders identified using a directed acyclic graph.

Nonresolving Axillary Lymphadenopathy: An Unexpected Case of Metastatic Jejunal Adenocarcinoma in a Small-Bowel Transplant Recipient Masquerading as Posttransplant Lymphoproliferative Disorder.

Intestinal transplant is an uncommon treatment of intestinal failure that has provided many patients with reduced morbidity and mortality. However, there are associated risks, including an increased risk of cancer, such as posttransplant lymphoproliferative disorder and solid-organ malignancy. Here, we report a unique case of primary jejunal adenocarcinoma presenting initially only with axillary lymphadenopathy in a patient with recurrent posttransplant lymphoproliferative disorder after multiple solid-organ transplants, including small intestine and 2 renal transplants.

Mitochondrial calcium uniporter deficiency in dentate granule cells remodels neuronal metabolism and impairs reversal learning.

The mitochondrial calcium uniporter (MCU) is the main route of calcium (Ca) entry into neuronal mitochondria. This channel has been linked to mitochondrial Ca overload and cell death under neurotoxic conditions, but its physiologic roles for normal brain function remain poorly understood. Despite high expression of MCU in excitatory hippocampal neurons, it is unknown whether this channel is required for learning and memory.

Progressive cognitive impairment after recovery from neuroinvasive and non-neuroinvasive infection.

Background: Neuro-cognitive impairment is a deleterious complication of bacterial infections that is difficult to treat or prevent. () is a neuroinvasive bacterial pathogen and commonly used model organism for studying immune responses to infection. Antibiotic-treated mice that survive systemic infection have increased numbers of CD8 and CD4 T-lymphocytes in the brain that include tissue resident memory (T) T cells, but post-infectious cognitive decline has not been demonstrated.

Cognitive heterogeneity reveals molecular signatures of age-related impairment.

The greatest risk factor for cognitive decline is aging. The biological mechanisms for this decline remain enigmatic due, in part, to the confounding of normal aging mechanisms and those that contribute to cognitive impairment. Importantly, many individuals exhibit impaired cognition in age, while some retain functionality despite their age.

Light curves and colours of the ejecta from Dimorphos after the DART impact.

On 26 September 2022, the Double Asteroid Redirection Test (DART) spacecraft struck Dimorphos, a satellite of the asteroid 65803 Didymos. Because it is a binary system, it is possible to determine how much the orbit of the satellite changed, as part of a test of what is necessary to deflect an asteroid that might threaten Earth with an impact. In nominal cases, pre-impact predictions of the orbital period reduction ranged from roughly 8.

Engineered matrix microenvironments reveal the heterogeneity of liver sinusoidal endothelial cell phenotypic responses.

Fibrosis is one of the hallmarks of chronic liver disease and is associated with aberrant wound healing. Changes in the composition of the liver microenvironment during fibrosis result in a complex crosstalk of extracellular cues that promote altered behaviors in the cell types that comprise the liver sinusoid, particularly liver sinusoidal endothelial cells (LSECs). Recently, it has been observed that LSECs may sustain injury before other fibrogenesis-associated cells of the sinusoid, implicating LSECs as key actors in the fibrotic cascade.

Direct incorporation of patient-specific efficacy and toxicity estimates in radiation therapy plan optimization.

Purpose: Current radiation therapy (RT) treatment planning relies mainly on pre-defined dose-based objectives and constraints to develop plans that aim to control disease while limiting damage to normal tissues during treatment. These objectives and constraints are generally population-based, in that they are developed from the aggregate response of a broad patient population to radiation. However, correlations of new biologic markers and patient-specific factors to treatment efficacy and toxicity provide the opportunity to further stratify patient populations and develop a more individualized approach to RT planning.

Selective Ablation of in Astrocytes Induces Sex-Specific Effects on Cognitive Function, d-Serine Availability, and Astrogliosis.

Cognitive decline is a debilitating aspect of aging and neurodegenerative diseases such as Alzheimer's disease are closely associated with mitochondrial dysfunction, increased reactive oxygen species, neuroinflammation, and astrogliosis. This study investigated the effects of decreased mitochondrial antioxidant response specifically in astrocytes on cognitive performance and neuronal function in C57BL/6J mice using a tamoxifen-inducible astrocyte-specific knockout of manganese superoxide dismutase (aSOD2-KO), a mitochondrial matrix antioxidant that detoxifies superoxide generated during mitochondrial respiration. We reduced astrocyte SOD2 levels in male and female mice at 11-12 months of age and tested in an automated home cage (PhenoTyper) apparatus for diurnal patterns, spatial learning, and memory function at 15 months of age.

Investigating the Incidence of Pulmonary Abnormalities as Identified by Parametric Response Mapping in Patients With Lung Cancer Before Radiation Treatment.

Purpose: Parametric response mapping (PRM) of high-resolution, paired inspiration and expiration computed tomography (CT) scans is a promising analytical imaging technique that is currently used in diagnostic applications and offers the ability to characterize and quantify certain pulmonary pathologies on a patient-specific basis. As one of the first studies to implement such a technique in the radiation oncology clinic, the goal of this work was to assess the feasibility for PRM analysis to identify pulmonary abnormalities in patients with lung cancer before radiation therapy (RT).

Methods And Materials: High-resolution, paired inspiration and expiration CT scans were acquired from 23 patients with lung cancer as part of routine treatment planning CT acquisition.

Genome Sequences of 22 T1-like Bacteriophages That Infect .

Here, the full genome sequences of 22 T1-like bacteriophages isolated from wastewater are reported. Eight (BlueShadow, Brooksby, Devorator, ElisaCorrea, Reinasaurus, SorkZaugg, Supreme284, ZeroToHero) were isolated on , six on Klebsiella (Chell, FairDinkum, HazelMika, Opt-817, P528, PeteCarol), and eight on Escherichia (Fulano1, Mishu, Opt-719, PhleaSolo, Punny, Poky, Phunderstruck, Sadiya).

U.S. bound journey of migrant peoples InTransit across Dante's Inferno and Purgatory in the Americas.

Rapid rise of population migration is a defining feature of the 21st century due to the impact of climate change, political instability, and socioeconomic downturn. Over the last decade, an increasing number of migrant peoples travel across the Americas to reach the United States seeking asylum or cross the border undocumented in search of economic opportunities. In this journey, migrant people experience violations of their human rights, hunger, illness, violence and have limited access to medical care.

Combining Serial and Parallel Functionality in Functional Lung Avoidance Radiation Therapy.

Purpose: Functional lung avoidance (FLA) radiation therapy (RT) aims to minimize post-RT pulmonary toxicity by preferentially avoiding dose to high-functioning lung (HFL) regions. A common limitation is that FLA approaches do not consider the conducting architecture for gas exchange. We previously proposed the functionally weighted airway sparing (FWAS) method to spare airways connected to HFL regions, showing that it is possible to substantially reduce risk of radiation-induced airway injury.

Percutaneous delivery of self-propelling hemostatic powder for managing non-compressible abdominal hemorrhage: a proof-of-concept study in swine.

Introduction: Non-compressible intra-abdominal hemorrhage (NCIAH) is a major cause of preventable death on the battlefield and in civilian trauma. Currently, it can only be definitively managed with surgery, as there are limited strategies for controlling ongoing NCIAH in the prehospital environment. We hypothesized that a self-propelling thrombin-containing powder (SPTP) could increase survival in a swine model of NCIAH when delivered percutaneously into the closed abdomen using an engineered spray system.

Investigating the SPECT Dose-Function Metrics Associated With Radiation-Induced Lung Toxicity Risk in Patients With Non-small Cell Lung Cancer Undergoing Radiation Therapy.

Purpose: Dose to normal lung has commonly been linked with radiation-induced lung toxicity (RILT) risk, but incorporating functional lung metrics in treatment planning may help further optimize dose delivery and reduce RILT incidence. The purpose of this study was to investigate the impact of the dose delivered to functional lung regions by analyzing perfusion (Q), ventilation (V), and combined V/Q single-photon-emission computed tomography (SPECT) dose-function metrics with regard to RILT risk in patients with non-small cell lung cancer (NSCLC) patients who received radiation therapy (RT).

Methods And Materials: SPECT images acquired from 88 patients with locally advanced NSCLC before undergoing conventionally fractionated RT were retrospectively analyzed.

Interleukin 6 reduces allopregnanolone synthesis in the brain and contributes to age-related cognitive decline in mice.

Cognitive decline with age is a harmful process that can reduce quality of life. Multiple factors have been established to contribute to cognitive decline, but the overall etiology remains unknown. Here, we hypothesized that cognitive dysfunction is mediated, in part, by increased levels of inflammatory cytokines that alter allopregnanolone (AlloP) levels, an important neurosteroid in the brain.

Automated classification of three-dimensional reconstructions of coral reefs using convolutional neural networks.

Coral reefs are biologically diverse and structurally complex ecosystems, which have been severally affected by human actions. Consequently, there is a need for rapid ecological assessment of coral reefs, but current approaches require time consuming manual analysis, either during a dive survey or on images collected during a survey. Reef structural complexity is essential for ecological function but is challenging to measure and often relegated to simple metrics such as rugosity.

Disparate Central and Peripheral Effects of Circulating IGF-1 Deficiency on Tissue Mitochondrial Function.

Age-related decline in circulating levels of insulin-like growth factor (IGF)-1 is associated with reduced cognitive function, neuronal aging, and neurodegeneration. Decreased mitochondrial function along with increased reactive oxygen species (ROS) and accumulation of damaged macromolecules are hallmarks of cellular aging. Based on numerous studies indicating pleiotropic effects of IGF-1 during aging, we compared the central and peripheral effects of circulating IGF-1 deficiency on tissue mitochondrial function using an inducible liver IGF-1 knockout (LID).

Accelerated decline in cognition in a mouse model of increased oxidative stress.

Mice deficient in the antioxidant enzyme Cu/Zn-superoxide dismutase (Sod1KO mice) have a significant reduction in lifespan, exhibit many phenotypes of accelerated aging, and have high levels of oxidative stress in various tissues. Age-associated cognitive decline is a hallmark of aging and the increase in oxidative stress/damage with age is one of the mechanisms proposed for cognitive decline with age. Therefore, the goal of this study was to determine if Sod1KO mice exhibit an accelerated loss in cognitive function similar to that observed in aged animals.

Modeling Patient-Specific Dose-Function Response for Enhanced Characterization of Personalized Functional Damage.

Purpose: Functional-guided radiation therapy (RT) plans have the potential to limit damage to normal tissue and reduce toxicity. Although functional imaging modalities have continued to improve, a limited understanding of the functional response to radiation and its application to personalized therapy has hindered clinical implementation. The purpose of this study was to retrospectively model the longitudinal, patient-specific dose-function response in non-small cell lung cancer patients treated with RT to better characterize the expected functional damage in future, unknown patients.