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Abstract We report the first detection and prevalence of Beak and feather disease virus (BFDV) in Australia’s Red Goshawk (Erythrotriorchis radiatus). This is a new host for this pervasive pathogen amongst a growing list of non-psittacine species including birds of prey from the orders Accipitriformes (hawks, eagles, kites), Falconiformes (falcons and caracas), and Strigiformes (owls). The Red Goshawk is the first non-psittacine species listed as Endangered to be diagnosed with BFDV. We report an initial case of infection discovered post-mortem in a dead nestling and subsequent surveillance of birds from across northern Australia. We reveal BFDV prevalence rates in a wild raptor population for the first time, with detections in 25% (n = 7/28) of Red Goshawks sampled. Prevalence appears higher in juveniles compared to adults, although not statistically significant, but is consistent with studies of wild psittacines. BFDV genotypes were associated with the Loriinae (lorikeets, budgerigar, and fig parrots), Cacatuini (Cockatoos), and Polytelini (long-tailed parrots) tribes; species which are preyed upon by Red Goshawks. A positive BFDV status may be associated with lower body mass but small sample sizes precluded robust statistical analysis. We postulate the possible impacts of the virus on Red Goshawks and discuss future research priorities given these preliminary observations.

Abstract Gape‐limited predators (e.g., snakes, many fish) are not generally expected to pose a predation threat to prey that are too large for them to swallow. However, the extent to which snakes predate on prey that exceed their gape limitation remains largely unknown. We conducted the first study to investigate the influence of both prey and predator sizes on the frequency of ingestion success by snakes in a natural system. We combined survival monitoring of an avian prey species (Aplonis opaca) via radio‐telemetry with a survey of the size distribution of their major predator (Boiga irregularis) on Guam. This allowed us to assess (1) the frequency of unsuccessful ingestion by the predator, (2) whether the size of the prey predicts ingestion success, (3) whether the size of the predator predicts ingestion success, and (4) the relationship between prey and predator sizes in successful ingestion attempts. We found that nearly half (47.95%) of ingestion attempts by snakes on fledgling birds were unsuccessful, and no instances where unsuccessful ingestion caused the mortality of the snake. Attempts to consume smaller fledglings were as likely to be unsuccessful as attempts to swallow larger fledglings. However, snakes that successfully ingested fledglings were among the largest snakes in the population, and larger than average conspecifics attracted to endothermic prey. The smallest snakes that successfully ingested fledglings attained remarkably high relative prey mass values for their species, consuming prey weighing up to 79.9% of their own mass. Our study indicates that B. irregularis routinely predate prey that are too large for them to successfully ingest, which causes mortality to the prey but poses little risk to the predator. The potential reward for snakes in consuming oversized prey may outweigh the inherent risks, while instances of predation that do not result in consumption may have considerable impacts on prey populations.

IntroductionMany military service members and civilians suffer from lower extremity trauma. Despite recent advancements in lower limb bracing technology, it remains unclear whether these newer advanced braces offer improved comfort and functionality compared to conventional options. The IDEO (Intrepid Dynamic Exoskeletal Orthosis), a type of “advanced” orthosis was developed to assist in maintaining high functional performance in patients who have experienced high-energy lower extremity trauma and underwent limb salvage surgeries.MethodsA cross-sector multi-site initiative was completed to study the efficacy of advanced ankle foot orthoses (AFO) for lower limb trauma and injury compared to a conventional AFO. Following fitting, training, and accommodation, the subjects were assessed in each AFO system for mobility, self-reported function, safety and pain, and preference.ResultsThey preferred the advanced over the conventional AFO and the mobility and exertion perception improved with the advanced AFO with no difference in pain or overall health status scores.DiscussionThus, an advanced AFO is an option for trauma affecting the lower limb. Long-term studies are required to better understand the accommodation and learning process of using an advanced AFO.

In October 2020, a new population of invasive brown treesnakes (Boiga irregularis) was discovered on the 33-ha Cocos Island, 2.5 km off the south coast of Guam. Cocos Island is a unique conservation resource, providing refuge for many lizards and birds, including endangered species, which were extirpated from mainland Guam by invasive predators including brown treesnakes. We sought to evaluate the usefulness of toxic baiting with acetaminophen-treated carrion baits and cage trapping, common tools for the control of brown treesnakes on mainland Guam, as potential eradication tools on Cocos Island. We evaluated multiple bait types and bait presentations: on the ground, suspended in the canopy emulating aerial bait applications and in four plastic-tube bait station configurations intended to exclude non-target species. We monitored all baits with time-lapse cameras. Despite improved exclusion of non-targets by bait station design, most baits were quickly removed by non-target species, particularly coconut crabs (Birgus latro) and Mariana monitors (Varanus tsukamotoi). Monitoring of 1,250 baits available for 2,427 bait nights resulted in no observations of brown treesnakes taking any bait. Subsequently, we tested two trap types commonly used on Guam and compared trapping success with live versus dead mouse lures. In 10,553 trap nights using live and dead mouse lures, we only captured one brown treesnake, in a trap with a live mouse lure. These baiting and trapping rates are so low as to be ineffectual for all practical purposes. Concurrent visual searching and hand capture of brown treesnakes during initial rapid response efforts demonstrates that these low baiting and trapping success rates are not a result of low snake density. We make a case for our assumption that the ineffectiveness of these tools on Cocos Island is due to the context of extremely high abundance of preferred live prey, primarily large geckos and birds. Our results have profound conservation ramifications, because any future island invasions by brown treesnakes are likely to occur within similarly prey-rich environments where these baiting and trapping methods might be similarly ineffective.

Thioredoxin Reductase (TrxR) functions to recycle thioredoxin (Trx) during hydroperoxide metabolism mediated by peroxiredoxins and is currently being targeted using the FDA-approved anti-rheumatic drug, auranofin (AF), to selectively sensitize cancer cells to therapy. AF treatment decreased TrxR activity and clonogenic survival in small cell lung cancer (SCLC) cell lines (DMS273 and DMS53) as well as the H727 atypical lung carcinoid cell line. AF treatment also significantly sensitized DMS273 and H727 cell lines in vitro to sorafenib, an FDA-approved multi-kinase inhibitor that depleted intracellular glutathione (GSH). The pharmacokinetic, pharmacodynamic, and safety profile of AF was examined in nude mice with DMS273 xenografts administered AF intraperitoneally at 2 mg/kg or 4 mg/kg (IP) once (QD) or twice daily (BID) for 1−5 d. Plasma levels of AF were 10–20 μM (determined by mass spectrometry of gold), and the optimal inhibition of TrxR activity was obtained at 4 mg/kg once daily, with no effect on glutathione peroxidase 1 activity. This AF treatment extended for 14 d, inhibited TrxR (>75%), and resulted in a significant prolongation of median overall survival from 19 to 23 d (p = .04, N = 30 controls, 28 AF). In this experiment, there were no observed changes in animal bodyweight, complete blood counts (CBCs), bone marrow toxicity, blood urea nitrogen, or creatinine. These results support the hypothesis that AF effectively inhibits TrxR both in vitro and in vivo in SCLC, sensitizes NETs and SCLC to sorafenib, and could be repurposed as an adjuvant therapy with targeted agents that induce disruptions in thiol metabolism.

Radiation therapy (RT) has long been fundamental for the curative treatment of breast cancer. While substantial progress has been made in the anatomical and technological precision of RT delivery, and some approaches to de-escalate or omit RT based on clinicopathologic features have been successful, there remain substantial opportunities to refine individualised RT based on tumour biology.A major area of clinical and research interest is to ascertain the individualised risk of loco-regional recurrence to direct treatment decisions regarding escalation and de-escalation of RT. Patient-tailored treatment with RT is considerably lagging behind compared with the massive progress made in the field of personalised medicine that currently mainly applies to decisions on the use of systemic therapy or targeted agents.Herein we review select literature surrounding the use of tumour genomic biomarkers and biomarkers of the immune system, including tumour infiltrating lymphocytes (TILs), within the management of breast cancer, specifically as they relate to progress in moving toward analytically validated and clinically tested biomarkers utilized in RT.

Introduction Public health efforts to reduce opioid overdose fatalities include educating people at risk and expanding access to naloxone, a medication that reverses opioid-induced respiratory depression. People receiving long-term opioid therapy (LTOT) are at increased risk for overdose, yet naloxone uptake in this population remains low. The objective of this study was to determine if a targeted, digital health intervention changed patient risk behaviour, increased naloxone uptake and increased knowledge about opioid overdose prevention and naloxone.Methods We conducted a pragmatic randomised clinical trial among patients prescribed LTOT in a healthcare delivery system in Colorado. Participants were randomly assigned to receive an animated overdose prevention and naloxone educational video (intervention arm) or usual care (control arm). The 6 min video was designed to educate patients about opioid overdose and naloxone, increase overdose risk perception and prompt them to purchase naloxone from the pharmacy. Over an 8-month follow-up, opioid risk behaviour was assessed with the Opioid-Related Behaviours in Treatment survey instrument, and overdose and naloxone knowledge was measured with the Prescription Opioid Overdose Knowledge Scale after viewing the video at baseline. Naloxone dispensations were evaluated using pharmacy data over a 12-month period. Data were analysed with generalised linear mixed effects and log-binomial regression models.Results There were 519 participants in the intervention arm and 485 participants in the usual care arm. Opioid risk behaviour did not differ between the study arms over time (study arm by time interaction p=0.93). There was no difference in naloxone uptake between the arms (risk ratio 1.13, 95% CI 0.77 to 1.66). Knowledge was significantly greater in the intervention arm compared with usual care (p

Maternal separation in early life has been observed to have lasting, detrimental effects that impair personal and social development and can persist into adulthood. Maternal separation during infancy can be most detrimental during adolescence, leading to long-term adverse effects on development and social behavior. This research study compared the effects of sibling and maternal separation in infancy on anxiety, sociability, or memory later in adolescence (postnatal day, PND, 50-58) in male and female Long-Evans Rats (Rattus norvegicus). Rat pups were semi-randomly assigned into eight conditions for daily isolation (PND 1-14). The groups were separated by the duration of isolation between 15 minutes (control group) or 180 minutes (experimental group) and the sex of the rat. They were also separated by comfort conditions with the dam present in an adjoining cage versus not present and siblings present or not present during isolation. The result was a 2 (15-min vs. 180-min) x 2 (dam vs. no dam) x 2 (single vs. grouped) x 2 (male vs. female) design. Once pups had reached adolescence (PND 50), researchers tested for differences in anxiety, activity, and social behavior using elevated plus-maze, open field habituation, a three-chamber social interaction, and a social discrimination task. Results indicate that longer isolation was more stressful and caused lower body weight. The female rats showed more anxious behavior in the open field but only if they were in the shorter isolation group. Social interaction showed that the rats isolated with the dam had different effects of isolation. In males, shorter isolation with the dam increased sociability but decreased sociability in females. These complicated findings may be due to the effects of inoculation, which describes how moderate stress combined with comfort may produce adaptation or immunity to stress and affect males and females differently.

Jupiter’s largest moon Ganymede has its own intrinsic magnetic field, which forms a magnetosphere that is embedded within Jupiter’s corotating magnetospheric plasma. This scenario has been shown to lead to complex ion precipitation patterns that have been connected to heterogeneous space weathering across Ganymede’s surface. We present the first simulations of energetic neutral atoms (ENAs) from backscattered H, O, and S ions, accounting for magnetospheric plasma precipitation and Ganymede’s heterogeneous surface composition. Our model shows that backscattering introduces significant atomic H and O populations to Ganymede’s ENA environment, which will allow remote observation of ion–surface interactions at Ganymede. There are distinct differences between H ENA emissions at Ganymede and the Moon, with orders of magnitude lower fluxes below 1 keV but a significant tail above 1 keV. Backscattered H ENAs will also dominate over sputtered H contributions above energies of around 1 keV, while O ENAs are less likely to be distinguished from sputtered ENAs. The backscattered H ENAs thus represent a promising candidate for studying the plasma–surface interaction on Ganymede with future observations of ESA’s JUICE mission.

Coronary artery disease (CAD) and myocardial infarction (MI) remain leading causes of death and disability worldwide. CAD begins with the formation of atherosclerotic plaques within the intimal layer of the coronary arteries, a process driven by persistent arterial inflammation and oxidation. Myeloperoxidase (MPO), a mammalian haem peroxidase enzyme primarily expressed within neutrophils and monocytes, has been increasingly recognised as a key pro-inflammatory and oxidative enzyme promoting the development of vulnerable coronary atherosclerotic plaques that are prone to rupture, and can precipitate a MI. Mounting evidence also implicates a pathogenic role for MPO in the inflammatory process that follows a MI, which is characterised by the rapid infiltration of activated neutrophils into the damaged myocardium and the release of MPO. Excessive and persistent cardiac inflammation impairs normal cardiac healing post-MI, resulting in adverse cardiac outcomes and poorer long-term cardiac function, and eventually heart failure. This review summarises the evidence for MPO as a significant oxidative enzyme contributing to the inappropriate inflammatory responses driving the progression of CAD and poor cardiac healing after a MI. It also details the proposed mechanisms underlying MPO’s pathogenic actions and explores MPO as a novel therapeutic target for the treatment of unstable CAD and cardiac damage post-MI.

Neutrophil-myeloperoxidase (MPO) is a heme-containing peroxidase which produces excess amounts of hypochlorous acid during inflammation. While pharmacological MPO inhibition mitigates all indices of experimental colitis, no studies have corroborated the role of MPO using knockout (KO) models. Therefore, we investigated MPO deficient mice in a murine model of colitis. Wild type (Wt) and MPO-deficient mice were treated with dextran sodium sulphate (DSS) in a chronic model of experimental colitis with three acute cycles of DSS-induced colitis over 63 days, emulating IBD relapse and remission cycles. Mice were immunologically profiled at the gut muscoa and the faecal microbiome was assessed via 16S rRNA amplicon sequencing. Contrary to previous pharmacological antagonist studies targeting MPO, MPO-deficient mice showed no protection from experimental colitis during cyclical DSS-challenge. We are the first to report drastic faecal microbiota shifts in MPO-deficient mice, showing a significantly different microbiome profile on Day 1 of treatment, with a similar shift and distinction on Day 29 (half-way point), via qualitative and quantitative descriptions of phylogenetic distances. Herein, we provide the first evidence of substantial microbiome shifts in MPO-deficiency, which may influence disease progression. Our findings have significant implications for the utility of MPO-KO mice in investigating disease models.

Abstract Triple-negative breast cancer (TNBC) patients with residual disease (RD) after neoadjuvant systemic therapy (NAST) are at high risk for recurrence. Biomarkers to risk-stratify patients with RD could help individualize adjuvant therapy and inform future adjuvant therapy trials. We aim to investigate the impact of circulating tumor DNA (ctDNA) status and residual cancer burden (RCB) class on outcomes in TNBC patients with RD. We analyze end-of-treatment ctDNA status in 80 TNBC patients with residual disease who are enrolled in a prospective multisite registry. Among 80 patients, 33% are ctDNA positive (ctDNA+) and RCB class distribution is RCB-I = 26%, RCB-II = 49%, RCB-III = 18% and 7% unknown. ctDNA status is associated with RCB status, with 14%, 31%, and 57% of patients within RCB-I, -II, and -III classes demonstrating ctDNA+ status (P = 0.028). ctDNA+ status is associated with inferior 3-year EFS (48% vs. 82%, P

Summary: Pseudomonas aeruginosa (Pa) is a pathogen causing chronic pulmonary infections in patients with cystic fibrosis (CF). Manipulation of lipids is an important feature of Pa infection and on a tissue-level scale is poorly understood. Using a mouse model of acute Pa pulmonary infection, we explored the whole-lung phospholipid response using mass spectrometry imaging (MSI) and spatial lipidomics. Using a histology-driven analysis, we isolated airways and parenchyma from both mock- and Pa-infected lungs and used systems biology tools to identify enriched metabolic pathways from the differential phospholipid identities. Infection was associated with a set of 26 ions, with 11 unique to parenchyma and 6 unique to airways. Acyl remodeling was differentially enriched in infected parenchyma as the predominant biological function. These functions correlated with markers of polymorphonuclear (PMN) cell influx, a defining feature of the lung response to Pa infection, implicating enzymes active in phospholipid remodeling.

Social work practice is grounded in the symbiotic relationship between macrosystemic community work and direct practice with individuals; however, following a resurgence in emphasis on evidence-based clinical social work in higher education, research on community-building efforts within social work has waned. Among sexual and gender minority populations (SGM), research has indicated a vast array of negative outcomes associated with added stressors, such as stigma, discrimination, and marginalization impacting the population. As such, this study attempts to re-focus the attention of social work practice on the importance of building community, especially for SGM populations. Via a multi-group analysis, the relationship between community (positive social institutions), hope, and flourishing was explored in both the cisgender-heterosexual population and that of the sexual and gender minority population (n = 586) within the United States. Results indicate that there are differences with positive social institutions directly impacting flourishing and indirectly through hope, whereas among the cisgender-heterosexual population, positive social institutions impact flourishing indirectly through hope, and not directly. As such, it is imperative that social workers focus on building strong supportive communities for SGM populations in order to directly and indirectly impact their overall flourishing and wellbeing.

Abstract Triple-negative breast cancer (TNBC) is classically defined by estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry expression

Objective: To determine the role of multiple factors on general well-being for upper limb prosthesis users. Design: Retrospective cross-sectional observational design. Setting: Prosthetic clinics across the United States. Participants: At the time of analysis, the database consisted of 250 patients with unilateral upper limb amputation seen between July 2016 and July 2021. Intervention: Not applicable. Main Outcomes Measures: Dependent variable: well-being (Prosthesis Evaluation Questionnaire- Well-Being). Independent variables included in analysis: activity and participation (Patient Reported Outcomes Measurement Information System [PROMIS] Ability to Participate in Social Roles and Activities), bimanual function (PROMIS-9 UE), prosthesis satisfaction (Trinity Amputation and Prosthesis Experience Scales-Revised; TAPES-R), PROMIS pain interference, age, gender, average daily hours worn, time since amputation, and amputation level. Results: A multivariate linear regression model using a forward enter method was applied. The model included 1 dependent variable (well-being) and 9 independent variables. Within the multiple linear regression model, the strongest predictors of well-being were activity and participation (β=0.303, P

Measurement(s) Wildfire half-daily perimeters and attributes Technology Type(s) Remote sensing Sample Characteristic - Organism Wildfires Sample Characteristic - Environment Ecosystems Sample Characteristic - Location California

Excessive inflammation and impaired healing of cardiac tissue following a myocardial infarction (MI) can drive the development of heart failure. Cardiac repair begins immediately after the onset of MI and continues for months. The repair process can be divided into the following 3 overlapping phases, each having distinct functions and sequelae: the inflammatory phase, the proliferative phase, and the maturation phase. Macrophages, neutrophils, and lymphocytes are present in the myocardium throughout the repair process and govern the duration and function of each of these phases. However, changes in the functions of these cell types across each phase are poorly characterized. Numerous immunomodulatory therapies that specifically target inflammation have been developed for promoting cardiac repair and preventing heart failure after MI. However, these treatments have been largely unsuccessful in large‐scale clinical randomized controlled trials. A potential explanation for this failure is the lack of a thorough understanding of the time‐dependent evolution of the functions of immune cells after a major cardiovascular event. Failure to account for this temporal plasticity in cell function may reduce the efficacy of immunomodulatory approaches that target cardiac repair. This review is concerned with how the functions of different immune cells change with time following an MI. Improved understanding of the temporal changes in immune cell function is important for the future development of effective and targeted treatments for preventing heart failure after MI.

Western Boundary Currents and the eddies they shed are high priorities for numerical estimation and forecasting due to their economic, ecological and dynamical importance. However, the rapid evolution, complex dynamics and baroclinic structure that is typical of eddies and the relatively sparse sampling in western boundary currents leads to significant challenges in understanding the 3-dimensional structure of these boundary currents and mesoscale eddies. Here, we use Observing System Simulation Experiments (OSSEs) to explore the impact of assimilating synthetic subsurface temperature observations at a range of temporal resolutions, to emulate expendable bathythermograph transects with different repeat frequencies (weekly to quarterly). We explore the improvement in the representation of mesoscale eddies and subsurface conditions in a dynamic western boundary current system, the East Australian Current, with a data-assimilating regional ocean model. A characterisation of the spatial and temporal ocean variability spectrum demonstrates the potential for undersampling and aliasing by a lower sampling frequency. We find that assimilating subsurface temperature data with at least a weekly repeat time best improves subsurface representation of this dynamic, eddy-rich region. However, systemic biases introduced by the data assimilation system hinder the ability of the model to produce more accurate subsurface representation with fortnightly or monthly sampling. Removal of this bias may improve subsurface representation in eddy-rich regions with fortnightly or even less frequent observations. These results highlight the value of both increased subsurface observation density in regions of dynamic oceanography as well as continued development of data assimilation techniques in order to optimise the impact of existing observations.

Abnormally thin eggshells can reduce avian reproductive success, and have caused rapid population declines. The best known examples of this phenomenon are the widespread population crashes in birds, mostly raptors, fish eating birds, and scavengers, caused by the pesticide DDT and its isomers in the 1960s. A variety of other chemicals have been reported to cause eggshell thinning. Non-steroidal anti-inflammatory drugs (NSAIDs), which are extensively and increasingly used in human and veterinary medicine, may be one particularly concerning group of chemicals that demonstrate an ability to impair eggshell development, based both on laboratory studies and on their known mechanism of action. In this review, we outline environmental and wildlife exposure to NSAIDs, describe the process of eggshell formation, and discuss pathways affected by NSAIDs. We list pharmaceuticals, including NSAIDs, and other compounds demonstrated to reduce eggshell thickness, and highlight their main mechanisms of action. Dosing studies empirically demonstrated that NSAIDs reduce eggshell thickness through cyclooxygenase inhibition, which suppresses prostaglandin synthesis and reduces the calcium available for the mineralization of eggshell. Using the US EPA’s CompTox Chemicals Dashboard, we show that NSAIDs are predicted to strongly inhibit cyclooxygenases. NSAIDs have been observed both in the putative diet of scavenging birds, and we report examples of NSAIDs detected in eggs or tissues of wild and captive Old World vultures. We suggest that NSAIDs in the environment represent a hazard that could impair reproduction in wild birds.

Pigeon circovirus (PiCV) is considered to be genetically diverse, with a relatively small circular single-stranded DNA genome of 2 kb that encodes for a capsid protein (Cap) and a replication initiator protein (Rep). Australasia is known to be the origin of diverse species of the Order Columbiformes, but limited data on the PiCV genome sequence has hindered phylogeographic studies in this species. To fill this gap, this study was conducted to investigate PiCV in 118 characteristic samples from different birds across Australia using PCR and sequencing. Eighteen partial PiCV Rep sequences and one complete PiCV genome sequence were recovered from reservoir and aberrant hosts. Phylogenetic analyses revealed that PiCV circulating in Australia was scattered across three different subclades. Importantly, one subclade dominated within the PiCV sequenced from Australia and Poland, whereas other PiCV sequenced in this study were more closely related to the PiCV sequenced from China, USA and Japan. In addition, PiCV Rep sequences obtained from clinically affected plumed whistling duck, blue billed duck and Australian magpie demonstrated natural spillover of PiCV unveiled host generalist characteristics of the pigeon circovirus. These findings indicate that PiCV genomes circulating in Australia lack host adapted population structure but demonstrate natural spillover infection.

Abstract Background Precisely how silver nanoparticles (AgNPs) kill mammalian cells still is not fully understood. It is not clear if AgNP-induced damage differs from silver cation (Ag+), nor is it known how AgNP damage is transmitted from cell membranes, including endosomes, to other organelles. Cells can differ in relative sensitivity to AgNPs or Ag+, which adds another layer of complexity to identifying specific mechanisms of action. Therefore, we determined if there were specific effects of AgNPs that differed from Ag+ in cells with high or low sensitivity to either toxicant. Methods Cells were exposed to intact AgNPs, Ag+, or defined mixtures of AgNPs with Ag+, and viability was assessed. The level of dissolved Ag+ in AgNP suspensions was determined using inductively coupled plasma mass spectrometry. Changes in reactive oxygen species following AgNP or Ag+ exposure were quantified, and treatment with catalase, an enzyme that catalyzes the decomposition of H2O2 to water and oxygen, was used to determine selectively the contribution of H2O2 to AgNP and Ag+ induced cell death. Lipid peroxides, formation of 4-hydroxynonenol protein adducts, protein thiol oxidation, protein aggregation, and activation of the integrated stress response after AgNP or Ag+ exposure were quantified. Lastly, cell membrane integrity and indications of apoptosis or necrosis in AgNP and Ag+ treated cells were examined by flow cytometry. Results We identified AgNPs with negligible Ag+ contamination. We found that SUM159 cells, which are a triple-negative breast cancer cell line, were more sensitive to AgNP exposure less sensitive to Ag+ compared to iMECs, an immortalized, breast epithelial cell line. This indicates that high sensitivity to AgNPs was not predictive of similar sensitivity to Ag+. Exposure to AgNPs increased protein thiol oxidation, misfolded proteins, and activation of the integrated stress response in AgNP sensitive SUM159 cells but not in iMEC cells. In contrast, Ag+ cause similar damage in Ag+ sensitive iMEC cells but not in SUM159 cells. Both Ag+ and AgNP exposure increased H2O2 levels; however, treatment with catalase rescued cells from Ag+ cytotoxicity but not from AgNPs. Instead, our data support a mechanism by which damage from AgNP exposure propagates through cells by generation of lipid peroxides, subsequent lipid peroxide mediated oxidation of proteins, and via generation of 4-hydroxynonenal (4-HNE) protein adducts. Conclusions There are distinct differences in the responses of cells to AgNPs and Ag+. Specifically, AgNPs drive cell death through lipid peroxidation leading to proteotoxicity and necrotic cell death, whereas Ag+ increases H2O2, which drives oxidative stress and apoptotic cell death. This work identifies a previously unknown mechanism by which AgNPs kill mammalian cells that is not dependent upon the contribution of Ag+ released in extracellular media. Understanding precisely which factors drive the toxicity of AgNPs is essential for biomedical applications such as cancer therapy, and of importance to identifying consequences of unintended exposures.

Abstract Members of the cytochrome p450 (CYP) enzyme family are abundantly expressed in insect olfactory tissues, where they are thought to act as Odorant Degrading Enzymes (ODEs). However, their contribution to olfactory signaling in vivo is poorly understood. This is due in part to the challenge of identifying which of the dozens of antennal-expressed CYPs might inactivate a given odorant. Here, we tested a high-throughput deorphanization strategy in Drosophila to identify CYPs that are transcriptionally induced by exposure to odorants. We discovered three CYPs selectively upregulated by geranyl acetate using transcriptional profiling. Although these CYPs are broadly expressed in the antenna in non-neuronal cells, electrophysiological recordings from CYP mutants did not reveal any changes in olfactory neuron responses to this odorant. Neurons were desensitized by pre-exposing flies to the odorant, but this effect was similar in CYP mutants. Together, our data suggest that the induction of a CYP gene by an odorant does not necessarily indicate a role for that CYP in neuronal responses to that odorant. We go on to show that some CYPs have highly restricted expression patterns in the antenna, and suggest that such CYPs may be useful candidates for further studies on olfactory CYP function.

Toxoplasma gondii is a protozoan parasite that infects 30–40% of the world’s population. Infections are typically subclinical but can be severe and, in some cases, life threatening. Central to the virulence of T. gondii is an unusual form of substrate-dependent motility that enables the parasite to invade cells of its host and to disseminate throughout the body. A hetero-oligomeric complex of proteins that functions in motility has been characterized, but how these proteins work together to drive forward motion of the parasite remains controversial. A key piece of information needed to understand the underlying mechanism(s) is the directionality of the forces that a moving parasite exerts on the external environment. The linear motor model of motility, which has dominated the field for the past two decades, predicts continuous anterior-to-posterior force generation along the length of the parasite. We show here using three-dimensional traction force mapping that the predominant forces exerted by a moving parasite are instead periodic and directed in toward the parasite at a fixed circular location within the extracellular matrix. These highly localized forces, which are generated by the parasite pulling on the matrix, create a visible constriction in the parasite’s plasma membrane. We propose that the ring of inward-directed force corresponds to a circumferential attachment zone between the parasite and the matrix, through which the parasite propels itself to move forward. The combined data suggest a closer connection between the mechanisms underlying parasite motility and host cell invasion than previously recognized. In parasites lacking the major surface adhesin, TgMIC2, neither the inward-directed forces nor the constriction of the parasite membrane are observed. The trajectories of the TgMIC2-deficient parasites are less straight than those of wild-type parasites, suggesting that the annular zone of TgMIC2-mediated attachment to the extracellular matrix normally constrains the directional options available to the parasite as it migrates through its surrounding environment.

Multiple factors contribute to community practice’s ongoing challenge of developing effective, evidence-informed, and socially just practice interventions. Currently, rationally driven systematic reviews dominate intervention design and development in various interprofessional applied health and human service fields, including community practice. As a result, community interventions often undergo significant development outside complex community contexts in which social problems manifest. Drawing from a case example of one author’s participation in a community engaged intervention development study based on mobilizing across differences, this piece advances an inclusive approach to community-based participatory intervention development driven by critical grounded theory. Undergirded by critical research perspectives, the article offers an early-stage intervention development methodology derived from the field in collaboration with community practitioners and resident leaders. Built upon existing interdisciplinary scholarship, it blends prominent intervention development frameworks, participatory research approaches, and critical grounded theory methods. Authors aim to aid scholars, practitioners, and community leaders in developing socially just, inclusive, and contextually relevant intervention approaches that originate from within communities directly impacted by social problems.

Abstract The treatment of periodontitis has numerous positive effects on established chronic health conditions, including cardiovascular disease and diabetes. However, ethical considerations do limit the establishment of human trials to investigate whether periodontitis promotes the early stages of chronic conditions. Therefore, the aim of this study was to investigate whether periodontitis induces endothelial dysfunction in hyperlipidemic apolipoprotein E gene-deficient (ApoE-/-) mice. Forty-five 8-week-old ApoE-/- mice were challenged by oral lavage with Porphyromonas gingivalis and Streptococcus gordonii for 4 weeks. A subgroup of animals (n = 15–17/group) was placed in a metabolic chamber immediately before euthanasia at 4 weeks to measure VO2/CO2 concentrations and voluntary locomotion. In infected and control animals alveolar bone levels were measured by x-ray imaging and endothelial function was determined by measuring endothelial-dependent vasorelaxation of aortic rings. The mRNA expression levels of serum amyloid A and tumor necrosis factor were determined in liver tissues by qRT PCR and protein concentrations in serum by ELISA. Caecal contents were analysed by sequencing to determine changes to the gut microbiota to investigate linkages between microbiome and systemic changes. The results showed that oral lavage of P. gingivalis and S. gordonii for 4 weeks, initiated periodontitis in ApoE-/- mice, similar to the human situation. The oral inflammation was accompanied by a significant increase in mRNA expression of pro-inflammatory mediators serum amyloid A1 and tumor necrosis factor in the liver. Mice with periodontitis also exhibited impaired endothelial-dependent vasorelaxation responses to acetylcholine. This systemic response was connected to increased energy expenditure, locomotion and respiratory quotient. No differences were detected in caecal microbiota between the infected and control animals. Overall, this is the first report that provide evidence that periodontitis induces endothelial dysfunction in mice. Other systemic responses observed in response to the local reaction need further investigation. The study suggests that early prevention of periodontitis may help limit the early stages of endothelial dysfunction that is linked to atherogenesis in humans.

Recent advances in irrigation technologies have led many states to incentivize homeowners to purchase United States Environmental Protection Agency WaterSense-labeled, smart irrigation controllers. However, previous research of smart controllers has shown that their use may still result in excess water application when compared with controllers manually programmed to replace actual water loss. This study compared kentucky bluegrass (Poa pratensis) irrigation applications using three smart irrigation controllers, a conventional irrigation controller programmed according to Cooperative Extension recommendations, and the average irrigation rate of area homeowners in Utah during 2018 and 2019. Of all the controllers tested, the manually programmed controller applied water at amounts closest to the actual evapotranspiration rates; however, smart controllers applied from 30% to 63% less water than area homeowners, depending on the controller and year of the study. Kentucky bluegrass health and quality indicators—percent green cover and normalized difference vegetation indices—varied between years of the study and were lower than acceptable levels on several occasions in 2019 for three of the four controllers tested. Compared with the results of similar studies, these findings suggest that the effects of smart irrigation controllers on turfgrass health and quality may vary by location and over time.

Flesh-footed shearwater (Ardenna carneipes) is recognized as vulnerable seabird species in Western Australia and New South Wales, Australia, and its genetic variability and a well-resolved phylogeny is imperative for the species’ conservation. Here, we report the first sequenced mitogenome of the Australian A. carneipes. The mitogenome of A. carneipes was 16,370 bp in total length and encompassed 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and one non-coding region (D-loop). All of the genes were encoded on the H-strand with the exception of ND6 and eight tRNAs, which is a conserved pattern of the mitogenome for other vertebrates. The mitogenome of A. carneipes was dominated by higher AT (56.5%) than GC (43.5%) content. In the resulting phylogenetic tree using complete mitogenome sequences, flesh-footed shearwater and gray petrel (Procellaria cinerea) grouped together despite the high genetic distance (11.0%) between them, belonging to family Procellariidae. However, the phylogenetic tree was consistent with a previous study using partial nucleotide sequences of the cytochrome b gene. These results highlight that further mitogenome sequences will be required from the closely related species under the genus Ardenna to delineate well-resolved phylogenetic classification at the genus and or species level. The present study provides a reference mitochondrial genome of flesh-footed shearwater for further molecular studies.

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.

The SOX2 pioneer transcription factor performs critical roles in pluripotency and self-renewal of embryonic stem cells. Here the authors show that SOX2’s two nuclear localization signal sequences form a contiguous binding interface on the nuclear import receptor importin-α3, and provide a structural basis for the preference of SOX2 binding to IMPα3.

Jeremy To et al. develop an ultra-high-content assay platform used to interrogate T-cell-mediated killing of 3D multicellular tumor spheroids. They screen 1,800 annotated compounds to identify small molecules that enhance cytotoxic CD8+ T-cell activity in an antigen-dependent manner, demonstrating the utility of this assay platform.

The vertical propagation of wave energy into a planet’s exosphere, a process that affects atmospheric evolution, is calculated here using 1D molecular kinetic simulations. Effects sensitive to molecular interactions are examined by comparing simulation results to solutions of linear fluid models for steady wave activity using parameters associated with Mars’ upper atmosphere. In addition to correctly describing the wave behavior in the exobase region, these simulations directly yield nonlinear effects such as atmospheric heating. They also readily include the transient behavior due to the onset and decay of waves propagating into the rarefied region of a planet’s atmosphere. This is a first step in understanding the effects of variable wave activity in the region where the atmosphere evolves from collisional to collisionless.

We report results from far-ultraviolet observations by the Hubble Space Telescope of Jupiter’s largest moon, Ganymede, transiting across the planet’s dayside hemisphere. Within a targeted campaign on 2021 September 9 two exposures were taken during one transit passage to probe for attenuation of Jupiter's hydrogen Ly α dayglow above the moon limb. The background dayglow is slightly attenuated over an extended region around Ganymede, with stronger attenuation in the second exposure, when Ganymede was near the planet’s center. In the first exposure, when the moon was closer to Jupiter’s limb, the effects from the Ganymede corona are hardly detectable, likely because the Jovian Ly α dayglow is spectrally broader and less intense at this viewing geometry. The obtained vertical H column densities of around (1–2) × 10 ^12 cm ^−2 are consistent with previous results. Constraining angular variability around Ganymede’s disk, we derive an upper limit on a local H _2 O column density of (2–3) × 10 ^16 cm ^−2 , such as could arise from outgassing plumes in regions near the observed moon limb.

PURPOSEFormal education in the radiation sciences is critical for the safe and effective delivery of radiotherapy. Practices and patterns of radiation sciences education and trainee performance in the radiation sciences are poorly described. This study assesses the current state of radiation sciences education in Africa and evaluates a high-yield, on-site educational program in radiation biology and radiation physics for oncology and radiation therapy trainees in Africa.METHODSAn anonymous survey was distributed to members of the African Organization for Research and Treatment in Cancer Training Interest Group to assess current attitudes and practices toward radiation sciences education. A 2-week, on-site educational course in radiation biology and radiation physics was conducted at the Cancer Diseases Hospital in Lusaka, Zambia. Pre- and postcourse assessments in both disciplines were administered to gauge the effectiveness of an intensive high-yield course in the radiation sciences.RESULTSSignificant deficiencies were identified in radiation sciences education, especially in radiation biology. Lack of expert instructors in radiation biology was reported by half of all respondents and was the major contributing factor to deficient education in the radiation sciences. The educational course resulted in marked improvements in radiation biology assessment scores (median pre- and posttest scores, 27% and 55%, respectively; P < .0001) and radiation physics assessment scores (median pre- and posttest scores, 30% and 57.5%, respectively; P < .0001).CONCLUSIONRadiation sciences education in African oncology training programs is inadequate. International collaboration between expert radiation biology and radiation physics instructors can address this educational deficiency and improve trainee competence in the foundational radiation sciences that is critical for the safe and effective delivery of radiotherapy.

Stochastic resonance has been successfully used to improve human movement when using subthreshold vibration. Recent work has shown promise in improving mobility in individuals with unilateral lower limb amputations. Furthering this work, we present an investigation of two different signal structures in the use of stochastic resonance to improve mobility in individuals with unilateral lower limb amputations. Cutaneous somatosensation and standing balance measures using spatial and temporal analysis were assessed. There were no differences in the somatosensation measures, but differences in the temporal characteristics of the standing measures were seen with the various vibration structures when compared to no vibration, one of which suggesting mass may play an important role in determining who may or may not benefit from this intervention. Stochastic resonance employed with subthreshold vibration influences mobility in individuals with unilateral amputations, but the full direction and extent of influence is yet to be understood.

In our previous studies, we demonstrated the usefulness of TanDEM-X interferometric bistatic mode with single polarization to obtain forest heights for the purposes of large area mapping. A key feature of our approach has been the use of a simplified Random Volume Over Ground (RVOG) model that locally estimates forest height. The model takes TanDEM-X interferometric coherence amplitude as an input and uses an external Digital Surface Model (DSM) to account for local slope variations due to terrain topography in order to achieve accurate forest height estimation. The selection of DSM for use as a local slope reference is essential, as an inaccurate DSM will result in less accurate terrain-correction and forest height estimation. In this paper, we assessed TanDEM-X height estimates associated with scale variations in different DSMs used in the model over a remote sensing supersite in Petawawa, Canada. The DSMs used for assessments and comparisons included ASTER GDEM, ALOS GDSM, airborne DRAPE DSM, Canadian DSM and TanDEM-X DSM. Airborne Laser Scanning (ALS) data were used as reference for terrain slope and forest height comparisons. The results showed that, with the exception of the ASTER GDEM, all DSMs were sufficiently accurate for the simplified RVOG model to provide a satisfactory estimate of stand-level forest height. When compared to the ALS 95th height percentile, the modeled forest heights had R2 values greater than 80% and Root-Mean-Square Errors (RMSE) less than 2 m. For a close similarity in slope estimation with the ALS reference, coverage across Canada and open data access, the 0.75 arc-second (20 m) resolution Canadian DSM was selected as a preferred choice for the simplified RVOG model to provide TanDEM-X height estimation in Canada.

Abstract Background The specific identification of animals through the analysis of faecal DNA is important in many areas of scientific endeavour, particularly in the field of parasitology. Methods Here, we designed and assessed two multiplex PCR assays using genetic markers in a mitochondrial cytochrome b (cytb) gene region for the unequivocal identification and discrimination of animal species based on the specific amplification of DNA from faecal samples collected from water catchment areas in Victoria, Australia. One of these assays differentiates three marsupial species (eastern grey kangaroo, swamp wallaby and common wombat) and the other distinguishes three deer species (fallow, red and sambar deer). We tested these two assays using a total of 669 faecal samples, collected as part of an ongoing programme to monitor parasites and microorganisms in these animals. Results These two PCR assays are entirely specific for these animal species and achieve analytical sensitivities of 0.1–1.0 picogram (pg). We tested 669 faecal samples and found that some previous inferences of species based on faecal morphology were erroneous. We were able to molecularly authenticate all of the 669 samples. Conclusions We have established PCR assays that accurately distinguish the faecal samples of some of the prominent large mammalian herbivores found within a water catchment system in the state of Victoria, Australia. The multiplex assays for marsupials and deer produce amplicons that are easily differentiable based on their size on an agarose gel, and can be readily sequenced for definitive species authentication. Although established for marsupials and deer, the methodology used here can be applied to other host-parasite study systems to ensure data integrity.

Abstract Short‐range endemic plants often have edaphic specializations that, with their restricted distributions, expose them to increased risk of anthropogenic extinction. Here, we present a modeling approach to understand habitat suitability for Ricinocarpos brevis R.J.F.Hend. & Mollemans (Euphorbiaceae), a threatened shrub confined to three isolated populations in the semi‐arid south‐west of Western Australia. The model is a maximum entropy species distribution projection constructed on the basis of physical soil characteristics and geomorphology data at approximately 25 m2 (1 arc‐second) resolution. The model predicts the species to occur on shallow, low bulk density soils that are located high in the landscape. The model shows high affinity (72.1% average likelihood of occurrence) for the known populations of R. brevis, as well as identifying likely locations that are not currently known to support the species. There was a strong relationship between the likelihood of R. brevis occurrence and soil moisture content that the model estimated at a depth of 20 cm. We advocate that our approach should be standardized using publicly available data to generate testable hypotheses for the distribution and conservation management of short‐range endemic plant species for all of continental Australia.

Abstract Mass spectrometry imaging (MSI) is a technique for mapping the spatial distributions of molecules in sectioned tissue. Histology-preserving tissue preparation methods are central to successful MSI studies. Common fixation methods, used to preserve tissue morphology, can result in artifacts in the resulting MSI experiment including delocalization of analytes, altered adduct profiles, and loss of key analytes due to irreversible cross-linking and diffusion. This is especially troublesome in lung and airway samples, in which histology and morphology is best interpreted from 3D reconstruction, requiring the large and small airways to remain inflated during analysis. Here, we developed an MSI-compatible inflation containing as few exogenous components as possible, forgoing perfusion, fixation, and addition of salt solutions upon inflation that resulted in an ungapped 3D molecular reconstruction through more than 300 microns. We characterized a series of polyunsaturated phospholipids (PUFA-PLs), specifically phosphatidylinositol (-PI) lipids linked to lethal inflammation in bacterial infection and mapped them in serial sections of inflated mouse lung. PUFA-PIs were identified using spatial lipidomics and determined to be determinant markers of major airway features using unsupervised hierarchical clustering. Deep lung architecture was preserved using this inflation approach and the resulting sections are compatible with multiple MSI modalities, automated interpretation software, and serial 3D reconstruction.

Abstract Background Colorectal cancer (CRC) diagnosed at ages

Abstract Identifying internal waves in complex flow fields is a long‐standing problem in fluid dynamics, oceanography and atmospheric science, owing to the overlap of internal waves temporal and spatial scales with other flow regimes. Lagrangian filtering—that is, temporal filtering in a frame of reference moving with the flow—is one proposed methodology for performing this separation. Here we (a) describe an improved implementation of the Lagrangian filtering methodology and (b) introduce a new freely available, parallelized Python package that applies the method. We show that the package can be used to directly filter output from a variety of common ocean models including MITgcm, Regional Ocean Modeling System and MOM5 for both regional and global domains at high resolution. The Lagrangian filtering is shown to be a useful tool to both identify (and thereby quantify) internal waves, and to remove internal waves to isolate the non‐wave flow field.

Isoflavonoid synthase (IFS) is a critical enzyme for the biosynthesis of over 2400 isoflavonoids. Isoflavonoids are an important class of plant secondary metabolites that have a range of pharmaceutical and nutraceutical properties. With growing interest in isoflavonoids from both research and industrial perspectives, efforts are being forwarded to enhance isoflavonoid production in-planta and ex-planta; therefore, in-silico analysis and characterisation of available IFS protein sequences are needed. The present study is the first-ever attempt toward phylogenetic analysis and protein modelling of available IFS protein sequences. Phylogenetic analysis has shown that IFS amino acid sequences have 86.4% pairwise identity and 26.5% identical sites, and the sequences were grouped into six different clades. The presence of a β-hairpin and extra loop at catalytic sites of Trifolium pratense, Beta vulgaris and Medicago truncatula, respectively, compared with Glycyrrhiza echinata are critical structural differences that may affect catalytic function. Protein docking highlighted the preference of selected IFS for liquiritigenin compared with naringenin and has listed T. pratense as the most efficient candidate for heterologous biosynthesis of isoflavonoids. The in-silico characterisation of IFS represented in this study is vital in realising the new bioengineering endeavours and will help in the characterisation and selection of IFS candidate enzymes for heterologous biosynthesis of isoflavonoids.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and its management places a huge burden on healthcare systems through hospitalisation and treatment. Atherosclerosis is a chronic inflammatory disease of the arterial wall resulting in the formation of lipid-rich, fibrotic plaques under the subendothelium and is a key contributor to the development of CVD. As such, a detailed understanding of the mechanisms involved in the development of atherosclerosis is urgently required for more effective disease treatment and prevention strategies. Heparanase is the only mammalian enzyme known to cleave heparan sulfate of heparan sulfate proteoglycans, which is a key component of the extracellular matrix and basement membrane. By cleaving heparan sulfate, heparanase contributes to the regulation of numerous physiological and pathological processes such as wound healing, inflammation, tumour angiogenesis, and cell migration. Recent evidence suggests a multifactorial role for heparanase in atherosclerosis by promoting underlying inflammatory processes giving rise to plaque formation, as well as regulating lesion stability. This review provides an up-to-date overview of the role of heparanase in physiological and pathological processes with a focus on the emerging role of the enzyme in atherosclerosis.

Abstract Enhanced ecosystem carbon storage is a key component of many climate mitigation pathways. The State of California has set an ambitious goal of carbon neutrality by 2045, relying in part on enhanced carbon sequestration in natural and working lands. We used statistical modeling, including random forest and climate analog approaches, to explore the climate‐driven challenges and uncertainties associated with the goal of long‐term carbon sequestration in forests and shrublands. We found that seasonal patterns of temperature and precipitation are strong controllers of the spatial distribution of aboveground live carbon. RCP8.5 projections of temperature and precipitation are estimated to drive decreases of 16.1% ± 7.5% in aboveground live carbon by the end of the century, with coastal areas of central and northern California and low/mid‐elevation mountain areas being most vulnerable. With RCP4.5 projections, declines are less severe, with 8.8% ± 5.3% carbon loss. In either scenario, increases in temperature systematically cause biomass declines, and the spread of projected precipitation across 32 CMIP5 models contributes to substantial uncertainty in the magnitude of that decline. Projected changes in the environmental niche for the 20 most biomass‐dominant tree species revealed widespread replacement of conifers by oak species in low elevation regions of central and northern California, with a corresponding decline in carbon storage depending on expected migration rates. The spatial patterns of vulnerability we identify may allow policymakers to assess where carbon sequestration in aboveground biomass is an appropriate part of a climate mitigation portfolio, and where future climate‐driven carbon losses may be a liability.

Prostate cancer is the fourth most common cancer worldwide with definitive diagnosis reliant on biopsy and human-graded histopathology. As with other pathologies, grading based on classical haematoxylin and eosin (H&E) staining of formalin fixed paraffin-embedded material can be prone to variation between pathologists, prompting investigation of biomolecular markers. Comprising around 50% of cellular mass, and with known metabolic variations in cancer, lipids provide a promising target for molecular pathology. Here we apply isomer-resolved lipidomics in combination with imaging mass spectrometry to interrogate tissue sections from radical prostatectomy specimens. Guided by the histopathological assessment of adjacent tissue sections, regions of interest are investigated for molecular signatures associated with lipid metabolism, especially desaturation and elongation pathways. Monitoring one of the most abundant cellular membrane lipids within these tissues, phosphatidylcholine (PC) 34:1, high positive correlation was observed between the n-9 isomer (site of unsaturation 9-carbons from the methyl terminus) and epithelial cells from potential pre-malignant lesions, while the n-7 isomer abundance was observed to correlate with immune cell infiltration and inflammation. The correlation of lipid isomer signatures with human disease states in tissue suggests a future role for isomer-resolved mass spectrometry imaging in assisting pathologists with prostate cancer diagnoses and patient stratification.