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Abstract Neutrophil extracellular traps (NETs) have been implicated in the pathology of various inflammatory conditions. In cancer, NETs have been demonstrated to induce systemic inflammation, impair peripheral vessel and organ function and promote metastasis. Here we show that the plasma level of NETs is significantly higher in patients with metastatic breast cancer compared to those with local disease, or those that were considered cured at a 5‐year follow‐up, confirming NETs as interesting therapeutic targets in metastatic breast cancer. Administration of DNase I is one strategy to eliminate NETs but long‐term treatment requires repeated injections and species‐specific versions of the enzyme. To enhance administration and therapeutic efficacy, we have developed an adeno‐associated virus (AAV) vector system for delivery of murine DNase I and addressed its potential to counteract cancer‐associated pathology in the murine MMTV‐PyMT model for metastatic mammary carcinoma. The AAV vector is comprised of capsid KP1 and an expression cassette encoding hyperactive murine DNase I (AAV‐mDNase I) under the control of a liver‐specific promotor. This AAV‐mDNase I vector could support elevated expression and serum activity of murine DNase I over at least 8 months. Neutrophil Gelatinase‐Associated Lipocalin (NGAL), a biomarker for kidney hypoperfusion that is upregulated in urine from MMTV‐PyMT mice, was suppressed in mice receiving AAV‐mDNase I compared to an AAV‐null control group. Furthermore, the proportion of mice that developed lung metastasis was reduced in the AAV‐mDNase I group. Altogether, our data indicate that AAV‐mDNase I has the potential to reduce cancer‐associated impairment of renal function and development of metastasis. We conclude that AAV‐mDNase I could represent a promising therapeutic strategy in metastatic breast cancer.

Abstract Background Unfettered movement among habitats is crucial for fish to access patchily distributed resources and complete their life cycle, but many riverscapes in the American Southwest are fragmented by dams and dewatering. The endangered Rio Grande silvery minnow (Hybognathus amarus, RGSM) persists in a fragmented remnant of its former range (ca. 5%), and its movement ecology is understudied. Methods We tracked movements of hatchery-reared RGSM, tagged with passive integrated transponder tags, using stationary and mobile antennas from 2019 to 2022. We quantified probability of movement and total distance moved by RGSM released above and below a dam. We then assessed how well two prevailing riverine movement theories (i.e., restricted movement paradigm [RMP] and colonization cycle hypothesis [CCH]) explained RGSM movement patterns. Results We detected 36.8% of released RGSM (n = 37,215) making at least one movement. Movements were leptokurtic and substantially greater than expected based on the RMP for both stationary (1.7–5.9 m) and mobile (30.3–77.8 m) individuals. On average, RGSM were detected at large for 75 days and moved a total of 12.2 rkm within a year. The maximum total distance moved by RGSM was 103 rkm. Similarly, we observed a multimodal distribution of detected range sizes with a mean detected range of 2.4 rkm and a maximum detected range of 78.2 rkm. We found little support for an upstream movement bias, as expected under the CCH, and most movements (74%) were directed downstream. Conclusions Our data suggest RGSM are highly mobile, with the ability to make long-distance movements. Neither movement theory adequately described movement patterns of RGSM; instead, our findings support a nomadic movement pattern and an apparent drift paradox matching recent studies of other pelagic-broadcast spawning minnows where populations persist upstream despite experiencing downstream drift as larvae. Resolution of the drift paradox may be achieved through further, targeted studies into different aspects of the species’ life history. Quantification of RGSM movement provides crucial insights into the species’ movement ecology and may help define the appropriate scale of recovery efforts.

Summary: Mammals typically heal with fibrotic scars, and treatments to regenerate human skin and hair without a scar remain elusive. We discovered that mice lacking C-X-C motif chemokine receptor 2 (CXCR2 knockout [KO]) displayed robust and complete tissue regeneration across three different injury models: skin, hair follicle, and cartilage. Remarkably, wild-type mice receiving plasma from CXCR2 KO mice through parabiosis or injections healed wounds scarlessly. A comparison of circulating proteins using multiplex ELISA revealed a 24-fold higher plasma level of granulocyte colony stimulating factor (G-CSF) in CXCR2 KO blood. Local injections of G-CSF into wild-type (WT) mouse wound beds reduced scar formation and increased scarless tissue regeneration. G-CSF directly polarized macrophages into an anti-inflammatory phenotype, and both CXCR2 KO and G-CSF-treated mice recruited more anti-inflammatory macrophages into injured areas. Modulating macrophage activation states at early time points after injury promotes scarless tissue regeneration and may offer a therapeutic approach to improve healing of human skin wounds.

Objectives: Most prior advance care planning (ACP) interventions lack integration of the social context of patients' ACP process, which patients indicate is critically important. The current study developed the Planning Advance Care Together (PACT) website to foster inclusion of loved ones in the ACP process. Methods: To provide feedback about the PACT website, patients with advanced cancer (N = 11), their caregivers (N = 11), and experts (N = 10) participated in semi-structured interviews. Patients and caregivers also completed standardized ratings of acceptability and usability. Results: Overall, patient (n = 11) and caregiver (n = 11) ratings of acceptability and usability of the website exceeded benchmark cut-offs (≥24 on the Acceptability E-Scale and ≥ 68 on the System Usability Scale). Patients, caregivers, and experts liked the topic of ACP but felt that it could be emotionally challenging. They recommended focusing more on planning and less on end of life. They appreciated being able to include loved ones and recommended adding resources for caregivers. Conclusions: Study findings support the preliminary usability and acceptability of the PACT website. Findings will be used to inform a modified prototype of the PACT website that is interactive and ready for field testing with patients with advanced cancer and their loved ones. Innovation: We utilized a novel application of the shared mind framework to support patients with advanced cancer in engaging their loved ones in the ACP process.

Abstract We previously reported the results of a randomized phase II trial (NCT02904954) in patients with early-stage non-small cell lung cancer (NSCLC) who were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation (DRT). The trial met its primary endpoint of major pathological response, which was significantly higher following DRT with no new safety signals. Here, we report on the prespecified secondary endpoint of disease-free survival (DFS) regardless of treatment assignment and the prespecified exploratory analysis of DFS in each arm of the trial. DFS at 2 and 3 years across patients in both arms of the trial were 73% (95% CI: 62.1–84.5) and 65% (95% CI: 52.5–76.9) respectively. For the exploratory endpoint of DFS in each arm of the trial, three-year DFS was 63% (95% CI: 46.0–80.4) in the durvalumab monotherapy arm compared to 67% (95% CI: 49.6–83.4) in the dual therapy arm. In addition, we report post hoc exploratory analysis of progression-free survival as well as molecular correlates of response and recurrence through high-plex immunophenotyping of sequentially collected peripheral blood and gene expression profiles from resected tumors in both treatment arms. Together, our results contribute to the evolving landscape of neoadjuvant treatment regimens for NSCLC and identify easily measurable potential biomarkers of response and recurrence.

Abstract Fragmentation isolates individuals and restricts access to valuable habitat with severe consequences for populations, such as reduced gene flow, disruption of recolonization dynamics, reduced resiliency to disturbance, and changes in aquatic community structure. Translocations to mitigate the effects of fragmentation and habitat loss are common, but few are rigorously evaluated, particularly for fishes. Over six years, we translocated 1215 individuals of four species of imperiled fish isolated below a barrier on the San Juan River, Utah, USA, that restricts access to upstream habitat. We used re‐encounter data (both passive integrated transponder tag and telemetry detections and physical recaptures) collected between 2016 and 2023, to inform a spatially explicit multistate mark–recapture model that estimated survival and transition probabilities of translocated and non‐translocated individuals, both below and above the barrier. Individuals of all four species moved large (>200 km) distances upstream following translocation, with the maximum upstream encounter distance varying by species. Results from the multistate mark–recapture model suggested translocated fish survived at a higher rate compared with non‐translocated fish below the barrier for three of the four species. Above the barrier, translocated individuals survived at similar rates as non‐translocated fish for bluehead sucker (Catostomus discobolus) and flannelmouth sucker (Catostomus latipinnis), while survival rates of translocated endangered Colorado pikeminnow (Ptychocheilus lucius; mean, 95% CI: 0.75, 0.55–0.88) and endangered razorback sucker (Xyrauchen texanus; 0.86, 0.75–0.92) were higher relative to non‐translocated individuals (Colorado pikeminnow: 0.52, 0.51–0.54; razorback sucker: 0.75, 0.74–0.75). Transition probabilities from above the barrier to below the barrier were generally low for three of the four species (all upper 95% CI ≤ 0.23), but they were substantially higher for razorback sucker. Our results suggest translocation to mitigate fragmentation and habitat loss can have demographic benefits for large‐river fish species by allowing movements necessary to complete their life history in heterogeneous riverscapes. Further, given the costs or delays in providing engineered fish passage structures or in achieving dam removal, we suggest translocations may provide an alternative conservation strategy in fragmented river systems.

Abstract Background Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. Results To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets of 27 unique factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax (Ubx), Abdominal-A (Abd-A), and Abdominal-B (Abd-B), suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other factors that target the histone gene array: JIL-1, hormone-like receptor 78 (Hr78), the long isoform of female sterile homeotic (1) (fs(1)h) as well as the general transcription factors TBP associated factor 1 (TAF-1), Transcription Factor IIB (TFIIB), and Transcription Factor IIF (TFIIF). Conclusions Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.

Altered ankyrin-R (AnkR; encoded by ANK1) expression is associated with diastolic function, left ventricular remodeling, and heart failure with preserved ejection fraction (HFpEF). First identified in erythrocytes, the role of AnkR in other tissues, particularly the heart, is less studied. Here, we identified the expression of both canonical and small isoforms of AnkR in the mouse myocardium. We demonstrate that cardiac myocytes primarily express small AnkR (sAnkR), whereas cardiac fibroblasts predominantly express canonical AnkR. As canonical AnkR expression in cardiac fibroblasts is unstudied, we focused on expression and localization in these cells. AnkR is expressed in both the perinuclear and cytoplasmic regions of fibroblasts with considerable overlap with the trans-Golgi network protein 38, TGN38, suggesting a potential role in trafficking. To study the role of AnkR in fibroblasts, we generated mice lacking AnkR in activated fibroblasts (Ank1-ifKO mice). Notably, Ank1-ifKO mice fibroblasts displayed reduced collagen compaction, supportive of a novel role of AnkR in normal fibroblast function. At the whole animal level, in response to a heart failure model, Ank1-ifKO mice displayed an increase in fibrosis and T-wave inversion compared with littermate controls, while preserving cardiac ejection fraction. Collagen type I fibers were decreased in the Ank1-ifKO mice, suggesting a novel function of AnkR in the maturation of collagen fibers. In summary, our findings illustrate the novel expression of AnkR in cardiac fibroblasts and a potential role in cardiac function in response to stress.

Abstract General anaesthetics are widely used for their analgesic, immobilising, and hypnotic effects. The mechanisms underlying these effects remain unclear, but likely arise from alterations to cell microstructure, and potentially mechanics. Here we investigate this hypothesis using a custom experimental setup combining calcium imaging and nanoindentation to quantify the firing activity and mechanical properties of dorsal root ganglion-derived neurons exposed to a clinical concentration of 1% isoflurane gas, a halogenated ether commonly used in general anaesthesia. We found that cell viscoelasticity and functional activity are simultaneously and dynamically altered by isoflurane at different stages of exposure. Particularly, cell firing count correlated linearly with the neuronal loss tangent, the ratio of mechanical energy dissipation and storage by the cell. Our results demonstrate that anaesthetics affect cells as a whole, reconciling seemingly contradictory theories of how anaesthetics operate, and highlight the importance of considering cell mechanics in neuronal functions, anaesthesia, and clinical neuroscience in general.

Adeno-associated virus (AAV) vectors are currently the most efficient option for intracranial gene therapies to treat neurodegenerative disease. Increased efficacy and safety will depend upon robust and specific expression of therapeutic genes into target cell-types within the human brain. In this study, we set out with two objectives: (1) to identify capsids with broader transduction of the striatum upon intracranial injection in mice and (2) to test a truncated human choline acetyltransferase (ChAT) promoter that would allow efficient and selective transduction of cholinergic neurons. We compared AAV9 and an engineered capsid, AAV-S, to mediate widespread reporter gene expression throughout the striatum. We observed that AAV-S transduced a significantly greater area of the injected hemisphere primarily in the rostral direction compared with AAV9 (CAG promoter). We tested AAV9 vectors packaging a reporter gene expression cassette driven by either the ChAT or CAG promoter. Specificity of transgene expression of ChAT neurons over other cells was 7-fold higher, and efficiency was 3-fold higher for the ChAT promoter compared with the CAG promoter. The AAV-ChAT transgene expression cassette should be a useful tool for the study of cholinergic neurons in mice, and the broader transduction area of AAV-S warrants further evaluation of this capsid.

IntroductionMetabolism plays a complex role in the evolution of cancerous tumors, including inducing a multifaceted effect on the immune system to aid immune escape. Immune escape is, by definition, a collective phenomenon by requiring the presence of two cell types interacting in close proximity: tumor and immune. The microenvironmental context of these interactions is influenced by the dynamic process of blood vessel growth and remodelling, creating heterogeneous patches of well-vascularized tumor or acidic niches.MethodsHere, we present a multiscale mathematical model that captures the phenotypic, vascular, microenvironmental, and spatial heterogeneity which shapes acid-mediated invasion and immune escape over a biologically-realistic time scale. The model explores several immune escape mechanisms such as i) acid inactivation of immune cells, ii) competition for glucose, and iii) inhibitory immune checkpoint receptor expression (PD-L1). We also explore the efficacy of anti-PD-L1 and sodium bicarbonate buffer agents for treatment. To aid in understanding immune escape as a collective cellular phenomenon, we define immune escape in the context of six collective phenotypes (termed “meta-phenotypes”): Self-Acidify, Mooch Acid, PD-L1 Attack, Mooch PD-L1, Proliferate Fast, and Starve Glucose.ResultsFomenting a stronger immune response leads to initial benefits (additional cytotoxicity), but this advantage is offset by increased cell turnover that leads to accelerated evolution and the emergence of aggressive phenotypes. This creates a bimodal therapy landscape: either the immune system should be maximized for complete cure, or kept in check to avoid rapid evolution of invasive cells. These constraints are dependent on heterogeneity in vascular context, microenvironmental acidification, and the strength of immune response.DiscussionThis model helps to untangle the key constraints on evolutionary costs and benefits of three key phenotypic axes on tumor invasion and treatment: acid-resistance, glycolysis, and PD-L1 expression. The benefits of concomitant anti-PD-L1 and buffer treatments is a promising treatment strategy to limit the adverse effects of immune escape.

Rates of youth behavioral health concerns have been steadily rising. Administrative data can be used to study behavioral health service utilization among youth, but current methods that rely on identifying an associated behavioral health diagnosis or provider specialty are limited. We reviewed all procedure codes billed to Medicaid for youth in one U.S. county over a 10-year period. We identified 158 outpatient behavioral health procedure codes and classified them according to service type. This classification system can be used by health services researchers to better characterize youth behavioral health service utilization.

ABSTRACTResearch experiences provide diverse benefits for undergraduates. Many academic institutions have adopted course-based undergraduate research experiences (CUREs) to improve student access to research opportunities. However, potential instructors of a CURE might still face financial or practical hurdles that prevent implementation. Bioinformatics research offers an alternative that is free, safe, compatible with remote learning, and may be more accessible for students with disabilities. Here, we describe a bioinformatics CURE that leverages publicly available datasets to discover novel proteins that target an instructor-determined genomic locus of interest. We use the free, user-friendly bioinformatics platform Galaxy to map ChIP-seq datasets to a genome, which removes the computing burden from students. Both faculty and students directly benefit from this CURE, as faculty can perform candidate screens and publish CURE results. Students gain not only basic bioinformatics knowledge, but also transferable skills, including scientific communication, database navigation, and primary literature experience. The CURE is flexible and can be expanded to analyze different types of high-throughput data or to investigate different genomic loci in any species.

Due to the projected decline of demand for gasoline in light duty engines and the advent of ethanol as a green fuel, the use of gasoline/ethanol blend fuels in heavy duty applications are being investigated as they are projected to have lower cost and lower lifecycle green house gas (GHG) emissions. In heavy duty engines, the primary mode of combustion is mixing controlled combustion where wide range of mixture conditions (equivalence ratio) exist. Soot emissions of these fuels in richer conditions are not well understood. The goal of this research is to evaluate some commercially available soot modeling codes for the particulate matter emissions from gasoline/ethanol fuel blends, especially at fuel rich conditions. A Rapid Compression Machine (RCM) is modeled in a three-dimensional numerical simulation using CONVERGE computational software using a reduced chemical kinetic mechanism with SAGE chemistry solver and a RANS k-ϵ turbulence model with a sector model including the creviced piston. The creviced piston is used in the experimental setup to reduce boundary layer effects and to maintain a homogeneous core in the reaction cylinder. Computational fluid dynamics simulations are conducted for different gasoline-ethanol fuel blends from E10 (10% ethanol v/v) to E100. The fuel blend is modeled as a surrogate mixture of toluene, iso-octane, n-heptane for gasoline content, and ethanol. The computational results were validated against experimental results using pressure measurements and laser extinction diagnostics. Different soot models are investigated to evaluate their capability of predicting the sooting tendencies of fuel blends, especially in richer conditions experienced during mixing-controlled combustion. The experimental combustion characteristics such as the ignition delay of different blends of fuel are reasonably well predicted. The Particulate Size Mimic (PSM) model accurately predicts the soot generation characteristics of the different fuels, but the Hiroyasu-NSC model falls short in this regard. For accurate prediction of soot with the PSM model, the thermodynamic conditions during combustion must be accurately modeled. While the current computational modeling tools can produce accurate results for the prediction of particulate matter emissions, there is much work to be done in improving our understanding of the underlying fundamental processes.

This article examines genderqueer writer/director Ester Martin Bergsmark’s film Something Must Break (2014) and the trans gaze created through the film’s disjunctive imagery. I argue the film’s aestheticization of polluted environments and trans bodies posits a queer alliance between transness and trash. Similarly, Something Must Break’s repeated imagery of urination and body fluids representationally relates transness, waste, and transgressive sexuality to a politics of marginality, which Bergsmark employs in Something Must Break to express these relationalities as sites for creative difference and possibilities of being that exist outside of heterosexual norms. I use post-structuralist and queer interpretations of perversion to reimagine the film’s polluted environments and abject fluids as sites/sights of creation and liveability for trans bodies. I find in the refractions of polluted waters, blood, saliva, and urine in Something Must Break the same cinematic fissures that Eliza Steinbock argues allows for a uniquely trans gaze in their theory of shimmering. In considering a cinematic transgender gaze, Steinbock describes a cinema that eschews the visual reveal and instead portrays a lived trans experience not defined by dualities, but by disjunctions; thus, the unsettled, the (un)becoming, the “shimmering” aesthetics of trans embodiment. I argue Bergsmark achieves a cinematic trans gaze in their imagining of a queer space where pollution, trash, urine, and blood are not symbols of abjection and shame, but embody an opening-up, a vulnerability: a becoming that molds new forms of relationships, new forms of love, and new forms of creation.

Professional counselors must act as anti-racist social justice advocates throughout the counseling relationship, including assessment, diagnosis, and treatment planning. Due to internalized racism and inappropriate instruments, assessment and diagnosis are two critical areas where marginalized populations have historically experienced misdiagnosis and pathologizing impacting overall client care and wellbeing. Inappropriate instruments, inadequate training, and counselor bias have profound impacts on access to treatment and resources for individuals holding marginalized racial identities. Although the call for anti-racist counseling is clear, the profession is still unclear on how to teach these concepts to counselor trainees. Counselor educators must be intentional about incorporating anti-racist concepts into all counseling courses including assessment and diagnosis. Situated by the historical context of racism within helping professions, we aim to provide practical teaching implications for infusing anti-racist content into assessment and diagnosis courses in counselor education.

Teaching about trauma theory and practice is an integral part of counselor preparation. The purpose of this multiple case study was to understand how counselor educators (CEs) designed and facilitated significant learning experiences regarding trauma theory and practice. The researchers aimed to answer two research questions (1.) how do CEs choose which content to address in trauma courses and (2.) which teaching methods do CEs use to facilitate significant learning experiences in trauma courses? The study participants were three CEs teaching trauma courses in multiple formats (face-to-face, online, and hybrid) in CACREP programs. The results indicated that instructors faced unique situational factors that impacted their choice of teaching and learning activities and assessment measures. The themes Instructor Role, Instructor Identity, and Eliciting Fundamental Change in Learners impacted which teaching methods were chosen to facilitate significant learning experiences. The manuscript includes implications for CEs designing and teaching trauma courses.

Loss of function of the neurofibromatosis type 2 (NF2) tumor suppressor gene leads to the formation of schwannomas, meningiomas, and ependymomas, comprising ∼50% of all sporadic cases of primary nervous system tumors. NF2 syndrome is an autosomal dominant condition, with bi-allelic inactivation of germline and somatic alleles resulting in loss of function of the encoded protein merlin and activation of mammalian target of rapamycin (mTOR) pathway signaling in NF2-deficient cells. Here we describe a gene replacement approach through direct intratumoral injection of an adeno-associated virus vector expressing merlin in a novel human schwannoma model in nude mice. In culture, the introduction of an AAV1 vector encoding merlin into CRISPR-modified human NF2-null arachnoidal cells (ACs) or Schwann cells (SCs) was associated with decreased size and mTORC1 pathway activation consistent with restored merlin activity. In vivo, a single injection of AAV1-merlin directly into human NF2-null SC-derived tumors growing in the sciatic nerve of nude mice led to regression of tumors over a 10-week period, associated with a decrease in dividing cells and an increase in apoptosis, in comparison with vehicle. These studies establish that merlin re-expression via gene replacement in NF2-null schwannomas is sufficient to cause tumor regression, thereby potentially providing an effective treatment for NF2.

Subject-specific hip capsule models could offer insights into impingement and dislocation risk when coupled with computer-aided surgery, but model calibration is time-consuming using traditional techniques. This study developed a framework for instantaneously generating subject-specific finite element (FE) capsule representations from regression models trained with a probabilistic approach. A validated FE model of the implanted hip capsule was evaluated probabilistically to generate a training dataset relating capsule geometry and material properties to hip laxity. Multivariate regression models were trained using 90% of trials to predict capsule properties based on hip laxity and attachment site information. The regression models were validated using the remaining 10% of the training set by comparing differences in hip laxity between the original trials and the regression-derived capsules. Root mean square errors (RMSEs) in laxity predictions ranged from 1.8° to 2.3°, depending on the type of laxity used in the training set. The RMSE, when predicting the laxity measured from five cadaveric specimens with total hip arthroplasty, was 4.5°. Model generation time was reduced from days to milliseconds. The results demonstrated the potential of regression-based training to instantaneously generate subject-specific FE models and have implications for integrating subject-specific capsule models into surgical planning software.

Scavenging constitutes an understudied energy pathway in terrestrial ecosystems, with important connections to disease ecology. A prevailing null hypothesis in scavenging ecology is that carcasses serve as a risk-free meal for whatever animal first encounters them on the landscape. We tested this hypothesis by focusing on a suspected risk that scavengers would face at carcasses: the risk of pathogen exposure. We conducted field trials with mouse carcasses in which we manipulated potential cues to pathogen risk and then monitored scavenger foraging decisions. Separately, we studied pathogen and commensal bacteria dynamics within mouse carcasses through time in the laboratory to better understand how carcass age might impact pathogen risk to scavengers. A visual cue to pathogen risk in the field (carcasses deployed in groups of 7 in 1 m2) caused facultative vertebrate scavengers to pass on the opportunity to feed at a rate six-times higher than for carcasses deployed singly (46.9% vs. 7.7%), suggesting an ability to perceive cues to pathogen risk at carcasses. The cues to carcass age, however, produced no effect on facultative scavenger behavior in our field trials. Laboratory trials demonstrated that both commensal enteric bacteria and a known pathogen (Listeria monocytogenes) increased at least through bloat and active decay stages in carcasses, suggesting that cues to carcass age may not help scavengers reduce pathogen risk early in decomposition. In providing evidence counter to the free meal hypothesis, our results support the continued formation of an alternative risk-based framework to understand scavenger behavior at carcasses.

Abstract Background Approximately 40% of the 110,000 adolescents living with HIV (ALHIV) in Kenya have not achieved viral suppression. Despite the increasing availability of adolescent-friendly services, adolescents face barriers that impact ART adherence. This study aimed to identify key stigma-related barriers to ART adherence and strategies used by adolescents in overcoming these barriers. Methods Data were collected by LVCT Health, a Kenyan organization with a programmatic focus on HIV testing, prevention, and care. 122 participants were recruited from 3 clinical sites affiliated with LVCT Health in Nairobi, Kisumu, and Mombasa. In-depth interviews were conducted with ALHIV (n = 12). Focus group discussions were conducted with ALHIV (n = 5), peer leaders (n = 3), and adolescents receiving HIV services in community settings (AIC) irrespective of HIV status (n = 3). Interviews and focus groups were audio recorded, translated, and transcribed. Data were analyzed thematically, with a focus on stigma and resilience. Results While AIC primarily focused on adherence barriers and stigma, ALHIV and, to some extent, peer leaders, also identified resilience factors that helped overcome stigma. Four major themes emerged: 1) knowledge and future-oriented goals can drive motivation for ALHIV to remain healthy; 2) disclosure to others strengthens support systems for ALHIV; 3) medication-taking strategies and strategic disclosure can overcome adherence challenges in school; and 4) a supportive clinic environment promotes continuous adolescent engagement in HIV care. These concepts were used to develop a conceptual stigma/resilience model depicting how resilience moderates negative effects of stigma among ALHIV. Conclusions This study demonstrates the positive effects of ALHIV resilience on ART adherence and illuminates how stigma impacts ALHIV differently depending on their resilience. Strengths-based interventions, focused on increasing resilience among ALHIV in Kenya, and more formal involvement of adolescent peers to bolster adolescent support, have the potential to improve ART adherence among ALHIV.

Abstract Phoenixin (PNX) is a highly conserved, novel hormone with diverse functions, including hypothalamic control of reproduction, appetite modulation, and regulation of energy metabolism and inflammation. While some functions appear conserved across vertebrates, additional research is required to fully characterize these complex pleiotropic effects. For instance, very little is known about transcriptome level changes associated with PNX exposure, including responses in the hypothalamic–pituitary–gonadal (HPG) axis, which is critical in vertebrate reproduction. In addition, the PNX system may be especially complex in fish, where an additional receptor is likely present in some species. The purpose of this study was to assess hypothalamic and ovarian transcriptomes after PNX-14 administration in female vitellogenic green-spotted puffer (Dichotomyctere nigroviridis). Steroid-related changes were also assessed in the liver and blood plasma. Hypothalamic responses included pro-inflammatory signals such as interleukin 1β, possibly related to gut–brain axis functions, as well as suppression of cell proliferation. Ovarian responses were more widely downregulated across all identified pathways, which may reflect progression to a less transcriptionally active state in oocytes. Both organs shared regulation in transforming growth factor-β and extracellular matrix remodeling (periostin) pathways. Reproductive processes were in general downregulated, but both inhibiting (bone morphogenetic protein 15 and follistatin) and promoting (17-hydroxyprogesterone) factors for oocyte maturation were identified. Select genes involved in reproduction (vitellogenins, estrogen receptors) in the liver were unresponsive to PNX-14 and higher doses may be needed to induce reproductive effects in D. nigroviridis. These results reinforce the complexity of PNX actions in diverse tissues and highlight important roles for this hormone in regulating the immune response, energy metabolism, and cell growth.

Skeletal muscles have a highly organized hierarchical structure, whose main function is to generate forces for movement and stability. To understand the complex heterogeneous behaviors of muscles, computational modeling has advanced as a non-invasive approach to evaluate relevant mechanical quantities. Aiming to improve musculoskeletal predictions, this paper presents a framework for modeling 3D deformable muscles that includes continuum constitutive representation, parametric determination, model validation, fiber distribution estimation, and integration of multiple muscles into a system level for joint motion simulation. The passive and active muscle properties were modeled based on the strain energy approach with Hill-type hyperelastic constitutive laws. A parametric study was conducted to validate the model using experimental datasets of passive and active rabbit leg muscles. The active muscle model with calibrated material parameters was then implemented to simulate knee bending during a squat with multiple quadriceps muscles. A computational fluid dynamics (CFD) fiber simulation approach was utilized to estimate the fiber arrangements for each muscle, and a cohesive contact approach was applied to simulate the interactions among muscles. The single muscle simulation results showed that both passive and active muscle elongation responses matched the range of the testing data. The dynamic simulation of knee flexion and extension showed the predictive capability of the model for estimating the active quadriceps responses, which indicates that the presented modeling pipeline is effective and stable for simulating multiple muscle configurations. This work provided an effective framework of a 3D continuum muscle model for complex muscle behavior simulation, which will facilitate additional computational and experimental studies of skeletal muscle mechanics. This study will offer valuable insight into the future development of multiscale neuromuscular models and applications of these models to a wide variety of relevant areas such as biomechanics and clinical research.

Depression is common during pregnancy, yet pregnant women often do not engage in standard mental health treatments, which is concerning due to negative consequences associated with untreated maternal depression. Given that exercise can help to decrease depressive symptoms, and most pregnant women are able to safely engage in mild to moderate physical activity, physical activity interventions may be helpful in improving mood among pregnant women, even those with clinical levels of depression. In an open trial, we piloted a 10-week prenatal walking intervention in 18 depressed pregnant women (mean age=28.7 years). Participants wore a pedometer daily to track activity and attended 6 brief counseling sessions over the 10-week period. Indicators of acceptability and feasibility were assessed, as were changes in depression, physical activity, and other clinical outcomes. Results suggest that the prenatal walking intervention is feasible and acceptable. No adverse events were observed, and most women (83%) completed the intervention, attending on average 5.5 of 6 intervention sessions. Findings also support preliminary efficacy of the intervention: depression scores were reduced by endpoint, and physical activity levels increased based on self-report and objective measurement. Women also reported lower anxiety, and positive changes in affect at endpoint. Participants reported high satisfaction on a questionnaire. Though preliminary, findings suggest that a lifestyle physical activity intervention could be a valuable strategy to improve mood during pregnancy. Further research is needed to evaluate the intervention in a more rigorous randomized trial. If proven efficacious, this simple, low-cost intervention could be implemented in prenatal care settings.

# Background Despite shoulder and elbow injuries being common in athletics, return to sport and reinjury rates are less than ideal. These outcomes may be driven by the absence of evidence-informed testing to determine an athlete's readiness for sport. # Purpose The purpose of this study was to explore the reported frequency of physical performance testing for return to sport readiness by physical therapists treating athletes with upper extremity injuries and to identify potential barriers that may limit use of these tests. A secondary aim was to compare practice patterns of clinicians with sports physical therapy specialty certification to clinicians without. # Study Design International, cross-sectional survey using purposive sampling. # Methods A survey instrument was created to assess the frequency of use of physical performance tests by physical therapists treating athletes with upper extremity injuries, as well as the barriers limiting the use of these tests. The 19-question online survey was distributed via email and Twitter among sports physical therapists. Independent t-tests and Chi Square analyses were conducted to determine differences in practice patterns between physical therapists with and without specialization and the frequency of potential barriers that may limit the use of these tests. # Results Four hundred ninety-eight participants met study eligibility and completed the survey. Fewer than half of participants reported using any physical performance test in making return to sport decisions for athletes with upper extremity injuries. The greatest barriers to the use of physical performance tests were a lack of equipment followed by lack of understanding of the literature, lack of time, and lack of supporting literature. Sports specialist clinicians were significantly more likely (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