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Effectively utilizing MEK inhibitors in the clinic remains challenging due to off-target toxicity and lack of predictive biomarkers. Recent findings propose E-cadherin, a breast cancer diagnostic indicator, as a predictor of MEK inhibitor success. To address MEK inhibitor toxicity, traditional methodologies have systemically delivered nanoparticles, which require frequent, high-dose injections. Here, we present a different approach, employing a thermosensitive, biodegradable hydrogel with functionalized liposomes for local, sustained release of MEK inhibitor PD0325901 and doxorubicin. The poly(δ-valerolactone-co-lactide)-b-poly(ethylene-glycol)-b-poly(δ-valerolactone-co-lactide) triblock co-polymer gels at physiological temperature and has an optimal degradation time in vivo. Liposomes were functionalized with PR_b, a biomimetic peptide targeting the α5β1 integrin receptor, which is overexpressed in E-cadherin-positive triple negative breast cancer (TNBC). In various TNBC models, the hydrogel-liposome system delivered via local injection reduced tumor progression and improved animal survival without toxic side effects. Our work presents the first demonstration of local, sustained delivery of MEK inhibitors to E-cadherin-positive tumors alongside traditional chemotherapeutics, offering a safe and promising therapeutic strategy.

This study was designed to evaluate the microbiological, physical, and chemical effects of ginger extracts and sterilization on palm oil samples sourced from markets in the Southern Senatorial District of Ondo State, Nigeria. Water and ethanol ginger extracts were used for palm oil treatment. Microbial isolation was performed by serial dilution and pour plating techniques. Pure isolates were obtained by repeated streaking. Isolates were identified based on cultural, biochemical, and morphological characterization. Biochemical parameters, such as free fatty acid, peroxide value, moisture content, impurity level, and iodine value, were determined. Sterilized palm oil had no microbial growth with low values in all evaluated parameters. The bacterial genera isolated from the palm oil samples included Pseudomonas, Bacillus, Enterococcus, Staphylococcus, and Micrococcus. The discovered fungal species included Aspergillus niger, A. flavus, Cochliobolus sp., Penicillium citrinum, P. italicum, P. chrysogenum, Geotrichum clavatum, Mucor spp., Chrysosporium tropicum, Fusarium solani, Microsporum canis, and Meyerozyma guilliermondii. These microorganisms indicated the unhygienic condition of palm oil production chain from processing to packaging and market display. Both ginger extracts and sterilization were efficient in combating oxidative rancidity of palm oil and controlling microbial growth that might alter oil quality. Therefore, adequate quality control measures of palm oil during processing and marketing and treatments will help to reduce post-production contamination and deterioration under storage conditions.

Learning by Evaluating (LbE) is an instructional approach that involves students making comparative judgements of pairs of artifacts, such as student work, portfolios, prototypes, or curated images related to a topic of instruction to enhance critical thinking and decision-making skills. Situated as a primer for learning, the efficacy of LbE stems from actively engaging students in the evaluation process, scaffolding their learning, fostering self-reflection in decision-making, and facilitating the transfer of acquired skills and concepts to academic contexts and project work. However, there is an opportunity to gain deeper insights into classroom integration of LbE and the factors that may influence the student experience. This study adopts a design-based research approach to analyze LbE within a secondary STEM education setting, with the objective of optimizing classroom integration. By analyzing student comments generated during LbE, the research explores factors shaping the students' learning experiences, examining the extent to which students engage in informed decision-making, offer justifications, and express sentiments throughout the process. Additionally, the study explores how teachers strategically incorporate LbE into their classroom, aligning LbE sessions with curriculum objectives. Findings indicate a diverse pattern of student engagement, sentiments, and decision-making approaches across STEM classrooms. This study contributes to research on LbE by offering insights into the dynamics between teacher implementation and student engagement. The insights gained highlight the potential for refining the effectiveness of LbE within the classroom. Notably, the research emphasizes the significance of how LbE sessions are framed and strategically integrated to enrich the overall educational experience for both students and educators.

Background: Excessive worry during adolescence can significantly impact mental health. Understanding adolescent concerns may help inform mental health early intervention strategies. Objective: This study aimed to identify frequent concerns among Australian secondary school students, exploring individual and demographic differences. Whether adolescents' most frequently reported concern was associated with mental health and wellbeing was also investigated. Methods: A total of N = 4086 adolescents (Mage = 13.92) participated in an online survey, reporting their top concerns alongside demographic characteristics, mental health, and wellbeing. Data were analysed using both qualitative and quantitative approaches. Results: Thematic analysis identified 11 different themes of adolescent concerns. A frequency analysis showed concerns relating to 'School and Academics' were most common (24.52% of all responses), consistent across females, males, school location (regional vs metropolitan areas), and socioeconomic background. Sexuality and gender diverse adolescents more frequently reported concerns about 'Mental Health and Wellbeing' and 'Social Relationships'. Linear mixed models found 'School and Academic' concerns were associated with lower symptoms of depression (p < 0.001, d = 0.16) and anxiety (p < 0.001, d = 0.19) and higher wellbeing (p = 0.03, d = 0.07) compared to all other concerns. Conclusion: 'School and Academic' concerns were most common, however not associated with poorer mental health or wellbeing. Sexuality and gender diverse adolescents were more likely to report concerns regarding 'Mental Health and Wellbeing' and 'Social Relationships'. Efforts aimed solely at reducing academic stress may not be the most effective approach to improving adolescent mental health. Longitudinal data into how concerns evolve over time could provide a nuanced understanding of their relationship with future mental health challenges.

Abstract Biofouling is the accumulation of organisms on surfaces immersed in water. It is of particular concern to the international shipping industry because it increases fuel costs and presents a biosecurity risk by providing a pathway for non-indigenous marine species to establish in new areas. There is growing interest within jurisdictions to strengthen biofouling risk-management regulations, but it is expensive to conduct in-water inspections and assess the collected data to determine the biofouling state of vessel hulls. Machine learning is well suited to tackle the latter challenge, and here we apply deep learning to automate the classification of images from in-water inspections to identify the presence and severity of fouling. We combined several datasets to obtain over 10,000 images collected from in-water surveys which were annotated by a group biofouling experts. We compared the annotations from three experts on a 120-sample subset of these images, and found that they showed 89% agreement (95% CI: 87–92%). Subsequent labelling of the whole dataset by one of these experts achieved similar levels of agreement with this group of experts, which we defined as performing at most 5% worse (p $$=$$ = 0.009–0.054). Using these expert labels, we were able to train a deep learning model that also agreed similarly with the group of experts (p $$=$$ = 0.001–0.014), demonstrating that automated analysis of biofouling in images is feasible and effective using this method.

Abstract Objective Adult polyglucosan body disease (APBD) is an adult‐onset neurological variant of glycogen storage disease type IV. APBD is caused by recessive mutations in the glycogen branching enzyme gene, and the consequent accumulation of poorly branched glycogen aggregates called polyglucosan bodies in the nervous system. There are presently no treatments for APBD. Here, we test whether downregulation of glycogen synthesis is therapeutic in a mouse model of the disease. Methods We characterized the effects of knocking out two pro‐glycogenic proteins in an APBD mouse model. APBD mice were crossed with mice deficient in glycogen synthase (GYS1), or mice deficient in protein phosphatase 1 regulatory subunit 3C (PPP1R3C), a protein involved in the activation of GYS1. Phenotypic and histological parameters were analyzed and glycogen was quantified. Results APBD mice deficient in GYS1 or PPP1R3C demonstrated improvements in life span, morphology, and behavioral assays of neuromuscular function. Histological analysis revealed a reduction in polyglucosan body accumulation and of astro‐ and micro‐gliosis in the brains of GYS1‐ and PPP1R3C‐deficient APBD mice. Brain glycogen quantification confirmed the reduction in abnormal glycogen accumulation. Analysis of skeletal muscle, heart, and liver found that GYS1 deficiency reduced polyglucosan body accumulation in all three tissues and PPP1R3C knockout reduced skeletal muscle polyglucosan bodies. Interpretation GYS1 and PPP1R3C are effective therapeutic targets in the APBD mouse model. These findings represent a critical step toward the development of a treatment for APBD and potentially other glycogen storage disease type IV patients.

In design courses, reviewing how others have solved design problems or completed projects is common practice and often encouraged by educators. Using student work as examples can provide context for assessment criteria and help students approach new design problems. While studies have explored the use of exemplars in various disciplines, little research has focused on which exemplars to use (e.g., high-quality, low-quality) in design, technology, and engineering fields. To address this gap, researchers conducted a literature review of 33 articles on exemplar use in secondary and post-secondary education. The analysis revealed nine themes related to exemplar use and their impact on student learning, including (1) Clarity of instruction, (2) Learner focus, (3) Motivation for learning, (4) Student reflection on learning, (5) Building student self-efficacy, (6) Identifying instructional challenges, (7) Providing contrasting cases, (8) The relationship between exemplar quality and student work quality, and (9) Raising the bar for learning outcomes. Findings suggest that simply providing an exemplar is not enough and that the selection of an exemplar can have positive or negative impacts on student motivation, understanding, and application. Carefully selecting exemplars and engaging in dialogue with students can help them identify expectations, recognize quality work, and identify potential misconceptions. These findings have implications for those involved in design, technology, and engineering education. Educators can use these findings to guide their selection of exemplars and engage students in meaningful dialogue to aid their learning. Researchers can also use these findings to further investigate the use of exemplars in these fields.

The purpose of this study was to determine the influence that a novel, industry-situated, Science, Technology, Engineering, and Mathematics (STEM) Learning Laboratory (STEM Lab) experience may have on students' (ages 10-18) perceptions of manufacturing-related careers as well as to identify any challenges/strategies for the implementation of these informal learning spaces within manufacturing facilities. STEM labs, which are similar to makerspaces, can be defined as physical spaces where students can learn integrated skills and content through hands-on experiences (Roy and Love, 2017). While STEM labs can be found in a variety of settings (e.g., school libraries, museums, or even theme parks), the industry-situated STEM lab that is the focus of this study is a unique application of such a learning environment in an informal space within a manufacturing facility. However, the aim for this specific space is to offer local students an opportunity to see manufacturing, the people that work there, and the skills that might be necessary to pursue a future career in the various aspects of this industry. This type of career awareness and preparation initiative has become an area of interest for manufacturers as they continue to face increasing challenges with attracting employees and confronting negative, potentially outdated, perceptions of manufacturing-related careers. That being said, this research will not attempt to justify the STEM lab initiative, but will instead provide a critical view of this novel context and this type of informal learning environment. This research objective was pursued by interviewing key industry stakeholders and analyzing an existing dataset-consisting of both student surveys and drawing tests-collected by the host manufacturer over the first year of the lab's operation. By triangulating the data gathered from stakeholder interviews and both student surveys and drawing tests, which were collected before and after their experience with the STEM lab at the manufacturing facilities, this research sheds light on the challenges that similar industry-situated learning environments might face, as well as provides opportunities to potentially enhance the experience from both the student and industry perspective.

Classroom research has demonstrated the capacity for significantly influencing student learning by engaging students in evaluation of previously submitted work as an intentional priming exercise for learning; we call this experience "Learning by Evaluating" (LbE). Expanding on current LbE research, we set forth to investigate the impact on student learning by intentionally differing the quality of examples evaluated by the students using adaptive comparative judgement. In this research, university design students (N = 468 students) were randomly assigned to one of three treatment groups; while each group evaluated previously collected student work as an LbE priming activity, the work evaluated by each group differed in quality. Using a three-group experimental design, one group of students only evaluated high quality examples, the second only evaluated low quality examples, and the third group of students evaluated a set of mixed-quality examples of the assignment they were about to work on. Following these LbE priming evaluations, students completed the assigned work and then their projects were evaluated to determine if there was a difference between student performance by treatment condition. Additional qualitative analysis was completed on student LbE rationales to explore similarities and differences in student cognitive judgments based on intervention grouping. No significant difference was found between the groups in terms of achievement, but several differences in group judgement approach were identified and future areas needing investigation were highlighted.

Adaptive comparative judgment (ACJ) has been widely used to evaluate classroom artifacts with reliability and validity. In the ACJ experience we examined, students were provided a pair of images related to backpack design. For each pair, students were required to select which image could help them ideate better. Then, they were prompted to provide a justification for their decision. Data were from 15 high school students taking engineering design courses. The current study investigated how students' reasoning differed based on selection. Researchers analyzed the comments in two ways: (1) computer-aided quantitative content analysis and (2) qualitative content analysis. In the first analysis, we performed sentiment analysis and word frequency analysis using natural language processing. Based on the findings, we explored how the design thinking process was embedded in student reasoning, and if the reasoning varied depending on the claim. Results from sentiment analysis showed that students tend to reveal more strong positive sentiment with short comments when providing reasoning for the selected design. In contrast, when providing reasoning for those items not chosen, results showed a weaker negative sentiment with more detailed reasons. Findings from word frequency analysis showed that students valued the function of design as well as the user perspective, specifically, convenience. Additionally, students took aesthetic features of each design into consideration when identifying the best of the two pairs. Within the engineering design thinking context, we found students empathize by identifying themselves as users, define user's needs, and ideate products from provided examples.

Biology is perhaps the most complex of the sciences, given the incredible variety of chemical species that are interconnected in spatial and temporal pathways that are daunting to understand. Their interconnections lead to emergent properties such as memory, consciousness, and recognition of self and non-self. To understand how these interconnected reactions lead to cellular life characterized by activation, inhibition, regulation, homeostasis, and adaptation, computational analyses and simulations are essential, a fact recognized by the biological communities. At the same time, students struggle to understand and apply binding and kinetic analyses for the simplest reactions such as the irreversible first-order conversion of a single reactant to a product. This likely results from cognitive difficulties in combining structural, chemical, mathematical, and textual descriptions of binding and catalytic reactions. To help students better understand dynamic reactions and their analyses, we have introduced two kinds of interactive graphs and simulations into the online educational resource, Fundamentals of Biochemistry, a LibreText biochemistry book. One is available for simple binding and kinetic reactions. The other displays progress curves (concentrations vs. time) for simple reactions and complex metabolic and signal transduction pathways. Users can move sliders to change dissociation and kinetic constants as well as initial concentrations and see instantaneous changes in the graphs. They can also export data into a spreadsheet for further processing, such as producing derivative Lineweaver-Burk and traditional Michaelis-Menten graphs of initial velocity (v[subscript 0]) versus substrate concentration.

Explicitly incorporating the effects of chemical phenomena such as chemical pretreatment and mineral scaling during the design of treatment systems is critical; however, the complexity of these phenomena and limitations on data have historically hindered the incorporation of detailed water chemistry into the modeling and optimization of water desalination systems. Thus, while qualitative assessments and experimental studies on chemical pretreatment and scaling are abundant in the literature, very little has been done to assess the technoeconomic implications of different chemical pretreatment alternatives within the context of end-to-end water treatment train optimization. In this work, we begin to address this challenge by exploring the impact of pH control during pretreatment on the cost and operation of a high-recovery desalination train. We compare three pH control methods used in water treatment (H2SO4, HCl, and CO2) and assess their impact on the operation of a desalination plant for brackish water and seawater. Our results show that the impact of the acid choice on the cost can vary widely depending on the water source, with CO2 found to be up to 11% and 49% more expensive than HCl in the seawater and brackish cases, respectively. We also find that the acid chemistry can significantly influence upstream processes, with use of H2SO4 requiring more calcium removal in the softening step to prevent gypsum scaling in HPRO system. Our work highlights why incorporating water chemistry information is critical when evaluating the key cost and operational drivers for high-recovery desalination treatment trains.

The stability of fractional Chern insulators is widely believed to be predicted by the resemblance of their single-particle spectra to Landau levels. We investigate the scope of this geometric stability hypothesis by analyzing the stability of a set of fractional Chern insulators that explicitly do not have a Landau level continuum limit. By computing the many-body spectra of Laughlin states in a generalized Hofstadter model, we analyze the relationship between single-particle metrics, such as trace inequality saturation, and many-body metrics, such as the magnitude of the many-body and entanglement gaps. We show numerically that the geometric stability hypothesis holds for Chern bands that are not continuously connected to Landau levels, as well as conventional Chern bands, albeit often requiring larger system sizes to converge for these configurations.

Cost-optimization models are powerful tools for evaluating emerging water treatment processes. However, to date, optimization models do not incorporate detailed chemical reaction phenomena, limiting the assessment of pretreatment and mineral scaling. Moreover, novel approaches for high-salinity and high-recovery desalination are typically proposed without direct quantification of pretreatment needs or mineral scaling. This work addresses a critical gap in the literature by presenting a modeling framework that includes complex water chemistry predictions with process-scale optimization. We use this approach to conduct a technoeconomic assessment on a conceptual high-recovery treatment train that includes chemical pretreatment (i.e., soda ash softening and recarbonation) and membrane-based desalination (i.e., standard and high-pressure reverse osmosis). We demonstrate how to develop and integrate accurate multidimensional surrogate models for predicting precipitation, pH, and mineral scaling tendencies. Our findings show that cost-optimal results balance the costs of pretreatment with reverse osmosis system design. Optimizing across a range of water recoveries (i.e., 50-90%) reveals multiple cost-optimal schemas that vary the chemical dosing in pretreatment and the design and operation of reverse osmosis. Our results reveal that pretreatment costs can be more than double the cost of the primary desalination process at high recoveries due to the extensive pretreatment required to control scaling. This work emphasizes the importance of and provides a framework for including chemistry and mineral scaling predictions in the evaluation of emerging technologies in high-recovery desalination.

Summary: Browning induction or transplantation of brown adipose tissue (BAT) or brown/beige adipocytes derived from progenitor or induced pluripotent stem cells (iPSCs) can represent a powerful strategy to treat metabolic diseases. However, our poor understanding of the mechanisms that govern the differentiation and activation of brown adipocytes limits the development of such therapy. Various genetic factors controlling the differentiation of brown adipocytes have been identified, although most studies have been performed using in vitro cultured pre-adipocytes. We investigate here the differentiation of brown adipocytes from adipose progenitors in the mouse embryo. We demonstrate that the formation of multiple lipid droplets (LDs) is initiated within clusters of glycogen, which is degraded through glycophagy to provide the metabolic substrates essential for de novo lipogenesis and LD formation. Therefore, this study uncovers the role of glycogen in the generation of LDs. : Lipid droplet formation is a major feature of brown adipocyte differentiation. Mayeuf-Louchart et al. characterize the different steps of brown adipocyte differentiation in the mouse embryo and report the essential role of glycogen production and degradation by glycophagy for lipid droplet biogenesis. Keywords: brown adipose tissue, adipocyte differentiation, lipid droplet biogenesis, lipid, glycogen, autophagy, glycophagy, embryonic development, adipocyte metabolism, BAT

Abstract: Climate change is increasing the frequency, severity, and extent of wildfires and drought in many parts of the world, with numerous repercussions for the physical, chemical, and biological characteristics of streams. However, information on how these perturbations affect top predators and their impacts on lower trophic levels in streams is limited. The top aquatic predator in southern California streams is native Oncorhynchus mykiss, the endangered southern California steelhead trout (trout). To examine relationships among the distribution of trout, environmental factors, and stream invertebrate resources and assemblages, we sampled pools in 25 stream reaches that differed in the presence (nine reaches) or absence (16 reaches) of trout over 12 years, including eight reaches where trout were extirpated during the study period by drought or post‐fire flood disturbances. Trout were present in deep pools with high water and habitat quality. Invertebrate communities in trout pools were dominated by a variety of medium‐sized collector–gatherer and shredder invertebrate taxa with non‐seasonal life cycles, whereas tadpoles and large, predatory invertebrates (Odonata, Coleoptera, Hemiptera [OCH]), often with atmospheric breather traits, were more abundant in troutless than trout pools. Structural equation modelling of the algal‐based food web indicated a trophic cascade from trout to predatory invertebrates to collector–gatherer taxa and weaker direct negative trout effects on grazers; however, both grazers and collector–gatherers also were positively related to macroalgal biomass. Structural equation modelling also suggested that bottom‐up interactions and abiotic factors drove the detritus‐based food web, with shredder abundance being positively related to leaf litter (coarse particulate organic matter) levels, which, in turn, were positively related to canopy cover and negatively related to flow. These results emphasise the context dependency of trout effects on prey communities and of the relative importance of top‐down versus bottom‐up interactions on food webs, contingent on environmental conditions (flow, light, nutrients, disturbances) and the abundances and traits of component taxa. Invertebrate assemblage structure changed from a trout to a troutless configuration within a year or two after trout were lost owing to post‐fire scouring flows or drought. Increases in OCH abundance after trout were lost were much more variable after drought than after fire. The reappearance of trout in one stream resulted in quick, severe reductions in OCH abundance. These results indicate that climate‐change induced disturbances can result in the extirpation of a top predator, with cascading repercussions for stream communities and food webs. This study also emphasises the importance of preserving or restoring refuge habitats, such as deep, shaded, perennial, cool stream pools with high habitat and water quality, to prevent the extirpation of sensitive species and preserve native biodiversity during a time of climate change.

IntroductionPeople who use drugs (PWUD) are at increased risk for HIV infection. HIV self-testing (HIVST) is a promising method for identifying new infections, but optimal distribution strategies remain understudied.MethodsTo characterize PWUD by HIVST distribution strategy (peers vs. mail), we examined data from July 2022 to June 2023 collected from a real-world HIVST program led by the non-profit, Florida Harm Reduction Collective. We used descriptive statistics and Poisson regressions with robust error variance to compare those who received HIVST through peers or via mail by socio-demographics, Ending the HIV Epidemic (EHE) county designation, and HIV testing experience.ResultsAmong 728 participants, 78% received HIVST from peers, 47% identified as cisgender female, 48% as heterosexual, and 45% as non-White; 66% resided in an EHE county, and 55% had no HIV testing experience. Compared to those who received an HIV self-test from peers, those who received tests via mail were less likely to be cisgender male (vs. cisgender female; prevalence ratio [PR] = 0.59, 95% confidence interval [CI]: 0.43, 0.81), non-Hispanic Black (vs. non-Hispanic White; PR = 0.57, 95% CI: 0.36, 0.89) or from EHE counties (vs. non-EHE counties; PR = 0.33, 95% CI: 0.25, 0.44). Those who received tests via mail were also more likely to identify their sexual orientation as "Other/Undisclosed" (vs. straight/heterosexual; PR = 2.00, 95% CI: 1.51, 2.66).ConclusionOur findings support the role of community-based HIVST distribution strategies in increasing HIV testing coverage among PWUD. Additional research could help inform the equitable reach of HIVST.

BackgroundXylazine is an increasingly common adulterant in the North American unregulated drug supply that is associated with adverse health outcomes (e.g., skin infections, overdose). However, there are significant knowledge gaps regarding how xylazine was initially identified and how syringe services program (SSP) staff and clients (people who use drugs) responded to its emergence.MethodsFrom June-July 2023, we conducted qualitative interviews with medical (e.g., clinicians) and frontline SSP staff (e.g., outreach workers) and adult clients with a history of injection drug use at a Miami-based SSP. Inductive memos identified emergent codes; thematic analysis involving team consensus established final themes.ResultsFrom interviews with SSP staff (n = 8) and clients (n = 17), xylazine emergence was identified at different times, in various ways. Initially, during summer 2022, clients identified a "tranquilizer-like substance" that worsened sedation and withdrawal and caused wounds. SSP medical staff later identified this adulterant as xylazine by treating new medical cases and through diverse information-sharing networks that included professional societies and news sources; however, frontline SSP staff and clients needed additional educational resources about xylazine and its side effects. With limited guidance on how to reduce harm from xylazine, SSP clients altered their drug consumption routes, reduced drug use, and relied on peers' experiences with the drug supply to protect themselves. Some individuals also reported preferring xylazine-adulterated opioids and increasing their drug use, including the use of stimulants to avoid over sedation.ConclusionsXylazine's emergence characterizes the current era of unprecedented shifts in the unregulated drug supply. We found that xylazine spurred important behavioral changes among people who use drugs (e.g., transitioning from injecting to smoking). Incorporating these experiences into early drug warning surveillance systems and scaling up drug-checking services and safer smoking supply distribution could help mitigate significant health harms caused by xylazine and other emergent adulterants.

BackgroundPeople who use drugs (PWUD) experience elevated HIV risk and numerous barriers to facility-based HIV testing. HIV self-testing (HIVST) could circumvent many of those barriers and is acceptable among PWUD, yet HIVST implementation for PWUD is limited. Service providers' perspectives on specific HIVST delivery strategies could help increase availability for PWUD.MethodsFrom April-November 2021, we interviewed 16 health, harm reduction, and social service providers working with PWUD in San Diego, CA. Interviews and rapid thematic analysis explored perspectives on HIVST's utility and appropriateness, as well as the feasibility of and anticipated challenges with specific HIVST delivery strategies, including peer or secondary distribution.ResultsParticipants viewed HIV as a significant threat to PWUD health and confirmed the presence of numerous barriers to local facility-based HIV testing. Participants viewed HIVST as a promising and potentially empowering solution. Based on community familiarity with secondary distribution of harm reduction supplies (i.e., naloxone) and information, participants viewed secondary distribution of HIVST kits as an appropriate and feasible strategy for increasing the reach of HIVST, but also described potential barriers (e.g., engaging socially disconnected individuals, ensuring linkages to services following HIVST) and provided suggestions for alternative HIVST kit delivery models (e.g., harm reduction vending machines).ConclusionsService providers viewed secondary distribution of HIVST kits among PWUD as promising, appropriate, and feasible, yet specialized efforts may be needed to reach the most marginalized individuals and ensure consistent provision of educational information and referral supports that maximize the impact of this approach.