Cancer-stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies.

Brain metastatic breast cancer is particularly lethal largely due to therapeutic resistance. Almost half of the patients with metastatic HER2-positive breast cancer develop brain metastases, representing a major clinical challenge. We previously described that cancer-associated fibroblasts are an important source of resistance in primary tumors. Here, we report that breast cancer brain metastasis stromal cell interactions in 3D cocultures induce therapeutic resistance to HER2-targeting agents, particularly to the small molecule inhibitor of HER2/EGFR neratinib. We investigated the underlying mechanisms using a synthetic Notch reporter system enabling the sorting of cancer cells that directly interact with stromal cells. We identified mucins and bulky glycoprotein synthesis as top-up-regulated genes and pathways by comparing the gene expression and chromatin profiles of stroma-contact and no-contact cancer cells before and after neratinib treatment. Glycoprotein gene signatures were also enriched in human brain metastases compared to primary tumors. We confirmed increased glycocalyx surrounding cocultures by immunofluorescence and showed that mucinase treatment increased sensitivity to neratinib by enabling a more efficient inhibition of EGFR/HER2 signaling in cancer cells. Overexpression of truncated MUC1 lacking the intracellular domain as a model of increased glycocalyx-induced resistance to neratinib both in cell culture and in experimental brain metastases in immunodeficient mice. Our results highlight the importance of glycoproteins as a resistance mechanism to HER2-targeting therapies in breast cancer brain metastases.

Project GRIP: An Illustration of Participatory Action Research with Communities of People Who Own and Use Firearms.

Firearm-related injury and mortality prevention strategies are often incompatible with and potentially ineffective for the very populations at risk. Such incompatibility is reflective of a cultural disconnect between investigators and prevention specialists and those who own and use firearms. The current paper describes Project GRIP, a research study that was guided by the principles of Participatory Action Research (PAR). We present the project as a case-example and demonstration of how PAR principles can inform an approach to partner with firearm owners in injury prevention research. Though PAR is a general approach and not a set of techniques, we describe the strategies we used in the hopes that they may be useful for investigators using PAR with firearm owners. We discuss the project and our approach across different stages of the process, including entering into PAR with firearm owners, building partnerships, developing a shared vision, mutual understanding, and co-learning, building and maintaining positive relationships, and executing the project tasks. The PAR approach and the intentional emphasis on partnership is, in our opinion, vital to ensuring that the perspectives of firearm owners are incorporated into the research literature so that more ecologically valid and potentially effective injury and mortality prevention strategies can be developed and disseminated.

Mixed methods evaluation of a jail diversion program: Impact on arrests and functioning.

This mixed methods study had two aims: (1) to examine the effectiveness of a jail diversion program in reducing recidivism and promoting educational and employment outcomes; and (2) to qualitatively explore mechanisms through which the program was effective. Participants were 17 individuals arrested for drug offenses who participated in an intensive, law enforcement-based jail diversion program, and 17 individuals in a comparison group. Arrests were extracted from police records, and education and employment were extracted from program data. Four intervention participants completed qualitative interviews. Arrest rates in the intervention group decreased significantly postintervention, and arrest rates in the intervention group were numerically lower than those in the comparison group. Participants experienced significant increases in employment and driver's license status. Participants also identified mechanisms through which the program was effective. This jail diversion program shows promise in reducing recidivism and promoting adaptive functioning. Jail diversion programs that include mentorship, peer support, and removal of barriers to success may be particularly effective.

A subpopulation of luminal progenitors secretes pleiotrophin to promote angiogenesis and metastasis in inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in IBC patients, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for crosstalk between LPs, endothelial tip cells, and immature perivascular cells via PTN-NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC.

Out of touch? How trauma shapes the experience of social touch - Neural and endocrine pathways.

Trauma can shape the way an individual experiences the world and interacts with other people. Touch is a key component of social interactions, but surprisingly little is known about how trauma exposure influences the processing of social touch. In this review, we examine possible neurobiological pathways through which trauma can influence touch processing and lead to touch aversion and avoidance in trauma-exposed individuals. Emerging evidence indicates that trauma may affect sensory touch thresholds by modulating activity in the primary sensory cortex and posterior insula. Disturbances in multisensory integration and oxytocin reactivity combined with diminished reward-related and anxiolytic responses may induce a bias towards negative appraisal of touch contexts. Furthermore, hippocampus deactivation during social touch may reflect a dissociative state. These changes depend not only on the type and severity of the trauma but also on the features of the touch. We hypothesise that disrupted touch processing may impair social interactions and confer elevated risk for future stress-related disorders.

TBCRC 039: a phase II study of preoperative ruxolitinib with or without paclitaxel for triple-negative inflammatory breast cancer.

BACKGROUND: Patients with inflammatory breast cancer (IBC) have overall poor clinical outcomes, with triple-negative IBC (TN-IBC) being associated with the worst survival, warranting the investigation of novel therapies. Preclinical studies implied that ruxolitinib (RUX), a JAK1/2 inhibitor, may be an effective therapy for TN-IBC. METHODS: We conducted a randomized phase II study with nested window-of-opportunity in TN-IBC. Treatment-naïve patients received a 7-day run-in of RUX alone or RUX plus paclitaxel (PAC). After the run-in, those who received RUX alone proceeded to neoadjuvant therapy with either RUX + PAC or PAC alone for 12 weeks; those who had received RUX + PAC continued treatment for 12 weeks. All patients subsequently received 4 cycles of doxorubicin plus cyclophosphamide prior to surgery. Research tumor biopsies were performed at baseline (pre-run-in) and after run-in therapy. Tumors were evaluated for phosphorylated STAT3 (pSTAT3) by immunostaining, and a subset was also analyzed by RNA-seq. The primary endpoint was the percent of pSTAT3-positive pre-run-in tumors that became pSTAT3-negative. Secondary endpoints included pathologic complete response (pCR). RESULTS: Overall, 23 patients were enrolled, of whom 21 completed preoperative therapy. Two patients achieved pCR (8.7%). pSTAT3 and IL-6/JAK/STAT3 signaling decreased in post-run-in biopsies of RUX-treated samples, while sustained treatment with RUX + PAC upregulated IL-6/JAK/STAT3 signaling compared to RUX alone. Both treatments decreased GZMB+ T cells implying immune suppression. RUX alone effectively inhibited JAK/STAT3 signaling but its combination with PAC led to incomplete inhibition. The immune suppressive effects of RUX alone and in combination may negate its growth inhibitory effects on cancer cells. CONCLUSION: In summary, the use of RUX in TN-IBC was associated with a decrease in pSTAT3 levels despite lack of clinical benefit. Cancer cell-specific-targeting of JAK2/STAT3 or combinations with immunotherapy may be required for further evaluation of JAK2/STAT3 signaling as a cancer therapeutic target. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , NCT02876302. Registered 23 August 2016.

A Systematic Review of Criminal Justice Initiatives to Strengthen the Criminal Investigation and Prosecution of Sexual Violence in East Africa.

Sexual violence (SV) is a widespread public health and human rights problem, with countries in East Africa having higher rates than the global average. Prosecutions of SV in East Africa are rare, and survivors face many challenges accessing medico-legal justice and services. Developing initiatives that support survivors in navigating the criminal justice system is vital, yet there is limited research on efforts to improve the criminal justice system's management and treatment of survivors. We conducted a scoping review of research on initiatives to strengthen responses toward investigating and prosecuting cases. We identified 25 academic articles and reports through a search of electronic databases and gray literature that address these initiatives in East Africa. The results reveal that seven types of initiatives have been studied: one-stop centers (OSCs), multisectoral referral networks, gender desks, community interventions, mobile applications, and specialized police and prosecution units. Upon review, we found that barriers to success include a lack of resources and facilities, a lack of trained health care, police, and judicial personnel to perform services, weak medico-legal partnerships, and stigma and impunity restricting the uptake and fair distribution of services. Overall, limited systematic evidence on the effectiveness and adaptability of initiatives exists, showing that SV interventions in East Africa remain an under-researched and under-resourced area, and need greater scientific rigor to inform practice and coordinated advocacy. This review is a call to action for policy makers and service providers working in East Africa-and for international bodies working toward achieving Sustainable Development Goals 5-to improve criminal justice initiatives.

Heterogeneity and transcriptional drivers of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with limited treatment options. To characterize TNBC heterogeneity, we defined transcriptional, epigenetic, and metabolic subtypes and subtype-driving super-enhancers and transcription factors by combining functional and molecular profiling with computational analyses. Single-cell RNA sequencing revealed relative homogeneity of the major transcriptional subtypes (luminal, basal, and mesenchymal) within samples. We found that mesenchymal TNBCs share features with mesenchymal neuroblastoma and rhabdoid tumors and that the PRRX1 transcription factor is a key driver of these tumors. PRRX1 is sufficient for inducing mesenchymal features in basal but not in luminal TNBC cells via reprogramming super-enhancer landscapes, but it is not required for mesenchymal state maintenance or for cellular viability. Our comprehensive, large-scale, multiplatform, multiomics study of both experimental and clinical TNBC is an important resource for the scientific and clinical research communities and opens venues for future investigation.

Facilitating Harmonization of Variables in Framingham, MESA, ARIC, and REGARDS Studies Through a Metadata Repository.

BACKGROUND: High-quality research in cardiovascular prevention, as in other fields, requires inclusion of a broad range of data sets from different sources. Integrating and harmonizing different data sources are essential to increase generalizability, sample size, and representation of understudied populations-strengthening the evidence for the scientific questions being addressed. METHODS: Here, we describe an effort to build an open-access repository and interactive online portal for researchers to access the metadata and code harmonizing data from 4 well-known cohort studies-the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, FHS (Framingham Heart Study), MESA (Multi-Ethnic Study of Atherosclerosis), and ARIC (Atherosclerosis Risk in Communities) study. We introduce a methodology and a framework used for preprocessing and harmonizing variables from multiple studies. RESULTS: We provide a real-case study and step-by-step guidance to demonstrate the practical utility of our repository and interactive web page. In addition to our successful development of such an open-access repository and interactive web page, this exercise in harmonizing data from multiple cohort studies has revealed several key themes. These themes include the importance of careful preprocessing and harmonization of variables, the value of creating an open-access repository to facilitate collaboration and reproducibility, and the potential for using harmonized data to address important scientific questions and disparities in cardiovascular disease research. CONCLUSIONS: By integrating and harmonizing these large-scale cohort studies, such a repository may improve the statistical power and representation of understudied cohorts, enabling development and validation of risk prediction models, identification and investigation of risk factors, and creating a platform for racial disparities research. REGISTRATION: URL: https://precision.heart.org/duke-ninds.

Enabling witnesses to actively explore faces and reinstate study-test pose during a lineup increases discriminability.

Accurate witness identification is a cornerstone of police inquiries and national security investigations. However, witnesses can make errors. We experimentally tested whether an interactive lineup, a recently introduced procedure that enables witnesses to dynamically view and explore faces from different angles, improves the rate at which witnesses identify guilty over innocent suspects compared to procedures traditionally used by law enforcement. Participants encoded 12 target faces, either from the front or in profile view, and then attempted to identify the targets from 12 lineups, half of which were target present and the other half target absent. Participants were randomly assigned to a lineup condition: simultaneous interactive, simultaneous photo, or sequential video. In the front-encoding and profile-encoding conditions, Receiver Operating Characteristics analysis indicated that discriminability was higher in interactive compared to both photo and video lineups, demonstrating the benefit of actively exploring the lineup members' faces. Signal-detection modeling suggested interactive lineups increase discriminability because they afford the witness the opportunity to view more diagnostic features such that the nondiagnostic features play a proportionally lesser role. These findings suggest that eyewitness errors can be reduced using interactive lineups because they create retrieval conditions that enable witnesses to actively explore faces and more effectively sample features.

The Role of Dorsal Raphe Nucleus Serotonergic Systems in Emotional Learning and Memory in Male BALB/c Mice.

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for a variety of anxiety-, trauma- and stressor-related disorders. Although they are efficacious, therapeutic improvements require several weeks of treatment and are often associated with an initial exacerbation of symptoms. The dorsal raphe nucleus (DR) has been proposed as an important target for the modulation of emotional responses and the therapeutic effects of SSRIs. Using a fear-conditioning paradigm we aimed to understand how SSRIs affect emotional learning and memory, and their effects on serotonergic circuitry. Adult male BALB/c mice were treated with vehicle (n = 16) or the SSRI fluoxetine (18 mg/kg/d) acutely (n = 16), or chronically (21d, n = 16), prior to fear conditioning. Treatment was stopped, and half of the mice (n = 8/treatment group) were exposed to cued fear memory recall 72 h later. Activation of DR serotonergic neurons during fear conditioning (Experiment 1) or fear memory recall (Experiment 2), was measured using dual-label immunohistochemistry for Tph2 and c-Fos. Acute and chronic fluoxetine treatment reduced associative fear learning without affecting memory recall and had opposite effects on anxiety-like behaviour. Acute fluoxetine decreased serotonergic activity in the DR, while chronic treatment led to serotonergic activity that was indistinguishable from that of control levels in DRD and DRV subpopulations. Chronic fluoxetine facilitated fear extinction, which was associated with rostral DRD inhibition. These findings provide further evidence that SSRIs can alter aspects of learning and memory processes and are consistent with a role for discrete populations of DR serotonergic neurons in regulating fear- and anxiety-related behaviours.

Evaluation of in vitro antiviral activity of SARS-CoV-2 Mpro inhibitor pomotrelvir and cross-resistance to nirmatrelvir resistance substitutions.

The unprecedented scale of the COVID-19 pandemic and the rapid evolution of SARS-CoV-2 variants underscore the need for broadly active inhibitors with a high barrier to resistance. The coronavirus main protease (Mpro) is an essential cysteine protease required for viral polyprotein processing and is highly conserved across human coronaviruses. Pomotrelvir is a novel Mpro inhibitor that has recently completed a phase 2 clinical trial. In this report, we demonstrated that pomotrelvir is a potent competitive inhibitor of SARS-CoV-2 Mpro with high selectivity against human proteases. In the enzyme assay, pomotrelvir is also active against Mpro proteins derived from human coronaviruses CoV-229E, CoV-OC43, CoV-HKU1, CoV-NL63, MERS, and SARS-CoV. In cell-based SARS-CoV-2 replicon and SARS-CoV-2 infection assays, pomotrelvir has shown potent inhibitory activity and is broadly active against SARS-CoV-2 clinical isolates including Omicron variants. Many resistance substitutions of the Mpro inhibitor nirmatrelvir confer cross-resistance to pomotrelvir, consistent with the finding from our enzymatic analysis that pomotrelvir and nirmatrelvir compete for the same binding site. In a SARS-CoV-2 infection assay, pomotrelvir is additive when combined with remdesivir or molnupiravir, two nucleoside analogs targeting viral RNA synthesis. In conclusion, our results from the in vitro characterization of pomotrelvir antiviral activity support its further clinical development as an alternative COVID-19 therapeutic option.

Longitudinal Trends in Cardiovascular Risk Factor Profiles and Complications Among Patients Hospitalized for COVID-19 Infection: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry.

BACKGROUND: The COVID-19 pandemic has evolved through multiple phases characterized by new viral variants, vaccine development, and changes in therapies. It is unknown whether rates of cardiovascular disease (CVD) risk factor profiles and complications have changed over time. METHODS: We analyzed the American Heart Association COVID-19 CVD registry, a national multicenter registry of hospitalized adults with active COVID-19 infection. The time period from April 2020 to December 2021 was divided into 3-month epochs, with March 2020 analyzed separately as a potential outlier. Participating centers varied over the study period. Trends in all-cause in-hospital mortality, CVD risk factors, and in-hospital CVD outcomes, including a composite primary outcome of cardiovascular death, cardiogenic shock, new heart failure, stroke, and myocardial infarction, were evaluated across time epochs. Risk-adjusted analyses were performed using generalized linear mixed-effects models. RESULTS: A total of 46 007 patient admissions from 134 hospitals were included (mean patient age 61.8 years, 53% male, 22% Black race). Patients admitted later in the pandemic were younger, more likely obese, and less likely to have existing CVD (Ptrend ≤0.001 for each). The incidence of the primary outcome increased from 7.0% in March 2020 to 9.8% in October to December 2021 (risk-adjusted Ptrend=0.006). This was driven by an increase in the diagnosis of myocardial infarction and stroke (Ptrend<0.0001 for each). The overall rate of in-hospital mortality was 14.2%, which declined over time (20.8% in March 2020 versus 10.8% in the last epoch; adjusted Ptrend<0.0001). When the analysis was restricted to July 2020 to December 2021, no temporal change in all-cause mortality was seen (adjusted Ptrend=0.63). CONCLUSIONS: Despite a shifting risk factor profile toward a younger population with lower rates of established CVD, the incidence of diagnosed cardiovascular complications of COVID increased from the onset of the pandemic through December 2021. All-cause mortality decreased during the initial months of the pandemic and thereafter remained consistently high through December 2021.

Site-level variability in the processes of care and outcomes over time among patients with COVID-19 and myocardial injury: Insights from the American Heart Association's COVID-19 Cardiovascular Disease Registry.

Background: Elevated cardiac troponin (cTn) levels in patients with COVID-19 has been associated with worse outcomes. Guidelines on best practices of those patients remain uncertain. Methods: We included patients with COVID-19 and cTn above the assay-specific upper limit of normal (ULN) enrolled in the American Heart Association's COVID-19 registry between March 2020-January 2021. Site-level variability in invasive coronary angiography, LVEF assessment, ICU utilization, and inpatient mortality were determined by calculating adjusted median odds ratio (MOR) using hierarchical logistic regression models. Temporal trends were assessed with Cochran-Armitage trend test. Results: Among 32,636 patients, we included 6234 (19.4 %) with cTn above ULN (age 68.7 ± 16.0 years, 56.5 % male, 51.5 % Caucasian), of whom 1365 (21.6 %) had ≥5-fold elevations. Across 55 sites, the median rate of invasive coronary angiography was 0.1 % with adjusted MOR 1.5(1.0,2.3), median LVEF assessment was 25.5 %, MOR 3.0(2.2,3.9), ICU utilization was 41.7 %, MOR 2.2(1.8,2.6), and mortality was 20.9 %, MOR 1.7(1.5,2.0). Over time, we noted a significant increase in invasive coronary angiography (p-trend = 0.001), and LVEF assessment (p-trend<0.001), and reduction in mortality (p-trend<0.001), without significant change in ICU admissions (p-trend = 0.08). Similar variability and temporal trends were seen among patients with ≥5-fold cTn elevation. Conclusions: The use of invasive coronary angiography among patients with COVID-19 and myocardial injury was very low during the early pandemic. We found moderate institutional variability in processes of care with an uptrend in invasive catheterization and LVEF assessment, and downtrend in mortality. Comparative effectiveness studies are needed to examine whether variability in care is associated with differences in outcomes.

Lateral Subdermic Venous Plexus Insufficiency: The Association of Varicose Veins with Restless Legs Syndrome and Nocturnal Leg Cramps.

PURPOSE: To determine whether nocturnal symptoms of restless legs syndrome (RLS) and muscle cramps in the legs are associated specifically with lateral subdermic venous plexus (LSVP) insufficiency and whether treatment can provide symptomatic relief. MATERIALS AND METHODS: A retrospective cross-sectional observational study of 506 patients at a single site analyzed whether RLS or nighttime leg cramping symptoms were associated with venous reflux in the LSVP using comprehensive venous ultrasound. The treatment outcomes of ultrasound-guided foam sclerotherapy (USGFS) were followed up for 1 year. RESULTS: Of 209 patients who reported restless legs symptoms, 179 (85%) demonstrated an abnormal LSVP. A total of 214 patients reported nighttime muscle cramping, of whom 197 (92%) demonstrated an abnormal LSVP. Among 124 patients presenting with both the symptoms, 113 (91%) demonstrated an abnormal LSVP. Conversely, of 83 patients who presented with neither RLS nor nocturnal cramping, 2 (2%) had an abnormal LSVP. Among 242 symptomatic patients with an abnormal LSVP who underwent treatment, the technical success rate was 100%. At 90-day follow-up, 224 patients (93%) reported continued relief, which was maintained at 93% (224/242) at follow-up at 1 year. When substratified, 90 patients presented primarily with RLS or cramping and showed only LSVP reflux, and when treated, all 90 (100%) had significant or complete relief of the symptoms. CONCLUSIONS: LSVP insufficiency demonstrates an association with symptoms of RLS and nocturnal leg cramps. LSVP treatment using USGFS demonstrated high technical and clinical success rates, with symptomatic relief up to 1 year, most pronounced when the LSVP was the only treated vein.

JAK-STAT Signaling in Inflammatory Breast Cancer Enables Chemotherapy-Resistant Cell States.

Inflammatory breast cancer (IBC) is a difficult-to-treat disease with poor clinical outcomes due to high risk of metastasis and resistance to treatment. In breast cancer, CD44+CD24- cells possess stem cell-like features and contribute to disease progression, and we previously described a CD44+CD24-pSTAT3+ breast cancer cell subpopulation that is dependent on JAK2/STAT3 signaling. Here we report that CD44+CD24- cells are the most frequent cell type in IBC and are commonly pSTAT3+. Combination of JAK2/STAT3 inhibition with paclitaxel decreased IBC xenograft growth more than either agent alone. IBC cell lines resistant to paclitaxel and doxorubicin were developed and characterized to mimic therapeutic resistance in patients. Multi-omic profiling of parental and resistant cells revealed enrichment of genes associated with lineage identity and inflammation in chemotherapy-resistant derivatives. Integrated pSTAT3 chromatin immunoprecipitation sequencing and RNA sequencing (RNA-seq) analyses showed pSTAT3 regulates genes related to inflammation and epithelial-to-mesenchymal transition (EMT) in resistant cells, as well as PDE4A, a cAMP-specific phosphodiesterase. Metabolomic characterization identified elevated cAMP signaling and CREB as a candidate therapeutic target in IBC. Investigation of cellular dynamics and heterogeneity at the single cell level during chemotherapy and acquired resistance by CyTOF and single cell RNA-seq identified mechanisms of resistance including a shift from luminal to basal/mesenchymal cell states through selection for rare preexisting subpopulations or an acquired change. Finally, combination treatment with paclitaxel and JAK2/STAT3 inhibition prevented the emergence of the mesenchymal chemo-resistant subpopulation. These results provide mechanistic rational for combination of chemotherapy with inhibition of JAK2/STAT3 signaling as a more effective therapeutic strategy in IBC. SIGNIFICANCE: Chemotherapy resistance in inflammatory breast cancer is driven by the JAK2/STAT3 pathway, in part via cAMP/PKA signaling and a cell state switch, which can be overcome using paclitaxel combined with JAK2 inhibitors.

Creative Technology-Based Strategies for Engaging Young People with Serious Mental Health Conditions in Longitudinal Mental Health Services Research.

A better understanding of the transition from child to adult community mental health services is important given the high rates of service drop-out. Conducting longitudinal research is challenging during a major service provider change. Developmentally-typical transition-to-adulthood instability can deter study engagement. This study examines the efficacy of creative technology-based strategies to recruit and engage adolescents and young adults (AYA) with serious mental health diagnoses in a qualitative study during their transition from child to adult services. Participants were recruited from one agency to complete three in-depth qualitative interviews and monthly surveys exploring mental health service experiences over 12-months. Participants received a smartphone and data plan for 6-months at initial interview, $50 at 6-month interview and $55 at 12-month interview. Four research assistants used a shared Google Voice account to text monthly online surveys and to communicate with participants. 19 participants enrolled; 74% remained enrolled across the 12-months. Smartphones and data plans were not effective in recruiting nor sustaining study engagement for most participants. Participants preferred a mix of texting and phone calls to prompt study engagement; 60% of online surveys were completed. Unanticipated participant-researcher communication outside of research scope suggests that the formation of strong relationships and additional support during this transitional time is critical for sustained study engagement. Study findings have practical implications for social work longitudinal research design and effective study implementation. Future social work research is warranted on innovative strategies to boost study and service engagement among AYA with serious co-occurring mental health and developmental instability.

A critical analysis of gender-based violence reporting and evidence building applications (GBVxTech) for capturing memory reports.

Introduction: Gender-based violence (GBV) is under-reported to the authorities owing to the stigma, shame, and fear of reprisal that surrounds these crimes. To address this, there has been an influx of technologies, including mobile phone and online applications that allow victim-survivors (hereafter, victims) to document and report GBV (hereafter referred to as GBVxTech). We critically analysed the extent to which GBVxTech applications align with the scientific knowledge base on gathering accounts of crimes from victims and witnesses. Methods: We identified 41 reporting and evidence building applications from around the world but found many (n = 19) were no longer accessible. A total of 13 applications met the study criteria and were available for download. We evaluated each application on how well its design and features align with established minimum best practice standards for gathering complete and accurate accounts from witnesses and victims, such as the pre-interview instructions (e.g., setting ground rules), questioning approach (e.g., using open-ended questions), and the adequacy of security features (e.g., password protection). Results and Discussion: We found most applications employ open questions, encourage victims to report information in an independent voice, and seek to elicit information pertinent to a criminal investigation. None of the applications use leading questions. However, most applications do not establish ground rules, and many use forced-choice questions, do not time stamp the information gathered, or document when users change their answers. Many applications have limited security features, potentially compromising users' safety. Further, some applications do not provide information about how to use the app, an informed consent procedure, or data usage information. We discuss the findings and offer recommendations for future GBVxTech development.

Cultivating Cooperative Relationships: Identifying Learning Gaps When Teaching Students Systems Thinking Biomimicry.

The methodology of biomimicry design thinking is based on and builds upon the overarching patterns that all life abides by. "Cultivating cooperative relationships" within an ecosystem is one such pattern we as humans can learn from to nurture our own mutualistic and symbiotic relationships. While form and process translations from biology to design have proven accessible by students learning biomimicry, the realm of translating biological functions in a systematic approach has proven to be more difficult. This study examines how higher education students can approach the gap that many companies in transition are struggling with today; that of thinking within the closed loops of their own ecosystem, to do good without damaging the system itself. Design students should be able to assess and advise on product design choices within such systems after graduation. We know when tackling a design challenge, teams have difficulties sifting through the mass of information they encounter, and many obstacles are encountered by students and their professional clients when trying to implement systems thinking into their design process. While biomimicry offers guidelines and methodology, there is insufficient research on complex, systems-level problem solving that systems thinking biomimicry requires. This study looks at factors found in course exercises, through student surveys and interviews that helped (novice) professionals initiate systems thinking methods as part of their strategy. The steps found in this research show characteristics from student responses and matching educational steps which enabled them to develop their own approach to challenges in a systems thinking manner. Experiences from the 2022 cohort of the semester "Design with Nature" within the Industrial Design Engineering program at The Hague University of Applied Sciences in the Netherlands have shown that the mixing and matching of connected biological design strategies to understand integrating functions and relationships within a human system is a promising first step.