Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships.

Synapses are fundamental units of communication in the brain. The prototypical synapse-organizing complex neurexin-neuroligin mediates synapse development and function and is central to a shared genetic risk pathway in autism and schizophrenia. Neurexin's role in synapse development is thought to be mediated purely by its protein domains, but we reveal a requirement for a rare glycan modification. Mice lacking heparan sulfate (HS) on neurexin-1 show reduced survival, as well as structural and functional deficits at central synapses. HS directly binds postsynaptic partners neuroligins and LRRTMs, revealing a dual binding mode involving intrinsic glycan and protein domains for canonical synapse-organizing complexes. Neurexin HS chains also bind novel ligands, potentially expanding the neurexin interactome to hundreds of HS-binding proteins. Because HS structure is heterogeneous, our findings indicate an additional dimension to neurexin diversity, provide a molecular basis for fine-tuning synaptic function, and open therapeutic directions targeting glycan-binding motifs critical for brain development.

Molecular and Cellular Mechanisms of Salt Taste.

Salt taste, the taste of sodium chloride (NaCl), is mechanistically one of the most complex and puzzling among basic tastes. Sodium has essential functions in the body but causes harm in excess. Thus, animals use salt taste to ingest the right amount of salt, which fluctuates by physiological needs: typically, attraction to low salt concentrations and rejection of high salt. This concentration-valence relationship is universally observed in terrestrial animals, and research has revealed complex peripheral codes for NaCl involving multiple taste pathways of opposing valence. Sodium-dependent and -independent pathways mediate attraction and aversion to NaCl, respectively. Gustatory sensors and cells that transduce NaCl have been uncovered, along with downstream signal transduction and neurotransmission mechanisms. However, much remains unknown. This article reviews classical and recent advances in our understanding of the molecular and cellular mechanisms underlying salt taste in mammals and insects and discusses perspectives on human salt taste.

Examining the generalizability of research findings from archival data.

This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.

A new electrochemical method that mimics phosphorylation of the core tau peptide K18 enables kinetic and structural analysis of intermediates and assembly.

Tau protein's reversible assembly and binding of microtubules in brain neurons are regulated by charge-neutralizing phosphorylation, while its hyperphosphorylation drives the irreversible formation of cytotoxic filaments associated with neurodegenerative diseases. However, the structural changes that facilitate these diverse functions are unclear. Here, we analyzed K18, a core peptide of tau, using newly developed spectroelectrochemical instrumentation that enables electroreduction as a surrogate for charge neutralization by phosphorylation, with simultaneous, real-time quantitative analyses of the resulting conformational transitions and assembly. We observed a tipping point between behaviors that paralleled the transition between tau's physiologically required, reversible folding and assembly and the irreversibility of assemblies. The resulting rapidly electroassembled structures represent the first fibrillar tangles of K18 that have been formed in vitro at room temperature without using heparin or other charge-complementary anionic partners. These methods make it possible to (i) trigger and analyze in real time the early stages of conformational transitions and assembly without the need for preformed seeds, heterogenous coacervation, or crowding; (ii) kinetically resolve and potentially isolate never-before-seen early intermediates in these processes; and (iii) develop assays for additional factors and mechanisms that can direct the trajectory of assembly from physiologically benign and reversible to potentially pathological and irreversible structures. We anticipate wide applicability of these methods to other amyloidogenic systems and beyond.

Final outcomes analysis of the cell product SQZ-PBMC-HPV Phase 1 trial in incurable HPV16+ solid tumors shows improved overall survival in patients with increased CD8+ T cell tumor infiltration.

Cancer vaccines strive to induce robust, antigen-targeted, T-cell-mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ-PBMC-HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA-A*02+ patients. The SQZ-PBMC-HPV-101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the relationship between Posttreatment CD8+ T cell infiltration and patient outcomes. SQZ-PBMC-HPV was administered as monotherapy every 3 weeks. Tumor samples were collected pre-dose and post-dose 4 weeks after treatment start. Biomarkers including CD8, MHC-I, E6, E7, GZMB, and Ki67 were evaluated by immunohistochemistry, immunofluorescence, and RNA in situ hybridization, and were correlated with clinical response, survival, and drug product composition. Eighteen patients had paired pre- and post-dose biopsies. Six (33%) had an increase in CD8+ T cell density in tumor parenchyma between screening and C2D8. Patients with increased CD8+ T cell density had improved disease control rate (66.7% vs 16.7%) and median overall survival (606.5 days vs 170.0 days, p = 0.0078). Drug product was significantly enriched for higher T cells and lower monocytes in the increased CD8+ T cell density group. In patients with incurable HPV16+ solid tumors treated with SQZ-PBMC-HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells.

Transmission and Management of Pathogenic Agrobacterium tumefaciens and Rhodococcus fascians in Select Ornamentals.

Pathogenic Agrobacterium tumefaciens and Rhodococcus fascians are phytobacteria that induce crown gall and leafy gall disease, respectively, resulting in undesirable growth abnormalities. When present in nurseries, plants infected by either bacterium are destroyed, resulting in substantial losses for growers, especially those producing plants valued for their ornamental attributes. There are many unanswered questions regarding pathogen transmission on tools used to take cuttings for propagation and whether products used for bacterial disease control are effective. We investigated the ability to transmit pathogenic A. tumefaciens and R. fascians on secateurs and the efficacy of registered control products against both bacteria in vitro and in vivo. Experimental plants used were Rosa × hybrida, Leucanthemum × superbum, and Chrysanthemum × grandiflorum for A. tumefaciens and Petunia × hybrida and Oenothera 'Siskiyou' with R. fascians. In separate experiments, we found secateurs could convey both bacteria in numbers sufficient to initiate disease in a host-dependent manner and that bacteria could be recovered from secateurs after a single cut through an infected stem. In in vivo assays, none of six products tested against A. tumefaciens prevented crown gall disease, although several products appeared promising in in vitro trials. Likewise, four compounds trialed against R. fascians failed to prevent disease. Sanitation and clean planting material remain the primary means of disease management.

Avelumab Plus Axitinib as First-Line Therapy for Advanced Renal Cell Carcinoma: Long-Term Results from the JAVELIN Renal 100 Phase Ib Trial.

BACKGROUND: Progression-free survival was significantly longer in patients who received avelumab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma (aRCC) in a randomized phase III trial. We report long-term safety and efficacy of avelumab plus axitinib as first-line treatment for patients with aRCC from the JAVELIN Renal 100 phase Ib trial (NCT02493751). MATERIALS AND METHODS: In this open-label, multicenter, phase Ib study, patients with untreated aRCC received avelumab 10 mg/kg every 2 weeks plus axitinib 5 mg twice daily or with axitinib for 7 days followed by avelumab plus axitinib. Safety and efficacy were assessed in all patients receiving at least one dose of avelumab or axitinib. RESULTS: Overall, 55 patients were enrolled and treated. Median follow-up was 55.7 months (95% CI, 54.5-58.7). Treatment-related adverse events of any grade or grade ≥3 occurred in 54 (98.2%) and 34 (61.8%) patients, respectively. The confirmed objective response rate was 60.0% (95% CI, 45.9-73.0), including complete response in 10.9% of patients. Median duration of response was 35.9 months (95% CI, 12.7-52.9); the probability of response was 65.8% (95% CI, 46.7-79.4) at 2 years. Median progression-free survival was 8.3 months (95% CI, 5.3-32.0). Median overall survival was not reached (95% CI, 40.8-not estimable); the 5-year overall survival rate was 57.3% (95% CI, 41.2-70.5). CONCLUSION: Five-year follow-up for combination treatment with avelumab plus axitinib in previously untreated patients with aRCC showed long-term clinical activity with no new safety signals, supporting use of this regimen within its approved indication in clinical practice (Clinicaltrials.gov NCT02493751).

Extending the diatom's color palette: non-iridescent, disorder-mediated coloration in marine diatom-inspired nanomembranes.

The intricate, siliceous exoskeleton of many marine diatoms (single-celled phytoplankton) is decorated with an array of sub-micron, quasi-ordered pores that are known to provide protective and multiple life-sustaining functions. However, the optical functionality of any given diatom valve is limited because valve geometry, composition, and ordering are genetically programmed. Nonetheless, the near- and sub-wavelength features of diatom valves provide inspiration for novel photonic surfaces and devices. Herein, we explore the optical design space for optical transmission, reflection, and scattering in diatom-like structures by computationally deconstructing the diatom frustule, assigning and nondimensionalizing Fano-resonant behavior with configurations of increasing refractive index contrast (Δn), and gauging the effects of structural disorder on the resulting optical response. Translational pore disorder, especially in higher-index materials, was found to evolve Fano resonances from near-unity reflection and transmission to modally confined, angle-independent scattering, which is key to non-iridescent coloration in the visible wavelength range. High-index, frustule-like TiO2 nanomembranes were then designed to maximize backscattering intensity and fabricated using colloidal lithography. These synthetic diatom surfaces showed saturated, non-iridescent coloration across the visible spectrum. Overall, this diatom-inspired platform could be useful in designing tailored, functional, and nanostructured surfaces for applications in optics, heterogeneous catalysis, sensing, and optoelectronics.

Phase 1 study to determine the safety and dosing of autologous PBMCs modified to present HPV16 antigens (SQZ-PBMC-HPV) in HLA-A*02+ patients with HPV16+ solid tumors.

We conducted a dose escalation Phase 1 study of autologous PBMCs loaded by microfluidic squeezing (Cell Squeeze® technology) with HPV16 E6 and E7 antigens (SQZ-PBMC-HPV), in HLA-A*02+ patients with advanced/metastatic HPV16+ cancers. Preclinical studies in murine models had shown such cells resulted in stimulation and proliferation of antigen specific CD8+ cells, and demonstrated antitumor activity. Administration of SQZ-PBMC-HPV was every 3 weeks. Enrollment followed a modified 3+3 design with primary objectives to define safety, tolerability, and the recommended Phase 2 dose. Secondary and exploratory objectives were antitumor activity, manufacturing feasibility, and pharmacodynamic evaluation of immune responses. Eighteen patients were enrolled at doses ranging from 0.5 × 106 to 5.0 × 106 live cells/kg. Manufacture proved feasible and required < 24 h within the overall vein-to-vein time of 1 - 2 weeks; at the highest dose, a median of 4 doses were administered. No DLTs were observed. Most related TEAEs were Grade 1 - 2, and one Grade 2 cytokine release syndrome SAE was reported. Tumor biopsies in three patients showed 2 to 8-fold increases in CD8+ tissue infiltrating lymphocytes, including a case that exhibited increased MHC-I+ and PD-L1+ cell densities and reduced numbers of HPV+ cells. Clinical benefit was documented for the latter case. SQZ-PBMC-HPV was well tolerated; 5.0 × 106 live cells/kg with double priming was chosen as the recommended Phase 2 dose. Multiple participants exhibited pharmacodynamic changes consistent with immune responses supporting the proposed mechanism of action for SQZ-PBMC-HPV, including patients previously refractory to checkpoint inhibitors.

Management of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Case Report and Literature Review.

INTRODUCTION: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare and dangerous dermatologic emergency. It can have different presentations, especially in patients with multiple drug causes, and definitive management of SJS/TEN in these presentations remains unclear. Systemic corticosteroids, TNF inhibitors, and cyclosporine A are promising therapies. CASE REPORT: In this case report, we present a 55-year-old man who developed SJS/TEN while on pembrolizumab and lamotrigine. The patient was treated with corticosteroids and a single dose of etanercept. After a one-week follow-up, the patient’s SJS/TEN had no new activity. DISCUSSION: This literature review highlights how SJS/TEN may present differently in patients on immune checkpoint inhibitors. Treatments in these cases may vary from those with classic SJS/TEN.  Specifically, etanercept given days late into the disease course is effective in speeding re-epithelialization and tapering of already given corticosteroids in classic SJS/TEN. J Drugs Dermatol. 2023;22(11):e24-e28     doi:10.36849/JDD.6999e.

Viewing Then Doing?: Problem-Solving Court Coordinators' Perceptions of Medications for Opioid Use Disorders from a Nationally Representative Survey in the United States.

Background. Overdose deaths in the United States (U.S.) surpassed 100,000 in 2021. Problem-solving courts (PSCs), which originally began as drug courts, divert people with nonviolent felonies and underlying social issues (e.g. opioid use disorders (OUDs)) from the carceral system to a community-based treatment court program. PSCs are operated by a collaborative court staff team including a judge that supervises PSC clients, local court coordinators that manage PSC operations, among other staff. Based on staff recommendations, medications for opioid use disorders (MOUDs) can be integrated into court clients' treatment plans. MOUDs are an evidence-based treatment option. However, MOUDs remain widely underutilized within criminal justice settings partially due to negative perceptions of MOUDs held by staff. Objective. PSCs are an understudied justice setting where MOUD usage would be beneficial. This study sought to understand how court coordinators' perceptions and attitudes about MOUDs influenced their uptake and utilization in PSCs. Methods. A nationally representative survey of 849 local and 42 state PSC coordinators in the U.S. was conducted to understand how coordinators' perceptions influenced MOUD utilization. Results. Generally, court coordinators hold positive views of MOUDs, especially naltrexone. While state and local coordinators' views do not differ greatly, their stronger attitudes align with different aspects of and issues in PSCs such as medication diversion (i.e. misuse). Conclusions. This study has implications for PSCs and their staff, treatment providers, and other community supervision staff (e.g. probation/parole officers, court staff) who can promote and encourage the use of MOUDs by clients.

Evaluating the Effect of Parent-Child Interactive Groups in a School-Based Parent Training Program: Parenting Behavior, Parenting Stress and Sense of Competence.

The Exploring Together program is a group-based parent training program that comprises separate parent, child, and teacher components, and a combined parent-child interactive component. A cluster-randomized trial design was used to compare the Exploring Together program with (Exploring Together; ET) and without (Exploring Together-Adapted; ET-Adapted) the parent-child interactive component. One hundred and thirty-six parents and their children (aged 5-10 years) with externalizing and/or internalizing problems participated in the trial, recruited from primary schools. There was a significant reduction in negative parenting behavior across both treatment groups (ET and ET-Adapted) but no significant improvement in positive parenting behaviors. Parenting self-efficacy improved significantly across both treatment groups however there was no significant change in parenting satisfaction or parenting stress. There was no consistent evidence of superiority of one version of the Exploring Together program over the other. Further investigation regarding treatment dosage and mastery of parenting skills associated with the program is warranted.

Pandemic Procedures: Adapting Problem-Solving Court (PSC) Operations and Treatment Protocols During COVID-19.

With an ongoing pandemic claiming hundreds of lives a day, it is unclear how COVID-19 has affected court operations, particularly problem-solving courts (PSCs) which have goals rooted in rehabilitation for participants in their programs. Even with practical recommendations from national organizations directing courts on how to manage COVID-19, whether and how PSCs met the needs of PSC participants during this time is underexplored. This study, drawn from a larger national study using a survey of PSC coordinators, examines the COVID-19 responses of PSCs to remain safely operational for participants. A sub-sample of survey respondents (n = 82 PSC coordinators) detailed how the COVID-19 pandemic led to changes to their court and treatment operations amidst the constraints of the pandemic. The courts' shifts in policy and practice have important impacts for court participants' treatment retention and success in the PSC program, and these shifts need more in-depth research in the future.

Medication-Assisted Treatment in Problem-solving Courts: A National Survey of State and Local Court Coordinators.

Problem-solving courts (PSCs) are a critical part of a societal effort to mitigate the opioid epidemic's devastating consequences. This paper reports on a national survey of PSCs (N = 42 state-wide court coordinators; N = 849 local court coordinators) and examines the structural factors that could explain the likelihood of a local PSC authorizing medication-assisted treatment (MAT) and MAT utilization. Results of the analyses indicate that MAT availability at the county level was a significant predictor of the likelihood of local courts authorizing MAT. The court's location in a Medicaid expansion state was also a significant predictor of local courts allowing buprenorphine and methadone, but not naltrexone. Problem-solving courts are in the early stages of supporting the use of medications, even when funding is available through Medicaid expansion policies. Adoption and use of treatment innovations like MAT are affected by coordinators' perceptions of MAT as well as structural factors such as the availability of the medications in the community and funding resources. The study has important implications for researchers, policymakers, and practitioners.

Adolescent psychiatric inpatients' perceptions of treatment and seclusion.

Objectives: A great deal of attention is being directed at the use of seclusion in adolescent inpatient psychiatric units due to its forceful nature and negative impact on inpatients and staff. This mixed methods study aimed to explore and compare the level of satisfaction with the services received and perspectives on seclusion in secluded and non-secluded adolescent inpatients.Methods: This study included 188 participants, across three adolescent inpatient psychiatric units in Australia; 17% reported having experienced seclusion. A mixed methods approach was employed. Participants completed the Consumer Satisfaction Questionnaire-8 and Perceptions of Treatment and Seclusion Questionnaire shortly before or at discharge. Qualitative data was analysed using thematic analysis.Results: Secluded participants were more likely to report issues with broader care experiences on the Consumer Satisfaction Questionnaire-8. Secluded individuals reported ongoing negative effects from seclusion but were more likely than non-secluded participants to believe seclusion is necessary. Qualitative analyses showed that both secluded and non-secluded individuals considered seclusion to be traumatic, many did not agree with its use.Conclusions: Communication between inpatients and staff regarding seclusion needs to be improved and there needs to be ongoing support in relation to seclusion during and after discharge. Many adolescent inpatients acknowledge the necessity of seclusion whilst advocating for reduced seclusion.

Low Voltage Voltammetry Probes Proton Dissociation Equilibria of Amino Acids and Peptides.

Platinum-catalyzed electrochemical reduction of dissociable protons at low potentials was used to investigate proton dissociation equilibria of freely diffusing and peptide-incorporated charged amino acids. We first demonstrate with five charged essential amino acids and their analogs that the electrochemically induced deprotonation of each amino acid occurs at distinct formal reduction potential. Moreover, the observed direct reduction for all the charged species, excluding arginine, occurs at low potentials suitable for investigation under aqueous conditions (-0.4 to -0.9 V vs Ag/AgCl). The direct proton reduction was resolved via deconvolution of the observed differential pulse voltammogram (DPV) from background hydronium reduction and water electrolysis. A linear correlation was found between the formal reduction potentials and the pKa values of the dissociable protons hosted by various molecular moieties in the amino acids and their analogs and further verified with tripeptides. DPV of poly(l-lysine) decamer (Lys10) distinctively resolved the pKa values of the amino groups in the side chains and N-terminus, at a resolution not possible by conventional acid-base titration. This work demonstrates selective electrochemical titration of dissociable protons in charged amino acids in the free state and as residues in biomolecules, as well as the utility of DPV to indirectly interrogate local electrostatic environments that are essential to the stability and function of biomolecules.

Computational design and optimization of nanostructured AlN deep-UV grating reflectors.

Deep-ultraviolet (DUV) optoelectronics require innovative light collimation and extraction schemes for wall-plug efficiency improvements. In this work, we computationally survey material limitations and opportunities for intense, wavelength-tunable DUV reflection using AlN-based periodic hole and pillar arrays. Refractive-index limitations for underlayer materials supporting reflection were identified, and MgF2 was chosen as a suitable low-index underlayer for further study. Optical resonances giving rise to intense reflection were then analyzed in AlN/MgF2 nanostructures by varying film thickness, duty cycle, and illumination incidence angle, and were categorized by the emergence of Fano modes sustained by guided mode resonances (holes) or Mie-like dipole resonances (pillars). The phase-offset conditions between complementary modes that sustain high reflectance (%R) were related to a thickness-to-pitch ratio (TPR) parameter, which depended on the geometry-specific resonant mechanism involved (e.g., guided mode vs. Mie dipole resonances) and yielded nearly wavelength-invariant behavior. A rational design space was constructed by pointwise TPR optimization for the entire DUV range (200-320 nm). As a proof of concept, this optimized phase space was used to design reflectors for key DUV wavelengths and achieved corresponding maximum %R of 85% at λ = 211 nm to >97% at λ = 320 nm.

A phase 1 study to assess the safety, pharmacokinetics, and anti-tumor activity of the androgen receptor n-terminal domain inhibitor epi-506 in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: EPI-506 is the first of a new class of drugs targeting the N-terminal domain (NTD) of the androgen receptor (AR), potentially overcoming known resistance mechanisms to androgen receptor pathway inhibitors (ARPIs) among men with metastatic castration resistant prostate cancer (mCRPC). METHODS: Patients with mCRPC who had progressed on prior ARPI were enrolled in this phase 1 open-label, adaptive 3 + 3 dose escalation study. The primary outcome was safety and tolerability of oral EPI-506. Secondary objectives included determination of the maximal tolerated dose (MTD), pharmacokinetic profile, and antitumor efficacy. RESULTS: 28 mCRPC patients were enrolled into 7 dose cohorts of EPI-506 ranging from 80-3600 mg given once daily and 1800 mg given twice daily. Six DLTs occurred in 4 patients; Grade 4 elevated amylase; Grade 3 abdominal pain; Grade 3 elevated ALT and Grade 3 elevated AST; Grade 2 nausea and Grade 1 vomiting which resulted in study drug intake of < 75% of the expected dose during the DLT assessment period. The most common drug-related adverse events included diarrhea, nausea and fatigue. Six patients had a PSA decline not meeting PSA response criteria. The study was terminated prior to reaching the MTD due to poor oral bioavailability. CONCLUSIONS: This phase 1 trial established the safety of EPI-506 and provides proof of concept for targeting the AR NTD. Next generation compounds with improved bioavailability and potency are in clinical development.

The association between tryptophan levels and postpartum mood disorders: a systematic review and meta-analysis.

Over 50% of women experience mood disturbance in the postpartum period, with significant implications for maternal and infant health but identifying those at risk is not easily possible. The essential amino acid, tryptophan (TRP) through its neuroactive metabolites, has been implicated in the pathology of mood disorders. Thus, TRP levels tested in the peripartum period have been proposed as a potential biomarker for subsequent development of postpartum mood disturbances, in particular postpartum depression (PPD). A systematic review and meta-analysis following PROSPERO guidelines [CRD42021252462] was conducted on peer-reviewed, English language studies that measured blood levels of TRP during the postpartum period in women who were also evaluated for postpartum "blues" or PPD. Thirteen studies met the inclusion criteria, of which five studies contained sufficient data to conduct a meta-analysis. Low total TRP levels in postpartum days 1 to 5 were significantly associated with PPD (SMD: -5.39, 95%CI [-7.72, -3.05]). No significant association was found between free TRP levels in the postpartum period and PPD (SMD: -3.43, 95%CI [-7.76, 0.89]). Our findings confirm the necessity for more replicable designed studies regarding TRP and its relationship to postpartum depression. If there were greater clarity regarding TRP metabolism during pregnancy, then the next step would be to consider measuring total plasma TRP levels on postpartum days 1 to 5 to identify women at greater risk of developing PPD.

Continuing Care App for Probationers and Parolees with Substance use Disorders.

This pilot proof-of-concept study examined the feasibility and acceptability of a Continuing Care mobile application (app) designed to meet the recovery and personal support needs of individuals under justice supervision who were receiving outpatient substance use disorder (SUD) treatment. The study included adults on probation or parole who were enrolled in an outpatient SUD treatment program (N = 15; 86.7% males). Participants were instructed to utilize the Continuing Care app daily for 4 weeks. At the end of the study, they completed a satisfaction questionnaire. Of the 15 participants enrolled in the study, 12 (80%) completed the Continuing Care app modules and the satisfaction questionnaire, and all of these participants indicated high levels of satisfaction with the app (on a scale of 1-10, Mean = 1.8, SD = 1.2). The Continuing Care app was well-utilized and perceived as valuable by this group of low-income, underserved, and hard-to-reach individuals. Further research is needed to refine app content and evaluate its ability to meaningfully enhance and extend the benefits of SUD treatment.