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Hydrogels are often employed as temporary platforms for cell proliferation and tissue organization in vitro. Researchers have incorporated photodegradable moieties into synthetic polymeric hydrogels as a means of achieving spatiotemporal control over material properties. In this study protein-based photodegradable hydrogels composed of methacrylated gelatin (GelMA) and a crosslinker containing o-nitrobenzyl ester groups have been developed. The hydrogels are able to degrade rapidly and specifically in response to UV light and can be photopatterned to a variety of shapes and dimensions in a one-step process. Micropatterned photodegradable hydrogels are shown to improve cell distribution, alignment and beating regularity of cultured neonatal rat cardiomyocytes. Overall this work introduces a new class of photodegradable hydrogel based on natural and biofunctional polymers as cell culture substrates for improving cellular organization and function.

Hydrogels are often employed as temporary platforms for cell proliferation and tissue organization in vitro. Researchers have incorporated photodegradable moieties into synthetic polymeric hydrogels as a means of achieving spatiotemporal control over material properties. In this study protein-based photodegradable hydrogels composed of methacrylated gelatin (GelMA) and a crosslinker containing o-nitrobenzyl ester groups have been developed. The hydrogels are able to degrade rapidly and specifically in response to UV light and can be photopatterned to a variety of shapes and dimensions in a one-step process. Micropatterned photodegradable hydrogels are shown to improve cell distribution, alignment and beating regularity of cultured neonatal rat cardiomyocytes. Overall this work introduces a new class of photodegradable hydrogel based on natural and biofunctional polymers as cell culture substrates for improving cellular organization and function.

Abstract Background A dramatic decline in mental health of people worldwide in the early COVID-19 pandemic years has not recovered. In rural and remote Australia, access to appropriate and timely mental health services has been identified as a major barrier to people seeking help for mental ill-health. From 2020 to 2021 a care navigation model, Navicare, was co-designed with rural and remote communities in the Greater Whitsunday Region of Central Queensland in Australia. The Exploration, Preparation, Implementation and Sustainment (EPIS) framework was used to design and guide multiple aspects of a multisite study, The Bridging Study, to evaluate the implementation of Navicare in Australia. Methods A community-engaged hybrid effectiveness-implementation study design will focus on the tailored implementation of Navicare at three new sites as well as monitoring implementation at an existing site established since 2021. Study outcomes assessed will include sustained access as the co-primary outcome (measured using access to Navicare mental health referral services) and Proctor’s Implementation Outcomes of feasibility, acceptability, appropriateness, adoption, fidelity, implementation cost, and sustainability. Data collection for the implementation evaluation will include service usage data, community consultations, interviews, and workshops; analysed using mixed methods and guided by EPIS and other implementation frameworks. Pre-post effectiveness and cost-consequence study components are embedded in the implementation and sustainment phases, with comparison to pre-implementation data and value assessed for each EPIS phase using hospital, service, and resource allocation data. A scaling up strategy will be co-developed using a national roundtable forum in the final year of the study. Qualitative exploration of other aspects of the study (e.g., mechanisms of action and stakeholder engagement) will be conducted. Discussion Our study will use tailoring to local sites and a community-engaged approach to drive implementation of a mental health care navigation service in rural and remote Australia, with expected benefits to mental healthcare access. This approach is consistent with policy recommendations nationally and internationally as building blocks for rural health including the World Health Organization Framework for Action on Strengthening Health Systems to Improve Health Outcomes. Trial registration Prospectively registered on April 2, 2024, on the Australian New Zealand Clinical Trials Registry, no. ACTRN12624000382572. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386665&isReview=true .

Abstract Introduction This study aimed to gain insight from patients with refractory Mycobacterium avium complex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS). Methods We conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants’ descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants’ ratings of strategies’ effectiveness. Concept saturation was also assessed. Results Twenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) were interviewed. At the time of the interview, 15 participants (75%) had received ALIS for > 1 month and 13 (65%) were currently receiving ALIS. Participants described 44 unique AE mitigation strategies, which can be categorized into three groups: prepare for treatment; prevent increased emergence of AEs; and persist on treatment by mitigating AEs. Common strategies (reported by ≥ 50% of participants) included use of educational materials from the patient support program, localized management of throat irritation, and symptom management to reduce fatigue. Evidence of concept saturation was observed: no new strategies were identified in the last five interviews, which suggests the sample was robust enough to identify all mitigation strategies likely to be used by the broader patient population. Conclusions This real-world study identified a diverse set of potential AE mitigation strategies intended to help individual patients prepare for ALIS treatment, prevent the increased emergence of certain AEs, and mitigate the impact of AEs on treatment persistence. Developing a comprehensive accounting of the types of mitigation strategies in use among patients in real-world settings can inform future investigation of the effectiveness of such strategies, and support evidence-based recommendations for treatment management.

Abstract We present Dystrophic Epidermolysis Bullosa Cell Therapy (DEBCT), a scalable platform producing autologous organotypic iPS cell-derived induced skin composite (iSC) grafts for definitive treatment. Clinical-grade manufacturing integrates CRISPR-mediated genetic correction with reprogramming into one step, accelerating derivation of COL7A1-edited iPS cells from patients. Differentiation into epidermal, dermal and melanocyte progenitors is followed by CD49f-enrichment, minimizing maturation heterogeneity. Mouse xenografting of iSCs from four patients with different mutations demonstrates disease modifying activity at 1 month. Next-generation sequencing, biodistribution and tumorigenicity assays establish a favorable safety profile at 1-9 months. Single cell transcriptomics reveals that iSCs are composed of the major skin cell lineages and include prominent holoclone stem cell-like signatures of keratinocytes, and the recently described Gibbin-dependent signature of fibroblasts. The latter correlates with enhanced graftability of iSCs. In conclusion, DEBCT overcomes manufacturing and safety roadblocks and establishes a reproducible, safe, and cGMP-compatible therapeutic approach to heal lesions of DEB patients.

Objective To highlight progress in facilitating and supporting pan-Canadian data analysis research that is supported by a central coordinating center. This process will be illustrated with the use of a recently completed project that has been supported using data from Alberta, British Columbia, and Ontario. Approach The project represents a significant endeavor within the central coordinating center, as it necessitates coordination for data access, data importation and analytical support across three provinces. The focus will be on the administrative processes refined to support collaborative research endeavors. While specific project details will remain undisclosed, procedural enhancements within the central coordinating center framework will be highlighted. Key discussion points include standardized protocols for data access, collaborative efforts to streamline data importation, and facilitation of analytical support across jurisdictions. The type of cross-jurisdictional analytic support will as well be highlighted; data variables harmonization and sharing of data algorithms cohorts across the participating provincial data centers in support of the meta-analysis. Results The successful completion of the final data analysis underscores the effectiveness of a unified data access coordination center for researchers seeking multi-regional health data in Canada. By highlighting advancements enabled by the central coordinating center and provincial data centers, this submission aims to inform researchers about the current landscape of pan-Canadian research and foster opportunities for future collaboration. Implications Sharing insights and lessons from this project emphasizes the advancements facilitated by the central coordinating center and provincial data centers, informing researchers about the potential of pan-Canadian research, and encouraging future collaborative endeavors.

Post-stroke gait asymmetry leads to inefficient gait and a higher fall risk, often causing limited home and community ambulation. Two types of treadmills are typically used for training focused on symmetry: split-belt and single belt treadmills, but there is no consensus on which treadmill is superior to improve gait symmetry in individuals with stroke. To comprehensively determine which intervention is superior, we considered multiple spatial and temporal gait parameters (step length, stride time, swing time, and stance time) and their symmetries. Ten individuals with stroke underwent a single session of split-belt treadmill training and single belt treadmill training on separate days. The changes in step length, stride time, swing time, stance time and their respective symmetries were compared to investigate which training improves both spatiotemporal gait parameters and symmetries immediately after the intervention and after 5 min of rest. Both types of treadmill training immediately increased gait velocity (0.08 m/s faster) and shorter step length (4.15 cm longer). However, split-belt treadmill training was more effective at improving step length symmetry (improved by 27.3%) without sacrificing gait velocity or step length. However, this step length symmetry effect diminished after a 5-min rest period. Split-belt treadmill training may have some advantages over single belt treadmill training, when targeting step length symmetry. Future research should focus on comparing the long-term effects of these two types of training and examining the duration of the observed effects to provide clinically applicable information.

Introduction: Elevating Voices, Addressing Depression, Toxic Stress and Equity (EleVATE) is a group prenatal care (GC) model designed to improve pregnancy outcomes and promote health equity for Black birthing people. This article outlines the foundational community-engaged process to develop EleVATE GC and pilot study results. Methods: We used community-based participatory research principles and the Ferguson Commission Report to guide creation of EleVATE GC. The intervention, designed by and for Black birthing people, centers trauma-informed care, antiracism, and integrates behavioral health strategies into group prenatal care to address unmet mental health needs. Using a convenience sample of patients seeking care at one of three safety-net health care sites, we compared preterm birth, small for gestational age, depression scores, and other pregnancy outcomes between patients in individual care (IC), CenteringPregnancy? (CP), and EleVATE GC. Results: Forty-eight patients enrolled in the study (n=11 IC; n=14 CP; n=23 EleVATE GC) and 86% self-identified as Black. Patients participating in group prenatal care (EleVATE GC or CP) were significantly less likely to experience a preterm birth

Abstract Therapeutic angiogenesis represents a promising avenue to revascularize the ischemic heart. Its limited success is partly due to our poor understanding of the cardiac stroma, specifically mural cells, and their response to ischemic injury. Here, we combine single-cell and positional transcriptomics to assess the behavior of mural cells within the healing heart. In response to myocardial infarction, mural cells adopt an altered state closely associated with the infarct and retain a distinct lineage from fibroblasts. This response is concurrent with vascular rarefaction and reduced vascular coverage by mural cells. Positional transcriptomics reveals that the infarcted heart is governed by regional-dependent and temporally regulated programs. While the remote zone acts as an important source of pro-angiogenic signals, the infarct zone is accentuated by chronic activation of anti-angiogenic, pro-fibrotic, and inflammatory cues. Together, our work unveils the spatiotemporal programs underlying cardiac repair and establishes an association between vascular deterioration and mural cell dysfunction.

Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALKtSTIM) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALKtSTIM therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALKtSTIM on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALKtSTIM will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALKtSTIM; Placebo + WALKtSTIM; and tAIH + WALKtSHAM. Participants receive daily tAIH (fifteen 90-sec episodes at 10% O2 with 60-sec intervals at 21% O2) or daily placebo (fifteen 90-sec episodes at 21% O2 with 60-sec intervals at 21% O2) before a 45-min session of WALKtSTIM or WALKtSHAM. Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI. Trial Registration: ClinicalTrials.gov, NCT05563103.

Abstract Background Depression is a common psychiatric disorder and a leading cause of disability worldwide. Conventional monoaminergic antidepressants have limited efficacy and take weeks to exert a therapeutic effect. Single infusions of subanaesthetic doses of ketamine exhibit rapid antidepressant action but effects are transient and relapse is common. One potential strategy for increasing ketamine’s antidepressant efficacy and/or prolonging its therapeutic benefit may be serial infusions. There is limited evidence on the efficacy and safety of repeated ketamine infusions against an active comparator. Methods This protocol describes an ongoing pragmatic, randomised, controlled, parallel-group, patient- and rater-blind, superiority trial. Eligible adult inpatients with a confirmed DSM-5 diagnosis of a major depressive episode (unipolar or bipolar) are randomly allocated in a 1:1 ratio to a course of up to eight infusions of ketamine or midazolam twice-weekly over four weeks. The primary objective is to assess the efficacy of serial adjunctive ketamine infusions versus active comparator midazolam by measuring Montgomery-Åsberg Depression Rating Scale score difference between arms from before the first infusion to 24 h after the final infusion, supplemented by a 95% confidence interval. To facilitate generalisability of results, the trial takes place under “real world” conditions with both groups continuing to receive regular inpatient care including treatment-as-usual pharmacotherapy, nursing care, and psychological and other therapies during the randomised treatment phase and regular outpatient care thereafter. Participants are monitored for relapse during a 24-week follow-up after the end of the randomised phase. Secondary objectives of the trial are to assess: response and remission rates at the end of randomised phase; relapse status during the 24-week follow-up after the end of the randomised phase; the safety and tolerability of repeated ketamine infusions regarding psychotomimetic and other psychiatric side effects, cognitive side effects, as well as withdrawal symptoms, haemodynamic stability, neurological, urological, and other physical side effects; and quality of life and cost-effectiveness. Discussion There is an unmet clinical need for rapidly-acting novel antidepressants. This trial will provide efficacy, safety and health economic data on serial ketamine infusions and thus help inform clinical practice on the potential role of this treatment in the management of depression. Trial registration EudraCT 2019-003109-92. Registered 2 October 2019. ClinicalTrials.gov NCT04939649. Registered 25 June 2021.

The education of a physician is a life-long process that starts in medical school and extends throughout their career. Healthcare is a dynamic field characterized by continuous advancements in medicine, evolving treatment options, changing regulations, care models, and technology. Physicians must keep up-to-date with new practices, procedures, medications, and diseases and fulfill the educational requirements to maintain their medical licensure. Continuing education for physicians serves the essential purpose of nurturing lifelong learning, ensuring that medical practices align with the latest standards, and ultimately enhancing the quality of patient care and outcomes. In a broader context, physician education encompasses all activities designed to enhance skills, professional performance, and relationships that physicians employ to provide services to patients and the public and to improve collaborations within the field. This paper outlines a step-by-step plan for designing high-quality educational conferences for practicing physicians in any field. It aims to assist in developing ongoing education, aligning physician practices with the latest medical care standards, and optimizing their clinical performance to improve patient and community health.

In this study we combined non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) with 40 h of constraint induced movement therapy (CIMT) in infants. All infants completed the full intervention with no adverse events. Therapists were able to maintain high treatment fidelity and reported high ratings for ease of use and child tolerance. Preliminary results show promising gains on motor outcomes: Mean QUEST increase 19.17 (minimal clinically important difference, MCID 4.89); Mean GMFM increase 13.33 (MCID 1%–3%). Infants also exceeded expectations on Goal Attainment Scores (+1). Early data is promising that taVNS paired with intensive motor CIMT is feasible, reliable, and safe in young infants with hemiplegia, and may help harness activity-dependent plasticity to enhance functional movement.

In January 2020, increased mortality was reported in a small broiler breeder flock in County Fermanagh, Northern Ireland. Gross pathological findings included coelomitis, oophoritis, salpingitis, visceral gout, splenomegaly, and renomegaly. Clinical presentation included inappetence, pronounced diarrhoea, and increased egg deformation. These signs, in combination with increased mortality, triggered a notifiable avian disease investigation. High pathogenicity avian influenza virus (HPAIV) was not suspected, as mortality levels and clinical signs were not consistent with HPAIV. Laboratory investigation demonstrated the causative agent to be a low-pathogenicity avian influenza virus (LPAIV), subtype H6N1, resulting in an outbreak that affected 15 premises in Northern Ireland. The H6N1 virus was also associated with infection on 13 premises in the Republic of Ireland and six in Great Britain. The close genetic relationship between the viruses in Ireland and Northern Ireland suggested a direct causal link whereas those in Great Britain were associated with exposure to a common ancestral virus. Overall, this rapidly spreading outbreak required the culling of over 2 million birds across the United Kingdom and the Republic of Ireland to stamp out the incursion. This report demonstrates the importance of investigating LPAIV outbreaks promptly, given their substantial economic impacts.

Abstract Background The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome (PRO) measure scored by body system composites to assess signs/symptoms of coronavirus disease 2019 (COVID-19). In addition to cross-sectional and longitudinal psychometric evaluations, qualitative exit interviews were conducted to support the content validity of the SIC. Methods In a cross-sectional study, adults diagnosed with COVID-19 in the United States completed the web-based SIC and additional PRO measures. A subset was invited to participate in phone-based exit interviews. Longitudinal psychometric properties were assessed in ENSEMBLE2, a multinational, randomized, double-blind, placebo-controlled, phase 3 trial of the Ad26.COV2.S COVID-19 vaccine. Psychometric properties evaluated included structure, scoring, reliability, construct validity, discriminating ability, responsiveness, and meaningful change thresholds of SIC items and composite scores. Results In the cross-sectional study, 152 participants completed the SIC (mean age, 51.0 ± 18.6 years) and 20 completed follow-up interviews. Fatigue (77.6%), feeling unwell (65.8%), and cough (60.5%) were symptoms most frequently reported. SIC inter-item correlations were all positive and mostly moderate (r ≥ 0.3) and statistically significant. SIC items and Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) scores correlated as hypothesized (all r ≥ 0.32). Internal consistency reliabilities of all SIC composite scores were satisfactory (Cronbach’s alpha, 0.69–0.91). SIC composite scores correlated moderately (r = 0.30–0.49) to strongly (r ≥ 0.50) with PROMIS-29 scores and Patient Global Impression of Severity (PGIS) ratings (all P

Abstract Background Recruiting to multi-site trials is challenging, particularly when striving to ensure the randomized sample is demographically representative of the larger disease-suffering population. While previous studies have reported disparities by race and ethnicity in enrollment and randomization, they have not typically investigated whether disparities exist in the recruitment process prior to consent. To identify participants most likely to be eligible for a trial, study sites frequently include a prescreening process, generally conducted by telephone, to conserve resources. Collection and analysis of such prescreening data across sites could provide valuable information to improve understanding of recruitment intervention effectiveness, including whether traditionally underrepresented participants are lost prior to screening. Methods We developed an infrastructure within the National Institute on Aging (NIA) Alzheimer’s Clinical Trials Consortium (ACTC) to centrally collect a subset of prescreening variables. Prior to study-wide implementation in the AHEAD 3–45 study (NCT NCT04468659), an ongoing ACTC trial recruiting older cognitively unimpaired participants, we completed a vanguard phase with seven study sites. Variables collected included age, self-reported sex, self-reported race, self-reported ethnicity, self-reported education, self-reported occupation, zip code, recruitment source, prescreening eligibility status, reason for prescreen ineligibility, and the AHEAD 3–45 participant ID for those who continued to an in-person screening visit after study enrollment. Results Each of the sites was able to submit prescreening data. Vanguard sites provided prescreening data on a total of 1029 participants. The total number of prescreened participants varied widely among sites (range 3–611), with the differences driven mainly by the time to receive site approval for the main study. Key learnings instructed design/informatic/procedural changes prior to study-wide launch. Conclusion Centralized capture of prescreening data in multi-site clinical trials is feasible. Identifying and quantifying the impact of central and site recruitment activities, prior to participants signing consent, has the potential to identify and address selection bias, instruct resource use, contribute to effective trial design, and accelerate trial enrollment timelines.

IntroductionPeople living in rural and remote areas face substantial barriers to accessing timely and appropriate mental health services. In the Bowen Basin region of Queensland, Australia, barriers include: limited local providers, long waiting lists, unreliable telecommunication, and reluctance to trial telehealth. Isaac Navicare is a new, community co-designed care navigation service which addresses these barriers by coupling care navigation with supported telehealth, and referrals to mental health providers and other supports. We aimed to understand the reach and effectiveness of Isaac Navicare in improving access to mental health services and address an evidence gap on strategies for improving telehealth acceptability.MethodsThis mixed-methods implementation science evaluation used the RE-AIM Framework. It involved a client database review, survey and semi-structured interviews with service users during the 12-month pilot from November 2021.Results197 clients (128 adults, 69 minors) were referred to Navicare during the pilot. Half of adult clients were unemployed, meaning referral options were limited to low-cost or bulk-billed services. Participants described Navicare as supportive and effective in helping to access timely and appropriate mental health supports. Most clients who expressed a treatment modality preference selected face-to-face (n = 111, 85.4%), however most referrals were for telehealth (n = 103, 66.0%) due to a lack of suitable alternatives. The rapport and trust developed with the care navigator was critical for increasing willingness to trial telehealth. Barriers to telehealth included privacy issues, technical difficulties, unreliable internet/phone, and perceived difficulties developing therapeutic rapport. The supported telehealth site was under-utilised. The majority (88.3%, n = 182) of referrals to Navicare were from local health or community service providers or schools.DiscussionCoupling supportive, individualised care navigation with tele-mental health provider options resulted in increased uptake and acceptance of telehealth. Many barriers could be addressed through better preparation of clients and improving promotion and uptake of the supported telehealth site.ConclusionAttitudes towards telehealth have changed during the COVID-19 pandemic, however although the need exists, barriers remain to uptake. Telehealth alone is not enough. Coupling telehealth with other supports such as care navigation improves acceptance and uptake.

The education of a physician is a life-long process. Healthcare is a dynamic field characterized by continuous advancements in medicine, evolving treatment options, changing regulations, care models, and technology. Physicians must keep up-to-date with new practices, procedures, medications, and diseases and fulfill the educational requirements to maintain their medical licensure. Continuing education for physicians serves the essential purpose of nurturing lifelong learning, ensuring that medical practices align with the latest standards, and ultimately enhancing the quality of patient care and outcomes. In a broader context, physician education encompasses all activities designed to enhance skills, professional performance, and relationships that physicians employ to provide services to patients and the public and to improve collaborations within the field. This paper outlines a step-by-step plan for designing high-quality education programs for physicians. It aims to assist in ongoing education, aligning their practices with the latest medical care standards, and optimizing their clinical performance to improve patient and community health.

This article explores questions of disability access justice within the academy through the lens of an online digital/multimedia storytelling (DS) research workshop conducted during the COVID-19 pandemic. Our investigation uncovers how the shift from in-person to online DS methodologies created newfound opportunities for participation, particularly for individuals with episodic disabilities (EDs). Through an analysis of three co-author participants’ multimedia/digital stories and their reflective insights, we investigate the interplay between research methodologies and the broader context of disability access within the academy. Participants’ stories of inventive adaptations unfold against a backdrop of experiences in traditional academic settings that privilege normative ways of working and seldom accommodate diverse rhythms and access needs, including of students, faculty and staff. In light of these narratives, we advocate for an ongoing commitment to access-centered practices in research and work beyond crisis situations. The article concludes that academic research enterprises can accommodate a wider spectrum of participants—particularly those with episodic disabilities—and enhance research outcomes by recognizing and anticipating diverse bodyminds within the design of research methodologies and techniques.

Objective: To investigate trends and rates of severe perineal trauma (SPT), also known as obstetric anal sphincter injury (OASI), between midwife-led and obstetrician-led care in the Netherlands, and factors associated with SPT. Methods: This nationwide cohort study included registry data from 2000 to 2019 (n = 2,169,950) of spontaneous vaginal births of term, live, cephalic, single infants, without a (previous) caesarean section or assisted vaginal birth.First, trends of SPT and episiotomy were shown. Second, differences in SPT rates between midwife- and obstetrician-led care were assessed. Third, associations of care factors with SPT were examined. Multivariable logistic regression analyses were used to determine which factors were important in the associations. All outcomes were stratified for parity. Results: Over time, the SPT incidence increased mainly in midwife-led care and episiotomy rates decreased. Compared to midwife-led care, SPT rates were lower in obstetrician-led care among primiparous women (aOR 0.78; 99 % CI 0.74–0.81) and comparable among multiparous women (aOR 1.04; 99 % CI 0.99–1.10). Among women without epidural analgesia, these differences were smaller for primiparous women (aOR 0.88; 99 % CI 0.84–0.92), but the SPT rate was higher in obstetrician-led care among multiparous women (aOR 1.09; 99 % CI 1.03–1.15). Among women without shoulder dystocia, induction, augmentation, and pain medication, SPT rates were comparable among primiparous women, but higher among multiparous women in obstetrician-led care. In midwife-led care, SPT occurred more often among hospital versus home births. In obstetrician-led care, lower SPT incidences were found among births with epidural analgesia and for multiparous women with induction or augmentation. Conclusions: Iinduction, augmentation, and epidural analgesia in obstetrician-led care may be an explanatory factor for the higher incidence of SPT among primiparous women in midwife-led care. More research is needed to explain differences in SPT rates and to understand how SPT can be prevented, while maintaining a high intact perineum rate.

Students enrolled in online courses tend to be less successful as measured by the rate of A’s, B’s, and C’s than students enrolled in face-to-face courses. Yet little work has been done addressing whether these gaps vary depending on students’ broader relationship with the university, including whether they are degree-seeking students and whether they take any face-to-face courses. We use institutional data on Economics enrollments between 2012 and 2018 at a mid-sized land-grant university to deconstruct online/face-to-face success gaps into a student’s term modality (or modalities) and institutional affiliation components. We identify these components by using a fixed effects regression methodology and comparing outcomes across four student groups: affiliated students who are enrolled in exclusively online courses, exclusively face-to-face courses, or in a mix of courses each term, as well as unaffiliated (external) students exclusively taking online courses. Although students in online courses are less successful on average, part of this gap is explained by the student’s institutional affiliation and whether they exclusively take online courses. External students are the least successful in online courses while students who are affiliated with the institution fare much better. We examine potential reasons for these patterns using survey data from several online courses. These findings suggest that institutions should take steps to ensure that institutional support services and activities exist and extend to students in online courses.

A teaching statement offers a written summary of one’s beliefs, approaches, and successes in teaching. In this article, I use the teaching statement that I wrote in library school as an autoethnographic artifact to consider my own development as a teacher, and to reflect on the teaching statement as a genre. How do we declare ourselves as teachers, and how does that identity develop and shift over time? I conclude with considerations of how a teaching statement can serve academic librarians.

ABSTRACTIn higher education, syllabi have traditionally served as written contracts between instructors and their students, providing first-hand information about the course and expectations. Reading the syllabus may provide students with first impressions or mental images of the instructor, thereby initiating a student-instructor relationship even before any interaction has occurred. Instructors can use syllabi to directly communicate values and practices of equity and inclusion, but students can perceive indirect messages through tone and language that may support or contradict stated values. Here, we share empirically derived recommendations for improving the tone of syllabi with inviting language and stylistic features that promote relationship-building with students.

AbstractBackground: The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals. The exposures and key molecular mechanisms driving this progression are unknown. Persistent IA is the primary outcome of ENDIA; defined as a positive antibody for at least one of IAA, GAD, ZnT8 or IA2 on two consecutive occasions and signifies high risk of clinical T1D.Method: A nested case-control (NCC) study design with 54 cases and 161 matched controls aims to investigate associations between persistent IA and longitudinal omics exposures in ENDIA. The NCC study will analyse samples obtained from ENDIA children who have either developed persistent IA or progressed to clinical T1D (cases) and matched control children at risk of developing persistent IA. Control children were matched on sex and age, with all four autoantibodies absent within a defined window of the case’s onset date. Cases seroconverted at a median of 1.37 years (IQR 0.95, 2.56). Longitudinal omics data generated from approximately 16,000 samples of different biospecimen types, will enable evaluation of changes from pregnancy through childhood.Conclusions: This paper describes the ENDIA NCC study, omics platform design considerations and planned univariate and multivariate analyses for its longitudinal data. Methodologies for multivariate omics analysis with longitudinal data are discovery-focused and data driven. There is currently no single multivariate method tailored specifically for the longitudinal omics data that the ENDIA NCC study will generate and therefore omics analysis results will require either cross validation or independent validation.KEY MESSAGESThe ENDIA nested case-control study will utilize longitudinal omics data on approximately 16,000 samples from 190 unique children at risk of type 1 diabetes (T1D), including 54 who have developed islet autoimmunity (IA), followed during pregnancy, at birth and during early childhood, enabling the developmental origins of T1D to be explored.

Prostate cancer is generally considered an immunologically “cold” tumor type that is insensitive to immunotherapy. Targeting surface antigens on tumors through cellular therapy can induce a potent antitumor immune response to “heat up” the tumor microenvironment. However, many antigens expressed on prostate tumor cells are also found on normal tissues, potentially causing on-target, off-tumor toxicities and a suboptimal therapeutic index. Our studies revealed that six-transmembrane epithelial antigen of prostate-2 (STEAP2) was a prevalent prostate cancer antigen that displayed high, homogeneous cell surface expression across all stages of disease with limited distal normal tissue expression, making it ideal for therapeutic targeting. A multifaceted lead generation approach enabled development of an armored STEAP2 chimeric antigen receptor T cell (CAR-T) therapeutic candidate, AZD0754. This CAR-T product was armored with a dominant-negative TGF-β type II receptor, bolstering its activity in the TGF-β–rich immunosuppressive environment of prostate cancer. AZD0754 demonstrated potent and specific cytotoxicity against antigen-expressing cells in vitro despite TGF-β–rich conditions. Further, AZD0754 enforced robust, dose-dependent in vivo efficacy in STEAP2-expressing cancer cell line–derived and patient-derived xenograft mouse models, and exhibited encouraging preclinical safety. Together, these data underscore the therapeutic tractability of STEAP2 in prostate cancer as well as build confidence in the specificity, potency, and tolerability of this potentially first-in-class CAR-T therapy.

Abstract Background Distribution of naloxone and training on its proper use are evidence-based strategies for preventing opioid overdose deaths. In-person naloxone training was conducted in major metropolitan areas and urban centers across Texas as part of a state-wide targeted opioid response program. The training program transitioned to a live, virtual format during the COVID-19 public health emergency declaration. This manuscript describes the impact of this transition through analyses of the characteristics of communities reached using the new virtual training format. Case presentation Training participant addresses were compared to county rates of opioid overdose deaths and broadband internet access, and census block comparison to health services shortages, rural designation, and race/ethnicity community characteristics. Conclusions The virtual training format reached more learners than the in-person events. Training reached nearly half of the counties in Texas, including all with recent opioid overdose deaths. Most participants lived in communities with a shortage of health service providers, and training reached rural areas, those with limited broadband internet availability, and majority Hispanic communities. In the context of restrictions on in-person gathering, the training program successfully shifted to a live, online format. This transition increased participation above rates observed pre-pandemic and reached communities with the need for equipping those most likely to witness an opioid overdose with the proper use of naloxone.

Abstract Artificial Intelligence is revolutionizing many aspects of the pharmaceutical industry. Deep learning models are now routinely applied to guide drug discovery projects leading to faster and improved findings, but there are still many tasks with enormous unrealized potential. One such task is the reaction yield prediction. Every year more than one fifth of all synthesis attempts result in product yields which are either zero or too low. This equates to chemical and human resources being spent on activities which ultimately do not progress the programs, leading to a triple loss when accounting for the cost of opportunity in time wasted. In this work we pre-train a BERT model on more than 16 million reactions from 4 different data sources, and fine tune it to achieve an uncertainty calibrated global yield prediction model. This model is an improvement upon state of the art not just from the increase in pre-train data but also by introducing a new embedding layer which solves a few limitations of SMILES and enables integration of additional information such as equivalents and molecule role into the reaction encoding, the model is called BERT Enriched Embedding (BEE). The model is benchmarked on an open-source dataset against a state-of-the-art synthesis focused BERT showing a near 20-point improvement in r2 score. The model is fine-tuned and tested on an internal company data benchmark, and a prospective study shows that the application of the model can reduce the total number of negative reactions (yield under 5%) ran in Janssen by at least 34%. Lastly, we corroborate the previous results through experimental validation, by directly deploying the model in an on-going drug discovery project and showing that it can also be used successfully as a reagent recommender due to its fast inference speed and reliable confidence estimation, a critical feature for industry application.

OBJECTIVES/GOALS: Thiswork is an evidential study that demonstrates the positive impactof integrating Community Health Workers (CHWs) and SocialDeterminants of Health on an important health outcome, notably in decreasing the 30-day unplanned hospital ED readmissions at Sinai Health Systems. METHODS/STUDY POPULATION: Using datafrom the Sinai Urban Health Institute (SUHI), we compare predictingthe readmissions of patients with and without data pertainingto Social Determinants of Health (SDoH). We thoroughly describe the data cleaning and data pre-processing, done in collaboration with experts in community health. We use a fundamental and ubiquitous classifier in Random Forest for its feature characterization capability in order to translate models results into insights and recommendations for the CHW program. RESULTS/ANTICIPATED RESULTS: We show that when patients are simply engaged byCHWs, regardless of the content of those conversations, we canincrease the predictive accuracy of our classifier by 5%. We usethis result to make recommendations for improving patient careand discuss limitations and future work. Importantly our workpoints directly to the human connection between patients andCHWs as an important feature in the readmission rate. DISCUSSION/SIGNIFICANCE: Our work shows that the predictive capabilities of the classifier increases with CHW logs and SDoH survey data, highlighting the benefit of collecting this information. This is the first step in early identification of such patients so that CHWs are focusing on and providing resources to patients who will most benefit from the program.

Unionid mussels are among the most imperiled group of organisms in North America, and Pustulosa pustulosa is a freshwater species with a relatively wide latitudinal distribution that extends from southern Ontario, Canada, to Texas, USA. Considerable morphological and geographic variation in the genus Pustulosa (formerly Cyclonaias) has led to uncertainty over species boundaries, and recent studies have suggested revisions to species-level classifications by synonymizing C. aurea, C. houstonensis, C. mortoni, and C. refulgens with C. pustulosa (currently P. pustulosa). Owing to its wide range and shallow phylogenetic differentiation, we analyzed individuals of P. pustulosa using mitochondrial DNA sequence data under a population genetics framework. We included 496 individuals, which were comprised of 166 samples collected during this study and 330 additional sequences retrieved from GenBank. Pairwise ΦST measures based on ND1 data suggested there may be up to five major geographic groups present within P. pustulosa. Genetic differentiation between regions within Texas was higher compared to populations from the Mississippi and Great Lakes populations, which may reflect differences in historical connectivity. Mitochondrial sequence data also revealed varying demographic histories for each major group suggesting each geographic region has also experienced differential population dynamics in the past. Future surveys should consider exploring variation within species after phylogeographic delimitation has been performed. In this study, we begin to address this need for freshwater mussels via the P. pustulosa system.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

A growing consensus recognises the impact of the built environment on creating thriving communities, particularly as societies face significant social challenges, including increasing population densification and diversification. This raises important questions about how buildings and neighbourhoods play a role in improving people’s lives; and the inherent social value of good building design. A social values framework is used to explore a unique Australian case study: U City in the City of Adelaide, an extreme mixed-use, high-rise building hosting retirement living, disability accommodation, services for some of the communities’ most vulnerable groups, commercial tenants, café/retail outlets and corporate conference facilities. Three public spaces in U City are examined for their role in fostering positive emotions and a sense of belonging among diverse groups of residents, workers and casual users. Qualitative data are gathered from regular focus groups, surveys, observations and innovative resident audits of building spaces. The focus here is on results showing that public spaces in U City are key to fostering ‘community’—expressed in ways that are dynamic, evolving and inclusive—where the successful generation of community is as much about championing the actors involved as it is about the provision and design of building spaces. Practice relevance What social outcomes can the creation of quality spaces for ‘public good’ provide? What social value can be placed on incorporating non-hierarchical, dynamic and flexible public spaces into high-rise building design, and what impact does it have on the appeal and functionality of the building? This case study reveals that the design and operation of public places can bring diverse groups of users together by providing opportunities for interaction, engagement, expression and community-building. This study supports improved design/project briefings and promotes new market opportunities for innovative, regenerative vertical urban villages that incorporate flexible, engaging public spaces for community to thrive. Providing end-user benefits for a more diverse community than is typically seen in traditional architectural brief formulation, U City showcases the versatility that can be incorporated into building design to create highly functional, multipurpose, socially engaging and highly valued collective spaces.

Summary: Background: COVID-19 vaccines have been critical for protection against severe disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but gaps remain in our understanding of the immune responses that contribute to controlling subclinical and mild infections. Methods: Vaccinated, active-duty US military service members were enrolled in a non-interventional, minimal-risk, observational study starting in May, 2021. Clinical data, serum, and saliva samples were collected from study participants and were used to characterise the humoral immune responses to vaccination and to assess its impact on clinical and subclinical infections, as well as virologic outcomes of breakthrough infections (BTI) including viral load and infection duration. Findings: The majority of VIRAMP participants had received the Pfizer COVID-19 vaccine and by January, 2022, N = 149 had a BTI. The median BTI duration (PCR+ days) was 4 days and the interquartile range was 1–8 days. Participants that were nucleocapsid seropositive prior to their BTI had significantly higher levels of binding and functional antibodies to the spike protein, shorter median duration of infections, and lower median peak viral loads compared to seronegative participants. Furthermore, levels of neutralising antibody, ACE2 blocking activity, and spike-specific IgA measured prior to BTI also correlated with the duration of infection. Interpretation: We extended previous findings and demonstrate that a subset of vaccine-induced humoral immune responses, along with nucleocapsid serostatus are associated with control of SARS-CoV-2 breakthrough infections in the upper airways. Funding: This work was funded by the DoD Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) in collaboration with the Defense Health Agency (DHA) COVID-19 funding initiative for the VIRAMP study.

Abstract Background Inflammation is present in neurological and peripheral disorders. Thus, targeting inflammation has emerged as a viable option for treating these disorders. Previous work indicated pretreatment with beta-funaltrexamine (β-FNA), a selective mu-opioid receptor (MOR) antagonist, inhibited inflammatory signaling in vitro in human astroglial cells, as well as lipopolysaccharide (LPS)-induced neuroinflammation and sickness-like-behavior in mice. This study explores the protective effects of β-FNA when treatment occurs 10 h after LPS administration and is the first-ever investigation of the sex-dependent effects of β-FNA on LPS-induced inflammation in the brain and peripheral tissues, including the intestines. Results Male and female C57BL/6J mice were administered LPS followed by treatment with β-FNA-immediately or 10 h post-LPS. Sickness- and anxiety-like behavior were assessed using an open-field test and an elevated-plus-maze test, followed by the collection of whole brain, hippocampus, prefrontal cortex, cerebellum/brain stem, plasma, spleen, liver, large intestine (colon), proximal small intestine, and distal small intestine. Levels of inflammatory chemokines/cytokines (interferon γ-induced-protein, IP-10 (CXCL10); monocyte-chemotactic-protein 1, MCP-1 (CCL2); interleukin-6, IL-6; interleukin-1β, IL-1β; and tumor necrosis factor-alpha, TNF-α) in tissues were measured using an enzyme-linked immunosorbent assay. Western blot analysis was used to assess nuclear factor-kappa B (NF-κB) expression. There were sex-dependent differences in LPS-induced inflammation across brain regions and peripheral tissues. Overall, LPS-induced CXCL10, CCL2, TNF-α, and NF-κB were most effectively downregulated by β-FNA; and β-FNA effects differed across brain regions, peripheral tissues, timing of the dose, and in some instances, in a sex-dependent manner. β-FNA reduced LPS-induced anxiety-like behavior most effectively in female mice. Conclusion These findings provide novel insights into the sex-dependent anti-inflammatory effects of β-FNA and advance this agent as a potential therapeutic option for reducing both neuroinflammation an intestinal inflammation.

Abstract Background The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome measure to evaluate the presence and severity of COVID-19 signs/symptoms in adults. This study expanded the context of use of the adult SIC among adolescents aged 12–17 years and supported a pediatric adaptation (the Pediatric SIC [PedSIC]) for caregiver assessment of signs/symptoms in children aged

Due to their biocompatibility, ease of surface modification, and heating capabilities, gold nanomaterials are considered excellent candidates for the advancement of photothermal therapy techniques and related applications in cancer treatment. Various morphologies of gold nanomaterials have been shown to heat when exposed to high-powered laser irradiation, especially that which is from the near-infrared (NIR) region. While these lasers work well and are effective, light-emitting diodes (LEDs) may offer a safe and low-powered alternative to these high energy lasers. We investigated the heating capability of NIR-dye conjugated gold nanorods when exposed to an 808 nm LED light source using polyethylene glycol (PEG)-coated gold nanorods as the control. In this way, since the rods exhibited a surface plasmon resonance peak between 795 and 825 nm for both the PEG-coated rods and the dye-conjugated rods, which are fairly close to the frequency of the 530 mW, 850 nm LED light source, we were able to reveal the heating effect of the dye modification. While both morphologies heat when irradiated with the LED light, we demonstrated that the addition of an NIR dye increases the rate of heating and cooling, compared to the PEGylated counterpart. To our knowledge, the complementary effect given by the conjugated NIR-dye has not been previously reported in the literature. The targeting abilities of the NIR-dye combined with the increased heating rate of the modified particles used in this proof-of-concept work suggests that these particles may be exceptional candidates for theranostic applications.

Abstract Dissolved organic phosphorus (DOP) concentration distributions in the global surface ocean inform our understanding of marine biogeochemical processes such as nitrogen fixation and primary production. The spatial distribution of DOP concentrations in the surface ocean reflect production by primary producers and consumption as an organic nutrient by phytoplankton including diazotrophs and other microbes, as well as other loss processes such as photolysis. Compared to dissolved organic carbon and nitrogen, however, relatively few marine DOP concentration measurements have been made, largely due to the lack of automated analysis techniques. Here we present a database of marine DOP concentration measurements (DOPv2021) that includes new (n = 730) and previously published (n = 3140) observations made over the last ~30 years (1990–2021), including 1751 observations in the upper 50 m. This dataset encompasses observations from all major ocean basins including the poorly represented Indian, South Pacific, and Southern Oceans and provides insight into spatial distributions of DOP in the ocean. It is also valuable for researchers who work on marine primary production and nitrogen fixation.

Objective: To analyze the use of services regarding fertility preservation (FP) in cancer patients at a single institution. Design: A retrospective cohort study. Setting: Academic medical center. Patient(s): A total of 208 FP referrals. Intervention(s): None. Main Outcome Measure(s): Method of FP; time from referral to FP intervention. Result(s): A total of 553 patients were referred to a reproductive specialist for FP in the setting of a medical diagnosis from 2011 to 2016. Of these, 208 patients satisfied the inclusion criteria and met with a reproductive specialist. Ninety patients underwent FP services. The average age at referral was 30.9 ± 7.9 years. Breast cancer (n=94, 45%) and leukemia/lymphoma (n=62, 30%) were the most prevalent cancer diagnoses. A 68.9% of patients underwent oocyte cryopreservation (n=62), 26.7% underwent embryo cryopreservation (n=24) and 4.4% underwent ovarian tissue preservation (n=4). The time interval from the referral to the FP intervention ranged from 1 to 810 days, with a median of 17 days. Conclusion(s): In the setting of a cancer diagnosis, most patients undergoing FP intervention underwent oocyte cryopreservation, were

Abstract Background Arizona’s Health Start Program is a statewide community health worker (CHW) maternal and child health home visiting intervention. The objective of this study was to test if participation in Health Start during 2006–2016 improved early childhood vaccination completion rates. Methods This retrospective study used 11 years of administrative, birth certificate, and immunization records. Propensity score matching was used to identify control groups, based on demographic, socioeconomic, and geographic characteristics. Results are reported by historically disadvantaged subgroups and/or with a history of low vaccine uptake, including Hispanic/Latinx and American Indian children, and children of low socioeconomic status and from rural areas, children with teen mothers and first-born children. The average treatment-on-the-treated (ATT) effect estimated the impact of Health Start on timely completion of seven early childhood vaccine series: diphtheria/tetanus toxoids and acellular/whole-cell pertussis (DTaP/DTP), Haemophilus influenzae type b (Hib), hepatitis B (Hep. B), measles-mumps-rubella (MMR), pneumococcal conjugate vaccine (PCV13), poliovirus, and varicella. Results Vaccination completion rates (by age five) were 5.0% points higher for Health Start children as a group, and on average 5.0% points higher for several subgroups of mothers: women from rural border counties (ATT 5.8), Hispanic/Latinx women (ATT 4.8), American Indian women (ATT 4.8), women with less than high school education (ATT 5.0), teen mothers (ATT 6.1), and primipara women (ATT 4.5), compared to matched control groups (p-value ≤ 0.05). Time-to-event analyses show Health Start children complete vaccination sooner, with a hazard rate for full vaccination 13% higher than their matches. Conclusion A state-operated home visiting intervention with CHWs as the primary interventionist can effectively promote early childhood vaccine completion, which may reduce the incidence of preventable diseases and subsequently improve children’s health. Effects of CHW interventions on vaccination uptake is particularly relevant given the rise in vaccine-preventable diseases in the US and globally. Trial registration Approved by the University of Arizona Research Institutional Review Board (Protocol 1701128802), 25 January 2017.

Introduction: Patients with advanced-stage non-small cell lung cancer (NSCLC) may benefit from a short time-to-treatment (TTT). Predictive biomarker testing is performed prior to treatment, as recommended by various international expert consensus bodies. Genetic testing is more time-intensive than immunohistochemistry (IHC) and commonly contributes to prolonged TTT. For epidermal growth factor receptor-positive patients (EGFR+), further genetic testing may not be required due to the mutual exclusivity of actionable mutations. Methods: The trial cohort (N = 238) received both BC Cancer NGS panel (Oncopanel) and Idylla EGFR testing. Data were also collected for a control cohort (N = 220) that received Oncopanel testing. For each patient, the time that the lab received the sample, the time taken to report the NGS and Idylla tests, the time of first treatment, and the final treatment regimen were recorded. Results: A concordance frequency of 98.7% (232/235) was observed between the Idylla and NGS panel. The lab turnaround time (TAT) was faster for the Idylla test by an average of 12.4 days (N = 235, p < 0.01). Overall, the average TTT in the trial cohort (N = 114) was 10.1 days faster (p < 0.05) than the control (N = 114), leading to a 25% reduction in TTT. For patients treated based on EGFR positivity, the mean TTT was 16.8 days faster (p < 0.05) in the trial cohort (N = 33) than the control cohort (N = 28), leading to a 48% reduction in TTT. Conclusion: Using the Idylla EGFR test as part of the molecular testing repertoire in advanced-stage NSCLC patients could significantly reduce TTT.

BackgroundDespite experiencing many adversities, American Indian and Alaska Native populations have demonstrated tremendous resilience during the COVID-19 pandemic, drawing upon Indigenous determinants of health (IDOH) and Indigenous Nation Building. ObjectiveOur multidisciplinary team undertook this study to achieve two aims: (1) to determine the role of IDOH in tribal government policy and action that supports Indigenous mental health and well-being and, in turn, resilience during the COVID-19 crisis and (2) to document the impact of IDOH on Indigenous mental health, well-being, and resilience of 4 community groups, specifically first responders, educators, traditional knowledge holders and practitioners, and members of the substance use recovery community, working in or near 3 Native nations in Arizona. MethodsTo guide this study, we developed a conceptual framework based on IDOH, Indigenous Nation Building, and concepts of Indigenous mental well-being and resilience. The research process was guided by the Collective benefit, Authority to control, Responsibility, Ethics (CARE) principles for Indigenous Data Governance to honor tribal and data sovereignty. Data were collected through a multimethods research design, including interviews, talking circles, asset mapping, and coding of executive orders. Special attention was placed on the assets and culturally, socially, and geographically distinct features of each Native nation and the communities within them. Our study was unique in that our research team consisted predominantly of Indigenous scholars and community researchers representing at least 8 tribal communities and nations in the United States. The members of the team, regardless of whether they identified themselves as Indigenous or non-Indigenous, have many collective years of experience working with Indigenous Peoples, which ensures that the approach is culturally respectful and appropriate. ResultsThe number of participants enrolled in this study was 105 adults, with 92 individuals interviewed and 13 individuals engaged in 4 talking circles. Because of time constraints, the team elected to host talking circles with only 1 nation, with participants ranging from 2 to 6 in each group. Currently, we are in the process of conducting a qualitative analysis of the transcribed narratives from interviews, talking circles, and executive orders. These processes and outcomes will be described in future studies. ConclusionsThis community-engaged study lays the groundwork for future studies addressing Indigenous mental health, well-being, and resilience. Findings from this study will be shared through presentations and publications with larger Indigenous and non-Indigenous audiences, including local recovery groups, treatment centers, and individuals in recovery; K-12 and higher education educators and administrators; directors of first responder agencies; traditional medicine practitioners; and elected community leaders. The findings will also be used to produce well-being and resilience education materials, in-service training sessions, and future recommendations for stakeholder organizations. International Registered Report Identifier (IRRID)DERR1-10.2196/44727