mRNA-encoded Cas13 treatment of Influenza via site-specific degradation of genomic RNA.

The CRISPR-Cas13 system has been proposed as an alternative treatment of viral infections. However, for this approach to be adopted as an antiviral, it must be optimized until levels of efficacy rival or exceed the performance of conventional approaches. To take steps toward this goal, we evaluated the influenza viral RNA degradation patterns resulting from the binding and enzymatic activity of mRNA-encoded LbuCas13a and two crRNAs from a prior study, targeting PB2 genomic and messenger RNA. We found that the genome targeting guide has the potential for significantly higher potency than originally detected, because degradation of the genomic RNA is not uniform across the PB2 segment, but it is augmented in proximity to the Cas13 binding site. The PB2 genome targeting guide exhibited high levels (>1 log) of RNA degradation when delivered 24 hours post-infection in vitro and maintained that level of degradation over time, with increasing multiplicity of infection (MOI), and across modern influenza H1N1 and H3N2 strains. Chemical modifications to guides with potent LbuCas13a function, resulted in nebulizer delivered efficacy (>1-2 log reduction in viral titer) in a hamster model of influenza (Influenza A/H1N1/California/04/09) infection given prophylactically or as a treatment (post-infection). Maximum efficacy was achieved with two doses, when administered both pre- and post-infection. This work provides evidence that mRNA-encoded Cas13a can effectively mitigate Influenza A infections opening the door to the development of a programmable approach to treating multiple respiratory infections.

Discovery of GS-7682, a Novel 4'-Cyano-Modified C-Nucleoside Prodrug with Broad Activity against Pneumo- and Picornaviruses and Efficacy in RSV-Infected African Green Monkeys.

Acute respiratory viral infections, such as pneumovirus and respiratory picornavirus infections, exacerbate disease in COPD and asthma patients. A research program targeting respiratory syncytial virus (RSV) led to the discovery of GS-7682 (1), a novel phosphoramidate prodrug of a 4'-CN-4-aza-7,9-dideazaadenosine C-nucleoside GS-646089 (2) with broad antiviral activity against RSV (EC50 = 3-46 nM), human metapneumovirus (EC50 = 210 nM), human rhinovirus (EC50 = 54-61 nM), and enterovirus (EC50 = 83-90 nM). Prodrug optimization for cellular potency and lung cell metabolism identified 5'-methyl [(S)-hydroxy(phenoxy)phosphoryl]-l-alaninate in combination with 2',3'-diisobutyrate promoieties as being optimal for high levels of intracellular triphosphate formation in vitro and in vivo. 1 demonstrated significant reductions of viral loads in the lower respiratory tract of RSV-infected African green monkeys when administered once daily via intratracheal nebulized aerosol. Together, these findings support additional evaluation of 1 and its analogues as potential therapeutics for pneumo- and picornaviruses.

High-Intensity Interval vs. Moderate-Intensity Continuous Training in Parkinson's Disease: A Randomized Trial.

Exercise training is recommended to improve quality of life in those living with Parkinson's Disease (PD); however, the optimal prescription to improve cardiorespiratory fitness and disease-related motor symptoms remains unknown. Twenty-nine participants with PD were randomly allocated to either 10-weeks of high-intensity interval training (HIIT) (n=15; 6 female) or moderate-intensity continuous training (MICT) (n=14; 5 female). The primary outcome was the change in maximal oxygen consumption (VO2peak). Secondary outcomes included changes in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor score, Parkinson's Disease Fatigue Scale (PFS-16), resting and exercise cardiovascular measures, gait, balance, and knee extensor strength and fatigability. Exercise training increased VO2peak (main effect of time, P<0.01), with a clinically-meaningful difference in the change following HIIT vs. MICT (∆3.7±3.7 vs. 1.7±3.2 ml∙kg-1∙min-1, P=0.099). The UPDRS motor score improved over time (P<0.001) but without any differences between HIIT vs. MICT (∆-9.7±1.3 vs. -8.4±1.4, P=0.51). Self-reported subjective fatigue (PFS-16) decreased over time (P<0.01) but was similar between HIIT and MICT groups (P=0.6). Gait, balance, blood pressure, and heart rate were unchanged with training (all P>0.09). Knee extensor strength increased over time (P=0.03) but did not differ between HIIT vs. MICT (∆8.2±5.9 vs. 11.7±6.2 Nm, P=0.69). HIIT alone increased muscular endurance of the knee extensors during an isotonic task to failure (P=0.04). In participants with PD, HIIT and MICT both increased VO2peak and led to improvements in motor symptoms and perceived fatigue; HIIT may offer the potential for larger changes in VO2peak and reduced knee extensor fatigability.

Self-reported hearing loss in urban Aboriginal and Torres Strait Islander adults: unmeasured, unknown and unmanaged.

Background Effective management of hearing loss in adults is fundamental for communication, relationships, employment, and learning. This study examined the rates and management of self-reported hearing loss in urban Aboriginal and Torres Strait Islander adults. Methods A retrospective, observational study of Aboriginal and Torres Strait Islander people aged ≥15years who had annual health checks at an urban Aboriginal and Torres Strait Islander primary healthcare clinic in Inala, Queensland, was conducted to determine self-reported hearing loss rates by age and ethnic groups stratified by sex. A medical record audit of patients who self-reported hearing loss from January to June 2021 was performed to identify current management approaches, and the proportion of patients that were appropriately managed. Results Of the 1735 patients (average age 40.7years, range 15.0-88.5years, 900 [52.0%] women) who completed 3090 health checks between July 2018 and September 2021, 18.8% self-reported hearing loss. Rates did not differ between men and women. However, significant effects were noted for age, with rates increasing from 10.7% for patients aged 15-24years to 38.7% for those aged ≥65years. An audit of 73 patient medical records revealed that 39.7% of patients with self-reported hearing loss were referred to Ear, Nose and Throat/audiology or received other management. A total of 17.8% of patients owned hearing aids. Conclusions Only 40% of Aboriginal and Torres Strait Islander adults who self-reported hearing loss were referred for management. Significant changes to clinical management and government-funded referral options for hearing services are required to improve the management of self-reported hearing loss in this population.

Unveiling the Deadly Dance of Hypocalcemia and Lactic Acidosis in a 59-Year-Old Woman with B-Cell Lymphoma.

Calcium plays a crucial role in the heart's electrical conduction system and facilitating the contraction of cardiac muscles. Hypocalcemia can result in electrocardiogram findings such as a prolonged QTC interval and eventually torsade de pointes, which in severe cases can progress to cardiac arrest. In cases of B-cell lymphoma, hypocalcemia may arise from various factors. Tumor infiltration can disrupt calcium homeostasis by affecting the parathyroid glands or bone tissue. Acidosis in the context of B-cell lymphoma can cause significant cardiovascular adverse effects. It will reduce peripheral vascular resistance and cardiac muscle contractility, promote dysrhythmias, and disturb oxygen uptake in the lungs. These combined effects markedly compromise cardiac function, increasing the likelihood of cardiac arrest. These mechanisms necessitate comprehensive management strategies in B-cell lymphoma patients. In this case report we present a case of cardiac arrest in a 59-year-old female woman with hypocalcemia and lactic acidosis secondary to B-cell lymphoma. LEARNING POINTS: Lactic acidosis in B-cell lymphoma can be multifactorial. Contributing factors include inability of liver lactate clearance, tumor cell metabolism or impaired oxygenation.Patients with B-cell lymphoma may have hypocalcemia secondary to tumor lysis syndrome, paraneoplastic syndrome, or secondary to treatment.These reversible causes should always be considered in cardiac arrest in cancer patients.

Incidence and survival of pediatric and adult hepatocellular carcinoma, United States, 2001-2020.

BACKGROUND: Hepatocellular carcinoma accounts for approximately 80 % of liver neoplasms. Globally, hepatocellular carcinoma ranks as the third most lethal cancer, with the number of deaths expected to further increase by 2040. In adults, disparities in incidence and survival are well described while pediatric epidemiology is not well characterized. We describe incidence and survival for pediatric (ages 0-19 years) hepatocellular carcinoma cases and compare these measures to adults (ages ≥ 20 years) diagnosed with hepatocellular carcinoma. METHODS: We assessed incidence data from the US Cancer Statistics database during 2003-2020 and 5-year survival from the National Program of Cancer Registries during 2001-2019. Incidence trends were determined by annual percent change (APC) and average APC (AAPC) using joinpoint regression. Five-year survival was evaluated by relative survival, and all-cause survival was estimated using multivariate Cox modeling. Corresponding 95 % confidence intervals (CI) were calculated for all analyses. RESULTS: Incidence rate per 100,000 persons was 0.056 (95 %CI:0.052-0.060) for pediatric cases and 7.793 (7.767-7.819) for adults. Incidence was stable in the pediatric population (0.3 AAPC, - 1.1 to 1.7). In contrast, after periods of increase, incidence declined in adults after 2015 (-1.5 APC). Relative survival increased over time for both pediatric and adult ages and was higher for children and adolescents (46.4 %, 95 %CI:42.4-50.3) than adults (20.7 %, 95 %CI:20.5-20.9). Regression modeling showed that non-Hispanic Black race and ethnicity was associated with higher risk of death in children and adolescents (1.48, 95 %CI:1.07-2.05) and adults (1.11, 95 %CI:1.09-1.12) compared to non-Hispanic white race and ethnicity. CONCLUSIONS: Between 2003 and 2020 in the United States, pediatric incidence was stable while incidence in adults began to decline after 2015. Survival was higher across all stages for children and adolescents compared to adults. Non-Hispanic Black race and ethnicity showed a higher risk of death for both age groups. Further studies could explore the factors that influence these outcome disparities.

Age of First Exposure to Contact Sports Is Not Associated With Worse Later-In-Life Brain Health in a Cohort of Community-Dwelling Older Men.

OBJECTIVE: To evaluate whether early age of first exposure to contact sports (AFE-CS) is associated with worse long-term brain health outcomes. DESIGN: A cross-sectional, survey study of older men with a history of contact sport participation was completed. SETTING: Tertiary care facility. PARTICIPANTS: A cohort of community-dwelling older men dichotomized by using AFE-CS (<12 years vs ≥12 years). INTERVENTIONS: Independent variables included a dichotomized group of AFE-CS (<12 years vs ≥12 years). MAIN OUTCOME MEASURES: Brain health outcomes measured by depression, anxiety, cognitive difficulties, and neurobehavioral symptoms. Endorsements of general health problems, motor symptoms, and psychiatric history were also collected. Age of first exposure groups was compared using t tests, χ2 tests, and multivariable linear regressions, which included the following covariates: age, number of prior concussions, and total years of contact sport. RESULTS: Of 69 men aged 70.5 ± 8.0 years, approximately one-third of the sample (34.8%) reported AFE-CS before age 12 years. That group had more years of contact sports (10.8 ± 9.2 years) compared with those with AFE-CS ≥12 (5.6 ± 4.5 years; P = 0.02). No differences were found after univariate testing between AFE-CS groups on all outcomes (P-values >0.05). Multivariable models suggest that AFE-CS is not a predictor of depression or anxiety. Those in the AFE-CS <12 group had fewer cognitive difficulties (P = 0.03) and fewer neurobehavioral symptoms (P = 0.03). CONCLUSIONS: Those with AFE-CS <12 to contact sports did not have worse long-term brain health outcomes compared with those with AFE-CS ≥12. Individuals with AFE-CS <12 had significantly lower British Columbia Cognitive Complaints Inventory and Neurobehavioral Symptom Inventory scores compared with those with AFE-CS ≥12. CLINICAL RELEVANCE: The benefits of earlier AFE-CS may outweigh the risks of head strikes and result in comparable long-term brain health outcomes.

Custom silicone Y-stents for the management of anastomotic stenosis in lung transplant recipients.

BACKGROUND: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.

Staff and client preferences for the design and delivery of an outcomes monitoring system in a mental health service.

BACKGROUND: Outcome monitoring can support the delivery of quality service that meets the needs of clients, clinicians and services. However, few studies have examined client or staff perspectives on the design and implementation of outcomes monitoring within a service. Implementation of outcomes monitoring requires understanding the preferences and expectations of relevant stakeholders. OBJECTIVE: Informed by the Consolidated Framework for Implementation Research, this study aimed to investigate the preferences and priorities of relevant staff, clients and family members to inform the design and implementation of an effective outcomes monitoring system in the context of a mental health service for military veterans and their families. METHOD: Twenty-nine staff participated across five online focus groups, including clinical staff, peer workers, policy staff and supervisors. Ten clients participated in online or telephone semi-structured interviews. Thematic analysis was used to develop themes from the data. RESULTS: Clients and staff agreed that outcomes monitoring should cover more than symptoms, particularly by incorporating functional outcomes. Assessing mental health over time was considered a valuable tool for supporting treatment processes and providing actionable information. Challenges identified by clients and staff included the need for efficient processes, ensuring measures are relevant and acceptable, and maintaining client privacy. The ability to personalise data collection and have a streamlined, responsive system were key attributes of a quality outcomes monitoring framework. CONCLUSIONS: Findings suggest that an effective outcome monitoring framework should be client-led, tailored to the individual's needs, and provide feedback on progress. Outcomes monitoring should also be efficient, accessible and allow for safe information sharing.

Triphasic Oxygen Storage in Wet Nanoparticulate Polymer of Intrinsic Microporosity (PIM-1) on Platinum: An Electrochemical Investigation.

The triphasic interaction of gases with electrode surfaces immersed in aqueous electrolyte is crucial in electrochemical technologies (fuel cells, batteries, sensors). Some microporous materials modify this interaction locally via triphasic storage capacity for gases in aqueous environments linked to changes in apparent oxygen concentration and diffusivity (as well as activity and reactivity). Here, a nanoparticulate polymer of intrinsic microporosity (PIM-1) in aqueous electrolyte is shown to store oxygen gas and thereby enhance electrochemical signals for oxygen reduction in aqueous media. Oxygen reduction current transient data at platinum disk electrodes suggest that the reactivity of ambient oxygen in aqueous electrolyte (typically Doxygen = 2.8 × 10-9 m2 s-1; coxygen = 0.3 mM) is substantially modified (to approximately Dapp,oxygen = 1.6 (±0.3) × 10-12 m2 s-1; capp,oxygen = 50 (±5) mM) with important implications for triphasic electrode processes. The considerable apparent concentration of oxygen even for ambient oxygen levels is important. Potential applications in oxygen sensing, oxygen storage, oxygen catalysis, or applications associated with other types of gases are discussed.

Patient-Led Research to Develop a Training Programme for Restoring Musical Joy in Cochlear Implant Recipients: A Reflexive Process Evaluation.

BACKGROUND: The role of patients in healthcare research is slowly evolving, although patient roles in the research process are limited. This paper reports on a patient-led research project aiming to develop a musical hearing training programme for patients with a cochlear implant (CI): the Musi-CI programme. A CI is an inner ear prosthesis that allows people with severe hearing loss to hear. However, while speech can be understood, CI users cannot fully enjoy music or feel aversion to it. The Musi-CI programme aims to reduce this music aversion to ultimately improve music enjoyment and social participation. The development of the Musi-CI programme was supported by a consortium of professionals in CI rehabilitation and research. The aim of this paper is to describe and evaluate the Musi-CI programme development process and its impact on professional CI rehabilitation and research. METHODS: Programme development was described using a 3-layered process model of action research, distinguishing the CI user process, the healthcare professional process and the research process. To evaluate perceptions on the programme development process, consortium partners provided written comments and participated in a reflexive evaluation session that was video-recorded. Reflexive evaluation aims for collective learning and strengthening collaboration among participants. Written comments and video data were analysed using template analysis. RESULTS: The involvement of an expert by experience was perceived as challenging but rewarding for all consortium partners, opening up new perspectives on CI-rehabilitation practice and research. Data analysis revealed two themes on the programme development process, professional space and acknowledgement, and two themes on the outcomes on CI rehabilitation and research: critical reflection and paradigm shift. CONCLUSION: Experts by experience represent a different knowledge domain that may contribute to change in rehabilitation and research. PATIENT OR PUBLIC CONTRIBUTION: The development of the programme was initiated by a professional musician and CI user who organized the funding, had a leading role throughout the research process, including the write-up of the results, and co-authored this paper.

An optical photothermal infrared investigation of lymph nodal metastases of oral squamous cell carcinoma.

In this study, optical photothermal infrared (O-PTIR) spectroscopy combined with machine learning algorithms were used to evaluate 46 tissue cores of surgically resected cervical lymph nodes, some of which harboured oral squamous cell carcinoma nodal metastasis. The ratios obtained between O-PTIR chemical images at 1252 cm-1 and 1285 cm-1 were able to reveal morphological details from tissue samples that are comparable to the information achieved by a pathologist's interpretation of optical microscopy of haematoxylin and eosin (H&E) stained samples. Additionally, when used as input data for a hybrid convolutional neural network (CNN) and random forest (RF) analyses, these yielded sensitivities, specificities and precision of 98.6 ± 0.3%, 92 ± 4% and 94 ± 5%, respectively, and an area under receiver operator characteristic (AUC) of 94 ± 2%. Our findings show the potential of O-PTIR technology as a tool to study cancer on tissue samples.

Does using artificial intelligence assistance accelerate skill decay and hinder skill development without performers' awareness?

Artificial intelligence in the workplace is becoming increasingly common. These tools are sometimes used to aid users in performing their task, for example, when an artificial intelligence tool assists a radiologist in their search for abnormalities in radiographic images. The use of artificial intelligence brings a wealth of benefits, such as increasing the efficiency and efficacy of performance. However, little research has been conducted to determine how the use of artificial intelligence assistants might affect the user's cognitive skills. In this theoretical perspective, we discuss how artificial intelligence assistants might accelerate skill decay among experts and hinder skill acquisition among learners. Further, we discuss how AI assistants might also prevent experts and learners from recognizing these deleterious effects. We then discuss the types of questions: use-inspired basic cognitive researchers, applied researchers, and computer science researchers should seek to answer. We conclude that multidisciplinary research from use-inspired basic cognitive research, domain-specific applied research, and technical research (e.g., human factors research, computer science research) is needed to (a) understand these potential consequences, (b) design artificial intelligence systems to mitigate these impacts, and (c) develop training and use protocols to prevent negative impacts on users' cognitive skills. Only by answering these questions from multidisciplinary perspectives can we harness the benefits of artificial intelligence in the workplace while preventing negative impacts on users' cognitive skills.

Daily Light Onset and Plasma Membrane Tethers Regulate Mitochondria Redistribution within the Retinal Pigment Epithelium.

The retinal pigment epithelium (RPE) is an essential component of the retina that plays multiple roles required to support visual function. These include light onset- and circadian rhythm-dependent tasks, such as daily phagocytosis of photoreceptor outer segments. Mitochondria provide energy to the highly specialized and energy-dependent RPE. In this study, we examined the positioning of mitochondria and how this is influenced by the onset of light. We identified a population of mitochondria that are tethered to the basal plasma membrane pre- and post-light onset. Following light onset, mitochondria redistributed apically and interacted with melanosomes and phagosomes. In a choroideremia mouse model that has regions of the RPE with disrupted or lost infolding of the plasma membrane, the positionings of only the non-tethered mitochondria were affected. This provides evidence that the tethering of mitochondria to the plasma membrane plays an important role that is maintained under these disease conditions. Our work shows that there are subpopulations of RPE mitochondria based on their positioning after light onset. It is likely they play distinct roles in the RPE that are needed to fulfil the changing cellular demands throughout the day.

Exploring the conceptualisation, measurement, clinical utility and treatment of formal thought disorder in psychosis: A Delphi study.

BACKGROUND: Formal Thought Disorder (FTD) is a recognised psychiatric symptom, yet its characterisation remains debated. This is problematic because it contributes to poor efficiency and heterogeneity in psychiatric research, with salient clinical impact. OBJECTIVE: This study aimed to investigate expert opinion on the concept, measurement and clinical utility of FTD using the Delphi technique. METHOD: Across three rounds, experts were queried on their definitions of FTD, methods for the assessment and measurement of FTD, associated clinical outcomes and treatment options. RESULTS: Responses were obtained from 56 experts, demonstrating varying levels of consensus across different aspects of FTD. While consensus (>80 %) was reached for some aspects on the concept of FTD, including its definition and associated symptomology and mechanisms, others remained less clear. Overall, the universal importance attributed to the clinical understanding, measurement and treatment of FTD was clear, although consensus was infrequent as to the reasons behind and methods for doing so. CONCLUSIONS: Our results contribute to the still elusive formal definition of FTD. The multitude of interpretations regarding these topics highlights the need for further clarity with this phenomenon. Our findings emphasised that the measurement and clinical utility of FTD are closely tied to the concept; hence, until there is agreement on the concept of FTD, difficulties with measuring and understanding its clinical usefulness to inform treatment interventions will persist. Future FTD research should focus on clarifying the factor structure and dimensionality to determine the latent structure and elucidate the core clinical phenotype.

Mechanisms of inclusion of thallium-201 into Prussian blue nanoparticles for nuclear medicine applications.

Prussian blue is known for its high affinity for thallium and other univalent metal cations and has been used as a treatment for radiocaesium and thallium/radiothallium poisoning. While Prussian blue nanoparticles (PBNPs) show potential for binding radioactive thallium for further use in nuclear medicine applications, the inclusion mechanism remains elusive. Understanding the interaction between PBNPs and 201Tl is essential for identifying the physicochemical and radiochemical properties required for optimal in vivo performance. In this work, we evaluated the binding mechanism between Tl and PBNPs with different coatings and core shapes. Combining PBNPs with [201Tl] thallium(I) chloride provided high radiolabelling yields and radiochemical stabilities under physiological conditions. Comprehensive characterisation by different X-ray techniques confirmed that Tl ions are located in the interstitial sites within the crystal structure, maintaining the integrity of the iron (Fe) 4p electronic distribution and inducing local modifications in the nearby C-N ligands. Additionally, this inclusion does not impact the core or the shell of the nanoparticles but does alter their ionic composition. The PB ionic network undergoes significant changes, with a substantial drop in K+ content, confirming that Tl+ ions replace K+ and occupy additional spaces within the crystal structure. These results open new opportunities in nuclear medicine applications with 201Tl-PBNPs where the size, shape and composition of the particles can be specifically tuned depending on the desired biological properties without affecting the radiochemical performance as a vehicle for 201Tl.

Biological and genetic determinants of glycolysis: Phosphofructokinase isoforms boost energy status of stored red blood cells and transfusion outcomes.

Mature red blood cells (RBCs) lack mitochondria and thus exclusively rely on glycolysis to generate adenosine triphosphate (ATP) during aging in vivo or storage in blood banks. Here, we leveraged 13,029 volunteers from the Recipient Epidemiology and Donor Evaluation Study to identify associations between end-of-storage levels of glycolytic metabolites and donor age, sex, and ancestry-specific genetic polymorphisms in regions encoding phosphofructokinase 1, platelet (detected in mature RBCs); hexokinase 1 (HK1); and ADP-ribosyl cyclase 1 and 2 (CD38/BST1). Gene-metabolite associations were validated in fresh and stored RBCs from 525 Diversity Outbred mice and via multi-omics characterization of 1,929 samples from 643 human RBC units during storage. ATP and hypoxanthine (HYPX) levels-and the genetic traits linked to them-were associated with hemolysis in vitro and in vivo, both in healthy autologous transfusion recipients and in 5,816 critically ill patients receiving heterologous transfusions, suggesting their potential as markers to improve transfusion outcomes.

Finding Our Lanes: A Roadmap for Collaboration Between Academic Medical Centers and Behavioral Telehealth Companies.

ABSTRACT: Outpatient mental health care in the United States is delivered by an uncoordinated patchwork of public and private entities that struggle to effectively differentiate the care they provide. The COVID-19 pandemic catalyzed transformative changes in this space, including rapid adoption of telehealth and escalating private sector investment to provide services for individuals wishing to obtain care through insurance. In this article, we briefly review the current landscape of ambulatory mental health care. Utilizing Kissick's Iron Triangle model of health care delivery, we compare the relative strengths and weaknesses of academic medical centers and the growing private sector, entities potentially positioned to synergistically foster a mental health ecosystem with improved quality, access, and cost-effectiveness. A roadmap for strategic integration is presented for how academic centers-institutions frequently overwhelmed by patient volume-might leverage partnerships with a private sector eager to utilize novel technology to improve access, demonstrate data-driven outcomes, and advocate for improved reimbursement from payers. We also assess the potential risks and pitfalls of such collaboration. In return, academic institutions can refocus on their strengths, including research, systems knowledge, quality-improvement initiatives, education and training, and specialty clinical care.