Complete genome sequence of a Marinococcus sp. PL1-022 isolated from the pink hypersaline Pearse Lakes, Rottnest Island, Western Australia.

Marinococcus sp. PL1-022 was isolated from Pearse Lakes, Western Australia. The sequenced genome consists of a chromosome (3,140,198 bp; 48.2% GC) and two plasmids (58,083 bp and 19,399 bp; 41.4 and 50.7% GC-content, respectively). Isolation of Marinococcus sp. PL1-022 adds to the increasing repertoire of culturable extremophiles.

Complete genome sequence of Idiomarina sp. PL1-037 isolated from the pink hypersaline Pearse Lakes, Rottnest Island, Western Australia.

Idiomarina sp. PL1-037 was isolated from Pearse Lakes, Rottnest Island, Western Australia. The sequenced completed genome for PL1-037 is composed of a single chromosome (2,804,934 bp) with a GC content of 47.1%. Isolation of Idiomarina sp. PL1-037 provides insights about culturable extremophiles from the Pearse lakes microbiome.

Advances in Legume Systematics 14. Classification of Caesalpinioideae. Part 2: Higher-level classification.

Caesalpinioideae is the second largest subfamily of legumes (Leguminosae) with ca. 4680 species and 163 genera. It is an ecologically and economically important group formed of mostly woody perennials that range from large canopy emergent trees to functionally herbaceous geoxyles, lianas and shrubs, and which has a global distribution, occurring on every continent except Antarctica. Following the recent re-circumscription of 15 Caesalpinioideae genera as presented in Advances in Legume Systematics 14, Part 1, and using as a basis a phylogenomic analysis of 997 nuclear gene sequences for 420 species and all but five of the genera currently recognised in the subfamily, we present a new higher-level classification for the subfamily. The new classification of Caesalpinioideae comprises eleven tribes, all of which are either new, reinstated or re-circumscribed at this rank: Caesalpinieae Rchb. (27 genera / ca. 223 species), Campsiandreae LPWG (2 / 5-22), Cassieae Bronn (7 / 695), Ceratonieae Rchb. (4 / 6), Dimorphandreae Benth. (4 / 35), Erythrophleeae LPWG (2 /13), Gleditsieae Nakai (3 / 20), Mimoseae Bronn (100 / ca. 3510), Pterogyneae LPWG (1 / 1), Schizolobieae Nakai (8 / 42-43), Sclerolobieae Benth. & Hook. f. (5 / ca. 113). Although many of these lineages have been recognised and named in the past, either as tribes or informal generic groups, their circumscriptions have varied widely and changed over the past decades, such that all the tribes described here differ in generic membership from those previously recognised. Importantly, the approximately 3500 species and 100 genera of the former subfamily Mimosoideae are now placed in the reinstated, but newly circumscribed, tribe Mimoseae. Because of the large size and ecological importance of the tribe, we also provide a clade-based classification system for Mimoseae that includes 17 named lower-level clades. Fourteen of the 100 Mimoseae genera remain unplaced in these lower-level clades: eight are resolved in two grades and six are phylogenetically isolated monogeneric lineages. In addition to the new classification, we provide a key to genera, morphological descriptions and notes for all 163 genera, all tribes, and all named clades. The diversity of growth forms, foliage, flowers and fruits are illustrated for all genera, and for each genus we also provide a distribution map, based on quality-controlled herbarium specimen localities. A glossary for specialised terms used in legume morphology is provided. This new phylogenetically based classification of Caesalpinioideae provides a solid system for communication and a framework for downstream analyses of biogeography, trait evolution and diversification, as well as for taxonomic revision of still understudied genera.

Nature's Plastic Predators: A Comprehensive and Bibliometric Review of Plastivore Insects.

Unprecedented plastic production has resulted in over six billion tons of harmful waste. Certain insect taxa emerge as potential agents of plastic biodegradation. Through a comprehensive manual and bibliometric literature analysis, this review analyses and consolidates the growing literature related to insect-mediated plastic breakdown. Over 23 insect species, representing Coleoptera, Lepidoptera, and 4 other orders, have been identified for their capacity to consume plastic polymers. Natural and synthetic polymers exhibit high-level similarities in molecular structure and properties. Thus, in conjunction with comparative genomics studies, we link plastic-degrading enzymatic capabilities observed in certain insects to the exaptation of endogenous enzymes originally evolved for digesting lignin, cellulose, beeswax, keratin and chitin from their native dietary substrates. Further clarification is necessary to distinguish mineralisation from physicochemical fragmentation and to differentiate microbiome-mediated degradation from direct enzymatic reactions by insects. A bibliometric analysis of the exponentially growing body of literature showed that leading research is emerging from China and the USA. Analogies between natural and synthetic polymer's degradation pathways will inform engineering robust enzymes for practical plastic bioremediation applications. By aggregating, analysing, and interpreting published insights, this review consolidates our mechanistic understanding of insects as a potential natural solution to the escalating plastic waste crisis.

NUAK: never underestimate a kinase.

NUAK1 and NUAK2 belong to a family of kinases related to the catalytic α-subunits of the AMP-activated protein kinase (AMPK) complexes. Despite canonical activation by the tumour suppressor kinase LKB1, both NUAKs exhibit a spectrum of activities that favour tumour development and progression. Here, we review similarities in structure and function of the NUAKs, their regulation at gene, transcript and protein level, and discuss their phosphorylation of specific downstream targets in the context of the signal transduction pathways and biological activities regulated by each or both NUAKs.

Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC-Alarmin Axis.

Despite advances in understanding the genetic abnormalities in myeloproliferative neoplasms (MPN) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly for patients with triple-negative (TN) myelofibrosis (MF) who lack mutations in the JAK2 kinase pathway and have very poor clinical outcomes. Here we report that MYC copy number gain and increased MYC expression frequently occur in TN-MF and that MYC-directed activation of S100A9, an alarmin protein that plays pivotal roles in inflammation and innate immunity, is necessary and sufficient to drive development and progression of MF. Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves numerous hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation of S100A9 or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC-alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs. Significance: This study establishes that MYC expression is increased in TN-MPNs via trisomy 8, that a MYC-S100A9 circuit manifest in these cases is sufficient to provoke myelofibrosis and inflammation in diverse hematopoietic cell types in the BM niche, and that the MYC-S100A9 circuit is targetable in TN-MPNs.

Development and Implementation of a Digital Quality Measure of Emergency Cancer Diagnosis.

PURPOSE: Missed and delayed cancer diagnoses are common, harmful, and often preventable. Automated measures of quality of cancer diagnosis are lacking but could identify gaps and guide interventions. We developed and implemented a digital quality measure (dQM) of cancer emergency presentation (EP) using electronic health record databases of two health systems and characterized the measure's association with missed opportunities for diagnosis (MODs) and mortality. METHODS: On the basis of literature and expert input, we defined EP as a new cancer diagnosis within 30 days after emergency department or inpatient visit. We identified EPs for lung cancer and colorectal cancer (CRC) in the Department of Veterans Affairs (VA) and Geisinger from 2016 to 2020. We validated measure accuracy and identified preceding MODs through standardized chart review of 100 records per cancer per health system. Using VA's longitudinal encounter and mortality data, we applied logistic regression to assess EP's association with 1-year mortality, adjusting for cancer stage and demographics. RESULTS: Among 38,565 and 2,914 patients with lung cancer and 14,674 and 1,649 patients with CRCs at VA and Geisinger, respectively, our dQM identified EPs in 20.9% and 9.4% of lung cancers, and 22.4% and 7.5% of CRCs. Chart reviews revealed high positive predictive values for EPs across sites and cancer types (72%-90%), and a substantial percent represented MODs (48.8%-84.9%). EP was associated with significantly higher odds of 1-year mortality for lung cancer and CRC (adjusted odds ratio, 1.78 and 1.83, respectively, 95% CI, 1.63 to 1.86 and 1.61 to 2.07). CONCLUSION: A dQM for cancer EP was strongly associated with both mortality and MODs. The findings suggest a promising automated approach to measuring quality of cancer diagnosis in US health systems.

A cohort study of sodium-glucose cotransporter-2 inhibitors after acute kidney injury among Veterans with diabetic kidney disease.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk for several adverse outcomes among patients with diabetic kidney disease. Yet, optimal timing for SGLT2i after acute kidney injury (AKI) is uncertain, as are the providers responsible for post-AKI SGLT2i initiation. Using a retrospective cohort of United States Veterans with diabetes mellitus type 2 and proteinuria, we examined encounters by provider specialty before SGLT2i initiation and subsequent all-cause mortality after hospitalization with AKI, defined by a 50% or more rise in serum creatinine. Covariates included recovery, defined by return to a 110% or less of baseline creatinine, and time since AKI hospitalization. Among 21,330 eligible Veterans, 7,798 died (37%) and 6,562 received a SGLT2i (31%) over median follow-up of 2.1 years. Post-AKI SGLT2i use was associated with lower mortality risk [adjusted hazard ratio 0.63 (95% confidence interval 0.58-0.68)]. Compared with neither SGLT2i use nor recovery, mortality risk was similar with recovery without SGLT2i use [0.97 (0.91-1.02)] but was lower without recovery prior to SGLT2i use [0.62 (0.55-0.71)] and with SGLT2i use after recovery [0.60 (0.54-0.67)]. Finally, the effect of SGLT2i was stable over time (P for time-interaction 0.19). Thus, we observed reduced mortality with SGLT2i use after AKI among Veterans with diabetic kidney disease whether started earlier or later or before or after observed recovery. Hence, patients with diabetic kidney disease who receive a SGLT2i earlier after AKI experience no significant harm impacting mortality and experience a lower mortality risk than those who do not.

An electronic trigger to detect telemedicine-related diagnostic errors.

INTRODUCTION: The COVID-19 pandemic advanced the use of telehealth-facilitated care. However, little is known about how to measure safety of clinical diagnosis made through telehealth-facilitated primary care. METHODS: We used the seven-step Safer Dx Trigger Tool framework to develop an electronic trigger (e-trigger) tool to identify potential missed opportunities for more timely diagnosis during primary care telehealth visits at a large Department of Veterans Affairs facility. We then applied the e-trigger algorithm to electronic health record data related to primary care visits during a 1-year period (1 April 2020-31 March 2021). The algorithm identified patients with unexpected visits within 10 days of an index telemedicine visit and classified such records as e-trigger positive. We then validated the e-trigger's ability to detect missed opportunities in diagnosis using chart reviews based on a structured data collection instrument (the Revised Safer Dx instrument). RESULTS: We identified 128,761 telehealth visits (32,459 unique patients), of which 434 visits led to subsequent unplanned emergency department (ED), hospital, or primary care visits within 10 days of the index visit. Of these, 116 were excluded for clinical reasons (trauma, injury, or childbirth), leaving 318 visits (240 unique patients) needing further evaluation. From these, 100 records were randomly selected for review, of which four were falsely flagged due to invalid data (visits by non-providers or those incorrectly flagged as completed telehealth visits). Eleven patients had a missed opportunity in diagnosis, yielding a positive predictive value of 11%. DISCUSSION: Electronic triggers that identify missed opportunities for additional evaluation could help advance the understanding of safety of clinical diagnosis made in telehealth-enabled care. Better measurement can help determine which patients can safely be cared for via telemedicine versus traditional in-person visits.

Kinase signalling adaptation supports dysfunctional mitochondria in disease.

Mitochondria form a critical control nexus which are essential for maintaining correct tissue homeostasis. An increasing number of studies have identified dysregulation of mitochondria as a driver in cancer. However, which pathways support and promote this adapted mitochondrial function? A key hallmark of cancer is perturbation of kinase signalling pathways. These pathways include mitogen activated protein kinases (MAPK), lipid secondary messenger networks, cyclic-AMP-activated (cAMP)/AMP-activated kinases (AMPK), and Ca2+/calmodulin-dependent protein kinase (CaMK) networks. These signalling pathways have multiple substrates which support initiation and persistence of cancer. Many of these are involved in the regulation of mitochondrial morphology, mitochondrial apoptosis, mitochondrial calcium homeostasis, mitochondrial associated membranes (MAMs), and retrograde ROS signalling. This review will aim to both explore how kinase signalling integrates with these critical mitochondrial pathways and highlight how these systems can be usurped to support the development of disease. In addition, we will identify areas which require further investigation to fully understand the complexities of these regulatory interactions. Overall, this review will emphasize how studying the interaction between kinase signalling and mitochondria improves our understanding of mitochondrial homeostasis and can yield novel therapeutic targets to treat disease.

Medical Home Implementation and Follow-Up of Cancer-Related Abnormal Test Results in the Veterans Health Administration.

Importance: Lack of timely follow-up of cancer-related abnormal test results can lead to delayed or missed diagnoses, adverse cancer outcomes, and substantial cost burden for patients. Care delivery models, such as the Veterans Affairs' (VA) Patient-Aligned Care Team (PACT), which aim to improve patient-centered care coordination, could potentially also improve timely follow-up of abnormal test results. PACT was implemented nationally in the VA between 2010 and 2012. Objective: To evaluate the long-term association between PACT implementation and timely follow-up of abnormal test results related to the diagnosis of 5 different cancers. Design, Setting, and Participants: This multiyear retrospective cohort study used 14 years of VA data (2006-2019), which were analyzed using panel data-based random-effects linear regressions. The setting included all VA clinics and facilities. The participants were adult patients who underwent diagnostic testing related to 5 different cancers and had abnormal test results. Data extraction and statistical analyses were performed from September 2021 to December 2023. Exposure: Calendar years denoting preperiods and postperiods of PACT implementation, and the PACT Implementation Progress Index Score denoting the extent of implementation in each VA clinic and facility. Main Outcome and Measure: Percentage of potentially missed timely follow-ups of abnormal test results. Results: This study analyzed 6 data sets representing 5 different types of cancers. During the initial years of PACT implementation (2010 to 2013), percentage of potentially missed timely follow-ups decreased between 3 to 7 percentage points for urinalysis suggestive of bladder cancer, 12 to 14 percentage points for mammograms suggestive of breast cancer, 19 to 22 percentage points for fecal tests suggestive of colorectal cancer, and 6 to 13 percentage points for iron deficiency anemia laboratory tests suggestive of colorectal cancer, with no statistically significant changes for α-fetoprotien tests and lung cancer imaging. However, these beneficial reductions were not sustained over time. Better PACT implementation scores were associated with a decrease in potentially missed timely follow-up percentages for urinalysis (0.3-percentage point reduction [95% CI, -0.6 to -0.1] with 1-point increase in the score), and laboratory tests suggestive of iron deficiency anemia (0.5-percentage point reduction [95% CI,-0.8 to -0.2] with 1-point increase in the score). Conclusions and Relevance: This cohort study found that implementation of PACT in the VA was associated with a potential short-term improvement in the quality of follow-up for certain test results. Additional multifaceted sustained interventions to reduce missed test results are required to prevent care delays.

Germline knockout of Nr2e3 protects photoreceptors in three distinct mouse models of retinal degeneration.

Retinitis pigmentosa (RP) is a common form of retinal dystrophy that can be caused by mutations in any one of dozens of rod photoreceptor genes. The genetic heterogeneity of RP represents a significant challenge for the development of effective therapies. Here, we present evidence for a potential gene-independent therapeutic strategy based on targeting Nr2e3, a transcription factor required for the normal differentiation of rod photoreceptors. Nr2e3 knockout results in hybrid rod photoreceptors that express the full complement of rod genes, but also a subset of cone genes. We show that germline deletion of Nr2e3 potently protects rods in three mechanistically diverse mouse models of retinal degeneration caused by bright-light exposure (light damage), structural deficiency (rhodopsin-deficient Rho-/- mice), or abnormal phototransduction (phosphodiesterase-deficient rd10 mice). Nr2e3 knockout confers strong neuroprotective effects on rods without adverse effects on their gene expression, structure, or function. Furthermore, in all three degeneration models, prolongation of rod survival by Nr2e3 knockout leads to lasting preservation of cone morphology and function. These findings raise the possibility that upregulation of one or more cone genes in Nr2e3-deficient rods may be responsible for the neuroprotective effects we observe.

Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response.

Mitochondrial outer membrane permeabilisation (MOMP) is often essential for apoptosis, by enabling cytochrome c release that leads to caspase activation and rapid cell death. Recently, MOMP has been shown to be inherently pro-inflammatory with emerging cellular roles, including its ability to elicit anti-tumour immunity. Nonetheless, how MOMP triggers inflammation and how the cell regulates this remains poorly defined. We find that upon MOMP, many proteins localised either to inner or outer mitochondrial membranes are ubiquitylated in a promiscuous manner. This extensive ubiquitylation serves to recruit the essential adaptor molecule NEMO, leading to the activation of pro-inflammatory NF-κB signalling. We show that disruption of mitochondrial outer membrane integrity through different means leads to the engagement of a similar pro-inflammatory signalling platform. Therefore, mitochondrial integrity directly controls inflammation, such that permeabilised mitochondria initiate NF-κB signalling.

Pharmacist-driven outreach initiative to increase prescribing of sodium-glucose cotransporter-2 inhibitors in eligible VHA patients with chronic kidney disease: a study protocol.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for multiple adverse events, several of which have been proven to be less likely with the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i). As a result, guidelines now recommend SGLT2i be given to those with mild to moderate CKD and type 2 diabetes. The objective of this study is to evaluate if a pharmacist-driven SGLT2i prescribing initiative among eligible patients with CKD and diabetes within the VA could more rapidly improve the adoption of SGLT2i via a pragmatic approach aligned with learning health systems. METHODS: Eligible patients will be identified through an established VA diabetes dashboard. Veterans with an odd social security number (SSN), which is effectively a random number, will be the intervention group. Those with even SSNs will serve as the control while awaiting a second iteration of the same interventional program. The intervention will be implemented in a rolling fashion across one Veterans Integrated Service Network. Our primary outcome is initiation of an SGLT2i. Secondary outcomes will include medication adherence and safety-related outcomes. DISCUSSION: This project tests the impact of a pharmacist-driven medication outreach initiative as a strategy to accelerate initiation of SGLT2i. The results of this work will not only illustrate the effectiveness of this strategy for SGLT2is but may also have implications for increasing other guideline-concordant care. Furthermore, the utilization of SSNs to select Veterans for the first wave of this program has created a pseudo-randomized interventional trial supporting a pragmatic learning health system approach. TRIAL REGISTRATION: ISRCTN12374636.

Aldose Reductase (AR) Mediates and Perivascular Adipose Tissue (PVAT) Modulates Endothelial Dysfunction of Short-Term High-Fat Diet Feeding in Mice.

Increased adiposity of both visceral and perivascular adipose tissue (PVAT) depots is associated with an increased risk of diabetes and cardiovascular disease (CVD). Under healthy conditions, PVAT modulates vascular tone via the release of PVAT-derived relaxing factors, including adiponectin and leptin. However, when PVAT expands with high-fat diet (HFD) feeding, it appears to contribute to the development of endothelial dysfunction (ED). Yet, the mechanisms by which PVAT alters vascular health are unclear. Aldose reductase (AR) catalyzes glucose reduction in the first step of the polyol pathway and has been long implicated in diabetic complications including neuropathy, retinopathy, nephropathy, and vascular diseases. To better understand the roles of both PVAT and AR in HFD-induced ED, we studied structural and functional changes in aortic PVAT induced by short-term HFD (60% kcal fat) feeding in wild type (WT) and aldose reductase-null (AR-null) mice. Although 4 weeks of HFD feeding significantly increased body fat and PVAT mass in both WT and AR-null mice, HFD feeding induced ED in the aortas of WT mice but not of AR-null mice. Moreover, HFD feeding augmented endothelial-dependent relaxation in aortas with intact PVAT only in WT and not in AR-null mice. These data indicate that AR mediates ED associated with short-term HFD feeding and that ED appears to provoke 'compensatory changes' in PVAT induced by HFD. As these data support that the ED of HFD feeding is AR-dependent, vascular-localized AR remains a potential target of temporally selective intervention.

Pharmacogenomic Considerations for Anticoagulant Prescription in Patients with Hereditary Haemorrhagic Telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia that commonly results in bleeding but with frequent indications for therapeutic anticoagulation. Our aims were to advance the understanding of drug-specific intolerance and evaluate if there was an indication for pharmacogenomic testing. Genes encoding proteins involved in the absorption, distribution, metabolism, and excretion of warfarin, heparin, and direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran were identified and examined. Linkage disequilibrium with HHT genes was excluded, before variants within these genes were examined following whole genome sequencing of general and HHT populations. The 44 genes identified included 5/17 actionable pharmacogenes with guidelines. The 76,156 participants in the Genome Aggregation Database v3.1.2 had 28,446 variants, including 9668 missense substitutions and 1076 predicted loss-of-function (frameshift, nonsense, and consensus splice site) variants, i.e., approximately 1 in 7.9 individuals had a missense substitution, and 1 in 71 had a loss-of-function variant. Focusing on the 17 genes relevant to usually preferred DOACs, similar variant profiles were identified in HHT patients. With HHT patients at particular risk of haemorrhage when undergoing anticoagulant treatment, we explore how pre-emptive pharmacogenomic testing, alongside HHT gene testing, may prove beneficial in reducing the risk of bleeding and conclude that HHT patients are well placed to be at the vanguard of personalised prescribing.

Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.

Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated fibroblasts which mediate tumour progression and poor prognosis. However, understanding of the crosstalk between cancer cells and fibroblasts in this disease is mostly lacking. Here, using co-cultures of patient-derived mesothelioma cell lines and lung fibroblasts, we demonstrate that fibroblast activation is a self-propagated process producing a fibrotic extracellular matrix (ECM) and triggering drug resistance in mesothelioma cells. Following characterisation of mesothelioma cells/fibroblasts signalling crosstalk, we identify several FDA-approved targeted therapies as far more potent than standard-of-care Cisplatin/Pemetrexed in ECM-embedded co-culture spheroid models. In particular, the SRC family kinase inhibitor, Saracatinib, extends overall survival well beyond standard-of-care in a mesothelioma genetically-engineered mouse model. In short, we lay the foundation for the rational design of novel therapeutic strategies targeting mesothelioma/fibroblast communication for the treatment of mesothelioma patients.

Study protocol: maintaining preventive care during public health emergencies through effective coordination.

BACKGROUND: Screening lies at the heart of preventive care. However, COVID-19 dramatically disrupted routine screening efforts, resulting in excess mortality not directly attributable to COVID-19. Screening rates during COVID varied markedly by facility and clinical condition, suggesting susceptibilities in screening and referral process workflow. To better understand these susceptibilities and identify new practices to mitigate interrupted care, we propose a qualitative study comparing facilities that exhibited high, low, and highly variable performance (respectively) in screening rates before and during the pandemic. We will be guided by Weaver et al.'s multi-team systems (MTS) model of coordination, using cancer and mental health screening rates as exemplars. METHOD: Qualitative analysis of interviews and focus groups with primary care personnel, leadership, and patients at 10 VA medical centers. We will select sites based on rurality, COVID-19 caseload at the beginning of the pandemic, and performance on five outpatient clinical performance indicators of cancer and mental health screening. Sites will be categorized into one of five screening performance groups: high performers, low performers, improvers, plummeters, and highly variable. We will create process maps for each performance measure to create a workflow baseline and then interview primary care leadership to update the map at each site. We will clinician conduct focus groups to elicit themes regarding clinician coordination patterns (e.g., handoffs), strategies, and barriers/facilitators to screening during COVID. We will also conduct patient interviews to examine their screening experience during this period, for context. All interviews and focus groups will be audio-recorded, transcribed, and enhanced by field notes. We will analyze clinician transcripts and field notes using iterative, rapid analysis. Patient interviews will be analyzed using inductive/deductive content analysis. DISCUSSION: Our study represents a unique opportunity to inform the multi-team systems literature by identifying specific forms of information exchange, collective problem solving, and decision-making associated with higher and improved clinical performance. Specifically, our study aims to detect the specific points in the screening and referral process most susceptible to disruption and coordination processes that, if changed, will yield the highest value. Findings apply to future pandemics or any event with the potential to disrupt care.