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Double Lung Transplantation For End-Stage Kartagener Syndrome: A Case Report And Literature Review, Bo Wang, Xinghua Zhang, Wenyang Jiang, Jie Huang, Jingyu Chen, Daniel Kreisel, Jose Luis J Danguilan, Michael Hsin, Huiqing Lin

Open Access Publications

Kartagener syndrome (KS) is an autosomal recessive disorder characterized by situs inversus, paranasal sinusitis and bronchiectasis. We report the successful use of double lung transplant (DLTx) to treat end-stage KS. A 49-year-old Han woman was admitted to Renmin Hospital (Wuhan University, China) in September 2017 with a ≥15 year history of chronic productive cough that had worsened during the past year. Clinical examination and imaging investigations revealed respiratory failure and situs inversus consistent with KS. The patient was successfully treated with DLTx involving bilateral bronchial anastomoses. DLTx is a feasible treatment option for end-stage KS.

Role Of Yttrium-90 Selective Internal Radiation Therapy In The Treatment Of Liver-Dominant Metastatic Colorectal Cancer: An Evidence-Based Expert Consensus Algorithm, D Rohan Jeyarajah, Maria B Majella Doyle, N Joseph Espat, Paul D Hansen, David A Iannitti, Joseph Kim, Thavam Thambi-Pillai, Brendan C. Visser

Open Access Publications

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a …

Differences In The Chitinolytic Activity Of Mammalian Chitinases On Soluble And Insoluble Substrates, Benjamin A Barad, Lin Liu, Roberto E Diaz, Ralp Basilio, Steven J Van Dyken, Richard M Locksley, James S Fraser

Open Access Publications

Chitin is an abundant polysaccharide used by many organisms for structural rigidity and water repulsion. As such, the insoluble crystalline structure of chitin poses significant challenges for enzymatic degradation. Acidic mammalian chitinase, a processive glycosyl hydrolase, is the primary enzyme involved in the degradation of environmental chitin in mammalian lungs. Mutations to acidic mammalian chitinase have been associated with asthma, and genetic deletion in mice increases morbidity and mortality with age. We initially set out to reverse this phenotype by engineering hyperactive acidic mammalian chitinase variants. Using a screening approach with commercial fluorogenic substrates, we identified mutations with consistent increases …

Incomplete Vesicular Docking Limits Synaptic Strength Under High Release Probability Conditions, Gerardo Malagon, Takafumi Miki, Van Tran, Laura C. Gomez, Alain Marty

Open Access Publications

Central mammalian synapses release synaptic vesicles in dedicated structures called docking/release sites. It has been assumed that when voltage-dependent calcium entry is sufficiently large, synaptic output attains a maximum value of one synaptic vesicle per action potential and per site. Here we use deconvolution to count synaptic vesicle output at single sites (mean site number per synapse: 3.6). When increasing calcium entry with tetraethylammonium in 1.5 mM external calcium concentration, we find that synaptic output saturates at 0.22 vesicle per site, not at 1 vesicle per site. Fitting the results with current models of calcium-dependent exocytosis indicates that the 0.22 …

The Sterlet Sturgeon Genome Sequence And The Mechanisms Of Segmental Rediploidization, Kang Du, Chad Tomlinson, Et Al

Open Access Publications

Sturgeons seem to be frozen in time. The archaic characteristics of this ancient fish lineage place it in a key phylogenetic position at the base of the ~30,000 modern teleost fish species. Moreover, sturgeons are notoriously polyploid, providing unique opportunities to investigate the evolution of polyploid genomes. We assembled a high-quality chromosome-level reference genome for the sterlet, Acipenser ruthenus. Our analysis revealed a very low protein evolution rate that is at least as slow as in other deep branches of the vertebrate tree, such as that of the coelacanth. We uncovered a whole-genome duplication that occurred in the Jurassic, early …

Perspectives On Program Mis-Implementation Among U.S. Local Public Health Departments, Peg Allen, Rebekah R Jacob, Renee G Parks, Stephanie Mazzucca, Hengrui Hu, Mackenzie Robinson, Maureen Dobbins, Debra Dekker, Margaret Padek, Ross C Brownson

Open Access Publications

BACKGROUND: Public health resources are limited and best used for effective programs. This study explores associations of mis-implementation in public health (ending effective programs or continuing ineffective programs) with organizational supports for evidence-based decision making among U.S. local health departments.

METHODS: The national U.S. sample for this cross-sectional study was stratified by local health department jurisdiction population size. One person was invited from each randomly selected local health department: the leader in chronic disease, or the director. Of 600 selected, 579 had valid email addresses; 376 completed the survey (64.9% response). Survey items assessed frequency of and reasons for mis-implementation. …

Unc-4 Acts To Promote Neuronal Identity And Development Of The Take-Off Circuit In The Drosophila Cns, Haluk Lacin, W. Ryan Williamson, Gwyneth M. Card, James B. Skeath, James W. Truman

Open Access Publications

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Development Of A Hybrid Magnetic Resonance/Computed Tomography-Compatible Phantom For Magnetic Resonance Guided Radiotherapy, Min-Joo Kim, Seu-Ran Lee, Kyu-Ho Song, Hyeon-Man Baek, Bo-Young Choe, Tae Suk Suh

Open Access Publications

The purpose of the present study was to develop a hybrid magnetic resonance/computed tomography (MR/CT)-compatible phantom and tissue-equivalent materials for each MR and CT image. Therefore, the essential requirements necessary for the development of a hybrid MR/CT-compatible phantom were determined and the development process is described. A total of 12 different tissue-equivalent materials for each MR and CT image were developed from chemical components. The uniformity of each sample was calculated. The developed phantom was designed to use 14 plugs that contained various tissue-equivalent materials. Measurement using the developed phantom was performed using a 3.0-T scanner with 32 channels and …

Long Non-Coding Rna Graslnd Enhances Chondrogenesis Via Suppression Of The Interferon Type Ii Signaling Pathway, Nguyen P.T. Huynh, Catherine C. Gloss, Jeremiah Lorentz, Ruhang Tang, Jonathan M. Brunger, Audrey Mcalinden, Bo Zhang, Farshid Guilak

Open Access Publications

The roles of long noncoding RNAs (lncRNAs) in musculoskeletal development, disease, and regeneration remain poorly understood. Here, we identified the novel lncRNA

Abnormally Increased Carotid Intima Media-Thickness And Elasticity In Patients With Morquio A Disease, Raymond Y Wang, Kyle D Rudser, Donald R Dengel, Nicholas Evanoff, Julia Steinberger, Nina Movsesyan, Robert Garrett, Katherine Christensen, Deborah Boylan, Stephen R Braddock, Marwan Shinawi, Qi Gan, Adriana M Montaño

Open Access Publications

BACKGROUND: Cardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities.

METHODS: Prospective, multi-center echocardiogram and carotid ultrasound evaluations of 12 Morquio A patients were compared with other MPS and healthy control subjects. Average differences between groups were adjusted for age, sex, and height with robust variance estimation for confidence intervals …

Cerebrospinal Fluid Phospho-Tau T217 Outperforms T181 As A Biomarker For The Differential Diagnosis Of Alzheimer's Disease And Pet Amyloid-Positive Patient Identification, Nicolas R Barthélemy, Randall J Bateman, Christophe Hirtz, Philippe Marin, François Becher, Chihiro Sato, Audrey Gabelle, Sylvain Lehmann

Open Access Publications

BACKGROUND: Cerebrospinal fluid biomarker profiles characterized by decreased amyloid-beta peptide levels and increased total and phosphorylated tau levels at threonine 181 (pT181) are currently used to discriminate between Alzheimer's disease and other neurodegenerative diseases. However, these changes are not entirely specific to Alzheimer's disease, and it is noteworthy that other phosphorylated isoforms of tau, possibly more specific for the disease process, have been described in the brain parenchyma of patients. The precise detection of these isoforms in biological fluids remains however a challenge.

METHODS: In the present study, we used the latest quantitative mass spectrometry approach, which achieves a sensitive …

Select Atrophied Regions In Alzheimer Disease (Sara): An Improved Volumetric Model For Identifying Alzheimer Disease Dementia, Lauren N Koenig, Gregory S Day, Amber Salter, Sarah Keefe, Laura M Marple, Justin Long, Pamela Lamontagne, Parinaz Massoumazada, B Joy Snider, Manasa Kanthamneni, Cyrus A Raji, Nupur Ghoshal, Brian A Gordon, Michelle Miller-Thomas, John C Morris, Joshua S Shimony, Tammie L S Benzinger, Alzheimer's Disease Neuroimaging Initiative (Adni) And The Dominantly Inherited Alzheimer Network (Dian)

Open Access Publications

INTRODUCTION: Volumetric biomarkers for Alzheimer disease (AD) are attractive due to their wide availability and ease of administration, but have traditionally shown lower diagnostic accuracy than measures of neuropathological contributors to AD. Our purpose was to optimize the diagnostic specificity of structural MRIs for AD using quantitative, data-driven techniques.

METHODS: This retrospective study assembled several non-overlapping cohorts (total n = 1287) with publicly available data and clinical patients from Barnes-Jewish Hospital (data gathered 1990-2018). The Normal Aging Cohort (n = 383) contained amyloid biomarker negative, cognitively normal (CN) participants, and provided a basis for determining age-related atrophy in other cohorts. …

Awareness And Bispectral Index (Bis) Monitoring In Mechanically Ventilated Patients In The Emergency Department And Intensive Care Unit: A Systematic Review Protocol, Ryan D Pappal, Brian W Roberts, Winston Winkler, Lauren H Yaegar, Robert J Stephens, Brian M Fuller

Open Access Publications

INTRODUCTION: Accidental awareness with recall is one of the most feared complications for patients undergoing general anaesthesia and can lead to post-traumatic stress disorder in up to 70% of patients experiencing it. To reduce the incidence of awareness with recall, the bispectral index monitor is recommended for patients receiving total intravenous anaesthetics, especially those receiving neuromuscular blockers. While extensive investigation into awareness and bispectral index monitoring has occurred for operating room patients, this has not extended to other clinical arenas where sedated and mechanically ventilated patients are cared for, namely the intensive care unit and emergency department. The purpose of …

Variant R94c In Tnnt2‐Encoded Troponin T Predisposes To Pediatric Restrictive Dardiomyopathy And Sudden Death Through Impaired Thin Filament Relaxation Resulting In Myocardial Diastolic Dysfunction, Jordan E Ezekian, Sarah R Clippinger, Jaquelin M Garcia, Qixin Yang, Susan Denfield, Aamir Jeewa, William J Dreyer, Wenxin Zou, Yuxin Fan, Hugh D Allen, Jeffrey J Kim, Michael J Greenberg, Andrew P Landstrom

Open Access Publications

Background Pediatric-onset restrictive cardiomyopathy (RCM) is associated with high mortality, but underlying mechanisms of disease are under investigated. RCM-associated diastolic dysfunction secondary to variants in

Acetate Coordinates Neutrophil And Ilc3 Responses Against C. Difficile Through Ffar2, José Luís Fachi, Cristiane Sécca, Blanda Di Luccia, Marco Colonna, Et Al

Open Access Publications

Antibiotic-induced dysbiosis is a key predisposing factor for Clostridium difficile infections (CDIs), which cause intestinal disease ranging from mild diarrhea to pseudomembranous colitis. Here, we examined the impact of a microbiota-derived metabolite, short-chain fatty acid acetate, on an acute mouse model of CDI. We found that administration of acetate is remarkably beneficial in ameliorating disease. Mechanistically, we show that acetate enhances innate immune responses by acting on both neutrophils and ILC3s through its cognate receptor free fatty acid receptor 2 (FFAR2). In neutrophils, acetate-FFAR2 signaling accelerates their recruitment to the inflammatory sites, facilitates inflammasome activation, and promotes the release of …

Operative Versus Nonoperative Treatment Of Acute Achilles Tendon Ruptures: A Pilot Economic Decision Analysis, Alvin W Su, Ljiljana Bogunovic, Jeffrey Johnson, Sandra Klein, Matthew J Matava, Jeremy Mccormick, Matthew V Smith, Rick W Wright, Robert H Brophy

Open Access Publications

Background: The operative treatment of Achilles tendon ruptures has been associated with lower rerupture rates and better function but also a risk of surgery-related complications compared with nonoperative treatment, which may provide improved outcomes with accelerated rehabilitation protocols. However, economic decision analyses integrating the updated costs of both treatment options are limited in the literature.

Purpose: To compare the cost-effectiveness of operative and nonoperative treatment of acute Achilles tendon tears.

Study Design: Economic and decision analysis; Level of evidence, 2.

Methods: An economic decision model was built to assess the cost-utility ratio (CUR) of open primary repair versus nonoperative treatment …

Antibody-Mediated Rejection After Lung Transplantation, Amit I. Bery, Ramsey R. Hachem

Open Access Publications

Antibody-mediated rejection (AMR) has been identified as a significant form of acute allograft dysfunction in lung transplantation. The development of consensus diagnostic criteria has created a uniform definition of AMR; however, significant limitations of these criteria have been identified. Treatment modalities for AMR have been adapted from other areas of medicine and data on the effectiveness of these therapies in AMR are limited. AMR is often refractory to these therapies, and graft failure and death are common. AMR is associated with increased rates of chronic lung allograft dysfunction (CLAD) and poor long-term survival. In this review, we discuss the history …

Surveyed Dermatologists Are Less Likely To Curette Invasive Squamous Cell Carcinoma In Solid Organ Transplant Recipients, Kathleen M Nemer, Tyler M Bauman, M Laurin Council, Eva A Hurst

Open Access Publications

Background: The risk of squamous cell carcinoma (SCC) is increased in solid organ transplant recipients (OTRs), and preferential treatment modalities vary among clinicians.

Objectives: The purpose of this study was to survey dermatologists regarding practice patterns for electrodesiccation and curettage (EDC) of SCC in OTRs and nontransplant patients.

Methods: An 18-question survey was sent to dermatologist members of the International Transplant Skin Cancer Collaborative, Association of Professors of Dermatology, and American College of Mohs Surgery. Differences in EDC practice patterns for treatment of SCC in OTRs and nontransplant patients were evaluated.

Results: Dermatologists in this study (

Conclusions: In OTRs …

Civicpy: A Python Software Evelopment And Analysis Toolkit For The Civic Knowledgebase, Alex H Wagner, Susanna Kiwala, Adam C Coffman, Joshua F Mcmichael, Kelsy C Cotto, Thomas B Mooney, Erica K Barnell, Kilannin Krysiak, Arpad M Danos, Jason Walker, Obi L Griffith, Malachi Griffith

Open Access Publications

PURPOSE: Precision oncology depends on the matching of tumor variants to relevant knowledge describing the clinical significance of those variants. We recently developed the Clinical Interpretations for Variants in Cancer (CIViC; civicdb.org) crowd-sourced, expert-moderated, and open-access knowledgebase. CIViC provides a structured framework for evaluating genomic variants of various types (eg, fusions, single-nucleotide variants) for their therapeutic, prognostic, predisposing, diagnostic, or functional utility. CIViC has a documented application programming interface for accessing CIViC records: assertions, evidence, variants, and genes. Third-party tools that analyze or access the contents of this knowledgebase programmatically must leverage this application programming interface, often reimplementing redundant functionality …

Platelet Activation In Experimental Murine Neonatal Pulmonary Hypertension, Pavel Davizon-Castillo, Ayed Allawzi, Matthew Sorrells, Susan Fisher, Kristina Baltrunaite, Keith Neeves, Eva Nozik-Grayck, Jorge Dipaola, Cassidy Delaney

Open Access Publications

Serotonin (5-HT) contributes to the pathogenesis of experimental neonatal pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD). Platelets are the primary source of circulating 5-HT and is released upon platelet activation. Platelet transfusions are associated with neonatal mortality and increased rates of BPD. As BPD is often complicated by PH, we tested the hypothesis that circulating platelets are activated and also increased in the lungs of neonatal mice with bleomycin-induced PH associated with BPD. Newborn wild-type mice received intraperitoneal bleomycin (3 units/kg) three times weekly for 3 weeks. Platelets from mice with experimental PH exhibited increased adhesion to collagen under …

The Struggling Infectious Diseases Fellow: Remediation Challenges And Opportunities, Michael T. Melia, Gerome Escota, Et Al

Open Access Publications

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with …

Direct Cost Of Surgically Treated Adult Traumatic Brachial Plexus Injuries, Christopher J Dy, Nithya Lingampalli, Kate Peacock, Margaret A Olsen, Wilson Z Ray, David M Brogan

Open Access Publications

PURPOSE: The economic implications of brachial plexus injuries (BPI) in the United States are not well understood. The purpose of our study was to quantify the direct costs associated with surgical treatment of BPI after traumatic injury in adults, which would enable future study of the societal value of surgical reconstruction.

METHODS: Using an administrative database of patients with commercial insurance, a cohort of patients aged 18 to 64 years with BPI treated surgically from 2007 to 2015 was assembled and assessed for index admission associated with BPI surgery and all payments toward claims (including medical, surgical, therapy, and pharmacy …

Age And Tightness Of Repair Are Predictors Of Heel-Rise Height After Achilles Tendon Rupture, Michael R Carmont, Jennifer A Zellers, Annelie Brorsson, Katarina Nilsson-Helander, Jón Karlsson, Karin Grävare Silbernagel

Open Access Publications

Background: Achilles tendon rupture leads to weakness of ankle plantarflexion. Treatment of Achilles tendon rupture should aim to restore function while minimizing weakness and complications of management.

Purpose: To determine the influence of factors (age, sex, body mass index [BMI], weight, time from injury to operative repair, and tightness of repair) in the initial surgical management of patients after an acute Achilles tendon rupture on 12-month functional outcome assessment after percutaneous and minimally invasive repair.

Study Design: Cohort study; Level of evidence, 3.

Methods: From May 2012 to January 2018, patients sustaining an Achilles tendon rupture receiving operative repair were …

Impaired Tumor Necrosis Factor-Α Secretion By Cd4 T Cells During Respiratory Syncytial Virus Bronchiolitis Associated With Recurrent Wheeze, Maleewan Kitcharoensakkul, Leonard B Bacharier, Huiqing Yin-Declue, Jonathan S Boomer, Geneline Sajol, Marilyn K Leung, Brad Wilson, Kenneth B Schechtman, John P Atkinson, Jonathan M Green, Mario Castro

Open Access Publications

BACKGROUND: Infants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro-stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life.

METHODS: We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV-confirmed bronchiolitis. Granzyme B (GZB) expression, and interleukin-10, interferon-γ, tumor necrosis factor-α (TNF-α), IL-4, and IL-5 production by in vitro anti-CD3/CD28- and anti-CD3/CD46-activated CD4+ T cells, and percentage of peripheral Treg …

Tgfβ1 Orchestrates Renal Fibrosis Following Escherichia Coli Pyelonephritis, Teri N Hreha, Christina A Collins, Allyssa L Daugherty, Joy Twentyman, Nitin Paluri, David A Hunstad

Open Access Publications

Renal scarring after pyelonephritis is linked to long-term health risks for hypertension and chronic kidney disease. Androgen exposure increases susceptibility to, and severity of, uropathogenic Escherichia coli (UPEC) pyelonephritis and resultant scarring in both male and female mice, while anti-androgen therapy is protective against severe urinary tract infection (UTI) in these models. This work employed androgenized female C57BL/6 mice to elucidate the molecular mechanisms of post-infectious renal fibrosis and to determine how these pathways are altered by the presence of androgens. We found that elevated circulating testosterone levels primed the kidney for fibrosis by increasing local production of TGFβ1 before …

Intraoperative Suprachoroidal Hemorrhage During Xen Gel Stent Implantation, James C Liu, Wesley Green, Arsham Sheybani, John T Lind

Open Access Publications

Purpose: To report a rare case of intraoperative suprachoroidal hemorrhage during Xen gel stent implantation with accompanying surgical video and subsequent 6-month follow-up.

Observations: Our patient required incisional glaucoma surgery after inadequate pressure reduction with four classes of topical medication, methazolamide, and selective laser trabeculoplasty. The patient underwent Xen gel stent implantation and developed an intraoperative suprachoroidal hemorrhage, which was managed in the operating room. The patient recovered his baseline visual acuity with a functioning bleb out to 6 months postoperatively.

Conclusions and Importance: Micro-invasive glaucoma surgeries offer a new repertoire of surgical options, purportedly with safer and less invasive …

Endoscopic Retrograde Cholangiopancreatography (Ercp) Assisted Enucleation Of Deep Pancreatic Neuroendocrine Tumors (Pnets): A Novel Technique To Increase Procedure Safety And Decrease Risk Of Post-Operative Pancreatic Fistula, Adeel S. Khan, Mohamed A. Abdallah, Muslim Atiq, Daniel Mullady, Koushik K. Das, William C. Chapman, Maria B. Doyle

Open Access Publications

No abstract provided.

The Dual-Specificity Kinase Dyrk1a Modulates The Levels Of Cyclin L2 To Control Hiv Replication In Macrophages, Javan K. Kisaka, Lee Ratner, George B. Kyei

Open Access Publications

HIV replication in macrophages contributes to the latent viral reservoirs, which are considered the main barrier to HIV eradication. Few cellular factors that facilitate HIV replication in latently infected cells are known. We previously identified cyclin L2 as a critical factor required by HIV-1 and found that depletion of cyclin L2 attenuates HIV-1 replication in macrophages. Here we demonstrate that cyclin L2 promotes HIV-1 replication through interactions with the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Cyclin L2 and DYRK1A were colocalized in the nucleus and were found together in immunoprecipitation experiments. Knockdown or inhibition of DYRK1A increased HIV-1 replication in …

How To Stop The Bleed: First Care Provider Model For Developing Public Trauma Response Beyond Basic Hemorrhage Control, Joshua P Bobko, Dylan J Badin, Leila Danishgar, Kate Bayhan, Kevin J Thompson, William J Harris, R. Todd Baldridge, Gerald R Fortuna

Open Access Publications

INTRODUCTION: Since 2013, the First Care Provider (FCP) model has successfully educated the non-medical population on how to recognize life-threatening injuries and perform interventions recommended by the Committee for Tactical Emergency Casualty Care (C-TECC) and the Hartford Consensus in the disaster setting. Recent programs, such as the federal "Stop The Bleed" campaign, have placed the emphasis of public training on hemorrhage control. However, recent attacks demonstrate that access to wounded, recognition of injury, and rapid evacuation are equally as important as hemorrhage control in minimizing mortality. To date, no training programs have produced a validated study with regard to training …

Agonist-Selective Recruitment Of Engineered Protein Probes And Of Grk2 By Opioid Receptors In Living Cells, Miriam Stoeber, Damien Jullié, Joy Li, Soumen Chakraborty, Susruta Majumdar, Nevin A. Lambert, Aashish Manglik, Mark Von Zastrow

Open Access Publications

G protein-coupled receptors (GPCRs) signal through allostery, and it is increasingly clear that chemically distinct agonists can produce different receptor-based effects. It has been proposed that agonists selectively promote receptors to recruit one cellular interacting partner over another, introducing allosteric 'bias' into the signaling system. However, the underlying hypothesis - that different agonists drive GPCRs to engage different cytoplasmic proteins in living cells - remains untested due to the complexity of readouts through which receptor-proximal interactions are typically inferred. We describe a cell-based assay to overcome this challenge, based on GPCR-interacting biosensors that are disconnected from endogenous transduction mechanisms. Focusing …