tbuckley/cabot-search huggingface dataset:
Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge
Authors: Kerry L. Hilligan, Sivaranjani Namasivayam, Chad S. Clancy, Danielle O’Mard, Sandra D. Oland, Shelly J. Robertson, Paul J. Baker, Ehydel Castro, Nicole L. Garza, Bernard A.P. Lafont, Reed Johnson, Franca Ronchese, Katrin D. Mayer-Barber, Sonja M. Best, Alan Sher
Journal: The Journal of Experimental Medicine (2021)

In addition to providing partial protection against pediatric tuberculosis, vaccination with bacille Calmette-Guérin (BCG) has been reported to confer nonspecific resistance to unrelated pulmonary pathogens, a phenomenon attributed to the induction of long-lasting alterations within the myeloid cell compartment. Here, we demonstrate that intravenous, but not subcutaneous, inoculation of BCG protects human-ACE2 transgenic mice against lethal challenge with SARS-CoV-2 (SCV2) and results in reduced viral loads in non-transgenic animals infected with an α variant. The observed increase in host resistance was associated with reductions in SCV2-induced tissue pathology, inflammatory cell recruitment, and cytokine production that multivariate analysis revealed as only partially related to diminished viral load. We propose that this protection stems from BCG-induced alterations in the composition and function of the pulmonary cellular compartment that impact the innate response to the virus and ensuing immunopathology. While intravenous BCG vaccination is not a clinically acceptable practice, our findings provide an experimental model for identifying mechanisms by which nonspecific stimulation of the pulmonary immune response promotes host resistance to SCV2 lethality.
Association Between 2-Dose vs 3-Dose Hepatitis B Vaccine and Acute Myocardial Infarction
Authors: Katia Bruxvoort, Jeff Slezak, Lei Qian, Lina S. Sy, Bradley Ackerson, Kristi Reynolds, Runxin Huang, Zendi Solano, William Towner, Cheryl Mercado, Steven J. Jacobsen
Journal: JAMA (2022)

The 2-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine; Heplisav-B) generated higher seroprotection in prelicensure trials than did a 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine; Engerix-B). However, in 1 trial, a higher number of acute myocardial infarction (MI) events were observed among those who received the HepB-CpG vaccine than among those who received the HepB-alum vaccine, an outcome requiring further study.
OUTCOMES OF PRE-DIABETES COMPARED WITH NORMOGLYCEMIA OR DIABETES MELLITUS IN PATIENTS WITH CORONARY ARTERY DISEASE UNDERGOING PCI: A SYSTEMATIC REVIEW AND META-ANALYSIS.
Authors: Muhammad Ahsan, Noman Lateef, Azka Latif, Claire Willman, Sarah Aurit, Magdi G.H. Ghali, Emmanouil S. Brilakis, Jolanta M. Siller-Matula, J. Dawn Abbott, Mamas A. Mamas, Deepak L. Bhatt, Poonam Velagapudi, Mercy One
Journal: Journal of the American College of Cardiology (2022)
Machine learning of language use on Twitter reveals weak and non-specific predictions
Authors: Sean W. Kelley, Caoimhe Ní Mhaonaigh, Louise Burke, Robert Whelan, Claire M. Gillan
Journal: npj Digital Medicine (2022)

Abstract Depressed individuals use language differently than healthy controls and it has been proposed that social media posts can be used to identify depression. Much of the evidence behind this claim relies on indirect measures of mental health and few studies have tested if these language features are specific to depression versus other aspects of mental health. We analysed the Tweets of 1006 participants who completed questionnaires assessing symptoms of depression and 8 other mental health conditions. Daily Tweets were subjected to textual analysis and the resulting linguistic features were used to train an Elastic Net model on depression severity, using nested cross-validation. We then tested performance in a held-out test set (30%), comparing predictions of depression versus 8 other aspects of mental health. The depression trained model had modest out-of-sample predictive performance, explaining 2.5% of variance in depression symptoms ( R 2 = 0.025, r = 0.16). The performance of this model was as-good or superior when used to identify other aspects of mental health: schizotypy, social anxiety, eating disorders, generalised anxiety, above chance for obsessive-compulsive disorder, apathy, but not significant for alcohol abuse or impulsivity. Machine learning analysis of social media data, when trained on well-validated clinical instruments, could not make meaningful individualised predictions regarding users’ mental health. Furthermore, language use associated with depression was non-specific, having similar performance in predicting other mental health problems.
ECHOCARDIOGRAPHIC AND NONINVASIVE HEMODYNAMIC SIGNATURE OF SICKLE CELL DISEASE PATIENTS WITH ATRIAL FIBRILLATION
Authors: David Tofovic, Rachel Brett, Chinonso Ukeje, Logan Schwarzman, Baha’A Al-azzam, Saraf Santosh, Dawood Darbar
Journal: Journal of the American College of Cardiology (2022)
Trained immunity: A Yin‐Yang balance
Authors: Zhidong Hu, Shui‐Hua Lu, Douglas B. Lowrie, Xiao‐Yong Fan
Journal: MedComm (2022)

Abstract Traditionally, immune memory is regarded as an exclusive hallmark of adaptive immunity. However, a growing body of evidence suggesting that innate immune cells show adaptive characteristics has challenged this dogma. In the past decade, trained immunity, a de facto innate immune memory, has been defined as a long‐term functional reprogramming of cells of the innate immune system: the reprogramming is evoked by endogenous or exogenous insults, the cells return to a nonactivated state and subsequently show altered inflammatory responses against a second challenge. Trained immunity became regarded as a mechanism selected in evolution to protect against infection; however, a maladaptive effect might result in hyperinflammation. This dual effect is consistent with the Yin‐Yang theory in traditional Chinese philosophy, in which Yang represents active, positive, and aggressive factors, whereas Yin represents passive, negative, and inhibitory factors. In this review, we give a brief overview of history and latest progress about trained immunity, including experimental models, inductors, molecular mechanisms, clinical application and so on. Moreover, this is the first time to put forward the theory of Yin‐Yang balance to understand trained immunity. We envision that more efforts will be focused on developing novel immunotherapies targeting trained immunity in the coming years.
ABDOMINAL VISCERAL ADIPOSITY IS ASSOCIATED WITH POSITIVE HIGH-SENSITIVITY TROPONIN PARTLY MEDIATED THROUGH NON-CALCIFIED CORONARY BURDEN
Authors: Grigory A. Manyak, Nidhi Patel, Wunan Zhou, Alexander Sorokin, Philip Parel, Amit Dey, Martin Peter Playford, Nehal N. Mehta
Journal: Journal of the American College of Cardiology (2022)
In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice
Authors: Kristen C. Browder, Pradeep Reddy, Mako Yamamoto, Amin Haghani, Isabel Guillen Guillen, Sanjeeb Sahu, Chao Wang, Yosu Luque, Javier Prieto, Lei Shi, Kensaku Shojima, Tomoaki Hishida, Zijuan Lai, Qingling Li, Feroza K. Choudhury, Weng R. Wong, Yuxin Liang, Dewakar Sangaraju, Wendy Sandoval, Concepcion Rodriguez Esteban, Estrella Nuñez Delicado, Pedro Guillen Garcia, Michal Pawlak, Jason A. Vander Heiden, Steve Horvath, Heinrich Jasper, Juan Carlos Izpisua Belmonte
Journal: Nature Aging (2022)
GENDER BASED DIFFERENCES IN CARDIOVASCULAR OUTCOMES ASSOCIATED WITH COVID-19 INFECTION: A SYSTEMIC REVIEW AND META-ANALYSIS
Authors: Sanskriti Shrivastava, Raza Naseer, Hamza Hanif, Muhammad Sabih Saleem, Najam U. Saqib, Muhammad Siddique Pir
Journal: Journal of the American College of Cardiology (2022)
CLINICAL CHARACTERISTICS OF MALE PATIENTS WITH TAKOTSUBO SYNDROME
Authors: Yuki Nishimura, Junya Komatsu, Hiroki Sugane, Hayato Hosoda, Ryuichirou Imai, Yoko Nakaoka, Koji Nishida, Shuichi Seki, Shoichi Kubokawa, Kazuya Kawai, Naohisa Hamashige, Yoshinori L. Doi
Journal: Journal of the American College of Cardiology (2022)
When I use a word . . . . Remembrance of things past
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

A single word with medical relevance sums up remembrance of things past, the phrase that Shakespeare coined in Sonnet 30, which C K Scott Moncrieff used for his 1922 translation of the title of Proust’s novel <i>À la recherché du temps perdu</i>. The word is “anamnesis.” The <i>Oxford English Dictionary</i> lists only two meanings of “anamnesis”: (a) the recalling of things past; recollection, reminiscence; and (b) that part of the Eucharistic canon in which the sacrifice of Christ is recalled and pleaded. Antedatings of the examples that the dictionary gives of the uses of these words are available. Furthermore, other meanings could be added. The first meaning could be supplemented by being specifically designated as referring to the patient’s history. A modern immunological meaning, a reaction to an antigen that stimulates production of an antibody to another antigen previously encountered, could be added, and the dung beetle known as <i>Deltochilum Eschscholz</i>, or <i>Anamnesis Vigors</i> could also be included.
ATRIAL TACHYCARDIA MASQUERADING AS ATRIAL FIBRILLATION IN A PATIENT WITH TETRALOGY OF FALLOT AND ATRIOTOMY SCAR
Authors: Ninad M. Zaman, George Prousi, James Davis, Meer Fakhry, William Lorson, William Meeks, Christopher Salmon, Sultan M. Siddique
Journal: Journal of the American College of Cardiology (2022)
Correction to: SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex
Authors: Chunling Ma, Fang Wang, Bing Han, Xiaoli Zhong, Fusheng Si, Jian Ye, Eddy C. Hsueh, Lynn Robbins, Susan M. Kiefer, Yanping Zhang, Pamela Hunborg, Mark A. Varvares, Michael Rauchman, Guangyong Peng
Journal: Molecular Cancer (2022)
OUTCOMES IN AFRICAN AMERICAN PATIENTS WITH ST- SEGMENT ELEVATION MYOCARDIAL INFARCTION AND COEXISTING ALCOHOL USE: ANALYSIS OF NATIONWIDE INPATIENT SAMPLE
Authors: Bidhya Timilsina, Ngwa Julius, Prem Parajuli, Nitheesha Ganta, Jin Yi, Mohamed E. Taha, Prince Alebna, Prafulla P. Mehrotra
Journal: Journal of the American College of Cardiology (2022)
CLO22-035: Treatment Outcome of Ruxolitinib and Decitabine Combination Chemotherapy Among Transplant Ineligible Advanced Stage Myeloproliferative Neoplasm: A Meta-analysis
Authors: Ma. Rosario Irene D. Castillo
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-035: Treatment Outcome of Ruxolitinib and Decitabine Combination Chemotherapy Among Transplant Ineligible Advanced Stage Myeloproliferative Neoplasm: A Meta-analysis" published on 31 Mar 2022 by National Comprehensive Cancer Network.
The Potential of Current Polygenic Risk Scores to Predict High Myopia and Myopic Macular Degeneration in Multiethnic Singapore Adults
Authors: Irfahan Kassam, Li-Lian Foo, Carla Lanca, LingQian Xu, Quan V. Hoang, Ching-Yu Cheng, Pirro Hysi, Seang-Mei Saw
Journal: Ophthalmology (2022)
Effectiveness of mRNA Vaccination in Preventing COVID-19–Associated Invasive Mechanical Ventilation and Death — United States, March 2021–January 2022
Authors: Mark W. Tenforde, Wesley H. Self, Manjusha Gaglani, Adit A. Ginde, David J. Douin, H. Keipp Talbot, Jonathan D. Casey, Nicholas M. Mohr, Anne Zepeski, Tresa McNeal, Shekhar Ghamande, Kevin W. Gibbs, D. Clark Files, David N. Hager, Arber Shehu, Matthew E. Prekker, Anne E. Frosch, Michelle N. Gong, Amira Mohamed, Nicholas J. Johnson, Vasisht Srinivasan, Jay S. Steingrub, Ithan D. Peltan, Samuel M. Brown, Emily T. Martin, Arnold S. Monto, Akram Khan, Catherine L. Hough, Laurence W. Busse, Abhijit Duggal, Jennifer G. Wilson, Nida Qadir, Steven Y. Chang, Christopher Mallow, Carolina Rivas, Hilary M. Babcock, Jennie H. Kwon, Matthew C. Exline, Mena Botros, Adam S. Lauring, Nathan I. Shapiro, Natasha Halasa, James D. Chappell, Carlos G. Grijalva, Todd W. Rice, Ian D. Jones, William B. Stubblefield, Adrienne Baughman, Kelsey N. Womack, Jillian P. Rhoads, Christopher J. Lindsell, Kimberly W. Hart, Yuwei Zhu, Katherine Adams, Diya Surie, Meredith L. McMorrow, Manish M. Patel
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) are effective at preventing COVID-19-associated hospitalization (1-3). However, how well mRNA vaccines protect against the most severe outcomes of these hospitalizations, including invasive mechanical ventilation (IMV) or death is uncertain. Using a case-control design, mRNA vaccine effectiveness (VE) against COVID-19-associated IMV and in-hospital death was evaluated among adults aged ≥18 years hospitalized at 21 U.S. medical centers during March 11, 2021-January 24, 2022. During this period, the most commonly circulating variants of SARS-CoV-2, the virus that causes COVID-19, were B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Previous vaccination (2 or 3 versus 0 vaccine doses before illness onset) in prospectively enrolled COVID-19 case-patients who received IMV or died within 28 days of hospitalization was compared with that among hospitalized control patients without COVID-19. Among 1,440 COVID-19 case-patients who received IMV or died, 307 (21%) had received 2 or 3 vaccine doses before illness onset. Among 6,104 control-patients, 4,020 (66%) had received 2 or 3 vaccine doses. Among the 1,440 case-patients who received IMV or died, those who were vaccinated were older (median age = 69 years), more likely to be immunocompromised* (40%), and had more chronic medical conditions compared with unvaccinated case-patients (median age = 55 years; immunocompromised = 10%; p<0.001 for both). VE against IMV or in-hospital death was 90% (95% CI = 88%-91%) overall, including 88% (95% CI = 86%-90%) for 2 doses and 94% (95% CI = 91%-96%) for 3 doses, and 94% (95% CI = 88%-97%) for 3 doses during the Omicron-predominant period. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated death and respiratory failure treated with IMV. CDC recommends that all persons eligible for vaccination get vaccinated and stay up to date with COVID-19 vaccination (4).
Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma
Authors: Yixuan Lin, Yiqi Yang, Kai Yuan, Shengbing Yang, Shuhong Zhang, Hanjun Li, Tingting Tang
Journal: Bioactive Materials (2022)

Current in vitro models for osteosarcoma investigation and drug screening, including two-dimensional (2D) cell culture and tumour spheroids (i.e. cancer stem-like cells), lack extracellular matrix (ECM). Therefore, results from traditional models may not reflect real pathological processes in genuine osteosarcoma histological structures. Here, we report a three-dimensional (3D) bioprinted osteosarcoma model (3DBPO) that contains osteosarcoma cells and shrouding ECM analogue in a 3D frame. Photo-crosslinkable bioinks composed of gelatine methacrylamide and hyaluronic acid methacrylate mimicked tumour ECM. We performed multi-omics analysis, including transcriptomics and DNA methylomics, to determine differences between the 3DBPO model and traditional models. Compared with 2D models and tumour spheroids, our 3DBPO model showed significant changes in cell cycle, metabolism, adherens junctions, and other pathways associated with epigenetic regulation. The 3DBPO model was more sensitive to therapies targeted to the autophagy pathway. We showed that simulating ECM yielded different osteosarcoma cell metabolic characteristics and drug sensitivity in the 3DBPO model compared with classical models. We suggest 3D printed osteosarcoma models can be used in osteosarcoma fundamental and translational research, which may contribute to novel therapeutic strategy discovery.
PREMATURE MORTALITY IN MALES DUE TO HEART FAILURE IN THE UNITED STATES FROM 2010-2018
Authors: Mohsin Mughal, Ali Ghani, Sundeep Kumar, Hasan Mirza, Howard L. Levitt, Sergio Waxman, Muhammad Khakwani, Jagpreet Grewal, Muhammad Zahid A. Raza, Mohammed Haris U. Usman, Ammar Nasir, Mahboob Alam, Deana Mikhalkova
Journal: Journal of the American College of Cardiology (2022)
OUTCOMES OF ACUTE DECOMPENSATED HEART FAILURE IN PATIENTS WITH HISTORY OF UPPER GASTROINTESTINAL BLEEDING
Authors: Awfa Zain Elabidin, Vahid Namdarizandi, Michael A. Fatuyi, Leanne Pereira, Amer AlSamman, Vivek Sharma, Leonid Khokhlov, Kamal Shemisa
Journal: Journal of the American College of Cardiology (2022)
Field validation of the performance of paper-based tests for the detection of the Zika and chikungunya viruses in serum samples
Authors: Margot Karlikow, Severino Jefferson Ribeiro da Silva, Yuxiu Guo, Seray Cicek, Larissa Krokovsky, Paige Homme, Yilin Xiong, Talia Xu, Maria-Angelica Calderón-Peláez, Sigrid Camacho-Ortega, Duo Ma, Jurandy Júnior Ferraz de Magalhães, Bárbara Nayane Rosário Fernandes Souza, Diego Guerra de Albuquerque Cabral, Katariina Jaenes, Polina Sutyrina, Tom Ferrante, Andrea Denisse Benitez, Victoria Nipaz, Patricio Ponce, Darius G. Rackus, James J. Collins, Marcelo Paiva, Jaime E. Castellanos, Varsovia Cevallos, Alexander A. Green, Constância Ayres, Lindomar Pena, Keith Pardee
Journal: Nature Biomedical Engineering (2022)

Abstract In low-resource settings, resilience to infectious disease outbreaks can be hindered by limited access to diagnostic tests. Here we report the results of double-blinded studies of the performance of paper-based diagnostic tests for the Zika and chikungunya viruses in a field setting in Latin America. The tests involved a cell-free expression system relying on isothermal amplification and toehold-switch reactions, a purpose-built portable reader and onboard software for computer vision-enabled image analysis. In patients suspected of infection, the accuracies and sensitivities of the tests for the Zika and chikungunya viruses were, respectively, 98.5% (95% confidence interval, 96.2–99.6%, 268 serum samples) and 98.5% (95% confidence interval, 91.7–100%, 65 serum samples) and approximately 2 aM and 5 fM (both concentrations are within clinically relevant ranges). The analytical specificities and sensitivities of the tests for cultured samples of the viruses were equivalent to those of the real-time quantitative PCR. Cell-free synthetic biology tools and companion hardware can provide de-centralized, high-capacity and low-cost diagnostics for use in low-resource settings.
The relative contribution of the decreasing trend in tumour thickness to the 2010s increase in net survival from cutaneous malignant melanoma in Italy: a population‐based investigation*
Authors: Federica Zamagni, Lauro Bucchi, Silvia Mancini, Emanuele Crocetti, Luigino Dal Maso, Stefano Ferretti, Annibale Biggeri, Simona Villani, Flavia Baldacchini, Orietta Giuliani, Alessandra Ravaioli, Rosa Vattiato, Angelita Brustolin, Giuseppa Candela, Simona Carone, Giuliano Carrozzi, Rossella Cavallo, Ylenia Maria Dinaro, Margherita Ferrante, Silvia Iacovacci, Guido Mazzoleni, Antonino Musolino, Roberto Vito Rizzello, Diego Serraino, Fabrizio Stracci, Rosario Tumino, Carla Masini, Laura Ridolfi, Giuseppe Palmieri, Ignazio Stanganelli, Fabio Falcini
Journal: British Journal of Dermatology (2022)

The long-term increase in survival from cutaneous malignant melanoma (CMM) is generally attributed to the decreasing trend in tumour thickness, the single most important prognostic factor.
THE INFLUENCE OF COMPLETE REVASCULARIZATION AND COMPREHENSIVE CARDIAC REHABILITATION IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION (MI). RESULTS FROM THE COORDINATED CARE AFTER MI PROGRAM IN POLAND.
Authors: Marta Konopko, Aleksandra Kolarczyk-Haczyk, Marta Mazur, Paweł Kaźmierczak, Aleksander Żurakowski, Mariusz Gąsior, Piotr Jankowski, Pawel E. Buszman, Krzysztof Milewski, Piotr P. Buszman
Journal: Journal of the American College of Cardiology (2022)
Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis
Authors: Jie Li, Jian Luo, Ivan Pavlov, Yonatan Perez, Wei Tan, Oriol Roca, Elsa Tavernier, Aileen Kharat, Bairbre McNicholas, Miguel Ibarra-Estrada, David L Vines, Nicholas A Bosch, Garrett Rampon, Steven Q Simpson, Allan J Walkey, Michael Fralick, Amol Verma, Fahad Razak, Tim Harris, John G Laffey, Claude Guerin, Stephan Ehrmann, Jie Li, Jian Luo, Ivan Pavlov, Yonatan Perez, Wei Tan, Oriol Roca, Elsa Tavernier, Aileen Kharat, Bairbre McNicholas, Miguel Ibarra-Estrada, David Vines, Nicholas A Bosch, Garrett Rampon, Steven Q Simpson, Allan J Walkey, Michael Fralick, Amol Verma, Fahad Razak, Tim Harris, John G Laffey, Claude Guerin, Stephan Ehrmann, Sara Mirza, Luzheng Xue, Ian D Pavord, Patrice Plamondon, Dev Jayaraman, Jason Shahin, Joseph Dahine, Anne Kulenkamp, Andrés Pacheco
Journal: The Lancet Respiratory Medicine (2022)
Integration of genetic colocalizations with physiological and pharmacological perturbations identifies cardiometabolic disease genes
Authors: Michael J. Gloudemans, Brunilda Balliu, Daniel Nachun, Theresia M. Schnurr, Matthew G. Durrant, Erik Ingelsson, Martin Wabitsch, Thomas Quertermous, Stephen B. Montgomery, Joshua W. Knowles, Ivan Carcamo-Orive
Journal: Genome Medicine (2022)

Abstract Background Identification of causal genes for polygenic human diseases has been extremely challenging, and our understanding of how physiological and pharmacological stimuli modulate genetic risk at disease-associated loci is limited. Specifically, insulin resistance (IR), a common feature of cardiometabolic disease, including type 2 diabetes, obesity, and dyslipidemia, lacks well-powered genome-wide association studies (GWAS), and therefore, few associated loci and causal genes have been identified. Methods Here, we perform and integrate linkage disequilibrium (LD)-adjusted colocalization analyses across nine cardiometabolic traits (fasting insulin, fasting glucose, insulin sensitivity, insulin sensitivity index, type 2 diabetes, triglycerides, high-density lipoprotein, body mass index, and waist-hip ratio) combined with expression and splicing quantitative trait loci (eQTLs and sQTLs) from five metabolically relevant human tissues (subcutaneous and visceral adipose, skeletal muscle, liver, and pancreas). To elucidate the upstream regulators and functional mechanisms for these genes, we integrate their transcriptional responses to 21 relevant physiological and pharmacological perturbations in human adipocytes, hepatocytes, and skeletal muscle cells and map their protein-protein interactions. Results We identify 470 colocalized loci and prioritize 207 loci with a single colocalized gene. Patterns of shared colocalizations across traits and tissues highlight different potential roles for colocalized genes in cardiometabolic disease and distinguish several genes involved in pancreatic β-cell function from others with a more direct role in skeletal muscle, liver, and adipose tissues. At the loci with a single colocalized gene, 42 of these genes were regulated by insulin and 35 by glucose in perturbation experiments, including 17 regulated by both. Other metabolic perturbations regulated the expression of 30 more genes not regulated by glucose or insulin, pointing to other potential upstream regulators of candidate causal genes. Conclusions Our use of transcriptional responses under metabolic perturbations to contextualize genetic associations from our custom colocalization approach provides a list of likely causal genes and their upstream regulators in the context of IR-associated cardiometabolic risk.