tbuckley/cabot-search huggingface dataset:
Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial
Authors: Julia Ware, Charlotte K Boughton, Janet M Allen, Malgorzata E Wilinska, Martin Tauschmann, Louise Denvir, Ajay Thankamony, Fiona M Campbell, R Paul Wadwa, Bruce A Buckingham, Nikki Davis, Linda A DiMeglio, Nelly Mauras, Rachel E J Besser, Atrayee Ghatak, Stuart A Weinzimer, Korey K Hood, D Steven Fox, Lauren Kanapka, Craig Kollman, Judy Sibayan, Roy W Beck, Roman Hovorka, R Hovorka, C L Acerini, A Thankamony, J M Allen, C K Boughton, K Dovc, D B Dunger, J Ware, G Musolino, M Tauschmann, M E Wilinska, J F Hayes, S Hartnell, S Slegtenhorst, Y Ruan, M Haydock, J Mangat, L Denvir, SK Kanthagnany, J Law, T Randell, P Sachdev, M Saxton, A Coupe, S Stafford, A Ball, R Keeton, R Cresswell, L Crate, H Cripps, H Fazackerley, L Looby, H Navarra, C Saddington, V Smith, V Verhoeven, S Bratt, N Khan, L Moyes, K Sandhu, C West, R P Wadwa, G Alonso, G Forlenza, R Slover, L Towers, C Berget, A Coakley, E Escobar, E Jost, S Lange, L Messer, K Thivener, F M Campbell, J Yong, E Metcalfe, M Allen, S Ambler, S Waheed, J Exall, J Tulip, B A Buckingham, L Ekhlaspour, D Maahs, L Norlander, T Jacobson, M Twon, C Weir, B Leverenz, J Keller, N Davis, A Kumaran, N Trevelyan, H Dewar, G Price, G Crouch, R Ensom, L Haskell, LM Lueddeke, N Mauras, M Benson, K Bird, K Englert, J Permuy, K Ponthieux, J Marrero-Hernandez, L A DiMeglio, H Ismail, H Jolivette, J Sanchez, S Woerner, M Kirchner, M Mullen, M Tebbe, R EJ Besser, S Basu, R London, T Makaya, F Ryan, C Megson, J Bowen-Morris, J Haest, R Law, I Stamford, A Ghatak, M Deakin, K Phelan, K Thornborough, J Shakeshaft, S A Weinzimer, E Cengiz, J L Sherr, M Van Name, K Weyman, L Carria, A Steffen, M Zgorski, J Sibayan, R W Beck, S Borgman, J Davis, J Rusnak, A Hellman, P Cheng, L Kanapka, C Kollman, C McCarthy, S Chalasani, K K Hood, S Hanes, J Viana, M Lanning, D S Fox, G Arreaza-Rubin, T Eggerman, N Green, R Janicek, D Gabrielson, S H Belle, J Castle, J Green, L Legault, S M Willi, C Wysham
Journal: The Lancet Digital Health (2022)

Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population.
Neuropsychiatric reactions with the use of montelukast
Authors: Corine Ekhart, Florence van Hunsel, Vanessa Sellick, Tjalling de Vries
Journal: BMJ (2022)

### What you need to know A 13 year old boy was started on 5 mg montelukast daily in addition to low dose inhaled corticosteroids to treat his asthma. Within a few days, his mother noted that he was constantly arguing and wanted to hit and kick other people. He had not shown this behaviour earlier. At the time of prescribing, their doctor had asked for any history of psychiatric illnesses in their family, which they had none. The doctor had advised her to observe the child and report any changes in behaviour after starting the drug. Montelukast, used in patients with asthma or allergic rhinitis, is associated with a risk of neuropsychiatric adverse reactions (see box 1). These are uncommon and usually mild but can be worrisome and affect quality of life for patients and their families. Rarely, serious adverse reactions such as depression and suicide have been reported, mostly with prolonged use.8 Neuropsychiatric symptoms may be attributed to normal behavioural changes in children or to other conditions. Failure to recognise these adverse drug reactions early can result in serious harm to patients and their families. Box 1 ### Regulatory approval and safety warningsRETURN TO TEXT
Addendum: A tissue-engineered scale model of the heart ventricle
Authors: Luke A. MacQueen, Sean P. Sheehy, Christophe O. Chantre, John F. Zimmerman, Francesco S. Pasqualini, Xujie Liu, Josue A. Goss, Patrick H. Campbell, Grant M. Gonzalez, Sung-Jin Park, Andrew K. Capulli, John P. Ferrier, T. Fettah Kosar, L. Mahadevan, William T. Pu, Kevin Kit Parker
Journal: Nature Biomedical Engineering (2022)
HOSPITAL VALUE-BASED PURCHASING PROGRAM ASSOCIATED WITH LONG-TERM IMPROVEMENTS IN 30-DAY MORTALITY FOR HEART FAILURE AND ACUTE MYOCARDIAL INFARCTION AT BOTH MINORITY- AND NON-MINORITY SERVING US HOSPITALS
Authors: Prihatha Narasimmaraj, Ashley Kyalwazi, Andrew Oseran, Jiaman Xu, Rishi Wadhera
Journal: Journal of the American College of Cardiology (2022)
U.S. PATTERNS OF DRUG UTILIZATION AND PRESCRIPTION FILLS FOR PROVEN CARDIOPROTECTIVE ANTI-HYPERGLYCEMIC AGENTS
Authors: Arash Aghajani Nargesi, Callahan Clark, Mengni Liu, Lian Chen, Abraham Reddy, Samuel Amodeo, Evangelos K. Oikonomou, Marc Suchard, Kasia Lipska, Darren K. McGuire, Zhenqiu Lin, Silvio E. Inzucchi, Harlan M. Krumholz, Rohan Khera
Journal: Journal of the American College of Cardiology (2022)
HEART TEAM IS EVEN MORE CRITICAL WHEN DEALING WITH UNIQUE CLINICAL CONDITIONS: SUCCESSFUL PERCUTANEOUS INTERVENTION OF BILATERAL PULMONARY ARTERY STENOSIS AS A TREATMENT FOR SEVERE TRICUSPID REGURGITATION
Authors: Amy E. Simone, Vivek Rajagopal, Andrew J. Klein, Chad E. Miller, Vinod H. Thourani, Mani A. Vannan, Peter Flueckiger, Arun Krishnamoorthy, Pradeep Yadav
Journal: Journal of the American College of Cardiology (2022)
PEDIATRIC CONTINUOUS-FLOW TOTAL ARTIFICIAL HEART IN CONGENITAL POPULATION: REPORT ON VISUAL AND VIRTUAL DEVICE FITTING ASSESSMENT
Authors: Chihiro Miyagi, Munir Ahmad, Jamshid Karimov, Raymond Dessoffy, Anthony R. Polakowski, Christine R. Flick, Tara Karamlou, Kiyotaka Fukamachi, Hani K. Najm
Journal: Journal of the American College of Cardiology (2022)
Abstract P3-19-28: The impact of PM2.5 on the radiation-induced pneumonitis in patients with breast cancer
Authors: Dong-Yun Kim, In Ah Kim, Bum-Sup Jang
Journal: Cancer Research (2022)

Abstract Purpose: Exposure to particulate matter (PM) air pollution has been associated with adverse effect on respiratory disease, but no study has investigated its impact on radiation-induced pneumonitis (RIP) in patients with breast cancer who received adjuvant radiation therapy (RT). Materials and Methods: We conducted a retrospective review of 2,762 breast cancer patients who received postoperative RT between 2017 and 2020 in a single institution. Particulate matter data including PM2.5 and PM10 were retrieved from the open dataset in the ‘Gyeonggi Data Dream’. We used the average, median and maximum values of the PM2.5 and PM10 measured during daytime when a patient visited to the hospital for RT. We excluded the patients when missing PM data exceeded 50% of the total treatment period (N=26). Finally, altogether 2,736 patients were analyzed. Results: Overall incidence rate of RIP was 1.74%. There were no significant differences in average value of PM2.5 and number of RT fractions between RIP (+) and RIP (-) groups, but marginal differences were found in RT techniques (3-dimentional conformal RT vs. intensity modulated RT, P=0.053) and proportion of PM2.5 value ≥ 35 (μg/m3) (P=0.053) between the two groups. After adjusting for age, RT technique, regional irradiation, fractionation and boost, the average value of PM2.5 was significantly associated with a higher risk of RIP (Odds ratio [OR] 1.05, 95% confidential incidence [CI] 1.00-1.10, P=0.047) when patients received ≥ 20 fractions of RT. Especially, PM2.5 ≥ 35 (μg/m3) showed significant higher risk of RIP (OR 4.32, 95% CI 1.34-13.87, P=0.014) in patients with ≥ 20 fractions of RT after adjustment of aforementioned covariates. Other PM data (median, maximum value of PM2.5 and all PM10 values) were not related to the RIP regardless of the number of RT fractions. Conclusion: This is the first study to reveal the association between PM2.5 and RIP in breast cancer patients who received 20 fractions or more of postoperative RT. Citation Format: Dong-Yun Kim, In Ah Kim, Bum-Sup Jang. The impact of PM2.5 on the radiation-induced pneumonitis in patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-28.
Impact of the <scp>COVID</scp>‐19 pandemic on prescription of sacubitril/valsartan in Italy
Authors: Giuseppe M.C. Rosano, Simone Celant, Pier Paolo Olimpieri, Antonietta Colatrella, Graziano Onder, Andrea Di Lenarda, Giuseppe Ambrosio, Gianpaolo Reboldi, Gian Franco Gensini, Furio Colivicchi, Pierluigi Russo
Journal: European Journal of Heart Failure (2022)
Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease
Authors: Pedro R. Pereira, David F. Carrageta, Pedro F. Oliveira, Anabela Rodrigues, Marco G. Alves, Mariana P. Monteiro
Journal: Medicinal Research Reviews (2022)

Abstract Diabetic kidney disease (DKD) is one of the most prevalent comorbidities of diabetes mellitus and the leading cause of the end‐stage renal disease (ESRD). DKD results from chronic exposure to hyperglycemia, leading to progressive alterations in kidney structure and function. The early development of DKD is clinically silent and when albuminuria is detected the lesions are often at advanced stages, leading to rapid kidney function decline towards ESRD. DKD progression can be arrested or substantially delayed if detected and addressed at early stages. A major limitation of current methods is the absence of albuminuria in non‐albuminuric phenotypes of diabetic nephropathy, which becomes increasingly prevalent and lacks focused therapy. Metabolomics is an ever‐evolving omics technology that enables the study of metabolites, downstream products of every biochemical event that occurs in an organism. Metabolomics disclosures complex metabolic networks and provide knowledge of the very foundation of several physiological or pathophysiological processes, ultimately leading to the identification of diseases' unique metabolic signatures. In this sense, metabolomics is a promising tool not only for the diagnosis but also for the identification of pre‐disease states which would confer a rapid and personalized clinical practice. Herein, the use of metabolomics as a tool to identify the DKD metabolic signature of tubule interstitial lesions to diagnose or predict the time‐course of DKD will be discussed. In addition, the proficiency and limitations of the currently available high‐throughput metabolomic techniques will be discussed.
Screening potential P-glycoprotein inhibitors by combination of a detergent-free membrane protein extraction with surface plasmon resonance biosensor
Authors: Yuhong Cao, Jiahao Fang, Yiwei Shi, Hui Wang, Xiaofei Chen, Yue Liu, Zhenyu Zhu, Yan Cao, Zhanying Hong, Yifeng Chai
Journal: Acta Pharmaceutica Sinica B (2022)

P-glycoprotein (P-gp) highly expressed in cancer cells can lead to multidrug resistance (MDR) and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment. In this study, we established a label-free and detergent-free system combining surface plasmon resonance (SPR) biosensor with styrene maleic acid (SMA) polymer membrane proteins (MPs) stabilization technology to screen potential P-gp inhibitors. First, P-gp was extracted from MCF-7/ADR cells using SMA polymer to form SMA liposomes (SMALPs). Following that, SMALPs were immobilized on an SPR biosensor chip to establish a P-gp inhibitor screening system, and the affinity between P-gp and small molecule ligand was determined. The methodological investigation proved that the screening system had good specificity and stability. Nine P-gp ligands were screened out from 50 natural products, and their affinity constants with P-gp were also determined. The in vitro cell verification experiments demonstrated that tetrandrine, fangchinoline, praeruptorin B, neobaicalein, and icariin could significantly increase the sensitivity of MCF-7/ADR cells to Adriamycin (Adr). Moreover, tetrandrine, praeruptorin B, and neobaicalein could reverse MDR in MCF-7/ADR cells by inhibiting the function of P-gp. This is the first time that SMALPs-based stabilization strategy was applied to SPR analysis system. SMA polymer can retain P-gp in the environment of natural lipid bilayer and thus maintain the correct conformation and physiological functions of P-gp. The developed system can quickly and accurately screen small molecule ligands of complex MPs and obtain affinity between complex MPs and small molecule ligands without protein purification.
ADDITIONAL PROGNOSTIC VALUE OF PLEAQUE ANALYSIS FOR ON-SITE CT-DERIVED FFR IN CORONARY CT ANGIOGRAPHY ON MIDTERM PROGNOSIS
Authors: Yui Nozaki, Shinichiro Fujimoto, Chihiro Aoshima, Kawaguchi O. Yuko, Kazuhisa Takamura, Kudo Ayako, Takahashi Daigo, Hiki Makoto, Tomotaka Dohi, Nobuo Tomizawa, Tohru Minamino
Journal: Journal of the American College of Cardiology (2022)
RELATIONSHIP OF HEALTH STATUS TO ISCHEMIA AND CORONARY ANATOMY IN THE ISCHEMIA TRIAL
Authors: Lawrence M. Phillips, Judith Hochman, David Joel Maron, Leslee J. Shaw, Daniel S. Berman, John A. Spertus, Daniel B. Mark, Michael H. Picard, Bernard R. Chaitman, Philip Jones, Harmony Reynolds, Jelena Celutkiene, Gregg W. Stone, Joao V. Vitola, Nagaraja Moorthy
Journal: Journal of the American College of Cardiology (2022)
OXYGEN UPTAKE EFFICIENCY SLOPE IS ASSOCIATED WITH OUTCOME INDEPENDENTLY OF THE VE/VCO2 SLOPE: AN ANALYSIS OF HF-ACTION
Authors: Jonathan S. Gordon, Ambarish Pandey, Katherine C. Michelis, Colby Ayers, Jennifer T. Thibodeau, Justin Lee Grodin, Mark H. Drazner
Journal: Journal of the American College of Cardiology (2022)
PERCUTANEOUS CORONARY INTERVENTION OF TRIFURCATION LESIONS: INSIGHTS FROM THE PROSPECTIVE GLOBAL REGISTRY FOR THE STUDY OF BIFURCATION LESION INTERVENTIONS (PROGRESS-BIFURCATION) REGISTRY
Authors: Judit Karacsonyi, Spyridon Kostantinis, Alessandra Gutierrez, Vennela Avula, Bahadir Simsek, M. Nicholas Burke, Santiago Garcia, Mario Goessl, Paul Sorajja, Ivan J. Chavez, Michael R. Mooney, Anil K. Poulose, Jay H. Traverse, Yale L. Wang, Imre Ungi, Ilias Nikolakopoulos, Evangelia Vemmou, Raviteja Guddeti, Bavana V. Rangan, Emmanouil S. Brilakis
Journal: Journal of the American College of Cardiology (2022)
Effect of a low-cost, behaviour-change intervention on latrine use and safe disposal of child faeces in rural Odisha, India: a cluster-randomised controlled trial
Authors: Bethany A Caruso, Gloria D Sclar, Parimita Routray, Corey L Nagel, Fiona Majorin, Steven Sola, William J Koehne, Thomas Clasen
Journal: The Lancet Planetary Health (2022)

Uptake of Government-promoted sanitation remains a challenge in India. We aimed to investigate a low-cost, theory-driven, behavioural intervention designed to increase latrine use and safe disposal of child faeces in India.
Abstract P3-14-08: The influence of metabolic factors, migration, and ethnic disparities on breast cancer risk and treatment
Authors: Trygve Lofterød, Hanne Frydenberg, Marit Veierød, Anne Karen Jenum, Jon B Reitan, Erik Wist, Inger Thune
Journal: Cancer Research (2022)

Abstract Background: Migrant studies have shown an increase in breast cancer incidence rates among immigrants moving from a breast cancer low-incidence to a high-incidence country. However, 30 years after immigration, it remains equivocal to what degree metabolic factors and ethnic disparities affect breast cancer development and treatment. Methods: Using Cox regression models, we examined the association between ethnicity and breast cancer development, and whether this association varied by pre-diagnostic metabolic profiles among 13 802 women, aged 20-75 years, participating in the population-based Oslo Ethnic Breast Cancer Study. Ethnicity was categorized into: women of Western European descent (reference population) and women of non-western ethnicity (ethnic minority). The ethnic minority women were further subclassified into three groups: 1) South Asian, 2) Middle East and North African, and 3) all other non-western origin women. We defined four pre-diagnostic unfavorable metabolic factors (above median body mass index (&amp;gt;24.6 kg/m2), waist:hip ratio (&amp;gt;0.79), triglyceride:HDL-cholesterol ratio (&amp;gt;0.73), and blood pressure (&amp;gt;96.5 mmHg)), which were combined to define three metabolic profiles: (0-2, 3, and 4 unfavorable metabolic factors). A total of 557 women developed invasive breast cancer during a mean 16.5 years of follow-up. Detailed medical records were obtained. Results: Among women with an unfavorable metabolic profile, South Asian women, compared with Western European women, had a 2.3 times higher breast cancer risk (HR 2.30, 95% CI 1.18-4.49). Furthermore, the ethnic minority women, compared with the Western European women, were suggestively more likely to present with triple-negative breast cancer (OR 2.11, 95% CI 0.97-4.61), and less likely to complete all courses of planned taxane treatment (OR 0.26, 95% CI 0.08-0.82). No differences by ethnicity were observed in physicians’ decisions of planned breast cancer treatment, Conclusions: Our results support that metabolic factors, including body composition, serum lipids and blood pressure, are important when balancing breast cancer prevention and disease management among non-western women migrating from a breast cancer low-incidence to a high-incidence country. However, larger studies are needed. Citation Format: Trygve Lofterød, Hanne Frydenberg, Marit Veierød, Anne Karen Jenum, Jon B Reitan, Erik Wist, Inger Thune. The influence of metabolic factors, migration, and ethnic disparities on breast cancer risk and treatment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-08.
DIASTOLIC PLATEAU - INVASIVE HEMODYNAMIC MARKER OF ADVERSE OUTCOME AMONG LVAD PATIENTS
Authors: Avishay Grupper, Afek Kodesh, Jacob Lavee, Paul Fefer, Israel Barbash, Dan Elian, Avi Morgan, Dov Freimark, Amit Segev, Elad Maor
Journal: Journal of the American College of Cardiology (2022)
TRICUSPID AND PULMONARY VALVE REPLACEMENT IN CARCINOID HEART DISEASE: INSIGHTS AND TRENDS FROM A NATIONALLY REPRESENTATIVE DATABASE
Authors: Kevin Honan, Dominique Monlezun, Efstratios Koutroumpakis, Nicolas L. Palaskas, Mehmet Cilingiroglu, Juan C. Lopez-Mattei, Konstantinos Marmagkiolis, Bindu Akkanti, Biswajit Kar, Igor D. Gregoric, Anita Deswal, Cezar Iliescu, Saamir Hassan
Journal: Journal of the American College of Cardiology (2022)
SPLANCHNIC NERVE MODULATION EFFECTS ON SURROGATES MEASURES OF VENOUS COMPLIANCE
Authors: Veraprapas Kittipibul, Arun Ganesh, Aubrie Coburn, Brian J. Coyne, Jeroen Molinger, Neil Ray, Mihai Podgoreanu, Philipp Lurz, Curtis Fitzhugh, Cynthia L. Green, Adrian F. Hernandez, Manesh R. Patel, Marat Fudim
Journal: Journal of the American College of Cardiology (2022)
HYBRID CARDIAC ABLATION AND LEFT ATRIAL APPENDAGE CLOSURE: INSIGHT FROM NATIONAL DATABASE
Authors: Mohamed Hamed, Ramez Morcos, Muni Rubens, Anshul Saxena, Emad Samaan, Omar Hegazy, Mohamed Abdelazeem, Beshoy Elkatcha, Brian Blair, Daniel Jacobs, Brijeshwar Singh Maini, Emir Veledar, Houman Khalili
Journal: Journal of the American College of Cardiology (2022)
Detection of signs of disease in external photographs of the eyes via deep learning
Authors: Boris Babenko, Akinori Mitani, Ilana Traynis, Naho Kitade, Preeti Singh, April Y. Maa, Jorge Cuadros, Greg S. Corrado, Lily Peng, Dale R. Webster, Avinash Varadarajan, Naama Hammel, Yun Liu
Journal: Nature Biomedical Engineering (2022)
Lifestyle and Cardiovascular Risk Factors Associated With Heart Failure Subtypes in Postmenopausal Breast Cancer Survivors
Authors: Kerryn W. Reding, Richard K. Cheng, Alexi Vasbinder, Roberta M. Ray, Ana Barac, Charles B. Eaton, Nazmus Saquib, Aladdin H. Shadyab, Michael S. Simon, Dale Langford, Mary Branch, Bette Caan, Garnet Anderson
Journal: JACC CardioOncology (2022)

Breast cancer (BC) survivors experience an increased burden of long-term comorbidities, including heart failure (HF). However, there is limited understanding of the risk for the development of HF subtypes, such as HF with preserved ejection fraction (HFpEF), in BC survivors. This study sought to estimate the incidence of HFpEF and HF with reduced ejection fraction (HFrEF) in postmenopausal BC survivors and to identify lifestyle and cardiovascular risk factors associated with HF subtypes. Within the Women's Health Initiative, participants with an adjudicated diagnosis of invasive BC were followed to determine the incidence of hospitalized HF, for which adjudication procedures determined left ventricular ejection fraction. We calculated cumulative incidences of HF, HFpEF, and HFrEF. We estimated HRs for risk factors in relation to HF, HFpEF, and HFrEF using Cox proportional hazards survival models. In 2,272 BC survivors (28.6% Black and 64.9% White), the cumulative incidences of hospitalized HFpEF and HFrEF were 6.68% and 3.96%, respectively, over a median of 7.2 years (IQR: 3.6-12.3 years). For HFpEF, prior myocardial infarction (HR: 2.83; 95% CI: 1.28-6.28), greater waist circumference (HR: 1.99; 95% CI: 1.14-3.49), and smoking history (HR: 1.65; 95% CI: 1.01-2.67) were the strongest risk factors in multivariable models. With the exception of waist circumference, similar patterns were observed for HFrEF, although none were significant. In relation to those without HF, the risk of overall mortality in BC survivors with hospitalized HFpEF was 5.65 (95% CI: 4.11-7.76), and in those with hospitalized HFrEF, it was 3.77 (95% CI: 2.51-5.66). In this population of older, racially diverse BC survivors, the incidence of HFpEF, as defined by HF hospitalizations, was higher than HFrEF. HF was also associated with an increased mortality risk. Risk factors for HF were largely similar to the general population with the exception of prior myocardial infarction for HFpEF. Notably, both waist circumference and smoking represent potentially modifiable factors.
Protein Kinase A Downregulation Delays the Development and Progression of Polycystic Kidney Disease
Authors: Xiaofang Wang, Li Jiang, Ka Thao, Caroline R. Sussman, Timothy LaBranche, Michael Palmer, Peter C. Harris, G. Stanley McKnight, Klaus P. Hoeflich, Stefanie Schalm, Vicente E. Torres
Journal: Journal of the American Society of Nephrology (2022)

Upregulation of cAMP-dependent and cAMP-independent PKA signaling is thought to promote cystogenesis in polycystic kidney disease (PKD). PKA-I regulatory subunit RIα is increased in kidneys of orthologous mouse models. Kidney-specific knockout of RIα upregulates PKA activity, induces cystic disease in wild-type mice, and aggravates it in Pkd1RC/RC mice.PKA-I activation or inhibition was compared with EPAC activation or PKA-II inhibition using Pkd1RC/RC metanephric organ cultures. The effect of constitutive PKA (preferentially PKA-I) downregulation in vivo was ascertained by kidney-specific expression of a dominant negative RIαB allele in Pkd1RC/RC mice obtained by crossing Prkar1αR1αB/WT, Pkd1RC/RC , and Pkhd1-Cre mice (C57BL/6 background). The effect of pharmacologic PKA inhibition using a novel, selective PRKACA inhibitor (BLU2864) was tested in mIMCD3 3D cultures, metanephric organ cultures, and Pkd1RC/RC mice on a C57BL/6 × 129S6/Sv F1 background. Mice were sacrificed at 16 weeks of age.PKA-I activation promoted and inhibition prevented ex vivo P-Ser133 CREB expression and cystogenesis. EPAC activation or PKA-II inhibition had no or only minor effects. BLU2864 inhibited in vitro mIMCD3 cystogenesis and ex vivo P-Ser133 CREB expression and cystogenesis. Genetic downregulation of PKA activity and BLU2864 directly and/or indirectly inhibited many pro-proliferative pathways and were both protective in vivo. BLU2864 had no detectable on- or off-target adverse effects.PKA-I is the main PKA isozyme promoting cystogenesis. Direct PKA inhibition may be an effective strategy to treat PKD and other conditions where PKA signaling is upregulated. By acting directly on PKA, the inhibition may be more effective than or substantially increase the efficacy of treatments that only affect PKA activity by lowering cAMP.