Forschung

New drug targets/pharmacological research

Fischer L, Schmidt A, Dopychai A, Joussen S, Joeres N, Oslender-Bujotzek A, Schmalzing G, Gruender S. Physiologically relevant acid-sensing ion channel (ASIC) 2a/3 heteromers have a 1:2 stoichiometry. Commun Biol 2023 Jul 8; 6(1):701. doi: 10.1038/s42003-023-05087-4. PMID: 37422581.

Grohs L, Cheng L, Cönen S, Haddad BG, Bülow A, Toklucu I, Ernst L, Körner J, Schmalzing G, Lampert A,  Machtens JP, Hausmann R. Diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) are competitive antagonists of the human P2X3 receptor. Front Pharmacol 2023 Mar 16; 14:1120360. doi: 10.3389/fphar.2023.1120360. eCollection 2023. PMID: 37007008

Grohs L, Cheng L, Cönen S, Haddad BG, Bülow A, Toklucu I, Ernst L, Körner J, Schmalzing G, Lampert A,  Machtens JP, Hausmann R. Corrigendum: Diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) are competitive antagonists of the human P2X3 receptor. Front Pharmacol 2023 Jun 2: 14:1225522. doi: 10.3389/fphar.2023.1225522. eCollection 2023. PMID: 37332347.

Kriegeskorte S, Bott R, Hampl M, Korngreen A, Hausmann R*, Lampert A*. Cold and warmth intensify pain-linked sodium channel gating effects and persistent currents. J Gen Physiol 2023 Sep 4; 155(9): e202213312. doi: 10.1085/jgp.202213312. Epub 2023 Aug 2. PMID: 37531097, * corresponding authors.

Richter K, Asci N, Singh VK, Yakoob SH, Meixner M, Zakrzewicz A, Liese J, Hecker A, Wilker S, Stumpf S, Schlueter KD, Rohde M, Goedecke A, Padberg W, Manzini I, Schmalzing G, Grau V. Activation of endothelial NO synthase and P2X7 receptor modification mediates the cholinergic control of ATP-induced interleukin-1 beta release by mononuclear phagocytes. Front Immunol 2023 Mar; 14: 1140592. doi: 10.3389/fimmu.2023.1140592. eCollection 2023. PMID: 36969210.

Yang R, Shi L, Si H, Hu Z, Zou L, Li L, Xu X, Schmalzing G, Nie H, Li G, Liu S, Liang S, Xu C. Gallic Acid Improves Comorbid Chronic Pain and Depression Behaviors by Inhibiting P2X7 Receptor-Mediated Ferroptosis in the Spinal Cord of Rats. ACS Chem Neurosci 2023 Feb; 14(4): 667-676. doi: 10.1021/acschemneuro.2c00532. Epub 2023 Jan 31. PMID: 36719132.

Personalized drug safety/Clinical pharmacogenetic research

Alaeddin N, Pehlivan G, Stingl JC, Breteler MMB, de Vries FM. Prevalence and determinants of over- and undertreatment among users of antihypertensive drugs in the general population: The Rhineland Study. Eur J Prev Cardiol 2023 Aug 25: zwad274. doi: 10.1093/eurjpc/zwad274. Online ahead of print. PMID: 37622586

Alaeddin N, Jongejan RMS, Stingl JC, de Rijke YB, Peeters RP, Breteler MMB, de Vries FM. Over- and Undertreatment With Levothyroxine. Dtsch Arztebl Int 2023 Oct 20; 120(42): 711-718. doi: 10.3238/arztebl.m2023.0192. PMID: 37656481.

Bergs I, Just KS, Scholl C, Dreher M, Stingl JC. Inhalation therapies in COPD - adverse drug reactions impact on emergency department presentations. Eur J Clin Pharmacol 2023 Feb; 79(2): 219-227. doi: 10.1007/s00228-022-03433-9. Epub 2022 Dec 9. PMID: 36484792.

Desai P, Dasgupta A, Sofias AM, Peña Q, Göstl R, Slabu I, Schwaneberg U, Stiehl T, Wagner W, Jockenhövel S, Stingl J, Kramann R, Trautwein C, Brümmendorf TH, Kiessling F, Herrmann A, Lammers T. Transformative Materials for Interfacial Drug Delivery. Adv Healthc Mater 2023 Aug; 12(20): e2301062. doi: 10.1002/adhm.202301062. Epub 2023 Jun 6. PMID: 37282805.

Freitag M, Bülow T, Fleig S, Eisert A, Krause O, Bollheimer LC, Laurentius T. Continuation of Geriatric Discharge Medication in Primary Care and its Association with Rehospitalizations - A Cohort Study. Pharmazie 2023 Aug 1; 78(8): 150-161. doi: 10.1691/ph.2023.3558. PMID: 37592419.

Just KS, Schultze KA, Dormann H, Seufferlein T, Gräff I, Scholl C, Schwab M, Stingl JC. Use of overactive bladder anticholinergic medications associated with falls leading to emergency department visits: results from the ADRED study. Eur J Clin Pharmacol 2023 Sep; 79(9): 1185-1193. doi: 10.1007/s00228-023-03530-3. Epub 2023 Jun 29. PMID: 37382655.

Leitzen S, Dubrall D, Toni I, Stingl J, Christ P, Köberle U, Schmid M, Neubert A, Sachs B. Adverse Drug Reactions in Children: Comparison of Reports Collected in a Pharmacovigilance Project Versus Spontaneously Collected ADR Reports. Paediatr Drugs 2023 Mar; 25(2): 203-215. doi: 10.1007/s40272-022-00540-z. Epub 2022 Nov 12. PMID: 36369590.

Swen JJ, van der Wouden CH, Manson LE, Abdullah-Koolmees H, Blagec K, Blagus T, Böhringer S, Cambon-Thomsen A, Cecchin E, Cheung KC, Deneer VH, Dupui M, Ingelman-Sundberg M, Jonsson S, Joefield-Roka C,  Just KS, Karlsson MO, Konta L, Koopmann R, Kriek M, Lehr T, Mitropoulou C, Rial-Sebbag E, Rollinson V, Roncato R, Samwald M, Schaeffeler E, Skokou M, Schwab M, Steinberger D, Stingl JC, Tremmel R, Turner RM, van Rhenen MH, Dávila Fajardo CL, Dolžan V, Patrinos GP, Pirmohamed M, Sunder-Plassmann G, Toffoli G, Guchelaar HJ, Ubiquitous Pharmacogenomics Consortium. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet 2023 Feb 4; 401(10374): 347-356. doi: 10.1016/S0140-6736(22)01841-4. PMID: 36739136

Imaging and data research

Labek K, Sittenberger E, Kienhöfer V, Rabl L, Messina I, Schurz M, Stingl JC, Viviani R. The gradient model of brain organization in decisions involving "empathy for pain". Cereb Cortex 2023 May; 33(10): 5839-5850. doi: 10.1093/cercor/bhac464. PMID: 36537039.

Molecular modeling and ion channel biophysics

Kostritskii AY, Machtens JP. Domain- and state-specific shape of the electric field tunes voltage sensing in voltage-gated sodium channels. Biophys J 2023 May 16; 122(10): 1807-1821. doi: 10.1016/j.bpj.2023.04.013. Epub 2023 Apr 18. PMID: 37077046.

Kuwabara MF, Haddad BG, Lenz-Schwab D, Hartmann J, Longo P, Huckschlag BM, Fuß A, Questino A, Berger TK, Machtens JP, Oliver D. Elevator-like movements of prestin mediate outer hair cell electromotility. Nat Commun 2023 Nov 6; 14(1): 7145. doi: 10.1038/s41467-023-42489-8. PMID: 37932294.

Suslova M, Kortzak D, Machtens JP, Kovermann P, Fahlke C. Apo state pore opening as functional basis of increased EAAT anion channel activity in episodic ataxia 6. Front Physiol 2023 Jul 19; 14: 1147216. doi: 10.3389/fphys.2023.1147216. eCollection 2023. PMID: 37538371.

Pharmaceutical Research

Jibai N, Koch A, Ulmer TF, Erdmann P, Koeck JA, Eisert A. Pharmaceutical Interventions for Inpatients with Liver Cirrhosis and Liver Transplantation: A Systematic Review of Experimental Studies. J Clin Med 2023 Nov 10; 12(22): 7030. doi: 10.3390/jcm12227030. PMID: 38002644.

Koeck JA, Dohmen SM, Marx G, Eisert A. Comparison of Drug-Related Problems in COVID-19 and Non-COVID-19 Patients Provided by a German Telepharmacy Service for Rural Intensive Care Units. J Clin Med 2023 Jul 18; 12(14): 4739. doi: 10.3390/jcm12144739. PMID: 37510855

Conceptual papers, transformative materials in life sciences

Fernández-Colino A, Kiessling F, Slabu I, De Laporte L, Akhyari P, Nagel SK, Stingl J, Reese S, Jockenhoevel S. Lifelike Transformative Materials for Biohybrid Implants: Inspired by Nature, Driven by Technology. Adv Healthc Mater 2023 Aug; 12(20):e2300991. doi: 10.1002/adhm.202300991. Epub 2023 Jun 8. PMID: 37290055.

Gerardo-Nava JL, Jansen J, Günther D, Klasen L, Thiebes AL, Niessing B, Bergerbit C, Meyer AA, Linkhorst J, Barth M, Akhyari P, Stingl J, Nagel S, Stiehl T, Lampert A, Leube R, Wessling M, Santoro F, Ingebrandt S, Jockenhoevel S, Herrmann A, Fischer H, Wagner W, Schmitt RH, Kiessling F, Kramann R, De Laporte L. Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner. Adv Healthc Mater 2023 Aug; 12(20): e2301030. doi: 10.1002/adhm.202301030. Epub 2023 Jun 13. PMID: 37311209.

International diversity in drug metabolism and transport, pharmacogenetics

Mbavha BT, Kanji CR, Stadler N,  Stingl J, Stanglmair A, Scholl C, Wekwete W, Masimirembwa C.  Population genetic polymorphisms of pharmacogenes in Zimbabwe, a potential guide for the safe and efficacious use of medicines in people of African ancestry. Pharmacogenet Genomics. 2022 Jul 1;32(5):173-182. doi: 10.1097/FPC.0000000000000467. Epub 2022 Feb 21. PMID: 35190514.EM

New drug target/pharmacological research

Schiller IC, Jacobson KA, Wen Z,  Malisetty A,  Schmalzing G, Markwardt F.   Dihydropyridines Potentiate ATP-Induced Currents Mediated by the Full-Length Human P2X5 Receptor. Molecules. 2022 Mar 11;27(6):1846. doi: 10.3390/molecules27061846. PMID: 35335209.

Schmalzing G, Markwardt F.   Established Protocols for cRNA Expression and Voltage-Clamp Characterization of the P2X7 Receptor in Xenopus laevis Oocytes. Methods Mol Biol. 2022;2510:157-192. doi: 10.1007/978-1-0716-2384-8_9. PMID: 35776325.

Weinhausen S, Nagel J, Namasivayam V, Spanier C, Abdelrahman A, Hanck T,  Hausmann R, Müller CE.   Extracellular binding sites of positive and negative allosteric P2X4 receptor modulators. Life Sci. 2022 Dec 15;311(Pt A):121143. doi: 10.1016/j.lfs.2022.121143. Epub 2022 Nov 1. PMID: 36328074.

Xu X, Zhang H, Li L, Yang R, Li G, Liu S,  Schmalzing G, Nie H, Liang S. Study of the Involvement of the P2Y12 Receptor in Chronic Itching in Type 2 Diabetes Mellitus. Mol Neurobiol. 2022 Mar;59(3):1604-1618. doi: 10.1007/s12035-021-02676-4. Epub 2022 Jan 9. PMID: 35000152.

CYP2B6

Eum S, Sayre F, Lee AM, Stingl JC, Bishop JR. Association of CYP2B6 genetic polymorphisms with bupropion and hydroxybupropion exposure: A systematic review and meta-analysis. Pharmacotherapy. 2022 Jan;42(1):34-44. doi: 10.1002/phar.2644. Epub 2021 Nov 23. PMID: 34752647.

Personalized drug safety/Clinical pharmacogenetic research

Alaeddin N, Stingl JC, Breteler MMB, de Vries FM. Validation of Self-Reported Medication Use Applying Untargeted Mass Spectrometry-Based Metabolomics Techniques in the Rhineland Study. Br J Clin Pharmacol. 2022 May;88(5):2380-2395. doi: 10.1111/bcp.15175. Epub 2021 Dec 28. PMID: 34907581.

Bergs I,  Just KS, Müller A,  Stingl JC, Dreher M.   Emergency Department Visits Due to Dyspnea: Association with Inhalation Therapy in COPD and Cases with Adverse Drug Reactions. Int J Chron Obstruct Pulmon Dis. 2022 Aug 11;17:1827-1834. doi: 10.2147/COPD.S367062. eCollection 2022. PMID: 35983166.

Brücken D, Unterkofler J, Pauge S, Bienzeisler J, Hübel C, Zechbauer S, Rossaint R, Greiner W, Aufenberg B, Röhrig R, Bollheimer LC, Optimal@NRW Research Group , Brokmann JC.  Optimal@NRW: optimized acute care of nursing home residents using an intersectoral telemedical cooperation network - study protocol for a stepped-wedge trial. Trials. 2022 Sep 27;23(1):814. doi: 10.1186/s13063-022-06613-1. PMID: 36167557

Fracowiak J, Huebner T, Heß S, Roethlein C, Langner D, Schneider U, Falkenberg F, Scholl C, Linder R,  Stingl J, Haenisch B, Steffens M.   Evaluation of the EMPAR study population on the basis of metabolic phenotypes of selected pharmacogenes. Pharmacogenomics J. 2022 Mar;22(2):136-144. doi: 10.1038/s41397-022-00268-6. Epub 2022 Jan 31. PMID: 35102241.

Just KS, Schmitt J. Pharmacogenomics of peri-menopausal hormone therapy. GYNAKOLOGISCHE ENDOKRINOLOGIE. 2022. doi: 10.1007/s10304-022-00483-1.

Mathey CM, Maj C, Scheer AB, Fazaal J, Wedi B, Wieczorek D, Amann PM, Löffler H, Koch L, Schöffl C, Dickel H, Ganjuur N, Hornung T, Forkel S, Greve J, Wurpts G, Hallberg P, Bygum A, Von Buchwald C, Karawajczyk M, Steffens M,  Stingl J, Hoffmann P, Heilmann-Heimbach S, Mangold E, Ludwig KU, Rasmussen ER, Wadelius M, Sachs B, Nöthen MM, Forstner AJ.   Molecular Genetic Screening in Patients With ACE Inhibitor/Angiotensin Receptor Blocker-Induced Angioedema to Explore the Role of Hereditary Angioedema Genes. Front Genet. 2022 Jul 18;13:914376. doi: 10.3389/fgene.2022.914376. eCollection 2022. PMID: 35923707.

Seufferlein T, Ettrich TJ, Menzler S, Messmann H, Kleber G, Zipprich A, Frank-Gleich S, Algül H, Metter K, Odemar F, Heuer T, Hügle U, Behrens R, Berger AW, Scholl C, Schneider KL, Perkhofer L, Rohlmann F, Muche R, Stingl JC.  Green Tea Extract to Prevent Colorectal Adenomas, Results of a Randomized, Placebo-Controlled Clinical Trial. Am J Gastroenterol. 2022 Jun 1;117(6):884-894.        
doi: 10.14309/ajg.0000000000001706. Epub 2022 Feb 25. PMID: 35213393.

Stingl JC,  Radermacher J,  Wozniak J, Viviani R.   Pharmacogenetic Dose Modeling Based on CYP2C19 Allelic Phenotypes. Pharmaceutics. 2022 Dec 16;14(12):2833. doi: 10.3390/pharmaceutics14122833. PMID: 36559326.

Weber-Lassalle K, Ernst C, Reuss A, Möllenhoff K, Baumann K, Jackisch C, Hauke J, Dietrich D, Borde J, Park-Simon TW, Hanker L, Prieske K, Schmidt S, Weber-Lassalle N, Pohl-Rescigno E, Kommoss S, Marmé F, Heitz F, Stingl JC, Schmutzler RK, Harter P, Hahnen E. Clonal Hematopoiesis-Associated Gene Mutations in a Clinical Cohort of 448 Patients with Ovarian Cancer. J Natl Cancer Inst. 2022 Apr 11;114(4):565-570. doi: 10.1093/jnci/djab231. PMID: 34963005.

Yamoune S, Wintz K, Niederau C, Craveiro RB, Wolf M, Stingl J. Role of cytochrome P450 2C8 genetic polymorphism and epoxygenase uncoupling in periodontal remodelling affecting orthodontic treatment. Basic Clin Pharmacol Toxicol. 2022 Jan;130(1):132-140. doi: 10.1111/bcpt.13681. Epub 2021 Nov 16. PMID: 34740282.

Yamoune S,  Wintz K, Niederau C, Craveiro RB, Wolf M,  Stingl J. Pharmacogenetic and drug interaction aspects on ketamine safety in its use as antidepressant - implications for precision dosing in a global perspective. Br J Clin Pharmacol. 2022 Dec;88(12):5149-5165. doi: 10.1111/bcp.15467. Epub 2022 Aug 5. PMID: 35863300.

Imaging and data research

Labek K, Sittenberger E, Kienhöfer V, Rabl L, Messina I, Schurz M,  Stingl JC, Viviani R.  The gradient model of brain organization in decisions involving "empathy for pain". Cereb Cortex. 2022 Dec 19;bhac464. doi: 10.1093/cercor/bhac464. Online ahead of print. PMID: 36537039.

Molecular modeling and physiology

Alleva C,  Machtens JP, Kortzak D, Weyand I, Fahlke C . Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters.  Neurochem Res. 2022 Jan;47(1):9-22. doi: 10.1007/s11064-021-03252-x. Epub 2021 Feb 15. PMID: 33587237.  

Etges A, Hellmig N, Walenda G, Haddad BG,  Machtens JP, Morosan T, Rump LC, Scholl UI.   A Novel Homozygous KLHL3 Mutation as a Cause of Autosomal Recessive Pseudohypoaldosteronism Type II Diagnosed Late in Life. Nephron. 2022;146(4):418-428. doi: 10.1159/000521626. Epub 2022 Jan 28. PMID: 35093948.

Pharmaceutical Research

Bosch KE, Werner CJ, Rueckbeil MV,  Eisert A.  Use of electronic adverse drug reaction check to identify inpatients with a high drug-associated risk of falling: a case-control study at the Department of Neurology. Pharmazie. 2022 Feb 1;77(2):67-75. doi: 10.1691/ph.2022.1807. PMID: 35209966.

Keller L, Dempfle A, Dahmen B, Schreiber S, Adan RAH, Andreani NA, Danner UN,  Eisert A, Fetissov S, Fischmeister FPS, Karwautz A, Konrad K, Kooij KL, Trinh S, van der Vijgh B, van Elburg AA, Zeiler M, Baines J, Seitz J, Herpertz-Dahlmann B.  The effects of polyunsaturated fatty acid (PUFA) administration on the microbiome-gut-brain axis in adolescents with anorexia nervosa (the MiGBAN study): study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial. Trials. 2022 Jul 5;23(1):545. doi: 10.1186/s13063-022-06413-7. PMID: 35790976.

Schilling S, Koeck JA, Kontny U, Orlikowsky T, Erdmann H,  Eisert A.   High-alert medications for hospitalised paediatric patients - a two-step survey among paediatric clinical expert pharmacists in Germany. Pharmazie. 2022 Jun 1;77(6):207-215. doi: 10.1691/ph.2022.12025. PMID: 35751160.

Schmitz K, Lenssen R, Rückbeil M, Berning D, Thomeczek C, Brokmann JC, Jaehde U,  Eisert A.  The WHO High 5s project: medication reconciliation in a German university hospital. A prospective observational cohort study. Z Evid Fortbild Qual Gesundhwes. 2022 Feb;168:27-32. doi: 10.1016/j.zefq.2021.11.006. Epub 2022 Feb 9. PMID: 35148970.

Conceptual papers, regulatory science

Huber C, Friede T, Stingl J, Benda N. Classification of Companion Diagnostics: A New Framework for Biomarker-Driven Patient Selection. Ther Innov Regul Sci. 2022 Mar;56(2):244-254. doi: 10.1007/s43441-021-00352-2. Epub 2021 Nov 28. PMID: 34841493.

Covid-19-related or antiviral pharmacological issues

Hein S, Herrlein ML, Mhedhbi I, Bender D, Haberger V, Benz N, Eisert J, Stingl J, Dreher M, Oberle D, Schulze J, Mache C, Budt M, Hildt C, Wolff T, Hildt E. Analysis of BNT162b2- and CVnCoV-elicited sera and of convalescent sera toward SARS-CoV-2 viruses. Allergy. 2022 Jul; 77(7):2080-2089. doi: 10.1111/all.15189. Epub 2021 Dec 2. PMID: 34820854.

Herrlein ML, Hein S, Zahn T, Mhedhbi I, Raupach J, Husria Y, Benz NI, Eisert J, Bender D, Haberger V, Hastert FD, Henss L, Schnierle BS,  Stingl JC, Dreher M, Hildt E. Comparative Investigation of Methods for Analysis of SARS-CoV-2-Spike-Specific Antisera. Viruses. 2022 Feb 17;14(2):410. doi: 10.3390/v14020410. PMID: 35216003.

Herrlein ML, Schmanke P, Elgner F, Sabino C, Akhras S, Bender D, Glitscher M, Tabari D, Scholl C,  Stingl J, Hildt E.   Catch Me if You Can: the Crosstalk of Zika Virus and the Restriction Factor Tetherin. J Virol. 2022 Feb 23;96(4):e0211721. doi: 10.1128/jvi.02117-21. Epub 2021 Dec 22. PMID: 34935441.

International diversity in drug metabolism and transport, pharmacogenetics

Mufwambi W, Stingl J, Masimirembwa C, Manasa J, Nhachi C, Stadler N, Mwila C, Kalungia AC, Mukosha M, Mutiti CS, Kamoto A, Kaonga P, Godman B, Munkombwe D. Healthcare Professionals' Knowledge of Pharmacogenetics and Attitudes Towards Antimicrobial Utilization in Zambia: Implications for a Precision Medicine Approach to Reducing Antimicrobial Resistance. Front Pharmacol. 2021 Jan 12;11:551522. doi: 10.3389/fphar.2020.551522. PMID: 33510634; PMCID: PMC7835886.

Mutiti CS, Kapungu NN, Kanji CR, Stadler N, Stingl J, Nhachi C, Hakim J, Masimirembwa C, Thelingwani RS. Clinically relevant enantiomer specific R- and S-praziquantel pharmacokinetic drug-drug interactions with efavirenz and ritonavir. Pharmacol Res Perspect. 2021 May;9(3):e00769. doi: 10.1002/prp2.769. PMID: 33929078; PMCID: PMC8085964.

Pavez Loriè E, Baatout S, Choukér A, Buchheim JI, Baselet B, Dello Russo C, Wotring V, Monici M, Morbidelli L, Gagliardi D, Stingl JC, Surdo L, Yip VLM. The Future of Personalized Medicine in Space: From Observations to Countermeasures. Front Bioeng Biotechnol. 2021 Dec 13;9:739747. doi: 10.3389/fbioe.2021.739747. PMID: 34966726; PMCID: PMC8710508.

Rodeiro Guerra I, Herrea J, Cuétara E, Garrido G, Reyes E, Martínez I, Pérez CL, Fernández G, Hernández-Balmaseda I, Delgado R, Stingl JC, Berghe WV. Prevalence of ABCB1 3435C>T polymorphism in the Cuban population. Drug Metab Pers Ther. 2021 Dec 6. doi: 10.1515/dmpt-2020-0156. Epub ahead of print. PMID: 34860473.

New drug target/pharmacological research

Grohmann M, Schumacher M, Günther J, Singheiser SM, Nußbaum T, Wildner F, Gerevich Z, Jabs R, Hirnet D, Lohr C, Illes P, Schmalzing G, Franke H, Hausmann R. BAC transgenic mice to study the expression of P2X2 and P2Y1 receptors. Purinergic Signal. 2021 Sep;17(3):449-465. doi: 10.1007/s11302-021-09792-9. Epub 2021 May 28. PMID: 34050505; PMCID: PMC8410928.

Illes P, Müller CE, Jacobson KA, Grutter T, Nicke A, Fountain SJ, Kennedy C, Schmalzing G, Jarvis MF, Stojilkovic SS, King BF, Di Virgilio F. Update of P2X receptor properties and their pharmacology: IUPHAR Review 30. Br J Pharmacol. 2021 Feb;178(3):489-514. doi: 10.1111/bph.15299. Epub 2020 Dec 21. PMID: 33125712; PMCID: PMC8199792.

Shi L, Sun M, Ren X, Li Z, Yang R, Xu X, Li L, Li G, Liu S, Schmalzing G, Nie H, Li G, Liang S. LncRNA UC.360+ shRNA Improves Diabetic Cardiac Sympathetic Dysfunction Mediated by the P2X4 Receptor in the Stellate Ganglion. ACS Chem Neurosci. 2021 Apr 7;12(7):1210-1218. doi: 10.1021/acschemneuro.1c00050. Epub 2021 Mar 18. PMID: 33733741.

Strieder T, Puelles VG, Vogt M, Buhl EM, Saritas T, Hausmann R, Sterzer V, Leuchtle K, Boor P, Floege J, Moeller MJ, Stamellou E. Effects of Perfusion Pressures on Podocyte Loss in the Isolated Perfused Mouse Kidney. Cell Physiol Biochem. 2021 Apr 14;55(S4):1-12. doi: 10.33594/000000355. PMID: 33851800.

Yang R, Li Z, Zou Y, Yang J, Li L, Xu X, Schmalzing G, Nie H, Li G, Liu S, Liang S, Xu C. Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway. Front Pharmacol. 2021 Aug 25;12:680139. doi: 10.3389/fphar.2021.680139. PMID: 34512324; PMCID: PMC8423904.

CYP2B6

Langmia IM, Just KS, Yamoune S, Brockmöller J, Masimirembwa C, Stingl JC. CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations-Implication for Drug Safety, Dosing, and Individualized Therapy. Front Genet. 2021 Jul 12;12:692234. doi: 10.3389/fgene.2021.692234. PMID: 34322158; PMCID: PMC8313315.

Personalized drug safety/Clinical pharmacogenetic research

Just KS, Scholl C, Boehme M, Kastenmüller K, Just JM, Bleckwenn M, Holdenrieder S, Meier F, Weckbecker K, Stingl JC. Individualized versus Standardized Risk Assessment in Patients at High Risk for Adverse Drug Reactions (The IDrug Randomized Controlled Trial)-Never Change a Running System?
Pharmaceuticals (Basel). 2021 Oct 18;14(10):1056. doi: 10.3390/ph14101056. PMID: 34681280; PMCID: PMC8538435.

Just KS, Dormann H, Freitag M, Schurig M, Böhme M, Steffens M, Scholl C, Seufferlein T, Graeff I, Schwab M, Stingl JC. CYP2D6 in the Brain: Potential Impact on Adverse Drug Reactions in the Central Nervous System-Results From the ADRED Study. Front Pharmacol. 2021 May 7;12:624104. doi: 10.3389/fphar.2021.624104. PMID: 34025403; PMCID: PMC8138470.

Just KS, Tittel SR, Bollheimer C, Naudorf M, Laubner K, Zimny S, Zeyfang A, Hummel M, Stingl JC, Holl RW. Hypoglycemia in Older Adults: Time Trends and Treatment Differences in Patients Aged ≥75 Years With Type 2 Diabetes. J Am Med Dir Assoc. 2021 Sep;22(9):1898-1905.e1. doi: 10.1016/j.jamda.2021.05.006. Epub 2021 Jun 1. PMID: 34087226.

Just KS, Dallmeier D, Böhme M, Steffens M, Braisch U, Denkinger MD, Rothenbacher D, Stingl JC; ActiFE Study Group. Fall-Associated Drugs in Community-Dwelling Older Adults: Results from the ActiFE Ulm Study. J Am Med Dir Assoc. 2021 Oct;22(10):2177-2183.e10. doi: 10.1016/j.jamda.2020.12.032. Epub 2021 Jan 29. PMID: 33516672.

Kemski S, Molitor V, Steffens M, Nümm TJ, Herrmann N, Hornung T, Bieber T, Schumann C, Kächele V, Seufferlein T, Heinemann V, Scholl C, Stingl JC. Association between miRNA signatures in serum samples from epidermal growth factor inhibitor treated patients and skin toxicity. Oncotarget. 2021 May 11;12(10):982-995. doi: 10.18632/oncotarget.27953. PMID: 34012511; PMCID: PMC8121613.

de Vries FM, Stingl JC, Breteler MMB. Polypharmacy, potentially inappropriate medication and pharmacogenomics drug exposure in the Rhineland Study. Br J Clin Pharmacol. 2021 Jul;87(7):2732-2756. doi: 10.1111/bcp.14671. Epub 2021 Feb 5. PMID: 33232531.

Imaging and data research

Stingl JC, Scholl C, Bosch JE, Viviani R. Genetic polymorphism of CYP2C19 and subcortical variability in the human adult brain. Transl Psychiatry. 2021 Sep 8;11(1):467. doi: 10.1038/s41398-021-01591-5. PMID: 34497262; PMCID: PMC8426391.

Molecular modeling and physiology

Alleva C, Machtens JP, Kortzak D, Weyand I, Fahlke C. Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters. Neurochem Res. 2021 Feb 15. doi: 10.1007/s11064-021-03252-x. Epub ahead of print. PMID: 33587237.

Kostritskii AY, Machtens JP. Molecular mechanisms of ion conduction and ion selectivity in TMEM16 lipid scramblases. Nat Commun. 2021 May 14;12(1):2826. doi: 10.1038/s41467-021-22724-w. PMID: 33990555; PMCID: PMC8121942.

Kostritskii AY, Alleva C, Cönen S, Machtens JP. g_elpot: A Tool for Quantifying Biomolecular Electrostatics from Molecular Dynamics Trajectories. J Chem Theory Comput. 2021 May 11;17(5):3157-3167. doi: 10.1021/acs.jctc.0c01246. Epub 2021 Apr 29. PMID: 33914551.

Pharmaceutical Research

Eisert A, Lanckohr C, Frey J, Frey O, Wicha SG, Horn D, Ellger B, Schuerholz T, Marx G, Simon TP. Comparison of two empirical prolonged infusion dosing regimens for meropenem in patients with septic shock: A two-center pilot study. Int J Antimicrob Agents. 2021 Mar;57(3):106289. doi: 10.1016/j.ijantimicag.2021.106289. Epub 2021 Jan 27. PMID: 33515688.

Koeck JA, Mastragelopoulos N, Just KS, Eisert A. The prevalence of 'triple whammy' prescriptions in surgical inpatients and associated pharmacist recommendations. Pharmazie. 2021 Jul 1;76(7):317-327. doi: 10.1691/ph.2021.1323. PMID: 34256894.

Koeck JA, Young NJ, Kontny U, Orlikowsky T, Bassler D, Eisert A. Interventions to Reduce Medication Dispensing, Administration, and Monitoring Errors in Pediatric Professional Healthcare Settings: A Systematic Review. Front Pediatr. 2021 May 26;9:633064. doi: 0.3389/fped.2021.633064. PMID: 34123962; PMCID: PMC8187621.

Koeck JA, Young NJ, Kontny U, Orlikowsky T, Bassler D, Eisert A. Interventions to Reduce Pediatric Prescribing Errors in Professional Healthcare Settings: A Systematic Review of the Last Decade. Paediatr Drugs. 2021 May;23(3):223-240. doi: 10.1007/s40272-021-00450-6. Epub 2021 May 7. PMID: 33959936.

Masur S, Eisert A, Freitag M. Metformin-Therapie bei operativen Eingriffen und Gabe jodhaltiger Kontrastmittel [Metformin Therapy During Surgical Interventions and Iodinated Contrast Agent Use]. Dtsch Med Wochenschr. 2021 Jan;146(2):121-127. German. doi: 10.1055/a-1241-2407. Epub 2021 Jan 19. PMID: 33465808.

Puengel T, Weber B, Wirtz TH, Buendgens L, Loosen SH, Geisler L, Özdirik B, Karim H, Abu Jhaisha S, Brozat JF, Hohlstein P, Eisert A, Yagmur E, Trautwein C, Tacke F, Koch A. Low Serum Levels of Soluble Receptor Activator of Nuclear Factor κ B Ligand (sRANKL) Are Associated with Metabolic Dysregulation and Predict Long-Term Mortality in Critically Ill Patients. Diagnostics 2022, 12, 62. doi.org/10.3390/diagnostics12010062

Conceptual papers, regulatory science

Dubrall D, Leitzen S, Toni I, Stingl J, Schulz M, Schmid M, Neubert A, Sachs B. Descriptive analysis of adverse drug reaction reports in children and adolescents from Germany: frequently reported reactions and suspected drugs. BMC Pharmacol Toxicol. 2021 Oct 7;22(1):56. doi: 10.1186/s40360-021-00520-y. PMID: 34620231; PMCID: PMC8499510.

Eap CB, Gründer G, Baumann P, Ansermot N, Conca A, Corruble E, Crettol S, Dahl ML, de Leon J, Greiner C, Howes O, Kim E, Lanzenberger R, Meyer JH, Moessner R, Mulder H, Müller DJ, Reis M, Riederer P, Ruhe HG, Spigset O, Spina E, Stegman B, Steimer W, Stingl J, Suzen S, Uchida H, Unterecker S, Vandenberghe F, Hiemke C. Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests): focus on antidepressants. World J Biol Psychiatry. 2021 Oct;22(8):561-628. doi: 10.1080/15622975.2021.1878427. Epub 2021 May 12. PMID: 33977870.

Hausmann R, Franke H, Schmalzing G. How Prof. Burnstock's enthusiasm supported P2 receptor research in Germany. Purinergic Signal. 2021 Mar;17(1):139-140. doi: 10.1007/s11302-021-09768-9. Epub 2021 Feb 4. PMID: 33543379; PMCID: PMC7954914.

Leitzen S, Dubrall D, Toni I, Stingl J, Schulz M, Schmid M, Neubert A, Sachs B. Analysis of the reporting of adverse drug reactions in children and adolescents in Germany in the time period from 2000 to 2019. PLoS One. 2021 Mar 3;16(3):e0247446. doi: 10.1371/journal.pone.0247446. PMID: 33657139; PMCID: PMC7928460.

Schoretsanitis G, Westin AA, Stingl JC, Deligiannidis KM, Paulzen M, Spigset O. Antidepressant transfer into amniotic fluid, umbilical cord blood & breast milk: A systematic review & combined analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Apr 20;107:110228. doi: 10.1016/j.pnpbp.2020.110228. Epub 2021 Jan 2. PMID: 33358964; PMCID: PMC7882033.

Covid-19-related or antiviral pharmacological issues

Glitscher M, Martín DH, Woytinek K, Schmidt B, Tabari D, Scholl C, Stingl JC, Seelow E, Choi M, Hildt E. Targeting Cholesterol Metabolism as Efficient Antiviral Strategy Against the Hepatitis E Virus. Cell Mol Gastroenterol Hepatol. 2021;12(1):159-180. doi: 10.1016/j.jcmgh.2021.02.002. Epub 2021 Feb 15. PMID: 33601063; PMCID: PMC8099564.

Hein S, Benz NI, Eisert J, Herrlein ML, Oberle D, Dreher M, Stingl JC, Hildt C, Hildt E. Comirnaty-Elicited and Convalescent Sera Recognize Different Spike Epitopes. Vaccines (Basel). 2021 Dec 1;9(12):1419. doi: 10.3390/vaccines9121419. PMID: 34960165; PMCID: PMC8708883.

Stingl, JC. Antidepressant drug treatment protecting from COVID-19: one more piece in the repurposing puzzle. BJPsych Open. 2021 Dec 20;8(1):e20. doi: 10.1192/bjo.2021.1075.

Warnat-Herresthal S, Schultze H, Shastry KL, Manamohan S, Mukherjee S, Garg V, Sarveswara R, Händler K, Pickkers P, Aziz NA, Ktena S, Tran F, Bitzer M, Ossowski S, Casadei N, Herr C, Petersheim D, Behrends U, Kern F, Fehlmann T, Schommers P, Lehmann C, Augustin M, Rybniker J, Altmüller J, Mishra N, Bernardes JP, Krämer B, Bonaguro L, Schulte-Schrepping J, De Domenico E, Siever C, Kraut M, Desai M, Monnet B, Saridaki M, Siegel CM, Drews A, Nuesch-Germano M, Theis H, Heyckendorf J, Schreiber S, Kim-Hellmuth S; COVID-19 Aachen Study (COVAS), Nattermann J, Skowasch D, Kurth I, Keller A, Bals R, Nürnberg P, Rieß O, Rosenstiel P, Netea MG, Theis F, Mukherjee S, Backes M, Aschenbrenner AC, Ulas T; Deutsche COVID-19 Omics Initiative (DeCOI), Breteler MMB, Giamarellos-Bourboulis EJ, Kox M, Becker M, Cheran S, Woodacre MS, Goh EL, Schultze JL. Swarm Learning for decentralized and confidential clinical machine learning. Nature. 2021 Jun;594(7862):265-270. doi: 10.1038/s41586-021-03583-3. Epub 2021 May 26. PMID: 34040261; PMCID: PMC8189907.

Viviani R, Dommes L, Bosch J, Steffens M, Paul A, Schneider KL, Stingl JC, Beschoner P. Signals of anticipation of reward and of mean reward rates in the human brain. Sci Rep. 2020;10(1): 4287. doi: 10.1038/s41598-020-61257-y. PMCID: PMC7062891.

Pharmacovigilance/Therapeutic drug monitoring/Pharmacokinetics

Schoretsanitis G, Spigset O, Stingl JC, Deligiannidis KM, Paulzen M, Westin AA. The impact of pregnancy on the pharmacokinetics of antidepressants: a systematic critical review and meta-analysis. Expert Opin Drug Metab Toxicol. 2020 May;16(5): 431-440. doi: 10.1080/17425255.2020.1750598. PMCID: PMC7323120.

Paulzen M, Schoretsanitis G, Gründer G, Franz C, Stingl JC, Augustin M. Pregnancy exposure to venlafaxine-Therapeutic drug monitoring in maternal blood, amniotic fluid and umbilical cord blood and obstetrical outcomes. J Affect Disord. 2020;266: 578-584.

Dubrall D, Schmid M, Stingl JC, Sachs B. Angioedemas associated with renin-angiotensin system blocking drugs: Comparative analysis of spontaneous adverse drug reaction reports. PLoS ONE. 2020;15(3): e0230632. doi: 10.1371/journal.pone.0230632. PMCID: PMC7098604.

International diversity in drug metabolism and transport, pharmacogenetics

Mufwambi W, Stingl JC, Masimirembwa C, Manasa J, Nhachi C, Stadler N, Mwila C, Kalungia AC, Mukosha M, Mutiti CS, Kamoto A, Kaonga P, Godman B, Munkombwe D. Healthcare Professionals' Knowledge of Pharmacogenetics and Attitudes Towards Antimicrobial Utilization in Zambia: Implications for a Precision Medicine Approach to Reducing Antimicrobial Resistance.  Front Pharmacol. 2020;11: 551522. doi: 10.3389/fphar.2020.551522. PMCID: PMC7835886.

Tabari D, Scholl C, Steffens M, Weickhardt S, Elgner F, Bender D, Herrlein ML, Sabino C, Semkova V, Peitz M, Till A, Brüstle O, Hildt E, Stingl JC. Impact of Zika Virus Infection on Human Neural Stem Cell MicroRNA Signatures. Viruses. 2020 Nov;12(11): 1219. doi: 10.3390/v12111219. PMCID: PMC7693339.

New drug target/pharmacological research

Rühlmann AH, Körner J, Hausmann R, Bebrivenski N, Neuhof C, Detro-Dassen S, Hautvast P, Benasolo CA, Meents J, Machtens JP, Schmalzing G, Lampert A.  Uncoupling sodium channel dimers restores the phenotype of a pain-linked Na 1.7 channel mutation. Br J Pharmacol. 2020 Oct;177(19): 4481-4496. doi: 10.1111/bph.15196. PMCID: PMC7484505.

Thull S, Neacsu C, O'Reilly AO, Bothe S, Hausmann R, Huth T, Meents J, Lampert A. Dataset of electrophysiological patch-clamp recordings of the effect of the compounds deltamethrin, ATx-II and ß4-peptide on human cardiac Nav1.5 sodium channel gating properties. Data Brief. 2020 Aug;31: 105844.  doi: 10.1016/j.dib.2020.105844. PMCID: PMC7329930                .

Richter K, Ogiemwonyi-Schaefer R, Wilker S, Chaveiro AI, Agné A, Hecker M, Reichert M, Amati AL, Schlüter KD, Manzini I, Schmalzing G, McIntosh JM, Padberg W, Grau V, Hecker A. Amyloid Beta Peptide (Aß_1-42) Reverses the Cholinergic Control of Monocytic IL-1ß Release. J Clin Med. 2020 Sep; 9(9): 2887. doi: 10.3390/jcm9092887. PMCID: PMC7564705.

Trang M, Schmalzing G, Müller CE, Markwardt F. Dissection of P2X4 and P2X7 Receptor Current Components in BV-2 Microglia. Int J Mol Sci. 2020 Nov;21(22). doi: 10.3390/ijms21228489. PMCID: PMC7696836.

Thull S, Neacsu C, O'Reilly AO, Bothe S, Hausmann R, Huth T, Meents J, Lampert A. Mechanism underlying hooked resurgent-like tail currents induced by an insecticide in human cardiac Nav1.5.  Toxicol Appl Pharmacol. 2020;397: 115010.

Personalized drug safety/Clinical pharmacogenetic research

van der Wouden CH, Böhringer S, Cecchin E, Cheung KC, Dávila-Fajardo CL, Deneer VHM, Dolzan V, Ingelman-Sundberg M, Jönsson S, Karlsson MO, Kriek M, Mitropoulou C, Patrinos GP, Pirmohamed M, Rial-Sebbag E, Samwald M, Schwab M, Steinberger D, Stingl JC, Sunder-Plassmann G, Toffoli G, Turner RM, van Rhenen MH, van Zwet E, Swen JJ, Guchelaar HJ, Ubiquitous Pharmacogenomics Consortium. Generating evidence for precision medicine: considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study.  Pharmacogenet Genomics. 2020 Aug;30(6): 131-144. doi: 10.1097/FPC.0000000000000405. PMCID: PMC7331826.

Gaebler AJ, Schneider KL, Stingl JC, Paulzen M. Subtherapeutic bupropion and hydroxybupropion serum concentrations in a patient with CYP2C19*1/*17 genotype suggesting a rapid metabolizer status. Pharmacogenomics J. 2020;20(6): 840-844.

Barakat AK, Scholl C, Steffens M, Brandenburg K, Ising M, Lucae S, Holsboer F, Laje G, Kalayda GV, Jaehde U, Stingl JC. Citalopram-induced pathways regulation and tentative treatment-outcome-predicting biomarkers in lymphoblastoid cell lines from depression patients. Transl Psychiatry. 2020;10(1): 210. doi: 10.1038/s41398-020-00900-8. PMCID: PMC7329820.

Viviani R, Messina I, Bosch JE, Dommes L, Paul A, Schneider KL, Scholl C, Stingl JC. Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity. Transl Psychiatry. 2020;10(1): 338. doi: 10.1038/s41398-020-01020-z. PMCID: PMC7539151.

Dubrall D, Just KS, Schmid M, Stingl JC, Sachs B.  Adverse drug reactions in older adults: a retrospective comparative analysis of spontaneous reports to the German Federal Institute for Drugs and Medical Devices. BMC Pharmacol Toxicol. 2020;21(1): 25. doi: 10.1186/s40360-020-0392-9. PMCID: PMC7092423.

Huebner T, Steffens M, Linder R, Fracowiak J, Langner D, Garling M, Falkenberg F, Roethlein C, Gomm W, Haenisch B, Stingl JC. Influence of metabolic profiles on the safety of drug therapy in routine care in Germany: protocol of the cohort study EMPAR. BMJ Open. 2020;10(4): e032624. doi: 10.1136/bmjopen-2019-032624. PMCID: PMC7213853.

Just KS, Dormann H, Schurig M, Böhme M, Steffens M, Plank-Kiegele B, Ettrich K, Seufferlein T, Gräff I, Igel S, Schricker S, Jaeger SU, Schwab M, Stingl JC.  The phenotype of adverse drug effects: Do emergency visits due to adverse drug reactions look different in older people? Results from the ADRED study. Br J Clin Pharmacol. 2020 Nov;86(11): 2144-2154. doi: 10.1111/bcp.14304. PMCID: PMC7576634.

Weber S, Lampert A, Stingl JC, Peuckmann-Post V, Hiddemann S, Elsner F, Neuner I, Rolke R.     [Basic Knowledge of Drug Pain Therapy in the Palliative Situation].  Dtsch Med Wochenschr. 2020;145(13): 917-925. doi: 10.1055/a-1016-9941. PMID: 32615607  

Just KS, Dormann H, Böhme M, Schurig M, Schneider KL, Steffens M, Dunow S, Plank-Kiegele B, Ettrich K, Seufferlein T, Gräff I, Igel S, Schricker S, Jaeger SU, Schwab M, Stingl JC. Personalising drug safety-results from the multi-centre prospective observational study on Adverse Drug Reactions in Emergency Departments (ADRED). Eur J Clin Pharmacol. 2020;76(3): 439-448.

Just KS, Dormann H, Schurig M, Böhme M, Fracowiak J, Steffens M, Scholl C, Seufferlein T, Gräff I, Schwab M, Stingl JC. Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk? -Results from the ADRED Study.  J Clin Med. 2020 Jun; 9(6): 1801. doi: 10.3390/jcm9061801. PMCID: PMC7355597.

Stingl JC, Just KS, Schurig M, Böhme M, Steffens M, Schwab M, Seufferlein T, Dormann H. Prevalence of Psychotropic Drugs in Cases of Severe Adverse Drug Reactions Leading to Unplanned Emergency Visits in General Hospitals. Pharmacopsychiatry. 2020;53(3): 133-137.

Molecular modeling and physiology

Alberione MP, Moeller R, Kirui J, Ginkel C, Doepke M, Ströh LJ, Machtens JP, Pietschmann T, Gerold G. Single-nucleotide variants in human CD81 influence hepatitis C virus infection of hepatoma cells. Med Microbiol Immunol (Berl). 2020;209(4): 499-514. doi: 10.1007/s00430-020-00675-1. PMCID: PMC7176029.

Alleva C, Kovalev K, Astashkin R, Berndt MI, Baeken C, Balandin T, Gordeliy V, Fahlke C, Machtens JP. Na-dependent gate dynamics and electrostatic attraction ensure substrate coupling in glutamate transporters. Sci Adv. 2020 Nov;6(47).  doi: 10.1126/sciadv.aba9854. PMCID: PMC7673805.

Pharmaceutical Research

Wirtz TH, Buendgens L, Weiskirchen R, Loosen SH, Haehnsen N, Puengel T, Abu Jhaisha S, Brozat JF, Hohlstein P, Koek G, Eisert A, Mohr R, Roderburg C, Luedde T, Trautwein C, Tacke F, Koch A. Association of Serum Calprotectin Concentrations with Mortality in Critically Ill and Septic Patients. Diagnostics (Basel). 2020 Nov;10(11). doi: 10.3390/diagnostics10110990. PMCID: PMC7700375.

Amkreutz J, Lenssen R, Marx G, Deisz R, Eisert A. Medication safety in a German telemedicine centre: Implementation of a telepharmaceutical expert consultation in addition to existing tele-intensive care unit services.  J Telemed Telecare. 2020;26(1-2): 105-112.

Buendgens L, Yagmur E, Ginsberg A, Weiskirchen R, Wirtz T, Jhaisha SA, Eisert A, Luedde T, Trautwein C, Tacke F, Koch A. Midregional Proadrenomedullin (MRproADM) Serum Levels in Critically Ill Patients Are Associated with Short-Term and Overall Mortality during a Two-Year Follow-Up. Mediators Inflamm. 2020;2020: 7184803. doi: 10.1155/2020/7184803. PMCID: PMC7428945.