{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:35:20Z","timestamp":1791048920955,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>ARDS is a challenging syndrome in which the hallmark is alveolar epithelium damage, with the consequent extravasation of fluids into the interstitium and alveolar space. Patients with severe ARDS almost always require mechanical ventilation and aggressive fluid resuscitation, at least in the initial phases. The increased intrathoracic pressure during positive pressure ventilation reduces cardiac output, worsening the circulatory status of these patients even more. In this pathological context, fluid therapies serve as a means to restore intravascular volume but can simultaneously play a detrimental role, increasing the amount of liquid in the lungs and worsening gas exchange and lung mechanics. Indeed, clinical research suggests that fluid overload leads to worsening outcomes, mostly in terms of gas exchange, days of mechanical ventilation, and ICU stay duration. For these reasons, this review aims to provide basic information about ARDS pathophysiology and heart\u2013lung interactions, the understanding of which is essential to guide fluid therapy, together with the close monitoring of hemodynamics and fluid responsiveness.<\/jats:p>","DOI":"10.3390\/jcm14062067","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T07:20:00Z","timestamp":1742282400000},"page":"2067","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Acute Respiratory Distress Syndrome and Fluid Management: Finding the Perfect Balance"],"prefix":"10.3390","volume":"14","author":[{"given":"Irene","family":"Sbaraini Zernini","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6833-7480","authenticated-orcid":false,"given":"Domenico","family":"Nocera","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"D\u2019Albo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-3595","authenticated-orcid":false,"given":"Tommaso","family":"Tonetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"},{"name":"Anesthesiology and General Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","article-title":"Acute respiratory distress syndrome","volume":"5","author":"Matthay","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/S0140-6736(22)01485-4","article-title":"Acute respiratory distress syndrome: Causes, pathophysiology, and phenotypes","volume":"400","author":"Bos","year":"2022","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e154573","DOI":"10.1172\/jci.insight.154573","article-title":"Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome","volume":"7","author":"Rizzo","year":"2022","journal-title":"JCI Insight"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.bpa.2014.06.003","article-title":"Role of the glycocalyx in fluid management: Small things matter","volume":"28","author":"Chappell","year":"2014","journal-title":"Best. Pr. Res. Clin. Anaesthesiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1186\/s13054-014-0538-5","article-title":"Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx","volume":"18","author":"Chappell","year":"2014","journal-title":"Crit. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1186\/s13054-014-0707-6","article-title":"Fluid resuscitation should respect the endothelial glycocalyx layer","volume":"18","author":"Guidet","year":"2014","journal-title":"Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1097\/SLA.0b013e31818b73dc","article-title":"Impact of different crystalloid volume regimes on intestinal anastomotic stability","volume":"249","author":"Marjanovic","year":"2009","journal-title":"Ann. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1097\/CCM.0000000000004617","article-title":"Fluid Overload and Mortality in Adult Critical Care Patients-A Systematic Review and Meta-Analysis of Observational Studies","volume":"48","author":"Messmer","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e15429","DOI":"10.14814\/phy2.15429","article-title":"Effects of different fluid management on lung and kidney during pressure-controlled and pressure-support ventilation in experimental acute lung injury","volume":"10","author":"Carvalho","year":"2022","journal-title":"Physiol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1164\/rccm.202406-1240OC","article-title":"Impact of Fluid Balance on the Development of Lung Injury","volume":"211","author":"Gattarello","year":"2025","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1056\/NEJMra1208707","article-title":"Ventilator-induced lung injury","volume":"369","author":"Slutsky","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1186\/s13054-019-2673-5","article-title":"Cumulative fluid accumulation is associated with the development of acute kidney injury and non-recovery of renal function: A retrospective analysis","volume":"23","author":"Zhang","year":"2019","journal-title":"Crit. Care Lond. Engl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1097\/CCM.0000000000003507","article-title":"Effects of Fluid Bolus Therapy on Renal Perfusion, Oxygenation, and Function in Early Experimental Septic Kidney Injury","volume":"47","author":"Lankadeva","year":"2019","journal-title":"Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/cc968","article-title":"Pathophysiology of fluid imbalance","volume":"4","author":"Kreimeier","year":"2000","journal-title":"Crit. Care Lond. Engl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/2110-5820-3-12","article-title":"Clinical use of lactate monitoring in critically ill patients","volume":"3","author":"Bakker","year":"2013","journal-title":"Ann. Intensive Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/MCC.0b013e3283532b8a","article-title":"Lactate as a hemodynamic marker in the critically ill","volume":"18","author":"Fuller","year":"2012","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e12673","DOI":"10.1111\/micc.12673","article-title":"Effects of impaired microvascular flow regulation on metabolism-perfusion matching and organ function","volume":"28","author":"Roy","year":"2021","journal-title":"Microcirculation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"353","DOI":"10.21037\/atm.2018.04.40","article-title":"Physiology-guided management of hemodynamics in acute respiratory distress syndrome","volume":"6","author":"Oeckler","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1152\/ajplegacy.1957.189.3.609","article-title":"Venous return at various right atrial pressures and the normal venous return curve","volume":"189","author":"Guyton","year":"1957","journal-title":"Am. J. Physiol."},{"key":"ref_20","first-page":"w14491","article-title":"Basic concepts of heart-lung interactions during mechanical ventilation","volume":"147","author":"Wigger","year":"2017","journal-title":"Swiss Med. Wkly."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"349","DOI":"10.21037\/atm.2018.04.29","article-title":"Heart-lung interactions during mechanical ventilation: The basics","volume":"6","author":"Mahmood","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1164\/rccm.201303-0539OC","article-title":"Spontaneous effort causes occult pendelluft during mechanical ventilation","volume":"188","author":"Yoshida","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s13054-017-1750-x","article-title":"The future of mechanical ventilation: Lessons from the present and the past","volume":"21","author":"Gattinoni","year":"2017","journal-title":"Crit. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1097\/CCM.0000000000000345","article-title":"Mechanical ventilation-induced intrathoracic pressure distribution and heart-lung interactions","volume":"42","author":"Lansdorp","year":"2014","journal-title":"Crit. Care. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40635-023-00526-2","article-title":"Fluid management strategies and their interaction with mechanical ventilation: From experimental studies to clinical practice","volume":"11","author":"Battaglini","year":"2023","journal-title":"Intensive Care Med. Exp."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40635-024-00610-1","article-title":"Determinants of acute kidney injury during high-power mechanical ventilation: Secondary analysis from experimental data","volume":"12","author":"Gattarello","year":"2024","journal-title":"Intensive Care Med. Exp."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/00000542-198302000-00006","article-title":"Effect of PEEP ventilation on renal function, plasma renin, aldosterone, neurophysins and urinary ADH, and prostaglandins","volume":"58","author":"Annat","year":"1983","journal-title":"Anesthesiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1055\/s-2007-1022063","article-title":"The effect of PEEP ventilation on hemodynamics and regional blood flow with special regard to coronary blood flow","volume":"28","author":"Beyer","year":"1980","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1097\/00003246-198711000-00010","article-title":"Effects of continuous positive-pressure ventilation on hepatic blood flow and intrahepatic oxygen delivery in dogs","volume":"15","author":"Sha","year":"1987","journal-title":"Crit. Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"992401","DOI":"10.3389\/fphys.2022.992401","article-title":"Biological impact of restrictive and liberal fluid strategies at low and high PEEP levels on lung and distal organs in experimental acute respiratory distress syndrome","volume":"13","author":"Felix","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s12931-021-01811-y","article-title":"The impact of fluid status and decremental PEEP strategy on cardiac function and lung and kidney damage in mild-moderate experimental acute respiratory distress syndrome","volume":"22","author":"Rocha","year":"2021","journal-title":"Respir. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1164\/arrd.1987.135.4.924","article-title":"Fluid balance and the adult respiratory distress syndrome","volume":"135","author":"Simmons","year":"1987","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1378\/chest.97.5.1176","article-title":"Improved survival in ARDS patients associated with a reduction in pulmonary capillary wedge pressure","volume":"97","author":"Humphrey","year":"1990","journal-title":"Chest"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1164\/ajrccm\/145.5.990","article-title":"Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization","volume":"145","author":"Mitchell","year":"1992","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1378\/chest.128.5.3098","article-title":"High Tidal Volume and Positive Fluid Balance Are Associated with Worse Outcome in Acute Lung Injury","volume":"128","author":"Sakr","year":"2005","journal-title":"Chest"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann, H.P., Wheeler, A.P., Bernard, G.R., Thompson, B.T., Hayden, D., de Boisblanc, B., Connors, A.F., Hite, R.D., and Harabin, A.L. (2006). Comparison of two fluid-management strategies in acute lung injury. N. Engl. J. Med., 354, 2564\u20132575.","DOI":"10.1056\/NEJMoa062200"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.jamcollsurg.2009.01.026","article-title":"Less is more: Improved outcomes in surgical patients with conservative fluid administration and central venous catheter monitoring","volume":"208","author":"Stewart","year":"2009","journal-title":"J. Am. Coll. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1097\/CCM.0b013e318228234b","article-title":"Acute kidney injury in patients with acute lung injury: Impact of fluid accumulation on classification of acute kidney injury and associated outcomes","volume":"39","author":"Liu","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"966","DOI":"10.2215\/CJN.08781010","article-title":"Fluid Balance, Diuretic Use, and Mortality in Acute Kidney Injury","volume":"6","author":"Grams","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1164\/rccm.201111-2025OC","article-title":"The Adult Respiratory Distress Syndrome Cognitive Outcomes Study: Long-Term Neuropsychological Function in Survivors of Acute Lung Injury","volume":"185","author":"Mikkelsen","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1164\/rccm.201603-0645OC","article-title":"ARDS Network Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy","volume":"195","author":"Famous","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1177\/0885066608329850","article-title":"Review of A Large Clinical Series: Association of Cumulative Fluid Balance on Outcome in Acute Lung Injury: A Retrospective Review of the ARDSnet Tidal Volume Study Cohort","volume":"24","author":"Rosenberg","year":"2009","journal-title":"J. Intensive Care Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e0224563","DOI":"10.1371\/journal.pone.0224563","article-title":"Cumulative fluid balance predicts mortality and increases time on mechanical ventilation in ARDS patients: An observational cohort study","volume":"14","author":"Metske","year":"2019","journal-title":"PLoS ONE"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1097\/CCM.0000000000003276","article-title":"Deresuscitation of Patients with Iatrogenic Fluid Overload Is Associated with Reduced Mortality in Critical Illness","volume":"46","author":"Silversides","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00134-016-4573-3","article-title":"Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: A systematic review and meta-analysis","volume":"43","author":"Silversides","year":"2017","journal-title":"Intensive Care Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1097\/00003246-200210000-00001","article-title":"Albumin and furosemide therapy in hypoproteinemic patients with acute lung injury","volume":"30","author":"Martin","year":"2002","journal-title":"Crit. Care Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1097\/01.CCM.0000171539.47006.02","article-title":"A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury","volume":"33","author":"Martin","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.chest.2024.02.049","article-title":"Use of Intravenous Albumin","volume":"166","author":"Callum","year":"2024","journal-title":"Chest"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13613-018-0402-x","article-title":"Principles of fluid management and stewardship in septic shock: It is time to consider the four D\u2019s and the four phases of fluid therapy","volume":"8","author":"Malbrain","year":"2018","journal-title":"Ann. Intensive Care"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1007\/s00134-020-06310-0","article-title":"Fluid administration and monitoring in ARDS: Which management?","volume":"46","author":"Vignon","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13613-024-01356-5","article-title":"Heart-Lungs interactions: The basics and clinical implications","volume":"14","author":"Jozwiak","year":"2024","journal-title":"Ann. Intensive Care"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1007\/s00134-014-3525-z","article-title":"Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine","volume":"40","author":"Cecconi","year":"2014","journal-title":"Intensive Care Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13613-022-01022-8","article-title":"Prediction of fluid responsiveness. What\u2019s New?","volume":"12","author":"Monnet","year":"2022","journal-title":"Ann. Intensive Care"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1186\/s13054-015-1115-2","article-title":"Effects of passive leg raising and volume expansion on mean systemic pressure and venous return in shock in humans","volume":"19","author":"Teboul","year":"2015","journal-title":"Crit. Care"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1186\/s13054-017-1881-0","article-title":"Change in cardiac output during Trendelenburg maneuver is a reliable predictor of fluid responsiveness in patients with acute respiratory distress syndrome in the prone position under protective ventilation","volume":"21","author":"Yonis","year":"2017","journal-title":"Crit. Care"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"352","DOI":"10.21037\/atm.2018.05.03","article-title":"Prediction of fluid responsiveness in ventilated patients","volume":"6","author":"Jozwiak","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s13054-019-2545-z","article-title":"Functional hemodynamic tests: A systematic review and a metanalysis on the reliability of the end-expiratory occlusion test and of the mini-fluid challenge in predicting fluid responsiveness","volume":"23","author":"Messina","year":"2019","journal-title":"Crit. Care"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13054-023-04424-7","article-title":"The increase in cardiac output induced by a decrease in positive end-expiratory pressure reliably detects volume responsiveness: The PEEP-test study","volume":"27","author":"Lai","year":"2023","journal-title":"Crit. Care"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1097\/CCM.0b013e31826ab377","article-title":"Extravascular lung water is an independent prognostic factor in patients with acute respiratory distress syndrome","volume":"41","author":"Jozwiak","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1097\/CCM.0b013e3181a380a3","article-title":"Assessing fluid responsiveness in critically ill patients: False-positive pulse pressure variation is detected by Doppler echocardiographic evaluation of the right ventricle","volume":"37","author":"Mahjoub","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_61","first-page":"1734","article-title":"Superior vena caval collapsibility as a gauge of volume status in ventilated septic patients","volume":"30","author":"Chergui","year":"2004","journal-title":"Intensive Care Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1378\/chest.119.3.867","article-title":"Respiratory changes in aortic blood velocity as an indicator of fluid responsiveness in ventilated patients with septic shock","volume":"119","author":"Feissel","year":"2001","journal-title":"Chest"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13089-020-00163-w","article-title":"Quantifying systemic congestion with Point-Of-Care ultrasound: Development of the venous excess ultrasound grading system","volume":"12","author":"Rola","year":"2020","journal-title":"Ultrasound J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13613-020-00679-3","article-title":"Intravenous fluid therapy in the perioperative and critical care set-ting: Executive summary of the International Fluid Academy (IFA)","volume":"10","author":"Malbrain","year":"2020","journal-title":"Ann. Intensive Care"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/6\/2067\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:55:54Z","timestamp":1760028954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/6\/2067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":64,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jcm14062067"],"URL":"https:\/\/doi.org\/10.3390\/jcm14062067","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]}}}