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10/12/25

 



ABSTRACT


Artificial intelligence tools, particularly convolutional neural networks (CNNs), are transforming healthcare by enhancing predictive, diagnostic, and decision-making capabilities. This review provides an accessible and practical explanation of CNNs for clinicians and highlights their relevance in medical image analysis. CNNs have shown themselves to be exceptionally useful in computer vision, a field that enables machines to 'see' and interpret visual data. Understanding how these models work can help clinicians leverage their full potential, especially as artificial intelligence continues to evolve and integrate into healthcare. CNNs have already demonstrated their efficacy in diverse medical fields, including radiology, histopathology, and medical photography. In radiology, CNNs have been used to automate the assessment of conditions such as pneumonia, pulmonary embolism, and rectal cancer. In histopathology, CNNs have been used to assess and classify colorectal polyps, gastric epithelial tumours, as well as assist in the assessment of multiple malignancies. In medical photography, CNNs have been used to assess retinal diseases and skin conditions, and to detect gastric and colorectal polyps during endoscopic procedures. In surgical laparoscopy, they may provide intraoperative assistance to surgeons, helping interpret surgical anatomy and demonstrate safe dissection zones. The integration of CNNs into medical image analysis promises to enhance diagnostic accuracy, streamline workflow efficiency, and expand access to expert-level image analysis, contributing to the ultimate goal of delivering further improvements in patient and healthcare outcomes.


PMID:37794609 | DOI:10.1093/postmj/qgad095

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11:12

PubMed articles on: Cancer & VTE/PE

Unveiling Lung Adenocarcinoma: Non-bacterial Thrombotic Endocarditis as the Debut Sign


Cureus. 2023 Sep 14;15(9):e45271. doi: 10.7759/cureus.45271. eCollection 2023 Sep.


ABSTRACT


Non-bacterial thrombotic endocarditis (NBTE) involves the deposition of fibrin and platelets on heart valves, frequently leading to systemic embolism. The association between NBTE and cancer demands thorough investigation in cases lacking an evident cause. This case report elucidates the clinical course of a nonsmoking woman in her sixties with NBTE linked to pulmonary adenocarcinoma. The patient, who had a history of multiple sclerosis (MS) and was receiving dimethyl fumarate treatment, presented to the emergency department with stroke-like symptoms. Diagnostic challenges arose due to preexisting motor sensory impairment from MS. Initial evaluations revealed hypocapnia and elevated inflammatory markers. Blood cultures were obtained twice, and imaging confirmed pneumonia, left pleural effusion, and chronic pulmonary embolism while excluding acute vascular events or intracranial hemorrhage. The first transthoracic echocardiogram (TTE) indicated no cardiac abnormalities. Treatment encompassed parenteral antibiotics, systemic anticoagulation, and admission to medical floors. Although the initial treatment yielded a positive clinical response, subsequent complications emerged. On the tenth day, the patient required additional interventions, including broad-spectrum antibiotics and supplemental oxygen. A follow-up chest X-ray revealed persistent pneumonia and pleural effusion, and blood cultures upon admission returned negative. A subsequent head MRI confirmed an embolic stroke and displayed evidence of MS progression. Around the twentieth day, empirical treatment for infective endocarditis was initiated, and an 8 mm vegetation on the aortic valve was identified via transesophageal echocardiography (TOE). Acute pulmonary edema prompted a transfer to the intermediate care unit. Further investigations, including left thoracocentesis and CT, unveiled exudate and metastatic lesions in the liver, ilium, and kidney. Unfortunately, on the twenty-fifth day, the patient experienced acute myocardial infarction, right leg ischemia, disseminated intravascular coagulation, and shock. Pleural fluid analysis revealed malignant cells suggestive of lung adenocarcinoma. This case underscores the pivotal role of timely NBTE recognition and the search for malignancy when workup for infective endocarditis and autoimmune panels is negative. Moreover, it emphasizes the significance of vigilant monitoring, particularly in immunocompromised individuals or those with preexisting neurological deficits, especially when new neurological symptoms manifest. These insights significantly contribute to the comprehension of NBTE management and its implications for analogous patient cohorts.


PMID:37846253 | PMC:PMC10576842 | DOI:10.7759/cureus.45271

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11:13

PubMed articles on: Cancer & VTE/PE

Increased risk of venous and arterial thromboembolism in patients with colorectal cancer receiving cetuximab-based combination chemotherapy: A population-based study in Korea


Thromb Res. 2023 Oct 4;231:50-57. doi: 10.1016/j.thromres.2023.10.005. Online ahead of print.


ABSTRACT


INTRODUCTION: Limited data exist on the risk of venous and arterial thromboembolisms (VTE and ATE) in patients receiving cetuximab plus chemotherapy. We aimed to determine the thromboembolic risk of patients with recurrent/metastatic colorectal cancer (CRC) treated with cetuximab plus chemotherapy compared to chemotherapy alone.


METHODS: This population-based study used nationwide claims data from the Health Insurance Review and Assessment Service of South Korea from 2013 to 2020. Patients with recurrent/metastatic CRC treated with first-line oxaliplatin- or irinotecan-based doublets with or without cetuximab and no secondary prevention for VTE and ATE were included. Primary outcomes were the occurrence of any thromboembolic events, VTE, and ATE, which were determined using the cumulative incidence method incorporating death as a competing event.


RESULTS: We identified 19,723 patients (cetuximab plus chemotherapy, N = 7630; chemotherapy alone, N = 12,093). The cumulative incidence of any thromboembolic events in patients with cetuximab plus chemotherapy was significantly higher than in those receiving chemotherapy alone (6-month, 5.62 % vs. 3.58 %, P < 0.0001). The rates of VTE (6-month, 5.11 % vs. 3.28 %, P < 0.0001) and ATE (6-month, 0.53 % vs. 0.32 %, P = 0.0218) were also higher in patients receiving cetuximab plus chemotherapy. In multivariable analysis, cetuximab plus chemotherapy was independently associated with developing any thromboembolic events (hazard ratio [HR], 1.63; 95 % confidence interval [CI], 1.42-1.87), VTE (HR, 1.62; 95 % CI, 1.40-1.87), and ATE (HR, 1.77; 95 % CI, 1.16-2.71).


CONCLUSIONS: Cetuximab with irinotecan- or oxaliplatin-based doublet chemotherapy was associated with an increased risk of any thromboembolic events, VTE, and ATE; further studies are warranted to examine the underlying mechanisms.


PMID:37804738 | DOI:10.1016/j.thromres.2023.10.005

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11:13

PubMed articles on: Cancer & VTE/PE

Persistent underuse of extended venous thromboembolism prophylaxis in patients undergoing major abdominal cancer operations


J Surg Oncol. 2023 Oct 6. doi: 10.1002/jso.27473. Online ahead of print.


ABSTRACT


BACKGROUND: Guidelines recommend extended venous thromboembolism (VTE) prophylaxis for high-risk populations undergoing major abdominal cancer operations. Few studies have evaluated extended VTE prophylaxis in the Medicare population who are at higher risk due to age.


METHODS: We performed a retrospective study using a 20% random sample of Medicare claims, 2012-2017. Patients ≥65 years with an abdominal cancer undergoing resection were included. Primary outcome was the proportion of patients receiving new extended VTE prophylaxis prescriptions at discharge. Secondary outcomes included postdischarge VTE and hemorrhagic events.


RESULTS: The study included 72 983 patients with a mean age of 75. Overall, 8.9% of patients received extended VTE prophylaxis. This proportion increased (7.2% in 2012, 10.6% in 2017; p < 0.001). Incidence of postdischarge hemorrhagic events was 1.0% in patients receiving extended VTE prophylaxis and 0.8% in those who did not. The incidence of postdischarge VTE events was 5.2% in patients receiving extended VTE prophylaxis and 2.4% in those who did not.


CONCLUSION: Adherence to guideline-recommended extended VTE prophylaxis in high-risk patients undergoing major abdominal cancer operations is low. The higher rate of VTE in the prophylaxis group may suggest we captured some therapeutic anticoagulation, which would mean the actual rate of thromboprophylaxis is lower than reported herein.


PMID:37800390 | DOI:10.1002/jso.27473

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11:13

PubMed articles on: Cancer & VTE/PE

Catheter Directed Thrombectomy and Other Deep Venous Interventions in Cancer Patients

11:13

PubMed articles on: Cancer & VTE/PE

Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis

11:13

PubMed articles on: Cancer & VTE/PE

Chronic inflammatory diseases increase the risk of post-thrombotic syndrome: A prospective cohort study

11:13

PubMed articles on: Cancer & VTE/PE

Guidelines in Practice: Prevention of Venous Thromboembolism

11:13

PubMed articles on: Cancer & VTE/PE

Clinical Care of Pediatric Patients with or At-Risk of Post-Thrombotic Syndrome: Guidance from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Haemostasis

11:13

PubMed articles on: Cancer & VTE/PE

Crucial safety issues on Janus kinase inhibitors in rheumatoid arthritis might be associated with the lack of LDL-cholesterol management: a reasoned literature analysis

11:13

PubMed articles on: Cancer & VTE/PE

The prevalence of relevant drug-drug interactions and associated clinical outcomes in patients with cancer-associated thrombosis on concurrent anticoagulation and anticancer or supportive care therapies

11:13

PubMed articles on: Cancer & VTE/PE

Pulmonary Embolism Unplugged: Catheter-Directed Therapies for Intermediate-Risk Pulmonary Embolism

11:13

PubMed articles on: Cancer & VTE/PE

Retracted: Effect Evaluation of Bronchial Artery Embolization for Hemoptysis of Lung Cancer and Changes in Serum Tumor Markers and miR-34 Levels


Contrast Media Mol Imaging. 2023 Sep 27;2023:9839816. doi: 10.1155/2023/9839816. eCollection 2023.


ABSTRACT


[This retracts the article DOI: 10.1155/2022/2471039.].


PMID:37810512 | PMC:PMC10551532 | DOI:10.1155/2023/9839816

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11:13

PubMed articles on: Cardio-Oncology

11:13

PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prevention in cancer care: implementation strategies to address underuse


Res Pract Thromb Haemost. 2023 Aug 20;7(7):102173. doi: 10.1016/j.rpth.2023.102173. eCollection 2023 Oct.


ABSTRACT


BACKGROUND: Evidenced-based interventions have been developed to prevent venous thromboembolism (VTE) in ambulatory patients with cancer, including VTE-risk assessment for all patients and targeted primary thromboprophylaxis for high-risk patients. Despite supportive evidence and recommendations, oncologists rarely assess VTE risk or provide primary prophylaxis. Our previous work identified barriers and facilitators to using VTE prevention interventions in oncology practice.


OBJECTIVES: To identify potential strategies that address the identified barriers and leverage facilitators to achieve successful implementation of evidence-based interventions for VTE prevention in oncology practice.


METHODS: We used the Implementation Research Logic Model, an implementation science framework, to map the relationships among barriers and facilitators, feasible and effective implementation strategies, and implementation and clinical outcomes that will be used to evaluate the implementation strategies.


RESULTS: We identified 12 discrete implementation strategies (eg, conducting clinician education and training and staged implementation scale-up) that address barriers and leverage facilitators through their mechanisms of action (eg, increased clinician awareness of evidence and targeting the highest effectiveness). We identified key implementation (eg, penetration, adoption, acceptability, fidelity, appropriateness, and sustainability), system (eg, integration of VTE-risk assessment into clinical workflow), and clinical (eg, lower VTE rates) outcomes targeted by the selected strategies.


CONCLUSION: Using the Implementation Research Logic Model framework and building on our knowledge of barriers and facilitators, we identified implementation strategies and important outcomes to evaluate these strategies. We will use these results to test and measure the strategies to improve the uptake of evidence-based recommendations for VTE prevention in oncology practice.


PMID:37822563 | PMC:PMC10562910 | DOI:10.1016/j.rpth.2023.102173

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11:13

PubMed articles on: Cancer & VTE/PE

Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium

11:13

PubMed articles on: Cancer & VTE/PE

Impact of mild thrombocytopenia on bleeding and recurrent thrombosis in cancer

11:13

PubMed articles on: Cardio-Oncology

11:13

PubMed articles on: Cardio-Oncology

11:13

PubMed articles on: Cancer & VTE/PE

In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban

11:13

PubMed articles on: Cancer & VTE/PE

Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients

11:13

PubMed articles on: Cardio-Oncology

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15:14

Cardiotoxicity News

PubMed articles on: Cardio-Oncology

Chinese Clinical Trial Registry 13-year data collection and analysis: geographic distribution, financial support, research phase, duration, and disease categories


Front Med (Lausanne). 2023 Oct 12;10:1203346. doi: 10.3389/fmed.2023.1203346. eCollection 2023.


ABSTRACT


OBJECTIVE: To evaluate the current status of trial registration on the Chinese Clinical Trial Registry (ChiCTR).


DESIGN: In this descriptive study, a multi-dimensional grouping analysis was conducted to estimate trends in the annual trial registration, geographical distribution, sources of funding, targeted diseases, and trial subtypes.


SETTING: We have analyzed all clinical trial records (over 30,000) registered on the Chinese Clinical Trial Registry (ChiCTR) from 2007 to 2020 executed in China.


MAIN OUTCOMES AND MEASURES: The main outcome was the baseline characteristics of registered trials. These trials were categorized and analyzed based on geographical distribution, year of implementation, disease type, resource and funding type, trial duration, trial phase, and the type of experimental approach.


RESULTS: From 2008 to 2017, a consistent upward trend in clinical trial registrations was observed, showing an average annual growth rate of 29.2%. The most significant year-on-year (yoy%) growth in registrations occurred in 2014 (62%) and 2018 (68.5%). Public funding represented the predominant source of funding in the Chinese healthcare system. The top five ChiCTR registration sites for all disease types were highly populated urban regions of China, including Shanghai (5,658 trials, 18%), Beijing (5,127 trials, 16%), Guangdong (3,612 trials, 11%), Sichuan (2,448 trials, 8%), and Jiangsu (2,196 trials, 7%). Trials targeting neoplastic diseases accounted for the largest portion of registrations, followed by cardio/cerebrovascular disease (CCVD) and orthopedic diseases-related trials. The largest proportions of registration trial duration were 1-2 years, less than 1 year, and 2-3 years (at 27.36, 26.71, and 22.46%). In the case of the research phase, the top three types of all the registered trials are exploratory research, post-marketing drugs, and clinical trials of new therapeutic technology.


CONCLUSION AND RELEVANCE: Oncological and cardiovascular diseases receive the highest share of national public funding for medical clinical trial-based research in China. Publicly funded trials represent a major segment of the ChiCTR registry, indicating the dominating role of public governance in this health research sector. Furthermore, the growing number of analyzed records reflect the escalation of clinical research activities in China. The tendency to distribute funding resources toward exceedingly populated areas with the highest incidence of oncological and cardiovascular diseases reveals an aim to reduce the dominating disease burden in the urban conglomerates in China.


PMID:37901406 | PMC:PMC10602811 | DOI:10.3389/fmed.2023.1203346

15:14

PubMed articles on: Cardio-Oncology

Successful Rechallenge with Osimertinib following Osimertinib-Induced Ventricular Tachycardia: A Case Report


Case Rep Oncol. 2023 Oct 11;16(1):1100-1106. doi: 10.1159/000533826. eCollection 2023 Jan-Dec.


ABSTRACT


Osimertinib, a third-generation tyrosine kinase inhibitor, is the first-line treatment for metastatic non-small cell lung cancer (NSCLC) with sensitizing epidermal growth factor receptor (EGFR) mutations. It is known to cause drug-induced cardiotoxicity, including QT prolongation syndrome, heart failure, and ventricular arrhythmias, which can lead to sudden death. Once severe arrhythmias occur, it is difficult to continue osimertinib treatment. We report a case of a 66-year-old woman with recurrent NSCLC after concurrent chemoradiotherapy who experienced osimertinib-induced ventricular arrhythmia-causing syncope. The patient was initially treated with concurrent chemoradiotherapy, and genetic testing revealed EGFR exon 19 deletion. Three years following treatment initiation, the primary tumor progressed, and new bone metastases developed. The patient was diagnosed with recurrent NSCLC and was treated with targeted therapy with osimertinib. On the 10th day of osimertinib administration, syncope occurred. Electrocardiography showed polymorphic non-sustained ventricular tachycardia, which was believed to be the cause of syncope. The patient was switched to erlotinib. Two and a half years later, disease progression in the primary lesion was observed. A liquid biopsy revealed an EGFR T790M resistance mutation. Therefore, osimertinib (40 mg) was administered every alternate day. After confirming the absence of palpitations and arrhythmias on electrocardiogram, the osimertinib dosing was increased to 40 mg daily. Thereafter, no further events occurred, and tumor shrinkage was observed. Low-dose osimertinib rechallenge after induced ventricular arrhythmia may be considered an option under close monitoring; however, osimertinib rechallenge must be carefully selected based on the risk-benefit analysis.


PMID:37900846 | PMC:PMC10601787 | DOI:10.1159/000533826

15:15

PubMed articles on: Cardio-Oncology

Case report: Successful treatment of malignant pericardial effusion with pericardiocentesis, concurrent anti-inflammatory therapy and cancer therapy


Front Cardiovasc Med. 2023 Oct 12;10:1285233. doi: 10.3389/fcvm.2023.1285233. eCollection 2023.


ABSTRACT


Despite significant advancements in systemic anticancer therapies, cardiac tamponade remains a serious and potentially life-threatening complication in metastatic breast cancer (MBC). However, there is a paucity of comprehensive research investigating alternative management approaches, such as pericardiocentesis and anti-inflammatory therapy (AIT), to effectively address cardiac tamponade and mitigate the risk of heart failure arising from constrictive physiology (CP) in patients with MBC when traditional systemic anticancer drugs fail to yield favorable outcomes. Herein, we describe two cases of MBC with cardiac tamponade that occurred despite the administration of effective systemic anticancer drugs. In each case, pericardial effusion was detected in a patient who was undergoing palliative anticancer therapy for human epidermal growth factor receptor 2 (HER2)-positive MBC. The patients in these cases were successfully treated with pericardiocentesis and AIT (prednisolone and colchicine) for subsequent CP without substitution with their systemic anticancer drugs. Cardiac tamponade and CP are regarded as signs of advanced cancer and are associated with a worse clinical outcome in general; however, they can still be treated with an effective anticancer drug, pericardiocentesis, and management of CP by cardiooncology specialists.


PMID:37900575 | PMC:PMC10601458 | DOI:10.3389/fcvm.2023.1285233

15:15

PubMed articles on: Cardio-Oncology

SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Cancer Therapy-Related Cardiac Dysfunction


JACC Heart Fail. 2023 Oct 12:S2213-1779(23)00596-6. doi: 10.1016/j.jchf.2023.08.026. Online ahead of print.


ABSTRACT


BACKGROUND: Certain antineoplastic therapies are associated with an increased risk of cardiomyopathy and heart failure (HF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in patients with HF.


OBJECTIVES: This study aims to examine the efficacy of SGLT2 inhibitors in patients with cancer therapy-related cardiac dysfunction (CTRCD) or HF.


METHODS: The authors conducted a retrospective cohort analysis of deidentified, aggregate patient data from the TriNetX research network. Patients aged ≥18 years with a history of type 2 diabetes mellitus, cancer, and exposure to potentially cardiotoxic antineoplastic therapies, with a subsequent diagnosis of cardiomyopathy or HF between January 1, 2013, and April 30, 2020, were identified. Patients with ischemic heart disease were excluded. Patients receiving guideline-directed medical therapy were divided into 2 groups based on SGLT2 inhibitor use. After propensity score matching, odds ratios (ORs) and Cox proportional HRs were used to compare outcomes over a 2-year follow-up period.


RESULTS: The study cohort included 1,280 patients with CTRCD/HF (n = 640 per group; mean age: 67.6 years; 41.6% female; 68% White). Patients on SGLT2 inhibitors in addition to conventional guideline-directed medical therapy had a lower risk of acute HF exacerbation (OR: 0.483 [95% CI: 0.36-0.65]; P < 0.001) and all-cause mortality (OR: 0.296 [95% CI: 0.22-0.40]; P = 0.001). All-cause hospitalizations or emergency department visits (OR: 0.479; 95% CI: 0.383-0.599; P < 0.001), atrial fibrillation/flutter (OR: 0.397 [95% CI: 0.213-0.737]; P = 0.003), acute kidney injury (OR: 0.486 [95% CI: 0.382-0.619]; P < 0.001), and need for renal replacement therapy (OR: 0.398 [95% CI: 0.189-0.839]; P = 0.012) were also less frequent in patients on SGLT2 inhibitors.


CONCLUSIONS: SGLT2 inhibitor use is associated with improved outcomes in patients with CTRCD/HF.


PMID:37897456 | DOI:10.1016/j.jchf.2023.08.026

15:15

PubMed articles on: Cardio-Oncology

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy


Pharmaceuticals (Basel). 2023 Oct 11;16(10):1441. doi: 10.3390/ph16101441.


ABSTRACT


Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy regimen for colorectal, gastric, and breast cancers, cardiotoxicity caused by 5-fluorouracil might affect anywhere from 1.5% to 18% of patients. The precise mechanisms underlying cardiotoxicity associated with CRC treatment are complex and may involve the modulation of various signaling pathways crucial for maintaining cardiac health including TKI ErbB2 or NRG-1, VEGF, PDGF, BRAF/Ras/Raf/MEK/ERK, and the PI3/ERK/AMPK/mTOR pathway, resulting in oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis, ultimately damaging cardiac tissue. Thus, the identification and management of cardiotoxicity associated with CRC drug therapy while minimizing the negative impact have become increasingly important. The purpose of this review is to catalog the potential cardiotoxicities caused by anticancer drugs and targeted therapy used to treat colorectal cancer as well as strategies focused on early diagnosing, prevention, and treatment of cardiotoxicity associated with anticancer drugs used in CRC therapy.


PMID:37895912 | PMC:PMC10610064 | DOI:10.3390/ph16101441

15:15

PubMed articles on: Cardio-Oncology

Multimodality Cardiovascular Imaging of Cardiotoxicity Due to Cancer Therapy


Life (Basel). 2023 Oct 23;13(10):2103. doi: 10.3390/life13102103.


ABSTRACT


Cancer therapies have revolutionized patient survival rates, yet they come with the risk of cardiotoxicity, necessitating effective monitoring and management. The existing guidelines offer a limited empirical basis for practical approaches in various clinical scenarios. This article explores the intricate relationship between cancer therapy and the cardiovascular system, highlighting the role of advanced multimodality imaging in monitoring patients before, during, and after cancer treatment. This review outlines the cardiovascular effects of different cancer therapy classes, offering a comprehensive understanding of their dose- and time-dependent impacts. This paper delves into diverse imaging modalities such as echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography, and nuclear imaging, detailing their strengths and limitations in various conditions due to cancer treatment, such as cardiac dysfunction, myocarditis, coronary artery disease, Takotsubo cardiomyopathy, pulmonary hypertension, arterial hypertension, valvular heart diseases, and heart failure with preserved ejection fraction. Moreover, it underscores the significance of long-term follow-up for cancer survivors and discusses future directions.


PMID:37895484 | PMC:PMC10608651 | DOI:10.3390/life13102103

15:15

PubMed articles on: Cardio-Oncology

H-Dot Mediated Nanotherapeutics Mitigate Systemic Toxicity of Platinum-Based Anticancer Drugs


Int J Mol Sci. 2023 Oct 23;24(20):15466. doi: 10.3390/ijms242015466.

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