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المؤلفون: Mohamed K. Abdel-Rafei, Noura M Thabet, Nermeen M El Bakary, Ghada El Tawill, Khaled Shaaban Azab, Neama M El Fatih
المصدر: Journal of Radiation Research
مصطلحات موضوعية: Necrosis, Antioxidant, Health, Toxicology and Mutagenesis, medicine.medical_treatment, Fucoxanthin, Xanthophylls, Kidney, Antioxidants, chemistry.chemical_compound, Mice, 0302 clinical medicine, chemistry.chemical_classification, 0303 health sciences, Apelin Receptors, Radiation, Glutathione peroxidase, NF-kappa B, Apelin-13/APJ, Malondialdehyde, Oxidants, Apelin, medicine.anatomical_structure, Liver, Matrix Metalloproteinase 9, Organ Specificity, 030220 oncology & carcinogenesis, Intercellular Signaling Peptides and Proteins, Matrix Metalloproteinase 2, medicine.symptom, MMP-9, Whole-Body Irradiation, Signal Transduction, medicine.medical_specialty, α-7nAchR, 03 medical and health sciences, Lactate dehydrogenase, Internal medicine, medicine, Animals, Radiology, Nuclear Medicine and imaging, Fundamental Radiation Science, 030304 developmental biology, Inflammation, Tissue Inhibitor of Metalloproteinase-1, L-Lactate Dehydrogenase, Monocyte, Glutathione, γ-radiation, Endocrinology, chemistry, Gamma Rays, AcademicSubjects/SCI00960, AcademicSubjects/MED00870
الوصف: Apelin-13 and APJ are implicated in different key physiological processes. This work aims at exploring the radioprotective effect of fucoxanthin (FX) on γ-radiation (RAD)-induced changes in the apelin-13/APJ pathway, which causes damage in the liver, kidney, lung and spleen of mice. Mice were administered FX (10 mg kg–1 day–1, i.p) and exposed to γ-radiation (2.5 Gy week–1) for four consecutive weeks. The treatment of irradiated mice by FX resulted in a significant amendment in protein expression of the apelin-13/APJ/NF-κB signalling pathway concurrently with reduced hypoxia (hypoxia-inducible factor-1α), suppressed oxidative stress marker (malondialdehyde), enhanced antioxidant defence mechanisms (reduced glutathione and glutathione peroxidase), a modulated inflammatory response [interleukin-6 (IL-6), monocyte chemoattractant protein-1, IL-10 and α-7-nicotinic acetylcholine receptor) and ameliorated angiogenic regulators [matrix metalloproteinase (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1), as well as the tissue damage indicator (lactate dehydrogenase) in organ tissues. In addition, there were significant improvement in serum inflammatory markers tumour necrosis factor-α, IL-10, IL-1β and C-reactive protein compared with irradiated mice. The histopathological investigation of the FX + RAD organ tissues support the biochemical findings where the improvements in the tissues’ architecture were obvious when compared with those of RAD. FX was thus shown to have a noticeable radioprotective action mediated through its regulatory effect on the apelin-13/APJ/NF-κB signalling pathway attributed to its antioxidant and anti-inflammatory activity that was reflected in different physiological processes. It could be recommended to use FX in cases of radiation exposure to protect normal tissues.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e30214c17e6d8f3108e2b41351abd16bTest
http://europepmc.org/articles/PMC8273792Test -
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المؤلفون: Yasutomo Nakai, Motokiyo Komiyama, Naohisa Kusakabe, Motohide Uemura, Mikio Sugimoto, Satoshi Anai, Keita Tamura, Nobuo Shinohara, Kosuke Ueda, Ken Tanaka, Keita Minami, Kojiro Ohba, Tetsuya Shindo, Michinobu Ozawa, Naoki Kohei, Toshihiro Suzuki, Takahiro Osawa, Hideaki Miyake, Ario Takeuchi, Akira Yokomizo
المصدر: Japanese Journal of Clinical Oncology. 51:810-818
مصطلحات موضوعية: Male, Oncology, Cancer Research, medicine.medical_specialty, Axitinib, medicine.medical_treatment, Urologic Oncology, Antineoplastic Agents, Targeted therapy, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Japan, Risk Factors, Renal cell carcinoma, Albumins, Lactate dehydrogenase, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Carcinoma, Renal Cell, Aged, L-Lactate Dehydrogenase, biology, business.industry, C-reactive protein, Albumin, Cancer, General Medicine, Middle Aged, Prognosis, medicine.disease, Kidney Neoplasms, C-Reactive Protein, chemistry, 030220 oncology & carcinogenesis, biology.protein, Female, business, medicine.drug
الوصف: Purpose To externally validate the utility of the albumin, C-reactive protein and lactate dehydrogenase model to predict the overall survival of previously treated metastatic renal cell carcinoma patients. Patients and methods The ability of the albumin, C-reactive protein and lactate dehydrogenase model to predict overall survival was validated and compared with those of other prognostication models using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib therapy at 36 hospitals belonging to the Japan Urologic Oncology Group. Results The following factors in this cohort were independently associated with poor overall survival in a multivariate analysis: a low Karnofsky performance status, 50%. The superiority of the albumin, C-reactive protein and lactate dehydrogenase model to the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models, but not the Japan Urologic Oncology Group model, was demonstrated by multiple statistical analyses. Conclusions The utility of the albumin, C-reactive protein and lactate dehydrogenase model as a simple and objective prognostication tool was successfully validated using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6bbf92a5720e1bd1b2933673aa01ae3dTest
https://doi.org/10.1093/jjco/hyaa264Test -
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المؤلفون: Cornelia Mauch, Oana D. Persa
المصدر: Future Oncology. 17:3809-3817
مصطلحات موضوعية: Adult, Male, 0301 basic medicine, MAPK/ERK pathway, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Immune checkpoint inhibitors, education, 03 medical and health sciences, 0302 clinical medicine, Elevated lactate dehydrogenase, Internal medicine, medicine, Humans, Immune Checkpoint Inhibitors, Melanoma, Protein Kinase Inhibitors, Aged, Retrospective Studies, Advanced melanoma, Chemotherapy, Univariate analysis, business.industry, General Medicine, Middle Aged, medicine.disease, humanities, Treatment Outcome, 030104 developmental biology, MAPK Inhibitors, 030220 oncology & carcinogenesis, Retreatment, Female, business
الوصف: Background: When patients with advanced melanoma progress after MAPK inhibitor (MAPKI) and immune checkpoint inhibitor (ICI) treatment, they can either undergo chemotherapy or rechallenge with previously used treatments. Methods: The outcomes of 48 patients retreated with MAPKIs and 50 patients retreated with ICIs following progression were retrospectively analyzed. Results: Upon retreatment with MAPKIs, the disease control rate was 60%. Univariate analysis of possible risk factors associated with short progression-free survival upon MAPKI treatment showed elevated LDH to be associated with decreased progression-free survival. Disease control rate after ICI retreatment was 24%. Melanoma of unknown primary was associated with prolonged progression-free survival upon ICI retreatment. Conclusion: Retreatment with MAPKIs or ICIs is a feasible option for patients with advanced melanoma.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7bb6088a468b29625321685c0107e2b3Test
https://doi.org/10.2217/fon-2021-0446Test -
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المؤلفون: Asami Ikeda, Kenji Takakura, Kaoru Abiko, Ken Yamaguchi, Ikuo Konishi, Noriko Satoh-Asahara, Hajime Yamakage
المصدر: Obstetrics & Gynecology Science, Vol 63, Iss 6, Pp 709-718 (2020)
Obstetrics & Gynecology Scienceمصطلحات موضوعية: medicine.medical_specialty, Lymphocyte, medicine.medical_treatment, chemotherapy, Gastroenterology, lcsh:Gynecology and obstetrics, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Lactate dehydrogenase, Medicine, platinum, Neutrophil to lymphocyte ratio, lcsh:RG1-991, Chemotherapy, 030219 obstetrics & reproductive medicine, business.industry, Area under the curve, Obstetrics and Gynecology, Cancer, lactate dehydrogenase, Gynecologic Oncology, medicine.disease, medicine.anatomical_structure, ovarian cancer, chemistry, 030220 oncology & carcinogenesis, Original Article, business, Ovarian cancer, serum, Lipoprotein
الوصف: Objective The need for tailoring ovarian cancer treatments to individual patients is increasing. This study aimed to evaluate the prognostic value of pretreatment laboratory test data for predicting the response and survival outcomes of platinum-based chemotherapy in ovarian cancer. Methods We enrolled 270 patients with ovarian cancer diagnosed at the Kyoto Medical Center (n=120; group A) and Kyoto University (n=150; group B). Data on 9 blood parameters (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte rate [PLR], C-reactive protein, lactate dehydrogenase [LDH], glucose, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein, and triglyceride levels), cancer pathology, cancer stage, cytoreduction outcomes, serum cancer antigen 125 levels, platinum-free interval (PFI), disease-free survival (DFS), and overall survival were assessed retrospectively. Results NLR, PLR, LDH, and HDL were significantly different in advanced stage patients (P
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3b012cdae66b68c06eafa22f6e1aa80Test
http://www.ogscience.org/upload/pdf/ogs-20117.pdfTest -
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المصدر: Clinical Phytoscience, Vol 7, Iss 1, Pp 1-9 (2021)
مصطلحات موضوعية: Antioxidant, medicine.medical_treatment, Pharmacology, 01 natural sciences, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Rhamnus alaternus, Lactate dehydrogenase, medicine, Aluminum Chloride, General Environmental Science, chemistry.chemical_classification, biology, integumentary system, Glutathione peroxidase, Hepatotoxicity, RX1-681, Rhamnus alaternus Aqueous Extract, Glutathione, Homeopathy, biology.organism_classification, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Oxidative Stress, chemistry, Catalase, 030220 oncology & carcinogenesis, biology.protein, General Earth and Planetary Sciences, Alkaline phosphatase, Rat, Medicine
الوصف: Background This study was designed to evaluate the protective effects of a Rhamnus alaternus aqueous extract (RAAE) on aluminum chloride-induced hepatotoxicity in rats. A preliminary phytochemical study and antioxidant activity tests of the extract were performed. Methods A preliminary phytochemical study and antioxidant activity tests of the extract were performed. For the in vivo study, twenty-four male rats were divided into four groups. The control group (C); the RAAE group treated with 250 mg/kg b.w RAAE; the AlCl3 group, which received 50 mg/kg b.w AlCl3; and the AlCl3/RAAE group that was treated with AlCl3 plus RAAE. Results The RAAE contains several phenolic compounds. This plant extract showed a high radical scavenging effect and high antioxidant activity. Administration of AlCl3 resulted in a significant increase in the activities of aspartate aminotransferase and alanine aminotransferase (AST, ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and significant decreases in the plasma concentrations of total proteins and albumin. Moreover, AlCl3 induced a hepatic pro-oxidant effect leading to an increase in malonaldehyde (MDA) and carbonyl protein contents, the depletion of the content of reduced glutathione (GSH) and a decrease in the antioxidant enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). However, RAAE supplementation with AlCl3 treatment significantly decreased the levels of MDA and carbonyl proteins and markedly restored the activities of the antioxidant enzymes. These results are supported by the improvement in liver tissue restoration. Conclusions The Rhamnus alaternus aqueous extract was shown to have effective antioxidant activity owing to its phenolic compounds protecting against AlCl3-induced liver oxidative damage.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ca2e0d7f234cf34f754bd956cb798474Test
https://doaj.org/article/7737962bc27c4a31a39e1be550c53fb0Test -
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المؤلفون: Dai Takeuchi, Toyone Kikumori, Masahiro Shibata
المصدر: World Journal of Surgery. 45(7):2142-2145
مصطلحات موضوعية: Parathyroidectomy, Frozen section procedure, business.industry, medicine.medical_treatment, Thyroid, 030230 surgery, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine.anatomical_structure, chemistry, Postoperative hypoparathyroidism, 030220 oncology & carcinogenesis, Lactate dehydrogenase, Medicine, Surgery, Parathyroid surgery, business, Nuclear medicine, Primary hyperparathyroidism, Point of care
الوصف: Background: We reported that aspartate aminotransferase (AST)/lactate dehydrogenase (LDH) ratio of a tissue suspension can precisely differentiate normal and hyperfunctioning parathyroid tissue (PT) from other tissues. However, in these studies, LDH and AST were measured using the standard method for blood samples, with a turnaround time of approximately 1 h, hampering clinical application. Here, we developed a rapid and robust method to differentiate PT instead of using frozen sections. Methods: Excised specimens from 28 patients (n = 69) who underwent thyroid or parathyroid surgery between October 2019 and April 2020 were analyzed. AST and LDH were measured in suspensions of PT or other tissues, using both the standard method in the in-facility laboratory and a point-of-care testing device (NX500, Fujifilm, Japan). Results and conclusions: A good correlation was found between the standard method and NX500 for AST and LDH levels >10 IU/L. In the analyses using 52 specimens with ≥ 10 IU/L of both AST and LDH measured using the NX500, PT was distinguished with 100% sensitivity and specificity using an optimal cutoff AST/LDH ratio of 0.48. The turnaround time was estimated to be less than 10 min. This method could be a cost- and labor-effective alternative to frozen sections to reduce the incidence of postoperative hypoparathyroidism and improve the outcome of primary hyperparathyroidism in low-resource areas.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71cf4beb08b106b4fa98d9c3b19fd452Test
https://nagoya.repo.nii.ac.jp/records/2001616Test -
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المصدر: BMC Pharmacology and Toxicology, Vol 22, Iss 1, Pp 1-11 (2021)
BMC Pharmacology & Toxicologyمصطلحات موضوعية: 0301 basic medicine, Male, Bilirubin, medicine.medical_treatment, RM1-950, Pharmacology, Protective Agents, Melittin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, Malondialdehyde, RA1190-1270, medicine, Isoniazid, Animals, Tuberculosis, Pharmacology (medical), Aspartate Aminotransferases, Bee venom, Saline, Rifampicin, business.industry, Hepatotoxicity, Alanine Transaminase, Glutathione, Blood Proteins, Alkaline Phosphatase, Melitten, Rats, 030104 developmental biology, chemistry, Liver, 030220 oncology & carcinogenesis, Toxicology. Poisons, Alkaline phosphatase, Therapeutics. Pharmacology, Chemical and Drug Induced Liver Injury, Rifampin, business, medicine.drug, Research Article
الوصف: BackgroundThe present study investigated the ameliorative effect of melittin, a major polypeptide in the venom of honeybee (Apis mellifera), on isoniazid-(INH) and rifampicin-(RIF) induced hepatotoxicity in male albino rats.MethodThirty rats (140-200 g) were divided into five groups (n = 6): normal control (NC) received normal saline orally (NaCl, 0.9%; toxic (T) group received INH + RIF (each rat received 100 mg/kg, p.o.); melittin (Mel15, Mel30) groups (each rat received 15 or 30 μg/kg s.c); and normal recovery (NR) group received INH + RIF (each rat received 100 mg/kg, p.o.). Blood and liver samples were collected for biochemical, hematological and histopathological studies respectively.ResultsThe administration of melittin was found to prevent the antitubercular drug-induced alterations in the diagnostic markers; reduced glutathione (GSH), direct bilirubin (DB), total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and total serum protein (TSP). Besides, hematological alterations were significantly high in Mel groups when compared to the toxic group. The NR group exhibited lower levels of DB, TB, ALP, LDH and TSP. In addition, treatment with melittin offered protection in the NR group with respect to MDA levels.ConclusionEvidence from this study suggests that melittin is beneficial for the prevention of acute hepatic failure in antitubercular drug-induced hepatoxicity and could be used as a potential therapeutic agent.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf0dc8db1532b81b74f63f446338ebd8Test
https://doaj.org/article/bf86734e1c1e4ae18f70398a1043577fTest -
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المؤلفون: Roni Shouval, Angharad Pryce, Richard Szydlo, Avichai Shimoni, Jiri Pavlu, Mika Geva, Arnon Nagler, Noga Shem-Tov, Ivetta Danylesko, Joshua A Fein, Ronit Yerushalmi
المصدر: Bone Marrow Transplantation. 56:2690-2696
مصطلحات موضوعية: medicine.medical_specialty, Transplantation Conditioning, medicine.medical_treatment, Hematopoietic stem cell transplantation, Single Center, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Cumulative incidence, Adverse effect, Retrospective Studies, Transplantation, L-Lactate Dehydrogenase, business.industry, Lymphoma, Non-Hodgkin, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, medicine.disease, Lymphoma, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, business, 030215 immunology
الوصف: Risk stratification is important for balancing potential risks and benefits of allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. We retrospectively studied 1119 patients undergoing allogenic-HSCT in a single center for five hematological indications assessing the prognostic role of LDH at admission for survival (OS), progression-free survival (PFS), relapse incidence (RI), and nonrelapse mortality (NRM). In non-Hodgkin lymphoma (NHL) and acute myeloid leukemia (AML), higher than median LDH had an adverse effect on survival. The prognostic significance was strongest in AML, with higher LDH levels having lower 1-and 3-year survival 69.2% vs. 50.8%, P
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::29a58c3f0d32fc4bc86c23c2de7637c0Test
https://doi.org/10.1038/s41409-021-01377-9Test -
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المؤلفون: Vivek A. Kumar, Julia McNabb-Baltar, Ebrahim Barkoudah, David X. Jin, Daniel Andrade Tinoco de Souza
المصدر: European Journal of Gastroenterology & Hepatology. 33:695-700
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Severity of Illness Index, White People, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, Thromboembolism, Internal medicine, Severity of illness, medicine, Humans, Hospital Mortality, Sex Distribution, Aged, Retrospective Studies, Mechanical ventilation, Respiratory Distress Syndrome, L-Lactate Dehydrogenase, Hepatology, biology, Pancreatitis, Acute Necrotizing, SARS-CoV-2, business.industry, C-reactive protein, Gastroenterology, COVID-19, Retrospective cohort study, Hispanic or Latino, Lipase, Length of Stay, Middle Aged, medicine.disease, Pathophysiology, Black or African American, C-Reactive Protein, Pancreatitis, Respiratory failure, 030220 oncology & carcinogenesis, Ferritins, biology.protein, Acute pancreatitis, Female, 030211 gastroenterology & hepatology, business
الوصف: BACKGROUND: The data on clinical course and outcome of acute pancreatitis among patients with coronavirus disease 2019 (COVID-19) are sparse. In this study, we analyzed the clinical profiles of patients with COVID 19 and acute pancreatitis. METHODS: This retrospective study was conducted on Research Patient Data Registry data which was pooled from five Mass General Brigham Healthcare Network hospitals. We extracted data on demographics, symptoms, ICU transfer, mechanical ventilation, laboratories' profiles, imaging findings, and patient outcomes. RESULT: Of 985 screened adult patients, 17 were eligible for the study, 9 (52.9%) were admitted primarily for respiratory failure and developed acute pancreatitis after a median of 22.5 days (13-76 days) from the onset of COVID-19 symptoms. On contrary, eight patients presented with typical symptoms and were diagnosed with acute pancreatitis, the majority with mild severity (62.5%) on admission. Patients who were admitted primarily with severe COVID-19 illness were younger (median age 57 vs. 63 years), females (55.6 vs. 25%), of Hispanic ethnicity (55.6 vs. 25%), and obese (88.9 vs. 37.5%). The median peak lipase, C reactive protein, ferritin, lactate dehydrogenase, D-dimer were higher among patients who developed acute pancreatitis later during hospitalization. Patients who developed acute pancreatitis later also experienced higher episodes of necrotizing pancreatitis (11.1% vs. 0), thromboembolic complications (55.6 vs. 12.5%), and higher mortality (37.5 vs. 12.5%). CONCLUSION: Acute pancreatitis is not common among patients with COVID-19. Patients with COVID-19 who had acute pancreatitis on admission had more benign course and overall better outcome as compared to the patients who developed acute pancreatitis during hospitalization.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4446e8ff200e1906adeb09ab460f98faTest
https://doi.org/10.1097/meg.0000000000002160Test -
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المؤلفون: Giuseppe Luigi Banna, U. De Giorgi, Valeria Urzia, Helga Lipari, Giuseppe Fornarini, Marco Maruzzo, Lorenzo Malatino, Alfredo Addeo, R. Di Quattro, Umberto Basso, Francesco Rundo
المصدر: Clinical and Translational Oncology. 22:2130-2135
مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Urologic Neoplasms, Cancer Research, medicine.medical_specialty, Poor prognosis, LDH, Neutrophils, medicine.medical_treatment, Prognostic, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immune system, Lactate dehydrogenase, Internal medicine, Urothelial cancer, medicine, Humans, Lymphocytes, Neutrophil to lymphocyte ratio, Immune Checkpoint Inhibitors, Neutrophil-to-lymphocyte ratio, Aged, L-Lactate Dehydrogenase, business.industry, fungi, Biomarker, General Medicine, Immunotherapy, Middle Aged, medicine.disease, 030104 developmental biology, Oncology, chemistry, 030220 oncology & carcinogenesis, Biomarker (medicine), Female, Urothelium, business, Biomarkers, Progressive disease
الوصف: To identify patients with metastatic urothelial cancer (mUC) unlikely to benefit from immune-checkpoint inhibitors (ICIs). We explored the predictive and prognostic values of baseline neutrophil-to-lymphocyte ratio (NLR), with cut-offs ≥ 3 and ≥ 5, and of a urothelial immune prognostic index (UIPI, based on increased NLR and LDH), on 146 patients. NLR and UIPI significantly predicted progressive disease and progression-free survival with both cut-offs (p = 0.0069, p = 0.0034, p = 0.0160, p = 0.0063; p
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0ccd7de4b4b85400ae7e1057b16daafeTest
https://doi.org/10.1007/s12094-020-02337-3Test