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Article ; Online: Increased symmetric dimethylarginine, but not asymmetric dimethylarginine, concentrations are associated with transient myocardial ischemia and predict outcome

Zsuzsanna Szabo / Eva Bartha / Lajos Nagy / Tihamer Molnar

Journal of International Medical Research, Vol

2020 Volume 48

Abstract: Objective Asymmetric and symmetric dimethylarginines (ADMA and SDMA) are endothelial dysfunction markers. ADMA inhibits synthesis of nitric oxide. We aimed to analyze both markers in patients with coronary artery disease (CAD) who were referred for ... ...

Abstract	Objective Asymmetric and symmetric dimethylarginines (ADMA and SDMA) are endothelial dysfunction markers. ADMA inhibits synthesis of nitric oxide. We aimed to analyze both markers in patients with coronary artery disease (CAD) who were referred for stress/rest myocardial perfusion scintigraphy (MPS). Methods All patients underwent a 2-day dipyridamole (DP) stress/rest protocol. Thereafter, patients with transient myocardial perfusion abnormality were followed up and their coronary blood flow was quantitatively assessed. Venous blood was taken before and after DP stress to measure markers. Results Baseline ADMA and SDMA concentrations were significantly higher in patients with CAD compared with healthy subjects. Pre- and post-stress SDMA concentrations were significantly higher in patients with transient myocardial perfusion abnormality compared with those with negative MPS results. However, ADMA and L-arginine concentrations were not significantly different between the two groups. None of the markers were significantly different between patients with angiographically proven low coronary flow and those with normal coronary flow. Pre-stress SDMA concentrations were an independent predictor of cardiovascular mortality during a 8-year follow-up. Conclusions Elevated serum SDMA concentrations may be helpful for selecting high-risk patients with CAD if there is any doubt in interpreting MPS. SDMA concentrations may also predict cardiovascular outcome.
Keywords	Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Circulating Microvesicles in Convalescent Ischemic Stroke Patients

Diana Schrick / Tihamér Molnár / Margit Tőkés-Füzesi / Abigél Molnár / Erzsébet Ezer

Frontiers in Bioscience-Landmark, Vol 27, Iss 5, p

A Contributor to High-On-Treatment Residual Platelet Reactivity?

2022 Volume 158

Abstract: Introduction: Exploration of novel and effective antiplatelet strategies for the secondary prevention of ischemic stroke is utmost. Some platelet derived microparticles (PMVs) in convalescent stroke subjects were found to be predictive for the next ... ...

Abstract	Introduction: Exploration of novel and effective antiplatelet strategies for the secondary prevention of ischemic stroke is utmost. Some platelet derived microparticles (PMVs) in convalescent stroke subjects were found to be predictive for the next vascular event. Patients with high-on-treatment platelet reactivity (HTPR) had a significantly higher risk for ischemic stroke. Here, we aimed to explore associations among circulating microparticles and responsivness to antiplatelet (clopidogrel) therapy. Methods: A total of 18 patients on clopidogrel therapy due to secondary stroke prevention were rospectively recruited into this study. Twenty age-matched healthy subjects served as controls. Flow cytometric measurements of microparicles (MVs) and data analysis were performed on Beckman-Coulter FC-500 cytometer with CXP software. Besides, platelet aggregometry data were revealed. Both measurements were performed in whole blood and from the lower and upper blood fractions separated after 1-hour gravity sedimentation by the analogy with erythrocyte sedimentation rate. Results: The total number of circulating MVs, and particularly the platelet derived CD42+ and PAC-1+ were significantly higher in post-stroke patients (p < 0.001). The platelet aggregation in the whole blood (area under the curve, AUC) showed a significant negative correlation with the total number of MPs in the lower blood sample after 1-hour gravity sedimentation (r = –0.650, p = 0.005). Next, we analyzed associations among MPs and aggregometry data obtained from clopidogrel responders and non-responders. Both, area under the curve (AUC) and velocity in the whole blood showed opposite correlation with the total number of MVs in the lower blood sample after 1-hour gravity sedimentation. Importantly, a significant negative correlation was observed for the velocity (r = –0.801, p = 0.005), but not for the AUC in responders. Platelet derived CD42+ and PAC-1+ MVs showed positive correlations with neutrophils in the lower blood sample (p = 0.008 and p = ...
Keywords	microvesicles ; platelet ; neutrophil ; ischemic stroke ; antiplatelet therapy ; clopidogrel ; Biochemistry ; QD415-436 ; Biology (General) ; QH301-705.5
Subject code	630 ; 610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	IMR Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Biomarker Associations in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

Dora Spantler / Tihamer Molnar / Diana Simon / Timea Berki / Andras Buki / Attila Schwarcz / Peter Csecsei

International Journal of Molecular Sciences, Vol 23, Iss 8789, p

2022 Volume 8789

Abstract: The prognosis for patients with aneurysmal subarachnoid hemorrhage (aSAH) is heavily influenced by the development of delayed cerebral ischemia (DCI), but the adequate and effective therapy of DCI to this day has not been resolved. Multiplex serum ... ...

Abstract	The prognosis for patients with aneurysmal subarachnoid hemorrhage (aSAH) is heavily influenced by the development of delayed cerebral ischemia (DCI), but the adequate and effective therapy of DCI to this day has not been resolved. Multiplex serum biomarker studies may help to understand the pathophysiological processes underlying DCI. Samples were collected from patients with aSAH at two time points: (1) 24 h (Day 1) and (2) 5–7 days after ictus. Serum concentrations of eotaxin, FGF-2, FLT-3L, CX3CL1, Il-1b, IL-4, IP-10, MCP3, and MIP-1b were determined using a customized MILLIPLEX Human Cytokine/Chemokine/Growth Factor Panel A multiplex assay. The functional outcome was defined by the modified Rankin scale (favorable: 0–2, unfavorable: 3–6) measured on the 30th day after aSAH. One-hundred and twelve patients with aSAH were included in this study. The median level of CX3CL1 and MCP-3 measured on Days 5–7 were significantly higher in patients with DCI compared with those without DCI (CX3CL1: with DCI: 110.5 pg/mL, IQR: 82–201 vs. without DCI: 82.6, 58–119, p = 0.036; and MCP-3: with DCI: 22 pg/mL (0–32) vs. without DCI: 0 (0–11), p < 0.001). IP-10, MCP-3, and MIP-1b also showed significant associations with the functional outcome after aSAH. MCP-3 and CX3CL1 may play a role in the pathophysiology of DCI.
Keywords	aneurysmal subarachnoid hemorrhage ; delayed cerebral ischemia ; functional outcome ; MCP-3 ; CX3CL1 ; IP-10 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: General Anesthesia-Related Drop in Diastolic Blood Pressure May Impact the Long-Term Outcome in Stroke Patients Undergoing Thrombectomy

Alan Abada / Peter Csecsei / Erzsebet Ezer / Gabor Lenzser / Peter Hegyi / Alex Szolics / Akos Merei / Andrea Szentesi / Tihamer Molnar

Journal of Clinical Medicine, Vol 11, Iss 2997, p

2022 Volume 2997

Abstract: Background: Several factors affect the efficacy of endovascular thrombectomy (EVT); however, the anesthesia-related factors have not been fully explored. We aimed to identify independent predictors of outcome by analyzing procedural factors based on a ... ...

Abstract	Background: Several factors affect the efficacy of endovascular thrombectomy (EVT); however, the anesthesia-related factors have not been fully explored. We aimed to identify independent predictors of outcome by analyzing procedural factors based on a multicentric stroke registry. Methods: Data of consecutive patients with acute ischemic stroke (AIS) were extracted from the prospective STAY ALIVE stroke registry. Demographic, clinical, and periprocedural factors including hemodynamic values were analyzed in patients undergoing thrombectomy with either general anesthesia (GA) or conscious sedation (CS). Independent predictors of outcome both at 30 and 90 days based on the modified Rankin Scale (mRS: 0–2 as favorable outcome) were also explored. Results: A total of 199 patients (GA: 76 (38%) vs. CS: 117 (59%); in addition, six patients were converted from CS to GA) were included. The minimum value of systolic, diastolic, and mean arterial pressure was significantly lower in the GA compared to the CS group, and GA was associated with a longer onset to EVT time and a higher drop in all hemodynamic variables (all, p < 0.001). A higher drop in diastolic blood pressure (DBP) was even independently associated with a poor 90-day outcome ( p = 0.024). Conclusion: A GA-related drop in DBP may independently predict a poor long-term outcome in stroke patients undergoing thrombectomy.
Keywords	ischemic stroke ; endovascular treatment ; anesthesia ; blood pressure ; outcome ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Serum Level of Anti-Nucleocapsid, but Not Anti-Spike Antibody, Is Associated with Improvement of Long COVID Symptoms

Reka Varnai / Tihamer Molnar / Laszlo Zavori / Margit Tőkés-Füzesi / Zsolt Illes / Andrea Kanizsai / Peter Csecsei

Vaccines, Vol 10, Iss 165, p

2022 Volume 165

Abstract: Background: Long COVID is a condition characterized by long-term sequelae persisting after the typical convalescence period of COVID-19. Previous reports have suggested the role of an unsatisfactory immune response and impaired viral clearance in the ... ...

Abstract	Background: Long COVID is a condition characterized by long-term sequelae persisting after the typical convalescence period of COVID-19. Previous reports have suggested the role of an unsatisfactory immune response and impaired viral clearance in the pathogenesis of long COVID syndrome. We focused on potential associations between post-vaccination changes of antibody titers and the severity of long COVID symptoms and factors influencing the state of remission observed in patients with long COVID after vaccination. Methods: The severity of long COVID symptoms and serum anti-SARS-CoV-2 spike (S-Ig) and nucleocapsid (NC-Ig) levels were assessed in 107 post-COVID subjects at two time points: at baseline, and 17–24 weeks later. Besides, vaccination status was also assessed. Symptoms were evaluated based on the Chalder fatigue scale (CFQ-11) and visual analogue scale (VAS). Results: Serum level of S-Ig and NC-Ig at baseline were significantly higher in the patients with non-severe fatigue than those with severe fatigue, and this difference remained significant at follow-up in the case of NC-Ig. NC-Ig level above median was as an independent predictor for complete remission at follow-up. The difference in NC-Ig levels in subgroup analyses (severe fatigue vs. non-severe fatigue; complete remission vs. incomplete remission or progression) was found to be significant only in patients who received vaccination. Conclusions: The immune response against the SARS-CoV-2 nucleocapsid may play a more important role than the spike in the course of long-term COVID syndrome.
Keywords	long COVID ; fatigue ; spike ; nucleocapsid ; vaccination ; Medicine ; R
Subject code	150
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fever after Vaccination against SARS-CoV-2 with mRNA-Based Vaccine Associated with Higher Antibody Levels during 6 Months Follow-Up

Andrea Kanizsai / Tihamer Molnar / Reka Varnai / Laszlo Zavori / Margit Tőkés-Füzesi / Zoltan Szalai / Janos Berecz / Peter Csecsei

Vaccines, Vol 10, Iss 447, p

2022 Volume 447

Abstract: Background: The effect of post-vaccination adverse events on immunogenicity is unknown. We aimed to explore relationship between post-vaccination adverse reactions and antibody levels during 6-month follow-up. Methods: Blood was serially drawn from ... ...

Abstract	Background: The effect of post-vaccination adverse events on immunogenicity is unknown. We aimed to explore relationship between post-vaccination adverse reactions and antibody levels during 6-month follow-up. Methods: Blood was serially drawn from healthcare workers after the second dose of BNT162b2 mRNA vaccine (Day 12, 30, 60, 90, 120, 150, and 180) and anti-SARS-CoV-2 spike IgG (S-IgG) levels were measured. Following each vaccine dose, volunteers completed a questionnaire regarding adverse reactions (symptomatic vs. asymptomatic groups). Results: A total of 395 subjects received the second dose of the vaccine. The main results were as follows: (i) fever after the 2nd dose was independently associated with the median S-IgG level at all follow-up time points; (ii) significantly higher S-IgG levels were observed in the symptomatic group of patients without prior COVID-19 infection throughout the entire follow-up period; (iii) prior COVID-19 positivity resulted in higher S-IgG levels only in the asymptomatic group from Day 90 of the follow-up period; (iv) both prior COVID-19 disease with asymptomatic status and symptomatic status without prior COVID-19 infection resulted in similar S-IgG antibody levels; (v) significantly lower serum S-IgG levels were observed in smokers. Conclusion: Fever may play an important role in the post-vaccination immune response in the long term.
Keywords	COVID-19 ; anti-SARS-CoV-2 ; spike IgG ; mRNA vaccine ; adverse reaction ; fever ; Medicine ; R
Subject code	630
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Detailed severity assessment of Cincinnati Prehospital Stroke Scale to detect large vessel occlusion in acute ischemic stroke

Gabor Tarkanyi / Peter Csecsei / Istvan Szegedi / Evelin Feher / Adam Annus / Tihamer Molnar / Laszlo Szapary

BMC Emergency Medicine, Vol 20, Iss 1, Pp 1-

2020 Volume 6

Abstract: Abstract Background Selecting stroke patients with large vessel occlusion (LVO) based on prehospital stroke scales could provide a faster triage and transportation to a comprehensive stroke centre resulting a favourable outcome. We aimed here to explore ... ...

Abstract	Abstract Background Selecting stroke patients with large vessel occlusion (LVO) based on prehospital stroke scales could provide a faster triage and transportation to a comprehensive stroke centre resulting a favourable outcome. We aimed here to explore the detailed severity assessment of Cincinnati Prehospital Stroke Scale (CPSS) to improve its ability to detect LVO in acute ischemic stroke (AIS) patients. Methods A cross-sectional analysis was performed in a prospectively collected registry of consecutive patients with first ever AIS admitted within 6 h after symptom onset. On admission stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and the presence of LVO was confirmed by computed tomography angiography (CTA) as an endpoint. A detailed version of CPSS (d-CPSS) was designed based on the severity assessment of CPSS items derived from NIHSS. The ability of this scale to confirm an LVO was compared to CPSS and NIHSS respectively. Results Using a ROC analysis, the AUC value of d-CPSS was significantly higher compared to the AUC value of CPSS itself (0.788 vs. 0.633, p < 0.001) and very similar to the AUC of NIHSS (0.795, p = 0.510). An optimal cut-off score was found as d-CPSS≥5 to discriminate the presence of LVO (sensitivity: 69.9%, specificity: 75.2%). Conclusion A detailed severity assessment of CPSS items (upper extremity weakness, facial palsy and speech disturbance) could significantly increase the ability of CPSS to discriminate the presence of LVO in AIS patients.
Keywords	Acute stroke ; Large vessel occlusion ; Stroke scales ; Prehospital ; Emergency medicine ; Neurology ; Special situations and conditions ; RC952-1245 ; Medical emergencies. Critical care. Intensive care. First aid ; RC86-88.9
Subject code	616
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Different Kinetics of Serum ADAMTS13, GDF-15, and Neutrophil Gelatinase-Associated Lipocalin in the Early Phase of Aneurysmal Subarachnoid Hemorrhage

Peter Csecsei / Csaba Olah / Reka Varnai / Diana Simon / Szabina Erdo-Bonyar / Timea Berki / Mate Czabajszki / Laszlo Zavori / Attila Schwarcz / Tihamer Molnar

International Journal of Molecular Sciences, Vol 24, Iss 11005, p

2023 Volume 11005

Abstract: Growth differentiation factor 15 (GDF-15), neutrophil gelatinase-associated lipocalin (NGAL), and ADAMTS13 have previously been implicated in the pathophysiological processes of SAH. In the present study, we aim to examine their role in the early period ... ...

Abstract	Growth differentiation factor 15 (GDF-15), neutrophil gelatinase-associated lipocalin (NGAL), and ADAMTS13 have previously been implicated in the pathophysiological processes of SAH. In the present study, we aim to examine their role in the early period of SAH and their relationship to primary and secondary outcomes. Serum samples were collected at five time periods after SAH (at 24 h (D1), at 72 h (D3), at 120 h (D5), at 168 h (D7) and at 216 h (D9), post-admission) and) were measured by using MILLIPLEX Map Human Cardiovascular Disease (CVD) Magnetic Bead Panel 2. We included 150 patients with SAH and 30 healthy controls. GDF-15 levels at D1 to D9 were significantly associated with a 3-month unfavorable outcome. Based on the ROC analysis, in patients with a good clinical grade at admission (WFNS I-III), the GDF-15 value measured at time point D3 predicted a 3-month unfavorable outcome (cut-off value: 3.97 ng/mL, AUC:0.833, 95%CI: 0.728–0.938, sensitivity:73.7%, specificity:82.6%, p < 0.001). Univariate binary logistic regression analysis showed that serum NGAL levels at D1-D5 and ADAMTS13 levels at D7-D9 were associated with MVS following SAH. GDF-15 is an early indicator of a poor 3-month functional outcome even in patients with mild clinical conditions at admission.
Keywords	subarachnoid hemorrhage ; GDF-15 ; neutrophil gelatinase-associated lipocalin ; ADAMTS13 ; delayed cerebral ischemia ; macrovascular vasospasm ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cerebral and Systemic Stress Parameters in Correlation with Jugulo-Arterial CO 2 Gap as a Marker of Cerebral Perfusion during Carotid Endarterectomy

Zoltán Kovács-Ábrahám / Timea Aczél / Gábor Jancsó / Zoltán Horváth-Szalai / Lajos Nagy / Ildikó Tóth / Bálint Nagy / Tihamér Molnár / Péter Szabó

Journal of Clinical Medicine, Vol 10, Iss 5479, p

2021 Volume 5479

Abstract: Intraoperative stress is common to patients undergoing carotid endarterectomy (CEA); thus, impaired oxygen and metabolic balance may appear. In this study, we aimed to identify new markers of intraoperative cerebral ischemia, with predictive value on ... ...

Abstract	Intraoperative stress is common to patients undergoing carotid endarterectomy (CEA); thus, impaired oxygen and metabolic balance may appear. In this study, we aimed to identify new markers of intraoperative cerebral ischemia, with predictive value on postoperative complications during CEA, performed in regional anesthesia. A total of 54 patients with significant carotid stenosis were recruited and submitted to CEA. Jugular and arterial blood samples were taken four times during operation, to measure the jugulo-arterial carbon dioxide partial pressure difference (P(j-a)CO 2 ), and cortisol, S100B, L-arginine, and lactate levels. A positive correlation was found between preoperative cortisol levels and all S100B concentrations. In addition, they are positively correlated with P(j-a)CO 2 values. Conversely, postoperative cortisol inversely correlates with P(j-a)CO 2 and postoperative S100B values. A negative correlation was observed between maximum systolic and pulse pressures and P(j-a)CO 2 after carotid clamp and before the release of clamp. Our data suggest that preoperative cortisol, S100B, L-arginine reflect patients’ frailty, while these parameters postoperatively are influenced by intraoperative stress and injury. As a novelty, P(j-a)CO 2 might be an emerging indicator of cerebral blood flow during CEA.
Keywords	carotid endarterectomy ; carbon dioxide gap ; cerebrovascular circulation ; cortisol ; L-arginine ; S100B ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in Patients with Post-COVID Symptoms

Tihamer Molnar / Reka Varnai / Daniel Schranz / Laszlo Zavori / Zoltan Peterfi / David Sipos / Margit Tőkés-Füzesi / Zsolt Illes / Andras Buki / Peter Csecsei

Journal of Clinical Medicine, Vol 10, Iss 4337, p

2021 Volume 4337

Abstract: Background: Post-COVID manifestation is defined as persistent symptoms or long-term complications beyond 4 weeks from disease onset. Fatigue and memory impairment are common post-COVID symptoms. We aimed to explore associations between the timeline and ... ...

Abstract	Background: Post-COVID manifestation is defined as persistent symptoms or long-term complications beyond 4 weeks from disease onset. Fatigue and memory impairment are common post-COVID symptoms. We aimed to explore associations between the timeline and severity of post-COVID fatigue and anti-SARS-CoV-2 antibodies. Methods: Fatigue and memory impairment were assessed in a total of 101 post-COVID subjects using the Chalder fatigue scale (CFQ-11) and a visual analogue scale. Using the bimodal scoring system generated from CFQ-11, a score ≥4 was defined as severe fatigue. Serum anti-SARS-CoV-2 spike (anti-S-Ig) and nucleocapsid (anti-NC-Ig) antibodies were examined at two time points: 4–12 weeks after onset of symptoms, and beyond 12 weeks. Results: The serum level of anti-S-Ig was significantly higher in patients with non-severe fatigue compared to those with severe fatigue at 4–12 weeks ( p = 0.006) and beyond 12 weeks ( p = 0.016). The serum level of anti-NC-Ig remained high in patients with non-severe fatigue at both time points. In contrast, anti-NC-Ig decreased significantly in severe fatigue cases regardless of the elapsed time (4–12 weeks: p = 0.024; beyond 12 weeks: p = 0.005). The incidence of memory impairment was significantly correlated with lower anti-S-Ig levels (−0.359, p < 0.001). Conclusion: The systemic immune response reflected by antibodies to SARS-CoV-2 is strongly correlated with the severity of post-COVID fatigue.
Keywords	post-COVID fatigue ; anti-SARS-CoV-2 spike Ig ; anti-SARS-CoV-2 nucleocapsid Ig ; memory impairment ; Medicine ; R
Subject code	669 ; 616
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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