Person: Munoz Venturelli, Paula
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Munoz Venturelli
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Publication Diffusion-weighted imaging as predictor of acute ischemic stroke etiology(2022) brunser, alejandro; Mansilla, Eloy; NAVIA, VICTOR; Mazzon, Enrico; Rojo, Alexis; Cavada, Gabriel; Olavarría, Verónica V.; Munoz Venturelli, Paula; Lavados, PabloBackground: Topographic patterns may correlate with causes of ischemic stroke. Objective: To investigate the association between diffusion weighted imaging (DWI) and Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Methods: We included 1019 ischemic stroke patients. DWI were classified as: i) negative; ii) DWI single lesion (cortico-subcortical, cortical, subcortical ≥20 mm, or subcortical <20 mm); iii) scattered lesions in one territory (small scattered lesions or confluent with additional lesions); and iv) multiple lesions (multiple unilateral anterior circulation [MAC], multiple posterior circulation [MPC], multiple bilateral anterior circulation [MBAC], and multiple anterior and posterior circulations [MAP]). Results: There was a relationship between DWI patterns and TOAST classification (p<0.001). Large artery atherosclerosis was associated with small, scattered lesions in one vascular territory (Odds Ratio [OR] 4.22, 95% confidence interval [95%CI] 2.61–6.8), MPC (OR 3.52; 95%CI 1.54–8.03), and subcortical lesions <20 mm (OR 3.47; 95%CI 1.76–6.85). Cardioembolic strokes correlated with MAP (OR 4.3; 95%CI 1.64–11.2), cortico-subcortical lesions (OR 3.24; 95%CI 1.9–5.5) and negative DWI (OR 2.46; 95%CI 1.1–5.49). Cryptogenic strokes correlated with negative DWI (OR 4.1; 95%CI 1,84–8.69), cortical strokes (OR 3.3; 95%CI 1.25–8.8), MAP (OR 3.33; 95%CI 1.25–8.81) and subcortical lesion ≥20 mm (OR 2.44; 95%CI 1,04–5.73). Lacunar strokes correlated with subcortical lesions diameter <20 mm (OR 42.9; 95%CI 22.7–81.1) and negative DWI (OR 8.87; 95%CI 4.03–19.5). Finally, MBAC (OR 9.25; 95%CI 1.12–76.2), MAP (OR 5.54; 95%CI 1.94–15.1), and MPC (OR 3.61; 95%CI 1.5–8.7) correlated with stroke of other etiologies. Conclusions: A relationship exists between DWI and stroke subtypePublication Genetics of spontaneous cervical and coronary artery dissections(2023) Munoz Venturelli, Paula; Rada, Isabel; Calderón, Juan; Martínez, GonzaloObjectives: Spontaneous cervical artery dissections (SCeAD) and coronary artery dissections (SCoAD) are major causes of neurovascular and cardiovascular morbidity in young adults. Although multiple aspects of their etiology are still unknown, most consensuses are focused on the presence of constitutional genetic aspects and environmental triggers. Since recent evidence of genetic contribution points to a possible overlap between these conditions, we aimed to describe current information on SCeAD and SCoAD genetics and their potential shared pathological aspects. Materials and methods: A narrative review is presented. Publications in English and Spanish were queried using database search. The articles were evaluated by one team member in terms of inclusion criteria. After collecting, the articles were categorized based on scientific content. Results: Given that patients with SCeAD and SCoAD rarely present connective tissue disorders, other genetic loci are probably responsible for the increased susceptibility in some individuals. The common variant rs9349379 at PHACTR1 gene is associated with predisposition to pathologies of the arterial wall, likely mediated by variations in Endothelin-1 (ET-1) levels. The risk of arterial dissection may be increased for those who carry the rs9349379(A) allele, associated with lower expression levels of ET-1; however, the local effect of this vasomotor imbalance remains unclear. Sex differences seen in SCeAD and SCoAD support a role for sex hormones that could modulate risk, tilting the delicate balance and forcing vasodilator actions to prevail over vasoconstriction due to a reduction in ET-1 expression. Conclusions: New evidence points to a common gene variation that could explain dissection in both the cervical and coronary vasculatures. To further confirm the risk conferred by the rs9349379 variant, genome wide association studies are warranted, hopefully in larger and ethnically diverse populations.Publication Disparities in Stroke Incidence Over Time by Sex and Age in Latin America and the Caribbean Region 1997 to 2021: A Systematic Review and Meta-Analysis(2023) Nuñez, Marilaura; Delfino, Carlos; Asenjo, Claudia; Schilling, Andrea; Lavados, Pablo; Anderson, Craig; Munoz Venturelli, PaulaBackground High-income country studies show unfavorable trends in stroke incidence (SI) in younger populations. We aimed to estimate temporal change in SI disaggregated by age and sex in Latin America and the Caribbean region. Methods and Results A search strategy was used in MEDLINE, WOS, and LILACS databases from 1997 to 2021, including prospective population-based observational studies with first-ever stroke incidence in Latin America. Reports without data broken down by age and sex were excluded. Risk of bias was assessed with The Joanna Briggs Institute's guide. The main outcomes were incidence rate ratio and relative temporal trend ratio of SI, comparing time periods before 2010 with after 2010. Pooled relative temporal trend ratios considering only studies with 2 periods in the same population were calculated by random-effects meta-analysis. Meta-regression analysis was used to evaluate incidence rate determinants. From 9242 records identified, 6 studies were selected including 4483 first-ever stroke in 4 101 084 individuals. Crude incidence rate ratio in younger subjects (<55 years) comparing before 2010:after 2010 periods showed an increase in SI in the past decade (incidence rate ratio, 1.37 [95% CI, 1.23-1.50]), in contrast to a decrease in older people during the same period (incidence rate ratio, 0.83 [95% CI, 0.76-0.89]). Overall relative temporal trend ratio (<55:≥55 years) was 1.65 (95 CI%, 1.50-1.80), with higher increase in young women (pooled relative temporal trend ratio, 3.08 [95% CI, 1.18-4.97]; P for heterogeneity <0.001). Conclusions An unfavorable change in SI in young people, especially in women, was detected in population-based studies in the past decade in Latin America and the Caribbean. Further investigation of the explanatory variables is required to ameliorate stroke prevention and inform local decision-makers. Registration URL: https://www.crd.york.ac.uk/prospero/ Identifier: CRD42022332563.Publication The main Optimal Post rTpa-Iv Monitoring in Ischemic Stroke Trial (OPTIMISTmain): Protocol for a Pragmatic, Stepped Wedge, Cluster Randomized Controlled Trial(2023) Ouyang, Menglu; Faigle, Roland; Wang, Xia; Johnson, Brenda; Summers, Debbie; Khatri, Pooja; Billot, Laurent; Liu, Hueiming; Malavera, Alejandra; Munoz Venturelli, Paula; Gonzalez, Francisca; Urrutia, Francisca; Day, Diana; Songa, Lili; Sui, Yi; Delcourt, Candice; Robinson, Thompson; Durham, Alice; Ebraimo, Ahtasam; Wan Asyraf Wan Zaidin; Jan, Stephen; Lindley, Richard; Urrutia, Victor; Anderson, CraigIntroduction Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low-risk of symptomatic intracerebral hemorrhage (sICH) and other complications. \ Methods OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically-stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 hours post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, US and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 minutes for 2 hours, 2 hourly (versus every 30 minutes) for 8 hours, and 4 hourly (versus every 1 hour) until 24 hours, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH and serious adverse events. Conclusion OPTIMISTmain will provide Level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS.Publication The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial(2023) Ma, Lu; Hu, Xin; Song, Lili; Chen, Xiaoying; Ouyang, Menglu; Billot, Laurent; Li, Qiang; Malavera, Alejandra; Li, Xi; Munoz Venturelli, Paula; De Silva, Asita; Huy Thang, Nguyen; Wahab, Kolawole; Pandian, Jeyaraj; Wasay, Mohammad; Pontes, Octavio; Abanto, Carlos; Arauz, Antonio; Shi, Haiping; Tang, Guanghai; Zhu, Sheng; She, Xiaochun; Liu, Leibo; Sakamoto, Yuki; You, Shoujiang; Han, Qiao; Crutzen, Bernard; Cheung, Emily; Li, Yunke; Wang, Xia; Chen, Chen; Liu, Feifeng; Zhao, Yang; Li, Hao; Liu, Yi; Jiang, Yan; Chen, Lei; Wu, Bo; Liu, Ming; Xu, Jianguo; INTERACT3 InvestigatorsBackground: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. Methods: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. Findings: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). Interpretation: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. Funding: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.Publication Who is in the emergency room matters when we talk about door-to-needle time: a single-center experience(2023) brunser, alejandro; Nuñez, Juan Cristobal; Mansilla, Eloy; Cavada, Gabriel; Olavarría, Verónica V.; Munoz Venturelli, Paula; Lavados, PabloBackground: The efficacy of intravenous thrombolysis (IVT) is time-dependent. Objective: To compare the door-to-needle (DTN) time of stroke neurologists (SNs) versus non-stroke neurologists (NSNs) and emergency room physicians (EPs). Additionally, we aimed to determine elements associated with DTN ≤ 20 minutes. Methods: Prospective study of patients with IVT treated at Clínica Alemana between June 2016 and September 2021. Results: A total of 301 patients underwent treatment for IVT. The mean DTN time was 43.3 ± 23.6 minutes. One hundred seventy-three (57.4%) patients were evaluated by SNs, 122 (40.5%) by NSNs, and 6 (2.1%) by EPs. The mean DTN times were 40.8 ± 23, 46 ± 24.7, and 58 ± 22.5 minutes, respectively. Door-to-needle time ≤ 20 minutes occurred more frequently when patients were treated by SNs compared to NSNs and EPs: 15%, 4%, and 0%, respectively (odds ratio [OR]: 4.3, 95% confidence interval [95%CI]: 1.66-11.5, p = 0.004). In univariate analysis DTN time ≤ 20 minutes was associated with treatment by a SN (p = 0.002), coronavirus disease 2019 pandemic period (p = 0.21), time to emergency room (ER) (p = 0.21), presence of diabetes (p = 0.142), hypercholesterolemia (p = 0.007), atrial fibrillation (p < 0.09), score on the National Institutes of Health Stroke Scale (NIHSS) (p = 0.001), lower systolic (p = 0.143) and diastolic (p = 0.21) blood pressures, the Alberta Stroke Program Early CT Score (ASPECTS; p = 0.09), vessel occlusion (p = 0.05), use of tenecteplase (p = 0.18), thrombectomy (p = 0.13), and years of experience of the physician (p < 0.001). After multivariate analysis, being treated by a SN (OR: 3.95; 95%CI: 1.44-10.8; p = 0.007), NIHSS (OR: 1.07; 95%CI: 1.02-1.12; p < 0.002) and lower systolic blood pressure (OR: 0.98; 95%CI: 0.96-0.99; p < 0.003) remained significant. Conclusion: Treatment by a SN resulted in a higher probability of treating the patient in a DTN time within 20 minutes.Publication Effects of intensive blood pressure lowering on cerebral ischaemia in thrombolysed patients: insights from the ENCHANTED trial(2023) Chen, Chen; Ouyang, Menglu; Ong, Sheila; Zhang, Luyun; Zhang, Guobin; Delcourt, Candice; Mair, Grant; Liu, Leibo; Billot, Laurent; Li, Qiang; Chen, Xiaoying; Parsons, Mark; Broderick, Joseph; Demchuk, Andrew; Bath, Philip; Donnan, Geoffrey; Levi, Christopher; Chalmers, John; Lindley, Richard; Martins, Sheila; Pontes-Neto, Octavio; Munoz Venturelli, Paula; Olavarría, Verónica V.; Lavados, Pablo; Robinson, Thompson; Wardlaw, Joanna; Li, Gang; Wang, Xia; Song, Lili; Anderson, CraigBackground: Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled trial of intensive (systolic target 130-140 mm Hg within 1 h; maintained for 72 h) or guideline-recommended (systolic target <180 mm Hg) blood pressure management in patients with hypertension (systolic blood pressure >150 mm Hg) after thrombolysis treatment for acute ischaemic stroke between March 3, 2012 and April 30, 2018. Methods: All available brain imaging were analysed centrally by expert readers. Log-linear regression was used to determine the effects of intensive blood pressure lowering on the size of cerebral infarction, with adjustment for potential confounders. The primary analysis pertained to follow-up computerised tomography (CT) scans done between 24 and 36 h. Sensitivity analysis were undertaken in patients with only a follow-up magnetic resonance imaging (MRI) and either MRI or CT at 24-36 h, and in patients with any brain imaging done at any time during follow-up. This trial is registered with ClinicalTrials.gov, number NCT01422616. Findings: There were 1477 (67.3%) patients (mean age 67.7 [12.1] y; male 60%, Asian 65%) with available follow-up brain imaging for analysis, including 635 patients with a CT done at 24-36 h. Mean achieved systolic blood pressures over 1-24 h were 141 mm Hg and 149 mm Hg in the intensive group and guideline group, respectively. There was no effect of intensive blood pressure lowering on the median size (ml) of cerebral infarction on follow-up CT at 24-36 h (0.3 [IQR 0.0-16.6] in the intensive group and 0.9 [0.0-12.5] in the guideline group; log Δmean -0.17, 95% CI -0.78 to 0.43). The results were consistent in sensitivity and subgroup analyses. Interpretation: Intensive blood pressure lowering treatment to a systolic target <140 mm Hg within several hours after the onset of symptoms may not increase the size of cerebral infarction in patients who receive thrombolysis treatment for acute ischaemic stroke of mild to moderate neurological severity. Funding: National Health and Medical Research Council of Australia; UK Stroke Association; UK Dementia Research Institute; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda.Publication Who is in the emergency room matters when we talk about door-to-needle time: a single-center experience [Quien está en el servicio de emergencia importa al hablar de tiempo puerta-aguja: experiencia de un centro clínico](2023) brunser, alejandro; Nuñez; Juan; Mansilla, Eloy; Cavada, Gabriel; Olavarría, Verónica V.; Munoz Venturelli, Paula; Lavados, PabloBackground: The efficacy of intravenous thrombolysis (IVT) is time-dependent. Objective: To compare the door-to-needle (DTN) time of stroke neurologists (SNs) versus non-stroke neurologists (NSNs) and emergency room physicians (EPs). Additionally, we aimed to determine elements associated with DTN ≤ 20 minutes. Methods: Prospective study of patients with IVT treated at Clínica Alemana between June 2016 and September 2021. Results: A total of 301 patients underwent treatment for IVT. The mean DTN time was 43.3 ± 23.6 minutes. One hundred seventy-three (57.4%) patients were evaluated by SNs, 122 (40.5%) by NSNs, and 6 (2.1%) by EPs. The mean DTN times were 40.8 ± 23, 46 ± 24.7, and 58 ± 22.5 minutes, respectively. Door-to-needle time ≤ 20 minutes occurred more frequently when patients were treated by SNs compared to NSNs and EPs: 15%, 4%, and 0%, respectively (odds ratio [OR]: 4.3, 95% confidence interval [95%CI]: 1.66–11.5, p = 0.004). In univariate analysis DTN time ≤ 20 minutes was associated with treatment by a SN ( p = 0.002), coronavirus disease 2019 pandemic period ( p = 0.21), time to emergency room (ER) ( p = 0.21), presence of diabetes ( p = 0.142), hypercholesterolemia ( p = 0.007), atrial fibrillation ( p < 0.09), score on the National Institutes of Health Stroke Scale (NIHSS) ( p = 0.001), lower systolic ( p = 0.143) and diastolic ( p = 0.21) blood pressures, the Alberta Stroke Program Early CT Score (ASPECTS; p = 0.09), vessel occlusion ( p = 0.05), use of tenecteplase ( p = 0.18), thrombectomy ( p = 0.13), and years of experience of the physician ( p < 0.001). After multivariate analysis, being treated by a SN (OR: 3.95; 95%CI: 1.44–10.8; p = 0.007), NIHSS (OR: 1.07; 95%CI: 1.02–1.12; p < 0.002) and lower systolic blood pressure (OR: 0.98; 95%CI: 0.96–0.99; p < 0.003) remained significant. Conclusion: Treatment by a SN resulted in a higher probability of treating the patient in a DTN time within 20 minutes.Publication Dilated optic nerve sheath by ultrasound predicts mortality among patients with acute intracerebral hemorrhage(2023) Antunes, Francisco; Zanon, Maria; Fernandes, Frederico; Martins Filho, Kleber do Vale; Monteiro, Clara; Costa, Otavio; Munoz Venturelli, Paula; Boulouis, Gregoire; Norkin, Joshua; Marques, OctavioBackground: Intracerebral hemorrhage (ICH) is a deadly disease and increased intracranial pressure (ICP) is associated with worse outcomes in this context. Objective: We evaluated whether dilated optic nerve sheath diameter (ONSD) depicted by optic nerve ultrasound (ONUS) at hospital admission has prognostic value as a predictor of mortality at 90 days. Methods: Prospective multicenter study of acute supratentorial primary ICH patients consecutively recruited from two tertiary stroke centers. Optic nerve ultrasound and cranial computed tomography (CT) scans were performed at hospital admission and blindly reviewed. The primary outcome was mortality at 90-days. Multivariate logistic regression, ROC curve, and C-statistics were used to identify independent predictors of mortality. Results: Between July 2014 and July 2016, 57 patients were evaluated. Among those, 13 were excluded and 44 were recruited into the trial. Their mean age was 62.3 ± 13.1 years and 12 (27.3%) were female. On univariate analysis, ICH volume on cranial CT scan, ICH ipsilateral ONSD, Glasgow coma scale, National Institute of Health Stroke Scale (NIHSS) and glucose on admission, and also diabetes mellitus and current nonsmoking were predictors of mortality. After multivariate analysis, ipsilateral ONSD (odds ratio [OR]: 6.24; 95% confidence interval [CI]: 1.18-33.01; p = 0.03) was an independent predictor of mortality, even after adjustment for other relevant prognostic factors. The best ipsilateral ONSD cutoff was 5.6mm (sensitivity 72% and specificity 83%) with an AUC of 0.71 (p = 0.02) for predicting mortality at 90 days. Conclusion: Optic nerve ultrasound is a noninvasive, bedside, low-cost technique that can be used to identify increased ICP in acute supratentorial primary ICH patients. Among these patients, dilated ONSD is an independent predictor of mortality at 90 days. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).