Case Reports in Infectious Diseases

Case Reports in Infectious Diseases / 2018 / Article

Case Report | Open Access

Volume 2018 |Article ID 6549496 |

Beatrice Tiri, Giulia Priante, Lavinia Maria Saraca, Lucia Assunta Martella, Stefano Cappanera, Daniela Francisci, "Listeria monocytogenes Brain Abscess: Controversial Issues for the Treatment—Two Cases and Literature Review", Case Reports in Infectious Diseases, vol. 2018, Article ID 6549496, 9 pages, 2018.

Listeria monocytogenes Brain Abscess: Controversial Issues for the Treatment—Two Cases and Literature Review

Academic Editor: Tomoyuki Shibata
Received12 Mar 2018
Revised11 Jun 2018
Accepted08 Jul 2018
Published24 Jul 2018


Listeria monocytogenes (LM) is an opportunistic pathogen, and the most common central nervous system manifestation is meningitis while listerial brain abscesses are rare. We describe 2 cases of brain abscess due to LM and a literature review. Only 73 cases were reported in the literature from 1968 to 2017. The mean age was 51.9, and the mortality rate was 27.3%. In 19% of cases, no risk factors for neurolisteriosis were identified. Blood cultures were positive in 79.5% while CSF or brain abscess biopsy material was positive in 50.8%. In 40% was started a monotherapy regimen while in 60% a combination therapy without substantial differences in mortality. Fifty-two percent underwent neurosurgery while 45.3% has been treated only with medical therapy. The mortality rates were, respectively, 13% and 38.2%. Only 25% of patients who were treated for ≤6 weeks underwent neurosurgery, while 80% of those who were treated for ≥8 weeks were operated. The mortality rates were, respectively, 12.5% and 0%, suggesting that a combined approach of surgery and prolonged medical therapy would have an impact on mortality. We believe that it is essential to carry out this review as brain abscesses are rare, and there are no definitive indications on the optimal management, type, and duration of therapy.

1. Introduction

Listeria monocytogenes (LM) is a facultative intracellular Gram-positive bacillus, widely distributed in nature and therefore found in multiple ecological sites, which can cause listeriosis, a serious foodborne bacterial infection [1]. Invasive listeriosis is classified into three forms: bacteraemia, neurolisteriosis, and maternal-neonatal infection. The incidence of listeriosis in the western hemisphere is estimated to be approximately three to six cases per 1 million population per year [2]. Epidemiological studies have identified host risk factors for bacteraemia and neurolisteriosis which include old age, innate and cellular immune deficiencies, cancer, HIV infection, cirrhosis, diabetes mellitus, alcoholism, and immunosuppressive therapies [36]. The most common central nervous system manifestation is meningitidis, while meningoencephalitis, rhombencephalitis, and cerebritis are less common [7]. Brain abscesses are extremely rare as they account for approximately 1–10% of CNS listerial infections and are observed in 1% of all listerial infections [8]. There are unresolved issues regarding surgical drainage of the abscess, selection of antibiotic regimen, and optimal treatment duration. We describe two cases (the first without evident immunodeficiency and the second affected by bullous pemphigoid) of brain abscess due to Listeria monocytogenes and discuss them by reviewing the literature on this topic.

2. Case Report

2.1. Case 1

A 62-year-old immunocompetent man with no significant previous medical history was hospitalized for high-grade fever, intractable hiccup, and interscapular pain. On admission, his white blood cell count was 11 × 109/L (normal range 4.50–10.80 103 mmc), his C-reactive protein (CRP) was elevated at 4.30 mg/dl (normal range 0.00–0.75 mg/dl), while his chest radiograph, abdomen ultrasound, and echocardiography were normal. A computed tomography (CT) scan of the brain revealed a diffuse abnormal pattern (presence of aspecific inflammatory material) with hypodense lesions located in the trigonum of lateral ventricle in an underlying condition of demyelination and gliosis, suspicious for chronic ischemic vascular disease. A broad-spectrum antibiotic therapy with vancomycin and ceftriaxone was initiated. The patient became afebrile within a few days. A neurological examination found him to be alert and oriented, and he did not have a stiff neck. However, the patient had persistent hiccups and headache. Magnetic resonance imaging (MRI) showed enhancement of both trigeminal nerves and white spot lesions on the pons, cerebral peduncle, midbrain, and thalamus. He was then transferred to the Neurology Department where a lumbar puncture was carried out. His cerebrospinal fluid (CSF) was clear, WBC count was 50 cells/µl, 100% lymphocytes, normal glucose level (normal range 40–70 mg/dl), 103 mg/dl protein (normal range 15–45 mg/dl), and the CSF culture was negative. As a viral etiology was suspected, antibiotic therapy with vancomycin + ceftriaxone was discontinued and treatment with acyclovir and steroid was initiated. After 72 hours, a progressive deterioration of his clinical-neurological condition occurred: he became hyperpyretic and aphasic and Glasgow Coma Score (GCS) was 9. CT brain imaging showed the involvement of the subcortical left temporoparietal lobe, and he was then transferred to the Infectious Disease Department. Blood cultures were performed, and another lumbar puncture was carried out. A cerebrospinal fluid (CSF) analysis showed cloudy CSF with increased spinal column pressure, granulocytic pleocytosis (180 cells/µl, with PMN 90%), normoglychorrachia, and 145 mg/dl spinal fluid protein. A combination antimicrobial therapy with ampicillin 3 g/6 h + gentamicin 80 mg/8 h was initiated; 72 hours later, fever and other systemic signs and symptoms disappeared resulting in complete recovery (GCS15). Listeria monocytogenes were isolated from the patient’s blood and recognized from CSF using the molecular technique (Multiplex Real-Time PCR Meningitis/Encephalitis Filmarray bioMerieux). The patient was treated with intravenous ampicillin for 4 weeks, with combination intravenous gentamicin for the initial 2 weeks and switched to oral trimethoprim/sulfamethoxazole 160/800 mg/8 h for 1 month. An MRI was repeated after 8 weeks of antibiotic therapy due to the persistence of fluent aphasia. MR imaging showed a ring-enhancing lesion in the left fronto-temporoparietal lobe, consistent with a brain abscess with significant perilesional edema (Figure 1). Surgical excision of the lesion was performed. Molecular identification of the pus using polymerase chain reaction (PCR) identified DNA of Listeria monocytogenes. The patient was represcribed intravenous ampicillin + gentamicin for 4 weeks, and therapy was then switched to oral trimethoprim/sulfamethoxazole 160/800 mg/12 h for further 4 weeks. Patient’s condition has improved progressively and with a complete recovery of linguistic abilities.

2.2. Case 2

A 72-year-old man with a history of bullous pemphigoid treated with a monoclonal antibody was admitted to another hospital due to a balance disorder. A neurological examination identified a left hemiplegia with no sensory deficits. An immediate CT brain scan showed a ring-enhancing cortical-subcortical lesion on the right frontal-parietal hemisphere. In view of the CT scan findings, gadolinium MRI of the brain was performed. MRI showed a caudal extension of the lesion with irregular enhancement and a necrotic region (Figure 2). Blood cultures were collected before initiating antimicrobial therapy. A few days later, his blood cultures grew Listeria monocytogenes. Based on organism sensitivity, intravenous therapy with ampicillin 3 g/6 h + gentamicin 80 mg/8 h + vancomycin 1 g/12 h was initiated. Steroid therapy was also administered due to the associated moderate mass effect. The patient was then transferred to our Infectious Diseases Department for further workup and management. Forty-eight hours after the initiation of target therapy, the patient was afebrile. Twenty days later, he showed progressive clinical and neurologic deterioration characterized by visual hallucinations, frontal symptoms with disinhibition, and persistent hemiplegia. An MRI brain scan showed a substantial increase in lesion size, and new lesions appeared on splenium of corpus callosum and right temporal lobe with a significant mass effect on the right lateral ventricle. Trimethoprim/sulfamethoxazole 160/800 mg/8 h was added. The patient underwent a surgical biopsy of the lesion. Molecular identification of the brain tissue using PCR identified Listeria monocytogenes DNA. At the follow-up appointment five weeks later, additional imaging studies were performed which showed a considerable reduction in the size and enhancement of the lesions. Ampicillin, gentamicin, and vancomycin therapy was stopped while trimethoprim/sulfamethoxazole therapy was continued. The patient’s neurological condition improved. An MRI brain scan performed after 8 weeks of antibiotic therapy, showed significant improvement, with noticeable decrease in the amount of vasogenic edema. Trimethoprim/sulfamethoxazole therapy was discontinued, and the patient was discharged. A year after the listeria brain abscess diagnosis, the patient does not show any significant neurologic deficits and is able to carry out all activities of daily living.

3. Discussion

Listeria monocytogenes can invade tissues that are normally resistant to infection, such as the CNS, a gravid uterus, or a fetus. This bacterium reaches the CNS due to hematogenous spread from the gastrointestinal tract [9]. The epithelium of the choroid plexus enables LM to gain access to CNS and causes a meningitides infection. On the other hand, LM may reach the brain parenchyma via the cerebral capillary endothelium, a single layer of brain microvascular endothelial cells characterized by tight junctions. It has been reported that LM-infected macrophages may pass through endothelial cells via the middle cerebral artery resulting in cerebritis which leads to brain abscess formation [1013].

Furthermore, LM can use a peripheral intraneural route to invade the CNS. A recent animal study suggests that once the bacteria have gained access to the CNS via the peripheral nervous system, the infection can spread along the axons, producing additional lesions by traveling within the axons of the trigeminal nerve [1416]. According to Bojanowski et al., once inside the CNS, the bacterium may travel along the white fiber tracts of the brain, resulting in a distinct anatomical imaging thus enabling early diagnosis [17]. The spreading of multiple listeria brain abscess within the cerebral nervous system through the intrassonal pathway justified their specific pattern and why they have more detrimental effects than bacterial brain abscess. In our case 1, MRI shows that the spreading follows the arcuate fasciculus. In case 2, the caudal extension of the lesions may also suggest that the lesion follows the projection fiber tracts.

Brain abscesses are extremely rare, accounting for approximately 1–10% of CNS listerial infections. These abscesses are generally located in the subcortical grey matter, especially in the thalamus and basal ganglia [18, 19]. Protection against LM is predominantly cell-mediated. Individuals with impaired cell-mediated immunity are at risk of developing listerial infections [20].

To the best of our knowledge, only 73 cases of brain abscess caused by L. monocytogenes were reported in the literature between 1968 and 2017. We report further two cases (Table 1) [1, 13, 17, 2123].

N.Age/sexUnderlying diseasesBloodCSF/brain abscessSurgery/typeAntibioticDuration of therapyOutcomeReferences

170/MMyasthenia gravis in immunosuppressive TP+NDAmpicillin + gentamicin; trimethoprim/sulfamethoxazole6 weeks ampicillin + gentamicin for 10 days trimethoprim/ sulfamethoxazoleSurvivedChalouhi et al., 2013
257/FCirrhosis; DM++BiopsyAmpicillin + gentamicinNRDiedMatera et al., 2012
360/MDM; rheumatoid arthritis methotrexate+ND(a) Amoxicillin + trimethoprim/sulfamethoxazole
(b) Trimethoprim/sulfamethoxazole
(c) Linezolid
(d) Amoxicillin
(a) 17 days
(b) 20 days
(c) 33 days
(d) NR
SurvivedCoste et al., 2012
452/MOLT in HCC secondary to hepatitis C and alcoholic cirrhosis; cyclosporine++Craniotomy with resection of the lesionAmpicillin + gentamicin + penicillin G3 weeks (gentamicin only for 2 weeks)SurvivedChoudhury et al., 2013
556/FPrimary biliary cirrhosis; OLT; tacrolimus, azathioprine, prednisone++BiopsyAmpicillin + gentamicin8 weeks (gentamicin only for 2 weeks)SurvivedTseng et al., 2013
642/MNone++Biopsy and drainageAmpicillin + gentamicin + meropenemNRSurvivedBeynon et al., 2013
747/FSLE; mycophenolate+NDAmpicillin6 weeksSurvivedHorta-Baas et al., 2013
816/FSLE; mycophenolate+External ventricles deviceTrimethoprim/sulfamethoxazole + ampicillin + meropenem13 weeks trimethoprim/sulfamethoxazole; ampicillin for 4 weeks; meropenem for 5 weeks (total of 22 weeks)SurvivedPerini et al., 2014
981/MMyelodys plastic syndrome; basal cell skin carcinoma, prostate cancer treated++Craniotomy with resection of the lesionAmpicillinNRSurvivedWest et al., 2015
1052/FDM, hypothyroidism, prednisolone, azathioprine+BiopsyAmpicillin + gentamicin6 weeksSurvivedAl-HarabI et al., 2015
1181/FDMNR+BiopsyAmpicillin8 weeksSurvivedDejesus-Alvelo et al., 2015
1274/FDM+NRNRVancomycin + ampicillin + ceftriaxoneNRSurvivedBojanowski et al. [17]
1332/FLAC+NRNRAmpicillin + trimethoprim/sulfamethoxazole + linezolid8 weeks; linezolid for 10 daysSurvivedFervienza et al., 2016
1472/MNone+NDAmpicillinNRSurvivedMano et al., 2017
1552/MInflammatory myositis treated with prednisolone and azathioprine+NDAmpicillin6 weeksSurvivedOnder et al., 2016
1670/MAlcoholism++NDAmpicillin + gentamicin + vancomycin3–6 weeksDiedCone et al. [13]
1756/MAIDS+NDAmpicillin + gentamicinArticle not availableSurvivedPatey et al., 1989
1849/MRheumatic fever, alcoholism, DM+NDPenicillin G + streptomycin + tetracyclineNRDiedBuchner and Schneierson, 1968
1964/MDM, aortic valve replacement+NDAmpicillin + gentamicin4 weeks + ampicillin for 2 weeksSurvivedSoto and Sliman, 1992
2071/MDM, rheumatic heart disease+NDAmpicillin + gentamicinNRDiedEckburg et al. [22]
2156/MAIDS+NDAmpicillin + gentamicinArticle not availableSurvivedPatey et al., 1989
2270/FCirrhosis, DM, heart failure+NDNDAmpicillin + trimethoprim/sulfamethoxazoleArticle not availableDiedSivalinga et al., 1992
2325/FUlcerative colitisNRNRNDNRNRDiedLarsson and Linell, 1979
2487/MNone++NDPenicillin G + chloramphenicolNRDiedSpilkin et al., 1968
2563/MNone+NDAmpicillinNRDiedKennard et al., 1979
2624/MNone+NDAmpicillin + gentamicin6 weeks, gentamicin only for 10 daysSurvivedSmiatacz et al., 2006
2753/FNone+NDMinocycline, gentamicin2 weeksSurvivedMrowka et al., 2002
2863/FNoneNDNRNRDiedBrun-Buisson et al., 1985
2943/FNoneNDAmpicillinNRDiedBrun-Buisson et al., 1985
3039/MNoneNRNDNRNRDiedKwantes and Isaac, 1971
3154/FNoneNRNRNDNRNRDiedLarsson and Linell, 1979
321+1/4/MNoneNRNRNDAmoxicillinArticle not availableSurvivedMancini et al., 1990
3370/MNONE+Craniectomy and open biopsyAmpicillinNRSurvivedSalgado et al., 1996
3453/MCirrhosis, seizure++Penicillin G + erythtomycinArticle not availableSurvivedHalkin et al., 1971
3585/MDM++AmpicillinArticle not availableDiedBrown et al., 1991
3643/MOSAS, alcoholism++NRArticle not availableSurvivedDouen and Bourque, 1997
370/MPronatis++Ampicillin + gentamicinArticle not availableSurvivedBanerji and Noya, 1999
3863/MMM+Biopsy(a) Ampicillin(a) 5 weeksSurvivedLeiti et al. [20]
(b) Linezolid + rifampin(b) 15 weeks
3961/MDMNRNRBiopsyTrimethoprim/sulfamethoxazole + chloramphenicol3 weeks, trimethoprim/sulfamethoxazole alone for 20 weeksSurvivedSjostrom et al., 1995
4060/MHIVNR+Craniotomy and intraoperative culturesPenicillin G + chloramphenicolNRDiedHarris et al., 1989
4168/MLeukemiaNRNRNDChloramphenicolNRDiedLarsson et al., 1978
42NR/MNoneNRNRNDNRNRDiedPollock et al., 1984
432/MNRNR+Craniotomy with resection of the lesionNRNRSurvivedUmenai et al., 1978
4449/MRenal transplant++NDChloramphenicolNRDiedCrocker and Leicester, 1976
4516/MALL++NDPenicillin G + chloramphenicolNRSurvivedDykes et al., 1979
4620/MALL++NDAmpicillin + chloramphenicol + erythromycin, gentamicin8 weeksSurvivedHutchinson and Heyn, 1983
476/FALL++NDAmpicillin, vancomycin, netilmicinNRSurvivedViscoli et al., 1991
4846/FUlcerative colitis++NDAmpicillin, gentamicin8 weeks, 4 weeksSurvivedSoares-Fernandes et al., 2008
4958/FSLE+NDPenicillin G + tobramycinARTICLE NOT AVAILABLESurvivedTakano et al., 1999
5058/FImmunoblastic lymphadenopathy+NDAmpicillin8 weeksSurvivedMaezawa et al. [21]
5165/MDM+NRNDAmpicillin + gentamicin4 weeksDiedWu et al., 2010
5219/MJuvenile rheumatoid arthritis, tetralogy of FallotNR+NDVancomycin + ampicillinArticle not availableSurvivedTurner et al., 1995
5355/MRenal transplant++AmpicillinArticle not availableSurvivedLechtenberg et al., 1979
5445/MRenal transplant+Craniotomy and drainageAmpicillin10 weeksSurvivedStam et al., 1982
5560/FRheumatoid arthritis+BiopsyAmpicillin, amoxicillin8 weeks, 24 monthsSurvivedUpdike et al., 1990
5666/FAML, Crohn’s disease++BiopsyAmpicillin4 weeksSurvivedEckburg et al. [22]
5747/MAIDS+CraniotomyAmpicillin, gentamicin, vancomycinNRDiedCone et al. [13]
5854/FSarcoidosis+BiopsyAmpicillin + gentamicinNRDiedAckermann et al., 2001
5923/FITP+Drainage of the abscessTrimethoprim/sulfamethoxazole12 monthsSurvivedTreebupachatsaul et al., 2006
6058/MMM+Craniotomy and drainage(a) Trimethoprim/sulfamethoxazole + gentamicin (b) Trimethoprim/sulfamethoxazole(a) 12 weeks (gentamicin only 2 weeks) (b) 5 monthsSurvivedAl-Khatti and Al- Tawfiq, 2010
6155/MGlioblastoma multiforme+BiopsyAmoxicillin + gentamicin12 weeksSurvivedGaniere et al., 2006
6251/MCardiac transplant++Stereotactic brain aspirationAmpicillin + gentamicin6 weeks, gentamicin only 2 weeksSurvivedEckburg et al. [22]
6337/MCardiac transplant++Craniotomy with resection of the lesionpenicillin G8 weeksNREckburg et al. [22]
6456/FPrimary biliary cirrhosis++BiopsyAmpicillin + gentamicin6 weeks gentamicin only 2 weeksSurvivedCone et al. [13]
6550/MSarcoidosis+CraniotomyTrimethoprim/sulfamethoxazoleArticle not availableSurvivedPoropatich and Phillips, 1992
6651/FCrohn’s disease+BiopsyAmpicillin + gentamicin12 weeks (gentamicin not reported)SurvivedStefanovich et al., 2010
6750/MCardiac transplant, DM+Biopsy and aspirationAmpicillin + gentamicin18 weeks of ampicillin; 14 weeks gentamicinSurvivedEckburg et al. [22]
6875/MNoneND+Ampicillin + gentamicinArticle not availableSurvivedMylonakis et al., 1998
6977/MCLLNR+ChloramphenicolArticle not availableNRCleveland and Gelfand, 1993
7058/MCLL+BiopsyAmpicillin + gentamicin6 weeksSurvivedDee and Lorber, 1986
71ChildALLNRNR+NRArticle not availableSurvivedAntunes et al., 1998
7268/FBreast cancer+NDBiopsyAmpicillin, amoxicillin10 weeks, 24 weeksSurvivedLimmahakhun and Chayakulkeeree [1]
7347/FEvans syndrome, SLE, DM+NDAmpicillin, amoxicillin6 weeks, NRSurvivedLimmahakhun and Chayakulkeeree [1]
Case 162/MNone++Craniotomy with resection of the lesion(a) Ampicillin + gentamicin (b) Trimethoprim/sulfamethoxazole(a) 8 weeks (gentamicin only 4 weeks) (b) 8 weeksSurvived
Case 272/MBullous pemphigoid++Biopsy(a) Ampicillin + gentamicin + trimethoprim/sulfamethoxazole (b) Trimethoprim/sulfamethoxazole(a) 5 weeks (b) 3 weeksSurvived

Forty-eight of these patients were male (64%). The mean age of the patients was 51.9, and median age was 55 years (range 0–87 years). Fifty-nine out of 73 had one or more risk factors described in the literature for the development of neurolisteriosis (81%), 15/75 had no risk factors (19%), and in 1 case, nothing was specified. The mortality rate was 27.3%.

Blood cultures were reported for 63 cases: 50/63 were positive (79.5%).

L. monocytogenes was isolated from the CSF or brain abscesses in 31/61 patients (50.8%).

The therapeutic regimen was reported for 67/75 cases, while it is unknown in 8/75.

Twenty-seven out of 67 patients received a monotherapy regimen (40%), while a combination therapy was prescribed for 40/67 (60%) cases: a two-drug therapy was prescribed in 31 cases (50.8%) and a three-drug therapy was administered in 9 cases (14.7%).

The mortality rate in the monotherapy regimen group was 18.5% (five patients out of 27) while the group that received combination therapy showed a 20% mortality rate (eight patients out of 40). Fifty-nine out of 67 patients received a beta-lactam regimen, while 8/59 received a free beta-lactam regimen.

Considering the substantial numerical difference of the two samples, these are not comparable.

Ampicillin was the most commonly prescribed antibiotic as it was administered to 49 patients: in 21 patients, it was prescribed as monotherapy; in 23 cases, it was administered in combination with gentamicin; in 3 cases, it was administered in combination with trimethoprim/sulfamethoxazole while in 2 cases, it was administered in combination with other drugs such as vancomycin or macrolides.

There are currently no guidelines for brain abscess management. Starting from the 2010 consensus on the management and treatment of brain abscesses, we reviewed our case series [24].

Thirty-nine out of 75 patients underwent neurosurgery (52%). Four out of 31 died (13%). Thirty-four patients out of 75 (45.3%) had only been treated with medical therapy. Of these, 15/34 died (38.2%). In 2 cases, no data have been reported.

Therefore, in our case series, taking into account all of the possible bias, mortality would appear to be significantly higher in the group of patients treated exclusively with medical therapy.

In our opinion, this is a very interesting finding which requires further investigation.

However, as yet, there is no evidence concerning the appropriate duration of therapy for those patients who underwent neurosurgery.

According to a recent consensus study, antimicrobial treatment for brain abscesses should generally last 6–8 weeks and treatment for those undergoing neurosurgery should last 4–6 weeks [24].

From our literature review, the duration of therapy was known in 36/75 patients. Sixteen out of 36 received less than or equal to 6 weeks while 20/36 patients were treated for 8 weeks or more. Of the group of patients who received ≤6 weeks of therapy, 4/16 (25%) underwent neurosurgery, while of those belonging to the group who received ≥8 weeks, 16/20 (80%) underwent neurosurgery.

A 12.5% mortality rate was observed for the first group while 0% died in the second group, thus suggesting that a combination of surgery and prolonged medical therapy has a positive impact on mortality.

We believe that it is essential to carry out this review as brain abscesses are rare, and there are no definitive guidelines on the optimal management, type, and duration of therapy. LM infection should also be suspected in immunocompetent patients, and new molecular biology techniques play key roles in the early diagnosis of this rare pathology.

4. Conclusions

In our literature review, we found that listeria brain abscess is not related to advanced age and that it is related to high mortality (27.3%).

Diagnosis should not be suspected only in immunocompromised patients as it was found in 20% of patients who had no risk factor.

Blood cultures were positive in more than 80% of cases. Most patients received a beta-lactam regimen, and mortality appears to be lower in patients treated with combination regimens.

This result looks certainly very interesting and should be explored with dedicated studies (i.e., sharp difference in mortality between the group undergoing neurosurgery and the group that only received medical therapy). Furthermore, the specific pattern of brain diffusion, reported and highlighted in our two clinical cases, should be considered when this diagnosis is hypothesized.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this article.


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Copyright © 2018 Beatrice Tiri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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