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Strömberg, Nicklas
Publications (10 of 33) Show all publications
Sheng, N., Mårell, L., Tumkur Sitaram, R., Svensäter, G., Westerlund, A. & Strömberg, N. (2024). Human PRH1, PRH2 susceptibility and resistance and Streptococcus mutans virulence phenotypes specify different microbial profiles in caries. EBioMedicine, 101, Article ID 105001.
Open this publication in new window or tab >>Human PRH1, PRH2 susceptibility and resistance and Streptococcus mutans virulence phenotypes specify different microbial profiles in caries
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2024 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 101, article id 105001Article in journal (Refereed) Published
Abstract [en]

Background: Lifestyle- and sucrose-dependent polymicrobial ecological shifts are a primary cause of caries in populations with high caries prevalence. In populations with low prevalence, PRH1, PRH2 susceptibility and resistance phenotypes may interact with the Streptococcus mutans adhesin cariogenicity phenotype to affect caries progression, but studies are lacking on how these factors affect the microbial profile of caries.

Methods: We analysed how the residency and infection profiles of S. mutans adhesin (SpaP A/B/C and Cnm/Cbm) phenotypes and commensal streptococci and lactobacilli influenced caries progression in a prospective case–referent sample of 452 Swedish adolescents with high (P4a), moderate (P6), and low (P1) caries PRH1, PRH2 phenotypes. Isolates of S. mutans from participants were analysed for adhesin expression and glycosylation and in vitro and in situ mechanisms related to caries activity.

Findings: Among adolescents with the resistant (P1) phenotype, infection with S. mutans high-virulence phenotypes was required for caries progression. In contrast, with highly (P4a) or moderately (P6) susceptible phenotypes, caries developed from a broader polymicrobial flora that included moderately cariogenic oral commensal streptococci and lactobacilli and S. mutans phenotypes. High virulence involved unstable residency and fluctuating SpaP ABC, B-1, or Cnm expression/glycosylation phenotypes, whereas low/moderate virulence involved SpaP A phenotypes with stable residency. Adhesin phenotypes did not display changes in individual host residency but were paired within individuals and geographic regions.

Interpretation: These results suggest that receptor PRH1, PRH2 susceptibility and resistance and S. mutans adhesin virulence phenotypes specify different microbial profiles in caries. Funding: Swedish Research Council and funding bodies listed in the acknowledgement section.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Adhesion, Caries, Commensal pathogen, Host susceptibility, PRH1/PRH2, Streptococcus mutans
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-221645 (URN)10.1016/j.ebiom.2024.105001 (DOI)38364699 (PubMedID)2-s2.0-85185567071 (Scopus ID)
Funder
Swedish Research CouncilRegion VästerbottenSwedish Dental AssociationUmeå University
Available from: 2024-03-06 Created: 2024-03-06 Last updated: 2024-03-06Bibliographically approved
Enerbäck, H., Lövgren, M. L., Strömberg, N. & Westerlund, A. (2023). Effect of high-fluoride toothpaste and mouth rinse on the prevention of demineralized lesions during orthodontic treatment: a randomized controlled trial. European Journal of Orthodontics, 45(5), 477-484
Open this publication in new window or tab >>Effect of high-fluoride toothpaste and mouth rinse on the prevention of demineralized lesions during orthodontic treatment: a randomized controlled trial
2023 (English)In: European Journal of Orthodontics, ISSN 0141-5387, E-ISSN 1460-2210, Vol. 45, no 5, p. 477-484Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To evaluate the effect of high-fluoride mouth rinse and high-fluoride toothpaste on the development of demineralized lesions (DLs) during orthodontic treatment.

TRIAL DESIGN: Three-armed parallel-group randomized controlled trial.

METHODS: The trial was performed with 270 adolescent orthodontic patients. Randomization was performed in blocks of 30, enrolling the patients into one of the following groups: the fluoride mouth rinse (FMR) group receiving 0.2% sodium fluoride (NaF) mouth rinse plus 1450 ppm fluoride (F) toothpaste; high-fluoride toothpaste (HFT) group receiving 5000 ppm F toothpaste; and the Control (CTR) group receiving 1450 ppm F toothpaste. Inclusion criteria were patients scheduled for treatment in both arches with fixed appliances and age between 12 and 20 years. The primary outcome variable was the proportion of participants with at least one new demineralized lesion as assessed on digital photos taken before and after treatment, analysed by a blinded clinician. The analysis included all teeth or teeth in the aesthetic zone, i.e. all central incisors, lateral incisors, and canines. A random sample of 30 participants was assessed to check intra- and inter-reliability. For pairwise comparison between groups, Fisher's non-parametric permutation test was used for continuous variables. Blinding was employed during the caries registration and data analysis.

RECRUITMENT: October 2010 to December 2012.

RESULTS: In total, 270 patients were randomized, of which 22 were excluded during treatment. Therefore, 248 participants were included in the study. The number of patients with an increase of ≥1 DL, including only central- and lateral incisors and canines, during orthodontic treatment, was significantly lower in the HFT group, 51/85 60%, compared to the CTR group, 64/82 78%, RR 0.77 (CI 0.62; 0.95), P = .01 and in the FMR group, 47/81 58%, compared to the CTR group, RR 0.74 (CI 0.60; 0.92), P < .01.

CONCLUSIONS: To prevent demineralized lesions in the aesthetic zone, high-fluoride mouth rinse and high-fluoride toothpaste may be recommended.

LIMITATIONS: The protocol was not registered, and the present study did not use a double-blinded design.

Place, publisher, year, edition, pages
Oxford University Press, 2023
Keywords
demineralization, fixed appliance, fixed brace treatment, fluoride, high-fluoride toothpaste, mouth rinse, multi bracket appliance treatment, orthodontics, white spot lesion
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-215275 (URN)10.1093/ejo/cjad044 (DOI)001040069700001 ()37524332 (PubMedID)2-s2.0-85171601142 (Scopus ID)
Available from: 2023-10-17 Created: 2023-10-17 Last updated: 2023-10-17Bibliographically approved
Alharbi, A. F., Sheng, N., Nicol, K., Strömberg, N. & Hollox, E. J. (2022). Balancing selection at the human salivary agglutinin gene (DMBT1) driven by host-microbe interactions. iScience, 25(5), Article ID 104189.
Open this publication in new window or tab >>Balancing selection at the human salivary agglutinin gene (DMBT1) driven by host-microbe interactions
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2022 (English)In: iScience, E-ISSN 2589-0042 , Vol. 25, no 5, article id 104189Article in journal (Refereed) Published
Abstract [en]

Discovering loci under balancing selection in humans can identify loci with alleles that affect response to the environment and disease. Genome variation data have identified the 5′ region of the DMBT1 gene as undergoing balancing selection in humans. DMBT1 encodes the pattern-recognition glycoprotein DMBT1, also known as SALSA, gp340, or salivary agglutinin. DMBT1 binds to a variety of pathogens through a tandemly arranged scavenger receptor cysteine-rich (SRCR) domain, with the number of domains polymorphic in humans. We show that the signal of balancing selection is driven by one haplotype usually carrying a shorter SRCR repeat and another usually carrying a longer SRCR repeat. DMBT1 encoded by a shorter SRCR repeat allele does not bind a cariogenic and invasive Streptococcus mutans strain, in contrast to the long SRCR allele that shows binding. Our results suggest that balancing selection at DMBT1 is due to host-microbe interactions of encoded SRCR tandem repeat alleles.

Place, publisher, year, edition, pages
Cell Press, 2022
Keywords
biological sciences, evolutionary mechanisms, genetics
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-194336 (URN)10.1016/j.isci.2022.104189 (DOI)000826167700008 ()2-s2.0-85128260749 (Scopus ID)
Available from: 2022-05-04 Created: 2022-05-04 Last updated: 2023-09-05Bibliographically approved
Barman, M., Murray, F., Bernardi, A. I., Broberg, K., Bölte, S., Hesselmar, B., . . . Sandin, A. (2018). Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE): a prospective birth cohort in northern Sweden. BMJ Open, 8(10), Article ID e022013.
Open this publication in new window or tab >>Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE): a prospective birth cohort in northern Sweden
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2018 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 8, no 10, article id e022013Article in journal (Refereed) Published
Abstract [en]

Introduction Prenatal and neonatal environmental factors, such as nutrition, microbes and toxicants, may affect health throughout life. Many diseases, such as allergy and impaired child development, may be programmed already in utero or during early infancy. Birth cohorts are important tools to study associations between early life exposure and disease risk. Here, we describe the study protocol of the prospective birth cohort, 'Nutritional impact on Immunological maturation during Childhood in relation to the Environment' (NICE). The primary aim of the NICE cohort is to clarify the effect of key environmental exposures-diet, microbes and environmental toxicants-during pregnancy and early childhood, on the maturation of the infant's immune system, including initiation of sensitisation and allergy as well as some secondary outcomes: infant growth, obesity, neurological development and oral health. Methods and analysis The NICE cohort will recruit about 650 families during mid-pregnancy. The principal inclusion criterion will be planned birth at the Sunderby Hospital in the north of Sweden, during 2015-2018. Questionnaires data and biological samples will be collected at 10 time-points, from pregnancy until the children reach 4 years of age. Samples will be collected primarily from mothers and children, and from fathers. Biological samples include blood, urine, placenta, breast milk, meconium, faeces, saliva and hair. Information regarding allergic heredity, diet, socioeconomic status, lifestyle including smoking, siblings, pet ownership, etc will be collected using questionnaires. Sensitisation to common allergens will be assessed by skin prick testing and allergic disease will be diagnosed by a paediatrician at 1 and 4 years of age. At 4 years of age, the children will also be examined regarding growth, neurobehavioural and neurophysiological status and oral health. Ethics and dissemination The NICE cohort has been approved by the Regional Ethical Review Board in Umea, Sweden (2013/18-31M). Results will be disseminated through peer-reviewed journals and communicated on scientific conferences.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-155656 (URN)10.1136/bmjopen-2018-022013 (DOI)000454739500070 ()30344169 (PubMedID)2-s2.0-85055073603 (Scopus ID)
Available from: 2019-01-25 Created: 2019-01-25 Last updated: 2023-08-28Bibliographically approved
Strömberg, N., Esberg, A., Sheng, N., Mårell, L., Löfgren-Burström, A., Danielsson, K. & Källestål, C. (2017). Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH2. EBioMedicine, 26, 38-46
Open this publication in new window or tab >>Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH2
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2017 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 26, p. 38-46Article in journal (Refereed) Published
Abstract [en]

Dental caries is a chronic infectious disease that affects billions of people with large individual differences in activity. We investigated whether PRH1 and PRH2 polymorphisms in saliva acidic proline-rich protein (PRP) receptors for indigenous bacteria match and predict individual differences in the development of caries. PRH1 and PRH2 variation and adhesion of indigenous and cariogenic (Streptococcus mutans) model bacteria were measured in 452 12-year-old Swedish children along with traditional risk factors and related to caries at baseline and after 5-years. The children grouped into low-to-moderate and high susceptibility phenotypes for caries based on allelic PRH1, PRH2 variation. The low-to-moderate susceptibility children (P1 and P4a-) experienced caries from eating sugar or bad oral hygiene or infection by S. mutans. The high susceptibility P4a (Db, PIF, PRP12) children had more caries despite receiving extra prevention and irrespective of eating sugar or bad oral hygiene or S. mutans-infection. They instead developed 3.9-fold more caries than P1 children from plaque accumulation in general when treated with orthodontic multibrackets; and had basic PRP polymorphisms and low DMBT1-mediated S. mutans adhesion as additional susceptibility traits. The present findings thus suggest genetic autoimmune-like (P4a) and traditional life style (P1) caries, providing a rationale for individualized oral care.

Keywords
Acidic proline-rich proteins, Chronic infections, Dental caries, Host susceptibility, PRH1, PRH2
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-143131 (URN)10.1016/j.ebiom.2017.11.019 (DOI)29191562 (PubMedID)2-s2.0-85035200649 (Scopus ID)
Available from: 2017-12-18 Created: 2017-12-18 Last updated: 2023-05-22Bibliographically approved
Bugaytsova, J. A., Björnham, O., Chernov, Y. A., Gideonsson, P., Henriksson, S., Mendez, M., . . . Boren, T. (2017). Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence. Cell Host and Microbe, 21(3), 376-389
Open this publication in new window or tab >>Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence
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2017 (English)In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, no 3, p. 376-389Article in journal (Refereed) Published
Abstract [en]

The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.

Place, publisher, year, edition, pages
CELL PRESS, 2017
National Category
Microbiology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-132788 (URN)10.1016/j.chom.2017.02.013 (DOI)000396375600023 ()28279347 (PubMedID)2-s2.0-85014795847 (Scopus ID)
Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2023-03-24Bibliographically approved
Esberg, A., Sheng, N., Mårell, L., Claesson, R., Persson, K., Borén, T. & Strömberg, N. (2017). Streptococcus Mutans Adhesin Biotypes that Match and Predict Individual Caries Development. EBioMedicine, 24, 205-215
Open this publication in new window or tab >>Streptococcus Mutans Adhesin Biotypes that Match and Predict Individual Caries Development
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2017 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 24, p. 205-215Article in journal (Refereed) Published
Abstract [en]

Dental caries, which affects billions of people, is a chronic infectious disease that involves Streptococcus mutans, which is nevertheless a poor predictor of individual caries development. We therefore investigated if adhesin types of S.mutans with sucrose-independent adhesion to host DMBT1 (i.e. SpaP A, B or C) and collagen (i.e. Cnm, Cbm) match and predict individual differences in caries development. The adhesin types were measured in whole saliva by qPCR in 452 12-year-old Swedish children and related to caries at baseline and prospectively at a 5-year follow-up. Strains isolated from the children were explored for genetic and phenotypic properties. The presence of SpaP B and Cnm subtypes coincided with increased 5-year caries increment, and their binding to DMBT1 and saliva correlated with individual caries scores. The SpaP B subtypes are enriched in amino acid substitutions that coincided with caries and binding and specify biotypes of S. mutans with increased acid tolerance. The findings reveal adhesin subtypes of S. mutans that match and predict individual differences in caries development and provide a rationale for individualized oral care.

Keywords
Adhesion, Chronic infections, Dental caries, SpaP, Streptococcus mutans, Virulence
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-140203 (URN)10.1016/j.ebiom.2017.09.027 (DOI)000414392900033 ()28958656 (PubMedID)2-s2.0-85029795020 (Scopus ID)
Funder
Swedish Research Council, 10906
Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2023-05-22Bibliographically approved
Esberg, A., Löfgren-Burström, A., Öhman, U. & Strömberg, N. (2012). Host and bacterial phenotype variation in adhesion of streptococcus mutans to matched human hosts. Infection and Immunity, 80(11), 3869-3879
Open this publication in new window or tab >>Host and bacterial phenotype variation in adhesion of streptococcus mutans to matched human hosts
2012 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 80, no 11, p. 3869-3879Article in journal (Refereed) Published
Abstract [en]

The commensal pathogen Streptococcus mutans uses AgI/II adhesins to adhere to gp340 adsorbed on teeth. Here we analyzed isolates of S. mutans (n = 70 isolates) from caries and caries-free human extremes (n = 19 subjects) by multilocus sequence typing (MLST), AgI/II full-length gene sequencing, and adhesion to parotid saliva matched from the strain donors (nested from a case-control sample of defined gp340 and acidic proline-rich protein [PRP] profiles). The concatenated MLST as well as AgI/II gene sequences showed unique sequence types between, and identical types within, the subjects. The matched adhesion levels ranged widely (40% adhesion range), from low to moderate to high, between subjects but were similar within subjects (or sequence types). In contrast, the adhesion avidity of the strains was narrow, normally distributed for high, moderate, or low adhesion reference saliva or pure gp340 regardless of the sequence type. The adhesion of S. mutans Ingbritt and matched isolates and saliva samples correlated (r = 0.929), suggesting that the host specify about four-fifths (r(2) = 0.86) of the variation in matched adhesion. Half of the variation in S. mutans Ingbritt adhesion to saliva from the caries cases-controls (n = 218) was explained by the primary gp340 receptor and PRP coreceptor composition. The isolates also varied, although less so, in adhesion to standardized saliva (18% adhesion range) and clustered into three major AgI/II groups (groups A, B-1, and B-2) due to two variable V-region segments and diverse AgI/II sequence types due to a set of single-amino-acid substitutions. Isolates with AgI/II type A versus types B-1 and B-2 tended to differ in gp340 binding avidity and qualitative adhesion profiles for saliva gp340 phenotypes. In conclusion, the host saliva phenotype plays a more prominent role in S. mutans adhesion than anticipated previously.

Place, publisher, year, edition, pages
Washington: American Society Microbiology, 2012
National Category
Medical and Health Sciences
Research subject
Immunology
Identifiers
urn:nbn:se:umu:diva-61766 (URN)10.1128/IAI.00435-12 (DOI)000309971600015 ()2-s2.0-84867588241 (Scopus ID)
Available from: 2012-11-27 Created: 2012-11-26 Last updated: 2023-03-24Bibliographically approved
Persson, K., Esberg, A., Claesson, R. & Strömberg, N. (2012). The pilin protein FimP from Actinomyces oris: crystal structure and sequence analyses. PLOS ONE, 7(10), e48364
Open this publication in new window or tab >>The pilin protein FimP from Actinomyces oris: crystal structure and sequence analyses
2012 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 10, p. e48364-Article in journal (Refereed) Published
Abstract [en]

The Actinomyces oris type-1 pili are important for the initial formation of dental plaque by binding to salivary proteins that adhere to the tooth surface. Here we present the X-ray structure of FimP, the protein that is polymerized into the type-1 pilus stalk, assisted by a pili-specific sortase. FimP consists of three tandem IgG-like domains. The middle and C-terminal domains contain one autocatalyzed intramolecular isopeptide bond each, a feature used by Gram-positive bacteria for stabilization of surface proteins. While the N-terminal domain harbours all the residues necessary for forming an isopeptide bond, no such bond is observed in the crystal structure of this unpolymerized form of FimP. The monomer is further stabilized by one disulfide bond each in the N- and C-terminal domains as well as by a metal-coordinated loop protruding from the C-terminal domain. A lysine, predicted to be crucial for FimP polymerization by covalent attachment to a threonine from another subunit, is located at the rim of a groove lined with conserved residues. The groove may function as a docking site for the sortase-FimP complex. We also present sequence analyses performed on the genes encoding FimP as well as the related FimA, obtained from clinical isolates.

Keywords
crystal structure, pili
National Category
Structural Biology Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:umu:diva-61474 (URN)10.1371/journal.pone.0048364 (DOI)2-s2.0-84868282959 (Scopus ID)
Funder
Swedish Research Council
Available from: 2012-11-15 Created: 2012-11-15 Last updated: 2023-03-24Bibliographically approved
Maddocks, S. E., Wright, C. J., Nobbs, A. H., Brittan, J. L., Franklin, L., Strömberg, N., . . . Jenkinson, H. F. (2011). Streptococcus pyogenes antigen I/II-family polypeptide AspA shows differential ligand-binding properties and mediates biofilm formation. Molecular Microbiology, 81(4), 1034-1049
Open this publication in new window or tab >>Streptococcus pyogenes antigen I/II-family polypeptide AspA shows differential ligand-binding properties and mediates biofilm formation
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2011 (English)In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 81, no 4, p. 1034-1049Article in journal (Refereed) Published
Abstract [en]

The streptococcal antigen I/II (AgI/II)-family polypeptides are cell wall-anchored adhesins expressed by most indigenous oral streptococci. Proteins sharing 30-40% overall amino acid sequence similarities with AgI/II-family proteins are also expressed by Streptococcus pyogenes. The S. pyogenes M28_Spy1325 polypeptide (designated AspA) displays an AgI/II primary structure, with alanine-rich (A) and prolinerich (P) repeats flanking a V region that is projected distal from the cell. In this study it is shown that AspA from serotype M28 S. pyogenes, when expressed on surrogate host Lactococcus lactis, confers binding to immobilized salivary agglutinin gp-340. This binding was blocked by antibodies to the AspA-VP region. In contrast, the N-terminal region of AspA was deficient in binding fluid-phase gp-340, and L. lactis cells expressing AspA were not agglutinated by gp-340. Deletion of the aspA gene from two different M28 strains of S. pyogenes abrogated their abilities to form biofilms on saliva-coated surfaces. In each mutant strain, biofilm formation was restored by trans complementation of the aspA deletion. In addition, expression of AspA protein on the surface of L. lactis conferred biofilm-forming ability. Taken collectively, the results provide evidence that AspA is a biofilm-associated adhesin that may function in host colonization by S. pyogenes.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-104831 (URN)10.1111/j.1365-2958.2011.07749.x (DOI)000293752500015 ()21736640 (PubMedID)2-s2.0-80051570468 (Scopus ID)
Available from: 2015-06-17 Created: 2015-06-15 Last updated: 2023-03-23Bibliographically approved
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