{"id":"https://openalex.org/W7224302247","doi":"https://doi.org/10.20944/preprints202610.2871.v1","title":"Treating the Host, Not Only the Pathogen: The Macrolide-Resistance Paradox and Multi-Layer Computational Prioritization of Host-Directed Therapies in Pediatric Mycoplasma pneumoniae Pneumonia","display_name":"Treating the Host, Not Only the Pathogen: The Macrolide-Resistance Paradox and Multi-Layer Computational Prioritization of Host-Directed Therapies in Pediatric Mycoplasma pneumoniae Pneumonia","publication_year":2026,"publication_date":"2026-10-28","ids":{"openalex":"https://openalex.org/W7224302247","doi":"https://doi.org/10.20944/preprints202610.2871.v1"},"language":"en","primary_location":{"id":"doi:10.20944/preprints202610.2871.v1","doi":"https://doi.org/10.20944/preprints202610.2871.v1","is_oa":true,"landing_page_url":"https://doi.org/10.20944/preprints202610.2871.v1","pdf_url":null,"source":{"id":"https://openalex.org/S6309402219","display_name":"Preprints.org","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.20944/preprints202610.2871.v1","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5160098085","display_name":"Hao Chen","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Hao Chen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160105651","display_name":"Deze Li","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Deze Li","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160081778","display_name":"Xiaotong Wang","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Xiaotong Wang","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5103212678","display_name":"Chen Shen","orcid":"https://orcid.org/0000-0002-7806-5723","observed_orcids":["https://orcid.org/0000-0002-7806-5723"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Chen Shen","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-7806-5723","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5103212678"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11688","display_name":"Microbial infections and disease research","score":0.7519999742507935,"subfield":{"id":"https://openalex.org/subfields/2404","display_name":"Microbiology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11688","display_name":"Microbial infections and disease research","score":0.7519999742507935,"subfield":{"id":"https://openalex.org/subfields/2404","display_name":"Microbiology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10654","display_name":"Pneumonia and Respiratory Infections","score":0.13279999792575836,"subfield":{"id":"https://openalex.org/subfields/2713","display_name":"Epidemiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.031199999153614044,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/mycoplasma-pneumoniae-pneumonia","display_name":"Mycoplasma pneumoniae pneumonia","score":0.9959999918937683},{"id":"https://openalex.org/keywords/macrolide-resistance","display_name":"macrolide resistance","score":0.9950000047683716},{"id":"https://openalex.org/keywords/host-directed-therapy","display_name":"host-directed therapy","score":0.9139999747276306},{"id":"https://openalex.org/keywords/drug-repurposing","display_name":"drug repurposing","score":0.9629999995231628},{"id":"https://openalex.org/keywords/pediatric-respiratory-infection","display_name":"pediatric respiratory infection","score":0.7160000205039978},{"id":"https://openalex.org/keywords/antimicrobial-resistance","display_name":"antimicrobial resistance","score":0.7730000019073486},{"id":"https://openalex.org/keywords/jak-stat-signaling","display_name":"JAK/STAT signaling","score":0.968999981880188},{"id":"https://openalex.org/keywords/aim2","display_name":"AIM2","score":0.8960000276565552},{"id":"https://openalex.org/keywords/doxycycline","display_name":"doxycycline","score":0.8799999952316284},{"id":"https://openalex.org/keywords/corticosteroids","display_name":"corticosteroids","score":0.9079999923706055},{"id":"https://openalex.org/keywords/jak-inhibitors","display_name":"JAK inhibitors","score":0.9890000224113464},{"id":"https://openalex.org/keywords/lincs-l1000","display_name":"LINCS L1000","score":0.7580000162124634}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6633999943733215},{"id":"https://openalex.org/C2779215961","wikidata":"https://www.wikidata.org/wiki/Q310904","display_name":"Mycoplasma pneumoniae","level":3,"score":0.6000999808311462},{"id":"https://openalex.org/C2777914695","wikidata":"https://www.wikidata.org/wiki/Q12192","display_name":"Pneumonia","level":2,"score":0.5376999974250793},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.47119998931884766},{"id":"https://openalex.org/C2777027569","wikidata":"https://www.wikidata.org/wiki/Q420595","display_name":"Tigecycline","level":3,"score":0.4212000072002411},{"id":"https://openalex.org/C501593827","wikidata":"https://www.wikidata.org/wiki/Q12187","display_name":"Antibiotics","level":2,"score":0.39309999346733093},{"id":"https://openalex.org/C2777179404","wikidata":"https://www.wikidata.org/wiki/Q422442","display_name":"Doxycycline","level":3,"score":0.3515999913215637},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.34689998626708984},{"id":"https://openalex.org/C2777615720","wikidata":"https://www.wikidata.org/wiki/Q11888847","display_name":"Prioritization","level":2,"score":0.34549999237060547},{"id":"https://openalex.org/C177713679","wikidata":"https://www.wikidata.org/wiki/Q679690","display_name":"Intensive care medicine","level":1,"score":0.3431999981403351},{"id":"https://openalex.org/C2778275353","wikidata":"https://www.wikidata.org/wiki/Q415336","display_name":"Minocycline","level":3,"score":0.33059999346733093},{"id":"https://openalex.org/C761482","wikidata":"https://www.wikidata.org/wiki/Q118093","display_name":"Transmission (telecommunications)","level":2,"score":0.32409998774528503},{"id":"https://openalex.org/C94665300","wikidata":"https://www.wikidata.org/wiki/Q63391344","display_name":"Antibiotic resistance","level":3,"score":0.3208000063896179},{"id":"https://openalex.org/C519536355","wikidata":"https://www.wikidata.org/wiki/Q21021151","display_name":"Repurposing","level":2,"score":0.3203999996185303},{"id":"https://openalex.org/C159047783","wikidata":"https://www.wikidata.org/wiki/Q7215","display_name":"Virology","level":1,"score":0.3183000087738037},{"id":"https://openalex.org/C2779733811","wikidata":"https://www.wikidata.org/wiki/Q5531562","display_name":"Gene signature","level":4,"score":0.31679999828338623},{"id":"https://openalex.org/C7573103","wikidata":"https://www.wikidata.org/wiki/Q416481","display_name":"NOD2","level":4,"score":0.3109999895095825},{"id":"https://openalex.org/C89623803","wikidata":"https://www.wikidata.org/wiki/Q12184","display_name":"Pandemic","level":5,"score":0.2752000093460083},{"id":"https://openalex.org/C3019249092","wikidata":"https://www.wikidata.org/wiki/Q274493","display_name":"Antibacterial agent","level":3,"score":0.26589998602867126},{"id":"https://openalex.org/C2779259085","wikidata":"https://www.wikidata.org/wiki/Q418946","display_name":"Colistin","level":3,"score":0.2623000144958496},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.25999999046325684}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.20944/preprints202610.2871.v1","doi":"https://doi.org/10.20944/preprints202610.2871.v1","is_oa":true,"landing_page_url":"https://doi.org/10.20944/preprints202610.2871.v1","pdf_url":null,"source":{"id":"https://openalex.org/S6309402219","display_name":"Preprints.org","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.20944/preprints202610.2871.v1","doi":"https://doi.org/10.20944/preprints202610.2871.v1","is_oa":true,"landing_page_url":"https://doi.org/10.20944/preprints202610.2871.v1","pdf_url":null,"source":{"id":"https://openalex.org/S6309402219","display_name":"Preprints.org","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9940000176429749}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4242193383","https://openalex.org/W4401574385","https://openalex.org/W2086672751","https://openalex.org/W2598581258","https://openalex.org/W7172474754","https://openalex.org/W2732149706","https://openalex.org/W3092688053","https://openalex.org/W4388015596","https://openalex.org/W4280538717","https://openalex.org/W2981906986"],"abstract_inverted_index":{"Mycoplasma":[0],"pneumoniae":[1,12],"pneumonia":[2],"(MPP)":[3],"has":[4],"re-emerged":[5],"globally":[6],"since":[7],"2023,":[8],"with":[9,45,134],"macrolide-resistant":[10],"M.":[11],"(MRMP)":[13],"exceeding":[14],"80%":[15],"of":[16,23,100],"isolates":[17],"in":[18,31,64,182],"China":[19],"and":[20,27,55,79,96,111,131,164],"the":[21,65,101,112,117,147,168],"Republic":[22],"Korea;":[24],"because":[25],"tetracyclines":[26],"fluoroquinolones":[28],"are":[29,167],"age-restricted":[30],"children,":[32],"no":[33],"guideline-endorsed":[34],"antibiotic":[35],"class":[36],"outside":[37],"Japan":[38],"combines":[39],"reliable":[40],"activity":[41],"against":[42],"resistant":[43],"strains":[44],"an":[46,70],"unrestricted":[47],"pediatric":[48,77,184],"safety":[49],"profile.":[50],"Macrolide":[51],"resistance":[52],"prolongs":[53],"fever":[54],"hospitalization":[56],"without":[57],"worsening":[58],"severity,":[59],"implicating":[60],"dysregulated":[61],"host":[62,72],"inflammation":[63],"residual":[66],"burden.":[67],"We":[68],"derived":[69],"MPP":[71,103],"disease":[73,148],"signature":[74,94,119],"from":[75],"public":[76],"transcriptomes":[78],"prioritized":[80],"approved":[81],"compounds":[82],"through":[83],"four":[84],"executed":[85],"evidence":[86],"layers:":[87],"pathway":[88],"enrichment,":[89],"network":[90],"proximity,":[91],"LINCS":[92],"L1000":[93],"reversal,":[95],"literature":[97],"triangulation.":[98],"Re-analysis":[99],"largest":[102],"blood":[104],"cohort":[105],"identified":[106],"159":[107],"differentially":[108],"expressed":[109],"genes,":[110,122],"age-adjusted":[113],"MPP-versus-viral":[114],"model":[115],"reproduced":[116],"published":[118],"(2,976":[120],"shared":[121],"99.8%":[123],"concordance).":[124],"The":[125],"target":[126],"map":[127],"converges":[128],"on":[129],"NLRP3-IL-1\u03b2-pyroptosis":[130],"JAK-STAT":[132],"axes,":[133],"a":[135,176],"transcriptome-supported":[136],"AIM2":[137],"signal;":[138],"doxycycline":[139],"(z":[140,152],"=":[141,153],"-3.81)":[142],"was":[143],"significantly":[144],"proximal":[145],"to":[146],"module,":[149],"whereas":[150],"quercetin":[151],"-3.03)":[154],"is":[155],"discounted":[156],"for":[157,179],"annotation-density":[158],"artifacts.":[159],"Corticosteroids":[160],"anchor":[161],"Tier":[162],"1,":[163],"JAK":[165],"inhibitors":[166],"highest-priority":[169],"testable":[170],"hypothesis.":[171],"This":[172],"hypothesis-generating":[173],"framework":[174],"provides":[175],"reproducible":[177],"template":[178],"host-directed":[180],"repurposing":[181],"antimicrobial-resistant":[183],"respiratory":[185],"infections.":[186]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2026-10-30T00:00:00"}
