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Record W2808336191 · doi:10.1126/scitranslmed.aau4711

Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1–infected individuals

2018· article· en· W2808336191 on OpenAlexaff
Mathieu Uzzan, Minami Tokuyama, Adam Rosenstein, Costin Tomescu, Ivo N. SahBandar, Huaibin M. Ko, Louise Leyre, Anupa Chokola, Emma Kaplan‐Lewis, Gabriela Rodrı́guez, Akihiro Seki, Michael J. Corley, Judith A. Aberg, Annalena La Porte, Eun-young Park, Hideki Ueno, Ioannis Oikonomou, Itai Doron, Iliyan D. Iliev, Benjamin K. Chen, Jennifer Lui, Timothy W. Schacker, Gláucia C. Furtado, Sérgio A. Lira, Jean‐Frédéric Colombel, Amir Horowitz, Jean K. Lim, Nicolas Chomont, Adeeb Rahman, Luis J. Montaner, Lishomwa C. Ndhlovu, Saurabh Mehandru

Bibliographic record

VenueScience Translational Medicine · 2018
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsCentre Hospitalier de l’Université de Montréal
FundersNational Institute on Minority Health and Health DisparitiesNational Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteNIH Office of the DirectorNational Institute on Drug AbuseNational Cancer InstituteNational Institutes of Health
KeywordsImmunologyGastrointestinal tractSimian immunodeficiency virusHoming (biology)Monoclonal antibodyImmune systemMedicineVirologyDiseaseVirusAntibodyBiologyPathologyInternal medicine

Abstract

fetched live from OpenAlex

T cells expressing the integrin α4β7 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although simianized anti-α4β7 monoclonal antibodies have shown promise in preventing or attenuating the disease course of simian immunodeficiency virus in nonhuman primate studies, the mechanisms of drug action remain elusive. We present a cohort of individuals with mild inflammatory bowel disease and concomitant HIV-1 infection receiving anti-α4β7 treatment. By sampling the immune inductive and effector sites of the GI tract, we have discovered that anti-α4β7 therapy led to a significant and unexpected attenuation of lymphoid aggregates, most notably in the terminal ileum. Given that lymphoid aggregates serve as important sanctuary sites for maintaining viral reservoirs, their attrition by anti-α4β7 therapy has important implications for HIV-1 therapeutics and eradication efforts and defines a rational basis for the use of anti-α4β7 therapy in HIV-1 infection.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesScience and technology studies, Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.261
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.003
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.027
GPT teacher head0.312
Teacher spread0.285 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations75
Published2018
Admission routes1
Has abstractyes

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