Evidence map›Paper›PMID 38335224›Full record

ArticlePLoS computational biology2024

Mathematical model of oxygen, nutrient, and drug transport in tuberculosis granulomas.

Meenal Datta, McCarthy Kennedy, Saeed Siri, Laura E Via, James W Baish, Lei Xu, Véronique Dartois, Clifton E Barry, Rakesh K Jain

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
3.4field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
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  7. Toward better cures forClinical microbiology reviews · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 1 country.

Meenal DattaEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.ORCID 0000-0001-5727-8992
McCarthy KennedyDepartment of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana, United States of America.
Saeed SiriDepartment of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, Indiana, United States of America.ORCID 0000-0002-4185-0680
Laura E ViaTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health, Bethesda, Maryland, United States of America.
James W BaishDepartment of Biomedical Engineering, Bucknell University, Lewisburg, Pennsylvania, United States of America.
Lei XuEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Véronique DartoisCenter for Discovery and Innovation, Hackensack Meridian School of Medicine, Hackensack Meridian Health, Nutley, New Jersey, United States of America.
Clifton E BarryTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health, Bethesda, Maryland, United States of America.
Rakesh K JainEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.ORCID 0000-0001-7571-3548
University of Notre Dame · USHarvard University · USNational Institutes of Health · USBucknell University · USHackensack Meridian Health · US

Funding

Experimental Animal Models of TB: Chemotherapeutics and ImagingZIAAI000734 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2025
$19.6M
Dissecting Pediatric Brain Tumor Microenvironment to Improve TreatmentR35CA197743 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2015 to 2020
$5.7M
Targeting physical stress-driven mechanisms to overcome glioblastoma treatment resistanceU01CA261842 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K., MUNN, LANCE L. · 2021 to 2025
$3.1M
Reprogramming PDAC tumor microenvironment to improve immunotherapyU01CA224348 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BOUCHER, YVES, JAIN, RAKESH K. · 2017 to 2021
$2.9M
Improving treatment of HER2+ breast cancer brain metastasis by targeting lipid metabolismR01CA259253 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K., VANDER HEIDEN, MATTHEW G. · 2021 to 2025
$2.3M
Reengineering obesity-induced abnormal microenvironment to improve PDAC treatmentR01CA208205 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI, JAIN, RAKESH K. · 2017 to 2020
$2.2M
Reprogramming the tumormicroenvironment to improve immunotherapy of glioblastomaR01CA269672 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Rakesh K. Jain · 2022 to 2026
$1.9M
NCI NIH HHS R01 CA208205NCI NIH HHS R01 CA259253NCI NIH HHS R01 CA269672NCI NIH HHS R35 CA197743NCI NIH HHS U01 CA224348NCI NIH HHS U01 CA261842
6 · The paper itself

Abstract

Physiological abnormalities in pulmonary granulomas-pathological hallmarks of tuberculosis (TB)-compromise the transport of oxygen, nutrients, and drugs. In prior studies, we demonstrated mathematically and experimentally that hypoxia and necrosis emerge in the granuloma microenvironment (GME) as a direct result of limited oxygen availability. Building on our initial model of avascular oxygen diffusion, here we explore additional aspects of oxygen transport, including the roles of granuloma vasculature, transcapillary transport, plasma dilution, and interstitial convection, followed by cellular metabolism. Approximate analytical solutions are provided for oxygen and glucose concentration, interstitial fluid velocity, interstitial fluid pressure, and the thickness of the convective zone. These predictions are in agreement with prior experimental results from rabbit TB granulomas and from rat carcinoma models, which share similar transport limitations. Additional drug delivery predictions for anti-TB-agents (rifampicin and clofazimine) strikingly match recent spatially-resolved experimental results from a mouse model of TB. Finally, an approach to improve molecular transport in granulomas by modulating interstitial hydraulic conductivity is tested in silico.

Indexed as

Mycobacterium tuberculosisTuberculosisAnimalsDisease Models, AnimalGranulomaMiceNutrientsOxygenRabbitsNutrientsOxygen

Identifiers

PMID38335224
PMCPMC10883541
OpenAlexW4391677528

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.