cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.15139/s3/bpt6qb
title: Mathematical Modeling in Clinical Trials of Tuberculosis Therapeutics

description: The Stop TB Partnership has prioritized the development of shorter regimens as part of their global plan to eliminate TB. In pursuit of that goal, many entities have undertaken Phase II clinical trials using 2-month culture conversion as a surrogate endpoint to test the sterilizing ability of new drug regimens. However, the sequential testing of all proposed regimens is time-consuming and cost-prohibitive, so more efficient strategies for selecting regimens for testing are required. Furthermore, without prior evaluation of the costs of new therapies, there is a risk of developing a new treatment for TB that is not economically viable. Mathematical modeling can provide a solution to this problem by synthesizing data from prior human and mouse studies to generate estimates of relapse rates for new regimens that could be used in the design of clinical trials. First, a generic Markov model of TB treatment and relapse will be developed in which individuals with TB will be assigned to one of several treatment arms, then followed in monthly cycles through an interim evaluation of culture positivity at 1, 2, 3, or 4 months. They will then be assumed to complete a consolidation phase of therapy, after which they will be followed for two years for relapse. Toxicity and tolerability will be considered at each stage. We will use appropriate distributions for all relevant parameters, particularly culture conversion and relapse rates, and use probabilistic sensitivity analysis to produce point estimates of relapse rates with 95% confidence intervals that can be used to determine which regimens are worthy of further testing. This model will then be used to accomplish 3 specific aims: Aim 1 will be to use the model to examine the potential impact of substituting moxifloxacin for isoniazid during the first two months of TB treatment on TB relapse rates, given standard and abbreviated treatment durations. Aim 2 will be to determine the impact of high-dose rifapentine (administered during the first 2 months of TB treatment) on relapse rates and potential for reduction of the duration of TB treatment. Aim 3 will be to model the potential effect of linezolid on the treatment of MDR-TB, paying particular attention to the tradeoff between increased effectiveness and toxicity. Costs and cost-effectiveness will be calculated in each model.
DOI: 10.6084/m9.figshare.24038052
title: Magnitude of Incoherent Energy Flux

description: Magnitude of incoherent energy flux of internal tides in the South China Sea
DOI: 10.6084/m9.figshare.24038052.v1
title: Magnitude of Incoherent Energy Flux

description: Magnitude of incoherent energy flux of internal tides in the South China Sea
DOI: 10.15139/s3/wee8fj
title: High-Resolution Plasma Metabolomic Profiling to Identify Biomarkers for Tuberculosis Disease and Response to Therapy

description: Tuberculosis (TB) is the number one infectious disease killer in the world with 1.5 million deaths attributable to the disease in 2014. A critical knowledge gap exists given the lack of biological pathways and predictive biomarkers related to TB onset, progression and resolution. An improved diagnostic test for TB would have a major impact on global control of the disease and reduce mortality. Unfortunately, there are no validated biomarkers for TB onset, progression and resolution; the development of a TB biomarker is urgently needed. Current ultra-high-resolution metabolomics (HRM) methods have considerable promise for the development of TB-associated biomarkers. Several studies have identified distinguishing small molecule metabolic profiles in blood and other bio samples in individuals with active Mycobacterium tuberculosis (Mtb)-induced TB disease compared to uninfected controls, but no studies have explored whether metabolomics is predictive of TB outcomes, Mtb clearance from sputum. Further, all studies to date have used low-resolution metabolomics methods. Advances in mass spectrometer machine capability, coupled with recent advanced data extraction/analysis methods has considerably increased the dynamic range of metabolite detection by HRM in biologic samples, which now exceeds 20,000 species (&gt;100,000 ions). Our HRM processing scheme provides capability to detect very low abundance metabolites, including Mtb cell envelope glycolipids, and explore regulation of human metabolic pathways. In a pilot study, we successfully identified 61 plasma metabolites that differentiated adults with active pulmonary TB from household contacts without TB. Differentiating species included specific Mtb-derived cell wall glycolipids and endogenous lipid mediator resolvins. Our recent pilot data shows that specific metabolites and human metabolic pathways, including those involved in drug, amino acid, and lipid metabolism, are associated with the propensity for sputum Mtb culture clearance over time. The ultimate goal of this exploratory proposal is to obtain novel data that may lead to the development of new TB biomarkers. We hypothesize that plasma HRM analysis can: 1) predict the propensity for successful anti-TB treatment by identifying Mtb-derived and endogenous metabolites (biomarkers) and human metabolic pathways (pathophysiology) associated with sputum Mtb clearance; and 2) successfully differentiate patients with active TB from controls without latent TB infection (LTBI) or TB disease. To test these hypotheses, we propose the following Specific Aims in this exploratory R21 project: Specific Aim 1: To determine whether plasma HRM analysis can identify Mtb-derived and endogenous metabolites that predict clearance of Mtb from sputum (change from positive to negative culture). Specific Aim 2: To determine whether plasma HRM analysis can differentiate adults with drug- sensitive or MDR-TB ± HIV co-infection from asymptomatic controls without LTBI.
DOI: 10.15139/s3/gya6im
title: National Tuberculosis Surveillance System (NTSS)

description: The National Tuberculosis Surveillance System collects information on each newly reported case of tuberculosis (TB) disease in the United States. The program is a cooperative effort of the Centers for Disease Control and Prevention (CDC) and state and local health departments, who report cases of TB to CDC.
DOI: 10.15139/s3/4ktc7k
title: The Survival and HIV Outcomes in MDR TB Study

description: The Survival and HIV Outcomes in MDR TB Study (SHOUT) was a prospective cohort study of patients with multidrug-resistant tuberculosis (MDR TB) comparing treatment outcomes and adverse events in patients with and without HIV co-infection. We enrolled 206 participants ≥18 years of age with culture-confirmed MDR TB who were initiating therapy between 2011 and 2013. Participants were recruited from three TB referral hospitals in KwaZulu-Natal province, South Africa. Study participants were seen monthly for the duration of therapy (typically 24 months) and quarterly for one year following treatment completion. Each month, participants were interviewed regarding symptoms, adverse events, and medication adherence. Sputum samples were sent monthly for smear microscopy, culture, and drug-susceptibility testing as was routine blood testing. Pure tone audiometry and color vision testing was also performed at regular intervals. The SHOUT Study was the first prospective cohort study to show that—despite the increased pill burden associated with concurrent treatment of HIV and MDR TB—co-infected patients did not generally experience more adverse events or worse treatment outcomes. Selected publications: • Primary treatment outcomes: DOI: 10.1093/cid/cix1125 • Adverse events: DOI: 10.1097/QAI.0000000000002190 • Treatment adherence: DOI: 10.1097/QAI.0000000000002120
DOI: 10.34740/kaggle/dsv/6368463
title: COVID Vaccination in World (updated daily)
DOI: 10.15139/s3/rv9bnc
title: HIV/TB in Uganda: Punctuated Antiretroviral Therapy

description: Tuberculosis (TB) is a common and serious complication of human immunodeficiency virus-type 1 (HIV) infection in the developing world, especially in sub-Saharan Africa. Since the emergence of the HIV epidemic in Africa, the incidence rates of TB have risen dramatically, overwhelming national TB control programs across Africa. Over one-half of TB patients presenting to TB clinics in Africa are HIV-infected, often presenting in early stages of HIV infection. Recent WHO guidelines on the management of HIV-associated pulmonary TB recommend antiretroviral (ARV) therapy in patients with CD4+ T cells &lt; 200 cells/muL but not for HIV-infected TB patients who present with high CD4+ cells. In Uganda, over half of HIV-infected patients with active TB present with CD4+ counts above 200 cells/?L. There are clinical and scientific reasons for treating these TB patients with ARV therapy even when they present in early stages of HIV infection. First, mortality in HIV-associated TB is high, even when patients respond to effective anti-tuberculous therapy. Second, excess mortality associated with TB is most evident when CD4+ counts are above 200 cell/muL. Third, in dually-infected patients, TB results in prolonged immune activation which may enhance viral replication and accelerate the decline of CD4+ cells. The proposed study will test whether a novel approach of punctuated ARV therapy given during treatment of active TB will slow progression of HIV disease in TB patients with CD4+ cells &gt; 350 cells/muL. The study will also assess the possible risks (e.g., drug toxicities and resistance) and benefits (e.g., more rapid clearance of MTB and reduced TB relapse) of punctuated ARV therapy. The Specific Aims of this proposal will be addressed in an open label, randomized, clinical trial of HIV-infected TB patients (CD4+ greater than or equal too 350 cells/muL) with a concurrent, nonrandomized, observational comparison group of HIV-infected persons without active TB (CD4+ greater than or equal too 350 cells/muL). We will compare rates of CD4+ cell count decline over 2 years between TB patients who are randomized to either immediate, punctuated ARV therapy given for six months during TB treatment or delayed ARV therapy which is started when CD4+ cell counts fall below 200 cells/?L. We will also compare the rates of CD4+ cell count decline among TB patients with a concurrent, observational comparison group of patients with CD4+ counts greater than or equal too 350 cells/muL without TB to quantify the extent to which CD4+ cell decline is accelerated with active TB and to determine the extent to which the decline is neutralized in patients who receive punctuated ARV therapy. The research team from the Uganda-Case Western Reserve Research Collaboration and the Antiviral unit at the University of California, San Diego has the necessary experience in clinical trials, TB and HIV pathogenesis, and antiretroviral therapy to complete the study.
DOI: 10.6084/m9.figshare.24038082
title: lfw_funneled.zip

description: LFW 数据集（灰色）
DOI: 10.15139/s3/alcswx
title: An Exploratory Study of Anti-Tuberculosis Drug Penetration into Cerebrospinal Fluid

description: Tuberculosis meningitis (TBM) is the most lethal form of tuberculosis disease with close to half of all patients' affected experiencing severe disability or death and worse outcomes among patients with drug-resistant disease. Attaining adequate concentrations of anti-TB drugs in the central nervous system (CNS) is essential to the successful treatment of TBM, but critical knowledge gaps exist. Among the first-line TB drugs, available data has indicated that cerebrospinal fluid (CSF) concentrations of rifampin (RIF), considered the most important first-line drug, are approximately 20% of serum values and in most cases well below recommended Cmax concentrations. Regarding non-first-line drugs, two recent studies have examined the benefit of adding a fluoroquinolone for the treatment of drug-susceptible TBM with mixed results and there has been almost no report on the use of newly introduced drugs including delaminid and bedaquiline among patients with drug- resistant TBM. We propose a prospective observational study to evaluate the CSF drug concentrations of rifampin, levofloxacin (LEV), bedaquiline (BDQ), and delamanid (DEL) among patients being treated for TBM in the country of Georgia. Our overall study goals are to demonstrate to provide novel pilot data on a) factors associated with CNS penetration and on b) the CSF concentrations of newly introduced anti-TB drugs. We hypothesize that CSF drug concentrations of rifampin and levofloxacin will be associated with CSF inflammatory markers and time from initiating treatment and that CSF concentrations of bedaquiline and delamanid will be low. A better understanding of CSF drug concentrations will guide new and improved treatment options for patients afflicted TBM. The Specific AIMs of this proposal include: 1) To determine the clinical treatment outcomes of patients treated for drug-susceptible TBM with an intensified regimen. Primary outcomes of death and neurological disability and predictors of will be assessed 12 months after TBM treatment initiation. 2) To determine RIF and LEV CSF concentrations among patients being treated for drug-sensitive TBM. We will enroll 16 patients with confirmed or probable TBM from AIM 1 to compare the ratio of serum RIF (non- protein bound) and LEV to CSF concentrations and to estimate additional CSF parameters including Cmax and AUC. We will also evaluate whether time course of disease and the level of inflammation as characterized by CSF cellular and cytokine profile are associated with CSF drug concentrations. 3) To determine the CSF concentrations of newly introduced anti-TB drugs including BDQ and DEL among patient being treated for drug-resistant TBM. We will enroll 8 patients being treated for drug- resistant TBM with either BDQ or DEL. This exploratory aim will provide novel preliminary data on the CSF concentrations of these drugs and insight into whether current dosing strategies adopted from pulmonary TB recommendations are appropriate among patients with TBM.
DOI: 10.6084/m9.figshare.24038096
title: Table S3: Matrix of detected species by site for stream sites. from Deforestation strengthens environmental filtering and competitive exclusion in Neotropical streams and rivers

description: Understanding how anthropization impacts the assembly of species onto communities is pivotal to go beyond the observation of biodiversity changes and reveal how disturbances affect the environmental and biotic processes shaping biodiversity. Here, we propose a simple framework to measure the assembly processes underpinning functional convergence/divergence patterns. We apply this framework to Northern Amazonian fish communities inventoried using environmental DNA in 35 stream sites and 64 river sites. We found that the harsh and unstable environmental conditions characterizing streams convey communities towards functional convergence, by filter traits related to food acquisition and, to a lower extent, dispersal. Such environmental filtering also strengthens competition by excluding species having less competitive food acquisition traits. Instead, random species assembly was more marked in river communities, which may be explained by the downstream position of rivers facilitating the dispersion of species. Although fish assembly rules differed between streams and river fish communities, anthropogenic disturbances reduced functional divergence in both ecosystems, with a reinforcement of both environmental filtering and weaker competitor exclusion. This may explain the substantial biodiversity alterations observed under slight deforestation levels and underlines the vulnerability of Neotropical freshwater ecosystems to anthropic disturbances that not only affect species persistence but also modify community assembly rules.
DOI: 10.6084/m9.figshare.24038096.v1
title: Table S3: Matrix of detected species by site for stream sites. from Deforestation strengthens environmental filtering and competitive exclusion in Neotropical streams and rivers

description: Understanding how anthropization impacts the assembly of species onto communities is pivotal to go beyond the observation of biodiversity changes and reveal how disturbances affect the environmental and biotic processes shaping biodiversity. Here, we propose a simple framework to measure the assembly processes underpinning functional convergence/divergence patterns. We apply this framework to Northern Amazonian fish communities inventoried using environmental DNA in 35 stream sites and 64 river sites. We found that the harsh and unstable environmental conditions characterizing streams convey communities towards functional convergence, by filter traits related to food acquisition and, to a lower extent, dispersal. Such environmental filtering also strengthens competition by excluding species having less competitive food acquisition traits. Instead, random species assembly was more marked in river communities, which may be explained by the downstream position of rivers facilitating the dispersion of species. Although fish assembly rules differed between streams and river fish communities, anthropogenic disturbances reduced functional divergence in both ecosystems, with a reinforcement of both environmental filtering and weaker competitor exclusion. This may explain the substantial biodiversity alterations observed under slight deforestation levels and underlines the vulnerability of Neotropical freshwater ecosystems to anthropic disturbances that not only affect species persistence but also modify community assembly rules.
DOI: 10.6084/m9.figshare.24038099
title: Table S2: Site information with geographical locations, abiotic variables and biodiversity measures. from Deforestation strengthens environmental filtering and competitive exclusion in Neotropical streams and rivers

description: Understanding how anthropization impacts the assembly of species onto communities is pivotal to go beyond the observation of biodiversity changes and reveal how disturbances affect the environmental and biotic processes shaping biodiversity. Here, we propose a simple framework to measure the assembly processes underpinning functional convergence/divergence patterns. We apply this framework to Northern Amazonian fish communities inventoried using environmental DNA in 35 stream sites and 64 river sites. We found that the harsh and unstable environmental conditions characterizing streams convey communities towards functional convergence, by filter traits related to food acquisition and, to a lower extent, dispersal. Such environmental filtering also strengthens competition by excluding species having less competitive food acquisition traits. Instead, random species assembly was more marked in river communities, which may be explained by the downstream position of rivers facilitating the dispersion of species. Although fish assembly rules differed between streams and river fish communities, anthropogenic disturbances reduced functional divergence in both ecosystems, with a reinforcement of both environmental filtering and weaker competitor exclusion. This may explain the substantial biodiversity alterations observed under slight deforestation levels and underlines the vulnerability of Neotropical freshwater ecosystems to anthropic disturbances that not only affect species persistence but also modify community assembly rules.
DOI: 10.6084/m9.figshare.24038099.v1
title: Table S2: Site information with geographical locations, abiotic variables and biodiversity measures. from Deforestation strengthens environmental filtering and competitive exclusion in Neotropical streams and rivers

description: Understanding how anthropization impacts the assembly of species onto communities is pivotal to go beyond the observation of biodiversity changes and reveal how disturbances affect the environmental and biotic processes shaping biodiversity. Here, we propose a simple framework to measure the assembly processes underpinning functional convergence/divergence patterns. We apply this framework to Northern Amazonian fish communities inventoried using environmental DNA in 35 stream sites and 64 river sites. We found that the harsh and unstable environmental conditions characterizing streams convey communities towards functional convergence, by filter traits related to food acquisition and, to a lower extent, dispersal. Such environmental filtering also strengthens competition by excluding species having less competitive food acquisition traits. Instead, random species assembly was more marked in river communities, which may be explained by the downstream position of rivers facilitating the dispersion of species. Although fish assembly rules differed between streams and river fish communities, anthropogenic disturbances reduced functional divergence in both ecosystems, with a reinforcement of both environmental filtering and weaker competitor exclusion. This may explain the substantial biodiversity alterations observed under slight deforestation levels and underlines the vulnerability of Neotropical freshwater ecosystems to anthropic disturbances that not only affect species persistence but also modify community assembly rules.
DOI: 10.6084/m9.figshare.24038105
title: Table S3: Matrix of detected species by site for river sites. from Deforestation strengthens environmental filtering and competitive exclusion in Neotropical streams and rivers

description: Understanding how anthropization impacts the assembly of species onto communities is pivotal to go beyond the observation of biodiversity changes and reveal how disturbances affect the environmental and biotic processes shaping biodiversity. Here, we propose a simple framework to measure the assembly processes underpinning functional convergence/divergence patterns. We apply this framework to Northern Amazonian fish communities inventoried using environmental DNA in 35 stream sites and 64 river sites. We found that the harsh and unstable environmental conditions characterizing streams convey communities towards functional convergence, by filter traits related to food acquisition and, to a lower extent, dispersal. Such environmental filtering also strengthens competition by excluding species having less competitive food acquisition traits. Instead, random species assembly was more marked in river communities, which may be explained by the downstream position of rivers facilitating the dispersion of species. Although fish assembly rules differed between streams and river fish communities, anthropogenic disturbances reduced functional divergence in both ecosystems, with a reinforcement of both environmental filtering and weaker competitor exclusion. This may explain the substantial biodiversity alterations observed under slight deforestation levels and underlines the vulnerability of Neotropical freshwater ecosystems to anthropic disturbances that not only affect species persistence but also modify community assembly rules.