doi: 10.5061/dryad.9nb56
Daily weather data in 2006 in the Greater Toronto Areawea.csvR0.mA function m-file named R0.m related to sensitive analysisODE_WNV.mA function m-file named ODE_WNV.m related to sensitive analysis to define the dynamical systemLHS_Call.mA function m-file named LHS_Call.m related to sensitive analysisPara_settings.mM-file named Para_settings.m related to sensitive analysisPRCCM.mA function m-file named PRCCM.m related to sensitive analysisPRCCR0.mA function m-file named PRCCR0.m related to sensitive analysisMain script named Model.mMain script (related to sensitive analysis) calls functions R0.m, ODE_WNV.m, LHS_Call.m, PRCCM.m, PRCCR0.m and Para_settings.m.Model.mWeather.mA function m-file named Weather.m to define a weather-driven dynamical systemWeatherCases.mA function m-file named WeatherCases.m related to comparison of two cases (a region with multiple SWMPs)WeatherKappa.mA function m-file named WeatherKappa.m to show the role of intraspecific competitionMain script named WeatherSWMP.mMain script named WeatherSWMP calls functions Weather.m, WeatherCases.m, WeatherSWMP.m to show the influence of weather and SWMP on mosquito abundance and the transmission of WNV.WeatherSWMP.mWNV_SWMP_R0.mvA maple file named WNV_SWMP_R0.mw to show the variation of basic reproduction number R_0 along with combinations of weather conditions or SWMP properties.WNV_SWMP_R0.mw West Nile virus (WNV) is the most widely distributed arbovirus in the world and the spread is influenced by complex factors including weather conditions and urban environmental settings like storm water management ponds (SWMP). The purpose of this work was to develop an ordinary differential equation model to explore the impacts of SWMP, temperature and precipitation on WNV vector abundance and the transmission of WNV between mosquito and bird populations. The model was used to analyse how weather conditions and SWMP can influence the basic reproduction number. The results found that an excess of precipitation and fiercer intraspecific competition will reduce vector population and the peak value of infectious vectors and birds. This information can be used to identify measures that would be useful to control larval abundance in SWMP and the transmission of WNV.
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doi: 10.5061/dryad.p0c87
fMRI full experiment 3000 microTesla part 1fMRI full experiment 3000 microTesla part 1-10: MRI and fMRI DICOM images corresponding to the full study conducted with a 3000 microTesla exposure. These DICOM files have been produced by a Siemens 3T Verio (Siemens, Germany) MRI, as described in the paper. DICOM is a standard format for MRI images, and these can be analyzed with software packages such as BrainVoyager (Brain Innovation, The Netherlands), which we have used in the paper; or an open-access software package such as FSL (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/). The analysis procedure for the fMRI data is fully described in the Methods section of the paper. DICOM files are available for each subject pre- and post-exposure, for each of the two tasks presented in the paper (finger tapping and mental rotation). Two tasks were used in this experiment: a mental rotation task and a finger tapping task. The subject who have properly conducted the mental rotation task and have been included in the analysis are: S02, S03, S04, S06, S07, S09, S10, S11, S12, S13, S14, S16, S17, S18, S20, S21, S23, S24, S25, S27, S29. The subject who have properly conducted the finger tapping task and have been included in the analysis are: S03, S04, S06, S07, S08, S09, S10, S12, S13, S14, S16, S17, S20, S22, S23, S24, S25, S26, S27, S29. Please feel free to contact the authors if further guidance is required.fMRI full experiment 3000 microTesla part 2fMRI full experiment 3000 microTesla part 3fMRI full experiment 3000 microTesla part 4fMRI full experiment 3000 microTesla part 5fMRI full experiment 3000 microTesla part 6fMRI full experiment 3000 microTesla part 7fMRI full experiment 3000 microTesla part 8fMRI full experiment 3000 microTesla part 9fMRI full experiment 3000 microTesla part 10fMRI_Pilot_1800_microTesla_DICOM part 1fMRI_Pilot_1800_microTesla_DICOM part 1-2: MRI and fMRI DICOM images corresponding to the pilot study conducted with a 1800 microTesla exposure These DICOM files have been produced by a Siemens 1.5T Avanto (Siemens, Germany) MRI, as described in the paper. DICOM is a standard format for MRI images, and these can be analyzed with software packages such as BrainVoyager (Brain Innovation, The Netherlands), which we have used in the paper; or an open-access software package such as FSL (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/). The analysis procedure for the fMRI data is fully described in the Methods section of the paper. DICOM files are available for each subject pre- and post-exposure, for each of the two tasks presented in the paper (finger tapping and mental rotation). Please feel free to contact the authors if further guidance is required.fMRI_Pilot_1800_microTesla_DICOM part 2 Several aspects of the human nervous system and associated motor and cognitive processes have been reported to be modulated by extremely low-frequency (ELF, < 300 Hz) time-varying Magnetic Fields (MF). Due do their worldwide prevalence; power-line frequencies (60 Hz in North America) are of particular interest. Despite intense research efforts over the last few decades, the potential effects of 60 Hz MF still need to be elucidated, and the underlying mechanisms to be understood. In this study, we have used functional Magnetic Resonance Imaging (fMRI) to characterize potential changes in functional brain activation following human exposure to a 60 Hz MF through motor and cognitive tasks. First, pilot results acquired in a first set of subjects (N=9) were used to demonstrate the technical feasibility of using fMRI to detect subtle changes in functional brain activation with 60 Hz MF exposure at 1800 μT. Second, a full study involving a larger cohort of subjects tested brain activation during 1) a finger tapping task (N=20), and 2) a mental rotation task (N=21); before and after a one-hour, 60 Hz, 3000 μT MF exposure. The results indicate significant changes in task-induced functional brain activation as a consequence of MF exposure. However, no impact on task performance was found. These results illustrate the potential of using fMRI to identify MF-induced changes in functional brain activation, suggesting that a one-hour 60 Hz, 3000 μT MF exposure can modulate activity in specific brain regions after the end of the exposure period (i.e., residual effects). We discuss the possibility that MF exposure at 60 Hz, 3000 μT may be capable of modulating cortical excitability via a modulation of synaptic plasticity processes.
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doi: 10.5061/dryad.92cr7
Hydrogen sulfide (H2S), a gasotransmitter endogenously found in the central nervous system, has recently been suggested to act as a signalling molecule in the brain having beneficial effects on cardiovascular function. This study was thus undertaken to investigate the effect of NaHS (an H2S donor) in the subfornical organ (SFO), a central nervous system site important to blood pressure regulation. We used male Sprague-Dawley rats for both in vivo and in vitro experiments. We first used RT-PCR to confirm our previous microarray analyses showing that mRNAs for the enzymes required to produce H2S are expressed in the SFO. We then used microinjection techniques to investigate the physiological effects of NaHS in SFO, and found that NaHS microinjection (5 nmol) significantly increased blood pressure (mean AUC = 853.5±105.7 mmHg*s, n = 5). Further, we used patch-clamp electrophysiology and found that 97.8% (88 of 90) of neurons depolarized in response to NaHS. This response was found to be concentration dependent with an EC50 of 35.6 µM. Coupled with the depolarized membrane potential, we observed an overall increase in neuronal excitability using an analysis of rheobase and action potential firing patterns. This study has provided the first evidence of NaHS and thus H2S actions and their cellular correlates in SFO, implicating this brain area as a site where H2S may act to control blood pressure. miSFOH2S for plos paperRaw data for blood pressure recordingsH2S SFO Data AnalysisData summarizing every recording for current clamp and rheobase analyses
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Objective: To assess functional changes in lymphocyte repertoire and subsequent clinical implications during delayed-release dimethyl fumarate (DMF) treatment in patients with multiple sclerosis. Methods: Using peripheral blood from several clinical trials of DMF, immune cell subsets were quantified using flow cytometry. For some patients, lymphocyte counts were assessed after DMF discontinuation. Incidence of adverse events, including serious and opportunistic infections, was assessed. Results: In DMF-treated patients, absolute lymphocyte counts (ALCs) demonstrated a pattern of decline followed by stabilization, which also was reflected in the global reduction in numbers of circulating functional lymphocyte subsets. The relative frequencies of circulating memory T- and B-cell populations declined and naive cells increased. No increased incidence of serious infection or malignancy was observed for patients treated with DMF, even when stratified by ALC or T-cell subset frequencies. For patients who discontinued DMF due to lymphopenia, ALCs increased after DMF discontinuation; recovery time varied by ALC level at discontinuation. T-cell subsets closely correlated with ALCs in both longitudinal and cross-sectional analyses. Conclusions: DMF shifted the immunophenotype of circulating lymphocyte subsets. ALCs were closely correlated with CD4+ and CD8+ T-cell counts, indicating that lymphocyte subset monitoring is not required for safety vigilance. No increased risk of serious infection was observed in patients with low T-cell subset counts. Monitoring ALC remains the most effective way of identifying patients at risk of subsequently developing prolonged moderate to severe lymphopenia, a risk factor for progressive multifocal leukoencephalopathy in DMF-treated patients. Trial registration numbers: EUDRA CT 2015-001973-42, NCT00168701, NCT00420212, NCT00451451, and NCT00835770 Supplementary Table e-1 Flow cytometry cell surface markers to phenotype cell typesFlow cytometry cell surface markers to phenotype cell typesSupplementary Table e-1 v3.docxSupplementary Table e-2 Multiparameter flow cytometry immunophenotyping panelsMultiparameter flow cytometry immunophenotyping panelsSupplementary Table e-2 v3.docxSupplemental Table e-3 Major lymphocyte subsets by ALC category in the long-term ENDORSE integrated analysisMajor lymphocyte subsets by ALC category in the long-term ENDORSE integrated analysisSupplemental Table e-3 v3.docxSupplemental Table e-4 Mean absolute counts of Ig antibodies from baseline to week 24 (PROCLAIM)Mean absolute counts of Ig antibodies from baseline to week 24 (PROCLAIM)Supplemental Table e-4 v3.docxSupp Figure e-1 Mean levels of Ig antibodies at baseline through week 24 (PROCLAIM)Mean levels of Ig antibodies at baseline through week 24 (PROCLAIM)Mehta Lymphocyte Research Supp fig_e-1 v3.pdfSupp Figure e-2 Lymphocytes and subsets in individual patients after DMF discontinuationLymphocytes and subsets in individual patients after DMF discontinuationMehta Lymphocyte Research Supp fig_e-2 v3.pdf
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This is a local CSV file of YMDB 2.0 (http://www.ymdb.ca/) for MetFrag (https://msbi.ipb-halle.de/MetFrag/). Data was extracted to CSV from the SDF, with column headers for compulsory fields adjusted to fit the MetFrag format. One entry with no SMILES was filled in using the InChI in OpenBabel; entries with no monoisotopic mass or formula were filled in using functions in RChemMass (https://github.com/schymane/RChemMass/), finally one generic formula (row 746) was replaced with the formula from the InChI. This file is for users wanting to integrate the latest YMDB into MetFrag CL workflows (offline), this file will be integrated into MetFrag online; please use the file in the dropdown menu rather than uploading this one. Anyone using this resource should also cite the original publications from the Wishart Lab: YMDB 2.0: A Significantly Expanded Version of the Yeast Metabolome Database. Ramirez-Guana M, Marcu A, Pon A, Guo AC, Sajed T, Wishart NA, Karu N, Djoumbou Y, Arndt D and Wishart DS. Nucleic Acids Res. 2017 Jan 4;45(D1):D440-D445. PubMed: 27899612 YMDB: The Yeast Metabolome Database. Jewison T, Neveu V, Lee J, Knox C, Liu P, Mandal R, Murthy RK, Sinelnikov I, Guo AC, Wilson M, Djoumbou Y and Wishart DS. Nucleic Acids Res. 2012 Jan;40(Database ussue):D815-20. PubMed: 22064855
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doi: 10.5061/dryad.72c40
The use of interleukin-7 (IL-7) as an immunorestorative therapeutic has proven effective in HIV infection, cancer and bone marrow transplantation. Mediating its activity through membrane-bound IL-7 receptor α (mCD127), IL-7 therapy increases T-cell numbers and survival. A soluble form, sCD127, is found in plasma, and we have previously identified increased plasma sCD127 concentrations in HIV infection. Furthermore, patients with high sCD127 exhibited the best viral control, implicating a role for IL-7 or sCD127 directly in improved virologic/immunologic outcomes. The role of the cytokine IL-7 in elevating sCD127 levels was addressed here through assessment of retrospective samples obtained from SIV-infected antiretroviral (ART)-treated Rhesus macaques. IL-7 was administered in clustered weekly doses, allowing for an assessment prior, during and following IL-7 administration. The levels of sCD127 remained relatively unchanged during both early SIV infection and following initiation of ART. However, treatment with IL-7 increased sCD127 concentrations in most animals, transiently or persistently, paralleling increased T-cell numbers, correlating significantly with CD8+ T-cell levels. In addition, proliferating CD4+ or CD8+ T-cells (measured by Ki67) increased in association with elevated sCD127 concentrations. Finally, a high concentration of sCD127 in IL7-treated animals was associated with increased retention of T-cells (measured by BrDU). In addition, a lack, or loss of viral control was associated with more pronounced and frequent elevations in plasma sCD127 concentrations with IL-7 therapy. In summary, plasma sCD127 levels in SIV-infected ART-treated macaques was associated with therapeutic IL-7 administration, with higher sCD127 levels in macaques demonstrating the best T-cell responses. This study furthers our knowledge regarding the interrelationship between increased IL-7 levels and elevated sCD127 levels that may have implications for future IL-7 immunotherapeutic approaches in HIV-infected patients. Raw data for online uploadThis file contains the raw data for all of the data figures in this manuscript.
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This report identifies and maps contemporary global policy responses to, and initiatives on, international HRH migration, with particular reference to low‐income source countries. It reports on a systematic review and analysis of the responses and initiatives of twelve multilateral organisations and global fora: European Union; Global Forum on Migration and Development; Global Health Workforce Alliance; International Labour Organization; International Organization for Migration; Organisation for Economic Cooperation and Development; Pan‐American Health Organization; UN Global Migration Group; UN High‐Level Dialogue on Migration and Development; World Bank; World Health Organization; and the World Trade Organization.\ud \ud The report documents how these global policy actors are presently engaging with the HRH migration field through their activities, initiatives and policy responses. It situates this engagement within global policy initiatives spanning health, migration and development. In addition to reviewing and mapping current initiatives and policy responses and their outcomes, the report identifies emerging issues, upcoming promising initiatives and global policy scenarios.
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Background. The International Classification of Disease, ninth revision (ICD-9) is designed to code disease into categories which are placed into administrative databases. These databases have been used for epidemiological studies. However, the categories used in the ICD9-codes are not always the most effective for evaluating specific diseases or their outcomes, such as the outcomes of cancer treatment. Therefore a re-classification of the ICD-9 codes into new categories specific to cancer outcomes is needed. Methods. An expert panel comprised of two physicians created broad categories that would be most useful to researchers investigating outcomes and morbidities associated with the treatment of cancer. A Senior Data Coordinator with expertise in ICD-9 coding, then joined this panel and each code was re-classified into the new categories. Results. Consensus was achieved for the categories to go from the 17 categories in ICD-9 to 39 categories. The ICD-9 Codes were placed into new categories, and subcategories were also created for more specific outcomes. The results of this re-classification is available in tabular form. Conclusions. ICD-9 codes were re-classified by group consensus into categories that are designed for oncology survivorship research. The novel re-classification system can be used by those involved in cancer survivorship research.
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Note from the Ethics committee. "Gender and Health Research" group.
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doi: 10.5061/dryad.9nb56
Daily weather data in 2006 in the Greater Toronto Areawea.csvR0.mA function m-file named R0.m related to sensitive analysisODE_WNV.mA function m-file named ODE_WNV.m related to sensitive analysis to define the dynamical systemLHS_Call.mA function m-file named LHS_Call.m related to sensitive analysisPara_settings.mM-file named Para_settings.m related to sensitive analysisPRCCM.mA function m-file named PRCCM.m related to sensitive analysisPRCCR0.mA function m-file named PRCCR0.m related to sensitive analysisMain script named Model.mMain script (related to sensitive analysis) calls functions R0.m, ODE_WNV.m, LHS_Call.m, PRCCM.m, PRCCR0.m and Para_settings.m.Model.mWeather.mA function m-file named Weather.m to define a weather-driven dynamical systemWeatherCases.mA function m-file named WeatherCases.m related to comparison of two cases (a region with multiple SWMPs)WeatherKappa.mA function m-file named WeatherKappa.m to show the role of intraspecific competitionMain script named WeatherSWMP.mMain script named WeatherSWMP calls functions Weather.m, WeatherCases.m, WeatherSWMP.m to show the influence of weather and SWMP on mosquito abundance and the transmission of WNV.WeatherSWMP.mWNV_SWMP_R0.mvA maple file named WNV_SWMP_R0.mw to show the variation of basic reproduction number R_0 along with combinations of weather conditions or SWMP properties.WNV_SWMP_R0.mw West Nile virus (WNV) is the most widely distributed arbovirus in the world and the spread is influenced by complex factors including weather conditions and urban environmental settings like storm water management ponds (SWMP). The purpose of this work was to develop an ordinary differential equation model to explore the impacts of SWMP, temperature and precipitation on WNV vector abundance and the transmission of WNV between mosquito and bird populations. The model was used to analyse how weather conditions and SWMP can influence the basic reproduction number. The results found that an excess of precipitation and fiercer intraspecific competition will reduce vector population and the peak value of infectious vectors and birds. This information can be used to identify measures that would be useful to control larval abundance in SWMP and the transmission of WNV.
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doi: 10.5061/dryad.p0c87
fMRI full experiment 3000 microTesla part 1fMRI full experiment 3000 microTesla part 1-10: MRI and fMRI DICOM images corresponding to the full study conducted with a 3000 microTesla exposure. These DICOM files have been produced by a Siemens 3T Verio (Siemens, Germany) MRI, as described in the paper. DICOM is a standard format for MRI images, and these can be analyzed with software packages such as BrainVoyager (Brain Innovation, The Netherlands), which we have used in the paper; or an open-access software package such as FSL (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/). The analysis procedure for the fMRI data is fully described in the Methods section of the paper. DICOM files are available for each subject pre- and post-exposure, for each of the two tasks presented in the paper (finger tapping and mental rotation). Two tasks were used in this experiment: a mental rotation task and a finger tapping task. The subject who have properly conducted the mental rotation task and have been included in the analysis are: S02, S03, S04, S06, S07, S09, S10, S11, S12, S13, S14, S16, S17, S18, S20, S21, S23, S24, S25, S27, S29. The subject who have properly conducted the finger tapping task and have been included in the analysis are: S03, S04, S06, S07, S08, S09, S10, S12, S13, S14, S16, S17, S20, S22, S23, S24, S25, S26, S27, S29. Please feel free to contact the authors if further guidance is required.fMRI full experiment 3000 microTesla part 2fMRI full experiment 3000 microTesla part 3fMRI full experiment 3000 microTesla part 4fMRI full experiment 3000 microTesla part 5fMRI full experiment 3000 microTesla part 6fMRI full experiment 3000 microTesla part 7fMRI full experiment 3000 microTesla part 8fMRI full experiment 3000 microTesla part 9fMRI full experiment 3000 microTesla part 10fMRI_Pilot_1800_microTesla_DICOM part 1fMRI_Pilot_1800_microTesla_DICOM part 1-2: MRI and fMRI DICOM images corresponding to the pilot study conducted with a 1800 microTesla exposure These DICOM files have been produced by a Siemens 1.5T Avanto (Siemens, Germany) MRI, as described in the paper. DICOM is a standard format for MRI images, and these can be analyzed with software packages such as BrainVoyager (Brain Innovation, The Netherlands), which we have used in the paper; or an open-access software package such as FSL (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/). The analysis procedure for the fMRI data is fully described in the Methods section of the paper. DICOM files are available for each subject pre- and post-exposure, for each of the two tasks presented in the paper (finger tapping and mental rotation). Please feel free to contact the authors if further guidance is required.fMRI_Pilot_1800_microTesla_DICOM part 2 Several aspects of the human nervous system and associated motor and cognitive processes have been reported to be modulated by extremely low-frequency (ELF, < 300 Hz) time-varying Magnetic Fields (MF). Due do their worldwide prevalence; power-line frequencies (60 Hz in North America) are of particular interest. Despite intense research efforts over the last few decades, the potential effects of 60 Hz MF still need to be elucidated, and the underlying mechanisms to be understood. In this study, we have used functional Magnetic Resonance Imaging (fMRI) to characterize potential changes in functional brain activation following human exposure to a 60 Hz MF through motor and cognitive tasks. First, pilot results acquired in a first set of subjects (N=9) were used to demonstrate the technical feasibility of using fMRI to detect subtle changes in functional brain activation with 60 Hz MF exposure at 1800 μT. Second, a full study involving a larger cohort of subjects tested brain activation during 1) a finger tapping task (N=20), and 2) a mental rotation task (N=21); before and after a one-hour, 60 Hz, 3000 μT MF exposure. The results indicate significant changes in task-induced functional brain activation as a consequence of MF exposure. However, no impact on task performance was found. These results illustrate the potential of using fMRI to identify MF-induced changes in functional brain activation, suggesting that a one-hour 60 Hz, 3000 μT MF exposure can modulate activity in specific brain regions after the end of the exposure period (i.e., residual effects). We discuss the possibility that MF exposure at 60 Hz, 3000 μT may be capable of modulating cortical excitability via a modulation of synaptic plasticity processes.
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doi: 10.5061/dryad.92cr7
Hydrogen sulfide (H2S), a gasotransmitter endogenously found in the central nervous system, has recently been suggested to act as a signalling molecule in the brain having beneficial effects on cardiovascular function. This study was thus undertaken to investigate the effect of NaHS (an H2S donor) in the subfornical organ (SFO), a central nervous system site important to blood pressure regulation. We used male Sprague-Dawley rats for both in vivo and in vitro experiments. We first used RT-PCR to confirm our previous microarray analyses showing that mRNAs for the enzymes required to produce H2S are expressed in the SFO. We then used microinjection techniques to investigate the physiological effects of NaHS in SFO, and found that NaHS microinjection (5 nmol) significantly increased blood pressure (mean AUC = 853.5±105.7 mmHg*s, n = 5). Further, we used patch-clamp electrophysiology and found that 97.8% (88 of 90) of neurons depolarized in response to NaHS. This response was found to be concentration dependent with an EC50 of 35.6 µM. Coupled with the depolarized membrane potential, we observed an overall increase in neuronal excitability using an analysis of rheobase and action potential firing patterns. This study has provided the first evidence of NaHS and thus H2S actions and their cellular correlates in SFO, implicating this brain area as a site where H2S may act to control blood pressure. miSFOH2S for plos paperRaw data for blood pressure recordingsH2S SFO Data AnalysisData summarizing every recording for current clamp and rheobase analyses
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Objective: To assess functional changes in lymphocyte repertoire and subsequent clinical implications during delayed-release dimethyl fumarate (DMF) treatment in patients with multiple sclerosis. Methods: Using peripheral blood from several clinical trials of DMF, immune cell subsets were quantified using flow cytometry. For some patients, lymphocyte counts were assessed after DMF discontinuation. Incidence of adverse events, including serious and opportunistic infections, was assessed. Results: In DMF-treated patients, absolute lymphocyte counts (ALCs) demonstrated a pattern of decline followed by stabilization, which also was reflected in the global reduction in numbers of circulating functional lymphocyte subsets. The relative frequencies of circulating memory T- and B-cell populations declined and naive cells increased. No increased incidence of serious infection or malignancy was observed for patients treated with DMF, even when stratified by ALC or T-cell subset frequencies. For patients who discontinued DMF due to lymphopenia, ALCs increased after DMF discontinuation; recovery time varied by ALC level at discontinuation. T-cell subsets closely correlated with ALCs in both longitudinal and cross-sectional analyses. Conclusions: DMF shifted the immunophenotype of circulating lymphocyte subsets. ALCs were closely correlated with CD4+ and CD8+ T-cell counts, indicating that lymphocyte subset monitoring is not required for safety vigilance. No increased risk of serious infection was observed in patients with low T-cell subset counts. Monitoring ALC remains the most effective way of identifying patients at risk of subsequently developing prolonged moderate to severe lymphopenia, a risk factor for progressive multifocal leukoencephalopathy in DMF-treated patients. Trial registration numbers: EUDRA CT 2015-001973-42, NCT00168701, NCT00420212, NCT00451451, and NCT00835770 Supplementary Table e-1 Flow cytometry cell surface markers to phenotype cell typesFlow cytometry cell surface markers to phenotype cell typesSupplementary Table e-1 v3.docxSupplementary Table e-2 Multiparameter flow cytometry immunophenotyping panelsMultiparameter flow cytometry immunophenotyping panelsSupplementary Table e-2 v3.docxSupplemental Table e-3 Major lymphocyte subsets by ALC category in the long-term ENDORSE integrated analysisMajor lymphocyte subsets by ALC category in the long-term ENDORSE integrated analysisSupplemental Table e-3 v3.docxSupplemental Table e-4 Mean absolute counts of Ig antibodies from baseline to week 24 (PROCLAIM)Mean absolute counts of Ig antibodies from baseline to week 24 (PROCLAIM)Supplemental Table e-4 v3.docxSupp Figure e-1 Mean levels of Ig antibodies at baseline through week 24 (PROCLAIM)Mean levels of Ig antibodies at baseline through week 24 (PROCLAIM)Mehta Lymphocyte Research Supp fig_e-1 v3.pdfSupp Figure e-2 Lymphocytes and subsets in individual patients after DMF discontinuationLymphocytes and subsets in individual patients after DMF discontinuationMehta Lymphocyte Research Supp fig_e-2 v3.pdf
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This is a local CSV file of YMDB 2.0 (http://www.ymdb.ca/) for MetFrag (https://msbi.ipb-halle.de/MetFrag/). Data was extracted to CSV from the SDF, with column headers for compulsory fields adjusted to fit the MetFrag format. One entry with no SMILES was filled in using the InChI in OpenBabel; entries with no monoisotopic mass or formula were filled in using functions in RChemMass (https://github.com/schymane/RChemMass/), finally one generic formula (row 746) was replaced with the formula from the InChI. This file is for users wanting to integrate the latest YMDB into MetFrag CL workflows (offline), this file will be integrated into MetFrag online; please use the file in the dropdown menu rather than uploading this one. Anyone using this resource should also cite the original publications from the Wishart Lab: YMDB 2.0: A Significantly Expanded Version of the Yeast Metabolome Database. Ramirez-Guana M, Marcu A, Pon A, Guo AC, Sajed T, Wishart NA, Karu N, Djoumbou Y, Arndt D and Wishart DS. Nucleic Acids Res. 2017 Jan 4;45(D1):D440-D445. PubMed: 27899612 YMDB: The Yeast Metabolome Database. Jewison T, Neveu V, Lee J, Knox C, Liu P, Mandal R, Murthy RK, Sinelnikov I, Guo AC, Wilson M, Djoumbou Y and Wishart DS. Nucleic Acids Res. 2012 Jan;40(Database ussue):D815-20. PubMed: 22064855
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doi: 10.5061/dryad.72c40
The use of interleukin-7 (IL-7) as an immunorestorative therapeutic has proven effective in HIV infection, cancer and bone marrow transplantation. Mediating its activity through membrane-bound IL-7 receptor α (mCD127), IL-7 therapy increases T-cell numbers and survival. A soluble form, sCD127, is found in plasma, and we have previously identified increased plasma sCD127 concentrations in HIV infection. Furthermore, patients with high sCD127 exhibited the best viral control, implicating a role for IL-7 or sCD127 directly in improved virologic/immunologic outcomes. The role of the cytokine IL-7 in elevating sCD127 levels was addressed here through assessment of retrospective samples obtained from SIV-infected antiretroviral (ART)-treated Rhesus macaques. IL-7 was administered in clustered weekly doses, allowing for an assessment prior, during and following IL-7 administration. The levels of sCD127 remained relatively unchanged during both early SIV infection and following initiation of ART. However, treatment with IL-7 increased sCD127 concentrations in most animals, transiently or persistently, paralleling increased T-cell numbers, correlating significantly with CD8+ T-cell levels. In addition, proliferating CD4+ or CD8+ T-cells (measured by Ki67) increased in association with elevated sCD127 concentrations. Finally, a high concentration of sCD127 in IL7-treated animals was associated with increased retention of T-cells (measured by BrDU). In addition, a lack, or loss of viral control was associated with more pronounced and frequent elevations in plasma sCD127 concentrations with IL-7 therapy. In summary, plasma sCD127 levels in SIV-infected ART-treated macaques was associated with therapeutic IL-7 administration, with higher sCD127 levels in macaques demonstrating the best T-cell responses. This study furthers our knowledge regarding the interrelationship between increased IL-7 levels and elevated sCD127 levels that may have implications for future IL-7 immunotherapeutic approaches in HIV-infected patients. Raw data for online uploadThis file contains the raw data for all of the data figures in this manuscript.
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