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  1. Article: Iron therapy as a novel treatment of scleroderma-related pulmonary hypertension: A case report and literature review.

    Neumann, Melissa / Wong, Karen A / Lazo, Kevin / Stover, Diane

    Respirology case reports

    2022  Volume 10, Issue 2, Page(s) e0904

    Abstract: Pulmonary arterial hypertension (PAH) is the leading cause of death in patients with systemic sclerosis (SSc), with a 3-year mortality of 40%-50% despite optimal therapy. Treatment mirrors that of idiopathic PAH and is often ineffective. This is a case ... ...

    Abstract Pulmonary arterial hypertension (PAH) is the leading cause of death in patients with systemic sclerosis (SSc), with a 3-year mortality of 40%-50% despite optimal therapy. Treatment mirrors that of idiopathic PAH and is often ineffective. This is a case report of a patient with SSc evaluated for progressive dyspnoea with exertion and found to have elevated pulmonary artery systolic pressures (PASPs). She received ferritin-targeted iron infusions as a novel treatment of suspected SSc-associated PAH, with subsequent resolution of respiratory symptoms and PASPs that normalized. We review PAH especially associated with SSc, its treatment and identify a possible novel therapeutic approach for those with PAH-SSc.
    Language English
    Publishing date 2022-01-19
    Publishing country United States
    Document type Case Reports
    ZDB-ID 2750180-2
    ISSN 2051-3380
    ISSN 2051-3380
    DOI 10.1002/rcr2.904
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  2. Article ; Online: Screening for obstructive sleep apnea in patients with cancer - a machine learning approach.

    Wong, Karen A / Paul, Ankita / Fuentes, Paige / Lim, Diane C / Das, Anup / Tan, Miranda

    Sleep advances : a journal of the Sleep Research Society

    2023  Volume 4, Issue 1, Page(s) zpad042

    Abstract: Background: Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder associated with daytime sleepiness, fatigue, and increased all-cause mortality risk in patients with cancer. Existing screening tools for OSA do not account for the ... ...

    Abstract Background: Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder associated with daytime sleepiness, fatigue, and increased all-cause mortality risk in patients with cancer. Existing screening tools for OSA do not account for the interaction of cancer-related features that may increase OSA risk.
    Study design and methods: This is a retrospective study of patients with cancer at a single tertiary cancer institution who underwent a home sleep apnea test (HSAT) to evaluate for OSA. Unsupervised machine learning (ML) was used to reduce the dimensions and extract significant features associated with OSA. ML classifiers were applied to principal components and model hyperparameters were optimized using k-fold cross-validation. Training models for OSA were subsequently tested and compared with the STOP-Bang questionnaire on a prospective unseen test set of patients who underwent an HSAT.
    Results: From a training dataset of 249 patients, kernel principal component analysis (PCA) extracted eight components through dimension reduction to explain the maximum variance with OSA at 98%. Predictors of OSA were smoking, asthma, chronic kidney disease, STOP-Bang score, race, diabetes, radiation to head/neck/thorax (RT-HNT), type of cancer, and cancer metastases. Of the ML models, PCA + RF had the highest sensitivity (96.8%), specificity (92.3%), negative predictive value (92%), F1 score (0.93), and ROC-AUC score (0.88). The PCA + RF screening algorithm also performed better than the STOP-Bang questionnaire alone when tested on a prospective unseen test set.
    Conclusions: The PCA + RF ML model had the highest accuracy in screening for OSA in patients with cancer. History of RT-HNT, cancer metastases, and type of cancer were identified as cancer-related risk factors for OSA.
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Journal Article
    ISSN 2632-5012
    ISSN (online) 2632-5012
    DOI 10.1093/sleepadvances/zpad042
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  3. Article ; Online: Complement C3 Reduces Apoptosis via Interaction with the Intrinsic Apoptotic Pathway.

    Fang, Zhou / Lee, Haekyung / Liu, Junying / Wong, Karen A / Brown, Lewis M / Li, Xiang / Xiaoli, Alus M / Yang, Fajun / Zhang, Ming

    Cells

    2023  Volume 12, Issue 18

    Abstract: Myocardial ischemia/reperfusion (I/R) elicits an acute inflammatory response involving complement factors. Recently, we reported that myocardial necrosis was decreased in complement ... ...

    Abstract Myocardial ischemia/reperfusion (I/R) elicits an acute inflammatory response involving complement factors. Recently, we reported that myocardial necrosis was decreased in complement C3
    MeSH term(s) Mice ; Humans ; Animals ; Complement C3/metabolism ; Complement C3/pharmacology ; Myocardial Reperfusion Injury/metabolism ; Apoptosis ; Myocardium/metabolism ; Myocytes, Cardiac/metabolism ; Myocardial Ischemia/metabolism ; Ischemia/metabolism
    Chemical Substances Complement C3
    Language English
    Publishing date 2023-09-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12182282
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  4. Article ; Online: Complement factor B activation in patients with preeclampsia.

    Velickovic, Ivan / Dalloul, Mudar / Wong, Karen A / Bakare, Olufunke / Schweis, Franz / Garala, Maya / Alam, Amit / Medranda, Giorgio / Lekovic, Jovana / Shuaib, Waqas / Tedjasukmana, Andreas / Little, Perry / Hanono, Daniel / Wijetilaka, Ruvini / Weedon, Jeremy / Lin, Jun / Toledano, Roulhac d'Arby / Zhang, Ming

    Journal of reproductive immunology

    2015  Volume 109, Page(s) 94–100

    Abstract: Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Bb, the active fragment of complement factor B (fB), has been reported to be a predictor of preeclampsia. However, conflicting results have been found by some investigators. ... ...

    Abstract Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Bb, the active fragment of complement factor B (fB), has been reported to be a predictor of preeclampsia. However, conflicting results have been found by some investigators. We hypothesized that the disagreement in findings may be due to the racial/ethnic differences among various study groups, and that fB activation is significant in women of an ethnic minority with preeclampsia. We investigated the maternal and fetal levels of Bb (the activated fB fragment) in pregnant women of an ethnic minority with or without preeclampsia. We enrolled 291 pregnant women (96% of an ethnic minority, including 78% African-American). Thirteen percent of these were diagnosed with preeclampsia. Maternal venous blood was collected from all participants together with fetal umbilical cord blood samples from 154 deliveries in the 291 women. The results were analyzed using the Mann-Whitney U test and multivariate analyses. Maternal Bb levels were significantly higher in the preeclamptic group than in the nonpreeclamptic group. Levels of Bb in fetal cord blood were similar in both groups. Subgroup analyses of African-American patients' results confirmed the study hypothesis that there would be a significant increase in Bb in the maternal blood of the preeclamptic group and no increase in Bb in the fetal cord blood of this group. These results suggest that a maternal immune response through complement fB might play a role in the development of preeclampsia, particularly in African-American patients.
    MeSH term(s) Adult ; African Americans ; Complement Activation/immunology ; Complement Factor B/immunology ; Complement Factor B/metabolism ; Female ; Fetal Blood/immunology ; Fetal Blood/metabolism ; Humans ; Pre-Eclampsia/blood ; Pre-Eclampsia/ethnology ; Pre-Eclampsia/immunology ; Pre-Eclampsia/mortality ; Pregnancy
    Chemical Substances Complement Factor B (EC 3.4.21.47)
    Language English
    Publishing date 2015-06
    Publishing country Ireland
    Document type Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 424421-7
    ISSN 1872-7603 ; 0165-0378
    ISSN (online) 1872-7603
    ISSN 0165-0378
    DOI 10.1016/j.jri.2014.12.002
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  5. Article ; Online: Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury.

    Chun, Nicholas / Haddadin, Ala S / Liu, Junying / Hou, Yunfang / Wong, Karen A / Lee, Daniel / Rushbrook, Julie I / Gulaya, Karan / Hines, Roberta / Hollis, Tamika / Nistal Nuno, Beatriz / Mangi, Abeel A / Hashim, Sabet / Pekna, Marcela / Catalfamo, Amy / Chin, Hsiao-Ying / Patel, Foramben / Rayala, Sravani / Shevde, Ketan /
    Heeger, Peter S / Zhang, Ming

    PloS one

    2017  Volume 12, Issue 6, Page(s) e0179450

    Abstract: The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the ... ...

    Abstract The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB), a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been addressed. We induced regional myocardial I/R injury by transient coronary ligation in WT C57BL/6 mice, a manipulation that resulted in marked myocardial necrosis associated with activation of fB protein and myocardial deposition of C3 activation products. In contrast, in fB-/- mice, the same procedure resulted in significantly reduced myocardial necrosis (% ventricular tissue necrotic; fB-/- mice, 20 ± 4%; WT mice, 45 ± 3%; P < 0.05) and diminished deposition of C3 activation products in the myocardial tissue (fB-/- mice, 0 ± 0%; WT mice, 31 ± 6%; P<0.05). Reconstitution of fB-/- mice with WT serum followed by cardiac I/R restored the myocardial necrosis and activated C3 deposition in the myocardium. In translational human studies we measured levels of activated fB (Bb) in intracoronary blood samples obtained during cardio-pulmonary bypass surgery before and after aortic cross clamping (AXCL), during which global heart ischemia was induced. Intracoronary Bb increased immediately after AXCL, and the levels were directly correlated with peripheral blood levels of cardiac troponin I, an established biomarker of myocardial necrosis (Spearman coefficient = 0.465, P < 0.01). Taken together, our results support the conclusion that circulating fB is a crucial pathophysiological amplifier of I/R-induced, complement-dependent myocardial necrosis and identify fB as a potential therapeutic target for prevention of human myocardial I/R injury.
    MeSH term(s) Aged ; Animals ; Complement Factor B/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Myocardial Reperfusion Injury/metabolism
    Chemical Substances Complement Factor B (EC 3.4.21.47)
    Language English
    Publishing date 2017-06-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0179450
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