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Article: Supercontinuum intrinsic fluorescence imaging heralds free view of living systems.

Wang, Geng / Li, Lianhuang / Liao, Xiaoxia / Wang, Shu / Mitchell, Jennifer / Rabel, Chanaka / Luo, Shirui / Shi, Jindou / Sorrells, Janet Elise / Iyer, Rishyashring R / Aksamitiene, Edita / Renteria, Carlos A / Chaney, Eric J / Milner, Derek J / Wheeler, Matthew B / Gillette, Martha U / Schwing, Alexander / Chen, Jianxin / Tu, Haohua

bioRxiv : the preprint server for biology

2024

Abstract: Optimal imaging strategies remain underdeveloped to maximize information for fluorescence microscopy while minimizing the harm to fragile living systems. Taking hint from the supercontinuum generation in ultrafast laser physics, we generated ... ...

Abstract	Optimal imaging strategies remain underdeveloped to maximize information for fluorescence microscopy while minimizing the harm to fragile living systems. Taking hint from the supercontinuum generation in ultrafast laser physics, we generated supercontinuum fluorescence from untreated unlabeled live samples before nonlinear photodamage onset. Our imaging achieved high-content cell phenotyping and tissue histology, identified bovine embryo polarization, quantified aging-related stress across cell types and species, demystified embryogenesis before and after implantation, sensed drug cytotoxicity in real-time, scanned brain area for targeted patching, optimized machine learning to track small moving organisms, induced two-photon phototropism of leaf chloroplasts under two-photon photosynthesis, unraveled microscopic origin of autumn colors, and interrogated intestinal microbiome. The results enable a facility-type microscope to freely explore vital molecular biology across life sciences.
Language	English
Publishing date	2024-02-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.26.577383
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Article ; Online: Inhibition of EphB4-Ephrin-B2 Signaling Reprograms the Tumor Immune Microenvironment in Head and Neck Cancers.

Bhatia, Shilpa / Oweida, Ayman / Lennon, Shelby / Darragh, Laurel B / Milner, Dallin / Phan, Andy V / Mueller, Adam C / Van Court, Benjamin / Raben, David / Serkova, Natalie J / Wang, Xiao-Jing / Jimeno, Antonio / Clambey, Eric T / Pasquale, Elena B / Karam, Sana D

Cancer research

2019 Volume 79, Issue 10, Page(s) 2722–2735

Abstract: Identifying targets present in the tumor microenvironment that contribute to immune evasion has become an important area of research. In this study, we identified EphB4-ephrin-B2 signaling as a regulator of both innate and adaptive components of the ... ...

Abstract	Identifying targets present in the tumor microenvironment that contribute to immune evasion has become an important area of research. In this study, we identified EphB4-ephrin-B2 signaling as a regulator of both innate and adaptive components of the immune system. EphB4 belongs to receptor tyrosine kinase family that interacts with ephrin-B2 ligand at sites of cell-cell contact, resulting in bidirectional signaling. We found that EphB4-ephrin-B2 inhibition alone or in combination with radiation (RT) reduced intratumoral regulatory T cells (Tregs) and increased activation of both CD8
MeSH term(s)	Chemoradiotherapy ; Ephrin-B2/metabolism ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/metabolism ; Head and Neck Neoplasms/therapy ; Heterografts ; Humans ; Macrophages/immunology ; Receptor, EphB4/metabolism ; Signal Transduction ; Squamous Cell Carcinoma of Head and Neck/immunology ; Squamous Cell Carcinoma of Head and Neck/metabolism ; Squamous Cell Carcinoma of Head and Neck/therapy ; Tumor Microenvironment/immunology
Chemical Substances	EPHB4 protein, human ; Ephrin-B2 ; Receptor, EphB4 (EC 2.7.10.1)
Language	English
Publishing date	2019-03-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-18-3257
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Article: Free Surfaces Overcome Superheating in Simulated Melting of Isotactic Polypropylene

Chen, Qin / Chung T. C.Mike / Milner Scott T / Sirota Eric B / Zhang Min

Macromolecules. 2015 Dec. 22, v. 48, no. 24

2015

Abstract: ... phase isotactic polypropylene (αiPP) can exhibit superheating of over 100 °C. This superheating has been ...

Abstract	The equilibrium melting temperature Tm is a challenging experimental benchmark for molecular dynamics (MD) simulations of polymer melting and crystallization. Tm obtained from MD heating scans of α phase isotactic polypropylene (αiPP) can exhibit superheating of over 100 °C. This superheating has been attributed to the combined effects of periodic boundary conditions and ultrafast heating rates, both of which inhibit nucleation of the melt. We have developed a simple method to minimize this superheating; we replace the periodic crystal structure with a periodic array of finite thickness slabs, separated by vacuum gaps. Thermal disorder at the slab surface promotes melting by reducing the melt nucleation barrier. For experimental comparison, we synthesized and measured the melting temperatures of a series of low-molecular-weight iPP oligomers. In simulations of slab systems, melting initiates at the free surface; as the temperature rises above Tm, the interface advances into the crystal, with a velocity proportional to T – Tm. At a constant heating rate, this results in a quadratic rise in the system energy versus temperature. We obtained Tm as the onset of this quadratic rise in system energy, which corresponds well to the experimental melting points. The same simulations give reasonable values for the crystal–vacuum interfacial free energy, from the energy difference between crystalline slabs and periodic crystals.
Keywords	crystal structure ; crystallization ; crystals ; energy ; Gibbs free energy ; melting ; melting point ; molecular dynamics ; polypropylenes ; slabs ; temperature
Language	English
Dates of publication	2015-1222
Size	p. 8885-8896.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1491942-4
ISSN	1520-5835 ; 0024-9297
ISSN (online)	1520-5835
ISSN	0024-9297
DOI	10.1021%2Facs.macromol.5b02030
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Article ; Online: Twenty-first century bioarchaeology: Taking stock and moving forward.

Buikstra, Jane E / DeWitte, Sharon N / Agarwal, Sabrina C / Baker, Brenda J / Bartelink, Eric J / Berger, Elizabeth / Blevins, Kelly E / Bolhofner, Katelyn / Boutin, Alexis T / Brickley, Megan B / Buzon, Michele R / de la Cova, Carlina / Goldstein, Lynne / Gowland, Rebecca / Grauer, Anne L / Gregoricka, Lesley A / Halcrow, Siân E / Hall, Sarah A / Hillson, Simon /

Kakaliouras, Ann M / Klaus, Haagen D / Knudson, Kelly J / Knüsel, Christopher J / Larsen, Clark Spencer / Martin, Debra L / Milner, George R / Novak, Mario / Nystrom, Kenneth C / Pacheco-Forés, Sofía I / Prowse, Tracy L / Robbins Schug, Gwen / Roberts, Charlotte A / Rothwell, Jessica E / Santos, Ana Luisa / Stojanowski, Christopher / Stone, Anne C / Stull, Kyra E / Temple, Daniel H / Torres, Christina M / Toyne, J Marla / Tung, Tiffiny A / Ullinger, Jaime / Wiltschke-Schrotta, Karin / Zakrzewski, Sonia R

American journal of biological anthropology

2022 Volume 178 Suppl 74, Page(s) 54–114

Abstract: This article presents outcomes from a Workshop entitled "Bioarchaeology: Taking Stock and Moving Forward," which was held at Arizona State University (ASU) on March 6-8, 2020. Funded by the National Science Foundation (NSF), the School of Human Evolution ...

Abstract	This article presents outcomes from a Workshop entitled "Bioarchaeology: Taking Stock and Moving Forward," which was held at Arizona State University (ASU) on March 6-8, 2020. Funded by the National Science Foundation (NSF), the School of Human Evolution and Social Change (ASU), and the Center for Bioarchaeological Research (CBR, ASU), the Workshop's overall goal was to explore reasons why research proposals submitted by bioarchaeologists, both graduate students and established scholars, fared disproportionately poorly within recent NSF Anthropology Program competitions and to offer advice for increasing success. Therefore, this Workshop comprised 43 international scholars and four advanced graduate students with a history of successful grant acquisition, primarily from the United States. Ultimately, we focused on two related aims: (1) best practices for improving research designs and training and (2) evaluating topics of contemporary significance that reverberate through history and beyond as promising trajectories for bioarchaeological research. Among the former were contextual grounding, research question/hypothesis generation, statistical procedures appropriate for small samples and mixed qualitative/quantitative data, the salience of Bayesian methods, and training program content. Topical foci included ethics, social inequality, identity (including intersectionality), climate change, migration, violence, epidemic disease, adaptability/plasticity, the osteological paradox, and the developmental origins of health and disease. Given the profound changes required globally to address decolonization in the 21st century, this concern also entered many formal and informal discussions.
MeSH term(s)	Humans ; United States ; Archaeology ; Bayes Theorem ; Schools ; Universities ; Arizona
Language	English
Publishing date	2022-03-22
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ISSN	2692-7691
ISSN (online)	2692-7691
DOI	10.1002/ajpa.24494
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Article: Human innate B cells: a link between host defense and autoimmunity?

Milner, Eric C B / Anolik, Jennifer / Cappione, Amedeo / Sanz, Iñaki

Springer seminars in immunopathology

2005 Volume 26, Issue 4, Page(s) 433–452

Abstract: B cells play a variety of immunoregulatory roles through their antigen-presentation ability and ... through cytokine and chemokine production. Innate immune activation of B cells may play a beneficial role ... through the generation of natural cross-reactive antibodies, by maintaining B cell memory and by exercising ...

Abstract	B cells play a variety of immunoregulatory roles through their antigen-presentation ability and through cytokine and chemokine production. Innate immune activation of B cells may play a beneficial role through the generation of natural cross-reactive antibodies, by maintaining B cell memory and by exercising immunomodulatory functions that may provide protection against autoimmunity. In this article, we review human B cell populations and their functional properties, with a particular focus on a population of inherently autoreactive B cells, which seem to play an important physiological role in innate immunity, but which, if selected into adaptive immune responses, appear to become pathogenic agents in systemic lupus erythematosus.
MeSH term(s)	Antilymphocyte Serum/biosynthesis ; Autoimmunity ; B-Lymphocyte Subsets/cytology ; B-Lymphocyte Subsets/immunology ; Cell Differentiation ; Humans ; Immunity, Innate ; Lupus Erythematosus, Systemic/immunology ; Models, Immunological
Chemical Substances	Antilymphocyte Serum
Language	English
Publishing date	2005-01-05
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	6177-3
ISSN	1432-2196 ; 0344-4325 ; 0172-6641
ISSN (online)	1432-2196
ISSN	0344-4325 ; 0172-6641
DOI	10.1007/s00281-004-0188-9
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Article ; Online: Anergic responses characterize a large fraction of human autoreactive naive B cells expressing low levels of surface IgM.

Quách, Tâm D / Manjarrez-Orduño, Nataly / Adlowitz, Diana G / Silver, Lin / Yang, Hongmei / Wei, Chungwen / Milner, Eric C B / Sanz, Iñaki

Journal of immunology (Baltimore, Md. : 1950)

2011 Volume 186, Issue 8, Page(s) 4640–4648

Abstract: B cell anergy represents an important mechanism of peripheral immunological tolerance for mature ... autoreactive B cells that escape central tolerance enforced by receptor editing and clonal deletion ... Although well documented in mice, the extent of its participation in human B cell tolerance remains to be fully ...

Abstract	B cell anergy represents an important mechanism of peripheral immunological tolerance for mature autoreactive B cells that escape central tolerance enforced by receptor editing and clonal deletion. Although well documented in mice, the extent of its participation in human B cell tolerance remains to be fully established. In this study, we characterize the functional behavior of strictly defined human naive B cells separated on the basis of their surface IgM (sIgM) expression levels. We demonstrate that cells with lower sIgM levels (IgM(lo)) are impaired in their ability to flux calcium in response to either anti-IgM or anti-IgD cross-linking and contain a significantly increased frequency of autoreactive cells compared with naive B cells with higher levels of sIgM. Phenotypically, in healthy subjects, IgM(lo) cells are characterized by the absence of activation markers, reduction of costimulatory molecules (CD19 and CD21), and increased levels of inhibitory CD22. Functionally, IgM(lo) cells display significantly weaker proliferation, impaired differentiation, and poor Ab production. In aggregate, the data indicate that hyporesponsiveness to BCR cross-linking associated with sIgM downregulation is present in a much larger fraction of all human naive B cells than previously reported and is likely to reflect a state of anergy induced by chronic autoantigen stimulation. Finally, our results indicate that in systemic lupus erythematosus patients, naive IgM(lo) cells display increased levels of CD95 and decreased levels of CD22, a phenotype consistent with enhanced activation of autoreactive naive B cells in this autoimmune disease.
MeSH term(s)	Antibodies, Anti-Idiotypic/immunology ; Antibodies, Anti-Idiotypic/metabolism ; Antigens, CD19/immunology ; Antigens, CD19/metabolism ; Autoantigens/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Calcium/metabolism ; Cell Membrane/immunology ; Cell Membrane/metabolism ; Cells, Cultured ; Clonal Anergy/immunology ; Flow Cytometry ; Humans ; Immunoglobulin D/immunology ; Immunoglobulin M/immunology ; Immunoglobulin M/metabolism ; Ion Transport/immunology ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/metabolism ; Receptors, Complement 3d/immunology ; Receptors, Complement 3d/metabolism ; Self Tolerance/immunology ; Sialic Acid Binding Ig-like Lectin 2/immunology ; Sialic Acid Binding Ig-like Lectin 2/metabolism ; fas Receptor/immunology ; fas Receptor/metabolism
Chemical Substances	Antibodies, Anti-Idiotypic ; Antigens, CD19 ; Autoantigens ; Immunoglobulin D ; Immunoglobulin M ; Receptors, Complement 3d ; Sialic Acid Binding Ig-like Lectin 2 ; anti-IgD ; anti-IgM ; fas Receptor ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2011-03-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1001946
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Article ; Online: Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis: The ISABELA 1 and 2 Randomized Clinical Trials.

Maher, Toby M / Ford, Paul / Brown, Kevin K / Costabel, Ulrich / Cottin, Vincent / Danoff, Sonye K / Groenveld, Irene / Helmer, Eric / Jenkins, R Gisli / Milner, Julie / Molenberghs, Geert / Penninckx, Bjorn / Randall, Matthew J / Van Den Blink, Bernt / Fieuw, Ann / Vandenrijn, Charlotte / Rocak, Sanda / Seghers, Ineke / Shao, Lixin /

Taneja, Amit / Jentsch, Garrit / Watkins, Timothy R / Wuyts, Wim A / Kreuter, Michael / Verbruggen, Nadia / Prasad, Niyati / Wijsenbeek, Marlies S

JAMA

2023 Volume 329, Issue 18, Page(s) 1567–1578

Abstract: Importance: There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF).: Objective: To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF.: Design, setting, and ... ...

Abstract	Importance: There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF). Objective: To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF. Design, setting, and participants: The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA 2, were conducted in Africa, Asia-Pacific region, Europe, Latin America, the Middle East, and North America (26 countries). A total of 1306 patients with IPF were randomized (525 patients at 106 sites in ISABELA 1 and 781 patients at 121 sites in ISABELA 2). Enrollment began in November 2018 in both trials and follow-up was completed early due to study termination on April 12, 2021, for ISABELA 1 and on March 30, 2021, for ISABELA 2. Interventions: Patients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or placebo once daily in addition to local standard of care (pirfenidone, nintedanib, or neither) for at least 52 weeks. Main outcomes and measures: The primary outcome was the annual rate of decline for forced vital capacity (FVC) at week 52. The key secondary outcomes were disease progression, time to first respiratory-related hospitalization, and change from baseline in St George's Respiratory Questionnaire total score (range, 0 to 100; higher scores indicate poorer health-related quality of life). Results: At the time of study termination, 525 patients were randomized in ISABELA 1 and 781 patients in ISABELA 2 (mean age: 70.0 [SD, 7.2] years in ISABELA 1 and 69.8 [SD, 7.1] years in ISABELA 2; male: 82.4% and 81.2%, respectively). The trials were terminated early after an independent data and safety monitoring committee concluded that the benefit to risk profile of ziritaxestat no longer supported their continuation. Ziritaxestat did not improve the annual rate of FVC decline vs placebo in either study. In ISABELA 1, the least-squares mean annual rate of FVC decline was -124.6 mL (95% CI, -178.0 to -71.2 mL) with 600 mg of ziritaxestat vs -147.3 mL (95% CI, -199.8 to -94.7 mL) with placebo (between-group difference, 22.7 mL [95% CI, -52.3 to 97.6 mL]), and -173.9 mL (95% CI, -225.7 to -122.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, -26.7 mL [95% CI, -100.5 to 47.1 mL]). In ISABELA 2, the least-squares mean annual rate of FVC decline was -173.8 mL (95% CI, -209.2 to -138.4 mL) with 600 mg of ziritaxestat vs -176.6 mL (95% CI, -211.4 to -141.8 mL) with placebo (between-group difference, 2.8 mL [95% CI, -46.9 to 52.4 mL]) and -174.9 mL (95% CI, -209.5 to -140.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, 1.7 mL [95% CI, -47.4 to 50.8 mL]). There was no benefit with ziritaxestat vs placebo for the key secondary outcomes. In ISABELA 1, all-cause mortality was 8.0% with 600 mg of ziritaxestat, 4.6% with 200 mg of ziritaxestat, and 6.3% with placebo; in ISABELA 2, it was 9.3% with 600 mg of ziritaxestat, 8.5% with 200 mg of ziritaxestat, and 4.7% with placebo. Conclusions and relevance: Ziritaxestat did not improve clinical outcomes compared with placebo in patients with IPF receiving standard of care treatment with pirfenidone or nintedanib or in those not receiving standard of care treatment. Trial registration: ClinicalTrials.gov Identifiers: NCT03711162 and NCT03733444.
MeSH term(s)	Aged ; Humans ; Male ; Idiopathic Pulmonary Fibrosis/drug therapy ; Idiopathic Pulmonary Fibrosis/physiopathology ; Lung/drug effects ; Lung/physiopathology ; Quality of Life ; Randomized Controlled Trials as Topic ; Respiratory Physiological Phenomena/drug effects ; Treatment Outcome ; Clinical Trials, Phase III as Topic ; Multicenter Studies as Topic ; Administration, Oral ; Middle Aged ; Female ; Phosphodiesterase Inhibitors/pharmacology ; Phosphodiesterase Inhibitors/therapeutic use ; Respiratory System Agents/pharmacology ; Respiratory System Agents/therapeutic use
Chemical Substances	GLPG1690 ; alkylglycerophosphoethanolamine phosphodiesterase (EC 3.1.4.39) ; pirfenidone (D7NLD2JX7U) ; nintedanib (G6HRD2P839) ; Phosphodiesterase Inhibitors ; Respiratory System Agents
Language	English
Publishing date	2023-10-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2023.5355
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Article ; Online: A global map of genetic diversity in Babesia microti reveals strong population structure and identifies variants associated with clinical relapse.

Lemieux, Jacob E / Tran, Alice D / Freimark, Lisa / Schaffner, Stephen F / Goethert, Heidi / Andersen, Kristian G / Bazner, Suzane / Li, Amy / McGrath, Graham / Sloan, Lynne / Vannier, Edouard / Milner, Dan / Pritt, Bobbi / Rosenberg, Eric / Telford, Sam / Bailey, Jeffrey A / Sabeti, Pardis C

Nature microbiology

2016 Volume 1, Issue 7, Page(s) 16079

Abstract: ... the complete genomes of 42 B. microti samples from around the world, including deep coverage of clinical ... in the atovaquone-binding regions of cytochrome b (cytb) and the azithromycin-binding region of ribosomal protein ... subunit L4 (rpl4). Our results shed light on the origin, diversity and evolution of B. microti, suggest ...

Abstract	Human babesiosis caused by Babesia microti is an emerging tick-borne zoonosis of increasing importance due to its rising incidence and expanding geographic range(1). Infection with this organism, an intraerythrocytic parasite of the phylum Apicomplexa, causes a febrile syndrome similar to malaria(2). Relapsing disease is common among immunocompromised and asplenic individuals(3,4) and drug resistance has recently been reported(5). To investigate the origin and genetic diversity of this parasite, we sequenced the complete genomes of 42 B. microti samples from around the world, including deep coverage of clinical infections at endemic sites in the continental USA. Samples from the continental USA segregate into a Northeast lineage and a Midwest lineage, with subsequent divergence of subpopulations along geographic lines. We identify parasite variants that associate with relapsing disease, including amino acid substitutions in the atovaquone-binding regions of cytochrome b (cytb) and the azithromycin-binding region of ribosomal protein subunit L4 (rpl4). Our results shed light on the origin, diversity and evolution of B. microti, suggest possible mechanisms for clinical relapse, and create the foundation for further research on this emerging pathogen.
Language	English
Publishing date	2016-06-13
Publishing country	England
Document type	Journal Article
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/nmicrobiol.2016.79
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Article: Ventricular Function and Tissue Characterization By Cardiac MRI in Children Following Hospitalization for Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Study.

Dilorenzo, Michael P / Farooqi, Kanwal M / Shah, Amee M / Channing, Alexandra / Harrington, Jamie K / Connors, Thomas J / Martirosyan, Karen / Krishnan, Usha S / Ferris, Anne / Weller, Rachel J / Farber, Donna L / Milner, Joshua D / Gorelik, Mark / Rosenzweig, Erika B / Anderson, Brett R

Research square

2022

Abstract: Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe life-threatening ... in children with MIS-C. While most children recover rapidly from acute illness, the long-term impact ... performed on patients <21 years of age with a history of MIS-C, 6-9 months following hospitalization ...

Abstract	Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe life-threatening manifestation of SARS-CoV-2 infection. Acute cardiac dysfunction and resultant cardiogenic shock are common in children with MIS-C. While most children recover rapidly from acute illness, the long-term impact on the myocardium and cardiac function is unknown. Methods In this prospective study, cardiac MRI (CMR) was performed on patients <21 years of age with a history of MIS-C, 6-9 months following hospitalization. Per institutional protocol, patients with any history of LVEF<50%, persistent cardiorespiratory symptoms, or ECG abnormalities underwent clinical CMR. Research CMRs were offered to all others >10 years old. Native T1 and T2 mapping values were compared with 20 children with normal CMR examinations. Results We performed CMRs on 13 subjects at a median age of 13.6 years (interquartile range [IQR] 11.9-16.0) and a median time from hospitalization of 8.2 months (IQR 6.8-9.6). Twelve subjects displayed normal ventricular function with a median left ventricle ejection fraction (LVEF) of 57.2% (IQR 56.1-58.4) and median right ventricular (RV) EF of 53.1% (IQR 52.0-55.7). One subject had low normal EF (52%). There was normal T2 and native T1 as compared to normal controls. There was qualitatively no evidence of edema by T2 weighted imaging. One subject had late gadolinium enhancement (LGE) at the inferior insertion point and mid-ventricular inferolateral region, with normal EF, no evidence of edema or perfusion defects, and normal T1 and T2 times. When stratifying by a history of abnormal LVEF (LVEF <55%) on echocardiography, there was no difference in or parametric mapping values, though LVEF and LVEDV approached significance (p=0.06 and 0.05, respectively). Conclusions Although many children with MIS-C present acutely with cardiac dysfunction, myocardial recovery is overall excellent with minimal to no evidence of residual cardiac dysfunction or myocardial involvement. LVEF by CMR at 6-9 months among children with history of echocardiographic LV dysfunction is slightly lower, though does not meet statistical significance and is still within normal range. The long-term functional implications of this finding and the cardiac implications of MIS-C more broadly are unclear and warrant further study.
Language	English
Publishing date	2022-01-24
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-1254952/v1
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Article ; Online: Ventricular function and tissue characterization by cardiac magnetic resonance imaging following hospitalization for multisystem inflammatory syndrome in children: a prospective study.

DiLorenzo, Michael P / Farooqi, Kanwal M / Shah, Amee M / Channing, Alexandra / Harrington, Jamie K / Connors, Thomas J / Martirosyan, Karen / Krishnan, Usha S / Ferris, Anne / Weller, Rachel J / Farber, Donna L / Milner, Joshua D / Gorelik, Mark / Rosenzweig, Erika B / Anderson, Brett R

Pediatric radiology

2022 Volume 53, Issue 3, Page(s) 394–403

Abstract: Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe life-threatening ... months after their hospitalization with MIS-C against MRI findings in healthy controls to assess ... children 6-9 months following their hospitalization with MIS-C: eight of these children had a history ...

Abstract	Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe life-threatening manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that often presents with acute cardiac dysfunction and cardiogenic shock. While recovery from acute illness is excellent, the long-term myocardial impact is unknown. Objective: To compare cardiac MRI findings in children 6-9 months after their hospitalization with MIS-C against MRI findings in healthy controls to assess for residual myocardial disease. Materials and methods: We prospectively performed cardiac MRI on 13 children 6-9 months following their hospitalization with MIS-C: eight of these children had a history of left ventricle ejection fraction (LVEF) < 50%, persistent symptoms, or electrocardiogram (ECG) abnormalities and underwent clinical MRI; five of these children without cardiac abnormalities during their hospitalization underwent research MRIs. We compared their native T1 and T2 mapping values with those of 20 normal controls. Results: Cardiac MRI was performed at 13.6 years of age (interquartile range [IQR] 11.9-16.4 years) and 8.2 months (IQR 6.8-9.6 months) following hospitalization. Twelve children displayed normal ejection fraction: left ventricle (LV) 57.2%, IQR 56.1-58.4; right ventricle (RV) 53.1%, IQR 52.0-55.7. One had low-normal LVEF (52%). They had normal extracellular volume (ECV) and normal T2 and native T1 times compared to controls. There was no qualitative evidence of edema. One child had late gadolinium enhancement (LGE) with normal ejection fraction, no edema, and normal T1 and T2 times. When stratifying children who had MIS-C according to history of LVEF <55% on echocardiography, there was no difference in MRI values. Conclusion: Although many children with MIS-C present acutely with cardiac dysfunction, residual myocardial damage 6-9 months afterward appears minimal. Long-term implications warrant further study.
MeSH term(s)	Child ; Humans ; Infant ; Prospective Studies ; COVID-19 ; Contrast Media ; Magnetic Resonance Imaging, Cine/methods ; SARS-CoV-2 ; Gadolinium ; Magnetic Resonance Imaging ; Cardiomyopathies ; Myocardium ; Ventricular Function, Left ; Stroke Volume ; Hospitalization ; Predictive Value of Tests
Chemical Substances	Contrast Media ; Gadolinium (AU0V1LM3JT)
Language	English
Publishing date	2022-10-18
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124459-0
ISSN	1432-1998 ; 0301-0449
ISSN (online)	1432-1998
ISSN	0301-0449
DOI	10.1007/s00247-022-05521-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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