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Article ; Online: Age-related changes in left ventricular vortex and energy loss patterns: from newborns to adults.

Becker, Kristian C / Cohen, Jennifer / Nyce, Jon D / Yau, Jen Lie / Uppu, Santosh C / Sengupta, Partho P / Srivastava, Shubhika

American journal of physiology. Heart and circulatory physiology

2023 Volume 324, Issue 5, Page(s) H624–H629

Abstract: Left ventricular vortex formation optimizes the effective transport of blood volume while minimizing energy loss (EL). Vector flow mapping (VFM)-derived EL patterns have not been described in children, especially in those less than 1 yr of age. A ... ...

Abstract	Left ventricular vortex formation optimizes the effective transport of blood volume while minimizing energy loss (EL). Vector flow mapping (VFM)-derived EL patterns have not been described in children, especially in those less than 1 yr of age. A prospective cohort of 66 (0 days-22 yr, 14 patients ≤ 2 mo) cardiovascularly normal children was used to determine left ventricular (LV) vortex number, size (mm
MeSH term(s)	Infant, Newborn ; Young Adult ; Adolescent ; Humans ; Child ; Prospective Studies ; Blood Flow Velocity/physiology ; Echocardiography ; Diastole/physiology ; Heart Ventricles/diagnostic imaging ; Ventricular Function, Left/physiology
Language	English
Publishing date	2023-03-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00002.2023
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Article ; Online: The world through a lens: a history of the Royal Society of London, and the discovery of the red blood cell.

Becker, Kristian C

Journal of thrombosis and thrombolysis

2010 Volume 30, Issue 4, Page(s) 496–499

MeSH term(s)	Erythrocytes/cytology ; Famous Persons ; Fires/history ; Hematology/history ; History, 17th Century ; History, 18th Century ; Humans ; London ; Microscopy/history ; Netherlands ; Societies, Medical/history
Language	English
Publishing date	2010-10-06
Publishing country	Netherlands
Document type	Biography ; Historical Article ; Journal Article
ZDB-ID	1230645-9
ISSN	1573-742X ; 0929-5305
ISSN (online)	1573-742X
ISSN	0929-5305
DOI	10.1007/s11239-010-0521-1
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Article ; Online: Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.

Diederichsen, Axel C P / Lindholt, Jes S / Möller, Sören / Øvrehus, Kristian A / Auscher, Søren / Lambrechtsen, Jess / Hosbond, Susanne E / Alan, Dilek H / Urbonaviciene, Grazina / Becker, Søren W / Fredgart, Maise H / Hasific, Selma / Folkestad, Lars / Gerke, Oke / Rasmussen, Lars Melholt / Møller, Jacob E / Mickley, Hans / Dahl, Jordi S

Circulation

2022 Volume 145, Issue 18, Page(s) 1387–1397

Abstract: Background: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in ...

Abstract	Background: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis. Methods: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events. Results: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; Conclusions: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression. Registration: URL: https://www. Clinicaltrials: gov; Unique identifier: NCT03243890.
MeSH term(s)	Aged ; Aortic Valve/diagnostic imaging ; Aortic Valve/pathology ; Aortic Valve/surgery ; Aortic Valve Stenosis/diagnostic imaging ; Aortic Valve Stenosis/drug therapy ; Aortic Valve Stenosis/surgery ; Calcinosis ; Female ; Humans ; Male ; Vitamin D/therapeutic use ; Vitamin K 2/pharmacology ; Vitamin K 2/therapeutic use
Chemical Substances	Vitamin K 2 (11032-49-8) ; Vitamin D (1406-16-2)
Language	English
Publishing date	2022-04-25
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.121.057008
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Article ; Online: Identification of drug candidates targeting monocyte reprogramming in people living with HIV.

Frontiers in immunology

2023 Volume 14, Page(s) 1275136

Abstract: Introduction: People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger ...

Abstract	Introduction: People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared multiple omics data layers. Methods: Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis by ATAC-seq as well as Results: Single-cell RNA-seq analysis revealed that most immune cells in peripheral blood of PLHIV are altered in their transcriptomes and that a specific functional monocyte state previously described in acute HIV infection is still existing in PLHIV while other monocyte cell states are only occurring acute infection. Further, a reverse transcriptome approach on a rather small number of PLHIV was sufficient to identify drug candidates for reversing the transcriptional phenotype of monocytes in PLHIV. Discussion: These scientific findings and technological advancements for clinical application of single-cell transcriptomics form the basis for the larger 2000-HIV multicenter cohort study on PLHIV, for which a combination of bulk and single-cell transcriptomics will be included as the leading technology to determine disease endotypes in PLHIV and to predict disease trajectories and outcomes.
MeSH term(s)	Humans ; Anti-HIV Agents/therapeutic use ; Cohort Studies ; HIV Infections ; Monocytes ; Multicenter Studies as Topic
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2023-11-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1275136
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Article ; Online: Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements.

Becker, Kristian C / Kwee, Lydia Coulter / Neely, Megan L / Grass, Elizabeth / Jakubowski, Joseph A / Fox, Keith A A / White, Harvey D / Gregory, Simon G / Gurbel, Paul A / Carvalho, Leonardo de Pinto / Becker, Richard C / Magnus Ohman, E / Roe, Matthew T / Shah, Svati H / Chan, Mark Y

Scientific reports

2020 Volume 10, Issue 1, Page(s) 6169

Abstract: Changes in platelet physiology are associated with simultaneous changes in microRNA concentrations, suggesting a role for microRNA in platelet regulation. Here we investigated potential associations between microRNA and platelet reactivity (PR), a marker ...

Abstract	Changes in platelet physiology are associated with simultaneous changes in microRNA concentrations, suggesting a role for microRNA in platelet regulation. Here we investigated potential associations between microRNA and platelet reactivity (PR), a marker of platelet function, in two cohorts following a non-ST elevation acute coronary syndrome (NSTE-ACS) event. First, non-targeted microRNA concentrations and PR were compared in a case (N = 77) control (N = 76) cohort within the larger TRILOGY-ACS trial. MicroRNA significant in this analysis plus CVD-associated microRNAs from the literature were then quantified by targeted rt-PCR in the complete TRILOGY-ACS cohort (N = 878) and compared with matched PR samples. Finally, microRNA significant in the non-targeted & targeted analyses were verified in an independent post NSTE-ACS cohort (N = 96). From the non-targeted analysis, 14 microRNAs were associated with PR (Fold Change: 0.91-1.27, p-value: 0.004-0.05). From the targeted analysis, five microRNAs were associated with PR (Beta: -0.09-0.22, p-value: 0.004-0.05). Of the 19 significant microRNAs, three, miR-15b-5p, miR-93 and miR-126, were consistently associated with PR in the TRILOGY-ACS and independent Singapore post-ACS cohorts, suggesting the measurement of circulating microRNA concentrations may report on dynamic changes in platelet biology following a cardiovascular ischemic event.
MeSH term(s)	Acute Coronary Syndrome/blood ; Acute Coronary Syndrome/diagnosis ; Acute Coronary Syndrome/genetics ; Acute Coronary Syndrome/physiopathology ; Aged ; Blood Platelets/physiology ; Case-Control Studies ; Circulating MicroRNA/blood ; Circulating MicroRNA/metabolism ; Female ; Gene Expression Profiling ; Humans ; Male ; Middle Aged ; Platelet Aggregation/genetics ; Singapore
Chemical Substances	Circulating MicroRNA
Language	English
Publishing date	2020-04-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-63263-6
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Article ; Online: Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 18

Abstract: Synthetic embryo models have arisen as an approach to probe early development in vitro, facilitating the study of difficult to access stages. Here the authors present a simple system for generating embryo-like structures that resemble peri-implantation ... ...

Abstract	Synthetic embryo models have arisen as an approach to probe early development in vitro, facilitating the study of difficult to access stages. Here the authors present a simple system for generating embryo-like structures that resemble peri-implantation mouse embryos.
Keywords	Science ; Q
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease.

Kapellos, Theodore S / Baßler, Kevin / Fujii, Wataru / Nalkurthi, Christina / Schaar, Anna C / Bonaguro, Lorenzo / Pecht, Tal / Galvao, Izabela / Agrawal, Shobhit / Saglam, Adem / Dudkin, Erica / Frishberg, Amit / de Domenico, Elena / Horne, Arik / Donovan, Chantal / Kim, Richard Y / Gallego-Ortega, David / Gillett, Tessa E / Ansari, Meshal /

Schulte-Schrepping, Jonas / Offermann, Nina / Antignano, Ignazio / Sivri, Burcu / Lu, Wenying / Eapen, Mathew S / van Uelft, Martina / Osei-Sarpong, Collins / van den Berge, Maarten / Donker, Hylke C / Groen, Harry J M / Sohal, Sukhwinder S / Klein, Johanna / Schreiber, Tina / Feißt, Andreas / Yildirim, Ali Önder / Schiller, Herbert B / Nawijn, Martijn C / Becker, Matthias / Händler, Kristian / Beyer, Marc / Capasso, Melania / Ulas, Thomas / Hasenauer, Jan / Pizarro, Carmen / Theis, Fabian J / Hansbro, Philip M / Skowasch, Dirk / Schultze, Joachim L

Cell reports

2023 Volume 42, Issue 6, Page(s) 112525

Abstract: Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a ... ...

Abstract	Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.
MeSH term(s)	Humans ; Animals ; Mice ; Neutrophils ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Lung ; Pulmonary Emphysema ; Inflammation
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112525
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Article ; Online: Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs.

Nature communications

2021 Volume 12, Issue 1, Page(s) 7322

Abstract: Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that embryo-like structures can be generated solely based on transcription factor-mediated reprogramming ...

Abstract	Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that embryo-like structures can be generated solely based on transcription factor-mediated reprogramming of embryonic stem cells in a simple 3D co-culture system. Embryonic stem cells in these cultures self-organize into elongated, compartmentalized embryo-like structures reflecting aspects of the inner regions of the early post-implantation embryo. Single-cell RNA-sequencing reveals transcriptional profiles resembling epiblast, primitive-/visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5-E5.5. In this stem cell-based embryo model, progression from rosette formation to lumenogenesis accompanied by progression from naïve- to primed pluripotency was observed within Epi-like cells. Additionally, lineage specification of primordial germ cells and distal/anterior visceral endoderm-like cells was observed in epiblast- or visceral endoderm-like compartments, respectively. The system presented in this study allows for fast and reproducible generation of embryo-like structures, providing an additional tool to study aspects of early embryogenesis.
MeSH term(s)	Animals ; Blastocyst/cytology ; Blastocyst/metabolism ; Cell Culture Techniques, Three Dimensional ; Cellular Reprogramming ; Embryo, Mammalian/embryology ; Embryo, Mammalian/metabolism ; Embryoid Bodies/cytology ; Embryoid Bodies/metabolism ; Embryonic Development ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Endoderm/embryology ; Endoderm/metabolism ; Gene Expression Regulation, Developmental ; Mice ; RNA-Seq
Language	English
Publishing date	2021-12-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-27586-w
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Article ; Online: Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19.

Frishberg, Amit / Kooistra, Emma / Nuesch-Germano, Melanie / Pecht, Tal / Milman, Neta / Reusch, Nico / Warnat-Herresthal, Stefanie / Bruse, Niklas / Händler, Kristian / Theis, Heidi / Kraut, Michael / van Rijssen, Esther / van Cranenbroek, Bram / Koenen, Hans Jpm / Heesakkers, Hidde / van den Boogaard, Mark / Zegers, Marieke / Pickkers, Peter / Becker, Matthias /

Aschenbrenner, Anna C / Ulas, Thomas / Theis, Fabian J / Shen-Orr, Shai S / Schultze, Joachim L / Kox, Matthijs

Cell reports. Medicine

2022 Volume 3, Issue 6, Page(s) 100652

Abstract: Disease recovery dynamics are often difficult to assess, as patients display heterogeneous recovery courses. To model recovery dynamics, exemplified by severe COVID-19, we apply a computational scheme on longitudinally sampled blood transcriptomes, ... ...

Abstract	Disease recovery dynamics are often difficult to assess, as patients display heterogeneous recovery courses. To model recovery dynamics, exemplified by severe COVID-19, we apply a computational scheme on longitudinally sampled blood transcriptomes, generating recovery states, which we then link to cellular and molecular mechanisms, presenting a framework for studying the kinetics of recovery compared with non-recovery over time and long-term effects of the disease. Specifically, a decrease in mature neutrophils is the strongest cellular effect during recovery, with direct implications on disease outcome. Furthermore, we present strong indications for global regulatory changes in gene programs, decoupled from cell compositional changes, including an early rise in T cell activation and differentiation, resulting in immune rebalancing between interferon and NF-κB activity and restoration of cell homeostasis. Overall, we present a clinically relevant computational framework for modeling disease recovery, paving the way for future studies of the recovery dynamics in other diseases and tissues.
MeSH term(s)	COVID-19 ; Cell Differentiation ; Humans ; Interferons/metabolism ; NF-kappa B/genetics ; Neutrophils/metabolism ; Signal Transduction
Chemical Substances	NF-kappa B ; Interferons (9008-11-1)
Language	English
Publishing date	2022-05-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2022.100652
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Article ; Online: Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review.

Harskamp-van Ginkel, Margreet W / Hill, Kevin D / Becker, Kristian C / Becker, Kristian / Testoni, Daniela / Cohen-Wolkowiez, Michael / Gonzalez, Daniel / Barrett, Jeffrey S / Benjamin, Daniel K / Siegel, David A / Banks, Patricia / Watt, Kevin M

JAMA pediatrics

2015 Volume 169, Issue 7, Page(s) 678–685

Abstract: Importance: Obesity affects nearly one-sixth of US children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxic side effects. The depth of available literature ... ...

Abstract	Importance: Obesity affects nearly one-sixth of US children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxic side effects. The depth of available literature regarding obesity's effect on drug safety, pharmacokinetics, and dosing in obese children is unknown. Objective: To perform a systematic literature review describing the current evidence of the effect of obesity on drug disposition in children. Evidence review: We searched the MEDLINE, Cochrane, and EMBASE databases (January 1, 1970-December 31, 2012) and included studies if they contained data on drug clearance, volume of distribution, or drug concentration in obese children (aged ≤18 years). We compared exposure and weight-normalized volume of distribution and clearance between obese and nonobese children. We explored the association between drug physicochemical properties and clearance and volume of distribution. Findings: Twenty studies met the inclusion criteria and contained pharmacokinetic data for 21 drugs. The median number of obese children studied per drug was 10 (range, 1-112) and ages ranged from newborn to 29 years (1 study described pharmacokinetics in children and adults together). Dosing schema varied and were either a fixed dose (6 [29%]) or based on body weight (10 [48%]) and body surface area (4 [19%]). Clinically significant pharmacokinetic alterations were observed in obese children for 65% (11 of 17) of the studied drugs. Pharmacokinetic alterations resulted in substantial differences in exposure between obese and nonobese children for 38% (5 of 13) of the drugs. We found no association between drug lipophilicity or Biopharmaceutical Drug Disposition Classification System class and changes in volume of distribution or clearance due to obesity. Conclusions and relevance: Consensus is lacking on the most appropriate weight-based dosing strategy for obese children. Prospective pharmacokinetic trials in obese children are needed to ensure therapeutic efficacy and enhance drug safety.
MeSH term(s)	Body Composition ; Body Weight/physiology ; Child ; Child, Preschool ; Drug Dosage Calculations ; Humans ; Metabolic Clearance Rate/physiology ; Obesity/drug therapy ; Pharmacokinetics
Language	English
Publishing date	2015-04-25
Publishing country	United States
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 ; Systematic Review
ZDB-ID	2701223-2
ISSN	2168-6211 ; 2168-6203
ISSN (online)	2168-6211
ISSN	2168-6203
DOI	10.1001/jamapediatrics.2015.132
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