Publications by authors named "M Kramer"

4,268 Publications

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A novel free-breathing abdominal RAVE T/T hybrid MRI sequence in patients with cystic fibrosis: Preliminary results.

Eur J Radiol 2022 Jul 27;154:110454. Epub 2022 Jul 27.

Department of Radiology, University Hospital, Jena, Germany.

Objectives: Patients with cystic fibrosis (CF) increasingly require imaging for the diagnosis of abdominal complications. We prospectively evaluated the image quality and signal-to-noise ratio (SNR) of a modern radial volumetric encoding (RAVE) T/T hybrid sequence for abdominal magnetic resonance imaging (MRI). RAVET/T is a three-dimensional radial sequence with fat saturation and blood flow suppression that acquires T- and T-weighted contrasts in one scan in an identical slice position during free-breathing.

Methods: Sixteen CF patients underwent axial T HASTE (1000 ms/93 ms TR/TE), T DIXON (6.8 ms/2.4 ms/4.8 ms TR/TE/TE), and RAVE T/T hybrid sequence (1200 ms/1.7 ms/3.3 ms/4.9 ms/102 ms TR/TE/TE/TE/TE) of the upper abdomen at 1.5 Tesla. The SNR values in six different regions were assessed and compared using the Wilcoxon signed-rank test. The image quality criteria were rated on a 5-point Likert scale.

Results: In all regions, the SNR was significantly higher in the T weighted aspect of the RAVE T/T hybrid sequence compared to T HASTE (p < 0.05) and significantly lower in the T weighted in-phase aspect of the RAVE T/T hybrid sequence compared to the T DIXON sequence (p < 0.05). Qualitatively the T weighted aspect of the RAVE T/T hybrid sequence was rated significantly higher than the T HASTE in 6 of 7 categories (p < 0.05) and the T weighted in-phase aspect of the RAVE T/T hybrid sequence was rated significantly higher than the T DIXON in 2 of 6 categories (p < 0.05).

Conclusions: The abdominal radial RAVE T/T hybrid sequence provided higher image quality and SNR than the THASTEsequence. Together with increased robustness against motion artifacts, the RAVE T/T hybrid sequence appears to be a good tool for abdominal imaging in CF patients.
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http://dx.doi.org/10.1016/j.ejrad.2022.110454DOI Listing
July 2022

Multiple sources of fast traveling waves during human seizures: resolving a controversy.

J Neurosci 2022 Jul 29. Epub 2022 Jul 29.

Department of Mathematics and Statistics & Center for Systems Neuroscience, Boston University, Boston, MA 02215, USA

During human seizures organized waves of voltage activity rapidly sweep across the cortex. Two contradictory theories describe the source of these fast traveling waves: either a slowly advancing narrow region of multiunit activity (an ictal wavefront) or a fixed cortical location. Limited observations and different analyses prevent resolution of these incompatible theories. Here we address this disagreement by combining the methods and microelectrode array recordings (=11 patients, 2 females, =31 seizures) from previous human studies to analyze the traveling wave source. We find - inconsistent with both existing theories - a transient relationship between the ictal wavefront and traveling waves, and multiple stable directions of traveling waves in many seizures. Using a computational model that combines elements of both existing theories, we show that interactions between an ictal wavefront and fixed source reproduce the traveling wave dynamics observed We conclude that combining both existing theories can generate the diversity of ictal traveling waves.The source of voltage discharges that propagate across cortex during human seizures remains unknown. Two candidate theories exist, each proposing a different discharge source. Support for each theory consists of observations from a small number of human subject recordings, analyzed with separately developed methods. How the different, limited data and different analysis methods impact the evidence for each theory is unclear. To resolve these differences, we combine the unique, human microelectrode array recordings collected separately for each theory and analyze these combined data with a unified approach. We show that neither existing theory adequately describes the data. We then propose a new theory that unifies existing proposals and successfully reproduces the voltage discharge dynamics observed .
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http://dx.doi.org/10.1523/JNEUROSCI.0338-22.2022DOI Listing
July 2022

Proteomic and Phosphoproteomic Landscapes of Acute Myeloid Leukemia.

Blood 2022 Jul 27. Epub 2022 Jul 27.

Washington University School of Medicine, St Louis, Missouri, United States.

We have developed a deep-scale proteome and phosphoproteome database from 44 representative Acute Myeloid Leukemia (AML) patients from the LAML TCGA dataset, and 6 healthy bone marrow derived controls. After confirming data quality, we orthogonally validated several previously undescribed features of AML revealed by the proteomic data. We identified examples of post-transcriptionally regulated proteins both globally (i.e. in all AML samples), and also, in patients with recurrent AML driver mutations. For example, samples with IDH1/2 mutations displayed elevated levels of the 2‑oxoglutarate-dependent histone demethylases KDM4A/B/C, despite no changes in mRNA levels for these genes; we confirmed this finding in vitro. In samples with NPMc mutations, we identified several nuclear importins with post‑transcriptionally increased protein abundance, and showed that they interact with NPMc, but not wildtype NPM1. We identified two cell surface proteins (CD180 and MRC1/CD206) expressed on AML blasts of many patients (but not healthy CD34+ stem/progenitor cells) that could represent novel targets for immunologic therapies, and confirmed these targets via flow cytometry. Finally, we detected nearly 30,000 phosphosites in these samples; globally, AML samples were associated with the abnormal phosphorylation of specific residues in PTPN11, STAT3, AKT1 and PRKCD. FLT3‑TKD samples were associated with increased phosphorylation of activating tyrosines on the cytoplasmic Src-family tyrosine kinases FGR and HCK, and related signaling proteins. PML-RARA-initiated AML samples displayed a unique phosphorylation signature, and TP53-mutant samples showed abundant phosphorylation of serine-183 on TP53 itself. This publicly available database will serve as a foundation for further investigations of protein dysregulation in AML pathogenesis.
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http://dx.doi.org/10.1182/blood.2022016033DOI Listing
July 2022

A Polyclonal Aptamer Library for the Specific Binding of the Gut Bacterium in Mixtures with Other Gut Microbiome Bacteria and Human Stool Samples.

Int J Mol Sci 2022 Jul 13;23(14). Epub 2022 Jul 13.

Institute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.

has received attention as a potential probiotic bacterium. Recent studies have demonstrated that changes in its intestinal abundance can cause various diseases, such as obesity, enteritis and atherosclerosis. Probiotic administration or fecal transplantation alter the structure of the intestinal flora, offering possibilities for the prevention and treatment of these diseases. However, current monitoring methods, such as 16S rRNA sequencing, are complex and costly and require specialized personnel to perform the tests, making it difficult to continuously monitor patients during treatment. Hence, the rapid and cost-effective quantification of intestinal bacteria has become an urgent problem to be solved. Aptamers are of emerging interest because their stability, low immunogenicity and ease of modification are attractive properties for a variety of applications. We report a FluCell-SELEX polyclonal aptamer library specific for isolated after seven evolution rounds, that can bind and label this organism for fluorescence microscopy and binding assays. Moreover, can be distinguished from other major intestinal bacteria in complex defined mixtures and in human stool samples. We believe that this preliminary evidence opens new avenues towards aptamer-based electronic biosensors as new powerful and inexpensive diagnostic tools for the relative quantitative monitoring of in gut microbiomes.
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http://dx.doi.org/10.3390/ijms23147744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317077PMC
July 2022

Discovery of a radio emitting neutron star with an ultra-long spin period of 76 seconds.

Nat Astron 2022 Jul 30;6(7):828-836. Epub 2022 May 30.

Astrophysics, Department of Physics, University of Oxford, Keble road, Oxford, OX1 3RH, United Kingdom.

The radio-emitting neutron star population encompasses objects with spin periods ranging from milliseconds to tens of seconds. As they age and spin more slowly, their radio emission is expected to cease. We present the discovery of an ultra-long period radio-emitting neutron star, PSR J0901-4046, with spin properties distinct from the known spin and magnetic-decay powered neutron stars. With a spin-period of 75.88 s, a characteristic age of 5.3 Myr, and a narrow pulse duty-cycle, it is uncertain how radio emission is generated and challenges our current understanding of how these systems evolve. The radio emission has unique spectro-temporal properties such as quasi-periodicity and partial nulling that provide important clues to the emission mechanism. Detecting similar sources is observationally challenging, which implies a larger undetected population. Our discovery establishes the existence of ultra-long period neutron stars, suggesting a possible connection to the evolution of highly magnetized neutron stars, ultra-long period magnetars, and fast radio bursts.
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http://dx.doi.org/10.1038/s41550-022-01688-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613111PMC
July 2022
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