Brain macrophages in human cortical contusions as indicator of survival period

The aim of this study was to establish a morphologic time scheme with which cases of cerebral contusion with unknown survival periods can be dated. Our study of 275 cases was limited to qualitative and quantitative changes in macrophages. The appearance of macrophages and their distribution as well as their content of neutral fat, esterified cholesterol, erythrocytes, siderin, hematoidin, and ceroid were correlated with the survival period. For each cytologic criterium, the observation period, distribution-free limits of tolerance, and relative frequency of identification in different survival periods were determined, and the limits of confidence calculated. The findings permit the dating of trauma in cases with unknown survival periods. Moreover, the probability of this dating was calculated

PEDOT–CNT Composite Microelectrodes for Recording and Electrostimulation Applications: Fabrication, Morphology, and Electrical Properties

Composites of carbon nanotubes and poly(3,4-ethylenedioxythiophene, PEDOT) and layers of PEDOT are deposited onto microelectrodes by electropolymerization of ethylenedioxythiophene in the presence of a suspension of carbon nanotubes and polystyrene sulfonate. Analysis by FIB and SEM demonstrates that CNT–PEDOT composites exhibit a porous morphology whereas PEDOT layers are more compact. Accordingly, capacitance and charge injection capacity of the composite material exceed those of pure PEDOT layers. In vitro cell culture experiments reveal excellent biocompatibility and adhesion of both PEDOT and PEDOT–CNT electrodes. Signals recorded from heart muscle cells demonstrate the high S/N ratio achievable with these electrodes. Long-term pulsing experiments confirm stability of charge injection capacity. In conclusion, a robust fabrication procedure for composite PEDOT–CNT electrodes is demonstrated and results show that these electrodes are well suited for stimulation and recording in cardiac and neurophysiological research

Managing and publishing fungal community barcoding data by use of the process-oriented schema MOD-CO and a GFBio data publication pipeline

The need to fulfil FAIR guiding principles for data management and publication [1] directly affects researchers, i.e., data producers as well as data managers. Data management has to be set up well already at an early stage of the data life cycle. This is demonstrated by a best practice work- and dataflow 'Fungal community barcoding data', which has been established as side product in the context of the project 'GBOL 2 Mycology‘, German Barcode of Life initiative (https://www.bolgermany.de/). The work- and dataflow was set up by applying the newly published MOD-CO schema, Version 1.0 which has been implemented as an instance of the database application DiversityDescriptions for data management, and for making data compliant to GFBio infrastructure for data archiving and publication. The comprehensive conceptual schema MOD-CO for 'Meta-Omics Data of Collection Objects' Version 1.0 was published as Linked Open Data representation in spring 2018 [2]. The process-oriented schema describes operations and object properties along the work- and dataflow from gathering environmental samples, to the various transformation, transaction, and measurement steps in the laboratory up to sample and data publication and archiving. By supporting various kinds of relationships, the MOD-CO schema allows for the concatenation of individual records of the operational steps along a workflow. The MOD-CO descriptor structure in version 1.0 comprises 653 descriptors (concepts) and 1,810 predefined descriptor states, organised in 37 concept collections. The published version 1.0 is available as various schema representations of identical content (https://www.mod-co.net/wiki/Schema_Representations). This schema has been implemented as data structure in the relational database DiversityDescriptions (DWB-DD) (https://diversityworkbench.net/Portal/DiversityDescriptions), a generic component of the Diversity Workbench environment (https://diversityworkbench.net). DWB-DD is considered being appropriate to be applied as a LIMS (Laboratory Information Management System) and ELN (Electronic Laboratory Notebook) for organising Fungal community barcoding data' and similar data collections in molecular laboratories. Its data export interface provides guidance to generate data and metadata in the formats CSV and XML, the latter following the SDD metadata schema with involvement of extensions by metadata elements from EML and ABCD standards; for community standards see: https://gfbio.biowikifarm.net/wiki/Data_exchange_standards,_protocols_and_formats_relevant_for_the_collection_data_domain_within_the_GFBio_network. The research data themselves are organised according to the MOD-CO data schema. The data package of the work- and dataflow 'Fungal community barcoding data' is going to be submitted to GFBio after having been checked for GFBio compliance and to be published under a creative common license. Suggestions for standardized citation will be provided, a DOI assigned, and long-term data archiving ensured. KEYWORDS: DiversityDescriptions, German Barcode of Life (GBOL), German Federation for Biological Data (GFBio), MOD-CO conceptual schema, use case for community barcoding data REFERENCES: 1. Wilkinson, M.D. et al. 2016. The FAIR Guiding Principles for scientific data management and stewardship. – Sci. Data 3: 160018. DOI: 10.1038/sdata.2016.18. 2. Rambold, G., Yilmaz, P., Harjes, J., Link, A., Glöckner, F.O., Triebel, D. 2018. MOD-CO schema – a conceptual schema for processing sample data in meta’omics research (version 1.0). http://mod-co.net/wiki/MOD-CO_Schema_Reference

Photothermal Heterodyne Imaging of Individual Metallic Nanoparticles: Theory versus Experiments

We present the theoretical and detailed experimental characterizations of Photothermal Heterodyne Imaging. An analytical expression of the photothermal heterodyne signal is derived using the theory of light scattering from a fluctuating medium. The amplitudes of the signals detected in the backward and forward configurations are compared and their frequency dependences are studied. The application of the Photothermal Heterodyne detection technique to the absorption spectroscopy of individual gold nanoparticles is discussed and the detection of small individual silver nanoparticles is demonstrated

Single NanoParticle Photothermal Tracking (SNaPT) of 5 nm gold beads in live cells

Tracking individual nano-objets in live cells during arbitrary long times is an ubiquitous need in modern biology. We present here a method for tracking individual 5 nm gold nanoparticles on live cells. It relies on the photothermal effect and the detection of the Laser Induced Scattering around a NanoAbsorber (LISNA). The key point for recording trajectories at video rate is the use of a triangulation procedure. The effectiveness of the method is tested against Single fluorescent Molecule Tracking in live COS7 cells on subsecond time scales. We further demonstrate recordings for several minutes of AMPA receptors trajectories on the plasma membrane of live neurons. SNaPT has the unique potential to record arbitrary long trajectory of membrane proteins using non-fluorescent nanometer sized labels

Allogeneic Stem Cell Transplantation with Sequential Melphalan-Based Conditioning in AML: Residual Morphological Blast Count Determines the Risk of Relapse

Introduction: Allogeneic hematopoietic cell transplantation (HCT) during chemotherapy-induced aplasia may offer long-term survival in acute myeloid leukemia (AML) with otherwise poor prognosis including ELN adverse risk, relapsed or refractory disease. However, the value of residual morphologic disease prior HCT in this context has not been conclusively settled until yet. Therefore, we aimed to investigate variables predicting outcome in this unique setting of sequential conditioning therapy, with a focus on pretreatment morphologic blast count. In contrast to the most popular FLAMSA-RIC protocol, we used a melphalan-based conditioning regimen during aplasia. Methods: We retrospectively analyzed data from 173 AML patients who underwent a sequential melphalan-based conditioning therapy between 2003 and 2015 at our centre. All patients participated either in the prospective Phase 2 BRIDGE trial (NCT01295307), the Phase 3 AML2003 study (NCT00180102) or were treated according to this protocol and underwent allogeneic HCT after melphalan-based conditioning in treatment-induced aplasia. Results: Median bone marrow blast count prior to conditioning was 10% (range, 0–96%). Four year probabilities of EFS and OS were 34% (95% CI, 28–43%) and 43% (95% CI, 36–52%), respectively. In multivariate analysis, blast count >20% was associated with worse EFS (HR = 1.93; p = 0.009) and OS (HR = 1.80; p = 0.026). This effect was not significant anymore for HCT during 1st line therapy. Conclusion: Allogeneic HCT in aplasia with a melphalan-based conditioning regimen has the potential to cure a subset of adverse risk AML patients, even with persistent morphological disease prior HCT. However, a high pre-transplant blast count still indicates patients with a dismal prognosis, especially in the relapsed patient group, for whom post-transplant strategies should be considered to further optimize post HCT outcome

Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial

Abstract Early results of the randomized placebo-controlled SORAML trial showed that, in patients with newly diagnosed acute myeloid leukaemia (AML), sorafenib led to a significant improvement in event-free (EFS) and relapse-free survival (RFS). In order to describe second-line treatments and their implications on overall survival (OS), we performed a study after a median follow-up time of 78 months. Newly diagnosed fit AML patients aged ≤60 years received sorafenib (n = 134) or placebo (n = 133) in addition to standard chemotherapy and as maintenance treatment. The 5-year EFS was 41 versus 27% (HR 0.68; p = 0.011) and 5-year RFS was 53 versus 36% (HR 0.64; p = 0.035). Allogeneic stem cell transplantation (allo SCT) was performed in 88% of the relapsed patients. Four years after salvage allo SCT, the cumulative incidence of relapse was 54 versus 35%, and OS was 32 versus 50%. The 5-year OS from randomization in all study patients was 61 versus 53% (HR 0.82; p = 0.282). In conclusion, the addition of sorafenib to chemotherapy led to a significant prolongation of EFS and RFS. Although the OS benefit did not reach statistical significance, these results confirm the antileukaemic activity of sorafenib

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe