PSMA-positive nodal recurrence in prostate cancer

Purpose This analysis compares salvage lymph node dissection (SLND) to salvage lymph node radiotherapy (SLNRT) of 68Ga-PSMA PET-positive nodal recurrences after radical prostatectomy (RPE). Methods A total of 67 SLNRT and 33 SLND consecutive patients with pelvic and/or para-aortic nodal recurrences after RPE were retrospectively analyzed. Biochemical recurrence-free survival rates (bRFS; PSA <0.2 ng/mL) were calculated according to Kaplan–Meier and survival curves were compared using the log rank test. For multivariable analysis, binary logistic regression analysis was performed (p < 0.05). Results Median follow-up was 17 months (range, 6–53 months) in SLND patients and 31 months (range, 3–56 months) in SLNRT patients (p = 0.027). SLNRT patients had significantly more tumours of pT3 and pT4 category (82% vs. 67%; p = 0.006), pathologically involved lymph nodes (45% vs. 27%; p = 0.001) and positive surgical margins (54% vs. 12%; p = 0.001) at time of RPE than SLND patients. PSA persistence after RPE was significantly more frequently observed in the SLNRT cohort (73% vs. 27%; p = 0.001). There was no significant difference in the distribution of PET-positive lymph nodes. Median PSA before SLND was higher than before SLNRT (3.07 ng/ml vs. 1.3 ng/ml; p = 0.393). The 2‑year bRFS was significantly higher in the SLNRT vs. the SLND cohort (92% vs. 30%; p = 0.001) with lower rates of distant metastases (21% vs. 52%; p = 0.002) and secondary treatments (5% vs. 39%; p = 0.011) irrespective of ongoing androgen deprivation therapy at last contact. In multivariable analysis, SLNRT was significantly associated with prolonged bRFS (regression coefficient 1.436, hazard ratio 4.204, 95% CI 1.789–9.878; p = 0.001). Conclusion Based on this retrospective study SLNRT might be the preferred treatment option for patients with nodal recurrence after previous RPE

Outcome after PSMA-PET/CT-based salvage radiotherapy for nodal recurrence after radical prostatectomy

PURPOSE Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence. METHODS A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA 1~ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes. CONCLUSIONS Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome

Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa

West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak.status: publishe

Quasi-two-dimensional NaCl crystals encapsulated between graphene sheets and their decomposition under an electron beam

Quasi-two-dimensional (2D) sodium chloride (NaCl) crystals of various lateral sizes between graphene sheets were manufactured via supersaturation from a saline solution. Aberration-corrected transmission electron microscopy was used for systematic in situ investigations of the crystals and their decomposition under an 80 kV electron beam. Counterintuitively, bigger clusters were found to disintegrate faster under electron irradiation, but in general no correlation between crystal sizes and electron doses at which the crystals decompose was found. As for the destruction process, an abrupt decomposition of the crystals was observed, which can be described by a logistic decay function. Density-functional theory molecular dynamics simulations provide insights into the destruction mechanism, and indicate that even without account for ionization and electron excitations, free-standing NaCl crystals must quickly disintegrate due to the ballistic displacement of atoms from their surface and edges during imaging. However, graphene sheets mitigate damage development by stopping the displaced atoms and enable the immediate recombination of defects at the surface of the crystal. At the same time, once a hole in graphene appears, the displaced atoms escape, giving rise to the quick destruction of the crystal. Our results provide quantitative data on the stability of encapsulated quasi 2D NaCl crystals under electron irradiation and allow the conclusion that only high-quality graphene is suitable for protecting ionic crystals from beam damage in electron microscopy studies.Peer reviewe

High resolution modeling of CO2 over Europe: implications for representation errors of satellite retrievals

Satellite retrievals for column CO2 with better spatial and temporal sampling are expected to improve the current surface flux estimates of CO2 via inverse techniques. However, the spatial scale mismatch between remotely sensed CO2 and current generation inverse models can induce representation errors, which can cause systematic biases in flux estimates. This study is focused on estimating these representation errors associated with utilization of satellite measurements in global models with a horizontal resolution of about 1 degree or less. For this we used simulated CO2 from the high resolution modeling framework WRF-VPRM, which links CO2 fluxes from a diagnostic biosphere model to a weather forecasting model at 10&times;10 km2 horizontal resolution. Sub-grid variability of column averaged CO2, i.e. the variability not resolved by global models, reached up to 1.2 ppm with a median value of 0.4 ppm. Statistical analysis of the simulation results indicate that orography plays an important role. Using sub-grid variability of orography and CO 2 fluxes as well as resolved mixing ratio of CO2, a linear model can be formulated that could explain about 50% of the spatial patterns in the systematic (bias or correlated error) component of representation error in column and near-surface CO2 during day-and night-times. These findings give hints for a parameterization of representation error which would allow for the representation error to taken into account in inverse models or data assimilation systems

CC Chemokine Receptor 7 Expression by Effector/Memory CD4(+) T Cells Depends on Antigen Specificity and Tissue Localization during Influenza A Virus Infection

The lung is an important entry site for respiratory pathogens such as influenza A virus. In order to combat such invading infectious agents, effector/memory T cells home to the lung and other peripheral tissues as well as lymphoid organs. In this process, chemokines and their receptors fulfill important roles in the guidance of T cells into such organs and specialized microenvironments within tissues. In this study, we determined if CD4(+) T cells residing in different lung compartments and draining lymph nodes of influenza A virus-infected and naïve mice express receptors allowing their recirculation into secondary lymphoid tissues. We found high levels of l-selectin and CC chemokine receptor 7 (CCR7) expression in lung-derived CD4(+) T cells, similar to that detected on T cells in secondary lymphoid organs. Upon influenza A virus infection, the bulk of gamma interferon-positive (IFN-γ(+)) and IFN-γ(−) CD4(+) T cells recovered from lung parenchyma retained functional CCR7, whereas virus-specific IFN-γ-producing T cells were CCR7(−). In contrast, a majority of virus-specific IFN-γ(+) T cells in the lung draining lymph node were CCR7(+). Independent of infection, CD4(+) T cells obtained from the lung airways exhibited the lowest expression level of l-selectin and CCR7, indicating that T cells at this anatomical site represent the most differentiated effector cell type, lacking the ability to recirculate. Our results suggest that effector/memory T cells that enter inflammatory sites retain functional CCR7 expression, which is lost only upon response to viral antigen and after localization to the final effector site

Structural and Chemical Modifications of Few-Layer Transition Metal Phosphorous Trisulfides by Electron Irradiation

Funding Information: We want to thank all cooperation associates in the framework of this manuscript. Further, we especially thank the Institute Laue-Langevin, for the syntheses of the TMPT materials used in this work. We thank Gabriele Es-Samlaoui for successfully preparing the samples for TEM investigation. Further, we thank Hannu Pekka-Komsa for the fruitful discussions on Debye temperatures in TMPTs. This work is supported by a project funded by Carl Zeiss foundation. The computational support from the Technical University of Dresden computing cluster (TAURUS) and High-Performance Computing Center (HLRS) in Stuttgart is gratefully appreciated. We further thank the German Research Foundation (DFG) through projects KR 4866/8-1, the collaborative research center “Chemistry of Synthetic 2D Materials” CRC-1415-417590517, and the collaborative research center “Exploiting the Human Peptidome for Novel Antimicrobial and Anticancer Agents” CRC-1279-316249678 for financial support. Publisher Copyright: © 2022 The Authors. Published by American Chemical Society.Transition metal phosphorous trisulfides (TMPTs) are inorganic materials with inherent magnetic properties. Due to their layered structure, they can be exfoliated into ultra-thin sheets, which show properties different from their bulk counterparts. Herein, we present a detailed analysis of the interaction of the electron beam (30-80 kV) in a transmission electron microscope with freestanding few-layer TMPTs, with the aim of tailoring their properties. The irradiation-induced structure modifications were systematically investigated by various transmission electron microscopy methods on FePS3, MnPS3, and NiPS3, and the results are rationalized with the help of ab initio calculations, which predict that the knock-on threshold for removing sulfur is significantly lower than that for phosphorus. Therefore, a targeted removal of sulfur is feasible. Eventually, our experiments confirm the dose-dependent, predominant removal of sulfur by the impinging electrons, thus showing the possibility of tuning the sulfur concentration. Using ab initio calculations, we analyze the electronic structure of the TMPTs with single vacancies and oxygen impurities and predict distinct electronic properties depending on the type of defect. Therefore, our study shows the possibility of tuning the properties of ultra-thin freestanding TMPTs by controlling their stoichiometry.Peer reviewe

Defect Agglomeration and Electron-Beam-Induced Local-Phase Transformations in Single-Layer MoTe2

Funding Information: We acknowledge funding from the German Research Foundation (DFG), project KR 48661/1, and through the collaborative research center “Chemistry of Synthetic 2D Materials” SFB-1415-417590517. We acknowledge the German Research Foundation (DFG) and the Ministry of Science, Research and the Arts (MWK) of the federal state of Baden-Württemberg, Germany, in the frame of the SALVE (sub-Angström low-voltage electron microscopy) project (KA1295/21-1). We further thank HLRS, Stuttgart, Germany, and TU Dresden (Taurus cluster) for the generous grant of CPU time. Publisher Copyright: ©Atom migrations in single-layer 1H-MoTe2 are studied with Cc/Cs-corrected high-resolution transmission electron microscopy at an electron energy of 40 keV using the electron beam simultaneously for material modification and imaging. After creating tellurium vacancies and vacancy lines, we observe their migration pathways across the lattice. Furthermore, we analyze phase transformations from the 1H- to the 1T′-phase associated with the strain induced due to the formation of Te vacancy lines. Combining the experimental data with the results of first-principles calculations, we explain the energetics and driving forces of point- and line-defect migrations and the phase transformations due to an interplay of electron-beam-induced energy input, atom ejection, and strain spread. Our results enhance the understanding of defect dynamics in 2D transition metal dichalcogenides, which should facilitate tailoring their local optical and electronic properties.Peer reviewe

Electron-Beam- and Thermal-Annealing-Induced Structural Transformations in Few-Layer MnPS3

Funding Information: We want to thank all cooperation associates in the framework of this manuscript. Further, we especially thank the Institut Laue-Langevin for the synthesis of the TMPT materials and Gabriele Es-Samlaoui for the preparation of TEM samples used in this work. This work was supported by the German Science Foundation (DFG), project CRC 1279 (project number 316249678), projects KR 4866/8-1, and the collaborative research center “Chemistry of Synthetic 2D Materials” SFB-1415-417590517. This work was supported by a project funded by the Carl Zeiss foundation. The computational support from the Technical University of Dresden computing cluster (TAURUS) and High-Performance Computing Center (HLRS) in Stuttgart is gratefully appreciated. M.K.K. acknowledges funding from the Deutsche Forschungsgemeinschaft (DFG) within the project DFG: KI 2546/1-1. Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.Quasi-two-dimensional (2D) manganese phosphorus trisulfide, MnPS3, which exhibits antiferromagnetic ordering, is a particularly interesting material in the context of magnetism in a system with reduced dimensionality and its potential technological applications. Here, we present an experimental and theoretical study on modifying the properties of freestanding MnPS3 by local structural transformations via electron irradiation in a transmission electron microscope and by thermal annealing under vacuum. In both cases we find that MnS1-xPx phases (0 ≤ x < 1) form in a crystal structure different from that of the host material, namely that of the α- or γ-MnS type. These phase transformations can both be locally controlled by the size of the electron beam as well as by the total applied electron dose and simultaneously imaged at the atomic scale. For the MnS structures generated in this process, our ab initio calculations indicate that their electronic and magnetic properties strongly depend on both in-plane crystallite orientation and thickness. Moreover, the electronic properties of the MnS phases can be further tuned by alloying with phosphorus.Peer reviewe