FDG PET/CT to detect bone marrow involvement in the initial staging of patients with aggressive non-Hodgkin lymphoma: results from the prospective, multicenter PETAL and OPTIMAL>60 trials

Purpose Fluorine-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET/CT) is the standard for staging aggressive non-Hodgkin lymphoma (NHL). Limited data from prospective studies is available to determine whether initial staging by FDG PET/CT provides treatment-relevant information of bone marrow (BM) involvement (BMI) and thus could spare BM biopsy (BMB). Methods Patients from PETAL (NCT00554164) and OPTIMAL>60 (NCT01478542) with aggressive B-cell NHL initially staged by FDG PET/CT and BMB were included in this pooled analysis. The reference standard to confirm BMI included a positive BMB and/or FDG PET/CT confirmed by targeted biopsy, complementary imaging (CT or magnetic resonance imaging), or concurrent disappearance of focal FDG-avid BM lesions with other lymphoma manifestations during immunochemotherapy. Results Among 930 patients, BMI was detected by BMB in 85 (prevalence 9%) and by FDG PET/CT in 185 (20%) cases, for a total of 221 cases (24%). All 185 PET-positive cases were true positive, and 709 of 745 PET-negative cases were true negative. For BMB and FDG PET/CT, sensitivity was 38% (95% confidence interval [CI]: 32–45%) and 84% (CI: 78–88%), specificity 100% (CI: 99–100%) and 100% (CI: 99–100%), positive predictive value 100% (CI: 96–100%) and 100% (CI: 98–100%), and negative predictive value 84% (CI: 81–86%) and 95% (CI: 93–97%), respectively. In all of the 36 PET-negative cases with confirmed BMI patients had other adverse factors according to IPI that precluded a change of standard treatment. Thus, the BMB would not have influenced the patient management. Conclusion In patients with aggressive B-cell NHL, routine BMB provides no critical staging information compared to FDG PET/CT and could therefore be omitted. Trial registration NCT00554164 and NCT0147854

Influence of 3D geometry and surface roughness on plasma-wall interaction processes on tungsten surfaces

Plasma-Wand-Wechselwirkungen in Fusionsreaktoren bestimmen die Erosion und Deposition von Plasma- und Wandteilchen auf und zwischen Wandkacheln. Diese Wechselwirkungen werden u.a. durch die Oberflächenrauigkeit und Kachelgeometrie stark beeinflusst. In C-W-Ionenstrahl-Oberflächen-Experimenten wurde der Effekt der Rauigkeit auf Teilchenreflektion und Selbstzerstäubung nachgewiesen und quantifiziert. Die Rauigkeit ändert signifikant die Winkelverteilung reflektierter Teilchen. Eine Erweiterung von SDTrimSP verbessert die Annäherung an die experimentellen Resultate. In Experimenten an rauen W-Kacheln mit zwei Geometrien in TEXTOR und DIII-D wurden C- und D-Ablagerungen an den oberen Spaltenkanten nachgewiesen. Eine Optimierung der Geometrie beeinflusst das elektrische Potential positiv und führte zu einer Halbierung der C-Ablagerung in den Spalten. Die Modellierung der C-Ablagerung mit dem MC-Code 3D-GAPS unter Berücksichtigung der Rauigkeit ergab eine gute Annäherung an die Experimente

Impact of Surface Roughness on Ion-Surface Interactions Studied with Energetic Carbon Ions 13C on Tungsten Surfaces+

The effect of surface roughness on angular distributions of reflected and physically sputtered particles is investigated by ultra-high vacuum (UHV) ion-surface interaction experiments. For this purpose, a smooth (R a = 5.9 nm) and a rough (R a = 20.5 nm) tungsten (W) surface were bombarded with carbon ions 13C+ under incidence angles of 30 ∘ and 80 ∘ . Reflected and sputtered particles were collected on foils to measure the resulting angular distribution as a function of surface morphology. For the qualitative and quantitative analysis, secondary ion mass spectrometry (SIMS) and nuclear reaction analysis (NRA) were performed. Simulations of ion-surface interactions were carried out with the SDTrimSP (Static Dynamic Transport of Ions in Matter Sputtering) code. For rough surfaces, a special routine was derived and implemented. Experimental as well as calculated results prove a significant impact of surface roughness on the angular distribution of reflected and sputtered particles. It is demonstrated that the effective sticking of C on W is a function of the angle of incidence and surface morphology. It is found that the predominant ion-surface interaction process changes with fluence

State-of-the-art analytical methods of viral infections in human lung organoids.

Human-based organ models can provide strong predictive value to investigate the tropism, virulence, and replication kinetics of viral pathogens. Currently, such models have received widespread attention in the study of SARS-CoV-2 causing the COVID-19 pandemic. Applicable to a large set of organoid models and viruses, we provide a step-by-step work instruction for the infection of human alveolar-like organoids with SARS-CoV-2 in this protocol collection. We also prepared a detailed description on state-of-the-art methodologies to assess the infection impact and the analysis of relevant host factors in organoids. This protocol collection consists of five different sets of protocols. Set 1 describes the protein extraction from human alveolar-like organoids and the determination of protein expression of angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and FURIN as exemplary host factors of SARS-CoV-2. Set 2 provides detailed guidance on the extraction of RNA from human alveolar-like organoids and the subsequent qPCR to quantify the expression level of ACE2, TMPRSS2, and FURIN as host factors of SARS-CoV-2 on the mRNA level. Protocol set 3 contains an in-depth explanation on how to infect human alveolar-like organoids with SARS-CoV-2 and how to quantify the viral replication by plaque assay and viral E gene-based RT-qPCR. Set 4 provides a step-by-step protocol for the isolation of single cells from infected human alveolar-like organoids for further processing in single-cell RNA sequencing or flow cytometry. Set 5 presents a detailed protocol on how to perform the fixation of human alveolar-like organoids and guides through all steps of immunohistochemistry and in situ hybridization to visualize SARS-CoV-2 and its host factors. The infection and all subsequent analytical methods have been successfully validated by biological replications with human alveolar-like organoids based on material from different donors

Event-related potential components as measures of aversive conditioning in humans

For more than 60 years, the gold standard for assessing aversive conditioning in humans has been the skin conductance response (SCR), which arises from the activation of the peripheral nervous system. Although the SCR has been proven useful, it has some properties that impact the kinds of questions it can be used to answer. In particular, the SCR is slow, reaching a peak 4-5 s after stimulus onset, and it decreases in amplitude after a few trials (habituation). The present study asked whether the late positive potential (LPP) of the ERP waveform could be a useful complementary method for assessing aversive conditioning in humans. The SCR and LPP were measured in an aversive conditioning paradigm consisting of three blocks in which one color was paired with a loud noise (CS+) and other colors were not paired with the noise (CS-). Participants also reported the perceived likelihood of being exposed to the noise for each color. Both SCR and LPP were significantly larger on CS+ trials than on CS- trials. However, SCR decreased steeply after the first conditioning block, whereas LPP and self-reports were stable over blocks. These results indicate that the LPP can be used to assess aversive conditioning and has several useful properties: (a) it is a direct response of the central nervous system, (b) it is fast, with an onset latency of 300 ms, (c) it does not habituate over time

Uncropped and unadjusted blots.

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Analysis of <i>ACE2</i>, <i>TMPRSS2</i>, and <i>FURIN</i> expression in human alveolar-like organoids.

Expression of ACE2, TMPRSS2, FURIN and GAPDH and β-ACTIN as housekeeping genes measured by qPCR on bulk RNA of human alveolar-like organoids. Shown are Ct values of four different donors (P4-P7) and two technical replicates.</p

Replication kinetics of SARS-CoV-2-infected human alveolar-like organoids.

Human alveolar-like organoids were infected with SARS-CoV-2 (MOI = 1) and viral replication was assessed by plaque assay (A) and via viral E gene-based RT-qPCR (B). Data of seven (plaque assay) and four (RT-qPCR) biological replicates are shown as individual data points. The mean is visualized by a horizontal black line.</p

Overview of plasma–material interaction experiments on EAST employing MAPES

The Material and Plasma Evaluation System (MAPES) in the EAST tokamak has been built up and used to address a variety of plasma–material interaction (PMI) issues relevant to ITER in 2012 EAST campaign. The topics studied cover erosion/redeposition of plasma-facing materials and components, hydrogenic retention in the gaps of castellation structure, deterioration of diagnostic mirrors from impurity deposition and protective technique. An introduction of MAPES system and an overview of the recent experimental results are presented

LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer

Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high‐density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis‐free survival in node‐negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress‐induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression