Acoustic radiation force impulse imaging for differentiation of thyroid nodules

Background: Acoustic Radiation Force Impulse (ARFI)-imaging is an ultrasound-based elastography method enabling quantitative measurement of tissue stiffness. The aim of the present study was to evaluate sensitivity and specificity of ARFI-imaging for differentiation of thyroid nodules and to compare it to the well evaluated qualitative real-time elastography (RTE). Methods: ARFI-imaging involves the mechanical excitation of tissue using acoustic pulses to generate localized displacements resulting in shear-wave propagation which is tracked using correlation-based methods and recorded in m/s. Inclusion criteria were: nodules $5 mm, and cytological/histological assessment. All patients received conventional ultrasound, real-time elastography (RTE) and ARFI-imaging. Results: One-hundred-fifty-eight nodules in 138 patients were available for analysis. One-hundred-thirty-seven nodules were benign on cytology/histology, and twenty-one nodules were malignant. The median velocity of ARFI-imaging in the healthy thyroid tissue, as well as in benign and malignant thyroid nodules was 1.76 m/s, 1.90 m/s, and 2.69 m/s, respectively. While no significant difference in median velocity was found between healthy thyroid tissue and benign thyroid nodules, a significant difference was found between malignant thyroid nodules on the one hand and healthy thyroid tissue (p = 0.0019) or benign thyroid nodules (p = 0.0039) on the other hand. No significant difference of diagnostic accuracy for the diagnosis of malignant thyroid nodules was found between RTE and ARFI-imaging (0.74 vs. 0.69, p = 0.54). The combination of RTE with ARFI did not improve diagnostic accuracy. Conclusions: ARFI can be used as an additional tool in the diagnostic work up of thyroid nodules with high negative predictive value and comparable results to RTE

Methods for determining the CO2 removal capacity of enhanced weathering in agronomic settings

Recent analysis by the IPCC suggests that, across an array of scenarios, both GHG emissions reductions and various degrees of carbon removal will be required to achieve climate stabilization at a level that avoids the most dangerous climate changes in the future. Among a large number of options in the realm of natural climate solutions, atmospheric carbon dioxide removal (CDR) via enhanced silicate weathering (EW) in global working lands could, in theory, achieve billions of tons of CO2 removal each year. Despite such potential, however, scientific verification and field testing of this technology are still in need of significant advancement. Increasing the number of EW field trials can be aided by formal presentation of effective study designs and methodological approaches to quantifying CO2 removal. In particular, EW studies in working lands require interdisciplinary “convergence” research that links low temperature geochemistry and agronomy. Here, drawing on geologic and agronomic literature, as well as demonstration-scale research on quantifying EW, we provide an overview of (1) existing literature on EW experimentation as a CO2 removal technique, (2) agronomic and geologic approaches to studying EW in field settings, (3) the scientific bases and tradeoffs behind various techniques for quantifying CO2 removal and other relevant methodologies, and (4) the attributes of effective stakeholder engagement for translating scientific research in action. In doing so, we provide a guide for establishing interdisciplinary EW field trials, thereby advancing the verification of atmospheric CO2 in working lands through the convergence of geochemistry and agronomy

Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination

SARS-CoV-2 variants of concern (VOCs) can trigger severe endemic waves and vaccine breakthrough infections (VBI). We analyzed the cellular and humoral immune response in 8 patients infected with the alpha variant, resulting in moderate to fatal COVID-19 disease manifestation, after double mRNA-based anti-SARS-CoV-2 vaccination. In contrast to the uninfected vaccinated control cohort, the diseased individuals had no detectable high-avidity spike (S)-reactive CD4+ and CD8+ T cells against the alpha variant and wild type (WT) at disease onset, whereas a robust CD4+ T-cell response against the N- and M-proteins was generated. Furthermore, a delayed alpha S-reactive high-avidity CD4+ T-cell response was mounted during disease progression. Compared to the vaccinated control donors, these patients also had lower neutralizing antibody titers against the alpha variant at disease onset. The delayed development of alpha S-specific cellular and humoral immunity upon VBI indicates reduced immunogenicity against the S-protein of the alpha VOC, while there was a higher and earlier N- and M-reactive T-cell response. Our findings do not undermine the current vaccination strategies but underline a potential need for the inclusion of VBI patients in alternative vaccination strategies and additional antigenic targets in next-generation SARS-CoV-2 vaccines

Change of Hemoglobin Levels in the Early Post-cardiac Arrest Phase Is Associated With Outcome

Background: The post-cardiac arrest (CA) phase is characterized by high fluid requirements, endothelial activation and increased vascular permeability. Erythrocytes are large cells and may not leave circulation despite massive capillary leak. We hypothesized that dynamic changes in hemoglobin concentrations may reflect the degree of vascular permeability and may be associated with neurologic function after CA.Methods: We included patients ≥18 years, who suffered a non-traumatic CA between 2013 and 2018 from the prospective Vienna Clinical Cardiac Arrest Registry. Patients without return of spontaneous circulation (ROSC), with extracorporeal life support, with any form of bleeding, undergoing surgery, receiving transfusions, without targeted temperature management or with incomplete datasets for multivariable analysis were excluded. The primary outcome was neurologic function at day 30 assessed by the Cerebral Performance Category scale. Differences of hemoglobin concentrations at admission and 12 h after ROSC were calculated and associations with neurologic function were investigated by uni- and multivariable logistic regression.Results: Two hundred and seventy-five patients were eligible for analysis of which 143 (52%) had poor neurologic function. For every g/dl increase in hemoglobin from admission to 12 h the odds of poor neurologic function increased by 26% (crude OR 1.26, 1.07–1.49, p = 0.006). The effect remained unchanged after adjustment for fluid balance and traditional prognostication markers (adjusted OR 1.27, 1.05–1.54, p = 0.014).Conclusion: Increasing hemoglobin levels in spite of a positive fluid balance may serve as a surrogate parameter of vascular permeability and are associated with poor neurologic function in the early post-cardiac arrest period

R-Flurbiprofen Reduces Neuropathic Pain in Rodents by Restoring Endogenous Cannabinoids

Background: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. Methodology/Principal Findings: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB), which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH) and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPAR gamma and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. Conclusion: Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain

EZH2 Depletion Blocks the Proliferation of Colon Cancer Cells

The Enhancer of Zeste 2 (EZH2) protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi)-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer

The Cell Cycle Regulated Transcriptome of Trypanosoma brucei

Progression of the eukaryotic cell cycle requires the regulation of hundreds of genes to ensure that they are expressed at the required times. Integral to cell cycle progression in yeast and animal cells are temporally controlled, progressive waves of transcription mediated by cell cycle-regulated transcription factors. However, in the kinetoplastids, a group of early-branching eukaryotes including many important pathogens, transcriptional regulation is almost completely absent, raising questions about the extent of cell-cycle regulation in these organisms and the mechanisms whereby regulation is achieved. Here, we analyse gene expression over the Trypanosoma brucei cell cycle, measuring changes in mRNA abundance on a transcriptome-wide scale. We developed a “double-cut” elutriation procedure to select unperturbed, highly synchronous cell populations from log-phase cultures, and compared this to synchronization by starvation. Transcriptome profiling over the cell cycle revealed the regulation of at least 430 genes. While only a minority were homologous to known cell cycle regulated transcripts in yeast or human, their functions correlated with the cellular processes occurring at the time of peak expression. We searched for potential target sites of RNA-binding proteins in these transcripts, which might earmark them for selective degradation or stabilization. Over-represented sequence motifs were found in several co-regulated transcript groups and were conserved in other kinetoplastids. Furthermore, we found evidence for cell-cycle regulation of a flagellar protein regulon with a highly conserved sequence motif, bearing similarity to consensus PUF-protein binding motifs. RNA sequence motifs that are functional in cell-cycle regulation were more widespread than previously expected and conserved within kinetoplastids. These findings highlight the central importance of post-transcriptional regulation in the proliferation of parasitic kinetoplastids

Compression of Deep Convolutional Neural Network Using Additional Importance-Weight-Based Filter Pruning Approach

The success of the convolutional neural network (CNN) comes with a tremendous growth of diverse CNN structures, making it hard to deploy on limited-resource platforms. These over-sized models contain a large amount of filters in the convolutional layers, which are responsible for almost 99% of the computation. The key question here arises: Do we really need all those filters? By removing entire filters, the computational cost can be significantly reduced. Hence, in this article, a filter pruning method, a process of discarding a subset of unimportant or weak filters from the original CNN model, is proposed, which alleviates the shortcomings of over-sized CNN architectures at the cost of storage space and time. The proposed filter pruning strategy is adopted to compress the model by assigning additional importance weights to convolutional filters. These additional importance weights help each filter learn its responsibility and contribute more efficiently. We adopted different initialization strategies to learn more about filters from different aspects and prune accordingly. Furthermore, unlike existing pruning approaches, the proposed method uses a predefined error tolerance level instead of the pruning rate. Extensive experiments on two widely used image segmentation datasets: Inria and AIRS, and two widely known CNN models for segmentation: TernausNet and standard U-Net, verify that our pruning approach can efficiently compress CNN models with almost negligible or no loss of accuracy. For instance, our approach could significantly reduce 85% of all floating point operations (FLOPs) from TernausNet on Inria with a negligible drop of 0.32% in validation accuracy. This compressed network is six-times smaller and almost seven-times faster (on a cluster of GPUs) than that of the original TernausNet, while the drop in the accuracy is less than 1%. Moreover, we reduced the FLOPs by 84.34% without significantly deteriorating the output performance on the AIRS dataset for TernausNet. The proposed pruning method effectively reduced the number of FLOPs and parameters of the CNN model, while almost retaining the original accuracy. The compact model can be deployed on any embedded device without any specialized hardware. We show that the performance of the pruned CNN model is very similar to that of the original unpruned CNN model. We also report numerous ablation studies to validate our approach

Effect of vaginal probiotics containing Lactobacillus casei rhamnosus (Lcr regenerans) on vaginal dysbiotic microbiota and pregnancy outcome, prospective, randomized study

Abstract The intermediate bacterial microbiota is a heterogeneous group that varies in the severity of the dysbiosis, from minor deficiency to total absence of vaginal Lactobacillus spp. We treated women with this vaginal dysbiosis in the first trimester of pregnancy using a vaginally applied lactobacilli preparation to restore the normal microbiota in order to delay the preterm delivery rate. Pregnant women with intermediate microbiota of the vagina and a Nugent score of 4 were enrolled in two groups: intermediate vaginal microbiota and a Nugent score of 4 with lactobacilli (IMLN4) and intermediate vaginal microbiota and a Nugent score of 4 without lactobacilli (IM0N4), with and without vaginal lactobacilli at baseline, respectively. Half of the women in each group received the treatment. Among women without lactobacilli (the IM0N4 group), the Nugent sore decreased by 4 points only in the women who received treatment, and gestational age at delivery and neonatal birthweight were both significantly higher in the treated subgroup than in the untreated subgroup (p = 0.047 and p = 0.016, respectively). This small study found a trend toward a benefit of treatment with vaginal lactobacilli during pregnancy