Accuracy of Radiomics in Predicting IDH Mutation Status in Diffuse Gliomas: A Bivariate Meta-Analysis

Purpose: To perform a systematic review and meta-analysis assessing the predictive accuracy of radiomics in the noninvasive determination of isocitrate dehydrogenase (IDH) status in grade-4 and lower-grade diffuse gliomas. Materials and Methods: A systematic search was performed in the PubMed, Scopus, Embase, Web of Science and Cochrane library databases for relevant articles published between January 1, 2010 and July 7, 2021. Pooled sensitivity and specificity across studies was estimated. Risk of bias was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), and methodology was evaluated using the radiomics quality score (RQS). Additional subgroup analyses were performed according to tumor grade, RQS, and number of sequences used (PROSPERO ID: CRD42021268958). Results: Twenty-six studies that included a total of 3,280 patients were included for analysis. The pooled sensitivity and specificity of radiomics for the detection of IDH mutation were 79% (95%CI: 76%–83%) and 80% (95%CI: 76%–83%), respectively. Low RQS scores were found overall for the included works. Subgroup analyses showed lower false positive rates in very low RQS studies (RQS < 6) (meta-regression z = −1.9, P = .02) compared with adequate RQS studies. No substantial differences were found in pooled sensitivity/specificity for the pure grade-4 gliomas group compared with the all-grade gliomas group (81%/86% versus 79%/79% respectively) and for studies using single versus multiple sequences (80%/77% versus 79%/82% respectively). Conclusion: The pooled data showed that radiomics achieved good accuracy performance in distinguishing IDH mutation status in patients with grade-4 and lower-grade diffuse gliomas. Overall methodological quality (RQS) is low and introduces potential bias

Thermomechanical response of liquid crystal elastomers: role of crosslinker density

In this work thermomechanical properties of main-chain liquid crystal elastomers (MC-LCEs) with different degrees of crosslinking were investigated, and gradual loss of thermomechanical response was observed on repetitive measurements. Specifically, six samples of MC-LCEs were prepared, with crosslinker-to-mesogen relative concentration ranging from 5% to 10% in steps of 1%. The obtained results were then compared to thermomechanical response of side-chain liquid crystal elastomers (SC-LCEs). Additionally, thermomechanical response of polymer dispersed main-chain liquid crystal elastomers (MC-PDLCEs) was investigated. Results indicate that in MC-LCEs the concentration of crosslinker defines thermomechanical response and affects stability of the system. The loss of thermomechanical response is negligible in the case of crosslinker to mesogen ratio being the smallest, namely in 5% sample, and it is unaffected by glasslike to nematic phase transition. SC-LCEs do not show any sign of such behaviour and remain stable after several cycles of thermomechanical measurements

Multiscale ecological drivers of Echinococcus multilocularis spatial distribution in wild hosts: A systematic review

: Understanding the ecological factors that drive the spatial patterns of parasites transmission is essential to predict their distribution under global change and to direct proactive surveillance efforts. Here, we systematically reviewed the literature to assess the main ecological drivers responsible for the spatial distribution and transmission of the zoonotic cestode Echinococcus multilocularis, the aetiological agent of alveolar echinococcosis, focusing on wild hosts. The 23 retrieved studies suggested that the dispersal of definitive hosts, climatic and biotic factors (distribution of intermediate hosts, composition of host communities) shape continental-scale distribution patterns of E. multilocularis, whereas the relative importance of climate and land cover in driving E. multilocularis distribution at a smaller (country/regional) scale varies with the geographic area considered. At a local scale, two additional factors contribute to determine the distribution of micro-foci of transmission: the trophic relationships between carnivores definitive hosts and small mammals intermediate hosts, and the defecation and marking behaviour of definitive hosts

Critical Needs for Integrated Surveillance: Wastewater-Based and Clinical Epidemiology in Evolving Scenarios with Lessons Learned from SARS-CoV-2

: During the COVID-19 pandemic, wastewater-based epidemiology (WBE) and clinical surveillance have been used as tools for analyzing the circulation of SARS-CoV-2 in the community, but both approaches can be strongly influenced by some sources of variability. From the challenging perspective of integrating environmental and clinical data, we performed a correlation analysis between SARS-CoV-2 concentrations in raw sewage and incident COVID-19 cases in areas served by medium-size wastewater treatment plants (WWTPs) from 2021 to 2023. To this aim, both datasets were adjusted for several sources of variability: WBE data were adjusted for factors including the analytical protocol, sewage flow, and population size, while clinical data adjustments considered the demographic composition of the served population. Then, we addressed the impact on the correlation of differences among sewerage networks and variations in the frequency and type of swab tests due to changes in political and regulatory scenarios. Wastewater and clinical data were significantly correlated when restrictive containment measures and limited movements were in effect (ρ = 0.50) and when COVID-19 cases were confirmed exclusively through molecular testing (ρ = 0.49). Moreover, a positive (although weak) correlation arose for WWTPs located in densely populated areas (ρ = 0.37) and with shorter sewerage lengths (ρ = 0.28). This study provides methodological approaches for interpreting WBE and clinical surveillance data, which could also be useful for other infections. Data adjustments and evaluation of possible sources of bias need to be carefully considered from the perspective of integrated environmental and clinical surveillance of infections

Physiological Noise: Definition, Estimation, and Characterization in Complex Biomedical Signals

Background: Nonlinear physiological systems exhibit complex dynamics driven by intrinsic dynamical noise. In cases where there is no specific knowledge or assumption about system dynamics, such as in physiological systems, it is not possible to formally estimate noise. Aim: We introduce a formal method to estimate the power of dynamical noise, referred to as physiological noise, in a closed form, without specific knowledge of the system dynamics. Methodology: Assuming that noise can be modeled as a sequence of independent, identically distributed (IID) random variables on a probability space, we demonstrate that physiological noise can be estimated through a nonlinear entropy profile. We estimated noise from synthetic maps that included autoregressive, logistic, and Pomeau-Manneville systems under various conditions. Noise estimation is performed on 70 heart rate variability series from healthy and pathological subjects, and 32 electroencephalographic (EEG) healthy series. Results: Our results showed that the proposed model-free method can discern different noise levels without any prior knowledge of the system dynamics. Physiological noise accounts for around 11% of the overall power observed in EEG signals and approximately 32% to 65% of the power related to heartbeat dynamics. Cardiovascular noise increases in pathological conditions compared to healthy dynamics, and cortical brain noise increases during mental arithmetic computations over the prefrontal and occipital regions. Brain noise is differently distributed across cortical regions. Conclusion: Physiological noise is very part neurobiological dynamics and can be measured using the proposed framework in any biomedical series

Liver transplantation with uncontrolled versus controlled DCD donors using normothermic regional perfusion and ex-situ machine perfusion

In Italy, 20 minutes of continuous, flat-line electrocardiogram are required for death declaration, which significantly increases the risks of donation after circulatory death (DCD) LT. Despite prolonged warm ischemia time, Italian centers reported good outcomes in controlled donation after circulatory death LT by combining normothermic regional and end-ischemic machine perfusion. However, data on uncontrolled DCD (uDCD) LT performed by this approach are lacking. This was a multicenter, retrospective study performed at 3 large-volume centers comparing clinical outcomes of uncontrolled versus controlled DCD LT. The aim of the study was to assess outcomes of sequential normothermic regional perfusion and end-ischemic machine perfusion in uncontrolled DCD liver transplantation (LT). Of 153 DCD donors evaluated during the study period, 40 uDCD and 59 donation after circulatory death grafts were transplanted (utilization rate 52% vs. 78%, p = 0.004). Recipients of uDCD grafts had higher MEAF (4.9 vs. 3.5, p < 0.001) and CCI scores at discharge (24.4 vs. 8.7, p = 0.026), longer ICU stay (5 vs. 4 d, p = 0.047), and a trend toward more severe AKI. At multivariate analysis, 90-day graft loss was associated with recipient BMI and lactate downtrend during normothermic regional perfusion. One-year graft survival was lower in uDCD (75% vs. 90%, p = 0.007) but became comparable when non-liver-related graft losses were treated as censors (77% vs. 90%, p = 0.100). The incidence of ischemic cholangiopathy was 10% in uDCD versus 3% in donation after circulatory death, p = 0.356. uDCD LT with prolonged warm ischemia is feasible by the sequential use of normothermic regional perfusion and end-ischemic machine perfusion. Proper donor and recipient selection are key to achieving good outcomes in this setting

Development of Potent and Selective Monoacylglycerol Lipase Inhibitors. SARs, Structural Analysis, and Biological Characterization

New potent, selective monoacylglycerol lipase (MAGL) inhibitors based on the azetidin-2-one scaffold ((±)-5a-v, (±)-6a-j, and (±)-7a-d) were developed as irreversible ligands, as demonstrated by enzymatic and crystallographic studies for (±)-5d, (±)-5l, and (±)-5r. X-ray analyses combined with extensive computational studies allowed us to clarify the binding mode of the compounds. 5v was identified as selective for MAGL when compared with other serine hydrolases. Solubility, in vitro metabolic stability, cytotoxicity, and absence of mutagenicity were determined for selected analogues. The most promising compounds ((±)-5c, (±)-5d, and (±)-5v) were used for in vivo studies in mice, showing a decrease in MAGL activity and increased 2-arachidonoyl-sn-glycerol levels in forebrain tissue. In particular, 5v is characterized by a high eudysmic ratio and (3R,4S)-5v is one of the most potent irreversible inhibitors of h/mMAGL identified thus far. These results suggest that the new MAGL inhibitors have therapeutic potential for different central and peripheral pathologies

Strategies for single base gene editing in an immortalized human cell line by CRISPR/Cas9 technology

The use of CRISPR/Cas9 system has rapidly grown in the last years. Here, the optimization of gene editing of a single-nucleotide polymorphism in a human non-malignant somatic cell line of thyrocytes (Nthy-Ori) was described highlighting strategies for overcoming the problems concerning the delivery and off-targets. We employed both lentivirus and chemical lipids as delivery agents and two strategies for creating the double-strand breaks (DSB). The former induced a DSB by a classical Cas9 nuclease (standard strategy), while the second one employed a modified Cas9 creating a single-strand break (SSB). The knock-in was carried out using a single-stranded donor oligonucleotide or the HR410-PA donor vector (HR). The desired cells could be obtained by combining the double nickase system with the HR vector transfected chemically. This result could be due to the type of DSB, likely processed mainly by non-homologous end joining when blunt (standard strategy) and by HR when overhanging (double nickase). Our results showed that the double nickase is suitable for knocking-in the immortalized Nthy-Ori cell line, while the standard CRISPR/Cas9 system is suitable for gene knock-out creating in/del mutations

The Lord of Ucupe mask from Moche culture (Peru). A multianalytical study of the materials from the metals to the adhesive

The aim of this paper is to characterize materials belonging to one of the masks coming from the Lord of Ucupe's tomb in the region of Lambayeque in Peru. The mask belongs to the Moche culture which lived in the north of Peru since 100 CE. Along with the study of the extraordinary metal alloy technique using X-ray fluorescence (ED XRF) integrated with the Monte Carlo simulation, this paper investigates the blackish material used as an adhesive for its inlaid eyes. This material was analysed through the ATR FT-IR and characterized through Py-GC/MS and GC/MS for the organic components and SEM-EDS for the inorganic components. The chemical characterization of the adhesive material coming from this type of artefact, based on our knowledge of current literature, is the first on this material and allows us to take a further step into the understanding of the constituents used for this purpose