Showing papers by "Sapienza University of Rome published in 2022"

Lipid-Associated Macrophages Are Induced by Cancer-Associated Fibroblasts and Mediate Immune Suppression in Breast Cancer

Abstract: Tumor-associated macrophages (TAM) play a detrimental role in triple-negative breast cancer (TNBC). In-depth analysis of TAM characteristics and interactions with stromal cells, such as cancer-associated fibroblast (CAF), could provide important biological and therapeutic insights. Here we identify at the single-cell level a monocyte-derived STAB1+TREM2high lipid-associated macrophage (LAM) subpopulation with immune suppressive capacities that is expanded in patients resistant to immune checkpoint blockade (ICB). Genetic depletion of this LAM subset in mice suppressed TNBC tumor growth. Flow cytometry and bulk RNA sequencing data demonstrated that coculture with TNBC-derived CAFs led to reprogramming of blood monocytes towards immune suppressive STAB1+TREM2high LAMs, which inhibit T-cell activation and proliferation. Cell-to-cell interaction modeling and assays in vitro demonstrated the role of the inflammatory CXCL12-CXCR4 axis in CAF-myeloid cell cross-talk and recruitment of monocytes in tumor sites. Altogether, these data suggest an inflammation model whereby monocytes recruited to the tumor via the CAF-driven CXCL12-CXCR4 axis acquire protumorigenic LAM capacities to support an immunosuppressive microenvironment.This work identifies a novel lipid-associated macrophage subpopulation with immune suppressive functions, offering new leads for therapeutic interventions in triple-negative breast cancer.

Microglia modulate hippocampal synaptic transmission and sleep duration along the light/dark cycle

Abstract: Microglia, the brain's resident macrophages, actively contributes to the homeostasis of cerebral parenchyma by sensing neuronal activity and supporting synaptic remodeling and plasticity. While several studies demonstrated different roles for astrocytes in sleep, the contribution of microglia in the regulation of sleep/wake cycle and in the modulation of synaptic activity in the different day phases has not been deeply investigated. Using light as a zeitgeber cue, we studied the effects of microglial depletion with the colony stimulating factor-1 receptor antagonist PLX5622 on the sleep/wake cycle and on hippocampal synaptic transmission in male mice. Our data demonstrate that almost complete microglial depletion increases the duration of NREM sleep and reduces the hippocampal excitatory neurotransmission. The fractalkine receptor CX3CR1 plays a relevant role in these effects, because cx3cr1GFP/GFP mice recapitulate what found in PLX5622-treated mice. Furthermore, during the light phase, microglia express lower levels of cx3cr1 and a reduction of cx3cr1 expression is also observed when cultured microglial cells are stimulated by ATP, a purinergic molecule released during sleep. Our findings suggest that microglia participate in the regulation of sleep, adapting their cx3cr1 expression in response to the light/dark phase, and modulating synaptic activity in a phase-dependent manner.

Use of Parallel ResNet for High-Performance Pavement Crack Detection and Measurement

Abstract: In the process of road pavement health and safety assessment, crack detection plays a pivotal role in a preventive maintenance strategy. Recently, Convolutional Neural Networks (CNNs) have been applied to automatically identify the cracks on concrete pavements. The effectiveness of a CNN-based road crack detection and measurement method depends on several factors, including the image segmentation of cracks with complex topology, the inference of noises with similar texture to the distress, and the sensitivity to thin cracks. The presence of shadows, strong light reflections, and road markings can also severely affect the accuracy in detection and measurement. In this study, a review of the state-of-the-art CNN methods for crack identification is presented, paying attention to existing limitations. Then, a novel deep residual convolutional neural network (Parallel ResNet) is proposed with the aim of creating a high-performance pavement crack detection and measurement system. The challenge and special feature of Parallel ResNet is to remove the noise inference, identifying even thin and complex cracks correctly. The performance of Parallel ResNet has been investigated on two publicly available datasets (CrackTree200 and CFD), comparing it with that of competing methods suggested in the literature. Parallel ResNet reached the maximum scores in Precision (94.27%), Recall (92.52%), and F1 (93.08%) using the CrackTree200 dataset. Similarly, for the CFD dataset the novel method achieved high values in Precision (96.21%), Recall (95.12%), and F1 (95.63%). Based on the crack detection and image recognition results, mathematical morphology was then used to further minimize noise and accurately segment the road diseases, obtaining the outer contours of the connected domain in crack images. Therefore, crack skeletons have been extracted to measure the distress length, width, and area on images of rigid pavements. The experimental results show that Parallel ResNet can effectively minimize noise to obtain the geometry of cracks. The results of crack characteristic measurements are accurate and Parallel ResNet can be assumed as a reliable method in pavement crack image analysis, in order to plan the best road maintenance strategy.

Magnitude, frequency and climate forcing of global volcanism during the last glacial period as seen in Greenland and Antarctic ice cores (60–9 ka)

Abstract: Abstract. Large volcanic eruptions occurring in the last glacial period can be detected by their accompanying sulfuric acid deposition in continuous ice cores. Here we employ continuous sulfate and sulfur records from three Greenland and three Antarctic ice cores to estimate the emission strength, the frequency and the climatic forcing of large volcanic eruptions that occurred during the second half of the last glacial period and the early Holocene, 60–9 kyr before 2000 CE (b2k). Over most of the investigated interval the ice cores are synchronized, making it possible to distinguish large eruptions with a global sulfate distribution from eruptions detectable in one hemisphere only. Due to limited data resolution and large variability in the sulfate background signal, particularly in the Greenland glacial climate, we only list Greenland sulfate depositions larger than 20 kg km−2 and Antarctic sulfate depositions larger than 10 kg km−2. With those restrictions, we identify 1113 volcanic eruptions in Greenland and 737 eruptions in Antarctica within the 51 kyr period – for which the sulfate deposition of 85 eruptions is found at both poles (bipolar eruptions). Based on the ratio of Greenland and Antarctic sulfate deposition, we estimate the latitudinal band of the bipolar eruptions and assess their approximate climatic forcing based on established methods. A total of 25 of the identified bipolar eruptions are larger than any volcanic eruption occurring in the last 2500 years, and 69 eruptions are estimated to have larger sulfur emission strengths than the Tambora, Indonesia, eruption (1815 CE). Throughout the investigated period, the frequency of volcanic eruptions is rather constant and comparable to that of recent times. During the deglacial period (16–9 ka b2k), however, there is a notable increase in the frequency of volcanic events recorded in Greenland and an obvious increase in the fraction of very large eruptions. For Antarctica, the deglacial period cannot be distinguished from other periods. This confirms the suggestion that the isostatic unloading of the Northern Hemisphere (NH) ice sheets may be related to the enhanced NH volcanic activity. Our ice-core-based volcanic sulfate records provide the atmospheric sulfate burden and estimates of climate forcing for further research on climate impact and understanding the mechanism of the Earth system.

What drives the solar energy transition? The effect of policies, incentives and behavior in a cross-country comparison

Abstract: The development of photovoltaic (PV) systems in Southern Europe has been boosted by favourable sunshine levels but also by the policies implemented. Europe's ambitious plans for a green transition require new power to be installed but also new consumption habits that tend to be more responsible. The transformation of cities goes through the emergence of prosumers and the percentage of self-consumption is the variable that determines the profitability of PV systems. This work is based on an online energy survey conducted in two southern European countries (i.e. Italy and Spain), in which both expectations and behaviour of consumers with regards to solar energy are compared between countries. Among other things, interviewees were asked to quantify the introduction of a subsidy for self-consumption. Interestingly, results show an average of 4 cent€/kWh and 3 cent€/kWh for Italy and Spain, respectively. Additionally, the survey allowed eliciting the price subjects believe one ought to pay for both fossil fuel-based and renewable energy, resulting in a green premium of 10 cent€/kWh and 8 cent€/kWh for Italy and Spain, respectively. Finally, the crucial role played by policies in shaping consumers’ perceptions emerged as decisive in fostering the development of PV systems in European countries.

Volcanic stratospheric sulfur injections and aerosol optical depth during the Holocene (past 11 500 years) from a bipolar ice-core array

Abstract: Abstract. The injection of sulfur into the stratosphere by volcanic eruptions is the dominant driver of natural climate variability on interannual to multidecadal timescales. Based on a set of continuous sulfate and sulfur records from a suite of ice cores from Greenland and Antarctica, the HolVol v.1.0 database includes estimates of the magnitudes and approximate source latitudes of major volcanic stratospheric sulfur injection (VSSI) events for the Holocene (from 9500 BCE or 11 500 years BP to 1900 CE), constituting an extension of the previous record by 7000 years. The database incorporates new-generation ice-core aerosol records with a sub-annual temporal resolution and a demonstrated sub-decadal dating accuracy and precision. By tightly aligning and stacking the ice-core records on the WD2014 chronology from Antarctica, we resolve long-standing inconsistencies in the dating of ancient volcanic eruptions that arise from biased (i.e., dated too old) ice-core chronologies over the Holocene for Greenland. We reconstruct a total of 850 volcanic eruptions with injections in excess of 1 teragram of sulfur (Tg S); of these eruptions, 329 (39 %) are located in the low latitudes with bipolar sulfate deposition, 426 (50 %) are located in the Northern Hemisphere extratropics (NHET) and 88 (10 %) are located in the Southern Hemisphere extratropics (SHET). The spatial distribution of the reconstructed eruption locations is in agreement with prior reconstructions for the past 2500 years. In total, these eruptions injected 7410 Tg S into the stratosphere: 70 % from tropical eruptions and 25 % from NH extratropical eruptions. A long-term latitudinally and monthly resolved stratospheric aerosol optical depth (SAOD) time series is reconstructed from the HolVol VSSI estimates, representing the first Holocene-scale reconstruction constrained by Greenland and Antarctica ice cores. These new long-term reconstructions of past VSSI and SAOD variability confirm evidence from regional volcanic eruption chronologies (e.g., from Iceland) in showing that the Early Holocene (9500–7000 BCE) experienced a higher number of volcanic eruptions (+16 %) and cumulative VSSI (+86 %) compared with the past 2500 years. This increase coincides with the rapid retreat of ice sheets during deglaciation, providing context for potential future increases in volcanic activity in regions under projected glacier melting in the 21st century. The reconstructed VSSI and SAOD data are available at https://doi.org/10.1594/PANGAEA.928646 (Sigl et al., 2021).

A novel unsupervised approach based on the hidden features of Deep Denoising Autoencoders for COVID-19 disease detection

Abstract: Chest imaging can represent a powerful tool for detecting the Coronavirus disease 2019 (COVID-19). Among the available technologies, the chest Computed Tomography (CT) scan is an effective approach for reliable and early detection of the disease. However, it could be difficult to rapidly identify by human inspection anomalous area in CT images belonging to the COVID-19 disease. Hence, it becomes necessary the exploitation of suitable automatic algorithms able to quick and precisely identify the disease, possibly by using few labeled input data, because large amounts of CT scans are not usually available for the COVID-19 disease. The method proposed in this paper is based on the exploitation of the compact and meaningful hidden representation provided by a Deep Denoising Convolutional Autoencoder (DDCAE). Specifically, the proposed DDCAE, trained on some target CT scans in an unsupervised way, is used to build up a robust statistical representation generating a target histogram. A suitable statistical distance measures how this target histogram is far from a companion histogram evaluated on an unknown test scan: if this distance is greater of a threshold, the test image is labeled as anomaly, i.e. the scan belongs to a patient affected by COVID-19 disease. Some experimental results and comparisons with other state-of-the-art methods show the effectiveness of the proposed approach reaching a top accuracy of 100% and similar high values for other metrics. In conclusion, by using a statistical representation of the hidden features provided by DDCAEs, the developed architecture is able to differentiate COVID-19 from normal and pneumonia scans with high reliability and at low computational cost.

A consensus document on definition and diagnostic criteria for orthorexia nervosa

Abstract: Abstract Purpose Since the term orthorexia nervosa (ON) was coined from the Greek (ὀρθός, right and ὄρεξις, appetite) in 1997 to describe an obsession with “correct” eating, it has been used worldwide without a consistent definition. Although multiple authors have proposed diagnostic criteria, and many theoretical papers have been published, no consensus definition of ON exists, empirical primary evidence is limited, and ON is not a standardized diagnosis. These gaps prevent research to identify risk and protective factors, pathophysiology, functional consequences, and evidence-based therapeutic treatments. The aims of the current study are to categorize the common observations and presentations of ON pathology among experts in the eating disorder field, propose tentative diagnostic criteria, and consider which DSM chapter and category would be most appropriate for ON should it be included. Methods 47 eating disorder researchers and multidisciplinary treatment specialists from 14 different countries across four continents completed a three-phase modified Delphi process, with 75% agreement determined as the threshold for a statement to be included in the final consensus document. In phase I, participants were asked via online survey to agree or disagree with 67 statements about ON in four categories: A–Definition, Clinical Aspects, Duration; B–Consequences; C–Onset; D–Exclusion Criteria, and comment on their rationale. Responses were used to modify the statements which were then provided to the same participants for phase II, a second round of feedback, again in online survey form. Responses to phase II were used to modify and improve the statements for phase III, in which statements that met the predetermined 75% of agreement threshold were provided for review and commentary by all participants. Results 27 statements met or exceeded the consensus threshold and were compiled into proposed diagnostic criteria for ON. Conclusions This is the first time a standardized definition of ON has been developed from a worldwide, multidisciplinary cohort of experts. It represents a summary of observations, clinical expertise, and research findings from a wide base of knowledge. It may be used as a base for diagnosis, treatment protocols, and further research to answer the open questions that remain, particularly the functional consequences of ON and how it might be prevented or identified and intervened upon in its early stages. Although the participants encompass many countries and disciplines, further research will be needed to determine if these diagnostic criteria are applicable to the experience of ON in geographic areas not represented in the current expert panel. Level of evidence Level V: opinions of expert committees

Stillbirth and fetal capillary infection by SARS-CoV-2.

Abstract: We present the case of a stillbirth in a paucisymptomatic mother affected by SARS-CoV-2. At gross examination, the placenta showed a diffuse marbled appearance and a focal hemorrhagic area. Multiple areas of hemorrhagic/ischemic necrosis with central and peripheral villous infarctions and thrombosis of several maternal and fetal vessels with luminal fibrin and platelet deposition was observed. All the lesions appeared to be synchronous. Virus particles were identified by Electron Microscopy within the cytoplasm of endothelial cells whereas, by real time rRT-PCR assay, SARS-CoV-2 RNA was detected in placental tissue. In this case, fetal vascular malperfusion was likely casually associated with the infection; indeed, our EM images clearly showed that the marked SARS-CoV-2 endotheliotropism involved the intravillous fetal capillaries. We confirmed that syncytiotrophoblast is the major target cell type for SARS-CoV-2 infection of the placenta. In conclusion, the possible consequences of the action of the placentotropic SARS-CoV-2 include the occurrence of vertical transmission, as reported in literature, and/or stillbirth: this latter possibility may be triggered by a hampered maternal and/or fetal perfusion of the placenta. The diffuse thrombosis and subsequent ischemia of fetal capillaries induced by COVID-19 cannot be predicted by standard clinical surveillance.

Be good to be wise: Environmental, Social, and Governance awareness as a potential credit risk mitigation factor

Abstract: Integrating Environmental, Social, and Governance (ESG) factors into credit risk assessment is the new frontier for credit risk management as regulators and investors increasingly require banks to channel loans to “sustainable” borrowers and ultimately foster sustainable growth. Our findings show that higher ESG awareness is strongly associated with better creditworthiness (proxied by the Altman Z-score). We apply a two-step methodology to 3331 companies from various industries and geographies in the 2000–2016 period which reveals that high ESG awareness scores are strongly and very significantly associated with a reduction in firm credit risk. We check the robustness by using the Probability of Default as a dependent variable and an instrumental variable constructed with a factor analysis. Our results support the appropriateness of the introduction of ESG awareness parameters in the creditworthiness assessment of borrowers.

Acute Intoxications and Fatalities Associated With Benzimidazole Opioid (Nitazene Analog) Use: A Systematic Review

Abstract: Synthetic benzimidazole opioids (BOs) are highly potent µ-opioid receptor agonists with heroin-like effects. Isotonitazene was first available in 2019 in the drug market, although new analogs have multiplied recently. The authors aimed to identify BO use trends and gather toxicological data from BO-related cases to assist in clinical and forensic investigations.A systematic literature search was conducted according to the PRISMA guidelines. PubMed and Scopus databases were accessed in October 2021 to identify scientific reports of BO-related intoxication and fatalities. Publication dates, case descriptions, symptoms, autopsy findings, and concentrations of BOs and metabolites in biological matrices were compiled.Data from 8 case reports with 93 fatalities involving isotonitazene ( n = 65), metonitazene ( n = 20), etonitazepyne ( N -pyrrolidino etonitazene) ( n = 8), flunitazene ( n = 4), and/or butonitazene ( n = 1), and 1 acute intoxication involving etonitazepyne were collected. Autopsy findings included pulmonary congestion/high lung weight (66%), cardiomegaly/high cardiac weight (39%), cerebral edema (22%), gastric contents in the airways (22%), and organ congestion (22%). Median peripheral blood concentrations were 1.7 ng/mL for isotonitazene (0.4-9.5 ng/mL, n = 13), 5.4 ng/mL for metonitazene (0.52-33 ng/mL, n = 17), 5.4 ng/mL for etonitazepyne (2.4-8.3 ng/mL, n = 2), 1.3 ng/mL for flunitazene (0.58-2.1 ng/mL, n = 2), and 3.2 ng/mL for butonitazene ( n = 1). Central nervous system depressants were almost always coadministered.Isotonitazene was predominant in cases from 2019 to mid-2020 and was replaced by metonitazene after scheduling in the United States. Typical findings on opioid overdoses have been reported. Peripheral blood concentrations were consistent with a potency similar to that of fentanyl. These results must be interpreted carefully, considering the scarcity of reports on BO-related cases and drug co-exposures.