Showing papers by "Marche Polytechnic University published in 2021"
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
TL;DR: Six human placentas, collected from consenting women with physiological pregnancies, were analyzed by Raman Microspectroscopy to evaluate the presence of microplastics, finding 12 microplastic fragments, with spheric or irregular shape, in total.
894 citations
06 Jun 2021
TL;DR: In this article, a RNN-free Transformer-based neural network for speech separation is proposed, which achieves state-of-the-art performance on the standard WSJ0-2/3mix datasets.
Abstract: Recurrent Neural Networks (RNNs) have long been the dominant architecture in sequence-to-sequence learning. RNNs, however, are inherently sequential models that do not allow parallelization of their computations. Transformers are emerging as a natural alternative to standard RNNs, replacing recurrent computations with a multi-head attention mechanism.In this paper, we propose the SepFormer, a novel RNN-free Transformer-based neural network for speech separation. The Sep-Former learns short and long-term dependencies with a multi-scale approach that employs transformers. The proposed model achieves state-of-the-art (SOTA) performance on the standard WSJ0-2/3mix datasets. It reaches an SI-SNRi of 22.3 dB on WSJ0-2mix and an SI-SNRi of 19.5 dB on WSJ0-3mix. The SepFormer inherits the parallelization advantages of Transformers and achieves a competitive performance even when downsampling the encoded representation by a factor of 8. It is thus significantly faster and it is less memory-demanding than the latest speech separation systems with comparable performance.
138 citations
TL;DR: In this article, the authors examined relevant clinical trial results with ICIs in patients with metastatic urothelial carcinoma (mUC) alone or as part of drug combinations; emphasis is also placed on the adjuvant and neoadjuvant setting.
Abstract: A number of immune checkpoint inhibitors (ICIs) have been approved as first-line therapy in case of cisplatin-ineligible patients or as second-line therapy for patients with metastatic urothelial carcinoma (mUC) of the bladder. About 30% of patients with mUC will respond to ICIs immunotherapy. Programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry seems to predict response to immune checkpoint inhibitors in patients with mUC as supported by the objective response rate (ORR) and overall survival (OS) associated with the response observed in most clinical trials. Pembrolizumab, an anti-PD-1 antibody, demonstrated better OS respective to chemotherapy in a randomized phase 3 study for second-line treatment of mUC. Nivolumab, a PD-1 antibody, also demonstrated an OS benefit when compared to controls. Atezolizumab, Durvalumab, and Avelumab antibodies targeting PD-L1 have also received approval as second-line treatments for mUC with durable response for more than 1 year in selected patients. Atezolizumab and Pembrolizumab also received approval for first-line treatment of patients that are ineligible for cisplatin. A focus on the utility of ICIs in the adjuvant or neoadjuvant setting, or as combination with chemotherapy, is the basis of some ongoing trials. The identification of a clinically useful biomarker, single or in association, to determine the optimal ICIs treatment for patients with mUC is very much needed as emphasized by the current literature. In this review, we examined relevant clinical trial results with ICIs in patients with mUC alone or as part of drug combinations; emphasis is also placed on the adjuvant and neoadjuvant setting. The current landscape of selected biomarkers of response to ICIs including anti-PD-L1 immunohistochemistry is also briefly reviewed.
116 citations
Johns Hopkins University1, Marche Polytechnic University2, University of Tennessee Health Science Center3, Cleveland Clinic4, Emory University5, Memorial Sloan Kettering Cancer Center6, Ohio State University7, University of Bern8, University of Southern California9, Koç University10, University of Texas Southwestern Medical Center11, Champalimaud Foundation12, St. Luke's Hospital13, McGill University14, Jikei University School of Medicine15, Mayo Clinic16, Federal University of Ceará17, University of Washington18, Pierre-and-Marie-Curie University19, Vanderbilt University20, University of Texas MD Anderson Cancer Center21, Northwestern University22, Oregon Health & Science University23, Tufts University24, Harvard University25, University of California, Los Angeles26, University of Calgary27, Kaiser Permanente28, Yale University29, Cornell University30, University of Miami31, University of Michigan32, University of Pennsylvania33, Université de Montréal34, Macquarie University35, University of Alabama at Birmingham36, Tata Memorial Hospital37, University of Rochester38, University of North Carolina at Chapel Hill39
TL;DR: Reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice and molecular testing is reviewed.
Abstract: Context— Controversies and uncertainty persist in prostate cancer grading Objective— To update grading recommendations Data Sources— Critical review of the literature along with pathology and
110 citations
University of Bologna1, National Research Council2, Humanitas University3, University of Turin4, University of Florence5, Catholic University of the Sacred Heart6, University of Rome Tor Vergata7, University of Milano-Bicocca8, University of Insubria9, University of Milan10, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico11, King's College London12, Marche Polytechnic University13, Carlos III Health Institute14, Leipzig University15, University of Paris16
TL;DR: In this paper, the authors integrate these genomic features into disease classification and prune classification in myelodysplastic syndromes (MDS) using a genetic algorithm.
Abstract: PURPOSERecurrently mutated genes and chromosomal abnormalities have been identified in myelodysplastic syndromes (MDS). We aim to integrate these genomic features into disease classification and pr...
105 citations
TL;DR: In this article, the authors focus on the role and potential of logistics in improving the effectiveness and sustainability of short food supply chains (SFSCs) and highlight its possible impact on SFSC development.
93 citations
TL;DR: In this article, the authors study the pricing of green bonds at the time of their issue and find a premium for green bonds issued by supranational institutions and corporates but no yield differences in case of issuances by financial institutions.
90 citations
TL;DR: In this article, the authors examined the double-stranded RNA (dsRNA) uptake in multiple pathogenic and non-pathogenic fungi, and an oomycete pathogen, and found that dsRNA uptake efficiencies vary across eukaryotic microbe species and cell types.
Abstract: Recent discoveries show that fungi can take up environmental RNA, which can then silence fungal genes through environmental RNA interference. This discovery prompted the development of Spray-Induced Gene Silencing (SIGS) for plant disease management. In this study, we aimed to determine the efficacy of SIGS across a variety of eukaryotic microbes. We first examined the efficiency of RNA uptake in multiple pathogenic and non-pathogenic fungi, and an oomycete pathogen. We observed efficient double-stranded RNA (dsRNA) uptake in the fungal plant pathogens Botrytis cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani, Aspergillus niger and Verticillium dahliae, but no uptake in Colletotrichum gloeosporioides, and weak uptake in a beneficial fungus, Trichoderma virens. For the oomycete plant pathogen, Phytophthora infestans, RNA uptake was limited and varied across different cell types and developmental stages. Topical application of dsRNA targeting virulence-related genes in pathogens with high RNA uptake efficiency significantly inhibited plant disease symptoms, whereas the application of dsRNA in pathogens with low RNA uptake efficiency did not suppress infection. Our results have revealed that dsRNA uptake efficiencies vary across eukaryotic microbe species and cell types. The success of SIGS for plant disease management can largely be determined by the pathogen's RNA uptake efficiency.
89 citations
Columbia University1, Cornell University2, George Washington University3, Yale University4, Universidade Federal do Rio Grande do Sul5, University Hospital of Basel6, University of Milano-Bicocca7, Carlos III Health Institute8, Hospital General Universitario Gregorio Marañón9, Hospital Authority10, Tianjin Medical University11, Aston University12, Mexican Social Security Institute13, Kyorin University14, Imperial College Healthcare15, University of São Paulo16, Tehran University of Medical Sciences17, University of Modena and Reggio Emilia18, University of Padua19, Marche Polytechnic University20, Rutgers University21, University of California, San Francisco22, Stanford University23, East Carolina University24, International Medical University25, Taiping Hospital26, Keimyung University27, University of Siena28, University of Texas Southwestern Medical Center29
87 citations
TL;DR: Radiologists had a mostly positive attitude toward the implementation of AI in their working practice, and were not concerned that AI will replace them, but rather that it might diminish their professional reputation.
Abstract: To report the results of a nationwide online survey on artificial intelligence (AI) among radiologist members of the Italian Society of Medical and Interventional Radiology (SIRM). All members were invited to the survey as an initiative by the Imaging Informatics Chapter of SIRM. The survey consisted of 13 questions about the participants’ demographic information, perceived advantages and issues related to AI implementation in radiological practice, and their overall opinion about AI. In total, 1032 radiologists (equaling 9.5% of active SIRM members for the year 2019) joined the survey. Perceived AI advantages included a lower diagnostic error rate (750/1027, 73.0%) and optimization of radiologists’ work (697/1027, 67.9%). The risk of a poorer professional reputation of radiologists compared with non-radiologists (617/1024, 60.3%), and increased costs and workload due to AI system maintenance and data analysis (399/1024, 39.0%) were seen as potential issues. Most radiologists stated that specific policies should regulate the use of AI (933/1032, 90.4%) and were not afraid of losing their job due to it (917/1032, 88.9%). Overall, 77.0% of respondents (794/1032) were favorable to the adoption of AI, whereas 18.0% (186/1032) were uncertain and 5.0% (52/1032) were unfavorable. Radiologists had a mostly positive attitude toward the implementation of AI in their working practice. They were not concerned that AI will replace them, but rather that it might diminish their professional reputation.
TL;DR: This paper provides a collection of the papers published on LAES and it classifies the various studies conducted in different categories, showing that hybrid LAES solutions with efficient design of the waste energy recovery sections are the most promising configuration to enhance the techno-economic performance of the stand-alone system.
Abstract: Liquid air energy storage (LAES) represents one of the main alternatives to large-scale electrical energy storage solutions from medium to long-term period such as compressed air and pumped hydro energy storage. Indeed, characterized by one of the highest volumetric energy density (≈200 kWh/m3), LAES can overcome the geographical constraints from which the actual mature large-scale electrical energy storage technologies suffer from. LAES is based on the concept that air can be liquefied, stored, and used at a later time to produce electricity. Although the liquefaction of air has been studied for over a century, the first concept of using cryogenics as energy storage was proposed for the first time in 1977 and rediscovered only in recent times. Indeed, the need for alternative energy vectors in the energy system attracted many researchers to discover the potential of the use of cryogenic media. This has brought the realization of a first LAES pilot plant and a growing number of studies regarding LAES systems. The main drawback of this technology is the low round-trip efficiency that can be estimated around 50–60% for large-scale systems. However, due to its thermo-mechanical nature, LAES is a versatile energy storage concept that can be easily integrated with other thermal energy systems or energy sources in a wide range of applications. Most of the literature published is based on thermodynamic and economic analysis focusing on different LAES configurations. This paper provides a collection of the papers published on LAES and it classifies the various studies conducted in different categories. Future perspectives show that hybrid LAES solutions with efficient design of the waste energy recovery sections are the most promising configuration to enhance the techno-economic performance of the stand-alone system.
12 Jan 2021
TL;DR: In this paper, the authors isolated and purified EPDENs from the strawberry juice of Fragaria x ananassa (cv. Romina), a new cultivar characterized by a high content of anthocyanins, folic acid, flavonols, and vitamin C and an elevated antioxidant capacity.
Abstract: Plant-derived exosome-like nanovesicles (EPDENs) have recently been isolated and evaluated as potential bioactive nutraceutical biomolecules. It has been hypothesized that EPDENs may exert their activity on mammalian cells through their specific cargo. In this study, we isolated and purified EPDENs from the strawberry juice of Fragaria x ananassa (cv. Romina), a new cultivar characterized by a high content of anthocyanins, folic acid, flavonols, and vitamin C and an elevated antioxidant capacity. Fragaria-derived EPDENs were purified by a series of centrifugation and filtration steps. EPDENs showed size and morphology similar to mammalian extracellular nanovesicles. The internalization of Fragaria-derived EPDENs by human mesenchymal stromal cells (MSCs) did not negatively affect their viability, and the pretreatment of MSCs with Fragaria-derived EPDENs prevented oxidative stress in a dose-dependent manner. This is possibly due to the presence of vitamin C inside the nanovesicle membrane. The analysis of EPDEN cargo also revealed the presence of small RNAs and miRNAs. These findings suggest that Fragaria-derived EPDENs may be considered nanoshuttles contained in food, with potential health-promoting activity.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico1, University of Milan2, University of Turin3, University of Catania4, University of Verona5, University of Bologna6, University of Pisa7, Sapienza University of Rome8, University of Rome Tor Vergata9, University of Florence10, Marche Polytechnic University11, University of Cagliari12, University of Ferrara13, University of Messina14, University of Brescia15, University of Palermo16, University of Naples Federico II17, Catholic University of the Sacred Heart18
TL;DR: The anti‐tumour necrosis factor (TNF)‐α adalimumab is the only licenced biologic for moderate‐to‐severe hidradenitis suppurativa (HS).
Abstract: BACKGROUND The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28-2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04-2·91, P = 0·0342). CONCLUSIONS Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a 'window of opportunity' in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non-TNF-α-driven pathways.
TL;DR: In this paper, a review of the role of non-coding RNA (miRNAs) in inflammaging is presented, focusing on two miRNAs, i.e., miR-21−5p and miR146a-5p, which target a variety of molecules belonging to the NF-κB/NLRP3 pathways.
TL;DR: The data show that a blood-based biomarker, such as miR-146a-5p, can provide clues about the molecular link between inflammaging and COVID-19 clinical course, thus allowing to better understand the use of biologic drug armory against this worldwide health threat.
Imperial College London1, Hebron University2, Institut Gustave Roussy3, Guy's and St Thomas' NHS Foundation Trust4, Université libre de Bruxelles5, Cardiff University6, Barts Health NHS Trust7, University College London8, University of Genoa9, University of Barcelona10, University of Trieste11, University of Pavia12, King's College London13, Ludwig Maximilian University of Munich14, Università Campus Bio-Medico15, University of Milan16, University of L'Aquila17, Marche Polytechnic University18, Humanitas University19
TL;DR: The OnCovid study as discussed by the authors evaluated the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer following SARS-CoV-2 infection.
Abstract: Summary Background The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection. Methods OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients' death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974. Findings 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4–57·8) from cancer diagnosis and 44 days (28–329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p Interpretation Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely affect survival and oncological outcomes after recovery. Adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients. Funding National Institute for Health Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.
TL;DR: Overall, main HAB risks derive from cases of massive development of microalgal biomass and consequent impacts of reduced coastal water quality on tourism, which represents the largest part of the marine economy along the MS coasts.
Imperial College London1, University of L'Aquila2, University of Turin3, Erasmus University Rotterdam4, Agostino Gemelli University Polyclinic5, Catholic University of the Sacred Heart6, University of Insubria7, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico8, Marche Polytechnic University9, Sapienza University of Rome10, Università Campus Bio-Medico11, Academy for Urban School Leadership12, Gonzaga University13, University of Messina14, University of Portsmouth15, University of Eastern Piedmont16
TL;DR: In this paper, the authors presented the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic non-small cell lung cancer (NSCLC) with a PD-L1 expression ≥ 50, receiving first-line pembrolizumab monotherapy.
Abstract: BACKGROUND Some concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate. METHODS We present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses. RESULTS 950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pembrolizumab and shorter OS (HR=1.12 (95% CI 1.02 to 1.24), p=0.0139), with chemotherapy. At the pooled analysis, there was a statistically significant interaction with treatment (pembrolizumab vs chemotherapy) for corticosteroids (p=0.0020) and PPIs (p=0.0460) with respect to OS, for corticosteroids (p<0.0001), ATB (p=0.0290), and PPIs (p=0.0487) with respect to PFS, and only corticosteroids (p=0.0033) with respect to objective response rate. CONCLUSION In this study, we validate the significant negative impact of ATB on pembrolizumab monotherapy but not chemotherapy outcomes in NSCLC, producing further evidence about their underlying immune-modulatory effect. Even though the magnitude of the impact of corticosteroids and PPIs is significantly different across the cohorts, their effects might be driven by adverse disease features.
TL;DR: A clustering-based approach, called cluster centers (CC), and a neural architecture based on the Siamese Autoencoders (SAE) are introduced, which are tailored for weakly supervised settings with very few labeled data samples and outperform state-of-the-art anomaly detection approaches very robustly for many different hyperparameter settings on all performance measures.
Abstract: The continuously growing amount of monitored data in the Industry 4.0 context requires strong and reliable anomaly detection techniques. The advancement of Digital Twin technologies allows for realistic simulations of complex machinery; therefore, it is ideally suited to generate synthetic datasets for the use in anomaly detection approaches when compared to actual measurement data. In this article, we present novel weakly supervised approaches to anomaly detection for industrial settings. The approaches make use of a Digital Twin to generate a training dataset, which simulates the normal operation of the machinery, along with a small set of labeled anomalous measurement from the real machinery. In particular, we introduce a clustering-based approach, called cluster centers (CC), and a neural architecture based on the Siamese Autoencoders (SAE), which are tailored for weakly supervised settings with very few labeled data samples. The performance of the proposed methods is compared against various state-of-the-art anomaly detection algorithms on an application to a real-world dataset from a facility monitoring system, by using a multitude of performance measures. Also, the influence of hyperparameters related to feature extraction and network architecture is investigated. We find that the proposed SAE-based solutions outperform state-of-the-art anomaly detection approaches very robustly for many different hyperparameter settings on all performance measures.
TL;DR: The study shows that the effect of corticosteroid treatment on mortality might be limited to critically ill COVID-19 patients.
University of Oxford1, Oxford Health NHS Foundation Trust2, St George’s University Hospitals NHS Foundation Trust3, University College London4, Faculty of Medicine and Pharmacy of Rabat5, Yarmouk University6, Marche Polytechnic University7, University of Auckland8, The Chinese University of Hong Kong9, University of Calgary10, King's College London11
TL;DR: The results show that students in all 12 countries report very high levels of ‘caseness’ on validated measures of psychiatric symptoms and burnout, and rates of substance misuse also varied across cultures.
Abstract: High levels of stress, burnout, and symptoms of poor mental health have been well known among practicing doctors for a number of years. Indeed, many health systems have formal and informal mechanisms to offer support and treatment where needed, though this varies tremendously across cultures. There is increasing evidence that current medical students, our doctors of the future, also report very high levels of distress, burnout, and substance misuse. We sampled large groups of medical students in 12 countries at the same time and with exactly the same method in order to aid direct comparison. 3766 students responded to our survey across five continents in what we believe is a global first. Our results show that students in all 12 countries report very high levels of 'caseness' on validated measures of psychiatric symptoms and burnout. Rates of substance misuse, often a cause of or coping mechanism for this distress, and identified sources of stress also varied across cultures. Variations are strongly influenced by cultural factors. Further quantitative and qualitative research is required to confirm our results and further delineate the causes for high rates of psychiatric symptoms and burnout. Studies should also focus on the implementation of strategies to safeguard and identify those most at risk.
TL;DR: The main empirical findings are that: (i) bitcoin exchange prices are positively related with each other and, among them, the largest exchanges, such as Bitstamp, drive the prices.
Abstract: We aim to understand the dynamics of crypto asset prices and, specifically, how price information is transmitted among different bitcoin market exchanges, and between bitcoin markets and traditional ones. To this aim, we hierarchically cluster bitcoin prices from different exchanges, as well as classic assets, by enriching the correlation based minimum spanning tree method with a preliminary filtering method based on the random matrix approach. Our main empirical findings are that: (i) bitcoin exchange prices are positively related with each other and, among them, the largest exchanges, such as Bitstamp, drive the prices; (ii) bitcoin exchange prices are not affected by classic asset prices, but their volatilities are, with a negative and lagged effect.
TL;DR: The magnitude of benefit of the ICI-TKI combination over sunitinib monotherapy in treatment-naïve mRCC patients was consistent across the clinicopathological subgroups and could assist clinicians and researchers in the design and interpretation of future clinical trials on combination therapies in this setting.
Abstract: Context Immune checkpoint inhibitors (ICIs) have reported unprecedented results in the treatment of metastatic renal cell carcinoma (mRCC) patients, as monotherapy or in combination with other anticancer agents. However, little information is available regarding the association between different clinicopathological features and survival in this setting. Objective We performed a meta-analysis aimed at exploring the predictive value of routinely collected clinicopathological data in randomized controlled trials (RCTs) evaluating ICIs plus tyrosine kinase inhibitors (TKIs) in treatment-naive patients with mRCC. Evidence acquisition We retrieved all the relevant RCTs through PubMed/Medline, Cochrane Library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible studies included RCTs assessing first-line ICI-TKI versus sunitinib in treatment-naive mRCC patients; the primary endpoint was overall survival (OS), measured as hazard ratio (HR) with corresponding 95% confidence interval (CI). Evidence synthesis Overall, three phase III RCTs involving 1769 patients with advanced or metastatic RCC were included. Compared with sunitinib, the ICI-TKI combination significantly decreased the risk of death in patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) 0 (HR, 0.66; 95% CI, 0.57–0.76) and ECOG-PS 1 (HR, 0.64; 95% CI, 0.54–0.77). Similarly, the combination was associated with prolonged OS in patients who were Conclusions According to our results, the magnitude of benefit of the ICI-TKI combination over sunitinib monotherapy in treatment-naive mRCC patients was consistent across the clinicopathological subgroups. Despite the limitations affecting the analysis, we believe that the results of the current meta-analysis could assist clinicians and researchers in the design and interpretation of future clinical trials on combination therapies in this setting. Patient summary First-line combinations of an immune checkpoint inhibitor plus a tyrosine kinase inhibitor improved survival in metastatic renal cell carcinoma (mRCC) patients. This survival benefit was consistent across all subgroups of mRCC patients irrespective of clinicopathological features such as patient performance status, age
TL;DR: In this article, an analysis of industry 4.0's key technologies' impact on company performance and performance is presented, which is one of the primary paradigms of the current industrial context.
Abstract: Industry 4.0 is one of the primary paradigms of the current industrial context. Despite the widespread research on this topic, an analysis of its key technologies' impact on company performance and...
TL;DR: Support is provided to a reliable use of alternative/underexploited protein and lipid sources [(HM) or (PBM)] in developing a new generation of sustainable and healthy trout diets that meet the circular economy principles.
TL;DR: The results are the first to report of PP-MPs inhibition on anaerobic processes and suggested the need to further investigate the effects of MPs on an aerobic processes.
TL;DR: In this paper, high blood pressure variability (BPV) was linked with stroke and cerebrovascular disease, however, its association with cognition remains unclear and it remains uncertain which BP-derive...
Abstract: Research links high blood pressure variability (BPV) with stroke and cerebrovascular disease, however, its association with cognition remains unclear. Moreover, it remains uncertain which BP-derive...
TL;DR: In this article, the authors report the prevalence and outcome of silent hypoxemia in a series of hypoxemic patients upon emergency department admission, and the presence of dyspnea is associated with a more severe clinical condition.
Abstract: BACKGROUND: In the early stages of COVID-19 pneumonia, hypoxemia has been described in absence of dyspnea ("silent" or "happy" hypoxemia). Our aim was to report its prevalence and outcome in a series of hypoxemic patients upon Emergency Department admission. METHODS: In this retrospective observational cohort study we enrolled a study population consisting of 213 COVID-19 patients with PaO 2 /FiO 2 ratio 2 /FiO 2 ratio was 225±68 mmHg and 192±78 mmHg in silent and dyspneic hypoxemia respectively (P=0.002). Eighteen percent of the patients with PaO 2 /FiO 2 from 50 to 150 mmHg presented silent hypoxemia. Silent and dyspneic hypoxemic patients had similar PaCO 2 (34.2±6.8 mmHg vs. 33.5±5.7 mmHg, P=0.47) but different respiratory rates (24.6±5.9 bpm vs. 28.6±11.3 bpm respectively, P=0.002). Even when CXR was severely abnormal, 25% of the population was silent hypoxemic. Twenty-six point five percent and 38.6% of silent and dyspneic patients were admitted to the ICU respectively (P=0.082). Mortality rate was 17.6% and 29.7% (log-rank P=0.083) in silent and dyspneic patients. CONCLUSIONS: Silent hypoxemia is remarkably present in COVID-19. The presence of dyspnea is associated with a more severe clinical condition.
TL;DR: In this paper, the authors used matched bond-issuer data to test whether green bond issues are associated with a reduction in total and direct (Scope 1) emissions of nonfinancial companies.
Abstract: Although green bonds are becoming increasingly popular in the corporate finance practice, little is known about their implications and effectiveness in terms of issuers' environmental engagement. With the use of matched bond‐issuer data, we test whether green bond issues are associated to a reduction in total and direct (Scope 1) emissions of nonfinancial companies. We find that, compared with conventional bond issuers with similar financial characteristics and environmental ratings, green issuers display a decrease in the carbon intensity of their assets after borrowing on the green segment. The decrease in emissions is more pronounced, significant and long‐lasting when we exclude green bonds with refinancing purposes, which is consistent with an increase in the volume of climate‐friendly activities due to new projects. We also find a larger reduction in emissions in case of green bonds that have external review, as well as those issued after the Paris Agreement.