Relaxing the Forget Constraints in Open World Recognition

In the last few years deep neural networks has significantly improved the state-of-the-art of robotic vision. However, they are mainly trained to recognize only the categories provided in the training set (closed world assumption), being ill equipped to operate in the real world, where new unknown objects may appear over time. In this work, we investigate the open world recognition (OWR) problem that presents two challenges: (i) learn new concepts over time (incremental learning) and (ii) discern between known and unknown categories (open set recognition). Current state-of-the-art OWR methods address incremental learning by employing a knowledge distillation loss. It forces the model to keep the same predictions across training steps, in order to maintain the acquired knowledge. This behaviour may induce the model in mimicking uncertain predictions, preventing it from reaching an optimal representation on the new classes. To overcome this limitation, we propose the Poly loss that penalizes less the changes in the predictions for uncertain samples, while forcing the same output on confident ones. Moreover, we introduce a forget constraint relaxation strategy that allows the model to obtain a better representation of new classes by randomly zeroing the contribution of some old classes from the distillation loss. Finally, while current methods rely on metric learning to detect unknown samples, we propose a new rejection strategy that sidesteps it and directly uses the model classifier to estimate if a sample is known or not. Experiments on three datasets demonstrate that our method outperforms the state of the art

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Manifesto on the overuse of SABA in the management of asthma: new approaches and new strategies

The risks of overusing short-acting beta(2)-agonists (SABA), including an increase in asthma-related deaths, are many and well known. The Global Initiative on Asthma (GINA) 2019 and 2020 updates recommend as-needed inhaled corticosteroid (ICS)/formoterol as the preferred rescue medication in mild asthma as monotherapy and also in moderate to severe asthma when the maintenance and reliever therapy (MART) strategy is used. Using SABA for symptom relief, however, was the standard of treatment for many years, and consequently this practice persists, particularly in patients not taking ICS regularly. Here, we examine the rationale for this shift from a long-standing recommendation for as-needed SABA treatment to the use of as-needed ICS/formoterol and consider clinical evidence on strategies for asthma treatment and patient management

Clinical Evaluation of the Optical Filter for Autofluorescence Glasses for Oral Cancer Curing Light Exposed (GOCCLES®) in the Management of Potentially Premalignant Disorders: A Retrospective Study

Background: Any oral potentially malignant disorders (OPMDs) must be regularly monitored through clinical examination to detect any possible malignant transformation. Conventional intraoral exams, however, can be difficult because these conditions may resemble benign lesions. For this reason, several non-invasive diagnostic technologies have been developed to help the clinician in detecting and distinguishing between cancerous and benign lesions. Epithelial dysplasia can be considered the most important predictor of malignant evolution. Therefore, in this study we aim to evaluate the ability of an optical filter for autofluorescence Glasses for Oral Cancer Curing Light Exposed (GOCCLES®) and of toluidine blue staining in identifying dysplastic areas in patients with OPMDs. Methods: In this retrospective study, medical records, photographs and videos of 25 patients with oral lesions were analyzed. Forty-two biopsy samples in 25 patients with OPMDs and at least one suspicious oral mucosa lesion that were evaluated in white light, autofluorescence with optical filter GOCCLES®, toluidine blue staining and then biopsied with histopathological analysis were analyzed. Results: The sensitivity and specificity for the autofluorescence evaluation with GOCCLES® for identifying dysplasia or carcinoma were 66% and 48%, respectively. The positive and negative predictive values were 34% and 77%, respectively, and the accuracy was 53%. The sensitivity and specificity for toluidine blue staining were 91% and 68%, respectively. The positive and negative predictive values were 55% and 95%, respectively, and the accuracy was 75%. Conclusions: The optical filter for autofluorescence (GOCCLES®) and toluidine blue staining are simple, inexpensive, rapid and non-invasive procedures that can assist the clinician in distinguishing OPMDs from healthy mucosa but they are not able to distinguish benign and malignant lesions

Diagnosis and management of moderate to severe atopic dermatitis in adolescents. A Consensus by the Italian Society of Dermatology and Venereology (SIDeMaST), the Italian Association of Hospital Dermatologists and Public Health (ADOI), the Italian Association of Hospital and Territorial Allergists and Immunologists (AAIITO), the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC), the Italian Society of Pediatric Allergy and Immunology (SIAIP), the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA), and the Italian Society of Pediatric Dermatology (SIDerP)

Atopic dermatitis (AD) is a chronic inflammatory disease with increasing global incidence, which has a multifactorial pathogenesis and a variable expressivity. Clinical features of AD are different in adults compared to children, but it is well recognized the substantial impact of the disease on patients' quality of life at any age. Indeed, little is known about AD in adolescence, a period of life generally associated with high psychological burden and vulnerability to depression. Guidelines for the management of AD are available for both children and adults but specific guidelines for the diagnosis and treatment of AD in adolescents are lacking. Seven Italian scientific societies of dermatologists, allergists, and pediatric allergists joined in a specific meeting to provide practical guidance for the diagnosis and management of moderate-to-severe adolescent AD suitable for the Italian clinical practice. Through a modified Delphi procedure, consensus was reached by 59 Italian experts in the management of AD on 20 statements covering five areas of interest about adolescent AD, including disease complexity, burden and social impact, diagnosis and definition of severity, current treatments, and new biologic therapies. This paper reports recommendations for the diagnosis and management of AD specifically in adolescents, pointing out some peculiar clinical features and focusing on the choice of medications. Dupilumab, the first biologic approved for the treatment of adolescents with AD, represents a useful treatment option due to its efficacy and reassuring safety profile

Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration

The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString® technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field

Mepolizumab effectiveness and allergic status in real life

It is not clear whether mepolizumab is differently effective in allergic and nonallergic severe eosinophilic asthmatics (SEA) in real life