End-to-End Supervised Multilabel Contrastive Learning

Multilabel representation learning is recognized as a challenging problem that can be associated with either label dependencies between object categories or data-related issues such as the inherent imbalance of positive/negative samples. Recent advances address these challenges from model- and data-centric viewpoints. In model-centric, the label correlation is obtained by an external model designs (e.g., graph CNN) to incorporate an inductive bias for training. However, they fail to design an end-to-end training framework, leading to high computational complexity. On the contrary, in data-centric, the realistic nature of the dataset is considered for improving the classification while ignoring the label dependencies. In this paper, we propose a new end-to-end training framework -- dubbed KMCL (Kernel-based Mutlilabel Contrastive Learning) -- to address the shortcomings of both model- and data-centric designs. The KMCL first transforms the embedded features into a mixture of exponential kernels in Gaussian RKHS. It is then followed by encoding an objective loss that is comprised of (a) reconstruction loss to reconstruct kernel representation, (b) asymmetric classification loss to address the inherent imbalance problem, and (c) contrastive loss to capture label correlation. The KMCL models the uncertainty of the feature encoder while maintaining a low computational footprint. Extensive experiments are conducted on image classification tasks to showcase the consistent improvements of KMCL over the SOTA methods. PyTorch implementation is provided in \url{https://github.com/mahdihosseini/KMCL}

Biochemical responses of Alfalfa (Medicago sativa L.) cultivars subjected to NaCl salinity stress

This investigation was conducted to determine NaCl salinity effects on antioxidant enzyme s activities, reducing sugar contents and lipid peroxidation in two alfalfa cultivars. Plants grown in solution cultures were subjected to 0, 100, 150 and 200 mM solutions of sodium chloride. Yazdi and Diabolourde alfalfa were used as tolerant and sensitive cultivars, respectively, in a germination experiment under similar conditions. Results show that the amount of reducing sugars and the activities of peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX) and superoxide dismutase (SOD) enzymes increased with the increase in salt concentration. However, SOD activities decreased at high salt concentrations. The increase in the activities of antioxidant enzymes in response to salt treatments was higher in the tolerant cultivar. The results also show that salt treatment provoked an oxidative stress in both cultivars, as shown by the increase in lipid peroxidation. However, the level of lipid peroxidation was higher in the sensitive cultivar. The increase in antioxidant activities could also be a response to the cellular damage induced by NaCl. It seems that the tolerant cultivar has a better mechanism to cope with the deleterious effects ROS produced under salt stress.Key words: Alfalfa, antioxidant enzymes, malondialdehyde, salt stress

Motor Developmental Delay in 7500 Iranian Infants: Prevalence and Risk Factors

ObjectiveThe purpose of this study was to determine the prevalence and the most common risk factors of motor developmental delay in infants.Materials & MethodsFollowing ethical approval, a study was carried out on the prevalence and risk factors of infants with motor developmental delay. The first stage was conducted through a cross-sectional study to determine the prevalence of motor developmental delay on 7500 infants and the second stage was an analytic case - control survey to identify the most common risk factors on 140 infants, aged one month to three years with motor developmental delay. Data was collected using a demographic questionnaire, the Parents Evaluation of Developmental Status questionnaire, the Denver Developmental Screening Test II, a neurological assessment form, and the movement and tone assessment form.ResultsThe prevalence of motor developmental delay in 7500 infants was 18.7/1000. The most common risk factors in infants with motor developmental delay were prematurity (25.6%), low birth weight (19.2%), neonatal seizures (7.5%), hyaline membrane disease (6.7%), systemic infections of mothers during pregnancy (5.9%), severe neonatal hyperbilirubinemia (5%) in sequence. Motor developmental delay was significantly correlated with consanguinity of parents (p=0.001), prematurity (p=0.046), abnormal head circumference at birth (p=0.038), and low birth weight (p=0.026).ConclusionThe prevalence of motor developmental delay appears to be high and further studies should focus on different preventive strategies, controlling the most common risk factors and emphasizing on early detection and treatment of high risk infants.

Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer's disease

Tau deposition in the brain is a pathological hallmark of many neurodegenerative disorders, including Alzheimer’s disease (AD). During the course of these tauopathies, tau spreads throughout the brain via synaptically-connected pathways. Such propagation of pathology is thought to be mediated by tau species (“seeds”) containing the microtubule binding region (MTBR) composed of either three repeat (3R) or four repeat (4R) isoforms. The tau MTBR also forms the core of the neuropathological filaments identified in AD brain and other tauopathies. Multiple approaches are being taken to limit tau pathology, including immunotherapy with anti-tau antibodies. Given its key structural role within fibrils, specifically targetting the MTBR with a therapeutic antibody to inhibit tau seeding and aggregation may be a promising strategy to provide disease-modifying treatment for AD and other tauopathies. Therefore, a monoclonal antibody generating campaign was initiated with focus on the MTBR. Herein we describe the pre-clinical generation and characterisation of E2814, a humanised, high affinity, IgG1 antibody recognising the tau MTBR. E2814 and its murine precursor, 7G6, as revealed by epitope mapping, are antibodies bi-epitopic for 4R and mono-epitopic for 3R tau isoforms because they bind to sequence motif HVPGG. Functionally, both antibodies inhibited tau aggregation in vitro. They also immunodepleted a variety of MTBR-containing tau protein species. In an in vivo model of tau seeding and transmission, attenuation of deposition of sarkosyl-insoluble tau in brain could also be observed in response to antibody treatment. In AD brain, E2814 bound different types of tau filaments as shown by immunogold labelling and recognised pathological tau structures by immunohistochemical staining. Tau fragments containing HVPGG epitopes were also found to be elevated in AD brain compared to PSP or control. Taken together, the data reported here have led to E2814 being proposed for clinical developmen

On the problem of Dirac cones in fullerenes on gold

Artificial graphene based on molecular networks enables the creation of novel 2D materials with unique electronic and topological properties. Landau quantization has been demonstrated by CO molecules arranged on the two dimensional electron gas on Cu 111 and the observation of electron quantization may succeed based on the created gauge fields. Recently, it was reported that instead of individual manipulation of CO molecules, simple deposition of nonpolar C60 molecules on Cu 111 and Au 111 produces artificial graphene as evidenced by Dirac cones in photoemission spectroscopy. Here, we show that C60 induced Dirac cones on Au 111 have a different origin. We argue that those are related to umklapp diffraction of surface electronic bands of Au on the molecular grid of C60 in the final state of photoemission. We test this alternative explanation by precisely probing the dimensionality of the observed conical features in the photoemission spectra, by varying both the incident photon energy and the degree of charge doping via alkali adatoms. Using density functional theory calculations and spin resolved photoemission we reveal the origin of the replicating Au 111 bands and resolve them as deep leaky surface resonances derived from the bulk Au sp band residing at the boundary of its surface projection. We also discuss the manifold nature of these resonances which gives rise to an onion like Fermi surface of Au 11

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study

Background: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. Methods: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. Findings: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9) patients had a stroke�123(79) ischaemic stroke, 27(17) intracerebral/subarachnoid hemorrhage, and 6(4) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5 among all centres in all countries, and 0.7 among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95 CI:1.1�3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95 CI:1.4�4.7, p = 0.006) were predictive of stroke. Interpretation: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5(pooled risk: 0.9). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. Funding: None. © 2020 The Author