SGDE: Secure Generative Data Exchange for Cross-Silo Federated Learning

Privacy regulation laws, such as GDPR, impose transparency and security as design pillars for data processing algorithms. In this context, federated learning is one of the most influential frameworks for privacy-preserving distributed machine learning, achieving astounding results in many natural language processing and computer vision tasks. Several federated learning frameworks employ differential privacy to prevent private data leakage to unauthorized parties and malicious attackers. Many studies, however, highlight the vulnerabilities of standard federated learning to poisoning and inference, thus raising concerns about potential risks for sensitive data. To address this issue, we present SGDE, a generative data exchange protocol that improves user security and machine learning performance in a cross-silo federation. The core of SGDE is to share data generators with strong differential privacy guarantees trained on private data instead of communicating explicit gradient information. These generators synthesize an arbitrarily large amount of data that retain the distinctive features of private samples but differ substantially. In this work, SGDE is tested in a cross-silo federated network on images and tabular datasets, exploiting beta-variational autoencoders as data generators. From the results, the inclusion of SGDE turns out to improve task accuracy and fairness, as well as resilience to the most influential attacks on federated learning

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

SGDE: Secure Generative Data Exchange for Cross-Silo Federated Learning

Privacy regulation laws, such as GDPR, impose transparency and security as design pillars for data processing algorithms. In this context, federated learning is one of the most influential frameworks for privacy-preserving distributed machine learning, achieving astounding results in many natural language processing and computer vision tasks. Several federated learning frameworks employ differential privacy to prevent private data leakage to unauthorized parties and malicious attackers. Many studies, however, highlight the vulnerabilities of standard federated learning to poisoning and inference, thus raising concerns about potential risks for sensitive data. To address this issue, we present SGDE, a generative data exchange protocol that improves user security and machine learning performance in a cross-silo federation. The core of SGDE is to share data generators with strong differential privacy guarantees trained on private data instead of communicating explicit gradient information. These generators synthesize an arbitrarily large amount of data that retain the distinctive features of private samples but differ substantially. In this work, SGDE is tested in a cross-silo federated network on images and tabular datasets, exploiting beta-variational autoencoders as data generators. From the results, the inclusion of SGDE turns out to improve task accuracy and fairness, as well as resilience to the most influential attacks on federated learning

Palliative needs for heart failure or chronic obstructive pulmonary disease: Results of a multicenter observational registry

Background: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) share a common organ failure trajectory marked by prognostic uncertainty, which is a barrier to appropriate provision of palliative care. We describe in a prospective cohort from specialist hospital services the epidemiology and late clinical course of these chronic diseases to trace criteria for transition to palliative care in the community. Methods and results: Seven centers enrolled 267 patients with advanced HF (n = 174) or COPD (n = 93) using common (multiple hospitalizations or severely impaired functional status or cachexia) and disease-specific (HF: systolic dysfunction, NYHA classes III-IV, end-organ hypoperfusion; COPD: very severe airflow obstruction, hypoxemia, hypercapnia, or long-term oxygen therapy) entry criteria. These patients represented 7.2% and 13% respectively of the overall HF and COPD population hospitalized during one year. They showed similar symptom burden, functional and quality of life impairment, recurrent hospitalizations, and 6-month mortality (39% and 37%, respectively). Organ failure progression was the cause of death in >75%. In-hospital overall stay during the previous year was the main mortality predictor in both. Disease-specific predictors included anemia, hyponatremia, no beta-blockers in HF; older age, hypercapnia in COPD. Conclusions: Patients with advanced HF/COPD represent almost 10% of subjects hospitalized yearly with a primary diagnosis of HF or COPD, have similarly impaired functional status, disabling symptoms and reduced survival. Overall days spent in-hospital during the previous year, a "red flag" in the late clinical course of both diseases, might be used as a simple, reliable screening tool for appropriate transition to palliative care in the community

Usefulness of intracardiac echocardiography for the diagnosis of cardiovascular implantable electronic device-related endocarditis

The goal of this study was to compare transesophageal echocardiography (TEE) and intracardiac echocardiography (ICE) for the diagnosis of cardiac device-related endocarditis (CDI)