ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy

This article is a preprint and has not been peer-reviewed. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.medRxiv 2020.03.30.20047878. This article is a preprint and has not been peer-reviewed. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.Background: As the outbreak of coronavirus disease 2019 (COVID-19) progresses, prognostic markers for early identification of high-risk individuals are an urgent medical need. Italy has the highest rate of SARS-CoV-2 infection, the highest number of deaths, and the highest mortality rate among large countries. Worldwide, a more severe course of COVID-19 is associated with older age, comorbidities, and male sex. Hence, we searched for possible genetic components of the peculiar severity of COVID-19 among Italians, by looking at expression levels and variants in ACE2 and TMPRSS2 genes, which are crucial for viral infection. Methods: Exome and SNP array data from a large Italian cohort representative of the country's population were used to compare the burden of rare variants and the frequency of polymorphisms with European and East Asian populations. Moreover, we looked into gene expression databases to check for sex-unbalanced expression. Results: While we found no significant evidence that ACE2 is associated with disease severity/sex bias in the Italian population, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, contributing to the observed epidemiological data among Italian patients. Conclusions: Our analysis suggests a role for TMPRSS2 variants and expression levels in modulating COVID-19 severity, a hypothesis that fosters a rapid experimental validation on large cohorts of patients with different clinical manifestations.Preprin

Above and Beyond Robotic Surgery and 3D Modelling in Paediatric Cancer Surgery

Although the survival rates for children's cancers have more than doubled in the last few decades, the surgical practise has not significantly changed. Among the most recent innovations introduced in the clinic, robotic surgery and augmented reality are two of the most promising, even if they are not widespread. The increased flexibility of the motion, the magnification of the surgical field and the tremor reduction provided by robotic surgery have been beneficial to perform complex oncological procedures in children. Besides, augmented reality has been proven helpful in planning for tumour removal, facilitating early discrimination between cancer and healthy organs. Nowadays, research in the field of surgical oncology is moving fast, and new technologies and innovations wich will help to shape a new way to perform cancer surgery. Paediatric surgeons need to be ready to adopt these novel devices and intraoperative techniques to allow more radical tumour resections with fewer complications. This review aims to present the mechanism of action and indications of several novel technologies such as optical imaging surgery, high definition cameras, and intraoperative loco-regional treatments. We hope this will enhance early adoption and more research on how to employ technology for the benefit of children

Supporting Concurrency and Multiple Indexes in Private Access to Outsourced Data

Data outsourcing has recently emerged as a successful solution allowing individuals and organizations to delegate data and service management to external third parties. A major challenge in the data outsourcing scenario is how to guarantee proper privacy protection against the external server. Recent promising approaches rely on the organization of data in indexing structures that use encryption and the dynamic allocation of encrypted data to physical blocks for destroying the otherwise static relationship between data and the blocks in which they are stored. However, dynamic data allocation implies the need to re-write blocks at every read access, thus requesting exclusive locks that can affect concurrency. Also, these solutions only support search conditions on the values of the attribute used for building the indexing structure. In this paper, we present an approach that overcomes such limitations by extending the recently proposed shuffle index structure with support for concurrency and multiple indexes. Support for concurrency relies on the use of several differential versions of the data index that are periodically reconciled and applied to the main data structure. Support for multiple indexes relies on the definition of secondary shuffle indexes that are then combined with the primary index in a single data structure whose content and allocation is unintelligible to the server. We show how using such differential versions and combined index structure guarantees privacy, provides support for concurrent accesses and multiple search conditions, and considerably increases the performance of the system and the applicability of the proposed solution

Minimizing disclosure of private information in credential-based interactions : a graph-based approach

We address the problem of enabling clients to regulate disclosure of their credentials and properties when interacting with servers in open scenarios. We provide a means for clients to specify the sensitivity of information in their portfolio at a fine-grain level and to determine the credentials and properties to disclose to satisfy a server request while minimizing the sensitivity of the information disclosed. Exploiting a graph modeling of the problem, we develop a heuristic approach for determining a disclosure minimizing released information, that offers execution times compatible with the requirements of interactive access to Web resources

Novel Treatments and Technologies Applied to the Cure of Neuroblastoma

Neuroblastoma (NB) is the most common extracranial solid tumour in childhood, accounting for approximately 15% of all cancer-related deaths in the paediatric population1. It is characterised by heterogeneous clinical behaviour in neonates and often adverse outcomes in toddlers. The overall survival of children with high-risk disease is around 40–50% despite the aggressive treatment protocols consisting of intensive chemotherapy, surgery, radiation therapy and hematopoietic stem cell transplantation2,3. There is an ongoing research effort to increase NB’s cellular and molecular biology knowledge to translate essential findings into novel treatment strategies. This review aims to address new therapeutic modalities emerging from preclinical studies offering a unique translational opportunity for NB treatment

Long-term active problems in patients with cloacal exstrophy: a systematic review

BACKGROUND: Cloacal exstrophy (CE) is the most severe end of the Exstrophy-Epispadias Complex malformations spectrum. Improvements in postnatal management and well-established operative techniques have resulted in survival rates approaching 100%. This systematic review aims to define the prevalence of long-term active medical problems affecting CE patients after the first decade of life. METHODS: PubMed/Medline, Embase, Scopus, and ISI Web of Knowledge databases were used for the literature search. Original articles related to medical, surgical, and psychosocial long-term problems in CE patients >10 years of age were included in the study. Quality assessment of the articles was performed through the Newcastle-Ottawa Scale. Prevalence estimates and 95% CI were assessed for each outcome. RESULTS: Twelve studies were included. The most common long-term active problems identified were: urinary incontinence with a prevalence ranging from 9.1% to 85%; sexual function issues related to vaginal anomalies with a prevalence ranging from 8.3% to 71.3%, and uterine anomalies, with a prevalence from 14.3% to 71%; gender identity issues in 46, XY patients raised female had a prevalence from 11.1% to 66.7%. There is no documented history of paternity. Impairment of ambulatory capacity was recorded in 13.8% of patients. Only one paper studied psychological well-being, reporting significantly higher levels of depression among gender reassigned patients. CONCLUSIONS: Teenagers and adults born with CE have well defined long-term problems compared to the general population. Recognition and expert management are crucial to improve care and quality of life during and after the transition into adulthood

Dynamic Allocation for Resource Protection in Decentralized Cloud Storage

Decentralized Cloud Storage (DCS) networks represent an interesting solution for data storage and management. DCS networks rely on the voluntary effort of a considerable number of (possibly untrusted) nodes, which may dynamically join and leave the network at any time. To profitably rely on DCS for data storage, data owners therefore need solutions that guarantee confidentiality and availability of their data. In this paper, we present an approach enabling data owners to keep data confidentiality and availability under control, limiting the owners intervention with corrective actions when availability or confidentiality is at risk. Our approach is based on the combined adoption of AONT (All-Or-Nothing-Transform) and fountain codes. It provides confidentiality of outsourced data also against malicious coalitions of nodes, and guarantees data availability even in case of node failures. Our experimental evaluation clearly shows the benefits of using fountain codes with respect to other approaches adopted by current DCS networks

Multi-Provider Secure Processing of Sensors Data

We describe the implementation of an approach for supporting secure query processing over sensors data in a multi-provider scenario. Our solution relies on the definition of authorizations regulating access to data according to three different visibility levels (no visibility, encrypted visibility, and plaintext visibility). Data processing is performed by multiple providers based on the restrictions imposed by authorizations, which may require to adjust data visibility on the fly. We describe the structure of the query optimizer and show how the operations of a computation can be assigned to different cloud providers to build an efficient, secure, and economical plan for collaborative data processing

Outcomes and costs analysis of Externalized PyeloUreteral versus internal Double-J ureteral stents after paediatric laparoscopic Anderson-Hynes pyeloplasty

BACKGROUND: The gold standard treatment for Uretero-Pelvic Junction Obstruction (UPJO) is laparoscopic dismembered pyeloplasty according to the Anderson-Hynes technique. The internal Double-J ureteral (DJ) and the Externalized PyeloUreteral (EPU) stents are usually the drainage of choice. Only a few articles have compared the clinical impact of the different drainage techniques on the perioperative morbidity and none presented a cost analysis of the incurred hospital stay. OBJECTIVE: To present the clinical outcome and financial analysis of a cohort of children who underwent a laparoscopic pyeloplasty comparing the use of the DJ versus EPU stent. STUDY DESIGN: Retrospective study of consecutives children who underwent laparoscopic Anderson-Hynes pyeloplasty in a single tertiary paediatric referral centre from January 2017 to March 2020. Patients were grouped according to the type of stent used: DJ stent vs EPU stent. RESULTS: Fifty-three laparoscopic pyeloplasties were performed on 51 patients: 27 (50.9%) had an EPU stent and 26 (49.1%) a DJ stent. There was no statistically significant difference between the two patient groups with regards to surgical time, hospital stay, stent-related complications or the need for re-do surgery. All the EPU stents were removed with an outpatient admission 8.1 days ± 3.1 after surgery while the DJ stents were removed with a cystoscopy 61.6 days ± 30.2 after surgery (p value < 0.001). On a financial analysis (Figure), the hospital costs for stent removal were significantly lower for the EPU stent group (£ 686.7 ± 263.4 vs £ 1425 ± 299.5, p value < 0.01). DISCUSSION: Both drainage methods have some disadvantages. Possible complications associated with DJ stents include migration and artificial vesicoureteral reflux which may lead to higher incidence of Urinary Tract Infections. Possible disadvantages of the EPU stent insertion are related to the damage of the renal parenchyma and to the risk of developing skin site infections and urinary leaks. However, in our series the EPU stent has not been associated with a higher incidence of bleeding, leakage or discomfort. In addition to clinical considerations, there is a financial implication to be considered. With this regard, the EPU stent was associated with a significant reduction in the incurred hospital costs. CONCLUSIONS: The use of DJ and EPU stents is equivalent in regards of overall complications and success rates. DJ and EPU stents provided comparable success and complication rates, however the latter avoids the need of an additional general anaesthesia and reduces the overall incurred hospital costs

Efficient integrity checks for join queries in the cloud

Cloud computing is receiving massive interest from users and companies for its convenient support of scalable access to data and services. The variety and diversification of offers by cloud providers allow users to selectively adopt storage and computational services as they best suit their needs, including cost saving considerations. In such an open context, security remains a major concern, as confidentiality and integrity of data and queries over them can be at risk. In this paper, we present efficient techniques to verify the integrity of join queries computed by potentially untrusted cloud providers, while also protecting data and computation confidentiality. Our techniques support joins among multiple data sources and introduce a limited overhead in query computation, enabling also economical savings, as the ability to assess integrity increases the spectrum of offers that can be considered for performing the computation. Formal analysis and experimental evaluations confirm the effectiveness and efficiency of our solutions