DNA Damage Response Gene Signature as Potential Treatment Markers for Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is a rapidly progressive cancer that often develops resistance against DNA damage inducers, such as radiotherapy and chemotherapy, which are still the standard of care regimens for this tumor. Thus, the identification of biomarkers capable of monitoring the clinical progression of OSCC and its responsiveness to therapy is strongly required. To meet this need, here we have employed Whole Genome Sequencing and RNA-seq data from a cohort of 316 patients retrieved from the TCGA Pan-Cancer Atlas to analyze the genomic and transcriptomic status of the DNA damage response (DDR) genes in OSCC. Then, we correlated the transcriptomic data with the clinical parameters of each patient. Finally, we relied on transcriptomic and drug sensitivity data from the CTRP v2 portal, performing Pearson's correlation analysis to identify putative vulnerabilities of OSCC cell lines correlated with DDR gene expression. Our results indicate that several DDR genes show a high frequency of genomic and transcriptomic alterations and that the expression of some of them correlates with OSCC grading and infection by the human papilloma virus. In addition, we have identified a signature of eight DDR genes (namely CCNB1, CCNB2, CDK2, CDK4, CHECK1, E2F1, FANCD2, and PRKDC) that could be predictive for OSCC response to the novel antitumor compounds sorafenib and tipifarnib-P1. Altogether, our data demonstrate that alterations in DDR genes could have an impact on the biology of OSCC. Moreover, here we propose a DDR gene signature whose expression could be predictive of OSCC responsiveness to therapy

Protection from environmental enteric dysfunction and growth improvement in malnourished newborns by amplification of secretory IgA.

Environmental enteric dysfunction (EED) is a condition associated with malnutrition that can progress to malabsorption and villous atrophy. Severe EED results in linear growth stunting, slowed neurocognitive development, and unresponsiveness to oral vaccines. Prenatal exposure to malnutrition and breast feeding by malnourished mothers replicates EED. Pups are characterized by deprivation of secretory IgA (SIgA) and altered development of the gut immune system and microbiota. Extracellular ATP (eATP) released by microbiota limits T follicular helper (Tfh) cell activity and SIgA generation in Peyer's patches (PPs). Administration of a live biotherapeutic releasing the ATP-degrading enzyme apyrase to malnourished pups restores SIgA levels and ameliorates stunted growth. SIgA is instrumental in improving the growth and intestinal immune competence of mice while they are continuously fed a malnourished diet. The analysis of microbiota composition suggests that amplification of endogenous SIgA may exert a dominant function in correcting malnourishment dysbiosis and its consequences on host organisms, irrespective of the actual microbial ecology

Apyrase-mediated amplification of secretory IgA promotes intestinal homeostasis.

Secretory immunoglobulin A (SIgA) interaction with commensal bacteria conditions microbiota composition and function. However, mechanisms regulating reciprocal control of microbiota and SIgA are not defined. Bacteria-derived adenosine triphosphate (ATP) limits T follicular helper (Tfh) cells in the Peyer's patches (PPs) via P2X7 receptor (P2X7R) and thereby SIgA generation. Here we show that hydrolysis of extracellular ATP (eATP) by apyrase results in amplification of the SIgA repertoire. The enhanced breadth of SIgA in mice colonized with apyrase-releasing Escherichia coli influences topographical distribution of bacteria and expression of genes involved in metabolic versus immune functions in the intestinal epithelium. SIgA-mediated conditioning of bacteria and enterocyte function is reflected by differences in nutrient absorption in mice colonized with apyrase-expressing bacteria. Apyrase-induced SIgA improves intestinal homeostasis and attenuates barrier impairment and susceptibility to infection by enteric pathogens in antibiotic-induced dysbiosis. Therefore, amplification of SIgA by apyrase can be leveraged to restore intestinal fitness in dysbiotic conditions

Designing greenhouse subsystems for a lunar mission: the LOOPS - M Project

The 2020s is a very important decade in the space sector, where international cooperation is moving towards the exploration of the Moon and will lead to stable lunar settlements, which will require new, innovative, and efficient technologies. In this context, the project LOOPS–M (Lunar Operative Outpost for the Production and Storage of Microgreens) was created by students from Sapienza University of Rome with the objective of designing some of the main features of a lunar greenhouse. The project was developed for the IGLUNA 2021 campaign, an interdisciplinary platform coordinated by Space Innovation as part of the ESA Lab@ initiative. The LOOPS-M mission was successfully concluded during the Virtual Field Campaign that took place in July 2021. This project is a follow-up of the V-GELM Project, which took part in IGLUNA 2020 with the realization in Virtual Reality of a Lunar Greenhouse: a simulation of the main operations connected to the cultivation module, the HORT3 , which was already developed by ENEA (Italian National Agency for New Technologies, Energy and Sustainable Economic Development) during the AMADEE-18 mission inside the HORTSPACE project. This paper will briefly describe the main features designed and developed for the lunar greenhouse and their simulation in a VR environment: an autonomous cultivation system able to handle the main cultivation tasks of the previous cultivation system, a bioconversion system that can recycle into new resources the cultivation waste with the use of insects as a biodegradation system, and a shield able of withstanding hypervelocity impacts and the harsh lunar environment. A wide overview of the main challenges faced, and lessons learned by the team to obtain these results, will be given. The first challenge was the initial inexperience that characterized all the team members, being for most the first experience with an activity structured as a space mission, starting with little to no know-how regarding the software and hardware needed for the project, and how to structure documentation and tasks, which was acquired throughout the year. An added difficulty was the nature of LOOPS-M, which included very different objectives that required different fields of expertise, ranging from various engineering sectors to biology and entomology. During the year, the team managed to learn how to handle all these hurdles and the organizational standpoint, working as a group, even if remotely due to the Covid-19 pandemic. Through careful planning, hard work and the help of supervisors, the activity was carried out through reviews, up to the prototyping phase and the test campaign with a successful outcome in each aspect of the project. By the end of the year everyone involved had acquired new knowledge, both practical and theoretical, and learned how to reach out and present their work to sponsors and to the scientific community

Safehaul: Risk-Averse Learning for Reliable mmWave Self-Backhauling in 6G Networks

Wireless backhauling at millimeter-wave frequencies (mmWave) in static scenarios is a well-established practice in cellular networks. However, highly directional and adaptive beamforming in today’s mmWave systems have opened new possibilities for self-backhauling. Tapping into this potential, 3GPP has standardized Integrated Access and Backhaul (IAB) allowing the same base station to serve both access and backhaul traffic. Although much more cost-effective and flexible, resource allocation and path selection in IAB mmWave networks is a formidable task. To date, prior works have addressed this challenge through a plethora of classic optimization and learning methods, generally optimizing a Key Performance Indicator (KPI) such as throughput, latency, and fairness, and little attention has been paid to the reliability of the KPI. We propose Safehaul, a risk-averse learning-based solution for IAB mmWave networks. In addition to optimizing average performance, Safehaul ensures reliability by minimizing the losses in the tail of the performance distribution. We develop a novel simulator and show via extensive simulations that Safehaul not only reduces the latency by up to 43.2% compared to the benchmarks, but also exhibits significantly more reliable performance, e.g., 71.4% less variance in achieved latency

Effectiveness of Ball Attachment Systems in Implant Retained- and Supported-Overdentures: A Three- to Five-Year Retrospective Examination

Purpose: To evaluate implant and prosthetic survival rates, complications, patient satisfaction, and biological outcomes of patients rehabilitated with a ball attachment system for implant retained- and supported-overdentures (IOV), which was in function for 3 to 5 years. Methods: This retrospective study evaluated data collected from patients treated between April 2001 and May 2018 with IOV on splinted and non-splinted implants and a ball attachment system. Patients were followed for 36 to 206 months (mean follow-up was 128.1 ± 51.9 months). Data were collected at the 3- and 5-year follow-up examination. Outcome measures were implant and prosthetic survival rates, technical complications, marginal bone loss (MBL), oral health impact profile (OHIP), and periodontal parameters (bleeding on probing and plaque index). Results: A total of 46 patients (16 males and 30 females) with 124 implants were included in this study. Twenty-five implant-retained overdentures were delivered on 53 unsplinted implants, while the other 21 patients received an implant-supported overdentures and the implants were splinted. At the five-year follow-up examination, one implant and one prosthesis failed in the unsplinted group, resulting in a cumulative survival rate of 97.8% at the patient level. Two minor technical complications were experienced. Conclusions: Implant overdenture retained or supported by ball attachment systems showed high implant and prosthetic survival and success rates. A low number of complications, high patient satisfaction, and successful biological parameters were experienced in the mid-term follow-up. Data need to be confirmed by further randomized trials

End-to-End Simulation of 5G Networks Assisted by IRS and AF Relays

The high propagation and penetration loss experienced at millimeter wave (mmWave) frequencies requires ultra-dense deployments of 5th generation (5G) base stations, which may be infeasible and costly for network operators. Integrated Access and Backhaul (IAB) has been proposed to partially address this issue, though raising concerns in terms of power consumption and scalability. Recently, the research community has been investigating Intelligent Reflective Surfaces (IRSs) and Amplify-and-Forward (AF) relays as more energy-efficient alternatives to solve coverage issues in 5G scenarios. Along these lines, this paper relies on a new simulation framework, based on ns-3, to simulate IRS/AF systems with a full-stack, end-to-end perspective, with considerations on the impact of the channel model and the protocol stack of 5G NR networks. Our goal is to demonstrate whether these technologies can be used to relay 5G traffic requests and, if so, how to dimension IRS/AF nodes as a function of the number of end users

Effect of Simultaneous Immediate Implant Placement and Guided Bone Reconstruction with Ultra-Fine Titanium Mesh Membranes on Radiographic and Clinical Parameters after 18 Months of Loading

Background: The aim of the present prospective case series study was to evaluate the implant and prosthetic survival rates, complications and marginal bone loss using ultra-fine titanium mesh membrane with simultaneous implant placement, to provide space maintenance mandatory for guided bone reconstruction of alveolar bone defects. Materials and Methods: patients were recruited and treated at a private clinic in Rome, Italy, between March 2016 and October 2017. Self-tapping tapered implants were placed through a computer-guided template-assisted approach. Autogenous bone was placed alone over the exposed implant surface, then mixed with inorganic bovine bone material. Finally, the membrane was connected and shaped in order to securely enclose the graft area, and the healing cap was connected and screwed onto the height connector. Outcome measures were: implant and prosthetic failure, biological and mechanical complications, marginal and volumetric bone level changes, esthetic evaluation performed according to the pink aesthetic score (PES). Results: in total, seven patients (five women, two men) with a mean age of 52.7 ± 20.3 years (range: 27−71) received 10 self-tapping tapered implants and simultaneous guided bone regeneration with ultra-fine titanium mesh membranes. No implants and no prostheses failed during the entire follow-up period. One slightly membrane exposure was observed one month after implant placement in one patient. The mean marginal bone loss (MBL) at implant loading was 0.13 ± 0.09 mm (95% CI 0.08−0.19). At the 18-month follow-up examination, the mean MBL was 0.28 ± 0.33 mm (95% CI 0.07−0.50) The difference was not statistically significant (0.15 ± 0.31; 95% CI 0.05−0.35; P = 0.1888). The mean horizontal alveolar ridge width was 3.72 ± 1.08 mm (95% CI 3.22−4.22 mm). At the II-stage surgery, the mean bone width was 8.79 ± 0.98 mm (95% CI 8.51−9.07 mm). The mean bone gain was 5.06 ± 1.13 mm (95% CI 4.68−5.44 mm; P = 0.000). The mean volume of the grafted bone calculated using the superimposition technique was 0.99 ± 0.38 CC (95% CI 0.75−1.23 CC). The mean PES at implant loading was 8.2 ± 0.8 mm (95% CI 7.7−8.7). At the 18-month follow-up examination, the mean PES was 12.0 ± 0.7 mm (95% CI 11.5−12.5) The difference was statistically significant (3.8 ± 0.4; 95% CI 3.5−4.1; P = 0.0000); Conclusion: with the limitation of the present prospective study, the guided bone reconstruction using an ultra-fine titanium mesh membrane with simultaneous implant placement seems to provide good and stable results in implant/prosthesis success. Further research with a longer follow-up and a higher sample size are needed to confirm the results from this preliminary report