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Safe and effective vaccines against coronavirus disease 2019 (COVID-19) are urgently needed to control the ongoing pandemic. Although impressive progress has been made with several COVID-19 vaccines already approved, it is clear that those developed so far cannot meet the global vaccine demand. We have developed a COVID-19 vaccine based on a replication-defective gorilla adenovirus expressing the stabilized pre-fusion SARS-CoV-2 Spike protein, named GRAd-COV2. We aimed to assess the safety and immunogenicity of a single-dose regimen of this vaccine in healthy younger and older adults to select the appropriate dose for each age group. To this purpose, a phase 1, dose-escalation, open-label trial was conducted including 90 healthy subjects, (45 aged 18-55 years and 45 aged 65-85 years), who received a single intramuscular administration of GRAd-CoV2 at three escalating doses. Local and systemic adverse reactions were mostly mild or moderate and of short duration, and no serious AE was reported. Four weeks after vaccination, seroconversion to Spike/RBD was achieved in 43/44 young volunteers and in 45/45 older subjects. Consistently, neutralizing antibodies were detected in 42/44 younger age and 45/45 older age volunteers. In addition, GRAd-COV2 induced a robust and Th1-skewed T cell response against the S antigen in 89/90 subjects from both age groups. Overall, the safety and immunogenicity data from the phase 1 trial support further development of this vaccine.One Sentence SummaryGRAd-COV2, a candidate vaccine for COVID-19 based on a novel gorilla adenovirus, is safe and immunogenic in younger and older adults

Sleeping Beauty (SB) is the first DNA transposon employed for efficient transposition in vertebrate cells, opening new applications for genetic engineering and gene therapies. A transposon-based gene delivery system holds the favourable features of non-viral vectors and an attractive safety profile. Here, we employed SB to engineer HEK293 cells for optimizing the production of a chimpanzee Adenovector (chAd) belonging to the Human Mastadenovirus C species. To date, chAd vectors are employed in several clinical settings for infectious diseases, last but not least COVID-19. A robust, efficient and quick viral vector production could advance the clinical application of chAd vectors. To this aim, we firstly swapped the hAd5 E1 with chAd-C E1 gene by using the CRISPR/Cas9 system. We demonstrated that in the absence of human Ad5 E1, chimp Ad-C E1 gene did not support HEK293 survival. To improve chAd-C vector production, we engineered HEK293 cells to stably express the chAd-C precursor terminal protein (ch.pTP), which plays a crucial role in chimpanzee Adenoviral DNA replication. The results indicate that exogenous ch.pTP expression significantly ameliorate the packaging and amplification of recombinant chAd-C vectors thus, the engineered HEK293ch.pTP cells could represent a superior packaging cell line for the production of these vectors.

In this work, we introduce a set of robot's behavior aimed at being used for monitoring and interaction with elderly people affected by Alzheimer disease. Robot's behaviors for a low cost robotic device rely on the use of microservices running on a local server. A microservice is an independent, self-contained, self-scope, and self-responsibility component of the robotic system proposed for decoupling the implemented functions needed to obtain the proper robot behaviors. The developed robotic behaviors include navigation, interaction, and monitoring capabilities. The requests and the signals of the patients are handled and managed relying on event-based communications between the system components. The use of design patterns like this one increases the overall reliability of a service composition. The system is currently operating in a private house with an elderly couple.

Socially Assistive Robots used for elderly care are required to determine the location of a person and to approach him/her in order to provide assistance. Human tracking systems are applied to detect and track people that are already in the proximity of the robot, while its limited field of view makes the user easily lost. Moreover, navigation algorithms typically need the availability of reliable sensors on the robot and the possibility of marking possible user locations. On the contrary, in this work, we investigate the opportunity to use a reactive control mechanism for detecting and approaching people. Our approach is tested on two commercial mobile robots that present a different sensors configuration and by using off-the-shelf algorithms for people localization and tracking. Results show the feasibility of the approach with respect to the considered domain that does not require precise positioning, but hopes for a real application of such low-cost robot into the wild. Features of the considered robots and their impact on performance are also discussed.

Genetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all, studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioral traits, we set out to develop a mouse model of the human 5-HTT-LPR. Here we describe the creation and characterization of a set of mouse lines with single-copy human transgenes carrying the short and long 5-HTT-LPR variants. Although we were not able to detect differences in expression between the short and long variants, we encountered several technical issues concerning the design of our humanized mice that are likely to have influenced our findings. Our study serves as a cautionary note for future studies aimed at studying human transgene regulation in the context of the living mouse.

Social Assistive Robots may potentially distract the user from his/her current activity while performing non-interactive tasks. In this work, we consider a robotic system approaching an elder man, in order to monitor his/her behavior, as the human is occupied in carrying out a specific daily activity. We conducted a pilot study to assess the possibility of an automatic evaluation of the human awareness and how the robot presence interferes with his/her current activity. First conclusions have been obtained comparing questionnaire results with video analysis.

The aim of this study was to evaluate the results of rehabilitative treatment of incontinent patients with anal sphincter lesions in order to verify whether these lesions influence the outcome of rehabilitation.Between January 2008 and June 2011, 48 patients [36 women, age range 51-77 years; 12 men, age range 57-70 years] affected by fecal incontinence were included in the study. After a preliminary clinical evaluation, including the Fecal Incontinence Severity Index (FISI) score, all patients were studied by means of endoanal ultrasound and anorectal manometry. Two patients groups were identified: Group 1 comprised 27 patients with sphincter lesions and Group 2 had 21 patients without sphincter lesions. All 48 underwent a multimodal rehabilitation program. At the end of the rehabilitation program, all patients were reassessed by means of clinical evaluation and anorectal manometry and their data were analyzed.Although we obtained an overall significantly lower FISI score in all patients after rehabilitation (p0.001) when compared with pre-treatment values, our study revealed that patients with sphincter lesions had a significantly worse post-rehabilitative FISI score (p0.003) when compared with those patients with intact anal sphincters and that there is a linear relationship between post-rehabilitative FISI scores and severity of sphincter lesions (ρ s 0.69).These data suggest that rehabilitation may be less effective in patients affected by sphincter defects.

Rehabilitation is the first therapeutic step of obstructed defecation, after failure of conservative therapy with high-fiber diet and laxatives. This study evaluates the usefulness of psyllium, a bulk-forming agent, when used during rehabilitation of obstructed defecation.Between January 2008 and December 2010, 45 patients affected by obstructed defecation were included in the study. Two randomized groups were selected. Group 1 (21 women; age range 25-67 (mean, 51.8) years) continued to consume a high-fiber diet (approximately 30 g fiber per day) during rehabilitation. Group 2 (24 women; age range 46-71 (mean, 59.8) years) consumed only psyllium (3.6 g × 2/day; Psyllogel(®) Fibra, Nathura, Montecchio Emilia, Italy) during the rehabilitative cycle. After a preliminary clinical evaluation, including the obstructed defecation syndrome (ODS) score, patients underwent defecography and anorectal manometry as well as rehabilitative treatment according to the "multimodal rehabilitative program" for obstructive defecation. At the end of the program, patients were reassessed by clinical evaluation and anorectal manometry. Post-rehabilitative ODS scores were used for an arbitrary schedule of patients divided into three classes: Class I, good (score ≤ 4); Class II, fair (score 4 to ≤ 8); Class III, poor (score 8).The number of bowel movements per week did not increase significantly after rehabilitation. Both groups had a significantly better Bristol stool form scale score (Group 1: P 0.034; Group 2: P 0.02). The overall mean ODS score from Groups 1 and 2 showed significant improvement after treatment (P 0.001). Twenty-eight patients (82.3%) were Class I (good results) without significant differences between groups. Nine women were symptom-free. Significant differences were found between pre-rehabilitative and post-rehabilitative manometric data from the straining test (P 0.001) and duration of maximal voluntary contraction (Group 1: P 0.004; Group 2: P 0.02). A significant difference was found between the pre-rehabilitative and post-rehabilitative conscious rectal sensitivity threshold (CRST) in Group 2 women (P 0.02). The Group 2 women who underwent volumetric rehabilitation (11 patients) had significantly lower post-rehabilitative CRST values than pre-rehabilitative values (P 0.002); the length of volumetric rehabilitation was also significantly shorter in Group 2 patients (P 0.04) than in Group 1 patients.After rehabilitation of obstructed defecation, some patients became symptom-free and many had an improved ODS score. Psyllium is helpful for volumetric rehabilitation: patients who consumed psyllium had lower post-rehabilitative CRST values than subjects were on high-fiber diet.

Background Fine-needle aspiration biopsy (FNAB) is the primary means to distinguish benign from malignant nodules and select patients for surgery. However, adjunctive diagnostic tests are needed because in 20-40% of cases the FNAB result is uncertain. Objective We investigated whether a search for the oncogenes RET/PTC, TRK and BRAF(V600E) in thyroid aspirates could refine an uncertain diagnosis. Patients and methods A total of 132 thyroid aspirates, including colloid nodules, inadequate samplings, indeterminate and suspicious for malignancy were analysed by reverse transcription polymerase chain reaction (RT-PCR) and mutant allele-specific amplification techniques for the presence of oncogenes. Results No oncogenes were detected in 48 colloid nodules, 46 inadequate and 19 indeterminate FNABs, then confirmed to be benign at histology. No oncogenes were detected in one follicular thyroid cancer (FTC) with indeterminate cytology. Five out of six papillary thyroid cancers (83%) with FNAB suspicious for malignancy were correctly diagnosed by the presence of oncogenes. Among these, four (67%) contained the BRAF mutation and one (17%) contained RET/PTC-3. On final analysis, no false-positive results were reported in 131 samples and five out of seven carcinomas (71%) were correctly diagnosed. The finding of oncogenes in FNAB specimens suspicious for malignancy guided the extent of surgical resection, changing the surgery from diagnostic to therapeutic in five cases. Conclusions Detection of RET/PTC, TRK and BRAF(V600E) in FNAB specimens is proposed as a diagnostic adjunctive tool in the evaluation of thyroid nodules with suspicious cytological findings.

This paper describes a semantic search tool based on our experience in using a new lexical domain ontology for aerospace integrated with an open source general purpose ontology to support aerospace engineers in the timely semantic retrieval of the knowledge. The semantic search module represents an integrated tool dedicated to the semantic search, extraction and classification of information and knowledge in aerospace domain. It describes the implementation of a disambiguation algorithm based upon these ontologies and a new interesting graphical user interface for semantic searches is presented. Furthermore, next to the domain ontology, a taxonomy for classifying aerospace documents is also proposed. The document classification algorithm that leverages the deep integration between the proposed lexical domain ontology and taxonomy is also described. Finally, some considerations about the usage of the semantic search module by the side of domain experts, semantic experts or common users are reported.

Canonical Wnt signaling is repeatedly used during development to control cell fate, and it is often implicated in human cancer. β-catenin, the effector of Wnt signaling, has a dual function in the cell and is involved in both cell adhesion and transcription. Nuclear β-catenin controls transcription through association with transcription factors of the TCF family and the recruitment of epigenetic modifiers. In this study, we used a strategy combining the genetic manipulation of mouse embryonic stem cells with affinity purification and quantitative mass spectroscopy utilizing stable isotope labeling with amino acids in cell culture to study the interactome of chromatin-bound β-catenin with and without Wnt3a stimulation. We uncovered previously unknown interactions of β-catenin with transcription factors and chromatin-modifying complexes. Our proof-of-principle experiments show that β-catenin can recruit the H3K4me2/1 demethylase LSD1 to regulate the expression of the tumor suppressor Lefty1 in mouse embryonic stem cells. The mRNA levels of LSD1 and β-catenin are inversely correlated with the levels of Lefty1 in pancreas and breast tumors, implying that this mechanism is common to mouse embryonic stem cells and cancer cells.

From Wnt Signals to Telomerase Activity Telomerase activity is associated with stem cell renewal and cancers, whereas a decrease in telomerase activity is seen during cell differentiation and senescence. Wnt/β-catenin signaling is also a critical regulator of stem cells, and deregulation of the pathway is associated with cancer. Now, Hoffmeyer et al. (p. 1549 ; see the Perspective by Greider ) have found a link between these two pathways. In embryonic stem cells, β-catenin was able to regulate telomerase expression and activity directly. Similar observations were obtained in adult stem cells, a model of intestinal tumors, and human cancer cells.

Julia is an intelligent system to reduce user frustration and improve personal communications. It allows an human machine interaction by voice while the speech understanding system is based on a set of keywords. The system is able to draw inference from a known domain and execute some reasoning and answering tasks in response to the user requests. A large collection of sentences is used to address questions to the user when the reasoning process cannot go on. The sentences are selected in order to obtain a natural, not repetitive dialog between the user and the machine. An intelligent graphical interface learns the user skill degree and matches its help level to the user needs.