Miracle-dz/UniFAR-FTUs huggingface dataset:
Rational Design of Live-Attenuated Vaccines against Herpes Simplex Viruses

Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed “latency”, which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish. Currently, there are no effective FDA-approved vaccines for either prophylactic or therapeutic treatment of human herpes simplex infections, while several recent clinical trials have failed to achieve their endpoint goals. Historically, live-attenuated vaccines have successfully combated viral diseases, including polio, influenza, measles, and smallpox. Vaccines aimed to protect against the devastation of smallpox led to the most significant achievement in medical history: the eradication of human disease by vaccination. Recently, novel approaches toward developing safe and effective live-attenuated vaccines have demonstrated high efficacy in various preclinical models of herpetic disease. This next generation of live-attenuated vaccines has been tailored to minimize vaccine-associated side effects and promote effective and long-lasting immune responses. The ultimate goal is to prevent or reduce primary infections (prophylactic vaccines) or reduce the frequency and severity of disease associated with reactivation events (therapeutic vaccines). These vaccines’ “rational” design is based on our current understanding of the immunopathogenesis of herpesviral infections that guide the development of vaccines that generate robust and protective immune responses. This review covers recent advances in the development of herpes simplex vaccines and the current state of ongoing clinical trials in pursuit of an effective vaccine against herpes simplex virus infections and associated diseases.
Exploring the Multifunctional Roles of Odontoglossum Ringspot Virus P126 in Facilitating Cymbidium Mosaic Virus Cell-to-Cell Movement during Mixed Infection

Synergistic interactions among viruses, hosts and/or transmission vectors during mixed infection can alter viral titers, symptom severity or host range. Viral suppressors of RNA silencing (VSRs) are considered one of such factors contributing to synergistic responses. Odontoglossum ringspot virus (ORSV) and cymbidium mosaic virus (CymMV), which are two of the most significant orchid viruses, exhibit synergistic symptom intensification in Phalaenopsis orchids with unilaterally enhanced CymMV movement by ORSV. In order to reveal the underlying mechanisms, we generated infectious cDNA clones of ORSV and CymMV isolated from Phalaenopsis that exerted similar unilateral synergism in both Phalaenopsis orchid and Nicotiana benthamiana. Moreover, we show that the ORSV replicase P126 is a VSR. Mutagenesis analysis revealed that mutation of the methionine in the carboxyl terminus of ORSV P126 abolished ORSV replication even though some P126 mutants preserved VSR activity, indicating that the VSR function of P126 alone is not sufficient for viral replication. Thus, P126 functions in both ORSV replication and as a VSR. Furthermore, P126 expression enhanced cell-to-cell movement and viral titers of CymMV in infected Phalaenopsis flowers and N. benthamiana leaves. Taking together, both the VSR and protein function of P126 might be prerequisites for unilaterally enhancing CymMV cell-to-cell movement by ORSV.
Buprenorphine Increases HIV-1 Infection In Vitro but Does Not Reactivate HIV-1 from Latency

Background: medication-assisted treatment (MAT) with buprenorphine is now widely prescribed to treat addiction to heroin and other illicit opioids. There is some evidence that illicit opioids enhance HIV-1 replication and accelerate AIDS pathogenesis, but the effect of buprenorphine is unknown. Methods: we obtained peripheral blood mononuclear cells (PBMCs) from healthy volunteers and cultured them in the presence of morphine, buprenorphine, or methadone. We infected the cells with a replication-competent CCR5-tropic HIV-1 reporter virus encoding a secreted nanoluciferase gene, and measured infection by luciferase activity in the supernatants over time. We also surveyed opioid receptor expression in PBMC, genital epithelial cells and other leukocytes by qPCR and western blotting. Reactivation from latency was assessed in J-Lat 11.1 and U1 cell lines. Results: we did not detect expression of classical opioid receptors in leukocytes, but did find nociception/orphanin FQ receptor (NOP) expression in blood and vaginal lymphocytes as well as genital epithelial cells. In PBMCs, we found that at physiological doses, morphine, and methadone had a variable or no effect on HIV infection, but buprenorphine treatment significantly increased HIV-1 infectivity (median: 8.797-fold increase with 20 nM buprenorphine, eight experiments, range: 3.570–691.9, p = 0.0078). Using latently infected cell lines, we did not detect reactivation of latent HIV following treatment with any of the opioid drugs. Conclusions: our results suggest that buprenorphine, in contrast to morphine or methadone, increases the in vitro susceptibility of leukocytes to HIV-1 infection but has no effect on in vitro HIV reactivation. These findings contribute to our understanding how opioids, including those used for MAT, affect HIV infection and reactivation, and can help to inform the choice of MAT for people living with HIV or who are at risk of HIV infection.
Reynoutria Rhizomes as a Natural Source of SARS-CoV-2 Mpro Inhibitors–Molecular Docking and In Vitro Study

More than a year has passed since the world began to fight the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the Coronavirus disease 2019 (COVID-19) pandemic, and still it spreads around the world, mutating at the same time. One of the sources of compounds with potential antiviral activity is Traditional Chinese Medicinal (TCM) plants used in China in the supportive treatment of COVID-19. Reynoutria japonica is important part of the Shu Feng Jie Du Granule/Capsule-TCM herbal formula, recommended by China Food and Drug Administration (CFDA) for treatment of patients with H1N1- and H5N9-induced acute lung injury and is also used in China to treat COVID-19, mainly combined with other remedies. In our study, 25 compounds from rhizomes of R. japonica and Reynoutria sachalinensis (related species), were docked into the binding site of SARS-CoV-2 main protease. Next, 11 of them (vanicoside A, vanicoside B, resveratrol, piceid, emodin, epicatechin, epicatechin gallate, epigallocatechin gallate, procyanidin B2, procyanidin C1, procyanidin B2 3,3’-di-O-gallate) as well as extracts and fractions from rhizomes of R. japonica and R. sachalinensis were tested in vitro using a fluorescent peptide substrate. Among the tested phytochemicals the best results were achieved for vanicoside A and vanicoside B with moderate inhibition of SARS-CoV-2 Mpro, IC50 = 23.10 µM and 43.59 µM, respectively. The butanol fractions of plants showed the strongest inhibition of SARS-CoV-2 Mpro (IC50 = 4.031 µg/mL for R. sachalinensis and IC50 = 7.877 µg/mL for R. japonica). As the main constituents of butanol fractions, besides the phenylpropanoid disaccharide esters (e.g., vanicosides), are highly polymerized procyanidins, we suppose that they could be responsible for their strong inhibitory properties. As inhibition of SARS-CoV-2 main protease could prevent the replication of the virus our research provides data that may explain the beneficial effects of R. japonica on COVID-19 and identify the most active compounds worthy of more extensive research.
Reliability and Validity of the Brief Illness Perception Questionnaire in Bahasa Malaysia for Patients with Cancer

Objective: The main purpose of this study was to identify the psychometric properties and validate the Bahasa Malaysia version of the Brief Illness Perception Questionnaire among patients with cancer. Methods: A total of 129 newly diagnosed patients with cancer were consecutively sampled. Reliability and validity of the questionnaire were tested using translation validity, test-retest reliability, Principal Component Analysis, Cronbach’s alpha coefficient for domains and item-total correlation. Results: The questionnaire indicates excellent test-retest reliability. The Principal Component Analysis (PCA) revealed that Kaiser-Meyer-Olkin (KMO) is 0.60 for the two-factor structure of the Brief Illness Perception Questionnaire of the Bahasa Malaysia version which consists of cognitive illness representation and emotional illness representation. Conclusion: The Brief Illness Perception Questionnaire in the Bahasa Malaysia version is a useful tool to use among patients with cancer in Malaysia context despite moderate psychometric properties. This is based on the premise that the questionnaire can be used as a quick tool to assess illness perceptions among Malaysian with cancer in routine oncology practice.
Adaptive Content Precaching Scheme Based on the Predictive Speed of Vehicles in Content-Centric Vehicular Networks

Content-Centric Vehicular Networks (CCVNs) are considered as an attractive technology to efficiently distribute and share contents among vehicles in vehicular environments. Due to the large size of contents such as multimedia data, it might be difficult for a vehicle to download the whole of a content within the coverage of its current RoadSide Unit (RSU). To address this issue, many studies exploit mobility-based content precaching in the next RSU on the trajectory of the vehicle. To calculate the amount of the content precaching, they use a constant speed such as the current speed of the vehicle requesting the content or the average speed of vehicles in the next RSU. However, since they do not appropriately reflect the practical speed of the vehicle in the next RSU, they could incorrectly calculate the amount of the content precaching. Therefore, we propose an adaptive content precaching scheme (ACPS) that correctly estimates the predictive speed of a requester vehicle to reflect its practical speed and calculates the amount of the content precaching using its predictive speed. ACPS adjusts the predictive speed to the average speed starting from the current speed with the optimized adaptive value. To compensate for a subtle error between the predictive and the practical speeds, ACPS appropriately adds a guardband area to the precaching amount. Simulation results verify that ACPS achieves better performance than previous schemes with the current or the average speeds in terms of the content download delay and the backhaul traffic overhead.
Waterproof Graphene-PVDF Wearable Strain Sensors for Movement Detection in Smart Gloves

In this work, new highly sensitive graphene-based flexible strain sensors are produced. In particular, polyvinylidene fluoride (PVDF) nanocomposite films filled with different amounts of graphene nanoplatelets (GNPs) are produced and their application as wearable sensors for strain and movement detection is assessed. The produced nanocomposite films are morphologically characterized and their waterproofness, electrical and mechanical properties are measured. Furthermore, their electromechanical features are investigated, under both stationary and dynamic conditions. In particular, the strain sensors show a consistent and reproducible response to the applied deformation and a Gauge factor around 30 is measured for the 1% wt loaded PVDF/GNP nanocomposite film when a deformation of 1.5% is applied. The produced specimens are then integrated in commercial gloves, in order to realize sensorized gloves able to detect even small proximal interphalangeal joint movements of the index finger.
Edge Caching Based on Collaborative Filtering for Heterogeneous ICN-IoT Applications

The substantial advancements offered by the edge computing has indicated serious evolutionary improvements for the internet of things (IoT) technology. The rigid design philosophy of the traditional network architecture limits its scope to meet future demands. However, information centric networking (ICN) is envisioned as a promising architecture to bridge the huge gaps and maintain IoT networks, mostly referred as ICN-IoT. The edge-enabled ICN-IoT architecture always demands efficient in-network caching techniques for supporting better user’s quality of experience (QoE). In this paper, we propose an enhanced ICN-IoT content caching strategy by enabling artificial intelligence (AI)-based collaborative filtering within the edge cloud to support heterogeneous IoT architecture. This collaborative filtering-based content caching strategy would intelligently cache content on edge nodes for traffic management at cloud databases. The evaluations has been conducted to check the performance of the proposed strategy over various benchmark strategies, such as LCE, LCD, CL4M, and ProbCache. The analytical results demonstrate the better performance of our proposed strategy with average gain of 15% for cache hit ratio, 12% reduction in content retrieval delay, and 28% reduced average hop count in comparison to best considered LCD. We believe that the proposed strategy will contribute an effective solution to the related studies in this domain.
The Pharmaceutical Technology Approach on Imaging Innovations from Italian Research

Many modern therapeutic approaches are based on precise diagnostic evidence, where imaging procedures play an essential role. To date, in the diagnostic field, a plethora of agents have been investigated to increase the selectivity and sensitivity of diagnosis. However, the most common drawbacks of conventional imaging agents reside in their non-specificity, short imaging time, instability, and toxicity. Moreover, routinely used diagnostic agents have low molecular weights and consequently a rapid clearance and renal excretion, and this represents a limitation if long-lasting imaging analyses are to be conducted. Thus, the development of new agents for in vivo diagnostics requires not only a deep knowledge of the physical principles of the imaging techniques and of the physiopathological aspects of the disease but also of the relative pharmaceutical and biopharmaceutical requirements. In this scenario, skills in pharmaceutical technology have become highly indispensable in order to respond to these needs. This review specifically aims to collect examples of newly developed diagnostic agents connoting the importance of an appropriate formulation study for the realization of effective products. Within the context of pharmaceutical technology research in Italy, several groups have developed and patented promising agents for fluorescence and radioactive imaging, the most relevant of which are described hereafter.
Synthesis of Nanostructure TiO2 Nanorod Array on FTO Substrate using Hydrothermal Method and its Photocatalytic Activity

In this work, one dimensional TiO2 nanorods array (NRA) was prepared by using hydrothermal method. The TiO2 NRA was grown on FTO substrate without using seed layer substrate. The effect of hydrothermal temperature and time on the morphology of TiO2 NRA was studied. The synthesized TiO2 nanostructure was characterized by different techniques. The structural properties were studied using X-Ray diffraction (XRD) technique, The morphological studied was done with Field emission scanning electron microscope (FE-SEM), UV-Visible spectroscopy and photoluminescence (PL) were used to evaluate optical properties of synthesized TiO2 nanostructures. The results showed that synthesized TiO2 nanorod array were grown vertically on FTO substrate with average diameter 50 nm and length up to 1 μm was achieved at about 1 μm. The photodegradation performance of TiO2 NRA was also studied and it was achieved up to 47% in 180 min under UV irradiation.
Xenograft Zebrafish Models for the Development of Novel Anti-Hepatocellular Carcinoma Molecules

Hepatocellular carcinoma (HCC) is the sixth most common type of tumor and the second leading cause of tumor-related death worldwide. Liver cirrhosis is the most important predisposing factor for HCC. Available therapeutic approaches are not very effective, especially for advanced HCC, which is the most common form of the disease at diagnosis. New therapeutic strategies are therefore urgently needed. The use of animal models represents a relevant tool for preclinical screening of new molecules/strategies against HCC. However, several issues, including animal husbandry, limit the use of current models (rodent/pig). One animal model that has attracted the attention of the scientific community in the last 15 years is the zebrafish. This freshwater fish has several attractive features, such as short reproductive time, limited space and cost requirements for husbandry, body transparency and the fact that embryos do not show immune response to transplanted cells. To date, two different types of zebrafish models for HCC have been developed: the transgenic zebrafish and the zebrafish xenograft models. Since transgenic zebrafish models for HCC have been described elsewhere, in this review, we focus on the description of zebrafish xenograft models that have been used in the last five years to test new molecules/strategies against HCC.
An Outbreak of COVID-19 among mRNA-Vaccinated Nursing Home Residents

An outbreak was described among the guests of a Long-Term Care Facility in the North of Italy. Among 23 guests, 20 of whom were fully vaccinated with BNT162b2 vaccine, the outbreak led to a final count of 11 positive guests, 9 of whom were vaccinated, and 4 positive healthcare workers, of whom only 1 was vaccinated. Eight of the positive guests (six vaccinated and two unvaccinated) had symptoms that in five cases (three vaccinated and two unvaccinated) led to death. The risk of infection and the risk of death appeared not to be correlated with the health status neither with the serological titer, but only with age.
Cartilaginous spheroid-assembly design considerations for endochondral ossification: towards robotic-driven biomanufacturing

Spheroids have become essential building blocks for biofabrication of functional tissues. Spheroid formats allow high cell-densities to be efficiently engineered into tissue structures closely resembling the native tissues. In this work, we explore the assembly capacity of cartilaginous spheroids (d ∼ 150 µm) in the context of endochondral bone formation. The fusion capacity of spheroids at various degrees of differentiation was investigated and showed decreased kinetics as well as remodeling capacity with increased spheroid maturity. Subsequently, design considerations regarding the dimensions of engineered spheroid-based cartilaginous mesotissues were explored for the corresponding time points, defining critical dimensions for these type of tissues as they progressively mature. Next, mesotissue assemblies were implanted subcutaneously in order to investigate the influence of spheroid fusion parameters on endochondral ossification. Moreover, as a step towards industrialization, we demonstrated a novel automated image-guided robotics process, based on targeting and registering single-spheroids, covering the range of spheroid and mesotissue dimensions investigated in this work. This work highlights a robust and automated high-precision biomanufacturing roadmap for producing spheroid-based implants for bone regeneration.
Purinergic P2Y2 and P2X4 Receptors Are Involved in the Epithelial-Mesenchymal Transition and Metastatic Potential of Gastric Cancer Derived Cell Lines

Gastric cancer (GC) is a major health concern worldwide, presenting a complex pathophysiology that has hindered many therapeutic efforts so far. In this context, purinergic signaling emerges as a promising pathway for intervention due to its known role in cancer cell proliferation and migration. In this work, we explored in more detail the role of purinergic signaling in GC with several experimental approaches. First, we measured extracellular ATP concentrations on GC-derived cell lines (AGS, MKN-45, and MKN-74), finding higher levels of extracellular ATP than those obtained for the non-tumoral gastric cell line GES-1. Next, we established the P2Y2 and P2X4 receptors (P2Y2R and P2X4R) expression profile on these cells and evaluated their role on cell proliferation and migration after applying overexpression and knockdown strategies. In general, a P2Y2R overexpression and P2X4R downregulation pattern were observed on GC cell lines, and when these patterns were modified, concomitant changes in cell viability were observed. These modifications on gene expression also modified transepithelial electrical resistance (TEER), showing that higher P2Y2R levels decreased TEER, and high P2X4R expression had the opposite effect, suggesting that P2Y2R and P2X4R activation could promote and suppress epithelial-mesenchymal transition (EMT), respectively. These effects were confirmed after treating AGS cells with UTP, a P2Y2R-agonist that modified the expression patterns towards mesenchymal markers. To further characterize the effects of P2Y2R activation on EMT, we used cDNA microarrays and observed that UTP induced important transcriptional changes on several cell processes like cell proliferation induction, apoptosis inhibition, cell differentiation induction, and cell adhesion reduction. These results suggest that purinergic signaling plays a complex role in GC pathophysiology, and changes in purinergic balance can trigger tumorigenesis in non-tumoral gastric cells.
The comparative safety of human papillomavirus vaccines: A Bayesian network meta‐analysis

The safety of human papillomavirus (HPV) vaccines, one of the major challenges to public vaccination, has been controversial. This study assessed the adverse reactions of various HPV vaccines, including bivalent HPV (2vHPV), quadrivalent HPV (4vHPV), and 9‐valent HPV (9vHPV) vaccines.