Tunable dipolar magnetism in high-spin molecular clusters

We report on the Fe17 high-spin molecular cluster and show that this system is an exemplification of nanostructured dipolar magnetism. Each Fe17 molecule, with spin S=35/2 and axial anisotropy as small as D=-0.02K, is the magnetic unit that can be chemically arranged in different packing crystals whilst preserving both spin ground-state and anisotropy. For every configuration, molecular spins are correlated only by dipolar interactions. The ensuing interplay between dipolar energy and anisotropy gives rise to macroscopic behaviors ranging from superparamagnetism to long-range magnetic order at temperatures below 1K.Comment: Replaced with version accepted for publication in Physical Review Letter

A 3D Platform to Investigate Dynamic Cell-to-Cell Interactions Between Tumor Cells and Mesenchymal Progenitors

We here investigated the dynamic cell-to-cell interactions between tumor and mesenchymal stromal/stem cells (MSCs) by the novel VITVOⓇ 3D bioreactor that was customized to develop in vivo-like metastatic nodules of Ewing’s sarcoma (ES). MSCs are known to contribute to tumor microenvironment as cancer associated fibroblast (CAF) precursors and, for this reason, they have also been used as anti-cancer tools. Using dynamic conditions, the process of tissue colonization and formation of metastatic niches was recreated through tumor cell migration aiming to mimic ES development in patients. ES is an aggressive tumor representing the second most common malignant bone cancer in children and young adults. An urgent and unmet need exists for the development of novel treatment strategies to improve the outcomes of metastatic ES. The tumor-tropic ability of MSCs offers an alternative approach, in which these cells can be used as vehicles for the delivery of antitumor molecules, such as the proapoptotic TNF-related apoptosis inducing ligand (TRAIL). However, the therapeutic targeting of metastases remains challenging and the interaction occurring between tumor cells and MSCs has not yet been deeply investigated. Setting up in vitro and in vivo models to study this interaction is a prerequisite for novel approaches where MSCs affinity for tumor is optimized to ultimately increase their therapeutic efficacy. Here, VITVOⓇ integrating a customized scaffold with an increased inter-fiber distance (VITVO50) was used to develop a dynamic model where MSCs and tumor nodules were evaluated under flow conditions. Colonization and interaction between cell populations were explored by droplet digital PCR (ddPCR). VITVO50 findings were then applied in vivo. An ES metastatic model was established in NSG mice and biodistribution of TRAIL-expressing MSCs in mice organs affected by metastases was investigated using a 4-plex ddPCR assay. VITVOⓇ proved to be an easy handling and versatile bioreactor to develop in vivo-like tumor nodules and investigate dynamic cell-to-cell interactions with MSCs. The proposed fluidic system promises to facilitate the understanding of tumor-stroma interaction for the development of novel tumor targeting strategies, simplifying the analysis of in vivo data, and ultimately accelerating the progress towards the early clinical phase

Nano-Hall sensors with granular Co-C

We analyzed the performance of Hall sensors with different Co-C ratios, deposited directly in nano-structured form, using $Co_2(CO)_8$ gas molecules, by focused electron or ion beam induced deposition. Due to the enhanced inter-grain scattering in these granular wires, the Extraordinary Hall Effect can be increased by two orders of magnitude with respect to pure Co, up to a current sensitivity of $1 \Omega/T$. We show that the best magnetic field resolution at room temperature is obtained for Co ratios between 60% and 70% and is better than $1 \mu T/Hz^{1/2}$. For an active area of the sensor of $200 \times 200 nm^2$, the room temperature magnetic flux resolution is $\phi_{min} = 2\times10^{-5}\phi_0$, in the thermal noise frequency range, i.e. above 100 kHz.Comment: 5 pages, 4 figure

Multimodal sensing in rewritable, data matrix azobenzene-based devices

Here, we exploited the UV light and thermal triggered E <-> Z photoisomerization of an azobenzene compound to fabricate multimodal readable and rewritable data matrix based devices. We first demonstrated that the UV light sensing capabilities can be simultaneously monitored by the change in optical, spectroscopic, and electrical properties. Then we exploited this capability by integrating tetra(azobenzene)methane crystals in a micrometric TAG whose information can be modified and repristinated by local UV treatment and thermal annealing. The system was characterized by polarized optical microscopy, Raman spectroscopy, conductive atomic force microscopy and Kelvin Probe Force Microscopy

A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology.

Tumors develop within complex cell-to-cell interactions, with accessory cells playing a relevant role starting in the early phases of cancer progression. This event occurs in a three-dimensional (3D) environment, which to date, has been difficult to reproduce in vitro due to its complexity. While bi-dimensional cultures have generated substantial data, there is a progressive awareness that 3D culture strategies may rapidly increase the understanding of tumor development and be used in anti-cancer compound screening and for predicting response to new drugs utilizing personalized approaches. However, simple systems capable of rapidly rebuilding cancer tissues ex-vivo in 3D are needed and could be used for a variety of applications. Therefore, we developed a flat, handheld and versatile 3D cell culture bioreactor that can be loaded with tumor and/or normal cells in combination which can be monitored using a variety of read-outs. This biocompatible device sustained 3D growth of tumor cell lines representative of various cancers, such as pancreatic and breast adenocarcinoma, sarcoma, and glioblastoma. The cells repopulated the thin matrix which was completely separated from the outer space by two gas-permeable membranes and was monitored in real-time using both microscopy and luminometry, even after transportation. The device was tested in 3D cytotoxicity assays to investigate the anti-cancer potential of chemotherapy, biologic agents, and cell-based therapy in co-cultures. The addition of luciferase in target cancer cells is suitable for comparative studies that may also involve parallel in vivo investigations. Notably, the system was challenged using primary tumor cells harvested from lung cancer patients as an innovative predictive functional assay for cancer responsiveness to checkpoint inhibitors, such as nivolumab. This bioreactor has several novel features in the 3D-culture field of research, representing a valid tool useful for cancer investigations, drug screenings, and other toxicology approaches

Morphologic, phenotypic, and genotypic similarities between primary tumors and corresponding 3D cell cultures grown in a repeatable system—preliminary results

BackgroundThree-dimensional (3D) cell cultures are the new frontier for reproducing the tumor micro-environment in vitro. The aims of the study were (1) to establish primary 3D cell cultures from canine spontaneous neoplasms and (2) to demonstrate the morphological, phenotypic and genotypic similarities between the primary canine neoplasms and the corresponding 3D cultures, through the expression of tumor differentiation markers.ResultsSeven primary tumors were collected, including 4 carcinomas and 3 soft tissue sarcomas. 3D cell cultures reproduced the morphological features of the primary tumors and showed an overlapping immunophenotype of the primary epithelial tumors. Immunohistochemistry demonstrated the growth of stromal cells and macrophages admixed with the neoplastic epithelial component, reproducing the tumor microenvironment. Mesenchymal 3D cultures reproduced the immunophenotype of the primary tumor completely in 2 out of 3 examined cases while a discordant expression was documented for a single marker in one case. No single nucleotide variants or small indel were detected in TP53 or MDM2 genes, both in primary tumors and in 3D cell cultures specimens. In one sample, MDM2 amplicons were preferentially increased in number compared to TP53 ones, indicating amplification of MDM2, detectable both in the primary tumor and in the corresponding cell culture specimen.ConclusionHere we demonstrate a good cell morphology, phenotype and genetic profile overlap between primary tumors and the corresponding 3D cultures grown in a repeatable system

COVID-19 Vaccine Hesitancy in Italy: Predictors of Acceptance, Fence Sitting and Refusal of the COVID-19 Vaccination

Background: The hesitancy in taking the COVID-19 vaccine is a global challenge. The need to identify predictors of COVID-19 vaccine reluctance is critical. Our objectives were to evaluate sociodemographic, psychological, and behavioral factors, as well as attitudes and beliefs that influence COVID-19 vaccination hesitancy in the general population of Italy. Methods: A total of 2,015 people were assessed in two waves (March, April and May, 2021). Participants were divided into three groups: (1) individuals who accepted the vaccination (“accepters”); (2) individuals who refused the vaccination (“rejecters”); and (3) individuals who were uncertain about their attitudes toward the vaccination (“fence sitters”). Group comparisons were performed using ANOVA, the Kruskal-Wallis test and chi-square tests. The strength of the association between the groups and the participants' characteristics was analyzed using a series of multinomial logistic regression models with bootstrap internal validation (one for each factor). Results: The “fence sitters” group, when compared to the others, included individuals of younger age, lower educational level, and worsening economic situation in the previous 3 months. After controlling for sociodemographic factors, the following features emerged as the main risk factors for being “fence sitters” (compared with vaccine “accepters”): reporting lower levels of protective behaviors, trust in institutions and informational sources, frequency of use of informational sources, agreement with restrictions and higher conspirative mentality. Higher levels of COVID-19 perceived risk, trust in institutions and informational sources, frequency of use of informational sources, agreement with restrictions and protective behaviors were associated with a higher likelihood of becoming “fence sitters” rather than vaccine “rejecters.” Conclusions: The “fence sitters” profile revealed by this study is intriguing and should be the focus of public programmes aimed at improving adherence to the COVID-19 vaccination campaign

Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review

Identified 50 years ago, mesenchymal stromal/stem cells (MSCs) immediately generated a substantial interest among the scientific community because of their differentiation plasticity and hematopoietic supportive function. Early investigations provided evidence of a relatively low engraftment rate and a transient benefit for challenging congenital and acquired diseases. The reasons for these poor therapeutic benefits forced the entire field to reconsider MSC mechanisms of action together with their ex vivo manipulation procedures. This phase resulted in advances in MSCs processing and the hypothesis that MSC-tissue supportive functions may be prevailing their differentiation plasticity, broadening the spectrum of MSCs therapeutic potential far beyond their lineage-restricted commitments. Consequently, an increasing number of studies have been conducted for a variety of clinical indications, revealing additional challenges and suggesting that MSCs are still lagging behind for a solid clinical translation. For this reason, our aim was to dissect the current challenges in the development of still promising cell types that, after more than half a century, still need to reach their maturity. Stem Cells Translational Medicine 2019;8:1135–1148

Is psychiatric residential facility discharge possible and predictable? A multivariate analytical approach applied to a prospective study in Italy

A growing number of severely ill patients require long-term care in non-hospital residential facilities (RFs). Despite the magnitude of this development, longitudinal studies surveying fairly large resident samples and yielding important information on this population have been very few