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Extraction-site alveolar remodeling is a major concern due to negative volumetric hard and soft tissue changes that inevitably limit rehabilitation options and diminish esthetic outcomes. Surgical techniques employed to minimize alveolar dimensional changes are not always predictable. Utilizing a socket shield with an immediate surgical implant procedure helps maintain a thin portion of the root in the vestibular area and thus minimizes bone resorption, especially at the coronal cortical aspect. This case series assesses the dimensional changes in peri-alveolar structures via superimposition of the preoperative and 6-month postoperative 3D digital quantification of soft tissue. Fifty patients with 50 sites fulfilled the inclusion criteria. Implant survival was 100%, with no incidence of complications. Tissue changes were as follows: -0.85 mm at the mesial papilla, -0.95 mm at the distal papilla, -0.7 mm at both the vertical and horizontal central margins, -0.21 mm at a distance 4 mm from the margin, and -0.64 mm at the palatal central margin. The buccal contour was clinically convex in all cases. The site with highest frequency of > 1 mm of dimensional loss was the distal papilla (42% of sites), and the site with the lowest frequency was the point 4 mm from the midfacial margin (0% of sites).

Aspergillus fumigatus is the most common opportunistic fungal pathogen and causes invasive pulmonary aspergillosis (IPA), with high mortality among immunosuppressed patients. The fungistatic activity of all- trans retinoic acid (ATRA) has been recently described in vitro We evaluated the efficacy of ATRA in vivo and its potential synergistic interaction with other antifungal drugs. A rat model of IPA and in vitro experiments were performed to assess the efficacy of ATRA against Aspergillus in association with classical antifungal drugs and in silico studies used to clarify its mechanism of action. ATRA (0.5 and 1 mM) displayed a strong fungistatic activity in Aspergillus cultures, while at lower concentrations, synergistically potentiated fungistatic efficacy of subinhibitory concentration of amphotericin B (AmB) and posaconazole (POS). ATRA also enhanced macrophagic phagocytosis of conidia. In a rat model of IPA, ATRA reduced mortality similarly to posaconazole. Fungistatic efficacy of ATRA alone and synergistically with other antifungal drugs was documented in vitro , likely by inhibiting fungal heat shock protein 90 ( Hsp90 ) expression and Hsp90-related genes. ATRA treatment reduced mortality in a model of IPA in vivo Those findings suggest ATRA as a suitable fungistatic agent that can also reduce dosage and adverse reactions of classical antifungal drugs and add to the development of new therapeutic strategies against IPA and systemic fungal infections., (Copyright © 2021 Campione et al.)

This paper focuses on ultra-reliable low-latency Vehicle-to-Anything (V2X) communications able to meet the extreme requirements of high Levels of Automation (LoA) use cases. We introduce a system architecture and processing algorithms for the alignment of highly collimated V2X beams based either on millimeter-Wave (mmW) or Free-Space Optics (FSO). Beam-based V2X communications mainly suffer from blockage and pointing misalignment issues. This work focuses on the latter case, which is addressed by proposing a V2X architecture that enables a sensor-aided beam-tracking strategy to counteract the detrimental effect of vibrations and tilting dynamics. A parallel low-rate, low-latency, and reliable control link, in fact, is used to exchange data on vehicle kinematics (i.e., position and orientation) that assists the beam-pointing along the line-of-sight between V2X transceivers (i.e., the dominant multipath component for mmW, or the direct link for FSO). This link can be based on sub-6 GHz V2X communication, as in 5G frequency range 1 (FR1). Performance assessments are carried out to validate the robustness of the proposed methodology in coping with misalignment induced by vehicle dynamics. Numerical results show that highly directional mmW and/or FSO communications are promising candidates for massive data-rate vehicular communications even in high mobility scenarios.

Embryonic stem cells (ESCs) are derived from inner cell mass (ICM) of the blastocyst. In serum/LIF culture condition, they show variable expression of pluripotency genes that mark cell fluctuation between pluripotency and differentiation metastate. The ESCs subpopulation marked by zygotic genome activation gene (ZGA) signature, including Zscan4 , retains a wider differentiation potency than epiblast-derived ESCs. We have recently shown that retinoic acid (RA) significantly enhances Zscan4 cell population. However, it remains unexplored how RA initiates the ESCs to 2-cell like reprogramming. Here we found that RA is decisive for ESCs to 2C-like cell transition, and reconstructed the gene network surrounding Zscan4 . We revealed that RA regulates 2C-like population co-activating Dux and Duxbl1 . We provided novel evidence that RA dependent ESCs to 2C-like cell transition is regulated by Dux , and antagonized by Duxbl1 . Our suggested mechanism could shed light on the role of RA on ESC reprogramming., (Copyright © 2020 Tagliaferri, Mazzone, Noviello, Addeo, Angrisano, Del Vecchio, Visconte, Ruggieri, Russi, Caivano, Cantone, De Felice, Ceccarelli, Cerulo and Falco.)

Embryonic stem cells (ESCs) fluctuate among different levels of pluripotency defined as metastates. Sporadically, metastable cellular populations convert to a highly pluripotent metastate that resembles the preimplantation two-cell embryos stage (defined as 2C stage) in terms of transcriptome, DNA methylation, and chromatin structure. Recently, we found that the retinoic acid (RA) signaling leads to a robust increase of cells specifically expressing 2C genes, such as members of the Prame family. Here, we show that Gm12794c, one of the most highly upregulated Prame members, and previously identified as a key player for the maintenance of pluripotency, has a functional role in conferring ESCs resistance to RA signaling. In particular, RA-dependent expression of Gm12794c induces a ground state-like metastate, as evaluated by activation of 2C-specific genes, global DNA hypomethylation and rearrangement of chromatin similar to that observed in naive totipotent preimplantation epiblast cells and 2C-like cells. Mechanistically, we demonstrated that Gm12794c inhibits Cdkn1A gene expression through the polycomb repressive complex 2 (PRC2) histone methyltransferase activity. Collectively, our data highlight a molecular mechanism employed by ESCs to counteract retinoic acid differentiation stimuli and contribute to shed light on the molecular mechanisms at grounds of ESCs naive pluripotency-state maintenance.

Acute myeloid leukemias (AML) are clonal disorders of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). miRNAs are small non-coding RNAs that regulate, at post-transcriptional level, translation and stability of mRNAs. It is now established that deregulated miRNA expression is a prominent feature in AML. Functional studies have shown that miRNAs play an important role in AML pathogenesis and miRNA expression signatures are associated with chemotherapy response and clinical outcome. In this review we summarized miRNA signature in AML with different cytogenetic, molecular and clinical characteristics. Moreover, we reviewed the miRNA regulatory network in AML pathogenesis and we discussed the potential use of cellular and circulating miRNAs as biomarkers for diagnosis and prognosis and as therapeutic targets., Competing Interests: The authors declare no conflict of interest.

Lin28A is a highly conserved RNA-binding protein that concurs to control the balance between stemness and differentiation in several tissue lineages. Here, we report the role of miR-128a/Lin28A axis in blocking cell differentiation in acute myeloid leukemia (AML), a genetically heterogeneous disease characterized by abnormally controlled proliferation of myeloid progenitor cells accompanied by partial or total inability to undergo terminal differentiation. First, we found Lin28A underexpressed in blast cells from AML patients and AML cell lines as compared with CD34+ normal precursors. In vitro transfection of Lin28A in NPM1-mutated OCI-AML3 cell line significantly triggered cell-cycle arrest and myeloid differentiation, with increased expression of macrophage associate genes (EGR2, ZFP36 and ANXA1). Furthermore, miR-128a, a negative regulator of Lin28A, was found overexpressed in AML cells compared with normal precursors, especially in acute promyelocytic leukemia (APL) and in 'AML with maturation' (according to 2016 WHO classification of myeloid neoplasms and acute leukemia). Its forced overexpression by lentiviral infection in OCI-AML3 downregulated Lin28A with ensuing repression of macrophage-oriented differentiation. Finally, knockdown of miR-128a in OCI-AML3 and in APL/AML leukemic cells (by transfection and lentiviral infection, respectively) induced myeloid cell differentiation and increased expression of Lin28A, EGR2, ZFP36 and ANXA1, reverting myeloid differentiation blockage. In conclusion, our findings revealed a new mechanism for AML differentiation blockage, suggesting new strategies for AML therapy based upon miR-128a inhibition.

Pluripotency confers Embryonic Stem Cells (ESCs) the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. Although the majority of ESCs divide without losing pluripotency, it has become evident that ESCs culture consists of multiple cell populations with different degrees of potency that are spontaneously induced in regular ESC culture conditions. Zscan4, a key pluripotency factor, marks ESC subpopulation that is referred to as high-level of pluripotency metastate. Here, we report that in ESC cultures treated with retinoic acid (RA), Zscan4 ESCs metastate is strongly enhanced. In particular, we found that induction of Zscan4 metastate is mediated via RA receptors (RAR-alpha, RAR-beta, and RAR-gamma), and it is dependent on phosphoinositide-3-kinase (PI3K) signaling. Remarkably, Zscan4 metastate induced by RA lacks canonical pluripotency genes Oct3/4 and Nanog but retained both self-renewal and pluripotency capabilities. Finally we demonstrated that the conditional ablation of Zscan4 subpopulation is dispensable for both endoderm and mesoderm but is required for ectoderm lineage. In conclusion, our research provides new insights about the role of RA signaling during ESCs high pluripotency metastate fluctuation.

Embryonic stem cells (ESCs) are characterized by two remarkable peculiarities: the capacity to propagate as undifferentiated cells (self-renewal) and the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives (pluripotency). Although the majority of ESCs divide without losing the pluripotency, it has become evident that ESC cultures consists of multiple cell populations highlighted by the expression of early germ lineage markers during spontaneous differentiation. Hence, the identification and characterization of ESCs subpopulations represents an efficient approach to improve the comprehension of correlation between gene expression and cell specification status. To study markers of ESCs heterogeneity, we developed an analysis pipeline which can automatically process images of stem cell colonies in optical microscopy. The question we try to address is to find out the statistically significant preferred locations of the marked cells. We tested our algorithm on a set of images of stem cell colonies to analyze the expression pattern of the Zscan4 gene, which was an elite candidate gene to be studied because it is specifically expressed in subpopulation of ESCs. To validate the proposed method we analyzed the behavior of control genes whose pattern had been associated to biological status such as differentiation (EndoA), pluripotency (Pou5f1), and pluripotency fluctuation (Nanog). We found that Zscan4 is not uniformly expressed inside a stem cell colony, and that it tends to be expressed towards the center of the colony, moreover cells expressing Zscan4 cluster each other. This is of significant importance because it allows us to hypothesize a biological status where the cells expressing Zscan4 are preferably associated to the inner of colonies suggesting pluripotent cell status features, and the clustering between themselves suggests either a colony paracrine effect or an early phase of cell specification through proliferation. Also, the analysis on the control genes showed that they behave as expected.

Renal involvement during lymphoma can be extrinsic, i.e., renal compression or displacement due to lymph node masses, or intrinsic, i.e., parenchymal involvement secondary to blood or lymphatic spread, or primary, as initial neoplastic site. Primary renal lymphoma is very rare (3% of all renal lymphomas) for the absence of lymphatic tissue in the kidney. The disease might be due to parapyelic lymph nodes or to blood spreading from an unknown site. In our study we reviewed the CT findings of five cases of primary non-Hodgkin's renal lymphoma with surgical or histologic confirmation. Renal alterations due to lymphomatous involvement were classified according to macroscopic pathologic findings: type I (single nodular disease, 2 patients), type II (multinodular disease, 1 patient), and type III (infiltrating disease with retroperitoneal involvement, 2 patients). In the two patients with single nodular involvement (type I), CT showed a solid, hypodense and clear-cut nodule. In the only patient with multinodular disease (type II), renal tissue was replaced by multiple hypodense nodular masses, which were partially confluent. In the two infiltrating forms with retroperitoneal involvement (type III), renal structure was diffusely disorganized, with thickening of soft tissues and perirenal fasciae, peripyelic infiltration and, in one case, urinary tract obstruction. To conclude, CT always allowed the accurate assessment of the presence, site and size of renal lesions and of perirenal and urinary involvement. However, CT findings were completely aspecific, not allowing an unquestionable differential diagnosis with other conditions, e.g., hypernephroma, transitional cell carcinoma, metastatic lesions or chronic inflammations. Therefore, a biopsy specimen is necessary to make an unquestionable diagnosis.