Strong YB-1 Expression Predicts Liver Recurrence Following Resection for Colorectal Metastases

Introduction

The Y-box binding protein-1 (YB-1) is a multifunctional oncoprotein involved in the proliferation and aggressiveness of cancer cells. The aim of this study was to determine whether strong YB-1 expression in neoplastic cells of colorectal liver metastases (CRLM) may have an impact on liver disease-free survival following liver resection.

Materials and Methods

Immunohistochemistry was performed to evaluate YB-1 in 66 patients who underwent liver resection for CRLM. YB-1 expression was classified as weak (low-staining intensity) and strong (high-staining intensity).

Results

YB-1 expression was observed in the cytoplasm of all CRLM. YB-1 expression was weak in 17 patients (25.8 %) and strong in 49 patients (74.2 %). Liver recurrence rate was significantly higher in the strong than in the weak expression group: 55.1 vs. 23.5 % (p?=?0.023). Multivariable logistic regression analysis showed that YB-1 strong expression was the only independent risk factor for liver recurrence. The 5-year specific liver disease-free survival rate was 76.0 % in the weak expression group and 41.5 % in the strong expression group (p?=?0.034). These results were not influenced by clinical prognostic factors of tumor recurrence.

Conclusions

This is the first study showing that the degree of YB-1 expression in tissue specimens of CRLM predicts liver recurrence following liver resection.     

A State-of-the-Art Review on Advanced Joining Processes for Metal-Composite and Metal-Polymer Hybrid Structures

Multi-materials of metal-polymer and metal-composite hybrid structures (MMHSs) are highly demanded in several fields including land, air and sea transportation, infrastructure construction, and healthcare. The adoption of MMHSs in transportation industries represents a pivotal opportunity to reduce the product’s weight without compromising structural performance. This enables a dramatic reduction in fuel consumption for vehicles driven by internal combustion engines as well as an increase in fuel efficiency for electric vehicles. The main challenge for manufacturing MMHSs lies in the lack of robust joining solutions. Conventional joining processes, e.g., mechanical fastening and adhesive bonding involve several issues. Several emerging technologies have been developed for MMHSs’ manufacturing. Different from recently published review articles where the focus is only on specific categories of joining processes, this review is aimed at providing a broader and systematic view of the emerging opportunities for hybrid thin-walled structure manufacturing. The present review paper discusses the main limitations of conventional joining processes and describes the joining mechanisms, the main differences, advantages, and limitations of new joining processes. Three reference clusters were identified: fast mechanical joining processes, thermomechanical interlocking processes, and thermomechanical joining processes. This new classification is aimed at providing a compass to better orient within the broad horizon of new joining processes for MMHSs with an outlook for future trends.     

Spatiotemporal Analysis of COVID-19 Incidence Data

(1) Background: A better understanding of COVID-19 dynamics in terms of interactions among individuals would be of paramount importance to increase the effectiveness of containment measures. Despite this, the research lacks spatiotemporal statistical and mathematical analysis based on large datasets. We describe a novel methodology to extract useful spatiotemporal information from COVID-19 pandemic data. (2) Methods: We perform specific analyses based on mathematical and statistical tools, like mathematical morphology, hierarchical clustering, parametric data modeling and non-parametric statistics. These analyses are here applied to the large dataset consisting of about 19,000 COVID-19 patients in the Veneto region (Italy) during the entire Italian national lockdown. (3) Results: We estimate the COVID-19 cumulative incidence spatial distribution, significantly reducing image noise. We identify four clusters of connected provinces based on the temporal evolution of the incidence. Surprisingly, while one cluster consists of three neighboring provinces, another one contains two provinces more than 210 km apart by highway. The survival function of the local spatial incidence values is modeled here by a tapered Pareto model, also used in other applied fields like seismology and economy in connection to networks. Model’s parameters could be relevant to describe quantitatively the epidemic. (4) Conclusion: The proposed methodology can be applied to a general situation, potentially helping to adopt strategic decisions such as the restriction of mobility and gatherings.     

Perioperative identifications of non-palpable pulmonary nodules: a narrative review

Early detection of lung cancer is the key to improving treatment and prognosis of this disease, and the advent of advances in computed tomography (CT) imaging and national screening programs have improved the detection rate of very small pulmonary lesions. As such, the management of this sub-centimetric and often sub-solid lesions has become quite challenging for clinicians, especially for choosing the most suitable diagnostic method. In clinical practice, to fulfill this diagnostic yield, transthoracic needle biopsy (TTNB) is often the first choice especially for peripheral nodules. For lesions for which TTNB could present technical difficulties or failed, other diagnostic strategies are needed. In this case, video-assisted thoracic surgery (VATS) is the gold standard to reach the diagnosis of lung nodules suspect of being malignant. Nonetheless it’s often not easy the identification of such lesions during VATS because of their little dimensions, non-firm consistency, deep localization. In literature various marking techniques have been described, in order to improve intraoperative nodules detection and to reduce conversion rate to thoracotomy: CT-guided hookwire positioning, methylene blue staining, intra-operative ultrasound and electromagnetic navigation bronchoscopy are the most used. The scientific evidence on this matter is weak because there are no randomized clinical trials but only case series on single techniques with no comparison on efficacy, so there are no guidelines to refer. From this standing, in this article we conducted a narrative review of the existing literature on the subject, with the aim of outlining a framework as complete as possible. We analyzed strengths and weaknesses of the main techniques reported, so as to allow the clinician to orient himself with greater ease.     

Rapamycin-mediated induction of gamma-globin mRNA accumulation in human erythroid cells

The present study aimed to determine whether rapamycin could increase the expression of gamma-globin genes in human erythroid cells. Rapamycin is a macrocyclic lactone that possesses immunosuppressive, antifungal and anti-tumour properties. This molecule is approved as an immunosuppressive agent for preventing rejection in patients receiving organ transplantation. To verify the activity of rapamycin, we employed two experimental cell systems, the human leukaemia K562 cell line and the two-phase liquid culture of human erythroid progenitors isolated from normal donors and patients with beta-thalassaemia. The results suggested that rapamycin, when compared with cytosine arabinoside, mithramycin and cisplatin, is a powerful inducer of erythroid differentiation and gamma-globin mRNA accumulation in human leukaemia K562 cells. In addition, when normal human erythroid precursors were cultured in the presence of rapamycin, gamma-globin mRNA accumulation and fetal haemoglobin (HbF) production increased to levels that were higher than those obtained using hydroxyurea. These effects were not associated with inhibition of cell growth. Furthermore, rapamycin was found to increase HbF content in erythroid precursor cells from four beta-thalassaemia patients. These results could have practical relevance, because pharmacologically mediated regulation of the expression of human gamma-globin genes, leading to increased HbF, is considered a potential therapeutic approach in haematological disorders, including beta-thalassaemia and sickle cell anaemia.     

Redefining the prognostic likelihood of chronic lymphocytic leukaemia patients with borderline percentage of immunoglobulin variable heavy chain region mutations

In chronic lymphocytic leukaemia (CLL), caution is warranted regarding the clinical implications of immunoglobulin variable heavy chain region (IGHV) rearrangements with a ‘borderline’ (BL) percentage of mutations (i.e. 97–97·9% IGHV identity). We analysed the IGHV mutational status in 759 untreated CLL patients (cohort 1). BL-CLL (n = 36, 5%) showed a time to first treatment (TFT) similar to that of M-CLL (n = 338) and significantly longer than that of UM-CLL (n = 385), despite the enrichment in subset #2 cases. In fact, CLLs belonging to subset #2 (n = 15/759, 2%) were significantly more frequent among BL-CLLs (n = 5/36, 14%), with a brief TFT. TFT of BL-CLL remained comparable to that of M-CLL also considering the 327 CLL patients evaluated at diagnosis. These findings were then validated in an independent cohort 2 of 759 newly diagnosed CLL patients (BL-CLL: n = 11, 1·4%) and in all newly diagnosed patients from cohorts 1 and 2 (n = 1 086, 84% stage A; BL-CLL: n = 47, 4·3%). BL-CLL at diagnosis showed a biological profile comparable to that of M-CLL with a low frequency of unfavourable prognostic markers, except for a significant enrichment in subset #2. Our data suggest that the prognosis of BL-CLL is good and similar to that of M-CLL, with the exception of subset #2 cases.