Innovation and profitability in a population of Italian listed companies during a time of crisis

The analysis examines the relationship between the number of patents registered and the trend of performance indicators, such as turnover and return on invested capital (ROI), in a population Italian listed companies. Although the results do not identify a precise trend for the entire sample, regular behaviours appear: with the approaching crisis, a high reduction in the average number of patents and a worse performance are recorded. Nevertheless, with reference to these trends, no positive relationship between the two variables was identified

Going "beyond the mean" in analysing immigrant health disparities

Background: On arrival, immigrants are on average healthier than Italian natives, but their health advantage tends to dissipate over time. This constitutes a relevant public health issue for the hosting societies, as it implies higher health care costs, lower labor market participation among immigrants, and lower tax revenues. Objective: This study is the first to take a "beyond the mean" perspective in analyzing health differences between Italians and short-say immigrants, as well as between short- and long-stay immigrants. It highlights whether health differences are concentrated in specific parts of the distributions and which observed or unobserved factors contribute to these differences. Methods: We use unconditional quantile regressions combined with Oaxaca-Blinder decompositions on data from the Italian Health Condition Survey. Results: We find that the health advantage of short-stay immigrants over both Italians and long- stay immigrants is concentrated in the lower part of the health distributions. In both cases, this is mainly due to unobserved factors. Observed economic characteristics are actually associated with better health for long-stay immigrants compared to short-stay immigrants. Our results reveal the need of monitoring immigrants' health, particularly of those with poorer initial health conditions. Contribution: We examine immigrant health disparities across the entire health distribution. This helps in shaping effective health policies. Policy interventions should be tailored to immigrants with poor health conditions, for example, by improving their access to the health care system

Obinutuzumab-mediated high-affinity ligation of FcγRIIIA/CD16 primes NK cells for IFNγ production

Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC), based on the recognition of IgG-opsonized targets by the low-affinity receptor for IgG FcγRIIIA/CD16, represents one of the main mechanisms by which therapeutic antibodies (mAbs) mediate their antitumor effects. Besides ADCC, CD16 ligation also results in cytokine production, in particular, NK-derived IFNγ is endowed with a well-recognized role in the shaping of adaptive immune responses. Obinutuzumab is a glycoengineered anti-CD20 mAb with a modified crystallizable fragment (Fc) domain designed to increase the affinity for CD16 and consequently the killing of mAb-opsonized targets. However, the impact of CD16 ligation in optimized affinity conditions on NK functional program is not completely understood. Herein, we demonstrate that the interaction of NK cells with obinutuzumab-opsonized cells results in enhanced IFNγ production as compared with parental non-glycoengineered mAb or the reference molecule rituximab. We observed that affinity ligation conditions strictly correlate with the ability to induce CD16 down-modulation and lysosomal targeting of receptor-associated signaling elements. Indeed, a preferential degradation of FcεRIγ chain and Syk kinase was observed upon obinutuzumab stimulation independently from CD16-V158F polymorphism. Although the downregulation of FcεRIγ/Syk module leads to the impairment of cytotoxic function induced by NKp46 and NKp30 receptors, obinutuzumab-experienced cells exhibit an increased ability to produce IFNγ in response to different stimuli. These data highlight a relationship between CD16 aggregation conditions and the ability to promote a degradative pathway of CD16-coupled signaling elements associated to the shift of NK functional progra

Foot Reconstruction

Since the conquest of the upright position, the foot has gained more importance as an organ that supports both the lower limb and the whole body weight and that allows humans to stand up, walk, run, jump, and climb. Human evolution determined progressive changes in both the skeleton architecture and the soft tissue of the foot to cope with the new environmental requirements. From the orangutan to the chimpanzee, from the gorilla to the human, the most important modifications of the skeleton included the progressive reduction of the distal area of the phalanxes with the loss of the grasping function and the enlargement of the proximal bones (astragalus, calcaneum) to obtain a resistant yet flexible structure. See the image below

Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukaemia

The most recent clinical trials on adult acute lymphoid leukaemia (ALL) have shown complete remission and disease-free survival (DFS) rates of 80-85% and 30-40%, respectively (Annino, et al, Durrant, et al, Kantarjian, et al, Larson, et al, Ribera, et al, Rowe). Intensified consolidation, particularly with high-dose methotrexate and high-dose cytarabine, may be one of the reasons for the improved outcome in recent series (Bassan and Hoelzer, Hoelzer and Gokbuget, Kebriaei and Larson). In addition, risk-adapted and subtype-oriented therapy may have contributed to this better outcome. However, the long term outcome of adult patients is still dismal, with approximately one third of the cases only being cured. At present, therapeutic options include conventional chemotherapy (CHT), high dose therapy with autologous and, especially, allogeneic stem cells transplantation (SCT) and, for certain subsets, such as BCR-ABL1+ ALL, specific targeted therapy (Piccaluga, et al). Although SCT has been used in adult ALL for more than 20 years, its role remains controversial as demonstrated by conflicting results in various studies. Previous casecontrolled studies did not show that allogeneic SCT (alloSCT) provided any advantage over CHT (Horowitz, et al, Zhang, et al) while in some studies there was an advantage, but restricted to young adults (Oh, et al). The number of controlled published or ongoing trials is remarkably small and some of them did not include both standard-risk and high-risk patients. Thus, it is difficult to draw definitive conclusions from their results. In fact, while some authors did not report any differences between alloSCT and chemotherapy or autologous SCT (ASCT)(Gupta, et al, Labar, et al), others only found differences favouring allogeneic SCT in standard risk (Goldstone, et al) or high-risk ALL patients (Sebban, et al, Thiebaut, et al, Thomas, et al). In this chapter, the Authors reviewed data concerning alloSCT in adult ALL and discuss current controversial and possible perspectives

The Effectiveness of Therapeutic Vaccines for the Treatment of Cervical Intraepithelial Neoplasia 3: A Systematic Review and Meta-Analysis

Cervical cancer (CC) is a disease that affects many women worldwide, especially in low-income countries. The human papilloma virus (HPV) is the main causative agent of this disease, with the E6 and E7 oncoproteins being responsible for the development and maintenance of transformed status. In addition, HPV is also responsible for the appearance of cervical intraepithelial neoplasia (CIN), a pre-neoplastic condition burdened by very high costs for its screening and therapy. So far, only prophylactic vaccines have been approved by regulatory agencies as a means of CC prevention. However, these vaccines cannot treat HPV-positive women. A search was conducted in several databases (PubMed, Scopus, Web of Science, and ClinicalTrials.gov) to systematically identify clinical trials involving therapeutic vaccines against CIN 3. Histopathological regression data, immunological parameters, safety, DNA clearance, and vaccine efficacy were considered from each selected study, and from the 102 articles found, 8 were selected based on the defined inclusion criteria. Histopathological regression from CIN 3 to CIN < 1 was 22.1% (95% CI: 0.627–0.967; p-value = 0.024), showing a vaccine efficacy of 23.6% (95% CI; 0.666–0.876; p-value < 0.001). DNA clearance was assessed, and the risk of persistent HPV DNA was 23.2% (95% CI: 0.667–0.885; p-value < 0.001). Regarding immunological parameters, immune responses by specific T-HPV cells were more likely in vaccinated women (95% CI: 1.245–9.162; p-value = 0.017). In short, these studies favored the vaccine group over the placebo group. This work indicated that therapeutic vaccines are efficient in the treatment of CIN 3, even after accounting for publication bias.info:eu-repo/semantics/publishedVersio

The IMiDs targets IKZF-1/3 and IRF4 as novel negative regulators of NK cell-activating ligands expression in multiple myeloma

Immunomodulatory drugs (IMiDs) have potent anti-tumor activities in multiple myeloma (MM) and are able to enhance the cytotoxic function of natural killer (NK) cells, important effectors of the immune response against MM. Here, we show that these drugs can enhance the expression of the NKG2D and DNAM-1 activating receptor ligands MICA and PVR/CD155 in human MM cell lines and primary malignant plasma cells. Depletion of cereblon (CRBN) by shRNA interference strongly impaired upregulation of these ligands and, more interestingly, IMiDs/CRBN-mediated downregulation of the transcription factors Ikaros (IKZF1), Aiolos (IKZF3) and IRF4 was critical for these regulatory mechanisms. Indeed, shRNA knockdown of IKZF1 or IKZF3 expression was both necessary and sufficient for the upregulation of MICA and PVR/CD155 expression, suggesting that these transcription factors can repress these genes; accordingly, the direct interaction and the negative role of IKZF1 and IKZF3 proteins on MICA and PVR/CD155 promoters were demonstrated. Finally, MICA expression was enhanced in IRF4-silenced cells, indicating a specific suppressive role of this transcription factor on MICA gene expression in MM cells. Taken together, these findings describe novel molecular pathways involved in the regulation of MICA and PVR/CD155 gene expression and identify the transcription factors IKZF-1/IKZF-3 and IRF4 as repressors of these genes in MM cells

Calsequestrin-1 is Required for Association but not for Targeting of Triadin to the Junctional Sarcoplasmic Reticulum Membranes

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From grape to wine: a thorough compound specific isotopic, enantiomeric and quali-quantitative investigation by means of gas chromatographic analysis

In this study, multiple analytical approaches, including simultaneous enantiomeric and isotopic analysis, were employed to thoroughly investigate the volatile fraction in Moscato giallo grape berries and wines. For the qualitative and quantitative profiling, a fast GC-QqQ/MS approach was successfully utilized. However, prior to isotopic analysis, the extracts underwent an additional concentration step, necessitating an assessment of isotopic fractionation during the concentration process. Once the absence of carbon isotopic fractionation was confirmed, this research aimed to develop a suitable gas chromatographic method for the simultaneous detection of both enantiomeric and isotopic ratios of target monoterpenoids in Moscato giallo samples. To address the limitations associated with a one-dimensional approach, multidimensional gas chromatography was employed to enhance separation before IRMS and qMS detections. Utilizing a Deans switch transfer device, the coupling of an apolar column in the first dimension and a chiral cyclodextrin-based stationary phase in the second dimension proved effective for this purpose. The data obtained from the analysis of Moscato giallo samples allowed for the assessment of natural isotopic and enantiomeric distributions in grapes and wines for the first time in the literature. Significant enantiomeric excesses were observed for the target terpenoids investigated. Regarding isotopic distribution, a consistent trend was observed for all detected target terpenols, including the linalool enantiomers. To date, this study represents the first investigation of simultaneous δ13C and chiral investigation of the main terpenoids in oenological products in the literatur