Mesothelioma among seamen: a systematic review and meta-analysis

Objectives: Navy personnel and seafarers live and work 24 h per day in the shipboard environment and they are exposed to asbestos fibers released into the confined spaces aboard ships. We conducted a systematic review and meta-analysis to quantify the mesothelioma risk of seamen working aboard ships, either commercial or naval vessels, as compared to that of the general population. Methods: We carried out a literature search in MEDLINE through PubMed and EMBASE, from inception to 31 December 2021, of all studies on seamen working aboard ships, either commercial or naval vessels, characterized by exposure to asbestos and providing mesothelioma risk estimates. The Newcastle-Ottawa Scale was used to assess the quality of the studies included. The pooled standardized mortality ratio (SMR) was computed across eligible studies. The study protocol was registered on PROSPERO and reporting followed the preferred reporting items for systematic reviews and meta-analyses guidelines. Results: A total of 10 studies published from 1990 to 2020 were considered eligible and included in the systematic review and meta-analysis. All the included studies were of good quality, with a median score of seven out of nine. Overall, there were 235 mesothelioma cases/deaths in the included studies versus 115.6 expected, with a pooled SMR of 2.11 (95% confidence intervals, 1.70-2.62), in the absence of a significant between-study heterogeneity (I2 = 39%, P = 0.11). Conclusion: A more than double excess risk for mesothelioma among seamen working aboard ships emerged from our meta-analysis

Covered self-expandable metal stents for pancreatic duct stricture: a systematic review and meta-analysis

Background and study aims Placement of a covered (C)-self-expandable metal stent (SEMS) has been recently investigated as an alternative endoscopic treatment for main pancreatic duct stricture (MPDS) in chronic pancreatitis. Our aim was to carry out a systematic review and meta-analysis of studies quantifying efficacy and safety of C-SEMSs in the management of MPDS.Methods A multiple database search was performed, including MEDLINE, Embase and Cochrane Library, from January 2000 to September 2020, to identify studies reporting the efficacy and safety of C-SEMSs in patients with MPDS. Stricture and pain resolution were investigated. Other outcomes included technical success, stent migration, stricture recurrence and need for repeated stent placement. Pancreatitis, severe abdominal pain requiring stent removal and de-novo stricture were recorded as complications.Results Nineteen studies were identified, which included a total of 300 patients. C-SEMSs showed a pooled stricture resolution rate of 91 % [95 % confidence interval (CI), 85 %-96 %] and a pooled pain resolution rate of 92 % (95 % CI, 85 %-98 %). The pooled proportion for stricture recurrence was equal to 6 % (95 % CI, 1 %-14 %), while stent migration occurred in 33 of 300 patients, the pooled proportion being 7 % (95 % CI 1 %-15 %). The pooled mean stent duration was 133 days (95 % CI, 100-166 days). The most common complication was pancreatitis (3 %, 95 % CI 0 %-8 %), while de-novo stricture pooled proportion was 2 % (95 % CI, 0 %-5 %).Conclusions C-SEMSs are effective and safe in the treatment of MPDS. However, there is a significant need for further high-quality, well-designed studies to produce evidence-based data on short and long-term efficacy, safety, costs of C-SEMSs, and also optimal stent duration

Moduli spaces on the Kuznetsov component of Fano threefolds of index 2

General hyperplane sections of a Fano threefold $Y$ of index 2 and Picard rank 1 are del Pezzo surfaces, and their Picard group is related to a root system. To the corresponding roots, we associate objects in the Kuznetsov component of $Y$ and investigate their moduli spaces, using the stability condition constructed by Bayer, Lahoz, Macr\`i, and Stellari, and the Abel--Jacobi map. We identify a subvariety of the moduli space isomorphic to $Y$ itself, and as an application we prove a (refined) categorical Torelli theorem for general quartic double solids.Comment: 34 pages, substantially rewritten to improve exposition, references updated. Comments are very welcome

Satisfaction with online teaching of medical statistics during the COVID-19 pandemic: A survey by the Education Committee of the Italian Society of Medical Statistics and Clinical Epidemiology

: On May 2020, after 2 months of online teaching with no face-to-face lectures, the Education Committee of the Italian scientific Society of Medical Statistics and Clinical Epidemiology conceived an online survey to assess satisfaction of Italian academics of medical statistics with online teaching and remote exams. This survey highlighted teachers' perceptions as well as opportunities and limitations of online teaching of medical statistics, biostatistics, and epidemiology. Although 61% of Italian academics of medical statistics declared to be favorable to provide online teaching of medical statistics, biostatistics, and epidemiology in the future, we recognize that distance education cannot substitute the unique value of teaching and knowledge exchange that could only be transmitted through a personal interaction between students and teachers. These indications may be useful to improve the quality of the teaching process in the future

New Insights on the Nuclear Functions and Targeting of FAK in Cancer

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed and activated in both adult and pediatric cancers, where it plays important roles in the regulation of pathogenesis and progression of the malignant phenotype. FAK exerts its functions in cancer by two different ways: a kinase activity in the cytoplasm, mainly dependent on the integrin signaling, and a scaffolding activity into the nucleus by networking with different gene expression regulators. For this reason, FAK has to be considered a target with high therapeutic values. Indeed, evidence suggests that FAK targeting could be effective, either alone or in combination, with other already available treatments. Here, we propose an overview of the novel insights about FAK's structure and nuclear functions, with a special focus on the recent findings concerning the roles of this protein in cancer. Additionally, we provide a recent update on FAK inhibitors that are currently in clinical trials for patients with cancer, and discuss the challenge and future directions of drug-based anti-FAK targeted therapies

FAK Signaling in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children and adolescents. The fusion-positive (FP)-RMS variant expressing chimeric oncoproteins such as PAX3-FOXO1 and PAX7-FOXO1 is at high risk. The fusion negative subgroup, FN-RMS, has a good prognosis when non-metastatic. Despite a multimodal therapeutic approach, FP-RMS and metastatic FN-RMS often show a dismal prognosis with 5-year survival of less than 30%. Therefore, novel targets need to be discovered to develop therapies that halt tumor progression, reducing long-term side effects in young patients. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that regulates focal contacts at the cellular edges. It plays a role in cell motility, survival, and proliferation in response to integrin and growth factor receptors' activation. FAK is often dysregulated in cancer, being upregulated and/or overactivated in several adult and pediatric tumor types. In RMS, both in vitro and preclinical studies point to a role of FAK in tumor cell motility/invasion and proliferation, which is inhibited by FAK inhibitors. In this review, we summarize the data on FAK expression and modulation in RMS. Moreover, we give an overview of the approaches to inhibit FAK in both preclinical and clinical cancer settings

THERMOCOUPLES POSITIONING FOR EARLY-WARNING DETECTION OF THERMAL RUNAWAY

Runaway reactions have always been a serious issue for the chemical industry. Failures that may lead to this type of accident are different: block of the impeller, loss of the reactor temperature control, error in the loading of reagents, just to name a few. The rapid detection of this phenomena is crucial. One of the most widely used preventive systems is the so-called early warning system, which allows to give an early warning at the beginning of the fugitive reaction. Due to non-homogeneity of the temperature inside the reactor, the positioning of the sensors is of crucial importance. In fact, an incorrect localization of the temperature probe could lead to a false alarm, which would undermine the early warning system. The objective of this work is the computational fluid dynamic (CFD) simulation of different failure scenarios, in order to determine the best location of the temperature sensors

DNA Damage Response Gene Signature as Potential Treatment Markers for Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is a rapidly progressive cancer that often develops resistance against DNA damage inducers, such as radiotherapy and chemotherapy, which are still the standard of care regimens for this tumor. Thus, the identification of biomarkers capable of monitoring the clinical progression of OSCC and its responsiveness to therapy is strongly required. To meet this need, here we have employed Whole Genome Sequencing and RNA-seq data from a cohort of 316 patients retrieved from the TCGA Pan-Cancer Atlas to analyze the genomic and transcriptomic status of the DNA damage response (DDR) genes in OSCC. Then, we correlated the transcriptomic data with the clinical parameters of each patient. Finally, we relied on transcriptomic and drug sensitivity data from the CTRP v2 portal, performing Pearson's correlation analysis to identify putative vulnerabilities of OSCC cell lines correlated with DDR gene expression. Our results indicate that several DDR genes show a high frequency of genomic and transcriptomic alterations and that the expression of some of them correlates with OSCC grading and infection by the human papilloma virus. In addition, we have identified a signature of eight DDR genes (namely CCNB1, CCNB2, CDK2, CDK4, CHECK1, E2F1, FANCD2, and PRKDC) that could be predictive for OSCC response to the novel antitumor compounds sorafenib and tipifarnib-P1. Altogether, our data demonstrate that alterations in DDR genes could have an impact on the biology of OSCC. Moreover, here we propose a DDR gene signature whose expression could be predictive of OSCC responsiveness to therapy

Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis

Many clinical trials have investigated the role of ICIs in PM, with contrasting results. We performed a systematic review and meta-analysis of clinical trials testing single-agent anti-Programmed Death -1 (PD-1)/Programmed Death-Ligand 1 (PD-L1), anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or combined treatment in PM patients, analyzing response and survival rate as well as safety data. We selected 17 studies including 2328 patients. Both OS and PFS rates were significantly higher with combined ICI treatments than with single agent anti-PD-1/PD-L1 (p < 0.001 and p = 0.006, respectively) or anti CTLA-4 (p < 0.001) treatments. ORR and DCR for all ICI treatments were 20% (95% CI 13–27%) and 56% (95% CI 45–67%), respectively, and they did not significantly differ between combined and single agent treatments (p = 0.088 and p = 0.058, respectively). The 12-month OS and 6-month PFS rates did not differ significantly (p = 0.0545 and p = 0.1464, respectively) among pre-treated or untreated patients. Combined ICI treatments had a significantly higher rate of Adverse Events (AEs) (p = 0.01). PD-L1-positive patients had a higher probability of response and survival. In conclusion, combined ICI treatments have higher efficacy than single agents but are limited by higher toxicity. Efficacy was independent of treatment line, so a customized sequential strategy should still be speculated. PD-L1 expression could influence response to ICIs; however, reliable biomarkers are warranted