Features and prognostic impact of distant metastases in 45 dogs with de novo stage IV cutaneous mast cell tumours: A prospective study

BACKGROUND: Distant metastases in dogs with cutaneous mast cell tumors (cMCT) are rare and incurable. The aims of this prospective study were to clarify the clinico-pathological features of stage IV cMCTs and to identify possible prognostic factors for progression-free interval (PFI) and survival time (ST). MATERIAL AND METHODS: Dogs were eligible for recruitment if they had a previously untreated, histologically confirmed cMCT and if they underwent complete staging demonstrating stage IV disease. Dogs were uniformly followed-up, whereas treatment was not standardized and included no therapy, surgery, radiation therapy, chemotherapy, tyrosine-kinase inhibitors or a combination of these. RESULTS: 45 dogs with stage IV cMCT were enrolled. All dogs had distant metastatic disease, and 41 (91.1%) dogs had also metastasis in the regional lymph node. Histopathological grade and mutational status greatly varied among dogs. Median ST was 110 days. Notably, PFI and ST were independent of well-known prognostic factors, including anatomic site, histological grade, and mutational status. Conversely, tumor diameter >3\u2009cm, more than 2 metastatic sites, bone marrow infiltration, and lack of tumor control at the primary site were confirmed to be negative prognostic factors by multivariate analysis. CONCLUSION: Currently, there is no satisfactory treatment for stage IV cMCT. Asymptomatic dogs with tumor diameter <3\u2009cm and a low tumor burden, without bone marrow infiltration may be candidates for multimodal treatment. Stage IV dogs without lymph node metastasis may enjoy a surprisingly prolonged survival. The achievement of local tumor control seems to predict a better outcome in dogs with stage IV cMCT

Conformity and controversies in the diagnosis, staging and follow-up evaluation of canine nodal lymphoma: a systematic review of the last 15 years of published literature

Diagnostic methods used in the initial and post-treatment evaluation of canine lymphoma are heterogeneous and can vary within countries and institutions. Accurate reporting of clinical stage and response assessment is crucial in determining the treatment efficacy and predicting prognosis. This study comprises a systematic review of all available canine multicentric lymphoma studies published over 15 years. Data concerning diagnosis, clinical stage evaluation and response assessment procedures were extracted and compared. Sixty-three studies met the eligibility criteria. Fifty-five (87.3%) studies were non-randomized prospective or retrospective studies. The survey results also expose variations in diagnostic criteria and treatment response assessment in canine multicentric lymphoma. Variations in staging procedures performed and recorded led to an unquantifiable heterogeneity among patients in and between studies, making it difficult to compare treatment efficacies. Awareness of this inconsistency of procedure and reporting may help in the design of future clinical trials

A practical algorithmic approach to mature aggressive B cell lymphoma diagnosis in the double/triple hit era. Selecting cases, matching clinical benefit. A position paper from the Italian Group of Haematopathology (G.I.E.)

An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient

Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective B therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P&lt;0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo

Robotic Wireless Sensor Networks

In this chapter, we present a literature survey of an emerging, cutting-edge, and multi-disciplinary field of research at the intersection of Robotics and Wireless Sensor Networks (WSN) which we refer to as Robotic Wireless Sensor Networks (RWSN). We define a RWSN as an autonomous networked multi-robot system that aims to achieve certain sensing goals while meeting and maintaining certain communication performance requirements, through cooperative control, learning and adaptation. While both of the component areas, i.e., Robotics and WSN, are very well-known and well-explored, there exist a whole set of new opportunities and research directions at the intersection of these two fields which are relatively or even completely unexplored. One such example would be the use of a set of robotic routers to set up a temporary communication path between a sender and a receiver that uses the controlled mobility to the advantage of packet routing. We find that there exist only a limited number of articles to be directly categorized as RWSN related works whereas there exist a range of articles in the robotics and the WSN literature that are also relevant to this new field of research. To connect the dots, we first identify the core problems and research trends related to RWSN such as connectivity, localization, routing, and robust flow of information. Next, we classify the existing research on RWSN as well as the relevant state-of-the-arts from robotics and WSN community according to the problems and trends identified in the first step. Lastly, we analyze what is missing in the existing literature, and identify topics that require more research attention in the future

Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified

Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK - . Differentially expressed miRNAs were validated in an independent set of 20 PTCLs/NOS, 20 AITLs, 19 ALCLs/ALK - and 15 ALCLs/ALK+. Two hundred and thirty-six miRNAs were found to differentiate PTCLs/NOS from activated T-lymphocytes. To assess which miRNAs impacted on GEP, a multistep analysis was performed, which identified all miRNAs inversely correlated to different potential target genes. One of the most discriminant miRNAs was selected and its expression was found to affect the global GEP of the tumours. Moreover, two sets of miRNAs were identified distinguishing PTCL/NOS from AITL and ALCL/ALK - , respectively. The diagnostic accuracy of this tool was very high (83.54%) and its prognostic value validated

A fuzzy multi-criteria decision making approach for managing performance and risk in integrated procurement-production planning

Nowadays in Supply Chain (SC) networks, a high level of risk comes from SC partners. An effective risk management process becomes as a consequence mandatory, especially at the tactical planning level. The aim of this article is to present a risk-oriented integrated procurement–production approach for tactical planning in a multi-echelon SC network involving multiple suppliers, multiple parallel manufacturing plants, multiple subcontractors and several customers. An originality of the work is to combine an analytical model allowing to build feasible scenarios and a multi-criteria approach for assessing these scenarios. The literature has mainly addressed the problem through cost or profit-based optimisation and seldom considers more qualitative yet important criteria linked to risk, like trust in the supplier, flexibility or resilience. Unlike the traditional approaches, we present a method evaluating each possible supply scenario through performance-based and risk-based decision criteria, involving both qualitative and quantitative factors, in order to clearly separate the performance of a scenario and the risk taken if it is adopted. Since the decision-maker often cannot provide crisp values for some critical data, fuzzy sets theory is suggested in order to model vague information based on subjective expertise. Fuzzy Technique for Order of Preference by Similarity to Ideal Solution is used to determine both the performance and risk measures correlated to each possible tactical plan. The applicability and tractability of the proposed approach is shown on an illustrative example and a sensitivity analysis is performed to investigate the influence of criteria weights on the selection of the procurement–production plan

Histologic Grading of Canine Mast Cell Tumor

Mast cell tumor (MCT) is a common canine cutaneous neoplasm with variable biological behavior. A 2-tier histologic grading system was recently proposed by Kiupel et al to reduce interobserver variation and eliminate prognostic uncertainty of the Patnaik system. This study compared the ability of these 2 grading systems to predict survival in a cohort of dogs with MCTs. However, surgical margins were unknown, and the risk of developing new/metastatic MCTs was not studied. Histologic grade was assessed according to both systems for 137 surgically resected cutaneous MCTs. The relationship between grade and survival was evaluated. According to the Patnaik system, 18 MCTs (13.1%) were classified as grade I, 83 (60.6%) as grade II, and 36 (26.3%) as grade III. Grade III was associated with a poorer prognosis ( P < .001), but no significant difference between grades I and II was detected. Grading according to the Patnaik system was based on consensus grading among 3 pathologists, and interobserver variability was not considered. All grade I MCTs were low grade in the Kiupel system, and all grade III were high grade. Among grade II, 71 (85.6%) were low grade, and 12 (14.4%) were high grade, with a 1-year survival probability of 94% and 46%, respectively ( P < .001). The 2-tier system had a high prognostic value and was able to correctly predict the negative outcomes of some grade II MCTs. Data also confirm that histologic grading cannot predict biological behavior of each MCT and should be supplemented with molecular methods for more accurate prognostication

Reproducibility of the WHO histological criteria for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms.

This study, performed on behalf of the Italian Registry of Thrombocythaemias (Registro Italiano Trombocitemie), aimed to test the inter-observer reproducibility of the histological parameters proposed by the WHO classification for the diagnosis of the Philadelphia chromosome-negative myeloproliferative neoplasms. A series of 103 bone marrow biopsy samples of Philadelphia chromosome-negative myeloproliferative neoplasms consecutively collected in 2004 were classified according to the WHO criteria as follows: essential thrombocythaemia (n=34), primary myelofibrosis (n=44) and polycythaemia vera (n=25). Two independent groups of pathologists reviewed the bone marrow biopsies. The first group was asked to reach a collegial 'consensus' diagnosis. The second group reviewed individually all the cases to recognize the main morphological parameters indicated by the WHO classification and report their results in a database. They were subsequently instructed to individually build a 'personal' diagnosis of myeloproliferative neoplasms subtype just assembling the parameters collected in the database. Our results indicate that high levels of agreement ( 6570%) have been reached for about all of the morphological features. Moreover, among the 18 evaluated histological features, 11 resulted statistically more useful for the differential diagnosis among the different Philadelphia chromosome-negative myeloproliferative neoplasms. Finally, we found a high percentage of agreement (76%) between the 'personal' and 'consensus' diagnosis (Cohen's kappa statistic >0.40). In conclusion, our results support the use of the histological criteria proposed by the WHO classification for the Philadelphia chromosome-negative myeloproliferative neoplasms to ensure a more precise and early diagnosis for these patients

Assessing operator stress in collaborative robotics: A multimodal approach

In the era of Industry 4.0, the study of Human-Robot Collaboration (HRC) in advancing modern manufacturing and automation is paramount. An operator approaching a collaborative robot (cobot) may have feelings of distrust, and experience discomfort and stress, especially during the early stages of training. Human factors cannot be neglected: for efficient implementation, the complex psycho-physiological state and responses of the operator must betaken into consideration. In this study, volunteers were asked to carry out a set of cobot programming tasks, while several physiological signals, such as electroencephalogram (EEG), electrocardiogram (ECG), Galvanic skin response (GSR), and facial expressions were recorded. In addition, a subjective questionnaire (NASA-TLX) was administered at the end, to assess if the derived physiological parameters are related to the subjective perception of stress. Parameters exhibiting a higher degree of alignment with subjective perception are mean Theta (76.67%), Alpha (70.53%) and Beta (67.65%) power extracted from EEG, recovery time (72.86%) and rise time (71.43%) extracted from GSR and heart rate variability (HRV) metrics PNN25 (71.58%), SDNN (70.53%), PNN50 (68.95%) and RMSSD (66.84%). Parameters extracted from raw RR Intervals appear to be more variable and less accurate (42.11%) so as recorded emotions (51.43%)