Role of advanced imaging techniques in the evaluation of oncological therapies in patients with colorectal liver metastases

In patients with colorectal liver metastasis(CRLMs)unsuitable for surgery,oncological treatments,such as chemotherapy and targeted agents,can be performed.Cross-sectional imaging[computed tomography(CT),magnetic resonance imaging(MRI),18-fluorodexoyglucose positron emission tomography with CT/MRI]evaluates the response of CRLMs to therapy,using post-treatment lesion shrinkage as a qualitative imaging parameter.This point is critical because the risk of toxicity induced by oncological treatments is not always balanced by an effective response to them.Consequently,there is a pressing need to define biomarkers that can predict treatment responses and estimate the likelihood of drug resistance in individual patients.Advanced quantitative imaging(diffusionweighted imaging,perfusion imaging,molecular imaging)allows the in vivo evaluation of specific biological tissue features described as quantitative parameters.Furthermore,radiomics can represent large amounts of numerical and statistical information buried inside cross-sectional images as quantitative parameters.As a result,parametric analysis(PA)translates the numerical data contained in the voxels of each image into quantitative parameters representative of peculiar neoplastic features such as perfusion,structural heterogeneity,cellularity,oxygenation,and glucose consumption.PA could be a potentially useful imaging marker for predicting CRLMs treatment response.This review describes the role of PA applied to cross-sectional imaging in predicting the response to oncological therapies in patients with CRLMs.

Non-invasive diagnostic imaging of colorectal liver metastases

Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases(CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liverdirected therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs.

Role of colonoscopy in the diagnostic work-up of bowel endometriosis

AIM:To evaluate the accuracy of colonoscopy for the prediction of intestinal involvement in deep pelvic endometriosis.METHODS:This prospective observational study was performed between September 2011 and July 2014.Only women with both a clinical and imaging diagnosis of deep pelvic endometriosis were included.The study was approved by the local ethics committee and written informed consent was obtained in all cases.Both colonoscopy and laparoscopy were performed by expert surgeons with a high level of expertise with these techniques.Laparoscopy was performed within4 wk of colonoscopic examination.All hypothetical colonoscopy findings(eccentric wall thickening with or without surface nodularities and polypoid lesions with or without surface nodularities of endometriosis)were compared with laparoscopic and histological findings.We calculated the sensitivity,specificity,positive predictive value and negative predictive value for the presence of colonoscopic findings of intestinal endometriosis.RESULTS:A total of 174 consecutive women aged between 21-42 years with a diagnosis of deep pelvic endometriosis who underwent colonoscopy andsurgical intervention were included in our analysis.In 76 of the women(43.6%),intestinal endometrial implants were found at surgery and histopathological examination.Specifically,38 of the 76 lesions(50%)were characterized by the presence of serosal bowel nodules;28 of the 76 lesions(36.8%)reached the muscularis layer;8 of the 76 lesions(10.5%)reached the submucosa;and 2 of the 76 lesions(2.6%)reached the mucosa.Colonoscopic findings suggestive of intestinal endometriosis were detected in 7 of the174(4%)examinations.Colonoscopy failed to diagnose intestinal endometriosis in 70 of the 76 women(92.1%).A colonoscopic diagnosis of endometriosis was obtained in all cases of mucosal involvement,in 3of 8 cases(37.5%)of submucosal involvement,in no cases of muscularis layer involvement and in 1 of 38cases(2.6%)of serosa involvement.The sensitivity,specificity,positive predictive and negative predictive values of colonoscopy for the diagnosis of intestinal endometriosis were 7%,98%,85%and 58%,respectively.CONCLUSION:Being an invasive procedure,colonoscopy should not be routinely performed in the diagnostic work-up of bowel endometriosis.

Application of Trichoderma harzianum (T22) and Trichoderma atroviride (P1) as plant growth promoters, and their compatibility with copper oxychloride

Trichoderma strains are used in agriculture because they provide to the plants the following benefits: i) are rhizosphere competence and establish stable rhizosphere microbial communities; ii) control plant disease caused by pathogenic and competitive microflora, by using a variety of mechanisms; iii) improve vegetative growth, root development and yield; iv) make nutrients more available to the plant. In this work we have investigated the ability of T. harzianum T22 and T. atroviride P1 to improve plant growth of locally important horticultural crops: lettuce, tomatoes and peppers and to prevent disease in the greenhouse and field. The effect of the Trichoderma treatment was evaluated by determining the weight of fresh and dry roots and above ground plant biomass, measuring plants height, counting the number of emerged leaves (lettuce, tomatoes and peppers) and quantifying production (tomatoes and peppers). No disease symptoms were found during production, although Fusarium sp. strains pathogenic to tomato were detected in the soil. Compounds containing copper oxychloride are frequently used for fungal disease control in agriculture. In order to investigate the compatibility of T. harzianum T22 and T. atroviride P1 with copper oxychloride applications, the effect on mycelia growth was monitored in both liquid and solid medium. In general, the tests indicated a high level of tolerance of the Trichoderma strains to concentrations of copper oxychloride varying from 0.1 to 5 mmol/L.

Anti-inflammatory and analgesic activities with gastroprotective effect of semi-purified fractions and isolation of pure compounds from Mediterranean gorgonian Eunicella singularis

Objective: To explore anti-inflammatory activities of organic extract and its semi-purified fractions(ethanol, acetone, methanol/dichloromethane) from the Mediterranean gorgonian Eunicella singularis. Methods: The anti-inflammatory and analgesic activities were evaluated, using the carrageenan-induced rat paw edema model and the acetic acid writhing test in mice. The gastroprotective activity was determined using HCl/Et OH induced gastric ulcers in rats. The purification and structure elucidation of compound(s) from the more effective fraction were determined by chromatographic and spectroscopic methods and in comparison with data reported in the literature. Results: The fraction F-Et OH showed an important antiinflammatory activity associated with significant analgesic and gastroprotective properties. The purification and structure elucidation of compound(s) from this fraction lead to the identification of one diterpenoid and four sterols. Conclusions: These results suggested that components from the active fraction can be used to treat various anti-inflammatory diseases.

Extracellular proteome of Trichoderma harzianum to identify proteins with biotechnological value

Trichoderma harzianum strain T22 parasitizes and controls many phytopatogenic fungi and is applied commercially as biological control agent. The production of hydrolitic enzymes appears to be a key factor in the parasitic process. We tested the endo-esochitinolitic and glucanolitic activities of culture filtrates of T22 grown under carbon and nitrogen starvation or in presence of biomass or cell walls of the phytopathogenic fungi Botrytis cinerea, Rhizoctonia solani and Pythium ultimum. The highest level of enzimatic activities was found in culture where the mycoparasite interacted with a phytopathogenic fungus. Therefore we used a proteomic approach to investigate changes in the complex mixture of extracellular proteins secreted by T. harzianum strain T22 in order to identify proteins of potential biotechnology value for commercial and industrial use.Proteome technology has greatly enhanced our ability to conduct functional genomics studies. Nevertheless only a few studies have been published so far on the fungal extracellular proteome. Sample preparation remains the most critical step in analyses based on two-dimensional gel electrophoresis (2-DE), and it requires to be optimized for each specific application. In this study, our first aim was to set up the extraction protocol of the extracellular proteins secreted by T . harzianum strain T22 when it was grown in vitro .The secreted proteins were analysed by two-dimensional electrophoresis (2-DE) and substantial changes in the extracellular proteome of the mycoparasite have been observed. Comparing the 2D maps of the fungus grown in minimal medium with glycerol as carbon source (used as control condition) with those obtained in inducing conditions, a lot of novel proteins appeared. The higher number of novel and up-regulated spots was obtained in the presence of Rhizoctonia solani biomass. Other spots were specifically up-regulated by the interaction with different plant pathogens. Differentially expressed proteins were subjected to matrix assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry (MS) and N-terminal Edman sequencing. The in silico analyses of some of the novel and up-regulated spots showed interesting homology to hypothetical and putative proteins from other fungal species. These include novel enzymes, such as glycosylhydrolases and metalloprotease, proteins with conserved domains involved in pathogen-host interactions, such as Ras that regulates signal transduction pathways or LRRs that is involved in host recognition, etc. Work is in progress to demonstrate the role of some of these proteins in biocontrol and ability to induce systemic resistance.

Colorectal cancer: Parametric evaluation of morphological,functional and molecular tomographic imaging

Colorectal cancer (CRC) represents one of the leading causes of tumor-related deaths worldwide. Among the various tools at physicians’ disposal for the diagnostic management of the disease, tomographic imaging (e.g., CT, MRI, and hybrid PET imaging) is considered essential. The qualitative and subjective evaluation of tomographic images is the main approach used to obtain valuable clinical information, although this strategy suffers from both intrinsic and operator-dependent limitations. More recently, advanced imaging techniques have been developed with the aim of overcoming these issues. Such techniques, such as diffusion-weighted MRI and perfusion imaging, were designed for the “in vivo” evaluation of specific biological tissue features in order to describe them in terms of quantitative parameters, which could answer questions difficult to address with conventional imaging alone (e.g., questions related to tissue characterization and prognosis). Furthermore, it has been observed that a large amount of numerical and statistical information is buried inside tomographic images, resulting in their invisibility during conventional assessment. This information can be extracted and represented in terms of quantitative parameters through different processes (e.g., texture analysis). Numerous researchers have focused their work on the significance of these quantitative imaging parameters for the management of CRC patients. In this review, we aimed to focus on evidence reported in the academic literature regarding the application of parametric imaging to the diagnosis, staging and prognosis of CRC while discussing future perspectives and present limitations. While the transition from purely anatomical to quantitative tomographic imaging appears achievable for CRC diagnostics, some essential milestones, such as scanning and analysis standardization and the definition of robust cut-off values, must be achieved before quantitative tomographic imaging can be incorporated into daily clinical practice.

Percutaneous approach to treatment of coronary disease in a patient with uremic cardiomyopathy

Uremic cardiomyopathy is chronic ischemic left ventricular dysfunction characterized by heart failure, myocardial ischemia, hypotension in dialysis and arrhythmia. This nosologic entity represents a leading cause of morbidity and mortality among patients with endstage renal disease receiving long-term hemodialysis. It is intuitive that revascularization in the presence of coronary artery disease in these patients represents an effective option for improving their prognosis. Although the surgical option seems to be followed by the best clinical outcome, some patients refuse this option and others are not good candidates for surgery. The present report describes the case of a patient affected by uremic cardiomyopathy and severe coronary artery disease in whom revascularization with percutaneous coronary angioplasty was followed by a significant improvement in quality of life.

The Impact of International Accounting Standards Board （IASB）＇s Guidelines for Preparing Management Commentary （MC）： Evidence From Italian Listed Firms

This paper investigates the Italian firms＇ disclosure in response to the new guidance on the management commentary （MC） contained in the International Financial Reporting Standard （IFRS） practice statement issued by International Accounting Standards Board （IASB） in 2010. The study is organized as follows. After reviewing the relevant literature on financial disclosure and MC, this paper examines the content of the Italian management＇s report-----known as ＂Relazione sulla Gestione＂ and that of the recent IASB＇s IFRS practice statement. Hence, it applies a self-constructed disclosure index and a multiple correspondence analysis （MCA） on MC of a sample of 66 Italian non-financial listed firms. The results show that the level of disclosures provided by the Italian listed firms does not seem to be affected by the IASB＇s guidelines. However, the survey highlights large differences in the level and type of disclosure provided in MC among the sectors and firms. This paper aims to contribute to the financial reporting debate by understanding the IASB＇s guidelines and their impacts on the voluntary disclosure practices of Italian listed firms.

Current trends of artificial intelligence in cancer imaging

In this editorial,we discussed the current research status of artificial intelligence(AI)in Oncology,reviewing the basics of machine learning(ML)and deep learning(DL)techniques and their emerging applications on clinical and imaging cancer workflow.The growing amounts of available“big data”coupled to the increasing computational power have enabled the development of computerbased systems capable to perform advanced tasks in many areas of clinical care,especially in medical imaging.ML is a branch of data science that allows the creation of computer algorithms that can learn and make predictions without prior instructions.DL is a subgroup of artificial neural network algorithms configurated to automatically extract features and perform high-level tasks;convolutional neural networks are the most common DL models used in medical image analysis.AI methods have been proposed in many areas of oncology granting promising results in radiology-based clinical applications.In detail,we explored the emerging applications of AI in oncological risk assessment,lesion detection,characterization,staging,and therapy response.Critical issues such as the lack of reproducibility and generalizability need to be addressed to fully implement AI systems in clinical practice.Nevertheless,AI impact on cancer imaging has been driving the shift of oncology towards a precision diagnostics and personalized cancer treatment.

An update on microbiological causes of canine otitis externa in Campania Region,Italy

Objective: To update the recent knowledge of the microbiological causes of canine otitis externa in Campania Region(Italy) and the antibiotic susceptibility patterns of the isolated strains.Methods: A total of 122 dogs were examined by otoscopy, and auricular swab samples were collected from both ears in 74 dogs presenting clinical bilateral otitis and from single ears in 48 dogs displaying clinical unilateral otitis. Cytological examination,bacteriological analysis and antimicrobial susceptibility tests were performed.Results: Thirty-one out of 122 dogs were positive for yeast species(25.4%, 95% confidence interval(CI): 18.2%–34.2%) with a higher prevalence of Malassezia pachydermatis(21/31 isolates, 67.7%, CI: 48.5%–82.7%), and a total of 91 out of 122 dogs were positive for bacterial species(74.6%; CI: 65.8%–81.8%) with a higher prevalence of Staphylococcus pseudintermedius(45/143 isolates, 31.5%, CI: 24.1%–39.8%). These results are the first description of Streptococcus agalactiae-associated otitis. The yeasts isolated showed high levels of susceptibility to all antifungal agents tested; on the contrary all the isolated bacterial strains were highly resistant to at least four out of ten antimicrobial classes. Both Gram-positive and Gram-negative bacteria showed high resistance to amoxicillin/clavulanate and kanamycin hence they are not recommended as initial empirical therapy for the otitis treatment.Conclusions: This update illustrates an increase in antibiotic resistances providing an insight into the current knowledge of the therapeutic procedures followed on canine otitis externa in Italy. It also emphasizes the importance of considering the results of the microbiological and sensitivity tests to decide on an appropriate antibiotic therapy.

Intestinal amyloidosis:Two cases with different patterns of clinical and imaging presentation

The involvement of the small bowel in systemic forms of amyloidosis may be diffuse or very rarely focal.Some cases of focal amyloidomas of the duodenum and jejunum without extraintestinal manifestations have been reported.The focal amyloidomas consisted of extensive amyloid infiltration of the entire intestinal wall thickness.Radiological barium studies,ultrasound and computed tomography(CT)patterns of diffuse small bowel amyloidosis have been described:the signs are non-specific and may include small-bowel dilatation,symmetric bowel wall thickening,mesenteric infiltration,and mesenteric adenopathy.No data are available about the positron emission tomography (PET)/CT and magnetic resonance imaging(MRI)patterns of intestinal amyloidosis.We report two cases of small bowel amyloidosis:the former characterized by focal deposition of amyloid proteins exclusively within blood vessel walls of the terminal ileum,the latter characterized by diffuse intestinal involvement observed on MRI and PET/CT studies.

The ＂Production＂ of Accounting Information Between Regulatory and Free Market Approach： An （Eternally） Open Issue

Accounting information has gained utmost importance over the years, and it now plays a vital role in our society. Indeed, the trends of a global economy, especially one relying on a capital market-based financial system, are greatly influenced by reliable accounting information. However, it is sometimes difficult to assess the ＂reliability＂ of such information, given the clear differences in the needs and goals of its different users. In this respect, the possible ways to guarantee the appropriateness of the accounting information provided to users doubtlessly deserve a careful investigation. The second half of the 1970s can be considered as the starting point of a debate, within the Anglo-Saxon accounting literature, concerning the most effective methods to provide users with accounting data effectively meeting their very specific needs. In this context, two antithetical schools of thought developed： （1） free market approach; and （2） regulatory approach. Although it is possible to state that accounting regulation has now become a concrete reality both inside and outside the Anglo-Saxon accounting context, after more than halfa century, its efficacy is still an open issue.

Adipose tissue in the pathophysiology of cardiovascular disease: Who is guilty?

Epidemiological evidence has shown how abdominal obesity is closely associated with the development of cardiovascular disease. It has been demonstrated that patients with extensive adipose tissue usually have other concomitant cardiovascular risk factors, such insulin resistance, hypertension and dyslipidemia. Moreover,obese patients have a significantly higher risk of developing thrombophilic events compared with the nonobese. Thus, obesity is actually considered an independent cardiovascular risk factor. The pathophysiological mechanisms responsible for the association between obesity and cardiovascular disease remain largely unknown. However, it has been postulated that obese patients have an "inflammatory milieu" responsible for their metabolic disorders and vascular disease. In this context, adipocyte-derived molecules with inflammatory activity might play a pivotal role in the development of these mechanisms. In the present report, we provide an updated overview on the molecules produced by adipose tissue that are potentially involved in cardiovascular pathophysiology.

The Theoretical Perspectives and Managerial Implications of the Balanced Scorecard （BSC） in the Italian Public Utilities

The present work aims to conduct a critical analysis of control systems and tools of performance assessment in local public services companies, with a particular reference to the public transport sector. The interest in this issue arises for various reasons, from the growing economic significance of the sector at a national level, measurable in terms of production value and the number of operators involved, to the spread of outsourcing policies, liberalization and privatization, and the use of the standard cost to establish the level of funding. In the field of public utilities, until a few years ago, the concept of control was intended only in a ＂bureaucratic＂ sense as the capacity to fulfill the formal obligations linked to the strong regulatory context, ignoring aspects that have become fundamental today, such as economy, efficiency, and effectiveness of management. The approach used is deductive and the study ends with the presentation of the possible implications of the use of standard cost and the presentation of an application hypothesis of a balanced scorecard （BSC） for local public transport （LPT）.

Polymorphism AGT2(rs4762)is involved in the development of dermatologic events:Proof-of-concept in hepatocellular carcinoma patients treated with sorafenib

BACKGROUND Dermatologic adverse events(DAEs)are associated with a better outcome in patients with hepatocellular carcinoma(HCC)irrespective of the therapeutic agent received.The exact mechanisms associated with the development of DAEs are unknown although several studies point to direct toxicity of tyrosine kinase inhibitors(TKIs)to the skin or an immune-mediated reaction triggered by the oncologic treatment.As is the case in other conditions,individual genetic variants may partially explain a higher risk of DAEs.AIM To evaluate the contribution of several gene variants to the risk of developing DAEs in HCC patients treated with TKIs.METHODS We first analyzed 27 single-nucleotide polymorphisms(SNPs)from 12 genes selected as potential predictors of adverse event(AE)development in HCC patients treated with sorafenib[Barcelona Clinic Liver Cancer 1(BCLC1)cohort].Three additional cohorts were analyzed for AGT1(rs699)and AGT2(rs4762)polymorphisms-initially identified as predictors of DAEs:BCLC2(n=79),Northern Italy(n=221)and Naples(n=69)cohorts,respectively.The relation between SNPs and DAEs and death were assessed by univariate and multivariate Cox regression models,and presented with hazard ratios and their 95%confidence intervals(95%CI).RESULTS The BCLC1 cohort showed that patients with arterial hypertension(AHT)(HR=1.61;P value=0.007)and/or AGT SNPs had an increased risk of DAEs.Thereafter,AGT2(rs4762)AA genotype was found to be linked to a statistically significant increased probability of DAEs(HR=5.97;P value=0.0201,AA vs GG)in the Northern Italy cohort by multivariate analysis adjusted for BCLC stage,ECOG-PS,diabetes and AHT.The value of this genetic marker was externally validated in the cohort combining the BCLC1,BCLC2 and Naples cohorts[HR=3.12(95%CI:1.2-8.14),P value=0.0199,AGT2(rs4762)AA vs AG genotype and HR=2.73(95%CI:1.18-6.32)P value=0.0188,AGT2(rs4762)AA vs GG genotype].None of the other gene variants tested were found to be associated with the risk of DAE development.CONCLUSION DAE development in HCC patients receiving TKIs could be explained by the AGT2(rs4762)gene variant.If validated in other anti-oncogenic treatments,it might be considered a good prognosis marker.

Aerodynamic optimization of an adaptive flap for next-generation green aircraft

Adaptive,morphing flaps are taking ever-increasing attention in civil aviation thanks to the expected benefits this technology can bring at the aircraft level in terms of high-lift performance improvement and related fuel burnt reduction per flight.Relying upon morphing capabilities,it is possible to fix a unique setting for the flap and adapt the flap shape to match the aerodynamic requirements for take-off or landing.The proper morphed shapes can assure better high-lift performances than those achievable by referring to a conventional flap.Moreover,standing the unique flap setting for take-off and landing,a dramatic simplification of the flap deployment systems may be achieved.As a consequence of this simplification,the deployment system can be fully hosted in the wing,thus avoiding under-wing nacelles with significantly better aerodynamics and fuel consumption.The first step for a rational design of an adaptive flap consists in defining the target morphed shapes and the unique optimal flap setting in the take-off and landing phases.In this work,aerodynamic optimization analyses are carried out to determine the best flap setting and related morphed shapes in compliance with the take-off and landing requirements of a reference civil transport aircraft.Four different initial conditions are adopted to avoid the optimization falling into local optima,thus obtaining four groups of optimal candidate configurations.After comparing each candidate’s performance through 2D and 3D simulations,the optimal configuration has been selected.2D simulations show that the optimal configuration is characterized by a maximum lift increase of 31.92%in take-off and 9.04%in landing.According to 3D simulations,the rise in maximum lift equals 22.26%in take-off and 3.50%in landing.Numerical results are finally verified through wind tunnel tests,and the aerodynamic mechanism behind the obtained improvements is explained by carefully analyzing the flow field around the flap.

Radiomics and machine learning applications in rectal cancer:Current update and future perspectives

The high incidence of rectal cancer in both sexes makes it one of the most common tumors,with significant morbidity and mortality rates.To define the best treatment option and optimize patient outcome,several rectal cancer biological variables must be evaluated.Currently,medical imaging plays a crucial role in the characterization of this disease,and it often requires a multimodal approach.Magnetic resonance imaging is the first-choice imaging modality for local staging and restaging and can be used to detect high-risk prognostic factors.Computed tomography is widely adopted for the detection of distant metastases.However,conventional imaging has recognized limitations,and many rectal cancer characteristics remain assessable only after surgery and histopathology evaluation.There is a growing interest in artificial intelligence applications in medicine,and imaging is by no means an exception.The introduction of radiomics,which allows the extraction of quantitative features that reflect tumor heterogeneity,allows the mining of data in medical images and paved the way for the identification of potential new imaging biomarkers.To manage such a huge amount of data,the use of machine learning algorithms has been proposed.Indeed,without prior explicit programming,they can be employed to build prediction models to support clinical decision making.In this review,current applications and future perspectives of artificial intelligence in medical imaging of rectal cancer are presented,with an imaging modality-based approach and a keen eye on unsolved issues.The results are promising,but the road ahead for translation in clinical practice is rather long.