Contrast-enhanced ultrasonography parameters in neural network diagnosis of liver tumors

AIM:To study the role of time-intensity curve(TIC) analysis parameters in a complex system of neural networks designed to classify liver tumors.METHODS:We prospectively included 112 patients with hepatocellular carcinoma(HCC)(n = 41),hypervascular(n = 20) and hypovascular(n = 12) liver metastases,hepatic hemangiomas(n = 16) or focal fatty changes(n = 23) who underwent contrast-enhanced ultrasonography in the Research Center of Gastroenterology and Hepatology,Craiova,Romania.We recorded full length movies of all contrast uptake phases and post-processed them offline by selecting two areas of interest(one for the tumor and one for the healthy surrounding parenchyma) and consecutive TIC analysis.The difference in maximum intensities,the time to reaching them and the aspect of the late/portal phase,as quantified by the neural network and a ratio between median intensities of the central and peripheral areas were analyzed by a feed forward back propagation multi-layer neural network which was trained to classify data into five distinct classes,corresponding to each type of liver lesion.RESULTS:The neural network had 94.45% training accuracy(95% CI:89.31%-97.21%) and 87.12% testing accuracy(95% CI:86.83%-93.17%).The automatic classification process registered 93.2% sensitivity,89.7% specificity,94.42% positive predictive value and 87.57% negative predictive value.The artificial neural networks(ANN) incorrectly classified as hemangyomas three HCC cases and two hypervascular metastases,while in turn misclassifying four liver hemangyomas as HCC(one case) and hypervascular metastases(three cases).Comparatively,human interpretation of TICs showed 94.1% sensitivity,90.7% specificity,95.11% positive predictive value and 88.89% negative predictive value.The accuracy and specificity of the ANN diagnosis system was similar to that of human interpretation of the TICs(P = 0.225 and P = 0.451,respectively).Hepatocellular carcinoma cases showed contrast uptake during the arterial phase followed by wash-out in the portal and first seconds of the late phases.For the hypovascular metastases did not show significant contrast uptake during the arterial phase,which resulted in negative differences between the maximum intensities.We registered wash-out in the late phase for most of the hypervascular metastases.Liver hemangiomas had contrast uptake in the arterial phase without agent wash-out in the portallate phases.The focal fatty changes did not show any differences from surrounding liver parenchyma,resulting in similar TIC patterns and extracted parameters.CONCLUSION:Neural network analysis of contrastenhanced ultrasonography-obtained TICs seems a promising field of development for future techniques,providing fast and reliable diagnostic aid for the clinician.

A multilevel pan-cancer map links gene mutations to cancer hallmarks

Background:A central challenge in cancer research is to create models that bridge the gap between the molecular level on which interventions can be designed and the cellular and tissue levels on which the disease phenotypes are manifested.This study was undertaken to construct such a model from functional annotations and explore its use when integrated with large-scale cancer genomics data.Methods:We created a map that connects genes to cancer hallmarks via signaling pathways.We projected gene mutation and focal copy number data from various cancer types onto this map.We performed statistical analyses to uncover mutually exclusive and co-occurring oncogenic aberrations within this topology.Results:Our analysis showed that although the genetic fingerprint of tumor types could be very different,there were less variations at the level of hallmarks,consistent with the idea that different genetic alterations have similar functional outcomes.Additionally,we showed how the multilevel map could help to clarify the role of infrequently mutated genes,and we demonstrated that mutually exclusive gene mutations were more prevalent in pathways,whereas many co-occurring gene mutations were associated with hallmark characteristics.Conclusions:Overlaying this map with gene mutation and focal copy number data from various cancer types makes it possible to investigate the similarities and differences between tumor samples systematically at the levels of not only genes but also pathways and hallmarks.

Early tacrolimus exposure does not impact long-term outcomes after liver transplantation

BACKGROUND Tacrolimus trough levels(TTL)during the first weeks after liver transplantation(LT)have been related with long-term renal function and hepatocellular carcinoma recurrence.Nevertheless,the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate AIM To evaluate the effect of TTL during the first month on the long-term outcomes after LT.METHODS One hundred fifty-five LT recipients treated de novo with once-daily tacrolimus were retrospectively studied.Patients with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction therapy.Patients were classified into 2 groups according to their mean TTL within the first month after transplantation:≤10(n=98)and>10 ng/mL(n=57).Multivariate analyses were performed to assess risk factors for patient mortality.RESULTS Mean levels within the first month post-transplant were 7.4±1.7 and 12.6±2.2 ng/mL in the≤10 and>10 groups,respectively.Donor age was higher in the high TTL group 62.9±16.8 years vs 45.7±17.5 years(P=0.002)whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7%vs 15.8%(P=0.02).Recipient features were generally similar across groups.After a median follow-up of 52.8 mo(range 2.8-81.1),no significant differences were observed in:Mean estimated glomerular filtration rate(P=0.69),hepatocellular carcinoma recurrence(P=0.44),de novo tumors(P=0.77),new-onset diabetes(P=0.13),or biopsy-proven acute rejection rate(12.2%and 8.8%,respectively;P=0.50).Eighteen patients died during the follow-up and were evenly distributed across groups(P=0.83).Five-year patient survival was 90.5%and 84.9%,respectively(P=0.44),while 5-year graft survival was 88.2%and 80.8%,respectively(P=0.42).Early TTL was not an independent factor for patient mortality in multivariate analyses.CONCLUSION Differences in tacrolimus levels restricted to the first month after transplant did not result in significant differences in long-term outcomes of LT recipients.

Dissecting Maize Productivity:Ideotypes Associated with Grain Yield under Drought Stress and Well-watered Conditions

To increase maize （Zea mays L.） yields in drought-prone environments and offset predicted maize yield losses under future climates, the development of improved breeding pipelines using a multi-disciplinary approach is essential. Elucidating key growth processes will provide opportunities to improve drought breeding progress through the identification of key phenotypic traits, ideotypes, and donors. In this study, we tested a large set of tropical and subtropical maize inbreds and single cross hybrids under reproductive stage drought stress and well-watered conditions. Patterns of biomass production, senescence, and plant water status were measured throughout the crop cycle. Under drought stress, early biomass production prior to anthesis was important for inbred yield, while delayed senescence was important for hybrid yield. Under well-watered conditions, the ability to maintain a high biomass throughout the growing cycle was crucial for inbred yield, while a stay-green pattern was important for hybrid yield. While new quantitative phenotyping tools such as spectral reflectance （Normalized Difference Vegetation Index, NDVI） allowed for the characterization of growth and senescence patterns as well as yield, qualitative measurements of canopy senescence were also found to be associated with grain yield.