Artificial intelligence for predictive biomarker discovery in immuno-oncology: a systematic review.

BACKGROUND: The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology. MATERIALS AND METHODS: We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data. RESULTS: A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data. CONCLUSION: AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice.

Peripheral arterial occlusive disease: role of MR angiography.

PURPOSE: Magnetic resonance angiography (MRA) has recently become instrumental in the diagnosis of arterial disease in various body districts and is gaining an increasingly important role in the study of peripheral vascularisation. The aim of our study was to evaluate the reliability of MRA using digital subtraction angiography (DSA) as the reference standard. MATERIALS AND METHODS: Between November 2003 and August 2004, 30 patients with known peripheral arterial disease were studied by MRA and DSA. MRA was performed with a Philips Intera 1.5 T, with acquisitions from the coeliac trunk to the feet. For acquisitions of the feet and ankles we used unenhanced time-of-flight (TOF) sequences with a head coil. The angiographic sequence was acquired in three volumes of 40-45 cm after administration of paramagnetic contrast material. RESULTS: In the patients with peripheral arterial disease, the technique provided a precise evaluation of the stenosis (mild, moderate, severe) or obstruction of the peripheral district as well as the detection of other diseases, such as stenosis of the renal arteries or aneurysms. CONCLUSIONS: Total-body three-dimensional (3D) MRA allows a fast, safe, and accurate assessment of the arterial system in patients with arteriosclerosis and can be considered an alternative to DSA in the management of patients with steno-obstructive disease of the peripheral arteries.

Catharanthus roseus L. plants and explants infected with phytoplasmas: alkaloid production and structural observations.

The results of several experiments concerning the presence and composition of alkaloids in different tissues (stems, leaves, roots) of Catharanthus roseus L. plants and explants, healthy and infected by clover phyllody phytoplasmas, are reported. The alkaloids extracted and determined by the reverse phase high-pressure liquid chromatography were vindoline, ajmalicine, serpentine, vinblastine, and vincristine. The total alkaloid concentration was higher in infected plants than in the controls, in particular the increase of vinblastine in infected roots was very significant. The ultrastructural observations of infected roots showed alterations of the cell walls and of the nuclei. These results demonstrate that phytoplasmas, detected in all infected tissues by light fluorescence and transmission electron microscopy, play an important role on secondary metabolism of the diseased plants, modifying both the total content of alkaloids and their ratio.

Recovery in apple trees infected with the apple proliferation phytoplasma: an ultrastructural and biochemical study.

ABSTRACT Localization of hydrogen peroxide (H(2)O(2)) and the roles of peroxidases, malondialdehyde, and reduced glutathione in three apple cultivars were compared in healthy trees, trees infected with apple proliferation phytoplasma (APP), and trees that had recovered from the infection. In recovered apple trees, symptoms of the disease and the pathogen had disappeared from the canopy, but phytoplasmas remained in the roots. H(2)O(2) was detected cytochemically by its reaction with cerium chloride to produce electron-dense deposits of cerium perhydroxides.H(2)O(2) occurred in the plasmalemma of the phloem of leaves of recovered apple trees, but not in healthy or APP-infected leaves. In all cultivars, the peroxidase activity detected in tissue from APP-diseased trees was greater than or equal to that of tissue from recovered trees, which equaled or exceeded that of tissue from healthy trees, at two sampling times (May and September). In contrast, the glutathione content of leaves decreased in the reverse order. More malondialdehyde was observed in leaves from recovered trees than in leaves from healthy or APP-infected trees in three of six cultivar-date combinations; in the other three combinations, the malondialdehyde contents of leaves from healthy, infected, and recovered trees were not significantly different from one another. The results suggest that some components of the oxidant-scavenging system in recovered leaves are not very active, leading to an overproduction of H(2)O(2) and, possibly, to a membrane lipid peroxidation.The production of H(2)O(2) appears to be involved in counteracting pathogen virulence.

Cytological modifications in maize plants infected by barley yellow dwarf virus and maize dwarf mosaic virus.

Three inbred lines of maize (33-16, MO17 and B73) differing in their susceptibility to Barley yellow dwarf virus and Maize dwarf mosaic virus were studied to compare the ultrastructural modifications induced by the two viruses in leaf tissues of different age. The results demonstrate that the alterations induced by the two viruses in the different maize lines could depend on the particular line tested.

Histopathology and polyphenol content in plants infected by phytoplasmas.

The alterations of cell walls and the localization of several compounds such as polyphenols, suberin, lignin, in plum and apple plants infected with plum leptonecrosis (PLN) and apple proliferation (AP) phytoplasmas respectively, were investigated. Catharanthus roseus plants, infected with AP or PLN were also studied. The 4,6-diamidino-2-phenylindole (DAPI) test and transmission electron microscopy showed the presence of phytoplasmas in all infected plants. Specific histological stainings for cutinized/suberinized cell walls, tannin deposits and vacuolar polyphenol inclusions, performed on leaf and stem tissues, revealed an increase of these substances in infected plum and apple plants. No differences occurred in C. roseus. Total polyphenol analysis confirmed a strong increase (3-fold) in the polyphenol content in infected tissues, particularly in plum leaves. From the data obtained it appears that polyphenols can be considered as defence-related metabolites in plum and apple plants infected by phytoplasmas. Further investigations are necessary to determine whether these compounds play a specific role in the development of all phytoplasma/host interactions and in the defence-related processes.

Primary endoleakage in endovascular treatment of the thoracic aorta: importance of intraoperative transesophageal echocardiography.

OBJECTIVES: Endovascular treatment of the thoracic aorta has developed as an efficacious alternative to open surgical repair. However, despite the high primary success rate, perigraft leakage constitutes the major concern in long-term follow-up. Endoleaks are widely reported both in abdominal and thoracic endovascular series and are usually identified by intraoperative angiography. Transesophageal echocardiography is a sensitive imaging technique in the evaluation of aortic diseases, widely used to monitor cardiac surgery. The aim of this study was to evaluate the efficacy of transesophageal echocardiography in leakage detection during endovascular stent procedures of the thoracic aorta. METHODS: Intraoperative transesophageal echocardiography was used in conjunction with angiography in 25 patients subjected to endovascular stent treatment of the descending thoracic aorta. Spiral computed tomographic scanning was performed before discharge and 3, 6, and 12 months after treatment. RESULTS: Information from transesophageal echocardiography was relevant in the selection of the landing zone in 62% of cases. In 8 patients, transesophageal echocardiography with color Doppler sonography showed a perigraft leak, 6 of which were not visible on angiography, suggesting the need for further balloon expansion or graft extension. Postoperative computed tomographic scanning in the 25 patients showed 1 endoleak, which sealed spontaneously. At 3 months, computed tomographic examination confirmed the absence of perigraft leakage in all patients. CONCLUSIONS: During implantation of a stent-graft in the descending thoracic aorta, transesophageal echocardiography provides information in addition to that provided by angiography, improving immediate and late procedural results.

X-ray microanalysis of leaf tumors from maize plants experimentally infected with maize rough dwarf virus: scanning and transmission electron microscopic study.

X-Ray microanalysis, performed by both scanning and transmission electron microscopes equipped with energy-dispersive spectrometers (EDS), was used to analyze the element distribution in phloem tumors induced by maize rough dwarf virus (MRDV) in Zea mays L. The content of both Si and Ca was lower in tumors than in the nontumoral surrounding tissues. The Si content increased in old tumors where this element was mainly concentrated in the trichomes growing at their surface. The peaks of other detectable elements, P, K, and S, were higher in tumor than in nontumor tissues. The distribution of inorganic cations in the cells was also studied by the potassium pyroantimonate (KPA) precipitation technique. The KPA precipitates have proved to be primarily of calcium salts and they occurred quite frequently in the cells at the tumor periphery.