Initial Results and Literature Review

Aim: To evaluate the role of stereotactic body radiation therapy in the retreatment of locally recurrent cervical cancers. Brachytherapy is the main choice to treat gynecologic cancers. Methods: Patients with recurrent cervical cancer, previously submitted to radiotherapy, were treated with stereotactic body radiation therapy using a CyberKnife system (Accuray Incorporated, Sunnyvale, California) with a fiducial tracking system. Results: From August 2011 to October 2014, 5 patients have been treated. Median age was 81 years (range, 70-84 years). Two patients were diagnosed with adenocarcinoma endometrioid and 3 with squamous cell carcinoma. Toxicity was scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. After a median follow-up of 12 months (range, 8-34 months), no severe (>grade 3) acute/late genitourinary or low gastrointestinal toxicity was observed. Conclusion: Our preliminary results of stereotactic body radiation therapy "simulating" high dose rate for recurrent cervical cancers confirm a minimal toxicity and an optimal outcome. The stereotactic body radiation therapy is an alternative to high dose rate brachytherapy for gynecologic tumors

Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients

Background: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnoea and exercise capacity limitation.Objectives: the present study was designed to evaluate whether an extra-fine combination of beclomethasone and formoterol (BDP/F) was effective in reducing air trapping in COPD patients with hyperinflation. Fluticasone salmeterol (FP/S) combination treatment was the active control.Methods: COPD patients with FEV1 <65% and plethysmographic functional residual capacity 120% of predicted were randomized to a double-blind, double-dummy, 12 week, parallel group, treatment with either BDP/F 400/24 \ub5g/day or FP/S 500/100\ub5g/day. Lung volumes were measured with full body plethysmography and dyspnoea was measured with transition dyspnoea index.Results: 18 patients were evaluable for intention to treat. A significant reduction in air trapping and clinically meaningful improvement in transition dyspnoea index total score was detected in the BDP/F group but not in the FP/S group. Functional residual capacity, residual volume (RV) and total lung capacity significantly improved from baseline in the BDP/F group only. With regard to group comparison, a significantly greater reduction in RV was observed with BDP/F vs. FP/S. Conclusion: BDP/F extra-fine combination is effective in reducing air trapping and dyspnoea in COPD patients with lung hyperinflation

Fronto-Temporal Circuits in Musical Hallucinations: A PET-MR Case Study

The aim of the study is to investigate morphofunctional circuits underlying musical hallucinations (MH) in a 72-years old female that underwent a simultaneous 18fluoredeoxyglucose positron emission tomography (PET) and advanced magnetic resonance (MR) exam. This represents a particular case of MH occurred in an healthy subject, not displaying neurological or psychopathological disorders, and studied simultaneously with a multimodal approach. For the resting-state fMRI analysis a seed to seed approach was chosen. For the task-based fMRI, 4 different auditory stimuli were presented. Imaging findings were compared with data obtained by ten healthy controls matched for age and sex. Neuropsychological evaluation and questionnaires investigating depression and anxiety were also administered. PET findings showed hypermetabolism of: superior temporal gyri, anterior cingulate, left orbital frontal, and medial temporal cortices. Structural MRI did not show macroscopical lesions except for gliotic spots along the uncinate fascicle pathways with an increased cortical thickness for the right orbitofrontal cortex (p = 0.003). DTI showed increased fractional anisotropy values in the left uncinate fascicle, when compared to controls (p = 0.04). Resting-state fMRI showed increased functional connectivity between the left inferior frontal gyrus and the left temporal fusiform cortex (p = 0.01). Task-based fMRI confirmed PET findings showing an increased activation of the superior temporal gyrus in all the auditory tasks except for the monotone stimulus, with a significant activation of the left orbital frontal cortex only during the song in foreign language, object of MH. Results on cognitive test did not show cognitive impairment, excepting for the performance on Frontal Assessment Battery where the patient fails in the cognitive domains of conceptualization, sensitive to interference, and inhibitory control. The subject did not show depressive or anxiety symptoms. Summarizing, multimodal imaging analyses in the MH case showed a microstructural alteration of the left uncinate fascicle paralleled by an increased metabolism and functional connectivity of cortical regions that receive left uncinate projections (orbital frontal cortex, and medial temporal cortex). This alteration of fronto-hyppocampal circuits could be responsible of retrieval of known songs even in the absence of real stimuli

Radiolabeled PET/MRI Nanoparticles for Tumor Imaging

The development of integrated positron emission tomography (PET)/ magnetic resonance imaging (MRI) scanners opened a new scenario for cancer diagnosis, treatment, and follow-up. Multimodal imaging combines functional and morphological information from different modalities, which, singularly, cannot provide a comprehensive pathophysiological overview. Molecular imaging exploits multimodal imaging in order to obtain information at a biological and cellular level; in this way, it is possible to track biological pathways and discover many typical tumoral features. In this context, nanoparticle-based contrast agents (CAs) can improve probe biocompatibility and biodistribution, prolonging blood half-life to achieve specific target accumulation and non-toxicity. In addition, CAs can be simultaneously delivered with drugs or, in general, therapeutic agents gathering a dual diagnostic and therapeutic effect in order to perform cancer diagnosis and treatment simultaneous. The way for personalized medicine is not so far. Herein, we report principles, characteristics, applications, and concerns of nanoparticle (NP)-based PET/MRI CAs

A customized anthropomorphic 3D-printed phantom to reproducibility assessment in computed tomography: an oncological case study

IntroductionStudies on computed tomography (CT) reproducibility at different acquisition parameters have to take into account radiation dose administered and related ethical issues. 3D-printed phantoms provide the possibility to investigate these features deeply and to foster CT research, also taking advantage by outperforming new generation scanners. The aim of this study is to propose a new anthropomorphic 3D-printed phantom for chest lesions, tailored on a real patient CT scan, to investigate the variability of volume and Hounsfield Unit (HU) measurements at different CT acquisition parameters.MethodsThe chest CT of a 75-year-old patient with a paramediastinal lung lesion was segmented based on an eight-compartment approach related to HU ranges (air lung, lung interstitium, fat, muscle, vascular, skin, bone, and lesion). From each mask produced, the 3D.stl model was exported and linked to a different printing infill value, based on a preliminary test and HU ratios derived from the patient scan. Fused deposition modeling (FDM) technology printing was chosen with filament materials in polylactic acid (PLA). Phantom was acquired at 50 mAs and three different tube voltages of 80, 100, and 120 kVp on two different scanners, namely, Siemens Somatom Force (Siemens Healthineers, Erlangen, Germany; same setting of real patient for 80 kVp acquisition) and GE 750 HD CT (GE Healthcare, Chicago, IL). The same segmentation workflow was then applied on each phantom acquisition after coregistration pipeline, and Dice Similarity Coefficient (DSC) and HU averages were extracted and compared for each compartment.ResultsDSC comparison among real patient versus phantom scans at different kVp, and on both CT scanners, demonstrated a good overlap of different compartments and lesion vascularization with a higher similarity for lung and lesion masks for each setting (about 0.9 and 0.8, respectively). Although mean HU was not comparable with real data, due to the PLA material, the proportion of intensity values for each compartment remains respected.DiscussionThe proposed approach demonstrated the reliability of 3D-printed technology for personalized approaches in CT research, opening to the application of the same workflow to other oncological fields

Development of a High Oleic Cardoon Cell Culture Platform by SAD Overexpression and RNAi-Mediated FAD2.2 Silencing

The development of effective tools for the sustainable supply of phyto-ingredients and natural substances with reduced environmental footprints can help mitigate the dramatic scenario of climate change. Plant cell cultures-based biorefineries can be a technological advancement to face this challenge and offer a potentially unlimited availability of natural substances, in a standardized composition and devoid of the seasonal variability of cultivated plants. Monounsaturated (MUFA) fatty acids are attracting considerable attention as supplements for biodegradable plastics, bio-additives for the cosmetic industry, and bio-lubricants. Cardoon (Cynara cardunculus L. var. altilis) callus cultures accumulate fatty acids and polyphenols and are therefore suitable for large-scale production of biochemicals and valuable compounds, as well as biofuel precursors. With the aim of boosting their potential uses, we designed a biotechnological approach to increase oleic acid content through Agrobacterium tumefaciens-mediated metabolic engineering. Bioinformatic data mining in the C. cardunculus transcriptome allowed the selection and molecular characterization of SAD (stearic acid desaturase) and FAD2.2 (fatty acid desaturase) genes, coding for key enzymes in oleic and linoleic acid formation, as targets for metabolic engineering. A total of 22 and 27 fast-growing independent CcSAD overexpressing (OE) and CcFAD2.2 RNAi knocked out (KO) transgenic lines were obtained. Further characterization of five independent transgenic lines for each construct demonstrated that, successfully, SAD overexpression increased linoleic acid content, e.g., to 42.5%, of the relative fatty acid content, in the CcSADOE6 line compared with 30.4% in the wild type (WT), whereas FAD2.2 silencing reduced linoleic acid in favor of the accumulation of its precursor, oleic acid, e.g., to almost 57% of the relative fatty acid content in the CcFAD2.2KO2 line with respect to 17.7% in the WT. Moreover, CcSADOE6 and CcFAD2.2KO2 were also characterized by a significant increase in total polyphenolic content up to about 4.7 and 4.1 mg/g DW as compared with 2.7 mg/g DW in the WT, mainly due to the accumulation of dicaffeoyl quinic and feruloyl quinic acids. These results pose the basis for the effective creation of an engineered cardoon cells-based biorefinery accumulating high levels of valuable compounds from primary and specialized metabolism to meet the industrial demand for renewable and sustainable sources of innovative bioproducts

Use of Machine Learning to Investigate the Quantitative Checklist for Autism in Toddlers (Q-CHAT) towards Early Autism Screening.

In the past two decades, several screening instruments were developed to detect toddlers who may be autistic both in clinical and unselected samples. Among others, the Quantitative CHecklist for Autism in Toddlers (Q-CHAT) is a quantitative and normally distributed measure of autistic traits that demonstrates good psychometric properties in different settings and cultures. Recently, machine learning (ML) has been applied to behavioral science to improve the classification performance of autism screening and diagnostic tools, but mainly in children, adolescents, and adults. In this study, we used ML to investigate the accuracy and reliability of the Q-CHAT in discriminating young autistic children from those without. Five different ML algorithms (random forest (RF), naïve Bayes (NB), support vector machine (SVM), logistic regression (LR), and K-nearest neighbors (KNN)) were applied to investigate the complete set of Q-CHAT items. Our results showed that ML achieved an overall accuracy of 90%, and the SVM was the most effective, being able to classify autism with 95% accuracy. Furthermore, using the SVM-recursive feature elimination (RFE) approach, we selected a subset of 14 items ensuring 91% accuracy, while 83% accuracy was obtained from the 3 best discriminating items in common to ours and the previously reported Q-CHAT-10. This evidence confirms the high performance and cross-cultural validity of the Q-CHAT, and supports the application of ML to create shorter and faster versions of the instrument, maintaining high classification accuracy, to be used as a quick, easy, and high-performance tool in primary-care settings

PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration

PATZ1, a POZ-Zinc finger protein, is emerging as an important regulator of development and cancer, but its cancer-related function as oncogene or tumor-suppressor is still debated. Here, we investigated its possible role in thyroid carcinogenesis. We demonstrated PATZ1 is down-regulated in thyroid carcinomas compared to normal thyroid tissues, with an inverse correlation to the degree of cell differentiation. In fact, PATZ1 expression was significantly further down-regulated in poorly differentiated and anaplastic thyroid cancers compared to the papillary histotype, and it resulted increasingly delocalized from the nucleus to the cytoplasm proceeding from differentiated to undifferentiated thyroid carcinomas. Restoration of PATZ1 expression in three thyroid cancer-derived cell lines, all characterized by fully dedifferentiated cells, significantly inhibited their malignant behaviors, including in vitro proliferation, anchorage-independent growth, migration and invasion, as well as in vivo tumor growth. Consistent with recent studies showing a role for PATZ1 in the p53 pathway, we showed that ectopic expression of PATZ1 in thyroid cancer cells activates p53-dependent pathways opposing epithelial-mesenchymal transition and cell migration to prevent invasiveness. These results provide insights into a potential tumor-suppressor role of PATZ1 in thyroid cancer progression, and thus may have potential clinical relevance for the prognosis and therapy of thyroid cancer