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BACKGROUND: The molecular characterization of thyroid nodules in cytological samples has so far been focused on discriminating between benign and malignant forms in a purely diagnostic setting. The evidence on the impact of molecular biomarkers to determine the risk of aggressiveness in cytologically "neoplastic" lesions is limited to genomic alterations (such as BRAF and TERT mutations). The aim of our study was to assess the preoperative role of microRNAs (miRNAs) in predicting the nodal status of patients with papillary thyroid cancer. METHODS: A pilot series of histological samples of papillary thyroid carcinoma with (6 cases) or without (6 cases) lymph node metastases, matched for other major clinical and pathological features, was analyzed for global miRNA expression in a screening phase. A set of miRNAs was then validated in a series of 63 consecutive cytological samples of papillary carcinomas: 48 pN‐negative and 15 pN‐positive at histology. RESULTS: Unsupervised cluster analysis segregated surgical pN‐negative and pN‐positive samples, except for 1 case. The 45 differentially expressed miRNAs in pN‐positive versus pN‐negative cases were predicted to regulate a wide range of cellular pathways, enriched for Wnt, gonadotropin‐releasing hormone receptor, and cerulein/cholecystokinin receptor signaling. In agreement with their profiles in surgical samples, 4 miRNAs of the 10 selected for validation (miR‐154‐3p, miR‐299‐5p, miR‐376a‐3p, and miR‐302E) had a significant differential expression in cytological samples of papillary carcinoma with lymph node metastases and predicted the positive nodal status with a relatively good performance. CONCLUSIONS: MiRNA profiling is a potential promising strategy to define papillary carcinoma aggressiveness in the preoperative setting. ; Preoperative biomarkers predictive of aggressive behavior in thyroid cancer are needed. Our study indicate that a microRNA‐based approach is a feasible, methodologically robust, and accurate strategy to identify biomarkers to predict the presence of lymph node metastases in papillary thyroid carcinoma in the preoperative setting. [ABSTRACT FROM AUTHOR]

To feed a world population, which will reach 9.7 billion in 2050, agricultural production will have to increase by 35–56%. Therefore, more food is urgently needed. Yield improvements for any given crop would require adequate fertilizer, water, and plant protection from pests and disease, but their further abuse will be economically disadvantageous and will have a negative impact on the environment. Using even more agricultural inputs is simply not possible, and the availability of arable land will be increasingly reduced due to climate changes. To improve agricultural production without further consumption of natural resources, farmers have a powerful ally: the beneficial microorganisms inhabiting the rhizosphere. However, to fully exploit the benefits of these microorganisms and therefore to widely market microbial-based products, there are still gaps that need to be filled, and here we will describe some critical issues that should be better addressed. [ABSTRACT FROM AUTHOR]

Spread through air spaces (STAS) have been recently recognized as a prognostic factor for adenocarcinoma and squamous cell carcinoma of the lung. Pulmonary neuroendocrine neoplasms (NENs) include tumors with different morphology and a heterogeneous clinical behavior. Among atypical carcinoids (ACs), new prognostic factors able to refine prognosis are needed. In the present study, a retrospective series of 91 surgically resected ACs was investigated, in parallel with 191 control cases of typical carcinoids (TCs) and of high-grade small- and large-cell neuroendocrine carcinomas, to assess the presence and potential prognostic role of STAS. STAS was defined by the presence of neoplastic nests or single cells in air spaces beyond the tumor edge. Clinicopathological parameters and survival were correlated by univariate and multivariate analyses. STAS was identified in 48% of ACs (44/91) compared to 20.5% of TCs and 71-88% of high-grade large- and small-cell carcinomas in the control group. In the carcinoid group, presence of STAS was significantly correlated with unfavorable parameters, such as high tumor stage, positive nodal status, high Ki-67 index, presence of angioinvasion, and with adverse disease outcome, shorter overall survival, and time to progression. In conclusion, the presence of STAS is an additional relevant adverse prognostic factor in pulmonary AC that currently has the most unpredictable outcome and the most controversial treatment strategy. [ABSTRACT FROM AUTHOR]

Objectives: To assess the use of hyper‐accuracy three‐dimensional (HA3D™; MEDICS, Moncalieri, Turin, Italy) reconstruction based on multiparametric magnetic resonance imaging (mpMRI) and superimposed imaging during augmented‐reality robot‐assisted radical prostatectomy (AR‐RARP). Patients and methods: Patients with prostate cancer (clinical stages cT1–3, cN0, cM0) undergoing RARP at our Centre, from June 2017 to April 2018, were enrolled. In all cases, cancer was diagnosed with targeted biopsy at the level of index lesion based on high‐resolution (1‐mm slices) mpMRI. HA3D reconstruction was created by dedicated software to obtain the 3D virtual model of the prostate and surrounding structures. A specific system was used to overlay virtual data on the endoscopic video displayed by the remote da Vinci® surgical console (Intuitive Surgical Inc., Sunnyvale, CA, USA), and the virtual images were superimposed by the surgeon by the means of the TilePro™ multi‐input display technology (Intuitive Surgical Inc.). The AR technology was used in four standardised key steps during RARP. The procedures were modulated differently in cases of prostate cancer without extracapsular extension (ECE) at mpMRI (Group A) or in cases of prostate cancer with ECE (Group B) at mpMRI. In Group A, the virtual image of the prostate was overlaid on the endoscopic view and the intraprostatic lesion was marked on the prostate surface by a metallic clip at the level of the suspicious lesion as identified by the 3D virtual AR image. In Group B, the same step was performed; moreover, a metallic clip was placed at the level of the suspicious ECE on the neurovascular bundles (NVBs) according to the virtual images. Finally, selective biopsies were taken from the NVBs at this level, and then, the entire NVBs were removed for final pathological examination, according to standard clinical indications. For Group A, the pathologist performed a targeted needle biopsy at the level of the metallic clip on the surface of prostate before the sample reduction. For Group B, the presence of tumour was evaluated during the reduction phase, at the level of metallic clip on the prostate surface and at the level of NVBs, sent separately. Finally, an image 3D scanner (Kinect, Microsoft) was used to perform a dimensional comparison between the mpMRI‐based 3D virtual reconstruction and the whole‐mount specimen. Results: In all, 30 patients were enrolled in the present study, 11 (36.6%) included in Group A and 19 (63.4%) in Group B. In all cases (30/30), final pathology confirmed the location of the index lesion, as cancer was found at the level of the metallic clip. The suspected ECE was confirmed on final pathology in 15/19 cases (79%). The AR‐guided selective biopsies at the level of the NVBs confirmed the ECE location, with 11/15 (73.3%) biopsies at the level of NVBs positive for cancer. The mismatch between the 3D virtual reconstruction and the prostate 3D scanning based on the whole‐mount specimen was <3 mm in >85% of the gland. Conclusion: Our results suggest that a HA3D virtual reconstruction of the prostate based on mpMRI data and real‐time superimposed imaging allow performance of an effective AR‐RARP. Potentially, this approach translates into better outcomes, as the surgeon can tailor the procedure for each patient. [ABSTRACT FROM AUTHOR]

Accrual of metastatic pulmonary carcinoid patients for therapy is usually relied on clinical and histologic characterization, with no role for the proliferation activity as defined by Ki-67 labelling index (LI). A total of 14 carcinoid patients with tumour primaries (TP) and 19 corresponding tumour metastases (TM) were blindly reviewed by 2 different pathologists for necrosis, mitotic count, and Ki-67 LI. Ki-67 LI outperformed histologic subtyping, mitotic count, and necrosis with good to almost excellent (0.40-0.75) inter-observer agreement. About 10% cut-off Ki-67 LI predicted survival better than histology for TP and TM for both observers. The TM patients survived differently according to diverse treatments (somatostatin analogues [SSAs], analogues plus additional treatments except for platinum; platinum-based chemotherapy) in close correlation with <10%, 10% to 20%, and >20% cut-off thresholds of Ki-67 LI, respectively. There was also a trend for an increase in Ki-67 LI in TM as compared with TP. This is the first proof of concept in which a clinical potential is preliminarily suggested for Ki-67 LI to better stratify pulmonary metastatic carcinoid patients for treatment according to a criterion of histology-independent biological aggressiveness. [ABSTRACT FROM AUTHOR]

ATPase/Helicases and nucleases play important roles in DNA end-resection, a critical step during homologous recombination repair in all organisms. In hyperthermophilic archaea the exo-endonuclease NurA and the ATPase HerA cooperate with the highly conserved Mre11-Rad50 complex in 3′ single-stranded DNA (ssDNA) end processing to coordinate repair of double-stranded DNA breaks. Little is known, however, about the assembly mechanism and activation of the HerA-NurA complex. In this study we demonstrate that the NurA exonuclease activity is inhibited by the Sulfolobus solfataricus RecQ-like Hel112 helicase. Inhibition occurs both in the presence and in the absence of HerA, but is much stronger when NurA is in complex with HerA. In contrast, the endonuclease activity of NurA is not affected by the presence of Hel112. Taken together these results suggest that the functional interaction between NurA/HerA and Hel112 is important for DNA end-resection in archaeal homologous recombination. [ABSTRACT FROM AUTHOR]

The TNM classification of malignant tumours is a mainstay tool in clinical practice and research for prognostic assessment of patients, treatment allocation and trial enrolment, as well as for epidemiological studies and data collection by cancer registries worldwide. Pathological TNM (pTNM) represents the pathological classification of a tumor, assigned after surgical resection or adequate sampling by biopsy, and periodical updates to the relative classification criteria are necessary to preserve its clinical relevance by integrating newly reported data. A structured approach has been put in place to fulfil this need and, based upon this process, the Eighth Edition of Union for International Cancer Control (UICC) TNM Classification of Malignant Tumours has been published, introducing many significant changes, including novel classification criteria for specific tumour types. In this review, we aim to describe the major changes introduced in the pTNM classification criteria and to summarize the evidence supporting these changes. [ABSTRACT FROM AUTHOR]

Typical (TCs) and atypical carcinoids (ACs) are defined based on morphological criteria, and no grading system is currently accepted to further stratify these entities. The 2015 WHO classification restricts the Ki-67 role to biopsy or cytology samples, rather than for prognostic prediction. We aimed to investigate whether values and patterns of Ki-67 alone would allow for a clinically meaningful stratification of lung carcinoids, regardless of histological typing. Ki-67 proliferation index and pattern (homogeneous versus heterogeneous expression) were assessed in a cohort of 171 TCs and 68 ACs. Cases were subdivided into three Ki-67 ranges (<4/4-9/≥10%). Correlations with clinicopathological data, univariate and multivariate survival analyses were performed. The majority of cases (61.5%) belonged to the <4% Ki-67 range; 25.1 and 13.4% had a proliferation index of 4-9% and ≥10%, respectively. The <4% Ki-67 subgroup was significantly enriched for TCs (83%, p < 0.0001); ACs were more frequent in the subgroup showing Ki-67 ≥ 10% (75%, p < 0.0001). A heterogeneous Ki-67 pattern was preferentially seen in carcinoids with a Ki-67 ≥10% (38%, p < 0.02). Mean Ki-67 values ≥4 and ≥10% identified categories of poor prognosis both in terms of disease-free and overall survival (p = 0.003 and <0.0001). At multivariate analysis, the two thresholds did not retain statistical significance; however, a Ki-67 ≥ 10% identified a subgroup of dismal prognosis even within ACs (p = 0.03) at univariate analysis. Here, we describe a subgroup of lung carcinoids showing brisk proliferation activity within the necrosis and/or mitotic count-based categories. These patients were associated with specific clinicopathological characteristics, to some extent regardless of histological subtyping. [ABSTRACT FROM AUTHOR]

Clear evidence has highlighted a role for hormones in the plant stress response, including salt stress. Interplay and cross-talk among different hormonal pathways are of vital importance in abiotic stress tolerance. A genome-wide transcriptional analysis was performed on leaves and roots of three-day salt treated and untreated plants of two Italian rice varieties, Baldo and Vialone Nano, which differ in salt sensitivity. Genes correlated with hormonal pathways were identified and analyzed. The contents of abscisic acid, indoleacetic acid, cytokinins, and gibberellins were measured in roots, stems, and leaves of seedlings exposed for one and three days to salt stress. From the transcriptomic analysis, a huge number of genes emerged as being involved in hormone regulation in response to salt stress. The expression profile of genes involved in biosynthesis, signaling, response, catabolism, and conjugation of phytohormones was analyzed and integrated with the measurements of hormones in roots, stems, and leaves of seedlings. Significant changes in the hormone levels, along with differences in morphological responses, emerged between the two varieties. These results support the faster regulation of hormones metabolism in the tolerant variety that allows a prompt growth reprogramming and the setting up of an acclimation program, leading to specific morpho-physiological responses and growth recovery. [ABSTRACT FROM AUTHOR]