Inflorescences of the tribe Triticeae, which includes wheat (Triticum sp. L.) and barley (Hordeum vulgare L.) are characterized by sessile spikelets directly borne on the main axis, thus forming a branchless spike. ‘Compositum-Barley’ and tetraploid ‘Miracle-Wheat’ (T. turgidum convar. compositum (L.f.) Filat.) display noncanonical spike-branching in which spikelets are replaced by lateral branch-like structures resembling small-sized secondary spikes. As a result of this branch formation ‘Miracle-Wheat’ produces significantly more grains per spike, leading to higher spike yield. In this study, we first isolated the gene underlying spike-branching in ‘Compositum-Barley,’ i.e., compositum 2 (com2). Moreover, we found that COM2 is orthologous to the branched headt (bht) locus regulating spike branching in tetraploid ‘Miracle-Wheat.’ Both genes possess orthologs with similar functions in maize BRANCHED SILKLESS 1 (BD1) and rice FRIZZY PANICLE/BRANCHED FLORETLESS 1 (FZP/BFL1) encoding AP2/ERF transcription factors. Sequence analysis of the bht locus in a collection of mutant and wild-type tetraploid wheat accessions revealed that a single amino acid substitution in the DNA-binding domain gave rise to the domestication of ‘Miracle-Wheat.’ mRNA in situ hybridization, microarray experiments, and independent qRT-PCR validation analyses revealed that the branch repression pathway in barley is governed through the spike architecture gene Six-rowed spike 4 regulating COM2 expression, while HvIDS1 (barley ortholog of maize INDETERMINATE SPIKELET 1) is a putative downstream target of COM2. These findings presented here provide new insights into the genetic basis of spike architecture in Triticeae, and have disclosed new targets for genetic manipulations aiming at boosting wheat’s yield potential.

Background: Pancreatic ductal adenocarcinoma (PDAC) detains a dismal prognosis and has a limited number of prognostic factors. Inflammation has been demonstrated to play a key role both in PDAC initiation and progression and several inflammation-based prognostic scores have been investigated in a wide range of malignancies. We compared the most analyzed inflammation-based prognostic scores in order to establish their potential impact on prediction of the outcome in advanced PDAC patients.Methods: A total of 234 advanced PDAC patients undergoing first-line chemotherapy in our institute were retrospectively analyzed. Baseline clinicopathological and pre-treatment laboratory data were collected.Survival was estimated using Kaplan-Meier method and survival differences were evaluated using the logrank test. Level of statistical significance P was set at 0.05. Only those variables that proved to be associated with statistically significant differences in outcome were compared in multivariate analysis using multiple Cox regression, as to identify their independent role and their relative power against each other.Results: In the whole cohort, median overall survival (OS) was 8.7 months (95% CI: 7.8-9.4 months), median progression-free survival (PFS) was 3.8 months (95% CI: 3.1-4.2 months). At univariate analysis high systemic immune-inflammation index (SII) was related to shorter OS [hazard ratio (HR) =2.04, 95% CI:

Background: We aimed at investigating outcome of systemic treatments in advanced breast PT.Methods: All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centres involved in the study, were retrospectively reviewed.Results: 56 female patients were identi ed. Median age was 52 (range 25-76) years. Patients re-ceived a median number of 2 systemic treatments (range 1-4). Best responses according to RECIST were: 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with highdose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were: 5.7 (IQR, 2.5-9.1) months with AI; 3.2 (IQR, 2.2-5.0) months with anthracycline alone; 3.4 (IQR, 1.4-6.7) months with HD-IFX; 2.1 (IQR, 1.4-5.2) months with gemcitabinebased chemotherapy; 1.8 (IQR, 0.7-6.6) months with trabectedin; 3.4 (IQR, 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR,) months, OS from the start of rst-line systemic treatment was 15.2 (IQR, 7.6-39.6) months. Conclusion:In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however with a median PFS of 5.7 months. Other systemic treatments were poorly active.

Tumour tissue samples were collected from vines grown in various regions of Italy and other parts of Europe and extracted for detection of Agrobacterium vitis. Fifty strains were isolated on agar plates and screened by PCR with consensus primers from the virD2 gene. They were confirmed as A. vitis with a species-specific monoclonal antibody. The isolates were further analyzed by PCR for their opine synthase genes and ordered into octopine, nopaline and vitopine strains. Primers designed on the octopine synthase gene did not detect octopine strains of Agrobacterium tumefaciens. For quantitative PCR, virD2 fragments were sequenced: two classes of virD2 genes were found and two primer sets designed, which detected octopine and nopaline strains or only vitopine strains. For simultaneous identification of all opine-type strains, multiplex real-time PCR with either primer pair and SYBR Green was performed: the combined sets of primers gave signals with DNA from any A. vitis strain. Specificity of the new primers for realtime PCR was evaluated using several unidentified bacterial isolates from grapevines and other plant species. An elevated level of non-specific background was observed when the combined primer sets were used in multiplex PCR assays. The real-time PCR protocol was also used to detect A. vitis cells directly from grapevine tumours; avoiding direct isolation procedures a sensitivity in the range of one to ten cells per assay was found. Inhibition of the PCR reaction by plant material was overcome by treating tumour extracts with a DNA purification kit as a step for the isolation of nucleic acids.

Hordeum bulbosum L., a wild grass and close relative of cultivated barley (Hordeum vulgare L.), gained importance in plant breeding as inducer of haploid plants in crosses with barley and also as a genetic resource for introgression of disease resistance/ tolerance genes into cultivated barley. Genetic mapping of genes introgressed from H. bulbosum is a prerequisite for their efficient utilization in barley breeding, but often hindered due to repressed recombination. The mechanism underlying the reduced frequency or lack of meiotic recombination between H. bulbosum and H. vulgare chromatin in introgressed segments is not understood. It may be explained by lack of genome collinearity or other structural differences between both genomes. In the present study, two F 1 mapping populations of H. bulbosum were analyzed by genotyping-by-sequencing (GBS) and four dense H. bulbosum genetic maps containing 1449, 996, 720, and 943 SNP markers, respectively, revealed overall a high degree of collinearity for all seven homeologous linkage groups of H. vulgare and H. bulbosum. The patterns of distribution of recombination along chromosomes differed between barley and H. bulbosum, indicating organizational differences between both genomes.

Background: Desmoid fibromatosis (DF) is a rare and locally infiltrative monoclonal fibroblastic proliferation arising from connective tissues, with lack of metastatic potential. About 10% of all DF cases are intra-abdominally sited. Complications in this site, due to the locally infiltrative nature of the disease, may be severe and potentially life threatening. However, data on incidence, management, and outcome of these complications are limited. Aim: Data of patients with sporadic or FAP-related intra-abdominal DF treated at Istituto Nazionale dei Tumori (INT) in Milano from 2005 to 2020 who developed a serious complication during the course of their disease were retrospectively collected and analyzed with a descriptive statistics. Methods and Results: Out of 72 intra-abdominal DF, 8 cases were identified (M/F: 5/3, median age: 35 years, FAP-related/sporadic: 2/6): 3 with bowel obstruction, 5 with bowel perforation. In 4 cases the serious complication was the first evidence of disease; in the other 4 cases it occurred at a time interval from diagnosis in the range of 4-44 months (during an active surveillance program in one case and duringchemotherapy in the other 3 cases). A surgical treatment was feasible and successful in 5 cases. In 3 surgically unmanageable patients, all progressing and experiencing acute complications while on chemotherapy, a non-surgical approach with intensive supportive treatment and with a prompt change of chemotherapy regimen was implemented, being successful in two, the other patient dying due to a concomitant progressive lymphoma thereafter. Conclusion:In this series of intra-abdominal DF, the incidence of serious complications was 11%. Most patients were successfully treated with surgery. When surgery was deemed to be unfeasible, a conservative management with intensive supportive care and a careful choice of chemotherapy was adopted, ensuring a favorable outcome in most.

Background Hereditary non-polyposis colorectal cancer (HNPCC) and Hereditary Breast and Ovarian Cancer Syndrome (HBOC) are the most common hereditary cancer syndromes in which a genetic test is available. Potential risks associated with testing include psychological harm, emotional distress and insurance problems. Methods The aim of the present study is to investigate determinants of distress in a sample of Italian subjects undergoing genetic counseling. Demographic information and psychological distress were assessed by using a self-reported questionnaire and the “Hospital Anxiety and Depression Scale” (HAD), before attending the first counseling session. Results Of the all subjects referred for the first time to our Center (January 2012–June 2013), a total of 227 were eligible (female/male = 174/53) for the survey, 134 (59%) were oncologic patients and of these, 116 received genetic test (36 for HNPCC and 80 for HBOC). The remaining 93 (41%) were healthy subjects referred for suspected familiar history and of this group, 65 subjects performed predictive test in a family with a known pathogenic mutation (53 for HBOC and 12 for HNPCC). Affected subjects had a significantly higher level of anxiety (p = 0.02) and HAD global score (p = 0.01) than healthy ones. There was no difference in HAD score between individuals testing for different syndromes (p = 0.3). In the affected subgroup, there was a significant linear correlation between the HAD anxiety score and how much subjects perceived their disease as hereditary (p = 0.01). Female and younger subjects had higher levels of anxiety (p = 0.05). Also healthy single subjects show more general distress (p = 0.02) than those with a partner. Conclusions Greater level of distress identified on females, single and younger subjects.

Background We aimed to investigate changes in volume and MRI T2‐weighted intensity in desmoid‐type fibromatosis (DF) receiving methotrexate plus vinca‐alkaloids (MTX‐VA) at Istituto Nazionale dei Tumori, Milan. Methods All cases of sporadic DF treated with MTX‐VA from 1999 to 2019 were reviewed. MRIs at baseline, 6 and 12 months of chemotherapy and at treatment withdrawal were retrospectively reviewed, contouring the tumor lesion and measuring diameters, volume, and mean T2‐signal intensity (normalized to muscle) changes. These parameters were also evaluated according to clinical variables. Results Thirty‐two DF patients were identified. Best RECIST response was: 25% partial response, 69% stable disease, 6% progression. A ≥65% tumor volume reduction was observed in 38%, <65% reduction in 53%, an increase in 9%. 22% had RECIST stable disease with a ≥65% tumor volume reduction. T2‐signal intensity decreased by ≥50% in 47%, <50% in 41% and increased in 12%. In patients with symptomatic improvement while on therapy and in patients maintaining symptomatic improvement during follow‐up, median T2‐signal intensity showed a reduction along the time points (3.0, 1.9, 1.2, 1.1; 2.9, 2.0, 1.2, 1.2, respectively); in patients without symptomatic improvement and in those clinically progressing during follow‐up, a reduction was not observed. High T2‐signal intensity at baseline was observed in patients showing RECIST progression during follow‐up. Conclusions In this series, RECIST detected a lower proportion of responses as compared to volumetric and T2‐signal changes. T2‐signal reduction seemed to better reflect symptomatic improvement. High T2‐signal intensity at baseline was related to a higher proportion of further progression.