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Studies investigating the effects of language intervention on the re-organization of language networks in chronic aphasia have resulted in mixed findings, likely related to-among other factors-the language function targeted during treatment. The present study investigated the effects of the type of treatment provided on neural reorganization. Seventy individuals with chronic stroke-induced aphasia, recruited from three research laboratories and meeting criteria for agrammatism, anomia or dysgraphia were assigned to either treatment (N = 51) or control (N = 19) groups. Participants in the treatment group received 12-weeks of language intervention targeting sentence comprehension/production, naming, or spelling. At baseline and post-testing, all participants performed an fMRI story comprehension task, with blocks of auditorily-presented stories alternated with blocks of reversed speech. Participants in the treatment, but not control, group significantly improved in the treated language domain. FMRI region-of-interest (ROI) analyses, conducted within regions that were either active (or homologous to active) regions in a group of 22 healthy participants on the story comprehension task, revealed a significant increase in activation from pre-to post-treatment in right-hemisphere homologues of these regions for participants in the sentence and spelling, but not naming, treatment groups, not predicted by left-hemisphere lesion size. For the sentence (but not the spelling) treatment group, activation changes within right-hemisphere homologues of language regions were positively associated with changes in measures of verb and sentence comprehension. These findings support previous research pointing to recruitment of right hemisphere tissue as a viable route for language recovery and suggest that sentence-level treatment may promote greater neuroplasticity on naturalistic, language comprehension tasks, compared to word-level treatment.

Introduction: Deficits in language comprehension and production have been repeatedly observed in Schizophrenia Spectrum Disorders (SSD). However, the characterization of the language profile of this population is far from complete, and the relationship between language deficits, impaired thinking and cognitive functions is widely debated. Objective: The aims of the present study were to assess production and comprehension of verbs with different argument structures, as well as production and comprehension of sentences with canonical and non-canonical word order in people with SSD. In addition, the study investigated the relationship between language deficits and cognitive functions. Methods: Thirty-four participants with a diagnosis of SSD and a group of healthy control participants (HC) were recruited and evaluated using the Italian version of the Northwestern Assessment of Verbs and Sentences (NAVS, Cho-Reyes & Thompson, 2012; Barbieri et al., 2019). Results: Results showed that participants with SSD were impaired – compared to HC – on both verb and sentence production, as well as on comprehension of syntactically complex (but not simple) sentences. While verb production was equally affected by verb-argument structure complexity in both SSD and HC, sentence comprehension was disproportionately more affected by syntactic complexity in SSD than in HC. In addition, in the SSD group, verb production deficits were predicted by performance on a measure of visual attention, while sentence production and comprehension deficits were explained by performance on measures of executive functions and working memory, respectively. Discussion: Our findings support the hypothesis that language deficits in SSD may be one aspect of a more generalized, multi-domain, cognitive impairment, and are consistent with previous findings pointing to reduced inter- and intra-hemispheric connectivity as a possible substrate for such deficits. The study provides a systematic characterization of lexical and syntactic deficits in SSD and demonstrates that psycholinguistically-based assessment tools may be able to capture language deficits in this population.

The dynamics of phytoplankton across a seasonal frontal system formed in San Jose Gulf (SJG, Patagonia Argentina) and in neighbouring shelf waters was assessed based on bio-optical satellite data (2003–2018) and spring and summer in situ samplings. Bio-optical properties of the water masses on the eastern (ED) and western (WD) domains of the seasonal frontal system of SJG showed clear differences: the year-round-vertically-mixed waters from the WD, strongly connected with the adjacent shelf waters, evidenced a brief and strong single phytoplankton bloom, while those from the ED, showing lower exchange with shelf waters and a strong vertical stratification during the warm season, displayed an earlier and long-lasting spring phytoplankton bloom, followed by a late-summer and autumn bloom, both associated with the development and erosion of the seasonal thermocline. Waters from the entire system are optically influenced by the absorption of coloured dissolved organic matter and detritus (cdom + detritus), suggesting a strong sediment load contribution from the continent and the seabed. To remark, a strong correlation between satellite chlorophyll-a (Chla-sat) and absorption by phytoplankton (aphy443) in the outer shelf waters differs from the weak correlation of those variables in the gulf's water masses, whose optical parameters are more complex. In situ Chla records may indicate wind-driven upwelling and downwelling areas in the northern and southern coasts of the ED. Dissolved nitrogen was identified as the limiting macronutrient for phytoplankton growth in the ED during summer. This work contributes relevant ecological information that may support management actions on the SJG shellfish artisanal fishery.

Background Although human epidermal growth factor receptor 2 (HER2) overexpression is associated with poor prognosis, patients (pts) with pT1a N0M0 breast cancers (BCs) have an excellent outcome across all subtypes. Interval cancers (ICs) have poorer survival than screen-detected (SD) tumours, and an association has been reported between ICs and HER2 overexpression. We aimed to determine, in a general population of pT1a N0M0 BCs with known screening status, whether HER2-positive ICs have a poorer outcome than HER2-positive SD cancers. Methods We evaluated all incident pT1a N0M0 BCs (n = 874) collected in the Emilia-Romagna region (Italy) from 2003 to 2009 and diagnosed in women aged 50–69. Pts unexposed to screening, with unknown HER2 status and/or treated with adjuvant trastuzumab were excluded from analysis. Results Sixty-one percent of the BCs were SD, whereas 19% were ICs. BCs with high histologic grade, hormone receptor–negative or HER2-positive status (odds ratio = 1.7; 95% confidence interval [CI]: 1.1–2.7) were more likely ICs. Median follow-up was 115 months. The 10-year invasive disease-free survival (iDFS) for HER2-positive ICs was lower than that for HER2-positive SD cancers: 75.0% (95% CI: 55.5%–94.5%) versus 93.8% (95% CI: 86.5%–100%). An interaction between ICs and HER2-positive status was found for poorer iDFS after adjusting for prognostic variables (HR = 5.3; 95% CI: 1.6–16.7). Conclusions IC detection may identify pts with HER2-positive pT1a N0M0 tumours in whom the rate of recurrence justifies consideration for conventional, anti-HER2, adjuvant treatment.

Purpose This study examined grammatical production impairments in primary progressive aphasia (PPA), as measured by structured tests and narrative samples. We aimed to quantify the strength of the relationship between grammatical measures across tasks, and identify factors that condition it. Three grammatical domains were investigated: overall sentence production, verb morphology, and verb-argument structure. Methods 77 participants with PPA (34 PPA-G, 16 PPA-L, 15 PPA-S and 12 other) completed a battery of grammatical tests and a narrative language sample was obtained. Accuracy scores were computed for the language tests and the narrative samples were analyzed for both accuracy of selected narrative variables as well as grammatical diversity across the three grammatical domains. Principal components analysis (PCA) and multiple regression were used to examine cross-task relationships for all measures. Results As expected on the basis of classification criteria, accuracy scores were lower for the PPA-G group as compared to the PPA-L and PPA-S participants for overall sentence production and verb morphology, but not argument structure. Grammatical accuracy in narratives strongly predicted overall language test performance in PPA-G, whereas grammatical diversity in narratives did so in PPA-L, and no significant correspondence between narrative and language test performance was found for PPA-S. For individuals with severe grammatical impairments only, error distribution for both morphology and argument structure was strongly associated in structured tasks and narratives. Conclusions Grammatical production in narrative language predicts accuracy elicited with structured language tests in PPA. However, unique narrative production patterns distinguish PPA by subtype: accuracy for PPA-G, and grammatical diversity for PPA-L. The impairment in PPA-G is likely to reflect a core impairment in grammar whereas that of PPA-L may be closely tied to the word retrieval and verbal working memory deficits that characterize this variant. This underscores the theoretical distinction between PPA-L and PPA-G, as well as the importance of including grammatical diversity measures in analyses of language production, especially for patients who do not display frank agrammatism. Further, the results suggest that measures of domain-specific language deficits (i.e., verb morphology vs. argument structure) are robust across tasks only in individuals with severe grammatical impairments.

Functional neuroimaging and lesion-symptom mapping investigations implicate a left frontal–temporal–parietal network for sentence processing. The majority of studies have focused on sentence comprehension, with fewer in the domain of sentence production, which have not fully elucidated overlapping and/or unique brain structures associated with the two domains, particularly for sentences with noncanonical word order. Using voxel-based lesion symptom mapping (VLSM) we examined the relationship between lesions within the left hemisphere language network and both sentence comprehension and production of simple and complex syntactic structures in 76 participants with chronic stroke-induced aphasia. Results revealed shared regions across domains in the anterior and posterior superior temporal gyri (aSTG, pSTG), and the temporal pole (adjusted for verb production/comprehension). Additionally, comprehension was associated with lesions in the anterior and posterior middle temporal gyri (aMTG, pMTG), the MTG temporooccipital regions, SMG/AG, central and parietal operculum, and the insula. Subsequent VLSM analyses (production versus comprehension) revealed critical regions associated with each domain: anterior temporal lesions were associated with production; posterior temporo-parietal lesions were associated with comprehension, implicating important roles for regions within the ventral and dorsal stream processing routes, respectively. Processing of syntactically complex, noncanonical (adjusted for canonical), sentences was associated with damage to the pSTG across domains, with additional damage to the pMTG and IPL associated with impaired sentence comprehension, suggesting that the pSTG is crucial for computing noncanonical sentences across domains and that the pMTG, and IPL are necessary for re-analysis of thematic roles as required for resolution of long-distance dependencies. These findings converge with previous studies and extend our knowledge of the neural mechanisms of sentence comprehension to production, highlighting critical regions associated with both domains, and further address the mechanism engaged for syntactic computation, controlled for the contribution of verb processing.

Background Combined endocrine/targeted approaches have been investigated as first-line treatment in hormone receptors positive metastatic breast cancer (BC). Randomized trials showed that the addiction of CDK (cyclin-dependent kinase) 4/6 inhibitors to endocrine therapy (ET) increase progression free survival (PFS). Elderly patients (aged >65 years) are under represented in most of the trials. Due to the multi-morbidity and the major toxicity associated with the targeted agents, the combination strategy in that subgroup is widely discussed. The present meta-analysis aimed to understand the role of the new endocrine approaches in elderly women. Methods This meta-analysis included first line phase II/III randomized published trials comparing ET to the experimental strategy. Trials with no data about hazard ratios (HR) for PFS in the subgroup of patients aged > 65 years were excluded. The heterogeneity of the data was evaluated by Chi-square Q test and I2 statistic. Prospero registration number: CRD42019120215. Results 8 studies were included: 4 (Paloma1/TRIO-18, Paloma2, Monaleesa2, Monarch3) investigated the role of CDK 4/6 inhibitors, 2 trials (SWOG and FACT) analysed the combination of Fulvestrant plus Aromatase Inhibitors, while other two trials explored the association of ET with Bevacizumab (LEA) and Temsirolimus (HORIZON), respectively. Overall, the meta-analysis showed a PFS advantage for the experimental arms [HR 0.77, p 0.016] with a significant high/moderate heterogeneity [I2 65.46%, p 0.005]. The 4 studies adding CDK4/6 inhibitors to ET showed a significant improvement in PFS compared to ET alone. No significant advantages for the addition of anti-angiogenic agents or Fulvestrant to ET have been found. Conclusions The novel experimental strategies showed an improvement in PFS in elderly patients. Adding CDK4/6 inhibitors to ET significantly prolongs PFS as compared to ET alone, the magnitude of PFS benefit is age-independent. To define the role of novel agents, future trials should be designed taking in account not only the age, but also adequate geriatric assessment and comorbidity status. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure L. Cortesi: Speaker Bureau / Expert testimony: Astazeneca; Speaker Bureau / Expert testimony: Pierre Fabre Pharma. F. Piacentini: Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Pfizer. S. Cascinu: Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly. L. Moscetti: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis. All other authors have declared no conflicts of interest.

Verbs are central to sentence processing, as they encode argument structure (AS) information, i.e., information about the syntax and interpretation of the phrases accompanying them. The behavioral and neural correlates of AS processing have primarily been investigated in sentence-level tasks, requiring both verb processing and verb-argument integration. In the current functional magnetic resonance imaging (fMRI) study, we investigated AS processing using a lexical decision task requiring only verb processing. We examined three aspects of AS complexity: number of thematic roles, number of thematic options, and mapping (non)canonicity (unaccusative vs. unergative and transitive verbs). Increased number of thematic roles elicited greater activation in the left posterior perisylvian regions claimed to support access to stored AS representations. However, the number of thematic options had no neural effects. Further, unaccusative verbs elicited longer response times and increased activation in the left inferior frontal gyrus, reflecting the processing cost of unaccusative verbs and, more generally, supporting the role of the IFG in noncanonical argument mapping.

Background Emerging literature data are showing that a change in human epidermal growth factor receptor (HER2) status adversely affects breast cancer patient's prognosis. The aim of this study was to evaluate the prognostic impact of HER2 loss in patients with HER2-positive disease treated with neoadjuvant therapy with or without anti-HER2 agents. Methods One hundred and seven consecutive HER2-positive patients were identified from a prospectively maintained database. The first cohort includes 40 patients treated with chemotherapy (CT) alone. The second cohort includes 67 patients treated with neoadjuvant CT plus anti-HER2 agents (trastuzumab and/or lapatinib). HER2 expression was evaluated by immunihistochemistry or fluorescence in situ hybridization on pretreatment core biopsy and on surgical specimen after therapy. Results The rates of pathologic complete response (pCR) and breast-conserving surgery were higher in the CT + anti-HER2 cohort. A loss of HER2 expression was observed in 40% of the patients with residual disease after CT alone versus 14.7% of the patients after CT + anti-HER2 agents (P = 0.019). Patients not achieving a pCR have a significant increase in the risk of relapse when compared with those achieving a pCR (hazard ratio [HR] 9.55, P = 0.028). Patients with HER2 loss tended to have a higher risk of relapse as comparing to patients with maintained HER2 positivity (HR 2.41, P = 0.063). Conclusion The pCR is confirmed as a powerful predictor of long-term outcome. The rate of HER2 loss is higher in patients receiving neoadjuvant CT without anti-HER2 agents. HER2 status on residual disease after preoperative therapy can be helpful in selecting patients at different risk of relapse, to be included in prospective trial exploring further adjuvant therapy.

Bacterial diversity of Fossa (pit) cheese during ripening and its related environment was investigated by culture-dependent and -independent methods. The dominant clones during cheese ripening, among 244 16S rRNA genes (rDNA), belonged to Firmicutes (99%) mainly affiliated with Lactococcus lactis and Streptococcus thermophilus starter species. Sequencing of 16S rDNA from 171 isolates cultured in M17 and MRS media showed an increasing occurrence of non-starter lactic acid bacteria (NSLAB) during ripening such as Lactobacillus plantarum, Lactobacillus casei, Lactobacillus paracasei, Lactobacillus fermentum, Lactobacillus rhamnosus. A greater diversity of NSLAB was found in the isolates than in the clone library. L. plantarum was the dominant species in Fossa cheese (42.9%). Bacterial species identified from pit air and surface samplings (271 clones, 63 strains) revealed 40 different operational taxonomic units belonging to seven taxonomic affiliations: Actinobacteria, Firmicutes, Bactereoidetes, α-, β-, γ-, δ-Proteobacteria; however, no evidence for environmental strains within the Fossa cheese was found.

Phenotypic and genotypic methods were used to identify filamentous fungi that characterize traditional Italian Fossa cheese and its ripening environment. After ageing for 60 days at a dairy, it was ripened for an additional three months in a pit. In the fully ripened cheese, moulds ranged from 3 to 3.4 log cfu g −1 and Penicillium was the prevalent species. Pit environmental fungi ranged from 530 to 750 cfu m −3 (air) and from 130 to 340 cfu cm −2 (surfaces). The dominant pit strains were Alternaria spp., Aspergillus spp., Cladosporium spp. and Penicillium spp. Phylogenetic analyses of 18S rRNA gene and ITS1-5.8S-ITS2 regions highlighted Penicillium camemberti , Aspergillus nidulans and Aspergillus versicolor as traceable species occurring in both the cheese and pit environment, suggesting their involvement in the development of typical Fossa cheese characteristics. This approach may be used for the identification of microflora on other cheese varieties to better understand the fungal contribution in cheese ripening.

The effects of different storage treatments on the most common edible truffle species, such as Tuber magnatum and Tuber borchii (white truffles), Tuber melanosporum and Tuber aestivum (black truffles), were analysed. Biochemical and microbiological profiles were monitored, in order to evaluate possible alterations during truffle preservation. After harvesting, some fresh samples were kept at 4°C for 30days, other samples were frozen at -20°C for one month, thawed and preserved at 4°C; the remainder were autoclaved. The biochemical parameters studied were sugar and protein content, the activity of some enzymes involved in the central metabolism of the fungi and the electrophoretic pattern of soluble proteins. Total mesophilic bacteria were also counted. The results obtained showed that the storage at 4°C is the treatment that best preserves the biochemical and microbiological characteristics of fresh truffles. Black truffles were more resistant to biochemical spoilage than the white ones, while T. magnatum was the most resistant to microbial spoilage.

A series of eight new cavitand receptors were prepared in an effort to obtain selective mass sensors for the detection of acetates. The desired synergy between the cavity inclusion and H-bonding was obtained introducing a carboxylic residue on one of the bridging groups, which delimitate the cavity at the upper rim. The orientation of the COOH group inward or outward (cavitands 3-in and 4-out) determines a different ability to detect acetates according to their chain length. Acetate versus ester discrimination has been obtained by extending the cavity rim using a 4-chloro-phenoxy substituent in the inward position (cavitand 8-out).

The presence of bacteria of the genera Salmonella, Campylobacter , Aeromonas and Yersinia in the Metauro and Foglia Rivers and the possible relationships with faecal indicators were studied. Monthly sampling was carried out and a total of 168 samples was obtained. Thirty-eight (22.6%) samples were positive for Salmonella spp., 52 (30.9%) for Campylobacter spp., 39 (23.2%) for Aeromonas spp. and 8 (4.7%) for Yersinia spp. No correlation was found between the microorganisms of the different bacterial genera and the indicators of faecal contamination.

Immersive virtual reality (IVR) is a technology already developed to assist cognitive psychologists and therapists in their clinical work with brain-damaged patients. The rationale, the software and the hardware of the first application (ARCANA 1) based on affordable technology are discussed here, in order to provide a concrete example of what the authors think may be the role of IVR as a clinical tool. Although prospects are exciting, extensive research is needed to validate this new approach and reveal its limitations and advantages.

Introduction. The Northwestern Assessment of Verb and Sentences (NAVS; Thompson, 2011) is a test battery that includes five tests aimed at assessing production and comprehension of verbs with different argument structure (AS) complexity and sentences with canonical/non-canonical order (i.e., active, passive, subject and object Wh-questions, and subject and object-relative structures). Both AS complexity and syntactic movement affect the performance of aphasic patients, particularly those with agrammatism, in both English (Thompson, 2003; Dickey et al.,2007) and Italian (Luzzatti et al., 2001, 2002; Barbieri et al., 2010). The present study reports preliminary data derived from an Italian version of the NAVS. Materials and methods. The original English version of the NAVS was translated and adapted into Italian. As part of this process, three verbs were replaced and – given the possible ambiguity in interpretation of Wh-questions due to the freer order of arguments in Italian as compared to English – subject-clefts and object-clefts were included in the Sentence Priming Production Test (SPPT) and the Sentence Comprehension Test (SCT) as replacements for Wh-questions. The test was computerized and items within each subtest were randomized to collect accuracy and reaction times (RT) on a group of healthy controls (N=21). A paper-and-pencil version of the test was then administered to a group of aphasic participants (N=18), following the same procedure as described in Cho-Reyes & Thompson (2012). Data were analyzed using multiple linear (for RT) and logistic (for accuracy) regression. Results and discussion. Controls’ performance was at ceiling for all subtests, with the exception of subject Wh-questions (82%) and object-cleft sentences (84%) on the SCT. On the Verb Naming Test (VNT), 3-place verbs elicited longer RTs than both 2-place and 1-place verbs (p=.004; p