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ObjectiveTo understand whether the clinical phenotype of nonfluent/agrammatic primary progressive aphasia (nfvPPA) could present differences depending on the patient's native language.MethodsIn this cross-sectional study, we analyzed connected speech samples in monolingual English (nfvPPA-E) and Italian speakers (nfvPPA-I) who were diagnosed with nfvPPA and matched for age, sex, and Mini-Mental State Examination scores. Patients also received a comprehensive neuropsychological battery. All patients and 2 groups of age-matched healthy controls underwent an MRI scan with 3D T1-weighted sequences. Connected speech measures and the other cognitive features were compared between patient groups. MRI variables, in terms of gray matter volume, were compared between each patient group and the corresponding controls.ResultsCompared to nfvPPA-E, nfvPPA-I had fewer years of education and shorter reported disease duration. The 2 groups showed similar regional atrophy compatible with clinical diagnosis. Patients did not differ in nonlanguage domains, comprising executive scores. Connected speech sample analysis showed that nfvPPA-E had significantly more distortions than nfvPPA-I, while nfvPPA-I showed reduced scores in some measures of syntactic complexity. On language measures, Italian speakers performed more poorly on syntactic comprehension.ConclusionsnfvPPA-E showed greater motor speech impairment than nfvPPA-I despite higher level of education and comparable disease severity and atrophy changes. The data also suggest greater grammatical impairment in nfvPPA-I. This study illustrates the need to take into account the possible effect of the individual's spoken language on the phenotype and clinical presentation of primary progressive aphasia variants.

Coenzyme A (CoA), which is widely distributed and vital for cellular metabolism, is a critical molecule essential in both synthesizing and breaking down key energy sources in the body. Inborn errors of metabolism in the cellular de novo biosynthetic pathway of CoA have been linked to human genetic disorders, emphasizing the importance of this pathway. The COASY gene encodes the bifunctional enzyme CoA synthase, which catalyzes the last two reactions of the CoA biosynthetic pathway and serves as one of the rate-limiting components of the pathway. Recessive variants of this gene cause an exceptionally rare and devastating disease called COASY protein-associated neurodegeneration (CoPAN) while complete loss-of-function variants in COASY have been identified in fetuses/neonates with Pontocerebellar Hypoplasia type 12 (PCH 12). Understanding why the different symptoms emerge in these disorders and what determines the development of one syndrome over the other is still not achieved. To shed light on the pathogenesis, we generated a new conditional animal model in which Coasy was deleted under the control of the human GFAP promoter. We used this mouse model to investigate how defects in the CoA biosynthetic pathway affect brain development. This model showed a broad spectrum of severity of the in vivo phenotype, ranging from very short survival (less than 2weeks) to normal life expectancy in some animals. Surviving mice displayed a behavioral phenotype with sensorimotor defects. Ex vivo histological analysis revealed variable but consistent cerebral and cerebellar cortical hypoplasia, in parallel with a broad astrocytic hyper-proliferation in the cerebral cortex. In addition, primary astrocytes derived from this model exhibited lipid peroxidation, iron dyshomeostasis, and impaired mitochondrial respiration. Notably, Coasy ablation in radial glia and astrocytic lineage triggers abnormal neuronal development and chronic neuroinflammation, offering new insights into disease mechanisms. [ABSTRACT FROM AUTHOR]

Current pharmacological treatments for major depressive disorder (MDD) are often only partially effective, with many patients experiencing no significant benefit, leading to treatment-resistant depression (TRD). Psilocybin, a classical serotonergic psychedelic, has emerged as a notable emerging treatment for such disorders. The aim of this systematic review and meta-analysis is to summarize and discuss the most recent evidence about the therapeutic effects of single-dose and two-dose psilocybin administration on the severity of depressive symptoms, as well as compare the efficacy of these interventions among patients with a primary diagnosis of MDD or TRD. Articles were collected from EBSCOhost and PubMed following the PRISMA guidelines, yielding 425 articles with 138 duplicates. After screening 287 records, 12 studies met the eligibility criteria and were included in the review. A quantitative analysis of the studies indicates that psilocybin is highly effective in reducing depressive symptoms severity among patients with primary MDD or TRD. Both single-dose and two-dose psilocybin treatments significantly reduced depressive symptoms severity, with two-dose administration sometimes yielding more pronounced and lasting effects. However, it is unclear if this was solely due to dosage or other factors. Future research should include standardized trials comparing these dosing strategies to better inform clinical practice. [ABSTRACT FROM AUTHOR]

The utilization of non-invasive neurostimulation techniques, such as transcranial magnetic stimulation (TMS), is increasingly prevalent in psychiatry due to their efficacy and safety. Although the precise therapeutic mechanisms remain partially unclear, repetitive TMS, particularly high-frequency stimulation, may enhance cognitive functions, contributing to therapeutic benefits. This within-subjects study examined the impact of TMS on cognitive and symptomatic outcomes in patients with obsessive–compulsive disorder (OCD), substance use disorder (SUD), and major depressive disorder (MDD). A total of 44 patients underwent cognitive tests and symptom assessments before and after an intensive four-week TMS treatment phase, followed by a four-week maintenance phase. Cognitive assessments included Raven's matrices, verbal fluency, and digit span tests, while symptom severity was measured using the Italian version of the SCL-90-R. Decision-making performance was also evaluated by administering a delay discounting (DD) test. Principal component analysis was used to generate a dimensional characterization of subjects along cognitive and symptom-related axes before and after treatment. The results indicated that TMS significantly improved symptom scores, but no significant cognitive enhancement was observed. Statistical analysis based on linear mixed-effects models confirmed these findings, showing a significant fixed effect of TMS treatment on symptoms but not on cognitive performance. DD metrics remained unchanged. These findings suggest that while TMS effectively alleviates clinical symptoms, it does not produce consistent or appreciable enhancement of cognitive functions in these protocols. This study highlights the need for more personalized and combined therapeutic approaches to maximize the benefits of TMS, potentially incorporating cognitive enhancement strategies. Future studies will be useful to explore whether the results we obtained are valid for other pathologies, cognitive tests, and stimulation protocols. [ABSTRACT FROM AUTHOR]

First-line treatments for post-traumatic stress disorder (PTSD) encompass a wide range of pharmacotherapies and psychotherapies. However, many patients fail to respond to such interventions, highlighting the need for novel approaches. Due to its ability to modulate cortical activity, non-invasive brain stimulation (NIBS) could represent a valuable therapeutic tool. Therefore, the aim of this systematic review is to summarize and discuss the existing evidence on the ameliorative effects of NIBS on PTSD and comorbid anxiety and depressive symptoms. Our goal is also to debate the effectiveness of an integrated approach characterized by the combination of NIBS and psychotherapy. This search was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines in the PubMed, PsycINFO, PsycARTICLES, PSYINDEX, MEDLINE, and ERIC databases. Overall, 31 studies met the eligibility criteria, yielding a total of 26 clinical trials employing transcranial magnetic stimulation (TMS) and 5 making use of transcranial direct-current stimulation (tDCS). From these studies, it emerged that NIBS consistently reduced overall PTSD symptoms' severity as well as comorbid anxiety and depressive symptoms. Moreover, we speculate that combining NIBS with prolonged exposure or cognitive processing therapy might represent a promising therapeutic approach for consistently ameliorating subjects' clinical conditions. [ABSTRACT FROM AUTHOR]

Our research explores the causes of Twitter activity in highly technological start‐ups that finance their activities via initial coin offerings (ICOs). By relying on weekly data of 297 ICOs for the period 2015–2020 (35,459 observations), we examine how major exogenous events affect the number of tweets issued by the start‐up. Then, we explore how the community of followers reacts to the tweets. We discover that events external to firms reduce ICOs' tweeting activity. Moreover, our evidence indicates that the followers' reaction is positively related to the tweets issued by the firm and negatively related to major events unrelated to the firm. Interestingly, followers' reaction has an inverted U‐shaped relation with the firm's Twitter volume, suggesting that excessive Twitter activity can harm the further dissemination of tweets. Our results, robust to alternative estimation techniques, emphasize the important role of Twitter as an information disseminator, legitimizer, and endorser for highly opaque firms. [ABSTRACT FROM AUTHOR]

Sustainability rating systems for the built environment involve a multitude of indicators that are based on different types of data. This work capitalizes on an existing multicriteria assessment method and supporting decision-making tool at building and neighbourhood scale, to develop an enhanced method and tool at city scale. The main sustainability issues at building and city scales include site and infrastructure, energy and resources consumption, environmental loadings, climate change, environmental quality, water, waste, transportation, services, social aspects, economy and governance. Approximately 300 indicators distributed among the different scales are used to describe and quantify the various facets of sustainability. Specifically, the building scale includes a pool of 80 indicators of which 17 are key performance indicators (KPIs), the neighbourhood scale has 133 indicators of which 14 are KPIs and the city scale has a total of 99 indicators of which 10 are KPIs that were new additions to the existing method. The emphasis in this paper is given on elaborating the key performance indicators for cities and demonstrating their applicability through a case study. The common method and tools provide a flexible assessment system for local authorities and stakeholders to develop and assess sustainability plans. [ABSTRACT FROM AUTHOR]