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In this review, the recently approved drugs avatrombopag and fostamatinib, which were not extensively covered within 2019 international recommendations for ITP, will be discussed in some detail. Avatrombopag appears more convenient than eltrombopag as it does not require dietary restrictions or subcutaneous administration like romiplostim. However, data on quality of life (QoL) are lacking and the rate of thromboembolic events in exposed patients is not negligible. Efficacy of fostamatinib, an inhibitor of macrophagic activity, is supported by placebo-controlled trials in patients refractory to several therapies, including TPO-RA. While hypertension and diarrhea have been reported, only one minor thrombotic event occurred in 146 exposed patients. In addition, several new treatment combinations and new agents entered clinical investigation in recent years. In a UK trial, combining mycophenolate mofetil with corticosteroids as first line therapy was more effective than corticosteroids alone, but at the cost of worse QoL. No combination, including oseltamivir or all-trans retinoic acid or danazol, resulted in convincing evidence of superior efficacy and safety when used in first or later lines of treatment. Agents targeting specific mechanisms are also discussed: sutimlimab (complement inhibitor); rilzabrutinib (BTK inhibitor) and efgartigimod (modified Fc fragment inhibiting FcRn). Only efgartigimod has completed phase 3 investigation.

Background Artificial intelligence (AI) chatbots are emerging educational tools for students in healthcare science. However, assessing their accuracy is essential prior to adoption in educational settings. This study aimed to assess the accuracy of predicting the correct answers from three AI chatbots (ChatGPT-4, Microsoft Copilot and Google Gemini) in the Italian entrance standardized examination test of healthcare science degrees (CINECA test). Secondarily, we assessed the narrative coherence of the AI chatbots’ responses (i.e., text output) based on three qualitative metrics: the logical rationale behind the chosen answer, the presence of information internal to the question, and presence of information external to the question. Methods An observational cross-sectional design was performed in September of 2023. Accuracy of the three chatbots was evaluated for the CINECA test, where questions were formatted using a multiple-choice structure with a single best answer. The outcome is binary (correct or incorrect). Chi-squared test and a post hoc analysis with Bonferroni correction assessed differences among chatbots performance in accuracy. A p -value of < 0.05 was considered statistically significant. A sensitivity analysis was performed, excluding answers that were not applicable (e.g., images). Narrative coherence was analyzed by absolute and relative frequencies of correct answers and errors. Results Overall, of the 820 CINECA multiple-choice questions inputted into all chatbots, 20 questions were not imported in ChatGPT-4 ( n  = 808) and Google Gemini ( n  = 808) due to technical limitations. We found statistically significant differences in the ChatGPT-4 vs Google Gemini and Microsoft Copilot vs Google Gemini comparisons ( p -value < 0.001). The narrative coherence of AI chatbots revealed “Logical reasoning” as the prevalent correct answer ( n  = 622, 81.5%) and “Logical error” as the prevalent incorrect answer ( n  = 40, 88.9%). Conclusions Our main findings reveal that: (A) AI chatbots performed well; (B) ChatGPT-4 and Microsoft Copilot performed better than Google Gemini; and (C) their narrative coherence is primarily logical. Although AI chatbots showed promising accuracy in predicting the correct answer in the Italian entrance university standardized examination test, we encourage candidates to cautiously incorporate this new technology to supplement their learning rather than a primary resource. Trial registration Not required.

Since its discovery, the thrombopoietin (TPO) pathway has been an important pharmaceutical target for the treatment of thrombocytopenia. The first generation of TPO mimetics included peptide agents sharing homology with endogenous TPO, but these introduced a risk of antibody formation to endogenous TPO and were not successful. However, second-generation TPO mimetics or TPO receptor agonists (RAs) are currently being used to treat thrombocytopenia associated with a number of conditions, such as immune thrombocytopenia (ITP), severe aplastic anaemia (SAA), and hepatitis C virus-associated chronic liver disease. Accumulating efficacy and safety data suggest that the role of TPO-RAs in the treatment of thrombocytopenia may evolve in the near future with broader use of these agents in ITP and SAA, as well as approval in other indications, potentially including myelodysplastic syndromes, chemotherapy-associated thrombocytopenia, and post-transplant thrombocytopenia. This review provides an overview of clinical data on the efficacy and safety of TPO-RAs, emphasising recent findings that may expand their clinical utility.

This paper investigates to what extent adverbial causal clauses and relative clauses can be reduced as one and the same phenomenon. Whereas causal clauses have always posed a challenge for a unified account of relativization and adverbial subordination in theoretical studies, typological research has long demonstrated that causal clauses are diachronically connected to relative clauses as well as to adverbial subordinates that have been theoretically analysed as relative clauses. We argue that at least some causal clauses are underlyingly relative clauses over situations (see Arsenijević 2021). Our claim is supported by the diachronic development of the Italian subordinator siccome ‘because/since’, an univerbated form morphologically composed of two items, the comparative-similative wh-pronoun come ‘how’ and the demonstrative adverbial pronoun sì ‘so’. We demonstrate that the causal subordinator is derived from the comparative-similative one via a three-stage diachronic change which is formally captured in terms of type of movement and null elements (Kayne 2005, Cinque 2020b). In so doing, our paper extends a relative clause analysis to causal clauses and adds a novel path to the diachronic development of causal clauses.

This paper investigates to what extent adverbial causal clauses and relative clauses can be reduced as one and the same phenomenon. Whereas causal clauses have always posed a challenge for a unified account of relativization and adverbial subordination in theoretical studies, typological research has long demonstrated that causal clauses are diachronically connected to relative clauses as well as to adverbial subordinates that have been theoretically analysed as relative clauses. We argue that at least some causal clauses are underlyingly relative clauses over situations (see Arsenijević 2021). Our claim is supported by the diachronic development of the Italian subordinator siccome ‘because/since’, an univerbated form morphologically composed of two items, the comparative-similative wh-pronoun come ‘how’ and the demonstrative adverbial pronoun sì ‘so’. We demonstrate that the causal subordinator is derived from the comparative-similative one via a three-stage diachronic change which is formally captured in terms of type of movement and null elements (Kayne 2005, Cinque 2020b). In so doing, our paper extends a relative clause analysis to causal clauses and adds a novel path to the diachronic development of causal clauses.

Under the auspices of an International Working Group, seven centers submitted diagnostic and follow-up information on 1545 patients with World Health Organization-defined polycythemia vera (PV). At diagnosis, median age was 61 years (51% females); thrombocytosis and venous thrombosis were more frequent in women and arterial thrombosis and abnormal karyotype in men. Considering patients from the center with the most mature follow-up information ( n =337 with 44% of patients followed to death), median survival (14.1 years) was significantly worse than that of the age- and sex-matched US population ( P <0.001). In multivariable analysis, survival for the entire study cohort ( n =1545) was adversely affected by older age, leukocytosis, venous thrombosis and abnormal karyotype; a prognostic model that included the first three parameters delineated risk groups with median survivals of 10.9–27.8 years (hazard ratio (HR), 10.7; 95% confidence interval (CI): 7.7–15.0). Pruritus was identified as a favorable risk factor for survival. Cumulative hazard of leukemic transformation, with death as a competing risk, was 2.3% at 10 years and 5.5% at 15 years; risk factors included older age, abnormal karyotype and leukocytes ⩾15 × 10 9 /l. Leukemic transformation was associated with treatment exposure to pipobroman or P32/chlorambucil. We found no association between leukemic transformation and hydroxyurea or busulfan use.

European beech is a species of both ecological and economic relevance in Europe. However, its high sensitivity to drought poses a significant risk amid increasing climate extremes. This study aimed to evaluate the physiological and spectral responses of beech to drought stress, combining in situ leaf-level measurements with hyperspectral remote sensing data. We set up the experiment in an Alpine European beech forest in northern Italy, which included three water treatments: control, water stress, and irrigation. Physiological data (i.e., leaf gas exchange and chlorophyll content), alongside airborne hyperspectral remote sensing data, were collected from 20 to 29 July 2022 during a compound drought and heatwave (CDHW) event. Water-stressed trees exhibited significantly reduced photosynthetic rates, lower photosystem II efficiency, and higher non-photochemical quenching, indicating impaired photosynthetic performance. Water-stressed beech exhibited up to 70% reduced photosynthesis and 35% lower leaf chlorophyll content under severe drought conditions. Hyperspectral vegetation indices, particularly the RENDVI, CIRE, and SPRI, successfully detected stress status. This exploratory study, based on an intensive analysis of four trees, demonstrates the feasibility of integrating physiological measurements with hyperspectral remote sensing to detect drought-stress signatures in European beech at the individual-tree level, establishing a methodological framework for more extensive future research.

The use of fetal bovine serum (FBS) as a cell culture supplement is discouraged by regulatory authorities to limit the risk of zoonoses and xenogeneic immune reactions in the transplanted host. Additionally, FBS production came under scrutiny due to animal welfare concerns. Platelet derivatives have been proposed as FBS substitutes for the ex-vivo expansion of mesenchymal stem/stromal cells (MSCs) since platelet-derived growth factors can promote MSC ex-vivo expansion. Platelet-derived growth factors are present in platelet lysate (PL) obtained after repeated freezing–thawing cycles of the platelet-rich plasma or by applying physiological stimuli such as thrombin or CaCl 2 . PL-expanded MSCs have been used already in the clinic, taking advantage of their faster proliferation compared with FBS-expanded preparations. Should PL be applied to other biopharmaceutical products, its demand is likely to increase dramatically. The use of fresh platelet units for the production of PL raises concerns due to limited availability of platelet donors. Expired units might represent an alternative, but further data are needed to define safety, including pathogen reduction, and functionality of the obtained PL. In addition, relevant questions concerning the definition of PL release criteria, including concentration ranges of specific growth factors in PL batches for various clinical indications, also need to be addressed. We are still far from a common definition of PL and standardized PL manufacture due to our limited knowledge of the mechanisms that mediate PL-promoting cell growth. Here, we concisely discuss aspects of PL as MSC culture supplement as a preliminary step towards an agreed definition of the required characteristics of PL for the requirements of manufacturers and users.

Increasing nitrogen (N) deposition may alter soil N status and dynamics, as well as the emission of soil greenhouse gases (GHGs). Most of the experimental N manipulations performed so far have neglected the interaction with the canopy, which influences both quantity and quality of the N input into the soil. Here, we assess the effects of N fertilizer application method on N mineralization, and soil GHG fluxes. The experimental site is a sessile oak ( Quercus petraea L.) stand in Northern Italy and consists of a set of three plots, replicated three times. In each replication, one plot is not fertilized (control plot); one plot receives the fertilization on the forest floor (below-canopy treatment), and one plot receives the fertilization above the canopy (above-canopy treatment). After 5 years of experimental N applications, equal to 20 kg N ha −1  y −1 distributed equally five times during the vegetative season, net soil N mineralization was assessed with the in-situ soil core incubation method. Soil CO 2 flux was measured with a portable infra-red gas analyzer, while the soil CH 4 and N 2 O fluxes were assessed using static closed chambers. No treatment effect was evidenced on soil mineral N content. However, during the last two vegetative seasons, topsoil N leaching increased in the treatment below, and not in the treatment above. On the contrary, N mineralization was lower compared to the control only in the treatment below. These results indicate that the tree canopy can mitigate the effect of N deposition on soil N cycling, which may therefore have been overestimated in previous studies using ground N fertilization. On the other hand, differences in soil GHG fluxes among treatments were not significant, even when the effect of soil temperature and soil moisture was considered. Nevertheless, given the complex relationships between N depositions, soil N dynamics and GHG emissions, long-term investigation is needed to determine whether the presence of the forest canopy, and/or differences in forest type, can mitigate or delay N saturation in the medium to long term.