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Roberto Gambari, Alessia Finotti Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, 44121, ItalyCorrespondence: Roberto Gambari, Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, 44121, Italy, Email gam@unife.it

Motivational (i.e., appetitive or aversive) cues can bias value-based decisions by affecting either direction and intensity of instrumental actions. Despite several findings describing important interindividual differences in these biases, whether biological sex can also play a role is still up to debate. By comparing females and males in both appetitive and aversive Pavlovian-to-Instrumental Transfer paradigms we found that, while motivational cues similarly bias the direction of instrumental actions in both sexes, the intensity of such actions is increased by the cue in male participants only. The present results constitute compelling evidence that a crucial motivational bias of daily actions directed to obtaining rewards or avoiding punishments is modulated by biological sex. This evidence sheds new light on the role of sex in motivational processes that underlie decision-making, highlighting the importance of considering sex as a crucial factor in future research on this topic.

Alessia Finotti,1–3 Laura Breda,4 Carsten W Lederer,6,7 Nicoletta Bianchi,1–3 Cristina Zuccato,1–3 Marina Kleanthous,6,7 Stefano Rivella,4,5 Roberto Gambari1–3 1Laboratory for the Development of Gene and Pharmacogenomic Therapy of Thalassaemia, Biotechnology Centre of Ferrara University, Ferrara, Italy; 2Associazione Veneta per la Lotta alla Talassemia, Rovigo, Italy; 3Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, Ferrara University, Ferrara, Italy; 4Department of Pediatrics, Division of Haematology/Oncology, Weill Cornell Medical College, New York, NY, USA; 5Department of Cell and Development Biology, Weill Cornell Medical College, New York, NY, USA; 6Department of Molecular Genetics Thalassaemia, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; 7Cyprus School of Molecular Medicine, Nicosia, Cyprus Abstract: The β-thalassemias are a group of hereditary hematological diseases caused by over 300 mutations of the adult β-globin gene. Together with sickle cell anemia, thalassemia syndromes are among the most impactful diseases in developing countries, in which the lack of genetic counseling and prenatal diagnosis have contributed to the maintenance of a very high frequency of these genetic diseases in the population. Gene therapy for β-thalassemia has recently seen steadily accelerating progress and has reached a crossroads in its development. Presently, data from past and ongoing clinical trials guide the design of further clinical and preclinical studies based on gene augmentation, while fundamental insights into globin switching and new technology developments have inspired the investigation of novel gene-therapy approaches. Moreover, human erythropoietic stem cells from β-thalassemia patients have been the cellular targets of choice to date whereas future gene-therapy studies might increasingly draw on induced pluripotent stem cells. Herein, we summarize the most significant developments in β-thalassemia gene therapy over the last decade, with a strong emphasis on the most recent findings, for β-thalassemia model systems; for β-, γ-, and anti-sickling β-globin gene addition and combinatorial approaches including the latest results of clinical trials; and for novel approaches, such as transgene-mediated activation of γ-globin and genome editing using designer nucleases. Keywords: Thalassemia, gene therapy, HbF induction, transcription factors, induced pluripotent stem cells, genome editing, TALEN, CRISPR, ZFN

Abstract N-acylhydrazones are considered privileged structures in medicinal chemistry, being part of antimicrobial compounds (for example). In this study we show the activity of N-acylhydrazone compounds, namely AH1, AH2, AH4, AH5 in in vitro tests against the chloroquine-resistant strain of Plasmodium falciparum (W2) and against WI26 VA-4 human cell lines. All compounds showed low cytotoxicity (LC50 > 100 µM). The AH5 compound was the most active against Plasmodium falciparum, with an IC50 value of 0.07 μM. AH4 and AH5 were selected among the tested compounds for molecular docking calculations to elucidate possible targets involved in their mechanism of action and the SwissADME analysis to predict their pharmacokinetic profile. The AH5 compound showed affinity for 12 targets with low selectivity, while the AH4 compound had greater affinity for only one target (3PHC). These compounds met Lipinski's standards in the ADME in silico tests, indicating good bioavailability results. These results demonstrate that these N-acylhydrazone compounds are good candidates for future preclinical studies against malaria. Graphical Abstract

Liver transplantation is the preferred treatment for end-stage liver disease. Emerging evidence suggests a potential role for liver transplantation in treating liver tumors such as colorectal liver metastases and cholangiocarcinoma. However, due to a limited donor pool, the use of marginal grafts from donation after circulatory death (DCD) donors is increasing to meet demand. Machine perfusion is crucial in this context for improving graft acceptance rates and reducing ischemia–reperfusion injury. Few studies have evaluated the role of machine perfusion in the context of transplant oncology. Perfusion machines can be utilized in situ (normothermic regional perfusion—NRP) or ex situ (hypothermic and normothermic machine perfusion), either in combination or as a complement to conventional in situ cold flush and static cold storage. The objective of this analysis is to provide an up-to-date overview of perfusion machines and their function in donation after circulatory death with particular attention to their current and likely potential effects on transplant oncology. A literature review comparing standard cold storage to machine perfusion methods showed that, so far, there is no evidence that these devices can reduce the tumor recurrence rate. However, some evidence suggests that these innovative perfusion techniques can improve graft function, reduce ischemia–reperfusion injury, and, based on this mechanism, may lead to future improvements in cancer recurrence. [ABSTRACT FROM AUTHOR]

Background/Objectives: Fibromyalgia (FM) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and impaired motor performance. This study aimed to investigate the effects of transcranial direct current stimulation (tDCS) during virtual reality (VR) tasks on the motor performance of women with FM. Methods: Participants were divided into two groups: Group A received active tDCS for 10 days followed by sham tDCS for 10 days, while Group B received the opposite sequence. Both groups performed VR tasks using MoveHero software (v. 2.4) during the tDCS sessions. Motor performance was assessed by the number of hits (movement with correct timing to reach the targets) and absolute (accuracy measure) and variable (precision measure) errors during VR tasks. Participants were 21 women, aged 30–50 years, and diagnosed with FM. Results: Group A, which received active tDCS first, presented significant improvements in motor performance (number of hits and absolute and variable errors). The benefits of active tDCS persisted into the sham phase, suggesting a lasting neuroplastic effect. Conclusions: tDCS during VR tasks significantly improved motor performance in women with FM, particularly in complex, extensive movements. These findings indicate that tDCS enhances neuroplasticity, leading to sustained motor improvements, making it a promising therapeutic tool in FM rehabilitation. [ABSTRACT FROM AUTHOR]