University of Verona

Alexander disease (AxD), an autosomal dominant leukodystrophy, is caused by mutations in the GFAP, the gene encoding glial fibrillary acidic protein (GFAP). The disease, classified by age of onset into infantile, juvenile, and adult forms, is characterized by white matter degeneration and astrocytic inclusions called Rosenthal fibers. A patient underwent clinical, radiological, and molecular analyses to confirm a suspected diagnosis of AxD. The functional effect of the variant identified was tested using computational tools and in HeLa and astrocytoma cell lines. We report a case of juvenile AxD that clinically developed acute respiratory distress due to bilateral vocal cord paralysis. Brain and spinal cord MRI revealed the typical findings of the disease, including bulbospinal atrophy and T2-weighted hyperintensities in the frontal periventricular white matter. Molecular genetic testing identified a novel de novo c.713 T > G (p.I238S) variant of GFAP. In silico analyses revealed that the variant at evolutionarily conserved residue likely affects protein function. In vitro assays confirmed its pathogenic effect, showing that p.I238S protein expression significantly associates with aggregate formation in cellular models. Extending the clinical and molecular characterization of new cases of AxD is an important achievement to better characterize the disease.

The present chapter situates within the burgeoning debate about the role of innovation in societal progress, particularly on the intricate and multifaceted relationship between workers and technology led by the digitalization of work. The digital area involves revisiting work and employment with job sectors using technology as the means for work, businesses, and organizations realizing ventures through technology. Moreover, digitalization is not only reimagining how work is performed (e.g., remote work, augmentation, advanced automation, collaborative robotics, machine learning, artificial intelligence, etc.) but also leading to revisiting workers’ relationships with work, organizations, and society. The disparate aspects of the digitalization of work echo the imperative for reflections on its definitions and implications. In parallel with the revisitation of work and employment in the digital era, the chapter revisits the role of human resources management. It proposes a series of reflections on what it means and what it takes to manage digital transformation. It does so by assuming a human-centric perspective that emphasizes the centrality of humans (workers) in digital transformation. Firstly, the chapter argues that the role of human resources in change management is the nexus between workers and organizations. It then discusses the role of leaders in driving this revolution and the role of organizational culture as a means for supporting workplace transformation. It concludes by reflecting on talent acquisition and workers’ training and education as fundamental processes to develop the required skills in the workforce.

Fetomaternal hemorrhage (FMH) is the passage of fetal blood through the maternal circulatory system before or during delivery. Due to the nonspecificity of clinical manifestations, FMH is rarely diagnosed. When it occurs rapidly, it could have catastrophic consequences. Decreased fetal movements and a sinusoidal cardiotocographic (CTG) for more than 30 min are characteristic findings. This paper presents a case report of a 34‐year‐old woman at 38 + 4 weeks with reduced fetal movements and a sinusoidal CTG. An emergency cesarean section was performed, delivering a pale newborn with a hemoglobin of 4.3 g/dL. A comprehensive review of the available literature is then reported.

The aim of this study was to test the hypothesis that individuals with an increase in HbA1c (i.e. above the regular but below the diabetic threshold) exhibit an impairment in the Achilles tendon structure and walking capacity, due to the adverse effect of the advanced glycation end-product. One hundred fifty-eight participants matched for gender, age, physical activity and BMI, were divided in two cohorts based on the HbA1c level: normal HbA1c (NGH; <39 mmol/molHb; n = 79) and altered HbA1c (AGH; >=39 mmol/molHb; n = 79). Each participant performed several walking trials to evaluate the kinematic parameters during walling at the self-selected speed and a quantitative MRI scan of the Achilles tendon (AT) to obtain its intrinsic characteristics (i.e. T2* relaxation time short and long component). The AT T2* relaxation time short component (a parameter related to the tendon collagen quality) was reduced in AGH compared to NGH. Furthermore, AGH exhibited a slower self-selected walking speed (NGH: 1.59 ± 0.18 m/s; AGH:1.54 ± 0.16 m/s) and a shorter stride length (NGH: 1.59 ± 0.13 m; AGH:1.55 ± 0.11 m). Our data suggest that a non-pathological increase in HbA1c is able to negatively affect AT collagen quality and walking capacity in healthy people. These results highlight the importance of glycemic control, even below the pathological threshold. Since diabetes could alter several biological pathways, further studies are necessary to determine which mechanisms and their timing, regarding the HbA1c rise, affect tendon composition and, consequently, walking capacity.

Physics-Informed Neural Networks (PINNs) have revolutionized solving differential equations by integrating physical laws into neural networks training. This paper explores PINNs for open-loop optimal control problems with incomplete information, such as sparse initial and boundary data and partially unknown system parameters. We derive optimality conditions from the Lagrangian multipliers and use PINNs to predict the state, adjoint, and control variables. In contrast with previous methods, our approach integrates these elements into a single neural network and addresses scenarios with consistently limited data. In addition, we address the study of partially unknown equations identifying underlying parameters online by searching for the optimal solution recurring to a 2-in-series architecture of PINNs, in which scattered data of the uncontrolled solution is used. Numerical examples show the effectiveness of the proposed method even in scenarios characterized by a considerable lack of information.

Purpose The anastomosis technique following laparoscopic right colectomy remains a subject of ongoing debate. One of the potential advantages of intracorporeal anastomosis is the flexibility it offers in selecting the location of the minilaparotomy. This study aimed to evaluate the differences in the rate of incisional hernia between intracorporeal and extracorporeal anastomosis after laparoscopic right colectomy. Methods We retrospectively analysed patients undergoing laparoscopic right colectomy for colon neoplasia between April 2013 and January 2024, retrieved from a prospectively maintained database. The occurrence of incisional hernia was assessed according to the anastomosis technique. Univariate and multivariate analyses were performed to investigate the relationship between incisional hernia and anastomosis technique, while controlling for other risk factors. Results Among 192 patients, 94 underwent intracorporeal anastomosis and 98 underwent extracorporeal anastomosis. The groups were comparable in terms of clinical, pathological, and surgical data. The intracorporeal group showed a lower incidence, although not statistically significant, of postoperative ileus (p = 0.052), and a shorter hospital stay (p = 0.003). No incisional hernias were observed at the minilaparotomy site in the intracorporeal anastomosis group, while 13.3% of patients in the extracorporeal anastomosis group developed an incisional hernia (p < 0.001). One incisional hernia at the umbilical trocar site occurred after intracorporeal anastomosis. Multivariate analysis identified postoperative general complications (OR [95% CI]: 4.1 [1.0–16.5], p = 0.049) and extracorporeal anastomosis (OR [95% CI]: 15.4 [1.0–126.9], p = 0.011) as independent risk factors for incisional hernia. Conclusions Intracorporeal anastomosis significantly reduces the incidence of incisional hernia at the minilaparotomy site. This finding is further supported by logistic regression analysis, which identified intracorporeal anastomosis as a significant and independent protective factor against incisional hernia.

We present multiplicity results for mass constrained Allen–Cahn equations on a Riemannian manifold with boundary, considering both Neumann and Dirichlet conditions. These results hold under the assumptions of small mass constraint and small diffusion parameter. We obtain lower bounds on the number of solutions according to the Lusternik–Schnirelmann category of the manifold in case of Dirichlet boundary conditions and of its boundary in the case of Neumann boundary conditions. Under generic non-degeneracy assumptions on the solutions, we obtain stronger results based on Morse inequalities. Our approach combines topological and variational methods with tools from Geometric Measure Theory.

The treatment of laryngeal carcinoma is directly influenced by the presence of metastatic cervical adenopathy that represents the most important predictable survivor factor. Management of cervical lymph nodes is determined by several factors, such as the site and stage of the laryngeal neoplasm, and the presence or absence of evident lymphatic metastases. Moreover, the pattern of spread of laryngeal squamous cells is site-specific and occurs in a predictable manner, strictly linked to the laryngeal lymphatic drainage.

The open partial supraglottic laryngectomy (OPHL I according to the ELS classification) was firstly described in 1947 but still represents an effective surgical procedure for low to selected high stage supraglottic laryngeal cancer and limited base of tongue tumors. Resection might be extended to one arytenoid, to the medial wall of one pyriform sinus, or to the base of tongue according to tumor extension. When adequately performed, OPHL I provides good oncological outcomes together with phonatory and swallowing ones. The present section describes the step-by-step surgical procedure.

Beginning with a reconstruction of the issues in the international debate about the ‘new’ ways of working and spatial-temporal configurations of hybrid work and organizing, this chapter traces the most recent Italian scientific discussions on this topic. As remote working practices were unusual before the pandemic, and managerial and work cultures were generally deeply anchored in traditional office work, the organizational and cultural change brought about by the flexible paradigm is particularly interesting in Italy and may lead to inequalities, contestation, and resistance. Based on some inductive traces from ongoing empirical research field on hybrid forms of flexible working and organizing in Italy, this chapter raises questions about topologies, boundaries, and mobility matters in and around organization that can help with understanding and theorizing ongoing changes of work. The insights suggest the post-pandemic need to address spatial-temporal configurations as emergent becomings through which workers make sense of organization and consider—both in theorization and organizational practice—issues of equity that can arise from hybrid forms of working and organizing.

This chapter delves into the Italian context concerning transgender individuals within the workplace. We commence by reading a significant event involving our Prime Minister, Giorgia Meloni, providing insight into the contemporary political right-wing climate in Italy. Proceeding from this, we navigate through the landscape of Italian legislation related to transgender individuals. Subsequently, we explore key thematic lines in contemporary organizational literature that scrutinizes the professional experiences of transgender individuals. The narrative then unfolds with a comprehensive examination of Nicola’s story, mirroring the challenges faced by transgender people in Italy. The chapter concludes with the identification of recommended practices and actions that (Italian) companies should embrace to combat discrimination against transgender individuals and foster their overall well-being.

In this Research Note, we introduce Intronomics-MIP, a snakemake-based pipeline for the automated analysis of multi-locus intron polymorphisms (MIPs) using intron-targeted amplicon sequencing. Building on established methodologies, our pipeline integrates tools such as Cutadapt, FLASH, and SeekDeep to efficiently process and analyze highly variable intron regions. These MIPs serve as powerful multiple-allelic markers, primarily useful for distinguishing species, identifying cryptic species, disentangling species complexes and detecting hybridization, but can also be informative for assessing population structure without prior species knowledge. Our pipeline enhances reproducibility and scalability, making it adaptable to a wide range of taxa, with a specific demonstration on teleost species. We provide a comprehensive overview of the pipeline’s design, along with performance assessments using representative datasets.

Cystathionine β‐synthase (CBS) is a pyridoxal‐phosphate (PLP)‐dependent enzyme essential for the reverse transsulfuration pathway, where homocysteine and serine combine to form cystathionine, the immediate precursor of cysteine. Mutations in the CBS gene cause homocystinuria, a disorder associated with intellectual disability, multisystem complications, and reduced life expectancy. The CBS p.R336C mutation, linked to severe pyridoxine non‐responsiveness, results in reduced enzyme activity, previously attributed to protein instability and weakened substrate and PLP binding. To clarify the effects of the pathological R336C mutation, we performed biochemical, biophysical, and crystallographic analyses, as well as molecular dynamics simulations. Our findings show that the R336C mutation minimally impacts the structural environment around residue 336, does not cause enzyme misfolding, and does not impair the binding of PLP or the allosteric activator S‐adenosylmethionine (AdoMet) binding. Instead, the mutation induces subtle reorientations in nearby hydrophobic residues, including F185 and Y381, altering intramolecular contacts that perturb the interaction between asparagine 149 and the O3 oxygen of PLP. This alteration is known to potentially shift the tautomeric equilibrium of the PLP Schiff base from its catalytically active ketoenamine form to the inactive enolimine form, which aligns with the reduced activity of the R336C variant. Additionally, the R336C mutation disrupts intermolecular contacts between the catalytic core and Bateman module, altering the Bateman module's intrinsic mobility in the enzyme's basal state and potentially affecting the cavity opening required for catalysis. Importantly, the R336C variant retains the native enzyme's ability to assemble into polymeric chains in crystals, preserving its filament formation capacity.

Wood-boring beetles and, in particular, Scolytinae (Coleoptera: Curculionidae) are one of the most successful groups of invasive species worldwide. They can be easily transported across continents at the larval stage as their development takes place inside the tissues of live plants, timber, wood products and wood-packaging materials. This grants them protection from adverse travel conditions and allows them to often go unnoticed by phytosanitary inspections at ports of entry. In this context, knowledge of biological traits of these species, particularly the recorded host plants, is essential for planning effective monitoring strategies. This kind of information is scattered through a large amount of papers, catalogs and books. Thus, the purpose of this paper is to provide a comprehensive list of host plants and their economic categorization for five scolytine tribes. This fourth contribution presents the list of host plants for 829 species belonging to five tribes that mainly, but not exclusively, infest conifers: Hylastini LeConte, Hylurgini Gistel, Ipini Bedel, Phloeosinini Nusslin, and Polygraphini Chapuis.

Milk thistle compounds have recently gained attention for their potential role in cancer prevention and treatment. Despite most evidence reporting this property refers to in vitro and animal studies, Milk thistle flavonoids may provide insightful suggestions about novel chemopreventive agents. This narrative review provides an overview of the current understanding of milk thistle's effects on cancer cells and highlights possible mechanisms of action. The active compounds in milk thistle mainly exhibit antioxidant and anti-inflammatory effects, which protect cells and enhance their survival responses, even inhibiting cancer development. In addition, the compounds possess immunomodulatory properties crucial in preventing cancer progression. Another important mechanism is the induction of apoptosis, promoting cancer cell death and inhibiting tumour growth. These compounds inhibit angiogenesis, preventing tumour growth and spread. Due to their potential to inhibit cancer progression, they modulate cell signalling pathways, including the MAPK and PI3K/Akt pathways, which are involved in cell growth and survival. Although current research is promising, it is crucial to address the current gaps in knowledge about milk thistle compounds in cancer prevention and treatment. Future studies should focus on rigorous clinical trials, dose optimization, mechanistic investigations, combination therapy approaches, and personalized medicine to maximize their potential. Basic experimental evidence can provide new clues to establish clinical trials to improve cancer care and reassure patients and healthcare professionals.

Cardiac injury, encompassing a spectrum of heart muscle damage, requires prompt and accurate diagnosis to improve patient outcomes. Early detection using cardiac biomarkers is vital for timely intervention and reducing mortality. This review highlights the role of high-sensitivity cardiac troponins (hs-cTns) in diagnosing cardiac injury. This article offers an overview of cardiac injury, including its causes, diagnostic challenges, and the evolution of biomarkers, up to the development and commercialization of "high-sensitivity" (hs-) cTns. The molecular structure of cardiac isoforms cTnI and cTnT, release kinetics, guidelines incorporation, diagnostic performance, and clinical application will be analyzed. It is concluded that the advent of hs-cTn assays has further expanded diagnostic capabilities by enabling the detection of low-level cTn elevations, which were previously undetectable using conventional methods. This enhanced sensitivity allows earlier identification of even minor cardiac injuries, facilitating prompt intervention and improving patient outcomes. However, this increased sensitivity also introduces interpretive challenges in understanding the nature of cardiac involvement, especially in distinguishing mild cTn elevations that may signify non-ischemic cardiac injury or be associated with other non-cardiac conditions.

Background Among patients with hepatocellular carcinoma (HCC), the impact of anatomic resection (AR) versus non-anatomic resection (NAR) on non-transplantable recurrence (NTR) remains poorly defined. We sought to compare the risk of NTR among patients treated with AR versus NAR as the primary surgical strategy for HCC. Patients and Methods Patients with HCC within Milan criteria who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. The inverse probability of treatment weighting (IPTW) method was utilized to compare short- and long-term outcomes among patients undergoing AR versus NAR. Results Among 1038 patients, 747 (72.0%) patients underwent AR, while 291 (28.0%) patients underwent NAR. After IPTW adjustment, patients who underwent AR had better 5-year recurrence-free survival than individuals treated with NAR (63.9 vs. 52.0%; hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.62–0.99); however, there was no difference in 5-year overall survival (80.2 vs. 75.6%; HR 0.76; 95% CI 0.55–1.05). Notably, individuals who underwent AR were less likely to have a NTR versus individuals treated with NAR (3-year NTR 9.8 vs. 14.4%; HR 0.62; 95% CI 0.40–0.96). In particular, AR was associated with a lower risk of NTR among patients with a medium tumor burden score (TBS) (HR 0.53; 95% CI 0.28–0.99), while the benefit among patients with a low TBS was less pronounced (HR 0.73; 95% CI 0.40–1.32). Conclusions AR was associated with a lower risk of NTR and improved recurrence-free survival (RFS) among patients with HCC, especially individuals with higher TBS. An anatomically defined surgical approach should be strongly considered in patients with a higher HCC tumor burden.

The interaction between the microtubule associated protein Tau and the tyrosine kinase Fyn is believed to play a pivotal role in the early stage of Alzheimer’s disease (AD). Previous studies have identified the SRC Homology 3 (SH3) domain of Fyn as the binding receptor of several proline‐rich motifs in Tau. However, the role of each proline rich motif and their interplay in molecular recognition are still unclear. In this work, we investigated the mechanism of Fyn‐SH3 recognition by the multiple PxxP sites inserted within the full‐length Tau protein by using NMR spectroscopy combined with computational, calorimetric and in‐cell FRET methods. Both in vitro and in‐cell experiments revealed no single binding site strictly necessary for the binding. Instead, Fyn‐SH3 contacts full‐length Tau on multiple hot spot regions, located over a distance of 85 residues, through global moderate‐to‐low affinity interactions. Beyond two principal regions containing classical PxxP motifs, we identified a novel non‐canonical binding site at the beginning of the microtubule binding domain. Our study indicates that multiple binding sites in Tau are involved in the interaction, making Tau an adaptable recognition surface that can function when single consensus motifs are deleted.