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Background: There is ongoing discussion around the optimal course of treatment for metastatic colorectal cancer (mCRC) following the second line. Trifluridine/tipiracil (T) and regorafenib (R) have been the mainstay of therapy in this situation, as they both increased overall survival (OS) in comparison to a placebo. Despite the paucity of evidence, therapy rechallenge is also recognized as an option for practical use. In the third-line scenario of mCRC, we planned to investigate the survival outcomes using (T) and (R), both with and without prior rechallenge treatment. Materials and methods: Between 2012 and 2023, we examined the medical records of 1156 patients with refractory mCRC who were enrolled in the multicenter retrospective ReTrITA study. We then separated the patients into two cohorts based on the rechallenge therapy that was given before regorafenib and/or trifluridine/tipiracil at 17 Italian centres. Results: A total of 981 patients underwent T and/or R therapy, while 175 patients had therapy rechallenge before T and/or R. The median overall survival (mOS) for patients treated with T/R and R/T sequences in the rechallenge therapy cohort was 14.5 months and 17.6 months, respectively (p = 0.1955). A statistically significant survival benefit was observed in patients who received monotheraphy with R (mOS: 6 months) compared to the T group (mOS: 4.2 months) (p = 0.0332). In the same cohort, a median progression-free survival (mPFS) benefit was demonstrated in favour of the R/T group (11.3 months) vs. 9 months of the reverse sequence (p = 0.4004). In the no-rechallenge cohort, the mOS was statistically longer in the R/T sequence than in the T/R sequence (16.2 months vs. 12.3 months, respectively; p = 0.0014). In terms of the mPFS, we saw the same significant result for the adoption of R/T treatment (11.5 months vs. 8.4 months, respectively; p < 0.0001). The two monotherapy groups did not reveal any significant differences. Conclusions: This study suggests that rechallenge therapy may improve survival rates in the third-line treatment of mCRC, particularly if it is administered before sequential R/T treatment. This could allow for the extension of mCRC treatment choices until prospective studies are finished or randomised trials are performed.

In this Symposium we link different perspectives and traditions of research on language and concepts in the cognitive sciences to better understand the process of abstraction from the social-interactive standpoint. In contrast to the usual benefits of abstraction – such as the ability to categorize and generalize – we underscore the possibility of abstract concepts and words to remain underspecified, “open to the context, the suggestions of others” (Borghi, 2023) or to processes of real-time negotiations (Christiansen & Chater, 2022). This is enabled by their largely non-perceptual rela-tional character (Gentner, 2005) and by the fact that they arise in cognitive systems continually embedded and active in their environments (Cisek 1999; Mannella & Tummolini 2023).

Are abstract sentences associated with specific constructs in dialogue, i.e., higher uncertainty, more curiosity and willingness to continue a conversation, and more causal questions? In three preregistered experiments we address these questions asking participants to evaluate the plausibility of linguistic exchanges referred to concrete and abstract concepts. Results support theories proposing that abstract concepts involve more inner monitoring and social dynamics compared to concrete concepts, and suggest that reaching alignment in dialogue is more effortful with abstract than with concrete concepts.

Contrasting the climate change emergency represents one of the major challenges of modern times. Knowing how people represent ecology-related phenomena is crucial to inform interventions aimed at promoting more effective pro-environmental behaviors. Despite this, literature on the topic is still scarce. To fill this gap, we asked 340 participants to rate 200 concepts—among which Ecological (N = 50, e.g., deforestation)—on numerous semantic dimensions (N = 39), drawing insights from the literature on conceptual organization. A Principal Component Analysis on our dataset revealed the presence of three major components explaining overall the variability of our set of concepts. Interestingly, Ecological concepts had a major role in all of them. Indeed, when compared to other conceptual categories—both related (i.e., Natural—e.g., water—and Geographical/Geopolitical—e.g., ocean, city) and not related (i.e., Technological—e.g., Internet) to the green domain—they figured among the most abstract (Component 1), impacting our political, social, and personal spheres (Component 2), scientific, emotionally charged, and evoking sensorimotor experiences (Component 3) concepts. Overall, our study has a threefold relevance. On a theoretical side, it can contribute to enriching theories on concepts by investigating a new semantic domain that jeopardizes the concrete-abstract dichotomy; on a scientific side, it might broaden categorization research by providing semantic norms for new conceptual domains (the TECo Database); on a societal side, it can enhance politics on these timely themes.

This study investigates vocal congruence across populations with different gender identities. Forty-four participants completed a self-voice perception task in three conditions (Silent Reading, Reading Aloud, and Listening to their recorded voice) after reading gender-stereotyped priming texts. Our findings show that transgender and gender non-conforming participants experience lower vocal congruence listening to their outer voice compared to cisgender participants, and they perceive their inner voice as more congruent to the self. Results confirm the role of interoceptive sensibility on general voice congruence perception, suggesting that it varies across gender identities. Further research is needed to deepen the relationship between inner experience and voice perception and to disentangle the reciprocal relationship between self-identity and self-voice perception.

Technological progress is increasing rapidly, and keeping up is particularly challenging for older adults. Thus, adapting technological innovations to human needs has become urgent. The first step toward this aim is to understand how people conceptualize technology. Here, we asked 54 younger and 54 older adults to perform a Go/No-Go, a rating, and a feature generation task to investigate the processing and representation of Technological concepts (e.g., “Internet”) compared to Abstract (e.g., “logic”) and Concrete concepts (e.g., “bottle”). Younger adults showed an elaboration advantage for Technological upon Abstract and Concrete concepts. Technological concepts exhibited a hybrid character, but in older adults, they had a more abstract characterization. Finally, the semantic knowledge associated with Technology was differently organized in content across generations and less structurally robust in older adults. Overall, our results highlight how concepts flexibly change across life and can help societal policies to increase awareness in technology-use across generations.

Peritoneal metastases (PM) are the spread of tumor forms into the peritoneum as metastases from another organ. PM is a frequent condition in metastatic gastrointestinal cancer (colorectal, gastric, pancreatic, appendiceal, and cholangiocarcinoma); their presence confers a poor prognosis, reducing patient survival. The standard treatment consists of systemic chemotherapy according to current guidelines. In recent years, scientific evidence has shown how combined cytoreductive surgery (CRS) techniques followed by hyperthermic intraperitoneal chemotherapy (HIPEC) can improve survival in this patient population. Despite the results still obtained, using this combined technique is still under discussion. This review aims to highlight the benefits and limitations of this combined procedure, which is already widely used to treat peritoneal metastases in gynecological tumors.

There are growing demands to proactively support students with disabilities in postsecondary education. This article examines a mixed-methods study with accessibility consultants and other faculty in a community college pilot program focussed on redesigning courses to increase inclusiveness. Findings highlight the successful and well-received role of the accessibility consultants collaborating in redesign triads. Challenges experienced by accessibility consultants are also discussed, for example, around time allocation for this type of work along with their daily support of students. Recommendations for accessibility consultants involvement in expanding inclusive course redesigns are made, such as, including them more in the process of curriculum design and ensuring appropriate time for their participation.

BackgroundRheumatological toxicity associated with immunotherapy, particularly Sjögren’s syndrome (SjS), has been observed with variable incidence in patients treated with immune checkpoint inhibitors (ICIs). Although SjS is a well-known autoimmune disease, its occurrence as an immune-related adverse event (irAE) during cancer treatment is less well understood. Current literature documents a range of incidence rates and clinical manifestations of SjS in patients undergoing ICI therapy, highlighting the need for early diagnosis and multidisciplinary management.Case presentationA 40-year-old woman underwent mammography, which revealed a 43 mm mass in the left breast. Core biopsy confirmed grade 3 infiltrating triple negative ductal carcinoma with high MIB-1. She received neoadjuvant chemotherapy, followed by surgery and radiotherapy. A CT scan in September 2022 showed lung nodules and lymph node involvement. A lung biopsy confirmed breast cancer metastasis. She started treatment with atezolizumab and nab-paclitaxel with evidence of a partial response. Nab-paclitaxel was discontinued due to side effects and atezolizumab was continued as maintenance therapy. After four cycles, the patient developed symptoms consistent with Sjögren’s syndrome (SjS), which were confirmed by diagnostic tests. Treatment with prednisone, pilocarpine and hydroxychloroquine was initiated alongside ongoing immunotherapy. The patient continues to receive atezolizumab with stable disease and good quality of life.ConclusionThis case highlights the importance of recognizing SjS as a potential irAE in patients treated with ICIs, particularly those with TNBC. Multidisciplinary collaboration is essential for the prompt diagnosis and effective management of SjS to maintain both cancer control and patient quality of life. Given the recent emergence of these events and the lack of specific guidelines, our case report may provide valuable insights into the management of a little-known adverse event and pave the way for further real-world data collection on the management of these rare but significant toxicities that impact on patient quality of life. Further research is needed to optimize treatment protocols and outcomes for patients experiencing rheumatological irAEs during cancer immunotherapy.

Immunotherapy is increasingly used in advanced non-small-cell lung cancer (NSCLC), offering a significant anti-tumor response, as well as causing rising immune-related adverse effects. The incidence of immune checkpoint inhibitor-induced myocarditis–myositis–myasthenia gravis is increasing and particularly concerning due to its high mortality rate. Prompt recognition, diagnosis, and management are crucial. A 40-year-old patient, diagnosed with stage IV non-oncogene addicted lung adenocarcinoma, with nivolumab–ipilimumab–chemotherapy as first-line treatment, developed a rare myocarditis–myositis–myasthenia gravis overlap syndrome. Following the treatment, the patient presented with flu-like symptoms and chest pain and subsequently transferred to the cardiac intensive care unit. The physical examination revealed a visual acuity deficit, diplopia, ophthalmoparesis, ptosis, mydriasis, dysphagia, dyspnea, headache, nausea, dry mouth, asthenia, myalgia, and muscle weakness. Imaging and laboratory tests confirmed the triad, showing an elevation of hs-cTnI and CK and positive results for anti-SAE1 and anti-PL-7 Abs. ECG revealed ST segment elevation and RBBB. The echo showed hyperechogenicity of the inferolateral wall, pericardial detachment, and thickening. The cardiac MRI demonstrated hypokinesia, edema, subepicardial LGE, and pericardial effusion. Muscle biopsy revealed muscle fiber necrosis and regeneration with B and T lymphocytic endomysial inflammatory infiltrate and expression of MHC-I. Treatment with oral prednisone, pyridostigmine, and IV Igs was started due to poor clinical response followed by methylprednisolone. Despite stopping immunotherapy, the patient continued to benefit from it, as highlighted on subsequent re-evaluation CT scans by partial disease response, and as the patient was in complete remission, we decided to resume chemotherapy by omitting immunotherapy. At the radiological control following the four cycles of double CHT and during CHT maintenance, there was a further reduction of the disease. This report aims to raise awareness among physicians about these serious side effects. A multidisciplinary approach led to clinical improvement and early intervention, optimizing patient outcomes.

α -1 antitrypsin (A1AT) is a 52 kDa acute-phase glycoprotein belonging to the serine protease inhibitor superfamily (SERPIN). It is primarily synthesized by hepatocytes and to a lesser extent by monocytes, macrophages, intestinal epithelial cells, and bronchial epithelial cells. A1AT is encoded by SERPINA1 locus, also known as PI locus, highly polymorphic with at least 100 allelic variants described and responsible for different A1AT serum levels and function. A1AT inhibits a variety of serine proteinases, but its main target is represented by Neutrophil Elastase (NE). However, recent attention has been directed towards its immune-regulatory and homeostatic activities. A1AT exerts immune-regulatory effects on different cell types involved in innate and adaptive immunity. Additionally, it plays a role in metal and lipid metabolism, contributing to homeostasis. An adequate comprehension of these mechanisms could support the use of A1AT augmentation therapy in many disorders characterized by a chronic immune response. The aim of this review is to provide an up-to-date understanding of the molecular mechanisms and regulatory pathways responsible for immune-regulatory and homeostatic activities of A1AT. This knowledge aims to support the use of A1AT in therapeutic applications. Furthermore, the review summarizes the current state of knowledge regarding the application of A1AT in clinical and laboratory settings human and animal models.

Using the framework of an investigation of the stimuli-responsive behavior of peptide assembly on a solid surface, this study on the behavior of a chemisorbed peptide on a gold surface was performed. The studied peptide is a dimeric form of the antimicrobial peptide Trichogin GAIV, which was also modified by substituting the glycine with lysine residues, while the N-terminus octanoyl group was replaced by a lipoic one that was able to bind to the gold surface. In this way, a chemically linked peptide assembly that is pH-responsive was obtained because of the protonation/deprotonation of the sidechains of the Lys residues. Information about the effect of protonation/deprotonation equilibria switching the pH from acid (pH = 3) to basic (pH = 11) conditions was obtained macroscopically by performing Quartz crystal microbalance with dissipation monitoring (QCM-D), Surface Plasmon Resonance (SPR), Nanoplasmonic Sensing (NPS), and FTIR techniques. Using molecular dynamics (MD) simulations, it is possible to explain, at the molecular level, our main experimental results: (1) pH changes induce a squeezing behavior in the system, consisting in thickness and mass variations in the peptide layer, which are mainly due to the pH-driven hydrophilic/hydrophobic character of the lysine residues, and (2) the observed hysteresis is due to small conformational rearrangements from helix to beta sheets occurring mainly on the first half of the peptide, closer to the surface, while the second half remains almost unaffected. The latter result, together with the evidence that the layer thickness is not simply double the assembly of the monomeric analog, indicates that the dimeric peptide does not behave as a double monomer, but assumes very peculiar features.

Mycotoxins, specifically aflatoxin B1 (AFB1), ochratoxin A (OTA), trichothecenes (TCNs), and patulin, are a group of secondary metabolites that can contaminate food, leading to severe health implications for humans. Their detection and analysis within forensic toxicology are crucial, particularly as they can be implicated in cases of poisoning, foodborne illnesses, or lethal chronic exposure. However, little is known about the application that mycotoxins could have in forensic investigations and especially about the possibility of extracting and quantifying these molecules on tissues or post-mortem fluids collected at autopsy. We propose a review of the scientific literature on autopsy case studies in which the presence of mycotoxins on cadavers in cases of acute and chronic exposure has been investigated and identified. This review demonstrates how the analysis of mycotoxins on cadavers could be fundamental in the study of mushroom poisonings or even in the investigation of the chronic effects of mycotoxins on the human organism, by virtue of the known carcinogenic and mutagenic effects of many of them. This paper aims to explore the multifaceted role of mycotoxins within forensic sciences, focusing on their detection methods, implications in criminal contexts, and their potential as forensic evidence, thereby underscoring the critical importance they could assume in post-mortem toxicology, public health prevention, and forensic investigations.

Investigating how people represent the natural environment and abstract it into geographical (e.g., mountain) and geopolitical (e.g., city) categories is pivotal to comprehending how they move and interact with the places they inhabit. Yet, the conceptualization of geographical and geopolitical domains has received scant attention so far. To deal with that, we reviewed 50 articles tackling this topic. Most studies have focused on assessing the universality of these concepts—especially geographical ones—mainly using free-listing and ethnophysiographic methods. Current perspectives tend to favor a non-universalistic characterization of these kinds of concepts, emphasizing their high cross-linguistic and cross-cultural variability, especially when compared to other semantic domains. Since geographical and geopolitical features are not pre-segmented by nature, the role of categories imposed by humans is crucial for these concepts. Significantly, their variability does not only depend on “cross” differences: evidence suggests that the cognitive demand requested by the task, idiosyncratic characteristics of individuals such as expertise level, and the typology of inhabited environments are further factors impacting the conceptual flexibility of these domains. Exploring the factors influencing our understanding of geographical and geopolitical categories can provide valuable insights for instructing effective communication policies to enhance sustainable development and address ecological emergencies, taking into consideration diverse cultural backgrounds within different populations.

Down’s syndrome (DS), or Trisomy 21, represents the most common chromosomal abnormality in live births, characterized by an extra chromosome 21. Children affected by Down’s syndrome are more susceptible to the development of obesity and of becoming overweight compared with other children. Furthermore, they seem to present a more unfavorable lipid profile than the non-DS obese pediatric population. Diet and physical activity are closely related to the development of overweight and obesity, and they can be assessed using questionnaires such as the Mediterranean Diet Quality Index in children and adolescents (KIDMED) and the Godin–Shephard Leisure-Time Physical Activity Questionnaire. This review aims to undertake a comprehensive analysis of the intricate interplay between diet and physical activity in children affected by Down’s syndrome. Specifically, it seeks to deepen understanding regarding the question of how diet and exercise can influence and prevent the development of overweight and obesity in that special pediatric population.

A penetrating thoracic aorta injury (PTAI) is a life-threatening condition with significant morbidity and mortality, often resulting from several traumatic mechanisms. Among these, gunshot wounds leading to aortic injury are exceedingly rare and pose unique challenges in terms of diagnosis, management, and surgical intervention. We present a case of a 47-year-old male victim of a gunshot wound resulting in penetrating chest trauma and a descending thoracic aorta injury. This report outlines the sequential management involving thoracic endovascular aortic repair (TEVAR), followed by surgical intervention for hematoma drainage and foreign body removal, highlighting the interdisciplinary approach required in managing complex cardiothoracic injuries.