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In this article, we present the results of the research carried out at the Gravettian occupation level of Cueva del Arco (Spain). For this purpose, a multidisciplinary investigation has been carried out in which all the elements recovered in the excavations carried out since 2015 at this site have been studied. The results are contextualised alongside all of the existing Gravettian sites in Mediterranean Iberia. The study of the material culture, the fauna, the landscape, and the dating has allowed us to approach the occupations of the site from many perspectives and has permitted us to conclude that Cueva del Arco was occupied sporadically at the beginning of the Gravettian period by a small human group in what would be the beginning of the consolidation of the anatomically modern humans (AMH) in this territory. Furthermore, these occupations were preceded by others belonging to the Aurignacian, which left hardly any remains in the cave. The data presented in this article lead us to believe that Cueva del Arco is a site of great importance for the knowledge of the beginning of the AMH settlement in the Iberian Mediterranean, both in its expansion towards the south and in its definitive consolidation in this territory.

Abstract Mycoplasma hominis can be a part of human urogenital tract microbiome, and it is a frequent cause of urogenital infections. In rare cases, it can also cause extragenital infections, especially in immunocompromised patients. In this case series, we report two cases and provide a literature review of extragenital infections caused by M. hominis in patients with hypogammaglobulinemia. Patient 1 was a 61-year-old woman with diffuse large B-cell lymphoma who, after rituximab-containing chemotherapy and CAR-T therapy, developed M. hominis spondylodiscitis. Patient 2 was a 50-year-old woman with congenital hypogammaglobulinemia who developed disseminated M. hominis infection involving pleura, muscles, and right ankle. Antibiotic therapy with levofloxacin and doxycycline for 10 weeks in patient 1 and with levofloxacin alone for 6 weeks in patient 2 led to infection resolution. The literature review identified 14 additional cases reporting M. hominis extragenital infection in patients with hypogammaglobulinemia. M. hominis should also be suspected as an etiological agent of extragenital infection in patients with B-cell immunodeficiency with a clinical picture of persistent, standard-culture negative infection, particularly with arthritis or abscess formation. Even if M. hominis can grow on standard bacterial medium, in suspected cases molecular methods should be promptly used for correct diagnostic work-up and successful therapy.

The poultry industry stands as a cornerstone in securing global food stability, both in the present and foreseeable future. To continue to uphold this critical role, the exploration of innovative, low-input feed sources is imperative. Hemp emerges as a promising candidate, offering locally sourced ingredients that not only reduce feed costs but also maintain high nutritional standards for livestock. This study delved into the utilisation of whole hemp seeds in the diet of 100 Naked-neck Kabir chicks that were divided randomly into two dietary groups, one fed a control diet (CTRL) and one fed a diet deprived of soybean meal with 10% inclusion of Carmagnola hemp seeds (HEMP). Birds were slaughtered at 81 days of age. Physicochemical characteristics of breast, thigh, and liver, besides the antioxidant content and the lipid oxidative status, were investigated. The HEMP birds exhibited higher daily weight gain and final live weight compared to the CTRL group. Results revealed improvements in the fatty acid profiles and antioxidant content in the HEMP group, leading to good levels of key nutrients such as α-tocopherol, retinol, and n-3 polyunsaturated fatty acids. These findings underscore the potential of hemp seeds as a feed ingredient, standing poised as a sustainable ally in fortifying the poultry productive chain.

Despite ongoing efforts by different levels of government, barriers still exist for diverse communities in Australia when it comes to accessing culturally and linguistically appropriate social services. These barriers have detrimental effects on the sense of belonging and social inclusion of migrants, as highlighted by recent events such as the COVID-19 pandemic and natural disasters. In rural and regional areas, where access to resources and support can already be limited, these issues are particularly pronounced during crisis situations. Non-professional interpreters and translators have played a crucial role in facilitating effective communication in these circumstances, as they are often trusted members of their communities and understand their needs. However, relying on volunteers to provide multilingual communication in times of crisis is neither equitable nor sustainable. In response to this issue, the IMPARO pilot project has been implemented in the regional hub of Shepparton, Victoria, with the aim of providing training and professional development opportunities for non-certified community interpreters and translators. This project utilises principles of co-design and participatory initiatives to foster relationships and associations that promote inclusive practices and solidarity. Using action research and digital platforms, the project ensures equitable access to resources for its participants, who not only strive for professional certification and improved employability but also recognise the value of building intercultural networks of solidarity as a solid foundation to promote sustainable forms of knowledge sharing among diverse communities.

Allostery is an important property of biological macromolecules which regulates diverse biological functions such as catalysis, signal transduction, transport, and molecular recognition. However, the concept was expressed using two different definitions by J. Monod and, over time, more have been added by different authors, making it fuzzy. Here, we reviewed the different meanings of allostery in the current literature and found that it has been used to indicate that the function of a protein is regulated by heterotropic ligands, and/or that the binding of ligands and substrates presents homotropic positive or negative cooperativity, whatever the hypothesized or demonstrated reaction mechanism might be. Thus, proteins defined to be allosteric include not only those that obey the two‐state concerted model, but also those that obey different reaction mechanisms such as ligand‐induced fit, possibly coupled to sequential structure changes, and ligand‐linked dissociation‐association. Since each reaction mechanism requires its own mathematical description and is defined by it, there are many possible ‘allosteries’. This lack of clarity is made even fuzzier by the fact that the reaction mechanism is often assigned imprecisely and/or implicitly in the absence of the necessary experimental evidence. In this review, we examine a list of proteins that have been defined to be allosteric and attempt to assign a reaction mechanism to as many as possible.

Abstract Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.

ABSTRACT: The optimization of animal welfare, meat quality, environmental impact, and economic sustainability in alternative poultry farming can be achieved by modulating several productive factors and improving the synergy between the chicken genotype and the outdoor environment. The objective of the study was to characterize 4 slow-growing chicken genotypes reared in free range conditions. Eight hundred chickens (SGs; 25 chickens/replicates/genotype/enrichment) belonging to the following genotypes, Red JA57 (RJ), Naked Neck (NN), Lohmann Dual meat-type (LD), and an Italian crossbreed (Robusta Maculata x Sasso, CB). were utilised and slaughtered at 81 d: The grazing areas were alternatively provided with enrichment constituted by strips of sorghum plants (ENR) or only grass (NO ENR). Productive performance (daily weight gain, daily feed intake, feed conversion ratio, live weight) were recorded weekly. Behaviour observations (walking and grass pecking), carcass and meat quality of breast and drumstick were also assessed in 15 chickens/replicate/genotypes/enrichment. Results demonstrated that both LD and CB showed the highest walking activity, but the different strains were differently capable of using the foraging resources (eating grass). The better productive performance was recorded in RJ followed by NN, CB and LD. In LD and CB, the different walking activities also affected the physico-chemical profiles (lower pHu, WHC, and lipids) of the breast and drumstick. The oxidative status was worse in CB than in the other groups (lower tocols, higher carbonyls), in both meat cuts. Fatty acid profile was also related to the genetic strain: a higher amount of n-3 polyunsaturated fatty acids was recorded both in the breast and drumstick of RJ and NN. The Healthy Fatty Index resulted excellent in all the chicken genotypes. In conclusion, the environment/animal interaction resulted as an important factor affecting the adaptability of genotypes to an extensive rearing system. All four genotypes, to different extents, showed good adaptability and production performance, with the exception of LD and CB, which were too light for the commercial supply chain requirements.

In the mammalian neocortex, inhibition is important for dynamically balancing excitation and shaping the response properties of cells and circuits. The various computational functions of inhibition are thought to be mediated by different inhibitory neuron types, of which a large diversity exists in several species. Current understanding of the function and connectivity of distinct inhibitory neuron types has mainly derived from studies in transgenic mice. However, it is unknown whether knowledge gained from mouse studies applies to the non-human primate, the model system closest to humans. The lack of viral tools to selectively access inhibitory neuron types has been a major impediment to studying their function in the primate. Here, we have thoroughly validated and characterized several recently developed viral vectors designed to restrict transgene expression to GABAergic cells or their parvalbumin (PV) subtype, and identified two types that show high specificity and efficiency in marmoset V1. We show that in marmoset V1, AAV-h56D induces transgene expression in GABAergic cells with up to 91–94% specificity and 79% efficiency, but this depends on viral serotype and cortical layer. AAV-PHP.eB-S5E2 induces transgene expression in PV cells across all cortical layers with up to 98% specificity and 86–90% efficiency, depending on layer. Thus, these viral vectors are promising tools for studying GABA and PV cell function and connectivity in the primate cortex.

Abstract CAR− CD4+ T cell lymphopenia is an emerging issue following CAR‐T cell therapy. We analyzed the determinants of CD4+ T cell recovery and a possible association with survival in 31 consecutive patients treated with commercial CAR‐T for diffuse large B‐cell (DLBCL) or mantle cell lymphoma. Circulating immune subpopulations were characterized through multiparametric‐flow cytometry. Six‐month cumulative incidence of CAR− CD4+ T cell recovery (≥200 cells/μL) was 0.43 (95% confidence interval [CI]: 0.28–0.65). Among possible determinants of CD4+ T cell recovery, we recognized infusion of a 4‐1BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene/brexucabtagene, AXI/BRX) (hazard ratio [HR] [95% CI]: 5.79 [1.16–24.12] p = 0.016). Higher CD4+ T cell counts resulted with TSA at month‐1, ‐2 and ‐3. Moderate‐to‐severe infections were registered with prolonged CD4+ T cell lymphopenia. Early, month‐1 CD4+ T cell recovery was associated with a worse outcome in the DLBCL cohort, upheld in a multivariate regression model for overall survival (HR: 4.46 [95% CI: 1.12–17.71], p = 0.03). We conclude that a faster CAR− CD4+ T cell recovery is associated with TSA as compared to AXI/BRX. Month‐1 CAR− CD4+ T cell subset recovery could represent a “red flag” for CAR‐T cell therapy failure in DLBCL patients.

Abstract Optogenetics has transformed studies of neural circuit function, but remains challenging to apply to non-human primates (NHPs). A major challenge is delivering intense, spatiotemporally-precise, patterned photostimulation across large volumes in deep tissue. Such stimulation is critical, for example, to modulate selectively deep-layer corticocortical feedback circuits. To address this need, we have developed the Utah Optrode Array (UOA), a 10×10 glass needle waveguide array fabricated atop a novel opaque optical interposer, and bonded to an electrically addressable µLED array. In vivo experiments with the UOA demonstrated large-scale, spatiotemporally precise, activation of deep circuits in NHP cortex. Specifically, the UOA permitted both focal (confined to single layers/columns), and widespread (multiple layers/columns) optogenetic activation of deep layer neurons, as assessed with multi-channel laminar electrode arrays, simply by varying the number of activated µLEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.

Introduction: In performance-based approaches and quality assessment protocols used both in the technological design of architecture and the environmental design of the built habitat, the concept of psycho-physical wellbeing is usually defined in purely quantitative human-techno-centric or eco-techno-centric terms. However, in socio-technical-environmental realities in continuous transition, wellbeing extends to areas that cannot be confined within the notions of comfort or healthiness because it involves material and immaterial, cultural and technical, aesthetic and performative, real and virtual aspects.Method: The aim of this article emerges from studies being conducted as part of Ex-Mind research. The working hypothesis is to broaden performance-based approaches in a technological-environmental sense to avoid reducing the goal of psycho-physical wellbeing just to the compliance with technical-constructive aspects. It could be possible combining the material and quantifiable dimensions with other aspects that extend the project to sensorial, perceptive, and emotional interactions. Important theoretical-scientific evidence is already emerging on this dichotomy to be overcome from areas of project evaluation responsive to the new paradigms of sustainability such as resilience, inclusive placemaking, and wellbeing according to the flourish model. Characteristics such as dimensions, proportions, shapes, colors, scents and immaterial aspects of spaces, for example, should be evaluated with respect to the complex physical and mental comfort conditions that they can produce.Results: In the technological-environmental vision of the human habitat project, the objective of psycho-physical wellbeing should be a function of the dynamic balance between the constantly evolving users’/inhabitants’ needs and the variability of context factors and agents. The concept of wellbeing therefore takes on a scalar and expanded declination. Considering the technological-environmental approach, a possible element of originality emerges in the integrated and balanced human-environmental centered vision aimed at broadening the framework of the qualitative-quantitative references of the project of the human habitat. This could be an alternative bio-psycho-socio-technological methodological vision starting from the determinants of wellbeing in a broad sense, including natural, cultural and socioeconomic environmental factors, social and collective networks of relationships and participation, individual behavioral, physical, and functional factors of people. Added to these determinants are the different technological-environmental interface systems with which the project is able to define, in a bio-psycho-socio-technological sense, multiple and variable regulatory conditions of wellbeing, at a building, urban, and territorial level.Discussion: The possible outcomes of this alternative and integrated hypothesis are related to the reconnection with the production and regeneration processes of the built material, to the reorganization and reinvention of spatial and perceptual relationships between individuals, communities, technologies, environment, and to the integration of non-directly quantifiable subjective variables into the design of the built environment. The proposed integrated bio-psycho-socio-technological vision may open for developments concerning the expansion of the determinants of psycho-physical wellbeing through new performative descriptors and the definition of agile tools, procedures, and metrics to integrate wellbeing assessments, including consensus-based approaches.

Recent political upheavals, such as Brexit, Trump's election, the rise of challenger parties in Europe, and Italy’s first "populist" government in 2018, challenge traditional theories of voting behaviour and party competition. Conventional explanations often point to populism and voter irrationality. However, recent research highlights that challenger parties leverage issue opportunities that transcend traditional ideological boundaries, suggesting a de-ideologized context where voters are drawn to post-ideological platforms. Despite these insights, a possible de-ideologization process remains insufficiently understood. The POSTGEN project seeks to fill this gap by analysing de-ideologization mechanisms and dynamics, particularly in Italy—a key case of contemporary political transformation. It adopts a generation-focused approach, emphasizing the role of younger generations in the evolving political landscape. The project examines how political attitudes develop and impact individuals, generations, and society over time. It investigates whether political issues integrate into coherent ideological structures or remain fragmented, and how non-political influencers affect these dynamics amid the crisis of traditional epistemic authorities. The project employs a mixed-method, multi-method, longitudinal strategy that features multiple components: from mass surveys, to social media content (also analysed through automated methods), to dedicated surveys aimed at secondary-school students, to qualitative in-depth interviews to young adults. By integrating these methods within a robust theoretical framework, POSTGEN aims to provide insights into the evolution of the Italian political systems, also to help understand broader changes in democratic representation in Western political systems.

Abstract Background The COVID-19 pandemic has ravaged many countries worldwide since December 2019. The high infection rates, and the need for health care assistance for individuals with comorbidities, strained the national health care systems around the world. Outbreak peaks increased the burden on hospitals that where perceived as high-risk places by people, who often decided to cancel or defer hospital visits. Thus, Italian Local Health Authorities had to develop new organizational models to meet the increased health care needs of the population. The aim of this study is to assess the impact of strengthened community health services on the hospital burden. Methods We analysed the number of Emergency Department access at the Hospital De Lellis covered by the Local Health Authority in Rieti, from March 2020 to November 2021. We then assessed the effects of community health services: the Special District Continuing Care Units (SDCUs) and the the COVID hub, on the COVID-19-related ED access, admission and mortality rates. A Chi-squared test for trend and three multivariable logistic regression models were used to investigate the trends and the possible predictors of COVID ED access, COVID hospital admissions, and deaths. Results Being male (OR = 1.41, CI95% 1.05–1.90; p = 0.022) and older age (OR = 1.03, CI95% 1.02–1.04; p

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) predominantly occurs in adults ≥60 years old; 10–20% of cases are pediatric or adolescent/young adult (AYA) patients. Tagraxofusp (TAG, Elzonris®) is the only approved treatment for BPDCN; in the United States it is approved for patients aged ≥2 years. Data on treating pediatric and AYA BPDCN patients are limited. We present a case series of pediatric and AYA patients with BPDCN treated with TAG. Eight patients (five newly diagnosed; three relapsed/refractory [R/R]), aged 2–21 years, received 12 mcg/kg TAG. Seven patients were female; most had skin (n = 6) and/or bone marrow (n = 4) involvement. No new safety signals were identified. Grade 3 adverse events were headache (n = 1) and transaminitis (n = 2). Three patients with newly diagnosed BPDCN achieved complete response, one achieved partial response, and one had stable disease (SD). One patient with R/R BPDCN achieved a minor response; one had SD. Seven patients (88%) were bridged to stem cell transplant: 80% of newly diagnosed patients and 100% of R/R patients. Five patients remained alive at last follow‐up. These cases highlight the efficacy and safety of TAG in pediatric and AYA patients for whom there is no other approved BPDCN therapy.

One of the most relevant physiological parameters in dogs is respiratory rate (RR). The aim of this paper is to present a novel wearable system that allows to accurately estimate RR in dogs, and to compare it to a gold standard in static conditions. Data from 12 dogs were acquired while the animals were anesthetized and attached to a vital signs monitor. The experimental setup consisted of three Inertial Measurement Units (IMUs) applied on the dog, and a video camera filming the RR value shown on the monitor. The range of RR values analyzed in the study is 0 to 29 breaths per minute, read by the vital signs monitor. The mean RMSE for the data acquisitions is 1.68 breaths per minute. The values of the filtering parameters that allow to obtain the best performance depend on the specific acquisition. This result demonstrates that adaptive filtering is a viable method for the application. Future developments include tests on a larger dataset, and trials on dogs in unconstrained environments and during movement.

Abstract Commercial laying hens have high frequency of damage to the keel bone (KB), which causes negative effects on health and welfare. KB damage may consist in fractures (KBF) and deviations (KBD). The aim of the present study was to compare the KB shape, by means of Geometric Morphometric, and the occurrence of fractures in different chicken genotypes reared either free-range (FR) or in enriched cages. Moreover, the relationship between KB shape, genotype and rearing system was analysed. Sixty birds/genotype (2 Italian local breeds, Bionda Piemontese and Robusta Maculata, their crossbreeds with Sasso and Lohmann Brown) were used. All the hens fed the same commercial feed throughout the trial. Body weight, egg production, feed intake and mortality were recorded from 25 to 66 weeks of age. Ca intake (IN) and output (OUT) were estimated and Ca OUT/IN was calculated. FR affected the occurrence of KB deviations but not the shape, whereas the fractures were mainly affected by genotype. Local breeds had a lower prevalence of KBF with similar level of KBD but with different shapes. Crossbreeds seemed to be a suitable compromise between egg deposition rate and occurrence of KB damages.