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Abstract Background In addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors. Methods In a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague–Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration. Results Both doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP. Conclusions The findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine.

Following the approach already employed in an earlier article on Archibald Joseph Cronin1, physician, and writer, this paper focuses on William Somerset Maugham, another physician who successfully ventured into literature, producing many plays, novels, and short stories adapted to the screen (cinema and TV), herein chronologically listed and described.

Background: Heart failure significantly impacts healthcare systems and society, affecting quality of life (QoL) due to its symptoms and continuous care needs. Nurses are crucial in managing heart failure, supporting both patients and caregivers who face physical, emotional, social, and spiritual challenges. The Family Caregiver Quality of Life (FAMQOL) scale evaluates caregivers’ QoL across all dimensions. This study aims to translate and culturally adapt the FAMQOL from English to Italian, enhancing its utility in nursing research and practice to better identify and support caregiver well-being. Methods: Following EORTC guidelines (2017), the FAMQOL underwent linguistic validation and cultural adaptation. This included independent forward translations from English to Italian, back translations, and reconciliation discussions to produce a testable translation. A pilot test with 15 caregivers assessed the questionnaire’s acceptability and comprehensibility. Results: Linguistic adjustments ensured the questionnaire’s understandability in Italian. Interviews confirmed its acceptability and comprehensibility, with minor modifications enhancing clarity. Conclusions: The translation process successfully adapted the FAMQOL for Italian caregivers. This tool is essential for nursing research and practice, providing a culturally relevant assessment of the burden of care. It allows targeted interventions to support health workers, intercepting the QoL of caregivers early and, consequently, the well-being of patients with heart failure.

The basolateral amygdala (BLA) is a key site where fear learning takes place through synaptic plasticity. Rodent research shows prominent low theta (~3–6 Hz), high theta (~6–12 Hz), and gamma (>30 Hz) rhythms in the BLA local field potential recordings. However, it is not understood what role these rhythms play in supporting the plasticity. Here, we create a biophysically detailed model of the BLA circuit to show that several classes of interneurons (PV, SOM, and VIP) in the BLA can be critically involved in producing the rhythms; these rhythms promote the formation of a dedicated fear circuit shaped through spike-timing-dependent plasticity. Each class of interneurons is necessary for the plasticity. We find that the low theta rhythm is a biomarker of successful fear conditioning. The model makes use of interneurons commonly found in the cortex and, hence, may apply to a wide variety of associative learning situations.

Traditional methods for assessing vine water status, such as the Scholander pressure chamber, are time-consuming, punctual and labour-intensive. The development of alternative methods which are accurate, reliable and can provide real-time information on vine water status is a necessity for farmers all over the world. This study proposes the use of plant electrophysiology as a novel approach for real-time water status assessment in grapevines. We conducted four climate chamber experiments with potted grapevines under different irrigation regimes. Various morphological and physiological assessments were performed in parallel with electrophysiological measurements to correlate classic water status assessment methods with plant electrophysiological signals. Two machine learning approaches based on classification and regression were employed to train the prediction models. Results obtained from both models indicate significant differences in irrigation status between well-watered and water-deficit plants, with the latter showing reduced growth and physiological activity, confirming the water stress status of the plant. While the binary classification model successfully differentiates between well-watered and water-deficit plants, its practical use is limited. Therefore, a regression model was developed to directly predict predawn leaf water potential. To the best of our knowledge, this is the first time that electrical signals are correlated with vine water potential measurements. The findings presented here thus provide a promising new tool for future real-time and remote monitoring of vine water status to manage irrigation and adapt agronomic strategies. Nevertheless, validation and optimisation of the models are still necessary, particularly under field conditions.

Le mouvement bricoleur (maker) connaît une popularité croissante dans les écoles du monde entier, mais la recherche, en particulier en français, est encore à un stade émergent. Cet article propose une revue de la portée des projets bricoleur dans les salles de classe de la 4e à la 8e année (secondaire 2) à l’échelle internationale, qui vise à analyser leurs descriptions, le déroulement, les outils utilisés et les retombées sur les élèves et le personnel enseignant. Sur 1 900 études initialement recensées et 68 articles scientifiques retenus aux fins d’analyse, l’étude définit trois phases principales des projets bricoleur : 1) l’inspiration et la préparation, 2) la mise en œuvre et la réalisation, et 3) la présentation et la recontextualisation, et elle souligne l’équilibre entre les outils numériques et physiques dans les études du corpus. Elle examine aussi les retombées sur les élèves à travers les dimensions affectives, sociales, disciplinaires et métacognitives, ainsi que sur le personnel en ce qui a trait aux dimensions pédagogiques, affectives et sociales. Des exemples de projets bricoleur disciplinaires, interdisciplinaires et transdisciplinaires sont présentés, illustrant l’ampleur et le potentiel du mouvement bricoleur. Ces résultats sont essentiels pour renforcer la formation enseignante, en s’appuyant sur les recommandations issues de recherches récentes, afin de favoriser la conception et l’intégration de projets bricoleur dans les salles de classe.

Background and objectiveAn important barrier to HIV prevention among transgender women (TGW) is the concern that oral pre-exposure prophylaxis (PrEP) negatively affects the efficacy of feminizing hormone therapy (FHT). We aimed to assess the impact of PrEP on FHT pharmacokinetics (PK) among TGW from Brazil.MethodsWe performed a drug-drug interaction sub-study among TGW enrolled in a daily oral PrEP demonstration study (PrEParadas, NCT03220152). Participants had a first PK assessment (PK1) 15 days after FHT (estradiol valerate 2-6 mg plus spironolactone 100-200 mg) initiation and then started PrEP (tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg). A second PK evaluation was performed 12 weeks later (PK2). Blood samples were collected prior and after the directly observed dosing (0, 0.5, 1, 2, 4, 6, 8, and 24 hours). Pharmacokinetic parameters of estradiol, spironolactone, and metabolites were estimated by non-compartmental analysis (Monolix 2021R2, Lixoft®) and compared as geometric mean ratios (GMRs, 90% confidence interval [CI]).ResultsAmong 19 TGW who completed the substudy, median age was 26 years (interquartile range: 23-27.5). Estradiol area under the plasma concentration-time curve (AUCτ) and trough concentrations did not differ between PK1 and PK2 evaluations (GMR [90% CI]: 0.89 [0.76-1.04] and 1.06 [0.94-1.20], respectively). Spironolactone and canrenone AUCτ were statistically lower at PK2 than PK1 (0.76 [0.65-0.89] and 0.85 [0.78-0.94], respectively). Canrenone maximum concentration was also lower at PK2 than PK1 (0.82 [0.74-0.91]).ConclusionEstradiol PK was not influenced by PrEP concomitant use. The small differences observed in some spironolactone and canrenone PK parameters should not prevent the concomitant use of estradiol-based FHT and PrEP.Trial registrationThis trial (NCT03220152) was registered on July 18, 2017.

The article offers a theoretical exploration of one of the infinite potentialities of the monstrous body, a body that appears as deviant, non-conforming, as it escapes the pre-established boundaries of what is deemed as acceptable; it exceeds and in this exceeding it imposes its diversity while imposing a re-vision. These potentialities have been recognised by feminist, posthuman, and in particular trans* and transfeminist literature and theory, and it is the latter that will be here tackled. The trans* body is one of those bodies that are still demonised as monstrous, and it is precisely on account of that perversity to which it is associated, that, in some instances, it has chosen to identify and align with the monster. Embracing monstrosity becomes not only a symbolic but a political act of disidentification that implies embracing otherness with strength and pride: rejecting the impositions of a normative body, acknowledging one’s own multiplicity and opening up to multiplicities; becoming a figure of ‘potent fusions,’ as well as of ‘potent alliances.’

The induced magnetic field is used to control the fluid motion and heat transfer in a variety of applications, such as in MHD devices, microfluidics, electrically conducting fluids in channels and in circular pipes, and clinical applications such as drug delivery and cooling of nuclear reactors. Henceforth this investigation aims to elucidate the behavior of viscoelastic (second-grade fluid) ternary nanofluid flow through a permeable stretching sheet with an induced magnetic field. The stretching surface is subjected to the Cattaneo-Christov heat and mass flux model to investigate heat and mass transfer properties. Solutions of reduced governing equations are obtained numerically via the shooting method and computed using the bvp-4c algorithm. The impacts of diverse active parameters such as porous medium, magnetic parameter, reciprocal magnetic Prandtl parameter, stretching parameter, HSS parameter, and relaxation time parameter for heat and mass flux are studied graphically. In addition, the values of significant engineering factors are calculated and comparative analysis is presented through bar graphs. It is seen that regular heat sink/source promotes thermal distribution and relaxation time for mass flux enhances the mass transfer rate between fluid flow and solid surface.

Summary: Among the side effects of chemotherapy, dysgeusia stands out a disturbance or damage to taste perception that profoundly affects the patient's biopsychosocial well-being. Recognizing and appropriately managing this issue is paramount. This study aims to develop a systematic review protocol for evaluating multidisciplinary strategies aimed at alleviating dysgeusia in chemotherapy-treated patients. The protocol involves a thorough examination of database articles related to dysgeusia, primarily concentrating on the disorder but extending to related topics. The methodology places a strong emphasis on both methodological rigor and the relevance of selected studies. Consistent data extraction is followed by a comprehensive synthesis, providing a holistic perspective. Key objectives of this protocol include analyzing the dysgeusia problem in chemotherapy patients, identifying multidisciplinary strategies to mitigate dysgeusia, determining the most effective interventions for reducing dysgeusia, and recommending a specific assessment tool for this condition.

In order to complement the picture of the atmospheric water cycle in the Southern Ocean, we have continuously monitored water vapor isotopes since January 2020 on Amsterdam Island in the Indian Ocean. We present here the first 2-year long water vapor isotopic record at this site. We show that the water vapor isotopic composition largely follows the water vapor mixing ratio, as expected in marine boundary layers. However, we detect 11 periods of a few days where there is a strong loss of correlation between water vapor δ18O and water vapor mixing ratio as well as abrupt negative excursions of water vapor δ18O. These excursions often occur toward the end of precipitation events. Six of these events show a decrease in gaseous elemental mercury, suggesting subsidence of air from a higher altitude. Our study aims to further explore the mechanism driving these negative excursions in water vapor δ18O. We used two different models to provide a data–model comparison over this 2-year period. While the European Centre Hamburg model (ECHAM6-wiso) at 0.9° was able to reproduce most of the sharp negative water vapor δ18O excursions, hence validating the physics process and isotopic implementation in this model, the Laboratoire de Météorologie Dynamique Zoom model (LMDZ-iso) at 2° (3°) resolution was only able to reproduce seven (one) of the negative excursions, highlighting the possible influence of the model resolution for the study of such abrupt isotopic events. Based on our detailed model–data comparison, we conclude that the most plausible explanations for such isotopic excursions are rain–vapor interactions associated with subsidence at the rear of a precipitation event.

The neurotrophin nerve growth factor (NGF) and its precursor proNGF are both bioactive and exert similar or opposite actions depending on the cell target and its milieu. The balance between NGF and proNGF is crucial for cell and tissue homeostasis and it is considered an indicator of pathological conditions. Proteolytical cleavage of proNGF to the mature form results in different fragments, whose function and/or bioactivity is still unclear. The present study was conducted to investigate the distribution of proNGF fragments derived from endogenous cleavage in brain and peripheral tissues of adult rats in the healthy condition and following inflammatory lipopolysaccharide (LPS) challenge. Different anti‐proNGF antibodies were tested and the presence of short peptides corresponding to the prodomain sequence (pdNGFpep) was identified. Processing of proNGF was found to be tissue‐specific and accumulation of pdNGFpeps was found in inflamed tissues, mainly in testis, intestine and heart, suggesting a possible correlation between organ functions and a response to insults and/or injury. The bioactivity of pdNGFpep was also demonstrated in vitro by using primary hippocampal neurons. Our study supports a biological function for the NGF precursor prodomain and indicates that short peptides from residues 1–60, differing from the 70–110 sequence, induce apoptosis, thereby opening the way for identification of new molecular targets to study pathological conditions.

Abstract Background Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation. Methods All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks.

The presence of the bacteria Bacillus cereus in milk reflects an important concern to dairy products due to its ability to sporulate and to the possibility of the spore resisting the thermal treatment known as UHT (ultra-high temperature), which can cause deterioration of the product. This study aimed to evaluate the presence of B. cereus in pasteurized and UHT milk samples commercialized in Serra Gaúcha, RS. For that, 50 samples of UHT milk and 10 samples of pasteurized milk from markets of Farroupilha, Nova Prata, Vila Flores, and Veranópolis were evaluated. Samples were inoculated with MYP agar, and the presence of B. cereus was confirmed by Gram staining, α-hemolysis test in 5% sheep blood agar, and rhizoid growth. Overall, 8.3% (5/60) of samples were contaminated by B. cereus. Among them, three were UHT milk, and two were pasteurized milk. The presence of B. cereus in samples of pasteurized and UHT milk presents a risk to public health since the bacteria can resist the heat treatment processes of the plants that produce the milk for consumption and cause foodborne illness outbreaks.

The geometric configuration, particularly the inner tube diameter, plays a significant role in the thermal performance of pulsating heat pipes (PHPs). Previous experimental research has demonstrated that single-loop triple-diameter PHPs (TD-PHPs) outperform single-loop single-diameter PHPs (SD-PHPs) and dual-diameter PHPs (DD-PHPs) in terms of thermal performance under moderate heating input powers ranging from 25 W to 75 W. However, a reduction in heat input from 75 W to 25 W leads to a diminished impact of TD-PHPs on the thermal performance. Therefore, to improve the overall performance of TD-PHPs, this study used two-dimensional transient computational fluid dynamics simulations to identify the optimal inner tube diameters for TD-PHPs at a low heat input by evaluating the thermal resistance of five TD-PHPs with various inner diameters. The findings reveal that the TD-PHP configuration exhibits minimum thermal resistance, with inner diameters of 4.5 mm for the upper arch (the condenser section), 4.0 mm for the wide branch, and 2.5 mm for the narrow branch, primarily due to its full circulation flow pattern. Furthermore, the overall heat transfer performance of the optimal TD-PHP was compared with that of an SD-PHP at low heat inputs (10 and 18 W), indicating that although the optimal TD-PHP shows lower thermal resistance, it does not significantly affect the start-up time.

Introduction: Air pollution from diesel combustion is linked in part to the generation of diesel exhaust particles (DEP). DEP exposure induces various processes, including inflammation and oxidative stress, which ultimately contribute to a decline in lung function. Cyclic AMP (cAMP) signaling is critical for lung homeostasis. The impact of DEP on cAMP signaling is largely unknown.Methods: We exposed human bronchial epithelial (BEAS-2B) cells to DEP for 24–72 h and evaluated mitochondrial bioenergetics, markers of oxidative stress and inflammation and the components of cAMP signaling. Mitochondrial bioenergetics was measured at 72 h to capture the potential and accumulative effects of prolonged DEP exposure on mitochondrial function.Results: DEP profoundly altered mitochondrial morphology and network integrity, reduced both basal and ATP-linked respiration as well as the glycolytic capacity of mitochondria. DEP exposure increased gene expression of oxidative stress and inflammation markers such as interleukin-8 and interleukin-6. DEP significantly affected mRNA levels of exchange protein directly activated by cAMP-1 and -2 (Epac1, Epac2), appeared to increase Epac1 protein, but left phospho-PKA levels unhanged. DEP exposure increased A-kinase anchoring protein 1, β2‐adrenoceptor and prostanoid E receptor subtype 4 mRNA levels. Interestingly, DEP decreased mRNA levels of adenylyl cyclase 9 and reduced cAMP levels stimulated by forskolin (AC activator), fenoterol (β2-AR agonist) or PGE2 (EPR agonist).Discussion: Our findings suggest that DEP induces mitochondrial dysfunction, a process accompanied by oxidative stress and inflammation, and broadly dampens cAMP signaling. These epithelial responses may contribute to lung dysfunction induced by air pollution exposure.

Background: Enteral nutrition (EN) is preferred when oral feeding is not possible. The use of the Nasogastric Tube (NGT) ensures rapid and low-risk nutrient administration. However, confirming the placement through chest radiography, besides delaying the initiation of nutritional therapy, exposes patients to radiation. The pH test of gastric aspirate provides a quicker check for NGT placement, but its reliability is compromised by challenges related to aspirating gastric secretions. Study objective: The main objective of this study is to assess the high-performance placement of NGTs for nutritional purposes, optimizing the evaluation of correct insertion through pH testing using an electronic pH meter. Additionally, the study aims to evaluate patient tolerance to the intervention. Materials and methods: This single-center RCT will include 150 EN candidate patients divided into three groups. Each group will use distinct NGTs, evaluating placement through pH testing and chest radiography for safety. Tolerance, complications related to NGT placement, and costs will be assessed, with data collected anonymously through a secure electronic database. Ethical considerations: authorization no. 3624, Territorial Ethical Committee Lombardy 5, October 20, 2023. Implications and perspectives: This protocol introduces innovative technologies, such as advanced NGTs and an electronic pH meter, aiming to optimize enteral nutrition management. This RCT focuses on replacing X-rays as the primary method for verifying NGT placement, thereby reducing costs, time, and patient exposure to radiation. Data analysis may provide insights into managing patients on pH-altering medication. Implementing innovative technologies has the potential to reduce errors and improve economic efficiency and process sustainability.

Accurate prediction of photovoltaic (PV) power generation is the key to daily dispatch management and safe and stable grid operation. In order to improve the accuracy of the prediction, a finite iterative PV power prediction model with long range dependence (LRD) characteristics was developed using fractional Lévy stable motion (fLsm) and applied to a real dataset collected in the DKASC photovoltaic system in Alice Springs, Australia. The LRD prediction model considers the influence of current and past trends in the stochastic series on the future trends. Firstly, the calculation of the maximum steps prediction was introduced based on the maximum Lyapunov. The maximum prediction steps could provide the prediction steps for subsequent prediction models. Secondly, the order stochastic differential equation (FSDE) which describes the fLsm can be obtained. The parameters of the FSDE were estimated by using a novel characteristic function method. The PV power forecasting model with the LRD characteristics was obtained by discretization of FSDE. By comparing statistical performance indicators such as root max error, mean square error with Conv-LSTM, BiLSTM, and GA-LSTM models, the performance of the proposed fLsm model has been demonstrated. The proposed methods can provide better theoretical support for the stable and safe operation of PV grid connection. They have high reference value for grid dispatching department.

We define a new class of linear canonical wavelet transform (LCWT) and study its properties like inner product relation, reconstruction formula and also characterize its range. We obtain Donoho-Stark’s uncertainty principle for the LCWT and give a lower bound for the measure of its essential support. We also give the Shapiro’s mean dispersion theorem for the proposed LCWT.

In order to improve the design of the actuators of a Dragon Fly prototype, we study the loads applied to the actuators in operation. Both external and inertial forces are taken into account, as well as internal loads, for the purposes of evaluating the influence of the compliance of the arms on that of the "end-effector". We have shown many inadequacies of the arms regarding the stiffness needed to meet the initial design requirements. In order to reduce these inadequacies, a careful structural analysis of the stiffness of the actuators is carried out with a FEM technique, aimed at identifying the design methodology necessary to identify the mechanical elements of the arms to be stiffened. As an example, the design of the actuators is presented, with the aim of proposing an indirect calibration strategy. We have shown that the performances of the Dragon Fly prototype can be improved by developing and including in the control system a suitable module to compensate the incoming errors. By implementing our model in some practical simulations, with a maximum load on the actuators, and internal stresses, we have shown the efficiency of our model by collected experimental data. A FEM analysis is carried out on each actuator to identify the critical elements to be stiffened, and a calibration strategy is used to evaluate and compensate the expected kinematic errors due to gravity and external loads. The obtained results are used to assess the size of the actuators. The sensitivity analysis on the effects of global compliance within the structure enables us to identify and stiffen the critical elements (typically the extremities of the actuators). The worst loading conditions have been evaluated, by considering the internal loads in the critical points of the machine structure results in enabling us the sizing of the actuators. So that the Dragon fly prototype project has been set up, and the first optimal design of the arms has been performed by means of FEM analysis.

The rising migration and travel from and towards endemic areas has brought renewed concerns about many parasitic infections, including neglected tropical diseases, such as schistosomiasis. Although serology is the most widely used method for the screening of schistosomiasis in non-endemic countries, this technique lacks sensitivity, especially to distinguish between past and ongoing infections. More recently, a molecular test based on the detection of Schistosoma cell-free DNA in the serum has been proposed as a diagnostic procedure for parasitosis. To test the performance of a blood PCR assay, this work investigated 102 serum samples collected from migrants coming from endemic areas by using primers specific to genomic regions of S. mansoni and S. haematobium patients. The results were then compared with the detection of specific IgG Abs with serological tests. Molecular analysis detected Schistosoma DNA in 32 patients. Among them, we characterized nine S. haematobium, 20 S. mansoni, and three coinfections. Compared with molecular assay, serological analysis detected specific antibodies against Schistosoma antigens in 52 out of 102 patients. Concordance between the two tests was found in 76 out of 102 patients (74.51%): in particular, both diagnostic tests were positive in 29 patients (28.43%) and negative in 47 (46.08%). The specificity of the molecular test was 94%. Overall, our data suggest that serological diagnosis could be combined with the molecular approach, providing the clinician with the serotyping of the parasite and useful information about the infection as well as the required further diagnostic procedures.

This paper presents a synthesis of the research carried out in the settlement of Poggio della Gaggiola, located in the upper Reno Valley, enriching the knowledge on the Bronze Age settlement pattern in the Apennines with particular reference to the territory of the province of Bologna. This framework is currently at the centre of a research project on “upland archaeology in the Bronze Age”. Unpublished materials from Renato Scarani’s excavations carried out from 1949 to 1951 are also presented, while the descriptions of the main finds discovered in the 19th century that were lost are revisited. A special in-depth look at the methodologies of investigation and the changing research perspectives in the Apennines, as well as the spatial analysis, suggests interpretations of the geographical and geomorphological context where Poggio della Gaggiola settlement is located.