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Abstract Introduction UVA-UVB increases skin matrix metalloproteinases and breaks down extracellular proteins and fibrillar type 1 collagen, leading to photodamage. Topical application of nicotinamide prevents UV-induced immunosuppression. Several studies have demonstrated the importance of protection against UV. This study aims to determine the biological effect of a high broad-spectrum UVB-UVA sunscreen containing nicotinamide and panthenol (SSNP) on photodamaged skin using linear confocal optical coherence tomography (LC-OCT), immunohistochemistry, and RNA profiling. Methods Two areas of severely photodamaged forearm skin (L01 and L02) and one less sun-damaged (naturally protected) area on the inner part of the forearm (L03) were identified in 14 subjects. These areas were imaged using LC-OCT and L01 and L03 were biopsied at baseline. After 4 weeks of treatment with SSNP, L02 was reimaged using LC-OCT, and biopsied. Histology, immunostaining with p21, p53, PCNA, and CPD, and RNA sequencing were performed in all samples. Results LC-OCT analysis showed that epidermis thickness and the number of keratinocytes is higher in the sun-exposed areas than in the non-exposed areas. Comparing before and after treatment, even though there is a trend towards normalization, the differences were not statistically significant. The expression of p21, PCNA, p53, and CPD increased in severely photodamaged skin compared to less-damaged skin. When comparing before and after treatment, only p21 showed a trend to decrease expression. RNA sequencing analysis identified 1552 significant genes correlating with the progression from non-visibly photodamaged skin to post-treatment and pre-treatment samples; in the analysis comparing pre- and post-treatment samples, 5429 genes were found to be significantly associated. A total of 1115 genes are common in these two analyses. Additionally, nine significant genes from the first analysis and eight from the second are related to collagen. Six of these collagen genes are common in the two analyses. MAPK and cGMP-PKG signalling pathways are upregulated in the progression to photodamage analysis. In the pre- and post-treatment analysis, 32 pathways are downregulated after treatment, the most statistically significant being the ErbB, Hippo, NOD-like receptor, TNF, and NF-kB signalling pathways. Conclusion This study demonstrates the role of SSNP in collagen generation, highlights the relevance of the cGMP-PKG and MAPK signalling pathways in photodamage, and shows the ability of SSNP to downregulate pathways activated by UV exposure. Additionally, it deepens our understanding of the effect of SSNP on immune-related pathways.

BACKGROUND: Teeth with defects in their structure, such as the ones affected by molar-incisor hypomineralization (MIH), are more susceptible to carious lesions. Caries is a complex and multifactorial disease highly prevalent in childhood. The present research evaluated the relationship between the stages of MIH and cariogenic bacteria in children. METHODS: After examining 566 schoolchildren, four groups of 10 children each were formed: healthy (G1), mild MIH (G2 and G3), and severe MIH + caries (G4). Dental biofilm was assessed to quantify Streptococcus mutans (SM) and Lactobacillus spp. (LB) using real-time polymerase chain reaction (RT-PCR). RESULTS: LB counting in biofilm samples of healthy children (G1) and those with mild MIH characterized by white opacities (G2) were not significantly different. The same happened when the ones with yellow opacities (G3) were compared with severe MIH + caries (G4) (P>0.05). The post hoc Tukey test proved that G4 had greater levels of SM and LB when compared with G2 (P0.05). Increased LB enhanced the severity of MIH [rate ratio (RR): 7.706; P=0.035]. CONCLUSIONS: LB was influenced by different degrees of MIH and the presence of caries and could guide clinical decisions and patients recommendations to prevent carious lesions in MIH children.

Abstract Introduction Hantavirus infection is a zoonotic disease from rodents to humans, necessitating seroprevalence assessment for disease burden clarification and control measure implementation. This study aimed to estimate global hantaviruses seroprevalence, examining variations by regions, populations or settings. Methods A comprehensive database search identified studies on human hantaviruses seroprevalence using IgG detection until january 2024. A random-effects meta-analysis estimated pooled seroprevalence, with subgroup analyses for geographical region, population, setting or occupation. Results Out of 3,382 abstracts reviewed, 110 studies were selected, comprising 81,815 observations and 3207 events. The global seroprevalence was calculated at 2.93% (2.34%-3.67%). In terms of geographical distribution, our analysis encompassed 61 studies from the Americas, where the seroprevalence was estimated at 2.43% (95% CI: 1.71%—3.46%), 33 studies from Europe indicating a seroprevalence of 2.98% (95% CI: 2.19%—4.06%), 10 studies from Asia revealing a seroprevalence of 6.84% (95% CI: 3.64%—12.50%), and 6 studies from Africa demonstrating a seroprevalence of 2.21% (95% CI: 1.82%—2.71%). Subgroup analysis underscored varying seroprevalence rates across different populations, settings, and occupations, highlighting the necessity for targeted interventions and preventive measures. Conclusion The analysis reveals a moderate global hantaviruses seroprevalence, emphasizing the viral family's complex transmission dynamics influenced by exposure and geographical factors. This highlights the need for targeted prevention and control strategies.

Abstract As major terrestrial carbon sinks, forests play an important role in mitigating climate change. The relationship between the seasonal uptake of carbon and its allocation to woody biomass remains poorly understood, leaving a significant gap in our capacity to predict carbon sequestration by forests. Here, we compare the intra-annual dynamics of carbon fluxes and wood formation across the Northern hemisphere, from carbon assimilation and the formation of non-structural carbon compounds to their incorporation in woody tissues. We show temporally coupled seasonal peaks of carbon assimilation (GPP) and wood cell differentiation, while the two processes are substantially decoupled during off-peak periods. Peaks of cambial activity occur substantially earlier compared to GPP, suggesting the buffer role of non-structural carbohydrates between the processes of carbon assimilation and allocation to wood. Our findings suggest that high-resolution seasonal data of ecosystem carbon fluxes, wood formation and the associated physiological processes may reduce uncertainties in carbon source-sink relationships at different spatial scales, from stand to ecosystem levels.

We present a comprehensive study of acral serpiginous hemangioma, a rare vascular pathology. This distinctive manifestation was examined for the first time using high-resolution video dermoscopy (HRVD), high-frequency ultrasound (HFUS), and line-field confocal optical coherence tomography (LC-OCT). The combined application of these techniques provides new and detailed morphological features able to determine the in vivo structure of lesional skin. This innovative non-invasive approach emphasizes the importance of incorporating advanced diagnostic tools able to provide a virtual histology in order to avoid unnecessary biopsies in benign lesions, often causing pain and functional/aesthetic discomfort.

Basal cell carcinoma (BCC) is the most frequent malignancy in the general population. To date, dermoscopy is considered a key tool for the diagnosis of BCC; nevertheless, line-field confocal optical coherence tomography (LC-OCT), a new non-invasive optical technique, has become increasingly important in clinical practice, allowing for in vivo imaging at cellular resolution. The present study aimed to investigate the possible correlation between the dermoscopic features of BCC and their LC-OCT counterparts. In total, 100 histopathologically confirmed BCC cases were collected at the Dermatologic Clinic of the University of Siena, Italy. Predefined dermoscopic and LC-OCT criteria were retrospectively evaluated, and their frequencies were calculated. The mean (SD) age of our cohort was 65.46 (13.36) years. Overall, BCC lesions were mainly located on the head (49%), and they were predominantly dermoscopically pigmented (59%). Interestingly, all dermoscopic features considered had a statistically significant agreement with the LC-OCT criteria (all p < 0.05). In conclusion, our results showed that dermoscopic patterns may be associated with LC-OCT findings, potentially increasing accuracy in BCC diagnosis. However, further studies are needed in this field.

Introduction: Antibiotic resistance has become a serious, severe problem worldwide. This issue does not only relate to the use of systemic antibiotics but to topical ones as well, like systemic therapies and local treatment of skin and mucosal infections. Antiseptics, an alternative to the topical treatment with antibiotics of wounds and some inflammatory dermatological conditions, tend to be microbicidal and have a broader spectrum of antimicrobial activity than antibiotics. Among these, polyhexanide (PHMB) allows for the control of the infection while avoiding the development of resistance. Objectives: Recommendations on the rules of good clinical practice for the management of small wounds, burns and post-traumatic ulcerative wounds, impetigo or folliculitis in the initial stages, and acne. Methods: Literature review on the principal topical therapies for small wounds, injuries, impetigo, folliculitis, and acne and a proposal of innovative, highly-tolerated treatments. Results and conclusions: Given the abuse of topical antibiotics in dermatology, for the treatment of small wounds, injuries, localized folliculitis, impetigo, and acne, the use of alternative topical treatments like polyhexanide and Rigenase® is recommended.

ABSTRACT New approaches for managing agricultural and forestry systems are needed to bring back inputs to levels that are within planetary boundaries and make greater and better use of ecosystem services based on biodiversity. A new scientific framework informed by ecology, agronomy, forestry, and agroforestry is key to designing resilient plant‐based ecosystems to meet this challenge. Integrating information on plant functional traits, ontogenetic development stages, site characteristics, and structural stand characteristics can unleash the power of diversity (in species traits and structural and temporal arrangements) as a crucial factor for sustaining environmental services in times of global change. To leverage the benefits of diversity, a general theoretical framework and scalable simulation models are needed to understand structural and species diversification effects and interactions at multiple levels, from plant to field/forest stand to landscape. By working across established research boundaries, the scientific community can harness the power of structural and functional diversity to develop resilient, production‐oriented ecosystems. With this integrative approach, our objectives are as follows: (i) to conceptualize processes and methodologies for managing resilient terrestrial ecosystems that can guarantee sustainable and diversified ecosystem services within planetary boundaries, and (ii) to outline the workflow for crafting a system capable of sustaining human well‐being amid space, resource, and energy constraints.

Un análisis crítico del concepto de utopía y la reivindicación de la ucronía como amalgama de flujos que se mueven sinuosos desde el cuerpo y el cuidado, al margen de la temporalidad univoca y linal. Pistas desbordantes (ucrónicas) para disputar los imaginarios de la hegemonía neoliberal. Ensayo de una escritura compartida que habita eróticamente el dentro/fuera de lo académico.

Abstract Tree mortality and forest dieback episodes are increasing due to drought and heat stress. Nevertheless, a comprehensive understanding of mechanisms enabling trees to withstand and survive droughts remains lacking. Our study investigated basal area increment (BAI), and δ13C-derived intrinsic water-use-efficiency (iWUE), to elucidate beech resilience across four healthy stands in Italy with varying climates and soil water availability. Additionally, fist-order autocorrelation (AR1) analysis was performed to detect early warning signals for potential tree dieback risks during extreme drought events. Results reveal a negative link between BAI and vapour pressure deficit (VPD), especially in southern latitudes. After the 2003 drought, BAI decreased at the northern site, with an increase in δ13C and iWUE, indicating conservative water-use. Conversely, the southern sites showed increased BAI and iWUE, likely influenced by rising CO2 and improved water availability. In contrast, the central site sustained higher transpiration rates due to higher soil water holding capacity (SWHC). Despite varied responses, most sites exhibited reduced resilience to future extreme events, indicated by increased AR1. Temperature significantly affected beech iWUE and BAI in northern Italy, while VPD strongly influenced the southern latitudes. The observed increase in BAI and iWUE in southern regions might be attributed to an acclimation response.

Dataset of annual monitoring of herbivory effects on the conservation status of the endangered species Androcymbium europaeum (Lange) K. Richt and its associated plant communities is presented in this manuscript. This dataset encompasses the annual monitoring of herbivory effects on the conservation status of the endangered species Androcymbium europaeum. Since 2010, the SERPAM Department (Service of Evaluation, Restoration and Protection of Mediterranean Agrosystems) at the Zaidin Experimental Station, belonging to the Spanish National Research Council (CSIC-EEZ), has conducted annual sampling to assess the impact of both domestic and wild livestock, specifically rabbits, on the pastures where A. europaeum lives. The study consisted of a randomised block design, implementing three distinct treatments to evaluate different management strategies: (1) rabbit and domestic herbivory, (2) exclusion of domestic livestock and (3) exclusion of rabbits and domestic livestock. Within each treatment, two types of monitoring were conducted. Firstly, the abundance of A. europaeum was estimated by counting individuals within 50 cm x 50 cm quadrats. Secondly, plant species diversity was assessed along 2-m long transects using the modified Point-Quadrat method. The research was conducted within the Cabo de Gata-Níjar Natural Park in southern Spain, specifically in the Amoladeras Nature Reserve in Almería.The dataset contains information spanning from 2010 to 2023, providing valuable insights into the annual monitoring of herbivory effects on the conservation status of A. europaeum, contributing to our understanding of the species' interaction with domestic and wild animal in the studied area.

Background/Objectives: Hidrocystomas, eccrine and apocrine, are rare cystic lesions that form benign tumors of the sweat glands. This study aimed to describe the clinical features of hidrocystomas and evaluate the role of non-invasive imaging techniques, including dermoscopy, Line-field Confocal Optical Coherence Tomography (LC-OCT), Reflectance Confocal Microscopy (RCM), and Ultra-High-Frequency Ultrasound (UHFUS), in their diagnosis. Methods: In total, seven cases of hidrocystomas were collected from the Dermatologic Clinic of the University of Siena, Italy. Predefined dermoscopic, LC-OCT, RCM, and UHFUS features were retrospectively described. Results: Overall, hidrocystomas were located on the face, mainly presenting as blue/purple-bluish translucent papules (71%). Dermoscopic examination revealed a homogeneous purple-bluish color (71%), white pale halo (71%), and shiny globules at the periphery (57%). LC-OCT identified a hyporeflective cupoliform round structure in the dermis with a bright and thick contour, while UHFUS showed a round structure in the dermis filled with hypoechoic content. Conclusions: Non-invasive imaging techniques could significantly enhance the diagnostic accuracy of hidrocystomas, aid in differentiation from other lesions, and minimize unnecessary biopsies.

Background/Objectives: Facial pigmented skin lesions are extremely common, starting from the fourth to fifth decades, especially in South-European countries, often located in the periorbital region. These include malignant forms, Lentigo maligna (LM) and lentigo maligna melanoma (LMM), characterized by growing incidence, and a series of benign simulators, including solar lentigo (SL), pigmented actinic keratosis (PAK), seborrheic keratosis (SK) and lichen planus-like keratosis (LPK). The clinical differential diagnosis of atypical pigmented skin lesions (aPFLs) can be difficult, even for dermatologists, leading to inappropriate skin biopsies with consequent aesthetic impacts. Dermoscopy of the facial area is a specific dermoscopic field that requires dedicated training and proved to increase diagnostic accuracy in dermatologists. Since these lesions are often seen by ophthalmologists at first, we aimed to evaluate the effect of a focused dermoscopy training course on a group of ophthalmologists naïve to the use of a dermatoscope. Methods: A set of 80 periorbital pigmented skin lesions with both clinical and dermoscopic images was selected and evaluated by six ophthalmologists before and after a one-day intensive dermoscopic training course. They were required to evaluate 80 periorbital lesions one month before and after a one-day intensive dermoscopic training course, illustrating second-level diagnostic options such as reflectance confocal microscopy (RCM), obtaining a total of 480 evaluations. Specifically, they had to provide, for each case, a punctual diagnosis and a management option among dermoscopic follow-up/skin biopsy/RCM/LC-OCT. Descriptive statistics were carried out, and the accuracy (ACC), sensitivity (SE), and specificity (SP), with their 95% confidence interval (95% CI), were estimated. Results: In the pre-course test, ophthalmologists achieved 84.0% SP, 33.3% SE and 63.7% ACC, while after the course, SE increased by +9% (i.e., 41.7%), SP decreased by 4%, and ACC remained comparable, i.e., 64.6%. In the management study, the percentage of benign lesions for which a close dermoscopic follow-up was suggested significantly decreased (51.6% versus 22.2%), in parallel with an increase in the number of lesions referred for RCM. As for malignant cases, the reduction in responses “close dermoscopic follow-up” decreased from 37.0% to 9.9%, (−27%), in favor of RCM (+15%) and skin biopsy (+12%). Conclusions: The ophthalmologists proved to be very receptive in quickly metabolizing and putting into practice the concepts learned during the one-day intensive dermoscopy training course. Indeed, after only a one-day lesson, they were able to increase their SE by 9% and to improve their management strategy. The present findings highlight the importance of providing training ophthalmologists in dermoscopy during residency programs, in terms of benefits for the correct patient care.

Introduction: Soon after birth, the clinical differential diagnosis between sebaceous of Jadassohn (NSJ), congenital triangular alopecia (CTA) and aplasia cutis congenita (ACC) may be challenging. A certain overlap of standard dermoscopic features can occur, especially in atypical cases, depending on scalp skin morphology and maturation age. The recently developed line-field confocal optical coherence tomography (LC-OCT) can provide morphological skin details with cellular resolution trough a rapid non-invasive examination. Objectives: To assess the LC-OCT features of 6 cases of congenital alopecia of different aetiologies, with both typical and atypical clinical appearance. Methods: A non-invasive imaging examination combining standard dermoscopy, high-resolution videodermoscopy (HRVD) and LC-OCT was realized in 7 babies presenting for congenital alopecia with overlapping features, aged between 5 months and 5 years. Results: Based on the specific LC-OCT features, and supported by HRVD features, a diagnosis of nevus sebaceous of Jadassohn (NSJ), congenital triangular alopecia (CTA) and aplasia cutis congenita (ACC) were made in 4, 2 and 1 case, respectively. Conclusions: The combined LC-OCT plus HRVD non-invasive imaging bring the advantage to have a real time diagnosis, to set the proper management and allows to avoid a skin biopsy in the perinatal age/first years of life at delicate skin site.

BackgroundSmell disorders are commonly reported with COVID-19 infection. The smell-related issues associated with COVID-19 may be prolonged, even after the respiratory symptoms are resolved. These smell dysfunctions can range from anosmia (complete loss of smell) or hyposmia (reduced sense of smell) to parosmia (smells perceived differently) or phantosmia (smells perceived without an odor source being present). Similar to the difficulty that people experience when talking about their smell experiences, patients find it difficult to express or label the symptoms they experience, thereby complicating diagnosis. The complexity of these symptoms can be an additional burden for patients and health care providers and thus needs further investigation. ObjectiveThis study aims to explore the smell disorder concerns of patients and to provide an overview for each specific smell disorder by using the longitudinal survey conducted in 2020 by the Global Consortium for Chemosensory Research, an international research group that has been created ad hoc for studying chemosensory dysfunctions. We aimed to extend the existing knowledge on smell disorders related to COVID-19 by analyzing a large data set of self-reported descriptive comments by using methods from natural language processing. MethodsWe included self-reported data on the description of changes in smell provided by 1560 participants at 2 timepoints (second survey completed between 23 and 291 days). Text data from participants who still had smell disorders at the second timepoint (long-haulers) were compared with the text data of those who did not (non–long-haulers). Specifically, 3 aims were pursued in this study. The first aim was to classify smell disorders based on the participants’ self-reports. The second aim was to classify the sentiment of each self-report by using a machine learning approach, and the third aim was to find particular food and nonfood keywords that were more salient among long-haulers than those among non–long-haulers. ResultsWe found that parosmia (odds ratio [OR] 1.78, 95% CI 1.35-2.37; P

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.7%, P = 0.006 compared to historical 1-year OS of 35%, n = 34) but was not met for sotiga/chemo (48.1%, P = 0.062, n = 36) or sotiga/nivo/chemo (41.3%, P = 0.223, n = 35). Secondary endpoints were progression-free survival, objective response rate, disease control rate, duration of response and safety. Treatment-related adverse event rates were similar across arms. Multi-omic circulating and tumor biomarker analyses identified distinct immune signatures associated with survival for nivo/chemo and sotiga/chemo. Survival after nivo/chemo correlated with a less suppressive tumor microenvironment and higher numbers of activated, antigen-experienced circulating T cells at baseline. Survival after sotiga/chemo correlated with greater intratumoral CD4 T cell infiltration and circulating differentiated CD4 T cells and antigen-presenting cells. A patient subset benefitting from sotiga/nivo/chemo was not identified. Collectively, these analyses suggest potential treatment-specific correlates of efficacy and may enable biomarker-selected patient populations in subsequent PDAC chemoimmunotherapy trials.

Data on primary cutaneous lymphomas (PCLs) patients in the Italian population are limited, and, despite the existence of several treatment options, the management of those patients remains challenging. Our study aimed to investigate the clinical and therapeutic features of PCL patients in a referral center in Italy. We conducted a retrospective study on 100 consecutive PCL patients between January 2017 and December 2022. The mean (SD) age of our cohort was 70.33 (14.14) years. Cutaneous T-cell lymphomas (CTCLs) represented 65% of all cases; the majority were mycosis fungoides (42%), followed by cases of Sezary syndrome (10%) and primary cutaneous anaplastic large cell lymphoma (4%). Cutaneous B-cell lymphomas (CBCLs) accounted for 35 % of PCLs, with 15 cases of primary cutaneous follicle center lymphoma, 10 cases of primary cutaneous diffuse large B-cell lymphoma leg type, and 9 cases of marginal zone B-cell lymphoma. A higher frequency of pruritus (p = 0.008) and higher peripheral blood levels of beta-2 microglobulin (p ≤ 0.001) and lactate dehydrogenase (p = 0.025) were found in CTCLs compared to those of CBCLs. Considering all therapeutic lines performed, treatments were extremely heterogeneous and skin-directed therapies represented the most frequently used approach. Our study confirms the distribution of PCL subtypes formerly reported in the literature and highlights the utility of real-life data in treatments to improve the current management of PCL patients.