Decoding Information Flow and Sensory Pollution: A Systematic Framework for Understanding Species Interactions.

Information transmission among species is a fundamental aspect of natural ecosystems that faces significant disruption from rapidly growing anthropogenic sensory pollution. Understanding the constraints of information flow on species' trophic interactions is often overlooked due to a limited comprehension of the mechanisms of information transmission and the absence of adequate analytical tools. To fill this gap, we developed a sensory information-constrained functional response (IFR) framework, which accounts for the information transmission between predator and prey. Through empirical evaluation, the IFR provided a biologically grounded explanation for the systematic variation of functional responses. Specifically, it posits that the variation of different functional-response shapes, associated with community stability, is attributable to limitations in sensory information transmission among species. This not only deepens our mechanistic understanding of species interactions but also elucidates how anthropogenic activities are reshaping species interactions and community dynamics by disrupting information exchange through sensory pollution.

Update on primary cutaneous T-cell lymphomas rare subtypes.

Rare subtypes of cutaneous T-cell lymphomas (CTCL) include four entities, primary cutaneous γδ T-cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, and primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorders, primary cutaneous acral CD8+ T-cell lymphoma, which were previously considered provisional and are now included in the new 5th World Health Organization classification of hematolymphoid tumors as distinct entities. An updated summary of the clinical, histological, and genomic characteristics of these uncommon CTCL subtypes is given in this review, with a focus on the growing body of knowledge regarding their classification and possible treatment strategies.

The environment to the rescue: can physics help predict predator-prey interactions?

Understanding the factors that determine the occurrence and strength of ecological interactions under specific abiotic and biotic conditions is fundamental since many aspects of ecological community stability and ecosystem functioning depend on patterns of interactions among species. Current approaches to mapping food webs are mostly based on traits, expert knowledge, experiments, and/or statistical inference. However, they do not offer clear mechanisms explaining how trophic interactions are affected by the interplay between organism characteristics and aspects of the physical environment, such as temperature, light intensity or viscosity. Hence, they cannot yet predict accurately how local food webs will respond to anthropogenic pressures, notably to climate change and species invasions. Herein, we propose a framework that synthesises recent developments in food-web theory, integrating body size and metabolism with the physical properties of ecosystems. We advocate for combination of the movement paradigm with a modular definition of the predation sequence, because movement is central to predator-prey interactions, and a generic, modular model is needed to describe all the possible variation in predator-prey interactions. Pending sufficient empirical and theoretical knowledge, our framework will help predict the food-web impacts of well-studied physical factors, such as temperature and oxygen availability, as well as less commonly considered variables such as wind, turbidity or electrical conductivity. An improved predictive capability will facilitate a better understanding of ecosystem responses to a changing world.

Primary cutaneous, epidermotropic mycosis fungoides-like presentation: critical appraisal and description of two novel cases, broadening the spectrum of ALK+ T-cell lymphoma.

Leading from a two-case series, including two patients receiving a diagnosis of epidermotropic T-cell lymphoma, featuring a mycosis fungoides (MF)-like clinical pattern and ALK expression and molecular alteration, we performed a critical appraisal of ALK+ primary cutaneous T-cell lymphomas (pcTCL). Considering our patients and the literature, 32 cases were retrieved, 7 of which featured an MF-like clinical picture over a 4-to-20-year period. MF-like cases show distinctive histology, comprising a predominantly epidermotropic infiltration of small-to-large, atypical-to-pleomorphic, with few anaplastic cells, negligible-to-intense CD30-expression, and a CD4+/cytotoxic granule+ phenotype. These features should prompt a search for ALK expression captured by the ALK D5F3 clone. Bona fide ALK+ pcTCL is very rare, and existent data suggest the presence of a broader pattern of disease, including instances mimicking MF and/or primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma. The major challenges in dealing with this subset include prodromal phases, misinterpreted as inflammatory dermatosis or parapsoriasis/early phase MF both clinically and histologically, while recognition of its ALK-driven biology is hampered both by the unusual clinic-pathologic pattern of the disease, which stands apart from the classical (i.e., nodal) picture of ALK+ anaplastic large cell lymphoma and by the low sensitivity of ALK1 clone. Data on its optimal management are far from being conclusive: An MF-like approach is currently chosen, but depending on CD30 and, most notably, ALK expression, a targeted therapy could be envisaged in advanced stages, as clinical response to ALK inhibition was documented in one patient.

Paediatric-onset lymphomatoid papulosis: results of a multicentre retrospective cohort study on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

BACKGROUND: Lymphomatoid papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population are scarce. OBJECTIVES: To characterize the epidemiological, clinical, histopathological and prognostic features of paediatric LyP. METHODS: This was a retrospective multicentre international cohort study that included 87 children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years at disease onset were included. LyP diagnosis was made in each centre, based on clinicopathological correlation. RESULTS: Eighty-seven patients from 12 centres were included. Mean age at disease onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2 : 1. Mean time between the onset of the first cutaneous lesions and diagnosis was 1.3 years (range 0-14). Initial misdiagnosis concerned 26% of patients. LyP was most often misdiagnosed as pityriasis lichenoides et varioliformis acuta, insect bites or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned in 21% of patients. The main histological subtype was type A in 55% of cases. When analysed, monoclonal T-cell receptor rearrangement was found in 77% of skin biopsies. The overall survival rate was 100%, with follow-up at 5 years available for 33 patients and at 15 years for 8 patients. Associated haematological malignancy (HM) occurred in 10% of cases (n = 7/73), including four patients with mycosis fungoides, one with primary cutaneous anaplastic large cell lymphoma (ALCL), one with systemic ALCL and one with acute myeloid leukaemia. If we compared incidence rates of cancer with the world population aged 0-19 years from 2001 to 2010, we estimated a significantly higher risk of associated malignancy in general, occurring before the age of 19 years (incidence rate ratio 87.49, 95% confidence interval 86.01-88.99). CONCLUSIONS: We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall, the disease prognosis is good, with excellent survival rates for all patients. Owing to an increased risk of associated HM, long-term follow-up should be recommended for patients with LyP.

Lymphomatoid papulosis is a very rare skin condition caused by an abnormal increase in white blood cells (called 'lymphocytes') in the skin. The condition rarely affects children, so most of the scientific data published about this disease focuses on adults. This study involved 12 academic dermatology centres in Europe, the Middle East and North America, and gathered data from about 87 children who presented with symptoms of lymphomatoid papulosis before the age of 19 years. The aim of this study was to better describe this disease in the paediatric population and discuss its treatment options and evolution. We found that the presentation of the disease in children is roughly the same as in adults. Safe and effective treatment options exist. The disease is not life threatening, but it requires investigation by a dermatologist, both to make a careful diagnosis and to monitor it as sometimes associated cancers that originate from blood cells can occur, mostly on the skin.

Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Background: Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods: A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t-tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results: After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety (p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) (p = 0.012), a lower impact of dermatological disease on quality of life (p = 0.015), and more severe depressive symptoms (p < 0.01), while for anxiety, the only predictor was found to be female gender (p = 0.03). Conclusions: Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight.

Paediatric cutaneous lymphomas including rare subtypes: A 40-year experience at a tertiary referral centre.

BACKGROUND: Primary cutaneous lymphomas are neoplasms of the immune system with a distinct tropism for the skin and an absence of extracutaneous manifestations at the time of diagnosis. Studies focusing on cutaneous lymphomas in children and adolescents remain scarce and often do not encompass the rare subtypes. OBJECTIVES: To address this knowledge gap by describing the clinical, histological and molecular characteristics of a large group of paediatric patients affected by primary cutaneous lymphoma. We also provided the Paediatric Primary Cutaneous Lymphoma Atlas that illustrates the clinicopathological spectrum of observed presentations, in the hope of supporting other physicians in the diagnostic process. METHODS: Retrospective chart review of paediatric patients diagnosed with primary cutaneous lymphomas between 1980 and 2022 at the Paediatric Dermatology Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan. RESULTS: A total of 101 patients (58 males, 43 females) met the inclusion criteria. The most common subtypes were lymphomatoid papulosis (n = 48) and mycosis fungoides (n = 31). These were followed by primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorders (n = 7), primary cutaneous anaplastic large-cell lymphomas (n = 5), primary cutaneous marginal zone B-cell lymphomas (n = 3), primary cutaneous follicle centre lymphomas (n = 2), subcutaneous panniculitis-like T-cell lymphomas (n = 2), primary cutaneous peripheral T-cell lymphoma not otherwise specified (n = 1), primary cutaneous precursor B-lymphoblastic lymphoma (n = 1) and Sézary syndrome (n = 1). Clinical follow-up data covering a median of 70.8 months (range 1-324) were available for 74 patients, of whom three died due to cutaneous lymphoma. CONCLUSIONS: Our findings shed light on the peculiar aspects and long-term outcomes of paediatric cutaneous lymphomas, particularly emphasizing their distinctive features in comparison to their adult counterparts and exploring the less common subtypes. Further larger-scale studies are warranted to better characterize these entities and to achieve a more rapid and accurate diagnosis.

Whole-exome sequencing is feasible on a fresh-frozen skin sample of intravascular large B cell lymphoma.

Intravascular large B-cell lymphoma (IVLBCL) is a rare aggressive extranodal non-Hodgkin lymphoma. The predominant, if not exclusive, growth of neoplastic cells within the lumina of small-sized vessels represents the hallmark of the disease. Diagnosis is challenging due to the absence of marked lymphadenopathy, the highly heterogeneous clinical presentation, and the rarity of the condition. Clinical presentation is characterized by variable combinations of nonspecific signs and symptoms (such as fever and weight loss), organ-specific focal manifestations due to altered perfusion, and hemophagocytic syndrome. The rarity of this entity and the paucity of neoplastic cells in biopsy samples hamper the study of recurrent molecular abnormalities. The purpose of this study was to explore the feasibility of a different approach to recover a sufficient amount of DNA of acceptable quality to perform next-generation sequencing studies. Here, we report the findings of whole-exome next-generation sequencing performed on a fresh-frozen cutaneous sample of IVLBCL, paired with the patient saliva used as germline DNA. To increase the cancer cell fraction, only the subcutaneous tissue was selected. With this approach, we obtained high-quality DNA and were able to identify oncogenic mutations specific for this entity and recapitulating its post-germinal center origin, even if the tumor fraction was low. Molecular studies performed on fresh-frozen cutaneous sample are feasible in IVLBCL, especially when analysis is restricted to the subcutaneous tissue. Wide adoption of this reproducible and cost-effective approach may foster further studies, which may be of help in supporting diagnosis, providing pathogenetic insights, and guiding treatment decisions.

Linking biodiversity, ecosystem function, and Nature's contributions to people: a macroecological energy flux perspective.

At macroecological scales, the provision of Nature's contributions to people (NCP) is mostly estimated with biophysical information, ignoring the ecological processes underlying them. This hinders our ability to properly quantify the impact of declining biodiversity and the provision of NCP. Here, we propose a framework that combines local-scale food web energy flux approaches and large-scale biodiversity models to evaluate ecosystem functions and flux-related NCP at extensive spatiotemporal scales. Importantly, this approach has the potential to upscale ecosystem functions, assess the vulnerability of flux-related NCP to the climate crisis, and support the development of multiscale mitigation policies.

Identifying and addressing unmet clinical needs in primary cutaneous B-cell lymphoma: A consensus-based paper from an ad-hoc international panel.

Primary cutaneous B-cell lymphomas (PCBCLs) are lymphoproliferative disorders that appear on the skin without evidence of extracutaneous manifestations at the time of diagnosis. There is a lack of evidence-based guidelines for their clinical management due to the availability of very few large scale studies and controlled clinical trials. Here we present and discuss a series of major unmet clinical needs (UCNs) in the management of PCBCLs by a panel of 16 experts involved in research and clinical practice of PCBCL. The Panel produced recommendations on the appropriateness of the clinical decisions concerning the identified clinical needs and proposed research for improving the knowledge needed to solve them. Recommendations and proposals were achieved by multiple-step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. Recommendations and proposals lay in the domain of classification uncertainties of PCBCL, optimization of diagnosis, optimization of prognosis, optimization of staging and critical issues on therapeutic strategies with particular focus on new treatments. These recommendations are intended for use not only by experts but above all by dermatologists and hematologists with limited experience in the field of PCBCLs as well as general practitioners.

Mental health in patients affected by atopic dermatitis: which effects of treatment with dupilumab?

Atopic dermatitis (AD) is an inflammatory skin disease. Patients with AD are prone to develop anxiety and mood disorders. Aim of this study is to investigate if treatment with dupilumab may improve mental health status of patients affected by AD. A total of 66 patients with severe AD were included: 24 subjects were candidate or have just started (one month) treatment with dupilumab, and 42 have been in treatment for one year. 25.8%, 30.3%, and 45.5% of the total sample showed, respectively, clinically significant anxiety, depression, and symptoms of Internet addiction. Patients with anxiety symptoms resulted to have more severe AD, more sleep problems ( P  = 0.028), less quality of life ( P  = 0.001), more severe depressive symptoms ( P  < 0.001), to be more frequently women ( P  = 0.016), to be less frequently treated with dupilumab for one year ( P  = 0.025). Similarly, patients with clinically significant depressive symptoms resulted to have more severe AD, more sleep problems ( P  = 0.003), less quality of life ( P  < 0.001), more severe anxiety symptoms ( P  < 0.001), to be less frequently treated with dupilumab for one year ( P  = 0.008). Patients with AD treated for one year with dupilumab showed a better mental health profile in terms of less severe anxiety and depression with respect to their counterparts.

Epidemiology and geographic clustering of Erdheim-Chester disease in Italy and France.

This geoepidemiological study, performed in Italy and France, shows that Erdheim-Chester disease is increasingly diagnosed and cases cluster in specific geographic areas, namely southern Italy and central France. Disease frequency inversely correlates with the Human Development Index.

Global patterns and drivers of lead concentration in inland waters.

Water bodies are important carriers for lead (Pb) biogeochemical cycling, which is a key pathway of Pb transport. Although existing studies on Pb loading in inland waters have developed rapidly, a quantitative assessment of the distribution patterns and drivers of Pb concentration in inland waters at the global scale remains unclear. Here, by analyzing 1790 observations collected from 386 independent publications, we assessed the spatial distribution and drivers of Pb concentration in inland waters worldwide. We found that (1) globally, the median of Pb concentration in inland waters was 5.81 µg L-1; (2) among different inland water types, Pb concentration was higher in rivers, and the highest Pb concentration was in industrial land in terms of land use type; (3) Pb concentration in inland waters were positively driven by potential evapotranspiration, elevation and road density; and (4) Pb concentration showed a negative relationship with absolute latitude, decreasing from tropic to boreal regions. Overall, our global assessment of the patterns and drivers of Pb concentration in inland waters contributed to a better understanding of the natural and anthropogenic attributions of Pb in the inland hydrological cycling.

A Microenvironment-Related Nine-Gene Signature May Predict Survival in Mycosis Fungoides Patients at Diagnosis.

Mycosis fungoides (MF) is the most common cutaneous lymphoma characterized by an indolent course. Prognosis is stage-based but this approach does not reflect the different outcomes within stages. Considering that tumor microenvironment is known to be involved in MF pathogenesis and progression, we decided to investigate 99 MF cases by using the PanCancer Immune Profiling Panel. We identified and validated a signature of 9 genes able to predict MF survival and distinguish a high-risk group with a worse outcome from a low-risk group of cases with a better outcome. At the molecular level, low-risk vs. high-risk cases reported a global upregulation of immune genes, enriched in cytokines, and a higher density of dendritic cells and mast cells, possibly associated with a more favorable clinical course.

The Relevant Oral Burden of Patients with Hidradenitis Suppurativa.

INTRODUCTION: Interleukin-17 plays a pivotal role in both hidradenitis suppurativa (HS) and in maintaining oral homeostasis, but their potential link remains unknown. Thus, we aimed to evaluate and quantify the oral burden of patients with HS. METHODS: In this real-life, multicenter, cross-sectional study, patients with HS were clinically evaluated by two board-certified dermatologists and two board-certified dentists. Oral comorbidities were carefully collected with medical history and therapeutic information. RESULTS: A total of 102 patients (44.0 ± 0.9 years, body mass index 27.0 ± 2.2 kg/m2) were enrolled. Remarkably, 48% and 43% did not undergo at least an oral hygiene or a dental visit each year, respectively. Oral disorders were found in 55.9% of patients with HS, in particular 39.2% had caries and 46.7% reported at least one missing tooth. The main oral manifestations in patients with HS were recurrent aphthous stomatitis (N = 19, 19.2%), amalgam tattoo (N = 14, 14.1%), leukoplakia (N = 11, 11.1%), nicotinic stomatitis (N = 9, 9.1%), papilloma (N = 8, 8.1%), and geographic tongue (N = 8, 8.1%). Whilst the main predictor of oral pathological conditions was Hurley staging (P = 0.0276), multivariate regression analysis indicated that gender and International Hidradenitis Suppurativa Severity Score System (IHS4) were the main predictors for the presence of caries and number of missing teeth. CONCLUSION: As a result of the relevant oral burden in patients with HS, dentists should be part of the multidisciplinary team and oral education should be promoted among patients with HS.

The travel speeds of large animals are limited by their heat-dissipation capacities.

Movement is critical to animal survival and, thus, biodiversity in fragmented landscapes. Increasing fragmentation in the Anthropocene necessitates predictions about the movement capacities of the multitude of species that inhabit natural ecosystems. This requires mechanistic, trait-based animal locomotion models, which are sufficiently general as well as biologically realistic. While larger animals should generally be able to travel greater distances, reported trends in their maximum speeds across a range of body sizes suggest limited movement capacities among the largest species. Here, we show that this also applies to travel speeds and that this arises because of their limited heat-dissipation capacities. We derive a model considering how fundamental biophysical constraints of animal body mass associated with energy utilisation (i.e., larger animals have a lower metabolic energy cost of locomotion) and heat-dissipation (i.e., larger animals require more time to dissipate metabolic heat) limit aerobic travel speeds. Using an extensive empirical dataset of animal travel speeds (532 species), we show that this allometric heat-dissipation model best captures the hump-shaped trends in travel speed with body mass for flying, running, and swimming animals. This implies that the inability to dissipate metabolic heat leads to the saturation and eventual decrease in travel speed with increasing body mass as larger animals must reduce their realised travel speeds in order to avoid hyperthermia during extended locomotion bouts. As a result, the highest travel speeds are achieved by animals of intermediate body mass, suggesting that the largest species are more limited in their movement capacities than previously anticipated. Consequently, we provide a mechanistic understanding of animal travel speed that can be generalised across species, even when the details of an individual species' biology are unknown, to facilitate more realistic predictions of biodiversity dynamics in fragmented landscapes.

SARS-CoV-2 Detection by Digital Polymerase Chain Reaction and Immunohistochemistry in Skin Biopsies from 52 Patients with Different COVID-19-Associated Cutaneous Phenotypes.

BACKGROUND: COronaVIrus Disease 19 (COVID-19) is associated with a wide spectrum of skin manifestations, but SARS-CoV-2 RNA in lesional skin has been demonstrated only in few cases. OBJECTIVE: The objective of this study was to demonstrate SARS-CoV-2 presence in skin samples from patients with different COVID-19-related cutaneous phenotypes. METHODS: Demographic and clinical data from 52 patients with COVID-19-associated cutaneous manifestations were collected. Immunohistochemistry and digital PCR (dPCR) were performed in all skin samples. RNA in situ hybridization (ISH) was used to confirm the presence of SARS-CoV-2 RNA. RESULTS: Twenty out of 52 (38%) patients presented SARS-CoV-2 positivity in the skin. Among these, 10/52 (19%) patients tested positive for spike protein on immunohistochemistry, five of whom had also positive testing on dPCR. Of the latter, one tested positive both for ISH and ACE-2 on immunohistochemistry while another one tested positive for nucleocapsid protein. Twelve patients showed positivity only for nucleocapsid protein on immunohistochemistry. CONCLUSIONS: SARS-CoV-2 was detected only in 38% of patients, without any association with a specific cutaneous phenotype, suggesting that the pathophysiology of cutaneous lesions mostly depends on the activation of the immune system. The combination of spike and nucleocapsid immunohistochemistry has higher diagnostic yield than dPCR. Skin persistence of SARS-CoV-2 may depend on timing of skin lesions, viral load, and immune response.

Indeterminate cell histiocytosis: A systematic review of the literature with a comprehensive revision of clinical, histopathological, and molecular features.

Indeterminate cell histiocytosis (ICH) is a very rare histiocytic disorder, primarily involving the skin. It affects more frequently adults, often presenting with a generalized papular eruption, and needs to be differentiated from other neoplastic, paraneoplastic, and infectious diseases through clinical and histological examination. The knowledge on ICH is limited to case reports and small series. Thus, the lack of larger multicentric studies has prevented recognizing and addressing the specific clinical need of the entity. In this systematic review, we comprehensively analysed the medical literature describing histologically-confirmed cases of ICH and divided the patients into epidemiologically and clinically different groups. We demonstrate that ICH in adulthood is strongly associated with the development of haematological (and especially myeloid) neoplasms. In this subset of patients, we identify blastic morphology of neoplastic cells as a novel independent prognostic factor and an early histopathological predictor of an associated myeloid neoplasm. Moreover, we highlight that even though ICH may also present in childhood, these patients often show indolent behaviour. Genetically, ICH emerges as a heterogeneous condition. While patients with associated myeloid neoplasms are enriched in pERK pathway gene mutations, in others a specific ETV3::NCOA2 rearrangement is described. We finally reviewe the nosology of ICH since its first description, its possible cell of origin, and summarize the therapeutic options reported for each different clinical subgroup. With this work, we hope to foster studies on rare cutaneous histiocytosis and their comprehensive multidisciplinary characterization.