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Amanda B Muir,1 Terri Brown-Whitehorn,2 Bridget Godwin,1 Antonella Cianferoni11Gastroenterology Division, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA; 2Allergy Division, The Children’s Hospital of Philadelphia, Philadelphia, PA, USACorrespondence: Antonella CianferoniGastroenterology Division, The Children’s Hospital of Philadelphia, ARC1216G, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USATel +1 267 294 1952Email Cianferonia@email.chop.eduAbstract: Eosinophilic esophagitis (EoE) is a disorder which affects all ages, from infancy through adulthood. It typically affects atopic individuals (Table 1) and is a chronic allergic disorder, with foods ubiquitous in the diet being the most described trigger of this isolated eosinophilic inflammation of the esophagus in both adults and children. This inflammatory process leads to esophageal symptoms such as dysphagia and feeding intolerance. In this review, we provide a brief overview of the current state of EoE therapy and symptomatology and then try to make the case for early diagnosis and treatment to prevent some of the long-term consequences of esophageal inflammation.Keywords: eosinophilic esophagitis, early, diagnosis, stenosis, pain

Antonella Cianferoni Department of Pediatrics, Division of Allergy and Immunology, The Children’s Hospital of Philadelphia, PA, USA Abstract: Triticum aestivum (bread wheat) is the most widely grown crop worldwide. In genetically predisposed individuals, wheat can cause specific immune responses. A food allergy to wheat is characterized by T helper type 2 activation which can result in immunoglobulin E (IgE) and non-IgE mediated reactions. IgE mediated reactions are immediate, are characterized by the presence of wheat-specific IgE antibodies, and can be life-threatening. Non-IgE mediated reactions are characterized by chronic eosinophilic and lymphocytic infiltration of the gastrointestinal tract. IgE mediated responses to wheat can be related to wheat ingestion (food allergy) or wheat inhalation (respiratory allergy). A food allergy to wheat is more common in children and can be associated with a severe reaction such as anaphylaxis and wheat-dependent, exercise-induced anaphylaxis. An inhalation induced IgE mediated wheat allergy can cause baker’s asthma or rhinitis, which are common occupational diseases in workers who have significant repetitive exposure to wheat flour, such as bakers. Non-IgE mediated food allergy reactions to wheat are mainly eosinophilic esophagitis (EoE) or eosinophilic gastritis (EG), which are both characterized by chronic eosinophilic inflammation. EG is a systemic disease, and is associated with severe inflammation that requires oral steroids to resolve. EoE is a less severe disease, which can lead to complications in feeding intolerance and fibrosis. In both EoE and EG, wheat allergy diagnosis is based on both an elimination diet preceded by a tissue biopsy obtained by esophagogastroduodenoscopy in order to show the effectiveness of the diet. Diagnosis of IgE mediated wheat allergy is based on the medical history, the detection of specific IgE to wheat, and oral food challenges. Currently, the main treatment of a wheat allergy is based on avoidance of wheat altogether. However, in the near future immunotherapy may represent a valid way to treat IgE mediated reactions to wheat. Keywords: IgE mediated food allergy, non-IgE mediated food allergy, wheat allergy, baker’s asthma, wheat dependent exercise induced anaphylaxis, eosinophilic esophagitis, eosinophilic gastritis

Abstract Proteins are often referred to as the workhorses of cells, and their interactions are necessary to facilitate specific cellular functions. Despite the recognition that protein-protein interactions, and thus protein functions, are determined by proteoform states, such as mutations and post-translational modifications (PTMs), methods for determining the differential abundance of proteoforms across conditions are very limited. Classically, immunoprecipitation coupled with mass spectrometry (IP-MS) has been used to understand how the interactome (preys) of a given protein (bait) changes between conditions to elicit specific cellular functions. Reversing this concept, we present here a new workflow for IP-MS data analysis that focuses on identifying the differential peptidoforms of the bait protein between conditions. This method can provide detailed information about specific bait proteoforms, potentially revealing pathogenic protein states that can be exploited for the development of targeted therapies.

The Scientific Committee for the Italian Fauna is managing the new checklist of the animal species of Italy. The previous checklist was published in 1993-1995 and included both protozoans and Metazoa (more than 57,000 species); the new project, which includes only Metazoa, started in 2020 and is aimed at updating the former checklist (with more than 60,000 expected species) by on-line datasets and data papers. The new checklist includes marine species recorded in the Italian seas, divided into nine marine sectors, within the Italian Economic Exclusive Zone, and terrestrial and freshwater species recorded in administrative regions, as well as in the three macro-regions (northern continental, southern peninsular and insular - Sicily and Sardinia - macro-regions). Records from geopolitical units biogeographically related to Italy (i.e., Canton Ticino, CH; Corsica, F; San Marino Republic and Vatican City) are also included. Over 180 Italian and foreign taxonomists have so far participated to the first phase of this new project, providing datasets for taxa at different hierarchical level, from phyla to subfamilies and tribes. The list is intended to be a fundamental instrument not only for the faunistic knowledge of Italy, but also for biodiversity conservation strategies in the country and in the European Union. The new Checklist of the Italian fauna will be available from the LifeWatch Italy platform, and it will be progressively updated. Furthermore, data papers for taxa at different hierarchical level could be published with continuity in a special section of the journal Biogeographia – The Journal of Integrative Biogeography.

We here present the first study on the consumed prey by an epigean population of the Italian cave salamander (Speleomantes italicus) from the Republic of San Marino. Using the harmless technique of stomach flushing, we aimed to provide the first data on the diet and on the degree of individual specialization that characterizes the studied population. We performed two-night surveys (one in autumn 2022 and one in spring 2023) in which we opportunistically searched for salamanders in forested areas and dry walls. Captured salamanders were sexed, weighed, photographed, measured and stomach flushed. Overall, we inspected the stomach contents of 67 individuals, recognizing 1,018 prey items belonging to 28 different prey categories. The examined population was mainly composed by generalist individuals, and no differences in number and diversity of prey consumed were observed among salamanders. Contrarily to what has been observed in other Speleomantes species, flying prey provided a minor contribution to the diet of the investigated population. Our study produced the first information on the diet of Speleomantes italicus from the Republic of San Marino, representing the starting point for future assessments on the dietary habits of this specific population.

Abstract Triple‐negative breast cancer (TNBC) often develops resistance to single‐agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro and in vivo. Mechanistically, LOXL2 interacts in the nucleus with the short isoform of BRD4 (BRD4S), MED1, and the cell cycle transcriptional regulator B‐MyB. These interactions sustain the formation of BRD4 and MED1 nuclear transcriptional foci and control cell cycle progression at the gene expression level. The pharmacological co‐inhibition of LOXL2 and BRD4 reduces BRD4 nuclear foci, BRD4‐MED1 colocalization, and the transcription of cell cycle genes, thus suppressing TNBC cell proliferation. Targeting the interaction between BRD4S and LOXL2 could be a starting point for the development of new anticancer strategies for the treatment of TNBC.

The Humboldt Archipelago, situated on Chile’s north-central coast, is renowned for its exceptional biodiversity. However, lizards of the Liolaemus genus are a particularly understudied group in this archipelago. Liolaemus genus is divided into two clades: chiliensis and nigromaculatus. Within the nigromaculatus clade the zapallarensis group is restricted to the semi-arid and arid coastal habitats of the Atacama Desert in north-central Chile. While it has been reported that lizards from the zapallarensis group inhabit various islands within the Humboldt Archipelago, there has been limited knowledge regarding their specific species identification. To identify the lizard species inhabiting these islands, we conducted phylogenetic analyses using a mitochondrial gene and examined morphological characteristics. Our findings reveal that lizards from the Damas, Choros, and Gaviota islands belong to Liolaemus silvai. In contrast, the lizards on Chañaral Island form a distinct and previously unrecognised group, clearly distinguishable from Liolaemus silvai. In conclusion, our study not only confirms the presence of L. silvai on the Damas, Choros, and Gaviota islands but also describes a new lizard species on Chañaral Island named Liolaemus carezzae sp. nov. These findings contribute valuable insights into the biodiversity of these islands and introduce a newly discovered endemic taxon to the region, enriching our understanding of Chile’s unique island ecosystems.

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods: Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from “strongly agree” to “strongly disagree”. Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as “strongly agree” to “agree” after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.

We here provide the first comprehensive analysis and discussion on prey consumed by the European cave salamanders of the genus Speleomantes. Our study stems from the need to shed light on the still unknown foraging behavior adopted by Speleomantes cave salamanders. Starting from the published datasets on gut contents from all Speleomantes species (including hybrids), we here discuss additional information (i.e., species ecology, lower taxonomic level), which were systematically omitted from those data sets. We analyzed a data set consisting of 17,630 records from 49 categories of consumed prey recognized from gut contents of 2060 adults and juveniles Speleomantes. Flying prey accounted for more than 58% of the prey items, while elongated crawling prey accounted for no more than 16% of the diet within a single population. Among the total recognized prey items, only three can be surely ascribed to the group of strictly-cave species (i.e., troglobites), meaning that European cave salamanders mostly forage in surface environment, and therefore represent one of the major drivers of allochthonous organic matter in subterranean environments. Some of the consumed prey seemed to be aquatic, allowing us to hypothesize whether Speleomantes are able to catch prey from a shallow body water. Furthermore, European cave salamanders possess the ability to prey upon taxa characterized by particular anti-predator defenses, while morphological constraints seem to be the most important limit to prey consumption. For each specific case, we provide insights and propose hypotheses concerning the foraging behavior that need to be tested to properly understand the foraging behavior of this cryptic salamanders.

The Consortium of Eosinophilic Gastrointestinal Diseases and the International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the recent 2018 Annual Meeting of the American Academy of Allergy, Asthma & Immunology, which was coupled for the first time with the World Allergy Organization meeting to create an international platform. The symposium featured experts in many facets of eosinophilic gastrointestinal diseases, including allergy, immunology, gastroenterology, pathology, and nutrition, and was a well-attended event. The basic science, genetics, cellular immunology, and clinical features of the diseases, with a focus on epithelial, eosinophil, and mast cell responses, as well as current and emerging treatment options, were reviewed. Here we briefly review some of the highlights of the material presented at the meeting.

The Consortium of Eosinophilic Gastrointestinal Diseases and the International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the recent 2018 Annual Meeting of the American Academy of Allergy, Asthma & Immunology, which was coupled for the first time with the World Allergy Organization meeting to create an international platform. The symposium featured experts in many facets of eosinophilic gastrointestinal diseases, including allergy, immunology, gastroenterology, pathology, and nutrition, and was a well-attended event. The basic science, genetics, cellular immunology, and clinical features of the diseases, with a focus on epithelial, eosinophil, and mast cell responses, as well as current and emerging treatment options, were reviewed. Here we briefly review some of the highlights of the material presented at the meeting.

Abstract Eosinophilic esophagitis (EoE) is a chronic clinical-pathologic disease characterized by eosinophilic infiltration of the esophageal epithelium with esophageal dysfunction symptoms. EoE can occur at any age and has different clinical manifestations depending on the age onset. To date, esophago-gastroduodenal endoscopy (EGD) with biopsy is the gold-standard for EoE diagnosis. According to the recent consensus guidelines, proton pump inhibitors, corticosteroids and elimination diets could be a first-line therapy option. The aim of the treatment is clinical and histological remission for preventing long-lasting untreatable fibrosis. A multidisciplinary approach (allergist, gastroenterology, dietitian, and pathologist) is recommended for managing patients affected by EoE, given the complexity of its treatment. This review will provide a practical guide to assist pediatricians treating children with EoE. Moreover, it highlights the unmet needs in diagnosis and treatment that require urgent attention from the scientific community in the aim of improving the management of patients with EoE.

In the last decades, the cultivation of quinoa and lupin became an important source of income for Andean farmers due to the demand for high nutrient-density foods from the Global North. The increase in the cultivation intensity caused by this exogenous demand led to the overexploitation of local ecosystems and a decrease in soil fertility. As an alternative to recover and improve soil quality, this work uses a pilot-scale auger pyrolysis reactor, implemented in the Andes, to assess the conversion of the agro residues generated in the post-harvesting processes of quinoa and lupin into biochar for soil amendment. Following the European Biochar Certificate guidelines, the pyrolyzed quinoa stems can be classified as biochar while the pyrolyzed quinoa husks can be classified as pyrogenic carbonaceous material. Both can be used for soil amendment considering their molar ratios (H/Corg, O/Corg) and carbon content. It was not possible to carbonize lupin stems and seedcases. Despite the altitude (2,632 m.a.s.l), the CO concentration during the carbonization of quinoa stems and husks were 1,024.4 and 559 mg/Nm3, this last, near the European eco-design standard of 500 mg/Nm3. A subsequent SWOT analysis showed the need to explore low-cost and low-complexity pyrolysis reactors that allow the decentralized conversion of agro residues at the farm-scale. The development of local standards to regulate the production and use of biochar is also essential to grant the safety of the processes, the quality of the products, and mobilize funds that allow implementation at relevant scales.

The assessment of working time recording practices and their impacts on the workers’ well-being, work-life balance and health is lacking in the scientific literature with only rare exceptions. Nevertheless, this issue is becoming increasingly important especially in Switzerland. Despite the fact that the Labour Law requires to record all working hours, some categories of workers are released from this legal obligation, in particular those who benefit from more autonomy and flexible working schedules. This paper assesses the potential risk that differentiated working time regimes can have on workers’ health. The analyses are based on a sample from eight companies that apply these legal exemptions. The main outcome is that long working hours represent the main health risk factor for workers that do not record all their working hours.

Food allergy affects approximately 2–4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.

Measurement(s) Gastric Content • Image Technology Type(s) light microscopy • Digital Photography Sample Characteristic - Organism Speleomantes • Hydromantes Sample Characteristic - Environment Subterranean • karst cave • mine Sample Characteristic - Location Italy • Region of Liguria • Municipality of Genova • Province of La Spezia Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14346176

BackgroundProtease resistance is considered a risk factor for allergenicity of proteins, although the correlation is low. It is nonetheless a part of the weight-of-evidence approach, proposed by Codex, for assessing the allergenicity risk of novel food proteins. Susceptibility of proteins to pepsin is commonly tested with purified protein in solution.ObjectiveFood proteins are rarely consumed in purified form. Our aim was to evaluate the impact of experimental and endogenous food matrices on protease susceptibility of homologous protein pairs with different degrees of allergenicity.MethodsPorcine and shrimp tropomyosin (ST) were subjected to sequential exposure to amylase, pepsin, and pancreatin in their respective endogenous matrix (pork tenderloin/boiled shrimp) and in three different experimental matrices (dessert mousse [DM], soy milk [SM], and chocolate bar [CB]). Digestion was monitored by immunoblotting using tropomyosin-specific antibodies. Recombinant peach and strawberry lipid transfer protein were biotinylated, spiked into both peach and strawberry fruit pulp, and subjected to the same sequential digestion protocol. Digestion was monitored by immunoblotting using streptavidin for detection.ResultsChocolate bar, and to a lesser extent SM, had a clear protective effect against pepsin digestion of porcine tropomyosin (PT) and to a lesser extent of ST. Increased resistance was associated with increased protein content. Spiking experiments with bovine serum albumin (BSA) confirmed the protective effect of a protein-rich matrix. The two tropomyosins were both highly resistant to pepsin in their protein-rich and lean native food matrix. Pancreatin digestion remained rapid and complete, independent of the matrix. The fat-rich environment did not transfer protection against pepsin digestion. Spiking of recombinant peach and strawberry lipid transfer proteins into peach and strawberry pulp did not reveal any differential protective effect that could explain differences in allergenicity of both fruits.ConclusionsProtein-rich food matrices delay pepsin digestion by saturating the protease. This effect is most apparent for proteins that are highly pepsin susceptible in solution. The inclusion of food matrices does not help in understanding why some proteins are strong primary sensitizers while homologs are very poor allergens. Although for induction of symptoms in food allergic patients (elicitation), a protein-rich food matrix that may contribute to increased risk, our results indicate that the inclusion of food matrices in the weight-of-evidence approach for estimating the potential risks of novel proteins to become allergens (sensitization), is most likely of very limited value.

In this study, we performed the first monitoring activities on one of the most endangered amphibians in Europe, the Sette Fratelli cave salamander Speleomantes sarrabusensis. The data presented here are derived from two monitoring activities aiming to assess the status and abundance of four populations of S. sarrabusensis. With the first monitoring, we surveyed the well-known population occurring within artificial springs during the period 2015–2018, providing monthly data on the number of active individuals. With the second monitoring performed during spring to early summer of 2022, we surveyed four populations at three time points (the one from artificial springs and three from forested areas) and we provided the first estimation of the populations’ abundance. Furthermore, we analyzed for the first time the stomach contents from a population of S. sarrabusensis only occurring in forested environments. With our study, we provided the first information on the abundance of different populations of S. sarrabusensis, representing the starting point for future status assessments for this endangered species.

The trophic niche is one of the most important ecological traits for any species, providing information about trophic position in the food web, habitat preferences, and interspecific interactions. In this study, we describe the autumn diet of two sympatric species of salamander from central Italy—Italian Cave Salamanders (Speleomantes italicus) and Fire Salamanders (Salamandra salamandra), assessing whether competition for the same prey occurs. Furthermore, we combine our data with those obtained for the same population during a different season (spring) and assess potential seasonal variation in the diet of these two salamander species. The overlap of the trophic niche between the two species was limited, with S. italicus consuming smaller and fast-moving prey (e.g., Diptera, Collembola), and S. salamandra consuming slow and often elongated prey (e.g., Gastropoda, Haplotaxida, Diplopoda). Seasonal differences in diet composition were observed in both species between spring and autumn; in autumn, both species narrowed their trophic niche breadth. This seasonal divergence is likely due to the variation of prey phenology and availability. The consumption of prey of different size was likely the main factor allowing the coexistence of these two salamander species. In both species we observed a general increase in the proportion of generalist individuals in autumn, most likely because of a reduction in prey availability. In addition to providing information on the trophic niche of these species, our study represented a further step that helps unravel the dynamics promoting the coexistence of potentially competing species. [ABSTRACT FROM AUTHOR]

In patients with 18q deletion syndrome (18q‐), immunodeficiency, autoimmunity, and allergies have been described in a subset. Pitt–Hopkins syndrome represents a specific subset of patients with 18q‐ who have a proximal deletion involving the TCF4 gene or a TCF4 variant. Immunodeficiency has been reported in the overall 18q‐ population; however, immunodeficiency with Pitt‐Hopkins syndrome has not been highlighted. This case report details the immunologic evaluations and the associated infections seen in a young adult with Pitt–Hopkins syndrome to underscore the challenges of managing adults with a complex phenotype who develop frequent infections. This patient with Pitt–Hopkins syndrome ultimately fulfilled the diagnostic criteria for common variable immunodeficiency. Immunoglobulin replacement has led to a somewhat improved infection pattern, although she continues to have aspiration events leading to pneumonia. This case highlights the clinical evolution of Pitt–Hopkins syndrome and serves as a reminder that immunodeficiency can occur in this syndrome. [ABSTRACT FROM AUTHOR]