Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa.

Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies, the endotypes of human RDEB are poorly understood.

Individuality Through Ecology: Rethinking the Evolution of Complex Life From an Externalist Perspective.

The evolution of complex life forms, exemplified by multicellular organisms, can be traced through a series of evolutionary transitions in individuality, beginning with the origin of life, followed by the emergence of the eukaryotic cell, and, among other transitions, culminating in the shift from unicellularity to multicellularity. Several attempts have been made to explain the origins of such transitions, many of which have been internalist (i.e.

Splice modulation strategy applied to deep intronic variants in causing recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and most often severe genetic disease characterized by recurrent blistering and erosions of the skin and mucous membranes after minor trauma, leading to major local and systemic complications. The disease is caused by loss-of-function variants in encoding type VII collagen (C7), the main component of anchoring fibrils, which form attachment structures stabilizing the cutaneous basement membrane zone. Alterations in C7 protein structure and/or expression lead to abnormal, rare or absent anchoring fibrils resulting in loss of dermal-epidermal adherence and skin blistering.

Context Matters: A Response to Autzen and Okasha's Reply to Takacs and Bourrat.

In a recent reply to Takacs and Bourrat's article (Biol Philos 37:12, 2022), Autzen and Okasha (Biol Philos 37:37, 2022) question our characterization of the relationship between the geometric mean and arithmetic mean measures of fitness. We here take issue with the claim that our characterization falls prey to the mistakes they highlight. Briefly revisiting what Takacs and Bourrat (Biol Philos 37:12, 2022) accomplished reveals that the key issue of difference concerns cases of deterministic but nonconstant growth.

Evolvability: filling the explanatory gap between adaptedness and the long-term mathematical conception of fitness.

The new foundation for the propensity interpretation of fitness (PIF), developed by Pence and Ramsey (Br J Philos Sci 64:851-881, 2013), describes fitness as a probability distribution that encompasses all possible daughter populations to which the organism may give rise, including daughter populations in which traits might change and the possible environments that members of the daughter populations might encounter. This long-term definition of fitness is general enough to avoid counterexamples faced by previous mathematical conceptions of PIF. However, there seem to be downsides to its generality: the ecological role of fitness involves describing the degree of adaptedness between an organism and the specific environment it inhabits.

Citrullinated Histone H3, a Marker for Neutrophil Extracellular Traps, Is Associated with Poor Prognosis in Cutaneous Squamous Cell Carcinoma Developing in Patients with Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients.

Clinical vs. molecular diagnosis of Gorlin syndrome: relevance of diagnostic criteria depends on the age of the patients.

Background: Gorlin syndrome (GS) is an autosomal dominant disorder characterized by a predisposition to basal cell carcinoma and developmental defects. It is caused by pathogenic variants in the PTCH1 or SUFU genes.

Objectives: To ascertain the effectiveness of molecular screening in a cohort of patients with a suspicion of GS and to describe the patients' clinical and genetic characteristics.

ECFS standards of care on CFTR-related disorders: Identification and care of the disorders.

This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided.

Cerebral dural arteriovenous fistulas in patients with PTEN-related hamartoma tumor syndrome.

Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN-related hamartoma tumor syndrome (PHTS). However, PHTS-associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available.

Effectiveness of topical sodium thiosulfate for ectopic calcifications and ossifications. Results of the CATSS-O study.

Introduction: Ectopic calcifications (ECs) and heterotopic ossifications (HOs) form in non-mineralized tissues, most often in subcutaneous and muscular areas. Local and systemic complications can cause severe disability. Systemic administration of sodium thiosulfate (STS) gives promising results but is difficult to use in clinical practice.

[Cutaneous squamous cell carcinomas in EBDR: how can they be detected?].

The occurrence of cutaneous squamous cell carcinoma is a frequent and potentially serious complication in people with recessive dystrophic epidermolysis bullosa and junctional epidermolysis bullosa with chronic leg sores. Early diagnosis of early-stage carcinomas enables limited surgical excision and rapid healing without sequelae. Screening during skin care of patients at risk is therefore of major interest, and any atypical lesion should be shown to a doctor specializing in the disease and biopsied at the slightest doubt, preferably in an expert center for the disease.

[Growing up with an EBH, an example of pediatric-adult transition in the field of rare diseases].

The transition from pediatrics to adult wards concerns all chronic diseases with a pediatric onset, but there are a number of specific features in the case of severe forms of hereditary epidermolysis bullosa: worsening wound surface and chronicity with age, appearance or increase in certain complications (carcinological, renal, nutritional, dental), sometimes difficult therapeutic choices, sometimes life-threatening prognosis. But one of the major problems limiting the patient's autonomy is the difficulty of finding a paramedic to take over skin care, often provided from birth by a parent who has become a caregiver through necessity.

Paradoxical inflammatory blepharitis in a patient with Crohn's disease.

We report the case of a 15-year-old boy with severe inflammatory blepharitis who was being treated with a TNFα inhibitor for Crohn's disease (CD). This case shows the potential utility of a skin biopsy in distinguishing metastatic CD associated with granulomatous blepharitis from a paradoxical blepharitis induced by anti-TNFα. It also demonstrates that ustekinumab can be considered in patients with CD who cannot tolerate TNFα inhibitors because of cutaneous paradoxical reactions.

When local causes are more explanatorily useful.

Madole & Harden plead for better integration of causal knowledge of different depths to understand complex human traits. Classically, local causes - a particular type of shallow causes - are considered less useful than more generalisable causes, giving a false impression that the latter causes are more useful and desirable. Using a simple example, I show that sometimes the contrary is true.