El enigma de la enfermedad de Enrique IV, rey de Castilla: ¿padeció síndrome de McCune-Albright/displasia fibrosa? / The enigma of Henry IV's disease: Did he suffer from McCune-Albright syndrome/fibrous dysplasia?

Introducción: Enrique IV Rey de Castilla, último rey de la dinastía Trastámara, era hermano de Isabel la Católica. Se le conoce como «el impotente». Basándose en las descripciones previas de los historiadores y biógrafos, Gregorio Marañón en 1922 lo catalogó de «Displásico eunucoide con reacción acromegálica y con netos rasgos esquizoides». Métodos: En 1946 se realizó una inspección post mortem del cadáver momificado hallado en el Monasterio de Guadalupe. Se dejó constancia de un documento escrito y algunas fotografías. Hemos recogido los signos y síntomas descritos y aplicado la clasificación internacional de las enfermedades recomendada por la Organización mundial de la Salud, CIE11-2023. También nos hemos apoyado en las monedas emitidas en el monetario de Enrique IV, en las que hemos identificado aumento de la glándula tiroides. Resultados: Con los datos que están accesibles hasta este momento, sugerimos que Enrique IV padeció de forma altamente probable: displasia ósea facial y poliostótica, cifosis, cojera de una extremidad, alteraciones endocrinas múltiples, acromegalia con macrognatia, enfermedad nodular tiroidea, diaforesis maloliente, disfunción eréctil, hipospadias, desarrollo sexual anómalo, «pelvis feminoide», cólicos abdominales, oligodoncia y desplazamientos dentales. Es posible que también padeciera: pubertad precoz, litiasis renal con fosfaturia debilitante, túnel carpiano, trombocitopenia e hiperplasia o adenoma hipofisario productor de hormona de crecimiento. Conclusión: Sugerimos que Enrique IV pudo sufrir un síndrome de McCune-Albrigth asociado a Displasia fibrosa, una enfermedad rara debida a mutaciones activadoras de función en el gen GNAS.(AU)

Background: Henry IV King of Castile, last king of the Trastámara dynasty, was the brother of Isabella the Catholic. He is known as “the impotent”. Based on previous descriptions by historians and biographers, Gregorio Marañón in 1922 described him as “eunuchoid dysplastic with acromegalic reaction and clear schizoid features”. Methods: In 1946, a post-mortem inspection was carried out on the mummified corpse found in the Monastery of Guadalupe. A written document and some photographs were recorded. We have collected the signs and symptoms described and applied the international classification of diseases recommended by the World Health Organisation, ICD11-2023. We have relied on the coins issued in the money of Henry IV, on which we have identified enlargement of the thyroid gland. Results: With the data available at this time, we suggest that Henry IV most probably suffered from: facial and polyostotic bone dysplasia, kyphosis, limb limping, multiple endocrine disorders, acromegaly with macrognatia, nodular thyroid disease, malodorous diaphoresis, erectile dysfunction, hypospadias, abnormal sexual development, “feminoid pelvis”, abdominal colic, oligodontia and dental displacement. It is possible that he also suffered from: precocious puberty, renal lithiasis with debilitating phosphaturia, carpal tunnel, thrombopenia and growth hormone-producing pituitary hyperplasia or adenoma. Conclusion: We suggest that Henry IV may have suffered from McCune–Albrigth syndrome associated with fibrous dysplasia, a rare disease due to gain-of-function mutations in the GNAS gene.(AU)

[The enigma of Henry IV's disease: Did he suffer from McCune-Albright syndrome/fibrous dysplasia?] / El enigma de la enfermedad de Enrique IV, rey de Castilla: ¿padeció síndrome de McCune-Albright/displasia fibrosa?

BACKGROUND: Henry IV King of Castile, last king of the Trastámara dynasty, was the brother of Isabella the Catholic. He is known as "the impotent". Based on previous descriptions by historians and biographers, Gregorio Marañón in 1922 described him as "eunuchoid dysplastic with acromegalic reaction and clear schizoid features". METHODS: In 1946, a post-mortem inspection was carried out on the mummified corpse found in the Monastery of Guadalupe. A written document and some photographs were recorded. We have collected the signs and symptoms described and applied the international classification of diseases recommended by the World Health Organisation, ICD11-2023. We have relied on the coins issued in the money of Henry IV, on which we have identified enlargement of the thyroid gland. RESULTS: With the data available at this time, we suggest that Henry IV most probably suffered from: facial and polyostotic bone dysplasia, kyphosis, limb limping, multiple endocrine disorders, acromegaly with macrognatia, nodular thyroid disease, malodorous diaphoresis, erectile dysfunction, hypospadias, abnormal sexual development, "feminoid pelvis", abdominal colic, oligodontia and dental displacement. It is possible that he also suffered from: precocious puberty, renal lithiasis with debilitating phosphaturia, carpal tunnel, thrombopenia and growth hormone-producing pituitary hyperplasia or adenoma. CONCLUSION: We suggest that Henry IV may have suffered from McCune-Albrigth syndrome associated with fibrous dysplasia, a rare disease due to gain-of-function mutations in the GNAS gene.

EFAR-MMLA: An Evaluation Framework to Assess and Report Generalizability of Machine Learning Models in MMLA.

Multimodal Learning Analytics (MMLA) researchers are progressively employing machine learning (ML) techniques to develop predictive models to improve learning and teaching practices. These predictive models are often evaluated for their generalizability using methods from the ML domain, which do not take into account MMLA's educational nature. Furthermore, there is a lack of systematization in model evaluation in MMLA, which is also reflected in the heterogeneous reporting of the evaluation results. To overcome these issues, this paper proposes an evaluation framework to assess and report the generalizability of ML models in MMLA (EFAR-MMLA). To illustrate the usefulness of EFAR-MMLA, we present a case study with two datasets, each with audio and log data collected from a classroom during a collaborative learning session. In this case study, regression models are developed for collaboration quality and its sub-dimensions, and their generalizability is evaluated and reported. The framework helped us to systematically detect and report that the models achieved better performance when evaluated using hold-out or cross-validation but quickly degraded when evaluated across different student groups and learning contexts. The framework helps to open up a "wicked problem" in MMLA research that remains fuzzy (i.e., the generalizability of ML models), which is critical to both accumulating knowledge in the research community and demonstrating the practical relevance of these techniques.