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1.
Gastroenterology ; 166(1): 155-167.e2, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37832924

RESUMEN

BACKGROUND & AIMS: Endoscopic assessment of ulcerative colitis (UC) typically reports only the maximum severity observed. Computer vision methods may better quantify mucosal injury detail, which varies among patients. METHODS: Endoscopic video from the UNIFI clinical trial (A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis) comparing ustekinumab and placebo for UC were processed in a computer vision analysis that spatially mapped Mayo Endoscopic Score (MES) to generate the Cumulative Disease Score (CDS). CDS was compared with the MES for differentiating ustekinumab vs placebo treatment response and agreement with symptomatic remission at week 44. Statistical power, effect, and estimated sample sizes for detecting endoscopic differences between treatments were calculated using both CDS and MES measures. Endoscopic video from a separate phase 2 clinical trial replication cohort was performed for validation of CDS performance. RESULTS: Among 748 induction and 348 maintenance patients, CDS was lower in ustekinumab vs placebo users at week 8 (141.9 vs 184.3; P < .0001) and week 44 (78.2 vs 151.5; P < .0001). CDS was correlated with the MES (P < .0001) and all clinical components of the partial Mayo score (P < .0001). Stratification by pretreatment CDS revealed ustekinumab was more effective than placebo (P < .0001) with increasing effect in severe vs mild disease (-85.0 vs -55.4; P < .0001). Compared with the MES, CDS was more sensitive to change, requiring 50% fewer participants to demonstrate endoscopic differences between ustekinumab and placebo (Hedges' g = 0.743 vs 0.460). CDS performance in the JAK-UC replication cohort was similar to UNIFI. CONCLUSIONS: As an automated and quantitative measure of global endoscopic disease severity, the CDS offers artificial intelligence enhancement of traditional MES capability to better evaluate UC in clinical trials and potentially practice.


Asunto(s)
Colitis Ulcerosa , Humanos , Inteligencia Artificial , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Colonoscopía/métodos , Computadores , Inducción de Remisión , Índice de Severidad de la Enfermedad , Ustekinumab/efectos adversos
2.
Diagnostics (Basel) ; 13(9)2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37175031

RESUMEN

Traumatic brain injury (TBI) is one of the major causes of disability and mortality worldwide. Rapid and precise clinical assessment and decision-making are essential to improve the outcome and the resulting complications. Due to the size and complexity of the data analyzed in TBI cases, computer-aided data processing, analysis, and decision support systems could play an important role. However, developing such systems is challenging due to the heterogeneity of symptoms, varying data quality caused by different spatio-temporal resolutions, and the inherent noise associated with image and signal acquisition. The purpose of this article is to review current advances in developing artificial intelligence-based decision support systems for the diagnosis, severity assessment, and long-term prognosis of TBI complications.

3.
Mol Endocrinol ; 29(2): 187-99, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25489906

RESUMEN

Dmrt transcription factors control sex determination or sex-specific differentiation across all invertebrate and vertebrate species, in which they have been studied so far. In addition to important functions in the reproductive system, also nongonadal roles have been assigned to several dmrt family members. One example is dmrt5, which was shown to guide neurogenesis in the forebrain of some vertebrates including fish. Here we show that in zebrafish, dmrt5 is also expressed adjacent to the pituitary anlage and later in the anterior pars distalis in which it organizes differentiation of endocrine cells. We find that pituitary induction, cell survival, proliferation, and early lineage specification in the pituitary is independent of dmrt5. Instead, dmrt5 is required for terminal differentiation of corticotropes and gonadotropes. Gene knockdown and mutant analysis revealed that dmrt5 promotes corticotrope differentiation via tbx19 expression, whereas it prevents gonadotrope differentiation in the anterior pars distalis. In dmrt5 morphants and mutants, reduced corticotrope numbers may result in irregular positioning and reduced maintenance of lactotropes. In conclusion, our study establishes a novel function for dmrt5 for cell differentiation in the anterior pituitary. Intriguingly, its effect on gonadotrope numbers defines a first nongonadal role for a dmrt family member that appears crucial for the activity of the reproductive system.


Asunto(s)
Diferenciación Celular , Corticotrofos/citología , Corticotrofos/metabolismo , Gonadotrofos/citología , Gonadotrofos/metabolismo , Factores de Transcripción/metabolismo , Proteínas de Pez Cebra/metabolismo , Pez Cebra/metabolismo , Animales , Apoptosis , Linaje de la Célula , Embrión no Mamífero/metabolismo , Regulación del Desarrollo de la Expresión Génica , Técnicas de Silenciamiento del Gen , Hipotálamo/embriología , Modelos Biológicos , Mutación/genética , Células Madre/citología , Proteína p53 Supresora de Tumor/metabolismo , Pez Cebra/embriología , Pez Cebra/genética
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