Artificial intelligence in endocrinology: a comprehensive review.

BACKGROUND AND AIM: Artificial intelligence (AI) has emerged as a promising technology in the field of endocrinology, offering significant potential to revolutionize the diagnosis, treatment, and management of endocrine disorders. This comprehensive review aims to provide a concise overview of the current landscape of AI applications in endocrinology and metabolism, focusing on the fundamental concepts of AI, including machine learning algorithms and deep learning models. METHODS: The review explores various areas of endocrinology where AI has demonstrated its value, encompassing screening and diagnosis, risk prediction, translational research, and "pre-emptive medicine". Within each domain, relevant studies are discussed, offering insights into the methodology and main findings of AI in the treatment of different pathologies, such as diabetes mellitus and related disorders, thyroid disorders, adrenal tumors, and bone and mineral disorders. RESULTS: Collectively, these studies show the valuable contributions of AI in optimizing healthcare outcomes and unveiling new understandings of the intricate mechanisms underlying endocrine disorders. Furthermore, AI-driven approaches facilitate the development of precision medicine strategies, enabling tailored interventions for patients based on their individual characteristics and needs. CONCLUSIONS: By embracing AI in endocrinology, a future can be envisioned where medical professionals and AI systems synergistically collaborate, ultimately enhancing the lives of individuals affected by endocrine disorders.

The transrepression arm of glucocorticoid receptor signaling is protective in mutant huntingtin-mediated neurodegeneration.

The unfolded protein response (UPR) occurs following the accumulation of unfolded proteins in the endoplasmic reticulum (ER) and orchestrates an intricate balance between its prosurvival and apoptotic arms to restore cellular homeostasis and integrity. However, in certain neurodegenerative diseases, the apoptotic arm of the UPR is enhanced, resulting in excessive neuronal cell death and disease progression, both of which can be overcome by modulating the UPR. Here, we describe a novel crosstalk between glucocorticoid receptor signaling and the apoptotic arm of the UPR, thus highlighting the potential of glucocorticoid therapy in treating neurodegenerative diseases. Several glucocorticoids, but not mineralocorticoids, selectively antagonize ER stress-induced apoptosis in a manner that is downstream of and/or independent of the conventional UPR pathways. Using GRT10, a novel selective pharmacological modulator of glucocorticoid signaling, we describe the importance of the transrepression arm of the glucocorticoid signaling pathway in protection against ER stress-induced apoptosis. Furthermore, we also observe the protective effects of glucocorticoids in vivo in a Drosophila model of Huntington's disease (HD), wherein treatment with different glucocorticoids diminished rhabdomere loss and conferred neuroprotection. Finally, we find that growth differentiation factor 15 has an important role downstream of glucocorticoid signaling in antagonizing ER stress-induced apoptosis in cells, as well as in preventing HD-mediated neurodegeneration in flies. Thus, our studies demonstrate that this novel crosstalk has the potential to be effectively exploited in alleviating several neurodegenerative disorders.

Giant pleomorphic adenoma of the parotid gland: an unusual case presentation and literature review.

Pleomorphic adenoma is the most common type of all salivary gland tumours. Although uncommon, cases of giant pleomorphic adenomas have been described in the medical literature, the majority involving the parotid gland. This paper describes an unusual case of a giant adenoma arising in the parotid gland. The patient underwent surgical resection of the giant tumour, which was one of the largest pleomorphic adenoma reported in recent literature. This case has prompted us to evaluate the behaviour of those benign tumours, which suggested that aesthetic and social morbidity is sufficient to justify, when possible, early tumour excision, despite the relatively low risk of malignant transformation. Management of this unusual tumour is discussed, and the literature on giant parotid tumours is reviewed.

DJ-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of Parkinson's disease.

Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by the loss of neurons in the substantia nigra pars compacta and the presence of Lewy bodies in surviving neurons. These intracellular protein inclusions are primarily composed of misfolded α-synuclein (aSyn), which has also been genetically linked to familial and sporadic forms of PD. DJ-1 is a small ubiquitously expressed protein implicated in several pathways associated with PD pathogenesis. Although mutations in the gene encoding DJ-1 lead to familial early-onset PD, the exact mechanisms responsible for its role in PD pathogenesis are still elusive. Previous work has found that DJ-1--which has protein chaperone-like activity--modulates aSyn aggregation. Here, we investigated possible physical interactions between aSyn and DJ-1 and any consequent functional and pathological relevance. We found that DJ-1 interacts directly with aSyn monomers and oligomers in vitro, and that this also occurs in living cells. Notably, several PD-causing mutations in DJ-1 constrain this interaction. In addition, we found that overexpression of DJ-1 reduces aSyn dimerization, whereas mutant forms of DJ-1 impair this process. Finally, we found that human DJ-1 as well as yeast orthologs of DJ-1 reversed aSyn-dependent cellular toxicity in Saccharomyces cerevisiae. Taken together, these data suggest that direct interactions between DJ-1 and aSyn constitute the basis for a neuroprotective mechanism and that familial mutations in DJ-1 may contribute to PD by disrupting these interactions.

Dendritic spine loss and neurodegeneration is rescued by Rab11 in models of Huntington's disease.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by expansion of a polyglutamine tract in the huntingtin protein (htt) that mediates formation of intracellular protein aggregates. In the brains of HD patients and HD transgenic mice, accumulation of protein aggregates has been causally linked to lesions in axo-dendritic and synaptic compartments. Here we show that dendritic spines - sites of synaptogenesis - are lost in the proximity of htt aggregates because of functional defects in local endosomal recycling mediated by the Rab11 protein. Impaired exit from recycling endosomes (RE) and association of endocytosed protein with intracellular structures containing htt aggregates was demonstrated in cultured hippocampal neurons cells expressing a mutant htt fragment. Dendrites in hippocampal neurons became dystrophic around enlarged amphisome-like structures positive for Rab11, LC3 and mutant htt aggregates. Furthermore, Rab11 overexpression rescues neurodegeneration and dramatically extends lifespan in a Drosophila model of HD. Our findings are consistent with the model that mutant htt aggregation increases local autophagic activity, thereby sequestering Rab11 and diverting spine-forming cargo from RE into enlarged amphisomes. This mechanism may contribute to the toxicity caused by protein misfolding found in a number of neurodegenerative diseases.

JUST in time health emergency interventions: an innovative approach to training the citizen for emergency situations using virtual reality techniques and advanced IT tools (the Web-CD).

This paper reports the results of the first of the two systems developed by JUST, a collaborative project supported by the European Union under the Information Society Technologies (IST) Programme. The most innovative content of the project has been the design and development of a complementary training course for non-professional health emergency operators, which supports the traditional learning phase, and which purports to improve the retention capability of the trainees. This was achieved with the use of advanced information technology techniques, which provide adequate support and can help to overcome the present weaknesses of the existing training mechanisms.

MSY2 and MSY4 bind a conserved sequence in the 3' untranslated region of protamine 1 mRNA in vitro and in vivo.

Y-box proteins are major constituents of ribonucleoprotein particles (RNPs) which contain translationally silent mRNAs in gametic cells. We have recently shown that a sequence-specific RNA binding activity present in spermatogenic cells contains the two Y-box proteins MSY2 and MSY4. We show here that MSY2 and MSY4 bind a sequence, 5'-UCCAUCA-3', present in the 3' untranslated region of the translationally repressed protamine 1 (Prm1) mRNA. Using pre- and post-RNase T1-digested substrate RNAs, it was determined that MSY2 and MSY4 can bind an RNA of eight nucleotides containing the MSY2 and MSY4 binding site. Single nucleotide mutations in the sequence eliminated the binding of MSY2 and MSY4 in an electrophoretic mobility shift assay, and the resulting mutants failed to compete for binding in a competition assay. A consensus site of U(AC)C(A)CAU(C)CA(CU) (subscripts indicate nucleotides which do not disrupt YRS binding by MSY2 and MSY4), denoted the Y-box recognition site (YRS), was defined from this mutational analysis. These mutations in the YRS were further characterized in vivo using a novel application of the yeast three-hybrid system. Experiments with transgenic mice show that disruption of the YRS in vivo relieves Prm1-like repression of a reporter gene. The conservation of the RNA binding motifs among Y-box protein family members raises the possibility that other Y-box proteins may have previously unrecognized sequence-specific RNA binding activities.

FOG-2, a novel F-box containing protein, associates with the GLD-1 RNA binding protein and directs male sex determination in the C. elegans hermaphrodite germline.

Male sex determination in the Caenorhabditis elegans hermaphrodite germline requires translational repression of tra-2 mRNA by the GLD-1 RNA binding protein. We cloned fog-2 by finding that its gene product physically interacts with GLD-1, forming a FOG-2/GLD-1/tra-2 3'untranslated region ternary complex. FOG-2 has an N-terminal F-box and a novel C-terminal domain called FTH. Canonical F-box proteins act as bridging components of the SCF ubiquitin ligase complex; the N-terminal F-box binds a Skp1 homolog, recruiting ubiquination machinery, while a C-terminal protein-protein interaction domain binds a specific substrate for degradation. However, since both fog-2 and gld-1 are necessary for spermatogenesis, FOG-2 cannot target GLD-1 for ubiquitin-mediated degradation. We propose that FOG-2 also acts as a bridge, bringing GLD-1 bound to tra-2 mRNA into a multiprotein translational repression complex, thus representing a novel function for an F-box protein. fog-2 is a member of a large, apparently rapidly evolving, C. elegans gene family that has expanded, in part, by local duplications; fog-2 related genes have not been found outside nematodes. fog-2 may have arisen during evolution of self-fertile hermaphroditism from an ancestral female/male species.

A sequence-specific RNA binding complex expressed in murine germ cells contains MSY2 and MSY4.

The protamine mRNAs are stored for up to 8 days as translationally repressed ribonucleoprotein particles during murine spermatogenesis. Translational repression of the protamine 1, Prm1, mRNA is controlled by sequences in its 3'-untranslated region (UTR). In this study we used the yeast three-hybrid system to clone Msy4, which encodes a novel member of the Y box family of nucleic acid binding proteins. MSY4 specifically binds to a site within the 5' most 37 nucleotides in the Prm1 3' UTR. Msy4 is highly expressed in the testis, and the protein is detected in the cytoplasm of germ cells in both the testis and the ovary, where repressed messages are stored. Analysis of a previously described 48/50-kDa binding activity in testis extracts by electrophoretic mobility shift assays and immunoprecipitation indicates the activity is composed of MSY4 and MSY2, another mouse Y box protein. Polysome analysis demonstrates MSY4 is associated with mRNPs, consistent with MSY4 having a role in storing repressed messages.

[Amniotic band syndrome. Clinico-therapeutic considerations on 3 cases]. / Sindrome da briglie amniotiche. Considerazioni clinico-terapeutiche su tre casi.

In three patients with "Congenital Annular Constricting Bands Syndrome" the monstrous leg and foot lymphedemas were aesthetically and functionally cured using the two-stage Ombredanne's crown-like operation. Plaster splints were useful in curing and consolidating the tibia and fibula pseudoarthrosis present in one case and in curing the clubfeet present in the other two cases. Some consideration is made to the different etiopathogenetic theories, proposed in the past and recently, to explain this syndrome.

[A case of lateral cleft lip. Embryology and surgical technic]. / Un caso di schisi laterale del labbro. Embriologia e tecnica chirurgica.

Lateral labial cleft is exceptionally rare. This malformation gives the opportunity to evaluate its origin (following the embryology of facial segments) and its association with other deformities. Surgical treatment must reconstruct an anatomic and functional situation which must give a good aestetic result.

[Treatment with Soave's technic and long-term results in 270 cases of Hirschsprung disease]. / Tratamiento y resultados a largo plazo de 270 casos de enfermedad de Hirschsprung con la técnica de Soave.

The authors present the surgical technique for the correction of Hirschsprung disease following SOAVE's original description. A series of 270 cases observed in 20 years at the Pediatric Surgery Department of the "Instituto Giannina Gaslini" in Genova, Italy, are examined. These cases, all treated by surgery, were followed up in long term for more than one year both clinically and radiologically. Additionally 73 cases treated from 1977 on were also followed up with the aid of ano-rectal electro-manometry. The most recent diagnostic aspects are discussed, such as ano-manometry, and some conclusions are drawn about long term results.