Impact of benzo[a]pyrene, PCB153 and sex hormones on human ESC-Derived thyroid follicles using single cell transcriptomics.

Introduction: Endocrine disruptors are compounds of manmade origin able to interfere with the endocrine system and constitute an important environmental concern. Indeed, detrimental effects on thyroid physiology and functioning have been described. Differences exist in the susceptibility of human sexes to the incidence of thyroid disorders, like autoimmune diseases or cancer.

A Modular Microfluidic Organoid Platform Using LEGO-Like Bricks.

The convergence of organoid and organ-on-a-chip (OoC) technologies is urgently needed to overcome limitations of current 3D in vitro models. However, integrating organoids in standard OoCs faces several technical challenges, as it is typically laborious, lacks flexibility, and often results in even more complex and less-efficient cell culture protocols. Therefore, specifically adapted and more flexible microfluidic platforms need to be developed to facilitate the incorporation of complex 3D in vitro models.

Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids.

Thyroid cancer is the most common endocrine malignancy and several genetic events have been described to promote the development of thyroid carcinogenesis. Besides the effects of specific mutations on thyroid cancer development, the molecular mechanisms controlling tumorigenesis, tumor behavior, and drug resistance are still largely unknown. Cancer organoids have been proposed as a powerful tool to study aspects related to tumor development and progression and appear promising to test individual responses to therapies.

Investigation of the effects of phthalates on thyroid models with RNA-Seq and ATAC-Seq.

Introduction: Phthalates are a class of endocrine-disrupting chemicals that have been shown to negatively correlate with thyroid hormone serum levels in humans and to cause a state of hyperactivity in the thyroid. However, their mechanism of action is not well described at the molecular level.

Methods: We analyzed the response of mouse thyroid organoids to the exposure to a biologically relevant dose range of the phthalates bis(2-ethylhexyl) phthalate (DEHP), di-iso-decylphthalate (DIDP), di-iso-nonylphthalate (DINP), and di-n-octylphthalate (DnOP) for 24 h and simultaneously analyzed mRNA and miRNA expression via RNA sequencing.

Progress Toward and Challenges Remaining for Thyroid Tissue Regeneration.

Thyroid hormones play a pivotal role in diverse physiological processes, and insufficient synthesis of these hormones results in hypothyroidism, a prevalent disorder with a significant global impact. Research has shown that the residual thyroid tissue following surgery fails to fully regenerate the gland and restore normal function. The slow turnover rate of the thyroid gland and the presence of resident stem cells, which may contribute to regeneration within adult thyroid tissue, are topics of ongoing debate.

Pediatric pulmonary arterial hypertension due to a novel homozygous GDF2 missense variant affecting BMP9 processing and activity.

Pulmonary arterial hypertension (PAH) is a rare and severe disorder characterized by progressive pulmonary vasculopathy. Growth differentiation factor (GDF)2 encodes the pro-protein bone morphogenetic protein (BMP) 9, activated after cleavage by endoproteases into an active mature form. BMP9, together with BMP10, are high-affinity ligands of activin receptor-like kinase 1 (ALK1) and BMP receptor type II (BMPR2).

The neonatal DAV-expert algorithm: a GAVeCeLT/GAVePed consensus for the choice of the most appropriate venous access in newborns.

In most NICUs, the choice of the venous access device currently relies upon the operator's experience and preferences. However, considering the high failure rate of vascular devices in the neonatal population, such clinical choice has a critical relevance and should preferably be based on the best available evidence. Though some algorithms have been published over the last 5 years, none of them seems in line with the current scientific evidence.

Thyroid-on-a-Chip: An Organoid Platform for In Vitro Assessment of Endocrine Disruption.

Thyroid is a glandular tissue in the human body in which the function can be severely affected by endocrine disrupting chemicals (EDCs). Current in vitro assays to test endocrine disruption by chemical compounds are largely based on 2D thyroid cell cultures, which often fail to precisely evaluate the safety of these compounds. New and more advanced 3D cell culture systems are urgently needed to better recapitulate the thyroid follicular architecture and functions and help to improve the predictive power of such assays.

CODA: a combo-Seq data analysis workflow.

The analysis of the combined mRNA and miRNA content of a biological sample can be of interest for answering several research questions, like biomarkers discovery, or mRNA-miRNA interactions. However, the process is costly and time-consuming, separate libraries need to be prepared and sequenced on different flowcells. Combo-Seq is a library prep kit that allows us to prepare combined mRNA-miRNA libraries starting from very low total RNA.

Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism.

The thyroid gland captures iodide in order to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism, which is one of the most common disorder in humans and is not always satisfactorily treated by lifelong hormone replacement. Therefore, in addition to the lack of in vitro tractable models to study human thyroid development, differentiation and maturation, functional human thyroid organoids could pave the way to explore new therapeutic approaches.

Long peripheral catheters in neonates: filling the gap between short peripheral catheters and epicutaneous-caval catheters?

Introduction: Non-critically ill neonates at times require venous access to provide peripherally compatible infusions for a limited period (more than 3 days). In such a situation, short peripheral cannulas are not appropriate as their average duration is about 2 days, while-on the other hand-epicutaneous-caval catheters may be too invasive. In these patients, insertion of long peripheral cannulas may be an effective option.

Single-Cell Trajectory Inference Guided Enhancement of Thyroid Maturation Using TGF-Beta Inhibition.

The thyroid gland regulates metabolism and growth secretion of thyroid hormones by thyroid follicular cells (TFCs). Loss of TFCs, by cellular dysfunction, autoimmune destruction or surgical resection, underlies hypothyroidism. Recovery of thyroid hormone levels by transplantation of mature TFCs derived from stem cells holds great therapeutic promise.

The BRAF mutation analysis and risk stratification in papillary thyroid carcinoma.

Objective: Although the prognostic role of BRAF mutation in papillary thyroid carcinoma (PTC) is controversial, the American Thyroid Association (ATA) includes the mutational status in their risk stratification system. To evaluate the impact of the BRAF mutation status on PTC risk stratification.

Methods: PTC patients attending a university-based hospital who had the analysis of the BRAF mutation were included.

Subcutaneously Anchored Sutureless Device for Securement of Chest Tubes in Neonates with Pleural Effusion: Three Case Reports.

We report the clinical cases of three neonates, all of them premature, requiring the placement of a chest tube for drainage of a massive pleural effusion. In all three patients, the chest tube was secured using a new subcutaneously anchored sutureless system. This new securement device was easy to insert and to remove, and highly effective in preventing dislodgment.

Field-induced glassy state in disordered cluster antiferromagnets.

We investigate the role of antiferromagnetic spin clusters on the glassiness induced by uniform and random fields. We consider an antiferromagnetic disordered model that is treated within the replica method, resulting in an effective single-cluster problem. Our results show that regimes of weak and intermediate disorder are suitable for highly unusual phenomena.

Current concepts and challenges to unravel the role of iodothyronine deiodinases in human neoplasias.

Thyroid hormones (THs) are essential for the regulation of several metabolic processes and the energy consumption of the organism. Their action is exerted primarily through interaction with nuclear receptors controlling the transcription of thyroid hormone-responsive genes. Proper regulation of TH levels in different tissues is extremely important for the equilibrium between normal cellular proliferation and differentiation.

Association between PCOS and autoimmune thyroid disease: a systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder affecting women of reproductive age. PCOS has been associated with distinct metabolic and cardiovascular diseases and with autoimmune conditions, predominantly autoimmune thyroid disease (AITD). AITD has been reported in 18-40% of PCOS women, depending on PCOS diagnostic criteria and ethnicity.

Global DNA methylation profile in medullary thyroid cancer patients.

Background: Changes in global DNA methylation have been suggested to cause genomic instability leading to increased risk of cancer. The accumulation of epigenetic changes is believed to contribute to tumorigenesis and dedifferentiation, but the effects of such changes in thyroid cancer are still yet defined.

Objective: To evaluate the global DNA methylation levels in thyroid cancer patients.

Role of thyroid hormones in the neoplastic process: an overview.

Thyroid hormones (TH) are critical regulators of several physiological processes, which include development, differentiation and growth in virtually all tissues. In past decades, several studies have shown that changes in TH levels caused by thyroid dysfunction, disruption of deiodinases and/or thyroid hormone receptor (TR) expression in tumor cells, influence cell proliferation, differentiation, survival and invasion in a variety of neoplasms in a cell type-specific manner. The function of THs and TRs in neoplastic cell proliferation involves complex mechanisms that seem to be cell specific, exerting effects via genomic and nongenomic pathways, repressing or stimulating transcription factors, influencing angiogenesis and promoting invasiveness.

Generation of Functional Thyroid Tissue Using 3D-Based Culture of Embryonic Stem Cells.

During the last decade three-dimensional (3D) cultures of pluripotent stem cells have been intensively used to understand morphogenesis and molecular signaling important for the embryonic development of many tissues. In addition, pluripotent stem cells have been shown to be a valid tool for the in vitro modeling of several congenital or chronic human diseases, opening new possibilities to study their physiopathology without using animal models. Even more interestingly, 3D culture has proved to be a powerful and versatile tool to successfully generate functional tissues ex vivo.

Effect of 3'UTR RET Variants on RET mRNA Secondary Structure and Disease Presentation in Medullary Thyroid Carcinoma.

Background: The RET S836S variant has been associated with early onset and increased risk for metastatic disease in medullary thyroid carcinoma (MTC). However, the mechanism by which this variant modulates MTC pathogenesis is still open to discuss. Of interest, strong linkage disequilibrium (LD) between RET S836S and 3'UTR variants has been reported in Hirschsprung's disease patients.

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma.

Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC.

Role of VEGF-A and its receptors in sporadic and MEN2-associated pheochromocytoma.

Pheochromocytoma (PHEO), a rare catecholamine producing tumor arising from the chromaffin cells, may occurs sporadically (76%-80%) or as part of inherited syndromes (20%-24%). Angiogenesis is a fundamental step in tumor proliferation and vascular endothelial growth factor (VEGF-A) is the most well-characterized angiogenic factor. The role of angiogenic markers in PHEO is not fully understood; investigations were therefore made to evaluate the expression of VEGF-A and its receptors in PHEO and correlate to clinical parameters.

Role of RET genetic variants in MEN2-associated pheochromocytoma.

Background: RET polymorphisms have been involved in the clinical presentation and prognosis of multiple endocrine neoplasia type 2 (MEN2)-associated medullary thyroid carcinoma.

Objective: To investigate the effect of RET variants on the penetrance of pheochromocytoma (PHEO) in MEN2 patients.

Methods: The RET variants L769L, S836S, and G691S/S904S were evaluated in a cohort of 153 MEN2 patients attending a tertiary teaching hospital.