Patient-Derived Papillary Thyroid Cancer Organoids for Radioactive Iodine Refractory Screening

Simple Summary Over the past three decades, the incidence of thyroid cancer has been rising, with 90% being the well-differentiated thyroid cancer subtype. After diagnosis and surgical removal of the thyroid gland, radioactive iodine is administered to induce a localized post-operative radiation treatment. However, in 15-33% of papillary thyroid cancer cases, the cells are unable to take up radioactive iodine, resulting in an ineffective treatment which sometimes has severe side effects. Pre-treatment diagnosis of non-responding patients would prevent ineffective and toxic iodine treatment. Therefore, in this study, we developed a patient-derived papillary thyroid cancer organoid model. Patient-derived organoids responding or not responding to radioactive iodine clearly resembled the tumor of origin, but showed clear differences in sodium/iodide symporter expression. Our results indicate that thyroid cancer organoids might be a suitable tool for the early diagnosis of non-responding patients, in order to eventually reduce radioactive iodine overtreatment and its many side effects for thyroid cancer patients. Patients with well-differentiated thyroid cancer, especially papillary thyroid cancer (PTC), are treated with surgical resection of the thyroid gland. This is followed by post-operative radioactive iodine (I-131), resulting in total thyroid ablation. Unfortunately, about 15-33% of PTC patients are unable to take up I-131, limiting further treatment options. The aim of our study was to develop a cancer organoid model with the potential for pre-treatment diagnosis of these I-131-resistant patients. PTC tissue from thirteen patients was used to establish a long-term organoid model. These organoids showed a self-renewal potential for at least five passages, suggesting the presence of cancer stem cells. We demonstrated that thyroid specific markers, a PTC marker, and transporters/receptors necessary for iodine uptake and thyroid hormone production were expressed on a gene and protein level. Additionally, we cultured organoids from I-131-resistant PTC material from three patients. When comparing PTC organoids to radioactive iodine (RAI)-refractory disease (RAIRD) organoids, a substantial discordance on both a protein and gene expression level was observed, indicating a treatment prediction potential. We showed that patient-derived PTC organoids recapitulate PTC tissue and a RAIRD phenotype. Patient-specific PTC organoids may enable the early identification of I-131-resistant patients, in order to reduce RAI overtreatment and its many side effects for thyroid cancer patients

HIV-related travel restrictions: trends and country characteristics

Introduction: Increasingly, HIV-seropositive individuals cross international borders. HIV-related restrictions on entry, stay, and residence imposed by countries have important consequences for this mobile population. Our aim was to describe the geographical distribution of countries with travel restrictions and to examine the trends and characteristics of countries with such restrictions. Methods: In 2011, data presented to UNAIDS were used to establish a list of countries with and without HIV restrictions on entry, stay, and residence and to describe their geographical distribution. The following indicators were investigated to describe the country characteristics: population at mid-year, international migrants as a percentage of the population, Human Development Index, estimated HIV prevalence (age: 15–49), presence of a policy prohibiting HIV screening for general employment purposes, government and civil society responses to having non-discrimination laws/regulations which specify migrants/mobile populations, government and civil society responses to having laws/regulations/policies that present obstacles to effective HIV prevention, treatment, care, and support for migrants/mobile populations, Corruption Perception Index, and gross national income per capita. Results: HIV-related restrictions exist in 45 out of 193 WHO countries (23%) in all regions of the world. We found that the Eastern Mediterranean and Western Pacific Regions have the highest proportions of countries with these restrictions. Our analyses showed that countries that have opted for restrictions have the following characteristics: smaller populations, higher proportions of migrants in the population, lower HIV prevalence rates, and lack of legislation protecting people living with HIV from screening for employment purposes, compared with countries without restrictions. Conclusion: Countries with a high proportion of international migrants tend to have travel restrictions – a finding that is relevant to migrant populations and travel medicine providers alike. Despite international pressure to remove travel restrictions, many countries continue to implement these restrictions for HIV-positive individuals on entry and stay. Since 2010, the United States and China have engaged in high profile removals. This may be indicative of an increasing trend, facilitated by various factors, including international advocacy and the setting of a UNAIDS goal to halve the number of countries with restrictions by 2015

Exploring Data Provenance in Handwritten Text Recognition Infrastructure: Sharing and Reusing Ground Truth Data, Referencing Models, and Acknowledging Contributions. Starting the Conversation on How We Could Get It Done

This paper discusses best practices for sharing and reusing Ground Truth in Handwritten Text Recognition infrastructures, as well as ways to reference and acknowledge contributions to the creation and enrichment of data within these systems. We discuss how one can place Ground Truth data in a repository and, subsequently, inform others through HTR-United. Furthermore, we want to suggest appropriate citation methods for ATR data, models, and contributions made by volunteers. Moreover, when using digitised sources (digital facsimiles), it becomes increasingly important to distinguish between the physical object and the digital collection. These topics all relate to the proper acknowledgement of labour put into digitising, transcribing, and sharing Ground Truth HTR data. This also points to broader issues surrounding the use of machine learning in archival and library contexts, and how the community should begin to acknowledge and record both contributions and data provenance

Patient-derived parathyroid organoids as a tracer and drug-screening application model

Parathyroid diseases are characterized by dysregulation of calcium homeostasis and alterations in parathyroid hormone (PTH) excretion. The development of parathyroid-targeted treatment and imaging tracers could benefit from in vitro models. Therefore, we aim to establish a patient-derived parathyroid organoid model representing human parathyroid tissue. Hyperplastic parathyroid tissue was dispersed, and parathyroid organoids (PTOs) were cultured and characterized. PTO-derived cells exhibited self-renewal over several passages, indicative of the presence of putative stem cells. Immunofluorescence and RNA sequencing confirmed that PTOs phenocopy hyperplastic parathyroid tissue. Exposure of PTOs to increasing calcium concentrations and PTH-lowering drugs resulted in significantly reduced PTH excretion. PTOs showed specific binding of the imaging tracers 11C-methionine and 99mTc-sestamibi. These data show the functionality of PTOs resembling the parathyroid. This PTO model recapitulates the originating tissue on gene and protein expression and functionality, paving the way for future physiology studies and therapeutic target and tracer discovery

Exploring Data Provenance in Handwritten Text Recognition Infrastructure: Sharing and Reusing Ground Truth Data, Referencing Models, and Acknowledging Contributions. Starting the Conversation on How We Could Get It Done

This paper discusses best practices for sharing and reusing Ground Truth in Handwritten Text Recognition infrastructures, as well as ways to reference and acknowledge contributions to the creation and enrichment of data within these systems. We discuss how one can place Ground Truth data in a repository and, subsequently, inform others through HTR-United. Furthermore, we want to suggest appropriate citation methods for ATR data, models, and contributions made by volunteers. Moreover, when using digitised sources (digital facsimiles), it becomes increasingly important to distinguish between the physical object and the digital collection. These topics all relate to the proper acknowledgement of labour put into digitising, transcribing, and sharing Ground Truth HTR data. This also points to broader issues surrounding the use of machine learning in archival and library contexts, and how the community should begin to acknowledge and record both contributions and data provenance